In recent years, the rising prevalence of obesity and its associated metabolic syndromes has emerged as a critical global public health concern. Sustained weight loss exceeding 10% of total body weight has been shown to ameliorate obesity-related comorbidities, including type 2 diabetes mellitus, hypertension, and hepatic steatosis. Recently, the potential of brown adipose tissue (BAT) to improve metabolism has garnered significant attention. However, evidence regarding weight loss therapies that promote BAT activation remains limited in preclinical models and is even scarcer in clinical studies, partly due to the paucity of appropriate BAT assessment techniques. This review aims to explore the potential impact of various weight loss therapies on BAT, with the goal of providing novel insights and strategies for the treatment of obesity.

AIM: To investigate differences in ocular biological parameters and refractive status among children with unilateral congenital ptosis.METHODS:This was a retrospective cohort study enrolling patients with unilateral congenital ptosis in the Department of Ophthalmology, Xi'an Children's Hospital between August 2018 and March 2025, with the contralateral healthy eyes serving as the control group. All patients underwent a detailed ophthalmic examination to assess the degree of ptosis and evaluate refractive errors. Biometric measurements were performed using the IOL Master 700 biometer, including axial length(AL), central corneal thickness(CCT), anterior chamber depth(ACD), lens thickness(LT), and astigmatism(AST).RESULTS:A total of 100 eyes from 100 children(affected eye group)with unilateral congenital ptosis were enrolled, and their 100 contralateral normal eyes without ptosis were set as the control group(healthy eyes group). Among the subjects, there were 67 males(67%)and 33 females(33%), with a mean age of 6.43±2.47 y; 45 affected eyes were the right eye and 55 were the left eye. Among the 100 patients, mild, moderate, and severe ptosis accounted for 7%, 21%, and 72%, respectively. The incidence of amblyopia in patients with unilateral congenital ptosis was 32%, all of which occurred in the affected eye. Compared with the healthy eye group, K2(total)and K2(severe ptosis)in eyes with severe ptosis were significantly lower(P<0.05), indicating that the cornea in the ptotic eye was flatter. In patients with moderate ptosis, the affected eye had a significantly greater corneal thickness(CCT)compared to the healthy eye(P<0.05), indicating that the corneas of eyes with moderate ptosis were thicker. The incidence of against-the-rule and oblique astigmatism in the affected eye group(39%)was significantly higher than that in the healthy eye group(14%); there was a significant difference in the corneal astigmatism axis between the affected and healthy eye groups(P<0.01). There were no differences in refractive status or biological parameters such as AL, K1, AST, ACD, and LT between the affected and healthy eyes.CONCLUSION:Congenital ptosis can affect refractive errors, lead to oblique and against-the-rule astigmatism, increase the prevalence of amblyopia, and also result in corneal thickening and flattening. However, it has minimal effects on AL, LT, and ACD.

Bacterial extracellular vesicles (BEVs) are nanoscale, lipid bilayer-enclosed vesicles that are actively or passively released by bacteria. They carry diverse bioactive cargos, including proteins, nucleic acids, and lipids, and mediate information exchange between microbial communities and hosts. Increasing evidence indicates that BEVs play important roles in the initiation and progression of dental caries and periodontitis. In dental caries, BEVs derived from cariogenic bacteria such as Streptococcus mutans can promote biofilm formation and maturation, enhance the acidic microenvironment, and exacerbate demineralization of dental hard tissues. In periodontitis, BEVs released by key periodontal pathogens, including Porphyromonas gingivalis and Fusobacterium nucleatum, may disrupt the mucosal barrier, trigger inflammatory responses, and activate bone resorption-related pathways, thereby promoting periodontal tissue destruction. Owing to their detectability, BEVs in oral samples such as saliva, dental plaque, and gingival crevicular fluid show promise as diagnostic biomarkers and also provide new therapeutic opportunities for targeted interventions. In addition, emerging studies suggest that oral BEVs may contribute to distal inflammatory amplification through an “oral-systemic axis”; therefore, while focusing on the local pathogenic mechanisms of BEVs in dental caries and periodontitis, this review also briefly outlines their potential systemic implications as an extension. Overall, BEVs may offer novel mechanistic insights and translational directions to support precise prevention and management of dental caries and periodontitis.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Microplastics and nanoplastics (MPs/NPs) are ubiquitous environmental pollutants that act as endocrine-disrupting chemicals (EDCs), raising significant concerns about their impact on human health. Research highlights the hazardous effects of MPs/NPs on both male and female reproductive systems, influencing germ cells, embryo development, and progeny. Additionally, studies show that MPs/NPs affect the gene expression of anabolic steroid hormones in vitro and in vivo, inducing reproductive toxicity through mechanisms such as oxidative stress and inflammation. Considering these adverse effects, identifying natural compounds that can mitigate the toxicity of MPs/NPs is increasingly important. Plants offer a wealth of antioxidants and anti-inflammatory compounds that can counteract these harmful effects. Among these, anthocyanins, natural colorants responsible for the vibrant hues of fruits and flowers, exhibit a wide range of biological activities, including antioxidant, anti-inflammatory, and anti-neoplastic properties. Moreover, anthocyanins can modulate sex hormone levels and alleviate reproductive toxicity. Cyanidin-3-glucoside (C3G), one of the most extensively studied anthocyanins, shows promise in reducing reproductive toxicity, particularly in females, and in protecting male reproductive organs, including the testis and epididymis. This protective effect is believed to result from its interaction with steroid receptors, specifically the androgen and estrogen receptors (ERs). These findings highlight the need to explore the mechanisms by which anthocyanins mitigate the reproductive toxicity caused by MPs/NPs. This review provides novel insights into how natural compounds can be leveraged to lessen the impact of environmental contaminants on human health, especially concerning reproductive health.

Negative logarithm of the acid dissociation constant (pK _a) significantly influences the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of molecules and is a crucial indicator in drug research. Given the rapid and accurate characteristics of computational methods, their role in predicting drug properties is increasingly important. Although many pK _a prediction models currently exist, they often focus on enhancing model precision while neglecting interpretability. In this study, we present GraFpK _a, a pK _a prediction model using graph neural networks (GNNs) and molecular fingerprints. The results show that our acidic and basic models achieved mean absolute errors (MAEs) of 0.621 and 0.402, respectively, on the test set, demonstrating good predictive performance. Notably, to improve interpretability, GraFpK _a also incorporates Integrated Gradients (IGs), providing a clearer visual description of the atoms significantly affecting the pK _a values. The high reliability and interpretability of GraFpK _a ensure accurate pK _a predictions while also facilitating a deeper understanding of the relationship between molecular structure and pK _a values, making it a valuable tool in the field of pK _a prediction.

Approximately 10% of the global adult population has diabetes, with accumulating evidence linking suboptimal vitamin D levels to an increased risk of type 2 diabetes and its complications. Current clinical studies suggest that vitamin D supplementation may enhance insulin sensitivity and improve glycemic control, prompting significant interest in its potential as a therapeutic intervention. However, further high-quality, large-scale randomized controlled trials are required to validate its efficacy in glucose metabolism regulation and clarify the underlying molecular mechanisms. These investigations will provide critical evidence to inform precision medicine approaches for diabetes prevention and management.

ObjectiveTo explore the differences in the accumulation of secondary metabolites of Dendrobium nobile cultivated on epiphytic stones and trees， so as to elucidate the scientific connotation of "only those that grow on stones has superior quality"， and provide a direction for the cultivation and quality evaluation of D. nobile. MethodsUltra-performance liquid chromatography-triple quadrupole/linear ion trap mass spectrometry（UPLC-QTRAP-MS/MS）-based widely targeted metabolomics was used to detect the metabolites of D. nobile cultivated on epiphytic stones and trees. And the combination of principal component analysis（PCA）， hierarchical cluster analysis（HCA）， and orthogonal partial least squares-discriminant analysis（OPLS-DA） was performed for multivariate statistical analysis of metabolites. Differential metabolites were screened by variable importance in the projection（VIP） value≥1 and log₂fold change（FC）≥1 or ≤-1， and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis was conducted. ResultsA total of 1 267 metabolites were identified in the stems of D. nobile from the two cultivation modes， dominated by flavonoids（292）， phenolic acids（284）， and alkaloids（189）. Through OPLS-DA screening， 473 differential metabolites were obtained. Compared to epiphytic tree-cultivated D. nobile， epiphytic stone-cultivated D. nobile exhibited upregulation of flavonoids， phenolic acids， alkaloids， lignans and coumarins， while quinones and terpenoids were down-regulated. The differential metabolites mainly included flavonoid glycosides and alkaloids， and these differential metabolites significantly contributed to characterizing the two cultivation patterns. KEGG enrichment analysis revealed significant enrichment in pathways of flavone and flavonol biosynthesis， flavonoid biosynthesis， tyrosine metabolism， and phenylalanine metabolism in epiphytic stone-cultivated D. nobile. ConclusionEpiphytic stone cultivation is beneficial for the accumulation of phenolic acids， flavonoids， and alkaloids in D. nobile， indicating that the "only those that grow on stones has superior quality" documented in the materia medica has certain scientific basis， and the findings also provide a reference for quality evaluation and discrimination research between epiphytic stone and tree cultivated D. nobile.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.