OBJECTIVE To study the improvement effect and mechanism of Dendrobium officinale on skin damage in mice with xeroderma. METHODS The mice were randomly divided into control group， model group， and D. officinale group， with 5 mice in each group. Except for the control group （which only underwent shaving treatment）， the mice in all other groups were induced to develop a xeroderma model using an acetone-ether mixture for five consecutive days. The mice in D. officinale group were treated with 200 μL of D. officinale suspension （0.2 mg/mL） two hours after the first modeling each day. Mice in the control group and the model group were applied with an equal volume of pure water； once a day， until the end of the modeling process. After last medication， skin lesions and pathological morphology of the mice were observed. Immunofluorescence was used to detect the expressions of Filaggrin， Loricrin and Ki67 proteins in skin tissue of the mice. The core pathways through which D. officinale improves skin damage in xeroderma were screened using 16S rRNA sequencing combined with gene ontology and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses， and subsequent validation was conducted. RESULTS Compared with the control group， the mice in the model group exhibited obvious scratching behavior， with a large amount of scale on the skin， excessive epidermal keratinization， and thickened stratum spinosum. The skin scale score， epidermal thickness， and the expression levels of Ki67， Filaggrin， and Loricrin proteins in the skin tissue were significantly increased/elevated （ P ＜0.05）. Compared with model group， the mice in the D. officinale group exhibited reduced scratching behavior and scaling， along with a mitigated degree of skin keratinization. The aforementioned quantitative indicators were significantly decreased/reduced （ P ＜0.05）. The results of core pathway screening revealed that the KEGG pathways involving differentially expressed genes included signaling pathways such as interleukin-17 （IL-17） and tumor necrosis factor （TNF）. Further validation experim ents found that after intervention with D. officinale ， mRNA expression of downstream effector molecules CCN1， Hbegf， Tnfrsf12a， and Thbs1 genes in skin tissues were all significantly reduced （ P ＜0.05）. CONCLUSIONS D. officinale can repair skin damage in mice with xeroderma， and its mechanism of action is related to restoring the balance of proliferation and differentiation in keratinocytes and down-regulating the mRNA expressions of CCN1， Hbegf， Tnfrsf12a， and Thbs1.

Objective To explore factors associated with early postoperative hormonal remission in patients with prolactinoma and to develop prediction models based on clinical and radiological features. Methods Data from 107 patients with prolactinoma who underwent transsphenoidal surgery at The First People’s Hospital of Huai’an, Nanjing Medical University between January 2020 and December 2024 was collected, included general clinical characteristics, preoperative laboratory indicators, and imaging features. Based on whether early postoperative prolactin (PRL) levels normalized, patients were divided into a remission group (n=76) and a non-remission group (n=31). Univariate logistic regression was used for preliminary evaluation of candidate variables, followed by LASSO regression for feature selection. Multiple machine learning models were constructed, including logistic regression, random forest, support vector machine, K-nearest neighbors, naive Bayes, decision tree, neural network, and gradient boosting decision tree (GBDT). All models were trained and evaluated using ten-fold cross-validation, with comprehensive assessment of model performance based on the area under the ROC curve (AUC), accuracy, sensitivity, specificity, precision, and F1 score. Results The maximum diameter of tumors in the non remission group was larger than that in the remission group (P=0.019), and the incidence of tumor stroke and preoperative PRL levels were significantly higher than those in the remission group (P＜0.001). Univariate analysis showed that sex, maximum tumor diameter, tumor stroke, and preoperative PRL levels were influencing factors for early postoperative hormone response in patients with prolactinoma (P＜0.05). The comparison results of machine learning models show that the neural network model performs the best (AUC=0.921) and has good clinical application value, followed by the GBDT model (AUC=0.893) and the support vector machine model (AUC=0.884). Other models also show certain predictive ability. Conclusions Sex, preoperative PRL levels, maximum tumor diameter, Hounsfield unit value, and tumor stroke are important factors affecting early hormone response after prolactinoma surgery. The machine learning model constructed based on the above variables has good predictive performance, and performs the best and has good clinical application value.

Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

With the advancement of science and technology and the rapid rise of artificial intelligence （AI） in recent years， intelligent and digitalized lifestyles have become the norm. AI-generated content （AIGC） has entered people’s lives and shown a blowout development trend. As a major output of AIGC， virtual digital humans have evolved from being “unbearable to look at” to being “indistinguishable” from real humans， exerting multiple impacts on people’s lives to a certain extent. AIGC and virtual digital humans can bring spiritual comfort to users， drive technological progress， and promote social stability. Meanwhile， they also face a series of risks， such as infringement behaviors of portraits， data privacy risks， and the alienation of human nature. This paper proposed solutions from various aspects， such as legal and technical supervision， embedding ethical standards into technology development， raising the market thresholds， and strengthening public publicity， striving to guide science and technology towards good.

To clarify the occurrence and distribution of broad bean wilt virus 2(BBWV2) on Rehmannia glutinosa, this study collected 87 R. glutinosa samples with typical symptoms of viral disease such as chlorosis and crumple from Wenxian county and Wuzhi county in Jiaozuo city, Henan province and Qiaocheng district in Bozhou city, Anhui province. The BBWV2 CP target band was amplified from 37 R. glutinosa samples by RT-PCR technology. The total detection rate reached 42.5%, among which 43.0% was detected in samples from Henan province. The detection rate in samples from Anhui province was 37.5%. 37 BBWV2 CP sequences were obtained by cloning and sequencing of BBWV2 positive samples(data has been submitted to GenBank, accession numbers: PP407959-PP407995), and the sequence analysis of these CP sequences with 91 other BBWV2 isolates in GenBank showed a high genetic diversity with a consistency rate of 70.8%-100%. Meanwhile, phylogenetic analysis showed that BBWV2 could be divided into three groups according to CP sequences, among which the BBWV2 in R. glutinosa isolates obtained in this study were all located in group 3. This study identified the differences in the occurrence, distribution, and genetic diversity of BBWV2 in R. glutinosa from Henan province and Anhui province and provided a theoretical basis for the prevention and control of BBWV2.
Rehmannia/virology* ; Phylogeny ; Plant Diseases/virology* ; China ; Molecular Sequence Data ; Fabavirus/classification*

Chronic heart failure(CHF)is the end-stage of a variety of heart diseases with complex pathogenesis,which may involve myocardial fibrosis,inflammation reaction and oxidative stress.Chinese materia medica has the characteristics of multiple pathways,levels,and targets in the treatment of CHF,with significant therapeutic effects.Based on the TCM theories,this article described the research progress of TCM and its effective components,TCM compounds and Chinese patent medicines in regulating TGF-β signaling pathway in the treatment of CHF,and summarized the mechanism and target of TCM regulating TGF-β pathway in the treatment of CHF,including inhibiting myocardial fibrosis,reducing inflammatory reaction and apoptosis,so as to provide a reference for the related research of Chinese materia medica in the treatment of CHF.

Objective:To establish a novel method for the early diagnosis of gastric cancer(GC)by screening for the microRNAs within tumor-specific exosomes in peripheral blood.Methods:The gene expression omnibus database was used to download the GSE148334 and GSE130654 datasets of GC exosomes,and differentially expressed RNAs were obtained according to logFC>1 or logFC<-1 and P<0.05.TargetScan and ENCORI databases were used to predict the regulatory relationship between mRNA,miRNA,and ln-cRNA,and Cytoscape software was used to construct a ceRNA network and identify hub genes for validation.A total of 27 patients with early-stage GC,25 healthy controls,and 25 patients with other types of cancer were enrolled,and the ultracentrifugation method was used to isolate exosomes in serum.RT-qPCR was performed for RNA in serum and exosome samples to analyze the expression of hub genes in each group.Results:Three hub genes were identified by the bioinformatics method,namely hsa-miR-105-5p,hsa-miR-219b-3p,and hsa-miR-889-3p,and RT-qPCR showed that the GC group had a significantly higher expression level of hsa-miR-219b-3p in serum and exosome samples than the healthy control group and the other cancer group(serum:4.050±2.697 vs.1.357±0.857/1.934±2.434,P<0.05;exosomes:2.525±1.518 vs.0.774±0.559/1.259±2.127,P<0.05),while there were no significant differences in the expression levels of hsa-miR-889-3p and hsa-miR-105-5p between the GC group and the other two groups(P>0.05).The re-ceiver operating characteristic(ROC)curve showed that hsa-miR-219b-3p in serum-derived exosomes had an area under the ROC curve of 0.896(95%CI=0.800-0.993),which was significantly better than the traditional tumor markers of carcinoembryonic antigen(P=0.015),CA19-9(P=0.021),and CA72-4(P=0.005),and there-fore,exosomal hsa-miR-219b-3p showed a better diagnostic efficacy in GC patients.Conclusion:This study shows that hsa-miR-219b-3p in serum-derived exosomes can be used as a potential marker for the early diagnosis of GC in clinical practice.

Liquiritigenin(LG)is a flavone of pharmacological importance,however,its application potential is severely limited due to its poor water solubility.LG could be disassociated slightly in water to form phenolate anion,therefore,better solubilization effect is expected by inclusion with cationic cyclodextrins(CCDs).In this work,four kinds of CCDs modified with amino groups at the primary face were synthesized,and their solid inclusion complexes with LG were successfully prepared by preparing their saturated solutions.The formation of the solid inclusion complexes was confirmed by scanning electron microscopy(SEM)and powder X-ray diffraction(PXRD),and their supramolecular binding behavior in solution was studied using multiple techniques.A 1∶1 inclusion stoichiometry of inclusion complexation was defined using Job plot by ultraviolet-visible(UV-vis)spectroscopy,and their binding stability constants(Ks)were determined as 2862.77,3494.70,6521.85 and 9599.48 L/mol using UV-vis spectroscopic titration,far more superior to that of nativeβ-CD(Ks=236.79 L/mol).This indicated that the amino side chains on CCDs could actively participate in the inclusion complexation through anion-cation interactions,significantly strengthening the host-guest binding between CCDs and LG.The inclusion modes were further elucidated based on proton and two-dimensional rotating-frame overhauser enhancement spectroscopy(2D-ROESY)nuclear magnetic resonance(NMR)experiments and molecular docking.Water solubility of LG was dramatically promoted up to 4.9 mg/mL,which was 70-fold higher than that of native LG.This study could draw inspiration for the binding and solubilization of phenols such as flavones by design of cationic macrocyclic molecules.

Haloacetic acids(HAAs),as a class of disinfection byproducts in drinking water,pose potential threats to human health,so the rapid,accurate and simultaneous detection of HAAs is of great significance for ensuring drinking water safety.Aiming at the challenges in HAAs detection and risk analysis,a novel method for synchronous rapid detection of seven kinds of HAAs in drinking water based on in situ derivatization technology and headspace gas chromatography was developed in this study.Through single-factor optimization experiments,the optimal reaction parameters for in situ derivatization were determined,including the type and dosage of salting-out agent,the acidity of reaction system,the amount of phase transfer catalyst,the dosage of derivatization agent,and the extraction solvent volume.Methodologic validation showed that the seven kinds of HAAs exhibited excellent linear relationships within their respective detection concentration ranges(R2>0.998).The method detection limits(MDLs)ranged from 0.04 to 0.33 μg/L,and the limits of quantification(LOQs)were between 0.14 and 1.34 μg/L.For real water samples,the average spiked recoveries of the seven HAAs ranged from 90.9%to 107.7%,with relative standard deviation(RSDs)between 1.55%and 6.49%,and the HAAs contents in all tested samples were below the limits specified in the Standards for Drinking Water Quality(GB 5749-2022)of China.This method was featured with simple operation,fast analysis speed,high sensitivity,and good accuracy,providing an efficient and reliable technical support for routine monitoring of HAAs contaminants in drinking water and showing promising application value for widespread promotion.