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Abstract Background With a series of clinical trials confirming the sensitivity of small cell lung cancer (SCLC) to immunotherapy, research on personalized treatment for SCLC has gained increasing attention. Currently, the most widely accepted subtype of SCLC is based on the expression levels of Achaete-Scute Family BHLH Transcription Factor 1 (ASCL1), neurogenic differentiation factor 1 (NEUROD1), and POU class 2 homeobox 3 (POU2F3). However, real-world studies on this classification remain limited. Methods We retrospectively collected biopsy specimens from patients who received immunotherapy at Shandong Provincial Hospital between January 2019 and July 2021. After determining the patient subtypes using immunohistochemistry, we analyzed the relationships between each subtype and survival as well as some clinical characteristics. Results In our study, we found that the subtype I achieved a significant survival advantage compared to the other groups. Additionally, the subtype A demonstrated a significant survival disadvantage. Among patients in the subtype I, there was a higher proportion of early brain metastasis and patients with a family history of tumors, while the subtype A had a lower proportion. Furthermore, the subtype A exhibited relatively poor immune infiltration. Conclusion In a diverse cohort of SCLC patients receiving immunotherapy, the subtype-I showed significant survival advantages while the subtype-A experienced a worse survival.

Abstract Dysregulation of splicing factor expression plays a crucial role in the progression of hepatocellular carcinoma (HCC). Our research found that the expression level of splicing factor ZMAT2 was increased in HCC, promoting the proliferation of HCC cells. RNAseq data indicated that the absence of ZMAT2 induced skipping exon of mRNA, while RIPseq data further revealed the mRNA binding motifs of ZMAT2. A comprehensive analysis of RNAseq and RIPseq data indicateed that ZMAT2 played a crucial role in the maturation process of TRIM28 mRNA. Knocking down of ZMAT2 led to the deletion of 25 bases in exon 11 of TRIM28, ultimately resulting in nonsense-mediated decay (NMD). Our data revealed that ZMAT2 could regulate TRIM28 to reduce the accumulation of ROS in HCC cells, thereby promoting their proliferation. Our research also discovered that ZMAT2 was capable of undergoing phase separation, resulting in the formation of liquid droplet condensates within HCC cells. Additionally, it was found that ZMAT2 was able to form protein-nucleic acid condensates with TRIM28 mRNA. In summary, this study is the first to reveal that ZMAT2 and TRIM28 mRNA form protein-nucleic acid condensates, thereby regulating the splicing of TRIM28 mRNA. The increased expression of ZMAT2 in HCC leads to upregulated TRIM28 expression and reduced ROS accumulation, ultimately accelerating the proliferation of HCC cells.

Abstract Background This study developed a nomogram model using CT-based delta-radiomics features and clinical factors to predict pathological complete response (pCR) in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy (nCRT). Methods The study retrospectively analyzed 232 ESCC patients who underwent pretreatment and post-treatment CT scans. Patients were divided into training (n = 186) and validation (n = 46) sets through fivefold cross-validation. 837 radiomics features were extracted from regions of interest (ROIs) delineations on CT images before and after nCRT to calculate delta values. The LASSO algorithm selected delta-radiomics features (DRF) based on classification performance. Logistic regression constructed a nomogram incorporating DRFs and clinical factors. Receiver operating characteristic (ROC) and area under the curve (AUC) analyses evaluated nomogram performance for predicting pCR. Results No significant differences existed between the training and validation datasets. The 4-feature delta-radiomics signature (DRS) demonstrated good predictive accuracy for pCR, with α-binormal-based and empirical AUCs of 0.871 and 0.869. T-stage (p = 0.001) and differentiation degree (p = 0.018) were independent predictors of pCR. The nomogram combined the DRS and clinical factors improved the classification performance in the training dataset (AUCαbin = 0.933 and AUCemp = 0.941). The validation set showed similar performance with AUCs of 0.958 and 0.962. Conclusions The CT-based delta-radiomics nomogram model with clinical factors provided high predictive accuracy for pCR in ESCC patients after nCRT.

Abstract Background Osteoporosis (OP) is a common chronic metabolic bone disease characterized by decreased bone mineral content and microstructural damage, leading to increased fracture risk. Traditional methods for measuring bone density have limitations in accurately distinguishing vertebral bodies and are influenced by vertebral degeneration and surrounding tissues. Therefore, novel methods are needed to quantitatively assess changes in bone density and improve the accurate diagnosis of OP. Methods This study aimed to explore the applicative value of the iterative decomposition of water and fat with echo asymmetry and least-squares estimation-iron (IDEAL-IQ) sequence combined with intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for the diagnosis of osteoporosis. Data from 135 patients undergoing dual-energy X-ray absorptiometry (DXA), IDEAL-IQ, and IVIM-DWI were prospectively collected and analyzed. Various parameters obtained from IVIM-DWI and IDEAL-IQ sequences were compared, and their diagnostic efficacy was evaluated. Results Statistically significant differences were observed among the three groups for FF, R2*, f, D, DDC values, and BMD values. FF and f values exhibited negative correlations with BMD values, with r=-0.313 and − 0.274, respectively, while R2*, D, and DDC values showed positive correlations with BMD values, with r = 0.327, 0.532, and 0.390, respectively. Among these parameters, D demonstrated the highest diagnostic efficacy for osteoporosis (AUC = 0.826), followed by FF (AUC = 0.713). D* exhibited the lowest diagnostic performance for distinguishing the osteoporosis group from the other two groups. Only D showed a significant difference between genders. The AUCs for IDEAL-IQ, IVIM-DWI, and their combination were 0.74, 0.89, and 0.90, respectively. Conclusions IDEAL-IQ combined with IVIM-DWI provides valuable information for the diagnosis of osteoporosis and offers evidence for clinical decisions. The superior diagnostic performance of IVIM-DWI, particularly the D value, suggests its potential as a more sensitive and accurate method for diagnosing osteoporosis compared to IDEAL-IQ. These findings underscore the importance of integrating advanced imaging techniques into clinical practice for improved osteoporosis management and highlight the need for further research to explore the full clinical implications of these imaging modalities.

Introduction: Although programmed death ligand 1 (PD-L1) inhibitor plus chemotherapy regimen is a promising strategy for malignant tumors, it can induce significant immune-related adverse events, such as immune-related pneumonitis. Here, we report the first case of lethal immune-related pneumonitis in an Asian patient receiving anti-PD-L1 treatment. Case Presentation: A 68-year-old man was diagnosed with small cell lung cancer and interstitial pneumonia. After his pulmonary infection was relieved by comprehensive treatment, the patient received first-line treatment with durvalumab plus etoposide and carboplatin. Two weeks after starting durvalumab treatment, the patient had chest pain and shortness of breath. He was diagnosed with immune-induced pneumonia and treated with methylprednisolone, cefoperazone, and sulbactam, followed by oxygen and pirfenidone. Oxygen partial pressure decreased to 58 mm Hg within next the 4 days and laboratory assessment suggested cytokine storm. The patient underwent 2 plasma exchanges, one double filtration plasmapheresis and oxygen saturation decreased continuously. The patient died 1 month after durvalumab treatment. Conclusion: Immune-related pneumonitis induced by PD-L1 inhibitors is rare but life-threatening. Infection should be ruled out before starting immunotherapy.

Abstract Numerous clinical studies speculated the association between multiple myeloma (MM) and inflammatory diseases; however, there is limited validation of these claims via establishing a causal relationship and revealing the underlying mechanism. This exploratory study employed bidirectional Mendelian randomization (MR) analysis to investigate the causal relationships between MM and inflammatory diseases, including atherosclerosis, asthma, ankylosing spondylitis, Alzheimer's disease (AD), Parkinson's disease (PD), sarcoidosis, inflammatory bowel disease, nonalcoholic fatty liver disease, type II diabetes, and schizophrenia (SZ). Transcriptomic and genome‐wide Bayesian colocalization analyses were further applied to reveal the underlying mechanism. A significant and previously unrecognized positive association was identified between genetic predisposition to MM and the risk of SZ. Two independent case reports showed that treatment‐resistant psychosis is due to underlying MM and is resolved by treating MM. From our MR analyses, various statistical methods confirmed this association without detecting heterogeneity or pleiotropy effects. Transcriptomic analysis revealed shared inflammation‐relevant pathways in MM and SZ patients, suggesting inflammation as a potential pathophysiological mediator of MM's causal effect on SZ. Bayesian colocalization analysis identified rs9273086, which maps to the protein‐coding region of HLA‐DRB1, as a common risk variant for both MM and SZ. Polymorphism of the HLA‐DRB1 allele has been implicated in AD and PD, further highlighting the impact of our results. Additionally, we confirmed that interleukin‐6 (IL‐6) is a risk factor for SZ through secondary MR, reinforcing the role of neuroinflammation in SZ etiology. Overall, our findings showed that genetic predisposition to MM, HLA‐DRB1 polymorphism, and enhanced IL‐6 signaling are associated with the increased risk of SZ, providing evidence for a causal role for neuroinflammation in SZ etiology.

Abstract Background Circular RNAs (circRNAs) are involved in the progression of osteoporosis; however, their impact on osteogenic differentiation has yet to be fully elucidated. In this study, we identified a novel circRNA known as circZfp644-205 and investigated its effect on osteogenic differentiation and apoptosis in osteoporosis. Methods CircZfp644-205, miR-445-3p, and SMAD2 levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). MC3T3-E1 cells were subjected to microgravity (MG) to establish a cell model. Osteogenic differentiation was assessed using qRT-PCR, Alizarin Red S staining, alkaline phosphatase staining, and western blot. The apoptosis was evaluated using flow cytometry. The relationship between miR-445-3p and circZfp644-205 or SMAD2 was determined using bioinformatics, RNA pull-down, and luciferase reporter assay. Moreover, a hindlimb unloading mouse model was generated to investigate the role of circZfp644-205 in vivo using Micro-CT. Results CircZfp644-205 expression was up-regulated significantly in HG-treated MC3T3-E1 cells. Further in vitro studies confirmed that circZfp644-205 knockdown inhibited the osteogenic differentiation and induced apoptosis of pre-osteoblasts. CircZfp644-205 acted as a sponge for miR-455-3p, which reversed the effects of circZfp644-205 on pre-osteoblasts. Moreover, miR-455-3p directly targeted SMAD2, thus inhibiting the expression of SMAD2 to regulate cellular behaviors. Moreover, circZfp644-205 alleviated the progression of osteoporosis in mice. Conclusions This study provides a novel circRNA that may serve as a potential therapeutic target for osteoporosis and expands our understanding of the molecular mechanism underlying the progression of osteoporosis.

Abstract Inorganic semiconductors typically have limited p-type behavior due to the scarcity of holes and the localized valence band maximum, hindering the progress of complementary devices and circuits. In this work, we propose an inorganic blending strategy to activate the hole-transporting character in an inorganic semiconductor compound, namely tellurium-selenium-oxygen (TeSeO). By rationally combining intrinsic p-type semimetal, semiconductor, and wide-bandgap semiconductor into a single compound, the TeSeO system displays tunable bandgaps ranging from 0.7 to 2.2 eV. Wafer-scale ultrathin TeSeO films, which can be deposited at room temperature, display high hole field-effect mobility of 48.5 cm2/(Vs) and robust hole transport properties, facilitated by Te-Te (Se) portions and O-Te-O portions, respectively. The nanosphere lithography process is employed to create nanopatterned honeycomb TeSeO broadband photodetectors, demonstrating a high responsibility of 603 A/W, an ultrafast response of 5 μs, and superior mechanical flexibility. The p-type TeSeO system is highly adaptable, scalable, and reliable, which can address emerging technological needs that current semiconductor solutions may not fulfill.

Abstract Background Hepatocellular carcinoma (HCC) represents one of the most significant causes of mortality due to cancer-related deaths. It has been previously reported that the TGF-β signaling pathway may be associated with tumor progression. However, the relationship between TGF-β signaling pathway and HCC remains to be further elucidated. The objective of our research was to investigate the impact of TGF-β signaling pathway on HCC progression as well as the potential regulatory mechanism involved. Methods We conducted a series of bioinformatics analyses to screen and filter the most relevant hub genes associated with HCC. E. coli was utilized to express recombinant protein, and the Ni–NTA column was employed for purification of the target protein. Liquid liquid phase separation (LLPS) of protein in vitro, and fluorescent recovery after photobleaching (FRAP) were utilized to verify whether the target proteins had the ability to drive force LLPS. Western blot and quantitative real-time polymerase chain reaction (qPCR) were utilized to assess gene expression levels. Transcription factor binding sites of DNA were identified by chromatin immunoprecipitation (CHIP) qPCR. Flow cytometry was employed to examine cell apoptosis. Knockdown of target genes was achieved through shRNA. Cell Counting Kit-8 (CCK-8), colony formation assays, and nude mice tumor transplantation were utilized to test cell proliferation ability in vitro and in vivo. Results We found that Smad2/3/4 complex could regulate tyrosine aminotransferase (TAT) expression, and this regulation could relate to LLPS. CHIP qPCR results showed that the key targeted DNA binding site of Smad2/3/4 complex in TAT promoter region is −1032 to −1182. In addition. CCK-8, colony formation, and nude mice tumor transplantation assays showed that Smad2/3/4 complex could repress cell proliferation through TAT. Flow cytometry assay results showed that Smad2/3/4 complex could increase the apoptosis of hepatoma cells. Western blot results showed that Smad2/3/4 complex would active caspase-9 through TAT, which uncovered the mechanism of Smad2/3/4 complex inducing hepatoma cell apoptosis. Conclusion This study proved that Smad2/3/4 complex could undergo LLPS to active TAT transcription, then active caspase-9 to induce hepatoma cell apoptosis in inhibiting HCC progress. The research further elucidate the relationship between TGF-β signaling pathway and HCC, which contributes to discover the mechanism of HCC development.

Methane explosion is one of the major disasters that seriously threaten the safety of coal mine production, the development of efficient methane explosion suppression technology can effectively improve the prevention and control level of methane explosion accidents, and its focus is on the function of explosion suppression materials. In order to systematically study the effect of typical haloalkanes extinguishing agents on methane explosion, the effects of typical haloalkanes such as heptafluoropropane (C3HF7), hexafluoropropane (C3H2F6) and trifluoromethane (CHF3) on the ignition and explosion characteristics of methane were systematically studied by combining experimental tests and theoretical analysis. The effects of haloalkanes on methane explosion pressure parameters and laminar burning velocity were tested by a 20 L spherical explosive vessel and a self-developed Bunsen burner laminar flame propagation velocity system. The variation laws of peak explosion pressure, maximum pressure rise rate, laminar burning velocity, and laminar flame morphology evolution were obtained. The results show that with the increase of the added volume fraction, the haloalkanes had a double effect of promoting and inhibiting the methane explosion process. Under the chemical equivalent condition, only C3HF7 can first promote and then inhibit the peak explosion pressure and maximum pressure rise rate of methane, while CHF3 and C3H2F6 can inhibit the effect. The three haloalkanes all showed inhibition on the combustion rate of methane laminar flow. In the oxygen-poor condition, the three haloalkanes inhibited the peak explosion pressure, the maximum pressure boost rate, and the laminar burning velocity of methane. In general, C3H2F6 and C3HF7 have better inhibition effects on methane explosion pressure characteristic parameters and laminar burning velocity than CHF3. The theoretical analysis results show that the double effect of promoting and inhibiting the haloalkanes with the increase of the mixture volume fraction can be attributed to the competition between the improvement of the heat release characteristics of the system reaction and the inhibition of the key free radicals such as H, O, and OH by the main intermediates containing F. The results of this paper provide a theoretical basis for the theoretical research and technical development of methane explosion prevention and control.

Objective: Sex-specific differences are observed in various liver diseases, but the influence of sex on the outcomes of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains to be determined. This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC. Methods: Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed. The associations between donor, recipient, or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching (PSM). The survival associated with different sex-based donor-recipient transplant patterns was further studied. Results: Among 3,769 patients enrolled in this study, the 1-, 3-, and 5-year overall survival (OS) rates of patients with HCC after LT were 96.1%, 86.4%, and 78.5%, respectively, in female recipients, and 95.8%, 79.0%, and 70.7%, respectively, in male recipients after PSM ( P = 0.009). However, the OS was comparable between recipients with female donors and male donors. Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival (HR = 1.381, P = 0.046). Among the donor-recipient transplant patterns, the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival ( P < 0.05). Conclusions: Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients, and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival. Livers from male donors may provide the most benefit to female recipients. Our results indicate that sex should be considered as a critical factor in organ allocation.

Abstract Background SARS-CoV-2 infection is described as asymptomatic, mild, or moderate disease in most children. SARS-CoV-2 infection related death in children and adolescents is rare according to the current reports. COVID-19 cases increased significantly in China during the omicron surge, clinical data regarding pediatric critical patients infected with the omicron variant is limited. In this study, we aim to provide an overview of the clinical characteristics and outcomes of critically ill children admitted to a national children’s medical center in Guangdong Province, China, during the outbreak of the omicron variant infection. Methods We conducted a retrospective study from November 25, 2022, to February 8, 2023, which included 63 critically ill children, under the age of 18, diagnosed with SARS-CoV-2 infection. The patients were referred from medical institutions of Guangdong province. The medical records of these patients were analyzed and summarized. Results The median age of patients was 2 years (Interquartile Range, IQR: 1.0–8.0), sex-ratio (male/female) was 1.52. 12 (19%) patients (age ≥ 3 years) were vaccinated. The median length of hospital stay was 14 days (IQR: 6.5–23) in 63 cases, and duration of fever was 5 days (IQR: 3-8.5), pediatric intensive care unit (PICU) stay was 8 days (IQR 4.0–14.0) in 57 cases. 30 (48%) cases had clear contact history with family members who were infected with SARS-CoV-2. Three children who tested positive for SARS-CoV-2 infection did not show any abnormalities on chest imaging examination. Out of the total patients, 33 (52%) had a bacterial co-infection, with Staphylococcus aureus being the most commonly detected bacterial pathogen. Our cohort exhibited respiratory and nervous system involvement as the primary features. Furthermore, fifty (79%) patients required mechanical ventilation, with a median duration of 7 days (IQR 3.75–13.0). Among these patients, 35 (56%) developed respiratory failure, 16 (25%) patients experienced a deteriorating progression of symptoms and ultimately succumbed to the illness, septic shock was the most common condition among these patients (15 cases), followed by multiple organ failure in 12 cases, and encephalopathy identified in 7 cases. Conclusion We present a case series of critically ill children infected with the SARS-CoV-2 omicron variant. While there is evidence suggesting that Omicron may cause less severe symptoms, it is important to continue striving for measures that can minimize the pathogenic impact of SARS-CoV-2 infection in children.

In order to reduce carbon emissions, the effects of gas composition and initial turbulence on the premixed flame dynamics of hydrogen-blended natural gas were investigated. The results show that an increase in hydrogen content leads to earlier formation of flame wrinkles. When the equivalence ratio is 1 and hydrogen blending ratio is below 20 %, Tulip flames appear approximately 2.25 m away from the ignition point. When hydrogen blending ratio exceeds 20 %, Tulip flames appear approximately 1.3 m away from the ignition point, and twisted Tulip flames appear approximately 2.5 m away from the ignition position. During the 0.05 m process of flame propagation downstream from ignition point, flame propagation velocity increases by about 2 m/s for every 10 % increase in hydrogen content. The increase in hydrogen content has the most significant impact on the flame propagation velocity during the ignition stage. The average flame propagation velocity increases with the increase of hydrogen blending ratio. The greater the initial turbulence, the more obvious the stretching deformation of flame front structure. With the increase of wind speed, the flame propagation velocity first increases and then decreases. At a wind speed of 3 m/s, the flame propagation velocity reaches its maximum value.

Abstract Background Mecapegfilgrastim, a long‐acting granulocyte‐colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. Objective We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S‐1/capecitabine‐based regimens or the fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. Method Five hundred and sixty‐one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. Results The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S‐1/capecitabine‐based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S‐1/capecitabine‐based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. Conclusion In a real‐world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high‐risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.

ObjectiveBiological studies have elucidated that phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme in the serine synthesis pathway in humans that is abnormally expressed in numerous cancers. Inhibition of the PHGDH activity is thought to be an attractive approach for novel anti-cancer therapy. The development of structurally diverse novel PHGDH inhibitors with high efficiency and low toxicity is a promising drug discovery strategy.MethodsA ligand-based 3D-QSAR pharmacophore model was developed using the HypoGen algorithm methodology of Discovery Studio. The selected pharmacophore model was further validated by test set validation, cost analysis, and Fischer randomization validation and was then used as a 3D query to screen compound libraries with various chemical scaffolds. The estimated activity, drug-likeness, molecular docking, growing scaffold, and molecular dynamics simulation processes were applied in combination to reduce the number of virtual hits.ResultsThe potential candidates against PHGDH were screened based on estimated activity, docking scores, predictive absorption, distribution, metabolism, excretion, and toxicity (ADME/T) properties, and molecular dynamics simulation.ConclusionFinally, an all-in-one combination was employed successfully to design and develop three potential anti-cancer candidates.

Objective: To evaluate the predictive performance of metagenomic next-generation sequencing (mNGS) in identifying and predicting pulmonary infections following liver transplantation and to investigate its association with patient outcomes within the initial four-week post-transplantation period. Methods: We retrospectively analyzed 41 liver transplant patients with suspected pulmonary infections from August 2022 to May 2023. Bronchoalveolar lavage fluid (BALF) samples were collected on the first postoperative day for metagenomic next generation sequencing (mNGS) and culture. The predictive capability of mNGS for subsequent infections was assessed by monitoring inflammatory biomarkers and comparing the detection rates with culture methods. Real-time Polymerase Chain Reaction (Rt-PCR) was used to monitor Human betaherpesvirus 5 (CMV) and Human parvovirus B19 (B19) weekly during a four-week postoperative period. Inflammatory biomarkers and blood coagulation function were evaluated on specific days throughout the first, third, fifth, and during four weeks following surgery. The study was conducted until August 2023 to evaluate the patients' prognostic survival outcome, classifying them into groups based on the mortality and survival. Results: The analysis included a total of 41 patients, comprising 32 males and 9 females, with an average age of 52 (47, 63) years. Within one week after liver transplantation, there were 7 cases of bacterial infections, 5 cases of fungal infections, 19 cases of mixed infections, 8 cases without any infection, and 2 cases with unidentified pathogen-associated infections. mNGS successfully predicted 39 (72 %) strains of pathogens, while culture-based methods only detected 28 (52 %) strains. Among the 8 patients diagnosed as non-infected, culture methods identified positive results in 4 cases (50 %), whereas mNGS yielded positive results in 7 cases (87.5 %). The detection rates of CMV and B19 by Rt-PCR within 4 weeks after liver transplantation were 61 % and 17 %, respectively (25/41, 7/41) among the patients. During the study period, a total of 9 patients succumbed while 32 patients survived. The death group and the survival group exhibited significant differences in CRP, HGB, and INR levels at specific monitoring time points. The proportion of CMV detection in blood was significantly higher in the death group compared to the surviving group. Elevated CRP level was identified as a prognostic risk factor. Conclusions: Despite the presence of false positives, mNGS still presents a potential advantage in predicting pulmonary infection pathogens following liver transplantation. Furthermore, the levels of CRP and CMV carrier status within four weeks post-surgery exhibit significant associations with patient survival and prognosis.

Sertoli cells (SCs) maintain testicular homeostasis and promote spermatogenesis by forming the blood-testis barrier (BTB) and secreting growth factors. The pro-proliferative and anti-apoptotic effects of nerve growth factor (NGF) on SCs have been proved previously. It is still unclear whether the damage effect of arsenic on testis is related to the inhibition of NGF expression, and whether NGF can mitigate arsenic-induced testicular damage by decreasing the damage of SCs induced by arsenic. Here, the lower expression of NGF in testes of arsenic exposed mice (freely drinking water containing 15 mg/l of NaAsO2) was observed through detection of Western blot and Real-time PCR. Subsequently, hematoxylin and eosin (HE) staining, Evans blue staining and transmission electron microscopy were used to evaluate the pathology, BTB permeability and tight junction integrity in testes of control mice, arsenic exposed mice (freely drinking water containing 15 mg/l of NaAsO2) and arsenic + NGF treated mice (freely drinking water containing 15 mg/l of NaAsO2 + intraperitoneal injection with 30 μg/kg of NGF), respectively. Evidently, spermatogenic tubule epithelial cells in testis of arsenic exposed mice were disordered and the number of cell layers was reduced, accompanied by increased permeability and damaged integrity of the tight junction in BTB, but these changes were less obvious in testes of mice treated with arsenic + NGF. In addition, the sperm count, motility and malformation rate of mice treated with arsenic + NGF were also improved. On the basis of the above experiments, the viability and apoptosis of primary cultured SCs treated with arsenic (10 μM NaAsO2) or arsenic + NGF (10 μM NaAsO2 + 100 ng/mL NGF) were detected by Cell counting kit-8 (CCK8) and transferase-mediated DUTP-biotin nick end labeling (TUNEL) staining, respectively. It is found that NGF ameliorated the decline of growth activity and the increase of apoptosis in arsenic-induced SCs. This remarkable biological effect that NGF inhibited the increase of Bax expression and the decrease of Bcl-2 expression in arsenic-induced SCs was also determined by western blot and Real-time PCR. Moreover, the decrease in transmembrane resistance (TEER) and the expression of tight junction proteins ZO-1 and occludin was mitigated in SCs induced by arsenic due to NGF treatment. In conclusion, the above results confirmed that NGF could ameliorate the injury effects of arsenic on testis, which might be related to the function of NGF to inhibit arsenic-induced SCs injury.

Abstract Background Gemcitabine is a cornerstone drug for the treatment of all stages of pancreatic cancer and can prolong the survival of patients with pancreatic cancer, but resistance to gemcitabine in pancreatic cancer patients hinders its efficacy. The overexpression of Early growth response 1(EGR1) in pancreatic ductal adenocarcinoma as a mechanism of gemcitabine chemoresistance in pancreatic cancer has not been explored. The major mechanisms of gemcitabine chemoresistance are related to drug uptake, metabolism, and action. One of the common causes of tumor multidrug resistance (MDR) to chemotherapy in cancer cells is that transporter proteins increase intracellular drug efflux and decrease drug concentrations by inducing anti-apoptotic mechanisms. It has been reported that gemcitabine binds to MDR1 with high affinity. The purpose of this research was to investigate the potential mechanisms by which EGR1 associates with MDR1 to regulate gemcitabine resistance in pancreatic cancer cells. Methods The following in vitro and in vivo techniques were used in this research to explore the potential mechanisms by which EGR1 binds to MDR1 to regulate gemcitabine resistance in pancreatic cancer cells. Cell culture; in vitro and in vivo study of EGR1 function by loss of function analysis. Binding of EGR1 to the MDR1 promoter was detected using the ChIP assay. qRT-PCR, Western blot assays to detect protein and mRNA expression; use of Annexin V apoptosis detection assay to test apoptosis; CCK8, Edu assay to test cell proliferation viability. The animal model of pancreatic cancer subcutaneous allograft was constructed and the tumours were stained with hematoxylin eosin and Ki-67 expression was detected using immunohistochemistry. Findings We revealed that EGR1 expression was increased in different pancreatic cancer cell lines compared to normal pancreatic ductal epithelial cells. Moreover, gemcitabine treatment induced upregulation of EGR1 expression in a dose- and time-dependent manner. EGR1 is significantly enriched in the MDR1 promoter sequence.Upon knockdown of EGR1, cell proliferation was impaired in CFPAC-1 and PANC-1 cell lines, apoptosis was enhanced and MDR1 expression was decreased, thereby partially reversing gemcitabine chemoresistance. In animal experiments, knockdown of EGR1 enhanced the inhibitory effect of gemcitabine on tumor growth compared with the sh-NC group. Conclusions Our study suggests that EGR1 may be involved in the regulation of MDR1 to enhance gemcitabine resistance in pancreatic cancer cells. EGR1 could be a novel therapeutic target to overcome gemcitabine resistance in pancreatic cancer.

As one of the most widely used personal protective equipment (PPE), body armors play an important role in protecting the human body from the high-velocity impact of bullets or projectiles. The body torso and critical organs of the wear may suffer severe behind-armor blunt trauma (BABT) even though the impactor is stopped by the body armor. A type of novel composite material through incorporating shear stiffening gel (STG) into ethylene-vinyl acetate (EVA) foam is developed and used as buffer layers to reduce BABT. In this paper, the protective performance of body armors composed of fabric bulletproof layers and a buffer layer made of foam material is investigated both experimentally and numerically. The effectiveness of STG-modified EVA in damage relief is verified by ballistic tests. In parallel with the experimental study, numerical simulations are conducted by LS-DYNA® to investigate the dynamic response of each component and capture the key mechanical parameters, which are hardly obtained from field tests. To fully describe the material behavior under the transient impact, the selected constitutive models take the failure and strain rate effect into consideration. A good agreement between the experimental observations and numerical results is achieved to prove the validity of the modelling method. The tests and simulations show that the impact-induced deformation on the human body is significantly reduced by using STG-modified EVA as the buffering material. The improvement of protective performance is attributed to better dynamic properties and more outstanding energy absorption capability of the composite foam.

Abstract Background Acetyl-CoA acetyltransferase 2 (ACAT2) is a lipid metabolism enzyme and rarely was researched in epithelial ovarian cancer (EOC). Methods ACAT2 expressions were confirmed in two pairs of cell lines (A2780 and A2780/DDP, OVCAR8 and OVCAR8/DDP) from Gene Expression Omnibus database by bioinformatics analysis, and in A2780 and A2780/DDP cell lines by quantitative real-time polymerase chain reaction and western blotting. Tissue samples were stained by immunohistochemistry and scored for ACAT2 expression. The relationships between ACAT2 expression and clinicopathological characteristics were analyzed by χ2 test. The prognosis of ACAT2 was analyzed by the log-rank tests and Cox regression models. Results ACAT2 was remarkably upregulated in the above drug-resistant cell lines by mRNA (all P

Abstract The accurate preoperative diagnosis and tracking of lung adenocarcinoma is hindered by non-targeting and diffusion of dyes used for marking tumors. Hence, there is an urgent need to develop a practical nanoprobe for tracing lung adenocarcinoma precisely even treating them noninvasively. Herein, Gold nanoclusters (AuNCs) conjugate with thyroid transcription factor-1 (TTF-1) antibody, then multifunctional nanoprobe Au-TTF-1 is designed and synthesized, which underscores the paramount importance of advancing the machine learning diagnosis and bioimaging-guided treatment of lung adenocarcinoma. Bright fluorescence (FL) and strong CT signal of Au-TTF-1 set the stage for tracking. Furthermore, the high specificity of TTF-1 antibody facilitates selective targeting of lung adenocarcinoma cells as compared to common lung epithelial cells, so machine learning software Lung adenocarcinoma auxiliary detection system was designed, which combined with Au-TTF-1 to assist the intelligent recognition of lung adenocarcinoma jointly. Besides, Au-TTF-1 not only contributes to intuitive and targeted visualization, but also guides the following noninvasive photothermal treatment. The boundaries of tumor are light up by Au-TTF-1 for navigation, it penetrates into tumor and implements noninvasive photothermal treatment, resulting in ablating tumors in vivo locally. Above all, Au-TTF-1 serves as a key platform for target bio-imaging navigation, machine learning diagnosis and synergistic PTT as a single nanoprobe, which demonstrates attractive performance on lung adenocarcinoma. Graphical Abstract

Abstract Background Antepartum depression has been reported to be associated with the intensity of maternal prenatal noise exposure; however, the association between noise exposure duration and the development of antepartum depression has not been established. This study aimed to determine the total and trimester-specific association of prenatal noise exposure duration with the development of antepartum depression. Methods From May 2018 to June 2021, we recruited 2,166 pregnant women from Shengjing Hospital, northeast China. We used a standardized questionnaire to assess women’s prenatal noise exposure and used the Edinburgh Postnatal Depression Scale to assess pregnant women’s antepartum depression during the 1st -, 2nd -, and 3rd - trimesters. We calculated a cumulative noise exposure score ranging from 0 to 3, with a higher score reflecting higher frequency and longer duration of noise exposure during pregnancy. Results Women who were exposed to noise for ≥ 15 min per day had an increased risk of antepartum depression compared with women who were not exposed to noise during pregnancy [odds ratio (OR) = 1.83, 95%CI:1.18, 2.83]. Noise exposure in a specific trimester was associated with higher risk of depression in the same trimester and subsequent trimesters. We observed increases in antepartum depression risk with increasing cumulative noise exposure scores (P for trend

Abstract High synthesis temperatures and specific growth substrates are typically required to obtain crystalline or oriented inorganic functional thin films, posing a significant challenge for their utilization in large-scale, low-cost (opto-)electronic applications on conventional flexible substrates. Here, we explore a pulse irradiation synthesis (PIS) to prepare thermoelectric metal chalcogenide (e.g., Bi2Se3, SnSe2, and Bi2Te3) films on multiple polymeric substrates. The self-propagating combustion process enables PIS to achieve a synthesis temperature as low as 150 °C, with an ultrafast reaction completed within one second. Beyond the photothermoelectric (PTE) property, the thermal coupling between polymeric substrates and bismuth selenide films is also examined to enhance the PTE performance, resulting in a responsivity of 71.9 V/W and a response time of less than 50 ms at 1550 nm, surpassing most of its counterparts. This PIS platform offers a promising route for realizing flexible PTE or thermoelectric devices in an energy-, time-, and cost-efficient manner.

Abstract Peritoneal metastasis (PM) has a suppressive tumor immune microenvironment (TIME) that limits the effects of immunotherapy. This study aimed to investigate the immunomodulatory effects of intraperitoneal administration of IL-33, a cytokine that is reported to potentiate antitumor immunity and inhibit metastasis. We found survival was significantly prolonged in patients with high IL-33 mRNA expression. In immunocompetent mice, intraperitoneal administration of IL-33 could induce a celiac inflammatory environment, activate immunologic effector cells, and reverse the immunosuppressive tumor microenvironment, which effectively delayed tumor progression and PM of gastric cancer. Mechanistically, IL-33 could induce M2 polarization by activating p38-GATA-binding protein 3 signaling. IL-33 combined with anti-CSF1R or p38 inhibitor to regulate tumor-associated macrophages (TAMs) had a synergistic antitumor effect. Inducing a local inflammatory milieu by IL-33 administration provided a novel approach for treating peritoneal metastasis, which, when combined with TAM reprogramming to reshape TIME, can achieve better treatment efficacy.

BackgroundMaternal atmospheric pollution during pregnancy may alter fetal intrauterine development programming, thereby increasing the risk of childhood obesity in the future.ObjectiveTo investigate the effects of atmospheric pollution exposure during pregnancy on the incidence of childhood obesity in offspring.MethodsEnglish databases (PubMed, Web of Science, and Medline) and Chinese databases (Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure, and VIP Information Chinese Journal Service Platform) were searched for literature reporting exposure to atmospheric pollution during pregnancy and childhood obesity published from 1 January 2000 to 31 August 2023. The quality of the included literature was evaluated using the quality assessment tools for observational cohort and cross-sectional studies recommended by the US National Institutes of Health.ResultsTwenty-four studies meeting the inclusion criteria were identified and the associated atmospheric pollutants included particulate matter, ozone, nitrogen oxide, carbon oxide, and sulfur oxide. In comparison to the non-exposed group, prenatal exposure to various common atmospheric pollutants were significantly associated with an elevated risk of childhood obesity in offspring.ConclusionMaternal exposure to atmospheric pollution during pregnancy is associated with an elevated risk of childhood obesity in subsequent years. Future studies should pay more attention to the effects of atmospheric pollution on the distribution of children's body fat and metabolic development, and further identify potential mechanisms of atmospheric pollutant exposure leading to childhood obesity.

The uncertainties of the power load, wind power, and photovoltaic power lead to errors between point prediction values and real values, which challenges the safe operation of distribution networks. In this paper, a robust reactive power scheduling (RRPS) model based on a modified bootstrap technique is proposed to consider the uncertainties of power loads and renewable energy sources. Firstly, a deterministic reactive power scheduling (DRPS) model and an RRPS model are formulated. Secondly, a modified bootstrap technique is proposed to estimate prediction errors of power loads and renewable energy sources without artificially assuming the probability density function of prediction errors. To represent all possible scenarios, point prediction values and prediction errors are combined to construct two worst-case scenarios in the RRPS model. Finally, the RRPS model is solved to find a scheduling scheme, which ensures the security of distribution networks for all possible scenarios in theory. Simulation results show that the worstcase scenarios constructed by the modified bootstrap technique outperform popular baselines. Besides, the RRPS model based on the modified bootstrap technique balances economics and security well.

The application of promising g-C3N4 has been limited by poor photogenerated electron-hole separation and limited absorption for visible light. Sulfamethoxazole (SMX) is a typical antibiotic drug that is used worldwide and hard to be disposed through conventional wastewater treatment methods. Herein, S-scheme Fe2O3/g-C3N4 heterojunction was successfully prepared via a facile one-step sintering method and applied to photodegrade SMX under visible light irradiation. The integration of Fe2O3 and g-C3N4 shows superior charge separation and light absorption ability. As a result, the removal efficiency of 11 wt% Fe2O3/g-C3N4 reaches to 99.2% within 30 min, which is visibly higher than 59.5% of pure g-C3N4. ·O2− and ·OH are demonstrated to be the predominant active species for SMX photodegradation, and the possible degradation pathway is also proposed based on electronic band structure of Fe2O3/g-C3N4 heterojunction. This study presents a facile construction of g-C3N4 based S-scheme photocatalyst and offers an environmentally friendly approach to effectively remove organic pollutants using renewable solar energy.

Objective We aimed to investigate the clinical findings of hospitalized paediatric COVID-19 patients by the end of 2022.Method All confirmed children with COVID-19 infection admitted into Chaozhou Central Hospital during the COVID-19 outbreak from 19 December 2022 to 1 February 2023 were included. Detailed clinical data of those children were evaluated retrospectively.Results A total of 286 children, ranging in age from 1 month to 13 years old, were diagnosed with SARS-CoV-2 infection. Among these cases, 138 (48.3%) were categorized as mild, 126 (44.0%) as moderate and 22 (7.7%) as severe/critical. Symptoms varied among the children and included fever, upper respiratory tract symptoms, convulsions, sore throat, poor appetite, dyspnoea and gastrointestinal symptoms. Notably, febrile convulsions were observed in 96 (33.6%) patients, while acute laryngitis was documented in 50 (17.5%) cases. Among the severe/critical patients, eight developed multisystem inflammatory syndrome in children (MIS-C), and tragically, one patient’s condition worsened and resulted in death. Furthermore, MRI scans revealed abnormal brain signals in six severe/critical patients. The severe/critical group also exhibited more pronounced laboratory abnormalities, including decreased haemoglobin and elevated ALT, AST, LDH and CK levels.Conclusions Febrile convulsions and acute laryngitis are frequently observed in children diagnosed with SARS-CoV-2 Omicron infection. Moreover, MIS-C and abnormal neuroimaging appear to be relatively common phenomena in severe/critical cases.

ObjectivesObstructive sleep apnea (OSA) and osteoarthritis (OA) are common comorbidities that significantly impact individuals’ quality of life. However, the relationship between OSA and OA remains unclear. This study aims to explore the connection between OSA and OA and evaluate causality using Mendelian randomization (MR).MethodsA total of 12,454 participants from the National Health and Nutrition Examination Survey (2009–2012) were included. OSA participants were identified based on self-reported interviews. The association between OA and OSA was assessed through multivariable logistic regression analysis. A two-sample MR was employed to investigate the relationship between OSA and OA, specifically hip OA and knee OA, utilizing the inverse variance-weighted (IVW) approach.ResultsBased on the observational study, individuals with OSA exhibited a higher risk of OA (OR = 1.67, 95% CI = 1.40–1.98). IVW demonstrated that the risk of OA (OR = 1.13, 95% CI: 1.05–1.21, p = 0.001), hip OA (OR = 1.11, 95% CI: 1.04–1.18, p = 0.002), and knee OA (OR = 1.08, 95% CI: 1.02–1.14, p = 0.005) was significantly associated with OSA. Reverse MR analyses indicated no effect of OA on OSA. Additionally, body mass index (BMI) was found to mediate 36.9% (95% CI, 4.64–73.2%, p = 0.026) of the OSA effects on OA risk.ConclusionThe cross-sectional observational analysis unveiled noteworthy associations between OSA and OA. Meanwhile, findings from the MR study provide support for a causal role.

Abstract Tertiary lymphoid structure (TLS) can predict the prognosis and sensitivity of tumors to immune checkpoint inhibitors (ICIs) therapy, whether it can be noninvasively predicted by radiomics in hepatocellular carcinoma with liver transplantation (HCC‐LT) has not been explored. In this study, it is found that intra‐tumoral TLS abundance is significantly correlated with recurrence‐free survival (RFS) and overall survival (OS). Tumor tissues with TLS are characterized by inflammatory signatures and high infiltration of antitumor immune cells, while those without TLS exhibit uncontrolled cell cycle progression and activated mTOR signaling by bulk and single‐cell RNA‐seq analyses. The regulators involved in mTOR signaling (RHEB and LAMTOR4) and S‐phase (RFC2, PSMC2, and ORC5) are highly expressed in HCC with low TLS. In addition, the largest cohort of HCC patients is studied with available radiomics data, and a classifier is built to detect the presence of TLS in a non‐invasive manner. The classifier demonstrates remarkable performance in predicting intra‐tumoral TLS abundance in both training and test sets, achieving areas under receiver operating characteristic curve (AUCs) of 92.9% and 90.2% respectively. In summary, the absence of intra‐tumoral TLS abundance is associated with mTOR signaling activation and uncontrolled cell cycle progression in tumor cells, indicating unfavorable prognosis in HCC‐LT.

Employing electric double-layer (EDL) capacitors to harvest low-grade heat (LGH) is a novel technique in the high-efficiency energy absorption field. This work reports the fabrication of a vertical thermoelectric cell, based on a nanoporous graphene electrode immersed in low-concentration saline solution, for use as thermo-charging supercapacitors to convert LGH to electricity via thermally induced voltage. Because of a large specific area and a large number of micropores of nanoporous graphene films, the effective thermoelectric coefficient of the thermoelectric cell containing 0.01 M KCl solution can reach as high as 4.73 mV/°C. However, many factors, such as electrode materials, electrolyte solutions, and energy conversion device components, determine the efficiency of a thermoelectric conversion device. In summary, the device has a lower internal resistance and higher output voltage when the concentration of KCl solution is 0.05 M, and demonstrates higher thermoelectric conversion efficiency. Moreover, improving the conductivity of the electrolyte solution without affecting the device output voltage is also a way to reduce the internal power consumption of the device. The specific power and thermoelectric conversion efficiency of the device are increased by several orders of magnitude when uniformly dispersed silver nanoparticles are added to the potassium chloride solution to enhance the conductivity of the solution. The specific power underwent an increase from 0.50 mW g−1 to 42.37 mW g−1, and the thermoelectric conversion efficiency also increased from 0.0022% to 0.1358%.

Background: Accurate evaluation of postoperative liver regeneration is essential to prevent postoperative liver failure. Aims: To analyze the predictors that affect liver regeneration after hemi-hepatectomy. Method: Patients who underwent hemi-hepatectomy in Hangzhou First People's Hospital and Hangzhou Shulan Hospital from January 2016 to December 2021 were enrolled in this study. The regeneration index (RI) was calculated by the following equation: RI = [(postoperative total liver volume {TLVpost} - future liver remnant volume {FLRV}/FLRV] × 100 %. Hepatic dysfunction was defined according to the “TBilpeak>7” standard, which was interpreted as (peak) total bilirubin (TBil) >7.0 mg/dL. Good liver regeneration was defined solely when the RI surpassed the median with hepatic dysfunction. Logistic regression analyses were performed to estimate prognostic factors affecting liver regeneration. Result: A total of 153 patients were enrolled, with 33 in the benign group and 120 patients in the malignant group. In the entire study population, FLRV% [OR 4.087 (1.405–11.889), P = 0.010], international normalized ratio (INR) [OR 2.763 (95%CI, 1.008–7.577), P = 0.048] and TBil [OR 2.592 (95%CI, 1.177–5.710), P = 0.018] were independent prognostic factors associated with liver regeneration. In the benign group, only the computed tomography (CT) parameter FLRV% [OR, 11.700 (95%CI, 1.265–108.200), P = 0.030] predicted regeneration. In the malignant group, parenchymal hepatic resection rate (PHRR%) [OR 0.141 (95%CI, 0.040–0.499), P = 0.002] and TBil [OR 3.384 (95%CI, 1.377–8.319), P = 0.008] were independent prognostic factors. Conclusion: FLRV%, PHRR%, TBil and INR were predictive factors associated with liver regeneration.

BackgroundElevated preoperative γ-glutamyl transferase (GGT) levels or reduced serum albumin levels have been established as negative prognostic factors for patients with hepatocellular carcinoma (HCC) and various other tumors. Nonetheless, the prognostic significance of the GGT to serum albumin ratio (GAR) in liver transplantation (LT) therapy for HCC is still not well-defined.MethodsA retrospective analysis was conducted on the clinical data of 141 HCC patients who underwent LT at Shulan (Hangzhou) Hospital from June 2017 to November 2020. Using the receiver operating characteristic (ROC) curve, the optimal GAR cutoff value to predict outcomes following LT was assessed. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent risk factors associated with both overall survival (OS) and recurrence-free survival (RFS).ResultsA GAR value of 2.04 was identified as the optimal cutoff for predicting both OS and RFS, with a sensitivity of 63.2% and a specificity of 74.8%. Among these patients, 80 (56.7%) and 90 (63.8%) met the Milan and the University of California San Francisco (UCSF) criteria, respectively. Univariate Cox regression analysis showed that microvascular invasion (MVI), maximum tumor size (>5 cm), total tumor size (>8 cm), liver cirrhosis, TNM stage (III), and GAR (≥2.04) were significantly associated with both postoperative OS and RFS in patients with HCC (all p

The Shear wave (S-wave) velocity is an essential parameter in reservoir characterization and evaluation, fluid identification, and prestack inversion. However, the cost of obtaining S-wave velocities directly from dipole acoustic logging is relatively high. At the same time, conventional data-driven S-wave velocity prediction methods exhibit several limitations, such as poor accuracy and generalization of empirical formulas, inadequate exploration of logging curve patterns of traditional fully connected neural networks, and gradient explosion and gradient vanishing problems of recurrent neural networks (RNNs). In this study, we present a reliable and low-cost deep learning (DL) approach for S-wave velocity prediction from real logging data to facilitate the solution of these problems. We designed a new network sensitive to depth sequence logging data using conventional neural networks. The new network is composed of one-dimensional (1D) convolutional, bidirectional long short-term memory (BiLSTM), attention, and fully connected layers. First, the network extracts the local features of the logging curves using a 1D convolutional layer, and then extracts the long-term sequence features of the logging curves using the BiLSTM layer, while adding an attention layer behind the BiLSTM network to further highlight the features that are more significant for S-wave velocity prediction and minimize the influence of other features to improve the accuracy of S-wave velocity prediction. Afterward, the nonlinear mapping relationship between logging data and S-wave velocity is established using several fully connected layers. We applied the new network to real field data and compared its performance with three traditional methods, including a long short-term memory (LSTM) network, a back-propagation neural network (BPNN), and an empirical formula. The performance of the four methods was quantified in terms of their coefficient of determination (R2), root mean square error (RMSE), and mean absolute error (MAE). The new network exhibited better performance and generalization ability, with R2 greater than 0.95 (0.9546, 0.9752, and 0.9680, respectively), RMSE less than 57 m/s (56.29, 23.18, and 30.17 m/s, respectively), and MAE less than 35 m/s (34.68, 16.49, and 21.47 m/s, respectively) for the three wells. The test results demonstrate the efficacy of the proposed approach, which has the potential to be widely applied in real areas where S-wave velocity logging data are not available. Furthermore, the findings of this study can help for a better understanding of the superiority of deep learning schemes and attention mechanisms for logging parameter prediction.

Abstract The combination of flexible sensors and deep learning has attracted much attention as an efficient method for the recognition of human postures. In this paper, an in situ polymerized MXene/polypyrrole (PPy) composite is dip-coated on a polydimethylsiloxane (PDMS) sponge to fabricate an MXene/PPy@PDMS (MPP) piezoresistive sensor. The sponge sensor achieves ultrahigh sensitivity (6.8925 kPa−1) at 0–15 kPa, a short response/recovery time (100/110 ms), excellent stability (5000 cycles) and wash resistance. The synergistic effect of PPy and MXene improves the performance of the composite materials and facilitates the transfer of electrons, making the MPP sponge at least five times more sensitive than sponges based on each of the individual single materials. The large-area conductive network allows the MPP sensor to maintain excellent electrical performance over a large-scale pressure range. The MPP sensor can detect a variety of human body activity signals, such as radial artery pulse and different joint movements. The detection and analysis of human motion data, which is assisted by convolutional neural network (CNN) deep learning algorithms, enable the recognition and judgment of 16 types of human postures. The MXene/PPy flexible pressure sensor based on a PDMS sponge has broad application prospects in human motion detection, intelligent sensing and wearable devices.

Abstract The study investigated the association between Serum Uric Acid (SUA) levels and all-cause as well as cardiovascular mortality in patients with Obstructive Sleep Apnea (OSA). This prospective cohort study enrolled participants with OSA from four cycles of the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2008, and 2015–2018. A weighted Cox proportional hazards model was used to assess adjusted hazard ratios (aHRs) and their corresponding 95% confidence intervals (CI) for all-cause and cardiovascular mortality. Additionally, multivariable logistic regression and restricted cubic splines (RCS) models were employed to examine nonlinear relationships between SUA and all-cause and cardiovascular mortality. Among the 5,584 OSA participants included in the study, covering the four NHANES cycles and with a median follow-up of 4.333 years, a total of 537 deaths were observed, including 108 deaths attributed to cardiovascular disease. Comparing the fourth quartile (Q4) of uric acid levels, both the fifth quartile (Q5) (aHRs = 1.51, 95% CI [1.08, 2.12]) and the second quartile (Q2) (aHRs = 1.53, 95% CI [1.04, 2.25]) of uric acid levels were independently associated with an increased risk of all-cause mortality. Furthermore, comparing the fourth quartile (Q4) of uric acid levels, the second quartile (Q2) (aHRs = 2.40, 95% CI [1.08, 5.35]) of uric acid levels were independently associated with an increased risk of cardiovascular mortality. The RCS model demonstrated a U-shaped pattern in the association between SUA and all-cause mortality in OSA, with an inflection point observed at 5.83 mg/dl. The findings of this study suggest a U-shaped association between serum SUA levels and all-cause mortality and nonlinearity association between serum SUA levels and all-cause mortality. Further studies are warranted to determine the causal relationship between SUA levels and all-cause and cardiovascular mortality.

Abstract Background Disulfidptosis is a recently discovered programmed cell death pathway. However, the exact molecular mechanism of disulfidptosis in cutaneous melanoma remains unclear. Methods In this study, clustering analysis was performed using data from public databases to construct a prognostic model, which was subsequently externally validated. The biological functions of the model genes were then investigated through various experimental techniques, including qRT-PCR, Western blotting, CCK-8 assay, wound healing assay, and Transwell assay. Results We constructed a signature using cutaneous melanoma (CM) data, which accurately predicts the overall survival (OS) of patients. The predictive value of this signature for prognosis and immune therapy response was validated using multiple external datasets. High-risk CM subgroups may exhibit decreased survival rates, alterations in the tumor microenvironment (TME), and increased tumor mutation burden. We initially verified the expression levels of five optimum disulfidptosis-related genes (ODRGs) in normal tissues and CM. The expression levels of these genes were further confirmed in HaCaT cells and three melanoma cell lines using qPCR and protein blotting analysis. HLA-DQA1 emerged as the gene with the highest regression coefficient in our risk model, highlighting its role in CM. Mechanistically, HLA-DQA1 demonstrated the ability to suppress CM cell growth, proliferation, and migration. Conclusion In this study, a novel signature related to disulfidptosis was constructed, which accurately predicts the survival rate and treatment sensitivity of CM patients. Additionally, HLA-DQA1 is expected to be a feasible therapeutic target for effective clinical treatment of CM.

Abstract Background Immune checkpoint blockade (ICB) represents a revolutionary advance in cancer treatment but remains limited success in triple-negative breast cancer (TNBC). Here we aim to explore the mechanism of RNA-binding protein (RBP) HuR in cancer immune evasion by post-transcriptionally regulating PD-L1 and evaluate the potential of HuR inhibition to improve immune response. Methods The binding between HuR and PD-L1 mRNA was determined by ribonucleoprotein immunoprecipitation and RNA pull-down assays. The HuR knockout clones were established by CRISPR/Cas9 technology. The protein levels were assessed by Western blot, immunohistochemistry, and immunocytochemistry. The function and molecular mechanism of HuR-PD-L1 were determined by in vitro T cell activation and killing assay and in vivo efficacy assay. Results We found that HuR directly bound to and stabilized PD-L1 mRNA. Knocking out HuR reduced PD-L1 levels and promoted T cell activation. We discovered that niclosamide reduced PD-L1 by inhibiting HuR cytoplasmic translocation, and diminished glycosylation of PD-L1. Niclosamide enhanced T cell-mediated killing of cancer cells and significantly improved the efficacy of anti-PD-1 immunotherapy in two syngeneic animal tumor models. Conclusion We identified HuR as a novel posttranscriptional regulator of PD-L1, which plays an important role in tumor immune evasion. Niclosamide might be a promising repurposed drug to improve the patient response to immunotherapy by targeting HuR-PD-L1 axis. Our study demonstrates a novel strategy for targeting HuR/PD-L1 and provides the first proof-of-principle for repurposing niclosamide as a HuR inhibitor to overcome cancer immune evasion and improve response to ICB immunotherapy.

Accurately calculating winding losses has always been a significant challenge in the design of large-capacity medium-frequency transformers. This paper presents an accurate design algorithm for calculating the winding losses of a large-capacity medium-frequency distribution transformer. First, the peculiarities of winding losses in medium-frequency distribution transformers are analyzed. Various commonly used winding conductor types for medium-frequency transformers are introduced. The mechanisms of and differences between AC and DC winding losses in medium-frequency transformers are explained, and an effective analytical method for calculating the AC-to-DC resistance ratio is provided. Finally, the analytical calculation results of different types of winding losses are compared with those obtained through finite element simulations and experimental methods applied to a real transformer prototype. The discrepancies between the analytical results and those obtained using the other two methods were found to be within acceptable error margins, thereby validating the accuracy and effectiveness of the proposed algorithm.

WO3 and silicone rubber (SR)-based gasochromic composites were fabricated to detect hydrogen leaks at room temperature. WO3 rod-like nanostructures were uniformly distributed in the SR matrix, with a particle size of 60–100 nm. The hydrogen permeability of these composites reached 1.77 cm3·cm/cm2·s·cmHg. At a 10% hydrogen concentration, the visible light reflectance of the composite decreased 49% during about 40 s, with a color change rate of 6.4% s−1. Moreover, the composite detected hydrogen concentrations as low as 0.1%. And a color scale was obtained for easily assessing hydrogen concentrations in the environment based on the color of composites. Finally, the composite materials as disposable sensors underwent testing at several Sinopec hydrogen refueling stations.

To establish a high-fidelity model of engineering structures, this paper introduces an improved Bayesian model updating method for stochastic dynamic models based on frequency response functions (FRFs). A novel validation metric is proposed first within the Bayesian theory by using the normalized half-power bandwidth frequency transformation (NHBFT) and the principal component analysis (PCA) method to process the analytical and experimental frequency response functions. Subsequently, traditional Bayesian and approximate Bayesian computation (ABC) are improved by integrating NHBFT-PCA metrics for different application scenarios. The efficacy of the improved Bayesian model updating method is demonstrated through a numerical case involving a three-degrees-of-freedom system and the experimental case of a bolted joint lap plate structure. Comparative analysis shows that the improved method outperforms conventional methods. The efforts of this study provide an effective and efficient updating method for dynamic model updating based on the FRFs, addressing some of the existing challenges associated with FRF-based model updating.

Abstract Deep learning, transforming input data into target prediction through intricate network structures, has inspired novel exploration in automated diagnosis based on medical images. The distinct morphological characteristics of chest abnormalities between drug‐resistant tuberculosis (DR‐TB) and drug‐sensitive tuberculosis (DS‐TB) on chest computed tomography (CT) are of potential value in differential diagnosis, which is challenging in the clinic. Hence, based on 1176 chest CT volumes from the equal number of patients with tuberculosis (TB), we presented a Deep learning‐based system for TB drug resistance identification and subtype classification (DeepTB), which could automatically diagnose DR‐TB and classify crucial subtypes, including rifampicin‐resistant tuberculosis, multidrug‐resistant tuberculosis, and extensively drug‐resistant tuberculosis. Moreover, chest lesions were manually annotated to endow the model with robust power to assist radiologists in image interpretation and the Circos revealed the relationship between chest abnormalities and specific types of DR‐TB. Finally, DeepTB achieved an area under the curve (AUC) up to 0.930 for thoracic abnormality detection and 0.943 for DR‐TB diagnosis. Notably, the system demonstrated instructive value in DR‐TB subtype classification with AUCs ranging from 0.880 to 0.928. Meanwhile, class activation maps were generated to express a human‐understandable visual concept. Together, showing a prominent performance, DeepTB would be impactful in clinical decision‐making for DR‐TB.

Northeast China has been facing a severe power shortage situation. Since September 2021, “power rationing” events occurring in many places in the three provinces of northeast China have been causing inconvenience to people’s production and life. Therefore, it is particularly important to accurately predict the power load combined with the influencing factors of local power consumption. At the same time, the northeast region is about to enter the heating season, and the pressure on coal and electricity will further increase. In Heilongjiang Province, due to coal capacity control, limited production led to the high price of thermal coal; wind power photovoltaic output fluctuations, the epidemic, and other reasons also resulted in a large gap in the power supply side. Improving the power demand forecasting ability is of great significance to strengthen the reliability of people’s daily electricity consumption, rational distribution of power generation plans, and deployment of power grid resources. In order to improve the accuracy of electricity consumption prediction in Heilongjiang Province, Markov error correction is carried out on the basis of the backpropagation (BP) neural network prediction model so that the final prediction results have the advantages of the BP neural network prediction model and Markov model. In addition, it is more suitable for the prediction of random series data with high volatility, the prediction accuracy can be improved significantly, and the overall trend of electricity consumption can be predicted more accurately.

ContextThe highly infectious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused large-scale transmission from Dec 2022 to Feb 2023 in China. After this event, a remarkable surge of influenza A (Flu A) occurred from March to May 2023, especially in pediatric patients.ObjectivesThis study aimed to investigate the differences between pediatric patients infected with COVID-19 Omicron and Flu A virus.MethodsA total of 1,063 hospitalized children who admitted into two tertiary general hospital of Guangdong province of China were included. Medical records were compared retrospectively in these patients during the pandemic periods of SARS-CoV-2 omicron and Flu A.ResultsA total of 592 Patients with Flu A were mostly preschool and school-aged (>3y, 76.0%), they showed higher ratio of high fever (≥39°C), cough, rhinorrhea, and vomiting than patients with SARS-CoV-2 omicron. Most of the 471 Omicron patients were young children (0–3y, 74.5%) and had more poor appetite and dyspnea symptom. Benign acute children myositis (BACM) was only observed in patients with Flu A, and a significant male predominance. Multisystem inflammatory syndrome in children (MIS-C) was only found in patients with SARS-CoV-2 Omicron. Compared to the SARS-CoV-2 Omicron group, for both age groups (0–3 years and > 3 years), the Flu A group showed significantly reduced lymphocyte (Lym) counts (P < 0.001), and elevated levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatinine kinase-MB (CK-MB) in laboratory indexes (all P < 0.001). Additionally, it was found that more children hospitalized with COVID-19 had increased C-reactive protein (CRP) levels compared to those with Flu A.ConclusionInfluenza A infections have notably surged in children, coinciding with the relaxation of COVID-19 related social restrictions. During the epidemic periods of Omicron and Flu A virus infection, different clinical and laboratory characteristics were observed in hospitalized children.

This study aims to investigate the effect of the ring plate on the mechanical performance of X-type tube-gusset joints. The failure modes, ultimate strengths, and failure mechanisms of X-joints with ring plates were investigated through experiments and finite element analyses. The results indicated that the ring plate and the chord within the effective range of the ring plate constituted the primary bearing structure of the X-joint. Increases in the ring plate thickness and width increased the ultimate strength of the X-joint. By considering the forces of the braces as a superposition of the bending moment and the force acting on the gusset of the X-joint, a simplified calculation method for the ultimate strength of X-joints was established. The derivation process was validated and refined through experiments and finite element analyses. Finally, a safe and reliable formula was derived for evaluating the ultimate strength of X-joints.

IntroductionIn recent years, the pursuit of a master’s degree has become a social phenomenon of wide concern. It is essential to understand why large number of students choose to pursue master’s degree. This study aims to empirically analyze the factors that influence the intent to pursue a master’s degree.MethodBased on the extended theory of planned behavior, this study conducts a questionnaire survey of university students in Shandong Province, which has had the highest number of people taking the postgraduate entrance examination in China for several years. A total of 440 questionnaires were finally collected, including 417 valid questionnaires. And then ordinary least squares (OLS) regression was used to analyze the factors that influence the intent to pursue a master’s degree.ResultsIn general, the intent to pursue a master’s degree is positively influenced by attitude (β = 0.161, p

Abstract We study the mixed-state entanglement for AdS Born-Infeld (BI) theory. We calculate the mixed-state entanglement and investigate the relationship between it and the system parameters. We find that the holographic entanglement entropy (HEE) and mutual information (MI) exhibit monotonically increasing and decreasing behavior with BI factor b. However, the entanglement wedge cross-section (EWCS) exhibits a very rich set of phenomena about system parameters. EWCS always increases with b when b is small and then monotonically decreases with b. These behaviors suggest that increasing the BI factor, which is essentially enhancing the coupling between the background geometry and the transport properties can always enhance the EWCS. The coupling between the entanglement and the transport behaviors has also been studied in condensed matter theories and is important to construct a stable quantum circuit. We also provide analytical understanding of the above phenomenon. Furthermore, we have tested two additional BI-like models and find the universality of these results, suggesting the crucial role of the BI term in governing the interplay between nonlinear electromagnetic effects and entanglement.

Abstract In the process of coping with energy and environmental protection issues, technologies such as energy materials, energy devices, and energy systems have made great progress. With excellent performance, film capacitors play an increasingly important role in energy‐related fields. With the increase of application scenarios and the continuous development of film material technology, it is urgent to establish a better theoretical connection from films to capacitors. First, the main components of the capacitor including the film and the positional relationships among them are given. Then, from the two perspectives of indirect calculation according to the volume and the direct calculation according to the winding process, the equation between the dielectric constant of films and the corresponding capacitance of capacitors is established. Further, the measurement data and error analysis results of the built test platform prove the accuracy and great potential of the proposed calculation methods. In addition, error sources, including film thickness uniformity, are listed. Finally, the challenges faced by the proposed calculation methods and the paths that can be referenced for future research are summarised and discussed.

Abstract Background Various data have been obtained on the relationship between body mass index (BMI) and C-reactive protein (CRP) and periodontitis. The aim of this study was to determine whether CRP/BMI are associated with periodontitis using data from the National Health and Nutrition Examination Survey (NHANES) database. Methods A cross-sectional analysis of data from 3602 participants in the 2009–2010 NHANES cycle was performed. The definition of periodontitis was used to divide participants into four groups according to the criteria of Eke. Correlations between CRP/BMI and periodontitis were tested for statistical significance by means of descriptive statistics, multivariate regression, and subgroup-stratified analyses, with and without adjustments for confounders (such as age and sex). Results There were no statistically significant differences (p > 0.05) regarding BMI and the development of periodontitis. After adjustment for age, sex, race, marital status, annual family income, alcohol consumption, hypertension, smoking, chronic pulmonary disease, cardiovascular disease, diabetes, flossing, and arthritis, CRP correlated significantly with the development of periodontitis in the subgroups stratified by obesity, with an odds ratio (OR) of 1.2 (95% CI, 1.0 to 1.5). Conclusion Through data analysis, we found an association between CRP levels and periodontitis prevalence in the American population, although this association was only present in the obese population. While there are several hypotheses about the underlying mechanism, further studies are needed to validate these findings.