Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we re...Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.展开更多
The coastal areas of the lower reaches of Oujiang River Basin are rich in groundwater resources.However,the unsustainable exploitation and utilization of groundwater have led to significant changes in the groundwater ...The coastal areas of the lower reaches of Oujiang River Basin are rich in groundwater resources.However,the unsustainable exploitation and utilization of groundwater have led to significant changes in the groundwater environment.Understanding the characteristics and genesis of groundwater salinization is crucial for preventing its deterioration and ensuring sustainable utilization.In this study,a comprehensive approach combining the ion ratio method,mineral saturation index method and multivariate statistical analysis was employed to investigate the hydrochemical characteristics and main controlling factors in the study area.The findings reveal that:(1)Groundwater samples in study area exhibit a neutral to slightly alkaline pH.The predominant chemical types of unconfined water are HCO_(3)-Ca·Na,HCO_(3)·Cl-Na·Ca and HCO_(3)·SO_(4)-Ca·Na,while confined water mainly exhibits Cl·HCO_(3)-Na and Cl-Na types.(2)Salinity coefficients indicate an increase in salinity from unconfined to confined water.TDS,Na^(+)and Cl^(–)concentrations show an increasing trend from mountainous to coastal areas in unconfined water,while confined water displays variability in TDS,Na^(+)and Cl^(–)concentrations.(3)Groundwater salinity is mainly influenced by water-rock interactions,including the dissolution of halite and gypsum,cation exchange,and seawater intrusion etc.Additionally,human activities and carbonate dissolution contribute to salinity in unconfined water.Seawater intrusion is identified as the primary factor leading to higher salinity in confined water compared to unconfined water,with increasing cation exchange and seawater interaction observed from unconfined to confined water.展开更多
Objective:To explore the treatment strategies and clinical effects for recurrent respiratory infections in children.Methods:From May 2022 to May 2024,100 pediatric patients with recurrent respiratory infections were s...Objective:To explore the treatment strategies and clinical effects for recurrent respiratory infections in children.Methods:From May 2022 to May 2024,100 pediatric patients with recurrent respiratory infections were selected in this study and evenly divided into two groups.The control group(50 patients)was treated with conventional therapy supplemented with budesonide,while the observation group(50 patients)received pidotimod treatment in addition to the control group’s treatment.Subsequently,the duration of clinical symptom improvement,respiratory function enhancement,serological index changes,reinfection status,and parental satisfaction were compared between the two groups.Results:In terms of clinical symptoms,the observation group showed significantly shorter durations of fever reduction,cough relief,tonsil swelling reduction,and disappearance of fine wet rales compared to the control group(average reduction times were 1.6 days,2.3 days,2.1 days,and 1.9 days,respectively,P<0.05).Regarding respiratory function,the observation group experienced a 12%increase in peak expiratory flow rate variability,a 0.6-liter increase in lung capacity,a 0.7-liter increase in forced lung capacity,and a 0.5-liter increase in forced expiratory volume in the first second after treatment,all significantly higher than the control group(P<0.05).Serological testing revealed that interferon-γand interleukin-2 levels increased by 15%and 18%,respectively,while interferon-α,interleukin-5,and interleukin-4 levels decreased by 10%,12%,and 9%,respectively,in the observation group,showing significant differences compared to the control group(P<0.05).Additionally,the reinfection rate in the observation group(10%)was significantly lower than that in the control group(30%),with an average reduction of two reinfections within one year and a 3.2-day shorter infection control time(P<0.05).In terms of parental satisfaction,the observation group achieved 95%,significantly higher than the 70%in the control group(P<0.05).Conclusion:The addition of pidotimod to conventional therapy for pediatric patients with recurrent respiratory infections can significantly alleviate clinical symptoms,promote the recovery of respiratory function,regulate serological indicators,effectively reduce the risk of reinfection,and improve parental satisfaction.This method deserves widespread clinical application.展开更多
Objective:This study aims to investigate the impact of early intervention on neuropsychological development in children with autism and attention deficit hyperactivity disorder(ADHD),providing effective intervention s...Objective:This study aims to investigate the impact of early intervention on neuropsychological development in children with autism and attention deficit hyperactivity disorder(ADHD),providing effective intervention strategies for clinical practice.Methods:A total of 130 children with autism and ADHD who visited the hospital between June 2023 and June 2024 were selected as study subjects and randomly divided into an intervention group and a control group,with 65 children in each group.The intervention group received a one-year early comprehensive intervention,including behavioral therapy,cognitive training,and family guidance,while the control group only received routine medical care.The neuropsychological development assessment scale was used to evaluate both groups before and after the intervention to compare changes in their neuropsychological development levels.Results:Children in the intervention group showed significant improvements in cognitive function,social skills,language ability,and attention concentration,with an average improvement score of 23.5 points.Children in the control group did not show significant improvements in these areas,with an average improvement score of only 5.8 points.The difference between the two groups was statistically significant(P<0.05).Conclusion:Early comprehensive intervention has a significant promoting effect on the neuropsychological development of children with autism and ADHD.Targeted behavioral therapy,cognitive training,and family guidance can effectively enhance children’s cognitive,social,language,and attention abilities,laying a solid foundation for their future overall development.Therefore,it is recommended to actively promote and apply early intervention strategies in clinical practice.展开更多
Obesity is one of the most serious global health problems,with an incidence that increases yearly and coincides with the development of cancer.Adipose tissue macrophages(ATMs)are particularly important in this context...Obesity is one of the most serious global health problems,with an incidence that increases yearly and coincides with the development of cancer.Adipose tissue macrophages(ATMs)are particularly important in this context and contribute to linking obesity-related inflammation and tumor progression.However,the functions of ATMs on the progression of obesity-associated cancer remain unclear.In this review,we describe the origins,phenotypes,and functions of ATMs.Subsequently,we summarize the potential mechanisms on the reprogramming of ATMs in the obesity-associated microenvironment,including the direct exchange of dysfunctional metabolites,inordinate cytokines and other signaling mediators,transfer of extracellular vesicle cargo,and variations in the gut microbiota and its metabolites.A better understanding of the properties and functions of ATMs under conditions of obesity will lead to the development of new therapeutic interventions for obesity-related cancer.展开更多
Single-atom materials have demonstrated attractive physicochemical characteristics.However,understanding the relationships between the coordination environment of single atoms and their properties at the atomic level ...Single-atom materials have demonstrated attractive physicochemical characteristics.However,understanding the relationships between the coordination environment of single atoms and their properties at the atomic level remains a considerable challenge.Herein,a facile waterassisted carbonization approach is developed to fabricate well-defined asymmetrically coordinated Co–N_(4)–O sites on biomass-derived carbon nanofiber(Co–N_(4)–O/NCF)for electromagnetic wave(EMW)absorption.In such nanofiber,one atomically dispersed Co site is coordinated with four N atoms in the graphene basal plane and one oxygen atom in the axial direction.In-depth experimental and theoretical studies reveal that the axial Co–O coordination breaks the charge distribution symmetry in the planar porphyrin-like Co–N_(4) structure,leading to significantly enhanced dielectric polarization loss relevant to the planar Co–N_(4) sites.Importantly,the film based on Co–N_(4)–O/NCF exhibits light weight,flexibility,excellent mechanical properties,great thermal insulating feature,and excellent EMW absorption with a reflection loss of−45.82 dB along with an effective absorption bandwidth of 4.8 GHz.The findings of this work offer insight into the relationships between the single-atom coordination environment and the dielectric performance,and the proposed strategy can be extended toward the engineering of asymmetrically coordinated single atoms for various applications.展开更多
Very low frequency(VLF)signals are propagated between the ground-ionosphere.Multimode interference will cause the phase to show oscillatory changes with distance while propagating at night,leading to abnormalities in ...Very low frequency(VLF)signals are propagated between the ground-ionosphere.Multimode interference will cause the phase to show oscillatory changes with distance while propagating at night,leading to abnormalities in the received VLF signal.This study uses the VLF signal received in Qingdao City,Shandong Province,from the Russian Alpha navigation system to explore the multimode interference problem of VLF signal propagation.The characteristics of the effect of multimode interference phenomena on the phase are analyzed according to the variation of the phase of the VLF signal.However,the phase of VLF signals will also be affected by the X-ray and energetic particles that are released during the eruption of solar flares,therefore the two phenomena are studied in this work.It is concluded that the X-ray will not affect the phase of VLF signals at night,but the energetic particles will affect the phase change,and the influence of energetic particles should be excluded in the study of multimode interference phenomena.Using VLF signals for navigation positioning in degraded or unavailable GPS conditions is of great practical significance for VLF navigation systems as it can avoid the influence of multimode interference and improve positioning accuracy.展开更多
Colorectal cancer has a high incidence and mortality rate in China, with the majority of cases being middle and low rectal cancer. Surgical intervention is currently the main treatment modality for locally advanced re...Colorectal cancer has a high incidence and mortality rate in China, with the majority of cases being middle and low rectal cancer. Surgical intervention is currently the main treatment modality for locally advanced rectal cancer, with the common goal of improving oncological outcomes while preserving function. The controversy regarding the circumferential resection margin distance in rectal cancer surgery has been resolved. With the promotion of neoadjuvant therapy concepts and advancements in technology, treatment strategies have become more diverse.Following tumor downstaging, there is an increasing trend towards extending the safe distance of distal rectal margin. This provides more opportunities for patients with low rectal cancer to preserve their anal function.However, there is currently no consensus on the specific distance of distal resection margin.展开更多
Objective: There are no comprehensive studies on survival outcomes and optimal treatment protocols for cervical esophageal cancer(CEC), due to its rare clinical prevalence. Our objective was to determine the relations...Objective: There are no comprehensive studies on survival outcomes and optimal treatment protocols for cervical esophageal cancer(CEC), due to its rare clinical prevalence. Our objective was to determine the relationship between pathological characteristics, treatment protocols, and survival outcomes in Chinese CEC patients.Methods: A total of 500 Chinese CEC patients were selected from our 500,000 esophageal and gastric cardia carcinoma database(1973–2018). There were two main groups: patients treated with surgery, and patients receiving non-surgical treatments(radiotherapy, radiochemotherapy, and chemotherapy). The Chi-square test and Kaplan–Meier method were used to compare the continuous variables and survival.Results: Among the 500 CEC patients, 278(55.6%) were male, and the median age was 60.9 ± 9.4 years. A total of 496 patients(99.2%) were diagnosed with squamous cell carcinoma. In 171(34.2%) patients who received surgery, 22(12.9%) had undergone laryngectomy. In 322(64.4%) patients who received non-surgical treatments, 245(76.1%) received radiotherapy. Stratified survival analysis showed that only T stage was related with survival outcomes for CEC patients in the surgical group, and the outcomes between laryngectomy and non-laryngectomy patients were similar. It was noteworthy that the 5-year survival rate was similar in CEC patients among the different groups treated with surgery, radiotherapy, chemotherapy, or radiochemotherapy(P = 0.244). Conclusions: The CEC patients had similar survival outcomes after curative esophagectomy and radiotherapy, including those with or without total laryngectomy. These findings suggest that radiotherapy could be the initial choice for treatment of Chinese CEC patients.展开更多
The loss-of-function mutations in the ALPL result in hypophosphatasia(HPP), an inborn metabolic disorder that causes skeletal mineralization defects. In adults, the main clinical features are early loss of primary or ...The loss-of-function mutations in the ALPL result in hypophosphatasia(HPP), an inborn metabolic disorder that causes skeletal mineralization defects. In adults, the main clinical features are early loss of primary or secondary teeth, osteoporosis, bone pain,chondrocalcinosis, and fractures. However, guidelines for the treatment of adults with HPP are not available. Here, we show that ALPL deficiency caused a reduction in intracellular Ca2+ influx, resulting in an osteoporotic phenotype due to downregulated osteogenic differentiation and upregulated adipogenic differentiation in both human and mouse bone marrow mesenchymal stem cells(BMSCs). Increasing the intracellular level of calcium in BMSCs by ionomycin treatment rescued the osteoporotic phenotype in alpl+/- mice and BMSC-specific(Prrx1-alpl-/-) conditional alpl knockout mice. Mechanistically, ALPL was found to be required for the maintenance of intracellular Ca2+ influx, which it achieves by regulating L-type Ca2+ channel trafficking via binding to the α2δsubunits to regulate the internalization of the L-type Ca2+ channel. Decreased Ca2+ flux inactivates the Akt/GSK3β/β-catenin signaling pathway, which regulates lineage differentiation of BMSCs. This study identifies a previously unknown role of the ectoenzyme ALPL in the maintenance of calcium channel trafficking to regulate stem cell lineage differentiation and bone homeostasis. Accelerating Ca2+ flux through L-type Ca2+ channels by ionomycin treatment may be a promising therapeutic approach for adult patients with HPP.展开更多
Primary liver cancer(PLC) is one of the most common malignant tumors in China. PLC is characterized by insidious onset, rapid progress, poor quality of life, and short survival time. Notably, current treatment strateg...Primary liver cancer(PLC) is one of the most common malignant tumors in China. PLC is characterized by insidious onset, rapid progress, poor quality of life, and short survival time. Notably, current treatment strategies remain unsatisfactory. Traditional Chinese medicines(TCM) have been used to treat a variety of diseases, including liver diseases, for more than 2000 years. In this study, we performed a review of the use frequency and clinical efficacy of TCM in treating PLC. Relevant literature from January 1, 2009, to January 1, 2021 was retrieved from network databases of China National Knowledge Infrastructure(CNKI), Chongqing VIP, Wanfang, PubMed, and SinoMed. The most frequently used TCM and their efficacy in PLC treatment were summarized. Based on the inclusion and exclusion criteria, 33 articles were selected. Overall, the efficacy of the combination of TCM and Western medicines in the treatment of PLC was higher than that in the control groups(i.e. treatment with Western medicines alone)(65.11% vs.44.31%, P <.05). Among the 33 selected articles, 11 were investigated for TCM preparation(marketed drugs) and 22 for TCM formulas. In total, 102 types of TCM(single herbs) were used to treat PLC. The top five most frequently used TCM were Poria(14.71%), Astragali radix(13.73%), Atractylodis Macrocephalae Rhizoma(12.75%), Bupleuri radix(12.75%), and Glycyrrhizae radix et Rhizoma(11.76%). Of the 102 types of TCM, tonics were the most frequently used categories, followed by heat-clearing medicines, blood-invigorating medicines, and stasis-resolving medicines. Of 207 papers, 174(84.06%) could not be subjected to statistical analysis due to research quality. Further high-quality research on herb sources, formula components and dosage, toxicology, and ethics of TCM is necessary. In conclusion, TCM play a promising role in the treatment and management of PLC, although further investigations are warranted.展开更多
Dear Editor,Cornealendotheliitisisacommonandintriguing clinicalentitycharacterizedbycornealedema,keratic precipitates,and mild to moderate anterior chamber reaction,which occupies the important pathogenic factor of co...Dear Editor,Cornealendotheliitisisacommonandintriguing clinicalentitycharacterizedbycornealedema,keratic precipitates,and mild to moderate anterior chamber reaction,which occupies the important pathogenic factor of corneal blindness[1].Robin et al[2]first described a patient who suffered from intraocular inflammation and progressive corneal endotheliitis associated with herpes simplex infection.Since then,accumulating clinical evidence confirmed that its etiology was mainly attributed to the family of herpesviridae,including herpes simplex virus,varicella zoster virus,and cytomegalovirus,which initiated the direct cell damage and immune-and inflammatory-mediated lesion on endothelial cells[1,3].展开更多
Recently, 3D display technology, and content creation tools have been undergone rigorous development and as a result they have been widely adopted by home and professional users. 3D digital repositories are increasing...Recently, 3D display technology, and content creation tools have been undergone rigorous development and as a result they have been widely adopted by home and professional users. 3D digital repositories are increasing and becoming available ubiquitously. However, searching and visualizing 3D content remains a great challenge. In this paper, we propose and present the development of a novel approach for creating hypervideos, which ease the 3D content search and retrieval. It is called the dynamic hyperlinker for 3D content search and retrieval process. It advances 3D multimedia navigability and searchability by creating dynamic links for selectable and clickable objects in the video scene whilst the user consumes the 3D video clip. The proposed system involves 3D video processing, such as detecting/tracking clickable objects, annotating objects, and metadata engineering including 3D content descriptive protocol. Such system attracts the attention from both home and professional users and more specifically broadcasters and digital content providers. The experiment is conducted on full parallax holoscopic 3D videos “also known as integral images”.展开更多
Compared with the traditional heteroatom doping,employing heterostructure is a new modulating approach for carbon-based electrocatalysts.Herein,a facile ball milling-assisted route is proposed to synthesize porous car...Compared with the traditional heteroatom doping,employing heterostructure is a new modulating approach for carbon-based electrocatalysts.Herein,a facile ball milling-assisted route is proposed to synthesize porous carbon materials composed of abundant graphene/hexagonal boron nitride(G/h-BN)heterostructures.Metal Ni powder and nanoscale h-BN sheets are used as a catalytic substrate/hard template and“nucleation seed”for the formation of the heterostructure,respectively.As-prepared G/h-BN heterostructures exhibit enhanced electrocatalytic activity toward H_(2)O_(2) generation with 86%-95%selectivity at the range of 0.45-0.75 V versus reversible hydrogen electrode(RHE)and a positive onset potential of 0.79 versus RHE(defined at a ring current density of 0.3 mA cm^(-2))in the alkaline solution.In a flow cell,G/h-BN heterostructured electrocatalyst has a H_(2)O_(2) production rate of up to 762 mmol g_(catalyst)^(-1) h^(-1) and Faradaic efficiency of over 75%during 12 h testing,superior to the reported carbon-based electrocatalysts.The density functional theory simulation suggests that the B atoms at the interface of the G/h-BN heterostructure are the key active sites.This research provides a new route to activate carbon catalysts toward highly active and selective O_(2)-to-H_(2)O_(2) conversion.展开更多
CMOS image sensors produced by the existing CMOS manufacturing process usually have difficulty achieving complete charge transfer owing to the introduction of potential barriers or Si/SiO_(2)interface state traps in t...CMOS image sensors produced by the existing CMOS manufacturing process usually have difficulty achieving complete charge transfer owing to the introduction of potential barriers or Si/SiO_(2)interface state traps in the charge transfer path,which reduces the charge transfer efficiency and image quality.Until now,scholars have only considered mechanisms that limit charge transfer from the perspectives of potential barriers and spill back effect under high illumination condition.However,the existing models have thus far ignored the charge transfer limitation due to Si/SiO_(2)interface state traps in the transfer gate channel,particularly under low illumination.Therefore,this paper proposes,for the first time,an analytical model for quantifying the incomplete charge transfer caused by Si/SiO_(2)interface state traps in the transfer gate channel under low illumination.This model can predict the variation rules of the number of untransferred charges and charge transfer efficiency when the trap energy level follows Gaussian distribution,exponential distribution and measured distribution.The model was verified with technology computer-aided design simulations,and the results showed that the simulation results exhibit the consistency with the proposed model.展开更多
Calcium(Ca^(2+))plays a pivotal role in various signal transduction pathways.Calcineurin B-like proteins(CBLs)are a unique group of Ca^(2+)sensors that decode Ca^(2+)signals by activating the plant specific protein ki...Calcium(Ca^(2+))plays a pivotal role in various signal transduction pathways.Calcineurin B-like proteins(CBLs)are a unique group of Ca^(2+)sensors that decode Ca^(2+)signals by activating the plant specific protein kinase known as the CBL-interacting protein kinase(CIPK).In plants,the CBL-CIPK signaling network regulates multiple signals in response to different extracellular cues including abiotic stress.However,the genome wide annotation and expression patterns of CBLs and CIPKs in woody cutting flower plants are still unclear.In this study,a total number of 7 CBLs(RcCBLs)and 17 CIPKs(RcCIPKs)genes,divided into four and five subfamilies,respectively,were identified from the rose genome.All RcCBLs possess a classic elongation factor-hand(EF-hand)domain,while all RcCIPKs possess both the classic kinase and NAF domains.Most RcCBLs were predicted to be plasma membrane localized,whereas most RcCIPKs were predicted to be cytoplasmic localized.Synteny analysis showed that one RcCBL gene pair and five RcCIPK gene pairs have gone through whole genome duplication events.Promoter cis-element prediction assays indicated that RcCBLs and RcCIPKs could function in different abiotic stress responses in rose plants.Further quantitative real-time PCR analysis demonstrated that RcCBLs and RcCIPKs were expressed in different organs with overlapped but distinct patterns in response to various abiotic stresses.The findings in this work will provide fundamental information and gene resources for further functional research on RcCBLs and RcCIPKs.展开更多
LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811)is the most promising cathode for high-energy Li-ion batteries,despite its poor cycling stability that originates from the reactions that occur with the electrolyte.Herein,to sol...LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811)is the most promising cathode for high-energy Li-ion batteries,despite its poor cycling stability that originates from the reactions that occur with the electrolyte.Herein,to solve this interfacial issue,a facile electrolytic electrochemical polymerization process was introduced in this paper,and a uniform conductive electrolyte interface(polyaniline)was successfully constructed on the surface of the NCM811 porous electrode(PANI-NCM),which facilitated the charge transfer during charge/discharge.The side reactions at the interface between the cathode and the electrolyte are suppressed,and thereby,the cycling performance and rate capability are considerably improved.PANI-NCM delivers an initial capacity of 157.2 mAh·g^(-1)as well as excellent cyclability(capacity retention of 88%after 500 cycles at 2C),whereas the capacity of the bare NCM811 has dropped to 31.3 mAh·g^(-1).In addition,polypyrrole and polythiophene also can be formed through electrolytic electrochemical polymerization process,which provides a practicable tactic to modify the interfacial stability of cathodes for high-energy Li-ion batteries.展开更多
Photodynamic therapy (PDT) is a clinically approved cancer treatment that uses energy of light to generate active substances that cause damage to the cancer. Photosensitizers are employed to absorb light and generate ...Photodynamic therapy (PDT) is a clinically approved cancer treatment that uses energy of light to generate active substances that cause damage to the cancer. Photosensitizers are employed to absorb light and generate toxic reactive oxygen species (ROS) to damage biomolecules like DNA. At the same time, some chemotherapy drugs like nucleotide analogues can provide mechanism-guided promotion in the treatment efficacy of PDT. However, the photosensitizer and chemotherapy drugs used in PDT is usually organic molecules, which suffers from bad solubility, fast clearance, and acute toxicity. To achieve targeted treatment, a reasonable delivery system is necessary. Therefore, we reported a metal-phenolic network where IR780 and gemcitabine were coupled chemically to overcome these shortcomings. The enhanced PDT effects can be realized by the promoted cell death both in vitro and in vivo. Moreover, the synergistic therapy also induced T-cell mediated anti-tumor immune response, which was significant for the inhibition of distant tumor growth. This work expanded the biomedical application of metal-phenolic materials and contribute to the wider application of photodynamic cancer therapy.展开更多
Type 2 diabetes mellitus(T2DM)exacerbates irreversible bone loss in periodontitis,but the mechanism of impaired bone regeneration caused by the abnormal metabolic process of T2DM remains unclear.Exosomes are regarded ...Type 2 diabetes mellitus(T2DM)exacerbates irreversible bone loss in periodontitis,but the mechanism of impaired bone regeneration caused by the abnormal metabolic process of T2DM remains unclear.Exosomes are regarded as the critical mediator in diabetic impairment of regeneration via organ or tissue communication.Here,we find that abnormally elevated exosomes derived from metabolically impaired liver in T2DM are significantly enriched in the periodontal region and induced pyroptosis of periodontal ligament cells(PDLCs).Mechanistically,fatty acid synthase(Fasn),the main differentially expressed molecule in diabetic exosomes results in ectopic fatty acid synthesis in PDLCs and activates the cleavage of gasdermin D.Depletion of liver Fasn effectively mitigates pyroptosis of PDLCs and alleviates bone loss.Our findings elucidate the mechanism of exacerbated bone loss in diabetic periodontitis and reveal the exosome-mediated organ communication in the“liver-bone”axis,which shed light on the prevention and treatment of diabetic bone disorders in the future.展开更多
基金supported by research funds from Zhangzhou Pien Tze Huang Pharmaceutical Co.Ltd(Grant Nos.:437b8f31,d6092dae,YHT-19064 to Chundong Yu)the National Natural Science Foundation of China(Grant Nos.:81970485,82173086 to Chundong Yu)the Natural Science Foundation of Fujian Province(Grant No.:2023J01249 to Shicong Wang).
文摘Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.
基金supported by investigation project of China Geological Survey(DD20230507).
文摘The coastal areas of the lower reaches of Oujiang River Basin are rich in groundwater resources.However,the unsustainable exploitation and utilization of groundwater have led to significant changes in the groundwater environment.Understanding the characteristics and genesis of groundwater salinization is crucial for preventing its deterioration and ensuring sustainable utilization.In this study,a comprehensive approach combining the ion ratio method,mineral saturation index method and multivariate statistical analysis was employed to investigate the hydrochemical characteristics and main controlling factors in the study area.The findings reveal that:(1)Groundwater samples in study area exhibit a neutral to slightly alkaline pH.The predominant chemical types of unconfined water are HCO_(3)-Ca·Na,HCO_(3)·Cl-Na·Ca and HCO_(3)·SO_(4)-Ca·Na,while confined water mainly exhibits Cl·HCO_(3)-Na and Cl-Na types.(2)Salinity coefficients indicate an increase in salinity from unconfined to confined water.TDS,Na^(+)and Cl^(–)concentrations show an increasing trend from mountainous to coastal areas in unconfined water,while confined water displays variability in TDS,Na^(+)and Cl^(–)concentrations.(3)Groundwater salinity is mainly influenced by water-rock interactions,including the dissolution of halite and gypsum,cation exchange,and seawater intrusion etc.Additionally,human activities and carbonate dissolution contribute to salinity in unconfined water.Seawater intrusion is identified as the primary factor leading to higher salinity in confined water compared to unconfined water,with increasing cation exchange and seawater interaction observed from unconfined to confined water.
文摘Objective:To explore the treatment strategies and clinical effects for recurrent respiratory infections in children.Methods:From May 2022 to May 2024,100 pediatric patients with recurrent respiratory infections were selected in this study and evenly divided into two groups.The control group(50 patients)was treated with conventional therapy supplemented with budesonide,while the observation group(50 patients)received pidotimod treatment in addition to the control group’s treatment.Subsequently,the duration of clinical symptom improvement,respiratory function enhancement,serological index changes,reinfection status,and parental satisfaction were compared between the two groups.Results:In terms of clinical symptoms,the observation group showed significantly shorter durations of fever reduction,cough relief,tonsil swelling reduction,and disappearance of fine wet rales compared to the control group(average reduction times were 1.6 days,2.3 days,2.1 days,and 1.9 days,respectively,P<0.05).Regarding respiratory function,the observation group experienced a 12%increase in peak expiratory flow rate variability,a 0.6-liter increase in lung capacity,a 0.7-liter increase in forced lung capacity,and a 0.5-liter increase in forced expiratory volume in the first second after treatment,all significantly higher than the control group(P<0.05).Serological testing revealed that interferon-γand interleukin-2 levels increased by 15%and 18%,respectively,while interferon-α,interleukin-5,and interleukin-4 levels decreased by 10%,12%,and 9%,respectively,in the observation group,showing significant differences compared to the control group(P<0.05).Additionally,the reinfection rate in the observation group(10%)was significantly lower than that in the control group(30%),with an average reduction of two reinfections within one year and a 3.2-day shorter infection control time(P<0.05).In terms of parental satisfaction,the observation group achieved 95%,significantly higher than the 70%in the control group(P<0.05).Conclusion:The addition of pidotimod to conventional therapy for pediatric patients with recurrent respiratory infections can significantly alleviate clinical symptoms,promote the recovery of respiratory function,regulate serological indicators,effectively reduce the risk of reinfection,and improve parental satisfaction.This method deserves widespread clinical application.
文摘Objective:This study aims to investigate the impact of early intervention on neuropsychological development in children with autism and attention deficit hyperactivity disorder(ADHD),providing effective intervention strategies for clinical practice.Methods:A total of 130 children with autism and ADHD who visited the hospital between June 2023 and June 2024 were selected as study subjects and randomly divided into an intervention group and a control group,with 65 children in each group.The intervention group received a one-year early comprehensive intervention,including behavioral therapy,cognitive training,and family guidance,while the control group only received routine medical care.The neuropsychological development assessment scale was used to evaluate both groups before and after the intervention to compare changes in their neuropsychological development levels.Results:Children in the intervention group showed significant improvements in cognitive function,social skills,language ability,and attention concentration,with an average improvement score of 23.5 points.Children in the control group did not show significant improvements in these areas,with an average improvement score of only 5.8 points.The difference between the two groups was statistically significant(P<0.05).Conclusion:Early comprehensive intervention has a significant promoting effect on the neuropsychological development of children with autism and ADHD.Targeted behavioral therapy,cognitive training,and family guidance can effectively enhance children’s cognitive,social,language,and attention abilities,laying a solid foundation for their future overall development.Therefore,it is recommended to actively promote and apply early intervention strategies in clinical practice.
基金supported by the Fundamental Research Funds for the Central Universities(2042021kf0102,2042021kf0083)supported by two National Natural Science Foundation of China(NSFC)Grants(81903166,82203629)+1 种基金a Natural Science Foundation of Hubei(2018CKB916)sponsored by Shanghai Pujiang Program(22PJD054).
文摘Obesity is one of the most serious global health problems,with an incidence that increases yearly and coincides with the development of cancer.Adipose tissue macrophages(ATMs)are particularly important in this context and contribute to linking obesity-related inflammation and tumor progression.However,the functions of ATMs on the progression of obesity-associated cancer remain unclear.In this review,we describe the origins,phenotypes,and functions of ATMs.Subsequently,we summarize the potential mechanisms on the reprogramming of ATMs in the obesity-associated microenvironment,including the direct exchange of dysfunctional metabolites,inordinate cytokines and other signaling mediators,transfer of extracellular vesicle cargo,and variations in the gut microbiota and its metabolites.A better understanding of the properties and functions of ATMs under conditions of obesity will lead to the development of new therapeutic interventions for obesity-related cancer.
基金supported by the National Natural Science Foundation of China(Grant No.52372283)China Postdoctoral Science Foundation(Grant No.2023M730826)+1 种基金Heilongjiang Postdoctoral Fund(Grant No.LBH-Z23121)Postdoctoral Fellowship Program of CPSF(Grant No.GZC20233425).
文摘Single-atom materials have demonstrated attractive physicochemical characteristics.However,understanding the relationships between the coordination environment of single atoms and their properties at the atomic level remains a considerable challenge.Herein,a facile waterassisted carbonization approach is developed to fabricate well-defined asymmetrically coordinated Co–N_(4)–O sites on biomass-derived carbon nanofiber(Co–N_(4)–O/NCF)for electromagnetic wave(EMW)absorption.In such nanofiber,one atomically dispersed Co site is coordinated with four N atoms in the graphene basal plane and one oxygen atom in the axial direction.In-depth experimental and theoretical studies reveal that the axial Co–O coordination breaks the charge distribution symmetry in the planar porphyrin-like Co–N_(4) structure,leading to significantly enhanced dielectric polarization loss relevant to the planar Co–N_(4) sites.Importantly,the film based on Co–N_(4)–O/NCF exhibits light weight,flexibility,excellent mechanical properties,great thermal insulating feature,and excellent EMW absorption with a reflection loss of−45.82 dB along with an effective absorption bandwidth of 4.8 GHz.The findings of this work offer insight into the relationships between the single-atom coordination environment and the dielectric performance,and the proposed strategy can be extended toward the engineering of asymmetrically coordinated single atoms for various applications.
基金supported by the National Natural Science Foundation of China(U1704134)。
文摘Very low frequency(VLF)signals are propagated between the ground-ionosphere.Multimode interference will cause the phase to show oscillatory changes with distance while propagating at night,leading to abnormalities in the received VLF signal.This study uses the VLF signal received in Qingdao City,Shandong Province,from the Russian Alpha navigation system to explore the multimode interference problem of VLF signal propagation.The characteristics of the effect of multimode interference phenomena on the phase are analyzed according to the variation of the phase of the VLF signal.However,the phase of VLF signals will also be affected by the X-ray and energetic particles that are released during the eruption of solar flares,therefore the two phenomena are studied in this work.It is concluded that the X-ray will not affect the phase of VLF signals at night,but the energetic particles will affect the phase change,and the influence of energetic particles should be excluded in the study of multimode interference phenomena.Using VLF signals for navigation positioning in degraded or unavailable GPS conditions is of great practical significance for VLF navigation systems as it can avoid the influence of multimode interference and improve positioning accuracy.
基金supported by “San Ming” Project of Shenzhen, China (No. SZSM201612051)National Natural Science Foundation of China (No. 81972240)。
文摘Colorectal cancer has a high incidence and mortality rate in China, with the majority of cases being middle and low rectal cancer. Surgical intervention is currently the main treatment modality for locally advanced rectal cancer, with the common goal of improving oncological outcomes while preserving function. The controversy regarding the circumferential resection margin distance in rectal cancer surgery has been resolved. With the promotion of neoadjuvant therapy concepts and advancements in technology, treatment strategies have become more diverse.Following tumor downstaging, there is an increasing trend towards extending the safe distance of distal rectal margin. This provides more opportunities for patients with low rectal cancer to preserve their anal function.However, there is currently no consensus on the specific distance of distal resection margin.
基金supported by the National Key R&D Program “Precision Medicine” of China (Grant No. 2016YFC0901403)the Major Science and Technology Projects of Henan Province (Grant No. 16110031 1300)+2 种基金the Doctoral Team Foundation of the First Affiliated Hospital of Zhengzhou University (Grant No. 2016-BSTDJJ-03)the National Natural Science Foundation of China (Grant No. 81872032, U1804262)the State Key Laboratory of Esophageal Cancer Prevention and Treatment (Grant No. Z2020-0010)。
文摘Objective: There are no comprehensive studies on survival outcomes and optimal treatment protocols for cervical esophageal cancer(CEC), due to its rare clinical prevalence. Our objective was to determine the relationship between pathological characteristics, treatment protocols, and survival outcomes in Chinese CEC patients.Methods: A total of 500 Chinese CEC patients were selected from our 500,000 esophageal and gastric cardia carcinoma database(1973–2018). There were two main groups: patients treated with surgery, and patients receiving non-surgical treatments(radiotherapy, radiochemotherapy, and chemotherapy). The Chi-square test and Kaplan–Meier method were used to compare the continuous variables and survival.Results: Among the 500 CEC patients, 278(55.6%) were male, and the median age was 60.9 ± 9.4 years. A total of 496 patients(99.2%) were diagnosed with squamous cell carcinoma. In 171(34.2%) patients who received surgery, 22(12.9%) had undergone laryngectomy. In 322(64.4%) patients who received non-surgical treatments, 245(76.1%) received radiotherapy. Stratified survival analysis showed that only T stage was related with survival outcomes for CEC patients in the surgical group, and the outcomes between laryngectomy and non-laryngectomy patients were similar. It was noteworthy that the 5-year survival rate was similar in CEC patients among the different groups treated with surgery, radiotherapy, chemotherapy, or radiochemotherapy(P = 0.244). Conclusions: The CEC patients had similar survival outcomes after curative esophagectomy and radiotherapy, including those with or without total laryngectomy. These findings suggest that radiotherapy could be the initial choice for treatment of Chinese CEC patients.
基金funded by grants from the National Natural Science Foundation of China (Nos. 81620108007 and 81870768)the National Key Research and Development Program of China (Nos. 2016YFC1101400 and 2017YFA0104800)the Scientific Young Alma of Shaanxi province (2018KJXX-015)。
文摘The loss-of-function mutations in the ALPL result in hypophosphatasia(HPP), an inborn metabolic disorder that causes skeletal mineralization defects. In adults, the main clinical features are early loss of primary or secondary teeth, osteoporosis, bone pain,chondrocalcinosis, and fractures. However, guidelines for the treatment of adults with HPP are not available. Here, we show that ALPL deficiency caused a reduction in intracellular Ca2+ influx, resulting in an osteoporotic phenotype due to downregulated osteogenic differentiation and upregulated adipogenic differentiation in both human and mouse bone marrow mesenchymal stem cells(BMSCs). Increasing the intracellular level of calcium in BMSCs by ionomycin treatment rescued the osteoporotic phenotype in alpl+/- mice and BMSC-specific(Prrx1-alpl-/-) conditional alpl knockout mice. Mechanistically, ALPL was found to be required for the maintenance of intracellular Ca2+ influx, which it achieves by regulating L-type Ca2+ channel trafficking via binding to the α2δsubunits to regulate the internalization of the L-type Ca2+ channel. Decreased Ca2+ flux inactivates the Akt/GSK3β/β-catenin signaling pathway, which regulates lineage differentiation of BMSCs. This study identifies a previously unknown role of the ectoenzyme ALPL in the maintenance of calcium channel trafficking to regulate stem cell lineage differentiation and bone homeostasis. Accelerating Ca2+ flux through L-type Ca2+ channels by ionomycin treatment may be a promising therapeutic approach for adult patients with HPP.
基金financially supported by the National Natural Science Foundation of China(81874356)the Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research from Hubei University of Medicine(WDCM2018002,WDCM201917,WDCM201918)+1 种基金the Chinese Medicine Project of Health Commission of Hubei Province(ZY2021010)the Foundation for Innovative Research Team of Hubei University of Medicine(2018YHKT01)。
文摘Primary liver cancer(PLC) is one of the most common malignant tumors in China. PLC is characterized by insidious onset, rapid progress, poor quality of life, and short survival time. Notably, current treatment strategies remain unsatisfactory. Traditional Chinese medicines(TCM) have been used to treat a variety of diseases, including liver diseases, for more than 2000 years. In this study, we performed a review of the use frequency and clinical efficacy of TCM in treating PLC. Relevant literature from January 1, 2009, to January 1, 2021 was retrieved from network databases of China National Knowledge Infrastructure(CNKI), Chongqing VIP, Wanfang, PubMed, and SinoMed. The most frequently used TCM and their efficacy in PLC treatment were summarized. Based on the inclusion and exclusion criteria, 33 articles were selected. Overall, the efficacy of the combination of TCM and Western medicines in the treatment of PLC was higher than that in the control groups(i.e. treatment with Western medicines alone)(65.11% vs.44.31%, P <.05). Among the 33 selected articles, 11 were investigated for TCM preparation(marketed drugs) and 22 for TCM formulas. In total, 102 types of TCM(single herbs) were used to treat PLC. The top five most frequently used TCM were Poria(14.71%), Astragali radix(13.73%), Atractylodis Macrocephalae Rhizoma(12.75%), Bupleuri radix(12.75%), and Glycyrrhizae radix et Rhizoma(11.76%). Of the 102 types of TCM, tonics were the most frequently used categories, followed by heat-clearing medicines, blood-invigorating medicines, and stasis-resolving medicines. Of 207 papers, 174(84.06%) could not be subjected to statistical analysis due to research quality. Further high-quality research on herb sources, formula components and dosage, toxicology, and ethics of TCM is necessary. In conclusion, TCM play a promising role in the treatment and management of PLC, although further investigations are warranted.
基金Supported by the National Natural Science Foundation of China (No.81870631)
文摘Dear Editor,Cornealendotheliitisisacommonandintriguing clinicalentitycharacterizedbycornealedema,keratic precipitates,and mild to moderate anterior chamber reaction,which occupies the important pathogenic factor of corneal blindness[1].Robin et al[2]first described a patient who suffered from intraocular inflammation and progressive corneal endotheliitis associated with herpes simplex infection.Since then,accumulating clinical evidence confirmed that its etiology was mainly attributed to the family of herpesviridae,including herpes simplex virus,varicella zoster virus,and cytomegalovirus,which initiated the direct cell damage and immune-and inflammatory-mediated lesion on endothelial cells[1,3].
文摘Recently, 3D display technology, and content creation tools have been undergone rigorous development and as a result they have been widely adopted by home and professional users. 3D digital repositories are increasing and becoming available ubiquitously. However, searching and visualizing 3D content remains a great challenge. In this paper, we propose and present the development of a novel approach for creating hypervideos, which ease the 3D content search and retrieval. It is called the dynamic hyperlinker for 3D content search and retrieval process. It advances 3D multimedia navigability and searchability by creating dynamic links for selectable and clickable objects in the video scene whilst the user consumes the 3D video clip. The proposed system involves 3D video processing, such as detecting/tracking clickable objects, annotating objects, and metadata engineering including 3D content descriptive protocol. Such system attracts the attention from both home and professional users and more specifically broadcasters and digital content providers. The experiment is conducted on full parallax holoscopic 3D videos “also known as integral images”.
基金supported by the“National Natural Science Foundation of China (Nos.51902162,21901154)”the FoundationResearch Project of Jiangsu Province (BK20221338)+1 种基金Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources,International Innovation Center for Forest Chemicals and Materials,Nanjing Forestry University,merit-based funding for Nanjing innovation and technology projects,Shanghai Pujiang Program (21PJD022)the Foundation of Jiangsu Key Lab of Biomass Energy and Material (JSBEM-S-202101).
文摘Compared with the traditional heteroatom doping,employing heterostructure is a new modulating approach for carbon-based electrocatalysts.Herein,a facile ball milling-assisted route is proposed to synthesize porous carbon materials composed of abundant graphene/hexagonal boron nitride(G/h-BN)heterostructures.Metal Ni powder and nanoscale h-BN sheets are used as a catalytic substrate/hard template and“nucleation seed”for the formation of the heterostructure,respectively.As-prepared G/h-BN heterostructures exhibit enhanced electrocatalytic activity toward H_(2)O_(2) generation with 86%-95%selectivity at the range of 0.45-0.75 V versus reversible hydrogen electrode(RHE)and a positive onset potential of 0.79 versus RHE(defined at a ring current density of 0.3 mA cm^(-2))in the alkaline solution.In a flow cell,G/h-BN heterostructured electrocatalyst has a H_(2)O_(2) production rate of up to 762 mmol g_(catalyst)^(-1) h^(-1) and Faradaic efficiency of over 75%during 12 h testing,superior to the reported carbon-based electrocatalysts.The density functional theory simulation suggests that the B atoms at the interface of the G/h-BN heterostructure are the key active sites.This research provides a new route to activate carbon catalysts toward highly active and selective O_(2)-to-H_(2)O_(2) conversion.
基金supported by the National Natural Science Foundation of China(62171172).
文摘CMOS image sensors produced by the existing CMOS manufacturing process usually have difficulty achieving complete charge transfer owing to the introduction of potential barriers or Si/SiO_(2)interface state traps in the charge transfer path,which reduces the charge transfer efficiency and image quality.Until now,scholars have only considered mechanisms that limit charge transfer from the perspectives of potential barriers and spill back effect under high illumination condition.However,the existing models have thus far ignored the charge transfer limitation due to Si/SiO_(2)interface state traps in the transfer gate channel,particularly under low illumination.Therefore,this paper proposes,for the first time,an analytical model for quantifying the incomplete charge transfer caused by Si/SiO_(2)interface state traps in the transfer gate channel under low illumination.This model can predict the variation rules of the number of untransferred charges and charge transfer efficiency when the trap energy level follows Gaussian distribution,exponential distribution and measured distribution.The model was verified with technology computer-aided design simulations,and the results showed that the simulation results exhibit the consistency with the proposed model.
基金funded by the following grants:the Natural Science Foundation of Shandong Province of China(ZR2021MC169)the Cooperation Project of University and Local Enterprise in Yantai of Shandong Province(2021XDRHXMPT09).
文摘Calcium(Ca^(2+))plays a pivotal role in various signal transduction pathways.Calcineurin B-like proteins(CBLs)are a unique group of Ca^(2+)sensors that decode Ca^(2+)signals by activating the plant specific protein kinase known as the CBL-interacting protein kinase(CIPK).In plants,the CBL-CIPK signaling network regulates multiple signals in response to different extracellular cues including abiotic stress.However,the genome wide annotation and expression patterns of CBLs and CIPKs in woody cutting flower plants are still unclear.In this study,a total number of 7 CBLs(RcCBLs)and 17 CIPKs(RcCIPKs)genes,divided into four and five subfamilies,respectively,were identified from the rose genome.All RcCBLs possess a classic elongation factor-hand(EF-hand)domain,while all RcCIPKs possess both the classic kinase and NAF domains.Most RcCBLs were predicted to be plasma membrane localized,whereas most RcCIPKs were predicted to be cytoplasmic localized.Synteny analysis showed that one RcCBL gene pair and five RcCIPK gene pairs have gone through whole genome duplication events.Promoter cis-element prediction assays indicated that RcCBLs and RcCIPKs could function in different abiotic stress responses in rose plants.Further quantitative real-time PCR analysis demonstrated that RcCBLs and RcCIPKs were expressed in different organs with overlapped but distinct patterns in response to various abiotic stresses.The findings in this work will provide fundamental information and gene resources for further functional research on RcCBLs and RcCIPKs.
基金financially supported by the National Natural Science Foundation of China(Nos.52172227 and Z190010)。
文摘LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811)is the most promising cathode for high-energy Li-ion batteries,despite its poor cycling stability that originates from the reactions that occur with the electrolyte.Herein,to solve this interfacial issue,a facile electrolytic electrochemical polymerization process was introduced in this paper,and a uniform conductive electrolyte interface(polyaniline)was successfully constructed on the surface of the NCM811 porous electrode(PANI-NCM),which facilitated the charge transfer during charge/discharge.The side reactions at the interface between the cathode and the electrolyte are suppressed,and thereby,the cycling performance and rate capability are considerably improved.PANI-NCM delivers an initial capacity of 157.2 mAh·g^(-1)as well as excellent cyclability(capacity retention of 88%after 500 cycles at 2C),whereas the capacity of the bare NCM811 has dropped to 31.3 mAh·g^(-1).In addition,polypyrrole and polythiophene also can be formed through electrolytic electrochemical polymerization process,which provides a practicable tactic to modify the interfacial stability of cathodes for high-energy Li-ion batteries.
基金the National Natural Science Foundation of China(NSFC,Nos.32171318,32222090 and 32101069)the Faculty of Health Sciences,University of Macao,the Multi-Year Research Grant(MYRG)of University of Macao(No.MYRG2022-00011-FHS)+2 种基金the Science and Technology Development Fund,Macao SAR(Nos.0103/2021/A and 0002/2021/AKP)Shenzhen Science and Technology Innovation Commission,Shenzhen-Hong Kong-Macao Science and Technology Plan C(No.SGDX20201103093600004)Dr.Stanley Ho Medical Development Foundation(No.SHMDF-OIRFS/2022/002)。
文摘Photodynamic therapy (PDT) is a clinically approved cancer treatment that uses energy of light to generate active substances that cause damage to the cancer. Photosensitizers are employed to absorb light and generate toxic reactive oxygen species (ROS) to damage biomolecules like DNA. At the same time, some chemotherapy drugs like nucleotide analogues can provide mechanism-guided promotion in the treatment efficacy of PDT. However, the photosensitizer and chemotherapy drugs used in PDT is usually organic molecules, which suffers from bad solubility, fast clearance, and acute toxicity. To achieve targeted treatment, a reasonable delivery system is necessary. Therefore, we reported a metal-phenolic network where IR780 and gemcitabine were coupled chemically to overcome these shortcomings. The enhanced PDT effects can be realized by the promoted cell death both in vitro and in vivo. Moreover, the synergistic therapy also induced T-cell mediated anti-tumor immune response, which was significant for the inhibition of distant tumor growth. This work expanded the biomedical application of metal-phenolic materials and contribute to the wider application of photodynamic cancer therapy.
基金supported by the Major Program of the National Natural Science Foundation of China(81991500,81991502,81991504)Shaanxi provincial key research and development program(2023-ZDLSF-49)the National Postdoctoral Program for Innovative Talents of China(BX20220394).
文摘Type 2 diabetes mellitus(T2DM)exacerbates irreversible bone loss in periodontitis,but the mechanism of impaired bone regeneration caused by the abnormal metabolic process of T2DM remains unclear.Exosomes are regarded as the critical mediator in diabetic impairment of regeneration via organ or tissue communication.Here,we find that abnormally elevated exosomes derived from metabolically impaired liver in T2DM are significantly enriched in the periodontal region and induced pyroptosis of periodontal ligament cells(PDLCs).Mechanistically,fatty acid synthase(Fasn),the main differentially expressed molecule in diabetic exosomes results in ectopic fatty acid synthesis in PDLCs and activates the cleavage of gasdermin D.Depletion of liver Fasn effectively mitigates pyroptosis of PDLCs and alleviates bone loss.Our findings elucidate the mechanism of exacerbated bone loss in diabetic periodontitis and reveal the exosome-mediated organ communication in the“liver-bone”axis,which shed light on the prevention and treatment of diabetic bone disorders in the future.