Identification and characterization of whole blood gene expression and splicing quantitative trait loci during early to mid-lactation of dairy cattle.

BACKGROUND: Characterization of regulatory variants (e.g., gene expression quantitative trait loci, eQTL; gene splicing QTL, sQTL) is crucial for biologically interpreting molecular mechanisms underlying loci associated with complex traits. However, regulatory variants in dairy cattle, particularly in specific biological contexts (e.g., distinct lactation stages), remain largely unknown. In this study, we explored regulatory variants in whole blood samples collected during early to mid-lactation (22-150 days after calving) of 101 Holstein cows and analyzed them to decipher the regulatory mechanisms underlying complex traits in dairy cattle. RESULTS: We identified 14,303 genes and 227,705 intron clusters expressed in the white blood cells of 101 cattle. The average heritability of gene expression and intron excision ratio explained by cis-SNPs is 0.28 ± 0.13 and 0.25 ± 0.13, respectively. We identified 23,485 SNP-gene expression pairs and 18,166 SNP-intron cluster pairs in dairy cattle during early to mid-lactation. Compared with the 2,380,457 cis-eQTLs reported to be present in blood in the Cattle Genotype-Tissue Expression atlas (CattleGTEx), only 6,114 cis-eQTLs (P < 0.05) were detected in the present study. By conducting colocalization analysis between cis-e/sQTL and the results of genome-wide association studies (GWAS) from four traits, we identified a cis-e/sQTL (rs109421300) of the DGAT1 gene that might be a key marker in early to mid-lactation for milk yield, fat yield, protein yield, and somatic cell score (PP4 > 0.6). Finally, transcriptome-wide association studies (TWAS) revealed certain genes (e.g., FAM83H and TBC1D17) whose expression in white blood cells was significantly (P < 0.05) associated with complex traits. CONCLUSIONS: This study investigated the genetic regulation of gene expression and alternative splicing in dairy cows during early to mid-lactation and provided new insights into the regulatory mechanisms underlying complex traits of economic importance.

Integrative analysis of senescence-related genes identifies robust prognostic clusters with distinct features in hepatocellular carcinoma.

INTRODUCTION: Senescence refers to a state of permanent cell growth arrest and is regarded as a tumor suppressive mechanism, whereas accumulative evidence demonstrate that senescent cells play an adverse role during cancer progression. The scarcity of specific and reliable markers reflecting senescence level in cancer impede our understanding of this biological basis. OBJECTIVES: Senescence-related genes (SRGs) were collected for integrative analysis to reveal the role of senescence in hepatocellular carcinoma (HCC). METHODS: Consensus clustering was used to subtype HCC based on SRGs. Several computational methods, including single sample gene set enrichment analysis (ssGSEA), fuzzy c-means algorithm, were performed. Data of drug sensitivities were utilized to screen potential therapeutic agents for different senescence patients. Additionally, we developed a method called signature-related gene analysis (SRGA) for identification of markers relevant to phenotype of interest. Experimental strategies consisting quantitative real-time PCR (qRT-PCR), ß-galactosidase assay, western blot, and tumor-T cell co-culture system were used to validate the findings in vitro. RESULTS: We identified three robust prognostic clusters of HCC patients with distinct survival outcome, mutational landscape, and immune features. We further extracted signature genes of senescence clusters to construct the senescence scoring system and profile senescence level in HCC at bulk and single-cell resolution. Senescence-induced stemness reprogramming was confirmed both in silico and in vitro. HCC patients with high senescence were immune suppressed and sensitive to Tozasertib and other drugs. We suggested that MAFG, PLIN3, and 4 other genes were pertinent to HCC senescence, and MAFG potentially mediated immune suppression, senescence, and stemness. CONCLUSION: Our findings provide insights into the role of SRGs in patients stratification and precision medicine.

Strong Interactions between Au Nanoparticles and BiVO4 Photoanode Boosts Hole Extraction for Photoelectrochemical Water Splitting.

Strong metal-support interaction (SMSI) is widely proposed as a key factor in tuning catalytic performances. Herein, the classical SMSI between Au nanoparticles (NPs) and BiVO4 (BVO) supports (Au/BVO-SMSI) is discovered and used innovatively for photoelectrochemical (PEC) water splitting. Owing to the SMSI, the electrons transfer from V4+ to Au NPs, leading to the formation of electron-rich Au species (Auδ-) and strong electronic interaction (i.e., Auδ--Ov-V4+), which readily contributes to extract photogenerated holes and promote charge separation. Benefitted from the SMSI effect, the as-prepared Au/BVO-SMSI photoanode exhibits a superior photocurrent density of 6.25 mA cm-2 at 1.23 V versus the reversible hydrogen electrode after the deposition of FeOOH/NiOOH cocatalysts. This work provides a pioneering view for extending SMSI effect to bimetal oxide supports for PEC water splitting, and guides the interfacial electronic and geometric structure modulation of photoanodes consisting of metal NPs and reducible oxides for improved solar energy conversion efficiency.

Histidine re-sensitizes pediatric acute lymphoblastic leukemia to 6-mercaptopurine through tetrahydrofolate consumption and SIRT5-mediated desuccinylation.

Despite progressive improvements in the survival rate of pediatric B-cell lineage acute lymphoblastic leukemia (B-ALL), chemoresistance-induced disease progression and recurrence still occur with poor prognosis, thus highlighting the urgent need to eradicate drug resistance in B-ALL. The 6-mercaptopurine (6-MP) is the backbone of ALL combination chemotherapy, and resistance to it is crucially related to relapse. The present study couples chemoresistance in pediatric B-ALL with histidine metabolism deficiency. Evidence was provided that histidine supplementation significantly shifts the 6-MP dose-response in 6-MP-resistant B-ALL. It is revealed that increased tetrahydrofolate consumption via histidine catabolism partially explains the re-sensitization ability of histidine. More importantly, this work provides fresh insights into that desuccinylation mediated by SIRT5 is an indispensable and synergistic requirement for histidine combination therapy against 6-MP resistance, which is undisclosed previously and demonstrates a rational strategy to ameliorate chemoresistance and protect pediatric patients with B-ALL from disease progression or relapse.

Establishment and validation of a multivariate predictive model for the efficacy of oral rehydration salts in children with postural tachycardia syndrome.

BACKGROUND: The therapeutic effectiveness of the empirical and unselected use of oral rehydration salts (ORS) on postural tachycardia syndrome (POTS) is not satisfactory in children. Therefore, looking for suitable predictors of the therapeutic effects of ORS before treatment is extremely necessary to implement individualised treatment for paediatric patients with POTS. METHODS: A retrospective case-control analysis of 130 patients (aged 5-18 years) who suffered from POTS with a 3-month treatment of ORS was conducted. A nomogram model was developed in the training set (n = 87) to predict the therapeutic response to ORS. Univariate analysis and logistic regression were applied to select the most useful predictors. ROC curves were applied to evaluate the discriminative performance of the nomogram model. The nomogram was then evaluated by calibration curves and the Hosmer-Lemeshow (H-L) test. The results were further validated using 1000 bootstrap resamples. External validation was performed in an independent validation set (n = 43). FINDINGS: Among the ten variables with significant differences between the responders and non-responders in univariate analysis, five variables were found to be independently associated factors for ORS therapeutic efficacy among POTS children in the further logistic regression, including mean corpuscular haemoglobin concentration (MCHC), mean corpuscular volume (MCV), mean arterial pressure (MAP) at the first minute of the upright position, urine specific gravity (SG), and P-wave voltage peaking ratio (PWP). The nomogram model was established in the training set (AUC 0.926 [95% CI: 0.865-0.988], yielding a sensitivity of 87.8% and a specificity of 86.8%). The calibration curves showed good agreement between the prediction of the nomogram and actual observation in both the training and validation sets. The nomogram also effectively predicted the external validation set (sensitivity 82.1%, specificity 73.3%, and accuracy 79.1%). INTERPRETATION: We established a feasible and high-precision nomogram model to predict the efficacy of ORS, which would help implement individualised treatment for children with POTS. FUNDING: This study was supported by National High-Level Hospital Clinical Research Funding (Multi-centre Clinical Research Project of Peking University First Hospital) (2022CR59).

Engineering organic polymers as emerging sustainable materials for powerful electrocatalysts.

Cost-effective and high-efficiency catalysts play a central role in various sustainable electrochemical energy conversion technologies that are being developed to generate clean energy while reducing carbon emissions, such as fuel cells, metal-air batteries, water electrolyzers, and carbon dioxide conversion. In this context, a recent climax in the exploitation of advanced earth-abundant catalysts has been witnessed for diverse electrochemical reactions involved in the above mentioned sustainable pathways. In particular, polymer catalysts have garnered considerable interest and achieved substantial progress very recently, mainly owing to their pyrolysis-free synthesis, highly tunable molecular composition and microarchitecture, readily adjustable electrical conductivity, and high stability. In this review, we present a timely and comprehensive overview of the latest advances in organic polymers as emerging materials for powerful electrocatalysts. First, we present the general principles for the design of polymer catalysts in terms of catalytic activity, electrical conductivity, mass transfer, and stability. Then, the state-of-the-art engineering strategies to tailor the polymer catalysts at both molecular (i.e., heteroatom and metal atom engineering) and macromolecular (i.e., chain, topology, and composition engineering) levels are introduced. Particular attention is paid to the insightful understanding of structure-performance correlations and electrocatalytic mechanisms. The fundamentals behind these critical electrochemical reactions, including the oxygen reduction reaction, hydrogen evolution reaction, CO2 reduction reaction, oxygen evolution reaction, and hydrogen oxidation reaction, as well as breakthroughs in polymer catalysts, are outlined as well. Finally, we further discuss the current challenges and suggest new opportunities for the rational design of advanced polymer catalysts. By presenting the progress, engineering strategies, insightful understandings, challenges, and perspectives, we hope this review can provide valuable guidelines for the future development of polymer catalysts.

Betaine eliminates CFA-induced depressive-like behaviour in mice may be through inhibition of microglia and astrocyte activation and polarization.

Chronic pain can induce not only nociceptive but also depressive emotions. A previous study demonstrated that betaine, a commonly used nutrient supplement, has an anti-nociceptive effect, but whether betaine can alleviate chronic pain-induced depressive emotion is elusive. Our current study found that betaine administration significantly eliminated complete Freund's adjuvant (CFA)-induced pain-related depressive-like behaviour. Mechanistically, betaine treatment inhibited microglia and astrocyte activation. Furthermore, betaine significantly promoted the transition of microglia from the M1 to the M2 phenotype, as well as the transition of astrocytes from the A1 to the A2 phenotype. Additionally, the release of pro-inflammatory factors such as IL-18, IL-1ß and IL-6 and anti-inflammatory factors such as IL-10 in the hippocampus induced by CFA were also reversed by betaine administration. Overall, betaine has therapeutic effects on pain-related depressive-like phenotypes caused by CFA, possibly through altering the polarization of microglia and astrocytes to reduce neuroinflammation.

5α-Hydroxycostic acid inhibits choroidal neovascularization in rats through a dual signalling pathway mediated by VEGF and angiopoietin 2.

BACKGROUND: 5α-Hydroxycostic acid is a eudemane sesquiterpene that is isolated from the natural plant, Laggera alata. It exerts anti-inflammatory and anti-angiogenic effects on human breast cancer cells, but its role and underlying mechanism in choroidal neovascularization (CNV) are still unclear. We conducted a study to verify that 5α-Hydroxycostic acid can inhibit the formation and leakage of CNV, and describe the possible dual pathway by which it exerts its inhibitory effects in this process. METHODS: An in vitro model of choroidal neovascularization was established using VEGF164, while a rat model of choroidal neovascularization was established using a 532 nm laser. In both models, the effects of 5α-Hydroxycostic acid in vivo and in vitro were evaluated to determine its inhibitory effect on abnormal cell proliferation, migration and tubule formation, as well as its effect on pathological changes in choroidal tissues and the area of neovascularization leakage in rats. The levels of components in the VEGF/VEGFR and Ang2/Tie2 signaling pathways were measured in tissues and cells. RESULTS: In vitro experiments have shown that 5α-Hydroxycostic acid can inhibit abnormal cell proliferation, migration and angiogenesis. Additionally, 5α-Hydroxycostic acid enhances cell adhesion by inhibiting the phosphorylation pathways of VEGFR2 and Tie2. In vivo experiments demonstrated that 5α-Hydroxycostic acid has a positive therapeutic effect on choroidal neovascularization in rats. It can effectively reduce vascular leakage, consistent with the results of the cell experiments. CONCLUSION: 5α-Hydroxycostic acid can inhibit choroidal neovascularization by interfering with the VEGF- and Ang2/Tie2-related pathways, and it may be a good candidate drug for treating CNV.

Optimal Control for Constrained Discrete-Time Nonlinear Systems Based on Safe Reinforcement Learning.

The state and input constraints of nonlinear systems could greatly impede the realization of their optimal control when using reinforcement learning (RL)-based approaches since the commonly used quadratic utility functions cannot meet the requirements of solving constrained optimization problems. This article develops a novel optimal control approach for constrained discrete-time (DT) nonlinear systems based on safe RL. Specifically, a barrier function (BF) is introduced and incorporated with the value function to help transform a constrained optimization problem into an unconstrained one. Meanwhile, the minimum of such an optimization problem can be guaranteed to occur at the origin. Then a constrained policy iteration (PI) algorithm is developed to realize the optimal control of the nonlinear system and to enable the state and input constraints to be satisfied. The constrained optimal control policy and its corresponding value function are derived through the implementation of two neural networks (NNs). Performance analysis shows that the proposed control approach still retains the convergence and optimality properties of the traditional PI algorithm. Simulation results of three examples reveal its effectiveness.

All-Fabric Capacitive Pressure Sensors with Piezoelectric Nanofibers for Wearable Electronics and Robotic Sensing.

Flexible pressure sensors are increasingly sought after for applications ranging from physiological signal monitoring to robotic sensing; however, the challenges associated with fabricating highly sensitive, comfortable, and cost-effective sensors remain formidable. This study presents a high-performance, all-fabric capacitive pressure sensor (AFCPS) that incorporates piezoelectric nanofibers. Through the meticulous optimization of conductive fiber electrodes and P(VDF-TrFE) nanofiber dielectric layers, the AFCPS exhibits exceptional attributes such as high sensitivity (4.05 kPa-1), an ultralow detection limit (0.6 Pa), an extensive detection range (∼100 kPa), rapid response time (<26 ms), and robust stability (>14,000 cycles). The sensor's porous structure enhances its compressibility, while its piezoelectric properties expedite charge separation, thereby increasing the interface capacitance and augmenting overall performance. These features are elucidated further through multiphysical field-coupling simulations and experimental testing. Owing to its comprehensive superior performance, the AFCPS has demonstrated its efficacy in monitoring human activity and physiological signals, as well as in discerning soft robotic grasping movements. Additionally, we have successfully implemented multiple AFCPS units as pressure sensor arrays to ascertain spatial pressure distribution and enable intelligent robotic gripping. Our research underscores the promising potential of the AFCPS device in wearable electronics and robotic sensing, thereby contributing significantly to the advancement of high-performance fabric-based sensors.

Requirement of WDR70 for POLE3-mediated DNA double-strand breaks repair.

H2BK120ub1 triggers several prominent downstream histone modification pathways and changes in chromatin structure, therefore involving it into multiple critical cellular processes including DNA transcription and DNA damage repair. Although it has been reported that H2BK120ub1 is mediated by RNF20/40 and CRL4WDR70, less is known about the underlying regulation mechanism for H2BK120ub1 by WDR70. By using a series of biochemical and cell-based studies, we find that WDR70 promotes H2BK120ub1 by interacting with RNF20/40 complex, and deposition of H2BK120ub1 and H3K79me2 in POLE3 loci is highly sensitive to POLE3 transcription. Moreover, we demonstrate that POLE3 interacts CHRAC1 to promote DNA repair by regulation on the expression of homology-directed repair proteins and KU80 recruitment and identify CHRAC1 D121Y mutation in colorectal cancer, which leads to the defect in DNA repair due to attenuated the interaction with POLE3. These findings highlight a previously unknown role for WDR70 in maintenance of genomic stability and imply POLE3 and CHRAC1 as potential therapeutic targets in cancer.

eIF3i promotes colorectal cancer cell survival via augmenting PHGDH translation.

Translational regulation is one of the decisive steps in gene expression, and its dysregulation is closely related to tumorigenesis. Eukaryotic translation initiation factor 3 subunit i (eIF3i) promotes tumor growth by selectively regulating gene translation, but the underlying mechanisms are largely unknown. Here, we show that eIF3i is significantly increased in colorectal cancer (CRC) and reinforces the proliferation of CRC cells. Using ribosome profiling and proteomics analysis, several genes regulated by eIF3i at the translation level were identified, including D-3-phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in the de novo serine synthesis pathway that participates in metabolic reprogramming of tumor cells. PHGDH knockdown significantly represses CRC cell proliferation and partially attenuates the excessive growth induced by eIF3i overexpression. Mechanistically, METTL3-mediated N6-methyladenosine modification on PHGDH mRNA promotes its binding with eIF3i, ultimately leading to a higher translational rate. In addition, knocking down eIF3i and PHGDH impedes tumor growth in vivo. Collectively, this study not only uncovered a novel regulatory mechanism for PHGDH translation but also demonstrated that eIF3i is a critical metabolic regulator in human cancer.

Molecular regulatory mechanism of key LncRNAs in subclinical mastitic cows with folic acid supplementation.

BACKGROUND: Folic acid is a water-soluble B vitamin (B9), which is closely related to the body's immune and other metabolic pathways. The folic acid synthesized by rumen microbes has been unable to meet the needs of high-yielding dairy cows. The incidence rate of subclinical mastitis in dairy herds worldwide ranged between 25%~65% with no obvious symptoms, but it significantly causes a decrease in lactation and milk quality. Therefore, this study aims at exploring the effects of folic acid supplementation on the expression profile of lncRNAs, exploring the molecular mechanism by which lncRNAs regulate immunity in subclinical mastitic dairy cows. RESULTS: The analysis identified a total of 4384 lncRNA transcripts. Subsequently, differentially expressed lncRNAs in the comparison of two groups (SF vs. SC, HF vs. HC) were identified to be 84 and 55 respectively. Furthermore, the weighted gene co-expression network analysis (WGCNA) and the KEGG enrichment analysis result showed that folic acid supplementation affects inflammation and immune response-related pathways. The two groups have few pathways in common. One important lncRNA MSTRG.11108.1 and its target genes (ICAM1, CCL3, CCL4, etc.) were involved in immune-related pathways. Finally, through integrated analysis of lncRNAs with GWAS data and animal QTL database, we found that differential lncRNA and its target genes could be significantly enriched in SNPs and QTLs related to somatic cell count (SCC) and mastitis, such as MSTRG.11108.1 and its target gene ICAM1, CXCL3, GRO1. CONCLUSIONS: For subclinical mastitic cows, folic acid supplementation can significantly affect the expression of immune-related pathway genes such as ICAM1 by regulating lncRNAs MSTRG.11108.1, thereby affecting related immune phenotypes. Our findings laid a ground foundation for theoretical and practical application for feeding folic acid supplementation in subclinical mastitic cows.

A Simple ICT-Based Fluorescent Probe for HOCl and Bioimaging Applications.

Over the past few decades, drug-induced liver damage (DILI) has become a serious public health problem due to drug abuse. Among multifarious reactive oxygen species, mounting evidence attests that ClO- has been used as a potential biomarker in DILI. In this work, a new "turn-on" fluorescent probe 1 was designed and synthesized by modifying 4'-hydroxybiphenyl-4-carbonitrile (dye 2) with N, N-dimethylthiocarbamate as a response site for detecting ClO-. Probe 1 displayed a low detection limit (72 nM), fast response time (30 s), wide pH operating range (6-8), great tissue penetration, large Stokes shift (125 nm) and 291-fold fluorescence enhancement at 475 nm in the mapping of ClO-. Probe 1 could trace amounts of exogenous and endogenous ClO- with high sensitivity in MCF-7 cells and HeLa cells. Expectantly, the fluoxetine-induced liver injury model is successfully established, and probe 1 has been used for detecting the fluctuation of ClO- levels in the mouse model of fluoxetine-induced liver injury. All in all, probe 1 with its high specificity, good biological compatibility and liver tissue penetration ability is expected to assist with the early diagnosis of DILI and the clinical screening of various new drugs. We expect that probe 1 could be efficiently used as a powerful molecular tool to predict clinical DILI and explore molecular mechanisms between molecules and disease.

Biosorption and bioreduction of aqueous chromium (VI) by different Spirulina strains.

Spirulina has emerged as a promising microorganism for the treatment of industrial heavy metal ions in wastewater due to their simplicity of cultivation and harvesting, rich functional binding groups, and high bioreductive activity during the uptake process. While the capacities of biosorption and bioreduction for heavy metal ions differ significantly among various algal strains. Therefore, the physiological characteristics were investigated to identify the different Spirulina strains, and the chromium (VI) adsorption capacities of the algal strains were also evaluated. In this study, it was found that algal strains YCX2643 and CLQ1848 performed higher removal efficiency (86.5% and 83.7%) than the other four Spirulina strains (59.4%, 56.3%, 65.6%, and 66.5%, respectively). Moreover, the mechanisms of chromium (VI) ions binding and biotransformation in the Spirulina cell were scrutinized by FTIR (Fourier transform infrared) spectroscopy and scanning electron microscopy (SEM), and it indicated that the varieties of cellular components involved in high binding affinity may cause the higher biosorption and bioreduction of aqueous chromium (VI) in algal strains YCX2643 and CLQ1848, which could be used as promising biosorbents in the removing heavy metal pollutants from wastewaters.

An Improved Genome-Wide Association Procedure Explores Gene-Allele Constitutions and Evolutionary Drives of Growth Period Traits in the Global Soybean Germplasm Population.

In soybeans (Glycine max (L.) Merr.), their growth periods, DSF (days of sowing-to-flowering), and DFM (days of flowering-to-maturity) are determined by their required accumulative day-length (ADL) and active temperature (AAT). A sample of 354 soybean varieties from five world eco-regions was tested in four seasons in Nanjing, China. The ADL and AAT of DSF and DFM were calculated from daily day-lengths and temperatures provided by the Nanjing Meteorological Bureau. The improved restricted two-stage multi-locus genome-wide association study using gene-allele sequences as markers (coded GASM-RTM-GWAS) was performed. (i) For DSF and its related ADLDSF and AATDSF, 130-141 genes with 384-406 alleles were explored, and for DFM and its related ADLDFM and AATDFM, 124-135 genes with 362-384 alleles were explored, in a total of six gene-allele systems. DSF shared more ADL and AAT contributions than DFM. (ii) Comparisons between the eco-region gene-allele submatrices indicated that the genetic adaptation from the origin to the geographic sub-regions was characterized by allele emergence (mutation), while genetic expansion from primary maturity group (MG)-sets to early/late MG-sets featured allele exclusion (selection) without allele emergence in addition to inheritance (migration). (iii) Optimal crosses with transgressive segregations in both directions were predicted and recommended for breeding purposes, indicating that allele recombination in soybean is an important evolutionary drive. (iv) Genes of the six traits were mostly trait-specific involved in four categories of 10 groups of biological functions. GASM-RTM-GWAS showed potential in detecting directly causal genes with their alleles, identifying differential trait evolutionary drives, predicting recombination breeding potentials, and revealing population gene networks.

Integrating sperm cell transcriptome and seminal plasma metabolome to analyze the molecular regulatory mechanism of sperm motility in Holstein stud bulls.

Considering that artificial insemination is the most widely used assisted reproductive technique in the dairy industry, the semen quality of bulls is very important for selecting excellent stud bulls. Sperm motility is one of the important traits of semen quality, and related genes may be regulated by environmental factors. Seminal plasma can affect sperm cell transcriptome and further affect sperm motility through exosome or other processes. However, the molecular regulation mechanism of bull sperm motility has not been studied by combining the sperm cell transcriptome with seminal plasma metabolome. The number of motile sperm per ejaculate (NMSPE) is an integrated indicator for assessing sperm motility in stud bulls. In the present study, we selected 7 bulls with higher NMSPE (5,698.55 million +/- 945.40 million) as group H and 7 bulls with lower NMSPE (2,279.76 million +/- 1,305.69 million) as group L from 53 Holstein stud bulls. The differentially expressed genes (DEGs) in sperm cells were evaluated between the two groups (H vs. L). We conducted gene co-expression network analysis (WGCNA) on H and L groups of bulls, as well as two monozygotic twin Holstein bulls with different NMSPE values, to screen candidate genes for NMSPE. The regulatory effect of seminal plasma metabolome on the candidate genes of NMSPE was also investigated. A total of 1,099 DEGs were identified in the sperm cells of H and L groups. These DEGs were primarily concentrated in energy metabolism and sperm cell transcription. The significantly enriched Kyoto encyclopedia of genes and genomes (KEGG) pathways of the 57 differential metabolites were the aminoacyl-tRNA biosynthesis pathway and vitamin B6 metabolism pathway. Our study discovered 14 genes as the potential candidate markers for sperm motility, including FBXO39. We observed a broad correlation between transcriptome of sperm cells and seminal plasma metabolome, such as three metabolites, namely, mesaconic acid, 2-coumaric acid, and 4-formylaminoantipyrine, might regulate FBXO39 expression through potential pathways. The genes related to seminal plasma metabolites expressed in sperm cells are not only located near the quantitative trait loci of reproductive traits, but also enriched in the genome-wide association study signal of sire conception rate. Collectively, this study was the first to investigate the interplays among transcriptome of sperm cells and seminal plasma metabolome from Holstein stud bulls with different sperm motility.

A Holstein stud bull can produce thousands of doses of frozen semen, which are used to distribute its selected genetics to dairy herds all over the world. The semen quality of stud bulls has an impact on the economics of the breeding centers. Our previous study found that monozygotic twin stud bulls showed different semen quality traits and different transcriptomic profiles in sperm cells. The number of motile sperm per ejaculate (NMSPE) is an integrated trait for assessing sperm motility in stud bulls, which is one of the most important semen quality traits. In the present study, we selected 7 stud bulls that had a high NMSPE (named as H group) and 7 stud bulls with low NMSPE (named as L group) from a Chinese Holstein bull population based on 9 yr of semen quality records. In this study, we investigated the sperm cells transcriptomic differences between the two groups and observed the influences of seminal plasma metabolites on the transcriptomic profiles of the sperm cells. The results showed that the expression level of the differentially expressed genes in the sperm cells is closely related to NMSPE. Our study discovered 14 genes as the potential candidate markers for sperm motility, including FBXO39. Our data provide new insights into the improvement of bovine semen quality traits.

Markers for predicting the efficacy of beta-blockers in vasovagal syncope management in children: A mini-review.

Vasovagal syncope (VVS) is a common subtype of neurally mediated syncope. It is prevalent in children and adolescents, and critically affects the quality of life of patients. In recent years, the management of pediatric patients with VVS has received extensive attention, and ß-blocker serves as an important choice of the drug therapy for children with VVS. However, the empirical use of ß-blocker treatment has limited therapeutic efficacy in patients with VVS. Therefore, predicting the efficacy of ß-blocker therapy based on biomarkers related to the pathophysiological mechanism is essential, and great progress has been made by applying these biomarkers in formulating individualized treatment plans for children with VVS. This review summarizes recent advances in predicting the effect of ß-blockers in the management of VVS in children.

Prohibitin mediates the cellular invasion of spring viremia of the carp virus.

Spring viremia of carp virus (SVCV) is strongly contagious and pathogenic to common carp and cyprinoid species. However, knowledge of how SVCV enters host cells is still inadequate. In this study, mass spectrometry (MS) was incorporated with tandem affinity purification (TAP) to identify host proteins that interact with SVCV glycoprotein, the main attachment protein of SVCV. Specifically, prohibitin (PHB) received the utmost attention from all the candidate proteins, and its interaction with the SVCV-G protein was confirmed by immunoprecipitation and immunofluorescence assays. Treatment with PHB-specific inhibitors or knockdown of the expression of PHB by siRNAs resulted in a marked reduction in binding and entry of SVCV on host cells, while overexpression of PHB increased SVCV attachment and invasion. Furthermore, binding of SVCV to ZF4 and FHM cells was inhibited by pre-incubating the virus with recombinant PHB protein (rPHB) or blocking the cell surface PHB with its polyclonal antibodies. In addition, overexpression of PHB on SVCV-nonpermissive Grouper spleen cells (GSs) conferred susceptibility to SVCV infection. In vivo, treatment of rPHB could significantly inhibit SVCV propagation within zebrafish and benefit the survival rate of SVCV-infected zebrafish. These results demonstrate that PHB plays a crucial role in both the attachment and entry stages of SVCV infection.

Defect-induced charge redistribution of MoO3-x nanometric wires for photocatalytic ammonia synthesis.

Photocatalytic ammonia synthesis technology has become one of the effective methods to replace the Haber method for nitrogen fixation in the future for its low energy consumption and green environment. However, limited by the weak adsorption/activation ability of N2 molecules at the photocatalyst interface, the efficient nitrogen fixation still remains a daunting job. Defect-induced charge redistribution as a catalytic site for N2 molecules is the most prominent strategy to enhance the adsorption/activation of N2 molecules at the interface of catalysts. In this study, MoO3-x nanowires containing asymmetric defects were prepared by a one-step hydrothermal method via using glycine as a defect inducer. It is shown that at the atomic scale, the defect-induced charge reconfiguration can significantly improve the nitrogen adsorption and activation capacity and enhance the nitrogen fixation capacity; at the nanoscale, the charge redistribution induced by asymmetric defects effectively improved the photogenerated charge separation. Given the charge redistribution on the atomic and nanoscale of MoO3-x nanowires, the optimal nitrogen fixation rate of MoO3-x reached 200.35 µmol g-1h-1.