PQBP1 promotes translational elongation and regulates hippocampal mGluR-LTD by suppressing eEF2 phosphorylation.

Eukaryotic elongation factor 2 (eEF2) mediates translocation of peptidyl-tRNA from the ribosomal A site to the P site to promote translational elongation. Its phosphorylation on Thr56 by its single known kinase eEF2K inactivates it and inhibits translational elongation. Extensive studies have revealed that different signal cascades modulate eEF2K activity, but whether additional factors regulate phosphorylation of eEF2 remains unclear. Here, we find that the X chromosome-linked intellectual disability protein polyglutamine-binding protein 1 (PQBP1) specifically binds to non-phosphorylated eEF2 and suppresses eEF2K-mediated phosphorylation at Thr56. Loss of PQBP1 significantly reduces general protein synthesis by suppressing translational elongation. Moreover, we show that PQBP1 regulates hippocampal metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) and mGluR-LTD-associated behaviors by suppressing eEF2K-mediated phosphorylation. Our results identify PQBP1 as a novel regulator in translational elongation and mGluR-LTD, and this newly revealed regulator in the eEF2K/eEF2 pathway is also an excellent therapeutic target for various disease conditions, such as neural diseases, virus infection, and cancer.

Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion.

BACKGROUND: The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. METHODS: In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. RESULTS: A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. CONCLUSIONS: In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban. (Funded by the National Natural Science Foundation of China; RESCUE BT2 Chinese Clinical Trial Registry number, ChiCTR2000029502.).

Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion.

BACKGROUND: Data from trials investigating the effects and risks of endovascular thrombectomy for the treatment of stroke due to basilar-artery occlusion are limited. METHODS: We conducted a multicenter, prospective, randomized, controlled trial of endovascular thrombectomy for basilar-artery occlusion at 36 centers in China. Patients were assigned, in a 2:1 ratio, within 12 hours after the estimated time of basilar-artery occlusion to receive endovascular thrombectomy or best medical care (control). The primary outcome was good functional status, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]), at 90 days. Secondary outcomes included a modified Rankin scale score of 0 to 2, distribution across the modified Rankin scale score categories, and quality of life. Safety outcomes included symptomatic intracranial hemorrhage at 24 to 72 hours, 90-day mortality, and procedural complications. RESULTS: Of the 507 patients who underwent screening, 340 were in the intention-to-treat population, with 226 assigned to the thrombectomy group and 114 to the control group. Intravenous thrombolysis was used in 31% of the patients in the thrombectomy group and in 34% of those in the control group. Good functional status at 90 days occurred in 104 patients (46%) in the thrombectomy group and in 26 (23%) in the control group (adjusted rate ratio, 2.06; 95% confidence interval [CI], 1.46 to 2.91, P<0.001). Symptomatic intracranial hemorrhage occurred in 12 patients (5%) in the thrombectomy group and in none in the control group. Results for the secondary clinical and imaging outcomes were generally in the same direction as those for the primary outcome. Mortality at 90 days was 37% in the thrombectomy group and 55% in the control group (adjusted risk ratio, 0.66; 95% CI, 0.52 to 0.82). Procedural complications occurred in 14% of the patients in the thrombectomy group, including one death due to arterial perforation. CONCLUSIONS: In a trial involving Chinese patients with basilar-artery occlusion, approximately one third of whom received intravenous thrombolysis, endovascular thrombectomy within 12 hours after stroke onset led to better functional outcomes at 90 days than best medical care but was associated with procedural complications and intracerebral hemorrhage. (Funded by the Program for Innovative Research Team of the First Affiliated Hospital of USTC and others; ATTENTION ClinicalTrials.gov number, NCT04751708.).

Association of intra-shift nap duration with heart rate variability in medical night shift workers.

Napping during night shifts effectively reduces disease risk and improves work performance, but few studies have investigated the association between napping and physiological changes, particularly in off-duty daily lives. Changes in the autonomic nervous system precede diseases like cardiovascular disease, diabetes, and obesity. Heart rate variability is a good indicator of autonomic nervous system. This study aimed to investigate the link between night shift nap durations and heart rate variability indices in the daily lives of medical workers. As indicators of chronic and long-term alterations, the circadian patterns of heart rate variability indices were evaluated. We recruited 146 medical workers with regular night shifts and divided them into four groups based on their self-reported nap durations. Heart rate variability circadian parameters (midline-estimating statistic of rhythm, amplitude, and acrophase) were obtained by obtaining 24-h electrocardiogram on a day without night shifts, plotting the data of the heart rate variability indices as a function of time, and fitting them into periodic cosine curves. Using clinical scales, depression, anxiety, stress, fatigue, and sleepiness were assessed. Linear regression analysis revealed a positive relationship between 61-120-min naps and 24-h, daytime, and night-time heart rate variability indices, and the parasympathetic activity oscillation amplitude (indexed by high-frequency power, the square root of the mean of the sum of squares of differences between adjacent normal intervals, standard deviation of short-term R-R-interval variability) within one circadian cycle. This study indicated that napping for 61-120 min during night shifts could benefit medical workers' health, providing physiological evidence to promote nap management.

The performance of a combination of heparin-binding protein with other biomarkers for sepsis diagnosis: an observational cohort study.

BACKGROUND: HBP, a novel biomarker released from neutrophils, may induce inflammatory responses and exacerbate vascular permeability, representing the pathophysiological characteristics of sepsis and septic shock. However, it remains uncertain whether the combination of HBP with other biomarkers yields enhanced diagnostic capacity for sepsis. We hypothesized that measurements included IL-6·IL-8·HBP, IL-6·IL-8·HBP/ALB and HBP/ALB which based on HBP will improve its diagnostic efficacy and even better than the traditional infection biomarkers. METHODS: Between July 2021 and June 2022, we carried out a comprehensive, multi-center, observational cohort study spanning six leading tertiary hospitals located in Heilongjiang Province, China. Patients were stratified into three categories based on the severity of infection: non-sepsis, sepsis, and septic shock. We collected clinical and laboratory data, along with infection and inflammation biomarkers, for analysis. RESULTS: A total of 195 patients were enrolled. Among the three groups, patients with septic shock (n = 75, 38.5%) had significantly higher baseline levels of HBP, WBC, Lac, CRP, PCT, IL-6, IL-8, and IL-10 compared to non-sepsis patients (n = 43, 22.0%) and sepsis patients (n = 77, 39.5%), with statistically significant differences (p < 0.05) observed for all parameters. When compared to SOFA score and traditional markers of CRP, PCT, IL-6 and IL-8, the combined indexes of IL-6·IL-8·HBP and IL-6·IL-8·HBP/ALB demonstrated significantly improved diagnostic performance for sepsis and septic shock (AUC 0.911 and 0.902 respectively, p < 0.001). CONCLUSIONS: The combined measurements of IL-6·IL-8·HBP and IL-6·IL-8·HBP/ALB can augment the diagnostic capacity of HBP for sepsis, and offer reliable early supplementary indicators to traditional biomarkers for assessing disease severity in patients with infection.

A review on the antibiotic florfenicol: Occurrence, environmental fate, effects, and health risks.

Florfenicol, as a replacement for chloramphenicol, can tightly bind to the A site of the 23S rRNA in the 50S subunit of the 70S ribosome, thereby inhibiting protein synthesis and bacterial proliferation. Due to the widespread use in aquaculture and veterinary medicine, florfenicol has been detected in the aquatic environment worldwide. Concerns over the effects and health risks of florfenicol on target and non-target organisms have been raised in recent years. Although the ecotoxicity of florfenicol has been widely reported in different species, no attempt has been made to review the current research progress of florfenicol toxicity, hormesis, and its health risks posed to biota. In this study, a comprehensive literature review was conducted to summarize the effects of florfenicol on various organisms including bacteria, algae, invertebrates, fishes, birds, and mammals. The generation of antibiotic resistant bacteria and spread antibiotic resistant genes, closely associated with hormesis, are pressing environmental health issues stemming from overuse or misuse of antibiotics including florfenicol. Exposure to florfenicol at µg/L-mg/L induced hormetic effects in several algal species, and chromoplasts might serve as a target for florfenicol-induced effects; however, the underlying molecular mechanisms are completely lacking. Exposure to high levels (mg/L) of florfenicol modified the xenobiotic metabolism, antioxidant systems, and energy metabolism, resulting in hepatotoxicity, renal toxicity, immunotoxicity, developmental toxicity, reproductive toxicity, obesogenic effects, and hormesis in different animal species. Mitochondria and the associated energy metabolism are suggested to be the primary targets for florfenicol toxicity in animals, albeit further in-depth investigations are warranted for revealing the long-term effects (e.g., whole-life-cycle impacts, multigenerational effects) of florfenicol, especially at environmental levels, and the underlying mechanisms. This will facilitate the evaluation of potential hormetic effects and construction of adverse outcome pathways for environmental risk assessment and regulation of florfenicol.

The Effects of a Complex Interactive Multimodal Intervention on Personalized Stress Management Among Health Care Workers in China: Nonrandomized Controlled Study.

BACKGROUND: Health care workers (HCWs) frequently face multiple stressors at work, particularly those working night shifts. HCWs who have experienced distress may find it difficult to adopt stress management approaches, even if they are aware of the effects of stress and coping processes. Therefore, an individualized intervention may be required to assist distressed HCWs in bridging the "knowledge-practice" gap in stress management and effectively alleviating stress symptoms. OBJECTIVE: The main objective of this research was to compare the effects of a complex interactive multimodal intervention (CIMI) to self-guided stress management interventions on stress symptoms of distressed HCWs, as measured by physiological (heart rate variability), psychological (perceived stress, mental distress, and subjective happiness), and sleep disorder (fatigue and sleepiness) indicators. METHODS: We conducted a nonrandomized, controlled study in 2 Chinese general hospitals. The participants in this study were 245 HCWs who fulfilled at least 1 of the 3 dimensions on the Depression, Anxiety, and Stress Scale. All eligible individuals were required to complete a questionnaire and wear a 24-hour Holter device to determine the physiological signs of stress as indexed by heart rate variability at both baseline and after the intervention. The CIMI group received a 12-week online intervention with 4 components-mobile stress management instruction, a web-based WeChat social network, personalized feedback, and a nurse coach, whereas the control group simply received a self-guided intervention. RESULTS: After a 12-week intervention, the Perceived Stress Scale (PSS) scores reduced significantly in the CIMI group (mean difference [MD] -5.31, 95% CI -6.26 to -4.37; P<.001) compared to the baseline levels. The changes in PSS scores before and after the intervention exhibited a significant difference between the CIMI and control groups (d=-0.64; MD -4.03, 95% CI -5.91 to -2.14; P<.001), and the effect was medium. In terms of physiological measures, both the control group (MD -9.56, 95% CI -16.9 to -2.2; P=.01) and the CIMI group (MD -8.45, 95% CI -12.68 to -4.22; P<.001) demonstrated a significant decrease in the standard deviation of normal-to-normal intervals (SDNN) within the normal clinical range; however, there were no significant differences between the 2 groups (d=0.03; MD 1.11, 95% CI -7.38 to 9.59; P=.80). CONCLUSIONS: The CIMI was an effective intervention for improving sleep disorders, as well as parts of the psychological stress measures in distressed HCWs. The findings provide objective evidence for developing a mobile stress management intervention that is adaptable and accessible to distressed HCWs, but its long-term effects should be investigated in future research. TRIAL REGISTRATION: ClinicalTrials.gov NCT05239065; https://clinicaltrials.gov/ct2/show/NCT05239065.

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke: The MARVEL Randomized Clinical Trial.

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.

Waste Biomass-Mediated Synthesis of TiO2/P, K-Containing Grapefruit Peel Biochar Composites with Enhanced Photocatalytic Activity.

In this study, TiO2/P, K-containing grapefruit peel biochar (TiO2/P, K-PC) composites were synthesized in situ biomimetically using grapefruit peel as the bio-template and carbon source and tetrabutyl titanate as the titanium source. This was achieved using the two-step rotary impregnation-calcination method. Adjusting the calcination temperature of the sample in an air atmosphere could regulate the mass ratio of TiO2 to carbon. The prepared samples were subjected to an analysis of their compositions, structures, morphologies, and properties. It demonstrated that the prepared samples were complexes of anatase TiO2 and P, K-containing carbon, with the presence of graphitic carbon. They possessed a unique morphological structure with abundant pores and a large surface area. The grapefruit peel powder played a crucial role in the induction and assembly of TiO2/P, K-PC composites. The sample PCT-400-550 had the best photocatalytic activity, with the degradation rate of RhB, MO, and MB dye solutions reaching more than 99% within 30 min, with satisfactory cyclic stability. The outstanding photocatalytic activity can be credited to its unique morphology and the efficient collaboration between TiO2 and P, K-containing biochar.

Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT): a multicentre, open-label, blinded-endpoint, randomised controlled trial.

BACKGROUND: The optimum systolic blood pressure after endovascular thrombectomy for acute ischaemic stroke is uncertain. We aimed to compare the safety and efficacy of blood pressure lowering treatment according to more intensive versus less intensive treatment targets in patients with elevated blood pressure after reperfusion with endovascular treatment. METHODS: We conducted an open-label, blinded-endpoint, randomised controlled trial at 44 tertiary-level hospitals in China. Eligible patients (aged ≥18 years) had persistently elevated systolic blood pressure (≥140 mm Hg for >10 min) following successful reperfusion with endovascular thrombectomy for acute ischaemic stroke from any intracranial large-vessel occlusion. Patients were randomly assigned (1:1, by a central, web-based program with a minimisation algorithm) to more intensive treatment (systolic blood pressure target <120 mm Hg) or less intensive treatment (target 140-180 mm Hg) to be achieved within 1 h and sustained for 72 h. The primary efficacy outcome was functional recovery, assessed according to the distribution in scores on the modified Rankin scale (range 0 [no symptoms] to 6 [death]) at 90 days. Analyses were done according to the modified intention-to-treat principle. Efficacy analyses were performed with proportional odds logistic regression with adjustment for treatment allocation as a fixed effect, site as a random effect, and baseline prognostic factors, and included all randomly assigned patients who provided consent and had available data for the primary outcome. The safety analysis included all randomly assigned patients. The treatment effects were expressed as odds ratios (ORs). This trial is registered at ClinicalTrials.gov, NCT04140110, and the Chinese Clinical Trial Registry, 1900027785; recruitment has stopped at all participating centres. FINDINGS: Between July 20, 2020, and March 7, 2022, 821 patients were randomly assigned. The trial was stopped after review of the outcome data on June 22, 2022, due to persistent efficacy and safety concerns. 407 participants were assigned to the more intensive treatment group and 409 to the less intensive treatment group, of whom 404 patients in the more intensive treatment group and 406 patients in the less intensive treatment group had primary outcome data available. The likelihood of poor functional outcome was greater in the more intensive treatment group than the less intensive treatment group (common OR 1·37 [95% CI 1·07-1·76]). Compared with the less intensive treatment group, the more intensive treatment group had more early neurological deterioration (common OR 1·53 [95% 1·18-1·97]) and major disability at 90 days (OR 2·07 [95% CI 1·47-2·93]) but there were no significant differences in symptomatic intracerebral haemorrhage. There were no significant differences in serious adverse events or mortality between groups. INTERPRETATION: Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischaemic stroke due to intracranial large-vessel occlusion. FUNDING: The Shanghai Hospital Development Center; National Health and Medical Research Council of Australia; Medical Research Futures Fund of Australia; China Stroke Prevention; Shanghai Changhai Hospital, Science and Technology Commission of Shanghai Municipality; Takeda China; Hasten Biopharmaceutic; Genesis Medtech; Penumbra.

Design, Screening, and Characterization of Engineered Phage Endolysins with Extracellular Antibacterial Activity against Gram-Negative Bacteria.

Phage-encoded endolysins are emerging antibacterial agents based on their ability to efficiently degrade peptidoglycan on Gram-positive bacteria, but the envelope characteristics of Gram-negative bacteria limit their application. Engineering modifications of endolysins can improve the optimization of their penetrative and antibacterial properties. This study constructed a screening platform to screen for engineered Artificial-Bp7e (Art-Bp7e) endolysins with extracellular antibacterial activity against Escherichia coli. An oligonucleotide of 20 repeated NNK codons was inserted upstream of the endolysin gene Bp7e to construct a chimeric endolysin library in the pColdTF vector. The chimeric Art-Bp7e proteins were expressed by transforming the plasmid library into E. coli BL21 and released by chloroform fumigation, and the protein activities were evaluated by the spotting method and the colony-counting method to screen for promising proteins. Sequence analysis showed that all screened proteins with extracellular activities had a chimeric peptide with a positive charge and an α-helical structure. Also, a representative protein, Art-Bp7e6, was further characterized. It exhibited broad antibacterial activity against E. coli (7/21), Salmonella enterica serovar Enteritidis (4/10), Pseudomonas aeruginosa (3/10), and even Staphylococcus aureus (1/10). In the transmembrane process, the chimeric peptide of Art-Bp7e6 depolarized the host cell envelope, increased the permeability of the cell, and facilitated the movement of Art-Bp7e6 across the envelope to hydrolyze the peptidoglycan. In conclusion, the screening platform successfully screened for chimeric endolysins with extracellular antibacterial activities against Gram-negative bacteria, which provides methodological support for the further screening of engineered endolysins with high extracellular activities against Gram-negative bacteria. Also, the established platform showed broad application prospects and can be used to screen various proteins. IMPORTANCE The presence of the envelope in Gram-negative bacteria limits the use of phage endolysins, and engineering endolysins is an efficient way to optimize their penetrative and antibacterial properties. We built a platform for endolysin engineering and screening. A random peptide was fused with the phage endolysin Bp7e to construct a chimeric endolysin library, and engineered Artificial-Bp7e (Art-Bp7e) endolysins with extracellular activity against Gram-negative bacteria were successfully screened from the library. The purposeful Art-Bp7e had a chimeric peptide with an abundant positive charge and an α-helical structure, which led Bp7e to acquire the ability for the extracellular lysis of Gram-negative bacteria and showed a broad lysis spectrum. The platform provides a huge library capacity without the limitations of reported proteins or peptides. It can be utilized for the further screening of optimal endolysins against Gram-negative bacteria as well as for the screening of additional proteins with specific modifications.

Prevalence of bovine coronavirus in cattle in China: A systematic review and meta-analysis.

Bovine coronavirus (BCoV) is one of the important pathogens that cause calf diarrhea (CD), winter dysentery (WD), and the bovine respiratory disease complex (BRDC), and spreads worldwide. An infection of BCoV in cattle can lead to death of young animals, stunted growth, reduced milk production, and milk quality, thus bringing serious economic losses to the bovine industry. Therefore, it is necessary to prevent and control the spread of BCoV. Here, a systematic review and meta-analysis was conducted to assess the prevalence of BCoV in cattle in China before 2022. A total of 57 articles regarding the prevalence of BCoV in cattle in China were collected from five databases (PubMed, ScienceDirect, CNKI, VIP, and Wan Fang). Based on the inclusion criteria, a total of 15,838 samples were included, and 6,136 were positive cases. The overall prevalence of BCoV was 30.8%, with the highest prevalence rate (60.5%) identified in South China and the lowest prevalence (15.6%) identified in Central China. We also analyzed other subgroup information, included sampling years, sample sources, detection methods, breeding methods, age, type of cattle, presence of diarrhea, and geographic and climatic factors. The results indicated that BCoV was widely prevalent in China. Among all subgroups, the sample sources, detection methods, breeding methods, and presence or absence of diarrheal might be potential risk factors responsible for BCoV prevalence. It is recommended to strengthen the detection of BCoV in cattle, in order to effectively control the spread of BCoV.

Meta-analysis of the prevalence of Giardia duodenalis in sheep and goats in China.

Giardia duodenum (G. duodenalis) can cause giardiasis and infect a variety of hosts. So far, there have been no detailed data regarding the positive rate of G. duodenalis in sheep and goats in China. Here, a systematic literature review was carried out to investigate the epidemiology of G. duodenalis in sheep and goats in China. To perform the meta-analysis, the databases CNKI, VIP, WanFang, PubMed, Web of science and ScienceDirect were employed for screening studies related to the prevalence of G. duodenalis in sheep and goats in China. The total prevalence of G. duodenalis in sheep and goats was estimated to be 7.00% (95% CI: 4.00-10.00). In the age subgroup, the prevalence of G. duodenalis in sheep and goats of >12 months (11.29%; 95% CI: 8.08-14.97) was higher than that in sheep and goats of ≤12 months (7.57%; 95% CI: 3.95-12.24). An analysis based on seasons showed that the prevalence of G. duodenalis in sheep and goats was higher in summer (11.90%; 95% CI: 0.50-35.05) than that in other seasons. The prevalence of G. duodenalis in sheep and goats after 2016 was 8.57% (95% CI: 5.34-11.79), which was higher than others. The highest prevalence of G. duodenalis in sheep and goats was 13.06% (95% CI: 6.26-19.86) recorded in Southwestern China. The prevalence of Giardia infection in sheep (7.28%; 95% CI: 2.30-14.73) was higher than that in goats (5.43%; 95% CI: 2.73-8.98). The NOAA's National Center for Environmental Information (https://gis.ncdc.noaa.gov/maps/ncei/cdo/monthly) was used to extract relevant geoclimatic data (latitude, longitude, elevation, temperature, precipitation, humidity, and climate). By analyzing the data of each subgroup, it was shown that region, genetype, and climate were potential risk factors for giardiasis prevalence in sheep and goats. Based on the analysis of common factors and geographical factors, it is recommended to strengthen effective management measures (e.g. ventilation and disinfection in warm and humid areas) and formulate relevant policies according to local conditions. Breeders should strengthen the detection of G. duodenalis in sheep and goats, customize corresponding control measures according to the diet and living habits of sheep and goats, and strengthen the protection of sheep and lamb calves, so as to reduce the incidence rate and reduce the economic loss of China's animal husbandry.

Whole genome sequencing and annotation of a lysogenic phage vB_EcoP_DE5 isolated from donkey-derived Escherichia coli.

A lysogenic phage vB_EcoP_DE5 (hereafter designated DE5) was isolated from donkey-derived Escherichia coli. The bacteriophage was examined by transmission electron microscopy, and the result showed that DE5 belonged to the genus Kuravirus. DE5 was sensitive to changes in temperature and pH, and it could maintain its activity at pH 7 and below 60 â„ƒ. The whole genome sequencing revealed that DE5 had a double-stranded DNA genome of 77, 305 bp with 42.09% G+C content. A total of 126 open reading frames (ORFs) were identified, including functional genes related to phage integration, DNA replication and modification, transcriptional regulation, structural and packaging proteins, and host cell lysis. One phage integrase gene, one autotransporter adhesin gene, and one tRNA gene were predicted in the whole genome, and no genes associated with drug resistance were identified. The phage DE5 integrase contained 187 amino acids and belonged to the small serine recombinase family. BLASTn analysis revealed that phage DE5 had a high-sequence identity (96%) with E. coli phage SU10. Phylogenetic analysis showed that phage DE5 was a member of the genus Kuravirus. The whole genome sequencing of lysogenic phage DE5 enhanced our understanding of lysogenic phages and their therapeutic applications.

Genomic characterization of three bacteriophages infecting donkey-derived Escherichia coli.

Bacteriophages are an important source of novel genetic diversity. Sequencing of phage genomes can reveal new proteins with potential uses in phage therapy and help unravel the diversity of biological mechanisms by which phages take over the machinery of the host during infection. To expand the available collection of phage genomes, we have isolated, sequenced, and assembled the genome sequences of three phages that infect three pathogenic Escherichia coli strains: vB_EcoM_DE15, vB_EcoM_DE16, and vB_EcoM_DE17. Morphological characterization and genomic analysis indicated that all three phages were strictly lytic and free from integrases, virulence factors, toxins, and antimicrobial resistance genes. All three phages contained tRNAs, and especially, vB_EcoM_DE17 contained 25 tRNAs. The genomic features of these phages indicate that natural phages are capable of lysing pathogenic E.coli and have great potential in the biocontrol of bacteria.

Atypical presentation of cutaneous meningioma.

Cutaneous meningiomas are rare tumors of ectopic meningeal tissue in the dermis or subcutis and are most commonly located on the scalp and around the eyes, ears, nose, and mouth. We present a case of cutaneous meningioma with an unusual presentation on the upper arm, but with positivity for epithelial membrane antigen to support the diagnosis of meningioma. Lack of pancytokeratin AE1/3 and p63 allowed us to rule out a keratinocytic tumor, such as squamous cell carcinoma and basal cell carcinoma. The absence of smooth muscle actin, FXIIIa, CD163, and CD34 allowed us to rule out a leiomyoma, dermatofibroma, and vascular neoplasm respectively. Weak staining of S100 allowed us to rule out a perineuroma. The purpose of this case report is to increase awareness of a rare presentation of cutaneous meningioma not located within the scalp/face region. This may broaden its inclusion within differential diagnoses of neoplasms of uncertain behavior and encourage correct clinical diagnosis, thus improving treatment outcomes.

Contribution of m5C RNA Modification-Related Genes to Prognosis and Immunotherapy Prediction in Patients with Ovarian Cancer.

Background: 5-Methylcytosine (m5C) RNA modification is closely implicated in the occurrence of a variety of cancers. Here, we established a novel prognostic signature for ovarian cancer (OC) patients based on m5C RNA modification-related genes and explored the correlation between these genes with the tumor immune microenvironment. Methods: Methylated-RNA immunoprecipitation sequencing helped us to identify candidate genes related to m5C RNA modification at first. Based on TCGA database, we screened the differentially expressed candidate genes related to the prognosis and constructed a prognostic model using LASSO Cox regression analyses. Notably, the accuracy of the model was evaluated by Kaplan-Meier analysis and receiver operator characteristic curves. Independent prognostic risk factors were investigated by Cox proportional hazard model. Furthermore, we also analyzed the biological functions and pathways involved in the signature. Finally, the immune response of the model was visualized in great detail. Results: Totally, 2,493 candidate genes proved to be involved in m5C modification of RNA for OC. We developed a signature with prognostic value consisting of six m5C RNA modification-related genes. Specially, samples have been split into two cohorts with low- and high-risk scores according to the model, in which the low-risk OC patients exhibited dramatically better overall survival time than those with high-risk scores. Besides, not only was this model a prognostic factor independent of other clinical characteristics but it predicted the intensity of the immune response in OC. Significantly, the accuracy and availability of the signature were verified by ICGC database. Conclusions: Our study bridged the gap between m5C RNA modification and the prognosis of OC and was expected to provide an effective breakthrough for immunotherapy in OC patients.

Microplastic size-dependent biochemical and molecular effects in alga Heterosigma akashiwo.

Micro- and nano-plastics (MNPs) are increasingly prevalent contaminants in marine ecosystems and have a variety of negative impacts on marine organisms. While their toxic impact on freshwater microalgae has been well-documented, limited research has been conducted on the influence of MNPs on marine red tide algae, despite their significant implications for human health and coastal ecological stability. This study investigated the physiological, biochemical and molecular reactions of the common harmful algal species, Heterosigma akashiwo, when exposed to polystyrene (PS) MNPs of 80 nm and 1 µm in size with the concentrations of 0, 1, 10, and 20 mg L-1 in 12 days. The results showed that 80 nm-sized MNPs (at concentrations of 10 mg L-1 and 20 mg L-1) inhibited algal growth. Despite the increased superoxide dismutase (SOD) activity and up-regulation of glutathione metabolism, exposure-induced oxidative stress remained the main cause of the inhibition. Up-regulation of aminoacyl-tRNA biosynthesis and amino acid biosynthesis pathways provide the necessary amino acid feedstock for the synthesis of antioxidant enzymes such as SOD. 1 µm sized PS MNPs increased chlorophyll a (Chl-a) content without significant effects on other parameters. In addition, H. akashiwo have an effective self-regulation ability to defend against two sized MNPs stress at concentrations of 1 mg L-1 by upregulating gene expression related to endocytosis, biotin metabolism, and oxidative phosphorylation. These results provided evidence that H. akashiwo was able to resist exposure to 1 µm MPs, whereas 80 nm NPs exerted a toxic effect on H. akashiwo. This study deepens our understanding of the interaction between MNPs and marine harmful algal at the transcriptional level, providing valuable insights for further evaluating the potential impact of PS MNPs on harmful algal blooms in marine ecosystems.

Mechanistic insights into hormesis induced by erythromycin in the marine alga Thalassiosira weissflogii.

Erythromycin (ERY) is a typical macrolide antibiotic with large production and extensive use on a global scale. Detection of ERY in both freshwaters and coaster seawaters, as well as relatively high ecotoxicity of ERY have been documented. Notably, hormesis has been reported on several freshwater algae under ERY stress, where growth was promoted at relatively lower exposures but inhibited at higher treatment levels. On the contrary, there is limited information of ERY toxicity in marine algae, hampering the risk assessment on ERY in the coaster waters. The presence of hormesis may challenge the current concept of dose-response adopted in chemical risk assessment. Whether and how exposure to ERY can induce dose-dependent toxicity in marine algae remain virtually unknown, especially at environmentally relevant concentrations. The present study used a model marine diatom Thalassiosira weissflogii (T. weissflogii) to reveal its toxicological responses to ERY at different biological levels and decipher the underlying mechanisms. Assessment of multiple apical endpoints shows an evident growth promotion following ERY exposure at an environmentally relevant concentration (1 µg/L), associated with increased contents reactive oxygen species (ROS) and chlorophyll-a (Chl-a), activated signaling pathways related to ribosome biosynthesis and translation, and production of total soluble protein. By contrast, growth inhibition in the 750 and 2500 µg/L treatments was attributed to reduced viability, increased ROS formation, reduced content of total soluble protein, inhibited photosynthesis, and perturbed signaling pathways involved in xenobiotic metabolism, ribosome, metabolism of amino acid, and nitrogen metabolism. Measurements of multiple apical endpoints coupled with de novo transcriptomics analysis applied in the present study, a systems biology approach, can generate detailed mechanistic information of chemical toxicity including dose-response and species sensitivity difference used in environmental risk assessment.

Circadian nuclear receptor Rev-erbα is expressed by platelets and potentiates platelet activation and thrombus formation.

AIMS: Adverse cardiovascular events have day/night patterns with peaks in the morning, potentially related to endogenous circadian clock control of platelet activation. Circadian nuclear receptor Rev-erbα is an essential and negative component of the circadian clock. To date, the expression profile and biological function of Rev-erbα in platelets have never been reported. METHODS AND RESULTS: Here, we report the presence and functions of circadian nuclear receptor Rev-erbα in human and mouse platelets. Both human and mouse platelet Rev-erbα showed a circadian rhythm that positively correlated with platelet aggregation. Global Rev-erbα knockout and platelet-specific Rev-erbα knockout mice exhibited defective in haemostasis as assessed by prolonged tail-bleeding times. Rev-erbα deletion also reduced ferric chloride-induced carotid arterial occlusive thrombosis, prevented collagen/epinephrine-induced pulmonary thromboembolism, and protected against microvascular microthrombi obstruction and infarct expansion in an acute myocardial infarction model. In vitro thrombus formation assessed by CD41-labelled platelet fluorescence intensity was significantly reduced in Rev-erbα knockout mouse blood. Platelets from Rev-erbα knockout mice exhibited impaired agonist-induced aggregation responses, integrin αIIbß3 activation, and α-granule release. Consistently, pharmacological inhibition of Rev-erbα by specific antagonists decreased platelet activation markers in both mouse and human platelets. Mechanistically, mass spectrometry and co-immunoprecipitation analyses revealed that Rev-erbα potentiated platelet activation via oligophrenin-1-mediated RhoA/ERM (ezrin/radixin/moesin) pathway. CONCLUSION: We provided the first evidence that circadian protein Rev-erbα is functionally expressed in platelets and potentiates platelet activation and thrombus formation. Rev-erbα may serve as a novel therapeutic target for managing thrombosis-based cardiovascular disease.