The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

AIM To establish LC-MS and GC-MS method and analyze the chemical constituents of Dendrobium huoshanense C.Z.Tang & S.J.Cheng flowers.METHODS LC-MS was performed on a Zorbax Eclipse C18 column(2.1 mm×100 mm,1.8 μm),with the mobile phase comprising of water(containing 0.1％formic acid)-acetonitrile flowing at 0.3 mL/min,and electrospray ionization was operated in both positive and negative ion modes.The GC-MS employed headspace solid-phase microextraction for sample preparation,and the analysis was performed on an HP-5MS column(30 m×0.25 mm,0.25 μm),with the following temperature program:initial temperature 50 ℃(held for 2 min),increased at 5 ℃/min to 180 ℃(held for 5 min),then raised at 10 ℃/min to 250 ℃(held for 5 min),and electron impact ion source was employed.RESULTS A total of 62 compounds were identified by LC-MS,including 35 flavonoids,4 coumarins,6 alkaloids,6 terpenoids,3 amino acids,2 polyphenols,2 ketones and 4 others.A total of 101 volatile components were identified by GC-MS,including ketones,aldehydes,alcohols,esters,ethers,and acid.CONCLUSION This method can comprehensively analyze the chemical constituents of D.huoshanense flowers,and provide a scientific basis for elucidating its pharmacodynamic material basis.

This paper uses literature and network data to systematically sort out the theoretical and practical foundations of global public health cooperation,combines expert interviews to conduct empirical analyses,and further explores China's strategies for participating in global public health cooperation through quantitative statistics and text mining of interview data,and proposes a plan for China's participation in global public health cooperation under the current international situation.Under the countercurrents to globalization,China should take its own public health capacity building as the foundation,put global security and health equity at the core,with a philosophy of open cooperation and sustainable development,actively promote bilateral and multilateral cooperation,focus on cultivating global health talents,and enhance the effectiveness of disease prevention and control by making use of existing platforms,international mechanisms and digital health technologies,so as to help build a Global Community of Health for All.

Steroid-induced osteonecrosis of femoral head (SONFH) is a disease characterized by femoral head collapse and local pain caused by excessive use of glucocorticoids. Peroxisome proliferator-activated receptor-γ (PPARγ) is mainly expressed in adipose tissue. Wnt/β-catenin, AMPK and other related signaling pathways play an important role in regulating adipocyte differentiation, fatty acid uptake and storage. Bone marrow mesenchymal cells (BMSCs) have the ability to differentiate into adipocytes or osteoblasts, and the use of hormones upregulates PPARγ expression, resulting in BMSCs biased towards adipogenic differentiation. The increase of adipocytes affects the blood supply and metabolism of the femoral head, and the decrease of osteoblasts leads to the loss of trabecular bone, which eventually leads to partial or total ischemic necrosis and collapse of the femoral head. MicroRNAs (miRNAs) are a class of short non-coding RNAs that regulate gene expression by inhibiting the transcription or translation of target genes, thereby affecting cell function and disease progression. Studies have shown that miRNAs affect the progression of SONFH by regulating PPARγ lipid metabolism-related signaling pathways. Therefore, it may be an accurate and feasible SONFH treatment strategy to regulate adipogenic-osteoblast differentiation in BMSCs by targeted intervention of miRNA differential expression to improve lipid metabolism. In this paper, the miRNA-mediated PPARγ-related signaling pathways were classified and summarized to clarify their effects on lipid metabolism in SONFH, providing a theoretical reference for miRNA targeted therapy of SONFH, and then providing scientific evidence for SONFH precision medicine.
MicroRNAs/physiology* ; PPAR gamma/metabolism* ; Femur Head Necrosis/metabolism* ; Humans ; Signal Transduction/physiology* ; Lipid Metabolism/physiology* ; Animals ; Cell Differentiation ; Mesenchymal Stem Cells/cytology* ; Glucocorticoids/adverse effects*

This paper aims to contribute to guaranteeing the stable development and enhancing the understanding of ecological agriculture of Chinese materia medica so that the national strategy and industrial demand can be better served. It first introduces current traditional Chinese medicine(TCM)policy and industrial development status from five aspects, including policy guarantee, theoretical support, technological innovation, standardization system, and brand influence. Then, the paper analyzes the development dilemma of TCM agriculture in production and quality increase and ecological environment protection. It also proposes the development goals of ecological agriculture of Chinese materia medica that meet the current industrial development demand, which are reducing chemical fertilizers, pesticides, and carbon emissions, improving quality, increasing efficiency, and protecting ecological environment. In addition, the new development goals are interpreted through case studies. Finally, this paper proposes four development strategies for ecological agriculture of Chinese materia medica: conducting research on the pattern and spatial and temporal variations of nationwide TCM production areas; studying the internal and external ecological memories of medicinal plant growth from the perspectives of genetic variations and environmental adaptation variations and elucidating their contributions to the formation of quality; carrying out selection and breeding of stress-resistant varieties for ecological agriculture of Chinese materia medica, the optimization of key technologies for soil improvement and restoration and green prevention and control against diseases and pests, and the improvement of quality; carrying out research on the quality assurance and value realization of ecological products made from TCM. This research can provide guidance for policy formulation, theoretical development of the discipline, and the enhancement of industrial technology for ecological agriculture of Chinese materia medica.
Agriculture/methods* ; China ; Drugs, Chinese Herbal ; Plants, Medicinal/chemistry* ; Ecosystem ; Materia Medica ; Medicine, Chinese Traditional

Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of ischemic stroke. Stenting is a treatment option for symptomatic ICAS, but it also has problems such as procedure-related complications and in-stent restenosis. This article reviews the application of stenting, particularly different stent systems, in patients with symptomatic ICAS.

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

Objective:To investigate the short-term efficacy of robotic versus laparoscopic-assisted right hemicolectomy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 99 patients of right colon cancer who were admitted to Tianjin Medical University General Hospital from January 2020 to December 2023 were collected. There were 50 males and 49 females, aged 69(range, 26?89)years. Of the 99 patients, 41 patients undergoing robotic-assisted right hemicolectomy were divided into the robotic group, and 58 patients undergoing laparoscopic-assisted right hemicolectomy were divided into the lapa-roscopic group. Patients received robotic-assisted or laparoscopic-assisted right hemicolectomy operated by the same major surgeon. Observation indicators:(1) propensity score matching status and com-parison of clinical data of patients between the two groups after matching; (2) intraoperative and postoperative conditions.Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶1 nearest neighbor matching method. The caliper value was set as 0.1. Results:(1) Propensity score matching status and comparison of clinical data of patients between the two groups after matching. Of the 99 patients, 82 patients were successfully matched, with 41 cases in each of the robotic group and the laparoscopic group. After propensity score matching, the elimination of history of abdominal operation confounding bias ensured comparability. (2) Intraoperative and postoperative conditions. After propensity score matching, the operation time of the robotic group was 215(range, 130?340)minutes, the volume of intraoperative blood loss was 50(range, 10?400)mL, the number of lymph node dissected was 21(range, 5?55), the number of intensive care unit stay was 15, time to postoperative first flatus was 3(range, 1?12)days, time to postoperative first food intake was 4(range, 2?14)days, duration of postoperative hospital stay was 8(range, 5?25)days. The above indicators of the laparoscopic group were 210(range, 140?370)minutes, 50(range, 5?150)mL, 19(range, 5?34),20, 3(range, 0?9)days, 5(range, 2?10)days, 8(range, 6?17)days, respectively. There was no significant difference in the above indicators between patients of the two groups ( Z=?0.94, ?1.87, ?1.32, χ2=1.25, Z=0.13, ?0.83, ?0.65, P>0.05). There was no patient converted to open operation in the robotic group, versus 1 patient converted to open operation in the laparoscopic group, showing no significant difference between patients of the two groups ( P>0.05). There were 6 cases in the robotic group and 4 cases in the laparoscopic group with complications, showing no significant difference between the two groups ( χ2=0.46, P>0.05). Both groups of patients achieved R 0 resection and had no readmission 30 days after surgery. The hospital expense was (11.0±1.8)×10 4 yuan of the robotic group, versus (9.0±1.7)×10 4 yuan of the laparoscopic group, showing a significant difference between the two groups ( t=?5.27, P<0.05). Conclusion:Robot-assisted right hemicolectomy is non inferior to laparoscopic-assisted right hemicolectomy in safety and efficacy, but with higher hospitalization costs.

This study investigated the types and distribution of rodents,and the infection status of eight pathogens in the high-altitude areas of western Sichuan,to provide a basis for control of rodent-borne diseases and pathogen surveillance in rodents in the area.From August to November of 2023,rodents were captured through the night method in high-altitude areas of western Sichuan.Nucleic acids were collected from the rodents'livers and lungs,and eight important pathogens were detected:Dabie bandavirus,Han-tavirus,Bartonella,Francisella tularensis,Anaplasma phagocytophilum,Rickettsia mooseri,Orientia tsutsugamushi,and Leptospira interrogans.The chi-square test was used to compare the composition ratios of rodent species and the difference in pathogen positivity rates among groups.A total of 114 rodents of nine species were captured.The dominant species in this area were Apodemus agrarius(22.81%),Apodemus chevrieri(18.42%),Niviventer confucianus(17.54%),Apodemus latronum(16.67%),and Apodemus peninsu-lae(13.16%).Other rodent species included Rattus nitidus(4.39%),Neodon irene(4.39%),Chodsigoa hypsibia(1.75%),and Nivi-venter excelsior(0.88%).Statistically significant differences in rodent species composition were observed among regions,altitudes,and habitats(χ2Region=112.358,P<0.05;χ2Altitude=96.843,P<0.05;χ2Habitat=48.842,P<0.05).The liver and lung pathogen results showed that the positivity rate of Bartonella was highest(29/114),whereas those of the other seven pathogens were 0%-4.39%.Five rodents were co-infected with two or more pathogens,and the composite positivity rate was 4.36%(5/114).Statistically significant differences in the positivity rates were observed for Leptospira interrogans among species(χ2=6.568,P=0.028)and Anaplasma phagocytophilum among habitats(χ2=7.596,P=0.027);however,no significant differences in the positivity rates of other pathogens were found among rodent species,regions,altitudes,habitats,and sexes(P>0.05).Thus,rodent species were abundant in the high-altitude areas of western Sichuan and carried a variety of pathogens.Multiple pathogens showed compound infections,among which the positivity rate of Bartonella was relatively high.The total infection rate of pathogens in living areas was relatively high,and the risk of pathogenesis to the population is greater.Therefore,rodent control and disease monitoring efforts should be strengthened.