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Abstract Lymphocyte decline, particularly the depletion of NK cells, is a prominent feature of immunosuppression following severe tissue injury, heightening the susceptibility of severe trauma patients to life-threatening infections. Previous research indicates that the reduction in the number of NK cells is closely associated with the process of cell death. Nonetheless, the precise mechanism of NK cell death remains unknown. Here, we discovered that following severe traumatic injury, NK cells undergo several cell death pathways, dominated by apoptosis and pyroptosis with coexistence of necrotic cell death, immunogenic cell death, ferroptosis, and autophagy. These NK cells with different paradigms of death have diverse cytokine expression profiles and diverse interactions with other immune cells. Further exploration revealed that hypoxia was strongly associated with this diverse paradigm of NK cell death. Detailed investigation of paradigms of cell death may help to enhance comprehension of lymphopenia post-severe trauma, to develop new strategy in preventing immunosuppression, and then to improve outcome for severe trauma population.

Abstract Background Evidence from observational studies indicates that lung cancer screening (LCS) guidelines with high rates of lung cancer (LC) underdiagnosis, and although current screening guidelines have been updated and eligibility criteria for screening have been expanded, there are no studies comparing the efficiency of LCS guidelines in Chinese population. Methods Between 2005 and 2022, 31,394 asymptomatic individuals were screened using low-dose computed tomography (LDCT) at our institution. Demographic data and relevant LC risk factors were collected. The efficiency of the LCS for each guideline criteria was expressed as the efficiency ratio (ER). The inclusion rates, eligibility rates, LC detection rates, and ER based on the different eligibility criteria of the four guidelines were comparatively analyzed. The four guidelines were as follows: China guideline for the screening and early detection of lung cancer (CGSL), the National Comprehensive Cancer Network (NCCN), the United States Preventive Services Task Force (USPSTF), and International Early Lung Cancer Action Program (I-ELCAP). Results Of 31,394 participants, 298 (155 women, 143 men) were diagnosed with LC. For CGSL, NCCN, USPSTF, and I-ELCAP guidelines, the eligibility rates for guidelines were 13.92%, 6.97%, 6.81%, and 53.46%; ERe for eligibility criteria were 1.46%, 1.64%, 1.51%, and 1.13%, respectively; and for the inclusion rates, they were 19.0%, 9.5%, 9.3%, and 73.0%, respectively. LCs which met the screening criteria of CGSL, NCCN, USPSTF, and I-ELCAP guidelines were 29.2%, 16.4%, 14.8%, and 86.6%, respectively. The age and smoking criteria for CGSL were stricter, hence resulting in lower rates of LC meeting the screening criteria. The CGSL, NCCN, and USPSTF guidelines showed the highest underdiagnosis in the 45–49 age group (17.4%), while the I-ELCAP guideline displayed the highest missed diagnosis rate (3.0%) in the 35–39 age group. Males and females significantly differed in eligibility based on the criteria of the four guidelines (P

Objective: To develop a deep learning model to predict lymph node (LN) status in clinical stage IA lung adenocarcinoma patients. Methods: This diagnostic study included 1,009 patients with pathologically confirmed clinical stage T1N0M0 lung adenocarcinoma from two independent datasets (699 from Cancer Hospital of Chinese Academy of Medical Sciences and 310 from PLA General Hospital) between January 2005 and December 2019. The Cancer Hospital dataset was randomly split into a training cohort (559 patients) and a validation cohort (140 patients) to train and tune a deep learning model based on a deep residual network (ResNet). The PLA Hospital dataset was used as a testing cohort to evaluate the generalization ability of the model. Thoracic radiologists manually segmented tumors and interpreted high-resolution computed tomography (HRCT) features for the model. The predictive performance was assessed by area under the curves (AUCs), accuracy, precision, recall, and F1 score. Subgroup analysis was performed to evaluate the potential bias of the study population. Results: A total of 1,009 patients were included in this study; 409 (40.5%) were male and 600 (59.5%) were female. The median age was 57.0 years (inter-quartile range, IQR: 50.0–64.0). The deep learning model achieved AUCs of 0.906 (95% CI: 0.873–0.938) and 0.893 (95% CI: 0.857–0.930) for predicting pN0 disease in the testing cohort and a non-pure ground glass nodule (non-pGGN) testing cohort, respectively. No significant difference was detected between the testing cohort and the non-pGGN testing cohort (P = 0.622). The precisions of this model for predicting pN0 disease were 0.979 (95% CI: 0.963–0.995) and 0.983 (95% CI: 0.967–0.998) in the testing cohort and the non-pGGN testing cohort, respectively. The deep learning model achieved AUCs of 0.848 (95% CI: 0.798–0.898) and 0.831 (95% CI: 0.776–0.887) for predicting pN2 disease in the testing cohort and the non-pGGN testing cohort, respectively. No significant difference was detected between the testing cohort and the non-pGGN testing cohort (P = 0.657). The recalls of this model for predicting pN2 disease were 0.903 (95% CI: 0.870–0.936) and 0.931 (95% CI: 0.901–0.961) in the testing cohort and the non-pGGN testing cohort, respectively. Conclusions: The superior performance of the deep learning model will help to target the extension of lymph node dissection and reduce the ineffective lymph node dissection in early-stage lung adenocarcinoma patients.

Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Purpose: This study aimed to compare the risk of vagal reflex during microsurgical subinguinal varicocelectomy (MSV) under general anesthesia (GA) with or without additional local anesthetic (LA) spermatic cord block (SCB). Method: A single-center randomized controlled trial was conducted between January 2022 and June 2023.300 patients with left-sided grade Ⅲ varicocele were randomly divided into two groups: SCB group (n = 153) and control group (n = 147)（computer-generated random numbers list）. During MSV under GA, the SCB group was given of ropivacaine for SCB before pulling the spermatic cord, while the control group was directly lifted. The primary outcome was the reduction in the lowest heart rate in the SCB group as compared with the control group during spermatic cord traction (SCT). Secondary outcomes included the reduction in the lowest blood pressure in the SCB group as compared with the control group; and the reductions in the lowest heart rate and lowest blood pressure as compared with baseline during SCT. The number of times that surgery and medications were suspended because of symptomatic reflex bradycardia was also recorded. Adverse events were also recorded as secondary outcomes. Result: Five patients in the SCB group and 10 patients in the CG were excluded. The lowest heart rate and systolic blood pressure during SCT in the SCB group and the control group were significantly lower than the baseline values (P

IntroductionWith the acceleration of urbanization, human population and built surface in urban areas have increased rapidly, triggering numerous environmental problems. Identification of ecological security pattern (ESP) can be helpful to optimize the interaction and relationship between ecological conservation and socioeconomic development in a given region. In this study, taking Chengdu City as an example, a methodology was used to analyze the city’s ESP.MethodologyEcological sources were identified based on their ecological security values, which were derived from the spatio-temporal evaluation of ecosystem services and ecological health. The ecological resistance surface was revised with nighttime light index. Linkage Mapper combined with circuit theory was used to extracted ecological corridors and key ecological nodes.Results:The results showed that the mean values of ecological security in Chengdu City presented a downward and then upward trend from 2000 to 2018. In 2018, the ESP in Chengdu City was formed by 140 ecological sources with the total area of 8,819.78 km2, 302 ecological corridors with the area of 456.91 km2, as well as 61 pinch-points and 17 barrier points. The ecological sources in Chengdu City were mainly distributed in or nearby Longmen Mountain and Longquan Mountain, two flanks of the Chengdu Plain, and connected each other with hundreds of ecological corridors. Most of ecological sources and corridors were composited of forests in mountainous areas and linpan units (wooded lots) in rural plain areas. On the contrary, pinch-points and barrier points were mainly distributed in the districts nearby the metropolitan urban center.ConclusionFinally, this study proposed that constructing ESP must adopt a dynamic and holistic approach in considering the change of restoring ecosystems, shift of urban demands for ecosystem services and transformation of urban-rural land use/cover. Restoring and managing corridors sustainably are important for improving the ecological connectivity of all over ecological sources in a city, all of which together, if functioning well, could further support the realization of sustainable urbanization.

Abstract Resident memory T (Trm) cells which are specifically located in non-lymphoid tissues showed distinct phenotypes and functions compared to circulating memory T cells and were vital for the initiation of robust immune response within tissues. However, the heterogeneity in the transcriptional features, development pathways, and cancer response of Trm cells in the small intestine was not demonstrated. Here, we integrated scRNA-seq and scTCR-seq data pan-tissue T cells to explore the heterogeneity of Trm cells and their development pathways. Trm were enriched in tissue-specific immune response and those in the DUO specially interacted with B cells via TNF and MHC-I signatures. T cell lineage analyses demonstrated that Trm might be derived from the T_CD4/CD8 subset within the same organ or migrated from spleen and mesenteric lymph nodes. We compared the immune repertoire of Trm among organs and implied that clonotypes in both DUO and ILE were less expanded and hydrophilic TRB CDR3s were enriched in the DUO. We further demonstrated that Trm in the intestine infiltrated the colorectal cancer and several effector molecules were highly expressed. Finally, the TCGA dataset of colorectal cancer implied that the infiltration of Trm from the DUO and the ILE was beneficial for overall survival and the response to immune checkpoint blockade.

CoCrNiFe multi-principal element alloy (MPEA) plates were prepared by melting and rolling. Thermomechanical treatment (cold rolling and aging) was developed to modify the formation of lattice defects and precipitates. The results show that the Co40Cr22Ni15Fe14Mo4Si3Mn2 MPEA have excellent room temperature ultimate tensile strength and hardness of 1946 MPa and 684 HV0.1. Electron backscatter diffraction (EBSD) and transmission electron microscope (TEM) techniques were used to reveal the microstructure and provide insight into the mechanism. The strengthening mechanism comes from the multiple factors, and most notably, the interaction between nano-twins and Lomer-Cottrell locks. The presence of nano-twins and stacking faults has a significant impact on the strain hardening behavior of the alloy. At the same time, the occurrence and development of deformation substructure dominated by dislocation configuration is the reasons for the material to achieve multi-stage strain hardening (MSSH). This method of realizing MSSH behavior by adjusting microstructure is of great significance in the design and application of FCC MPEA and can be extended to other FCC alloys.

In American men, the incidence of prostate cancer (PC) is the highest among all types of cancer, making it the second leading cause of mortality associated with cancer. For advanced or metastatic PC, antiandrogen therapies are standard treatment options. The administration of these treatments unfortunately carries the potential risk of inducing neuroendocrine prostate cancer (NEPC). Neuroendocrine differentiation (NED) serves as a crucial indicator of prostate cancer development, encompassing various factors such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), Yes-associated protein 1 (YAP1), AMP-activated protein kinase (AMPK), miRNA. The processes of autophagy and ferroptosis (an iron-dependent form of programmed cell death) play pivotal roles in the regulation of various types of cancers. Clinical trials and preclinical investigations have been conducted on many signaling pathways during the development of NEPC, with the deepening of research, autophagy and ferroptosis appear to be the potential target for regulating NEPC. Due to the dual nature of autophagy and ferroptosis in cancer, gaining a deeper understanding of the developmental programs associated with achieving autophagy and ferroptosis may enhance risk stratification and treatment efficacy for patients with NEPC.

Chemotherapy remains the cornerstone of pancreatic cancer treatment. However, the dense interstitial and immunosuppressive microenvironment frequently render the ineffective anti-tumor activity of chemotherapeutic agents. Macrophages play a key role in the tumor immunomodulation. In this study, we found that low molecular weight of fucoidan (LF2) directly regulated the differentiation of mononuclear macrophages into the CD86+ M1 phenotype. LF2 significantly upregulated the expressions of M1 macrophage-specific cytokines, including iNOS, IL-6, TNFα and IL-12. LF2 modulated macrophage phenotypic transformation through activation of TLR4-NFκB pathway. Furthermore, we observed that LF2 enhanced the pro-apoptotic activity of oxaliplatin (OXA) in vitro by converting macrophages to a tumoricidal M1 phenotype. Meanwhile, LF2 increased intratumoral M1 macrophage infiltration and ameliorated the immunosuppressed tumor microenvironment, which in turn enhanced the anti-pancreatic ductal adenocarcinoma (PDAC) activity of OXA in vivo. Taken together, our results suggested that LF2 could act as a TLR4 agonist targeting macrophages and has a synergistic effect against PDAC when combined with OXA.

Abstract Biosynthesis drives the cell volume increase during T cell activation. However, the contribution of cell volume regulation in TCR signaling during T lymphoblast formation and its underlying mechanisms remain unclear. Here we show that cell volume regulation is required for optimal T cell activation. Inhibition of VRACs (volume-regulated anion channels) and deletion of leucine-rich repeat-containing protein 8A (LRRC8A) channel components impair T cell activation and function, particularly under weak TCR stimulation. Additionally, LRRC8A has distinct influences on mRNA transcriptional profiles, indicating the prominent effects of cell volume regulation for T cell functions. Moreover, cell volume regulation via LRRC8A controls T cell-mediated antiviral immunity and shapes the TCR repertoire in the thymus. Mechanistically, LRRC8A governs stringent cell volume increase via regulated volume decrease (RVD) during T cell blast formation to keep the TCR signaling molecules at an adequate density. Together, our results show a further layer of T cell activation regulation that LRRC8A functions as a cell volume controlling “valve” to facilitate T cell activation.

Abstract Purpose To investigate the correlations between metabolic parameters (MPs) of 18F‐fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT), serum tumor markers (STMs), and tumor mutational burden (TMB) in patients with non‐small cell lung cancer (NSCLC). Materials and Methods In this retrospective study, we enrolled 129 patients with NSCLC (males, 78; females, 51) who underwent baseline TMB and STM tests and 18F‐FDG PET/CT scans before treatment between March 2018 and September 2022. Patients were categorized into TMB‐high (TMB ≥10 mutations/Mb; n = 27 [20.9%]) and non‐TMB‐high (TMB

Abstract Objective The purpose of this study is to reveal the dose-effect relationship of linear accelerator (LINAC)-based stereotactic radiotherapy (SRT) in patients with brain metastases (BM). Materials and methods The PubMed, Cochrane, and Web of Science databases were used to identify studies that reported local tumour control after LINAC-based SRT in patients with BMs. Studies of other approaches that could affect local tumour control, such as whole brain radiotherapy, targeted therapy, and immunotherapy, were excluded from the dose-effect relationship analysis. Data extracted included patient and treatment characteristics and tumour local control. Probit model in XLSTAT 2016 was used for regression analysis, and P

Abstract The global incidence of dengue fever has gradually increased in recent years, posing a serious threat to human health. In the absence of specific anti-dengue drugs, understanding the interaction of Dengue virus (DENV) with the host is essential for the development of effective therapeutic measures. Autophagy is often activated during DENV infection to promote viral replication, but the mechanism of how DENV's own proteins induce autophagy has not been clarified. In this study, we first preliminarily identified DENV-2 NS1 as the most likely viral protein for DENV-2-induced autophagy with the help of molecular docking techniques. Further experimental results confirmed that DENV-2 NS1 regulates DENV-2 infection of HUVEC-induced autophagy through the AMPK/ERK/mTOR signaling pathway. Mechanistically, DENV-2 NS1 mainly interacted with AMPK by means of its Wing structural domain, and NS1 bound to all three structural domains on the AMPKα subunit. Finally, the experimental results showed that DENV-2 NS1 promoted the interaction between LKB1 and AMPKα1 and thus activated AMPK by both increasing the expression of LKB1 and binding LKB1. In conclusion, the results of this study revealed that DENV-2 NS1 protein served as a platform for the interaction between AMPK and LKB1 after DENV-2 infection with HUVEC, and pulled AMPK and LKB1 together to form a complex. LKB1 to form a complex, promoting LKB1 action on the kinase structural domain of AMPKα1, which in turn promotes phosphorylation of the Thr172 site on the AMPK kinase structural domain and activates AMPK, thereby positively regulating the AMPK/ERK/mTOR signaling pathway and inducing autophagy. The present discovery improves our understanding of DENV-2-induced host autophagy and contributes to the development of anti-dengue drugs.

Abstract To evaluate the feasibility and clinical significance of the left perinephric fat sac vein (PFSV) as an anatomical landmark in locating left adrenal gland (LAD) during retroperitoneal laparoscopic left adrenalectomy (RLLA). In this study, a total of 36 patients who underwent RLLA were enrolled from February 2019 and March 2021. By following a vein vessel on the internal surface of perinephric fat sac (PFS), known as PFSV, LAD was searched finally along the upper edge of this vein. The demographic and clinical characteristics of these patients were acquired, including tumor features and perioperative outcomes (operating time, estimated blood loss, complications). The operations were successfully completed in all the 36 patients without conversion to open surgery. In addition, the LAD was successfully found along the upper edge of PFSV in 34 patients. For all operations, the mean operative time was 75 min (range 60–95) and the estimated blood loss was 20 ml (range 10–50). The median oral intake was 20.7 h (range 6–39). The median hospital stay was 6.3 days (range 4–9), and the median follow-up was 12.3 months (range 9–17). Moreover, no intraoperative complications were observed and no residual tumors were detected after 9 to 15 months follow-up. It may be a safe and efficient procedure to use PFSV as a landmark for searching LAD during RLLA, especially for beginners. However, more studies with larger sample size are need to be conducted to further evaluate the outcomes of this method and the significance of PFSV in searching LAD during RLLA.

Abstract Background In China, over 50% of lung cancer cases occur in nonsmokers. Thus, identifying high‐risk individuals for targeted lung cancer screening is crucial. Beyond age and smoking, determining other risk factors for lung cancer in the Asian population has become a focal point of research. Using 30,000 participants in the prospectively enrolled cohort at China's National Cancer Center (NCC) over the past 14 years, we categorized participants by risk, with an emphasis on nonsmoking females. Materials and Methods Between November 2005 and December 2019, 31,431 individuals voluntarily underwent low‐dose computed tomography (LDCT) scans for lung cancer screening at the NCC. We recorded details like smoking history, exposure to hazards, and family history of malignant tumors. Using the 2019 NCCN criteria, participants were categorized into high‐, moderate‐, and low‐risk groups. Additionally, we separated non‐high‐risk groups into female never smokers (aged over 40) exposed to second‐hand smoke (SHS) and others. Any positive results from initial scans were monitored per the I‐ELCAP protocol (2006), and suspected malignancies were addressed through collaborative decisions between patients and physicians. We analyzed and compared the detection rates of positive results, confirmed lung cancers, and cancer stages across risk, age, and gender groups. Results Out of 31,431 participants (55.9% male, 44.1% female), 3695 (11.8%) showed positive baseline LDCT scans with 197 (0.6%; 106 females, 91 males) confirmed as lung cancer cases pathologically. Malignancy rate by age was 0.1% among those aged under 40 years, 0.4% among those aged 40–49 years, 0.8% among those aged 50–59 years, and 1.2% among those aged 60 years and older. From the 25,763 participants (56.9% male, 43.1% female) who completed questionnaires, 1877 (7.3%) were categorized as high risk, 6500 (25.2%) as moderate risk, and 17,386 (67.5%) as low risk. Of the 23,886 in the non‐high‐risk category, 8041 (33.7%) were females over 40 years old exposed to SHS. The high‐risk group showed the highest lung cancer detection rate at 1.4%. However, females exposed to SHS had a notably higher detection rate than the rest of the non‐high‐risk group (1.1% vs. 0.5%; p

In starch gel foods processing, lactic acid fermentation is an effective strategy to improve the quality of the gel. This study revealed the effects of Lactobacillus plantarum fermentation for rice on the textural and rheological properties of the corresponding gels. The hardness, adhesiveness and chewiness of the gel showed ascending trends with the forwarding of fermentation. The role of Lactobacillus plantarum on rheological properties of gel depended on fermentation time. As the time was within 3 days, the process reduced the viscoelastic of the gel, while as the time was for 5 days, the process enhanced the viscoelastic of the gel. During fermentation, amylose content increased from 21.56 ± 1.17% to 27.39 ± 0.63%, and crude protein content descended from 12.60 ± 0.44 g/100 g DW to 4.8 ± 0.49 g/100 g DW. Total organic acids were ascending in the whole process, and lactic acid (LA), acetic acid (AA) and citric acid (CA) made the dominant contribution. The enthalpy change (ΔH) of the rice flour fermented for 5 days was significantly (p

Background: The cumulative effect of body mass index (BMI) on brain health remains ill-defined. The effects of overweight on brain health across different age groups need clarification. We analyzed the effect of cumulative BMI on neuroimaging features of brain health in adults of different ages. Methods: This study was based on a multicenter, community-based cohort study. We modeled the trajectories of BMI over 16 years to evaluate cumulative exposure. Multimodality neuroimaging data were collected once for volumetric measurements of the brain macrostructure, white matter hyperintensity (WMH), and brain microstructure. We used a generalized linear model to evaluate the association between cumulative BMI and neuroimaging features. Two-sample Mendelian randomization analysis was performed using summary level of BMI genetic data from 681,275 individuals and neuroimaging genetic data from 33,224 individuals to analyze the causal relationships. Results: Clinical and neuroimaging data were obtained from 1,074 adults (25 to 83 years). For adults aged under 45 years, brain volume differences in participants with a cumulative BMI of >26.2 kg/m2 corresponded to 12.0 years [95% confidence interval (CI), 3.0 to 20.0] of brain aging. Differences in WMH were statistically substantial for participants aged over 60 years, with a 6.0-ml (95% CI, 1.5 to 10.5) larger volume. Genetic analysis indicated causal relationships between high BMI and smaller gray matter and higher fractional anisotropy in projection fibers. Conclusion: High cumulative BMI is associated with smaller brain volume, larger volume of white matter lesions, and abnormal microstructural integrity. Adults younger than 45 years are suggested to maintain their BMI below 26.2 kg/m2 for better brain health. Trial Registration: This study was registered on clinicaltrials.gov (Clinical Indicators and Brain Image Data: A Cohort Study Based on Kailuan Cohort; No. NCT05453877; https://clinicaltrials.gov/ct2/show/NCT05453877).

Background RAD51 is a central protein involved in homologous recombination, which has been linked to cancer development and progression. systemic inflammatory indicator markers such as neutrophil-to-lymphocyte ratio and lymphocyte-to-monocyte ratio have also been implicated in cancer. However, the relationship between Rad51 and these inflammatory markers in esophageal cancer patients undergoing esophagectomy is not yet understood. Methods We retrospectively observed 320 esophageal cancer patients who underwent esophagectomy. We collected clinical characteristics, postoperative complications, and survival analysis data and analyzed the relationship between Rad51 expression, inflammatory markers, and prognosis. Results We found significant linear relationships among the inflammatory markers. There were also close relationships between Rad51 expression and neutrophil-to-lymphocyte ratio or C-reactive protein. Patients with low lymphocyte percentage were more likely to have low Rad51 expression ( P = .026), high C-reactive protein ( P = .007), and high neutrophil-to-lymphocyte ratio ( P = .006). Low lymphocyte-to-monocyte ratio was associated with poor overall survival and was an independent prognostic factor (HR = 2.214; 95% confidence interval: 1.044-4.695, P = .038). In patients without lymph node metastases, low albumin (HR= 0.131; 95% confidence interval: 0.025-0.687, P = .016), high neutrophil-to-lymphocyte ratio (HR = 0.002; 95% confidence interval: 0.000-0.221, P = .009), and high Rad51 expression (HR = 14.394; 95% confidence interval: 2.217-97.402, P = .006) were associated with poor overall survival. Conclusions Our study found a close correlation between elevated Rad51 expression and inflammatory markers. High Rad51 expression, high neutrophil-to-lymphocyte ratio, and low lymphocyte-to-monocyte ratio are associated with lower survival rates. The combined assessment of Rad51 and inflammatory markers can be useful for preoperative assessment and prognostic evaluation in esophageal squamous cell carcinoma patients.

Abstract Background The ability of lung cancer screening to manage pulmonary nodules was limited because of the high false‐positive rate in the current mainstream screening method, low‐dose computed tomography (LDCT). We aimed to reduce overdiagnosis in Chinese population. Methods Lung cancer risk prediction models were constructed using data from a population‐based cohort in China. Independent clinical data from two programs performed in Beijing and Shandong, respectively, were used as the external validation set. Multivariable logistic regression models were used to estimate the probability of lung cancer incidence in the whole population and in smokers and nonsmokers. Results In our cohort, 1,016,740 participants were enrolled between 2013 and 2018. Of 79,581 who received LDCT screening, 5165 participants with suspected pulmonary nodules were allocated into the training set, of which, 149 lung cancer cases were diagnosed. In the validation set, 1815 patients were included, and 800 developed lung cancer. The ages of patients and radiologic factors of nodules (calcification, density, mean diameter, edge, and pleural involvement) were included in our model. The area under the curve (AUC) values of the model were 0.868 (95% CI: 0.839–0.894) in the training set and 0.751 (95% CI: 0.727–0.774) in the validation set. The sensitivity and specificity were 70.5% and 70.9%, respectively, which could reduce the 68.8% false‐positive rate in simulated LDCT screening. There was no substantial difference between smokers' and nonsmokers' prediction models. Conclusion Our models could facilitate the diagnosis of suspected pulmonary nodules, effectively reducing the false‐positive rate of LDCT for lung cancer screening.

This is a paper in the field of mineral processing engineering. The mineral characteristics of a vanadium titanium iron concentrate sample from Panxi were studied using sieve analysis, polarizing microscope, X-ray diffractometer, Zeiss Sigma 500 scanning electron microscope, Bruker energy spectrometer, and AMICS automatic mineral analysis system. The main gangue minerals in the sample are magnetite pyrite, granular ilmenite, pyroxene, feldspar, etc. The contents of coarse and fine products TFe, S, SiO2, Al2O3, MgO, and gangue minerals are quite different. A small amount of Fe exists in ilmenite, magnetic pyrite, and non-metallic minerals. Ti mainly exists in the form of titanium magnetite. ilmenite and magnesium aluminum spinel are inlaid on the base of titanium magnetite in lamellar, veinlet, thin strip, grid, and needle shapes, The particle size of the guest crystal mineral is very fine, making it difficult to grind, separate, and post treat the product. The use of grinding magnetic separation can increase the TFe grade of vanadium titanium iron concentrate by 2-3 percentage points. The essence of the improvement is a significant decrease in the content of SiO2, Al2O3, and MgO in the concentrate, with a decrease of SiO2>MgO>Al2O3. The TiO2 content of the concentrate does not change much during the improvement process, with Fe/TiO2 increasing from 4.29 to 4.50, V2O5 grade slightly increasing, and S grade slightly decreasing.

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, and accumulating evidence suggests a link between dysbiosis of the gut microbiota and the onset and progression of PD. In our previous investigations, we discovered that intraperitoneal administration of glucuronomannan oligosaccharides (GMn) derived from Saccharina japonica exhibited neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. However, the complicated preparation process, difficulties in isolation, and remarkably low yield have constrained further exploration of GMn. In this study, we optimized the degradation conditions in the preparation process of GMn through orthogonal experiments. Subsequently, an MPTP-induced PD model was established, followed by oral administration of GMn. Through a stepwise optimization, we successfully increased the yield of GMn, separated from crude fucoidan, from 1~2/10,000 to 4~8/1000 and indicated the effects on the amelioration of MPTP-induced motor deficits, preservation of dopamine neurons, and elevation in striatal neurotransmitter levels. Importantly, GMn mitigated gut microbiota dysbiosis induced by MPTP in mice. In particular, GM2 significantly reduced the levels of Akkermansia, Verrucomicrobiota, and Lactobacillus, while promoting the abundance of Roseburia and Prevotella compared to the model group. These findings suggest that GM2 can potentially suppress PD by modulating the gut microbiota, providing a foundation for the development of a novel and effective anti-PD marine drug.

Post-traumatic stress disorder (PTSD) is the most common psychiatric disorder after a catastrophic event; however, the efficacious treatment options remain insufficient. Increasing evidence suggests that cannabidiol (CBD) exhibits optimal therapeutic effects for treating PTSD. To elucidate the cell-type-specific transcriptomic pathology of PTSD and the mechanisms of CBD against this disease, we conducted single-nucleus RNA sequencing (snRNA-seq) in the hippocampus of PTSD-modeled mice and CBD-treated cohorts. We constructed a mouse model by adding electric foot shocks following exposure to single prolonged stress (SPS+S) and tested the freezing time, anxiety-like behavior, and cognitive behavior. CBD was administrated before every behavioral test. The PTSD-modeled mice displayed behaviors resembling those of PTSD in all behavioral tests, and CBD treatment alleviated all of these PTSD-like behaviors (n = 8/group). Three mice with representative behavioral phenotypes were selected from each group for snRNA-seq 15 days after the SPS+S. We primarily focused on the excitatory neurons (ExNs) and inhibitory neurons (InNs), which accounted for 68.4% of the total cell annotations. A total of 88 differentially upregulated genes and 305 differentially downregulated genes were found in the PTSD mice, which were found to exhibit significant alterations in pathways and biological processes associated with fear response, synaptic communication, protein synthesis, oxidative phosphorylation, and oxidative stress response. A total of 63 overlapping genes in InNs were identified as key genes for CBD in the treatment of PTSD. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the anti-PTSD effect of CBD was related to the regulation of protein synthesis, oxidative phosphorylation, oxidative stress response, and fear response. Furthermore, gene set enrichment analysis (GSEA) revealed that CBD also enhanced retrograde endocannabinoid signaling in ExNs, which was found to be suppressed in the PTSD group. Our research may provide a potential explanation for the pathogenesis of PTSD and facilitate the discovery of novel therapeutic targets for drug development. Moreover, it may shed light on the therapeutic mechanisms of CBD.

The emergence of castration-resistant prostate cancer (CRPC) following androgen deprivation therapy (ADT) is associated with increased malignancy and limited treatment options. This study aims to investigate potential connections between immune cell infiltration and inflammatory cytokines with the YAP1/AR/PSA axis by exploring their interactions with autophagy. Our research reveals heightened levels of Yes-associated protein 1 (YAP1) expression in CRPC tissues compared with tissues from androgen-dependent prostate cancer (ADPC) and benign prostate hyperplasia (BPH). Additionally, a correlation was observed between YAP1 and PSA expressions in CRPC tissues, suggesting that YAP1 may exert a regulatory influence on PSA expression within CRPC. Enhanced YAP1 expression in C4-2 cells resulted in the upregulation of androgen receptor (AR) nuclear translocation and intracellular prostate-specific antigen (PSA) levels. Conversely, the suppression of YAP1 led to a decrease in PSA expression, suggesting that YAP1 may positively regulate the PSA in castration-resistant prostate cancer (CRPC) by facilitating AR nuclear import. The modulation of the autophagy activity exerts a significant impact on the expression levels of YAP1, the AR, and the PSA. Moreover, recent advancements in immunity and inflammation studies present promising avenues for potential therapies targeting prostate cancer (PC).

Objective The aim of this study was to explore the effect of depression on pain, disease activity, functional disability and health-related quality of life measured by Visual Analogue Scale, Systemic Lupus Erythematosus Disease Activity Index, Health Assessment Questionnaire and Short Form-36 in patients with systemic lupus erythematosus.Design Meta-analysis.Data sources The PubMed, EMBASE, Cochrane Library and Web of Science were searched for obtaining available studies from inception to 7 March 2023.Eligibility criteria for selecting studies Studies evaluating the impact of depression on pain, disease activity, functional disability and quality of life were included.Data extraction and synthesis Two authors independently screened publications and extracted data according to set inclusion and exclusion criteria. Statistical analyses were conducted with RevMan V.5.3.0. Data were pooled using a fixed-effects or random-effects model according to heterogeneity.Results A total of 13 identified studies met the inclusion criteria, reporting on a total of 1911 patients with systemic lupus erythematosus. The Visual Analogue Scale score was significantly higher in patients with depression than those without depression (standardised mean difference (SMD)=0.84 (95% CI 0.27 to 1.42), p=0.004). The Health Assessment Questionnaire score was significantly higher in patients with depression than those without depression (SMD=1.05 (95% CI 0.14 to 1.95), p

ABSTRACT: High-sensitivity mass sensors under ambient conditions are essential in various fields such as biological research, gas sensing and environmental monitoring. In the current work, a phonon lasing enhanced mass sensor was proposed based on an optomechanical crystal cavity under ambient conditions. The phonon lasing was harnessed to achieve ultra-high resolution since it resulted in an extremely narrow mechanical linewidth (less than 10 kHz). Masses with different weights were deposited on the cavity, it is predicted that the maximum resolution for mass sensing can be 65 ± 19 zg, which approaches the mass order of a protein and an oligonucleotide. This implies the potential application of the proposed method in the biomedical fields such as oligonucleotide drug delivery area and the Human Proteome Project.

The performance of fiber-reinforced composite materials is significantly influenced by the mechanical properties of the yarns. Predictive simulations of the mechanical response of yarns are, thus, necessary for fiber-reinforced composite materials. This paper developed a novel experiment equipment and approach to characterize the bending behavior of yarns, which was also analyzed by characterization parameters, bending load, bending stiffness, and realistic contact area. Inspired by the digital element approach, an improved modeling methodology with the probability distribution was employed to establish the geometry model of yarns and simulated bending behavior of yarns by defining the crimp strain of fibers in the yarn and the effective elastic modulus of yarns as random variables. The accuracy of the developed model was confirmed by the experimental approach. More bending behavior of yarns, including the twisted and plied yarns, was predicted by numerical simulation. Additionally, models revealed that twist level and number of plies affect yarn bending properties, which need to be adopted as sufficient conditions for the mechanical analysis of fiber-reinforced composite materials. This efficient experiment and modeling method is meaningful to be developed in further virtual weaving research.

Recent research has highlighted structural and functional abnormalities in the cerebral cortex of patients with premature ejaculation (PE). These anomalies could play a pivotal role in the physiological mechanisms underlying PE. This study leveraged functional magnetic resonance imaging (fMRI), a noninvasive technique, to explore these neural mechanisms. We conducted resting-state fMRI scans on 36 PE patients and 22 healthy controls (HC), and collected data on Premature Ejaculation Diagnostic Tool (PEDT) scores and intravaginal ejaculation latency time (IELT). Employing a surface-based regional homogeneity (ReHo) approach, we analyzed local neural synchronous spontaneous activity, diverging from previous studies that utilized a volume-based ReHo method. Areas with significant ReHo differences between PE and HC groups underwent surface-based functional connectivity (FC) analysis. Significant discrepancies in ReHo and FC across the cortical surface were observed in the PE cohort. Notably, PE patients exhibited decreased ReHo in the left triangular inferior frontal gyrus and enhanced ReHo in the right middle frontal gyrus. The latter showed heightened connectivity with the left lingual gyrus and the right orbital superior frontal gyrus. Furthermore, a correlation between ReHo and FC values with PEDT scores and IELT was found in the PE group. Our findings, derived from surface-based fMRI data, underscore specific brain regions linked to the neurobiological underpinnings of PE.

This paper describes MixGAN-TTS, an efficient and stable non-autoregressive speech synthesis based on diffusion model. The MixGAN-TTS uses a linguistic encoder based on soft phoneme-level alignment and hard word-level alignment approach which explicitly extracts word-level semantic information, and introduces pitch and energy predictors to optimally predict the rhythmic information of the audio. Specifically, we use the GAN to replace the Gaussian function to model the denoising distribution, aiming to enlarge the denoising steps size and reduce the number of denoising steps to accelerate the sampling speed of diffusion model. Diffusion model using GAN can significantly reduce the denoising steps, and to some extent solve the problem of not being able to apply in real-time. The mel-spectrogram is converted into the final audio by the HiFi-GAN vocoder. Experimental results show that the MixGAN-TTS outperforms the other models compared in terms of audio quality and mel-spectrogram modeling capability for 4 denoising steps. The ablation studies demonstrate that the structure of MixGAN-TTS is effective.

Abstract Background Dengue virus type 2 (DENV-2) was used to infect primary human umbilical vein endothelial cells (HUVECs) to examine autophagy induced by activation of the adenosine monophosphate-activated protein kinase (AMPK)/extracellular signal-regulated kinase (ERK)/mammalian target of rapamycin (mTOR) signaling pathway following tripartite motif-containing 22 (TRIM22)-mediated DENV-2 infection to further reveal the underlying pathogenic mechanism of DENV-2 infection. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was used to screen putative interference targets of TRIM22 and determine the knockdown efficiency. The effect of TRIM22 knockdown on HUVEC proliferation was determined using the CCK8 assay. Following TRIM22 knockdown, transmission electron microscopy (TEM) was used to determine the ultrastructure of HUVEC autophagosomes and expression of HUVEC autophagy and AMPK pathway-related genes were measured by qRT-PCR. Moreover, HUVEC autophagy and AMPK pathway-related protein expression levels were determined by western blot analysis. Cell cycle and apoptosis were assessed by flow cytometry (FCM) and the autophagosome structure of the HUVECs was observed by TEM. Results Western blot results indicated that TRIM22 protein expression levels increased significantly 36 h after DENV-2 infection, which was consistent with the proteomics prediction. The CCK8 assay revealed that HUVEC proliferation was reduced following TRIM22 knockdown (P

Abstract Background Colorectal cancer (CRC) is a prevalent malignancy of the gastrointestinal. Circular RNAs (circRNAs) act as important roles in CRC malignant progression. However, the role of circ_0039857 in CRC is still unclear. Therefore, this study aimed to explore the function and mechanism of hsa_circ_0039857 in the CRC. Methods The mRNA and protein expression were measured via RT-qPCR. RNase R assay and Actinomycin D were employed to evaluate the stability of circ_0039857. Functional experiments, such as proliferation and apoptosis, were applied to study the function of circ_0039857 in CRC cells. The underlying mechanisms of circ_0039857 were then analyzed by bioinformatics, dual-luciferase reporter gene assay, RNA pull-down and rescue experiments. Results We revealed that circ_0039857 was significantly enhanced in CRC. Circ_0039857 was stabler than linear RNA in cells and valuable for the disease diagnosis. In addition, circ_0039857 knockdown inhibited proliferation and promoted apoptosis. Mechanistically, circ_0039857 positively regulated the expression of RAB32 via sponging miR-338-3p. Conclusion This study demonstrated that circ_0039857 knockdown suppressed CRC malignant progression through miR-338-3p/RAB32 axis. Most importantly, this will help us to better understand the circRNA network in CRC, and may find potential biomarkers and targets for CRC clinical treatment.

Abstract Background Sarcopenia is defined as age-related low muscle mass and function, and can also describe the loss of muscle mass in certain medical conditions, such as sarcopenic obesity. Sarcopenic obesity describes loss of muscle and function in obese individuals; however, as sarcopenia is an age-related condition and obesity can occur in any age group, a more accurate term is obesity with low lean muscle mass (OLLMM). Given limited data on OLLMM (particularly in those aged < 65 years), the purpose of this study was to estimate the prevalence of OLLMM in adults aged ≥ 20 years in the USA. Methods Data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 and 1999–2006 were used. OLLMM was defined as an appendicular lean mass, adjusted for body mass index (BMI), cut-off point < 0.789 for males and < 0.512 for females, measured by dual-energy X-ray absorptiometry (DXA). DXA was only measured in individuals 20–59 years old in NHANES 2017–2018; we therefore utilized logistic regression models to predict OLLMM from NHANES 1999–2006 for those aged ≥ 60 years. The prevalence of OLLMM was estimated overall, and by sex, age, race/ethnicity, and clinical subgroup (high BMI, prediabetes, type 2 diabetes mellitus [T2DM], non-alcoholic fatty liver disease [NAFLD] with fibrosis, or post-bariatric surgery). Prevalence estimates were extrapolated to the USA population using NHANES sampling weights. Results We estimated that, during 2017–2018, 28.7 million or 15.9% of the USA population had OLLMM. The prevalence of OLLMM was greater in older individuals (8.1%, aged 20–59 years vs 28.3%, aged ≥ 60 years), highest (66.6%) in Mexican-American females aged ≥ 60 years, and lowest (2.6%) in non-Hispanic Black males aged 20–59 years. There was a higher prevalence of OLLMM in adults with prediabetes (19.7%), T2DM (34.5%), NAFLD with fibrosis (25.4%), or post-bariatric surgery (21.8%), compared with those without each condition. Conclusions Overall, the burden of OLLMM in the USA is substantial, affecting almost 30 million adults. The prevalence of OLLMM increased with age, and among those with prediabetes, T2DM, NAFLD with fibrosis, or post-bariatric surgery. A unified definition of OLLMM will aid diagnosis and treatment strategies.

ABSTRACTAirway epithelial cells function as both a physical barrier against harmful substances and pathogenic microorganisms and as an important participant in the innate immune system. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in modulating inflammatory responses during respiratory infections. However, the signalling cascade that induces MMP-9 secretion from epithelial cells infected with Mycoplasma pneumoniae remains poorly understood. In this study, we investigated the mechanism of MMP-9 secretion in airway epithelial cells infected with M. pneumoniae. Our data clearly showed that M. pneumoniae induced the secretion of MMP-9 from bronchial epithelial cells and upregulated its enzymatic activity in a time- and dose-dependent manner. Using specific inhibitors and chromatin co-precipitation experiments, we confirmed that the expression of MMP-9 is reliant on the activation of the Toll-like receptor 2 (TLR2) and TLR6-dependent mitogen-activated protein kinase/nuclear factor- κB/activator protein-1 (MAPK/NF-κB/AP-1) pathways. Additionally, epigenetic modifications such as histone acetylation and the nuclear transcription factor Sp1 also regulate MMP-9 expression. M. pneumoniae infection also decreased the expression of the tumour suppressor reversion-inducing cysteine-rich protein with Kazal motifs (RECK) by inducing Sp1 phosphorylation. Overexpression of RECK significantly impaired the M. pneumoniae-triggered increase in MMP-9 enzymatic activity, although the level of MMP-9 protein remained constant. The study demonstrated that M. pneumoniae-triggered MMP-9 expression is modulated by TLR2 and 6, the MAPK/NF-κB/AP-1 signalling cascade, and histone acetylation, and M. pneumoniae downregulated the expression of RECK, thereby increasing MMP-9 activity to modulate the inflammatory response, which could play a role in airway remodelling.

Summary: Obese individuals experience low grade inflammation initiated within their adipose tissue. However, the early events that lead to the release of these inflammatory factors from adipose tissue are poorly characterized. To separate glucose effects from lipid effects on adipose tissue, we used an adipose-specific TXNIP knockout model where excess basal glucose influx into adipocytes led to modest increase in adiposity without using high fat diet. We found an uncoupling of two events that are generally presumed to be coregulated: (1) an increase of adipose tissue macrophage (ATM) number; and (2) pro-inflammatory activation of ATMs. These two events are associated with different triggering signals: elevated free fatty acids output and extracellular matrix remodeling with increased ATM number, whereas decreased adiponectin level with activated ATM. This separation reflects non-overlapping pathways regulated by glucose and lipids in adipocytes, and neither group alone is sufficient to elicit the full inflammatory response in adipose tissue.

Abstract Background Nonvalvular atrial fibrillation (NVAF) and intracranial atherosclerotic stenosis (ICAS) are major causes of ischemic stroke. Relatively few studies have focused on the risk factors and clinical features of ischemic stroke caused by NVAF combined with ICAS. Method We retrospectively evaluated NVAF and/or ICAS in patients with acute ischemic stroke admitted within 72 h after stroke. All patients with acute ischemic stroke underwent diffusion‐weighted magnetic resonance imaging (DWI), magnetic resonance angiography (MRA), computed tomography angiography (CTA), and/or digital subtraction angiography (DSA). NVAF was detected by routine electrocardiogram or 24‐h Holter examination, Doppler echocardiography, and contrast echocardiography of the right heart. Results Among the 635 enrolled patients, NVAF, ICAS, and NVAF+ICAS were diagnosed in 170 (26.77%), 255 (40.16%), and 210 (33.07%) patients, respectively. Patients in the NVAF+ICAS group were older (p

Abstract Immune checkpoint inhibitors (ICIs) are standard-of-care as first-line (1L) therapy for advanced non-small cell lung cancer (aNSCLC) without actionable oncogenic driver mutations. While clinical trials demonstrated benefits of ICIs over chemotherapy, variation in outcomes across patients has been observed and trial populations may not be representative of clinical practice. Predictive models can help understand heterogeneity of treatment effects, identify predictors of meaningful clinical outcomes, and may inform treatment decisions. We applied machine learning (ML)-based survival models to a real-world cohort of patients with aNSCLC who received 1L ICI therapy extracted from a US-based electronic health record database. Model performance was evaluated using metrics including concordance index (c-index), and we used explainability techniques to identify significant predictors of overall survival (OS) and progression-free survival (PFS). The ML model achieved c-indices of 0.672 and 0.612 for OS and PFS, respectively, and Kaplan–Meier survival curves showed significant differences between low- and high-risk groups for OS and PFS (both log-rank test p

Abstract A common stage of advanced prostate cancer is castration-resistant prostate cancer (CRPC), greater understanding of which is required in order to address and solve the clinically difficult challenge. Cathepsin K (CTSK) is a cysteine protease that usually has a strong activity of degrading extracellular matrix and is related to osteoclast-mediated bone destruction. However, the mechanism of CTSK-regulation in CRPC is still unclear to us. The current study aimed to analyze the expression of differentially expressed genes (DEGs) in patient samples (from localized PC and CRPC). Interestingly, we found that CTSK to be significantly up-regulated in CRPC. Through further signal pathway enrichment analysis, we found that the IL-17 signaling pathway to be highly correlated with CTSK. The oncogenic functions of CTSK and IL-17 in CRPC were proven by a series of in vivo and in vitro experiments. Possible downstream molecules of CTSK were investigated, which could serve as control elements to regulate the expression of EMT, thereby facilitating the metastasis and excessive proliferation of PC cells. Expression of CTSK was related to high concentration of M2 tumor-associated macrophages (TAMs) M2 in CRPC. A CTSK-mediated feedback circuit between TAMs and CRPC tissues was indicated in the process of transfer, proving the possibility of CTSK could be use as an available therapeutic target for CRPC.

Abstract Background The insertion of self-expandable metallic stents (SEMS) for post-tuberculosis tracheobronchial stenosis (PTTS) was controversial. This study aimed to evaluate the efficacy and safety of SEMS for treating PTTS, and developed a scoring system for predicting the occurrence of restenosis after stenting in PTTS patients. Methods We conducted a retrospective review of 87 patients who were diagnosed with PTTS and experienced SEMS insertion between January 2000 and December 2017. All procedures were performed via flexible bronchoscopy under conscious sedation and local anesthesia. Results A total of 85 SEMS were successfully placed in 77 patients. Comparing with pre-stenting, there were significant improvements in the lumen diameters of the stenotic segment, mMRC scale and lung function after short-term SEMS placement. During the long-term (average 163.32 months) follow-up, 48 patients (62.3%) did not develop restenosis after stenting; the other 29 patients (37.7%) developed and eventually, 12 remained under interventional therapies and 11 had bronchial atresia. Multivariate Cox regression analysis revealed that the difference value between SEMS length and the stenosis-segment length, stenosis type, and the number of pre-stenting thermal ablation were independently related to restenosis occurrence and were subsequently used to establish the Restenosis Score. The model’s development group (0.83, 95% CI 0.74–0.92) and external validation set (0.94, 95% CI 0.77–1.00) showed excellent discrimination. Conclusion SEMS placement could serve as a safe and effective treatment option for most patients with PTTS. Further, we built a prediction model depending on the independent predictors of restenosis occurrence, the Restenosis Score. This validated tool might provide a decision support and a better management for PTTS patients who underwent SEMS implantation.

This paper proposes an intelligent diagnosis framework of microgrid based on cloud–edge integration. First, the digital twin model of the microgrid is established on the cloud server. Based on the model, the operation data of the microgrid in various conditions can be obtained. Then, the neural network-based fault diagnosis model is trained on the cloud server by using the data provided by the digital twin model. Next, the trained neural network is downloaded to the edge device for the offline fault diagnosis of the microgrid. The proposed method is implemented based on the well-known digital twin platform CloudPSS and test results demonstrate the effectiveness. Extensive tests have been conducted on this framework using fully connected neural network algorithms with an accuracy rate of over 95%.

In the practical applications of magnetically coupled wireless power transfer (MC-WPT) system, mutual inductance and load may change. In view of this situation, a parameter identification method, which based on the hybrid algorithm of particle swarm optimization algorithm and genetic algorithm, for Inductor–Capacitor–Capacitor Series( LCC-S) system under phase-shifted control is proposed in this paper. The method only needs the current sampling data of the primary side. By configuring the parameters of the serial genetic particle swarm optimization (GA-PSO) algorithm and planning its operation process, mutual inductance and load identification is achieved at any phase-shifted angle. Then the phase-shifted angle is adjusted according to the identification results, and the constant output voltage control of the system is realized. The accuracy of the parameter identification method and phase-shifted constant output voltage control is verified by simulation and experiment. The maximum relative error of mutual inductance identification is 3.17%. And the maximum relative error of the load identification results is 5.87%. The maximum error between the output voltage and the set value is 3.5%.

The traditional wired charging of robot has the disadvantages of inconvenient charging and manual operation for electrical connection. With the continuous development of radio power transmission, the disadvantages of wired charging are overcome, and the charging process does not need manual intervention. At present, a single compensation network is often used to charge the robot wirelessly, but the single compensation network only has constant current or constant voltage output capability. When the constant voltage or constant current mode is switched in the charging process, additional DC–DC​ circuit is needed for control, which increases the difficulty of system design and system volume, and the control is also more complex. In this paper, based on the robot wireless charging system, a coupling mechanism which can switch topology is designed. The LCC-S/ LCC compensation network is used. In the charging process, the constant current and constant voltage charging mode is switched by switching the compensation network at the receiving end, which simplifies the design difficulty, volume and control method of the system. Finally, an experimental platform is built, and the experimental results verify the feasibility of the proposed topology and control method.

Grades of Fe, TiO2 and S in the vanadium titanium magnetite concentrate in Panxi are 53.75%, 12.55% and 0.76%. Fe and Ti are mainly in the form of vanadium-titanium magnetite and ilmenite, while sulfur is mainly in the form of magnetic pyrite. In order to reduce the sulfur content of this vanadium titanium magnetite concentrate, a study on desulfurization was carried out by flotation. Results show that adopting the flotation closed circuit process with once roughing, four times cleaning and twice scavenging, the sulfur concentrate with S grade of 28.65% and S recovery of 59.46%, and iron concentrate with TFe grade of 53.79%, TFe recovery of 98.51%, S grade of 0.29 % can be obtained with the following conditions: sulfuric acid as pH regulator, butyl xanthate + ammonium butyrate (5:1) as collector, 2# oil as frother, of which the dosage were 2000 g/t, 300 g/t, 40 g/t in roughing and regrinding fineness of sulfide concentrate by roughing and scavenging was -38 μm content of 93.33 %.

Objective: The study objective was to determine the relationship between lung resection and the development of postoperative hiatal hernia. Methods: Preoperative and postoperative computed tomography imaging from 373 patients from the International Early Lung Cancer Action Program and the Initiative for Early Lung Cancer Research on Treatment were compared at a median of 31.1 months of follow-up after resection of clinical early-stage non–small cell lung cancer. Incidence of new hiatal hernia or changes to preexisting hernias were recorded and evaluated by patient demographics, surgical approach, extent of resection, and resection site. Results: New hiatal hernias were seen in 9.6% of patients after lung resection (5.6% after wedge or segmentectomy and 12.4% after lobectomy; P = .047). The median size of new hernias was 21 mm, and the most commonly associated resection site was the left lower lobe (24.2%; P = .04). In patients with preexisting hernias, 53.5% demonstrated a small but significant increase in size from 21 to 22 mm (P

Abstract. Background:. Non-smokers account for a large proportion of lung cancer patients, especially in Asia, but the attention paid to them is limited compared with smokers. In non-smokers, males display a risk for lung cancer incidence distinct from the females—even after excluding the influence of smoking; but the knowledge regarding the factors causing the difference is sparse. Based on a large multicenter prospective cancer screening cohort in China, we aimed to elucidate the interpretable sex differences caused by known factors and provide clues for primary and secondary prevention. Methods:. Risk factors including demographic characteristics, lifestyle factors, family history of cancer, and baseline comorbidity were obtained from 796,283 Chinese non-smoking participants by the baseline risk assessment completed in 2013 to 2018. Cox regression analysis was performed to assess the sex difference in the risk of lung cancer, and the hazard ratios (HRs) that were adjusted for different known factors were calculated and compared to determine the proportion of excess risk and to explain the existing risk factors. Results:. With a median follow-up of 4.80 years, 3351 subjects who were diagnosed with lung cancer were selected in the analysis. The lung cancer risk of males was significantly higher than that of females; the HRs in all male non-smokers were 1.29 (95% confidence interval [CI]: 1.20–1.38) after adjusting for the age and 1.38 (95% CI: 1.28–1.50) after adjusting for all factors, which suggested that known factors could not explain the sex difference in the risk of lung cancer in non-smokers. Known factors were 7% (|1.29–1.38|/1.29) more harmful in women than in men. For adenocarcinoma, women showed excess risk higher than men, contrary to squamous cell carcinoma; after adjusting for all factors, 47% ([1.30–1.16]/[1.30–1]) and 4% ([7.02–6.75]/[7.02–1])) of the excess risk was explainable in adenocarcinoma and squamous cell carcinoma. The main causes of gender differences in lung cancer risk were lifestyle factors, baseline comorbidity, and family history. Conclusions:. Significant gender differences in the risk of lung cancer were discovered in China non-smokers. Existing risk factors did not explain the excess lung cancer risk of all non-smoking men, and the internal causes for the excess risk still need to be explored; most known risk factors were more harmful to non-smoking women; further exploring the causes of the sex difference would help to improve the prevention and screening programs and protect the non-smoking males from lung cancers.

Although the expression of Mex3 RNA-binding family member B (MEX3B) is upregulated in human nasal epithelial cells (HNECs) predominately in the eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) subtype, its functions as an RNA binding protein in airway epithelial cells remain unknown. Here, we revealed the role of MEX3B based on different subtypes of CRS and demonstrated that MEX3B decreased the TGF-β receptor III (TGFBR3) mRNA level by binding to its 3′ UTR and reducing its stability in HNECs. TGF-βR3 was found to be a TGF-β2–specific coreceptor in HNECs. Knocking down or overexpressing MEX3B promoted or inhibited TGF-β2–induced phosphorylation of SMAD2 in HNECs, respectively. TGF-βR3 and phosphorylated SMAD2 levels were downregulated in CRSwNP compared with controls and CRS without nasal polyps with a more prominent downregulation in the eosinophilic CRSwNP. TGF-β2 promoted collagen production in HNECs. Collagen abundance decreased and edema scores increased in CRSwNP compared with control, again more prominently in the eosinophilic type. Collagen expression in eosinophilic CRSwNP was negatively correlated with MEX3B but positively correlated with TGF-βR3. These results suggest that MEX3B inhibits tissue fibrosis in eosinophilic CRSwNP by downregulating epithelial cell TGFBR3 expression; consequently, MEX3B might be a valuable therapeutic target against eosinophilic CRSwNP.

Summary: While TXNIP (thioredoxin interacting protein) in the plasma membrane and vesicular location is known to negatively regulate cellular glucose uptake by facilitating glucose transporter endocytosis, the function of TXNIP in the nucleus is far less understood. Herein, we sought to determine the function of nuclear TXNIP in vivo, using a new HA-tagged TXNIP knock-in mouse model. We observed that TXNIP can be found in the nucleus of a variety of cells from different tissues including hepatocytes (liver), enterocytes (small intestine), exocrine cells (pancreas), and brown adipocytes (BAT). Further investigations into the role of nuclear TXNIP in BAT revealed that cold stress rapidly and transiently activated HSF1 (heat shock factor 1). HSF1 interaction with TXNIP during its activation is required for optimal HSF1 directed cold shock response in BAT.