Search

There is a growing need to develop high-performance linepipes owing to the accelerated resource depletion attributable to the increasing interest in mining in extreme environments. (Ti, Mo)C precipitation can help secure the strength, low-temperature toughness, and sulfide stress corrosion cracking (SSCC) resistance required for linepipes. In this study, high-strength low-alloy (HSLA) steels with (Ti, Mo)C precipitation and without Ti and Mo were fabricated to analyze the effects of (Ti, Mo)C precipitation on the microstructure, impact toughness, and SSCC resistance of linepipes. The (Ti, Mo)C precipitation behavior varied and caused differences in the phase fraction, grain size, and dislocation density. Such differences in the microstructure improved the strength and low-temperature impact toughness. The SSCC resistance was significantly improved. In conclusion, (Ti, Mo)C precipitation has the potential to improve the properties required for fabricating linepipes.

AIM: To assess the utility and efficiency of endoscopy-assisted vitrectomy (EAV) for the treatment of corneal opacity in severe ocular trauma. METHODS: Patients who underwent fundus examination using a preoperative slit lamp and intraoperative endoscopy, followed by EAV and additional surgery were retrospectively recruited. Silicone oil removal and penetrating keratoplasty were used in selected eyes at postoperative follow-ups. Outcome measurements included the best corrected visual acuity (BCVA), intraocular pressure (IOP), findings of endoscopic fundus examination, and postoperative complications. RESULTS: Twenty-one eyes with severe ocular trauma and corneal opacity were followed up for 24–36mo. Retinal detachment (RD) and vitreous haemorrhage (VH) were identified in 16 eyes (76.2%), RD only in four eyes (19.0%), and VH combined with intraocular foreign body in one eye (4.8%). All eyes underwent at least three surgeries. Stage-I surgeries involved wound closure (100%), lens extraction (76.2%), and anterior vitrectomy (14.3%). Stage-II surgeries involved scleral buckling (28.6%), membrane peeling (47.6%), retinal laser photocoagulation (100%) and silicone oil tamponade (100%) using EAV. Stage-III surgeries were conducted using endoscopy including silicone oil removal (52.4%), retinal laser photocoagulation (52.4%) and penetrating keratoplasty (28.6%). Nearly all eyes showed improvements in BCVA and IOP. Although there were no severe complications, glaucoma was noted in one eye, chronic hypotony in another eye, and band keratopathy in three eyes. CONCLUSION: EAV is an effective adjunct for restoring ocular anatomical structures and visual function in the case of corneal opacity after severe ocular trauma.

Abstract The fibrogenic conversion of satellite cells contributes to the atrophy and fibrosis of skeletal muscle, playing a significant role in the pathogenesis of age-related sarcopenia. Melatonin, a hormone secreted by the pineal gland, exhibits anti-aging and anti-fibrotic effects in various conditions. However, the effect of melatonin on satellite cell fate and age-related sarcopenia remains under-explored. Here, we report that melatonin treatment mitigated the loss of muscle mass and strength in aged mice, replenished the satellite cell pool and curtailed muscle fibrosis. When primary SCs were cultured in vitro and subjected to aging induction via d-galactose, they exhibited a diminished myogenic potential and a conversion from myogenic to fibrogenic lineage. Notably, melatonin treatment effectively restored the myogenic potential and inhibited this lineage conversion. Furthermore, melatonin attenuated the expression of the fibrogenic cytokine, transforming growth factor-β1, and reduced the phosphorylation of its downstream targets Smad2/3 both in vivo and in vitro. In summary, our findings show melatonin's capacity to counteract muscle decline and inhibit fibrogenic conversion in aging SCs and highlight its potential therapeutic value for age-related sarcopenia. Graphical Abstract

Abstract Our previous research revealed a close association between the acetylation of peroxisome proliferator-activated receptor γ (PPARγ) histone H3K27 and the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). We preliminarily explored the epigenetic mechanism of steroid-induced avascular necrosis of the femoral head (SANFH) development, but the specific histone deacetylase (HDAC) involved in this regulatory process remains unknown. In this study, we combined cell, animal, and clinical specimen experiments to screen for specific HDAC genes that could regulate BMSC adipogenic differentiation and to explore their roles. The results showed that dexamethasone (DEX) significantly exacerbated the imbalance between the adipogenic and osteogenic differentiation of BMSCs, and there were differences in HDAC expression in the adipogenic differentiation cell models, with histone deacetylase 10 (HDAC10) showing the most significant decrease in expression. Subsequent use of a chromatin immunoprecipitation assay kit and quantitative polymerase chain reaction (ChIP‒qPCR) revealed a decrease in HDAC10 expression at predicted potential sites within the PPARγ promoter, indicating a significant decrease in HDAC10 enrichment in the PPARγ promoter region of BMSCs, thereby promoting sustained PPARγ expression. Additionally, immunohistochemistry of samples collected from mice and humans with SANFH and normal femoral heads revealed an imbalance between adipogenic and osteogenic differentiation in the necrotic area of femoral heads, with a significant decrease in the relative expression of HDAC10 in the necrotic area of femoral heads with SANFH. In summary, we speculate that HDAC10 affects the progression of SANFH by regulating BMSC adipogenic differentiation, a process possibly related to PPARγ histone acetylation. These findings provide a promising direction for the treatment of SANFH. Graphical abstract

Abstract Background By interacting with bone marrow mesenchymal stem cells (BMSCs) and regulating their function through exosomes, bone macrophages play crucial roles in various bone-related diseases. Research has highlighted a notable increase in the number of M1 macrophages in glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH). Nevertheless, the intricate crosstalk between M1 macrophages and BMSCs in the glucocorticoid-stimulated environment has not been fully elucidated, and the underlying regulatory mechanisms involved in the occurrence of GA-ONFH remain unclear. Methods We employed in vivo mouse models and clinical samples from GA-ONFH patients to investigate the interactions between M1 macrophages and BMSCs. Immunofluorescence staining was used to assess the colocalization of M1 macrophages and BMSCs. Flow cytometry and transcriptomic analysis were performed to evaluate the impact of exosomes derived from normal (n-M1) and glucocorticoid-stimulated M1 macrophages (GC-M1) on BMSC differentiation. Additionally, miR-1a-3p expression was altered in vitro and in vivo to assess its role in regulating adipogenic differentiation. Results In vivo, the colocalization of M1 macrophages and BMSCs was observed, and an increase in M1 macrophage numbers and a decrease in bone repair capabilities were further confirmed in both GA-ONFH patients and mouse models. Both n-M1 and GC-M1 were identified as contributors to the inhibition of osteogenic differentiation in BMSCs to a certain extent via exosome secretion. More importantly, exosomes derived from GC-M1 macrophages exhibited a heightened capacity to regulate the adipogenic differentiation of BMSCs, which was mediated by miR-1a-3p. In vivo and in vitro, miR-1a-3p promoted the adipogenic differentiation of BMSCs by targeting Cebpz and played an important role in the onset and progression of GA-ONFH. Conclusion We demonstrated that exosomes derived from GC-M1 macrophages disrupt the balance between osteogenic and adipogenic differentiation in BMSCs, contributing to the pathogenesis of GA-ONFH. Inhibiting miR-1a-3p expression, both in vitro and in vivo, significantly mitigates the preferential adipogenic differentiation of BMSCs, thus slowing the progression of GA-ONFH. These findings provide new insights into the regulatory mechanisms underlying GA-ONFH and highlight potential therapeutic targets for intervention. Graphical Abstract

Summary: Background: Ovarian cancer (OC) is a heterogeneous malignancy with multiple histological subtypes, showing global variability in incidence. Temporal changes in diagnostic criteria and risk factors might influence the incidence and distribution of OC and its subtypes. Methods: This study analyzed incidence patterns (2013–2017) and trends (1988–1992 to 2013–2017) of OC and its subtypes across 65 and 40 countries, respectively. Data were extracted from the Cancer Incidence in Five Continents (CI5 Ⅻ) and CI5plus databases (accessed in June 2024). Annual percent changes were computed to describe trends in age-standardized rates (ASRs) of OC and its subtypes. Proportions of ASR for each subtype relative to the ASR of OC for individual countries were calculated. Findings: The incidence of OC displayed marked disparities across regions and Human Development Index (HDI), with the highest ASRs in Eastern and Central Europe and very high HDI regions, and the lowest in Africa, Asia, and medium HDI regions. Despite stable trend in ASRs of OC globally, notable declines were observed in Europe, America, and Oceania, in contrast to increases in Asian countries like Japan and South Korea. Globally, serous carcinomas remained the most prevalent subtype. European countries exhibited a higher proportion of serous carcinomas, while Asian countries had a higher proportion of endometrioid and clear cell carcinomas. Although trends in subtypes also remained stable, ASRs increased over time for serous carcinomas and germ cell tumor in most countries, while mucinous carcinomas and adenocarcinoma NOS showed a decline. Interpretation: Variations in global patterns and trends in OC incidence and its subtypes might be influenced by genetic and reproductive factors. Consequently, region-specific prevention strategies and ongoing surveillance are essential to mitigate the burden of OC. Funding: The National Key Research and Development Program of China (No.2022YFC2704205), the Natural Science Foundation of China (No.82073647, 82373674, and 82103914), Outstanding Scientific Fund of Shengjing Hospital, 345 Talent Project of Shengjing Hospital of China Medical University, the Max Planck – University of Helsinki Center from the Jane and Aatos Erkko Foundation (No.210046), the Max Planck Society (No.5714240218), the University of Helsinki (No.77204227), and the European Union (ERC Synergy, BIOSFER, 101071773).

To replace the field-programmable gate array semiconductors used in the defense satellite industry, we conducted a technical investigation of application-specific integrated circuit (ASIC) semiconductors. The analysis results show that ASIC semiconductors have the heat dissipation, reliability, and radiation resistance capabilities required in a space environment and excellent performance indicators related to the resolution of synthetic aperture radar payloads, such as operating frequency. Research and development of mission-customized ASIC semiconductors that fit the requirements for NSP(new-space paradigm) should be preceded to expanse bases of the space industry, national security capabilities for next-generation space deveolpment also to secure competitiveness of technology and domestic supply chain as space parts itselfs.

Abstract Colorectal cancer (CRC) is a common digestive system tumor with high morbidity and mortality worldwide. At present, the use of computer-assisted colonoscopy technology to detect polyps is relatively mature, but it still faces some challenges, such as missed or false detection of polyps. Therefore, how to improve the detection rate of polyps more accurately is the key to colonoscopy. To solve this problem, this paper proposes an improved YOLOv5-based cancer polyp detection method for colorectal cancer. The method is designed with a new structure called P-C3 incorporated into the backbone and neck network of the model to enhance the expression of features. In addition, a contextual feature augmentation module was introduced to the bottom of the backbone network to increase the receptive field for multi-scale feature information and to focus on polyp features by coordinate attention mechanism. The experimental results show that compared with some traditional target detection algorithms, the model proposed in this paper has significant advantages for the detection accuracy of polyp, especially in the recall rate, which largely solves the problem of missed detection of polyps. This study will contribute to improve the polyp/adenoma detection rate of endoscopists in the process of colonoscopy, and also has important significance for the development of clinical work.

Abstract Background This study explores the diagnostic value of combining fractional-order calculus (FROC) diffusion-weighted model with simultaneous multi-slice (SMS) acceleration technology in distinguishing benign and malignant breast lesions. Methods 178 lesions (73 benign, 105 malignant) underwent magnetic resonance imaging with diffusion-weighted imaging using multiple b-values (14 b-values, highest 3000 s/mm2). Independent samples t-test or Mann-Whitney U test compared image quality scores, FROC model parameters (D,, ), and ADC values between two groups. Multivariate logistic regression analysis identified independent variables and constructed nomograms. Model discrimination ability was assessed with receiver operating characteristic (ROC) curve and calibration chart. Spearman correlation analysis and Bland-Altman plot evaluated parameter correlation and consistency. Results Malignant lesions exhibited lower D, and ADC values than benign lesions (P

Objective To explore the adjustment and impact of chronic kidney disease-mineral and bone disorder (CKD-MBD) parameters in maintenance dialysis patients utilizing the Doctor-Patient Care App (Renal Care App). Methods From August 2021 to March 2022, 102 maintenance dialysis (HD) and peritoneal dialysis (PD) patients were randomized into two groups of App management or control (n=51 each). Control group received standard treatment for CKD-MBD while App management group was treated with CKD-MBD management model facilitated by Renal Care App. Follow-up assessments occurred every 3 months over a 12-month period. Changes in serum calcium (Ca), serum phosphorus (P) and serum parathyroid hormone (iPTH) levels were recorded along with patient satisfaction and revisit rates. Results From August 2021 to March 2022, 102 maintenance dialysis (HD) and peritoneal dialysis (PD) patients were randomized into two groups of App management or control (n=51 each). Control group received standard treatment for CKD-MBD while App management group was treated with CKD-MBD management model facilitated by Renal Care App. Follow-up assessments occurred every 3 months over a 12-month period. Changes in serum calcium (Ca), serum phosphorus (P) and serum parathyroid hormone (iPTH) levels were recorded along with patient satisfaction and revisit rates. Conclusions Interventions utilizing the App management model prove advantageous in elevating the rate of CKD-MBD-related parameters attaining the standards among regular dialysis patients. This approach not only improves patient compliance and satisfaction but also demonstrates clinical significance for broader applications.

Abstract Background Hypertensive disorders of pregnancy (HDP) is the most common cause of indicated preterm delivery, but the impact of prenatal steroid exposure on the outcomes of preterm infants born to HDP mothers, who may be at risk for intrauterine hypoxia-ischemia, remains uncertain. The study objective is to evaluate the mortality and morbidities in HDP for very preterm infants (VPIs) exposed to different course of ANS. Methods This is a prospective cohort study comprising infants with

Abstract Background Echocardiography (ECHO) and cardiac magnetic resonance imaging (MRI) are used to observe changes in the left ventricular structure in patients with breast and gastric cancer after 6 cycles of chemotherapy. Based on the observed values, we aimed to evaluate the cardiotoxicity of anthracyclines in cancer patients and to analyze the consistency of the two examination methods in assessing left ventricular function after chemotherapy. Methods From January 2020 to January 2022, the data of 80 patients with malignant tumors who received anthracycline chemotherapy (breast cancer, n = 40; gastric cancer, n = 40) and 40 healthy volunteers (Control group) were retrospectively collected. Serum high-sensitivity cardiac troponin T (hs-cTnT) levels were detected by an automatic immunoassay analyzer. Left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were measured by cardiac MRI and 2-dimensional ECHO using the biplane Simpson’s method. Results Compared with baseline values, serum high-sensitivity cardiac troponin T (hs-cTnT) levels were significantly increased in patients with breast cancer and gastric cancer after 6 cycles of chemotherapy (P

ObjectiveCiprofol (also known as cipepofol and HSK3486), is a compound similar to propofol in chemical structure and hypnotic effect. Herein we evaluated the efficacy and safety of ciprofol for sedation in outpatient gynecological procedures.MethodsThis phase III multicenter randomized trial with a non-inferiority design was conducted in nine tertiary hospitals. We enrolled 135 women aged 18–65 years who were scheduled for ambulatory gynecological procedures. Patients were randomly assigned to receive either ciprofol (0.4 mg/kg for induction and 0.2 mg/kg for maintenance) or propofol (2.0 mg/kg for induction and 1.0 mg/kg for maintenance) sedation in a 2:1 ratio. Patients and investigators for data collection and outcome assessment were blinded to study group assignments. The primary outcome was the success rate of sedation, defined as completion of procedure without remedial anesthetics. The non-inferiority margin was set at −8%. Secondary outcomes included time to successful induction, time to full awake, time to meet discharge criteria, and satisfaction with sedation assessed by patients and doctors. We also monitored occurrence of adverse events and injection pain.ResultsA total of 135 patients were enrolled; 134 patients (90 patients received ciprofol sedation and 44 patients propofol sedation) were included in final intention-to-treat analysis. The success rates were both 100% in the two groups (rate difference, 0.0%; 95% CI, −4.1 to 8.0%), i.e., ciprofol was non-inferior to propofol. When compared with propofol sedation, patients given ciprofol required more time to reach successful induction (median difference [MD], 2 s; 95% CI, 1 to 7; p

Maternal immunity plays a vital role in protecting offspring from pathogen invasion, and it is present in nearly all vertebrates. As the most ancient vertebrates, teleost fish continuously secrete a substantial amount of mucus due to their unique living environment, and often exhibit schooling behavior. Previous studies have highlighted the presence of numerous immune components in the mucus of fish, that plays a crucial role in resisting pathogens. We hypothesize that this represents a distinctive maternal immune response mechanism in fish. In this study, we established a dextran sulfate sodium (DSS)-induced injury model by immersing zebrafish larvae in 0.5% DSS. This elicited robust inflammatory responses and showed DSS-induced alterations in microbial abundance via 16S rRNA sequencing. These changes included the disruption of normal gut structure; an increase in goblet cells; increased expression of inflammatory cytokines; and infiltration of neutrophils and macrophages into the gut, as well as an increase in pathogenic bacteria and a decline in probiotic bacteria. Furthermore, we conducted a mucus protection test by adding adult zebrafish mucus in fish tank water containing 0.5% DSS to test our hypothesis. As suspected, the mucus from adult zebrafish exhibited a protective role in defending zebrafish larvae against DSS-induced enteritis by alleviating excessive inflammatory responses and increasing probiotic abundance. In conclusion, our results confirm a significant role of adult fish mucus in the immune response of teleost fish to DSS-induced inflammation. Collectively, our findings show that the mucus of adult zebrafish may represent a novel form of maternal immunization, playing roles analogous to mammalian milk in immune regulatory functions.

Pseudoexfoliative glaucoma(PEXG)is an eye disease that seriously endangers vision. It is more invasive than primary open-angle glaucoma(POAG), with more serious damage to the optic nerve, worse prognosis and higher resistance to treatment. Early diagnosis of PEXG can help to treat the disease in time and delay the progress of the disease, so it is important to determine appropriate biomarkers. In recent years, more and more people have begun to study the biomarkers of PEXG, hoping to understand the pathogenesis of the disease, find out the potential early diagnosis and treatment targets of PEXG, and provide some help to the disease through the research of genomics, transcriptomics, proteomics, metabolomics and lipomics markers. This article will review the progress of biomarkers of PEXG in recent years, some biomarkers may provide new ideas for early diagnosis of PEXG in the future.

In order to determine the influence of measurement rack on local airflow deflection angle of the direction field in low-speed wind tunnel flow field calibration, the design parameters of different measurement racks were studied by numerical simulations. By comparing the numerical simulations and test results under the same working conditions, the effectiveness of the numerical calculation method was verified. Based on the verified numerical calculation method, influence para-meters such as blocking degree of measurement rack, distance from the center line of test section, installation angle and length of the test probe on the measurement of local airflow deflection angle were studied. The corresponding influence law was obtained, and the influence model was established. The results show that the rack blocking degree, distance from the center line of test section, installation angle and length of the test probe have obvious effects on test angle of local airflow deflection angle. If the test design or test method is improper, it will directly lead to a large error in test results, and ultimately affect the accuracy of the direction field quality evaluation results.

AIM: To report outcomes of endoscopy-assisted vitrectomy (EAV) in patients with chronic hypotony following severe ocular trauma or vitrectomy. METHODS: This was a retrospective, noncomparative case series. Ciliary bodies were evaluated using ultrasound biomicroscopy pre-operatively and direct visualisation intraoperatively. All selected individuals (seven patients/seven eyes) underwent EAV. Removal of ciliary membrane and traction, gas/silicone oil tamponade (GT/SOT), and scleral buckling (SB) were performed in selected eyes. Outcome measurements mainly included intraocular pressure (IOP) and best-corrected visual acuity (BCVA). RESULTS: Seven eyes from 7 male aphakic patients with a mean age of 45 (range, 20-68)y were included in this study; the average follow-up time was 12 (9-15)mo. GT was performed in 2 eyes; membrane peeling (MP) and SOT in 2 eyes; and MP, SOT, and SB in 3 eyes. The mean pre- and post-operative IOP were 4.5 (range, 4.0±0.11 to 4.8±0.2) mm Hg and 9.9 (range, 5.6±0.17 to 12.1±0.2) mm Hg at 52wk (12mo), respectively. BCVA improved in six eyes; one eye still showed light perception, and no bulbi phthisis was observed. CONCLUSION: Endoscopy offers improved judgment and recognition and has an improved prognosis for chronic hypotony. Therefore, endoscopy can be an effective and promising operative technique for chronic traumatic hypotony management.

Abstract Background Treatment of methicillin-resistant Staphylococcus aureus (MRSA) biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium (Ti) implants. There is a need to explore more effective approaches for the treatment of MRSA biofilm infections. Methods Herein, an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles (PDA), nitric oxide (NO) release donor sodium nitroprusside (SNP) and osteogenic growth peptide (OGP) onto Ti implants, denoted as Ti-PDA@SNP-OGP. The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy, X-ray photoelectron spectroscope, water contact angle, photothermal property and NO release behavior. The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe, 1-N-phenylnaphthylamine assay, adenosine triphosphate intensity, o-nitrophenyl-β-d-galactopyranoside hydrolysis activity, bicinchoninic acid leakage. Fluorescence staining, assays for alkaline phosphatase activity, collagen secretion and extracellular matrix mineralization, quantitative real‑time reverse transcription‑polymerase chain reaction, and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells (MSCs), RAW264.7 cells and their co-culture system. Giemsa staining, ELISA, micro-CT, hematoxylin and eosin, Masson’s trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms, inhibition of inflammatory response, and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo. Results Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light irradiation, and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species (ROS)-mediated oxidative stress, destroying bacterial membrane integrity and causing leakage of intracellular components (P

Background Recently, with the rapid development of the perinatal medical system and related life-saving techniques, both the short-term and long-term prognoses of extremely preterm infants (EPIs) have improved significantly. In rapidly industrialising countries like China, the survival rates of EPIs have notably increased due to the swift socioeconomic development. However, there is still a reasonably lower positive response towards the treatment of EPIs than we expected, and the current situation of withdrawing care is an urgent task for perinatal medical practitioners.Objective To develop and validate a model that is practicable for EPIs as soon as possible after birth by regression analysis, to assess the risk of mortality and chance of survival.Methods This multicentre prospective cohort study used datasets from the Sino-Northern Neonatal Network, including 46 neonatal intensive care units (NICUs). Risk factors including maternal and neonatal variables were collected within 1 hour post-childbirth. The training set consisted of data from 41 NICUs located within the Shandong Province of China, while the validation set included data from 5 NICUs outside Shandong Province. A total of 1363 neonates were included in the study.Results Gestational age, birth weight, pH and lactic acid in blood gas analysis within the first hour of birth, moderate-to-severe hypothermia on admission and adequate antenatal corticosteroids were influencing factors for EPIs’ mortality with important predictive ability. The area under the curve values for internal validation of our prediction model and Clinical Risk Index for Babies-II scores were 0.81 and 0.76, and for external validation, 0.80 and 0.51, respectively. Moreover, the Hosmer-Lemeshow test showed that our model has a constant degree of calibration.Conclusions There was good predictive accuracy for mortality of EPIs based on influencing factors prenatally and within 1 hour after delivery. Predicting the risk of mortality of EPIs as soon as possible after birth can effectively guide parents to be proactive in treating more EPIs with life-saving value.Trial registration number ChiCTR1900025234.

Most bacteria use type II fatty acid synthesis (FAS) systems for synthesizing fatty acids, of which the conserved FabA-FabB pathway is considered to be crucial for unsaturated fatty acid (UFA) synthesis in gram-negative bacteria. Xanthomonas campestris pv. campestris, the phytopathogen of black rot disease in crucifers, produces higher quantities of UFAs under low-temperature conditions for increasing membrane fluidity. The fabA and fabB genes were identified in the X. campestris pv. campestris genome by BLAST analysis; however, the growth of the X. campestris pv. campestris fabA and fabB deletion mutants was comparable to that of the wild-type strain in nutrient and minimal media. The X. campestris pv. campestris ΔfabA and ΔfabB strains produced large quantities of UFAs and, altogether, these results indicated that the FabA-FabB pathway is not essential for growth or UFA synthesis in X. campestris pv. campestris. We also observed that the expression of X. campestris pv. campestris fabA and fabB restored the growth of the temperature-sensitive Escherichia coli fabA and fabB mutants CL104 and CY242, respectively, under non-permissive conditions. The in-vitro assays demonstrated that the FabA and FabB proteins of X. campestris pv. campestris catalyzed FAS. Our study also demonstrated that the production of diffusible signal factor family signals that mediate quorum sensing was higher in the X. campestris pv. campestris ΔfabA and ΔfabB strains and greatly reduced in the complementary strains, which exhibited reduced swimming motility and attenuated host-plant pathogenicity. [Graphic: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Abstract Backgrounds Fasting blood glucose (FBG) variability may make an impact on adverse events in patients with diabetes mellitus. However, the association between long‐term changes in FBG and cancer remains unclear. We aimed to investigate this association in a large‐scale longitudinal study. Methods Data were collected from 46 761 patients with type 2 diabetes mellitus aged 20–80 years who participated in the Diabetes Standardized Management Program in Shanghai, China. We adopted four indicators, including standard deviation (SD), coefficient of variation (CV), variation independent of the mean (VIM), and average real variability (ARV) to describe FBG variability. Adjusted multivariable Cox regression analyses and restricted cubic splines were used to investigate the association between long‐term FBG variability and cancer risk. We also determined the interactive effect of FBG variability with hypertension and FBG‐mean with hypertension on cancer risk, respectively. Results In this study, we confirmed 2218 cancer cases (51.1% male) over a median follow‐up of 2.86 years. In the multivariable‐adjusted models, participants in the highest quartile of FBG variability had an increased risk of cancer compared with those in the lowest quartile. The nonlinear association was found when using FBG‐VIM, FBG‐ARV, and FBG‐SD in restricted cubic spline plots. There was a significant interaction effect of FBG variability with hypertension on cancer, whereas the effect of FBG‐mean with hypertension did not attain significance. Conclusions Our retrospective cohort study demonstrated a positive association between the long‐term changes in FBG and cancer risk in patients with type 2 diabetes mellitus. FBG variability may independently predict cancer incidence.

Background: The early detection of clinically significant prostate cancer (csPCa) through the integration of multidimensional parameters presents a promising avenue for improving survival outcomes for this fatal disease. This study aimed to assess the contribution of prostate transition zone (TZ) to predictive models based on the prostate health index (PHI), with the goal of enhancing early detection of csPCa in the prostate-specific antigen (PSA) gray zone. Methods: In this observational cross-sectional study, a total of 177 PSA gray zone patients (total prostate-specific antigen [tPSA] level ranging from 4.0 to 10.0 ng/mL) were recruited and received PHI detections from August 2020 to March 2022. Prostatic morphologies especially the TZ morphological parameters were measured by transrectal ultrasound (TRUS). Results: Univariable logistic regression indicated prostatic morphological parameters including total prostate volume (PV) indexes and transitional zone volume indexes were all associated with csPCa ( P

BackgroundPosttransplant lymphoproliferative disorders (PTLDs) are uncommon but serious complications in patients following solid organ transplantation. Primary Epstein-Barr virus (EBV) infection is a risk factor for the development of PTLD, especially early-onset PTLD, in EBV-negative recipients. To date, however, there are no specific guidelines on the threshold of EBV-DNA load for therapeutic intervention, the source for measurement (e.g., blood, bronchoalveolar fluid), or the use of antiviral agents as prophylaxis for early PTLD prevention in EBV-mismatched patients.MethodsThe present study describes a 56-year-old male lung transplant recipient diagnosed with EBV-associated PTLD.ResultsThis patient had a history of invasive fungal disease and Mucor and Aspergillus fumigatus infections in the early post-transplant period, necessitating antifungal therapy throughout the course of the disease. The patient was EBV-positive 15 days after transplantation, with lung CT showing multiple bilateral nodules of varying sizes beginning 98 days after transplantation. A lung biopsy showed PTLD, and next-generation sequencing (NGS) revealed EBV. This patient, however, did not receive any antiviral therapy for early PTLD prevention or any PTLD-related treatment. He died 204 days after lung transplantation.ConclusionThe present study describes a lung transplant recipient who developed EBV-associated PTLD, a non-negligible disease, after solid organ transplantation. Monitoring EBV-DNA load is important, as a sudden increase may be a sensitive indicator of PTLD. An earlier diagnosis may increase the likelihood of successful treatment.

X-ray diffraction (XRD) is extensively used in archaeometric investigation. Herein, we provide a novel XRD spectrum-based untargeted strategy for the classification of ancient painted pottery for various dynasties. It was accomplished using the original spectrum without a phase identification. To eliminate the influence of baseline drift, a new baseline drift correction algorithm was specifically designed for XRD spectra. The algorithm was implemented using local minimum values in the analyzed signal in an iterative optimization manner. The results indicated that with the aid of the algorithm, the baseline drift problem can be successfully resolved, and the classification of ancient painted pottery can be greatly improved. Finally, the developed strategy was successfully used to discriminate ancient painted pottery from the Han and Tang dynasties in the cities of Guyuan and Zhongwei, China. The developed untargeted strategy had the remarkable advantage of almost automatic data analysis. The toolbox of our strategy can be obtained from the authors.

Abstract Background 99mTc bone scintigraphy (BS) is the mainstay and most widely used technique in evaluation of bone metastasis (BM) in China. This study aimed to investigate the value of 99mTc BS in preoperative workup for patients with potentially resectable (cT1−4aN0−3) esophageal squamous cell carcinoma (ESCC). Methods This prospective cross‐section clinical trial (ChiCTR1800020304) enrolled a total of 385 patients with ESCC diagnosed at thoracic surgery clinic from October 2018 to September 2020. All patients were diagnosed with stage cT1−4aN0−3 and were potential candidates for surgical resection. BS was performed preoperatively and the treatment strategy was changed after confirmation of BM. The primary endpoint was the rate of change of the treatment regimen because of BM, while the secondary endpoint was the rate of positive BS findings. Results Out of the 385 patients, only two (0.5%) changed their treatment regimen because of BM. The rate of positive BS findings was 1%, while two patients (0.5%) had false‐positive or false‐negative results. The BS diagnostic performance for BM was sensitivity 50%, specificity 99.5%, positive predictive value 50%, negative predictive value 99.5%, and accuracy 99.0%. There was no significant difference in BM in relation to age, sex, tumor location or clinical stage. Conclusion Our data demonstrated that 99mTc bone scintigraphy does not significantly affect the preoperative workup in patients with potentially resectable ESCC, especially in early clinical stage patients.

A two-dimensional axisymmetric model, employing a dynamic mesh and user-defined functions, is used to numerically simulate the transient multiphase flow field produced by an underwater gun. Furthermore, a visualized shooting experiment platform with a high-speed camera is built to observe the evolution process of such a multiphase flow field. The simulated phase distribution diagram is agreed well with the shadow photo of the experiment, indicating that the numerical model is reasonable. Further examinations of the multiphase flow fields by using the submerged and sealed launch methods show that use of the sealed launch can significantly improve the interior ballistic performance of an underwater gun. In the cases by using these two types of underwater launch methods, the displacement of the projectile within the range of the muzzle flow field meets the exponential law over time. Moreover, a not fully developed bottle-shaped shock wave is formed when t = 0.4 ms, but this bottle-shaped shock wave expands more rapidly for the sealed launch. In addition, the amplitude of pressure oscillation for the sealed launch is larger than that of the submerged launch, but the pressure oscillation of the sealed launch lasts shorter.

Information entropy can be used for investigating the critical fluctuation phenomenon by describing multiplicity fluctuations in heavy-ion collisions. In this study, a multiphase transport (AMPT) model in the default version (AMPT-DEF) and with the string melting (AMPT-SM) were used as event generators to simulate the Au+Au reaction at different incident energies. Owing to the influence of the distribution bin number in extracting its information entropy, two methods, i.e., data binning and weighting factors, were proposed to correct the information entropy analysis. The comparison between information entropy and kurtosis also reflects the necessity to correct the information entropy analysis. The corrected information entropy of net-proton multiplicity was analyzed in central Au+Au collisions at sNN= 4.7, 6.4, 7.7, 8.8, 11.5, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 140, 170, and 200 GeV with the impact parameter b=3 fm. The results indicated that the fluctuations of net-proton multiplicity were essentially identical at collision energies ranging from sNN= 4.7 GeV to sNN= 200 GeV in the same model. No critical fluctuation phenomenon was found in the central Au+Au collisions simulated using the AMPT models, similar to the case of the AMPT model, which does not have. Comparing the information entropy of AMPT-SM to AMPT-DEF, the effect of partonic phase leads to a bigger fluctuation, indicating that the corrected information entropy can be a useful probe to explore the phase transition. The mid-rapidity net-proton multiplicity information entropy was also calculated, and the results led to the same conclusion. The corrected information entropy may be useful for investigating critical fluctuations, which is important for exploring critical endpoint.

Abstract Aging is characterized by inevitable organ function decline over time, with consequent body deterioration and increased susceptibility to death. Astragalus polysaccharide (APS) has been reported to have anti‐oxidative, anti‐apoptotic, and anti‐inflammatory properties. We investigated the potential protective effects of APS on hydrogen peroxide (H2O2) induced hepatocyte senescence and identified related mechanisms in L02, Huh7, and LM3 cell lines. Aged female C57BL/6 mice were given APS for 1 week by intraperitoneal injection, and APS provided the strongest protective effect against H2O2‐induced damage at 100 μM. APS reduced the expression of cell senescence markers and alleviated pathological damage in aged mouse liver. APS treatment decreased oxidative stress, apoptosis, NOD‐like receptor protein‐3‐mediated pyroptosis, and maintained mitochondrial homeostasis. Notably, the protective effect of APS was weakened in the presence of chloroquine. APS might enrich autophagy by activating AMP‐activated protein kinase (AMPK) and inhibiting mammalian target of rapamycin (mTOR). In conclusion, APS reduced reactive oxygen species levels, inhibited apoptosis and pyroptosis, and promoted mitophagy via AMPK/mTOR pathway to alleviate hepatocyte senescence in vitro and in vivo.

Abstract Background Admission hypothermia (AH, 37.5 °C or thermal burns between the two groups. The risk ratio of mortality in infants during the post-QI period was significantly lower in the post-QI period as compared to the pre-QI period [adjusted risk ratio (aRR): 0.26, 95% confidence interval (CI): 0.13–0.50]. The risk ratio of late-onset neonatal sepsis (LOS) also significantly lowered in the post-QI period (aRR: 0.66, 95% CI: 0.50–0.87). Conclusion Implementation of multicentric thermoregulatory QI resulted in a significant reduction in AH and AMSH in VLBW neonates with associated reduction in mortality. We gained a lot from the QI, and successfully aroused the attention of perinatal medical staff to neonatal AH. This provided a premise for continuous quality improvement of AH in the future, and might provide a reference for implementation of similar interventions in developing countries. Trial registration Trial registration number: ChiCTR1900020861 . Date of registration: 21 January 2019(21/01/2019). Prospectively registered.

Juronidine have attracted extensive investigations in the field of chromogenic and chemiluminescent materials. In this thesis, DFT and TDDFT methods are used to study the excited state hydrogen bond dynamics and excited state proton transfer mechanism of JDF, including the analysis of its geometric structure, infrared vibration spectrum, absorption and emission spectra, frontier molecular orbitals, and potential energy curve. Results show that the intramolecular hydrogen bond in the JDF molecule weakens after photoexcitation, leading to the relatively high barrier (6.7 kcal/mol) during proton transfer process in the S1 state. [ABSTRACT FROM AUTHOR]

In Xanthomonas spp., the biosynthesis of the yellow pigment xanthomonadin and fatty acids originates in the type II polyketide synthase (PKS II) and fatty acid synthase (FAS) pathways, respectively. The acyl carrier protein (ACP) is the central component of PKS II and FAS and requires posttranslational phosphopantetheinylation to initiate these pathways. In this study, for the first time, we demonstrate that the posttranslational modification of ACPs in X. campestris pv. campestris is performed by an essential 4′-phosphopantetheinyl transferase (PPTase), XcHetI (encoded by Xc_4132). X. campestris pv. campestris strain XchetI could not be deleted from the X. campestris pv. campestris genome unless another PPTase-encoding gene such as Escherichia coli acpS or Pseudomonas aeruginosa pcpS was present. Compared with wild-type strain X. campestris pv. campestris 8004 and mutant XchetI::PapcpS, strain XchetI::EcacpS failed to generate xanthomonadin pigments and displayed reduced pathogenicity for the host plant, Brassica oleracea. Further experiments showed that the expression of XchetI restored the growth of E. coli acpS mutant HT253 and, when a plasmid bearing XchetI was introduced into P. aeruginosa, pcpS, which encodes the sole PPTase in P. aeruginosa, could be deleted. In in vitro enzymatic assays, XcHetI catalyzed the transformation of 4′-phosphopantetheine from coenzyme A to two X. campestris pv. campestris apo-acyl carrier proteins, XcAcpP and XcAcpC. All of these findings indicate that XcHetI is a surfactin PPTase-like PPTase with a broad substrate preference. Moreover, the HetI-like PPTase is ubiquitously conserved in Xanthomonas spp., making it a potential new drug target for the prevention of plant diseases caused by Xanthomonas.[Graphic: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Polycyclic aromatic hydrocarbons (PAHs) are produced during combustion of organic matter, such as during cigarette smoking, and they exist widely in the environment. Exposure to 3,4-benzo[a]pyrene (BaP), as the most widely studied PAHs, relates to many cardiovascular diseases. However, the underlying mechanism of its involvement remains largely unclear. In this study, we developed a myocardial ischemia–reperfusion (I/R) injury mouse model and an oxygen and glucose deprivation–reoxygenation H9C2 cell model to evaluate the effect of BaP in I/R injury. After BaP exposure, the expression of autophagy-related proteins, the abundance of NLRP3 inflammasomes, and the degree of pyroptosis were measured. Our results show that BaP aggravates myocardial pyroptosis in a autophagy-dependent manner. In addition, we found that BaP activates the p53–BNIP3 pathway via the aryl hydrocarbon receptor to decrease autophagosome clearance. Our findings present new insights into the mechanisms underlying cardiotoxicity and reveal that the p53–BNIP3 pathway, which is involved in autophagy regulation, is a potential therapeutic target for BaP-induced myocardial I/R injury. Because PAHs are omnipresent in daily life, the toxic effects of these harmful substances should not be underestimated.

The effects of magnesium/polytetrafluoroethylene (Mg/PTFE) pyrotechnic compositions on the coupled flow field and reignition mechanism are important aspects governing the performance and range of base bleed projectiles (BBPs). Owing to a decrease in pressure and temperature when the BBP leaves the muzzle, rapid depressurization occurs, which extinguishes the base bleed propellant. The Mg/PTFE pyrotechnic composition pressed in the igniter of the base bleed unit (BBU) provides additional energy to the BBU via a chemical reaction. Thus, the extinguished base bleed propellant is reignited under the effect of high-temperature combustion gas jets from the igniter. In this study, a numerical analysis is conducted to evaluate the effects of PTFE and Mg granularity as well as Mg/PTFE pyrotechnic compositions. Owing to the rapid depressurization, the temperature and pressure was found to decrease for different Mg/PTFE pyrotechnic compositions. However, the depressurization time increased as the PTFE granularity increased, the Mg granularity decreased, and the Mg content increased. When the pressure in the combustion chamber of the BBU decreased to the atmospheric pressure, the combustion gas jets from the igniter expand upstream (rather than downstream). However, these combustion gas jets exhibit different axial and radial expansion characteristics depending on the pyrotechnic compositions used. The results show that the reignition delay time, td, of the base bleed propellant was 377.608, 94.27, 387.243, 523.966, and 221.094 ms for cases A–E, respectively. Therefore, it was concluded that the Mg/PTFE pyrotechnic composition of case B was the most beneficial for the reignition of the base bleed propellant, with the earliest addition of energy and mass to the BBP.

Thermal safety of modular charge which is fed into and retained in the chamber after gun fires consecutively is first investigated with cook-off method. A two-dimensional cook-off model of modular charge in gun chamber is established and the cook-off process of modular charge in gun chamber is numerically simulated. Then the effects of module number and firing condition on charge thermal safety are evaluated by researching the cook-off response characteristics of modules. The results show that, under conditions of different module numbers the cook-off responses all occur on the module closest to the boundary of missile, and the single-base propellants located at the inner surface of cartridge ignite first. When the number of loaded module changes from 1 to 6, the cook-off response temperatures vary little, only in a small range of 478.1 K–482.4 K. The cook-off response times decrease logarithmically in the range of 211.2 s–166.7 s with the increasing length of residual air gap in gun chamber. The simulation results are well matched with the experimental data. Furthermore, different firing conditions have great influence on the cook-off response time, minor influence on the initial response position and little influence on the response temperature. Under the three conditions of consecutive 32 launches with 5 rounds/min, 43 launches with 1 round/min, and 41 launches with different firing frequencies, the cook-off response temperatures are 479.2 K, 481.1 K and 479.9 K respectively and the response times are 709.2 s, 211.2 s and 214.4 s respectively. The response position is near the middle area of the inner cartridge surface in the former condition and near the right area in the latter two conditions.

Carbon isotope composition (δ13C) has been widely used to estimate the intrinsic water-use efficiency (iWUE) of plants in ecosystems around the world, providing an ultimate record of the functional response of plants to climate change. This approach relies on established relationships between leaf gas exchange and isotopic discrimination, which are reflected in different formulations of 13C-based iWUE models. In the current literature, most studies have utilized the simple, linear equation of photosynthetic discrimination to estimate iWUE. However, recent studies demonstrated that using this linear model for quantitative studies of iWUE could be problematic. Despite these advances, there is a scarcity of review papers that have comprehensively reviewed the theoretical basis, assumptions, and uncertainty of 13C-based iWUE models. Here, we 1) present the theoretical basis of 13C-based iWUE models: the classical model (iWUEsim), the comprehensive model (iWUEcom), and the model incorporating mesophyll conductance (iWUEmes); 2) discuss the limitations of the widely used iWUEsim model; 3) and make suggestions on the application of the iWUEmes model. Finally, we suggest that a mechanistic understanding of mesophyll conductance associated effects and post-photosynthetic fractionation are the bottlenecks for improving the 13C-based estimation of iWUE.

Background. Immune checkpoint inhibitors (ICIs) have become a standard care in non-small-cell lung cancer (NSCLC). However, its application to epidermal growth factor receptor (EGFR)-mutant NSCLC patients is confronted with drug resistance. This study aimed to clarify the potential role of Yes1-associated transcriptional regulator (YAP1) in ICIs treatment for EGFR-mutant NSCLC population. Methods. All the clinical data of NSCLC were downloaded from Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) for GSE11969 and GSE72094. Based on YAP1 expression, all the NSCLC patients including the EGFR-mutant and EGFR-wildtype (WT) patients were divided into two groups, YAP1_High and YAP1_Low. Using cBioPortal, genetic alterations were analyzed for identification of immunogenicity in EGFR-mutant NSCLC. MR analysis was used to analyze the hub gene of EGFR. The infiltration of immune cells and the expression of the identified tumor-associated antigens were identified with TIMER. By graph learning-based dimensionality reduction analysis, the immune landscape was visualized. Moreover, survival analysis was performed to verify the predictive value of YAP1 in ICIs treatment for EGFR-mutant NSCLC population using Ren’s research data (NCT03513666). Results. YAP1 was a poor prognostic factor of EGFR-mutant NSCLC population rather than lung adenocarcinoma (LUAD) patients. MR analysis revealed that the EGFR gene regulated YAP1 expression. YAP1 was identified as a hub gene closely associated with immunosuppressive microenvironment and poor prognosis in EGFR-mutant NSCLC population in TCGA LUAD. Tumors with YAP1_High showed an immune-“cold” and immunosuppressive phenotype, whereas those with YAP1_Low demonstrated an immune-“hot” and immunoactive phenotype. More importantly, it was verified that YAP1_High subpopulation had a significantly shorter progression-free survival (PFS) and overall survival (OS) after ICIs treatment in EGFR-mutant NSCLC patients in the clinical trial. Conclusions. YAP1 mediates immunosuppressive microenvironment and poor prognosis in EGFR-mutant NSCLC population. YAP1 is a novel negative biomarker of ICIs treatment in EGFR-mutant NSCLC population. Clinical Trials. This trial is registered with NCT03513666.

BackgroundCurrently, the role of immunotherapy in neoadjuvant setting for patients with locally advanced esophageal squamous cell carcinoma (ESCC) is gradually attracting attention. Few studies compared the efficacy of neoadjuvant immunochemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT). Our study aimed to compare treatment response and postoperative complications after NICT followed by surgery with that after conventional NCRT in patients with locally advanced ESCC.MethodsOf 468 patients with locally advanced ESCC, 154 received conventional NCRT, whereas 314 received NICT. Treatment response, postoperative complications and mortality between two groups were compared. Pathological response of primary tumor was evaluated using the Mandard tumor regression grade (TRG) scoring system. Pathological complete response (pCR) of metastatic lymph nodes (LNs) was defined as no viable tumor cell within all resected metastatic LNs. According to regression directionality, tumor regression pattern was summarized into four categories: type I, regression toward the lumen; type II, regression toward the invasive front; type III, concentric regression; and type IV, scattered regression. Inverse probability propensity score weighting was performed to minimize the influence of confounding factors.ResultsAfter adjusting for baseline characteristics, the R0 resection rates (90.9% vs. 89.0%, P=0.302) and pCR (ypT0N0) rates (29.8% vs. 34.0%, P=0.167) were comparable between two groups. Patients receiving NCRT showed lower TRG score (P