Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

Objective To assess the stability of the molluscicidal activity of the fermentation broth supernatant of Bacillus indicus F19, so as to provide insights into development of novel molluscicides derived from this isolate. Methods Healthy Oncomelania hupensis snails free from Schistosoma japonicum infections and acclimated in the laboratory for 7 days were selected. The fermentation broth supernatant of B. indicus F19 was prepared. For each treatment condition, four experimental groups and one control group were established, with 10 mL of the fermentation broth supernatant each group. O. hupensis snails were exposed to different pH values (3, 6, 9 and 12), temperatures (40, 60, 80 °C and 100 °C), and ultraviolet (UV) exposure durations (1, 2, 3 h and 4 h). Then, the supernatant was diluted with dechlorinated water to concentrations of 50%, 10%, and 5% (v/v), and 10 mL of each dilution solution was added to three separate tubes, with an equal volume of dechlorinated water as a blank control. Twenty O. hupensis snails were transferred to each tube, immersed for 48 h and 72 h, and collected for viability assessment using the shell-tapping method. The mortality of O. hupensis snails was calculated and compared among dilution groups and the blank control group to evaluate the molluscicidal activity of the fermentation broth supernatant of B. indicus F19. Results There was a significant difference in the mortality of O. hupensis snails immersed in 5% fermentation broth supernatants of B. indicus F19 for 48 h at various pH levels (χ² = 11.556, P < 0.05), and the mortality reduced to 13.33% (8/60) in the experimental groups at a pH value of 12, which was significantly lower than in the blank control group [33.33% (20/60)] (χ² = 6.708, P < 0.05). There was a significant difference in the mortality of O. hupensis snails immersed in 10% fermentation broth supernatants of B. indicus F19 for 72 h at various pH levels (χ² = 31.691, P < 0.001), and the mortality reduced to 71.67% (43/60) and 65.00% (39/60) in the experimental group at pH values of 9 and 12, which was significantly lower than in the blank control group [100.00% (60/60)] (χ² = 8.571 and 12.110, both P values < 0.01). The mortality of O. hupensis snails both reduced to 23.33% (14/60) following immersion in 5% fermentation broth supernatants of B. indicus F19 heated in a water bath at 80 °C and 100 °C for 48 h, which was lower than that of unheated O. hupensis snails [33.33% (20/60)] and snails heated in a water bath at 40 °C [35.00% (21/60)] and 60 °C [33.33% (20/60)], and there was no significant difference in the mortality of O. hupensis snails among groups (χ² = 3.898, P > 0.05). The mortality of O. hupensis snails was 68.33% (41/60), 66.67% (40/60), 65.00% (39/60), and 68.33% (41/60) following immersion in fermentation broth supernatants heated in a water bath at 40, 60, 80 °C and 100 °C for 72 h, which was all lower than that of snails in the control group [71.70% (43/60)]; however, there was no significant difference seen in the snail mortality among groups (χ² = 0.674, P > 0.05). The mortality of O. hupensis snails was 73.33% (44/60), 71.67% (43/60), 71.67% (43/60), and 75.00% (45/60) following 48 h immersion in 10% fermentation broth supernatants of B. indicus F19 irradiated by UV for 1, 2, 3 h and 4 h, 33.33% (20/60), 31.67% (19/60), 35.00% (21/60), and 33.33% (20/60) following 48 h immersion in 10% fermentation broth supernatants of B. indicus F19 irradiated by UV for 1, 2, 3 h and 4 h, and 71.67% (43/60) and 33.33% (20/60) following 48 h immersion in 10% fermentation broth supernatants of B. indicus F19 without UV irradiation, and no significant differences were found among groups (χ² = 0.229 and 0.150, both P values > 0.05). In addition, the mortality of O. hupensis snails was 76.67% (46/60), 71.67% (43/60), 70.00% (42/60), and 76.67% (46/60) following 72 h immersion in 5% fermentation broth supernatants of B. indicus F19 irradiated by UV for 1, 2, 3 h and 4 h, and 71.67% (43/60) in the control group, and there was no significant difference in the snail mortality among groups (χ² = 1.193, P > 0.05). Conclusion The molluscicidal action of the fermentation broth supernatants of B. indicus F19 is tolerant to high temperature and UV irradiation; however, the activity is attenuated under alkaline conditions.

The incidence rate of thyroid cancer has been rising in recent years. How to accurately distinguish malignant and benign thyroid nodules before surgery has become an important research direction. Ultrasound, as a non-invasive and fast examination method, has been widely used in clinical practice. Some typical ultrasound features, such as calcification, unclear boundaries, multiple lesions, low echo, and aspect ratio>1, can indicate the occurrence of thyroid cancer before surgery. Further analysis of these ultrasound features is still a focus of current research. This article will review the expression and distribution of calcification, a typical ultrasound feature, in benign and malignant thyroid nodules, in order to provide a basis for predicting the malignancy of thyroid nodules based on the characteristics of calcification under preoperative ultrasound.

Objective:To explore the research status and hotspots of TCM syndrome differentiation and treatment for headache using bibliometrics.Methods:Literature about TCM syndrome differentiation and treatment for headache was retrieved from CNKI, VIP, Wanfang Data, and CBM from the establishment of the databases to July 18, 2024. Excel 2023 was used to extract information such as publication time, author, unit and keywords of the literature. The authors' affiliation and keywords were preprocessed. VOSviewer software was used for keyword co-occurrence analysis and clustering analysis, and a keyword temporal overlay network was constructed.Results:Totally 1 513 articles were finally included. The journal with the largest number of publications was Henan Traditional Chinese Medicine. 346 authors were involved, initially forming research teams represented with Cao Kegang, Zhou Jianwei, Ni Jinjun, etc., mainly from Beijing University of Chinese Medicine, Henan University of Chinese Medicine, Shandong University of Traditional Chinese Medicine, etc.; the included literature included a total of 2 153 keywords, which the frequency of 5 931 times in total. The top three keywords in frequency were acupuncture and moxibustion therapy, clinical efficacy, and experience of famous doctors. Current research hotspots included data mining, network pharmacology, literature research, syndrome elements, medication law, venturing and bloodletting therapy, calcitonin gene-related peptide, classic prescriptions, nitric oxide, etc. Conclusions:At present, research on TCM syndrome differentiation and treatment for headache mainly focuses on three major sections: acupuncture, moxibustion and massage, clinical efficacy of TCM syndrome differentiation and treatment, and experience of famous doctors. Future research mainly focuses on data mining, medication law, network pharmacology, syndrome elements, and pathogenesis.

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

The applications of nuclear technology in industries, medicine, and other fields have increased the risk of radiation injury. Although some small-molecule drugs for radiation injury treatment have been applied clinically or are in preclinical research, their therapeutic efficacy is significantly limited by short circulation time and rapid metabolism. Nanomaterials have attracted growing attention with their outstanding bioactivity, chemical stability, tissue compatibility, and targeted delivery capabilities, therefore having the promise of offering the potential solutions to the limitations of current small-molecule drugs. However, their biosafety and clinical efficacy require further investigation. This review summarizes the design strategies and classifications of nanomaterials for radiation injury treatment, analyzes current research progress in their therapeutic applications, and introduces nanomaterial-based approaches for enhancing the elimination of internal radionuclide contamination. Finally, the challenges and future prospects of nanomaterials in radiation injury treatment are discussed. This review aims to provide researchers with a comprehensive understanding of recent advances in nanomaterial-based radiation injury therapeutics, thereby promoting further development in this field.

OBJECTIVE To construct novel central nervous system(CNS)-targeted lipid nanoparti-cles for the treatment of organophosphorus-induced brain injury in mice.METHODS(1)Preparation,screening,and characterization of lipid nanoparticles.① Lipid nanoreactivators were prepared using the thin-film hydration method,with asoxime(HI-6)as the therapeutic drug and lipid carriers composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine(POPS),1,2-dipalmitoyl-sn-glycero-3-phospho-choline(DPPC),and cholesterol(CHOL)(PDC)at varying molar ratios(1∶6∶3,3∶4∶3,5∶2∶3 and 7∶0∶3)(HI-6@PDC 1∶6∶3,3∶4∶3,5∶2∶3 and 7∶0∶3).② FLU-labeled lipid nanocarriers(FLU@PDC 1∶6∶3,3∶4∶3,5∶2∶3,and 7∶0∶3)were prepared and physically mixed with phospholipase A2(PLA2)solution(at the final PLA2 concentration of 10 kU·L-1)to obtain FLU@PDC+PLA2.Male KM mice were randomly divided into normal control(PBS),FLU,and FLU@PDC+PLA2(1∶6∶3,3∶4∶3,5∶2∶3,and 7∶0∶3)groups(n=7 per group).After intravenous(iv)administration(FLU dose:1 mg·kg-1,carrier dose:80 mg·kg-1),brain tissues were collected at 1 h,homogenized,centrifuged,and analyzed via fluorescence spectrophotom-etry to screen the optimal CNS-targeted lipid carrier composition.③ The morphology of HI-6@PDC 5∶2∶3 was characterized by transmission electron microscope(TEM).The particle size,polydispersity index(PDI),and zeta potential of HI-6@PDC 5∶2∶3 were measured using a Zeta potential and particle size analyzer.Encapsulation efficiency and loading efficiency of HI-6@PDC 5∶2∶3 were determined using an ultrafiltration centrifugation method combined with high-performance liquid chromatography(HPLC).In vitro release kinetics of HI-6@PDC 5∶2∶3 and HI-6@PDC+PLA2 5∶2∶3 were assessed using a dialysis bag diffusion method combined with fluorescence spectrophotometry.(2)Validation of CNS targeting.① Cyanine7(Cy7)-labeled PDC 5∶2∶3(Cy7@PDC)was prepared and mixed with PLA2 solution(Cy7@PDC+PLA2 5∶2∶3).Mice were divided into normal control,Cy7,Cy7@PDC 5∶2∶3 and Cy7@PDC+PLA2 5∶2∶3 groups(n=3 per group).After iv injection(Cy7 dose:1 mg·kg-1,carrier dose:80 mg·kg-1),brain fluorescence was visualized at 3 h using a small animal in vivo imaging(IVIS)system.② Cyanine 3(Cy3)-labeled PDC 5∶2∶3(Cy3@PDC 5∶2∶3)was prepared and mixed with PLA2 solution(Cy3@PDC+PLA2 5∶2∶3).Mice were divided into Cy3@PDC 5∶2∶3 and Cy3@PDC+PLA2 5∶2∶3 groups(n=3 per group).After iv injection(Cy3 dose:1 mg·kg-1,carrier dose:80 mg·kg-1),brain tissues were collected at 2 h for fluorescent staining and Cy3 fluorescence observation.(3)Therapeutic efficacy eval-uation.① Male KM mice were randomly divided into normal control,brain injury,HI-6 treatment,and HI-6@PDC+PLA2 5∶2∶3 treatment groups(n=6 per group).Except for the normal control,all the mice were subcutaneously(sc)injected with soman(120 μg·kg-1),followed by immediate iv treatment(HI-6 dose:22 mg·kg-1,carrier dose:80 mg·kg-1).At 10 min,orbital blood and brain tissues were collected before brain weight was recorded.Acetylcholinesterase(AChE)reactivation in blood and brain was measured using the Ellman method.② Grouping and treatment were identical to ①(n=3 per group).At 24 h,brain tissues were collected for HE staining to assess histopathological damage.③ Mice were divided into brain injury and HI-6@PDC+PLA2 5∶2∶3 treatment groups(n=10 per group)and treated as in ①(soman dose:220 ug·kg-1).Survival rates,neurotoxic symptoms(tremors,salivation),and seizure latency were recorded,and survival curves were plotted.RESULTS(1)PDC 5∶2∶3 exhibited the highest brain fluorescence,indicating optimal CNS targeting.HI-6@PDC 5∶2∶3 appeared in regular spherical shapes,and were negatively charged,with a size of(219.4±3.1)nm,PDI of 0.4±0.02,entrapment effi-ciency of 72.9％and loading efficiency of 49.7％.HI-6@PDC+PLA2 5∶2∶3 showed a cumulative release of 43.5％at 60 min,which was lower than that of rhodamine B(RB)but sufficient for CNS therapeutic timelines.(2)In vivo fluorescence and pathological fluorescence confirmed PLA2-mediated CNS delivery.(3)HI-6@PDC+PLA2 5∶2∶3 significantly enhanced AChE reactivation in the blood and brain compared to HI-6.Histopathology revealed mitigated brain injury in treated mice.HI-6@PDC+PLA2 5∶2∶3 prolonged survival,reduced convulsions,alleviated neurotoxicity,and extended seizure latency.CONCLUSION HI-6@PDC 5∶2∶3 can effectively cross the blood-brain barrier via PLA2 mediation,demonstrating strong CNS targeting.It can significantly improve AChE reactivation in peripheral and central tissues and offers potent therapeutic efficacy against organophosphate-induced brain injury.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

ObjectiveTo observe the prevention and control effect of processed Polygonatum cyrtonema on depression induced by chronic unpredictable mild stress （CUMS） in female rats. MethodsForty rats were assigned into control， model， and low-， medium-， and high-dose processed P. cyrtonema groups according to the random number table method， with 8 rats in each group. The rat model of depression was established with the CUMS method. The body mass， open field test， forced swimming test， Morris water maze test， levels of neurotransmitters ［dopamine （DA）， 5-hydroxytryptamine （5-TH）， and acetylcholine （ACh）］， serum levels of sex hormones ［gonadotropin-releasing hormone（GnRH）， testosterone （T）， and estradiol （E₂）］ and inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-10］， and mRNA and protein levels of factors in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TRKB）/cAMP-response element binding protein （CREB） pathway were employed to evaluate the effect of processed P. cyrtonema on the CUMS-induced depression in female rats. ResultsThe body mass， open field test results， and forced swimming test results showed that the rat model of depression was successfully established. The comparison of behaviors， neurotransmitters， sex hormones， inflammatory factors， and neural pathways among groups showed that processed P. cyrtonema had different effects of preventing the development of depression in female rats. SPSS 25 was used for statistical analysis of error and significance. T test was conducted between groups. Each treatment group showed significant therapeutic effect compared with the model group （P<0.05）. Processed P. cyrtonema elevated the level of 5-TH （P<0.01） and lowered the levels of DA and ACh （P<0.01） in the brain tissue of female rats. In addition， it reduced the serum levels of GnRH， T， E₂， TNF-α， and IL-6 （P<0.05） and up-regulated the mRNA levels of BDNF and TRKB in the rat brain. ConclusionProcessed P. cyrtonema has a non-hyperactive preventive effect on CUMS-induced depression in rats， which provides a theoretical basis for the development of processed P. cyrtonema as a functional food product.

ObjectiveTo observe the prevention and control effect of processed Polygonatum cyrtonema on depression induced by chronic unpredictable mild stress （CUMS） in female rats. MethodsForty rats were assigned into control， model， and low-， medium-， and high-dose processed P. cyrtonema groups according to the random number table method， with 8 rats in each group. The rat model of depression was established with the CUMS method. The body mass， open field test， forced swimming test， Morris water maze test， levels of neurotransmitters ［dopamine （DA）， 5-hydroxytryptamine （5-TH）， and acetylcholine （ACh）］， serum levels of sex hormones ［gonadotropin-releasing hormone（GnRH）， testosterone （T）， and estradiol （E₂）］ and inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-10］， and mRNA and protein levels of factors in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TRKB）/cAMP-response element binding protein （CREB） pathway were employed to evaluate the effect of processed P. cyrtonema on the CUMS-induced depression in female rats. ResultsThe body mass， open field test results， and forced swimming test results showed that the rat model of depression was successfully established. The comparison of behaviors， neurotransmitters， sex hormones， inflammatory factors， and neural pathways among groups showed that processed P. cyrtonema had different effects of preventing the development of depression in female rats. SPSS 25 was used for statistical analysis of error and significance. T test was conducted between groups. Each treatment group showed significant therapeutic effect compared with the model group （P<0.05）. Processed P. cyrtonema elevated the level of 5-TH （P<0.01） and lowered the levels of DA and ACh （P<0.01） in the brain tissue of female rats. In addition， it reduced the serum levels of GnRH， T， E₂， TNF-α， and IL-6 （P<0.05） and up-regulated the mRNA levels of BDNF and TRKB in the rat brain. ConclusionProcessed P. cyrtonema has a non-hyperactive preventive effect on CUMS-induced depression in rats， which provides a theoretical basis for the development of processed P. cyrtonema as a functional food product.