ATM protects against lipopolysaccaride-induced blood-brain barrier disruption by regulating ATK/DRP1-mediated mitochondrial homeostasis.

BACKGROUND: Protein kinase ataxia telangiectasia mutated (ATM) regulates the function of endothelial cells and responds quickly to endotoxin. However, the function of ATM in lipopolysaccharide (LPS) -induced blood-brain barrier (BBB) disruption remains unknown. This study aimed to investigate the role and underlying mechanism of ATM in the regulation of the BBB function in sepsis. METHODS: We used lipopolysaccharide (LPS) to induce BBB disruption in vivo and to establish an in vitro model of cerebrovascular endothelial cells. BBB disruption was assessed by measuring Evans blue leakage and expression of vascular permeability regulators. To investigate the role of ATM, its inhibitor AZD1390 and clinically approved doxorubicin, an anthracycline that can activate ATM, were administered as scheduled. To explore the underlying mechanism, protein kinase B (AKT) inhibitor MK-2206 was administered to block the AKT/dynamin-related protein 1 (DRP1) pathway. RESULTS: LPS challenge induced significant BBB disruption, ATM activation and mitochondrial translocation. Inhibiting ATM with AZD1390 aggravated BBB permeability as well as the following neuroinflammation and neuronal injury, while activation of ATM by doxorubicin abrogated these defects. Further results obtained in brain microvascular endothelial cells showed that ATM inhibition reduced the phosphorylation of DRP1 at serine (S) 637, promoted excessive mitochondrial fission, and resulted in mitochondrial malfunction. By activating ATM, doxorubicin increased the protein binding between ATM and AKT and promoted the phosphorylated activation of AKT at S473, which could directly phosphorylate DRP1 at S637 to repress excessive mitochondrial fission. Consistently, the protective role of ATM was abolished by the AKT inhibitor MK-2206. CONCLUSIONS: ATM protects against LPS-induced BBB disruption by regulating mitochondrial homeostasis, at least in part, through the AKT/DRP1 pathway.

Inhibition of Schwann Cell Pyroptosis Promotes Nerve Regeneration in Peripheral Nerve Injury in Rats.

Background: Peripheral nerve injury (PNI) is one of the most debilitating injuries, but therapies for PNI are still far from satisfactory. Pyroptosis, a recently identified form of cell death, has been demonstrated to participate in different diseases. However, the role of pyroptosis of Schwann cells in PNI remains unclear. Methods: We established a rat PNI model, and western blotting, transmission electron microscopy, and immunofluorescence staining were used to confirm pyroptosis of Schwann cells in PNI in vivo. In vitro, pyroptosis of Schwann cells was induced by lipopolysaccharides (LPS)+adenosine triphosphate disodium (ATP). An irreversible inhibitor of pyroptosis, acetyl (Ac)-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-cmk), was used to attenuate Schwann cell pyroptosis. Moreover, the influence of pyroptotic Schwann cells on the function of dorsal root ganglion neurons (DRGns) was analyzed by a coculture system. Finally, the rat PNI model was intraperitoneally treated with Ac-YVAD-cmk to observe the effect of pyroptosis on nerve regeneration and motor function. Results: Schwann cell pyroptosis was notably observed in the injured sciatic nerve. LPS+ATP treatment effectively induced Schwann cell pyroptosis, which was largely attenuated by Ac-YVAD-cmk. Additionally, pyroptotic Schwann cells inhibited the function of DRGns by secreting inflammatory factors. A decrease in pyroptosis in Schwann cells promoted regeneration of the sciatic nerve and recovery of motor function in rats. Conclusion: Given the role of Schwann cell pyroptosis in PNI progression, inhibition of Schwann cell pyroptosis might be a potential therapeutic strategy for PNI in the future.

Highly Selective Catalytic Oxi-upcycling Polyethylene to Aliphatic Dicarboxylic Acid under A Mild Hydrogen-free Process.

A low-temperature hydrogen-free process for upcycling polyethylene (PE) plastics into aliphatic dicarboxylic acid is developed using a heterogeneous catalyst Ru/TiO2. The low-density PE (LDPE) conversion can reach 95% in 24 h under a pressure of 1.5 MPa air at 160 °C with 85% of the liquid product yield, which mainly is low molecular weight aliphatic dicarboxylic acid. Excellent performances can be also achieved for different PE feedstocks. This catalytic oxi-upcycling process paving a new way of upcycling polyethylene waste.

Multimodal MRI diagnosis and transvenous embolization of a basicranial emissary vein dural arteriovenous fistula: A case report.

A dural arteriovenous fistula (DAVF) is an abnormal linkage connecting the arterial and venous systems within the intracranial dura mater. A basicranial emissary vein DAVF drains into the cavernous sinus and the ophthalmic vein, similar to a cavernous sinus DAVF. Precise preoperative identification of the DAVF location is a prerequisite for appropriate treatment. Treatment options include microsurgical disconnection, endovascular transarterial embolization (TAE), transvenous embolization (TVE), or a combination thereof. TVE is an increasingly popular approach for the treatment of DAVFs and the preferred approach for skull base locations, due to the risk of cranial neuropathy caused by dangerous anastomosis from arterial approaches. Multimodal magnetic resonance imaging (MRI) can provide anatomical and hemodynamic information for TVE. The therapeutic target must be precisely embolized in the emissary vein, which requires guidance via multimodal MRI. Here, we report a rare case of successful TVE for a basicranial emissary vein DAVF, utilizing multimodal MRI assistance. The fistula had vanished, pterygoid plexus drainage had improved, and the inferior petrosal sinus had recanalized, as observed on 8-month follow-up angiography. Symptoms and signs of double vision, caused by abduction deficiency, disappeared. Detailed anatomic and hemodynamic assessment by multimodal MRI is the key to guiding successful diagnosis and treatment.

Efficacy and adverse reaction management of oncolytic viral intervention combined with chemotherapy in patients with liver metastasis of gastrointestinal malignancy.

Background: The liver is a key target organ for colorectal and gastric cancer metastasis. One of the challenges in the treatment of colorectal and gastric cancers is the management of liver metastasis. This study aimed to investigate the efficacy, adverse effects, and coping strategies of oncolytic virus injection in patients with liver metastases of gastrointestinal malignancies. Methods: We prospectively analyzed patients treated at Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine from June 2021 to October 2022. 47 patients with gastrointestinal cancer liver metastasis were included in the study. The data, including clinical manifestations, imaging, tumor markers, postoperative adverse reactions, psychological intervention, dietary guidance, and adverse reaction management were evaluated. Results: Oncolytic virus injection was successful in all patients, and no drug injection-related deaths occurred. The adverse effects, such as fever, pain, bone marrow suppression, nausea, and vomiting, were mild and resolved subsequently. Based on the comprehensive intervention of nursing procedures, the postoperative adverse reactions of patients were effectively alleviated and treated. None of the 47 patients had any puncture point infections, and the pain caused by the invasive operation was relieved quickly. After 2 courses of oncolytic virus injection, postoperative liver MRI showed 5 partial remissions, 30 stable diseases, and 12 progressive diseases in target organs. Conclusion: Interventions based on nursing procedures can ensure the smooth treatment of recombinant human adenovirus type 5 in patients with liver metastases of gastrointestinal malignant tumors. This is of great importance for clinical treatment and significantly reduces patient complications and improves the patient's quality of life.

Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in our previous randomized, double-blind, placebo-controlled clinical trial (NCT04288102). METHODS: A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4 × 107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. Outcomes measured included: 6-min walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire (SF-36), COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, tumor markers, and MSC-related adverse events (AEs). FINDINGS: Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04-0.80, Fisher's exact test, p = 0.015). At month 18, the general health score from the SF-36 was higher in the MSC group than in the placebo group (50.00 vs. 35.00, 95% CI: 0.00-20.00, Wilcoxon rank sum test, p = 0.018). Total severity score of lung imaging and the titer of neutralizing antibodies were similar between the two groups at months 18 and 24. There was no difference in AEs or tumor markers at the 2-year follow-up between the two groups. INTERPRETATION: Long-term safety was observed for the COVID-19 patients who received MSC treatment. However, efficacy of MSC treatment was not significantly sustained through the end of the 2-year follow-up period. FUNDING: The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900, 2022YFC2304401), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRC-ID202105,413FZT6).

Buried Interface Passivation: A Key Strategy to Breakthrough the Efficiency of Perovskite Photovoltaics.

Owing to the merits of low cost and high power conversion efficiency (PCE), perovskite solar cells (PSCs) have become the best candidate to replace the commonly used silicon solar cells. However, PSCs have been slow to enter the market for a number of reasons, including poor stability, high toxicity, and rigorous preparation process. Passivation strategies including surface passivation and bulk passivation have been successfully applied to improve the device performance of PSCs. The passivation of the defects at the buried interface, which is regarded as a key strategy to breakthrough the device efficiency and stability of PSCs in the future, is ongoing with challenge. Herein, in detail the recent passivation of the buried interface is introduced from three aspects: perovskite layer, buried interlayer, and transport layer. The passivation effect of the buried interface is clearly demonstrated through three categories of salts, organics, and 2D materials. In addition, the transport layer is classified into electron transport layer (ETL) and hole transport layer (HTL). These classifications can help to have a clear understanding of substances which generate passivating effect and guide the continuous promotion of the follow-up buried interface passivating work.

Non-pharmacological interventions for older adults with postprandial hypotension: A scoping review.

BACKGROUND: Older adults frequently suffer from postprandial hypotension, associated with an increased risk of falls, syncope, acute cardiovascular and cerebrovascular diseases, and even death. Researchers use non-pharmacological interventions, but related literature is dispersed and lacks a latest summary. OBJECTIVE: The aim of this study was to map and examine non-pharmacological interventions currently employed to assist older adults with postprandial hypotension and lay a solid foundation for future studies. METHODS: This study adhered to the JBI methodology for scoping reviews and preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews. PubMed, Web of Science, Embase, Cochrane Library, CINAHL, SCOPUS, Chinese Biomedical Journal, China National Knowledge Infrastructure, VIP and WAN FANG Data were retrieved from their inception to 1 August 2022. RESULTS: Two randomized controlled trials and seven quasi-experimental studies were included. Small meals, exercise interventions, fibre with meals, green tea and water therapy have been reported to prevent postprandial hypotension effectively; however, position changes have been reported to have no impact on postprandial blood pressure decrease. Additionally, the blood pressure determination methods and test meals may affect observed trial effects. CONCLUSION: Large samples and long-term follow-up studies are needed to prove the efficacy and safety of existing non-pharmacological interventions. Future studies should develop a BP determination method based on the postprandial BP decline trajectory induced by a given test meal to improve the reliability of study results. RELEVANCE TO CLINICAL PRACTICE: This review broadly summarizes existing studies on developing and validating non-pharmacological interventions for older adults with postprandial hypotension. It also analyses special factors that may influence the trial effects. This may provide a useful reference for future research.

Gene signature developed for predicting early relapse and survival in early-stage pancreatic cancer.

BACKGROUND: The aim of this study was to construct a predictive signature integrating tumour-mutation- and copy-number-variation-associated features using machine learning to precisely predict early relapse and survival in patients with resected stage I-II pancreatic ductal adenocarcinoma. METHODS: Patients with microscopically confirmed stage I-II pancreatic ductal adenocarcinoma undergoing R0 resection at the Chinese PLA General Hospital between March 2015 and December 2016 were enrolled. Whole exosome sequencing was performed, and genes with different mutation or copy number variation statuses between patients with and without relapse within 1 year were identified using bioinformatics analysis. A support vector machine was used to evaluate the importance of the differential gene features and to develop a signature. Signature validation was performed in an independent cohort. The associations of the support vector machine signature and single gene features with disease-free survival and overall survival were assessed. Biological functions of integrated genes were further analysed. RESULTS: Overall, 30 and 40 patients were included in the training and validation cohorts, respectively. Some 11 genes with differential patterns were first identified; using a support vector machine, four features (mutations of DNAH9, TP53, and TUBGCP6, and copy number variation of TMEM132E) were further selected and integrated to construct a predictive signature (the support vector machine classifier). In the training cohort, the 1-year disease-free survival rates were 88 per cent (95 per cent c.i. 73 to 100) and 7 per cent (95 per cent c.i. 1 to 47) in the low-support vector machine subgroup and the high-support vector machine subgroup respectively (P < 0.001). Multivariable analyses showed that high support vector machine was significantly and independently associated with both worse overall survival (HR 29.20 (95 per cent c.i. 4.48 to 190.21); P < 0.001) and disease-free survival (HR 72.04 (95 per cent c.i. 6.74 to 769.96); P < 0.001). The area under the curve of the support vector machine signature for 1-year disease-free survival (0.900) was significantly larger than the area under the curve values of the mutations of DNAH9 (0.733; P = 0.039), TP53 (0.767; P = 0.024), and TUBGCP6 (0.733; P = 0.023), the copy number variation of TMEM132E (0.700; P = 0.014), TNM stage (0.567; P = 0.002), and differentiation grade (0.633; P = 0.005), suggesting higher predictive accuracy for prognosis. The value of the signature was further validated in the validation cohort. The four genes included in the support vector machine signature (DNAH9, TUBGCP6, and TMEM132E were novel in pancreatic ductal adenocarcinoma) were significantly associated with the tumour immune microenvironment, G protein-coupled receptor binding and signalling, cell-cell adhesion, etc. CONCLUSION: The newly constructed support vector machine signature precisely and powerfully predicted relapse and survival in patients with stage I-II pancreatic ductal adenocarcinoma after R0 resection.

Gustatory stimulus interventions for older adults with dysphagia: a scoping review.

BACKGROUND: Gustatory stimulus interventions have been shown to improve swallowing function in older adults with dysphagia. However, the optimal intervention strategies as well as their effects and safety remain unclear. AIMS: To explore current evidence regarding gustatory stimulus interventions for dysphagia in older adults. METHODS: Nine electronic databases (PubMed, Web of Science, Embase, CINAHL, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database, and Sinomed) were searched from their inception to August 2022. RESULTS: This review identified 263 articles, and 15 met the inclusion criteria. The types of gustatory stimulus interventions included spicy (n = 10), sour (n = 3), and mixed (sour-sweet) stimuli (n = 2), with most studies focusing on spicy stimuli. The most frequently reported spicy stimulus was capsaicin. Further, the most commonly reported intervention frequency was thrice a day before meals for 1-4 weeks. The stimuli concentrations and dosages could not be standardized due to the among-study heterogeneity. These studies reported 16 assessment tools and 42 outcomes, which mainly included videofluoroscopy and swallowing response time respectively. More than half of the included studies reported no adverse effects of gustatory stimulus interventions. CONCLUSION AND DISCUSSIONS: Gustatory stimulus interventions improved swallowing function in older adults with dysphagia. However, assessment tools and outcomes for dysphagia should be standardized in the future, and explore personalized interventions based on different diseases and their stages, to determine the most cost-effective interventions, and to prevent its complications.

Inhibition of sediment erosion and phosphorus release by remediation strategy of contaminated sediment backfilling.

The management of sediment-water interfaces, especially bed stability, is essential for controlling accumulated contaminants in the sediment. In this study, the relationship between sediment erosion and phosphorus (P) release under the remediation strategy of contaminated sediment backfilling (CSBT) was explored through a flume experiment, i.e. the dredged sediment was calcined into ceramsite after dewatering and detoxification and then backfilled to the dredged area for sediment capping, thus avoiding the introduction of foreign materials via in-situ remediation and the large-scale land occupation associated with ex-situ remediation. Acoustic Doppler velocimeter (ADV) and optical backscatter sensor (OBS) were used to measure the vertical distributions of flow velocity and sediment concentration in the overlying water, respectively, and diffusive gradients in thin films (DGT) was used to measure the P distribution in the sediment. The results revealed that improving bed stability from CSBT can considerably improve the robustness of sediment-water interface and reduce sediment erosion by more than 70%. The corresponding P release from the contaminated sediment could be inhibited with an inhibition efficiency as high as 80%. CSBT is a potent strategy for managing contaminated sediment. This study provides a theoretical reference for controlling sediment pollution, further supporting river and lake ecological management and environmental restoration.

Magnetic relaxation switch sensor based on aptamer-modified poly-L-lysine-ferroferric oxide magnetic nanoparticles and graphene oxide for the determination of insecticides in vegetables.

A simple and effective graphene oxide-magnetic relaxation switch (GO-MRS) sensor that combines graphene oxide (GO) and aptamer-modified poly-L-lysine(PLL)-Fe3O4 nanoparticles (Fe3O4@PLL-Apt NPs) was designed for the detection of acetamiprid (ACE). In this sensor, Fe3O4@PLL-Apt NPs acted as a relaxation signal probe and GO facilitated the generation of relaxation signal changes (dispersion/aggregation shift), while the aptamer is a molecular component that recognizes ACE. This GO-assisted magnetic signal probe improves the stability of magnetic nanoparticles in solution and enhances their sensitivity to small molecules while avoiding cross-reactions. Under optimal conditions, the sensor exhibits a wide working range (10-80 nM) and low detection limit (8.43 nM). The spiked recoveries ranged from 96.54 to 103.17%, with a relative standard deviation (RSD) of less than 2.3%. In addition, the performance of the GO-MRS sensor matched that of the standard method (liquid chromatography-mass spectrometry (LC-MS)), indicating that the GO-MRS sensor is suitable for the detection of ACE in vegetables.

Association between PM2.5 exposure and the outcomes of ART treatment: A prospective birth cohort study.

Exposure to fine particulate matter (PM2.5) has been reported to be adversely associated with reproductive health. However, current evidence on PM2.5 exposure adversely influencing pregnancy outcomes remains inconclusive. Women receiving assisted reproductive technology (ART) treatment are under close monitoring with regards to their treatment process, which make them great study population to assess the impact of PM2.5 in the post-implantation period. Therefore, within a prospective cohort study in Jiangsu, China, we assessed the associations between exposure to ambient PM2.5 and the outcomes of ART treatment, including implantation failure, biochemical pregnancy loss, clinical pregnancy and live birth, in 2431 women who underwent the first fresh embryo transfer or frozen embryo transfer cycle. High-performance machine-learning model was performed to estimate daily PM2.5 exposure concentrations at 1 km spatial revolution. Exposure windows were divided into seven periods according to the process of follicular and embryonic development in ART. Generalized estimation equations (GEE) was used to assess the association between PM2.5 and ART outcomes. Higher PM2.5 exposure was associated with decreased probability of clinical pregnancy (RR: 0.98, 95 % CI: 0.96-1.00). Each 10 µg/m3 increase in PM2.5 exposure in the duration from hCG test to 30 days after embryo transfer (Period 7) was positively associated with the risk of biochemical pregnancy loss (RR: 1.06, 95 % CI: 1.00-1.13), and more prominent effects were observed in women undergoing fresh embryo transfer. Null associations were observed between PM2.5 exposure and implantation failure or live birth at any exposure window. Collectively, our study suggested that exposure to PM2.5 increased the risk of adverse treatment outcomes in the ART population. Thus, for women opting for ART treatment, particularly those who select fresh embryo transfer cycles, additional evaluation of PM2.5 exposure before treatment might be of value in decreasing the risk of adverse pregnancy outcomes.

Genetic analysis of 23 Y-STR loci in the Va population from Yunnan Province, Southwest China.

BACKGROUND: Y-chromosomal short tandem repeat (Y-STR) polymorphisms are widely used in forensic DNA analysis. However, there is a lack of information about the Chinese Va population in the Y-STR Haplotype Reference Database. AIM: To establish the Y-chromosome Haplotype Reference Database of the Yunnan Va population and investigate the population genetic relationships with other geographically adjacent groups. SUBJECTS AND METHODS: In total, 23 Y-STR loci were genotyped with the PowerPlex Y23 Kit in 368 unrelated healthy Va males from Yunnan Province, Southwest China. Genetic polymorphism was analysed using the YHRD's AMOVA tools and the MEGA 6.0 software. RESULTS: The gene diversity (GD) of the 23 Y-STR loci ranged from 0.3092 (DYS19) to 0.7868 (DYS385a/b). According to haplotype analysis, 204 different haplotypes were obtained, out of which 144 were unique. The haplotype diversity (HD) and discrimination capacity (DC) were 0.9852 and 0.5543, respectively. By comparing the Yunnan Va group with the other 22 referential groups, the results revealed that Yunnan Va was isolated from other groups. CONCLUSIONS: The 23 Y-STR loci were highly polymorphic and informative in the Yunnan Va population, and the results enriched the basic genetic information for forensic investigation and population genetic studies.

The complete chloroplast genome sequence of Zannichellia palustris (Potamogetonaceae).

Zannichellia palustris Linnaeus 1753 is a cosmopolitan submerged species capable of rapidly responding to environmental changes, with potential applications in the ecological treatment of heavy metal pollution in water bodies. This study aimed to characterize the complete chloroplast genome of Z. palustris, which has not been reported previously. The chloroplast genome of Z. palustris displays a quadripartite structure with a length of 155,262 base pairs (bp), comprising a large single copy (LSC) region of 85,397 bp, a small single copy (SSC) region of 18,057 bp, and a pair of inverted repeat (IR) regions of 25,904 bp. The GC content of the genome is 35.8%, with corresponding values of 33.4% for the LSC, 28.2% for the SSC, and 42.5% for the IR regions. The genome contained 130 genes, including 85 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis within the order Alismatales revealed that Z. palustris clusters with the clade of Potamogeton perfoliatus, P. crispus and Stuckenia pectinata.

Characterization of A-to-I Editing in Pigs under a Long-Term High-Energy Diet.

Long-term high-energy intake has detrimental effects on pig health and elevates the risk of metabolic disease. RNA editing modifying RNA bases in a post-transcriptional process has been extensively studied for model animals. However, less evidence is available that RNA editing plays a role in the development of metabolic disorders. Here, we profiled the A-to-I editing in three tissues and six gut segments and characterized the functional aspect of editing sites in model pigs for metabolic disorders. We detected 64,367 non-redundant A-to-I editing sites across the pig genome, and 20.1% correlated with their located genes' expression. The largest number of A-to-I sites was found in the abdominal aorta with the highest editing levels. The significant difference in editing levels between high-energy induced and control pigs was detected in the abdominal aorta, testis, duodenum, ileum, colon, and cecum. We next focused on 6041 functional A-to-I sites that detected differences or specificity between treatments. We found functional A-to-I sites specifically involved in a tissue-specific manner. Two of them, located in gene SLA-DQB1 and near gene B4GALT5 were found to be shared by three tissues and six gut segments. Although we did not find them enriched in each of the gene features, in correlation analysis, we noticed that functional A-to-I sites were significantly enriched in gene 3'-UTRs. This result indicates, in general, A-to-I editing has the largest potential in the regulation of gene expression through changing the 3'-UTRs' sequence, which is functionally involved in pigs under a long-term high-energy diet. Our work provides valuable knowledge of A-to-I editing sites functionally involved in the development of the metabolic disorder.

Epidemiological updates of post-traumatic related limb osteomyelitis in china: a 10 years multicenter cohort study.

BACKGROUND: Post-traumatic related limb osteomyelitis (PTRLO) is a complex bone infection. Currently, there are no available microbial data on a national scale that can guide appropriate antibiotic selection, and explore the dynamic changes in dominant pathogens over time. This study aimed to conduct a comprehensive epidemiological analysis of PTRLO in China. METHODS: The study was approved by the Institutional Research Board (IRB), and 3,526 PTRLO patients were identified from 212,394 traumatic limb fracture patients at 21 hospitals between January 1st, 2008- December 31st, 2017. A retrospective analysis was conducted to investigate the epidemiology of PTRLO, including changes in infection rate (IR), pathogens, infection risk factors, and antibiotic resistance and sensitivity. RESULTS: The IR of PTRLO increased gradually from 0.93%-2.16% (Z=14.392, P<0.001). Monomicrobial infection (MI, 82.6%) was significantly higher than polymicrobial infection (PI, 17.4%) (P<0.001). The IR of Gram-Positive (GP) & Gram-Negative (GN) pathogens showed a significant increase from the lowest 0.41% to the highest 1.15% (GP) or 1.62% (GN), respectively. However, the longitudinal trend of GP versus GN's composition did not show any significance (Z=+/-1.1918, P>0.05). The most prevalent Gram-positive strains were MSSA (17.03%), MRSA (10.46%), E. faecalis (5.19%), and S. epidermidis (4.87%). In contrast, the dominant strains Gram-negative strains were Pseudomonas Aeruginosa (10.92%), E. cloacae (10.34%), E.coli (9.47%), Acinetobacter Baumannii (7.92%) and Klebsiella Pneumoniae (3.33%). In general, the high-risk factors for PI include opened-fracture (odds ratio, 2.223), hypoproteinemia (odds ratio, 2.328), and multiple fractures (odds ratio, 1.465). It is important to note that the antibiotics resistance and sensitivity analysis of the pathogens may be influenced by complications or comorbidities. CONCLUSIONS: This study provides the latest data of PTRLO in China and offers trustworthy guidelines for clinical practice. (China Clinical Trials.gov number, ChiCTR1800017597).

Hypertension Statistics for US Adults: An Open-Source Web Application for Analysis and Visualization of National Health and Nutrition Examination Survey Data.

BACKGROUND: Data from the US National Health and Nutrition Examination Survey are freely available and can be analyzed to produce hypertension statistics for the noninstitutionalized US population. The analysis of these data requires statistical programming expertise and knowledge of National Health and Nutrition Examination Survey methodology. METHODS: We developed a web-based application that provides hypertension statistics for US adults using 10 cycles of National Health and Nutrition Examination Survey data, 1999 to 2000 through 2017 to 2020. We validated the application by reproducing results from prior publications. The application's interface allows users to estimate crude and age-adjusted means, quantiles, and proportions. Population counts can also be estimated. To demonstrate the application's capabilities, we estimated hypertension statistics for noninstitutionalized US adults. RESULTS: The estimated mean systolic blood pressure (BP) declined from 123 mm Hg in 1999 to 2000 to 120 mm Hg in 2009 to 2010 and increased to 123 mm Hg in 2017 to 2020. The age-adjusted prevalence of hypertension (ie, systolic BP≥130 mm Hg, diastolic BP≥80 mm Hg or self-reported antihypertensive medication use) was 47.9% in 1999 to 2000, 43.0% in 2009 to 2010, and 44.7% in 2017 to 2020. In 2017 to 2020, an estimated 115.3 million US adults had hypertension. The age-adjusted prevalence of controlled BP, defined by the 2017 American College of Cardiology/American Heart Association BP guideline, among nonpregnant US adults with hypertension was 9.7% in 1999 to 2000, 25.0% in 2013 to 2014, and 21.9% in 2017 to 2020. After age adjustment and among nonpregnant US adults who self-reported taking antihypertensive medication, 27.5%, 48.5%, and 43.0% had controlled BP in 1999 to 2000, 2013 to 2014, and 2017 to 2020, respectively. CONCLUSIONS: The application developed in the current study is publicly available at https://bcjaeger.shinyapps.io/nhanesShinyBP/ and produced valid, transparent and reproducible results.

Metabolic Engineering of Pichia pastoris for the Production of Triacetic Acid Lactone.

Triacetic acid lactone (TAL) is a promising renewable platform polyketide with broad biotechnological applications. In this study, we constructed an engineered Pichia pastoris strain for the production of TAL. We first introduced a heterologous TAL biosynthetic pathway by integrating the 2-pyrone synthase encoding gene from Gerbera hybrida (Gh2PS). We then removed the rate-limiting step of TAL synthesis by introducing the posttranslational regulation-free acetyl-CoA carboxylase mutant encoding gene from S. cerevisiae (ScACC1*) and increasing the copy number of Gh2PS. Finally, to enhance intracellular acetyl-CoA supply, we focused on the introduction of the phosphoketolase/phosphotransacetylase pathway (PK pathway). To direct more carbon flux towards the PK pathway for acetyl-CoA generation, we combined it with a heterologous xylose utilization pathway or endogenous methanol utilization pathway. The combination of the PK pathway with the xylose utilization pathway resulted in the production of 825.6 mg/L TAL in minimal medium with xylose as the sole carbon source, with a TAL yield of 0.041 g/g xylose. This is the first report on TAL biosynthesis in P. pastoris and its direct synthesis from methanol. The present study suggests potential applications in improving the intracellular pool of acetyl-CoA and provides a basis for the construction of efficient cell factories for the production of acetyl-CoA derived compounds.

Dynamics of SARS-CoV-2 Antibody Responses up to 9 Months Post-Vaccination in Individuals with Previous SARS-CoV-2 Infection Receiving Inactivated Vaccines.

Humoral immunity confers protection against COVID-19. The longevity of antibody responses after receiving an inactivated vaccine in individuals with previous SARS-CoV-2 infection is unclear. Plasma samples were collected from 58 individuals with previous SARS-CoV-2 infection and 25 healthy donors (HDs) who had been vaccinated with an inactivated vaccine. The neutralizing antibodies (NAbs) and S1 domain-specific antibodies against the SARS-CoV-2 wild-type and Omicron strains and nucleoside protein (NP)-specific antibodies were measured using a chemiluminescent immunoassay. Statistical analysis was performed using clinical variables and antibodies at different timepoints after SARS-CoV-2 vaccination. NAbs targeting the wild-type or Omicron strain were detected in individuals with previous SARS-CoV-2 infection at 12 months after infection (wild-type: 81%, geometric mean (GM): 20.3 AU/mL; Omicron: 44%, GM: 9.4 AU/mL), and vaccination provided further enhancement of these antibody levels (wild-type: 98%, GM: 53.3 AU/mL; Omicron: 75%, GM: 27.8 AU/mL, at 3 months after vaccination), which were significantly higher than those in HDs receiving a third dose of inactivated vaccine (wild-type: 85%, GM: 33.6 AU/mL; Omicron: 45%, GM: 11.5 AU/mL). The level of NAbs in individuals with previous infection plateaued 6 months after vaccination, but the NAb levels in HDs declined continuously. NAb levels in individuals with previous infection at 3 months post-vaccination were strongly correlated with those at 6 months post-vaccination, and weakly correlated with those before vaccination. NAb levels declined substantially in most individuals, and the rate of antibody decay was negatively correlated with the neutrophil-to-lymphocyte ratio in the blood at discharge. These results suggest that the inactivated vaccine induced robust and durable NAb responses in individuals with previous infection up to 9 months after vaccination.