Geminiviruses cause substantial crop yield losses worldwide. The replication initiator protein (Rep) encoded by geminiviruses is indispensable for geminiviral replication. The Rep protein encoded by beet severe curly top virus (BSCTV, genus Curtovirus, family Geminiviridae) induces VARIANT IN METHYLATION 5 (VIM5) expression in Arabidopsis leaves upon BSCTV infection. VIM5 functions as a ubiquitination-related E3 ligase to promote the proteasomal degradation of methyltransferases, resulting in reduction of methylation levels in the BSCTV C2-3 promoter. However, the specific domains of Rep responsible for VIM5 induction remain poorly characterized. Although Rep proteins from several geminiviruses act as viral suppressors of RNA silencing (VSRs), whether BSCTV Rep also possesses VSR activity remains to be illustrated. In this study, we employed a transient expression system in the 16c-GFP transgenic and the wild-type Nicotiana benthamiana plants to analyze the VSR and the VIM5-inducing activities of different truncated Rep proteins haboring distinct domains. We found that the N-terminal domain (amino acids 1-180) of Rep suppressed GFP silencing in 16c-GFP transgenic N. benthamiana leaves. The minimal N-terminal fragment (amino acids 1-104) induced VIM5 expression upon co-infiltration, while C-terminal truncations lacked VIM5-inducing activity. Our results indicate that the N-terminal domain of Rep encoded by BSCTV mediates the suppression of RNA silencing and induces VIM5 expression. Thus, our findings contribute to a better understanding of interactions between geminiviral Rep and plant hosts.
Geminiviridae/genetics* ; Nicotiana/metabolism* ; Arabidopsis/metabolism* ; RNA Interference ; Viral Proteins/metabolism* ; Arabidopsis Proteins/metabolism* ; Plants, Genetically Modified/metabolism* ; Protein Domains ; Plant Diseases/virology* ; Methyltransferases/metabolism* ; Ubiquitin-Protein Ligases/metabolism* ; DNA Helicases/genetics*

Objective To investigate the expression levels of peroxisome proliferator-activated receptor gamma coactivator-1β(PGC-1β),hypoxia-inducible factor-1α(HIF-1α),and resistin(RETN)in gouty arthri-tis(GA),and analyze their correlation with the degree of joint damage.Methods A total of 134 patients with GA in the hospital from January 2022 to October 2023 were selected as GA group,and 134 healthy people who underwent the physical examination in the same period were selected as control group.The serum expression levels of PGC-1β,HIF-1α and Retn were compared between the two groups.The expression levels of PGC-1β,HIF-1α and Retn in serum and synovial fluid of patients with different clinical characteristics in GA group were compared,the degree of joint destruction was graded according to the subjective pain grading method(VAS)and the patients were divided into a severe GA subgroup of 78 cases and a mild GA subgroup of 56 ca-ses.The expression levels of PGC-1β,HIF-1α,RETN,bone destruction factors[β-cross linked degradation products(β-CTX),tartrate resistant acid phosphatase-5b(TRACP5b),receptor activator of nuclear factor kappa B ligand(RANKL)]and inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)]were compared among different degrees of joint destruction,and the correlation between serum and syno-vial fluid PGC-1β,HIF-1α,RETN and the degree of joint destruction,bone destruction factors,and inflamma-tory factors was analyzed.Results The expression level of PGC-1β in serum of GA group was lower than that of the control group,while the expression levels of HIF-1α and RETN in serum were higher than those of the control group(P＜0.05).There were statistically significant differences in serum and synovial fluid PGC-1β,HIF-1α,and RETN levels among GA patients with different clinical stages,affected joints,disease duration,and annual seizure frequency(P＜0.05).The expression levels of PGC-1β in the serum and synovial fluid of the severe GA subgroup were lower than those of the mild GA subgroup(P＜0.05),while the expression lev-els of HIF-1α and RETN were higher than those of the mild GA subgroup(P＜0.05).The expression levels ofβ-CTX and TRACP5b in the severe GA subgroup were higher than those in the mild GA subgroup(P＜0.05),while the expression level of RANKL was lower than that in the mild GA subgroup(P＜0.05).PGC-1βin serum and synovial fluid was negatively correlated with the degree of joint destruction,β-CTX,TRACP5b,TNF-α,and IL-1β,and positively correlated with RANKL.HIF-1α and RETN were positively correlated with the degree of joint destruction,β-CTX,TRACP5b,TNF-α,and IL-1β,and negatively correlated with RANKL.Conclusion PGC-1β,HIF-1α,and RETN are abnormally expressed in patients with GA,and are closely associ-ated with the degree of joint destruction,bone destruction factors,and inflammatory factors.They are expec-ted to become reliable indicators for evaluating the occurrence and progression of GA.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

Objective:To summarize the best evidence for lower limb rehabilitation robot exercise rehabilitation in stroke patients.Methods:Clinical decisions, best practices, guidelines, evidence summaries, expert consensus, systematic reviews, and randomized controlled trials on lower limb rehabilitation robot exercise rehabilitation in stroke patients were systematically searched in national and international guideline networks, websites of relevant professional societies, and databases. The search period was from database establishment to October 17, 2024. Two researchers independently conducted literature quality evaluation, evidence extraction, and integration.Results:A total of 13 papers were included, including four guidelines, seven systematic reviews, one expert consensus, and one randomized controlled trial. Twenty-six pieces of best evidence were summarized in seven aspects of multidisciplinary teamwork, applicable conditions, rehabilitation management, exercise implementation, evaluation of rehabilitation outcomes, abnormal training responses, and considerations.Conclusions:This study is based on a number of high-quality evidence, standardizing the relevant theories and clinical applications, with a certain degree of scientific and cutting-edge nature, providing practical, reliable and valuable evidence-based references and guidance for medical and nursing staff to use lower limb rehabilitation robots.

Objective:To explore the design requirements of nurses in the Neurointensive Care Unit (NICU) for the closed-eye pupil monitoring system, providing reference for the refinement and upgrade of the system.Methods:This study was descriptive and qualitative. From December 2024 to February 2025, 15 NICU nurses from Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, were selected using purposive sampling for semi-structured interviews. Content analysis method was used to analyze data and extract key themes.Results:NICU nurses' design requirements for closed-eye pupil monitoring system were categorized into six themes and 18 sub-themes, namely physical characteristics requirements (strong device stability, compact and lightweight design), comfort and safety requirements (wear comfort and safety, prevention of light source thermal injury, convenient disinfection and infection control, assisting eyelid closure), functional requirements (automated monitoring and data collection, intelligent alarm and alert mechanisms), operational requirements (ready-to-use, easy to wear, simple operation), data monitoring requirements (data storage and integrity, data visualization and timeliness, data analysis and prediction, system integration and data management), and extended functional requirements (consciousness state monitoring, fundus lesion examination, vision and visual field screening) .Conclusions:NICU nurses' design requirements for the closed-eye pupil monitoring system are multidimensional and multi-level. System developers should continuously optimize system design based on the actual needs of nurses.

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Objective:To explore the design requirements of nurses in the Neurointensive Care Unit (NICU) for the closed-eye pupil monitoring system, providing reference for the refinement and upgrade of the system.Methods:This study was descriptive and qualitative. From December 2024 to February 2025, 15 NICU nurses from Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, were selected using purposive sampling for semi-structured interviews. Content analysis method was used to analyze data and extract key themes.Results:NICU nurses' design requirements for closed-eye pupil monitoring system were categorized into six themes and 18 sub-themes, namely physical characteristics requirements (strong device stability, compact and lightweight design), comfort and safety requirements (wear comfort and safety, prevention of light source thermal injury, convenient disinfection and infection control, assisting eyelid closure), functional requirements (automated monitoring and data collection, intelligent alarm and alert mechanisms), operational requirements (ready-to-use, easy to wear, simple operation), data monitoring requirements (data storage and integrity, data visualization and timeliness, data analysis and prediction, system integration and data management), and extended functional requirements (consciousness state monitoring, fundus lesion examination, vision and visual field screening) .Conclusions:NICU nurses' design requirements for the closed-eye pupil monitoring system are multidimensional and multi-level. System developers should continuously optimize system design based on the actual needs of nurses.

Breast cancer is one of the most common cancers in the world， and its incidence rate is also rising in China and tends to happen in younger age groups. The classical Wnt/β-catenin signaling pathway is an important target in the treatment of breast cancer， playing a key role in the whole process of breast cancer development by regulating the expression of related signal proteins and genes. Traditional Chinese medicine has a profound history and practical experience in the treatment of malignant tumors， and the development of modern technology further highlights the therapeutic advantages of traditional Chinese medicine， which has multiple targets and components. Research shows that Chinese medicine can effectively slow down the proliferation of breast cancer cells by regulating the Wnt/β-catenin signaling pathway， and has a significant inhibitory effect on the development of breast cancer. Based on this， this paper summarized domestic and foreign relevant studies on the regulation of the Wnt/β-catenin signaling pathway with traditional Chinese medicine in the treatment of breast cancer， analyzed the mechanism of traditional Chinese medicine treating breast cancer by intervening in this signaling pathway， and summarized 44 different types of traditional Chinese medicine monomers， including terpenes （triptolide， andrographolide， etc.）， flavonoids （scutellarin， sinensetin， etc.）， polysaccharides （Angelica sinensis polysaccharides， etc.）， phenols （curcumin， polydatin， etc.）， and alkaloids （lycorine， etc.）. In addition， there are 3 traditional Chinese medicines （Ganoderma lucidum， Radix actinidia chinensis， and Antrodia camphorata）， 1 group of medicine pairs （Trionycis Carapax-Zedoary Turmeric）， and 8 traditional Chinese medicine formulas （Compound Tubeimu， Huangqi Jiedu Tang， Xihuang Wan， Liuwei Dihuang Wan， Jiazhu Tang， Aiduqing Fang， Sini San， and compound Kushen injection）. By regulating the Wnt/β-catenin signaling pathway and its key molecules， these single herbs， monomers， and compound herbs can reverse the epithelial mesenchymal transformation process， reduce the activity of stem cells， and inhibit the growth and metastasis of cancer cells. Besides， it can also enhance the sensitivity of drugs and radiotherapy and combat breast cancer， providing a new perspective for drug development and treatment strategies for breast cancer.

Prostate cancer is a malignant tumor that primarily arises from the epithelial tissue of the prostate in men. With the aggravation of population aging in China， the incidence rate of this disease has been continuously rising. Although the exact cause of prostate cancer remains unclear， it has been proven to be closely related to various factors， including individual genetic susceptibility， genetic mutations， dietary habits， and lifestyle. Research has shown that abnormal activation of the Wnt/β-catenin signaling pathway also plays an important role in the occurrence and development of prostate cancer. Multiple experimental results have revealed that traditional Chinese medicine （TCM）， with its multi-target and multi-stage mechanisms of action， exerts significant regulatory effects on key biological processes such as proliferation， migration， invasion， angiogenesis， and epithelial-mesenchymal transition （EMT） of prostate cancer cells. TCM has shown excellent potential in preventing prostate cancer progression and improving patient prognosis and has become a research focus in prostate cancer treatment in recent years. Based on this， this study reviewed the research on the regulation of the Wnt/β-catenin signaling pathway by TCM in the treatment of prostate cancer at home and abroad. It analyzed the mechanisms by which TCM intervention exerts anti-prostate cancer effects via this signaling pathway， identifying 29 different types of active ingredients in TCM， including alkaloids （e.g.， capsaicin， berberine）， flavonoids （e.g.， icariin and hyperoside）， polyphenols （e.g.， gastrodin and honokiol）， terpenes （e.g.， oridonin）， quinones （e.g.， aloe-emodin）， coumarins （e.g.， agrimonolide）， and saponins （e.g.， saikosaponin-d）. Additionally， one TCM medicinal substance （arsenic）， one drug pair （Danggui - Qieyi combination）， and two TCM formulae （Yishen Tonglong Tang and Guben Qingyuan Formula） were included. The study aims to deepen the understanding of the pathological mechanism of prostate cancer and to explore possible therapeutic targets， thereby providing new perspectives and approaches for clinical research and new drug development， and ultimately promoting the advancement and innovation of prostate cancer treatment strategies.