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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 ℃. The whole genome sequencing revealed that DE5 had a double-stranded DNA genome of 177, 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.

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

Data from trials investigating the effects and risks of endovascular thrombectomy for the treatment of stroke due to basilar-artery occlusion are limited.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.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, P0.001). 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.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.).

The glyoxalase pathway plays a vital role in the chemical detoxification of methylglyoxal (MG) in biological systems. Our previous study suggested that OsGLYI3 may be effective in seed natural aging. In this study, the rice OsGLYI3 gene was cloned and characterized as specifically expressed in the seed. The accelerated aging (AA) treatment results indicated significant roles of OsGLYI3 in seed longevity and vigor, as the seeds of the transgenic lines with overexpressed and knocked-out OsGLYI3 exhibited higher and lower germination, respectively. The AA treatment also increased the superoxide dismutase (SOD) activity in the overexpressed transgenic seeds compared to the wild-type seeds yet lowered the SOD activity in the CRISPR/Cas9-derived transgenic rice lines. Rice OsGLYI3 was markedly upregulated in response to NaCl induced stress conditions. Compared to wild-type plants, overexpressed transgenic rice lines exhibited increased GLYI activity, decreased MG levels and improved salt stress tolerance, while CRISPR/Cas9 knockout transgenic rice lines showed decreased glyoxalase I activity, increased MG levels, and greater sensitivity to stress treatments with NaCl. Collectively, our results confirmed for the first time that OsGLYI3 is specifically expressed in rice seeds and contributes to seed longevity and salt stress tolerance.

A lytic Pseudomonas aeruginosa phage, vB_PaeP_Lx18 (Lx18), was isolated from the sewage of a dairy farm. Biological characterization revealed that Lx18 was stable from 40 °C to 60 °C and over a wide range of pH values from 4 to 10. It was able to lyse 63.6% (21/33) of the P. aeruginosa strains tested and was able to reduce and disperse biofilms, with a biofilm reduction rate of 76.8%. Whole-genome sequencing showed that Lx18 is a dsDNA virus with a genome of 42,735 bp and G+C content of 62.16%. The genome contains 54 open reading frames (ORFs), 28 of which have known functions, including DNA replication and modification, transcriptional regulation, structural and packaging proteins, and host cell lysis. No virulence or tRNA genes were identified. Phylogenetic analysis showed that phage Lx18 belongs to the genus Phikmvvirus. The lysozyme of Lx18, Lys18, was cloned and expressed. The combined action of Lys18 and ethylenediaminetetraacetic acid (EDTA) had antibacterial activity against Pseudomonas aeruginosa. The study of phage Lx18 and its lysozyme will provide basic information for further research on the treatment of Pseudomonas aeruginosa infections.

A free-fall baited camera lander was launched for the first time on the Cosmonaut Sea shelf of East Antarctica at the depth of 694 m during the 38th Chinese National Antarctic Research Expedition (CHINARE) in 2022. We identified 31 unique taxa (23 of invertebrates and 8 of fishes) belonging to 8 phyla from 2403 pictures and 40 videos. The Antarctic jonasfish (Notolepis coatsi) was the most frequently observed fish taxa. Ten species of vulnerable marine ecosystem (VME) taxa were observed, accounting for 32% of all species. The maximum number (MaxN) of Natatolana meridionalis individuals per image frame was ten, and they were attracted to the bait. The macrobenthic community type was sessile suspension feeders with associated fauna (SSFA), which was shaped by the muddy substrata with scattered rocks. Rocks served as the best habitats for sessile fauna. The study reveals the megafauna community and their habitat by image survey in the Cosmonaut Sea for the first time. It helped us obtain Antarctic biodiversity baselines and monitoring data for future’s ecosystem health assessment and better protection.

IntroductionSalmonella is a ubiquitous foodborne pathogen and mainly transmitted to human farm-to-fork chain through contaminated foods of animal origin.MethodsIn this study, we investigated the serotypes, antimicrobial resistance and virulence of Salmonella from China.ResultsA total of 617 Salmonella isolates were collected from 4 major food animal species across 23 provi nces in China from 2015-2021. Highest Salmonella prevalence were observed in Guangdong (44.4%) and Sandong (23.7%). Chickens (43.0%) was shown to be the major source of Salmonella contamination, followed by pigs (34.5%) and ducks (18.5%). The number of Salmonella increased significantly from 5.51% to 27.23% during 2015–2020. S. Derby (17.3%), S. Enteritidis (13.1%) and S. Typhimurium (11.4%) were the most common serotypes among 41 serotypes identifiedin this study. Antibiotic susceptibility testing showing that the majority of the Salmonella isolates were resistant to neomycin (99.7%), tetracycline (98.1%), ampicillin (97.4%), sulfadiazine/trimethoprim (97.1%), nalidixic acid (89.1%), doxycycline (83.1%), ceftria xone (70.3%), spectinomycin (67.7%), florfenicol (60.0%), cefotaxime (52.0%) and lomefloxacin (59.8%). The rates of resistance to multiple antibiotics in S. Derby and S.Typhimurium were higher than that in S. Enteritidis. However, the rate of resistance to fosfomycin were observed from higher to lower by S. Derby, S. Enteritidis, and S. Typhimurium. Biofilm formation ability analysis found that 88.49%of the Salmonella were able to produce biofilms, of which 236 Salmonella isolates were strong biofilm producer. Among the 26 types of antibiotics resistance genes (ARGs) were identified in this study, 4 ARGs (tetB,sul2,aadA2, and aph(3’)-IIa) were highly prevalent. In addition, 5 β-lactam resistance genes (blaTEM, blaSHV, blaCMY-2, blaCTX-M, and blaOXA) and 7 quinolone resistance genes (oqxA, oqxB, qnrB, qnrC, qnrD, qnrS, and qeqA) were detected among these isolates. 12 out of 17 virulence genes selected in this study were commonly presented in the chromosomes of tested isolate, with a detection rate of over 80%, including misL, spiA, stn, pagC, iroN, fim, msgA, sopB, prgH, sitC, ttrC, spaN.DiscussionThis study provided a systematical updating on surveillance on prevalence of Salmonella from food animals in China, shedding the light on continued vigilance for Salmonella in food animals.

IntroductionOverfishing and climate change have combined to cause fishery stocks to decline and fish community composition to change, further threatening the predation and nutritional health of marine mammals.MethodsIn this study, we collected potential prey fishes catched by fishermen in six habitats of Indo-Pacific humpback dolphins and analyzed their proximate composition (moisture, water, fat and protein), the fatty acid composition and the amino acid composition to evaluate the possible health effect on humpback dolphins.ResultsThe results showed that the nutritional composition varied significantly with species and locations. Fishes in the families Sciaenidae and Engraulidae displayed richer fatty acid composition, while those in the family Clupeidae had the highest value of amino acid quality index. In Zhuhai, home to the largest Indo-Pacific humpback dolphin population, pelagic/neritic prey fishes possessed lower energy density, PUFA content, PUFA/SFA ratio, DHA content, and EAA content compared to demersal fish, suggesting nutritional stress when there is a dietary switch from demersal to pelagic/neritic fishes in Zhuhai population.DiscussionOur study provided a framework, with energy density and fatty acid composition as its most important indicator, for assessment of the marine top predators based on the nutritional composition of their prey fishes and revealed the potential threats. Data here is expected to facilitate the development of scientific programs for successful conservation of not only the Indo-Pacific humpback dolphins, but also other marine top predators, possibly through reconstructing their prey fish’s quantity and quality.

PDF file - 20K, The majority of CD11b+ cells were F4/80+ in the prostate of TRAMP mice

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PDF file - 46K, Lymphocytes promote prostate cancer in TRAMP mice

The ethylene response factor (ERF) transcription factors, which is one of the largest transcription factor families in plants, are involved in biological and abiotic stress response and play an important role in plant growth and development. In this study, the GmABR1 gene from the soybean inbred line Zhonghuang24 (ZH24)×Huaxia 3 (HX3) was investigated its aluminum (Al) tolerance. GmABR1 protein has a conserved domain AP2, which is located in the nucleus and has transcriptional activation ability. The results of real-time quantitative PCR (qRT-PCR) showed that the GmABR1 gene presented a constitutive expression pattern rich in the root tip, stem and leaf tissues of HX3. After Al stress, the GmABR1 transcript was significantly increased in the roots. The transcripts of GmABR1 in the roots of HX3 treated with 50 µM AlCl3 was 51 times than that of the control. The GmABR1 was spatiotemporally specific with the highest expression levels when Al concentration was 50 µM, which was about 36 times than that of the control. The results of hematoxylin staining showed that the root tips of GmABR1-overexpression lines were stained the lightest, followed by the control, and the root tips of GmABR1 RNAi lines were stained the darkest. The concentrations of Al3+ in root tips were 207.40 µg/g, 147.74 µg/g and 330.65 µg/g in wild type (WT), overexpressed lines and RNAi lines, respectively. When AlCl3 (pH4.5) concentration was 100 µM, all the roots of Arabidopsis were significantly inhibited. The taproot elongation of WT, GmABR1 transgenic lines was 69.6%, 85.6%, respectively. When treated with Al, the content of malondialdehyde (MDA) in leaves of WT increased to 3.03 µg/g, while that of transgenic Arabidopsis increased from 1.66-2.21 µg/g, which was lower than that of WT. Under the Al stress, the Al stress responsive genes such as AtALMT1 and AtMATE, and the genes related to ABA pathway such as AtABI1, AtRD22 and AtRD29A were up-regulated. The results indicated that GmABR1 may jointly regulate plant resistance to Al stress through genes related to Al stress response and ABA response pathways.

In this study, we isolated a lytic Pseudomonas aeruginosa phage (vB_PaeP_ASP23) from the sewage of a mink farm, characterized its complete genome and analyzed the function of its putative lysin and holin. Morphological characterization and genome annotation showed that phage ASP23 belonged to the Krylovirinae family genus Phikmvvirus, and it had a latent period of 10 min and a burst size of 140 pfu/infected cell. In minks challenged with P. aeruginosa, phage ASP23 significantly reduced bacterial counts in the liver, lung, and blood. The whole-genome sequencing showed that its genome was a 42,735-bp linear and double-stranded DNA (dsDNA), with a G + C content of 62.15%. Its genome contained 54 predicted open reading frames (ORFs), 25 of which had known functions. The lysin of phage ASP23 (LysASP), in combination with EDTA, showed high lytic activity against P. aeruginosa L64. The holin of phage ASP23 was synthesized by M13 phage display technology, to produce recombinant phages (HolASP). Though HolASP exhibited a narrow lytic spectrum, it was effective against Staphylococcus aureus and Bacillus subtilis. However, these two bacteria were insensitive to LysASP. The findings highlight the potential of phage ASP23 to be used in the development of new antibacterial agents.

Background. Ovarian cancer (OC) is the leading cause of gynecologic malignant tumors. The role of necroptosis-related lncRNAs (NRLs) in OC remains unclear. This study aims to explore the association between NRLs and prognosis in OC patients. Methods. The Cancer Genome Atlas (TCGA) and GTEx datasets were used to obtain OC’s data. A NRLs signature associated with overall survival (OS) was constructed by Cox-LASSO regression analysis in training cohort for calculating risk score and then validated in testing cohort. Subsequently, the area under the curve (AUC) and Kaplan–Meier survival analysis were used to evaluate the predictive accuracy of the risk score. Finally, the immune infiltration and functional enrichment were compared between different risk groups. Results. A 8-NRLs signature including AC245128.3, AL355488.1, AC092794.1, AC068888.2, AL590652.1, AC008982.2, FOXP4-AS1, and Z94721.1 was identified to assess the OS of OC. Kaplan–Meier survival analysis, AUC value, and Cox regression analysis confirmed its predictive value and showed that the clinical outcomes were worse for high-risk patients. There were also differences in immunological functioning and immune pathways between the high-risk and low-risk groups. Conclusions. The signature based on eight NRLs has significant values in predicting prognostic prediction in OC, as well as providing a new sight for targeted therapies.

Combining network pharmacology with molecular docking, our study revealed the candidate targets and mechanisms of Shu Yu Wan (SYW) for treating cervical cancer (CC). The targets associated with CC and active compounds in SYW were identified through TCGA, GeneCards and TCMSP databases. Consequently, a total of 16 active compounds in SYW and 38 common targets related to CC were predicted. Genes TP53 and CDK2 are among the hub genes in the PPI network. The results of GO and KEGG enrichment analyses suggested that SYW exerted pharmacological effects on CC by regulating cellular senescence, p53 signaling pathway, cell cycle, apoptosis, viral carcinogenesis and human papillomavirus infection (HPV) signaling pathway. Finally, molecular docking confirmed a strong binding affinity between the main active compounds of SYW with the core target proteins.

Few studies have reported the effect of cement content and surcharge pressure on the drying−wetting durability of cement-stabilised clayey soil. The aim of this research was thus to understand the effect of these two factors on the drying−wetting durability of cement-stabilised clayey soil. Clayey soil, dredged from Taihu Lake in Wuxi, China, was stabilised with three different cement contents. Drying−wetting tests were performed on the cement-stabilised clayey soil under five different surcharge pressures and direct shear tests were conducted using a modified conventional direct shear device. The cement content was found to have a significant effect on the drying−wetting durability of the cement-stabilised clayey soil. Drying−wetting appears to decrease the shear strength of clayey soil with a low cement content, whereas drying−wetting appears to increase the shear strength of clayey soil with a high cement content. The variation in shear strength of the cement-stabilised clayey soil is attributed to drying-induced bond damage and drying-temperature-induced hydration and pozzolanic reactions. The surcharge pressure had a significant impact on the drying−wetting durability in a certain range. The findings are interesting from a practical perspective for earthworks involving cement-stabilised clayey soils.

Evidence of a connection between living near major roadway and adverse health outcome has come to light. However, little is known about the effect of residential traffic exposure on aging-related physical disability and whether this effect can be modified. We used data derived from Chinese Longitudinal Healthy Longevity Surveys in 2018, with a total of 15,771 participants aged ≥ 65. Residential proximity to major roadway was used as a surrogate for traffic-related air pollution and physical function was measured using basic and instrumental activities of daily living. Logistic regression models were adopted for the analyses. Compared with those living300 m from major road, participants living within 200 m had higher risk of poorer physical functioning. The peak odds ratio was observed in severe disability caused by 101-200 m distance (OR = 1.34, 95% CI: 1.08, 1.66). And this association got stronger with longer duration of living close to major road. In dichotomized analyses using 200 m as a cutoff point, the effect associated with living close to major road was greater in male and current smoker. Specially, poor physical function appears earlier in female, but less severe than that in male. The result emphasizes the adverse effect of residential proximity to major roadways to aging-related declines in health-especially for basic living ability. This association was more pronounced in male and current smokers, which cannot be reversed by lowering the indoor air pollution.

The high incidence of Avian pathogenic Escherichia coli (APEC) in poultry has resulted in significant economic losses. It has become necessary to find alternatives to antibiotics due to the alarming rise in antibiotic resistance. Phage therapy has shown promising results in numerous studies. In the current study, a lytic phage vB_EcoM_CE1 (short for CE1) against Escherichia coli (E. coli) was isolated from broiler feces, showing a relatively wide host range and lysing 56.9% (33/58) of high pathogenic strains of APEC. According to morphological observations and phylogenetic analysis, phage CE1 belongs to the Tequatrovirus genus, Straboviridae family, containing an icosahedral capsid (80 ~ 100 nm in diameter) and a retractable tail (120 nm in length). This phage was stable below 60°C for 1 h over the pH range of 4 to 10. Whole-genome sequencing revealed that phage CE1 contained a linear double-stranded DNA genome spanning 167,955 bp with a GC content of 35.4%. A total of 271 ORFs and 8 tRNAs were identified. There was no evidence of virulence genes, drug-resistance genes, or lysogeny genes in the genome. The in vitro test showed high bactericidal activity of phage CE1 against E. coli at a wide range of MOIs, and good air and water disinfectant properties. Phage CE1 showed perfect protection against broilers challenged with APEC strain in vivo. This study provides some basic information for further research into treating colibacillosis, or killing E. coli in breeding environments.

IntroductionThis research explored the clinical application of grade ≥ 3 infection predictive models for the newly diagnosed multiple myeloma (NDMM) population.MethodsIt evaluated 306 patients with NDMM based on three different predictive models. The relationship between the grade ≥ 3 infection rates in NDMM and the scores was analyzed retrospectively. The cumulative incidence of early grade ≥ 3 infection was estimated using the Kaplan–Meier method and log-rank test to assess the statistical significance of the difference. To compare the predictive performance in the prediction of infection, the Receiver Operating Characteristic Curve (ROC) curve was used to show the area under the curve (AUC), and DeLong’s test was used to analyze the difference in AUC.ResultsThe incidence of grade ≥ 3 infection within the first 4 months of NDMM was 40.20%. Concerning the FIRST score (predictors: ECOG, β2-microglobulin, hemoglobin, and lactate dehydrogenase), GEM-PETHEMA score (predictors: albumin, male sex, ECOG, and non-IgA type MM), and Infection Risk model of Multiple Myeloma (IRMM) score (predictors: ECOG, serum β2-microglobulin, globulin, and hemoglobin), the probability of early grade ≥ 3 infection in the different groups showed statistically significant differences (low-risk vs. high-risk: 25.81% vs. 50.00%, p p= 0.045; low-risk vs. moderate-risk vs. high-risk: 20.00% vs. 43.75% vs. 52.04%, p p pp = 0.090, respectively). The FIRST score showed good discrimination and simple calculation with highest AUC. Further subgroup analysis showed that the FIRST score could still apply for patients treated with bortezomib-based regimen and frail patients.DiscussionOur findings indicate that the FIRST score (consisting of ECOG, β2-microglobulin, hemoglobin, and lactate dehydrogenase) is a simple and robust infection stratification tool for patients with NDMM and could be used in routine clinical work.

BACKGROUND Healthcare is considered one of the most stressful occupations because multiple stressors exist in the workplace. Mobile stress management intervention is currently widely used in mental health intervention as an affordable and accessible approach. However, one of the major challenges in applying mobile intervention is the low interaction and engagement of participants, which hinders the optimal effects of mobile intervention, especially in self-guided mobile interventions where employees receive no human support during the intervention. OBJECTIVE The present study aims to compare the effects of CIMI, a complex interactive multimodal intervention, on physiological and psychological stress measures in comparison to the self-guided mobile intervention. METHODS We conducted a non-randomized, controlled study in two Chinese general hospitals. This study enrolled 245 healthcare workers who met the inclusion criteria for at least one of the three dimensions of the Depression, Anxiety, and Stress scale. All eligible participants were required to complete a questionnaire and wear a 24-hour Holter device to assess the physiological indicators of stress as indexed by heart rate variability at both baseline and post-intervention. During the program, participants in the CIMI group received a 12-week online intervention with the following four components: mobile stress management education, a web-based WeChat social network, tailored feedback, and a nurse coach, while the control group only received a self-guided intervention. RESULTS After a 12-week intervention, the perceived stress, depression, anxiety, fatigue, sleepiness symptoms, and subjective happiness in the CIMI group improved more significantly than those in the self-guided group. Additionally, we found a reduction in HRV parameters in the control group rather than the CIMI group. CONCLUSIONS CIMI was an effective intervention for improving both psychological and physiological indicators of stress among distressed HCWs. The findings provide objective evidence for developing an effective and economically viable mobile stress management intervention with a minimum of human support, but further research is needed. CLINICALTRIAL ClinicalTrial.gov., NCT05239065; https://clinicaltrials.gov/ct2/show/NCT05239065.

Delineating priority areas for highly mobile marine megafauna represents a major challenge for conservation biology. To manage such areas, one must understand both their spatial properties (i.e., location, number, extent), and the level of exposure to a number of given pressures. Here, we used a combination of ensemble distribution models, field-based validation methods and a cumulative effect assessment to illustrate key foraging sites and risk hotspots for adult loggerhead sea turtles, Caretta caretta, in the Mediterranean Sea. We found that foraging sites covered about 10% of the neritic zone of the Mediterranean basin. We identified sites which are well recognized by scientists, but also other areas for which our knowledge on the potential importance is limited. The patterns of the habitat use generated by field data validated the accuracy of the distribution model. About one fifth of the foraging areas hosted in the Mediterranean could be considered as hotspots of risk, characterized by high or very high exposure to cumulative pressures. Our results suggest that management and conservation efforts should continue to be held at key, well-known foraging grounds of adult sea turtles (e.g., Northern Adriatic Sea, Tunisian Plateau) but there are several more potential sites (e.g., parts of the Aegean Sea and the Western Mediterranean) which deserve our attention in order to ensure viable populations. © 2022, The Author(s), under exclusive licence to Springer Nature B.V.

Cellular senescence is a key mechanism of age-related vascular endothelial dysfunction. Interleukin-17A (IL-17A) is an inflammatory cytokine produced by Th17 cells (a subgroup of helper T cells), which is a key factor in the development of atherosclerosis. However, the effect of IL-17A on the senescence of vascular endothelial cells is still unclear. In this study, we aimed to explore the role of IL-17A on endothelial cell senescence and its signaling pathways associated with senescence. The proportion of Th17 cells in the spleen and the expression levels of IL-17A, IL-6, and vascular cell adhesion molecule-1 (VCAM-1) in mice of different ages were increased with aging. In vitro experiments showed that proliferation was inhibited, senescent β-galactosidase and senescence-associated proteins (p16, p19, p21, and p53) of mouse aortic endothelial cells (MAECs) were increased with IL-17A treatment. Blocking the NF-κB pathway with ammonium pyrrolidinedithiocarbamate (PDTC) successfully inhibited IL-17A-induced expression of senescence-associated proteins. In conclusion, our data reveal a previously unsuspected link between IL-17A and endothelial cell senescence, which was mediated by the NF-κB /p53/Rb pathway. Cellular senescence is a key mechanism of age-related vascular endothelial dysfunction. The authors explored the role of IL-17A on endothelial cell senescence and its associated signaling pathways. Their data reveals a previously unsuspected link between IL-17A and endothelial cell senescence, mediated by the NF-κB /p53/Rb signaling pathway.

The use of tranexamic acid (TXA) in hip fracture surgery remains inconclusive. The aim of the present meta-analysis was to assess the role of TXA use in hip fracture surgery, and attempt to disclose possible factors which might influence TXA efficacy and safety. A systematic computerized literature search was conducted to retrieve all randomized controlled trials (RCTs) and cohort studies regarding TXA use in hip fracture surgery. Overall efficacy and safety were evaluated. Then, subgroup and meta-regression analyses were conducted to disclose the influence of geographic area, fracture type, administration route, frequency and dosage of TXA, blood transfusion threshold, and follow-up duration on the overall effect. Thirty-four RCTs and 11 cohort studies were included. Patients receiving TXA had a significant decrease in the need for blood transfusion, reduced total, intra-operative and post-operative blood loss, a decrease in pre- and postoperative hemoglobin difference, without increasing thromboembolic events risk. Subgroup analysis showed that topical TXA had a lower transfusion rate compared with controls, yet the result did not reach statistical significance. Also, TXA had similar efficacy and safety profiles in patients with different frequency and dosage of TXA. Current evidence indicated that intravenous administration of TXA could significantly reduce blood transfusion and blood loss without increasing risk of thromboembolic events. The frequency and dosage of TXA might not alter the beneficial effect. The application of topical TXA should be cautious.

Pharmaceuticals and personal care products (PPCPs) are contaminants of emerging concern. PPCPs have been detected in various environmental matrices, posing potential threat to human health and environment quality. Thus far, there are no water quality guidelines (WQGs) established for PPCPs for the protection of freshwater organisms and ecosystems. In this study, we used the species sensitivity distribution (SSD) and assessment factor (AF) approaches to derive the 5% hazardous concentrations (HC5) of 35 selected PPCPs using acute and chronic toxicity data. The predicted no-effect concentrations (PNECs) and the acute-to-chronic ratios (ACRs) of chemicals were inherently computed to support the derivation of WQGs and for ecological risk assessment. Among these, endocrine-disrupting chemicals and antipsychotics were shown to pose a greater threat to the freshwater environment and organisms. The highest PNEC was recorded for chloramphenicol (3,620 μg/L) and the lowest for fluoxetine (0.0000291 μg/L), which could have significant ecological risks. In addition, the commonly used default ACRs do not seem to provide adequate support for the prediction of chronic toxicity thresholds and WQGs, as the highest ACRs of these drugs reached 39,100 (e.g., chloramphenicol). The findings of this study provide critical scientific information regarding the development of WQGs for environmental management and the risk control of PPCPs.

Real-time fluorescent quantitative PCR is considered as the gold standard for diagnosing COVID-19 worldwide now. But RT-PCR which could yield semi-quantitative results only, and the sensitivity of this method is usually not sufficient to discriminate patients in early stages of infection or with a very low viral load. So, the false-negative phenomenon often brings difficulties to epidemic prevention and diagnosis. More accurate and robust determine method are required for accurate SARS-CoV-2 diagnosis. To offer an attractive platform for SARS-CoV-2 RNA quantification, we report a droplet digital PCR technique for efficient, accurate, and quantitative detection of SARS-CoV-2 RNA. Two pairs of primer and two double-quenched probes targeting the region of ORF1ab and N protein coding genes of SARS-CoV-2 were designed to develop ddPCR assay. The sensitivity, specificity, repeatability, and reproducibility were tested by standard cDNAs and clinical specimens. First, we found the optimal annealing temperature was 53.6℃, the optimal primer concentration was 500 nM per reaction. When both probes of ORF1ab and N protein are applied simultaneously, their concentrations are100 nM and 50 nM, respectively. The optimal concentration of SARS-CoV-2 standard cDNA ranged from 1×103 to 1×104 copies/µL. And under this condition, the trend line for the measured concentration is Y = 0.9978x-0.4435. Further, the ddPCR were approximately 10 folds greater sensitivity than RT-qPCR assay. The established ddPCR assay with both probes showed to be a highly effective, accurate and reliable method for the sensitive detection of SARS-CoV-2. And the ddPCR method is the most potential and valuable method for clinical detection of SARS-CoV-2 virus.

Background Insulin-like peptide 5 (INSL5) is involved in both reproductive and metabolic processes in polycystic ovary syndrome (PCOS). This study aimed to evaluate the relationship between INSL5 and anti-Müllerian hormone (AMH). Methods A retrospective case–control study was conducted in a university-based reproductive centre between December 2019 and January 2021. We included 117 women with PCOS and 100 healthy subjects from Zhejiang Province. All subjects were divided into four groups (1st–4th) based on quartiles of serum INSL5 levels. Serum INSL5 concentration was assayed using an enzyme-linked immunosorbent assay. Results A significant direct association was observed between serum INSL5 and AMH levels in women with PCOS. The mean AMH level in the 1st–4th INSL5 level quartiles were 4.64, 5.20, 6.46, and 9.48 ng/ml, respectively (P P for trend Conclusions INSL5 and AMH levels were significantly correlated and elevated in women with PCOS. INSL5 and AMH might be associated with increased androgen secretion and chronic anovulation in PCOS.