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Based on the 60 mm artillery grenade, a slow-release structure was designed to reduce the severity of ammunitions response to accidental thermal stimulation and improve the thermal stability of ammunitions. The slow-release structure was made of high-density polyethylene (HDPE) and connected the fuse and the projectile body through internal and external threads. To study the safety of the slow-release structure under artillery launching overload, mechanical analysis of the slow-release structure was simulated via finite element analysis (FEA). The impacts of various factors (e.g., fuse mass, number of threads, and nominal diameter of internal threads of the slow-release structure) on the connection strength of the slow-release structure were studied. A strength-prediction model based on the fuse mass and internal thread parameters was established by fitting the maximum effective stress of the slow-release structure. This led to good prediction results. In conclusion, this study provides references and theoretical support for the design of thermal protection structures insensitive to ammunition.

The mechanisms of mAb-induced ADCC have been well established. However, the ADCC bioassays used to quantify mAb-induced ADCC require continued development/refinement to properly assess and compare the potency of newly developed therapeutic mAbs and biosimilars to meet regulatory requirements. We used trastuzumab and a lactate dehydrogenase (LDH)-based ADCC bioassay as a model to define critical parameters of the ADCC bioassay, describing how several bioassay parameters, including preparation of effector cells, E/T ratio, target cell selection, bioassay media components, and treatment time can influence the data quality of the ADCC activity. We confirm that a 4 to 24 h recovery cultivation is required to restore peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cell activity toward ADCC when using cryopreserved PBMCs. Furthermore, we delineated the cellular mechanisms underlying the restored ADCC activity following the recovery cultivation. We observed that CD69, an early marker of NK cell activation, was upregulated and a new subset CD56dim/CD16dim population was dramatically increased in the recovered NK cells, which led to an increase in expression and secretion of perforin, granzyme B, and cytokine production. This study provides comprehensive technical insights into ADCC bioassay optimization to inform trastuzumab biosimilar development. The knowledge gained from this study can also be leveraged to guide bioassay development for therapeutic mAbs with ADCC as the primary mechanism of action.

Low-income households face long-standing challenges of energy insecurity and inequality (EII). During extreme events (e.g., disasters and pandemics) these challenges are especially severe for vulnerable populations reliant on energy for health, education, and well-being. However, many EII studies rarely incorporate the micro- and macro-perspectives of resilience and reliability of energy and internet infrastructure and social-psychological factors. To remedy this gap, we first address the impacts of extreme events on EII among vulnerable populations. Second, we evaluate the driving factors of EII and how they change during disasters. Third, we situate these inequalities within broader energy systems and pinpoint the importance of equitable infrastructure systems by examining infrastructure reliability and resilience and the role of renewable technologies. Then, we consider the factors influencing energy consumption, such as energy practices, socio-psychological factors, and internet access. Finally, we propose interdisciplinary research methods to study these issues during extreme events and provide recommendations.

Eukaryotic cells are constantly exposed to various environmental stimuli. It remains largely unexplored how environmental cues bring about epigenetic fluctuations and affect heterochromatin stability. In the fission yeast Schizosaccharomyces pombe, heterochromatic silencing is quite stable at pericentromeres but unstable at the mating-type (mat) locus under chronic heat stress, although both loci are within the major constitutive heterochromatin regions. Here, we found that the compromised gene silencing at the mat locus at elevated temperature is linked to the phosphorylation status of Atf1, a member of the ATF/CREB superfamily. Constitutive activation of mitogen-activated protein kinase (MAPK) signaling disrupts epigenetic maintenance of heterochromatin at the mat locus even under normal temperature. Mechanistically, phosphorylation of Atf1 impairs its interaction with heterochromatin protein Swi6HP1, resulting in lower site-specific Swi6HP1 enrichment. Expression of non-phosphorylatable Atf1, tethering Swi6HP1 to the mat3M-flanking site or absence of the anti-silencing factor Epe1 can largely or partially rescue heat stress-induced defective heterochromatic maintenance at the mat locus.

Abstract Aim To explore whether and to what extent, nurse–patient assessment differences mediate the association between nurse‐to‐patient ratios and readiness for hospital discharge, and examine whether nurse–patient characteristics moderate the indirect and/or direct effect of mediation model. Design A cross‐sectional study was carried out from March 2021 to December 2022. Methods A total of 523 pairs of gastrointestinal cancer patients with PICC and their nurses were recruited. All the participants were invited to complete the general information questionnaire and the Readiness for Hospital Discharge Scale. Outcome measure was patient‐reported readiness for hospital discharge. This study was reported according to the STROBE checklist. Results The patients reported a low level of readiness for hospital discharge. Nurse–patient assessment differences were positively associated with nurse‐to‐patient ratios but negatively associated with readiness for hospital discharge. Furthermore, nurse–patient assessment differences fully mediated the effect of nurse‐to‐patient ratios on readiness for hospital discharge, and age and gender of patients only moderated the indirect path of mediation model.

Summary: Previous bulk RNA sequencing or whole genome sequencing on clear cell renal cell carcinoma (ccRCC) subtyping mainly focused on ccRCC cell origin or the complex tumor microenvironment (TME). Based on the single-cell RNA sequencing (scRNA-seq) data of 11 primary ccRCC specimens, cancer stem-cell-like subsets could be differentiated into five trajectories, whereby we further classified ccRCC cells into three groups with diverse molecular features. These three ccRCC subgroups showed significantly different outcomes and potential targets to tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs). Tumor cells in three differentiation directions exhibited distinct interactions with other subsets in the ccRCC niches. The subtyping model was examined through immunohistochemistry staining in our ccRCC cohort and validated the same classification effect as the public patients. All these findings help gain a deeper understanding about the pathogenesis of ccRCC and provide useful clues for optimizing therapeutic schemes based on the molecular subtype analysis.

Gallbladder neuroendocrine carcinoma (GBNEC) is rare and characterized by a low degree of tumor differentiation. The clinical features of GBNEC versus gallbladder adenocarcinoma (GBADC) remain a subject of debate. A total of 201 GBADC and 36 GBNEC cases that underwent surgery resection between January 2010 and 2022 at the Department of Biliary Surgery, West China Hospital, Sichuan University were included. A 1:1 propensity score matching (PSM) was performed based on seven predefined variables: age, sex, the American Joint Committee on Cancer (AJCC) stage, resection status, perineural invasion (PNI), lymphovascular invasion (LVI), and degree of tumor differentiation. Compared with GBADC, GBNEC patients were younger (median age 56.0 vs 64.0 years; P = 0.001), and more patients presented with advanced stages of tumor (P = 0.003). Patients with GBNEC also had a higher rate of PNI (55.6% vs 22.4%; P < 0.001), and LVI (63.9% vs 45.80%; P = 0.658). Before PSM, GBNEC patients had inferior prognoses compared with GBADC patients with a shorter median overall survival (mOS) (15.02 vs 20.11 months; P = 0.0028) and a shorter median recurrence-free survival (mRFS) (10.30 vs 15.17 months; P = 0.0028). However, after PSM analyses, there were no differences in OS (mOS 18.6 vs 18.0 months; P=0.24) or RFS (mRFS 10.98 vs 12.02 months; P = 0.39) between the GBNEC and GBADC cases. After multivariate analysis, tumor diagnosis (GBNEC vs GBADC) was not identified as an independent risk factor for shorter RFS (P = 0.506) or OS (P = 0.731). Unfavorable pathological features, including advanced AJCC tumor stages, poor differentiation, presence of LVI, and positive resection margins (all P < 0.05), were independent risk factors for inferior OS and RFS. GBNEC is difficult to diagnose early and has a prognosis comparable to stage-matched poorly differentiated GBADC. Tumor diagnosis (either GBADC or GBNEC) was not an independent risk factor for the patient’s OS. Unfavorable pathological features of the neoplasm are the main determinants.

To investigate the embryonic development of the mud crab Scylla paramamosain, we analyzed three critical parameters: egg color of, embryo morphology (through conventional and laser scanning confocal microscopy), and the distribution of cell divisions. During embryonic development, the egg color exhibited a progressive transition, shifting from orange to reddish-orange, then to brown, before ultimately darkening to black. Each embryo displayed a spherical shape, measuring approximately 280 μm in diameter, characterized by a smooth surface devoid of any depressions. The embryonic cell division was in the form of mixed oogenesis, comprised of complete division in the early stage, spiral oogenesis in the middle stage and surface division in the late stage. It is noteworthy that the blastopore appeared at the position where the transparent area and cell aggregation just appeared under the microscope, and the blastomere was a characteristic of the embryo entering the gastrulation stage. After entering the gastrulation stage, the cells aggregated towards the blastopore and formed two symmetrical cell clusters, which formed a V-shape with the void of the classic blastopore. When the transparent region occupied approximately 1/5 of the embryo’s volume, the embryo entered the nauplius stage, and the thoracic and abdominal armor, as well as the optic lobe and abdominal limb primordia, could be clearly distinguished. The appearance of the compound eye pigment band indicated the stage of compound eye pigment formation. At this time, the transparent area accounted for 1/4 of the embryo and a large number of ganglia appeared. The change of the compound eye pigment band from red to black was also one of the reasons for the blackening of the egg color of the crabs. The data obtained through this study have potential applications in the determination of embryonic development status and obtaining of high-quality seeds for S. paramamosain culture.

Abstract Macrophages are immune cells crucial for host defense and homeostasis maintenance, and their dysregulation is involved in multiple pathological conditions, such as liver fibrosis. The transcriptional regulation in macrophage is indispensable for fine-tuning of macrophage functions, but the details have not been fully elucidated. Prolyl endopeptidase (PREP) is a dipeptidyl peptidase with both proteolytic and non-proteolytic functions. In this study, we found that Prep knockout significantly contributed to transcriptomic alterations in quiescent and M1/M2-polarized bone marrow-derived macrophages (BMDMs), as well as aggravated fibrosis in an experimental nonalcoholic steatohepatitis (NASH) model. Mechanistically, PREP predominantly localized to the macrophage nuclei and functioned as a transcriptional coregulator. Using CUT&Tag and co-immunoprecipitation, we found that PREP was mainly distributed in active cis-regulatory genomic regions and physically interacted with the transcription factor PU.1. Among PREP-regulated downstream genes, genes encoding profibrotic cathepsin B and D were overexpressed in BMDMs and fibrotic liver tissue. Our results indicate that PREP in macrophages functions as a transcriptional coregulator that finely tunes macrophage functions, and plays a protective role against liver fibrosis pathogenesis.

Objective To exploratively analyze the efficacy and safety of combined laparoscopy and cystoscopy in the treatment of bladder diverticula. Methods Clinical data of patients who received bladder diverticulectomy in Peking Union Medical College Hospital from March 2007 to September 2022 were retrospectively collected.The patients were divided into open/laparoscopy alone group and combined laparoscopy and cystoscopy group based on surgical approach.Surgery-related outcomes and complication rates were compared. Results A total of 11 patients with bladder diverticula who met the inclusion and exclusion criteria were enrolled in thestudy, including 6 patients in the open/laparoscopy alone group and 5 patients in the combined laparoscopy and cystoscopy group.The median maximum diameter of diverticula in the open/laparoscopy alone group and combined laparoscopy and cystoscopy group were 7.5(4.5, 11.5) cm and 5.2(5.0, 7.9) cm, respectively, and the median diameter of diverticula neck were 1.1(1.0, 1.6) cm and 1.5(1.1, 1.8) cm, respectively.Operations were successfully performed in both two groups and the patients had normal urination after drawing the catheter.No recurrence of bladder diverticulum at 6 to 60 months of follow-up.The median operative time[150.0(142.5, 180.0) min vs. 160.0(108.8, 300.0) min], blood loss[50.0(35.0, 50.0) mL vs. 50.0(45.0, 62.5) mL]and indwelling time of drainage tube[5.0(3.5, 5.5) d vs. 4.5(4.0, 6.8) d]were similar between the two group.Compared to the open/laparoscopy alone group, the combined laparoscopy and cystoscopy group had a shorter postoperative hospital stay[6.0(6.0, 8.5) d vs. 9.5(7.0, 16.0) d]and longer indwelling time of urinary catheter[14.0(10.5, 14.0) d vs. 11.5(6.5, 13.3) d].No complications occurred in the combined laparoscopy and cystoscopy group.In the open/laparoscopy alone group, 2 patients underwent postoperative complications, including 1 patient with deep vein thrombosis of the lower extremities and 1 patient with hyperpyrexia. Conclusion Preliminary results show that cystoscopy combined with laparoscopic resection for bladder diverticula can achieve similar outcomes as open surgery alone or laparoscopic surgery, and with greater safety and faster postoperative patient recovery.

Abstract Background Knee osteoarthritis (KOA) has a complex pathological mechanism and is difficult to cure. The traditional medicine Du Huo Ji Sheng Tang (DHJST) has been used for the treatment of KOA for more than one thousand years, but its mechanism for treating KOA has not been revealed. In our previous study, we confirmed that DHJST inhibited the activation of NLRP3 signaling in rats and humans. In the current study, we aimed to determine how DHJST inhibits NLRP3 to alleviate knee cartilage damage. Methods Mice were injected with NLRP3 shRNA or Notch1-overexpressing adenovirus into the tail vein to construct systemic NLRP3 low-expressing or Notch1 high-expressing mice. Mice were injected with papain into the knee joint to replicate the KOA model. DHJST was used to treat KOA model mice with different backgrounds. The thickness of the right paw was measured to evaluate toe swelling. The pathohistological changes and the levels of IL-1β, MMP2, NLRP3, Notch1, collagen 2, collagen 4, HES1, HEY1, and Caspase3 were detected by HE staining, ELISA, immunohistochemical staining, western blotting, or real-time qPCR. Results DHJST reduced tissue swelling and serum and knee cartilage IL-1β levels, inhibited cartilage MMP2 expression, increased collagen 2 and collagen 4 levels, decreased Notch1 and NLRP3 positive expression rates in cartilage, and decreased HES1 and HEY1 mRNA levels in KOA model mice. In addition, NLRP3 interference decreased cartilage MMP2 expression and increased collagen 2 and collagen 4 levels without affecting the expression levels of notch1, HES1 and HEY1 mRNA levels in the synovium of KOA mice. In KOA mice with NLRP interference, DHJST further reduced tissue swelling and knee cartilage damage in mice. Finally, Notch1-overexpressing mice not only showed more severe tissue swelling and knee cartilage degradation but also abolished the therapeutic effect of DHJST on KOA mice. Importantly, the inhibitory effects of DHJST on the mRNA expression of NLRP3, Caspase3 and IL-1β in the knee joint of KOA mice were completely limited after Notch1 overexpression. Conclusion DHJST significantly reduced inflammation and cartilage degradation in KOA mice by inhibiting Ntoch1 signaling and its subsequent NLRP3 activation in the knee joint.

A transparent ceramic glaze with good apparent quality and water wettability was successfully prepared by adjusting the mass fraction ratio of Na₂O/K₂O and R₂O/Al₂O₃ at 1280 °c. The effects of the Na₂O/K₂O and R₂O/Al₂O₃ ratios on the surface energy and glossiness of the ceramic glaze were studied in the present work. The results show that the mass fraction ratio of Na₂O/K₂O and R₂O/Al₂O₃ showed an obvious effect on the high temperature viscosity and melting temperature of the glaze, the density of the glaze network structure and the number of broken bonds on the glaze. When Na₂O/K₂O=0.8-1.6, R₂O/Al₂O₃=0.8-1.2, the glaze showed a glossiness of 88.3-108.3 with a 0.11%-12% increase, and the surface energy of 70.17-78.5 mJ · m-2 with a 5.62%-29.55% increase, being obviously higher than those of the basic glaze. The greater the surface energy of the glaze was, the greater the polarity component was, and the better the wettability of the water on the glaze was, which would be conducive to improving the antifouling and easy cleaning of ceramic products.

Strontium-doped hydroxyapatite ceramics with good ferroelectric properties were prepared using 5% bioactive phosphate glass as an additive at 700 °C in this paper. XRD, FTIR, SEM analyses and a ferroelectric tester were used to analyse the crystal structure, phase composition, microstructure and ferroelectric properties of the prepared ceramics. The results revealed that substitution of Ca2+ by Sr2+ in the HA lattice would lead to an increase in its lattice parameters and a decrease in crystallinity. Moreover, the lattice distortion and the increase in the electric dipole moment caused by the Sr2+ doping enhanced the ferroelectric properties of the Sr-HA ceramics. Increasing the density of the samples could enhance their ferroelectric properties. The remnant polarisation intensity increased from 0.0156 μC/cm² to 0.0728 μC/cm², the maximum polarisation intensity increased from 0.1210 μC/cm² to 0.1628 μC/cm².

The purpose of this systematic review was to examine the safety and effectiveness of mobile health applications in couples with infertility. Nineteen databases were searched from their inception to August 2022. Only randomized controlled trials (RCTs) in which mobile health was used as an intervention in infertile couples were included. A quantitative analysis of RCTs was employed using RevMan software. Study selection, data extraction and validation were performed by two independent reviewers according to the guidelines. The Cochrane criteria for risk-of-bias were used to evaluate the methodological quality of the trials. Eight RCTs met the inclusion criteria. Among the eight RCTs, two RCTs were from the Netherlands and the remaining six RCTs were from China. Meta-analysis showed that mobile health interventions in infertile couples in China were found to be superior to usual care in terms of clinical pregnancy rate (p = 0.001), psychological status (SAS (Self-Rating Anxiety Scale): p < 0.001; SDS (Self-Rating Depression Scale) p < 0.001;), infertility knowledge levels (p < 0.001), quality of life (p < 0.001), and serum levels of 5-hydroxytryptamine (p < 0.001). The effects on intervention groups using mobile health interventions in the Netherlands were not superior to the control groups that used usual care in terms of improving dietary factors (p > 0.05). In general, the positive effect of mobile health on improving clinical pregnancy rate, psychological status, infertility knowledge levels, quality of life and satisfaction with information was better than that of usual care. Mobile health interventions could be a viable supplement to the usual care for infertile couples. However, more high-quality RCTs need to be included in the future to provide additional evidence of the positive effects of mobile health in infertile couples.

On the basis of the investigation on the operating conditions of the pipeline and the operating environment of the cathodic protection system，the typical pipelines and test points were selected according to the principles of universality，representativeness and pertinence，and the corrosion rate and cathodic protection degree of the pipeline were measured by the on-site coupon hanging to evaluate the cathodic protection effect.Results showed that the corrosion rate of the pipeline was significantly lower than 0.01 mm/a and the protection degree was above 85%after applying cathodic protection in accordance with the minimum protection potential and cathode potential negative offset criteria specified in GB/T 21448-2017.The overall cathodic protection effect was good.For pipelines with high resistivity to soil，100 mV cathode potential negative offset criterion was recommended.In the actual operation process of pipeline cathodic protection，soil microorganism amount and types，stray current and the maximum protection potential needed to be heavily monitored for timely adjustment of the cathodic protection potential of the pipeline for the purpose of avoiding relatively serious uniform corrosion，local corrosion，hydrogen damage and unnecessary waste of resources.

Abstract The number of clinical trials conducted in mainland China, including investigator‐initiated trials (IITs), has increased rapidly in recent years. However, there are few data on the characteristics of cancer‐related IITs. We performed a comprehensive analysis of the landscape of cancer‐related IITs in mainland China in the past decade. All cancer‐related IITs registered on two clinical trial registries in the United States (www.clinicaltrials.gov, CT.gov) and mainland China (www.chictr.org.cn, ChiCTR) from 2010 to 2019 were identified. IITs were reviewed manually to validate classification, subcategorized by cancer type, and stratified by design characteristics to facilitate comparison across cancer types and with other specialties. A total of 8199 cancer‐related IITs were identified. The number of trials registered annually increased over time, especially in the last 5 years. Although interventional studies were predominant, randomized double‐blind studies accounted for only 8% of IITs. In the past decade, the trend for interventional studies conducted with different drugs increased year on year, although the increase in hormonal therapy IITs was not significant. Additionally, cancer‐related IITs were unevenly geographically distributed, with half concentrated in the economically developed cities Shanghai, Beijing, and Guangdong. We also found an increase in registration before participant enrollment (64.9% for trials in conducted in 2015–2019 vs. 40.2% in 2010–2014, p

Abstract Background The prevalence of impaired glucose tolerance and diabetes is much higher in people with cirrhosis than that in the general population. However, there are inadequate concrete guidelines for the management of diabetes in these patients, particularly in the early stage. Bile aids (BAs) have been found to exert hormone-like functions in the control of lipid and glucose metabolism. We studied the effect of ursodeoxycholic acid (UDCA) on glucose levels in rats with cirrhosis induced by bile duct ligation (BDL). Methods SD rats were divided into three groups: sham operation (Group A); BDL (Group B), and UDCA plus BDL (Group C). After 4 weeks, oral glucose tolerance tests were performed. Serum biochemical parameters and the levels of glucose, insulin, and glucagon-like peptide 1 (GLP-1) were measured. Histopathology of the liver and islet was observed. The gene expression of cholesterol 7α-hydroylase (CYP7A1), microsomal oxysterol 7a-hydroxylase (CYP7B1) in the liver, and Takeda G-protein-coupled receptor-5 (TGR5) in the intestine was determined by real-time PCR. Results Compared with Group A, fasting glucose and 1-h and 2-h postprandial glucose levels increased slightly (all P > 0.05), 2-h postprandial insulin levels increased significantly (P

Abstract Background: Diverticular disease has been inconsistently associated with colorectal cancer risk. We conducted a bidirectional Mendelian randomization study to assess this association. Methods: Forty-three and seventy single-nucleotide polymorphisms associated with diverticular disease and colorectal cancer at the genome-wide significance level (p

ObjectCognitive decline and obesity are major global public health issues, and their association has been widely acknowledged. The link between the visceral adiposity index (VAI) and cognitive function in the Chinese population remains uncertain. This study aims to investigate the effects of VAI levels on cognitive function in the Chinese middle-aged and elderly population.MethodsWe analyzed longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS) collected in 2011, 2013, 2015, and 2018. VAI levels were divided into three tertiles. Generalized estimating equation (GEE) models were used to explore the relationships between VAI levels and cognitive function, including overall cognitive scores, episodic memory, and mental status. Adjustments were made for potential confounders.ResultsThe study consisted of 2,677 participants. Contrary to expectations, higher VAI levels were associated with higher overall cognitive scores and improved episodic memory scores, while no significant effect was observed on mental status. The GEE models consistently indicated that higher VAI levels were associated with higher overall cognitive scores, primarily due to their association with episodic memory. Stratified analyses revealed that the VAI was associated with better cognitive function primarily in males, individuals under 60 years old, those with lower education levels, rural residents, and married individuals, mainly in relation to episodic memory. No significant interactions were observed between VAI and demographic factors.ConclusionOur findings suggest that higher visceral adiposity is associated with slower cognitive decline in the Chinese middle-aged and elderly population, especially in its association with episodic memory. These results underline the need to further investigate the potential protective role of visceral fat in cognitive function, potentially offering new insights for interventions to enhance cognitive function and prevent dementia in this population.