ObjectiveTo explore the role of the histone deacetylase Sirtuin-1 （SIRT1）/p53 signaling pathway in promoting apoptosis of non-small cell lung cancer cells （NSCLC） induced by the co-stimulatory molecule B7 homolog 3 （B7-H3）. MethodsThe GEPIA 2 platform was used for survival analysis of NSCLC patients based on B7⁃H3 gene expression levels. The Gene Enrichment Analysis （GSEA） method was used to analyze the enrichment characteristics of B7⁃H3 molecules in the gene set of cell apoptosis. In the non-small cell lung cancer A549 cell line， B7⁃H3 was knocked down， and the protein expression levels of SIRT1 and p53 were detected by Western blot. B7⁃H3 was overexpressed in A549 cells and the apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. Overexpression of B7⁃H3 and knockdown of SIRT1 were performed in A549 cell line. The expression levels of p53 and apoptosis-related proteins B-cell lymphoma/leukemia-2 （Bcl-2） and Bcl-2-associated X protein （Bax） were detected respectively by Western blot. Cell apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. ResultsThe overall survival of the B7-H3 high-expression group was significantly lower than that of the low-expression group （P<0.01）. B7-H3 was significantly enriched in the cell apoptosis signaling pathway and the p53 signaling pathway （P<0.05）. Compared with the control group， the expression of SIRT1 was significantly downregulated， and p53 was significantly upregulated in the B7⁃H3 knockdown group （both P<0.001）. Overexpression of B7-H3 significantly up-regulated SIRT1 protein expression （P<0.05）， down-regulated p53 expression （P<0.01）， and markedly increased the Bcl-2/Bax ratio of apoptosis-related proteins （P<0.001）. The results of Annexin V/PI double staining showed that the apoptosis rate of A549 cells with overexpressed B7⁃H3 decreased （the apoptosis rate of the control group was 26.72%±4.13%， while that of the B7⁃H3 overexpression group was 13.87%±0.82%； P<0.01）. In B7-H3-overexpressing cell lines， SIRT1 knockdown significantly reversed apoptosis （P<0.05）， up-regulated p53 protein expression （P<0.001）， and markedly reduced the Bcl-2/Bax ratio （P<0.001）. ConclusionB7-H3 molecule inhibits the apoptosis of non-small cell lung cancer cells via the SIRT1/p53 signaling pathway.

During habitation on low-Earth-orbit (LEO) space stations, astronauts are exposed to a combination of orbital microgravity, space radiation, an enclosed and artificially controlled cabin environment, altered sleep-wake rhythms, and sustained operational and psychosocial demands. These factors can modify sensorimotor inputs, body-fluid distribution, arousal state, and task-related neural processing, thereby affecting brain function and behavior. Because evidence from real spaceflight remains limited by small samples, heterogeneous mission durations, and different measurement time points, this review integrates findings from real human spaceflight with relevant ground-based analog studies while treating real orbital studies as the primary source of evidence. We focus on electroencephalography (EEG) and event-related potentials (ERPs), structural and functional neuroimaging, and sensorimotor and cognitive outcomes, with particular attention to the direction, anatomical distribution, temporal course, and possible physiological significance of the reported changes. EEG studies indicate that long-duration spaceflight is associated with increased resting-state beta activity, particularly in sensorimotor and frontotemporal regions, together with state-dependent alterations in beta-band functional connectivity. In contrast, alpha source power and functional connectivity associated with the default mode network are reduced during long-duration missions, and some of these effects may persist into the early postflight period. Task-related electrophysiological findings further suggest that sustained mental workload can weaken frontocentral theta-temporoparietal gamma phase-amplitude coupling, whereas in-flight decision-making is accompanied by reduced P300 amplitude and reorganization of feedback-related potentials. Short-duration missions, however, have shown relative preservation of posterior dominant rhythms and some ERP measures, indicating that mission duration, recording state, and task demands substantially influence the observed electrophysiological phenotype. Neuroimaging provides complementary evidence at structural and network levels. Long-duration spaceflight has been associated with upward brain displacement, ventricular and cerebrospinal fluid expansion, regional gray- and white-matter remodeling, and alterations in white-matter structural connectivity. Functional magnetic resonance imaging (fMRI) studies further indicate reorganization of vestibular-sensorimotor, visual, and default mode networks. Some network changes recover after return to Earth, whereas others may remain detectable for months. Importantly, most MRI measurements are obtained after landing rather than in orbit; therefore, postflight findings may reflect a mixture of in-flight adaptation, the rapid transition back to 1 g, and subsequent readaptation rather than a single spaceflight effect. Behavioral evidence is most consistent for sensorimotor function. Early after return, astronauts frequently show impaired postural control, gait, spatial orientation, and coordination, consistent with reweighting among vestibular, visual, and proprioceptive information. By comparison, simple cognition and some critical operational tasks are often preserved. More subtle or high-load processes-including sustained attention, feedback evaluation, temporal processing, error monitoring, and metacognitive calibration may be more sensitive than global cognitive performance. This dissociation between neural change and preserved behavior suggests that altered brain activity should not automatically be interpreted as functional deterioration. Integrating the available modalities, we propose that LEO space-station habitation is better characterized by system-specific and stage-dependent neural adaptation than by a generalized increase or decline in brain function. The most coherent cross-modal pattern involves sensorimotor reorganization: reduced gravitational reference and weight-bearing feedback under microgravity may drive reweighting of vestibular, visual, and proprioceptive inputs, accompanied by changes in beta activity and vestibular-sensorimotor networks and followed by transient postflight sensorimotor deficits. A second major process involves fluid-related structural remodeling, in which cephalad fluid shifts and altered hydrostatic gradients may contribute to changes in cerebrospinal fluid spaces, ventricular volume, and brain tissue configuration. Resting-state and cognitive electrophysiological changes likely represent additional adjustments in network regulation and resource allocation, but their functional interpretation remains more dependent on sleep, workload, recording conditions, and individual differences. Future studies should move beyond isolated pre-post comparisons and group averages toward standardized longitudinal designs spanning preflight, multiple in-flight time points, and postflight recovery. Synchronized assessment of brain function, behavior, sleep, and key environmental parameters should be used to characterize individual adaptation trajectories and determine which neural changes reflect successful compensation, which predict delayed recovery, and which have genuine value for brain-health risk prediction and individualized countermeasures.

ObjectiveTo characterize the changes of metabolites of Blumea balsamifera in the process of sweating by non-targeted metabolomics， and to investigate the influence of sweating processing on the constituents of B. balsamifera. MethodsUltra performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS） metabolomics was used to identify the metabolites in no sweating group（F1）， sweating 2 d group（F2） and sweating 4 d group（F3）， the differences of metabolites between the groups were compared by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， and differential metabolites were screened according to the variable importance in the projection（VIP） value>1 and P<0.05， and the pathway enrichment of the differential metabolites was analyzed by Kyoto Encyclopedia of Genes and Genomes（KEGG）. ResultsThe results of PCA and OPLS-DA showed a clear distinction between the three groups of samples， indicating significant differences in the compositions of the three groups of samples. A total of 433 differential metabolites were screened between the F1 and F2， with 154 up-regulated and 279 down-regulated， the significant up-regulated metabolites were tangeritin， 5-O-demethylnobiletin and so on， while the metabolites with significant down-regulation included alternariol， fortunellin， etc. A total of 379 differential metabolites were screened between the F2 and F3， with 150 up-regulated and 229 down-regulated， the significant up-regulated metabolites were isoimperatorin， helianyl octanoate and so on， and the significant down-regulated metabolites were hovenoside I， goyasaponin Ⅲ， etc. KEGG pathway enrichment analysis showed that tyrosine metabolism， isoquinoline alkaloid biosynthesis， phenylalanine， tyrosine and tryptophan biosynthesis， tryptophan metabolism， valine， leucine and isoleucine biosynthesis， pantothenate and coenzyme A biosynthesis may be the key pathways affecting metabolite differences of B. balsamifera after sweating treatment. ConclusionSweating can reduce the content of endophytic mycotoxins in B. balsamifera and has a great impact on the synthesis and metabolic pathways of total flavonoids and auxin. This study can provide a reference for the process research on the sweating conditions of B. balsamifera.

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

Cancer stem cells (CSCs) are proposed to account for the progression, metastasis, and recurrence of diverse malignancies. However, the disorganized vasculars in tumors hinder the accumulation and penetration of nanomedicines, posing a challenge in eliminating CSCs located distantly from blood vessels. Herein, a pair of twin-like small-sized nanoparticles, sunitinib (St)-loaded ROS responsive micelles (RM@St) and salinomycin (SAL)-loaded GSH responsive micelles (GM@SAL), are developed to normalize disordered tumor vessels and eradicate CSCs. RM@St releases sunitinib in response to the abundant ROS in the tumor extracellular microenvironment for tumor vessel normalization, which improved intratumor accumulation and homogeneous distribution of small-sized GM@SAL. Sequentially, GM@SAL effectively accesses CSCs and achieves reduction-responsive drug release at high GSH concentrations within CSCs. More importantly, RM@St significantly extends the window of vessel normalization and enhances vessel integrity compared to free sunitinib, thus further amplifying the anti-tumor effect of GM@SAL. The combination therapy of RM@St plus GM@SAL produces considerable depression of tumor growth, drastically reducing CSCs fractions to 5.6% and resulting in 78.4% inhibition of lung metastasis. This study offers novel insights into rational nanomedicines designed for superior therapeutic effects by vascular normalization and anti-CSCs therapy.

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Objective To evaluate the diagnostic value of intestinal ultrasound (IUS) for organic lesions in the intestines of patients with chronic abdominal pain or diarrhea. Methods The IUS signs in 263 patients with chronic abdominal pain or diarrhea were retrospectively analyzed.With the endoscopic examination results as the gold standard,comparison was performed for the IUS signs between the groups with positive and negative endoscopic results,as well as between the inflammatory bowel disease group and the non-specific intestinal inflammation group of positive cases.Furthermore,the detection rates of IUS in different intestinal segments were analyzed to evaluate the accuracy of IUS in the diagnosis and localization of intestinal lesions. Results Among the 263 patients,194 (73.8%) and 69 (26.2%) patients were in the groups with positive and negative endoscopic results,respectively.The diagnosis sensitivity,specificity,and accuracy of IUS were 82.0%,71.0%,and 79.1%,respectively.The proportions of positive IUS signs in the group with positive endoscopic results were higher than that in the group with negative endoscopic results (all P<0.001).The proportions of positive IUS signs in the inflammatory bowel disease group were higher than those in the non-specific bowel inflammation group (all P<0.001).When the lesion was located in the ileum,ileocecal region,and colon,IUS demonstrated good consistency with endoscopic results in locating the lesion (kappa=0.642,0.686,and 0.601,respectively),with sensitivity and specificity of 82.7% (95%CI=75.4%-88.6%) and 81.5% (95%CI=73.5%-87.9%),73.7% (95%CI=62.3%-83.1%) and 93.0% (95%CI=88.4%-96.2%),and 68.9% (95%CI=58.3%-78.2%) and 89.6% (95%CI=84.1%-93.7%),respectively. Conclusions IUS can be used for screening the patients with chronic abdominal pain or diarrhea to detect organic lesions in the intestines. Moreover,it can effectively locate the affected intestinal segment,which is helpful for the monitoring and follow-up of intestinal diseases.
Humans ; Diarrhea/diagnostic imaging* ; Female ; Male ; Abdominal Pain/diagnostic imaging* ; Middle Aged ; Adult ; Ultrasonography ; Retrospective Studies ; Aged ; Young Adult ; Intestines/diagnostic imaging* ; Adolescent ; Chronic Disease ; Sensitivity and Specificity ; Aged, 80 and over

This study was aimed at understanding the relationships among the drug resistance and genome characteristics of group A Streptococcus in Jiangsu Province.A total of 149 group A Streptococcus strains were collected from hospitals between 2016 and 2023.Thirteen antimicrobial minimal inhibitory concentrations were detected with the micro-dilution broth method.The GAS strains were typed with emm genotyping analysis and whole genome sequencing,to determine the carriage rates of drug resistance genes and the evolutionary relationships among strains.The resistance rates of 149 GAS strains to erythromy-cin,tetracycline,and clindamycin exceeded 90％,whereas the strains showed sensitivity to 8 different antibiotics,including penicillin.Notably,the resistance rates to erythromycin,tetracycline,and clindamycin consistently increased over time.All strains were classified into 9 emm types,among which emm12 accounted for the highest proportion(77/149;51.68％).Signifi-cant statistical differences were observed among emm types,in terms of the drug resistance rate,number of resistant species,and prevalence of drug resistance genes.Furthermore,SNP evolutionary tree analysis revealed 3 distinct clusters within the GAS strains:emm12,emm1,and other emm types.emm 12 and emm1 were the dominant GAS strains in Jiangsu Province.Most isolates were resistant to erythromycin,tetracycline,and clindamycin.Differences in phenotypes and genomic characteris-tics were observed among emm types.