Assessment of safety profile of ivabradine in real-world scenario using FDA adverse event reporting system database.

BACKGROUND: Ivabradine is primarily indicated for patients with sinus rhythm and a heart rate ≥ 75 beats/min, who have NYHA class II-IV chronic heart failure with systolic dysfunction. There is currently a lack of large-scale, real-world studies concerning its drug adverse reactions. RESEARCH DESIGN & METHODS: This research assesses the side effects of ivabradine by analyzing reports of adverse events (AEs) from the FDA's Adverse Event Reporting System (FAERS) database. To evaluate the importance of these AEs, four sequential analytic strategies were utilized. RESULTS: In total, 2,701 ivabradine-related AE reports were identified in the FAERS database. We identified 26 ivabradine-induced AEs, each with more than 20 reports, including some significant AEs not mentioned on the product label. The timing of AEs was also analyzed, with the majority of AEs occurring within the first month of ivabradine use. Gender-specific analysis indicates that female have a higher risk of AEs, such as off-label use, tachycardia, drug effectiveness for unapproved indications, and rash compared to male. CONCLUSION: This study provides important information for maximizing the usage of ivabradine, increasing its efficacy, and reducing any possible negative effects. The actual clinical use of the medication will be greatly aided by this knowledge.

Advanced electrolytes for high-performance aqueous zinc-ion batteries.

Aqueous zinc-ion batteries (AZIBs) have garnered significant attention in the realm of large-scale and sustainable energy storage, primarily owing to their high safety, low cost, and eco-friendliness. Aqueous electrolytes, serving as an indispensable constituent, exert a direct influence on the electrochemical performance and longevity of AZIBs. Nonetheless, conventional aqueous electrolytes often encounter formidable challenges in AZIB applications, such as the limited electrochemical stability window and the zinc dendrite growth. In response to these hurdles, a series of advanced aqueous electrolytes have been proposed, such as "water-in-salt" electrolytes, aqueous eutectic electrolytes, molecular crowding electrolytes, and hydrogel electrolytes. This comprehensive review commences by presenting an in-depth overview of the fundamental compositions, principles, and distinctive characteristics of various advanced aqueous electrolytes for AZIBs. Subsequently, we systematically scrutinizes the recent research progress achieved with these advanced aqueous electrolytes. Furthermore, we summarizes the challenges and bottlenecks associated with these advanced aqueous electrolytes, along with offering recommendations. Based on the optimization of advanced aqueous electrolytes, this review outlines future directions and potential strategies for the development of high-performance AZIBs. This review is anticipated to provide valuable insights into the development of advanced electrolyte systems for the next generation of stable and sustainable multi-valent secondary batteries.

Meta-Attention Deep Learning for Smart Development of Metasurface Sensors.

Optical metasurfaces with pronounced spectral characteristics are promising for sensor applications. Currently, deep learning (DL) offers a rapid manner to design various metasurfaces. However, conventional DL models are usually assumed as black boxes, which is difficult to explain how a DL model learns physical features, and they usually predict optical responses of metasurfaces in a fuzzy way. This makes them incapable of capturing critical spectral features precisely, such as high quality (Q) resonances, and hinders their use in designing metasurface sensors. Here, a transformer-based explainable DL model named Metaformer for the high-intelligence design, which adopts a spectrum-splitting scheme to elevate 99% prediction accuracy through reducing 99% training parameters, is established. Based on the Metaformer, all-dielectric metasurfaces based on quasi-bound states in the continuum (Q-BIC) for high-performance metasensing are designed, and fabrication experiments are guided potently. The explainable learning relies on spectral position encoding and multi-head attention of meta-optics features, which overwhelms traditional black-box models dramatically. The meta-attention mechanism provides deep physics insights on metasurface sensors, and will inspire more powerful DL design applications on other optical devices.

Novel Water-Splitting Electrolyzer Design Incorporating a Gas Diffusion Electrode and a Gel Membrane for Highly Efficient Hydrogen Production.

Advancements in cost-effective, high-performance alkaline water-splitting systems are crucial for the hydrogen industry. While the significance of electrode material design has been widely acknowledged, the practical implementation of these advancements remains challenging. In this study, we focused on the holistic design of the electrolysis system and successfully developed a novel alkaline water-splitting electrolyzer. The unique configuration of our electrolyzer allows the designed NiFe-LDH/carbon cloth gas diffusion anode to interact solely with the PVA-based gel membrane and air, enabling the direct discharge of oxygen into the gas phase. This innovative feature accelerates anode bubble overflow, reduces gas interference, and decreases the system impedance by minimizing electrode spacing. As a result, by utilizing the NiFeSn-alloy/nickel mesh cathode, our electrolyzer achieves a high current density of 308 mA cm-2 at a cell voltage of 2.0 V and demonstrates exceptional stability over 1000 h.

Multiplex assays reveal anti-EBV antibody profile and its implication in detection and diagnosis of nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) is detected in nearly 100% of nonkeratinizing nasopharyngeal carcinoma (NPC) and EBV-based biomarkers are used for NPC screening in endemic regions. Immunoglobulin A (IgA) against EBV nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA), and recently identified anti-BNLF2b antibodies have been shown to be the most effective screening tool; however, the screening efficacy still needs to be improved. This study developed a multiplex serological assay by testing IgA and immunoglobulin G (IgG) antibodies against representative EBV antigens that are highly transcribed in NPC and/or function crucially in viral reactivation, including BALFs, BNLF2a/b, LF1, LF2, and Zta (BZLF1). Among them, BNLF2b-IgG had the best performance distinguishing NPC patients from controls (area under the curve: 0.951, 95% confidence interval [CI]: 0.913-0.990). Antibodies to lytic antigens BALF2 and VCA were significantly higher in advanced-stage than in early-stage tumors; in contrast, antibodies to latent protein EBNA1 and early lytic antigen BNLF2b were not correlated with tumor progression. Accordingly, a novel strategy combining EBNA1-IgA and BNLF2b-IgG was proposed and validated improving the integrated discrimination by 15.8% (95% CI: 9.8%-21.7%, p < .0001) compared with the two-antibody method. Furthermore, we found EBV antibody profile in patients was more complicated compared with that in healthy carriers, in which stronger correlations between antibodies against different phases of antigens were observed. Overall, our serological assay indicated that aberrant latent infection of EBV in nasopharyngeal epithelial cells was probably a key step in NPC initiation, while more lytic protein expression might be involved in NPC progression.

Origin and dispersal history of Hepatitis B virus in Eastern Eurasia.

Hepatitis B virus is a globally distributed pathogen and the history of HBV infection in humans predates 10000 years. However, long-term evolutionary history of HBV in Eastern Eurasia remains elusive. We present 34 ancient HBV genomes dating between approximately 5000 to 400 years ago sourced from 17 sites across Eastern Eurasia. Ten sequences have full coverage, and only two sequences have less than 50% coverage. Our results suggest a potential origin of genotypes B and D in Eastern Asia. We observed a higher level of HBV diversity within Eastern Eurasia compared to Western Eurasia between 5000 and 3000 years ago, characterized by the presence of five different genotypes (A, B, C, D, WENBA), underscoring the significance of human migrations and interactions in the spread of HBV. Our results suggest the possibility of a transition from non-recombinant subgenotypes (B1, B5) to recombinant subgenotypes (B2 - B4). This suggests a shift in epidemiological dynamics within Eastern Eurasia over time. Here, our study elucidates the regional origins of prevalent genotypes and shifts in viral subgenotypes over centuries.

The physiological response of oriental river prawn Macrobrachium nipponense to starvation-induced stress.

Environmental stresses play critical roles in the physiology of crustaceans. Food deprivation is an important environmental factor and a regular occurrence in both natural aquatic habitats and artificial ponds. However, the underlying physiological response mechanisms to starvation-caused stress in crustaceans are yet to be established. In the present study, the hepatopancreas tissue of Macrobrachium nipponense was transcriptome analyzed and examined for starvation effects on oxidative stress, DNA damage, autophagy, and apoptosis across four fasting stages (0 (control group), 7, 14, and 21 days). These results indicated that a ROS-mediated regulatory mechanism is critical to the entire fasting process. At the initial stage of starvation (fasting 0 d ~ 7 d), ROS concentration increased gradually, activating antioxidant enzymes to protect the cellular machinery from the detrimental effects of oxidative stress triggered by starvation-induced stress. ROS content production (hydrogen peroxide and superoxide anion) then rose continuously with prolonged starvation (fasting 7 d ~ 14 d), reaching peak levels and resulting in autophagy in hepatopancreas cells. During the final stages of starvation (fasting 14 d ~ 21 d), excessive ROS induced DNA damage and cell apoptosis. Furthermore, autophagolysosomes and apoptosis body were further identified with transmission electron microscopy. These findings lay a foundation for further scrutiny of the molecular mechanisms combating starvation-generated stress in M. nipponense and provide fishermen with the theoretical guidance for adopting fasting strategies in M. nipponense aquaculture.

Global, Regional, and National Burden of COPD Attributable to Occupational Particulate Matter, Gases, and Fumes, 1990-2019: Findings from the Global Burden of Disease Study 2019.

Background: A study aimed to estimate the burden of Chronic obstructive pulmonary disease (COPD) caused by occupational exposure to particulate matter, gases, and fumes in 204 countries from 1990 to 2019. Methods: Data on the deaths number, age-standardized mortality rates (ASMR), and age-standardized disability-adjusted life years (DALYs) rates (ASDR) of COPD attributable to occupational particulate matter, gases, and fumes were collected from the GBD study 2019. We also investigated the association between the ASDR and SDI. Results: There were 517.7 thousand deaths [95% UI: 413.9 to 634.5] in 2019. The number of deaths increased from 1990 to 2019. The ASMR and ASDR were 6.61 (5.24 to 8.17) and 143.02 (118.56 to 168.69) in 2019, respectively, representing a 46% and 44.5% decrease since 1990. China had the highest number of deaths [200,748.4 (151,897.6 to 260,703.9)], while Nepal had the highest ASMR [39 (27.7 to 50)] and ASDR [724.5 (549 to 894.2)]. Males and females 75-79 and 80-84 years old had the highest number of COPD deaths. A negative correlation was observed when SDI > 0.4, whereas a positive correlation was found when SDI < 0.4. Conclusion: From 1990 to 2019, there was an increase in the number of deaths, but a decline in ASMR and ASDR globally. Besides, there was a heterogeneous burden of COPD attributable to occupational particulate matter, gases, and fumes across regions and countries. It is important to develop and implement strategies to prevent and reduce the burden of COPD attributable to occupational particulate matter, gases, and fumes.

Prognosis of comatose patients with reduced EEG montage by combining quantitative EEG features in various domains.

Objective: As the frontoparietal network underlies recovery from coma, a limited frontoparietal montage was used, and the prognostic values of EEG features for comatose patients were assessed. Methods: Collected with a limited frontoparietal EEG montage, continuous EEG recordings of 81 comatose patients in ICU were used retrospectively. By the 60-day Glasgow outcome scale (GOS), the patients were dichotomized into favorable and unfavorable outcome groups. Temporal-, frequency-, and spatial-domain features were automatically extracted for comparison. Partial correlation analysis was applied to eliminate redundant factors, and multiple correspondence analysis was used to explore discrimination between groups. Prognostic characteristics were calculated to assess the performance of EEG feature-based predictors established by logistic regression. Analyses were performed on all-patients group, strokes subgroup, and traumatic brain injury (TBI) subgroup. Results: By analysis of all patients, raised burst suppression ratio (BSR), suppressed root mean square (RMS), raised power ratio of ß to α rhythm (ß/α), and suppressed phase-lag index between F3 and P4 (PLI [F3, P4]) were associated with unfavorable outcome, and yielded AUC of 0.790, 0.811, 0.722, and 0.844, respectively. For the strokes subgroup, the significant variables were BSR, RMS, θ/total, θ/δ, and PLI (F3, P4), while for the TBI subgroup, only PLI (F3, P4) was significant. BSR combined with PLI (F3, P4) gave the best predictor by cross-validation analysis in the all-patients group (AUC = 0.889, 95% CI: 0.819-0.960). Conclusion: Features extracted from limited frontoparietal montage EEG served as valuable coma prognostic tools, where PLI (F3, P4) was always significant. Combining PLI (F3, P4) with features in other domains may achieve better performance. Significance: A limited-montage EEG coupled with an automated algorithm is valuable for coma prognosis.

Global burden of ischemic heart disease associated with high red and processed meat consumption: an analysis of 204 countries and territories between 1990 and 2019.

BACKGROUND: Multiple studies have indicated an association between red and processed meat consumption and the incidence of ischemic heart disease (IHD). In this study, we aimed to assess the burden of IHD caused by a diet high in red and processed meat in 204 countries and territories between 1990 and 2019, using data from the Global Burden of Disease (GBD) 2019. METHODS: We extracted data from the GBD 2019, which included the number of deaths, age-standardized mortality rates (ASMR), disability-adjusted life years (DALYs), and age-standardized DALYs rates (ASDR) attributed to IHD caused by a diet high in red and processed meat. We then calculated the burden of IHD attributable to a high intake of red and processed meat in each country and territory, stratified by age, sex, and socio-demographic index (SDI). RESULTS: Globally, a high intake of red meat was responsible for 351,200 (95% uncertainty interval (UI): 559,000-642,700) deaths from IHD in 2019, while a high intake of processed meat was associated with 171,700 (95% UI: 30,100-320,000) deaths from IHD. Between 1990 and 2019, while the corresponding age-standardized rates declined, the numbers of deaths and DALYs increased. China had the highest number of deaths [98,386.9 (95% UI: 14,999.3-189,812.7)] caused by a high intake of red meat, while United States of America [33,129.6 (95% UI: 7,150-59,593.8)] was associated with the highest number of deaths caused by high intake of processed meat for IHD in 2019. Males experienced a greater burden of IHD caused by a high intake of red and processed meat than females. The ASMR and ASDR of IHD attributed to a high intake of red meat decreased in countries with high SDI, high-middle SDI and low SDI, while the ASMR and ASDR of IHD attributed to a high intake of processed meat decreased only in countries with high SDI and high-middle SDI. CONCLUSION: Although there is a decline in the ASMR and ASDR of IHD caused by a high intake of red and processed meat, there is also an increase in deaths and DALYs number globally. Additionally, there is a heterogeneous burden of IHD related to a high intake of red and processed meat across regions and countries, with males experiencing a greater burden than females. Implementing targeted policies and interventions is required to reduce the burden of IHD caused by a high intake of red and processed meat.

Plasmonic metasurface enhanced by nanobumps for label-free biosensing of lung tumor markers in serum.

Plasmonic metasurface biosensing has excellent potential in label-free detection of tumor biomarkers. In general, a variety of plasmonic metasurface nanofabrication leads to various degree of metallic surface roughness. However, the metasurface roughness effects on plasmonic sensing of tumor markers have been barely reported. Here we fabricate high-roughness (HR) gold nanohole metasurfaces with nanobumps and investigate their biosensing in comparison with the low-roughness (LR) counterparts. The HR metasurfaces demonstrate the surface sensitivity of multilayer polyelectrolyte molecules, which is 57.0% higher than the LR ones. The HR metasurfaces also illuminate higher immunoassay sensitivity to multiple lung cancer biomarkers, including carcinoembryonic antigen, neuron-specific enolase and cytokeratin fragment 21-1. The highest increasement of tumor marker sensitivity is up to 71.4%. The biosensing enhancement is attributed to the introduction of gold nanobumps on metasurfaces, which provides more hot-spot regions, higher localized near-field intensity and better optical impedance matching. Furthermore, the biosensing of HR metasurfaces effectively covers the threshold values of tumor markers for early lung cancer diagnosis, and is used for the detection of clinical serum samples. The testing deviation is less than 4% compared with commercial immunoassay, which implies promising applications on medical examinations. Our research provides a scientific guide to surface roughness engineering for plasmonic metasensing in the future point-of-care testing.

Label-free plasmonic metasensing of PSA and exosomes in serum for rapid high-sensitivity diagnosis of early prostate cancer.

Prostate-specific antigen (PSA) test is widely used to diagnose early prostate cancer (PCa). Its low sensitivity, especially in the gray zone, usually incurs overtreatment or missed diagnosis. As an emerging tumor marker, exosomes have attracted great interest in non-invasive diagnosis of PCa. However, the quick direct detection of exosomes in serum is still a big challenge for convenient screening of early PCa due to their high-degree heterogeneity and complexity. Here we develop the label-free biosensors based on wafer-scale plasmonic metasurfaces, and establish a flexible spectral methodology of exosomes profiling, which facilitates their identification and quantification in serum. We combine the metasurfaces functionalized by anti-PSA and anti-CD63, respectively, and build a portable immunoassay system to detect serum PSA and exosomes simultaneously within 20 min. Our scheme can discriminate early PCa from benign prostatic hyperplasia with a diagnostic sensitivity of 92.3%, which is much higher that of 58.3% for conventional PSA tests. The receiver operating characteristic analysis in clinical trials demonstrates significant PCa distinguishing capability with an area under the curve up to 99.4%. Our work provides a rapid and powerful approach for precise diagnosis of early PCa, and will inspire more exosomes metasensing studies for other early cancer screening.

Integrated microRNA-mRNA analysis reveals a possible molecular mechanism of enteritis susceptibility in Litopenaeus vannamei.

Enteritis is one of the main diseases affecting Pacific whiteleg shrimp (Litopenaeus vannamei) in recent years, and it has resulted in huge losses to the aquaculture industry. Prior to this study, the molecular mechanism underlying enteritis in L. vannamei was unclear, and comprehensive multi-omics analysis had not been conducted. In this study, 1209 differentially expressed genes (DEGs) were identified from the hepatopancreas of L. vannamei with and without enteritis. Kyoto Encyclopedia of Genes and Genomes analysis showed that genes were significantly enriched in immune, metabolic, and endocrine regulatory pathways. Forty-eight significantly different microRNAs (miRNAs) were identified in the miRNA-Seq analysis. Further functional annotation analysis showed that the regulatory pathway of target gene enrichment of differentially expressed miRNAs was consistent with DEGs. Through miRNA-mRNA integration analysis, 47 meaningful miRNA-mRNA pairs were obtained, of which melanogenesis and pancreatic secretion were considered key pathways. Subsequent miRNA-mRNA interaction network analysis revealed that mja-miR-6493-3p, Mja-miR-6494, novel-198, novel-272, novel-261, novel-200, novel-183, novel-184, novel-237, and novel-192 may be key miRNAs involved in the regulation of these two signaling pathways. Finally, the RAS signaling pathway was found to inhibit the translation level of proteins in the hepatopancreas. These results suggest that target gene integration analysis of mRNA-miRNA can reveal the molecular mechanism underlying enteritis in L. vannamei and also provide valuable new insights for resisting enteritis.

Responses of bacterial and three sub-microeukaryote communities in the water of white shrimp Penaeus vannamei aquaculture ponds in two polyculture models.

Polyculture operations in freshwater aquaculture ponds can disrupt microbial communities. High-throughput sequencing was used to assess the impact of polyculture operations on bacterial and three sub-microeukaryote communities (fungi, zooplankton, and eukaryotic phytoplankton) in Penaeus vannamei aquaculture ponds containing oriental river prawns and giant freshwater prawns, respectively. The results showed that the bacterial community was less sensitive than the microeukaryote communities to both the polyculture activity and environmental variations. The polyculture of giant freshwater prawns rather than oriental river prawns was the primary factor affecting the beta diversity of the three sub-microeukaryote communities. This may be due to the larger biomass of the polyculture varieties of giant freshwater prawns compared with oriental river prawns. The polyculture activity of giant freshwater prawns with a higher density and that of oriental river prawns with a lower density increased the stochasticity of the community assembly of the three sub-microeukaryote communities. It also affected the topological properties of the microbial communities, including greater correlations between ecosystem elements, and reducing the correlations among zooplanktons. The eukaryotic phytoplankton was the only microbial community that could also be explained by nutrient variation (mainly the total nitrogen). This highlights the potential role of the eukaryotic phytoplankton as a suitable indicator of the effects of nutrient input into ecosystems.

Trends in the Burden of COPD Attributable to Ambient PM2.5 Exposure in China 1990-2019: An Age-Period-Cohort Analysis.

Objective: Exposure to ambient particulate matter (PM2.5) is the leading risk factor for developing chronic obstructive pulmonary disease (COPD) in China. The present study aimed to investigate the trends in COPD mortality attributable to ambient PM2.5 exposure in China from 1990 to 2019. Methods: Data on COPD burden attributable to ambient PM2.5 exposure in China were extracted from the Global Burden of Disease (GBD) study 2019. The estimated annual percentage change (EAPC) was used to assess COPD mortality from 1990 to 2019. The APC model was used to analyze the temporal trends in the rate of COPD mortality attributable to ambient PM2.5 exposure according to age, period, and cohort. Results: Exposure to ambient PM2.5 contributed to 192.4 thousand deaths in 1990 and 263.6 thousand deaths in 2019. The age-standardized mortality rate (ASMR) and the age-standardized disability-adjusted life year rate (ASDR) due to ambient PM2.5 exposure showed a gradual downward trend, the ASMR and ASDR in 2019 decreased to 16.6 per 100,000 with an EAPC of -2.82 (95% CI: -8.61 to 3.34) and 278.6 per 100,000 with an EAPC of -2.02 (95% CI: -7.85 to 4.19), compared to those in 1990, respectively. The relative risk (RR) of COPD increased with age in females, while in males, mortality significantly increased from the levels among those in the 60-64 age group to that among those in the 90-94 age group. In the period group, the RR of COPD in males remained above 1.0 from the 2000 to 2004 period, but it gradually decreased in females. The cohort effect showed an overall downward trend. Conclusion: Although the ASMR and ASDR are decreasing in Chinese patients with COPD, the number of deaths due to COPD is increasing. Ambient PM2.5 exposure is more harmful in males and older people above 60 years of age.

Long-term trends in human body size track regional variation in subsistence transitions and growth acceleration linked to dairying.

Evidence for a reduction in stature between Mesolithic foragers and Neolithic farmers has been interpreted as reflective of declines in health, however, our current understanding of this trend fails to account for the complexity of cultural and dietary transitions or the possible causes of phenotypic change. The agricultural transition was extended in primary centers of domestication and abrupt in regions characterized by demic diffusion. In regions such as Northern Europe where foreign domesticates were difficult to establish, there is strong evidence for natural selection for lactase persistence in relation to dairying. We employ broad-scale analyses of diachronic variation in stature and body mass in the Levant, Europe, the Nile Valley, South Asia, and China, to test three hypotheses about the timing of subsistence shifts and human body size, that: 1) the adoption of agriculture led to a decrease in stature, 2) there were different trajectories in regions of in situ domestication or cultural diffusion of agriculture; and 3) increases in stature and body mass are observed in regions with evidence for selection for lactase persistence. Our results demonstrate that 1) decreases in stature preceded the origins of agriculture in some regions; 2) the Levant and China, regions of in situ domestication of species and an extended period of mixed foraging and agricultural subsistence, had stable stature and body mass over time; and 3) stature and body mass increases in Central and Northern Europe coincide with the timing of selective sweeps for lactase persistence, providing support for the "Lactase Growth Hypothesis."

Affinity Exploration of SARS-CoV-2 RBD Variants to mAb-Functionalized Plasmonic Metasurfaces for Label-Free Immunoassay Boosting.

Plasmonic metasurfaces (PMs) functionalized with the monoclonal antibody (mAb) are promising biophotonic sensors for biomolecular interaction analysis and convenient immunoassay of various biomarkers, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Previous PM biosensing suffers from the slow affinity detection rate and lack of sufficient immunoassay studies on various SARS-CoV-2 variants. Here, we develop a high-efficiency affinity testing method based on label-free PM sensors with mAbs and demonstrate their binding characteristics to 12 spike receptor binding domain (RBD) variants of SARS-CoV-2. In addition to the research of plasmonic near-field influence on surface biomolecule sensing, we provide a comprehensive report about the Langmuir binding equilibrium of molecular kinetics between 12 SARS-CoV-2 RBD variants and mAb-functionalized PMs, which plays a crucial role in label-free immunosensing. A high-affinity mAb can be combined with the highly sensitive propagating plasmonic mode to boost the detection of SARS-CoV-2 variants. Owing to a better understanding of molecular dynamics on PMs, we develop an ultrasensitive biosensor of the SARS-CoV-2 Omicron variant. The experiments show great distinguishment of P < 0.0001 from respiratory diseases induced by other viruses, and the limit of detection is 2 orders smaller than the commercial colloidal gold immunoassay. Our study shows the label-free biosensing by low-cost wafer-scale PMs, which will provide essential information on biomolecular interaction and facilitate high-precision point-of-care testing for emerging SARS-CoV-2 variants in the future.

Analyses of lncRNAs, circRNAs, and the Interactions between ncRNAs and mRNAs in Goat Submandibular Glands Reveal Their Potential Function in Immune Regulation.

As part of one of the main ruminants, goat salivary glands hardly secrete digestive enzymes, but play an important role in immunity. The immune function of goat salivary glands significantly changes with age, while the expression profile and specific function of non-coding RNA during this process are unknown. In this study, transcriptome sequencing was performed on submandibular gland (SMG) tissues of 1-month-old, 12-month-old, and 24-month-old goats, revealing the expression patterns of lncRNA and circRNA at different ages. A total of 369 lncRNAs and 1699 circRNAs were found to be differentially expressed. Functional enrichment analyses showed that the lncRNA regulated target mRNAs and circRNA host genes were significantly enriched in immune-related GO terms and pathways. CeRNA network analysis showed that the key differentially expressed circRNAs and lncRNAs mainly regulate the key immune-related genes ITGB2, LCP2, PTPRC, SYK, and ZAP70 through competitive binding with miR-141-x, miR-29-y, and chi-miR-29b-3p, thereby affecting the natural killer cell-mediated cytotoxicity pathway, the T cell receptor signaling pathway, and other immune-related pathways. It should be noted that the expression of key circRNAs, lncRNAs, and key immune-related genes in goat SMGs decreased significantly with the growth of the goat. This is the first reporting of lncRNAs, circRNAs, and ceRNA network regulation in goat SMGs. Our study contributes to the knowledge of changes in the expression of non-coding RNAs during SMG development in goats and provides new insights into the relationship between non-coding RNAs and salivary gland immune function in goats.

Antagonism of tomato spotted wilt virus against tomato yellow leaf curl virus in Nicotiana benthamiana detected by transcriptome analysis.

BACKGROUND: Tomato spot wilt virus (TSWV) and tomato yellow leaf curl virus (TYLCV) are highly harmful viruses in agricultural production, which can cause serious economic losses to crops and even devastating consequences for vegetable yield in some countries and regions. Although the two viruses belong to different families and have different transmission vectors, they share most hosts. OBJECTIVE: This study aimed to examine the transcriptomic expression of single and mixed inoculations of TSWV and TYLCV, leading to antagonism using high-throughput RNA sequencing. METHODS: We confirmed the single and mixed infections of these viruses in Nicotiana benthamiana (N. benthamiana) by artificial inoculation. And the expression changes of related genes and their biological functions and pathways during the mixed infection of TSWV and TYLCV were analyzed by comparative transcriptome. RESULTS: Basically, similar symptoms were observed in the plants singly infected with TSWV and co-infected with TYLCV; the symptoms of TYLCV in the co-infected plants were not obvious compared with single TYLCV infections. When inoculated with TYLCV, the accumulation of the virus significantly reduced in single and mixed infections with TSWV; the TSWV accumulated slightly less in co-infection with TYLCV, whereas this reduction was much smaller than that of TYLCV. The results suggested that TSWV had an antagonistic effect on the accumulation of TYLCV in N. benthamiana. It mainly focused on the changes in unique differentially expressed genes (DEGs) caused by the co-infection of TSWV and TYLCV. The eight pathways enriched by upregulated DEGs mainly included amino acid biosynthesis, citrate cycle (or tricarboxylic acid cycle, TCA cycle), and so on. However, only pentose phosphate pathway (PPP) and peptidoglycan biosynthesis could be downregulated in the Kyoto Encyclopedia of Genes and Genomes pathway in which peptidoglycan biosynthesis was involved in upregulated and downregulated pathways. CONCLUSIONS: The antagonistic effect of TSWV on TYLCV in N.benthamiana and the change trends and specific pathways of DEGs in this process were found. Our study provided new insights into the host regulation and competition between viruses in response to TSWV and TYLCV mixed infection.

Rapid and Green Electric-Explosion Preparation of Spherical Indium Nanocrystals with Abundant Metal Defects for Highly-Selective CO2 Electroreduction.

Electrochemical conversion of CO2 into high-value-added chemicals has been considered a promising route to achieve carbon neutrality and mitigate the global greenhouse effect. However, the lack of highly efficient electrocatalysts has limited its practical application. Herein, we propose an ultrafast and green electric explosion method to batch-scale prepare spherical indium (In) nanocrystals (NCs) with abundant metal defects toward high selective electrocatalytic CO2 reduction (CO2RR) to HCOOH. During the electric explosion synthesis process, the Ar atmosphere plays a significant role in forming the spherical In NCs with abundant metal defects instead of highly crystalline In2O3 NCs formed under an air atmosphere. Analysis results reveal that the In NCs possess ultrafast catalytic kinetics and reduced onset potential, which is ascribed to the formation of rich metal defects serving as effective catalytic sites for converting CO2 into HCOOH. This work provides a feasible strategy to massively produce efficient In-based electrocatalysts for electrocatalytic CO2-to-formate conversion.