The pathogenesis of neurodegenerative diseases (NDDs) is fundamentally linked to complex and profound alterations in metabolic networks within the brain, which exhibit marked spatial heterogeneity. While conventional bulk metabolomics is powerful for detecting global metabolic shifts, it inherently lacks spatial resolution. This methodological limitation hampers the ability to interrogate critical metabolic dysregulation within discrete anatomical brain regions and specific cellular microenvironments, thereby constraining a deeper understanding of the core pathological mechanisms that initiate and drive NDDs. To address this critical gap, spatial metabolomics, with mass spectrometry imaging (MSI) at its core, has emerged as a transformative approach. It uniquely overcomes the limitations of bulk methods by enabling high-resolution, simultaneous detection and precise localization of hundreds to thousands of endogenous molecules—including primary metabolites, complex lipids, neurotransmitters, neuropeptides, and essential metal ions—directly in situ from tissue sections. This powerful capability offers an unprecedented spatial perspective for investigating the intricate and heterogeneous chemical landscape of NDD pathology, opening new avenues for discovery. Accordingly, this review provides a comprehensive overview of the field, beginning with a discussion of the technical features, optimal application scenarios, and current limitations of major MSI platforms. These include the widely adopted matrix-assisted laser desorption/ionization (MALDI)-MSI, the ultra-high-resolution technique of secondary ion mass spectrometry (SIMS)-MSI, and the ambient ionization method of desorption electrospray ionization (DESI)-MSI, along with other emerging technologies. We then highlight the pivotal applications of spatial metabolomics in NDD research, particularly its role in elucidating the profound chemical heterogeneity within distinct pathological microenvironments. These applications include mapping unique molecular signatures around amyloid β‑protein (Aβ) plaques, uncovering the metabolic consequences of neurofibrillary tangles composed of hyperphosphorylated tau protein, and characterizing the lipid and metabolite composition of Lewy bodies. Moreover, we examine how spatial metabolomics contributes to constructing detailed metabolic vulnerability maps across the brain, shedding light on the biochemical factors that render certain neuronal populations and anatomical regions selectively susceptible to degeneration while others remain resilient. Looking beyond current applications, we explore the immense potential of integrating spatial metabolomics with other advanced research methodologies. This includes its combination with three-dimensional brain organoid models to recapitulate disease-relevant metabolic processes, its linkage with multi-organ axis studies to investigate how systemic metabolic health influences neurodegeneration, and its convergence with single-cell and subcellular analyses to achieve unprecedented molecular resolution. In conclusion, this review not only summarizes the current state and critical role of spatial metabolomics in NDD research but also offers a forward-looking perspective on its transformative potential. We envision its continued impact in advancing our fundamental understanding of NDDs and accelerating translation into clinical practice—from the discovery of novel biomarkers for early diagnosis to the development of high-throughput drug screening platforms and the realization of precision medicine for individuals affected by these devastating disorders.

OBJECTIVE: This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China. METHODS: Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site. RESULTS: Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL. CONCLUSION The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans ; HIV Infections/virology* ; China/epidemiology* ; Drug Resistance, Viral ; Male ; Adult ; Female ; Middle Aged ; HIV-1/genetics* ; Anti-HIV Agents/therapeutic use* ; Myanmar/epidemiology* ; Young Adult ; Prevalence ; Adolescent ; Mutation

ObjectiveTo determine the optimal combination of the effective monomer components "quercetin-kaempferol-abietic acid-boswellic acid" in Fujin Shengjisan for promoting diabetic ulcer （DU） wound healing through uniform design， thereby achieving the modern application of the ancient formula. MethodsFollowing the principle of "uniform design-pharmacodynamic experiment-mathematical modeling and model verification"， the U₁₄（14⁵） uniform design table was adopted.The four monomer components of Chinese medicine were considered as the independent variables， and the proliferation rate of human umbilical vein endothelial cells （HUVECs） induced by glucose was used as the pharmacodynamic indicator. A mathematical model was constructed using DPS software to correlate the effective monomer components with the pharmacodynamic indicator. The results of uniform design were verified through CCK-8 assay， cell scratch healing， tube formation， Western blot， and Real-time PCR. ResultsAmong the 14 compatibility groups， compared with the high-glucose model group， compound compatibility group 6 showed the strongest proliferation effect and statistical significance （P<0.05）. Four quadratic polynomial regression equations （Y₁-Y₄） were obtained through DPS modeling. Considering the model's fit， stability， and practical application， equations Y₁-Y₃ were selected for the follow-up verification. To ensure experiment reproducibility， group 6 was used for validation. Group 6 and equations Y₁-Y₃ were renamed as compound prescription ① to compound prescription④， respectively， to represent the modern application of the ancient FJSJ Powder through compatibility of monomer components. Verification experiments showed that in the CCK-8， scratch healing， and tube formation assays， the cell viability， wound healing rate， and tube formation number of HUVECs stimulated with 50 mmol·L^-1 glucose were significantly reduced compared with the blank group. Moreover， the expression levels of angiogenesis-related cytokines， vascular endothelial growth factor （VEGF） and fibroblast growth factor 2 （FGF2）， and CD31 secretion were significantly down-regulated. However， after intervention with compound prescriptions ① to ④， compound prescriptions ① and ③ significantly improved the biological functions of HUVECs induced by 50 mmol·L^-1 glucose. Further analysis of the regression coefficients of compound prescriptions ① and ③， and the relative dose ratios of each monomer component， indicated that abietic acid， quercetin， and boswellic acid promoted angiogenesis of HUVECs in the high glucose environment， with a major effect （positive partial correlation coefficients， all > 0.9）. Abietic acid and boswellic acid， as well as kaempferol and boswellic acid， promoted angiogenesis in HUVECs through interaction （positive partial correlation coefficients）. ConclusionCompound prescriptions ① and ③ are the optimal combinations. They can reverse the inhibitory effects of high glucose， stimulate the proliferation， migration， and tube formation abilities of HUVECs in a high glucose environment， and promote the expression of vascular endothelial growth factorA（VEGFA）， FGF2， and CD31， thereby promoting angiogenesis and facilitating DU wound healing. This finding not only confirms the good reproducibility and feasibility of compound prescriptions ① and ③ but also provides new insights and methods for the rational construction of mathematical models to further study the compatibility theory of Chinese medicine.

AIM: To investigate the correlation between the expression of serum lipocalin 2(LCN2), chemokine like receptor 1(CMKLR1), and C-C motif chemokine ligand 11(CCL11)and the severity of disease in patients with type 2 diabetes mellitus(T2DM)and dry eye(DE).METHODS:A prospective selection of 97 patients(194 eyes)diagnosed with T2DM and DE at our hospital from May 2022 to May 2024 was made as the DE group, which was further divided into mild(47 cases, 94 eyes), moderate(34 cases, 68 eyes), and severe(16 cases, 32 eyes)subgroups based on the severity of dry eye. Additionally, 97 patients(194 eyes)of T2DM without DE were selected as non-DE group, and 97 healthy volunteers(194 eyes)who underwent physical examination during the same period were chosen as control group. Serum levels of LCN2, CMKLR1, and CCL11 were measured in all participants. Spearman correlation analysis was used to assess the relationship between serum levels of LCN2, CMKLR1, and CCL11 and the severity of DE in T2DM patients; multivariate Logistic analysis was used to analyze the factors affecting the severity of T2DM patients with DE. The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of serum LCN2, CMKLR1 and CCL11 levels for moderate to severe dry eye in T2DM patients.RESULTS: Serum levels of LCN2, CMKLR1, and CCL11 increased progressively from the control group to the non-DE group and then to the DE group(all P<0.05). Within the DE group, these levels also increased progressively from the mild to moderate and then to the severe subgroups(all P<0.05). Spearman correlation analysis showed that serum levels of LCN2, CMKLR1, and CCL11 were positively correlated with the severity of disease(rs=0.604, 0.591, 0.559, respectively; all P<0.05). Stepwise forward multivariate Logistic analysis showed that Schirmer's test(SⅠt), tear break-up time(BUT), serum levels of LCN2, CMKLR1 and CCL11 were the factors affecting the severity of T2DM patients with DE; ROC curve analysis indicated that the combined diagnosis of serum LCN2, CMKLR1, and CCL11 for the progression of T2DM with DE to moderate-to-severe stages had an area under curve(AUC)value of 0.896, which was significantly higher than that of individual diagnoses of LCN2, CMKLR1, and CCL11(Z=2.925, 2.704, 3.483, respectively; P=0.003, 0.007, <0.001).CONCLUSION: Serum LCN2, CMKLR1 and CCL11 levels are increased in T2DM patients with DE, and are positively correlated with the severity of DE. The combination of the three has a high diagnostic value for moderate to severe DE.

AIM: To investigate the expression and clinical diagnostic value of toll-like receptor 4(TLR4)and nuclear factor-κB(NF-κB)in conjunctival epithelial cells and tears of patients with dry eye.METHODS: From January 2023 to June 2024, 104 dry eye patients(104 eyes, disease group)who visited our hospital and 100 healthy individuals(100 eyes, control group)who underwent physical examination were selected. The changes of TLR4 and NF-κB in conjunctival epithelial cells and tears were analyzed. Pearson analysis was applied to analyze the correlation between TLR4 and NF-κB expression in conjunctival epithelial cells and tears. Logistic analysis was applied to analyze the factors that affected dry eye. ROC was applied to analyze the diagnostic value of TLR4 and NF-κB expression in conjunctival epithelial cells and tears for dry eye.RESULTS: The differences in the use of eye drops, tear film break-up time(BUT), Schirmer's test(SⅠt), tear film thickness(TFT), and corneal fluorescein staining(CFS)scores between the disease group and the control group were statistically significant(all P<0.01). The expression levels of TLR4 and NF-κB in conjunctival epithelial cells and tears in the disease group were significantly higher than those in the control group(all P<0.01). There was a positive correlation between TLR4 and NF-κB in conjunctival epithelial cells and tears(r=0.392, 0.348, all P<0.05). Frequent use of eye drops, CFS score, TLR4, and NF-κB were risk factors for dry eye(OR=2.153, 3.183, 1.578, 2.452, all P<0.05), while BUT, SⅠt, and TFT were protective factors for dry eye(OR=0.654, 0.755, 0.276, all P<0.05). The sensitivity, specificity, and AUC of TLR4 combined with NF-κB in conjunctival epithelial cells in the diagnosis of dry eye were 86.54%, 81.00%, and 0.889, respectively. The combination of TLR4 and NF-κB had higher diagnostic value for dry eye than uncombined diagnosis(Zcombination-TLR4=3.506, P=0.001; Zcombination-NF-κB=3.165, P=0.002). The sensitivity, specificity, and AUC of TLR4 combined with NF-κB in tears for diagnosing dry eye were 82.69%, 70.00%, and 0.818, respectively. The combination of TLR4 and NF-κB in tears had higher diagnostic value for dry eye than uncombined diagnosis(Zcombination-TLR4=3.117, P=0.002; Zcombination-NF-κB=2.363, P=0.018).CONCLUSION: The expression levels of TLR4 and NF-κB in conjunctival epithelial cells and tears of patients with dry eye are elevated. TLR4 and NF-κB are related to the development of dry eye, and that elevated levels of both are associated with an increased risk of dry eye disease. The combination of TLR4 and NF-κB has a certain diagnostic significance for dry eye.

Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

Iodine speciations in aquatic environments are affected by dissolved oxygen,redox potential,microbial activity,organic matter decomposition,light reaction,etc.Accurate quantification of iodine speciation can not only help to understand the geochemical cycle of iodine,but also help to trace and study environmental processes.Based on the combination of ion chromatography(IC)and inductively coupled plasma mass spectrometry(ICP-MS),a rapid and sensitive method was established for determining the speciations of iodine in environmental water samples including seawater,river water,lake water,rainwater,groundwater,etc.The results presented here showed that IO3?and I?in seawater were quickly separated and measured within 120 s when using guard column AG22 and 8 mmol/L(NH4)2CO3 as the mobile phase.While for lake water,river water and precipitation samples with high soluble organically bond iodine(SOI),an AS22 separation column(250 mm×4 mm)connected with a guard column and using 50 mmol/L(NH4)2CO3 as mobile phase could effectively separate unknown SOI from IO3? to achieve accurate quantification of IO3?.For accurate correction of iodine measurement signal fluctuations,133Cs was directly added to the(NH4)2CO3 mobile phase as an internal standard.The SOI content was calculated by the total iodine concentrations minus the sum of IO3?and I?.The precision of the established iodine speciation analytical method was better than 3.5%,and the standard addition experiment showed that the analytical method was accurate.When the injection volume was 25 μL,the detection limits were 0.011?0.025 μg/L for IO3? and 0.023?0.031 μg/L for I?,respectively.The method was successfully used to analyze IO3?,SOI and I? in environmental water samples,such as seawater,river water,rainwater and groundwater.

Neuroscience,a cutting-edge field in interdisciplinary research,consistently draws considerable research interest,of which quantitatively probing the neurochemical dynamics is essential for brain science research.In vivoelectrochemical analysis,featuring with high sensitivity,high spatiotemporal resolution,free from transfection,and designable electrode/solution interfaces,provides important tools for in vivo neurochemicals sensing.Fast scan cyclic voltammetry combined with microelectrodes can not only enable precise detection of dopamine but also is compatible with existing neurosurgical equipment.This offers new opportunities for the clinical application of in vivo electrochemical analysis and paves new avenues for the diagnosis and treatment of neurological diseases.This review summarized recent progress of in vivo electrochemical techniques for brain neurochemistry and addressed key clinical challenges and their potential solutions.

Approximately 300 million tons of plastic are produced globally each year,which has a serious impact on human health,marine life and the livestock industry.Microplastics have also been detected in meat and milk samples.Research has shown that nanoplastics(NP)(＜1 μm)and mi-croplastics(MP)(1 μm-5 mm)can affect the digestive,immune and reproductive systems of ani-mals.This experiment aims to investigate whether NP and MP regulate autophagy and damage the nervous system and spatial memory of animals.This experiment was divided into control group,nanoplastic group(PS-NP group,0.1 μm)and microplastic group(PS-MP group,1 μm),with 20 mice in each group.The mice were given 0.5 mL of PS-NP and PS-MP every day for 35 consecutive days,followed by neck amputation and brain analysis.The results showed that NPs and MPs of dif-ferent diameters caused varying degrees of damage to the brains of mice.In the behavioral tests of new object recognition,barnes maze and Y-shaped maze spatial memory,compared with the control group,the PS-NP group and PS-MP group showed a significant decrease in spatial memory ability of mice.HE staining results showed that neuronal cells in the PS-NP and PS-MP groups of mice exhibited shrinkage,decreased cell volume and deepened staining.The number of Nissl bodies de-creased,leading to dissolution and disappearance.RT-PCR and Western blot results showed that compared with the control group,the expression of glutamate receptors NR1,NR2A and NR2B in-creased in mice administered NP and MP orally,while the expression of autophagy related proteins Parkin,LC3B and Beclin1 was inhibited.In summary,this study suggests that nanoplastics and mi-croplastics stimulate glutamate receptors in mice by inhibiting the autophagy pathway,leading to impaired spatial memory.

Infectious diseases of the respiratory system are very common in clinical practice,among which pneumonia caused by in-fluenza virus infection is characterized by high morbidity and mortality.Current clinical treatments for respiratory viral infections still face challenges such as drug resistance and poor efficacy.Necroptosis,a form of programmed cell death,is closely associated with the progression of respiratory viral infections.Traditional Chinese medicine modulating necroptosis has demonstrated beneficial therapeu-tic effects in these diseases.This paper introduces the concept and mechanisms of necroptosis,reviews recent research on the relation-ship between necroptosis and respiratory virus infections diseases,and summarizes the therapeutic effects of traditional Chinese medi-cine in regulating necroptosis to intervene in these diseases,aiming to provide insights for the development and clinical application of therapeutic agents for respiratory viral infections.