Dry eye disease(DED)is a common ocular surface disorder worldwide, primarily characterized by a loss of homeostasis of the tear film, and frequently associated with meibomian gland dysfunction(MGD), decreased tear film stability, ocular discomfort, and visual impairment. In recent years, factors such as the widespread use of digital devices,the aging population, and environmental changes have contributed to a significant increase in its global prevalence, making it a major public health concern. Red light therapy(RLT), also known as low-level laser therapy(LLLT)or photobiomodulation(PBM), is a non-invasive treatment that utilizes low-energy red or near-infrared light to irradiate tissues. It exerts photobiomodulatory effects to promote cellular repair and functional recovery. This therapy has demonstrated considerable potential in treating various ocular conditions. Its broader clinical application could improve therapeutic outcomes, alleviate patient discomfort and financial burden, and reduce the consumption of healthcare resources, thereby yielding significant socio-economic benefits. This paper systematically reviews the multifaceted mechanisms and application prospects of RLT in managing DED, including its anti-inflammatory effects, improvement of meibomian gland function, promotion of conjunctival goblet cell repair, and alleviation of visual fatigue, aiming to provide a theoretical foundation and practical reference for its clinical adoption.

Objective To analyze the situation of rapid antiretroviral therapy (ART) and death of HIV/AIDS in Wuhan from 1994 to 2023, and to provide a scientific basis for further rapid initiation of ART and reduction of mortality rate. Methods According to the case follow-up and treatment database of China AIDS Prevention and Control Information System, data were obtained from all the cases reported from January 1, 1994 to December 31, 2023 with the current address in Wuhan City and the review status of the final review card. The data were analyzed using Kaplan-Meier and Cox proportional hazards models. Results The total mortality rate of HIV/AIDS in Wuhan from 1994 to 2023 was 12.76%. The proportion of receiving antiretroviral therapy within 30 days increased year by year, and the mortality rate decreased year by year. After adjusting for sex, age, occupation, ethnicity, education level, mobile population, history of STD, route of infection, source of sample, and first CD4 value, receiving antiretroviral therapy within 30 days (HR=0.08, 95%CI: 0.07-0.10) was a protective factor for HIV/AIDS mortality. Conclusion Rapid antiretroviral therapy can significantly reduce the risk of HIV/AIDS death. A sustainable model of rapid initiation of antiretroviral therapy should be further established to increase the proportion of rapid antiretroviral therapy for HIV/AIDS in Wuhan.

Objective Based on the visualization graph analysis of the research hotspots of Angelica sinensis, predict the future research trends, and provide references for the next step of Angelica sinensis research. Methods Chinese and English literatures on Angelica sinensis collected from CNKI, WanFang, VIP and Web of Science from 2012 to 2022 were retrieved. CiteSpace 6.1.R6 software was used to perform visualization econometrics analysis on the number of publications, authors, institutions, journals, keywords and other topics. Results 3490 Chinese literatures and 409 English literatures were included. Visual knowledge map analysis showed that Gansu University of Chinese Medicine and Nanjing University of Chinese Medicine were the research institutions with the largest number of literature publications in Chinese and English respectively. Journals published mainly include Shizhen Traditional Chinese Medicine and Materia medica, Evidence-based Complementary and Alternative Medicine. Current research hotspots include the effects of Angelica sinensis polysaccharides, volatile oils, and ferulic acid on the hematopoietic system, chronic diseases, and cognitive impairment, as well as clinical efficacy evaluations of classic prescriptions containing Angelica sinensis and their modified formulations. The research trend was characterized by a focus on the pharmacological study of Danggui Buxue Tang,employing various experimental approaches such as network pharmacology, serum pharmacology, and metabolomics to elucidate the mechanisms of Angelica sinensis. Conclusion The pharmacological effects of Angelica sinensis and its compound were extensive, which should be further researched.

Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

Objective To investigate the causes and management strategies for lower limb ischemic necrosis following xenogeneic heterotopic heart transplantation from a multigene-edited pig to a rhesus monkey. Methods A xenogeneic heterotopic heart transplantation was performed on December 16, 2023, at the Institute of Experimental Animals of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, using a quintuple-gene-edited pig as the donor and a rhesus monkey as the recipient. On postoperative day (POD) 9, the recipient monkey underwent left lower limb amputation due to ischemic necrosis. Blood samples were collected at various time points after transplantation for analysis of hematologic parameters, liver and renal function, myocardial enzymes, and coagulation profiles. Ultrasound and computed tomography (CT) were used to evaluate anastomotic patency and cardiac structure. Immunological assays, including complement-dependent cytotoxicity (CDC) and IgG/IgM antibody detection, combined with clinical observations, were employed to assess rejection type and therapeutic response. Results The recipient monkey survived for 46 days after transplantation. Echocardiography demonstrated preserved biventricular systolic function in the recipient’s native heart, with left ventricular ejection fraction (LVEF) consistently exceeding 50%. In the donor pig heart, left ventricular endocardial thickening was noted on POD 9, followed by right ventricular endocardial thickening on POD 24, while LVEF remained around 35%. No hyperacute or acute rejection was detected immunologically. CDC positivity ranged between 3.4% and 5.1%, with IgG/IgM antibody binding trends consistent with CDC results. Following amputation, the recipient exhibited elevated inflammatory markers, coagulopathy, and reactive thrombocytosis, which later normalized. Immunohistochemical staining of the necrotic limb revealed arterial and venous thrombosis; however, no T-cell or B-cell infiltration was observed in vascular structures, thrombi, nerves, muscles, fascia, or skin tissues, with CD3 and CD20 staining both negative. Conclusion Limb ischemia after xenogeneic heart transplantation may be associated with lower extremity vascular thrombosis triggered by local trauma in the context of transplantation-induced inflammatory activation and coagulation dysfunction. While no clear lymphocyte-mediated rejection was observed, further studies are needed to explore the potential role of non-lymphocyte-mediated immune mechanisms.

Bone remodeling is essential for maintaining skeletal integrity and mineral homeostasis and depends on the coordinated activities of osteoclasts, osteoblasts, and osteocytes. Osteoclast-mediated bone resorption must remain closely coupled with osteoblast-mediated bone formation, while osteocytes continuously sense mechanical loading and changes in the local and systemic environment. Reactive oxygen species are involved in these physiological processes, particularly in the regulation of osteoclast differentiation and osteoblast function. Once oxidative stress exceeds the capacity of cellular antioxidant systems, however, this balance may be disturbed, leading to enhanced bone resorption, impaired bone formation, and deterioration of bone quality. In recent years, ferroptosis has attracted increasing attention in studies of bone metabolism. Ferroptosis is characterized by iron-dependent accumulation of lipid peroxides, but ferroptosis-related alterations in bone tissue may occur before obvious cell death becomes detectable. Changes in the labile iron pool, membrane lipid composition, antioxidant capacity, and mitochondrial metabolism can already influence the biological behavior of bone cells at an earlier stage. On this basis, ferroptosis susceptibility may provide a useful way to describe a reversible metabolic state in which cells become increasingly vulnerable to lipid peroxidation while widespread membrane damage and terminal cell death have not yet occurred. Such a state should not be identified by a single molecular marker. A more appropriate assessment would combine changes in intracellular iron handling, lipid peroxidation, antioxidant defense, cell viability, bone-cell function, and the response to ferroptosis-related interventions. Measurements of Fe²⁺ or the labile iron pool, C11-BODIPY oxidation, 4-HNE and MDA, GPX4 activity or expression, GSH/GSSG balance, LDH release, and PI staining may therefore provide complementary information when interpreted together with functional changes and rescue experiments. Several metabolic processes may contribute to the development of ferroptosis susceptibility in the bone. Disturbances in iron uptake, ferritin storage, ferritinophagy, and ferroportin-mediated iron export can increase the availability of redox-active iron. At the same time, ACSL4- and LPCAT3-dependent incorporation of polyunsaturated fatty acids into membrane phospholipids increases the pool of oxidizable lipid substrates. Reduced activity of the system Xc^--GSH-GPX4 pathway further weakens the ability of cells to remove lipid hydroperoxides, while FSP1-CoQ and mitochondrial DHODH-CoQ systems provide additional antioxidant protection. Mitochondrial dysfunction, inflammation, and abnormalities in calcium-phosphate and endocrine regulation may further increase this metabolic pressure. Importantly, the consequences are unlikely to be identical among bone-cell populations. In osteoclasts, increased iron availability and oxidative stress may strengthen RANKL-NFATc1-associated differentiation and resorptive activity. In osteoblasts, persistent lipid peroxidation may interfere with RUNX2-related differentiation, collagen synthesis, matrix production, and mineralization before extensive cell loss occurs. Osteocytes, because of their long lifespan and specialized location within the mineralized matrix, may be particularly sensitive to chronic metabolic stress, resulting in impaired mechanosensing and disturbed RANKL- or FGF23-related feedback. Evidence linking these changes with osteoporosis, diabetes-related bone disorders, chronic kidney disease-mineral and bone disorder, inflammatory bone loss, and particle-induced osteolysis is increasing, although the strength of evidence differs among disease models. Changes in ROS, MDA, GPX4, or other individual indicators alone are insufficient to demonstrate ferroptosis-related susceptibility, and stronger conclusions require evidence of iron dependence, lipid peroxidation, temporal sequence, and reversibility. Emerging single-cell, spatial, proteomic, lipidomic, and metabolomic approaches may help identify susceptible cell populations and bone-remodeling regions more precisely, although the mineralized matrix and the effects of sample processing remain important technical limitations. Overall, ferroptosis susceptibility may represent an intermediate metabolic state linking disturbances in iron and redox homeostasis with progressive uncoupling of bone resorption and formation. Clarifying its cell-specific features, temporal development, and reversible window may improve our understanding of how chronic metabolic stress contributes to bone remodeling disorders and may also provide a basis for earlier and more targeted intervention.

Widespread utilization of glyphosate has led to environmental residues,posing potential threats to ecological systems and human health.Traditional methods for detection of glyphosate are limited by specialized equipment and operational techniques,resulting in inefficient responses.Therefore,it is urgent to develop a convenient,sensitive and accurate detection method for detection of glyphosate.Herein,a new naphthalenesulfonamide-based"Turn-on"fluorescent probe was synthesized using 2-chloroaniline and dansyl chloride as raw materials through a one-step process,which showed a good linear relationship between the glyphosate concentration in concentration range of 0.003-70 μmol/L and the fluorescence intensity(R2=0.995),with a detection limit of 2.73 nmol/L(S/N=3).Analytical techniques such as nuclear magnetic resonance(NMR)spectroscopy and high-resolution mass spectrometry(HRMS)were used to investigate the interaction mechanism between the fluorescent probe and glyphosate.The results indicated that a nucleophilic substitution reaction occurred between the probe and the secondary amine(—NH—)of glyphosate,inducing a photoinduced electron transfer(PET)effect which enhanced the fluorescence intensity by 11.2 times.The probe showed good anti-interference ability towards coexisting metal ions,anions and pesticides in water.When applied to determination of glyphosate in the samples such as tap water,river water(Xiangxi River Reservoir),soil,soybeans,and corn,the spiking recoveries ranged from 94.7％to 109.9％,demonstrating the high accuracy and broad applicability of this detection method.A portable test strip based on this fluorescent probe was developed for rapid semi-quantitative analysis of glyphosate.The developed method was rapid,sensitive,and portable,providing theoretical and technical support for on-site measurement of environmental contaminants.

6-Thioguanine(6-TG)is an antineoplastic agent used in treatment of acute leukemia.However,significant interindividual variability in dosing regimens and frequent clinical manifestations of hepatotoxicity and myelosuppression as adverse effects have affected its therapeutic efficacy.Consequently,the development of rapid analytical methods for 6-TG in clinical samples,enabling continuous therapeutic drug monitoring of plasma concentrations,holds substantial significance in optimizing dosage regimens,mitigating adverse reactions,and investigating drug metabolism mechanisms.In this study,multi-tipped gold nanostars(AuNSs)were prepared.With bis-(p-sulfonylphenyl)phenylphosphine molecule as the protecting agent and internal standard molecule,the AuNSs were assembled onto a highly sensitive surface-enhanced Raman(SERS)substrate for developing a ratio-based SERS quantitative analysis method for 6-TG in serum.The AuNSs containing multiple tips and gaps exhibited strong local surface plasmon resonance effect and SERS activity,ensuring the sensitivity of the analytical method.Furthermore,the introduction of internal standard molecules could improve the reproducibility,which guaranteed this method suitable for rapid analysis of drug molecules in complex samples.Quantitative analysis of 6-TG was achieved with linear detetion range of 1.0×10?4-1.0 mmol/L.In the spiked recovery experiments of serum,the RSD was less than 5.32%,and the recoveries were 94%-104%,which proved that this method could be used for rapid quantitative determination of 6-TG in serum.This method provided a powerful tool for studying drug pharmacokinetics,which could promote the optimization of the usage methods of anti-cancer drugs,and it was expected to further enhance the clinical efficacy and safety of 6-TG,enabling it to achieve the best therapeutic effect.

By using a strategy of leveraging the ability of metal-organic frameworks(MOFs)materials to precisely regulate the spatial orientation of cyclodextrins(CD),a polystyrene-modified γ-cyclodextrin metal-organic frameworks(PS-CD-MOFs)capillary coating was established and applied to the chiral separation of amino acids in open-tubular capillary electrochromatography(OT-CEC)based on the excellent film-forming property of polystyrene(PS).Characterization results by Fourier transform infrared spectroscopy(FT-IR),X-ray diffraction(XRD)indicated that PS was successfully grafted onto the surface of CD-MOFs.The modification significantly improved the structural stability and thermal stability of CD-MOFs while maintaining the integrity of the MOFs.The PS-CD-MOFs coated capillary electrophoresis system exhibited excellent performance in separating dansylated amino acid enantiomers(Dns-D,L-AAs).Specifically,under the optimal separation conditions(Sodium dodecyl sulfate/boric acid buffer system,20 cm capillary,and 10 kV effective voltage),good separation was achieved for D,L-methionine(D,L-Met)and D,L-serine(D,L-Ser).Further quantitative analysis showed that Dns-D,L-Met presented a good linear relationship in the concentration range of 10.0-1500.0 μmol/L,with a correlation coefficient close to 0.998,demonstrating high sensitivity and repeatability.Not only did it overcome the problem that traditional CD(used as additives in capillary electrophoresis)could not precisely control the spatial orientation of chiral resolvents,but also it solved the issues of insufficient stability and bonding amount of CD-MOFs coatings by utilizing the excellent film-forming property of polymers on the inner wall of capillaries.This study provided an efficient and controllable new strategy for construction of chiral separation stationary phases.

Objective To explore the mechanism of myocardial toxicity caused by N-methyl-3,4-methyle-nedioxyamphetamine(MDMA),the changes of intracellular calcium oscillation mode and calcium han-dling proteins during acute exposure to different concentrations of MDMA were detected,and the in-volvement of nuclear factor κB(NF-κB)and its effect on calcium handling proteins were investigated.Methods Primary rat cardiomyocytes were cultured to establish MDMA acute exposure model,and a control group was set up.The MDMA poisoning model was divided into three concentration groups of 10,100 and 1 000 μmol/L.After 1 h of exposure,the morphological changes of cardiomyocytes were ob-served,the cytotoxicity and changes in calcium signals were measured,and the changes in calcium handling proteins RyR2,SERCA2a,PLN,NCX1 and Cav1.2 were detected.The changes of NF-κB activity and the expression of nucleoprotein p-p65(Ser311)and PKCζ after MDMA exposure,and the intervention of NF-κB inhibitors pyrrolidine dithiocarbamate ammonium(PDTC)and protein kinase C(PKC)inhibitor chelerythrine(CHE)were detected by electrophoretic mobility shift assay(EMSA)and Western blotting.The effects of PDTC intervention on calcium signals,and the expressions of RyR2,SERCA2a,PLN,NCX1 and Cav1.2 after acute MDMA exposure were also observed.Results No obvious changes were observed in the morphology of cardiomyocytes after acute exposure to MDMA,whereas the oscillation waveform of intracytoplasmic calcium ion showed irregular changes with increased oscillation amplitude,intense fluctuations,irregular frequency,and increased fluctuation range of relative optical density values.The expression of RyR2,SERCA2a and NCX1 increased,while the expression of Cav1.2 and PLN de-creased.Acute MDMA exposure could increase NF-κB activity,while PDTC and CHE intervention could inhibit NF-κB activity.In MDMA exposed group,the expression of PKCζ and nucleoprotein p-p65(Ser311)both increased and could be inhibited by CHE.After the intervention of PDTC to block NF-κB,the amplitude of calcium oscillation was lower than that of the MDMA exposed group,and the expres-sion of RyR2,SERCA2a and NCX1 decreased.There was no significant change in PLN,while the ex-pression of Cav1.2 increased.Conclusion MDMA can lead to an increase of calcium ion concentration in cardiomyocytes.Calcium ions are involved in myocardial toxicity of MDMA.The mechanism is re-lated to changes in calcium handling proteins,mainly associated with the increased expression of RyR2.MDMA can up-regulate the intracellular activity of NF-κB through the PKCζ-NF-κB pathway and affect calcium handling proteins,which aggravate intracellular calcium overload during acute MDMA exposure.