Background: Home deliveries is still high globally at 42% WHO 2022, due to high home deliveries, maternal death is also high at 43% globally. In sub-Sahara region home deliveries still high. Giving birth at health fac...Background: Home deliveries is still high globally at 42% WHO 2022, due to high home deliveries, maternal death is also high at 43% globally. In sub-Sahara region home deliveries still high. Giving birth at health facilities in most of sub-Saharan African countries Zambia inclusive is still a challenge whereby more than 51% of first-time mothers give birth at home and this gives a risk of high maternal and perinatal deaths. Therefore Reducing number of home deliveries is important to improve maternal and perinatal health issues. In this study, the aim was to investigate the determinants of home deliveries by pregnant mothers in the Luumbo zone of Gwembe district, Zambia. Purpose: Access to skilled care and facilities with capacity to provide emergency and newborn care is critical to reduce maternal death. In Zambia 42% of women still deliveries from home, suggesting a persistent challenge for women to seek, reach, and receive quality maternity care. This study aimed investigate the determinants of home deliveries by pregnant mothers in Luumbo zone of Gwembe district, Zambia. Methods: The study was conducted among postnatal mothers who came for postnatal care at 6 weeks in Luumbo Chabbobboma clinic in Gwembe district southern province of Zambia. This was a descriptive cross-sectional study where a Simple random sampling technique was used to select 105 women of childbearing age who attended postnatal and had a recent delivery. Data were collected using a researcher-administered structured questionnaire to identify determinants of home deliveries in Luumbo Chabbobboma zone. Data analysis was done using SPSS computer software version 27.0. Both descriptive and inferential (chi-square test) analyses were performed and statistical significance was taken at α ≤ 0.05. Results: The results show that 46 (43.8%) respondents were in the age bracket 20 - 29 years. Of the 105 respondents included in the study, 24 (22.9%) of them delivered from home. The results show that high maternal age (p = 0.03), occupation (p = 0.024), distance to the facility (p = 0.014), means of transportation (p = 0.023), multiparity (p = 0.01), timing and number of ANC visits (p Conclusion: From this population. The major reason why women still deliver at home was long distance to the nearest facility. To reduce maternal and perinatal mortality access to health facilities by pregnant women needs to be improved. There should also be active engagement of the traditional and religious institutions in the area.展开更多
Background: Current guidelines recommend regional anesthesia versus general as a method of choice for women undergoing cesarean deliveries (CS). However, little is known about the surgical times in the operating room ...Background: Current guidelines recommend regional anesthesia versus general as a method of choice for women undergoing cesarean deliveries (CS). However, little is known about the surgical times in the operating room and a choice of anesthesia for cesarean deliveries. Objective: This study was designed to compare times from the arrival to the OR to the delivery of the fetus between regional and general anesthesia along with maternal and fetal outcomes, for patients undergoing cesarean sections for non-reassuring fetal tracing. Study Design: Records were reviewed for patients who underwent cesarean delivery for non-reassuring fetal heart rate tracing from February 2012 to May 2018. A total of 190 charts were selected. Seven patients who received epidural or spinal anesthesia and then converted to general anesthesia (GA) were excluded. The primary outcomes were: 1) entering the operating room to skin incision (min);2) the time from entering the operating room to delivery of the fetus (min). These times were compared among the patients who underwent epidural, spinal and general anesthesia. The secondary criteria included time from skin incision to delivery of the fetus (min), estimated blood loss (ml), Apgars scores, Arterial/venous cord pH, NICU admissions and fetal complications. ANOVA or Kruskal-Wallis Test was used for the continuous variable and Fisher’s exact test was used for the categorical variable to test the differences between groups. Logistic regression model was used for the binary outcomes after adjusting for age, BMI and number of prior laparotomies. Results: Infants in the GA group were delivered significantly faster when compared to epidural and spinal group separately with a P-value of 0.001. The mean time from arrival to OR to delivery of the newborn in GA group was 12.7 minutes, compared to 27 minutes in epidural group and 32.7 minutes in the spinal group. Time intervals from time in the OR to incision and time from incision to delivery of the fetus were also calculated and were significantly shorter in the GA group when compared to spinal and epidural groups, P Conclusion: The induction of general anesthesia for emergency cesarean section resulted in shorter times to delivery compared to spinal and epidural. General anesthesia was associated with lower, albeit not statistically significant Apgar scores and higher NICU admissions, and had similar cord gases compared to neuraxial anesthesia group.展开更多
This study examined the non-medical factors that influence expectant mothers to opt for caesarean deliveries in Ghana. Data on 395 expectant mothers across the ten regions of Ghana who were located in urban, semi-rura...This study examined the non-medical factors that influence expectant mothers to opt for caesarean deliveries in Ghana. Data on 395 expectant mothers across the ten regions of Ghana who were located in urban, semi-rural and rural areas, and spanned a period of five years (from 2012 to 2016) were obtained from the Ghana Health Service. In fitting the logistic regression model, data on 355 expectant mothers (i.e. 89.9% of the data) was assigned to the analysis sample while 40 (i.e. 10.1%) was assigned to the hold-out sample. The hold-out sample together with other statistical measures of overall model fit, pseudo R2 measures and classification accuracy were used to validate the results obtained from the analysis sample. Significance was tested at p = 0.05. Determinants including, educational level of expectant mother, parity of expectant mother, baby’s birth weight, previous caesarean delivery, location of expectant mother, age of expectant mother and, period within the year of childbirth had a significant effect on caesarean delivery. The study recommended that health practitioners should be able to foretell expectant mothers who are likely to undergo caesarean delivery in order for them to prepare financially and psychologically to avoid further complications. Due to the significant positive attitude of women towards caesarean delivery rather than normal delivery, it is necessary to inform them about the advantages of normal delivery and the health hazards associated with caesarean delivery to the mother and child.展开更多
The essential nutrition actions explain nutrition through life cycle approach addressing women’s nutrition during pregnancy and lactation, optimal infant and young children feeding, nutritional care for sick children...The essential nutrition actions explain nutrition through life cycle approach addressing women’s nutrition during pregnancy and lactation, optimal infant and young children feeding, nutritional care for sick children and control of anemia, iodine and vitamin A deficiencies. Essential nutrition action has been implemented and resulted in positive outcome in less developed countries. However, the status of practice and associated factors were not studied in Ethiopia. Thus, institution-based cross-sectional study was conducted to assess the practice of essential nutrition actions in healthcare deliveries of Shebedino District, South Ethiopia. Quantitative data were collected though face-to-face interview with health workers and triangulated with data obtained through in-depth interview with health managers in the district and non-participatory observation of client-provider interaction in health facilities. Data were analyzed using SPSS16.0 software. Descriptive and logistic regression analyses were undertaken. The study revealed that 61 (56.0%) health workers practiced essential nutrition actions. Seventy one (65.1%) health workers were trained on essential nutrition actions. The practice of essential nutrition actions was associated with career structure of the health workers (AOR = 6.79, 95%CI: 2.31, 19.98), essential nutrition actions knowledge of health workers (AOR = 6.87, 95%CI: 2.11, 21.51) and availability of monthly nutrition related report form (AOR = 4.95, 95%CI: 1.46, 16.81). The practice of essential nutrition actions was low. The factors affecting the practice were inadequate training and knowledge of essential nutrition actions, career structure of the health workers and availability of monthly report form. Training should be provided for health workers on essential nutrition actions;moreover, essential nutrition actions indicators should be included in monthly report forms of the health institutions.展开更多
In this study,we investigate a forest-based solution representation for split delivery vehicle routing problems(SDVRPs),which have several practical applications and are among the most difficult vehicle routing proble...In this study,we investigate a forest-based solution representation for split delivery vehicle routing problems(SDVRPs),which have several practical applications and are among the most difficult vehicle routing problems.The new solution representation fully reflects the nature of split delivery,and can help reduce the search space when used in heuristic algorithms.Based on the forest structure,we devise three neighborhood search operators.To highlight the effectiveness of this solution representation,we integrate these operators into a standard tabu search framework.We conduct extensive experiments on three main SDVRPs addressed in the literature:The basic SDVRP,the multidepot SDVRP,and the SDVRP with time windows.The experimental results show that the new forest-based solution representation is particularly effective in designing and implementing neighborhood operators,and that our new approach outperforms state-of-the-art algorithms on standard datasets.展开更多
The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alz...The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.展开更多
Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a p...Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.展开更多
Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a ty...Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.展开更多
The vehicle routing problem(VRP) is a well-known combinatorial optimization issue in transportation and logistics network systems. There exist several limitations associated with the traditional VRP. Releasing the res...The vehicle routing problem(VRP) is a well-known combinatorial optimization issue in transportation and logistics network systems. There exist several limitations associated with the traditional VRP. Releasing the restricted conditions of traditional VRP has become a research focus in the past few decades. The vehicle routing problem with split deliveries and pickups(VRPSPDP) is particularly proposed to release the constraints on the visiting times per customer and vehicle capacity, that is, to allow the deliveries and pickups for each customer to be simultaneously split more than once. Few studies have focused on the VRPSPDP problem. In this paper we propose a two-stage heuristic method integrating the initial heuristic algorithm and hybrid heuristic algorithm to study the VRPSPDP problem. To validate the proposed algorithm, Solomon benchmark datasets and extended Solomon benchmark datasets were modified to compare with three other popular algorithms. A total of 18 datasets were used to evaluate the effectiveness of the proposed method. The computational results indicated that the proposed algorithm is superior to these three algorithms for VRPSPDP in terms of total travel cost and average loading rate.展开更多
The low efficiency and high cost of fresh agricultural product terminal distribution directly restrict the operation of the entire supply network.To reduce costs and optimize the distribution network,we construct a mi...The low efficiency and high cost of fresh agricultural product terminal distribution directly restrict the operation of the entire supply network.To reduce costs and optimize the distribution network,we construct a mixed integer programmingmodel that comprehensively considers tominimize fixed,transportation,fresh-keeping,time,carbon emissions,and performance incentive costs.We analyzed the performance of traditional rider distribution and robot distribution modes in detail.In addition,the uncertainty of the actual market demand poses a huge threat to the stability of the terminal distribution network.In order to resist uncertain interference,we further extend the model to a robust counterpart form.The results of the simulation show that the instability of random parameters will lead to an increase in the cost.Compared with the traditional rider distribution mode,the robot distribution mode can save 12.7%on logistics costs,and the distribution efficiency is higher.Our research can provide support for the design of planning schemes for transportation enterprise managers.展开更多
Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects.Although several nDDS have been successfully approved for clinic...Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects.Although several nDDS have been successfully approved for clinical use up to now,biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment.Polyethylene glycol(PEG)-modification(or PEGylation)has been regarded as the gold standard for stabilising nDDS in complex biological environment.However,the accelerated blood clearance(ABC)of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications.Zwitterionic polymer,a novel family of antifouling materials,have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility.Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues.More impressively,zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution,pressure gradients,impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications.The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS,which could facilitate their better clinical translation.Herein,we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlyingmechanisms.Finally,prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.展开更多
Transplantation of probiotics to the intestine can positively regulate the gut microbiota,thereby promoting the immune system and treating various diseases.However,the harsh gastrointestinal environment and short rete...Transplantation of probiotics to the intestine can positively regulate the gut microbiota,thereby promoting the immune system and treating various diseases.However,the harsh gastrointestinal environment and short retention time in the gastrointestinal tract significantly limit the bioavailability and intestinal colonization of probiotics.Herein,we present a double-layer polysaccharide hydrogel(DPH)in the form of a double-layer structure composed of a carboxymethyl cellulose(CMCL)supramolecular inner layer and a dialdehyde alginate(DAA)cross-linked carboxymethyl chitosan(CMCS)outer layer.This doublelayer structure allows DPH to encapsulate and deliver probiotics in a targeted manner within the body.In the stomach,the cage structure of the DPH is closed,and the outer layer absorbs surrounding liquids to form a barrier to protect the probiotics from gastric fluids.In the intestine,the cage structure opens and disintegrates,releasing the probiotics.Thus,DPH endows probiotics with excellent intestine-targeted delivery,improved oral bioavailability,enhanced gastrointestinal tract tolerance,and robust mucoadhesion capacity.The encapsulated probiotics exhibit almost unchanged bioactivity in the gastrointestinal tract before release,as well as improved oral delivery.In particular,probiotics encapsulated by DPH exhibit 100.1 times higher bioavailability and 10.6 times higher mucoadhesion than free probiotics in an animal model 48 h post-treatment.In addition,with a remarkable ability to survive and be retained in the intestine,probiotics encapsulated by DPH show excellent in vitro and in vivo competition with pathogens.Notably,DAA-mediated dynamic crosslinking not only maintains the overall integrity of the hydrogels but also controls the release timing of the probiotics.Thus,it is expected that encapsulated substances(probiotics,proteins,etc.)can be delivered to specific sites of the intestinal tract by means of DPH,by controlling the dynamic covalent crosslinking.展开更多
Microparticles have demonstrated value for regenerative medicine.Attempts in this field tend to focus on the development of intelligent multifunctional microparticles for tissue regeneration.Here,inspired by erythrocy...Microparticles have demonstrated value for regenerative medicine.Attempts in this field tend to focus on the development of intelligent multifunctional microparticles for tissue regeneration.Here,inspired by erythrocytes-associated self-repairing process in damaged tissue,we present novel biomimetic erythrocyte-like microparticles(ELMPs).These ELMPs,which are composed of extracellular matrix-like hybrid hydrogels and the functional additives of black phosphorus,hemoglobin,and growth factors(GFs),are generated by using a microfluidic electrospray.As the resultant ELMPs have the capacity for oxygen delivery and near-infrared-responsive release of both GFs and oxygen,they would have excellent biocompatibility and multifunctional performance when serving as microscaffolds for cell adhesion,stimulating angiogenesis,and adjusting the release profile of cargoes.Based on these features,we demonstrate that the ELMPs can stably overlap to fill a wound and realize controllable cargo release to achieve the desired curative effect of tissue regeneration.Thus,we consider our biomimetic ELMPs with discoid morphology and cargo-delivery capacity to be ideal for tissue engineering.展开更多
Disorders of the musculoskeletal system are the major contributors to the global burden of disease and current treatments show limited efficacy.Patients often suffer chronic pain and might eventually have to undergo e...Disorders of the musculoskeletal system are the major contributors to the global burden of disease and current treatments show limited efficacy.Patients often suffer chronic pain and might eventually have to undergo end-stage surgery.Therefore,future treatments should focus on early detection and intervention of regional lesions.Microrobots have been gradually used in organisms due to their advantages of intelligent,precise and minimally invasive targeted delivery.Through the combination of control and imaging systems,microrobots with good biosafety can be delivered to the desired area for treatment.In the musculoskeletal system,microrobots are mainly utilized to transport stem cells/drugs or to remove hazardous substances from the body.Compared to traditional biomaterial and tissue engineering strategies,active motion improves the efficiency and penetration of local targeting of cells/drugs.This review discusses the frontier applications of microrobotic systems in different tissues of the musculoskeletal system.We summarize the challenges and barriers that hinder clinical translation by evaluating the characteristics of different microrobots and finally point out the future direction of microrobots in the musculoskeletal system.展开更多
The eye,a complex organ isolated from the systemic circulation,presents significant drug delivery challenges owing to its protective mechanisms,such as the blood-retinal barrier and corneal impermeability.Conventional...The eye,a complex organ isolated from the systemic circulation,presents significant drug delivery challenges owing to its protective mechanisms,such as the blood-retinal barrier and corneal impermeability.Conventional drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and compliance.Polysaccharidebased microneedles(PSMNs)have emerged as a transformative solution for ophthalmic drug delivery.However,a comprehensive review of PSMNs in ophthalmology has not been published to date.In this review,we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug delivery.We provide a thorough analysis of PSMNs,summarizing the design principles,fabrication processes,and challenges addressed during fabrication,including improving patient comfort and compliance.We also describe recent advances and the performance of various PSMNs in both research and clinical scenarios.Finally,we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.展开更多
HIGHLIGHTS The formation of peptide nanocapsules is facilitated by a gradient interface,where the differential solvent concentration drives the peptides to preferentially localize and assemble.The peptide nanocapsules...HIGHLIGHTS The formation of peptide nanocapsules is facilitated by a gradient interface,where the differential solvent concentration drives the peptides to preferentially localize and assemble.The peptide nanocapsules,characterized by their hollow structures,demonstrated potential as carriers for targeted drug delivery.1 Introduction Peptide nanocapsules are a type of nanoscale delivery system that encapsulates active substances within a shell composed of peptides,leveraging the unique properties of peptides such as biocompatibility and biodegradability[1].Historically,the development of peptide nanocapsules was inspired primordially by the natural biological processes.展开更多
The rapid development of 5G/6G and AI enables an environment of Internet of Everything(IoE)which can support millions of connected mobile devices and applications to operate smoothly at high speed and low delay.Howeve...The rapid development of 5G/6G and AI enables an environment of Internet of Everything(IoE)which can support millions of connected mobile devices and applications to operate smoothly at high speed and low delay.However,these massive devices will lead to explosive traffic growth,which in turn cause great burden for the data transmission and content delivery.This challenge can be eased by sinking some critical content from cloud to edge.In this case,how to determine the critical content,where to sink and how to access the content correctly and efficiently become new challenges.This work focuses on establishing a highly efficient content delivery framework in the IoE environment.In particular,the IoE environment is re-constructed as an end-edge-cloud collaborative system,in which the concept of digital twin is applied to promote the collaboration.Based on the digital asset obtained by digital twin from end users,a content popularity prediction scheme is firstly proposed to decide the critical content by using the Temporal Pattern Attention(TPA)enabled Long Short-Term Memory(LSTM)model.Then,the prediction results are input for the proposed caching scheme to decide where to sink the critical content by using the Reinforce Learning(RL)technology.Finally,a collaborative routing scheme is proposed to determine the way to access the content with the objective of minimizing overhead.The experimental results indicate that the proposed schemes outperform the state-of-the-art benchmarks in terms of the caching hit rate,the average throughput,the successful content delivery rate and the average routing overhead.展开更多
Flurbiprofen(FB),a nonsteroidal anti-inflammatory drug,is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory effects.However,the racemic nature of its commercially available form...Flurbiprofen(FB),a nonsteroidal anti-inflammatory drug,is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory effects.However,the racemic nature of its commercially available formulation(Ocufen^(R))limits the full potential of its therapeutic activity,as the(S)-enantiomer is responsible for the desired antiinflammatory effects.Additionally,the limited corneal permeability of FB significantly restricts its bioavailability.In this study,we successfully separated the chiral isomers of FB to obtain the highly active(S)-FB.Subsequently,utilizing ion-pairing technology,we coupled(S)-FB with various counter-ions,such as sodium,diethylamine,trimethamine(TMA),and l-arginine,to enhance its ocular bioavailability.A comprehensive evaluation encompassed balanced solubility,octanol-water partition coefficient,corneal permeability,ocular pharmacokinetics,tissue distribution,and in vivo ocular anti-inflammatory activity of each chiral isomer salt.Among the various formulations,S-FBTMA exhibited superior water solubility(about 1–12 mg/ml),lipid solubility(1<lgP_(ow)<3)and corneal permeability.In comparison to Ocufen^(R),S-FBTMA demonstrated significantly higher in vivo antiinflammatory activity and lower ocular irritability(such as conjunctival congestion and tingling).The findings from this research highlight the potential of chiral separation and ion-pair enhanced permeation techniques in providing pharmaceutical enterprises focused on drug development with a valuable avenue for improving therapeutic outcomes.展开更多
Microgels prepared from natural or synthetic hydrogel materials have aroused extensive attention as multifunctional cells or drug carriers,that are promising for tissue engineering and regenerative medicine.Microgels ...Microgels prepared from natural or synthetic hydrogel materials have aroused extensive attention as multifunctional cells or drug carriers,that are promising for tissue engineering and regenerative medicine.Microgels can also be aggregated into microporous scaffolds,promoting cell infiltration and proliferation for tissue repair.This review gives an overview of recent developments in the fabrication techniques and applications of microgels.A series of conventional and novel strategies including emulsification,microfluidic,lithography,electrospray,centrifugation,gas-shearing,three-dimensional bioprinting,etc.are discussed in depth.The characteristics and applications of microgels and microgel-based scaffolds for cell culture and delivery are elaborated with an emphasis on the advantages of these carriers in cell therapy.Additionally,we expound on the ongoing and foreseeable applications and current limitations of microgels and their aggregate in the field of biomedical engineering.Through stimulating innovative ideas,the present review paves new avenues for expanding the application of microgels in cell delivery techniques.展开更多
Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations th...Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@M.The results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in vivo.Additionally,this material demonstrated a capability for drug release triggered by low pH conditions.Moreover,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM cells.Notably,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice.Therefore,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.展开更多
文摘Background: Home deliveries is still high globally at 42% WHO 2022, due to high home deliveries, maternal death is also high at 43% globally. In sub-Sahara region home deliveries still high. Giving birth at health facilities in most of sub-Saharan African countries Zambia inclusive is still a challenge whereby more than 51% of first-time mothers give birth at home and this gives a risk of high maternal and perinatal deaths. Therefore Reducing number of home deliveries is important to improve maternal and perinatal health issues. In this study, the aim was to investigate the determinants of home deliveries by pregnant mothers in the Luumbo zone of Gwembe district, Zambia. Purpose: Access to skilled care and facilities with capacity to provide emergency and newborn care is critical to reduce maternal death. In Zambia 42% of women still deliveries from home, suggesting a persistent challenge for women to seek, reach, and receive quality maternity care. This study aimed investigate the determinants of home deliveries by pregnant mothers in Luumbo zone of Gwembe district, Zambia. Methods: The study was conducted among postnatal mothers who came for postnatal care at 6 weeks in Luumbo Chabbobboma clinic in Gwembe district southern province of Zambia. This was a descriptive cross-sectional study where a Simple random sampling technique was used to select 105 women of childbearing age who attended postnatal and had a recent delivery. Data were collected using a researcher-administered structured questionnaire to identify determinants of home deliveries in Luumbo Chabbobboma zone. Data analysis was done using SPSS computer software version 27.0. Both descriptive and inferential (chi-square test) analyses were performed and statistical significance was taken at α ≤ 0.05. Results: The results show that 46 (43.8%) respondents were in the age bracket 20 - 29 years. Of the 105 respondents included in the study, 24 (22.9%) of them delivered from home. The results show that high maternal age (p = 0.03), occupation (p = 0.024), distance to the facility (p = 0.014), means of transportation (p = 0.023), multiparity (p = 0.01), timing and number of ANC visits (p Conclusion: From this population. The major reason why women still deliver at home was long distance to the nearest facility. To reduce maternal and perinatal mortality access to health facilities by pregnant women needs to be improved. There should also be active engagement of the traditional and religious institutions in the area.
文摘Background: Current guidelines recommend regional anesthesia versus general as a method of choice for women undergoing cesarean deliveries (CS). However, little is known about the surgical times in the operating room and a choice of anesthesia for cesarean deliveries. Objective: This study was designed to compare times from the arrival to the OR to the delivery of the fetus between regional and general anesthesia along with maternal and fetal outcomes, for patients undergoing cesarean sections for non-reassuring fetal tracing. Study Design: Records were reviewed for patients who underwent cesarean delivery for non-reassuring fetal heart rate tracing from February 2012 to May 2018. A total of 190 charts were selected. Seven patients who received epidural or spinal anesthesia and then converted to general anesthesia (GA) were excluded. The primary outcomes were: 1) entering the operating room to skin incision (min);2) the time from entering the operating room to delivery of the fetus (min). These times were compared among the patients who underwent epidural, spinal and general anesthesia. The secondary criteria included time from skin incision to delivery of the fetus (min), estimated blood loss (ml), Apgars scores, Arterial/venous cord pH, NICU admissions and fetal complications. ANOVA or Kruskal-Wallis Test was used for the continuous variable and Fisher’s exact test was used for the categorical variable to test the differences between groups. Logistic regression model was used for the binary outcomes after adjusting for age, BMI and number of prior laparotomies. Results: Infants in the GA group were delivered significantly faster when compared to epidural and spinal group separately with a P-value of 0.001. The mean time from arrival to OR to delivery of the newborn in GA group was 12.7 minutes, compared to 27 minutes in epidural group and 32.7 minutes in the spinal group. Time intervals from time in the OR to incision and time from incision to delivery of the fetus were also calculated and were significantly shorter in the GA group when compared to spinal and epidural groups, P Conclusion: The induction of general anesthesia for emergency cesarean section resulted in shorter times to delivery compared to spinal and epidural. General anesthesia was associated with lower, albeit not statistically significant Apgar scores and higher NICU admissions, and had similar cord gases compared to neuraxial anesthesia group.
文摘This study examined the non-medical factors that influence expectant mothers to opt for caesarean deliveries in Ghana. Data on 395 expectant mothers across the ten regions of Ghana who were located in urban, semi-rural and rural areas, and spanned a period of five years (from 2012 to 2016) were obtained from the Ghana Health Service. In fitting the logistic regression model, data on 355 expectant mothers (i.e. 89.9% of the data) was assigned to the analysis sample while 40 (i.e. 10.1%) was assigned to the hold-out sample. The hold-out sample together with other statistical measures of overall model fit, pseudo R2 measures and classification accuracy were used to validate the results obtained from the analysis sample. Significance was tested at p = 0.05. Determinants including, educational level of expectant mother, parity of expectant mother, baby’s birth weight, previous caesarean delivery, location of expectant mother, age of expectant mother and, period within the year of childbirth had a significant effect on caesarean delivery. The study recommended that health practitioners should be able to foretell expectant mothers who are likely to undergo caesarean delivery in order for them to prepare financially and psychologically to avoid further complications. Due to the significant positive attitude of women towards caesarean delivery rather than normal delivery, it is necessary to inform them about the advantages of normal delivery and the health hazards associated with caesarean delivery to the mother and child.
文摘The essential nutrition actions explain nutrition through life cycle approach addressing women’s nutrition during pregnancy and lactation, optimal infant and young children feeding, nutritional care for sick children and control of anemia, iodine and vitamin A deficiencies. Essential nutrition action has been implemented and resulted in positive outcome in less developed countries. However, the status of practice and associated factors were not studied in Ethiopia. Thus, institution-based cross-sectional study was conducted to assess the practice of essential nutrition actions in healthcare deliveries of Shebedino District, South Ethiopia. Quantitative data were collected though face-to-face interview with health workers and triangulated with data obtained through in-depth interview with health managers in the district and non-participatory observation of client-provider interaction in health facilities. Data were analyzed using SPSS16.0 software. Descriptive and logistic regression analyses were undertaken. The study revealed that 61 (56.0%) health workers practiced essential nutrition actions. Seventy one (65.1%) health workers were trained on essential nutrition actions. The practice of essential nutrition actions was associated with career structure of the health workers (AOR = 6.79, 95%CI: 2.31, 19.98), essential nutrition actions knowledge of health workers (AOR = 6.87, 95%CI: 2.11, 21.51) and availability of monthly nutrition related report form (AOR = 4.95, 95%CI: 1.46, 16.81). The practice of essential nutrition actions was low. The factors affecting the practice were inadequate training and knowledge of essential nutrition actions, career structure of the health workers and availability of monthly report form. Training should be provided for health workers on essential nutrition actions;moreover, essential nutrition actions indicators should be included in monthly report forms of the health institutions.
文摘In this study,we investigate a forest-based solution representation for split delivery vehicle routing problems(SDVRPs),which have several practical applications and are among the most difficult vehicle routing problems.The new solution representation fully reflects the nature of split delivery,and can help reduce the search space when used in heuristic algorithms.Based on the forest structure,we devise three neighborhood search operators.To highlight the effectiveness of this solution representation,we integrate these operators into a standard tabu search framework.We conduct extensive experiments on three main SDVRPs addressed in the literature:The basic SDVRP,the multidepot SDVRP,and the SDVRP with time windows.The experimental results show that the new forest-based solution representation is particularly effective in designing and implementing neighborhood operators,and that our new approach outperforms state-of-the-art algorithms on standard datasets.
基金supported by the National Natural Science Foundation of China,Nos.82072051 and 81771964(both to JG)the Natural Science Foundation of Shanghai Municipal Science and Technology Commission,No.22ZR147750(to YY)+2 种基金Science and Technology Support Projects in Biomedicine Field of Shanghai Science and Technology Commission,No.19441907500(to YY)Innovative Clinical Research Project of Changzheng Hospital,No.2020 YLCYJ-Y02(to YY)Characteristic Medical Service Project for the Army of Changzheng Hospital,No.2020 CZWJFW12(to YY)。
文摘The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.
基金supported by the National Key Research and Development Program of China,Nos.2017YFE0122900(to BH),2019YFA0110800(to WL),2019YFA0903802(to YW),2021YFA1101604(to LW),2018YFA0108502(to LF),and 2020YFA0804003(to JW)the National Natural Science Foundation of China,Nos.31621004(to WL,BH)and 31970821(to YW)+1 种基金CAS Project for Young Scientists in Basic Research,No.YSBR-041(to YW)Joint Funds of the National Natural Science Foundation of China,No.U21A20396(to BH)。
文摘Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.
文摘Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.
基金Project supported by the National Natural Science Foundation of China(No.51138003)the National Social Science Foundation of Chongqing of China(No.2013YBJJ035)
文摘The vehicle routing problem(VRP) is a well-known combinatorial optimization issue in transportation and logistics network systems. There exist several limitations associated with the traditional VRP. Releasing the restricted conditions of traditional VRP has become a research focus in the past few decades. The vehicle routing problem with split deliveries and pickups(VRPSPDP) is particularly proposed to release the constraints on the visiting times per customer and vehicle capacity, that is, to allow the deliveries and pickups for each customer to be simultaneously split more than once. Few studies have focused on the VRPSPDP problem. In this paper we propose a two-stage heuristic method integrating the initial heuristic algorithm and hybrid heuristic algorithm to study the VRPSPDP problem. To validate the proposed algorithm, Solomon benchmark datasets and extended Solomon benchmark datasets were modified to compare with three other popular algorithms. A total of 18 datasets were used to evaluate the effectiveness of the proposed method. The computational results indicated that the proposed algorithm is superior to these three algorithms for VRPSPDP in terms of total travel cost and average loading rate.
文摘The low efficiency and high cost of fresh agricultural product terminal distribution directly restrict the operation of the entire supply network.To reduce costs and optimize the distribution network,we construct a mixed integer programmingmodel that comprehensively considers tominimize fixed,transportation,fresh-keeping,time,carbon emissions,and performance incentive costs.We analyzed the performance of traditional rider distribution and robot distribution modes in detail.In addition,the uncertainty of the actual market demand poses a huge threat to the stability of the terminal distribution network.In order to resist uncertain interference,we further extend the model to a robust counterpart form.The results of the simulation show that the instability of random parameters will lead to an increase in the cost.Compared with the traditional rider distribution mode,the robot distribution mode can save 12.7%on logistics costs,and the distribution efficiency is higher.Our research can provide support for the design of planning schemes for transportation enterprise managers.
基金financially supported by the National Natural Science Foundation of China(grant no.8217070298)Guangdong Basic and Applied Basic Research Foundation(grant no.2020A1515110770,2021A1515220011,2022A1515010335).
文摘Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects.Although several nDDS have been successfully approved for clinical use up to now,biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment.Polyethylene glycol(PEG)-modification(or PEGylation)has been regarded as the gold standard for stabilising nDDS in complex biological environment.However,the accelerated blood clearance(ABC)of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications.Zwitterionic polymer,a novel family of antifouling materials,have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility.Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues.More impressively,zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution,pressure gradients,impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications.The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS,which could facilitate their better clinical translation.Herein,we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlyingmechanisms.Finally,prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.
基金supported by the National Natural Science Foundation of China (U21A20271)the China Agriculture Research System of the MOF and MARA (CARS-48)+2 种基金the Natural Science Foundation of Shandong Province (ZR2020JQ15)the Taishan Scholar Project of Shandong Province (tsqn201812020)the Fundamental Research Funds for the Central Universities (201941002).
文摘Transplantation of probiotics to the intestine can positively regulate the gut microbiota,thereby promoting the immune system and treating various diseases.However,the harsh gastrointestinal environment and short retention time in the gastrointestinal tract significantly limit the bioavailability and intestinal colonization of probiotics.Herein,we present a double-layer polysaccharide hydrogel(DPH)in the form of a double-layer structure composed of a carboxymethyl cellulose(CMCL)supramolecular inner layer and a dialdehyde alginate(DAA)cross-linked carboxymethyl chitosan(CMCS)outer layer.This doublelayer structure allows DPH to encapsulate and deliver probiotics in a targeted manner within the body.In the stomach,the cage structure of the DPH is closed,and the outer layer absorbs surrounding liquids to form a barrier to protect the probiotics from gastric fluids.In the intestine,the cage structure opens and disintegrates,releasing the probiotics.Thus,DPH endows probiotics with excellent intestine-targeted delivery,improved oral bioavailability,enhanced gastrointestinal tract tolerance,and robust mucoadhesion capacity.The encapsulated probiotics exhibit almost unchanged bioactivity in the gastrointestinal tract before release,as well as improved oral delivery.In particular,probiotics encapsulated by DPH exhibit 100.1 times higher bioavailability and 10.6 times higher mucoadhesion than free probiotics in an animal model 48 h post-treatment.In addition,with a remarkable ability to survive and be retained in the intestine,probiotics encapsulated by DPH show excellent in vitro and in vivo competition with pathogens.Notably,DAA-mediated dynamic crosslinking not only maintains the overall integrity of the hydrogels but also controls the release timing of the probiotics.Thus,it is expected that encapsulated substances(probiotics,proteins,etc.)can be delivered to specific sites of the intestinal tract by means of DPH,by controlling the dynamic covalent crosslinking.
基金supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(T2225003,52073060,and 61927805)+3 种基金the Nanjing Medical Science and Technique Development Foundation(ZKX21019)the Clinical Trials from Nanjing Drum Tower Hospital(2022-LCYJ-ZD-01)the Guangdong Basic and Applied Basic Research Foundation(2021B1515120054)the Shenzhen Fundamental Research Program(JCYJ20190813152616459 and JCYJ20210324133214038).
文摘Microparticles have demonstrated value for regenerative medicine.Attempts in this field tend to focus on the development of intelligent multifunctional microparticles for tissue regeneration.Here,inspired by erythrocytes-associated self-repairing process in damaged tissue,we present novel biomimetic erythrocyte-like microparticles(ELMPs).These ELMPs,which are composed of extracellular matrix-like hybrid hydrogels and the functional additives of black phosphorus,hemoglobin,and growth factors(GFs),are generated by using a microfluidic electrospray.As the resultant ELMPs have the capacity for oxygen delivery and near-infrared-responsive release of both GFs and oxygen,they would have excellent biocompatibility and multifunctional performance when serving as microscaffolds for cell adhesion,stimulating angiogenesis,and adjusting the release profile of cargoes.Based on these features,we demonstrate that the ELMPs can stably overlap to fill a wound and realize controllable cargo release to achieve the desired curative effect of tissue regeneration.Thus,we consider our biomimetic ELMPs with discoid morphology and cargo-delivery capacity to be ideal for tissue engineering.
基金supported by the National Natural Science Foundation of China(No.81572187,No.81871812 and No.52205590)the Natural Science Foundation of Jiangsu Province(No.BK20220834)+1 种基金project supported by Ruihua Charity Foundation(YL20220525)the Start-up Research Fund of Southeast University(No.RF1028623098).
文摘Disorders of the musculoskeletal system are the major contributors to the global burden of disease and current treatments show limited efficacy.Patients often suffer chronic pain and might eventually have to undergo end-stage surgery.Therefore,future treatments should focus on early detection and intervention of regional lesions.Microrobots have been gradually used in organisms due to their advantages of intelligent,precise and minimally invasive targeted delivery.Through the combination of control and imaging systems,microrobots with good biosafety can be delivered to the desired area for treatment.In the musculoskeletal system,microrobots are mainly utilized to transport stem cells/drugs or to remove hazardous substances from the body.Compared to traditional biomaterial and tissue engineering strategies,active motion improves the efficiency and penetration of local targeting of cells/drugs.This review discusses the frontier applications of microrobotic systems in different tissues of the musculoskeletal system.We summarize the challenges and barriers that hinder clinical translation by evaluating the characteristics of different microrobots and finally point out the future direction of microrobots in the musculoskeletal system.
基金supported by the National Natural Science Foundation of China(82371032,82070923)the Major Basic Research Project of the Natural Science Foundation of Shandong Province(ZR2023ZD60)+1 种基金the Taishan Scholar Program(20231255)the Academic Promotion Program of Shandong First Medical University(2019RC009).
文摘The eye,a complex organ isolated from the systemic circulation,presents significant drug delivery challenges owing to its protective mechanisms,such as the blood-retinal barrier and corneal impermeability.Conventional drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and compliance.Polysaccharidebased microneedles(PSMNs)have emerged as a transformative solution for ophthalmic drug delivery.However,a comprehensive review of PSMNs in ophthalmology has not been published to date.In this review,we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug delivery.We provide a thorough analysis of PSMNs,summarizing the design principles,fabrication processes,and challenges addressed during fabrication,including improving patient comfort and compliance.We also describe recent advances and the performance of various PSMNs in both research and clinical scenarios.Finally,we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.
文摘HIGHLIGHTS The formation of peptide nanocapsules is facilitated by a gradient interface,where the differential solvent concentration drives the peptides to preferentially localize and assemble.The peptide nanocapsules,characterized by their hollow structures,demonstrated potential as carriers for targeted drug delivery.1 Introduction Peptide nanocapsules are a type of nanoscale delivery system that encapsulates active substances within a shell composed of peptides,leveraging the unique properties of peptides such as biocompatibility and biodegradability[1].Historically,the development of peptide nanocapsules was inspired primordially by the natural biological processes.
基金supported by the National Key Research and Development Program of China under Grant No.2019YFB1802800the National Natural Science Foundation of China under Grant No.62002055,62032013,61872073,62202247.
文摘The rapid development of 5G/6G and AI enables an environment of Internet of Everything(IoE)which can support millions of connected mobile devices and applications to operate smoothly at high speed and low delay.However,these massive devices will lead to explosive traffic growth,which in turn cause great burden for the data transmission and content delivery.This challenge can be eased by sinking some critical content from cloud to edge.In this case,how to determine the critical content,where to sink and how to access the content correctly and efficiently become new challenges.This work focuses on establishing a highly efficient content delivery framework in the IoE environment.In particular,the IoE environment is re-constructed as an end-edge-cloud collaborative system,in which the concept of digital twin is applied to promote the collaboration.Based on the digital asset obtained by digital twin from end users,a content popularity prediction scheme is firstly proposed to decide the critical content by using the Temporal Pattern Attention(TPA)enabled Long Short-Term Memory(LSTM)model.Then,the prediction results are input for the proposed caching scheme to decide where to sink the critical content by using the Reinforce Learning(RL)technology.Finally,a collaborative routing scheme is proposed to determine the way to access the content with the objective of minimizing overhead.The experimental results indicate that the proposed schemes outperform the state-of-the-art benchmarks in terms of the caching hit rate,the average throughput,the successful content delivery rate and the average routing overhead.
基金financially supported by the National Postdoctoral Foundation of China(No.2023M730375)Liaoning Province Department of Education Project(No.LJKMZ20221365)the State Key Laboratory of Natural and Biomimetic Drugs(No.K202215)。
文摘Flurbiprofen(FB),a nonsteroidal anti-inflammatory drug,is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory effects.However,the racemic nature of its commercially available formulation(Ocufen^(R))limits the full potential of its therapeutic activity,as the(S)-enantiomer is responsible for the desired antiinflammatory effects.Additionally,the limited corneal permeability of FB significantly restricts its bioavailability.In this study,we successfully separated the chiral isomers of FB to obtain the highly active(S)-FB.Subsequently,utilizing ion-pairing technology,we coupled(S)-FB with various counter-ions,such as sodium,diethylamine,trimethamine(TMA),and l-arginine,to enhance its ocular bioavailability.A comprehensive evaluation encompassed balanced solubility,octanol-water partition coefficient,corneal permeability,ocular pharmacokinetics,tissue distribution,and in vivo ocular anti-inflammatory activity of each chiral isomer salt.Among the various formulations,S-FBTMA exhibited superior water solubility(about 1–12 mg/ml),lipid solubility(1<lgP_(ow)<3)and corneal permeability.In comparison to Ocufen^(R),S-FBTMA demonstrated significantly higher in vivo antiinflammatory activity and lower ocular irritability(such as conjunctival congestion and tingling).The findings from this research highlight the potential of chiral separation and ion-pair enhanced permeation techniques in providing pharmaceutical enterprises focused on drug development with a valuable avenue for improving therapeutic outcomes.
基金supported by the National Key Research and Development Program of China(No.2022YFA1104600)the National Natural Science Foundation of China(NSFC)Program(Nos.32201183,31927801,32101105)the Science and Technology Program of Guangzhou(SL2022A04J00774).
文摘Microgels prepared from natural or synthetic hydrogel materials have aroused extensive attention as multifunctional cells or drug carriers,that are promising for tissue engineering and regenerative medicine.Microgels can also be aggregated into microporous scaffolds,promoting cell infiltration and proliferation for tissue repair.This review gives an overview of recent developments in the fabrication techniques and applications of microgels.A series of conventional and novel strategies including emulsification,microfluidic,lithography,electrospray,centrifugation,gas-shearing,three-dimensional bioprinting,etc.are discussed in depth.The characteristics and applications of microgels and microgel-based scaffolds for cell culture and delivery are elaborated with an emphasis on the advantages of these carriers in cell therapy.Additionally,we expound on the ongoing and foreseeable applications and current limitations of microgels and their aggregate in the field of biomedical engineering.Through stimulating innovative ideas,the present review paves new avenues for expanding the application of microgels in cell delivery techniques.
基金supported by the National Natural Science Foundation of China(52073145 and 82004081)the Jiangsu Talent Professor Program,Jiangsu Innovation Project of Graduate Student(KYCX23-2192)+1 种基金the National Natural Science Foundation of Nanjing University of Chinese Medicine(NZY82004081)the Special Grants of China Postdoctoral Science Foundation(2021T140792).
文摘Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@M.The results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in vivo.Additionally,this material demonstrated a capability for drug release triggered by low pH conditions.Moreover,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM cells.Notably,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice.Therefore,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.