The involvement of soluble epoxide hydrolase in the development of cardiovascular diseases through epoxyeicosatrienoic acids.

Arachidonic acid (AA) has three main metabolic pathways: the cycloxygenases (COXs) pathway, the lipoxygenases (LOXs) pathway, and the cytochrome P450s (CYPs) pathway. AA produces epoxyeicosatrienoic acids (EETs) through the CYPs pathway. EETs are very unstable in vivo and can be degraded in seconds to minutes. EETs have multiple degradation pathways, but are mainly degraded in the presence of soluble epoxide hydrolase (sEH). sEH is an enzyme of bifunctional nature, and current research focuses on the activity of its C-terminal epoxide hydrolase (sEH-H), which hydrolyzes the EETs to the corresponding inactive or low activity diol. Previous studies have reported that EETs have cardiovascular protective effects, and the activity of sEH-H plays a role by degrading EETs and inhibiting their protective effects. The activity of sEH-H plays a different role in different cells, such as inhibiting endothelial cell proliferation and migration, but promoting vascular smooth muscle cell proliferation and migration. Therefore, it is of interest whether the activity of sEH-H is involved in the initiation and progression of cardiovascular diseases by affecting the function of different cells through EETs.

Mechanistic and data-driven perspectives on plant uptake of organic pollutants.

Establishing reliable predictive models for plant uptake of organic pollutants is crucial for environmental risk assessment and guiding phytoremediation efforts. This study compiled an expanded dataset of plant cuticle-water partition coefficients (Kcw), a useful indicator for plant uptake, for 371 data points of 148 unique compounds and various plant species. Quantum/computational chemistry software and tools were utilized to compute various molecular descriptors, aiming to comprehensively characterize the properties and structures of each compound. Three types of models were developed to predict Kcw: a mechanism-driven pp-LFER model, a data-driven machine learning model, and an integrated mechanism-data-driven model. The mechanism-data-driven GBRT-ppLFER model exhibited superior performance, achieving RMSEtrain = 0.133 and RMSEtest = 0.301 while maintaining interpretability. The Shapley Additive Explanation analysis indicated that pp-LFER parameters, ESPI, FwRadicalmax, ExtFP607, and RDF70s are the key factors influencing plant uptake in the GBRT-ppLFER model. Overall, pp-LFER parameter, ESPI, and ExtFP607 show positive effects, while the remaining factors exhibit negative effects. Partial dependency analysis further indicated that plant uptake is not solely determined by individual factors but rather by the combined interactions of multiple factors. Specifically, compounds with ppLFER parameter >4, ESPI > -25.5, 0.098 < FwRadicalmax <0.132, and 2 < RFD70s < 3, are generally more readily taken up by plants. Besides, the predicted Kcw values from the GBRT-ppLFER model were effectively employed to estimate the plant-water partition coefficients and bioconcentration factors across different plant species and growth media (water, sand, and soil), achieving an outstanding performance with an RMSE of 0.497. This study provides effective tools for assessing plant uptake of organic pollutants and deepens our understanding of plant-environment-compound interactions.

The Influence of Emodin Succinyl Ethyl Ester on Non-Alcoholic Steatohepatitis Induced by a Diet High in Fructose, Cholesterol, and Fat in Mice.

Nonalcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis and evidence of hepatocyte injury (ballooning) and inflammation, with or without liver fibrosis. In this study, after 12 weeks of induction, the mice were treated with emodin succinyl ethyl ester (ESEE) for four weeks at doses of 10/30/90 mg/kg/day. The blood analysis of experimental endpoints showed that ESEE exhibited significant therapeutic effects on the progression of disorders of glycolipid metabolism and the induced liver injury in the model animals. Histopathological diagnosis of the liver and total triglyceride measurements revealed that ESEE had a significant therapeutic effect on the histopathological features of nonalcoholic fatty liver disease/hepatitis, such as cellular steatosis and activation of intrahepatic inflammation. Additionally, ESEE was able to improve hepatocyte fat deposition, steatosis, and the course of intrahepatic inflammatory activity. Furthermore, it showed some inhibitory effect on liver fibrosis in the model animals. In summary, this study confirms the therapeutic effects of ESEE on the NAFLD/NASH model in C57BL/6J mice induced by a high-fat, high cholesterol, and fructose diet. These effects were observed through improvements in liver function, inhibition of fibrosis, and inflammatory responses. Changes in blood glucose levels, blood lipid metabolism, liver histopathological staining, liver fibrosis staining, and related pathological scores further supported the therapeutic effects of ESEE. Therefore, this study has important implications for the exploration of novel drugs for nonalcoholic fatty liver disease.

An Improved TransMVSNet Algorithm for Three-Dimensional Reconstruction in the Unmanned Aerial Vehicle Remote Sensing Domain.

It is important to achieve the 3D reconstruction of UAV remote sensing images in deep learning-based multi-view stereo (MVS) vision. The lack of obvious texture features and detailed edges in UAV remote sensing images leads to inaccurate feature point matching or depth estimation. To address this problem, this study improves the TransMVSNet algorithm in the field of 3D reconstruction by optimizing its feature extraction network and costumed body depth prediction network. The improvement is mainly achieved by extracting features with the Asymptotic Pyramidal Network (AFPN) and assigning weights to different levels of features through the ASFF module to increase the importance of key levels and also using the UNet structured network combined with an attention mechanism to predict the depth information, which also extracts the key area information. It aims to improve the performance and accuracy of the TransMVSNet algorithm's 3D reconstruction of UAV remote sensing images. In this work, we have performed comparative experiments and quantitative evaluation with other algorithms on the DTU dataset as well as on a large UAV remote sensing image dataset. After a large number of experimental studies, it is shown that our improved TransMVSNet algorithm has better performance and robustness, providing a valuable reference for research and application in the field of 3D reconstruction of UAV remote sensing images.

Prevalence of Motoric Cognitive Risk Syndrome Among Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis.

PURPOSE: To systematically review the prevalence of motoric cognitive risk syndrome (MCR) among community-dwelling older adults and provide evidence-based support for policymakers planning health and social care policies. METHOD: Web of Science, PubMed, and Cochrane Library databases were searched for cross-sectional, prospective cohort, or population-based longitudinal studies of community-dwelling older adults aged ≥60 years with MCR from inception of the database through December 18, 2021. RESULTS: Seventeen studies were included. Pooled prevalence of MCR was found to be 10% (95% confidence interval [8%, 12%], I2 = 98.4%). Results of a subgroup analysis revealed a combined prevalence of MCR of 8.2% in males and 9.2% in females. Pooled prevalence of MCR was 9.7% in Asia and 10.2% in other regions. CONCLUSION: Prevalence of MCR in community-dwelling older adults is high. Our research may improve the epidemiological understanding of MCR, draw attention to older adults with MCR, and thus promote research of MCR and the formulation of relevant public health policies. With early identification and intervention of MCR, cognitive function can be improved, and the onset of dementia can be delayed or prevented. [Journal of Gerontological Nursing, 50(4), 16-24.].

Telomere dysfunction alters intestinal stem cell dynamics to promote cancer.

Telomere dynamics are linked to aging hallmarks, and age-associated telomere loss fuels the development of epithelial cancers. In Apc-mutant mice, the onset of DNA damage associated with telomere dysfunction has been shown to accelerate adenoma initiation via unknown mechanisms. Here, we observed that Apc-mutant mice engineered to experience telomere dysfunction show accelerated adenoma formation resulting from augmented cell competition and clonal expansion. Mechanistically, telomere dysfunction induces the repression of EZH2, resulting in the derepression of Wnt antagonists, which causes the differentiation of adjacent stem cells and a relative growth advantage to Apc-deficient telomere dysfunctional cells. Correspondingly, in this mouse model, GSK3ß inhibition countered the actions of Wnt antagonists on intestinal stem cells, resulting in impaired adenoma formation of telomere dysfunctional Apc-mutant cells. Thus, telomere dysfunction contributes to cancer initiation through altered stem cell dynamics, identifying an interception strategy for human APC-mutant cancers with shortened telomeres.

Effects of the novel sodium-dependent phosphate cotransporter 2b inhibitor DZ1462 on hyperphosphatemia in chronic kidney disease.

BACKGROUND: Serum phosphate levels remain insufficiently controlled in chronic kidney disease (CKD) patients, and novel therapeutic strategies are needed. Blocking intestinal phosphate absorption mediated by sodium-dependent phosphate cotransporter type 2b (NPT2b) holds promise as one such strategy. METHODS: The in vitro cellular potency of DZ1462 was evaluated using a radioactive Pi uptake assay on stable Chinese hamster ovary (CHO) cell clones transfected with human NPT2b (hNPT2b) or rat NPT2b (rNPT2b). The ability of DZ1462 to inhibit phosphate absorption was studied in vivo in an acute model after oral bolus challenge with 33PO4 and in an adenine-induced chronic hyperphosphatemia rat model. PK and minitox was also evaluated. RESULTS: The cellular assays with the hNPT2b-CHO and rNPT2b-CHO clones showed that DZ1462 significantly and potently inhibited phosphate uptake. In vivo, in a chronic Pi-fed rat model, DZ1462 effectively inhibited intestinal Pi uptake. In a hyperphosphatemia rat model, DZ1462 significantly inhibited Pi uptake, and DZ1462 in combination with sevelamer had a synergistic effect. The pharmacokinetics (PK) study confirmed that DZ1462 is a gastrointestinal (GI)-restricted compound that can remain in the intestine for a sufficient duration. In addition, DZ1462 also reduced cardiovascular events and ameliorated osteoporosis in a CKD animal model. CONCLUSIONS: This study revealed that a GI-restricted NPT2b inhibitor DZ1462 potently inhibits NPT2b in vitro and blocks intestinal phosphate uptake in multiple animal models with potential to reduce various cardiovascular events in CKD models. Therefore, DZ1462 may be useful to treat renal disease patients who have shown an unsatisfactory response to phosphate binders.

Proteinase 3 depletion attenuates leukemia by promoting myeloid differentiation.

Hematopoietic stem and progenitor cells (HSPCs) that have impaired differentiation can transform into leukemic blasts. However, the mechanism that controls differentiation remains elusive. Here, we show that the genetic elimination of Proteinase 3 (PRTN3) in mice led to spontaneous myeloid differentiation. Mechanistically, our findings indicate that PRTN3 interacts with the N-terminal of STAT3, serving as a negative regulator of STAT3-dependent myeloid differentiation. Specifically, PRTN3 promotes STAT3 ubiquitination and degradation, while simultaneously reducing STAT3 phosphorylation and nuclear translocation during G-CSF-stimulated myeloid differentiation. Strikingly, pharmacological inhibition of STAT3 (Stattic) partially counteracted the effects of PRTN3 deficiency on myeloid differentiation. Moreover, the deficiency of PRTN3 in primary AML blasts promotes the differentiation of those cells into functional neutrophils capable of chemotaxis and phagocytosis, ultimately resulting in improved overall survival rates for recipients. These findings indicate PRTN3 exerts an inhibitory effect on STAT3-dependent myeloid differentiation and could be a promising therapeutic target for the treatment of acute myeloid leukemia.

Tensile Strain-Mediated Bimetallene Nanozyme for Enhanced Photothermal Tumor Catalytic Therapy.

Nanozymes have demonstrated significant potential in combating malignant tumor proliferation through catalytic therapy. However, the therapeutic effect is often limited by insufficient catalytic performance. In this study, we propose the utilization of strain engineering in metallenes to fully expose the active regions due to their ultrathin nature. Here, we present the first report on a novel tensile strain-mediated local amorphous RhRu (la-RhRu) bimetallene with exceptional intrinsic photothermal effect and photo-enhanced multiple enzyme-like activities. Through geometric phase analysis, electron diffraction profile, and X-ray diffraction, it is revealed that crystalline-amorphous heterophase boundaries can generate approximately 2% tensile strain in the bimetallene. The ultrathin structure and in-plane strain of the bimetallene induce an amplified strain effect. Both experimental and theoretical evidence support the notion that tensile strain promotes multiple enzyme-like activities. Functioning as a tumor microenvironment (TME)-responsive nanozyme, la-RhRu exhibits remarkable therapeutic efficacy both in vitro and in vivo. This work highlights the tremendous potential of atomic-scale tensile strain engineering strategy in enhancing tumor catalytic therapy.

Integration of 3D bioprinting and multi-algorithm machine learning identified glioma susceptibilities and microenvironment characteristics.

Glioma, with its heterogeneous microenvironments and genetic subtypes, presents substantial challenges for treatment prediction and development. We integrated 3D bioprinting and multi-algorithm machine learning as a novel approach to enhance the assessment and understanding of glioma treatment responses and microenvironment characteristics. The bioprinted patient-derived glioma tissues successfully recapitulated molecular properties and drug responses of native tumors. We then developed GlioML, a machine learning workflow incorporating nine distinct algorithms and a weighted ensemble model that generated robust gene expression-based predictors, each reflecting the diverse action mechanisms of various compounds and drugs. The ensemble model superseded the performance of all individual algorithms across diverse in vitro systems, including sphere cultures, complex 3D bioprinted multicellular models, and 3D patient-derived tissues. By integrating bioprinting, the evaluative scope of the treatment expanded to T cell-related therapy and anti-angiogenesis targeted therapy. We identified promising compounds and drugs for glioma treatment and revealed distinct immunosuppressive or angiogenic myeloid-infiltrated tumor microenvironments. These insights pave the way for enhanced therapeutic development for glioma and potentially for other cancers, highlighting the broad application potential of this integrative and translational approach.

Integration of single-cell RNA-seq and bulk RNA-seq to construct liver hepatocellular carcinoma stem cell signatures to explore their impact on patient prognosis and treatment.

BACKGROUND: Liver hepatocellular carcinoma (LIHC) is a prevalent form of primary liver cancer. Research has demonstrated the contribution of tumor stem cells in facilitating tumor recurrence, metastasis, and treatment resistance. Despite this, there remains a lack of established cancer stem cells (CSCs)-associated genes signatures for effectively predicting the prognosis and guiding the treatment strategies for patients diagnosed with LIHC. METHODS: The single-cell RNA sequencing (scRNA-seq) and bulk RNA transcriptome data were obtained based on public datasets and computerized firstly using CytoTRACE package and One Class Linear Regression (OCLR) algorithm to evaluate stemness level, respectively. Then, we explored the association of stemness indicators (CytoTRACE score and stemness index, mRNAsi) with survival outcomes and clinical characteristics by combining clinical information and survival analyses. Subsequently, weighted co-expression network analysis (WGCNA) and Cox were applied to assess mRNAsi-related genes in bulk LIHC data and construct a prognostic model for LIHC patients. Single-sample gene-set enrichment analysis (ssGSEA), Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Tumor Immune Estimation Resource (TIMER) analysis were employed for immune infiltration assessment. Finally, the potential immunotherapeutic response was predicted by the Tumor Immune Dysfunction and Exclusion (TIDE), and the tumor mutation burden (TMB). Additionally, pRRophetic package was applied to evaluate the sensitivity of high and low-risk groups to common chemotherapeutic drugs. RESULTS: A total of four genes (including STIP1, H2AFZ, BRIX1, and TUBB) associated with stemness score (CytoTRACE score and mRNAsi) were identified and constructed a risk model that could predict prognosis in LIHC patients. It was observed that high stemness cells occurred predominantly in the late stages of LIHC and that poor overall survival in LIHC patients was also associated with high mRNAsi scores. In addition, pathway analysis confirmed the biological uniqueness of the two risk groups. Personalized treatment predictions suggest that patients with a low risk benefited more from immunotherapy, while those with a high risk group may be conducive to chemotherapeutic drugs. CONCLUSION: The current study developed a novel prognostic risk signature with genes related to CSCs, which provides novel ideas for the diagnosis, prognosis and treatment of LIHC.

Causal impact of gut microbiota and associated metabolites on pulmonary arterial hypertension: a bidirectional Mendelian randomization study.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated metabolites, and PAH remains elusive. We aimed to investigate this causal association and to explore whether dietary patterns play a role in its regulation. METHODS: Summary statistics of gut microbiota, associated metabolites, diet, and PAH were obtained from genome-wide association studies. The inverse variance weighted method was primarily used to measure the causal effect, with sensitivity analyses using the weighted median, weighted mode, simple mode, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger methods. A reverse Mendelian randomisation analysis was also performed. RESULTS: Alistipes (odds ratio [OR] = 2.269, 95% confidence interval [CI] 1.100-4.679, P = 0.027) and Victivallis (OR = 1.558, 95% CI 1.019-2.380, P = 0.040) were associated with an increased risk of PAH, while Coprobacter (OR = 0.585, 95% CI 0.358-0.956, P = 0.032), Erysipelotrichaceae (UCG003) (OR = 0.494, 95% CI 0.245-0.996, P = 0.049), Lachnospiraceae (UCG008) (OR = 0.596, 95% CI 0.367-0.968, P = 0.036), and Ruminococcaceae (UCG005) (OR = 0.472, 95% CI 0.231-0.962, P = 0.039) protected against PAH. No associations were observed between PAH and gut microbiota-derived metabolites (trimethylamine N-oxide [TMAO] and its precursors betaine, carnitine, and choline), short-chain fatty acids (SCFAs), or diet. Although inverse variance-weighted analysis demonstrated that elevated choline levels were correlated with an increased risk of PAH, the results were not consistent with the sensitivity analysis. Therefore, the association was considered insignificant. Reverse Mendelian randomisation analysis demonstrated that PAH had no causal impact on gut microbiota-derived metabolites but could contribute to increased the levels of Butyricicoccus and Holdemania, while decreasing the levels of Clostridium innocuum, Defluviitaleaceae UCG011, Eisenbergiella, and Ruminiclostridium 5. CONCLUSIONS: Gut microbiota were discovered suggestive evidence of the impacts of genetically predicted abundancy of certain microbial genera on PAH. Results of our study point that the production of SCFAs or TMAO does not mediate this association, which remains to be explained mechanistically.

5-HT4 receptor agonists treatment reduces tau pathology and behavioral deficit in the PS19 mouse model of tauopathy.

Background: Accumulation of tau in synapses in the early stages of Alzheimer's disease (AD) has been shown to cause synaptic damage, synaptic loss, and the spread of tau pathology through trans-synaptically connected neurons. Moreover, synaptic loss correlates with a decline in cognitive function, providing an opportunity to investigate therapeutic strategies to target synapses and synaptic tau to rescue or prevent cognitive decline in AD. One of the promising synaptic targets is the 5-HT4 serotonergic receptor present postsynaptically in the brain structures involved in the memory processes. 5-HT4R stimulation exerts synaptogenic and pro-cognitive effects involving synapse-to-nucleus signaling essential for synaptic plasticity. However, it is not known whether 5-HT4R activation has a therapeutic effect on tau pathology. Methods: The goal of this study was to investigate the impact of chronic stimulation of 5-HT4R by two agonists, prucalopride and RS-67333, in PS19 mice, a model of tauopathy. We utilized gradient assays to isolate pre- and post-synaptic compartments, followed by biochemical analyses for tau species and ubiquitinated proteins in the synaptic compartments and total brain tissue. Next, we performed kinetic assays to test the proteasome's hydrolysis capacity in treatment conditions. Moreover, behavioral tests such as the open field and non-maternal nest-building tests were used to evaluate anxiety-like behaviors and hippocampal-related cognitive functioning in the treatment paradigm. Results: Our results show that 5-HT4R agonism reduced tauopathy, reduced synaptic tau, increased proteasome activity, and improved cognitive functioning in PS19 mice. Our data suggest that enhanced proteasome activity by synaptic mediated signaling leads to the enhanced turnover of tau initially within synapses where the receptors are localized, and over time, the treatment attenuated the accumulation of tau aggregation and improved cognitive functioning of the PS19 mice. Conclusion: Therefore, stimulation of 5-HT4R offers a promising therapy to rescue synapses from the accumulation of toxic synaptic tau, evident in the early stages of AD.

Electrocatalytic C-H/S-H Coupling of Amino Pyrazoles and Thiophenols: Synthesis of Amino Pyrazole Thioether Derivatives.

A mild method for the C-H/S-H coupling of pyrazol-5-amines and thiophenols was developed via electrochemistry, giving diverse amino pyrazole thioether derivatives in 37-98% yields. This electrochemical reaction is sustainable and an atom-efficient approach with good functional group tolerance and scalability by avoiding metal and external chemical oxidants.

Increased ß2-adrenergic signaling promotes fracture healing through callus neovascularization in mice.

Traumatic brain injury (TBI) leads to skeletal changes, including bone loss in the unfractured skeleton, and paradoxically accelerates healing of bone fractures; however, the mechanisms remain unclear. TBI is associated with a hyperadrenergic state characterized by increased norepinephrine release. Here, we identified the ß2-adrenergic receptor (ADRB2) as a mediator of skeletal changes in response to increased norepinephrine. In a murine model of femoral osteotomy combined with cortical impact brain injury, TBI was associated with ADRB2-dependent enhanced fracture healing compared with osteotomy alone. In the unfractured 12-week-old mouse skeleton, ADRB2 was required for TBI-induced decrease in bone formation and increased bone resorption. Adult 30-week-old mice had higher bone concentrations of norepinephrine, and ADRB2 expression was associated with decreased bone volume in the unfractured skeleton and better fracture healing in the injured skeleton. Norepinephrine stimulated expression of vascular endothelial growth factor A and calcitonin gene-related peptide-α (αCGRP) in periosteal cells through ADRB2, promoting formation of osteogenic type-H vessels in the fracture callus. Both ADRB2 and αCGRP were required for the beneficial effect of TBI on bone repair. Adult mice deficient in ADRB2 without TBI developed fracture nonunion despite high bone formation in uninjured bone. Blocking ADRB2 with propranolol impaired fracture healing in mice, whereas the ADRB2 agonist formoterol promoted fracture healing by regulating callus neovascularization. A retrospective cohort analysis of 72 patients with long bone fractures indicated improved callus formation in 36 patients treated with intravenous norepinephrine. These findings suggest that ADRB2 is a potential therapeutic target for promoting bone healing.

Identification of the lateral organ boundary domain gene family and its preservation by exogenous salicylic acid in Cerasus humilis.

The gene family known as the Lateral Organ Boundary Domain (LBD) is responsible for producing transcription factors unique to plants, which play a crucial role in controlling diverse biological activities, including their growth and development. This research focused on examining Cerasus humilis'ChLBD gene, owing to its significant ecological, economic, and nutritional benefits. Examining the ChLBD gene family's member count, physicochemical characteristics, phylogenetic evolution, gene configuration, and motif revealed 41 ChLBD gene family members spread across 8 chromosomes, with ChLBD gene's full-length coding sequences (CDSs) ranging from 327 to 1737 base pairs, and the protein sequence's length spanning 109 (ChLBD30)-579 (ChLBD35) amino acids. The molecular weights vary from 12.068 (ChLBD30) to 62.748 (ChLBD35) kDa, and the isoelectric points span from 4.74 (ChLBD20) to 9.19 (ChLBD3). Categorizing them into two evolutionary subfamilies: class I with 5 branches, class II with 2, the majority of genes with a single intron, and most members of the same subclade sharing comparable motif structures. The results of collinearity analysis showed that there were 3 pairs of tandem repeat genes and 12 pairs of fragment repeat genes in the Cerasus humilis genome, and in the interspecific collinearity analysis, the number of collinear gene pairs with apples belonging to the same family of Rosaceae was the highest. Examination of cis-acting elements revealed that methyl jasmonate response elements stood out as the most abundant, extensively dispersed in the promoter areas of class 1 and class 2 ChLBD. Genetic transcript analysis revealed that during Cerasus humilis' growth and maturation, ChLBD developed varied control mechanisms, with ChLBD27 and ChLBD40 potentially playing a role in managing color alterations in fruit ripening. In addition, the quality of calcium fruit will be affected by the environment during transportation and storage, and it is particularly important to use appropriate means to preserve the fruit. The research used salicylic acid-treated Cerasus humilis as the research object and employed qRT-PCR to examine the expression of six ChLBD genes throughout storage. Variations in the expression of the ChLBD gene were observed when exposed to salicylic acid, indicating that salicylic acid could influence ChLBD gene expression during the storage of fruits. This study's findings lay the groundwork for additional research into the biological role of the LBD gene in Cerasus humilis. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01438-5.

Forkhead-associated phosphopeptide binding domain 1 (FHAD1) deficiency impaired murine sperm motility.

Background: Genetic knockout-based studies conducted in mice provide a powerful means of assessing the significance of a gene for fertility. Forkhead-associated phosphopeptide binding domain 1 (FHAD1) contains a conserved FHA domain, that is present in many proteins with phospho-threonine reader activity. How FHAD1 functions in male fertility, however, remains uncertain. Methods: Fhad1-/- mice were generated by CRISPR/Cas9-mediated knockout, after which qPCR was used to evaluate changes in gene expression, with subsequent analyses of spermatogenesis and fertility. The testis phenotypes were also examined using immunofluorescence and histological staining, while sperm concentrations and motility were quantified via computer-aided sperm analysis. Cellular apoptosis was assessed using a TUNEL staining assay. Results: The Fhad1-/-mice did not exhibit any abnormal changes in fertility or testicular morphology compared to wild-type littermates. Histological analyses confirmed that the testicular morphology of both Fhad1-/-and Fhad1+/+ mice was normal, with both exhibiting intact seminiferous tubules. Relative to Fhad1+/+ mice, however, Fhad1-/-did exhibit reductions in the total and progressive motility of epididymal sperm. Analyses of meiotic division in Fhad1-/-mice also revealed higher levels of apoptotic death during the first wave of spermatogenesis. Discussion: The findings suggest that FHAD1 is involved in both meiosis and the modulation of sperm motility.

Research on the spatial allocation of national fitness resources at the street scale-taking Fuzhou city as an example.

To explore the spatial allocation of national fitness resources at different spatial scales in Fuzhou city to provide useful references for optimizing and enhancing the spatial allocation of national fitness resources and urban planning. The equity, spatial distribution characteristics, accessibility and supply-demand balance of national fitness resources in Fuzhou city are analysed in depth by using the two-step mobile search method of multiple travel modes, the Gini coefficient, and exploratory spatial data analysis methods. The results show that the overall spatial allocation of national fitness resources is in a balanced state, but there are serious inequities and spatial mismatches in each district (county); the spatial distribution of national fitness resources is characterized by centralized agglomeration and surface dispersion, being dense in the south and sparse in the north. Areas with insufficient resources per capita have an agglomeration-type scattering distribution; areas with sufficient resources per capita have a dispersed patch distribution. Access to national fitness resources and the relationship between their supply and demand are characterized by positive spatial concentration; however, the layout of the national fitness resources planned for the old urban areas urgently needs to be optimized, with the Chating and Antai streets serving as centres, to increase the effective supply. Finally,we suggestions that Top-level design should be strengthened, the communalization of sports public services should be promoted, the service capacity and utilization efficiency of national fitness resources should be enhanced, and the construction of national fitness resources in new urban areas and new industrial agglomerations should be accelerated.

Iodine Nutrition, Thyroid-stimulating Hormone, and Related Factors of Postpartum Women from three Different Areas in China: A Cross-sectional Survey.

Objective: Studies on the relationship between iodine, vitamin A (VA), and vitamin D (VD) and thyroid function are limited. This study aimed to analyze iodine and thyroid-stimulating hormone (TSH) status and their possible relationships with VA, VD, and other factors in postpartum women. Methods: A total of 1,311 mothers (896 lactating and 415 non-lactating) from Hebei, Zhejiang, and Guangxi provinces were included in this study. The urinary iodine concentration (UIC), TSH, VA, and VD were measured. Results: The median UIC of total and lactating participants were 142.00 µg/L and 139.95 µg/L, respectively. The median TSH, VA, and VD levels in all the participants were 1.89 mIU/L, 0.44 µg/mL, and 24.04 ng/mL, respectively. No differences in the UIC were found between lactating and non-lactating mothers. UIC and TSH levels were significantly different among the three provinces. The rural UIC was higher than the urban UIC. Obese mothers had a higher UIC and a higher prevalence of excessive TSH. Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group. After adjustment, no linear correlation was observed between UIC and VA/VD. No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion: The mothers in the present study had no iodine deficiency. Region, area type, BMI, and VD may be related to the iodine status or TSH levels.