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Abstract Objective This study aimed to investigate the risk factors affecting the presence of carotid plaque in asymptomatic adults. Methods Asymptomatic adults (age > 40 years, no symptoms of cardiovascular and cerebrovascular diseases) undergoing routine health examinations from physical examination department were included in this study. Carotid plaque was measured by Resona 7OB and Resona 8EXP color Doppler ultrasound and L9-3U and L4-5WU probes. The focal carotid intima–media thickness was greater than 1.1 mm, and the local protrusion of the artery wall into the artery lumen suggested the presence of carotid atherosclerotic plaque. According to their ultrasound results, 1077 asymptomatic adults were divided into a group with carotid plaque (477) and a group without carotid plaque (600). Results A total of 1077 asymptomatic adults were included in this study, of whom 44.3% had carotid plaque. The proportion of men with carotid plaque was 84.5%. Multifactorial logistic analysis suggested that age, fasting blood glucose (FBG), total cholesterol (TC), homocysteine (Hcy) and male gender were risk factors for carotid atherosclerosis. The predictive probability of these risk factor indicators derived from the multifactorial model was calculated using receiver operating characteristic (ROC) curves with SPSS 25.0 software. The calculated area under the receiver operating characteristic curve (AUC) was 0.715 (95% CI, 0.685–0.746). Conclusion Age, FBG, TC, Hcy and male gender are risk factors for carotid atherosclerosis in asymptomatic adults. Gender differences in carotid atherosclerosis deserve further attention.

Abstract Metabolic memory (MM) is a major factor in the delayed wound healing observed in diabetic patients. While “Nocardia rubrum cell wall skeleton” (Nr-CWS) is utilized to enhance macrophage proliferation in immune diseases, its impact on MM wounds in diabetes is unclear. This study demonstrates that transient hyperglycemia leads to prolonged damage in vascular endothelial cells by decreasing METTL3 expression, leading to decreased RNA methylation and impaired cellular metabolism. Remarkably, Nr-CWS application increases METTL3 levels in these cells, facilitating the recovery of cell function. Further in vivo and in vitro analyses demonstrate that transient hyperglycemia-induced reduction in METTL3 hinders RNA methylation of the downstream gene Cds2, impacting mitochondrial function and energy metabolism and consequently reducing angiogenic capacity in endothelial cells. This impairment significantly influences diabetic wound healing. Our findings highlight the profound impact of transient hyperglycemia on wound healing, establishing METTL3 as a significant role in vascular complications of diabetes. This study not only elucidates the pathophysiological mechanisms behind MM in diabetic wounds but also suggests Nr-CWS as a potential therapeutic agent, offering a novel approach for treating diabetic wounds.

Abstract Background We studied the characteristics of carotid ultrasound plaque in a healthy physical-examination population and analyzed the risk factors for hypoechoic carotid plaque for early control and prevention of stroke. Results A total of 1333 healthy physical-examination individuals were included in this study, including 457 females and 876 males. According to the results of carotid artery ultrasound, they were divided into hyperechoic carotid plaque (n = 940) and hypoechoic carotid plaque (n = 393). Multivariate logistic analysis showed that male, alcohol consumption, and low-density lipoprotein were risk factors for hypoechoic carotid plaque. SPSS 25.0 software was used to draw the receive operating characteristic curve and calculate the prediction probability of the risk factor indicators obtained by the multifactor model. The area under the curve was also calculated to be 0.623 (95% CI = 0.591–0.655). Conclusion Male, alcohol consumption, and low-density lipoprotein are risk factors for hypoechoic carotid plaque in a healthy physical-examination population.

Abstract Background Osteo-sarcopenia (OS) has become a global public health problem and a frontier research problem, as a combination of sarcopenia (SP) and osteoporosis (OP) diseases. The clinical performances include muscle weakness, systemic bone pain, standing difficulty, even falls and fractures, etc., which seriously affect the patient’s life and work. The pathological mechanism of the OS may be the abnormal metabolism which disrupts the equilibrium stability of the musculoskeletal system. Therefore, this study combined vitamin D (Vit. D) and whole-body vibration training (WBVT) to intervene in subjects of OS, aiming to evaluate the effectiveness and safety of the diagnosis and treatment protocol and to explore the efficacy mechanism. Methods We propose a multicenter, parallel-group clinical trial to evaluate the efficacy and safety of Vit. D combined with WBVT intervention in OS. Subjects who met the inclusion or exclusion criteria and signed the informed consent form would be randomly assigned to the WBVT group, Vit. D group, or WBVT+ Vit. D group. All subjects will be treated for 1 month and followed up after 3 and 6 months. The primary outcomes are lumbar bone mineral density (BMD) and appendicular skeletal muscle mass (ASM) measured by dual-energy X-ray absorptiometry (DXA) and handgrip strength measured by grip strength meter. Secondary outcomes include serum markers of myostatin (MSTN), irisin and bone turnover markers (BTM), SARC-CalF questionnaire, 1-min test question of osteoporosis risk, patient health status (evaluated by the SF-36 health survey), physical performance measurement that includes 5-time chair stand test, 6-m walk, and the short physical performance battery (SPPB). Discussion If Vit. D combined with WBVT can well relieve OS symptoms without adverse effects, this protocol may be a new treatment strategy for OS. After therapeutic intervention, if the serum marker MSTN/irisin is significant, both have the potential to become sensitive indicators for screening OS effective drugs and treatments, which also indicates that WBVT combined with Vit. D plays a role in improving OS by regulating MSTN/irisin. Trial registration Chinese Clinical Trial Registry ChiCTR2400082269 . Registered on March 26, 2024.

Abstract Fungal diseases are the main factors affecting the quality and production of vegetables. Rapid and accurate detection of pathogenic spores is of great practical significance for early prediction and prevention of diseases. However, there are some problems with microscopic images collected in the natural environment, such as complex backgrounds, more disturbing materials, small size of spores, and various forms. Therefore, this study proposed an improved detection method of GCS-YOLOv8 (Global context and CARFAE and Small detector-optimized YOLOv8), effectively improving the detection accuracy of small-target pathogen spores in natural scenes. Firstly, by adding a small target detection layer in the network, the network’s sensitivity to small targets is enhanced, and the problem of low detection accuracy of the small target is effectively improved. Secondly, Global Context attention is introduced in Backbone to optimize the CSPDarknet53 to 2-Stage FPN (C2F) module and model global context information. At the same time, the feature up-sampling module Content-Aware Reassembly of Features (CARAFE) was introduced into Neck to enhance the ability of the network to extract spore features in natural scenes further. Finally, we used an Explainable Artificial Intelligence (XAI) approach to interpret the model’s predictions. The experimental results showed that the improved GCS-YOLOv8 model could detect the spores of the three fungi with an accuracy of 0.926 and a model size of 22.8 MB, which was significantly superior to the existing model and showed good robustness under different brightness conditions. The test on the microscopic images of the infection structure of cucumber down mildew also proved that the model had good generalization. Therefore, this study realized the accurate detection of pathogen spores in natural scenes and provided feasible technical support for early predicting and preventing fungal diseases.

Abstract This study addresses the complexities of maritime area information collection, particularly in challenging sea environments, by introducing a multi-agent control model for regional information gathering. Focusing on three key areas—regional coverage, collaborative exploration, and agent obstacle avoidance—we aim to establish a multi-unmanned ship coverage detection system. For regional coverage, a multi-objective optimization model considering effective area coverage and time efficiency is proposed, utilizing a heuristic simulated annealing algorithm for optimal allocation and path planning, achieving a 99.67% effective coverage rate in simulations. Collaborative exploration is tackled through a comprehensive optimization model, solved using an improved greedy strategy, resulting in a 100% static target detection and correct detection index. Agent obstacle avoidance is enhanced by a collision avoidance model and a distributed underlying collision avoidance algorithm, ensuring autonomous obstacle avoidance without communication or scheduling. Simulations confirm zero collaborative failures. This research offers practical solutions for multi-agent exploration and coverage in unknown sea areas, balancing workload and time efficiency while considering ship dynamics constraints.

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Abstract Background Functional endoscopic sinus surgery is a principal option for treating chronic rhinosinusitis with nasal polyps (CRSwNP) after medication failures. Unfortunately, some patients still have unsatisfactory postoperative recovery. The type of inflammatory cell infiltration in nasal polyp tissue has been reported available for recurrence prediction. As it is invasive and time-consuming, this technique is hard to promote clinically under the existing technical conditions. And during the course of clinical treatment, we have noted that differences in the postoperative recurrence rate of patients present among different traditional Chinese medicine syndrome types. Methods and analysis This is a non-randomized, single-center, and prospective cohort study started in Chengdu Sichuan Province, People’s Republic of China, in January 2021. A total of 200 participants will be recruited from patients who are diagnosed with CRSwNP and prepared for functional endoscopic sinus surgery. We collect preoperative data which includes general information, medical history, TCM syndromes, visual analogue scale (VAS) of subjective symptoms, Lund-Kennedy endoscopic score, and Lund-Mackay score of computed tomography (CT) scanning of sinuses. We acquire the VAS score and Lund-Kennedy score of subjective symptoms through multiple planned follow-up after surgery. After 1 year of follow-up, the recurrence rate will be calculated, and the curative effect will be assessed. Meanwhile, the patients’ pathological sections will be sorted out, and inflammatory cell infiltration will be analyzed. Statistical analysis will be carried out to evaluate the correlation among CRSwNP recurrence and TCM syndrome types and tissue inflammatory cell infiltration types. Then we will establish a predictive model for CRSwNP recurrence. Analyses of survey data include descriptive and inferential statistical approaches. Discussion This is the first prospective cohort study on investigating the correlation of CRSwNP recurrence with TCM syndrome types and tissue inflammatory cell infiltration types. Through this study, we hope to discover a new and simple, effective, and noninvasive way to predict the recurrence rate rapidly after CRSwNP and provide reference for the intervention timing of traditional Chinese medicine application, thereby achieving customized diagnosis and treatment, minimizing risks of surgical events, and delaying postoperative recurrence of CRSwNP. Systematic review registration PROSPERO ChiCTR2100041646.

Calystegia hederacea Wall. in Roxb. 1824 is a perennial herbaceous vine in the family Convolvulaceae and has several biological effects. Herein, we reported the first complete chloroplast genome of C. hederacea. The chloroplast genome sequence was 152,057 bp in length, comparing a large single-copy (LSC) region of 87,891 bp, a small single-copy (SSC) region of 19,866 bp, and a pair of inverted repeat (IR) regions of 22,150 bp. This sequenced chloroplast genome contained 126 predicted genes, including 81 protein-coding genes, 37 tRNA genes, and eight rRNA genes, and the total GC content of the chloroplast genome was 37.79%. Phylogenetic analysis revealed that C. hederacea was closely related to C. soldanella. The chloroplast genome presented in this study will enrich the genome information of the genus Calystegia and provide deeper insights into the evolution study of the family Convolvulaceae.

Abstract The formulation of an effective development plan, optimizing exploitation efficiency, relies heavily on accurate reservoir characterization. However, existing reservoir classification methodologies, which rely on macroscopic geological observations and well-logging data, have limitations in data availability and fail to capture micro-scale pore structure characteristics accurately. The emerging technology of digital rock, widely employed in the petroleum industry, also faces challenges in accurately capturing reservoir heterogeneity due to its single-scale nature and limited application for reservoir classification. To overcome these challenges, this study presents an innovative reservoir classification approach based on the multi-scale digital rock method. This approach integrates qualitative assessment of micro-CT images for particle contact relationships and pore types with quantitative evaluation of multi-scale characteristic parameters, obtained from micro-CT and scanning electron microscopy (SEM) images. The proposed classification method demonstrates excellent agreement with the prioritization of development and production data for offshore sandstone reservoirs. By establishing a robust evaluation methodology, this classification method facilitates exploration potential assessment and development strategy optimization within the field.

Abstract Background Alternative polyadenylation (APA), alternative splicing (AS), and long non-coding RNAs (lncRNAs) play regulatory roles in post-transcriptional processes in plants. However, little is known about their involvement in xylem development in Dalbergia odorifera, a valuable rosewood species with medicinal and commercial significance. We addressed this by conducting Isoform Sequencing (Iso-Seq) using PacBio’s SMRT technology and combined it with RNA-seq analysis (RNA sequencing on Illumina platform) after collecting xylem samples from the transition zone and the sapwood of D. odorifera. Results We identified 14,938 full-length transcripts, including 9,830 novel isoforms, which has updated the D. odorifera genome annotation. Our analysis has revealed that 4,164 genes undergo APA, whereas 3,084 genes encounter AS. We have also annotated 118 lncRNAs. Furthermore, RNA-seq analysis identified 170 differential alternative splicing (DAS) events, 344 genes with differential APA site usage (DE-APA), and 6 differentially expressed lncRNAs in the transition zone when compared to the sapwood. AS, APA, and lncRNAs are differentially regulated during xylem development. Differentially expressed APA genes were enriched for terpenoid and flavonoid metabolism, indicating their role in the heartwood formation. Additionally, DE-APA genes were associated with cell wall biosynthesis and terpenoid metabolism, implying an APA’s role in wood formation. A DAS gene (involved in chalcone accumulation) with a significantly greater inclusion of the last exon in the transition zone than in the sapwood was identified. We also found that differentially expressed lncRNAs targeted the genes related to terpene synthesis. Conclusions This study enhances our understanding of the molecular regulatory mechanisms underlying wood formation in D. odorifera, and provides valuable genetic resources and insights for its molecular-assisted breeding.

Abstract Background An extensive literature has shown a strong connection between maternal parenting practices and adolescent mental health problems. However, it has been difficult for previous research to map a dynamic concurrent and prospective relationships within and between types of parenting practices and adolescent mental health problems. The present study addressed these issues using a network analysis approach and a longitudinal design. Methods This study involved 591 Chinese adolescents (249 males; mean age at T1 = 13.53) and their mothers (mean age at T1 = 39.71) at two time points (T1 and T2) with eighteen months apart. Mothers reported their parenting practices including warmth, monitoring, inductive reasoning, hostility, and harshness, while adolescents reported their mental health problems including anxiety, depression, aggression, and conduct problems. Network analysis was conducted for contemporaneous networks at T1 and T2 and temporal networks from T1 to T2. Results The contemporaneous networks revealed the negative association between monitoring and conduct problems served as the main pathway through which parenting practices and adolescent mental health mutually influenced each other, and further, warmth was the most influential parenting practice on adolescent mental health. The temporal network revealed that maternal hostility exerted the most influence on adolescent mental health problems, whereas adolescents’ depression was most influenced by maternal parenting practices. Moreover, maternal hostility was most predicted by maternal harshness. Conclusions This study presents a novel perspective to gain a better understanding of the dynamics between and within maternal parenting practices and adolescent mental health problems. Findings highlight maternal harshness and warmth as potential prevention and intervention targets for adolescent mental health problems.

Pathogenic bacteria's metabolic adaptation for survival and proliferation within hosts is a crucial aspect of bacterial pathogenesis. Here, we demonstrate that citrate, the first intermediate of the tricarboxylic acid (TCA) cycle, plays a key role as a regulator of gene expression in Staphylococcus aureus. We show that citrate activates the transcriptional regulator CcpE and thus modulates the expression of numerous genes involved in key cellular pathways such as central carbon metabolism, iron uptake and the synthesis and export of virulence factors. Citrate can also suppress the transcriptional regulatory activity of ferric uptake regulator. Moreover, we determined that accumulated intracellular citrate, partly through the activation of CcpE, decreases the pathogenic potential of S. aureus in animal infection models. Therefore, citrate plays a pivotal role in coordinating carbon metabolism, iron homeostasis, and bacterial pathogenicity at the transcriptional level in S. aureus, going beyond its established role as a TCA cycle intermediate.

IntroductionAcinetobacter baumannii (A. baumannii) is an important opportunistic pathogen causing nosocomial infection in the clinic. The occurrence rate of antibiotic resistance is increasing year by year, resulting in a highly serious situation of bacterial resistance.MethodsTo better understand the local epidemiology of multidrug-resistant A. baumannii, an investigation was conducted on the antibiotic resistance of different types of A. baumannii and its relationship with the genes of A. baumannii. Furthermore, the molecular mechanism underlying antibiotic resistance in A. baumannii was investigated through transcriptome analysis.ResultsThese results showed that a total of 9 STs were detected. It was found that 99% of the strains isolated in the hospital belonged to the same STs, and the clone complex CC208 was widely distributed in various departments and all kinds of samples. Furthermore, these A. baumannii strains showed high resistance to ertapenem, biapenem, meropenem, and imipenem, among which the resistance to ertapenem was the strongest. The detection rate of blaOXA–51 gene in these carbapenem resistance A. baumannii (CRAB) reached 100%; Additionally, the transcriptome results showed that the resistance genes were up-regulated in resistance strains, and these genes involved in biofilm formation, efflux pumps, peptidoglycan biosynthesis, and chaperonin synthesis.DiscussionThese results suggest that the CC208 STs were the main clonal complex, and showed high carbapenem antibiotic resistance. All these resistant strains were distributed in various departments, but most of them were distributed in intensive care units (ICU). The blaOXA–23 was the main antibiotic resistance genotype; In summary, the epidemic trend of clinical A. baumannii in Guiyang, China was analyzed from the molecular level, and the resistance mechanism of A. baumannii to carbapenem antibiotics was analyzed with transcriptome, which provided a theoretical basis for better control of A. baumannii.

Let $ C_{n} $ be an $ n $-dimensional cross-polytope and $ \Gamma_{p}(C_{n}) $ be the smallest positive number $ \gamma $ such that $ C_{n} $ can be covered by $ p $ translates of $ \gamma C_{n} $. We obtain better estimates of $ \Gamma_{2^n}(C_n) $ for small $ n $ and a universal upper bound of $ \Gamma_{2^n}(C_n) $ for all positive integers $ n $.

In this study, the beneficial effects of EPA in ethyl esters (EE) and triacylglycerides (TAG) forms on high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) were studied and compared. Results indicated that both EPA-TAG and EPA-EE can alleviate pathological features of NAFLD, such as hepatic lipid accumulation and lobular inflammation, with a more pronounced protective effects observed in EPA-TAG treated mice. The integrated hepatic transcriptomic, metabolic and gut microbiota profiles suggest that EPA-TAG and EPA-EE improved hepatic steatosis by suppression of food intake and lipogenesis, promotion of lipid and phospholipid PUFA remodeling, ketogenesis and fatty acids oxidation, possibly via activating the AMPK/adipocytokine signaling pathway. The protective effect of EPA was also associated with the regulation of intestinal flora structure. In general, EPA-TAG was found to be more effective than EPA-EE in preventing HFD-induced NAFLD by reducing appetite, improving hepatic lipid metabolism, increasing energy expenditure, and enhancing gut-liver cross-talk.

IntroductionActivation of complement through the alternative pathway (AP) has a key role in the pathogenesis of IgA nephropathy (IgAN). We previously showed, by intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE), C57BL/6 mice develop mild kidney damage in association with glomerular IgA deposition. To further address complement activity in causing glomerular histological alterations as suggested in the pathogenesis of IgAN, here we used mice with factor H mutation (FHW/R) to render AP overactivation in conjunction with LCWE injection to stimulate intestinal production of IgA.MethodsDose response to LCWE were examined between two groups of FHW/R mice. Wild type (FHW/W) mice stimulated with LCWE were used as model control.ResultsThe FHW/R mice primed with high dose LCWE showed elevated IgA and IgA-IgG complex levels in serum. In addition to 100% positive rate of IgA and C3, they display elevated biomarkers of kidney dysfunction, coincided with severe pathological lesions, resembling those of IgAN. As compared to wild type controls stimulated by the same high dose LCWE, these FHW/R mice exhibited stronger complement activation in the kidney and in circulation.DiscussionThe new mouse model shares many disease features with IgAN. The severity of glomerular lesions and the decline of kidney functions are further aggravated through complement overactivation. The model may be a useful tool for preclinical evaluation of treatment response to complement-inhibitors.

The Sichuan Basin in Southeastern China contains extensive bedded cherts dating back to the Late Ordovician–Early Silurian period. To investigate the origin and depositional environment of these cherts, we conducted a comprehensive study using field observations, thin sections microscopic, silicon isotope analysis, and major and trace element geochemistry of samples from three sections. Our results indicate that the cherts from Wufeng and Longmaxi formations are non-hydrothermal, normal biogenic seawater deposits mainly affected by terrigenous input and slightly associated with volcanic ash. Al2O3/(Al2O3 + Fe2O3T) and LaN/CeN ratios, δCe values and Fe2O3T/TiO2 − Al2O3/(Al2O3 + Fe2O3T), Fe2O3T/(100 − SiO2) − Al2O3/(100 − SiO2), 100 × (Fe2O3T/SiO2) – 100 × (Al2O3/SiO2), and LaN/CeN − Al2O3/(Al2O3 + Fe2O3T) discrimination diagrams indicated that the bedded cherts deposited in the continental margin environment.

In recent years, English as a foreign language (EFL) reading instruction has emerged as a prominent and recurring research theme in the realm of education. Despite this growing interest, prior studies have not outlined the research status of EFL reading instruction from a bibliometric lens. Addressing this gap, the present study aims to provide valuable insights into the research landscape of EFL reading instruction by using scientific mapping analysis on documents sourced from the Web of Science Database between 1994 and 2023. The study found that: 1) The analysis of publication trends suggests that the field of EFL reading instruction continues to evolve, with a foreseeable ongoing increase in research output. 2) Asian countries, specifically Iran, China, and Saudi Arabia emerge as leading contributors and collaborators in terms of research on EFL reading instruction. 3) Authors mainly from Asian countries demonstrate the highest levels of productivity and citation impact. 4) The most productive and cited journals primarily originate from developed countries, notably the United Kingdom and the United States. 5) The research foci identified cover various aspects such as “technology-based instruction,” “critical thinking,” and “literacy skills.” However, there is an emerging shift in research focus towards themes “English proficiency,” “Covid-19,” “technology,” “blended learning” and “mobile-assisted language learning (MALL).” By shedding light on the significant concepts and trends of the research field, this study adds to the burgeoning body of literature and provides valuable guidance to new scholars seeking to enrich their knowledge and perspectives on this particular topic.

Abstract Background To improve the early detection rate of multiple myeloma (MM), the M‐protein screening system has been performed in the hospital population at Zhongshan Hospital Fudan University since 2014, with electrophoretic‐based monoclonal immunoglobulin (M‐protein) screening integrated into the blood biochemistry panel. This study updated 7‐year follow‐up findings of MM patients diagnosed by screening‐driven and symptom‐driven approaches. Methods The retrospective study compared the characteristics and outcomes of patients diagnosed through two patterns by reviewing the plasma cell disease database from January 2014 to October 2021. The screening‐driven group included patients diagnosed through the screening system during workups of unrelated medical conditions or routine checkups. In contrast, patients who visited or were referred to the hematological department due to myeloma‐related end‐organ damage were categorized into the symptom‐driven group. Results There were 3,110,218 serum protein electrophoresis (SPEP) tests performed during 7 years, with 1.95% (60,609) patients yielding positive SPEP results. Of 911 confirmed MM cases (excluding concurrent amyloidosis), 366 were assigned to the screening‐driven group, while 545 were to the symptom‐driven group. Compared to the symptom‐driven group, the screening group had more IgG subtypes, earlier International Stage System stages, fewer disease‐related symptoms, lower ECOG scores, less extramedullary disease, a lower percentage of bone marrow plasma cells, and a lower level of lactate dehydrogenase. Frontline response results of two groups were similar. Patients detected through screening had a significantly improved median progression‐free survival (PFS) than the symptom‐driven group (62.2 vs. 24.9 months, p

Background We assessed the impact of pre‐ and postprocedural plasma corin levels on the recurrence of atrial fibrillation (AF) after catheter ablation (CA). Methods and Results This prospective, single‐center, observational study included patients undergoing their first CA of AF. Corin was measured before and 1 day after CA. The primary end point was recurrent AF between 3 and 12 months after ablation. From April 2019 through May 2021, we analyzed 616 patients with AF (59.09% men) with a mean age of 62.86±9.42 years. Overall, 153 patients (24.84%) experienced recurrent AF. In the recurrence group, the pre‐ and postprocedure corin concentrations were 539.14 (329.24–702.08) and 607.37 (364.50–753.80) pg/mL, respectively, which were significantly higher than the nonrecurrence group's respective concentrations of 369.05 (186.36–489.28) and 489.12 (315.66–629.05) pg/mL (both P494.85 pg/mL predicted AF recurrence at 1 year. An increase of 1 SD in corin concentrations before CA (264.94 pg/mL) increased the risk of recurrent AF by 54.3% after adjusting for confounding variables (hazard ratio, 1.465 [95% CI, 1.282–1.655]; P

ABSTRACTIn many Gram-positive bacteria, the transpeptidase enzyme sortase A (SrtA) anchors surface proteins to cell wall and plays a critical role in the bacterial pathogenesis. Here, we show that in Staphylococcus aureus, an important human pathogen, the SrtA is phosphorylated by serine/threonine protein kinase Stk1. S. aureus SrtA can also be phosphorylated by small-molecule phosphodonor acetyl phosphate (AcP) in vitro. We determined that various amino acid residues of S. aureus SrtA are subject to phosphorylation, primarily on its catalytic site residue cysteine-184 in the context of a bacterial cell lysate. Both Stk1 and AcP-mediated phosphorylation inhibited the enzyme activity of SrtA in vitro. Consequently, deletion of gene (i.e. stp1) encoding serine/threonine phosphatase Stp1, the corresponding phosphatase of Stk1, caused an increase in the phosphorylation level of SrtA. The stp1 deletion mutant mimicked the phenotypic traits of srtA deletion mutant (i.e. attenuated growth where either haemoglobin or haem as a sole iron source and reduced liver infections in a mouse model of systemic infection). Importantly, the phenotypic defects of the stp1 deletion mutant can be alleviated by overexpressing srtA. Taken together, our finding suggests that phosphorylation plays an important role in modulating the activity of SrtA in S. aureus.

Abstract Background Significant advances in multiple myeloma (MM) over the past 15 years led to exciting changes in the management of MM patients in China, which in turn brought about the early diagnoses, precise risk stratifications, and improved prognoses. Methods We summarized the dynamic changes in the management of newly diagnosed (ND) MM in a national medical center, crossing the old and novel drug era. Demographics, clinical characteristics, first‐line treatment, response rate, and survival were retrospectively collected among NDMMs diagnosed in Zhongshan Hospital Fudan University from January 2007 to October 2021. Results Of the 1256 individuals, median age was 64 (range 31–89) with 45.1% patients >65 years. About 63.5% were male, 43.1% were at ISS stage III and 9.9% had light‐chain amyloidosis. Patients with abnormal ratio of free light chain (80.4%), extramedullary disease (EMD, 22.0%), and high‐risk cytogenetic abnormalities (HRCA, 26.8%) were detected by novel detection techniques. The best confirmed ORR was 86.5%, including 39.4% with CR. Short‐ and long‐term PFS and OS rates persistently increased each year along with increasing novel drug applications. Median PFS and OS were 30.9 and 64.7 months. Advanced ISS stage, HRCA, light‐chain amyloidosis and EMD independently predicted an inferior PFS. First‐line ASCT indicated a superior PFS. Advanced ISS stage, elevated serum LDH, HRCA, light‐chain amyloidosis, and receiving PI/IMiD‐based regimen versus PI+IMiD‐based regimen independently indicated a poorer OS. Conclusions In brief, we illustrated a dynamic landscape of MM patients in a national medical center. Chinese MM patients evidently benefited from newly introduced techniques and drugs in this field.

Abstract Coronary artery occlusion (CAO) is a rare but life‐threatening complication of transcatheter aortic valve implantation (TAVI). The mechanism of CAO is the displacement of the native calcified valve leaflet over the coronary ostium. Here, we report on a woman who experienced sudden cardiac arrest and abrupt CAO during TAVI, which was caused by two different original obstructions, a rupture of aortic plaque or a partial tear of the aortic intima blocking the upper 2/3 of the left main trunk (LMT) ostium, and the transcatheter heart valve (THV) blocking the lower 1/3 of the LMT ostium. She was eventually successfully treated with the chimney stenting technique. Aortography other than coronary angiography was used to ascertain CAO. In patients presenting with abrupt cardiac arrest or cardiogenic shock with LMT occlusion, there must be prompt identification, and the causes of CAO may be various and rare. The identification of CAO relies not only on CAG but also on aortography, especially if the locations and origins of obstructions are special. Supportive therapy with an attempt at percutaneous revascularization is necessary. Pre‐procedural assessment is crucial prior to TAVI interventions. In cases with high risk of CAO, upfront coronary artery protection can be provided.

The two-component regulatory system VraRS regulates transcription of penicillin-binding protein 2 in response to cell wall antimicrobials. Here, Lu et al. show that an enzyme from the wall teichoic acid biosynthetic pathway of MRSA can also modulate the expression of virulence factors such as Staphylococcal protein A via VraRS.

Abstract Aims To examine the perceived professional benefits (PPB) and associated factors among nurses during the coronavirus disease 2019 (COVID‐19) pandemic in China. Design Cross‐sectional study. Methods Using the snowball sampling method, 492 nurses (478 females, 14 males) were recruited. Data were collected using an online survey, including participants' socio‐demographic and working characteristics, psychological distress related to the COVID‐19 pandemic, dealing with professional frustration, professional self‐reflection and PPB from 1–30 April 2020. Results Nurses experienced high levels of PPB. In linear regression analysis, self‐perceived concerns about COVID‐19, emotional shock caused by it, risk perception towards their occupations, dealing with professional frustration and professional self‐reflection were positively associated with PPB among nurses. These factors explained 84% variance in PPB. Conclusions This study highlighted that although the nurses experienced psychological distress, they gained high PPB during the COVID‐19 pandemic. Additionally, to facilitate nurses' efforts to achieve professional growth, more educational resources and opportunities for engaging in reflective practices could be provided.

BackgroundTo determine the effect of different sterilization methods on shelf life and physicochemical parameters of fermented pork jerky.MethodsVarious sterilization techniques, including boiling, pasteurization, medium-temperature steam sterilization, high-temperature steam sterilization, ultrasonic sterilization, and ultraviolet sterilization, were employed in this study to treat vacuum-sealed fermented pork jerky. Changes in microbial populations, physicochemical parameters, and sensory evaluations were monitored throughout the storage period.ResultsThe results indicated the presence of Staphylococcus aureus on the 24th, 21st, 33rd, 24th, 18th, and 15th days in pork jerky subjected to boiling (100°C, 20 min), pasteurization (85°C, 15 min), medium-temperature steam sterilization (105°C, 0.5 Pa, 30 min), high-temperature steam sterilization (121°C, 1.0 Pa, 20 min), ultrasonic sterilization (480 W, 30 kHz, 30 min), and ultraviolet sterilization (254 nm, 100 W/m2, 60 min), respectively. Coliforms, salmonella, and Shigella were not detected in any group during storage. The medium-temperature steam sterilization method yielded the most favorable microbiological results, with an aerobic plate count of less than 1.0 lg CFU/g. However, other physicochemical parameters and sensory evaluations were moderate, with total volatile basic nitrogen (TVB-N) and thiobarbituric acid reactive substances (TBARS) measuring 14.023 mg N/100 g and 0.427 mg MDA/kg, respectively, remaining within acceptable limits.ConclusionTherefore, considering microbiological indicators as the primary determinant of shelf life and taking into account other physicochemical parameters, the medium-temperature steam sterilization method was identified as the most suitable approach for extending the shelf life of fermented pork jerky while preserving its flavor.

Electrocution is one of the main causes of workplace deaths in the construction industry. This paper presents a framework for identifying electrocution risk factors and exploring the correlations between them, with the aim of assisting accident prevention research. Specifically, the Haddon Matrix is used to extract the risk factors from 193 investigation reports of electrical shock accidents from 2012-2019, and the Apriori algorithm is applied to examine the potential relationships between these factors. Based on association rules using three criteria: support ( S), confidence ( C) and lift ( L), the betweenness centrality is then introduced to optimize association rules and find the most important rules though comparison. The results show that after optimization, some of these critical rules rise significantly in rank, such as Workplace: indoor → No CPR provided. Through these ranking changes, the focus of safety management is clarified, and finally, based on a comprehensive analysis of association rules, targeted accident prevention measures are suggested.

Abstract Formation damage is a common phenomenon and is impaired to the reservoir by reducing the productivity. Formation damage is usually caused by solids plugging, clay swelling, saturation changes, etc., and fracturing fluids with a series of chemical additives are pumped into the well for production enhancement. It is difficult to optimize the fracture fluids and well shut-in time due to lack of fundamental understandings. Currently, little research has been done to investigate the mechanisms of formation damage at the pore scale. In this study, a combination of digital rock technology and core sample laboratory soaking experiments is used to evaluate the formation damages for different fracture fluids in tight sandstone reservoir. Three core samples from a full-diameter core are soaked in three different fracture fluids (surfactant, polymer, and gel) for eight different durations (from 2 h to 15d) to simulate well shut-in process. The samples in various soak times are scanned by X-ray micro-computer tomography (Micro-CT) to obtain the 3D images of the true geometry. The images are then compared to optimize the fracture fluids and quantify the damage degree after various well shut-in times. Then, displacement processes are simulated using lattice Boltzmann method (LBM) to evaluate the residual oil saturations and optimize the well shut-in time. The study suggests that the well shut-in process can cause irreversible damage to tight sandstone reservoir even for optimized fracture fluid. In the initial shut-in stages, clays swelling dominates pore structure alteration and reduces the porosity. Calcite will dissolute after which lead to slight porosity increase. In the flowback process after well shut-in, the simulated residual oil saturation will decrease initially and then increase after, which is complied with the porosity variation. The digital rock technology combined with the soaking experiments will provide alternative method for the evaluation of formation damage and the optimization of well shut-in time in tight sandstone reservoir, which can guide the selection of the fracture fluids and onsite fracturing operation.

Abstract Microbial weathering processes can significantly promote soil properties and reduce rock-to-soil ratio. Some soil-inhabiting bacteria exhibit efficient rock-dissolution abilities by releasing organic acids and other chemical elements from the silicate rocks. However, our understanding of the molecular mechanisms involved during bacterial rock-dissolution is still limited. In this study, we performed silicate rock-dissolution experiments on a Pseudomonas sp. NLX-4 strain isolated from an over-exploited mining site. The results revealed that Pseudomonas sp. NLX-4 strain efficiently accelerates the dissolution of silicate rocks by secreting amino acids, exopolysaccharides, and organic acids. Through employing genome and transcriptome sequencing (RNA-seq), we identified the major regulatory genes. Specifically, 15 differentially expressed genes (DEGs) encoding for siderophore transport, EPS and amino acids synthesis, organic acids metabolism, and bacterial resistance to adverse environmental conditions were highly up-regulated in silicate rock cultures of NLX-4 strain. Our study reports a potential bacterial based approach for improving the ecological restoration of over-exploited rock mining sites. Graphical Abstract

ObjectiveThe objectives of this study were to analyze rhinogenic headache, i.e., noninflammatory frontal sinus headache, a headache caused by bony obstruction of the frontal sinus drainage channels that receives relatively insufficient attention clinically, and to propose endoscopic frontal sinus opening surgery as a treatment based on the etiology.Study DesignCase series.SettingFrom the data of patients with noninflammatory frontal sinus headache who underwent endoscopic frontal sinus surgery in Hospital of Chengdu University of Traditional Chinese Medicine during 2016–2021, data for three cases with detailed postoperative follow-up data were extracted for case series reports.MethodsThis report provides detailed information on three patients with noninflammatory frontal sinusitis headache. Treatment options include surgery and rechecking, with the visual analogue scale (VAS) scores of preoperative and postoperative symptoms, CT, and endoscopic images. Three patients had common characteristics: the clinical manifestations were recurrent or persistent with pain and discomfort in the forehead area, but there was no nasal obstruction or runny nose; the paranasal sinus CT revealed no signs of inflammation in the sinuses but suggested bony obstruction of the drainage channel of the frontal sinus.ResultsAll three patients had recovery from headache, nasal mucosal recovery, and patent frontal sinus drainage. The recurrence rate of forehead tightness and discomfort or pain was 0.ConclusionNoninflammatory frontal sinus headache does exist. Endoscopic frontal sinus opening surgery is a feasible treatment modality that can largely or even completely eliminate the stuffy swelling and pain in the forehead. The diagnosis and surgical indications for this disease are based on a combination of anatomical abnormalities and clinical symptoms.

Background: Alcohol abuse triggers neuroinflammation, leading to neuronal damage and further memory and cognitive impairment. Few satisfactory advances have been made in the management of alcoholic central nervous impairment. Therefore, novel and more practical treatment options are urgently needed. Butyrate, a crucial metabolite of short-chain fatty acids (SCFAs), has been increasingly demonstrated to protect against numerous metabolic diseases. However, the impact of butyrate on chronic alcohol consumption-induced central nervous system (CNS) lesions remains unknown. Methods: In this study, we assessed the possible effects and underlying mechanisms of butyrate on the attenuation of alcohol-induced CNS injury in mice. Firstly, sixty female C57BL/6 J mice were randomly divided into 4 groups: pair-fed (PF) group (PF/CON), alcohol-fed (AF) group (AF/CON), PF with sodium butyrate (NaB) group (PF/NaB) and AF with NaB group (AF/NaB). Each group was fed a modified Lieber-DeCarli liquid diet with or without alcohol. After six weeks of feeding, the mice were euthanized and the associated indicators were investigated. Results: As indicated by the behavioral tests and brain morphology, dietary NaB administration significantly ameliorated aberrant behaviors, including locomotor hypoactivity, anxiety disorder, depressive behavior, impaired learning, spatial recognition memory, and effectively reduced chronic alcoholic central nervous system damage. To further understand the underlying mechanisms, microglia-mediated inflammation and the associated M1/M2 polarization were measured separately. Firstly, pro-inflammatory TNF-α, IL-1β, and IL-6 in brain and peripheral blood circulation were decreased, but IL-10 were increased in the AF/NaB group compared with the AF/CON group. Consistently, the abnormal proportions of activated and resting microglial cells in the hippocampus and cortex regions after excessive alcohol consumption were significantly reduced with NaB treatment. Moreover, the rectification of microglia polarization (M1/M2) imbalance was found after NaB administration via binding GPR109A, up-regulating the expression of PPAR-γ and down-regulating TLR4/NF-κB activation. In addition to the direct suppression of neuroinflammation, intriguingly, dietary NaB intervention remarkably increased the levels of intestinal tight junction protein occludin and gut morphological barrier, attenuated the levels of serum lipopolysaccharide (LPS) and dysbiosis of gut microbiota, suggesting that NaB supplementation effectively improved the integrity and permeability of gut microecology. Finally, the neurotransmitters including differential Tryptophan (Trp) and Kynurenine (Kyn) were found with dietary NaB administration, which showed significantly altered and closely correlated with the gut microbiota composition, demonstrating the complex interactions in the microbiome-gut-brain axis involved in the efficacy of dietary NaB therapy for alcoholic CNS lesions. Conclusion: Dietary microbial metabolite butyrate supplementation ameliorates chronic alcoholic central nervous damage and improves related memory and cognitive functions through suppressing microglia-mediated neuroinflammation by GPR109A/PPAR-γ/TLR4-NF-κB signaling pathway and modulating microbiota−gut−brain axis.

Abstract Increasing research has uncovered the involvement of long noncoding RNAs (lncRNAs) in the progression of multiple cancers including lung adenocarcinoma (LUAD). RT-qPCR and western blot were done to measure RNAs and proteins. Functional assays assessed LUAD cell biological behaviors under knockdown or overexpression of LINC01468, SIX5, SERBP1 or SERPINE1, and the specific function of those genes in regulating LUAD progression was evaluated via animal experiments. Supported by bioinformatics analysis, the interaction among genes was verified via mechanism assays. Upregulation of LINC01468 in LUAD tissues and cells as well as its association with poor clinical outcome was predicted. LINC01468, transcriptionally activated by SIX5, could strengthen proliferative, migratory and invasive abilities of LUAD cells. The oncogenic role of LINC01468 was further validated via animal experiments. SIX5 was a positive transcription regulator of LINC01468 and could exacerbate LUAD cell malignant behaviors. LINC01468 could recruit SERBP1 to enhance SERPINE1 mRNA stability and interact with USP5 to affect PAI1 protein ubiquitination. The oncogenic role of SERBP1 and SERPINE1 was also confirmed. Rescue experiments finally verified LINC01468 modulated proliferation, migration and invasion of LUAD cells via upregulation of SERPINE1. Our observations could contribute to deeper understanding of LUAD.

Dalbergia odorifera is a valuable material used in the crafting of luxury furniture, and the chemical constituents from heartwood possess significant medicinal value. The WRKY gene family, one of the most extensively studied gene families, plays an important role in plants. However, a comprehensive genome-wide identification of the WRKY gene family in D. odorifera has not been reported yet. In this study, a total of 99 WRKY genes were identified in D. odorifera. The DoWRKY genes were categorized into three primary groups with five subgroups. A collinearity analysis revealed 38 segmental duplications and 3 tandem duplications within the DoWRKY genes, indicating the pivotal role of segmental duplication in gene family expansion. Through the analysis of DoWRKY transcriptomic data across diverse tissues and under wounding stress, we found that only eight genes were universally expressed, while a subset displayed distinct tissue-specific patterns. Notably, DoWRKY41 was exclusively expressed in leaves; DoWRKY04 was solely in roots; and DoWRKY17, DoWRKY28, DoWRKY47, and DoWRKY67 were uniquely in flowers. Furthermore, we identified 24 WRKY proteins that tightly respond to wounding stress (20 upregulated; 4 downregulated). This comprehensive investigation offered valuable insights into the WRKY gene family of D. odorifera, serving as a foundational resource for forthcoming explorations into the functional roles of these genes amid wounding stress.

Microporous carbon attracts attention as an electrode material for supercapacitors. However, a large number of deep and distorted mesoporous and macroporous structures are usually created by non-uniform etching, resulting in underutilized internal space. Homogeneous activation has been considered by researchers as a necessary condition for the formation of interconnected microporous structures in carbon materials. Herein, a simple strategy of hydrothermal introduction of defects followed by homogeneous activation for the preparation of microporous carbon was developed for the synthesis of electrode materials for high-performance supercapacitors. The optimized sample with defect-enriched microporous structure and large specific surface area has a specific capacity of 315 F g−1 (1 A g−1) in KOH solution, and the assembled symmetric supercapacitor achieves a high energy density of 7.3 Wh kg−1 at a power density of 250 W kg−1. This work is interesting because it not only demonstrates that rational design of electrode materials is important to boost the performance of supercapacitors, but also provides inspiration for the design of efficient supercapacitors in the future.

Cu-based electrocatalysts have become the focus in the field of electrochemical CO2 reduction reaction (ECO2RR) due to their ability to produce multicarbon products. However, the research on generating single carbon products with higher economic feasibility via ECO2RR based on Cu-based electrocatalysts is rather rare, and the roles of the surface architecture and oxides of the electrocatalysts have not been explained exactly. In this work, a two-step method including thermal oxidation and electroreduction is proposed to introduce Cu+ into pure Cu foil to form Cu2O/Cu electrocatalyst. By regulating the surface composition and morphology of the electrocatalyst in this way, the activity of ECO2RR to C1 products has been greatly improved. The Faradaic efficiency of carbon products of the Cu2O/Cu electrode reaches 84% at −0.7 V vs. RHE with good selectivity for HCOOH and CO. The current density of Cu2O/Cu electrode reaches −12.21 mA cm−2 at −0.8 V vs. RHE, which is much higher than that of the Cu foil electrode (−0.09 mA cm−2). In-situ Raman characterization shows that Cu+ in Cu2O/Cu electrode could inhibit hydrogen generation and promote ECO2RR by stabilizing the adsorption of CO2.

Abstract Aims There is an emerging interest in elucidating the natural history and prognosis for patients with heart failure with reduced ejection fraction (HFrEF) in whom left ventricular ejection fraction (LVEF) subsequently improves. The characteristics and outcomes were compared between heart failure with recovered ejection fraction (HFrecEF) and persistent HFrEF. Methods and results This is a retrospective study of adults who underwent at least two echocardiograms 3 months apart between 1 November 2015 and 31 October 2019 with an initial diagnosis of HFrEF. The subjects were divided into HFrecEF group (second LVEF > 40%, ≥10% absolute improvement in LVEF) and persistent HFrEF group (20% subgroups. The primary outcomes were all‐cause mortality and rehospitalization. A total of 1160 HFrEF patients were included [70.2% male, mean (standard deviation) age: 62 ± 13 years]. On the second echocardiogram, 284 patients (24.5%) showed HFrecEF and 876 patients (75.5%) showed persistent HFrEF. All‐cause mortality was identified in 23 (8.10%) HFrecEF and 165 (18.84%) persistent HFrEF, whilst 76 (26.76%) and 426 (48.63%) showed rehospitalizations, respectively. Survival analysis showed that the persistent HFrEF subgroup experienced a significantly higher mortality at 12 and 24 months and a higher hospitalization at 12, 24, 48, and more than 48 months following discharge. Multivariate Cox regression showed that persistent HFrEF had a higher risk of all‐cause mortality [hazard ratio (HR) 2.30, 95% confidence interval (CI) 1.49–3.56, P = 0.000] and rehospitalization (HR 1.85, 95% CI 1.45–2.36, P = 0.000) than the HFrecEF group. Subgroup analysis showed that the LVEF ≥ 20% improvement subgroup had lower rates of adverse outcomes compared with those with less improvement of 10–20%. Conclusions Heart failure with recovered ejection fraction is a distinct HF phenotype with better clinical outcomes compared with those with persistent HFrEF. HFrecEF patients have a relatively better short‐term mortality at 24 months but not thereafter.

Cartilage endplate (CEP) plays important roles in the onset and progression of intervertebral disc degeneration (IVDD). Icariin (ICA) is the major active ingredient of Herba Epimedii and has various biological activities such as anti-inflammatory and antioxidant, which is used to treat many degenerative diseases. However, the effects and mechanism of ICA on endplate chondrocytes are still unclear. Herein, we studied the effects of ICA on CEP degeneration and elucidated the underlying mechanisms. Endplate chondrocytes were isolated, and TNF-α and TBHP were applied to mimic an IVDD pathological environment. Also, an IVDD mice model was established by transection of bilateral facet joints to investigate the protective effect of ICA in vivo. We found that ICA treatment inhibited the chondrocytes apoptosis and the decrease of extracellular matrix production in a dose-dependent manner. Our in vivo experiments demonstrated that ICA could ameliorate IVDD development and CEP calcification. We also found that the ICA-activated Nrf-2/HO-1 pathway thus promoted the Parkin-mediated mitophagy process and inhibited chondrocytes ferroptosis, thus alleviated redox imbalance and mitochondrial dysfunction and eventually improved cell survival. Knockdown of Nrf-2 using siRNA reversed the protective effect of ICA on endplate chondrocytes apoptosis and degeneration. In conclusion, our study demonstrated that ICA could protect against CEP degeneration and calcification under IVDD pathological conditions, the associated mechanism may be related to Nrf-2/HO-1-mediated mitophagy activation and ferroptosis inhibition. Our results suggest that ICA may be a potential effective medicine for IVDD prevention and treatment.

Background: Autonomic nerve system (ANS) plays an important role in regulating cardiovascular function and cerebrovascular function. Traditional heart rate variation (HRV) and emerging skin sympathetic nerve activity (SKNA) analyses from ultra-short-time (UST) data cannot fully reveal neural activity, thereby quantitatively reflect ANS intensity.Methods: Electrocardiogram and SKNA from sixteen patients (seven cerebral hemorrhage (CH) patients and nine control group (CO) patients) were recorded using a portable device. Ten derived HRV (mean, standard deviation and root mean square difference of sinus RR intervals (NNmean, SDNN and RMSSD), ultra-low frequency (

A multifunctional biocatalyst EneIRED capable of catalyzing amine-activated conjugate alkene reduction and subsequent reductive amination was discovered. The enzyme realized the coupling of α, β-unsaturated carbonyls with amines to efficiently synthesize a broad set of chiral amine diastereomers based on its unusual active site structure and catalytic mechanism.

Annual and sporadic influenza outbreaks pose a great threat to human health and the economy worldwide. Moreover, the frequent mutation of influenza viruses caused by antigen drift complicates the application of antiviral therapeutics. As such, there is an urgent need for novel antiviral agents to tackle the problem of insufficient efficacy of licensed drugs. Inspired by the success of the newly emerged PROTACs (PROteolysis TArgeting Chimeras) strategy, we report herein the design and synthesis of novel PROTAC molecules based on an oseltamivir scaffold to combat severe annual influenza outbreaks. Among these, several compounds showed good anti-H1N1 activity and efficient influenza neuraminidase (NA) degradation activity. The best compound, 8e, effectively induced influenza NA degradation in a dose-dependent manner and relied on the ubiquitin–proteasome pathway. Moreover, Compound 8e exhibited potent antiviral activity toward both wild-type H1N1 virus and an oseltamivir-resistant strain (H1N1, H274Y). A molecular docking study demonstrated that Compound 8e had good hydrogen-bonding and hydrophobic interactions with both the active sites of NA and Von Hippel-Lindau (VHL) proteins, which could effectively drive the favorable interaction of these two proteins. Thus, as the first report of a successful anti-influenza PROTAC, this proof of concept will greatly widen the application range of the PROTAC technique to antiviral drug discovery.

Context Dacomitinib and poziotinib, irreversible ErbB family blockers, are often used for treatment of non-small cell lung cancer (NSCLC) in the clinic. Objective This study investigates the effect of dacomitinib on the pharmacokinetics of poziotinib in rats. Materials and methods Twelve Sprague–Dawley rats were randomly divided into two groups: the test group (20 mg/kg dacomitinib for 14 consecutive days) and the control group (equal amounts of vehicle). Each group was given an oral dose of 10 mg/kg poziotinib 30 min after administration of dacomitinib or vehicle at the end of the 14 day administration. The concentration of poziotinib in plasma was quantified by UPLC-MS/MS. Both in vitro effects of dacomitinib on poziotinib and the mechanism of the observed inhibition were studied in rat liver microsomes and human liver microsomes. Results When orally administered, dacomitinib increased the AUC, Tmax and decreased CL of poziotinib (p

We present the development of an As2S3 fiber-based reusable inline optical connector; and, for the first time to the best of our knowledge, integrated it into a 2 μm chirped pulse amplification system as the pulse stretcher. By this mechanism, a near 20 times pulse stretching ratio was achieved in 0.5 m-long this As2S3 fiber and the introduction of insertion loss as low as 2.84 dB while it was connected with silica fiber. After the follow-up fiber amplification and self-compression mechanism, the laser average output power was boosted to 1.97 W and pulse duration was optimized to 2.53 ps. Moreover, to further inspect the laser pulse property, the pulses were then delivered into a 5.3 m-long ZrF4-BaF2-LaF3-AlF3-NaF (ZBLAN) fiber which was fusion spliced to SM1950 fiber. Thanks to the 0.4-dB low fusion splice loss between these fibers, a 1.56-W supercontinuum source with bandwidth of 1.93-3.50 μm is obtained. The measured two hours of root-mean-square value of power fluctuation of this laser source is 0.13%, indicating an ultra-high long-term power stability. This work will lay a solid foundation in the realization of the all-fiber structured high-power thulium-doped fiber amplifier with high compactness.

Teachers involved in English as a foreign language (EFL) teaching play a significant role in the process of moving toward educational equity. Teacher cognition is very influential in shaping teacher practice and thus affects students’ academic performance. However, although the role of EFL teachers as equity agents has been recognized, few studies have explored EFL teachers in-depth in terms of their cognition and practice. Moreover, no review studies have given sufficient attention to the task of elucidating the interrelations between EFL teachers’ cognition and practices in the context of educational equity. Therefore, to provide a novel perspective and generate fresh insights into this research field, the current study attempts to explain the connotations of these constructs, highlights the interplay between EFL teachers’ equity-oriented cognition and practice, and identifies both experiential and contextual factors that might have an effect throughout the teaching process. Finally, practical implications and directions for teachers, researchers, policy-makers, and social justice leaders who are interested in actualizing education as a means of attaining equity are also discussed.

Background Avitinib is one type of the third‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for the treatment of non‐small cell lung cancer (NSCLC) with EGFR mutations. The purpose of this study was to investigate the effect of avitinib on the pharmacokinetics of osimertinib, one FDA approved third‐generation TIKI, both in vitro and in vivo. Methods The in vitro metabolic stability and inhibitory effect of avitinib on osimertinib were assessed with rat liver microsomes (RLM) to determine its IC50 values. For the in vivo study, 18 Sprague‐Dawley rats were randomly divided into three groups: the avitinib multiple dose group (30 mg/kg avitinib once daily for seven days), the avitinib single dose group (PEG200 once daily for six days and a dose of 30 mg/kg avitinib in PEG200 on day 7) and the control group (equal amounts of PEG200 once daily for seven days). Next, all rats were given osimertinib at a dosage of 10 mg/kg. UPLC/MS‐MS was used for the determination of the concentration of osimertinib in plasma. Results In vitro analysis revealed that the IC50 value of osimertinib in rat liver microsomes was 27.6 μM. When rats were pretreated with avitinib, the values of AUC and MRT of the osimertinib were increased, and its Cmax and Tmax were significantly extended, whereas the values of CLz/F were significantly decreased (P

Abstract Burkholderia pyrrocinia JK-SH007 is an important biocontrol strain for the prevention and treatment of poplar canker disease. Its powerful biocontrol function is inseparable from its successful colonization of poplar trees. Bacterial biofilms can ensure the long-term colonization of a host. To explore the mechanism of action of biofilms in the biocontrol process, we manipulated various exogenous factors to explore the morphology of the JK-SH007 biofilm in vitro. The addition of glycerol and MgSO4 to TSB medium stimulated biofilm production, increased the resistance of JK-SH007 to disease, enhanced the survival of JK-SH007 in nutrient-poor environments and maintained the antagonistic ability of JK-SH007 against the poplar canker pathogen. Therefore, we constructed and optimized a biofilm-forming system to produce a large number of stable JK-SH007 biofilms. The optimized system showed that the optimal incubation time for JK-SH007 biofilm formation was 14 h, the optimal temperature of the static culture was 25 °C, and the optimal pH was 5. The optimal medium for biofilm formation was TSB medium, 1% glycerol and 50 mM MgSO4. RT-qPCR experiments showed that an increase in the expression of the suhB gene promoted JK-SH007 biofilm formation, while an increase in the expression level of the ropN gene inhibited JK-SH007 biofilm formation. The possible mechanism by which JK-SH007 was inhibited by biofilm formation under natural culture was revealed. These results indicate the importance of adding nutrients to JK-SH007 biocides produced on a commercial scale. This is the first report of JK-SH007 producing a long-lasting biofilm that guarantees antagonism.

This paper studies the calibration of industrial robots. Aiming at the problems of cumbersome industrial robot modeling and poor calibration effects, this paper proposes a new calibration method for determining the DH frame and DH parameters of industrial robots by measuring first and modeling afterwards. Firstly, the theory of Fixed Axis-Invariant is proposed, the Axis-Invariant is determined based on dual-vectors, and the origin of Fixed Axis-Invariant is determined by intersection obtained through the projection from one measuring point to the Axis-Invariant. Secondly, a method for solving the D-H frame and D-H parameters of industrial robots based on Fixed Axis-Invariant is proposed. Then, combined with laser tracker and industrial robot control software for secondary development, the developed software can be used to automatically measure and obtain the D-H frame and D-H parameters of industrial robot. Finally, compared with other calibration methods, it can be seen that the calibration method based on Fixed Axis-Invariant proposed in this paper can obtain better results. It can improve the absolute positioning accuracy of industrial robots to less than 0.28 mm, which can solve the problems of cumbersome industrial robot modeling and poor calibration effects.

Context Naringenin and tofacitinib are often used together for treatment of rheumatoid arthritis in Chinese clinics. Objective This experiment investigates the effect of naringenin on the pharmacokinetics of tofacitinib in rats. Materials and methods Twelve Sprague-Dawley rats were randomly divided into two groups (experimental group and control group). The experimental group was pre-treated with naringenin (150 mg/kg/day) for two weeks before dosing tofacitinib, and equal amounts of CMC-Na solution in the control group. After a single oral administration of 5 mg/kg of tofacitinib, 50 μL blood samples were directly collected into 1.5 mL heparinized tubes via the caudal vein at 0.083, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h. The plasma concentration of tofacitinib was quantified by UPLC/MS–MS. Results Results indicated that naringenin could significantly affect the pharmacokinetics of tofacitinib. The AUC0–24 of tofacitinib was increased from 1222.81 ± 222.07 to 2016.27 ± 481.62 ng/mL/h, and the difference was significant (p 0.05). Conclusions This research demonstrated a drug-drug interaction between naringenin and tofacitinib possibly when preadministered with naringenin; thus, we should pay attention to this possibility in the clinic.

Context Rivaroxaban and ticagrelor are two common drugs for the treatment of atrial fibrillation and acute coronary syndrome. However, the drug–drug interaction between them is still unknown. Objective To investigate the effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats both in vivo and in vitro. Materials and methods A sensitive and reliable UPLC-MS/MS method was developed for the determination of rivaroxaban in rat plasma. Ten Sprague-Dawley rats were randomly divided into ticagrelor pre-treated group (10 mg/kg/day for 14 days) and control group. The pharmacokinetics of orally administered rivaroxaban (10 mg/kg, single dose) with or without ticagrelor pre-treatment was investigated with developed UPLC-MS/MS method. Additionally, Sprague-Dawley rat liver microsomes were also used to investigate the drug–drug interaction between these two drugs in vitro. Results The Cmax (221.34 ± 53.33 vs. 691.18 ± 238.31 ng/mL) and the AUC(0–t) (1060.97 ± 291.21 vs. 3483.03 ± 753.83 μg·h/L) of rivaroxaban increased significantly (p