Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders:drug stability,targeting efficiency,and safety

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

Correlation between psychological traits and the use of smart medical services in young and middle-aged adults: An observational study

BACKGROUND Psychological problems affect economic development.However,there is a huge gap between mental health service resources and mental health service needs.Existing mental health service technology and platforms cannot meet all the diverse mental health needs of people.Smart medicine is a new medical system based online that can effectively improve the quality and efficiency of medical services and make mental health services accessible.AIM To explore the level of intelligent medical use among young and middle-aged people and its correlation with psychological factors.METHODS Convenience sampling was used to select 200 young and middle-aged patients with medical experience at the Third People's Hospital of Chengdu between January 2022 and January 2023 as the research subjects.The general condition Questionnaire,Eysenck Personality Questionnaire,Symptom Checklist-90,General Health Questionnaire,and Smart Medical Service Use Intention Questionnaire were used to collect data.Pearson’s correlation was used to analyze the correlation between the participants’willingness to use smart medical services and their personality characteristics,psychological symptoms,and mental health.RESULTS The results revealed that the mental health of young and middle-aged people was poor,and some had psycho-logical problems such as anxiety,depression,and physical discomfort.Familiarity,acceptance,and usage of smart healthcare in this population are at a medium level,and these levels correlate with psychological characteristics.Acceptance was positively correlated with E,and negatively correlated with P,anxiety,fear,anxiety/insomnia,and social dysfunction.The degree of use was negatively correlated with P,obsessive-compulsive symptoms,depression,anxiety,hostility,paranoia,and somatic symptoms.CONCLUSION The familiarity,acceptance,and usage of smart medical services among the middle-aged and young groups are related to various psychological characteristics.

The impact of^(60)Co-γirradiation on the chemical constituents of Chuanxiong Rhizoma

Background:In order to clarify the inmpat ofγirradiation on the chemical composition of traditional Chinese medicine,this paper carefully choosed Chuanxiong Rhizoma to carry on a demonstration study.Methods:Through a meticulous assessment,a comprehensive comparison was made between the irradiated and unirradiated Chuanxiong Rhizoma samples.The property characteristics were investigated by colorimeter and electronic nose.The changes in chemical structures and contents was analyzed by fourier infrared spectroscopy,high performance liquid chromatography and fingerprinting.In a quest to uncover the presence of any new radiolysis products,cutting-edge techniques like ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry and gas chromatography-mass spectrometry were employed.Moreover,the difference of antioxidant activity were investigated.Results:The irradiation doses within 12 kGy had no significant effects on the content of the main chemical components,characteristics and in vitro antioxidant activity of Chuanxiong Rhizoma,while changes in some functional groups and degradation of some volatile oil components containing olefins need further study.Conclusion:This study indicates that^(60)Co-γirradiation is a stable method for sterilization of Chuanxiong Rhizoma.It’s also provide a reference for the establishment of irradiation standards for Chuanxiong Rhizoma and other aromatic medicinal plants.

Transplantation of erythropoietin gene-modified neural stem cells improves the repair of injured spinal cord

The protective effects of erythropoietin on spinal Here, the eukaryotic expression plasmid pcDNA3.1 cord injury have not been well described. human erythropoietin was transfected into rat neural stem cells cultured in vitro. A rat model of spinal cord injury was established using a free falling object. In the human erythropoietin-neural stem cells group, transfected neural stem cells were injected into the rat subarachnoid cavity, while the neural stem cells group was inject- ed with non-transfected neural stem cells. Dulbecco＇s modified Eagle＇s medium/F12 medium was injected into the rats in the spinal cord injury group as a control. At 1-4 weeks post injury, the motor function in the rat lower limbs was best in the human erythropoietin-neural stem ceils group, followed by the neural stem cells group, and lastly the spinal cord injury group. At 72 hours, compared with the spinal cord injury group, the apoptotic index and Caspase-3 gene and protein expressions were apparently decreased, and the bd-2 gene and protein expressions were noticeably increased, in the tissues surrounding the injured region in the human erythro- poietin-neural stem cells group. At 4 weeks, the somatosensory evoked potential latencies were cavities were clearly smaller and the motor and remarkably shorter in the human erythropoi- etin-neural stem cells group and neural stem cells group than those in the spinal cord injury group. These differences were particularly obvious in the human erythropoietin-neural stem cells group. More CM-Dil-positive cells and horseradish peroxidase-positive nerve fibers and larger amplitude motor and somatosensory evoked potentials were found in the human erythro- poietin-neural stem cells group and neural stem cells group than in the spinal cord injury group. Again, these differences were particularly obvious in the human erythropoietin-neural stem cells group. These data indicate that transplantation of erythropoietin gene-modified neural stem cells into the subarachnoid cavity to help repair spinal cord injury and promote the recovery of spinal cord function better than neural stem cell transplantation alone. These findings may lead to significant improvements in the clinical treatment of spinal cord injuries.

Transplantation of human telomerase reverse transcriptase gene-transfected Schwann cells for repairing spinal cord injury

Transfection of the human telomerase reverse transcriptase（h TERT）gene has been shown to increase cell proliferation and enhance tissue repair.In the present study,h TERT was transfected into rat Schwann cells.A rat model of acute spinal cord injury was established by the modified free-falling method.Retrovirus PLXSN was injected at the site of spinal cord injury as a vector to mediate h TERT gene-transfected Schwann cells（1×10^（10）/L;10μL）or Schwann cells（1×10^（10）/L;10μL）without h TERT gene transfection.Between 1 and 4 weeks after model establishment,motor function of the lower limb improved in the h TERT-transfected group compared with the group with non-transfected Schwann cells.Terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling and reverse transcription-polymerase chain reaction results revealed that the number of apoptotic cells,and gene expression of aquaporin 4/9 and matrix metalloproteinase 9/2decreased at the site of injury in both groups;however,the effect improved in the h TERT-transfected group compared with the Schwann cells without h TERT transfection group.Hematoxylin and eosin staining,PKH26 fluorescent labeling,and electrophysiological testing demonstrated that compared with the non-transfected group,spinal cord cavity and motor and sensory evoked potential latencies were reduced,while the number of PKH26-positive cells and the motor and sensory evoked potential amplitude increased at the site of injury in the h TERT-transfected group.These findings suggest that transplantation of h TERT gene-transfected Schwann cells repairs the structure and function of the injured spinal cord.

Hyperbaric oxygen therapy combined with Schwann cell transplantation promotes spinal cord injury recovery

Schwann cell transplantation and hyperbaric oxygen therapy each promote recovery from spinal cord injury, but it remains unclear whether their combination improves therapeutic results more than monotherapy. To investigate this, we used Schwann cell transplantation via the tail vein, hyperbaric oxygen therapy, or their combination, in rat models of spinal cord contusion injury. The combined treatment was more effective in improving hindlimb motor function than either treatment alone; injured spinal tissue showed a greater number of neurite-like structures in the injured spinal tissue, somatosensory and motor evoked potential latencies were notably shorter, and their amplitudes greater, after combination therapy than after monotherapy. These findings indicate that Schwann cell transplantation combined with hyperbaric oxygen therapy is more effective than either treatment alone in promoting the recovery of spinal cord in rats after injury.

Neuroprotective effects of electroacupuncture on early- and late-stage spinal cord injury

Previous studies have shown that the neurite growth inhibitor Nogo-A can cause secondary neural damage by activating Rho A. In the present study, we hypothesized that electroacupuncture promotes neurological functional recovery after spinal cord injury by inhibiting Rho A expression. We established a rat model of acute spinal cord injury using a modification of Allen＇s method. The rats were given electroacupuncture treatment at Dazhui（Du14）, Mingmen（Du4）, Sanyinjiao（SP6）, Huantiao（GB30）, Zusanli（ST36） and Kunlun（BL60） acupoints with a sparsedense wave at a frequency of 4 Hz for 30 minutes, once a day, for a total of 7 days. Seven days after injury, the Basso, Beattie and Bresnahan（BBB） locomotor scale and inclined plane test scores were significantly increased, the number of apoptotic cells in the spinal cord tissue was significantly reduced, and Rho A and Nogo-A m RNA and protein expression levels were decreased in rats given electroacupuncture compared with rats not given electroacupuncture. Four weeks after injury, pathological tissue damage in the spinal cord at the site of injury was alleviated, the numbers of glial fibrillary acidic protein- and neurofilament 200-positive fibers were increased, the latencies of somatosensory-evoked and motor-evoked potentials were shortened, and their amplitudes were increased in rats given electroacupuncture. These findings suggest that electroacupuncture treatment reduces neuronal apoptosis and decreases Rho A and Nogo-A m RNA and protein expression at the site of spinal cord injury, thereby promoting tissue repair and neurological functional recovery.

Improved Reduced Latency Soft-Cancellation Algorithm for Polar Decoding

Soft-cancellation(SCAN) is a soft output iterative algorithm widely used in polar decoding. This algorithm has better decoding performance than reduced latency soft-cancellation(RLSC) algorithm, which can effectively reduce the decoding delay of SCAN algorithm by 50% but has obvious performance loss. A modified reduced latency soft-cancellation(MRLSC) algorithm is presented in the paper. Compared with RLSC algorithm, LLR information storage required in MRLSC algorithm can be reduced by about 50%, and better decoding performance can be achieved with only a small increase in decoding delay. The simulation results show that MRLSC algorithm can achieve a maximum block error rate(BLER) performance gain of about 0.4 dB compared with RLSC algorithm when code length is 2048. At the same time, compared with the performance of several other algorithms under(1024, 512) polar codes, the results show that the throughput of proposed MRLSC algorithm has the advantage at the low and medium signal-to-noise ratio(SNR) and better BLER performance at the high SNR.

Senegenin inhibits neuronal apoptosis after spinal cord contusion injury

Senegenin has been shown to inhibit neuronal apoptosis,thereby exerting a neuroprotective effect.In the present study,we established a rat model of spinal cord contusion injury using the modified Allen＇s method.Three hours after injury,senegenin（30 mg/g） was injected into the tail vein for 3 consecutive days.Senegenin reduced the size of syringomyelic cavities,and it substantially reduced the number of apoptotic cells in the spinal cord.At the site of injury,Bax and Caspase-3 m RNA and protein levels were decreased by senegenin,while Bcl-2 m RNA and protein levels were increased.Nerve fiber density was increased in the spinal cord proximal to the brain,and hindlimb motor function and electrophysiological properties of rat hindlimb were improved.Taken together,our results suggest that senegenin exerts a neuroprotective effect by suppressing neuronal apoptosis at the site of spinal cord injury.

Differential Effects of Ammonium and Nitrate on Growth Performance of Glechoma longituba under Heterogeneous Cd Stress

Water,minerals,nutrients,etc.,can be shared by physiological integration among inter-connected ramets of clonal plants.Nitrogen plays an important role in alleviating cadmium(Cd)stress for clonal plants.But how different forms of nitrogen affect growth performance of clonal plants subjected to heterogeneous Cd stress still remains poorly understood.A pot experiment was conducted to investigate the differential effects of ammonium and nitrate on growth performance of Glechoma longituba under heterogeneous Cd stress.In the experiment,parent ramets of Glechoma longituba clonal fragments were respectively supplied with modified Hoagland solution containing 7.5 mM ammonium,7.5 mM nitrate or the same volume of nutrient solution without nitrogen.Cd solution with different concentrations(0,0.1 or 2.0 mM)was applied to offspring ramets of the clonal fragments.Compared with control(N-free),nitrogen addition to parent ramets,especially ammonium,significantly improved antioxidant capacity[glutathione(GSH),proline(Pro),peroxidase(POD,)superoxide dismutase(SOD)and catalase(CAT)],PSII activity[maximum quantum yield of PSII(F_(v)/F_(m))and effective quantum yield of PSII(ΦPSII)],chlorophyll content and biomass accumulation of the offspring ramets suffering from Cd stress.In addition,negative effects of nitrate on growth performance of whole clonal fragments were observed under Cd stress with high concentration(2.0 mM).Transportation or sharing of nitrogen,especially ammonium,can improve growth performance of clonal plants under heterogeneous Cd stress.The experiment provides insight into transmission mechanism of nitrogen among ramets of clonal plants suffering from heterogeneous nutrient supply.Physiological integration might be an important ecological strategy for clonal plants adapting to heterogeneous environment stress conditions.

Enhanced electrochemical performance of Li_(1.3)Al_(0.3)Ti_(1.7)(PO_(4))_(3) solid electrolyte by anion doping

Nowadays,the majority of the studies on the substitution are focused on cations(such as Y^(3+),Ti^(4+),P^(5+),etc.)in Li_(1.3)Al_(0.3)Ti_(1.7)(PO_(4))_(3)(LATP),while there are few studies on the substitution of anion O^(2-).In this work,the modified LATP with a series of LiCl(LATPClx,x=0.1,0.2,0.3,0.4)additives is prepared to enhance ionic conductivity.The successful introduction of Cl-makes the length of the c axis decrease from 20.822(2)to 20.792(1)Å,and the bulk conductivity of 2.13×10^(-3) S·cm^(-1) is achieved in LATPCl_(0.3).Moreover,the Al/Ti-O1/Cl1 and Al/Ti-O_(2)/Cl_(2) distance decrease,while the Li1-O_(2)/Cl_(2) distance increases.Lithium ions migrate more easily in the nanochannel of M3-M1-M3.In addition,the LiCl additive increases the relative density and the grain boundary conductivity of LATPClx compounds.Naturally,a higher ionic conductivity of 2.12×10^(–4) S·cm^(-1) and a low activation energy of 0.30 eV are obtained in LATPCl_(0.3).Correspondingly,the symmetric cell exhibits a low overpotential of±50 mV for over 200 h in LATPCl_(0.3).The solid-state Li|LATPCl_(0.3)|NCM811(NCM811=LiNi0.8Co0.1Mn0.1O_(2))battery exhibits high initial capacity 185.1 mAh·g^(-1) with a capacity retention rate of 95.4%after 100 cycles at 0.5 C.This result suggests that LiCl additive is an effective strategy to promote electrochemical properties of LATP solid electrolyte and can be considered for reference to other inorganic solid electrolytes systems.

三维打印光敏树脂牙列模型形态的长期稳定性研究

目的探讨自然光照与严格避光条件下三维打印光敏树脂牙列模型(简称树脂牙列模型)形态的长期稳定性。方法利用标准牙列模型数据,使用桌面三维打印机制作80副(共160个)树脂牙列模型,随机抽样分为自然光照组(40副共80个)与严格避光组(40副共80个)进行密闭储存。储存1、3、5、7、14、21、28、40、60、90 d(每组每个时间点各4副)后使用光学模型扫描仪获取树脂牙列模型三维数据,测量树脂牙列模型三维数据与标准牙列模型数据的均方根误差(root-mean-square error,RMSE),即树脂牙列模型表面平均形变量。选择3项线距指标(尖牙间宽度、第一磨牙间宽度和牙弓长度),测量树脂牙列模型三维数据与标准牙列模型数据3项线距指标的差值,比较不同光照条件、不同储存时间组线距指标差值的差异。结果储存90 d内96.9%(155/160)的树脂牙列模型RMSE值未超过0.1 mm。对于相同储存时间点,两组树脂牙列模型RMSE值差异均无统计学意义(P>0.05)。75.0%(360/480)线距指标测量值与标准模型数据差值的绝对值在0.2 mm内,0.1%(3/480)超过0.5 mm,总体范围为0~0.6 mm。结论三维打印光敏树脂牙列模型在自然光照与严格避光条件下密封储存的长期形态稳定性良好。

In Vivo Corrosion Resistance of Ca-P Coating on AZ60 Magnesium Alloy

Magnesium-based alloys are frequently reported as potential biodegradable orthopedic implant materials. Controlling the degradation rate and mechanical integrity of magnesium alloys in the physiological environment is the key to their applications. In this study, calcium phosphate （Ca-P） coating was prepared on AZ60 magnesium alloy using phosphating technology. AZ60 samples were immersed in a phosphating solution at 37 ± 2 ℃ for 30 min, and the solution pH was adjusted to 2.6 to 2.8 by adding NaOH solution. Then, the samples were dried in an attemperator at 60 ℃. The degradation behavior was studied in vivo using Ca-P coated and uncoated magnesium alloys. Samples of these two different materials were implanted into rabbit femora, and the corrosion resistances were evaluated after 1, 2, and 3 months. The Ca-P coated samples corroded slower than the uncoated samples with prolonged time. Significant differences （p 〈 0.05） in mass losses and corrosion rates between uncoated samples and Ca-P coated samples were observed by micro-computed tomography. The results indicate that the Ca-P coating could slow down the degradation of magnesium alloy in vivo.

DDX39B drives colorectal cancer progression by promoting the stability and nuclear translocation of PKM2

Metastasis is a major cause of colorectal cancer(CRC)mortality,but its molecular mechanisms are still not fully understood.Here,we show that upregulated DDX39B correlates with liver metastases and aggressive phenotypes in CRC.DDX39B is an independent prognostic factor associated with poor clinical outcome in CRC patients.We demonstrate that Sp1 potently activates DDX39B transcription by directly binding to the GC box of the DDX39B promoter in CRC cells.DDX39B overexpression augments the proliferation,migration,and invasion of CRC cells,while the opposite results are obtained in DDX39B-deficient CRC cells.Mechanistically,DDX39B interacts directly with and stabilizes PKM2 by competitively suppressing STUB1-mediated PKM2 ubiquitination and degradation.Importantly,DDX39B recruits importin a5 to accelerate the nuclear translocation of PKM2 independent of ERK1/2-mediated phosphorylation of PKM2,leading to the transactivation of oncogenes and glycolysis-related genes.Consequently,DDX39B enhances glucose uptake and lactate production to activate Warburg effect in CRC.We identify that Arg319 of DDX39B is required for PKM2 binding as well as PKM2 nuclear accumulation and for DDX39B to promote CRC growth and metastasis.In addition,blocking PKM2 nuclear translocation or treatment with glycolytic inhibitor 2-deoxy-D-glucose efficiently abolishes DDX39B-triggered malignant development in CRC.Taken together,ourfindings uncover akey role forDDX39B in modulating glycolytic reprogramming and aggressive progression,and implicate DDX39B as a potential therapeutic target in CRC.

Diketopyrrolopyrrole-Au(I) as singlet oxygen generator for enhanced tumor photodynamic and photothermal therapy

Diketopyrrolopyrrole(DPP)derivatived photosensitizers(PSs)with near infrared(NIR)absorption and good photophysical properties have drawn tremendous attention in cancer phototherapy.However,current DPP derivatives present unsatisfactory quantum yield of singlet oxygen(1O2)due to the large energy gap between the excited singlet and triplet states.To tackle this challenge,herein the DPP core is functionalized with triphenylphosphine-Au(I)group(Th DPP-Au),leading to a high1O2 quantum yield of 0.65.Theoretical calculation attributes the enhancement to spin-orbit coupling and population of the triplet excition upon photoexcitation.The hydrophilic Th DPP-Au nanoparticals(NPs)are prepared via nano-reprecipitation,which displays homogeneous size and excellent light absorption ability(ε=4.382×104 M-1cm-1).And the Th DPP-Au NPs exhibit low dark toxicity and high phototoxicity,which can effectively kill tumor cells via 1O2 induced mitochondrial apoptotic pathway upon irradiation.Furthermore,in vivo experiments demonstrate that Th DPP-Au NPs can selective accumulation in tumor and present excellent synergistic photodynamic/photothermal therapy guided by fluorescence and photothermal dual imaging.

A pH-responsive zinc(Ⅱ) metalated porphyrin for enhanced photodynamic/photothermal combined cancer therapy

The acidic tumor microenvironment is triggered by glycolysis in hypoxic condition, which can motivate the pHresponsive system to build certain triggers for efficiently tumor-targeted phototherapy. Additionally, the metalated porphyrin structures are widely studied in biomedical applications due to the favorable properties of high singlet oxygen quantum yield as well as strong fluorescence imaging ability. Herein, a pH-responsive zinc(II) metalated porphyrin(P-4) was designed and synthesized for amplifying cancer photodynamic/photothermal therapy with excellent fluorescence quantum yield(67.4%), superb singlet oxygen quantum yield(84.3%) and desired photothermal conversion efficiency(30.0%). In vitro, the self-assembled P-4 nanoparticles can specifically target to lysosome subcellular site and realize protonated process of dibutaneaminophenyl(DBAP) groups with high photo toxicity. Under single 660 nm laser illumination, the tumor can be ablated completely with no side effects in vivo. This work demonstrates that the p H-responsive P-4 nanoparticles provide a new avenue for highly efficient cancer combination therapy.

The Join of Split Graphs Whose Half-strong Endomorphisms Form a Monoid

In this paper, the half-strong endomorphisms of the join of split graphs are investigated. We give the conditions under which the half-strong endomorphisms of the join of split graphs form a monoid.

Biomineralized CO gas-releasing nanoprodrug for endoplasmic reticulum stress mediated cancer therapy

The anti-tumor effect of therapeutic carbon monoxide(CO)has been considered concerning the electron transport chain on the inner mitochondrial membrane.Herein,a tumor microenvironment and photo-responsive CO nanoplatform Ca-Flav nanoparticles(NPs)were constructed through biomineralizing acryloyl-modified flavonol,which could release CO both in normoxia and hypoxia conditions upon irradiation at tumor lesion.The in vitro experiments demonstrated that the endoplasmic reticulum stress-related signal pathways could be activated through oxidative stress caused by CO mediated mitochondrial biogenesis and calcium ion turbulence induced by Ca_(3)(PO_(4))_(2)acidolysis,resulting in mitochondrial dysfunction and cell apoptosis.In addition,the Ca-Flav NPs exhibited excellent biocompatibility and tumor inhibition effect in vivo.This work provides new insight into the potential characteristics of CO,paving a new way to engineer more efficient treatment based on CO.