Enhancement of Frozen-Thawed Human Sperm Quality with Zinc as a Cryoprotective Additive.

BACKGROUND Cryopreservation preserves male fertility, crucial in oncology, advanced age, and infertility. However, it damages sperm motility, membrane, and DNA. Zinc (Zn), an antioxidant, shows promise in improving sperm quality after thawing, highlighting its potential as a cryoprotectant in reproductive medicine. MATERIAL AND METHODS Gradient concentration of ZnSO4 (0, 12.5, 25, 50, and 100 µM) was added in the Glycerol-egg yolk-citrate (GEYC) cryopreservative medium as an extender. Alterations in sperm viability and motility parameters after cryopreservation were detected in each group. Sperm plasma membrane integrity (PMI), acrosome integrity (ACR), DNA fragment index (DFI), and changes in sperm mitochondrial function were examined, including: mitochondrial potential (MMP), sperm reactive oxygen species (ROS), and sperm ATP. RESULTS We found that 50 µM ZnSO4 was the most effective for the curvilinear velocity (VCL) and the average path velocity (VAP) of sperm after cryo-resuscitation. Compared to the Zn-free group, sperm plasma membrane integrity (PMI) was increased, DNA fragmentation index (DFI) was decreased, reactive oxygen species (ROS) was reduced, and mitochondrial membrane potential (MMP) was increased after cryorevival in the presence of 50 µM ZnSO4. CONCLUSIONS Zn ion is one of the antioxidants in the cell. The results of our current clinical study are sufficient to demonstrate that Zn can improve preserves sperm quality during cryopreservation when added to GEYC. The addition of 50 µM ZnSO4 increased curve velocity, mean path velocity, sperm survival (or plasma membrane integrity), and mitochondrial membrane potential while reducing ROS production and DNA breaks compared to GEYC thawed without ZnSO4.

Case report: Paralytic ileus resulted from nirmatrelvir/ritonavir-tacrolimus drug-drug interaction in a systemic lupus erythematosus patient with COVID-19.

Patients with systemic autoimmune rheumatic diseases are at a high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and effective antiviral treatments including nirmatrelvir/ritonavir can improve their outcomes. However, there might be potential drug-drug interactions when these patients take nirmatrelvir/ritonavir together with immunosuppressants with a narrow therapeutic window, such as tacrolimus and cyclosporine. We present a case of paralytic ileus resulting from tacrolimus toxicity mediated by the use of nirmatrelvir/ritonavir in a patient with systemic lupus erythematosus (SLE). A 37-year-old female SLE patient was prescribed nirmatrelvir/ritonavir without discontinuing tacrolimus. She presented to the emergency room with symptoms of paralytic ileus including persistent abdominal pain, nausea, and vomiting, which were verified to be associated with tacrolimus toxicity. The blood concentration of tacrolimus was measured >30 ng/mL. Urgent medical intervention was initiated, while tacrolimus was withheld. The residual concentration was brought within the appropriate range and tacrolimus was resumed 8 days later. Physicians must be aware of the potential DDIs when prescribing nirmatrelvir/ritonavir, especially to those taking immunosuppresants like tacrolimus.

Comprehensive prognostic assessment in kidney cancer: A multidimensional approach analyzing Fufang Sanling granules, genetic variants, and immune infiltration.

This study delves into the potential therapeutic benefits of Fufang Sanling Granules for kidney cancer, focusing on their active components and the underlying mechanisms of their interaction with cancer-related targets. By constructing a drug-active component-target network based on eight herbs, key active compounds such as kaempferol, quercetin, and linolenic acid were identified, suggesting their pivotal roles in modulating immune responses and cellular signaling pathways relevant to cancer progression. The research further identified 51 central drug-disease genes through comprehensive bioinformatics analyses, implicating their involvement in crucial biological processes and pathways. A novel risk score model, encompassing six genes with significant prognostic value for renal cancer, was established and validated, showcasing its effectiveness in predicting patient outcomes through mutation analysis and survival studies. The model's predictive power was further confirmed by its ability to stratify patients into distinct risk groups with significant survival differences, highlighting its potential as a prognostic tool. Additionally, the study explored the relationship between gene expression within the identified black module and the risk score, uncovering significant associations with the extracellular matrix and immune infiltration patterns. This reveals the complex interplay between the tumor microenvironment and cancer progression. The integration of the risk score with clinical parameters through a nomogram significantly improved the model's predictive accuracy, offering a more comprehensive tool for predicting kidney cancer prognosis. In summary, by combining detailed molecular analyses with clinical insights, this study presents a robust framework for understanding the therapeutic potential of Fufang Sanling Granules in kidney cancer. It not only sheds light on the active components and their interactions with cancer-related genes but also introduces a reliable risk score model, paving the way for personalized treatment strategies and improved patient management in the future.

Dynamic N6 -methyladenosine RNA modification regulates peanut resistance to bacterial wilt.

N6 -methyladenosine (m6 A) is the most abundant mRNA modification in eukaryotes and is an important regulator of gene expression as well as many other critical biological processes. However, the characteristics and functions of m6 A in peanut (Arachis hypogea L.) resistance to bacterial wilt (BW) remain unknown. Here, we analyzed the dynamic of m6 A during infection of resistant (H108) and susceptible (H107) peanut accessions with Ralstonia solanacearum (R. solanacearum), the causative agent of BW. Throughout the transcriptome, we identified 'URUAY' as a highly conserved motif for m6 A in peanut. The majority of differential m6 A located within the 3' untranslated region (UTR) of the transcript, with fewer in the exons. Integrative analysis of RNA-Seq and m6 A methylomes suggests the correlation between m6 A and gene expression in peanut R. solanacearum infection, and functional analysis reveals that m6 A-associated genes were related to plant-pathogen interaction. Our experimental analysis suggests that AhALKBH15 is an m6 A demethylase in peanut, leading to decreased m6 A levels and upregulation of the resistance gene AhCQ2G6Y. The upregulation of AhCQ2G6Y expression appears to promote BW resistance in the H108 accession.

Tandem Sulfonylative Annulation/Halogenation of 1,7-Enynes with Sodium Sulfinate and TBAX for the Assembly of 4-Methylenechromanes.

An effective and stereoselective synthesis of halogenated (E)-4-methylenechromanes with a sulfonyl group was developed via the copper-catalyzed sulfonylative annulation/halogenation of 1,7-enynes, in which sodium sulfinates were used as the sulfonyl reagents and tetrabutylammonium halide provided the halogen sources. The formed alkenyl C-X bonds were valuable and can efficiently undergo the subsequent hydrolysis, alkenylation, alkynylation, arylation, alkylthiolation, and alkoxylation to furnish a series of highly functionalized 4-methylenechromanes.

Natural resistance-associated macrophage proteins are involved in tolerance to heavy metal Cd2+ toxicity and resistance to bacterial wilt of peanut (Arachis hypogaea L.).

Peanut (Arachis hypogaea L.) is one of the most important oil and industrial crops. However, heavy-metal pollution and frequent soil diseases, poses a significant threat to the production of green and healthy peanuts. Herein, we investigated the effects of heavy metal Cd2+ toxicity to the peanuts, and screened out two peanut cultivars H108 and YZ 9102 with higher Cd2+-tolerance. RNA-seq revealed that Natural resistance-associated macrophage proteins (NRAMP)-like genes were involved in the Cd2+ stress tolerance in H108. Genome-wide identification revealed that 28, 13 and 9 Nramp-like genes existing in the A. hypogaea, A. duranensis and A. ipaensis, respectively. The 50 peanut NRAMP genes share conserved architectural characters, and they were classified into two groups. Expressions of AhNramps, particularly AhNramp4, AhNramp12, AhNramp19, and AhNramp25 could be greatly induced by not only cadmium toxicity, but also copper and zinc stresses. The expression profiles of AhNramp14, AhNramp16 and AhNramp25 showed significant differences in the H108 (resistance) and H107 (susceptible) under the infection of bacterial wilt. In addition, we found that the expression profiles of AhNramp14, AhNramp16, and AhNramp25 were greatly up- or down-regulated by the application of exogenous salicylic acid, methyl jasmonate, and abscisic acid. The AhNramp25, of which expression was affected by both heavy metal toxicity and bacterial wilt infection, were selected as strong candidate genes for peanut stress breeding. Our findings will provide an additional information required for further analysis of AhNramps involved in tolerance to heavy metal toxicity and resistance to bacterial wilt of peanut.

Cu-Catalyzed Carbocyclization for General Synthesis of N-Containing Heterocyclics Enabled by BrCF2COOEt as a C1 Source.

A practical and efficient copper-catalyzed carbocyclization of 2-functionalized anilines with ethyl bromodifluoroacetate has been developed. Ethyl bromodifluoroacetate is employed as the C1 source via quadruple cleavage in this transformation. This reaction can afford a variety of N-containing heterocyclics with satisfactory yields and excellent functional group compatibility.

Astragaloside IV inhibits epithelial-mesenchymal transition and pulmonary fibrosis via lncRNA-ATB/miR-200c/ZEB1 signaling pathway.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease involving multiple factors and genes. Astragaloside IV (ASV) is one of the main bioactive ingredients extracted from the root of Astragalus membranaceus, which plays an important role in anti-inflammatory, antioxidant and improve cardiopulmonary function. Epithelial-mesenchymal transition (EMT) is a key driver of the process of pulmonary fibrosis, and Zinc finger E-box-binding homeobox 1 (ZEB1) can promote pulmonary fibrosis in an EMT-dependent manner. Here, we found that ASV effectively inhibited the ZEB1 and EMT in both bleomycin (BLM)-induced rat pulmonary fibrosis and TGF-ß1-treated A549 cells. To further elucidate the molecular mechanisms underlying effects of ASV in IPF, we explored the truth using bioinformatics, plasmid construction, immunofluorescence staining, western blotting and other experiments. Dual luciferase reporter assay and bioinformatics proved that miR-200c not only acts as an upstream regulatory miRNA of ZEB1 but also has binding sites for the lncRNA-ATB. In A549 cell-based EMT models, ASV reduced the expression of lncRNA-ATB and upregulated miR-200c. Furthermore, overexpression of lncRNA-ATB and silencing of miR-200c reversed the down-regulation of ZEB1 and the inhibition of EMT processes by ASV. In addition, the intervention of ASV prevented lncRNA-ATB as a ceRNA from regulating the expression of ZEB1 through sponging miR-200c. Taken together, the results showed that ASV inhibited the EMT process through the lncRNA-ATB/miR-200c/ZEB1 signaling pathway, which provides a novel approach to the treatment of IPF.

Coordinated Lipid Mobilization during Seed Development and Germination in Peanut (Arachis hypogaea L.).

Peanut (Arachis hypogaea L.) is one of the most important oil crops in the world due to its lipid-rich seeds. Lipid accumulation and degradation play crucial roles in peanut seed maturation and seedling establishment, respectively. Here, we utilized lipidomics and transcriptomics to comprehensively identify lipids and the associated functional genes that are important in the development and germination processes of a large-seed peanut variety. A total of 332 lipids were identified; triacylglycerols (TAGs) and diacylglycerols were the most abundant during seed maturation, constituting 70.43 and 16.11%, respectively, of the total lipids. Significant alterations in lipid profiles were observed throughout seed maturation and germination. Notably, TAG (18:1/18:1/18:2) and (18:1/18:2/18:2) peaked at 23386.63 and 23392.43 nmol/g, respectively, at the final stage of seed development. Levels of hydroxylated TAGs (HO-TAGs) increased significantly during the initial stage of germination. Accumulation patterns revealed an inverse relationship between free fatty acids and TAGs. Lipid degradation was determined to be regulated by diacylglycerol acyltransferase, triacylglycerol lipase, and associated transcription factors, predominantly yielding oleic acid, linoleic acid, and linolenic acid. Collectively, the results of this study provide valuable insights into lipid dynamics during the development and germination of large-seed peanuts, gene resources, and guiding future research into lipid accumulation in an economically important crop.

The workload change and depression among emergency medical staff after the open policy during COVID-19: a cross-sectional survey in Shandong, China.

Introduction: In the middle of December 2022, the Chinese government adjusted the lockdown policy on coronavirus disease 2019 (COVID-19), a large number of infected patients flooded into the emergency department. The emergency medical staff encountered significant working and mental stress while fighting the COVID-19 pandemic. We aimed to investigate the workload change, and the prevalence and associated factors for depression symptoms among emergency medical staff after the policy adjustment. Methods: We conducted a cross-sectional online survey of emergency medical staff who fought against COVID-19 in Shandong Province during January 16 to 31, 2023. The respondents' sociodemographic and work information were collected, and they were asked to complete the 9-item Patient Health Questionnaire (PHQ-9) then. Univariate and multivariate logistic regression analyses were applied to identify the potential associated factors for major depression. Results: Nine hundred and sixteen emergency medical personnel from 108 hospitals responded to this survey. The respondents' weekly working hours (53.65 ± 17.36 vs 49.68 ± 14.84) and monthly night shifts (7.25 ± 3.85 vs 6.80 ± 3.77) increased after the open policy. About 54.3% of the respondents scored more than 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. In univariate analysis, being doctors, living with family members aged ≤16 or ≥ 65 years old, COVID-19 infection and increased weekly working hours after the open policy were significantly associated with a PHQ-9 score ≥ 10 points. In the multivariate analysis, only increased weekly working hours showed significant association with scoring ≥10 points. Conclusion: Emergency medical staff' workload had increased after the open policy announcement, which was strongly associated with a higher PHQ-9 scores, indicating a very high risk for major depression. Emergency medical staff working as doctors or with an intermediate title from grade-A tertiary hospitals had higher PHQ-9 scores, while COVID-19 infection and weekly working hours of 60 or more after the open policy were associated with higher PHQ-9 scores for those from grade-B tertiary hospitals. Hospital administrators should reinforce the importance of targeted emergency medical staff support during future outbreaks.

Hazardous risk of antibiotic resistance genes: Host occurrence, distribution, mobility and vertical transmission from different environments to corn silage.

Antibiotic resistance genes (ARGs) are one of the emerging contaminants posing a great deal of hazardous risk to public health. This study employed metagenomics and deciphered the potential risk of the antibiotic resistome and their vertical transfer to ensiled whole-crop corn silage harvested from six climate zones: 1. Warm temperate-fully humid-hot summer (Cfa), 2. Arid-desert-cold arid (BWk), 3. Snow-desert-cold summer (Dwc), 4. Snow-desert-hot summer (Dwa), 5. Arid-steppe-cold arid (BSk), and 6. Equatorial-desert (Aw) based on the Köppen-Geiger climate classification in China. The findings demonstrate a high diversity of ARGs, which is related to the drug classes of tetracycline, ciprofloxacin, lincosamide, fosfomycin, and beta lactam. Resistome variations are mostly related to variations in microbial composition and fermentation characteristics of the silages from different climate zones, which are indirectly influenced by environmental conditions. The most dominating ARGs in corn silage were tetM, acrA, H-NS, lnuA, emrR, and KpnG, which is primarily hosted by Klebsiella and Lactobacilli. There were 5 high-risk ARGs (tetM, bacA, SHV-1, dfrA17, and QnrS1) in silage from different climate zones, and the tetM was the most prevalent high-risk ARG. However, throughout the ensiling process, the abundance of ARGs, and mobile ARGs were reduced. The resistome contamination in silage from Tibet (Dwc) with high altitude and harsh environment was relatively low due to the low variety and abundance of ARGs, the low abundance of mobile ARGs and high-risk ARGs. In addition, most of the bacteria responsible for the silage fermentation were also found to be the hosts to the ARGs, although their abundance decreased after 90 d of silage fermentation. Hence, we alert the existence of ARGs-related biosafety risk in silages and call for more attention to the silage ARGs, their hosts, and mobile genetic elements in order to curtail their possible risk to public health.

Synthesis of Trifluoromethylated Dibenzoxepines via Palladium-Catalyzed Tandem C-O Bond Formation/C-H Arylation.

A palladium-catalyzed cyclization reaction of phenols with trifluoromethyl-containing ortho-bromo-ß-chlorostyrenes has been developed. In the presence of palladium(II) acetate, tricyclohexylphosphine, and cesium carbonate, a variety of 6-trifluoromethyldibenzo[b,d]oxepines were prepared in moderate to good yields through the tandem O-alkenylation of general phenols and subsequent C-H arylation.

Dynamic DNA methylation modification in peanut seed development.

Cytosine methylation is an important epigenetic modification involved in regulation of plant development. However, the epigenetic mechanisms governing peanut seed development remain unclear. Herein, we generated DNA methylation profiles of developmental seeds of peanut H2014 and its smaller seed mutant H1314 at 15 and 60 days after pegging (DAP, S1, S4). Accompanying seed development, globally elevated methylation was observed in both lines. The mutant had a higher methylation level of 31.1% than wild type at S4, and 27.1-35.9% of the differentially methylated regions (DMRs) between the two lines were distributed in promoter or genic regions at both stages. Integrated methylome and transcriptome analysis revealed important methylation variations closely associated with seed development. Furthermore, some genes showed significantly negative correlation of expression with the methylation level within promoter or gene body. The results provide insights into the roles of DNA methylation in peanut seed development.

Unmanned Aerial Vehicle Assisted Post-Disaster Communication Coverage Optimization Based on Internet of Things Big Data Analysis.

The rapid development of Internet of Things (IoT) communication devices has brought about significant convenience. However, simultaneously, the destruction of communication infrastructure in emergency situations often leads to communication disruptions and challenges in information dissemination, severely impacting rescue operations and the safety of the affected individuals. To address this challenge, IoT big data analytics and unmanned aerial vehicle (UAV) technologies have emerged as key elements in the solution. By analyzing large-scale sensor data, user behavior, and communication traffic, IoT big data analytics can provide real-time communication demand prediction and network optimization strategies, offering decision support for post-disaster communication reconstruction. Given the unique characteristics of post-disaster scenarios, this paper proposes a UAV-assisted communication coverage strategy based on IoT big data analytics. This strategy employs UAVs in a cruising manner to assist in communication by partitioning the target area into multiple cells, each satisfying the minimum data requirements for user communication. Depending on the distribution characteristics of users, flight-communication or hover-communication protocols are selectively employed to support communication. By optimizing the UAV's flight speed and considering the coverage index, fairness index, and average energy efficiency of the mission's target area, the Inner Spiral Cruise Communication Coverage (IS-CCC) algorithm is proposed to plan the UAV's cruising trajectory and achieve UAV-based communication coverage. Simulation results demonstrate that this strategy can achieve energy-efficient cruising communication coverage in regions with complex user distributions, thereby reducing energy consumption in UAV-based communication.

A Microservice and Serverless Architecture for Secure IoT System.

In cross-border transactions, the transmission and processing of logistics information directly affect the trading experience and efficiency. The use of Internet of Things (IoT) technology can make this process more intelligent, efficient, and secure. However, most traditional IoT logistics systems are provided by a single logistics company. These independent systems need to withstand high computing loads and network bandwidth when processing large-scale data. Additionally, due to the complex network environment of cross-border transactions, the platform's information security and system security are difficult to guarantee. To address these challenges, this paper designs and implements an intelligent cross-border logistics system platform that combines serverless architecture and microservice technology. This system can uniformly distribute the services of all logistics companies and divide microservices based on actual business needs. It also studies and designs corresponding Application Programming Interface (API) gateways to solve the interface exposure problem of microservices, thereby ensuring the system's security. Furthermore, asymmetric encryption technology is used in the serverless architecture to ensure the security of cross-border logistics data. The experiments show that this research solution validates the advantages of combining serverless architecture and microservices, which can significantly reduce the operating costs and system complexity of the platform in cross-border logistics scenarios. It allows for resource expansion and billing based on application program requirements at runtime. The platform can effectively improve the security of cross-border logistics service processes and meet cross-border transaction needs in terms of data security, throughput, and latency.

PSW1, an LRR receptor kinase, regulates pod size in peanut.

Pod size is a key agronomic trait that greatly determines peanut yield, the regulatory genes and molecular mechanisms that controlling peanut pod size are still unclear. Here, we used quantitative trait locus analysis to identify a peanut pod size regulator, POD SIZE/WEIGHT1 (PSW1), and characterized the associated gene and protein. PSW1 encoded leucine-rich repeat receptor-like kinase (LRR-RLK) and positively regulated pod stemness. Mechanistically, this allele harbouring a 12-bp insertion in the promoter and a point mutation in the coding region of PSW1 causing a serine-to-isoleucine (S618I) substitution substantially increased mRNA abundance and the binding affinity of PSW1 for BRASSINOSTEROID INSENSITIVE1-ASSOCIATED RECEPTOR KINASE 1 (BAK1). Notably, PSW1HapII (super-large pod allele of PSW1) expression led to up-regulation of a positive regulator of pod stemness PLETHORA 1 (PLT1), thereby resulting in larger pod size. Moreover, overexpression of PSW1HapII increased seed/fruit size in multiple plant species. Our work thus discovers a conserved function of PSW1 that controls pod size and provides a valuable genetic resource for breeding high-yield crops.

TBAI-Mediated Cyclization and Methylsulfonylation of Propargylic Amides with Dimethyl Sulfite.

A tetramethylammonium iodide (TBAI)-mediated cyclization and methylsulfonylation of propargylic amides enabled by dimethyl sulfite as a SO2 surrogate and methyl source have been developed. The transition metal-free and oxidant-free reaction provides a practical and efficient approach for the selective synthesis of methylsulfonyl oxazoles in moderate to excellent yields with good functional group compatibility.

An inkjet-printed bendable antenna for wearable electronics.

104Flexible antennas, which can conform to the skin and transfer signals to terminals, are particularly useful for wearable electronics. Bending, which frequently occurs to flexible devices, significantly affects the performance of flexible antennas. Inkjet printing has been used as an additive manufacturing technology for fabricating flexible antenna in recent years. However, there is little research on the bending performance of inkjet printing antenna in both simulation and experiment. This paper proposes a bendable coplanar waveguide antenna with a small size of 30 × 30 × 0.05 mm3 by combining the advantages of fractal antenna and serpentine antenna, which realizes the ultra-wideband feature and avoids the problems of large dielectric layer thickness (greater than 1 mm) and large volume of traditional microstrip antenna at the same time. The structure of the antenna was optimized by simulation using the Ansys high-frequency structure simulator, and the antenna was fabricated on a flexible polyimide substrate by inkjet printing. The experimental characterization results show that the central frequency of the antenna is 2.5 GHz, the return loss is -32 dB, and the absolute bandwidth is 850 MHz, which is consistent with the simulation results. The results demonstrate that the antenna has anti-interference capability and can meet the ultra-wideband characteristics. When the traverse and longitudinal bending radius are greater than 30 mm and skin proximity greater than 1 mm, the resonance frequency offsets are mostly within 360 MHz, and return losses of the bendable antenna are within the -14 dB compared with the no bending condition. The results exhibit that the proposed inkjet-printed flexible antenna is bendable and promising for wearable applications.

Effect of interstitial fluid pH on transdermal glucose extraction by reverse iontophoresis.

Reverse iontophoresis (RI) is a promising technology in the field of continuous glucose monitoring (CGM), offering significant advantages such as finger-stick-free operation, wearability, and non-invasiveness. In the glucose extraction process based on RI, the pH of the interstitial fluid (ISF) is a critical factor that needs further investigation, as it directly influences the accuracy of transdermal glucose monitoring. In this study, a theoretical analysis was conducted to investigate the mechanism by which pH affects the glucose extraction flux. Modeling and numerical simulations performed at different pH conditions indicated that the zeta potential was significantly impacted by the pH, thereby altering the direction and flux of the glucose iontophoretic extraction. A screen-printed glucose biosensor integrated with RI extraction electrodes was developed for ISF extraction and glucose monitoring. The accuracy and stability of the ISF extraction and glucose detection device were demonstrated with extraction experiments using different subdermal glucose concentrations ranging from 0 to 20 mM. The extraction results for different ISF pH values exhibited that at 5 mM and 10 mM subcutaneous glucose, the extracted glucose concentration was increased by 0.08212 mM and 0.14639 mM for every 1 pH unit increase, respectively. Furthermore, the normalized results for 5 mM and 10 mM glucose demonstrated a linear correlation, indicating considerable potential for incorporating a pH correction factor in the blood glucose prediction model used to calibrate glucose monitoring.