Alzheimer’s disease (AD) is pathologically characterized by cerebral amyloid β‑protein (Aβ) aggregation, neurofibrillary tangles and progressive cognitive deterioration. There is an urgent clinical demand for targeted therapeutic agents against AD, whereas the blood-brain barrier (BBB) acts as a critical physical barrier that blocks over 98% small-molecule drugs and nearly all biomacromolecules from entering brain parenchyma. Nanomedicine-based drug delivery systems (NDDSs) with tunable physicochemical properties can cross the BBB via multiple transcytosis pathways including adsorptive-mediated, receptor-mediated and transporter-mediated routes, opening a promising avenue for targeted AD treatment. A core academic viewpoint proposed herein is that robust in vitro endothelial penetration of nanocarriers cannot guarantee effective accumulation in brain target cells. Comprehensive evaluation of BBB-crossing delivery efficiency should not merely rely on in vitro permeability tests, but cover the full multi-step transcytosis cascade, cellular tropism in brain tissues and in vivo therapeutic outcomes. This review systematically sorts out diverse nanoplatforms applicable to BBB penetration for AD intervention. Inorganic nanomaterials such as gold and ceria nanoparticles possess large specific surface areas and intrinsic antioxidant capacity, which eliminate reactive oxygen species and hinder Aβ fibrillization. Liposomal formulations and solid lipid nanoparticles exhibit superior biocompatibility with biomimetic phospholipid bilayer architectures, capable of co-loading hydrophilic nucleic acids for Tau regulation and lipophilic Aβ inhibitors; relying on receptor-mediated transcytosis, they achieve sustained drug retention in the brain. Polymeric nanocarriers including nanogels and polyamidoamine dendrimers enable multi-target combinatorial therapy, and can be engineered to release cargo in response to inflammatory microenvironments, thereby suppressing excessive microglial activation and protecting neuronal mitochondria. Beyond conventional nanocarriers, this work elaborates two cutting-edge BBB-crossing delivery platforms: biomimetic nanosystems and metal-organic frameworks (MOFs). Biomimetic nanoparticles camouflaged with erythrocyte, platelet or macrophage membranes, as well as natural exosomes, evade immune clearance, prolong systemic circulation and inherently home to inflammatory lesions. Serving as “nano-decoys”, they neutralize Aβ neurotoxins and remodel cerebral inflammatory microenvironments simultaneously. MOFs feature high porosity and customizable pore channels for co-delivery of multiple therapeutics, and can be integrated with near-infrared photothermal and photooxidation modalities to facilitate focal brain lesion therapy. This review highlights a transformative paradigm shift in the field of BBB-targeted AD therapy: research focus has shifted from simply maximizing cerebral drug penetration toward active modulation and functional restoration of the BBB. Impaired BBB transporters intrinsically impede endogenous Aβ clearance. Accordingly, BBB-regulating nanocarriers are designed to remodel the low-density lipoprotein receptor-related protein 1 (LRP1) trafficking cascade, redirecting endocytic vesicles from lysosomal degradation to non-degradable transcytosis and restoring the intrinsic Aβ efflux capacity of the BBB. Distinct from conventional strategies that only exert local lesion inhibition, this systemic clearance strategy eliminates cerebral Aβ deposits by accelerating peripheral excretion.

Objective To observe the morphology of the superficial,middle,and deep layers of the masseter muscle and related bony structures in the lateral facial region of adults through gross anatomy,and to probe into the effects of these muscle layers on the bony structures of the lateral facial region.Methods The bilateral masseter muscles of 12 adult cadavers were exposed,and the superficial,middle,and deep layers were separated and measured for muscle length,tendon length,and muscle belly length.After the masseter muscles were stripped,the total thickness was measured,and the mandible and zygomatic arch were exposed to measure the angle of the mandibular angle,thickness of the zygomatic arch,and width of the zygomatic arch.Observations were made of the masseter tuberosities,and statistical analysis was conducted on their interrelations.Results The zygomatic arch thickness was positively correlated with the length of superficial,middle and deep masseter muscles and the length of superficial and middle masseter belly(r superficial masseter length=0.624,r middle masseter length=0.787,r deep masseter length=0.423,r superficial masseter belly length=0.493,r middle masseter belly length=0.548).The width of the zygomatic arch was positively correlated with the lengths of the superficial and middle muscle layers and the middle muscle belly length(r superficial masseter length=0.527,r middle masseter length=0.521,r middle masseterbelly length=0.437).The angle of the mandibular angle was only negatively correlated with the middle muscle belly length(r=-0.422).The tuberosities of the superficial and middle masseter muscles were not affected by the corresponding muscle layers;However,the tuberosity of the deep masseter was negatively correlated with the length of the deep muscle and the length of the deep tendon(r deep masseter length=-0.543,r deep masseter tendon length=-0.443).Conclusion In the masseter muscle layers of Chinese individuals,the superficial and middle layers have the most significant impact on the bony structures structures of the lateral facial region.These findings are of guiding significance for the remodeling of structures in the lateral facial region.

Objective To analyze the developmental trends and research hotspots of anoikis in cancer research from 2005 to 2024.Methods Relevant literature was retrieved from the Web of Sci-ence Core Collection.Visualization tools including CiteSpace,VOSviewer and SCImago Graphica were employed to analyze publication volume,countries,institutions,authors,journals,keywords and other bibliometric indicators.Results A total of 2,252 articles were included in this study,showing an overall upward trend in publication volume,with a notable increase after 2012.China and the United States ranked highest in terms of publication volume and citation frequency.Representative institutions included Shanghai Jiao Tong University,Chulalongkorn University and MD Anderson Cancer Center,while a representative scholar was CHANVORACHOTE Pithi.The core journal was Oncogene.Keyword and co-citation analyses revealed that research focused on genetic characteristics,cancer treatment,prognostic prediction and metabolic reprogramming,with core terms including"ex-pression""metastasis"and"anoikis".Conclusion Research interest in the field of anoikis contin-ues to rise,with future directions focusing on drug resistance mechanisms,the tumor microenvironment,immunotherapy,signaling pathways and epithelial-mesenchymal transition(EMT).

Objective To explore relationship between glucose metabolism and neonatal weight in high-risk gestational diabetes melli-tus(GDM).Method A retrospective study was conducted on 779 pregnant women who underwent prenatal examinations at Tongzhou Maternity and Child Health Care Hospital in Beijing from March to June 2022.The data on pre-pregnancy weight,mid-and late-preg-nancy glycated albumin(GA)and glycated hemoglobin(HbA1c),pre-delivery weight,gestational weight gain,and neonatal birth weight were collected.A GDM risk assessment model was established using multivariate logistic regression to classify pregnant women into high-risk and low-risk groups for GDM,followed by separate management strategies.Regression discontinuity(RD)analysis was applied to evaluate the relationship between gestational glucose metabolism status and neonatal birth weight.Results Among the 779 pregnant women,the overall incidence of macrosomia was 7.32％.The high-risk GDM group exhibited significantly higher pre-pregnan-cy weight,late-pregnancy HbA1c,and GA levels compared to the low-risk group(all P＜0.001).Neonatal birth weight in the high-risk group was significantly higher than that in the low-risk group(P＜0.05),with a significantly increased macrosomia incidence(13.55％vs 5.77％,P＜0.05).RD analysis revealed a jump reduction of 199.59 g(P=0.029)in neonatal birth weight at the risk score thresh-old.Conclusion Lifestyle glucose metabolism management in high-risk GDM pregnant women may effectively reduce neonatal birth weight,mitigated the trend of excessive gestational weight gain,and improved late-pregnancy HbA1c and GA levels,providing evi-dence-based support for maternal and child health services.

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.

Objective:The relationship between benign prostatic hyperplasia(BPH)and the oxidative balance score(OBS)will be discussed in this study.Methods:The clinical data on 16 dimensions of diet and 4 dimensions of lifestyle from the National Health and Nutrition Examination Survey(NHANES)from 2001 to 2008 were used to calculate OBS.We considered BPH as the out-come and investigated the linear and nonlinear relationships between the two.Additionally,subgroup analyses and interaction tests were conducted as well.Furthermore,the methods of machine learning including XGBoost,support vector machine(SVM)and naive Bayes(NB)were used to establish a predictive model for BPH.Results:Higher OBS was consistently associated with an increased preva-lence of BPH,with Restricted Cubic Splines highlighting a significant positive nonlinear association(P=0.015).Subgroup analyses revealed differences and interactive relationships based on alcohol consumption.Among the seven machine learning models that we in-cluded the OBS score in,the XGBoost model emerged as the best,with an AUC value of 0.769.Conclusion:There is a significant association between OBS and the prevalence of BPH in the American population,which provides a valuable insight for further diagnosis and research of the disease.

Objective To compare the gut fungal composition between gout patients and healthy individuals through high-throughput sequencing of ribosomal DNA internal transcribed spacer 1(ITS1).Methods Gout patients and healthy volunteers who visited our hospital from January 2023 to December 2024 were enrolled in this study.Then based on established medical guidelines,the gout patients were categorized into 3 groups:Group H(asymptomatic hyperuricemia,n=14),Group G(acute gouty arthritis,n=14),and Group I(intercritical period of gouty arthritis,n=15),and the healthy individuals were assigned into Group N(n=9).Fecal samples were collected from all the participants to undergo ITS1 sequencing analysis.The differences in diversity and composition of gut mycobiome,and FunGuild-derived fungal functions and nutritional status were compared among the 4 groups,and the correlation between the gut mycobiome and clinical indicators was analyzed.Results There were no significant differences in baseline features such as gender,age,glomerular filtration rate(GFR),and levels of serum creatinine(SCr)and serum urea among Group N and other gout groups,but obvious differences were observed in body mass index(BMI),erythrocyte sedimentation rate,and levels of C-reactive protein(CRP),serum uric acid(SUA),and IL-1β and IL-6(P<0.05).In terms of gut fungal diversity,ITS1 analysis showed there were no statistical differences in α-diversity or the principal coordinate analysis(PCoA)of β-diversity among the groups.However,as gout progressed,significant changes were observed in β-diversity indices,indicating a shift in the gut fungal community composition with disease advancement(P<0.05).The phyla Ascomycota,Basidiomycota,and Mucoromycotina were the dominant fungal phyla in all groups.Compared with the other 3 gout groups,the abundance of Pichia was significantly increased in Group N(P<0.05),that of Saccharomyces was in Group H(P<0.05),and that of Starmerella was in Group G(P<0.05).Correlation analysis between the gut mycobiome and clinical indices indicated that the relative abundance of Starmerella was significantly positively correlated with IL-1β(P<0.01)and IL-6(P<0.05).The relative abundance of Pichia was significantly positively correlated with IL-1β and IL-6 levels(P<0.05),and negatively correlated with serum urea level(P<0.05),and the relative abundance of Saccharomyces was negatively correlated with IL-1β and IL-6 levels(P<0.05).Conclusion There exist significant alterations in both the diversity and composition of gut fungi among patients with gout at various stages.Notably,the fluctuations in the relative abundance of Starmerella,Pichia and Saccharomyces appear to correlate with key clinical indicators.

Objective： To investigate the relationship between the lipid metabolism-related gene sterol carrier protein 2(SCP2) and prostate cancer (PCa) from a multi-omics perspective using single-cell transcriptomes combined with Mendelian randomization. Methods： Single-cell transcriptome data of benign and malignant prostate tissues were obtained from GSE120716, GSE157703 and GSE141445 datasets, respectively. Integration, quality control and annotation were performed on the data to categorize the epithelial cells into high and low SCP2 expression groups, followed by further differential and trajectory analyses. Single nucleotide polymorphism (SNP) data for SCP2 expression quantitative trait loci (eQTL) were subsequently downloaded from Genotype-Tissue Expression (GTEx) and investigated from the PCa Society Cancer-Related Genomic Alteration Panel for the Investigation of Cancer-Related Alterations (PRACTICAL) to obtain PCa outcome data for Mendelian randomization analysis to validate the causal relationship between SCP2 and PCa. Results： High SCP2-expressing epithelial cells had higher energy metabolism and proliferation capacity with low immunotherapy response and metastatic tendency. Trajectory analysis showed that epithelial cells with high SCP2 expression may have a higher degree of malignancy, and SCP2 may be a key marker gene for differentiation of malignant epithelial cells in the prostate. Further Mendelian randomization results showed a significant causal relationship between SCP2 and PCa development (OR=1.045, 95% CI: 1.010 －1.083, P=0.011). Conclusion： By combining single-cell transcriptome and Mendelian randomization, the role of the lipid metabolism-related gene SCP2 in PCa development has been confirmed, and new targets and therapeutic directions for PCa treatment have been provided.
Humans ; Prostatic Neoplasms/genetics* ; Male ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Single-Cell Analysis ; Sequence Analysis, RNA ; Carrier Proteins/genetics* ; Transcriptome ; Lipid Metabolism

BACKGROUND: Prolonged occupational noise exposure poses potential health risks, but its impact on mitochondrial DNA (mtDNA) damage and methylation patterns remains unclear. METHOD: We recruited 306 factory workers, using average binaural high-frequency hearing thresholds from pure-tone audiometry to assess noise exposure. MtDNA damage was evaluated through mitochondrial DNA copy number (mtDNAcn) and lesion rate, and mtDNA methylation changes were identified via pyrophosphate sequencing. RESULTS: There was a reduction in MT-RNR1 methylation of 4.52% (95% CI: -7.43% to -1.62%) among workers with abnormal hearing, whereas changes in the D-loop region were not statistically significant (β = -2.06%, 95% CI: -4.44% to 0.31%). MtDNAcn showed a negative association with MT-RNR1 methylation (β = -0.95, 95% CI: -1.23 to -0.66), while no significant link was found with D-loop methylation (β = -0.05, 95% CI: -0.58 to 0.48). Mediation analysis indicated a significant increase in mtDNAcn by 10.75 units (95% CI: 3.00 to 21.26) in those with abnormal hearing, with MT-RNR1 methylation mediating 35.9% of this effect. CONCLUSIONS These findings suggest that occupational noise exposure may influence compensatory increases in mtDNA content through altered MT-RNR1 methylation.
Humans ; DNA, Mitochondrial ; DNA Methylation ; Male ; Adult ; Noise, Occupational/adverse effects* ; Middle Aged ; Occupational Exposure/adverse effects* ; Biomarkers/blood* ; Female