OBJECTIVE: To identify the CDYL-interacting proteins in murine testis and investigate the mechanism of CDYL involved in spermatogenesis. METHODS: CDYL-interacting partners in testis were identified using co-immunoprecipitation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Expression pattern of CDYL-interacting protein MYH9 was analyzed through immunohistochemistry (IHC), confocal immunofluorescence (IF) and Western blot (WB) in mouse testicular cells. The effect of the Cdyl conditional knockout (CdylcKO) in spermatogenic cell on Myh9 expression was quantified via RT-qPCR, WB and IF imaging in both spermatids and spermatozoa from cauda epididymides. RESULTS: Direct interaction between MYH9 and CDYL was confirmed in murine testis. During spermiogenesis, MYH9 exhibited co-localization with CDYL at the manchette structure, and binding to F-ACTIN, the component of manchette. In cauda epididymal spermatozoa, MYH9 signal concentrated on acrosomal region and continuously distributed along the tail length. Conditional deletion of Cdyl in spermatogenic cell resulted in the transcriptional downregulation of Myh9. In spermatids, CdylcKO led to reduced but retained MYH9 localization to the disorganized manchette structure. In spermatozoa from CdylcKO mice, abnormalities of MYH9 localization were observed, including attenuation of acrosomal signal and/or partial vanishment/enhancement of tail signal. CONCLUSION In murine spermatids, MYH9 protein is localized to the manchette structure, with its expression and subcellular distribution is affected by CDYL protein. CDYL-MYH9 interaction is essential for the spermiogenesis.
Animals ; Male ; Mice ; Testis/metabolism* ; Myosin Heavy Chains/metabolism* ; Spermatogenesis ; Mice, Knockout

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

Objective To make a comprehensive review about transitional care practice for patients receiving percutaneous transhepatic biliary drainage(PTBD)and to analyze the current transitional care contents and evaluation indexes so as to provide guidance for improving the quality of transitional care services for discharged patients carrying a PTBD tube.Methods A scoping review study design was used to conduct a computerized retrieval of academic papers concerning the transitional care practice for discharged patients carrying a PTBD tube from the databases of PubMed,WOS Core Collection,CINAHL,Embase,Cochrane Library,CNKI,VIP,Wanfang med online,and Sinomed.The retrieval time period was from the establishment of the database to August 20,2024.Two investigators independently screened the literature to determine the studies to be included and the relevant information to be extracted.Results A total of 18 papers were enrolled in this study.The transitional care ways included telephone follow-up,home visit,online platform follow-up,and outpatient clinic follow-up.The intervention contents extended from in-hospital to out-of-hospital for up to 6 months.The evaluation indexes focused on the patient's knowledge about PTBD tube,the incidence of tube-related complications,the satisfaction with care,self-care ability,etc.Conclusion At present,the transitional care for discharged patients carrying a PTBD tube has a variety of content elements,which can improve the self-care ability and quality of life of the discharged patients carrying a PTBD tube to a certain extent,although more individualized transitional care modes need to be further explored.The evaluation indexes are mainly the outcome assessment of PTBD tube care.It is necessary to strengthen the quality supervision of organizational structure and nursing process.

Objective To investigate the relationship between cerebrovascular reserve (CVR) capacity and white matter lesions in elderly people. Methods We included 315 participants aged ≥ 60 years in Jinan area of Shandong Province from May 2018 to July 2019. They underwent transcranial Doppler ultrasonography for assessing CVR, breath holding index (BHI), and arterial pulsatility index (PI). According to CVR capacity, they were divided into normal CVR group (CVR ≥ 20%, n = 206) and impaired CVR group (CVR < 20%, n = 109). Magnetic resonance imaging was performed to evaluate periventricular, subcortical, and total white matter hyperintensity (WMH) volumes and Fazekas scores. Results Compared with the normal CVR group, the impaired CVR group showed significantly higher volumes of periventricular, subcortical, and total WMHs and significantly higher proportions of Fazekas scores ≥ 2 (P < 0.01). Periventricular, subcortical, and total WMH volumes were negatively correlated with CVR (r = −0.70, −0.66, −0.73, P < 0.01) and BHI (r = −0.64, −0.65, −0.68, P < 0.01) and positively correlated with PI (r = 0.60, 0.65, 0.65, P < 0.01). After adjusting for confounding factors, periventricular, subcortical, and total WMH volumes were still negatively correlated with CVR and BHI (P < 0.01) and positively correlated with PI (P < 0.01). The logistic regression analysis showed that the risks of periventricular, subcortical, and total Fazekas score ≥ 2 in the impaired CVR group were 1.96 times (95% confidence interval [CI]: 1.17−3.27, P < 0.01), 1.84 times (95% CI: 1.11−3.05, P < 0.05), and 2.33 times (95% CI: 1.30−4.18, P < 0.01) that of the normal CVR group, respectively. Conclusion Impaired CVR is an independent risk factor for white matter lesions in the elderly.

Decoction is the most commonly used dosage form in the clinical treatment of traditional Chinese medicine (TCM). During boiling, the violent movement of various active ingredients in TCM creates molecular forces such as hydrogen bonding, π-π stacking, hydrophobic interactions and electrostatic interactions, which results in the formation of self-assembled aggregates in decoction (SADs), including particles, gels, fibers, etc. It was found that SADs widely existed in decoction with biological activities superior to both effective monomers and their physical mixtures, providing a new idea to reveal the pharmacodynamic material basis of Chinese herbal medicine from the perspective of component interactions-phase structure. Recently, SADs have become a novel focus of research in TCM. This paper reviewed their relevant studies in recent years and found some issues to be concerned in the research, such as the polydispersity of decoction system, instability of active ingredient interactions during boiling, uncertainty of the aggregates self-assembly rules, and stability, purity, yield of the products. In this regard, some solutions and new ideas were presented for the integrated development and clinical application of SADs.

Objective To investigate the construction and value of radiation pneumonitis(RP)predic-tive model based on machine learning algorithm.Methods A retrospective analysis was conducted on the clin-ical data in 77 patients with breast cancer receiving radiotherapy and regular follow-up in this hospital from August 2019 to September 2022.The affected side lung was delineated on the localization CT as the area of in-terest and the radiomics features were extracted,meanwhile the affected side lung dosimetric parameters were extracted.After feature screening,the patients were divided into the training set and testing set by a 7∶3 rati-o.The features of positioning CT radiomics were extracted and combined with the dosimetry parameters of the affected side lung,and the model was established by using stochastic gradient descent(SGD)algorithm.The performance of the model was validated by using the area under the receiver operating characteristic(ROC)curve(AUC)and decision curve analysis(DCA).Results Among 77 patients,24 cases developed RP after ra-diotherapy end with an incidence rate of 31.17％.Compared with the patients without RP occurrence,V5,V10,V15,V20,V25,V30 and mean lung dose(MLD)in the patients with RP occurrence were higher,and the differ-ence was statistically significant(P＜0.05).In the training set,36 cases did not develop RP.17 cases devel-oped RP,in the testing set,17 cases did not develop RP and 7 cases developed RP.The affected side lung dosi-metric parameters had no statistical difference between the training set and testing set with and without RP occurrence(P＞0.05).After characteristics screening,the 8 optimal characteristics combinations were finally obtained.The average AUC of SGD model in 50％off cross-validation of the training set was 0.900 and AUC in the test set was 0.882.Conclusion The positioning CT radiomics features combined with dosimetry param-eters of the affected side lung has the good predictive value for RP after breast cancer radiotherapy.

Objective To construct curcumin pyrazole derivative by the reaction of diketone of curcumin and benzylhydrazine based on the above structure-activity relationship,and to explore its antioxidant activity to provide experimental basis for the development of curcumin antioxidant derivative.Methods Curcumin-N-substituted pyrazole derivative was synthesized from curcumin and benzylhydrazine.The structures of the derivative were confirmed by infrared spectroscopy(IR),nuclear magnetic resonance spectroscopy(1H-NMR,13C-NMR)and LC-MS.The antioxidant activity in vitro of the derivative was evaluated by determination of curcumin and its pyrazole derivative scavenging ability for 2,2-diphenyl-1-picrylhydrazyl(DPPH)free radical and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid(ABTS)free radical.Results Curcumin pyrazole derivative was successfully synthesized.Curcumin and its pyrazole derivative showed good free radical scavenging effects in the range of 4.6-73.6,6.25-100 μg·mL-1,respectively,with a significant dose-effect relationship.The half-maximal inhibition(IC50)values of curcumin and its pyrazole derivatives determined by DPPH method were 14.24,40.37 μg·mL-1,respectively,while the IC50 values of curcumin and its pyrazole derivatives determined by ABTS method were 36.65,19.26 μg·mL-1,respectively.Conclusion The antioxidant activity of β-dione of curcumin was retained through the substitution of the pyrazole ring,and the curcumin pyrazole derivative deserves further investigation as a potential antioxidant.

Purpose::Internal iliac artery ligation (IIAL) has been used as a damage control procedure to treat hemodynamically unstable pelvic fracture for many years. However, there is ongoing debate regarding the effectiveness and safety of this hemostatic method. Therefore, we performed a systematic literature review to assess the efficacy and safety of IIAL for pelvic fracture hemostasis.Methods::Three major databases, PubMed, Embase, and Google Scholar, were searched to screen eligible original studies published in English journals. Two reviewers independently read the titles, abstracts, and full texts of all literature. Articles were included if they reported the use and effects of IIAL.Results::A total of 171 articles were initially identified, with 22 fully meeting the inclusion criteria. Among the analyzed cases, up to 66.7% of patients had associated abdominal and pelvic organ injuries, with the urethra being the most frequently injured organ, followed by the bowel. The outcomes of IIAL for achieving hemostasis in pelvic fractures were found to be satisfactory, with an effective rate of 80%. Hemorrhagic shock was the leading cause of death, followed by craniocerebral injury. Notably, no reports of ischemic complications involving the pelvic organs due to IIAL were found.Conclusion::IIAL has a good effect in treating hemodynamically unstable pelvic fracture without the risk of pelvic organ ischemia. This procedure should be considered a priority for hemodynamically unstable pelvic fracture patients with abdominal organ injuries.

Objective To use network pharmacology to mine and predict the targets and related signaling pathways of Miaoyao Yiai Tang(Miao-Yi-Ai-Tang,MYAT)in the treatment of small cell lung cancer(SCLC).And animal experiments to verify its mechanism of action,to provide a theoretical basis for basic experiments and clinical applications.Methods The active ingredients of MYAT were obtained from the TCMSP database,combined with PubMed data,Swiss Target Prediction database and Uniprot database to obtain potential targets;SCLC-related genes were collected through the DrugBank database,Genecards database,OMIM database and TTD database,and the Venny 2.1 platform After obtaining the intersection genes of MYAT and SCLC,import them into the STRING database,construct a protein-protein interaction(PPI)network,use Cytoscape 3.9.1 software for visual analysis,and use Metascape database for GO enrichment analysis and KEGG pathway analysis,to predict the direct action target and signaling pathway of MYAT in the treatment of SCLC.Using AutoDock Tools 1.5.7 software for molecular docking to verify the close relationship between the two.For cytological experiment verification,the cultured cells were treated with MYAT and the expression of β-catenin,AXIN,c-myc was detected by qPCR,and the expression of β-catenin in the cells was detected by Western blot;animal experiments were established to establish a subcutaneous xenograft tumor model of lung cancer NCI-H446,to observe the effect of MYAT on tumor growth.Results A total of 65 effective components of MYAT,1368 SCLC genes,and 260 MYAT-SCLC intersection genes were obtained.Enrichment analysis showed that they were related to cancer pathways,PD-L1/PD-1 pathways,NF-κB pathways,Wnt and other signaling pathways.The results of molecular docking validation showed that the binding energies of active components and core target proteins were all<0 kJ·mol-1,which indicated that the protein could spontaneously bind to active components and be stable.Cell experiments showed that the expression levels of β-catenin,c-myc and AXIN mRNA were significantly down-regulated in the MYAT group(P<0.05).Animal experiments show that:MYAT can significantly inhibit the growth of tumors in vivo.Conclusion Miao-Yi-Ai-Tang can inhibit the proliferation of small cell lung cancer through Wnt/β-catenin signaling pathway.