New Monoterpenoid Glycosides from the Fruits of Hypericum patulum Thunb.

The whole Hypericum patulum Thunb. plant is utilized in traditional medicine for its properties of clearing heat, detoxifying, soothing meridians, relaxing the liver, and stopping bleeding. In folk medicine, it is frequently used to treat hepatitis, colds, tonsillitis, and bruises. Phytochemical investigation of a 30% ethanol extract of the fresh ripe fruits of H. patulum has resulted in the isolation of two new pinane-type monoterpenoid glycosides 1-2, named patulumside E-F, and three new chain-shaped monoterpenoid glycosides 3-5, named patulumside G-H, J. Their structures were determined using extensive spectroscopic techniques, such as HR-ESI-MS, 1D and 2D NMR spectroscopy, and electronic circular dichroism (ECD) calculation. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. This research represents the inaugural comprehensive phytochemical study of H. patulum, paving the way for further exploration of monoterpenoid glycosides.

Microbial fungicides can positively affect aubergine photosynthetic properties, soil enzyme activity and microbial community structure.

Background: This study examined the effects of microbial agents on the enzyme activity, microbial community construction and potential functions of inter-root soil of aubergine (Fragaria × ananassa Duch.). This study also sought to clarify the adaptability of inter-root microorganisms to environmental factors to provide a theoretical basis for the stability of the microbiology of inter-root soil of aubergine and for the ecological preservation of farmland soil. Methods: Eggplant inter-root soils treated with Bacillus subtilis (QZ_T1), Bacillus subtilis (QZ_T2), Bacillus amyloliquefaciens (QZ_T3), Verticillium thuringiensis (QZ_T4) and Verticillium purpureum (QZ_T5) were used to analyse the effects of different microbial agents on the inter-root soils of aubergine compared to the untreated control group (QZ_CK). The effects of different microbial agents on the characteristics and functions of inter-root soil microbial communities were analysed using 16S rRNA and ITS (internal transcribed spacer region) high-throughput sequencing techniques. Results: The bacterial diversity index and fungal diversity index of the aubergine inter-root soil increased significantly with the application of microbial fungicides; gas exchange parameters and soil enzyme activities also increased. The structural and functional composition of the bacterial and fungal communities in the aubergine inter-root soil changed after fungicide treatment compared to the control, with a decrease in the abundance of phytopathogenic fungi and an increase in the abundance of beneficial fungi in the soil. Enhancement of key community functions, reduction of pathogenic fungi, modulation of environmental factors and improved functional stability of microbial communities were important factors contributing to the microbial stability of fungicide-treated aubergine inter-root soils.

Comprehensive identification and expression analysis of FAR1/FHY3 genes under drought stress in maize (Zea mays L.).

Background: FAR1/FHY3 transcription factors are derived from transposase, which play important roles in light signal transduction, growth and development, and response to stress by regulating downstream gene expression. Although many FAR1/FHY3 members have been identified in various species, the FAR1/FHY3 genes in maize are not well characterized and their function in drought are unknown. Method: The FAR1/FHY3 family in the maize genome was identified using PlantTFDB, Pfam, Smart, and NCBI-CDD websites. In order to investigate the evolution and functions of FAR1 genes in maize, the information of protein sequences, chromosome localization, subcellular localization, conserved motifs, evolutionary relationships and tissue expression patterns were analyzed by bioinformatics, and the expression patterns under drought stress were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Results: A total of 24 ZmFAR members in maize genome, which can be divided into five subfamilies, with large differences in protein and gene structures among subfamilies. The promoter regions of ZmFARs contain abundant abiotic stress-responsive and hormone-respovensive cis-elements. Among them, drought-responsive cis-elements are quite abundant. ZmFARs were expressed in all tissues detected, but the expression level varies widely. The expression of ZmFARs were mostly down-regulated in primary roots, seminal roots, lateral roots, and mesocotyls under water deficit. Most ZmFARs were down-regulated in root after PEG-simulated drought stress. Conclusions: We performed a genome-wide and systematic identification of FAR1/FHY3 genes in maize. And most ZmFARs were down-regulated in root after drought stress. These results indicate that FAR1/FHY3 transcription factors have important roles in drought stress response, which can lay a foundation for further analysis of the functions of ZmFARs in response to drought stress.

Pesticide residues in vegetables from Gansu province, China and risk assessment by Monte Carlo simulation.

To assess the dietary exposure risks of pesticide residues in vegetables for the general population, the presence of 39 pesticides was determined in 70 samples, of which 13 were detected. The most frequently detected pesticide was bifenthrin, with a detection rate of 35.7%, mainly found in gingers, followed by isoprocarb and acephate (11.4%) and dimethoate (8.6%). In 17.1% of the samples two or more pesticide residues were found. Acute, chronic and chronic cumulative dietary exposure risk was assessed. Chronic exposure risks were determined by Monte Carlo Simulation (MCS). Estimated chronic exposure to carbofuran, omethoate, disulfoton and dimethoate of approximately 49%, 52%, 40% and 3%, respectively, were at non-carcinogenic human risk. Acute exposure risk to acephate was considered to be of concern due to the high acute hazard quotient (aHQ).

Optimising desired gain indices to maximise selection response.

Introduction: In plant breeding, we often aim to improve multiple traits at once. However, without knowing the economic value of each trait, it is hard to decide which traits to focus on. This is where "desired gain selection indices" come in handy, which can yield optimal gains in each trait based on the breeder's prioritisation of desired improvements when economic weights are not available. However, they lack the ability to maximise the selection response and determine the correlation between the index and net genetic merit. Methods: Here, we report the development of an iterative desired gain selection index method that optimises the sampling of the desired gain values to achieve a targeted or a user-specified selection response for multiple traits. This targeted selection response can be constrained or unconstrained for either a subset or all the studied traits. Results: We tested the method using genomic estimated breeding values (GEBVs) for seven traits in a bread wheat (Triticum aestivum) reference breeding population comprising 3,331 lines and achieved prediction accuracies ranging between 0.29 and 0.47 across the seven traits. The indices were validated using 3,005 double haploid lines that were derived from crosses between parents selected from the reference population. We tested three user-specified response scenarios: a constrained equal weight (INDEX1), a constrained yield dominant weight (INDEX2), and an unconstrained weight (INDEX3). Our method achieved an equivalent response to the user-specified selection response when constraining a set of traits, and this response was much better than the response of the traditional desired gain selection indices method without iteration. Interestingly, when using unconstrained weight, our iterative method maximised the selection response and shifted the average GEBVs of the selection candidates towards the desired direction. Discussion: Our results show that the method is an optimal choice not only when economic weights are unavailable, but also when constraining the selection response is an unfavourable option.

Influence of different penetrating cryoprotectants and egg yolk level on the post-thaw quality of sperm.

Objective: The Hu sheep is a renowned breed known for its high reproductive rate. It is in estrus all year round, and its breeding population is gradually expanding. However, the current techniques for cryopreserving semen have limited effectiveness, which hinders the continuous development of this species. The purpose of this study is to explore the effects of different penetrating cryoprotectants (CPAs) and egg yolk (EY) concentrations on the cryopreservation of Hu ram semen to determine the most effective combination. Methods: In this study, the effects of glycerol (GLY), ethylene glycol (EG), dimethylacetamide (DMA), dimethyl sulfoxide (DMSO), different proportions of GLY and EG, EY on sperm quality after thawing were investigated by detecting sperm total motility (TM), progressive motility (PM), straight-line velocity (VSL), curvilinear velocity (VCL), average path velocity (VAP), amplitude of lateral head displacement (ALH), wobble movement coefficient (WOB), average motion degree (MAD), functional integrity (plasma membrane integrity, acrosome integrity) and reactive oxygen species (ROS) level. Results: When GLY and EG were added together, compared to other concentration groups, 6% GLY significantly (p < 0.05) increased TM, PM, plasma membrane integrity, and acrosome integrity of thawed sperm. Additionally, it significantly (p < 0.05) decreased the ROS level of sperm. In this study, the TM, PM and membrane integrity of the 6% EG were significantly (p < 0.05) higher than those of the control, 1% GLY+5% EG and 6% GLY+6% EG groups. Compared to other concentration groups, 20% EY significantly (p < 0.05) improved the TM, PM, and plasma membrane integrity of thawed sperm. However, the integrity of the acrosome increased with the higher concentration of EY. Conclusion: In conclusion, the post-thawed Hu ram semen diluted with a diluent containing 6% GLY and 20% EY exhibited higher quality compared to the other groups.

Effects of Different Diluents and Freezing Methods on Cryopreservation of Hu Ram Semen.

The purpose of this study was to investigate the effects of different diluents and freezing methods on the quality of thawed sperm after cryopreservation and find an inexpensive and practical method for freezing Hu ram semen for use in inseminations under farm conditions. Ejaculates were collected from five Hu rams. In experiment I, ejaculates were diluted with eight different freezing diluents (basic diluents A, B, C, D, E, F, G, and H). After dilution and cooling, the samples were loaded into 0.25 mL straws and frozen using the liquid nitrogen fumigation method. In experiment II, diluent C was used as the basic diluent and the semen was frozen using liquid nitrogen fumigation and two program-controlled cooling methods. For analysis, frozen samples were evaluated in terms of motility parameters (total motility (TM), progressive motility (PM)), biokinetic characteristics (straight-line velocity (VSL), average path velocity (VAP), curvilinear velocity (VCL), amplitude of lateral head displacement (ALH), wobble movement coefficient (WOB), average motion degree (MAD)), reactive oxygen species (ROS) level, and membrane and acrosome integrity. In experiment I, diluent C had higher TM, PM, and acrosome and membrane integrity and lower ROS compared to other extenders (p < 0.05) except diluent A. Diluent C exhibited higher (p < 0.05) VCL, VAP, ALH, WOB, and MAD compared to diluents B, D, E, and F. In experiment II, TM and all biokinetic characteristics did not show significant differences (p > 0.05) amongst the three freezing methods. Liquid nitrogen fumigation resulted in higher (p < 0.05) PM, membrane integrity, acrosome integrity, and lower ROS level compared to the program. In conclusion, the thawed semen diluted with diluent C had higher quality compared to other diluents. The liquid nitrogen fumigation demonstrated superior semen cryopreservation effects compared to the program-controlled cooling method using diluent C.

Identification of potential crucial cuproptosis-related genes in myocardial ischemia-reperfusion injury through the bioinformatic analysis.

BACKGROUND: Cuproptosis is known to regulate diverse physiological functions in many diseases, but its role in regulating Myocardial Ischemia-Reperfusion Injury (MI/RI) remains unclear. METHODS: For this purpose, the MI/RI microarray datasets GSE61592 were downloaded from the Gene Expression Omnibus (GEO) database, and the Differently Expressed Genes (DEGs) in MI/RI were identified using R software. Moreover, the MI/RI mice model was established to confirm further the diagnostic value of Pyruvate Dehydrogenase B (Pdhb), Dihydrolipoamide S-acetyltransferase (Dlat), and Pyruvate dehydrogenase E1 subunit alpha 1 (Pdhα1). RESULTS: The analysis of microarray datasets GSE61592 revealed that 798 genes were upregulated and 768 were downregulated in the myocardial tissue of the ischemia-reperfusion injury mice. Furthermore, Dlat, Pdhb, Pdhα1, and cuproptosis-related genes belonged to the downregulated genes. The receiver operating characteristics curve analysis results indicated that the Dlat, Pdhb, and Pdhα1 levels were downregulated in MI/RI and were found to be potential biomarkers for MI/RI diagnosis and prognosis. Similarly, analysis of Dlat, Pdhb, and Pdhα1 levels in the MI/RI mice revealed Pdhb being the key diagnostic marker. CONCLUSIONS: This study demonstrated the prognostic value of cuproptosis-related genes (Dlat, Pdhb, and Pdhα1), especially Pdhb, MI/RI, providing new insight into the MI/RI treatment.

Weighted gene co-expression network analysis reveals genes related to growth performance in Hu sheep.

Hu sheep are a unique breed in our country with great reproductive potential, the extent of whose breeding has been steadily rising in recent years. The study subjects in this experiment were 8-month-old Hu sheep (n = 112). First of all, the growth performance, slaughter performance and meat quality of their eye muscle quality were assessed, meanwhile their live weight, carcass weight, body length, body height, chest circumference, chest depth and tube circumference were respectively 33.81 ± 5.47 kg, 17.43 ± 3.21 kg, 60.36 ± 4.41 cm, 63.25 ± 3.88 cm, 72.03 ± 5.02 cm, 30.70 ± 2.32 cm and 7.36 ± 0.56 cm, with a significant difference between rams and ewes (P < 0.01). Following that, transcriptome sequencing was done, and candidate genes related to growth performance were identified using the weighted co-expression network analysis (WGCNA) approach, which was used to identified 15 modules, with the turquoise and blue modules having the strongest association with growth and slaughter performance, respectively. We discovered hub genes such as ARHGAP31, EPS8, AKT3, EPN1, PACS2, KIF1C, C12H1orf115, FSTL1, PTGFRN and IFIH1 in the gene modules connected with growth and slaughter performance. Our research identifies the hub genes associated with the growth and slaughter performance of Hu sheep, which play an important role in their muscle growth, organ and cartilage development, blood vessel development and energy metabolic pathways. Our findings might lead to the development of potentially-useful biomarkers for the selection of growth and slaughterer performance-related attributes of sheep and other livestock.

Clinical Value of Bioresorbable Scaffolds in Patients with Non-left Main Bifurcation Lesions Undergoing Percutaneous Coronary Intervention.

Aim: To compare the operation-related indexes, complication rates, and cardiac function indexes of bioresorbable scaffolds with drug-eluting scaffolds in coronary non-left main stem lesions and to clarify the clinical value of bioresorbable scaffolds in percutaneous coronary intervention for non-left main stem lesions. Methods: The retrospective study sample consisted of 60 non-left main stem lesions treated using bioresorbable stent or drug-eluting stents between June 2022 and June 2023. Comparison of surgical operation-related indexes, intraoperative and postoperative complications, cardiac function indexes, adverse cardiovascular events, and surgical success rate between the two groups. Results: The surgical operation time and X-ray exposure time of the experimental group were shorter than those of the control group, and contrast agent dosage was lower than that of the control group (P < .05). Left ventricular ejection fraction (LVEF) was higher than that in the control group at one month after surgery, and left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) in the experimental group was lower than that in the control group, and the difference was statistically significant (P < .05). The total incidence of major adverse cardiovascular events was lower in the experimental group than in the control group (15.6% VS. 71.4%)(P < .05). Conclusion: Bioresorbable scaffolds are more effective than drug-eluting scaffolds in treating non-left main stem lesions by percutaneous coronary intervention. Furthermore, bioresorbable scaffolds could be considered a preferable option for certain patients undergoing percutaneous coronary intervention for non-left main stem lesions.

Cardioprotective role of oleanolic acid in patients with type 2 diabetes mellitus.

Background: Patients with type 2 diabetes mellitus (T2DM) experience a decline in cardiac function, resulting in poor prognosis. Therefore, restoration of cardiac function and improvement of myocardial fibrosis is an important treatment goal for patients with T2DM. Material and methods: The chemical structure of oleanolic acid(OA) was downloaded from PubChem and uploaded to PharmMapper. GeneCards and OMIM databases were searched for genes related to OA and disease and plotted into a Venn diagram. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using R software. Then, a mouse model of diabetes mellitus was established, and ELISA, echocardiographic analysis of cardiac function, TUNEL assay, and reactive oxygen species assay were performed. Results: Network pharmacology analysis identified the related targets and potential molecular mechanisms underlying the effects of OA in T2DM. ELISA, echocardiographic analysis of cardiac function, and TUNEL assay results showed that OA inhibits apoptosis and improves apoptotic indexes in mice with T2DM-induced myocardial injury. Conclusion: The results demonstrate the myocardial protective effect of OA in this mouse model.

[Discrimination of anti-tumor and cardioprotective effect quality markers from Aidi Injection based on "spider web" mode].

Chinese medicinal preparations play an equally important role in reducing toxicity and treating tumors. Few studies discriminate the quality markers(Q-markers) conferring different therapeutic effects of traditional Chinese medicine preparations. Therefore, we take Aidi Injection(AD) as an example to comprehensively identify the Q-markers of anti-tumor and cardioprotective effects based on the "spider web" mode. Firstly, based on the principle of measurability, the chemical components in the prescription were qualitatively analyzed, and then the components with high content and capable to be measured were quantitatively analyzed as measurable evaluation indexes. Based on the principle of stability, the effects of light and temperature on the content of each component of AD were investigated as indicators of stability. Based on the principle of compatibility, the compounds were classified according to the law of compatibility of sovereign, minister, assistant, and guide medicinal materials in the prescription. Based on the principle of efficacy, the anti-tumor and antiangiogenic activities of the Q-markers were evaluated, and their synergistic effects with doxorubicin(DOX) in inhibiting tumorigenesis and angiogenesis and lowering cardiotoxicity were evaluated as the evaluation indexes of effectiveness. The seven-dimensional spider web of "compatibility-content-stability-antitumor activity-synergistic anti-tumor activity with DOX-antiangiogenic activity-synergistic anti-angiogenic activity with DOX" and the four-dimensional spider web of "compatibility-content-stability-protective effects against DOX-induced myocardial toxicity" were established, on the basis of which the Q-markers of anti-tumor and cardioprotective effects of AD were comprehensively analyzed. The results showed that 12 components were selected as the Q-markers of AD, among which cantharidin, ginsenoside Re, ginsenoside Rb_1, astragaloside Ⅱ, cryptochlorogenic acid, and ginsenoside Rg_2 were the anti-tumor Q-markers of AD. Ginsenoside Rd, isofraxidin, syringin, eleutheroside E, calycosin-7-O-ß-D-glucoside, and azelaic acid were the cardioprotective Q-markers of AD. Taking into account both the anti-tumor and cardioprotective effects, these Q-markers could cover the four herbs constituting the prescription. The findings provides a scientific basis for the quality control of AD and an effective method for identifying comprehensive and reasonable Q-markers for the two effects of Chinese medicinal preparations.

Remote ischemic conditioning may improve graft function following kidney transplantation: a systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Remote ischemic conditioning (RIC) has the potential to benefit graft function following kidney transplantation by reducing ischemia-reperfusion injury; however, the current clinical evidence is inconclusive. This meta-analysis with trial sequential analysis (TSA) aimed to determine whether RIC improves graft function after kidney transplantation. METHODS: A comprehensive search was conducted on PubMed, Cochrane Library, and EMBASE databases until June 20, 2023, to identify all randomized controlled trials that examined the impact of RIC on graft function after kidney transplantation. The primary outcome was the incidence of delayed graft function (DGF) post-kidney transplantation. The secondary outcomes included the incidence of acute rejection, graft loss, 3- and 12-month estimated glomerular filtration rates (eGFR), and the length of hospital stay. Subgroup analyses were conducted based on RIC procedures (preconditioning, perconditioning, or postconditioning), implementation sites (upper or lower extremity), and graft source (living or deceased donor). RESULTS: Our meta-analysis included eight trials involving 1038 patients. Compared with the control, RIC did not significantly reduce the incidence of DGF (8.8% vs. 15.3%; risk ratio = 0.76, 95% confidence interval [CI], 0.48-1.21, P = 0.25, I2 = 16%), and TSA results showed that the required information size was not reached. However, the RIC group had a significantly increased eGFR at 3 months after transplantation (mean difference = 2.74 ml/min/1.73 m2, 95% CI: 1.44-4.05 ml/min/1.73 m2, P < 0.0001, I2 = 0%), with a sufficient evidence suggested by TSA. The secondary outcomes were comparable between the other secondary outcomes. The treatment effect of RIC did not differ between the subgroup analyses. CONCLUSION: In this meta-analysis with trial sequential analysis, RIC did not lead to a significant reduction in the incidence of DGF after kidney transplantation. Nonetheless, RIC demonstrated a positive correlation with 3-month eGFR. Given the limited number of patients included in this study, well-designed clinical trials with large sample sizes are required to validate the renoprotective benefits of RIC. TRIAL REGISTRATION: This systematic review and meta-analysis was registered at the International Prospective Register of Systematic Reviews (Number CRD42023464447).

Uncovering novel drug targets for bipolar disorder: a Mendelian randomization analysis of brain, cerebrospinal fluid, and plasma proteomes.

BACKGROUND: There is a clear demand for innovative therapeutics for bipolar disorder (BD). METHODS: We integrated the largest BD genome-wide association study (GWAS) dataset (NCase = 41 917, NControl = 371 549) with protein quantitative trait loci from brain, cerebrospinal fluid, and plasma. Using a range of integrative analyses, including Mendelian randomization (MR), Steiger filter analysis, Bayesian colocalization, and phenome-wide MR analysis, we prioritized novel drug targets for BD. Additionally, we incorporated data from the UK Biobank (NCase = 1064, NControl = 365 476) and the FinnGen study (NCase = 7006, NControl = 329 192) for robust biological validation. RESULTS: Through MR analysis, we found that in the brain, downregulation of DNM3, MCTP1, ABCB8 and elevation of DFNA5 and PDF were risk factors for BD. In cerebrospinal fluid, increased BD risk was associated with increased levels of FRZB, AGRP, and IL36A and decreased CTSF and LRP8. Plasma analysis revealed that decreased LMAN2L, CX3CL1, PI3, NCAM1, and TIMP4 correlated with increased BD risk, but ITIH1 did not. All these proteins passed Steiger filtering, and Bayesian colocalization confirmed that 12 proteins were colocalized with BD. Phenome-wide MR analysis revealed no significant side effects for potential drug targets, except for LRP8. External validation further underscored the concordance between the primary and validation cohorts, confirming MCTP1, DNM3, PDF, CTSF, AGRP, FRZB, LMAN2L, NCAM1, and TIMP4 are intriguing targets for BD. CONCLUSIONS: Our study identified druggable proteins for BD, including MCTP1, DNM3, and PDF in the brain; CTSF, AGRP, and FRZB in cerebrospinal fluid; and LMAN2L, NCAM1, and TIMP4 in plasma, delineating promising avenues to development of novel therapies.

Association between premature vascular smooth muscle cells senescence and vascular inflammation in Takayasu's arteritis.

OBJECTIVES: Arterial wall inflammation and remodelling are the characteristic features of Takayasu's arteritis (TAK). It has been proposed that vascular smooth muscle cells (VSMCs) are the main targeted cells of inflammatory damage and participate in arterial remodelling in TAK. Whether VSMCs are actively involved in arterial wall inflammation has not been elucidated. Studies have shown that cellular senescence in tissue is closely related to local inflammation persistence. We aimed to investigate whether VSMCs senescence contributes to vascular inflammation and the prosenescent factors in TAK. METHODS: VSMCs senescence and senescence-associated secretory phenotype were detected by histological examination, bulk RNA-Seq and single-cell RNA-seq conducted on vascular surgery samples of TAK patients. The key prosenescent factors and the downstream signalling pathway were investigated in a series of in vitro and ex vivo experiments. RESULTS: Histological findings, primary cell culture and transcriptomic analyses demonstrated that VSMCs of TAK patients had the features of premature senescence and contributed substantially to vascular inflammation by upregulating the expression of senescence-associated inflammatory cytokines. IL-6 was found to be the critical cytokine that drove VSMCs senescence and senescence-associated mitochondrial dysfunction in TAK. Mechanistically, IL-6-induced non-canonical mitochondrial localisation of phosphorylated STAT3 (Tyr705) prevented mitofusin 2 (MFN2) from proteasomal degradation, and subsequently promoted senescence-associated mitochondrial dysfunction and VSMCs senescence. Mitochondrial STAT3 or MFN2 inhibition ameliorated VSMCs senescence in ex vivo cultured arteries of TAK patients. CONCLUSIONS: VSMCs present features of cellular senescence and are actively involved in vascular inflammation in TAK. Vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence.

Effect of fumigation height and time on cryopreservation of ram semen.

The cooling rate is a crucial factor in the process of freezing semen, influencing the overall freezing effectiveness. The height and time of fumigation can significantly impact the rate of cooling. Appropriate cooling rates can help minimize the formation of ice crystals in spermatozoa and reduce potential damage to them. Therefore, the aim of this study was to evaluate the effect of different fumigation heights and time for the cryopreservation of Hu ram semen. Experiments I-IV assessed the effect of semen cryopreservation by testing the post-thawed spermatozoa total motility (TM), progressive motility (PM) and kinetic parameters fumigated at distances of 2, 4, 6 and 8 cm for durations of 5, 10, 15 and 20 min, respectively. Based on the results of experiments I to IV, experiment V evaluated the effect of semen cryopreservation by testing the post-thawed spermatozoa TM, PM, kinetic parameters, plasma membrane integrity, acrosome integrity and reactive oxygen species (ROS) level fumigated at distances of 2, 4, 6 and 8 cm for duration of 20 min. The results indicated that fumigation at 2 cm for 20 min significantly (P < 0.05) improved spermatozoa TM, PM, mean angular displacement (MAD), plasma membrane integrity and acrosome integrity compared to other groups. Additionally, it significantly (P < 0.05) reduced spermatozoa ROS level compared to the 6 and 8 cm groups. In conclusion, fumigation for 20 min at a distance of 2 cm from the liquid nitrogen surface is the most suitable cooling method for the cryopreservation of Hu ram semen.

Association between per- and poly-fluoroalkyl substances and nonalcoholic fatty liver disease: A nested case-control study in northwest China.

Per- and poly-fluoroalkyl substances (PFAS) have been reported to have hepatotoxic effects. However, it is unclear whether they are linked to non-alcoholic fatty liver disease (NAFLD). This nested case-control study focused on the epidemiological links between PFAS and the prevalence of NAFLD. We selected 476 new cases of NAFLD and 952 age- and sex-matched controls from the Jinchang cohort population between 2014 and 2019. Serum concentrations of PFAS were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Only PFAS with a detection rate of ≥90 % were included for analysis, which included PFPeA, PFOA, PFNA, PFHxS, PFOS, and 9Cl-PF3ONS. The relationship between single and co-exposure to PFAS and the occurrence of NAFLD was evaluated using conditional logistic regression, Quantile g-computation (QgC), and Bayesian kernel machine regression (BKMR) model. Logistic regression indicated that PFPeA, PFOA, and 9Cl-PF3ONS were positive correlation with the incidence of NAFLD after adjusting for confounders, with odds ratios (OR) and 95 % confidence interval (CI) of 3.13 (95 % CI: 2.53, 3.86), 1.39 (95 % CI: 1.12, 1.73), and 1.41 (95 % CI: 1.20, 1.66), respectively. PFNA, PFHxS, and PFOS were nonlinearly and negatively associated with the incidence of NAFLD, with OR (95 % CI) of 0.53 (0.46, 0.62), 0.83 (0.73, 0.95), and 0.52 (0.44, 0.61), respectively. QgC showed a significant joint effect of PFAS mixture on NAFLD onset (OR: 1.52, 95 % CI: 1.24, 1.88). BKMR showed a weak positive trend between PFAS mixtures and NAFLD incidence. Positive correlations were primarily driven by PFPeA and 9Cl-PF3ONS, while negative correlations were mainly influenced by PFNA and PFOS. The BKMR model also suggested that there was an interaction between PFOS and PFNA and other four PFAS compounds. In conclusion, our findings suggest that individual and co-exposure to PFAS is associated with a risk of NAFLD onset.

Pivotal Evaluation of Novel Dedicated Venous Stent for Iliofemoral Venous Obstruction: A Prospective Cohort Study.

PURPOSE: The purpose was to evaluate the clinical outcomes of a dedicated venous stent with the tripartite composite segments for the treatment of iliofemoral venous obstruction (IVO) in a mixed cohort of nonthrombotic iliac vein lesion (NIVL) and post-thrombotic syndrome (PTS) over a period of 12 months. METHODS: The Grency Trial is a prospective, multicenter, single-arm, open-label, pivotal study, which was conducted at 18 large tertiary hospitals in China from August 2019 to October 2020. A total of 133 hospitalized patients were screened and 110 patients with clinical, etiology, anatomical, and pathophysiology clinical class (CEAP) clinical grade C>3 and iliac vein stenosis >50% or occlusion, including 72 patients with NIVL and 38 patients with PTS, were implanted with Grency venous stents. Primary endpoint was stent patency at 12 months follow-up, and secondary outcomes were technical success; improvement in venous clinical severity score (VCSS) at 3, 6, and 12 month follow-up; and rates of clinical adverse events. RESULTS: Among 110 patients who were implanted with Grency venous stents, 107 patients completed the 12 month follow-up. All 129 stents were successfully implanted in 110 limbs. Twelve-month primary patency rate was 94.39% [95% confidence interval [CI]=88.19%-97.91%] overall, and 100% [94.94%-100%] and 83.33% [67.19%-93.63%] in the NIVL and PTS subgroups, respectively. Venous clinical severity score after iliac vein stenting improved significantly up to 12 months follow-up. There were 3 early major adverse events (1 intracerebral hemorrhage and 2 stent thrombosis events related to anticoagulation therapy), and 7 late major adverse events (1 cardiovascular death, 1 intracranial hemorrhage with uncontrolled hypertension, and 5 in-stent restenosis cases without stent fractures or migration). CONCLUSIONS: The Grency venous stent system appeared excellent preliminary safe and effective for IVO treatment. Further large-scale studies with longer-term follow-up are needed to evaluate long-term patency and durability of stent. CLINICAL IMPACT: The design of venous stents for iliofemoral venous obstruction (IVO) must address engineering challenges distinct from those encountered in arterial stenting. The Grency venous stent, a nitinol self-expanding stent specifically tailored for IVO, features a composite structure designed to meet the stent requirements of various iliac vein segments. The Grency Trial is a prospective, multicenter, single-arm, open-label pivotal study aimed at evaluating the efficacy and safety of the Grency stent system. Following a 12-month follow-up period, the Grency venous stent system has demonstrated both safety and efficacy in treating iliofemoral venous outflow obstruction.

Biased virus transmission following sequential coinfection of Aedes aegypti with dengue and Zika viruses.

BACKGROUND: Mosquito-borne arboviruses are expanding their territory and elevating their infection prevalence due to the rapid climate change, urbanization, and increased international travel and global trade. Various significant arboviruses, including the dengue virus, Zika virus, Chikungunya virus, and yellow fever virus, are all reliant on the same primary vector, Aedes aegypti. Consequently, the occurrence of arbovirus coinfection in mosquitoes is anticipated. Arbovirus coinfection in mosquitoes has two patterns: simultaneous and sequential. Numerous studies have demonstrated that simultaneous coinfection of arboviruses in mosquitoes is unlikely to exert mutual developmental influence on these viruses. However, the viruses' interplay within a mosquito after the sequential coinfection seems intricated and not well understood. METHODOLOGY/PRINCIPAL FINDINGS: We conducted experiments aimed at examining the phenomenon of arbovirus sequential coinfection in both mosquito cell line (C6/36) and A. aegypti, specifically focusing on dengue virus (DENV, serotype 2) and Zika virus (ZIKV). We firstly observed that DENV and ZIKV can sequentially infect mosquito C6/36 cell line, but the replication level of the subsequently infected ZIKV was significantly suppressed. Similarly, A. aegypti mosquitoes can be sequentially coinfected by these two arboviruses, regardless of the order of virus exposure. However, the replication, dissemination, and the transmission potential of the secondary virus were significantly inhibited. We preliminarily explored the underlying mechanisms, revealing that arbovirus-infected mosquitoes exhibited activated innate immunity, disrupted lipid metabolism, and enhanced RNAi pathway, leading to reduced susceptibility to the secondary arbovirus infections. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that, in contrast to simultaneous arbovirus coinfection in mosquitoes that can promote the transmission and co-circulation of these viruses, sequential coinfection appears to have limited influence on arbovirus transmission dynamics. However, it is important to note that more experimental investigations are needed to refine and expand upon this conclusion.

Two-Step Perovskite Solar Cells with > 25% Efficiency: Unveiling the Hidden Bottom Surface of Perovskite Layer.

While significant efforts in surface engineering have been devoted to the conversion process of lead iodide (PbI2) into perovskite and top surface engineering of perovskite layer with remarkable progress, the exploration of residual PbI2 clusters and the hidden bottom surface on perovskite layer have been limited. In this work, a new strategy involving 1-butyl-3-methylimidazolium acetate (BMIMAc) ionic liquid (IL) additives is developed and it is found that both the cations and the anions in ILs can interact with the perovskite components, thereby regulating the crystallization process and diminishing the residue PbI2 clusters as well as filling vacancies. The introduction of BMIMAc ILs induces the formation of a uniform porous PbI2 film, facilitating better penetration of the second-step organic salt and fostering a more extensive interaction between PbI2 and the organic salt. Surprisingly, the oversized residual PbI2 clusters at the bottom surface of the perovskite layer completely diminish. In addition, advanced depth analysis techniques including depth-resolved grazing-incidence wide-angle X-ray scattering (GIWAXS) and bottom thinning technology are employed for a comprehensive understanding of the reduction in residual PbI2. Leveraging effective PbI2 management and regulation of the perovskite crystallization process, the champion devices achieve a power conversion efficiency (PCE) of 25.06% with long-term stability.