Lithium-ion batteries(LIBs)have dominated the portable electronic and electrochemical energy markets since their commercialisation,whose high cost and lithium scarcity have prompted the development of other alkali-ion...Lithium-ion batteries(LIBs)have dominated the portable electronic and electrochemical energy markets since their commercialisation,whose high cost and lithium scarcity have prompted the development of other alkali-ion batteries(AIBs)including sodium-ion batteries(SIBs)and potassium-ion batteries(PIBs).Owing to larger ion sizes of Na^(+)and K^(+)compared with Li^(+),nanocomposites with excellent crystallinity orientation and well-developed porosity show unprecedented potential for advanced lithium/sodium/potassium storage.With enticing open rigid framework structures,Prussian blue analogues(PBAs)remain promising self-sacrificial templates for the preparation of various nanocomposites,whose appeal originates from the well-retained porous structures and exceptional electrochemical activities after thermal decomposition.This review focuses on the recent progress of PBA-derived nanocomposites from their fabrication,lithium/sodium/potassium storage mechanism,and applications in AIBs(LIBs,SIBs,and PIBs).To distinguish various PBA derivatives,the working mechanism and applications of PBA-templated metal oxides,metal chalcogenides,metal phosphides,and other nanocomposites are systematically evaluated,facilitating the establishment of a structure–activity correlation for these materials.Based on the fruitful achievements of PBA-derived nanocomposites,perspectives for their future development are envisioned,aiming to narrow down the gap between laboratory study and industrial reality.展开更多
Five tryptophan analogues with a hydrophobic indole ring and an amino group on each molecule were used as functional ligands of mixed-mode resins for human serum albumin(HSA) purification. Their adsorption performance...Five tryptophan analogues with a hydrophobic indole ring and an amino group on each molecule were used as functional ligands of mixed-mode resins for human serum albumin(HSA) purification. Their adsorption performance was evaluated and the effects of p H and salt addition on HSA adsorption were studied. The resins prepared showed typical p H-dependent adsorption and the highest adsorption capacity and affinity were found at pH 5.0for all the resins tested. The saturated adsorption capacity was 138.02 mg·g^(-1)with the tryptaminefunctionalized resin, which significantly decreased at p H below 4.0 due to electrostatic repulsion between ligands and HSA. Moreover, the addition of Na Cl or(NH_4)_2SO_4in media reduced HSA adsorption capacity, although the two salts showed different affecting profiles. The tryptamine-functionalized resin showed the best salt-tolerant performance, and its high adsorption capacity was maintained under high salt concentrations. In addition, the five resins prepared showed good adsorption selectivity for recombinant HSA from Pichia pastoris broth. Molecular docking results between tryptamine and HSA indicated that tryptamine was favorable to bind on Site II(indole-binding site) of HSA.展开更多
Abscisic acid(ABA)is a phytohormone that not only important for plant growth,but also mediating the stress response.The roles of ABA in plant immunity are especially multifaceted.Recently,the ABA functional analogues ...Abscisic acid(ABA)is a phytohormone that not only important for plant growth,but also mediating the stress response.The roles of ABA in plant immunity are especially multifaceted.Recently,the ABA functional analogues are of great significance to promote its application.Here,we reported an ABA functional analogue named 167A.167A inhibits plant growth and seeds germinating of Arabidopsis.Meanwhile,the 167A enhanced the plant immunity,which is opposite of ABA.We further investigated the PTI-response after 167A treatment,and the results show that the ROS burst,callose deposition accumulate with 167A treatment.Moreover,167A also influence the degree of stomal closed.RNA-seq assays show that the 167A down-regulated the ABA associated genes and upregulated the JA/SA/ET associated genes.Through genetic analysis,the 167A modulating the plant resistance through the PYR/PYL Receptors.Together,these results demonstrate that a novel ABA analogue 167A positive regulated plant immunity and has great potential for agricultural applications.展开更多
Prussian blue analogues (PBAs) are regarded as promising cathode materials for potassium-ion batteries(PIBs) owing to their low cost and high reversible capacity.Compared to other PBAs,potassium manganese hexacyanofer...Prussian blue analogues (PBAs) are regarded as promising cathode materials for potassium-ion batteries(PIBs) owing to their low cost and high reversible capacity.Compared to other PBAs,potassium manganese hexacyanoferrate (KMnHCF) stands out for its superior capacity and operating voltage.However,Jahn-Teller effect of Mn^(3+)and the structural collapse caused by potassium ion insertion/extraction still affect the structural stability and electrochemical performance of this material.Herein,a green and efficient synthesis method is adopted to substitute potassium ions in KMnHCF with an appropriate amount of cesium ions to form a column effect.Cesium-doped KMnHCF (Cs-KMnHCF) mitigates the irreversible structural damage caused by potassiation/depotassiation and the Jahn-Teller effect,thereby improving the cycling stability.In addition,it widens the lattice channels,reduces the diffusion barrier of potassium ions,and optimizes the diffusion kinetics.By rationally controlling the doping amount of Cs^(+),the obtained K_(1.71)Cs_(0.05)Mn[Fe(CN)_(6)]_(0.95·0.05)·0.88H_(2)O exhibits remarkable electrochemical performance,with an initial discharge capacity of 137.6 mA h g^(-1)at a current density of 20 mA g^(-1)and a capacity retention of 89.6%after 600 cycles at 200 mA g^(-1).More importantly,when assembled with a pitch-derived soft carbon anode,the full cell manifests excellent cycle stability and rate performance.This work is expected to provide a highly efficient cathode material for the practical application of PIBs.展开更多
To determine the effects of plant-based meat analogues on the metabolic health and the possible mechanisms,mice were fed with a real pork diet(AP),a real beef diet(AB),a plant-based pork analogue diet(PP)and plant-bas...To determine the effects of plant-based meat analogues on the metabolic health and the possible mechanisms,mice were fed with a real pork diet(AP),a real beef diet(AB),a plant-based pork analogue diet(PP)and plant-based beef analogue diet(PB)for 68 days.Compared with real meat,the plant-based meat analogues increased food and energy intake,body weight,white fat and liver weight and caused adipocyte hypertrophy,hepatic lipid droplet accumulation,and inflammatory responses in mice.Metabolomics revealed that plantbased meat analogues altered the composition of serum metabolites,which regulated lipid metabolism homeostasis.The PB diet upregulated gene expression related to lipid synthesis,lipolysis and adipocyte differentiation while the PP diet upregulated expression of lipolysis-related genes but downregulated expression of adipocyte differentiation-related genes in white adipose tissue.Meanwhile,both PP and PB diets upregulated lipid influx-and synthesis-related genes but downregulated lipid oxidation-related genes in liver.The specific metabolite biomarkers may affect fat accumulation mainly by direct lipid metabolism pathways or indirect amino acid metabolism,protein digestion and absorption,bile secretion,aminoacyl-tRNA biosynthesis,neuroactive ligand-receptor interaction and ABC transporters pathways.These findings provide a new insight into understanding the differences in nutritional functions of meat and plant-based meat analogues.展开更多
Plant-based meat analogues(PBMA)are formulated to mimic the sensory characteristics of traditional meat products(TMP)using vegetarian ingredients and are increasingly popular with the trend towards plantbased diets,ev...Plant-based meat analogues(PBMA)are formulated to mimic the sensory characteristics of traditional meat products(TMP)using vegetarian ingredients and are increasingly popular with the trend towards plantbased diets,even among meat-eating consumers.This narrative review compared the nutritional quality of PBMA and TMP to broaden the discussion on the suitability of simulated meat products to substitute TMP,while exploring other attributes for their comparison.The complexity of PBMA and TMP means they are not entirely interchangeable.Importantly,PBMA health effects extend beyond their basic nutrient content and quality.Postprandial metabolism and satiety,for example,can be affected by product formulation,ingredient interactions,and thermomechanical processing involved in producing organoleptically acceptable PBMA.There are specific opportunities for low-sodium PBMA products to contribute to a healthy shift toward plantbased diets.In conclusion,PBMA cannot be assumed to be healthier than TMP.They should be designed with comprehensive consideration of composition and processing to ensure they support consumers who are adopting plant-based diets in realizing the theoretical health benefits.展开更多
The recombinant Saccharomyces cerevisiae strain stably expressing recombinant human glucagon-like peptide-l(rhGLP-1) analogue, as a potential oral drug delivery system for diabetes type II treatment, was successfull...The recombinant Saccharomyces cerevisiae strain stably expressing recombinant human glucagon-like peptide-l(rhGLP-1) analogue, as a potential oral drug delivery system for diabetes type II treatment, was successfully constructed by the homologous recombination between chromosomal DNA and yeast and integrating vector pNK-GLP containing yeast ribosomal DNA fragments. The amount of rhGLP-I analogue fusion protein in transformant SG2 reached ca. 0.84 mg per gram of packed cells when SG2 was grown for 24 h in the YPD medium with a inoculum and medium ratio of 1:1. Oral administration of 5 g lyophilized SG2/kg to hyperglycemic rats decreased serum glucose from (24.8±1.40) to (21.2±1.36) mmol/L.展开更多
The evolution of faults within the same stress field is frequently influenced by numerous factors,involving the reactivation of pre-existing structures,stress transmission through ductile detachment layers,and the gro...The evolution of faults within the same stress field is frequently influenced by numerous factors,involving the reactivation of pre-existing structures,stress transmission through ductile detachment layers,and the growth,interaction,as well as linkage of new fault segments.This study analyses a complex multi-phase oblique extension fault system in the Nanpu Sag(NPS)of the Bohai Bay Basin(BBB),China.High-resolution three-dimensional(3D)seismic data and analogue modelling indicate that the oblique extensional reactivation of pre-existing structures governs the sequential arrangement of fault segments in the caprock,and they dip synthetically to the reactivated fault at depth.During the NW-SE extension in the Eocene,the predominant movement of the pre-existing fault is strike-slip.Subsequently,during the N-S extension since the Oligocene,inclined at 20.to the pre-existing fault,forming splay fault segments and ultimately creating large en-echelon arcuate faults linked by relay ramps.Using fault throw-distance(T-D)and laser scanning,we reconstructed the fault evolution model of oblique extension reactivation in the presence of a ductile detachment basement.Our study illustrates that the arcuate faults can be categorized into linear master fault segments controlled by pre-existing structures,bending splay faults in the termination zone,and normal fault segments responding to the regional stress field.The interaction between faults occurs among normal faults and strike-slip faults,and the kinematic unification of the two fault systems is accomplished in the intersection zone.As the faults continue to evolve,the new fault segments tend to relinquish the control of pre-existing structures and concentrate more on the development of planar and continuous major faults.The ductile detachment layer significantly contributes to the uniform distribution of strain,resulting in narrow shear zones and discontinuous normal faults in its absence.展开更多
BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explor...BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explore the effects of Zhibai dihuang pills and gonadotropin-releasing hormone analogue(GnRHa)on growth and ovarian function in girls with precocious puberty.METHODS The clinical data of 84 adolescent girls with precocious puberty and rapidly progressive puberty from February 2017 to August 2023 were retrospectively analyzed.Girls were divided into a control group and an observation group,with 42 cases in each group.The control group received diet intervention combined with GnRHa treatment,while the observation group received diet intervention combined with Zhibai dihuang pills+GnRHa treatment.Outcomes such as clinical efficacy,growth indicators,ovarian function,and adverse reactions were compared between the two groups.RESULTS The observation group showed superior clinical efficacy compared to the control group(P<0.05).Prior to the intervention,no significant differences were found in growth or ovarian function between the groups(P>0.05).Post-intervention,the observation group exhibited significantly lower rates in growth,height,and bone age,along with reduced levels of progesterone,testosterone,estradiol,prolactin,luteinizing hormone,and follicle-stimulating hormone compared to the control group(P<0.05).The incidence of adverse reactions was similar across both groups(P>0.05).CONCLUSION Combining Zhibai dihuang pills with GnRHa and dietary intervention effectively improves growth,enhances ovarian function,and minimizes adverse reactions in adolescent girls with precocious and rapidly progressive puberty.展开更多
UV-VIS spectroscopic investigations of interaction of bovine and human serum albumin with selected chalcones (1) and their cyclic chalcone analogues: (E)-2-(4’-X-benzylidene-1-tetralones (3), benzosuberones (4) with ...UV-VIS spectroscopic investigations of interaction of bovine and human serum albumin with selected chalcones (1) and their cyclic chalcone analogues: (E)-2-(4’-X-benzylidene-1-tetralones (3), benzosuberones (4) with dimethylamino and methoxy substituents and (E)-2-(2’,4’-dimethox- ybenzylidene)-1-indanone (2) were performed in polar respiration medium. Absorption maxima of the tested compounds were investigated in the presence of bovine and human serum albumin at the 0, 10, 30 and 60 minute timepoints of the interaction. The absorbance of all studied compounds in the presence of proteins decreased after one hour of the reaction. Molecule 4a showed the strongest and fastest kinet initial interaction with both albumins.展开更多
Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata...Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata et al.,2023).Mitochondrial dysfunction,characterized by an imbalance in ATP levels and excessive production of mitochondrial reactive oxygen species,is a key factor that impedes neural regeneration in neurodegenerative diseases and after neuronal injury(Han et al.,2016,2020;Zheng et al.,2016;Zong et al.,2024).展开更多
Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
Phosphoinositide-dependent protein kinase-1 (PDK1), the class of serine threonine kinase, is a master regulator of the AGC family of kinases. It is a main component of the PI3K pathway. As it is reported that this pat...Phosphoinositide-dependent protein kinase-1 (PDK1), the class of serine threonine kinase, is a master regulator of the AGC family of kinases. It is a main component of the PI3K pathway. As it is reported that this pathway is most commonly, and this pathway is the most commonly deregulated among many cancers. So designing a selective inhibitor of PDK1 may have the efficacy as an anticancer agent. Herein, we describe our work focused on the structure based on screening of 95% similar analogues of Myricetin deposited in PubChem database as earlier studies have been suggested that myricetin acts as an anti cancer agent. Further molecular docking as well as the in silico ADMET studies are incorporated on these compounds to evaluate the binding and pharmacokinetic properties of these compounds. Due to low oral bioavailability, clinical use of myricetin is limited. Therefore this study is an attempt towards screening of structurally similar better compounds as compare with myricetin which can act as better inhibitor against PDK-1.展开更多
Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied fo...Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.展开更多
Background and Aim of Study: The phosphodiesterase inhibitors (Sildenafil and Milrinone), Nitric Oxide donor Sodium Nitroprusside (SNP) and prostacyclin analogs are commonly used pulmonary vasodilators to treat pulmon...Background and Aim of Study: The phosphodiesterase inhibitors (Sildenafil and Milrinone), Nitric Oxide donor Sodium Nitroprusside (SNP) and prostacyclin analogs are commonly used pulmonary vasodilators to treat pulmonary hypertension. In the past few years, we have used human pulmonary artery rings in vitro to evaluate pulmonary vascular resistance. The main objective of the current study is to document the pharmacological impact of clinically used prostacyclin analogs on the human pulmonary system in parallel with phosphodiesterase inhibitors and SNP. Methods: The study used human pulmonary artery rings of internal diameter of 2 - 4 mm and length of 2 mm. These were extracted from patients with lung resections. These rings were then mounted on a multiwire myograph, and changes in isometric tension were noted. Then, concentration response curves were constructed to Sildenafil (Sd), Milrinone (Mil), Sodium Nitroprusside (SNP), Epoprostenol (Ep), Iloprost (Ip) and Treprostinil (Tp). Results: 52 pulmonary artery rings were used in these experiments. Sildenafil, Milrinone, SNP, Epoprostenol, Iloprost and Treprostinil caused a concentration-dependent vasodilation in small human pulmonary arteries (pEC50: 5.97 ± 0.22, 5.99 ± 0.12, 7.64 ± 0.08, 7.53 ± 0.14, 8.84 ± 0.15 and 9.48 ± 0.13 respectively, n = 8 to 12). The efficacy for the same was in the order: Tp = Ip > Ep > Mil > SNP > Sd. The potency varied in the order: Tp > Ip > SNP > Ep > Mil > Sd. Conclusion: This research showed the efficacy as well as the potency of SNP and phosphodiesterase inhibitors and prostacyclin analogs on the human pulmonary vasculature. Treprostinil and Iloprost exhibited maximum relaxation. However, Sildenafil and SNP showed lesser impact. These effects need to be considered for clinical studies for enhanced patient outcomes.展开更多
In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in ped...In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.展开更多
TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal...TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.展开更多
BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanis...BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanisms that target p16 and p53 proteins.However,research on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous SCC(HNCSCC),particularly in Asian populations,remains limited.This retrospective study surveyed 62 patients with HNSCC(2011-2020),excluding those with facial warts or other skin cancer.AIM To explore the prevalence of HPV and the predictive value of p16 and p53 expression in HNCSCC in Asian populations.METHODS All patients underwent wide excision and biopsy.Immunohistochemical staining for HPV,p16,and p53 yielded positive and negative results.The relevance of each marker was investigated by categorizing the tumor locations into high-risk and middle-risk zones based on recurrence frequency.RESULTS Of the 62 patients,20(32.26%)were male,with an average age of 82.27 years(range 26-103 years).High-risk included 19 cases(30.65%),with the eyelid and lip being the most common sites(five cases,8.06%).Middle-risk included 43 cases(69.35%),with the cheek being the most common(29 cases,46.77%).The p16 expression was detected in 24 patients(38.71%),p53 expression in 42 patients(72.58%),and HPV in five patients(8.06%).No significant association was found between p16 expression and the presence of HPV(P>0.99),with a positive predictive value of 8.33%.CONCLUSION This study revealed that p16,a surrogate HPV marker in oropharyngeal SCC,is not reliable in HNCSCC,providing valuable insights for further research in Asian populations.展开更多
Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocyt...Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous system.Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord.Here,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal cord.To explore the conservation and divergence across species,we compared these findings with those from mice.In the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic subclusters.In the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice.Additionally,we detected sex differences in gene expression in human spinal cord glial cells.Specifically,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in females.In all microglial subtypes,all differentially expressed genes were located on the sex chromosomes.In addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in males.Collectively,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cordrelated illnesses,including chronic pain,amyotrophic lateral sclerosis,and multiple sclerosis.展开更多
Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with t...Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.展开更多
基金financial support from the Special Funds for the Cultivation of Guangdong College Students’Scientific and Technological Innovation(“Climbing Program”Special Funds,pdjh2023b0145)the Scientific Research Innovation Project of Graduate School of South China Normal University(2024KYLX047)financial support from the Australian Research Council,Centre for Materials Science,Queensland University of Technology.
文摘Lithium-ion batteries(LIBs)have dominated the portable electronic and electrochemical energy markets since their commercialisation,whose high cost and lithium scarcity have prompted the development of other alkali-ion batteries(AIBs)including sodium-ion batteries(SIBs)and potassium-ion batteries(PIBs).Owing to larger ion sizes of Na^(+)and K^(+)compared with Li^(+),nanocomposites with excellent crystallinity orientation and well-developed porosity show unprecedented potential for advanced lithium/sodium/potassium storage.With enticing open rigid framework structures,Prussian blue analogues(PBAs)remain promising self-sacrificial templates for the preparation of various nanocomposites,whose appeal originates from the well-retained porous structures and exceptional electrochemical activities after thermal decomposition.This review focuses on the recent progress of PBA-derived nanocomposites from their fabrication,lithium/sodium/potassium storage mechanism,and applications in AIBs(LIBs,SIBs,and PIBs).To distinguish various PBA derivatives,the working mechanism and applications of PBA-templated metal oxides,metal chalcogenides,metal phosphides,and other nanocomposites are systematically evaluated,facilitating the establishment of a structure–activity correlation for these materials.Based on the fruitful achievements of PBA-derived nanocomposites,perspectives for their future development are envisioned,aiming to narrow down the gap between laboratory study and industrial reality.
基金Supported by the National Natural Science Foundation of China(21476198,21576233)the International Science&Technology Cooperation Program of China(2015DFG42070)
文摘Five tryptophan analogues with a hydrophobic indole ring and an amino group on each molecule were used as functional ligands of mixed-mode resins for human serum albumin(HSA) purification. Their adsorption performance was evaluated and the effects of p H and salt addition on HSA adsorption were studied. The resins prepared showed typical p H-dependent adsorption and the highest adsorption capacity and affinity were found at pH 5.0for all the resins tested. The saturated adsorption capacity was 138.02 mg·g^(-1)with the tryptaminefunctionalized resin, which significantly decreased at p H below 4.0 due to electrostatic repulsion between ligands and HSA. Moreover, the addition of Na Cl or(NH_4)_2SO_4in media reduced HSA adsorption capacity, although the two salts showed different affecting profiles. The tryptamine-functionalized resin showed the best salt-tolerant performance, and its high adsorption capacity was maintained under high salt concentrations. In addition, the five resins prepared showed good adsorption selectivity for recombinant HSA from Pichia pastoris broth. Molecular docking results between tryptamine and HSA indicated that tryptamine was favorable to bind on Site II(indole-binding site) of HSA.
基金supported by the National Key Research and Development Program(2022YFD1402100,2022YFD1401500)National Natural Science Foundation(32072500,32272557)+1 种基金Major Basic Research Project of Natural Science Foundation of Shandong Province(ZR2022ZD23)Shandong Province Key Research and Development Plan(2022TZXD0025,2021TZXD007-04-4),Taishan Scholar Program of Shandong Province.
文摘Abscisic acid(ABA)is a phytohormone that not only important for plant growth,but also mediating the stress response.The roles of ABA in plant immunity are especially multifaceted.Recently,the ABA functional analogues are of great significance to promote its application.Here,we reported an ABA functional analogue named 167A.167A inhibits plant growth and seeds germinating of Arabidopsis.Meanwhile,the 167A enhanced the plant immunity,which is opposite of ABA.We further investigated the PTI-response after 167A treatment,and the results show that the ROS burst,callose deposition accumulate with 167A treatment.Moreover,167A also influence the degree of stomal closed.RNA-seq assays show that the 167A down-regulated the ABA associated genes and upregulated the JA/SA/ET associated genes.Through genetic analysis,the 167A modulating the plant resistance through the PYR/PYL Receptors.Together,these results demonstrate that a novel ABA analogue 167A positive regulated plant immunity and has great potential for agricultural applications.
基金supported by the National Natural Science Foundation of China (22179063)。
文摘Prussian blue analogues (PBAs) are regarded as promising cathode materials for potassium-ion batteries(PIBs) owing to their low cost and high reversible capacity.Compared to other PBAs,potassium manganese hexacyanoferrate (KMnHCF) stands out for its superior capacity and operating voltage.However,Jahn-Teller effect of Mn^(3+)and the structural collapse caused by potassium ion insertion/extraction still affect the structural stability and electrochemical performance of this material.Herein,a green and efficient synthesis method is adopted to substitute potassium ions in KMnHCF with an appropriate amount of cesium ions to form a column effect.Cesium-doped KMnHCF (Cs-KMnHCF) mitigates the irreversible structural damage caused by potassiation/depotassiation and the Jahn-Teller effect,thereby improving the cycling stability.In addition,it widens the lattice channels,reduces the diffusion barrier of potassium ions,and optimizes the diffusion kinetics.By rationally controlling the doping amount of Cs^(+),the obtained K_(1.71)Cs_(0.05)Mn[Fe(CN)_(6)]_(0.95·0.05)·0.88H_(2)O exhibits remarkable electrochemical performance,with an initial discharge capacity of 137.6 mA h g^(-1)at a current density of 20 mA g^(-1)and a capacity retention of 89.6%after 600 cycles at 200 mA g^(-1).More importantly,when assembled with a pitch-derived soft carbon anode,the full cell manifests excellent cycle stability and rate performance.This work is expected to provide a highly efficient cathode material for the practical application of PIBs.
基金supported by Jiangsu Innovative Group of Meat Nutrition,Health and Biotechnologythe Postgraduate Research&Practice Innovation Program of Jiangsu Province(grant number:KYCX21_0575)。
文摘To determine the effects of plant-based meat analogues on the metabolic health and the possible mechanisms,mice were fed with a real pork diet(AP),a real beef diet(AB),a plant-based pork analogue diet(PP)and plant-based beef analogue diet(PB)for 68 days.Compared with real meat,the plant-based meat analogues increased food and energy intake,body weight,white fat and liver weight and caused adipocyte hypertrophy,hepatic lipid droplet accumulation,and inflammatory responses in mice.Metabolomics revealed that plantbased meat analogues altered the composition of serum metabolites,which regulated lipid metabolism homeostasis.The PB diet upregulated gene expression related to lipid synthesis,lipolysis and adipocyte differentiation while the PP diet upregulated expression of lipolysis-related genes but downregulated expression of adipocyte differentiation-related genes in white adipose tissue.Meanwhile,both PP and PB diets upregulated lipid influx-and synthesis-related genes but downregulated lipid oxidation-related genes in liver.The specific metabolite biomarkers may affect fat accumulation mainly by direct lipid metabolism pathways or indirect amino acid metabolism,protein digestion and absorption,bile secretion,aminoacyl-tRNA biosynthesis,neuroactive ligand-receptor interaction and ABC transporters pathways.These findings provide a new insight into understanding the differences in nutritional functions of meat and plant-based meat analogues.
基金supported by Mitacs through the Mitacs Business Strategy Internship.
文摘Plant-based meat analogues(PBMA)are formulated to mimic the sensory characteristics of traditional meat products(TMP)using vegetarian ingredients and are increasingly popular with the trend towards plantbased diets,even among meat-eating consumers.This narrative review compared the nutritional quality of PBMA and TMP to broaden the discussion on the suitability of simulated meat products to substitute TMP,while exploring other attributes for their comparison.The complexity of PBMA and TMP means they are not entirely interchangeable.Importantly,PBMA health effects extend beyond their basic nutrient content and quality.Postprandial metabolism and satiety,for example,can be affected by product formulation,ingredient interactions,and thermomechanical processing involved in producing organoleptically acceptable PBMA.There are specific opportunities for low-sodium PBMA products to contribute to a healthy shift toward plantbased diets.In conclusion,PBMA cannot be assumed to be healthier than TMP.They should be designed with comprehensive consideration of composition and processing to ensure they support consumers who are adopting plant-based diets in realizing the theoretical health benefits.
文摘The recombinant Saccharomyces cerevisiae strain stably expressing recombinant human glucagon-like peptide-l(rhGLP-1) analogue, as a potential oral drug delivery system for diabetes type II treatment, was successfully constructed by the homologous recombination between chromosomal DNA and yeast and integrating vector pNK-GLP containing yeast ribosomal DNA fragments. The amount of rhGLP-I analogue fusion protein in transformant SG2 reached ca. 0.84 mg per gram of packed cells when SG2 was grown for 24 h in the YPD medium with a inoculum and medium ratio of 1:1. Oral administration of 5 g lyophilized SG2/kg to hyperglycemic rats decreased serum glucose from (24.8±1.40) to (21.2±1.36) mmol/L.
基金funded by the National Natural Science Foundation of China (grant No.41472116)the Jidong Oil Company of China National Petroleum Corporation (grant No.JDYT-2017-JS-308)the Beijing Research Centre of China National Offshore Oil Company (grant No.CCL2022RCPS2017XNN)。
文摘The evolution of faults within the same stress field is frequently influenced by numerous factors,involving the reactivation of pre-existing structures,stress transmission through ductile detachment layers,and the growth,interaction,as well as linkage of new fault segments.This study analyses a complex multi-phase oblique extension fault system in the Nanpu Sag(NPS)of the Bohai Bay Basin(BBB),China.High-resolution three-dimensional(3D)seismic data and analogue modelling indicate that the oblique extensional reactivation of pre-existing structures governs the sequential arrangement of fault segments in the caprock,and they dip synthetically to the reactivated fault at depth.During the NW-SE extension in the Eocene,the predominant movement of the pre-existing fault is strike-slip.Subsequently,during the N-S extension since the Oligocene,inclined at 20.to the pre-existing fault,forming splay fault segments and ultimately creating large en-echelon arcuate faults linked by relay ramps.Using fault throw-distance(T-D)and laser scanning,we reconstructed the fault evolution model of oblique extension reactivation in the presence of a ductile detachment basement.Our study illustrates that the arcuate faults can be categorized into linear master fault segments controlled by pre-existing structures,bending splay faults in the termination zone,and normal fault segments responding to the regional stress field.The interaction between faults occurs among normal faults and strike-slip faults,and the kinematic unification of the two fault systems is accomplished in the intersection zone.As the faults continue to evolve,the new fault segments tend to relinquish the control of pre-existing structures and concentrate more on the development of planar and continuous major faults.The ductile detachment layer significantly contributes to the uniform distribution of strain,resulting in narrow shear zones and discontinuous normal faults in its absence.
文摘BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explore the effects of Zhibai dihuang pills and gonadotropin-releasing hormone analogue(GnRHa)on growth and ovarian function in girls with precocious puberty.METHODS The clinical data of 84 adolescent girls with precocious puberty and rapidly progressive puberty from February 2017 to August 2023 were retrospectively analyzed.Girls were divided into a control group and an observation group,with 42 cases in each group.The control group received diet intervention combined with GnRHa treatment,while the observation group received diet intervention combined with Zhibai dihuang pills+GnRHa treatment.Outcomes such as clinical efficacy,growth indicators,ovarian function,and adverse reactions were compared between the two groups.RESULTS The observation group showed superior clinical efficacy compared to the control group(P<0.05).Prior to the intervention,no significant differences were found in growth or ovarian function between the groups(P>0.05).Post-intervention,the observation group exhibited significantly lower rates in growth,height,and bone age,along with reduced levels of progesterone,testosterone,estradiol,prolactin,luteinizing hormone,and follicle-stimulating hormone compared to the control group(P<0.05).The incidence of adverse reactions was similar across both groups(P>0.05).CONCLUSION Combining Zhibai dihuang pills with GnRHa and dietary intervention effectively improves growth,enhances ovarian function,and minimizes adverse reactions in adolescent girls with precocious and rapidly progressive puberty.
基金thanks to the Austrian grant(ASO)SK-06/07-14/2007the Faculty of Mediccine Research Fund(University of Pécs)AOK-KA-213/20.
文摘UV-VIS spectroscopic investigations of interaction of bovine and human serum albumin with selected chalcones (1) and their cyclic chalcone analogues: (E)-2-(4’-X-benzylidene-1-tetralones (3), benzosuberones (4) with dimethylamino and methoxy substituents and (E)-2-(2’,4’-dimethox- ybenzylidene)-1-indanone (2) were performed in polar respiration medium. Absorption maxima of the tested compounds were investigated in the presence of bovine and human serum albumin at the 0, 10, 30 and 60 minute timepoints of the interaction. The absorbance of all studied compounds in the presence of proteins decreased after one hour of the reaction. Molecule 4a showed the strongest and fastest kinet initial interaction with both albumins.
文摘Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata et al.,2023).Mitochondrial dysfunction,characterized by an imbalance in ATP levels and excessive production of mitochondrial reactive oxygen species,is a key factor that impedes neural regeneration in neurodegenerative diseases and after neuronal injury(Han et al.,2016,2020;Zheng et al.,2016;Zong et al.,2024).
基金supported by the Christiane and Claudia Hempel Foundation for Regenerative Medicineby the James and Elisabeth Cloppenburg, Peek and Cloppenburg Düsseldorf Stiftung(to PK)。
文摘Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
文摘Phosphoinositide-dependent protein kinase-1 (PDK1), the class of serine threonine kinase, is a master regulator of the AGC family of kinases. It is a main component of the PI3K pathway. As it is reported that this pathway is most commonly, and this pathway is the most commonly deregulated among many cancers. So designing a selective inhibitor of PDK1 may have the efficacy as an anticancer agent. Herein, we describe our work focused on the structure based on screening of 95% similar analogues of Myricetin deposited in PubChem database as earlier studies have been suggested that myricetin acts as an anti cancer agent. Further molecular docking as well as the in silico ADMET studies are incorporated on these compounds to evaluate the binding and pharmacokinetic properties of these compounds. Due to low oral bioavailability, clinical use of myricetin is limited. Therefore this study is an attempt towards screening of structurally similar better compounds as compare with myricetin which can act as better inhibitor against PDK-1.
文摘Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.
文摘Background and Aim of Study: The phosphodiesterase inhibitors (Sildenafil and Milrinone), Nitric Oxide donor Sodium Nitroprusside (SNP) and prostacyclin analogs are commonly used pulmonary vasodilators to treat pulmonary hypertension. In the past few years, we have used human pulmonary artery rings in vitro to evaluate pulmonary vascular resistance. The main objective of the current study is to document the pharmacological impact of clinically used prostacyclin analogs on the human pulmonary system in parallel with phosphodiesterase inhibitors and SNP. Methods: The study used human pulmonary artery rings of internal diameter of 2 - 4 mm and length of 2 mm. These were extracted from patients with lung resections. These rings were then mounted on a multiwire myograph, and changes in isometric tension were noted. Then, concentration response curves were constructed to Sildenafil (Sd), Milrinone (Mil), Sodium Nitroprusside (SNP), Epoprostenol (Ep), Iloprost (Ip) and Treprostinil (Tp). Results: 52 pulmonary artery rings were used in these experiments. Sildenafil, Milrinone, SNP, Epoprostenol, Iloprost and Treprostinil caused a concentration-dependent vasodilation in small human pulmonary arteries (pEC50: 5.97 ± 0.22, 5.99 ± 0.12, 7.64 ± 0.08, 7.53 ± 0.14, 8.84 ± 0.15 and 9.48 ± 0.13 respectively, n = 8 to 12). The efficacy for the same was in the order: Tp = Ip > Ep > Mil > SNP > Sd. The potency varied in the order: Tp > Ip > SNP > Ep > Mil > Sd. Conclusion: This research showed the efficacy as well as the potency of SNP and phosphodiesterase inhibitors and prostacyclin analogs on the human pulmonary vasculature. Treprostinil and Iloprost exhibited maximum relaxation. However, Sildenafil and SNP showed lesser impact. These effects need to be considered for clinical studies for enhanced patient outcomes.
文摘In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.
基金supported by the Koeln Fortune Program/Faculty of Medicine,University of Cologne,the Alzheimer Forschung Initiative e.V.(grant#22039,to HZ)open-access funding from the DFG/GRC issued to the University of CologneAlzheimer Forschung Initiative e.V.for Open Access Publishing(a publication grant#P2401,to MAAK)。
文摘TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.
基金Supported by the National Research Foundation of Korea,No.2020R1A2C1100891Soonchunhyang University Research Fund,No.2024-05-014.
文摘BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanisms that target p16 and p53 proteins.However,research on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous SCC(HNCSCC),particularly in Asian populations,remains limited.This retrospective study surveyed 62 patients with HNSCC(2011-2020),excluding those with facial warts or other skin cancer.AIM To explore the prevalence of HPV and the predictive value of p16 and p53 expression in HNCSCC in Asian populations.METHODS All patients underwent wide excision and biopsy.Immunohistochemical staining for HPV,p16,and p53 yielded positive and negative results.The relevance of each marker was investigated by categorizing the tumor locations into high-risk and middle-risk zones based on recurrence frequency.RESULTS Of the 62 patients,20(32.26%)were male,with an average age of 82.27 years(range 26-103 years).High-risk included 19 cases(30.65%),with the eyelid and lip being the most common sites(five cases,8.06%).Middle-risk included 43 cases(69.35%),with the cheek being the most common(29 cases,46.77%).The p16 expression was detected in 24 patients(38.71%),p53 expression in 42 patients(72.58%),and HPV in five patients(8.06%).No significant association was found between p16 expression and the presence of HPV(P>0.99),with a positive predictive value of 8.33%.CONCLUSION This study revealed that p16,a surrogate HPV marker in oropharyngeal SCC,is not reliable in HNCSCC,providing valuable insights for further research in Asian populations.
基金supported by the National Natural Science Foundation of China,No.82301403(to DZ)。
文摘Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous system.Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord.Here,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal cord.To explore the conservation and divergence across species,we compared these findings with those from mice.In the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic subclusters.In the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice.Additionally,we detected sex differences in gene expression in human spinal cord glial cells.Specifically,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in females.In all microglial subtypes,all differentially expressed genes were located on the sex chromosomes.In addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in males.Collectively,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cordrelated illnesses,including chronic pain,amyotrophic lateral sclerosis,and multiple sclerosis.
文摘Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.