Search

Abstract Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.

Abstract Background Few studies have been conducted on treating temporomandibular disorders (TMDs) with new digital occlusal splints, which has increasingly attracted wide attention. Methods To evaluate the clinical efficacy and quality of life (QoL) of Kovacs digital occlusal splint (KDOS) treatment in patients with TMD. Materials and methods Eighty-nine patients with TMD who were treated using KDOS were analyzed. The patients were divided into three groups according to the Wilkes stage. The clinical symptoms and QoL scores of the patients in each group were recorded before and at least three months after treatment, and the data were statistically analyzed and compared. The relationships between the disease severity, sex, age, and level of QoL before treatment and improvement in the clinical symptoms were analyzed using binary logistic regression. Results The mean age and follow-up period of the patients were 28.0 ± 10.4 years and 4.9 ± 2.1 months, respectively. After KDOS treatment, the improvement rates of joint noise and pain were 80.4% and 69.8%, respectively. Additionally, the patients’ maximum mouth opening and global QoL mean scores significantly improved compared to those before treatment (p

Abstract Objective Sarcopenia is a geriatric syndrome that occurs with age and is characterized by a gradual decline in muscle mass, power, and functionality. It serves as a prominent contributor to frailty, disability, and mortality among older individuals. Currently, no standardized global guidelines exist for the diagnosis of sarcopenia. This study aimed to establish the correlation between sarcopenia and the constitutions of traditional Chinese medicine (TCM), considering the connection between physical functioning and sarcopenia. Methods A total of 1441 participants in this study were diagnosed with sarcopenia. The Asian Working Group for Sarcopenia (AWGS) proposed a sarcopenia definition algorithm. To determine the constitution of each participant, classification and determination standards were used in traditional Chinese medicine. This study evaluated the demographics, lifestyles, and self‐reported medical history of individuals diagnosed with sarcopenia through a self‐administered questionnaire. The constitution of the participants was determined using TCM classification and determination standards. Subsequently, we analyzed the results of univariate analysis and multivariate regression and constructed a receiver operating characteristic (ROC) curve. Results Participants who were diagnosed with sarcopenia had substantially lower original Neutral constitution scores (P

Abstract Microbial necromass carbon (MNC) can reflect soil carbon (C) sequestration capacity. However, changes in the reserves of MNC in response to warming in alpine grasslands across the Tibetan Plateau are currently unclear. Based on large-scale sampling and published observations, we divided eco-clusters based on dominant phylotypes, calculated their relative abundance, and found that their averaged importance to MNC was higher than most other environmental variables. With a deep learning model based on stacked autoencoder, we proved that using eco-cluster relative abundance as the input variable of the model can accurately predict the overall distribution of MNC under current and warming conditions. It implied that warming could lead to an overall increase in the MNC in grassland topsoil across the Tibetan Plateau, with an average increase of 7.49 mg/g, a 68.3% increase. Collectively, this study concludes that alpine grassland has the tendency to increase soil C sequestration capacity on the Tibetan Plateau under future warming.

ABSTRACT Objective Disulfidptosis was stimulated in high SLC7A11 expression cells starving to glucose. We attempted to identify disulfidptosis‐related lncRNAs (DRLs), built a prognostic model to predict survival, and analyzed the tumor microenvironment. Methods The TCGA database was utilized to procure the pertinent data. By utilizing both Cox regression and the least absolute shrinkage and selection operator (LASSO) method, a risk model based on DRLs was formulated for prognostic evaluation. The ability of survival prediction was validated by multiple approaches. The biological functions were screened through GO, KEGG, and GSEA. Various methods were employed to evaluate the tumor immune environment, which included ESTIMATE, tumor mutation burden (TMB) score, CIBERSORT algorithm, and tumor immune dysfunction and exclusion (TIDE) score. Results Ninety‐one DRLs were recognized, and lncRNA AC092718.4, AL365181.2, AL606489.1, EMSLR, and ENTPD3‐AS1 were involved in the risk model. The GEO database was used to verify the influence of these lncRNAs on survival. The following analyses showed that survival could be predicted excellently by the DRLs risk model. The results of enrichment analyses pointed toward the involvement of the cell cycle and IgA production pathways. In the low‐risk patient group, there was a notable surge in stromal, immune, and ESTIMATE scores, while the TMB scores took a tumble. Conversely, the high‐risk patient group displayed a converse trend. Notably, the group of patients with lower risk scores and higher TMB scores showed the most favorable survival outcomes, underscoring the importance of considering both risk score and TMB in predicting the response to immune checkpoint blockade therapy. Furthermore, patients classified as high‐risk might display resistance to both chemotherapy and targeted therapy. Cellular biological experiments proved that lncRNA AC092718.4 promoted invasion, migration, and proliferation abilities in vitro. These results provided valuable insights into the role of DRLs in LUAD and presented a possible effective treatment approach for LUAD. Conclusions We developed a disulfidptosis‐related risk model with 5 lncRNAs that enables survival prediciton for LUAD patients and aids cilinical decisions by forecasting the TME, TMB, and drug sensitivity, making it a valuable tool for outcomes prediction.

Congenital nephrogenic diabetes insipidus (NDI) primarily arises from an X-linked recessive inheritance caused by mutations in the AVPR2 gene, which is responsible for approximately 90% of cases. This condition has an incidence rate of 4–8 per million male live births, with females being much less frequently affected. Symptoms typically manifest shortly after birth, predominantly in males. The key clinical features of NDI include excessive urination (polyuria), compensatory excessive thirst (polydipsia), cognitive impairment, consistently low urine specific gravity, dehydration, and imbalances in electrolyte levels. This case study highlights an unusual occurrence of NDI in a 50-year-old Chinese woman attributed to a mutation in the AVPR2 gene. For more than a year, she had been suffering from excessive urination and severe thirst. The patient, who had undergone surgery for cervical cancer, developed polyuria and hypernatremia postoperatively. Initial laboratory analyses revealed normal blood sodium and chloride levels but reduced urine osmolality and specific gravity. Imaging assessments revealed no irregularities. To validate the diagnosis of NDI, she participated in a water deprivation and vasopressin test. Subsequent genetic tests revealed a thymine (T) to adenine (A) mutation, leading to a missense mutation in the AVPR2 gene. As part of her treatment, she was placed on a low-sodium diet and prescribed oral hydrochlorothiazide and indomethacin for 1 month, resulting in a marked improvement in her symptoms. To the best of our knowledge, this is the first documented case of NDI diagnosed postoperatively in an older female patient with AVPR2 heterozygosity. This case highlights an unusual instance of an X-linked recessive clinical presentation of NDI in an elderly female patient. This study also underscores the importance of conducting water deprivation, vasopressin tests, and genetic testing in establishing the underlying cause for individuals diagnosed with NDI.

Abstract TMEFF1 is a new protein involved in the physiological functions of the central nervous system, and we previously reported TMEFF1 can promote ovarian cancer. ST14 was determined to be involved in the processes of epidermal differentiation, epithelial cell integrity, and vascular endothelial cell migration, etc. The relationship between ST14 and TMEFF1 in the ovary remains unknown. In this study, we detected the expression of ST14 and TMEFF1 in 130 different ovarian cancer tissues through immunohistochemistry. We determined ST14 and TMEFF1 were highly expressed in ovarian cancer, indicating a higher degree of tumor malignancy and a worse prognosis. Tissues significantly expressing ST14 also highly expressed TMEFF1, and the expression of the two proteins was positively correlated. Consistently, immunofluorescence double staining demonstrated the co-localization of ST14 and TMEFF1 in the same region, and immunoprecipitation confirmed the interaction between ST14 and TMEFF1. TMEFF1 expression was also reduced after knocking down ST14 through Western blot. MTT, wound healing and Transwell assays results determined that knockdown of ST14 inhibited proliferation, migration and invasion of ovarian cancer cells in vitro, but the inhibitory effect was restored after adding TMEFF1 exogenous protein. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways analysis showed that ST14 and its related genes were enriched in the processes of epithelial formation, intercellular adhesion, protein localization, and mitosis regulation. We also clarified the kinase, microRNA, and transcription factor target networks and the impact of genetic mutations on prognosis. Overall, high expression of ST14 and TMEFF1 in ovarian cancer predicts higher tumor malignancy and a worse prognosis. ST14 and TMEFF1 co-localize and interact with each other in ovarian cancer. ST14 can regulate TMEFF1 expression to promote proliferation, migration and invasion of ovarian cancer cells. We speculate that the relationship between ST14 and TMEFF1 in ovarian cancer could become a potential target for anti-cancer therapy.

Abstract The specific genetic subtypes that gliomas exhibit result in variable clinical courses and the need to involve multidisciplinary teams of neurologists, epileptologists, neurooncologists and neurosurgeons. Currently, the diagnosis of gliomas pivots mainly around the preliminary radiological findings and the subsequent definitive surgical diagnosis (via surgical sampling). Radiomics and radiogenomics present a potential to precisely diagnose and predict survival and treatment responses, via morphological, textural, and functional features derived from MRI data, as well as genomic data. In spite of their advantages, it is still lacking standardized processes of feature extraction and analysis methodology among different research groups, which have made external validations infeasible. Radiomics and radiogenomics can be used to better understand the genomic basis of gliomas, such as tumor spatial heterogeneity, treatment response, molecular classifications and tumor microenvironment immune infiltration. These novel techniques have also been used to predict histological features, grade or even overall survival in gliomas. In this review, workflows of radiomics and radiogenomics are elucidated, with recent research on machine learning or artificial intelligence in glioma.

Abstract Background Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. Methods This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. Discussion This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. Trial registration ChiCTR1800017646.

Low-temperature and low-salt fermented Chinese kohlrabi (LSCK) represents a novel approach to producing low-salt kohlrabi without the need for desalination during processing, as compared to traditional techniques. However, the profile of its non-volatile metabolites remains unclear. In order to investigate the non-volatile metabolites and their changes in LSCK during fermentation, the LSCKs fermented for 0 day (0D), 45 days (45D) and 90 days (90D) were analyzed using LC-MS/MS non-targeted metabolomics coupled with multivariate statistical analysis. The results showed that 60, 74, and 68 differential metabolites were identified in the three groups A1 (0D and 45D), A2 (0D and 90D), and A3 (45D and 90D) (VIP >1, p 1), respectively. The differential metabolites were mainly amino acids, peptides, and analogues, fatty acyls, organic acids and derivatives, and carbohydrates and carbohydrate conjugates. Seventeen common differential metabolites were identified in A1, A2, and A3 groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that the alanine, aspartate and glutamate metabolism, butanoate metabolism, α-linolenic acid metabolism, arginine biosynthesis, and phenylalanine metabolism were significantly correlated with the differential metabolites. The present study elucidates for the first time the changes in non-volatile differential metabolites and their associated metabolic pathways in the novel Chinese low-salt kohlrabi, providing a theoretical basis for improving the industrial fermentation process of this innovative product.

ObjectiveSarcopenia is a gradually advancing systemic disorder affecting skeletal muscles, primarily distinguished by diminished muscle mass and functional decline. As of present, a universally accepted diagnostic criterion for sarcopenia has yet to be established. From the perspective of the constitution theory in traditional Chinese medicine (TCM), the Yin-deficiency constitution is believed to have a significant correlation with the development of sarcopenia. The primary objective of this study was to examine the potential association between sarcopenia and Yin-deficiency constitution.MethodsThe present study is a cross-sectional analysis. The Asian Working Group for Sarcopenia (AWGS) recommended a diagnostic criterion for sarcopenia. A total of 141 participants over 50 years of age were diagnosed with sarcopenia. To determine the constitution of each patient, classification and determination standards were used in traditional Chinese medicine. In this study, a combination of logistic regression and propensity score matching (PSM) was employed to analyze a dataset comprising 1,372 eligible observations. The diagnostic efficacy of the test in distinguishing sarcopenia was assessed through receiver operating characteristic (ROC) curve analysis.ResultsThe relationship between Yin-deficiency constitution and sarcopenia was examined using logistic regression analysis. In the crude model, the odds ratio (OR) was found to be 3.20 (95% confidence interval [CI]: 1.70–6.03). After adjusting for various confounding factors, including gender, sex, 6 m walking test/(m/s), SMI, and maximum grip strength/kg, the OR increased to 9.70 (95% CI: 3.20–69.38). The associations between seven other biased traditional Chinese medicine (TCM) constitutions and sarcopenia were not found to be statistically significant in the fully adjusted model. The propensity score matching (PSM) analysis yielded consistent results with the logistic regression analysis. Receiver operating characteristic (ROC) curve analysis showed that the AUC of the Yin-deficiency constitution combined with age and gender reached 0.707.ConclusionAmong the nine TCM constitutions examined, the Yin-deficiency constitution demonstrates an independent association with sarcopenia. Yin-deficiency constitution may serve as a potential risk factor for the development of sarcopenia. To establish a causal relationship, further experimental investigations are warranted. The diagnostic performance of sarcopenia is effectively demonstrated by the Yin-deficiency constitution combined with age and gender.

Background: Amauroderma rugosum (AR) is a medicinal mushroom commonly used to treat inflammation, gastric disorders, epilepsy, and cancers due to its remarkable anti-inflammatory and anti-oxidative properties. This study was designed to evaluate the pharmacological effects of AR and its underlying mechanism of action against ulcerative colitis (UC) in vitro and in vivo. Methods: A UC mouse model was established by administration of dextran sulfate sodium (DSS). AR extract was administered intragastrically to mice for 7 days. At the end of the experiment, histopathology, macrophage phenotype, oxidative stress, and inflammatory status were examined in vivo. Furthermore, RAW 264.7, THP-1, and Caco-2 cells were used to elucidate the mechanism of action of AR in vitro. Results: AR extract (0.5–2 mg/mL) significantly suppressed lipopolysaccharide (LPS) and interferon-gamma (IFN-γ)-induced M1 macrophage (pro-inflammatory) polarization in both RAW 264.7 and THP-1 cells. LPS-induced pro-inflammatory mediators (nitric oxide, TNF-α, IL-1β, MCP-1, and IL-6) were reduced by AR extract in a concentration-dependent manner. Similarly, AR extract downregulated MAPK signaling activity in LPS-stimulated RAW 264.7 cells. AR extract elicited a concentration-dependent increase in the mRNA expression of M2 (anti-inflammatory) phenotype markers (CD206, Arg-1, Fizz-1, and Ym-1) in RAW 264.7 cells. Moreover, AR extract suppressed DSS-induced ROS generation and mitochondrial dysfunction in Caco-2 cells. The in vivo experiment revealed that AR extract (200 mg/kg) increased colon length compared to the DSS-treated group. In addition, disease activity index, spleen ratio, body weight, oxidative stress, and colonic inflammation were markedly improved by AR treatment in DSS-induced UC mice. Finally, AR suppressed M1 and promoted M2 macrophage polarization in UC mice. Conclusion: The AR extract protected against DSS-induced UC by regulating macrophage polarization and suppressing oxidative stress. These valuable findings suggest that adequate intake of AR can prevent and/or treat UC.

The widespread utilization of plastic products ineluctably leads to the ubiquity of nanoplastics (NPs), causing potential risks for aquatic environments. Interactions of NPs with mineral surfaces may affect NPs transport, fate and ecotoxicity. This study aims to investigate systematically the deposition and aggregation behaviors of carboxylated polystyrene nanoplastics (COOH-PSNPs) by four types of clay minerals (illite, kaolinite, Na-montmorillonite, and Ca-montmorillonite) under various solution chemistry conditions (pH, temperature, ionic strength and type). Results demonstrate that the deposition process was dominated by electrostatic interactions. Divalent cations (i.e., Ca2+, Mg2+, Cd2+, or Pb2+) were more efficient for screening surface negative charges and compressing the electrical double layer (EDL). Hence, there were significant increases in deposition rates of COOH-PSNPs with clay minerals in suspension containing divalent cations, whereas only slight increases in deposition rates of COOH-PSNPs were observed in monovalent cations (Na+, K+). Negligible deposition occurred in the presence of anions (F−, Cl−, NO3−, CO32−, SO42−, or PO43−). Divalent Ca2+ could incrementally facilitate the deposition of COOH-PSNPs through Ca2+-assisted bridging with increasing CaCl2 concentrations (0–100 mM). The weakened deposition of COOH-PSNPs with increasing pH (2.0–10.0) was primarily attributed to the reduce in positive charge density at the edges of clay minerals. In suspensions containing 2 mM CaCl2, increased Na+ ionic strength (0–100 mM) and temperature (15–55 ◦C) also favored the deposition of COOH-PSNPs. The ability of COOH-PSNPs deposited by four types of clay minerals followed the sequence of kaolinite > Na-montmorillonite > Ca-montmorillonite > illite, which was related to their structural and surface charge properties. This study revealed the deposition behaviors and mechanisms between NPs and clay minerals under environmentally representative conditions, which provided novel insights into the transport and fate of NPs in natural aquatic environments.

Summary: The clinical success of immune checkpoint inhibitors is compromised by the fact of immune-related adverse events (irAEs), especially for older patients. To identify predictive biomarkers for older patients with irAEs, we used multiplex immunoassay and flow cytometry and liquid chromatography-tandem mass spectrometry to test immune factors and plasma protein and metabolites levels in non-small cell lung cancer (NSCLC) patients. The results showed that older patients with irAEs displayed lower CD28, CD4+ T cell, and B cell and higher interleukin (IL)-10 and CCL2 levels at baseline. Besides, lower aldolase, fructose-bisphosphate B (ALDOB), higher ST6GAL1, and lower lactate/pyruvate ratio at baseline were found in older patients with irAEs. Based on metabolomic markers, predictive models were developed to distinguish patients with grade 2–4 irAEs from grade 0–1 (Area under curve, AUC = 0.831) and to distinguish patients with grade 3–4 irAEs from grade 2 (AUC = 1). Our results confirmed the predictive value of plasma metabolites for irAEs in older patients with NSCLC.

Zinc oxide arresters, a major type of overvoltage protection equipment in power systems, can suppress transient lightning overvoltage, operation overvoltage, and other types of power surges. However, the response characteristics and protection effects under nanosecond pulses, such as those in a high-altitude electromagnetic pulse conduction region, remain unclear. Therefore, the surge protection performance of arresters should be properly understood, and high-performance arresters should be developed. In this study, critical parameters, including overshoot peak voltage, residual voltage, response time, and voltammetry characteristics of a representative 10 kV ZnO arrester under nanosecond pulses, were obtained using a double exponential pulse current injection source. The overshoot peak voltage of this arrester under a nanosecond pulse is 2.19 times of lightning impulse residual voltage, and the residual voltage ratio under a nanosecond pulse is 4.31. The average response time is approximately 45 ns, and the response time is independent of the nanosecond pulse amplitude. Furthermore, an electromagnetic transient model of this type of lightning arrester is established based on the CIGRE guidelines, as well as a method to determine the key parameters. The model can simultaneously account for the response characteristics of the small current region and the conduction region of the arrester, which properly agrees with the experimental results.

Building a broadband equivalent circuit model of a transformer is highly significant for studying the characteristics of high-altitude electromagnetic pulse conduction environments in real scenarios and guiding the high-altitude electromagnetic pulse effect tests of power equipment. This paper utilized an impedance analyzer to obtain the port impedance characteristics of distribution transformers with two insulation forms and five capacities within the range of 20Hz to 30MHz, based on the concept of passive system circuit modelling. By analysing the impedance characteristics of passive circuit components and observing the trend of changes in the port impedance curve, broadband port circuit models were constructed for both the high-voltage and low-voltage sides of transformers. Model parameter acquisition methods using a combination of function fitting and resonance point characteristics were provided. A high-altitude electromagnetic pulse injection test platform was constructed to verify the accuracy of the transformer model through comparison. Finally, the influence of transformer capacity and insulation form on the parameters of the transformer broadband port model was summarized. The results demonstrate that the proposed broadband port equivalent circuit model is suitable for different types and capacities of distribution transformers and can be employed to investigate the characteristics of high-altitude electromagnetic pulse conduction environments in transmission and distribution lines.

To investigate the dynamic changes and potential correlations between microbial diversity and volatile organic compounds (VOCs) during Chinese medium-temperature Daqu (MTD) manufacturing at different key stages, in this study, high-throughput sequencing (HTS) and gas chromatography–ion mobility spectrometry (GC–IMS) were employed to analyze the microbial diversity and VOCs of MTD, respectively. The results showed that Weissella, Staphylococcus, Thermoactinomyces, Kroppenstedtia, and Lactobacillus were the dominant bacterial genera, while Aspergillus, Alternaria, Thermoascus, Thermomyces, Wickerhamomyces, and Saccharomyces were the dominant fungal genera. A total of 61 VOCs were detected by GC–IMS, among which, 13 differential VOCs (VIP > 1) were identified, that could be used as potential biomarkers to judge the fermentation stage of MTD. Kroppenstedtia and Saccharopolyspora were positively correlated with 3-methyl-2-butenal and 2,2,4,6,6-pentamethylheptane-D, respectively, and both of these were positively correlated with butanal-D. Acetobacter, Streptomyces, and lactic acid bacteria (LAB) including Leuconostoc, Pediococcus, Weissella, and Lactobacillus were negatively correlated with their associated VOCs, while fungi were generally positively correlated with VOCs. Wickerhamomyces, Saccharomyces, and Candida were positively correlated with butan-2-one-M. This study provides a theoretical basis for explaining the mechanisms of MTD flavor formation and screening functional microorganisms to improve the quality of MTD.

Abstract Background The biomarkers of immune checkpoint inhibitors in the treatment of non‐small cell lung cancer (NSCLC) patients have limited predictive performance. In this study we aimed to investigate the feasibility of molecular tumor burden index (mTBI) in circulating tumor DNA (ctDNA) as a predictor for immunotherapy in patients with NSCLC. Methods From February 2017 to November 2020, pretreatment and on‐treatment (3~6 weeks after first cycle of immunotherapy) dynamic plasma ctDNA samples from NSCLC patients receiving immune monotherapy or combination therapy were analyzed by targeted capture sequencing of 1021 genes. PyClone was used to infer the mTBI. The impact of pretreatment mTBI on survival outcomes was verified in the POPLAR/OAK trials. Results We found that patients without detectable baseline ctDNA had better survival outcomes (median overall survival [OS]: not reached vs. 12.8 months; hazard ratio [HR], 0.15; p = 0.035]). RB1 and SMARCA4 mutations were remarkably associated with worse survival outcomes. Furthermore, lower pretreatment mTBI was associated with superior OS (median: not reached vs. 8.1 months; HR, 0.22; p = 0.024) and PFS (median: 32.9 vs. 5.4 months; HR, 0.35; p = 0.045), but not objective response, which was validated in the POPLAR/OAK cohort, suggesting that baseline mTBI was a prognostic factor for NSCLC immunotherapy. Early dynamic changes of mTBI (ΔmTBI) significantly distinguished responsive patients, and patients with mTBI decrease to more than 68% at the final tumor evaluation had longer OS (median: 38.2 vs. 4.0 months; HR, 0.18; p = 0.017) and PFS (median: not reached vs. 2.3 months; HR, 0.24; p = 0.030). Conclusion ΔmTBI had a good sensitivity to identify potential beneficial patients based on the best effect CT scans, demonstrating that mTBI dynamics were predictive of benefit from immune checkpoint blockade.

Abstract Background Temporomandibular joint (TMJ) disc repositioning through open suturing (OSu) is a new disc repositioning method. Its result for adolescents with condylar resorption and dentofacial deformities combined with and without postoperative occlusal splints (POS) has not been well studied. Objective This study was to evaluate and compare the effects of OSu with and without POS in the treatment of TMJ anterior disc displacement without reduction (ADDwoR) in adolescent skeletal Class II malocclusion. Methods A total of 60 adolescents with bilateral ADDwoR were enrolled in this study. They were randomly allocated into two groups: OSu with and without POS. Magnetic resonance imaging (MRI) and lateral cephalometric radiographs were used to measure changes in condylar height and the degree of skeletal Class II malocclusion from before operation and at 12 months postoperatively. Changes in these indicators were compared within and between the two groups. Results After OSu, both groups exhibited significant improvements in condylar height and occlusion at the end of 12 months follow-up (P

Abstract Background Coil embolization is a common method for treating unruptured intracranial aneurysms (UIAs). To effectively perform coil embolization for UIAs, clinicians must undergo extensive training with the assistance of senior physicians over an extended period. This study aimed to establish a deep-learning system for measuring the morphological features of UIAs and help the surgical planning of coil embolization for UIAs. Methods Preoperative computational tomography angiography (CTA) data and surgical data from UIA patients receiving coil embolization in our medical institution were retrospectively reviewed. A convolutional neural network (CNN) model was trained on the preoperative CTA data, and the morphological features of UIAs were measured automatically using this CNN model. The intraclass correlation coefficient (ICC) was utilized to examine the similarity between the morphologies measured by the CNN model and those determined by experienced clinicians. A deep neural network model to determine the diameter of first coil was further established based on the CNN model within the derivation set (75% of all patients) using neural factorization machines (NFM) model and was validated using a validation set (25% of all patients). The general match ratio (the difference was within ± 1 mm) between the predicted diameter of first coil by model and that used in practical scenario was calculated. Results One-hundred fifty-three UIA patients were enrolled in this study. The CNN model could diagnose UIAs with an accuracy of 0.97. The performance of this CNN model in measuring the morphological features of UIAs (i.e., size, height, neck diameter, dome diameter, and volume) was comparable to the accuracy of senior clinicians (all ICC > 0.85). The diameter of first coil predicted by the model established based on CNN model and the diameter of first coil used actually exhibited a high general match ratio (0.90) within the derivation set. Moreover, the model performed well in recommending the diameter of first coil within the validation set (general match ratio as 0.91). Conclusion This study presents a deep-learning system which can help to improve surgical planning of coil embolization for UIAs.

Evaluating irreducible water saturation is crucial for estimating reservoir capacity and developing effective extraction strategies. Traditional methods for predicting irreducible water saturation are limited by their reliance on specific logging data, which affects accuracy and applicability. This study introduces a predictive method based on fractal theory and deep learning for assessing irreducible water saturation in complex carbonate reservoirs. Utilizing the Mishrif Formation of the Halfaya oilfield as a case study, a new evaluation model was developed using the nuclear magnetic resonance (NMR) fractal permeability model and validated with surface NMR and mercury injection capillary pressure (MICP) data. The relationship between the logarithm mean of the transverse relaxation time (T2lm) and physical properties was explored through fractal theory and the Thomeer Function. This relationship was integrated with conventional logging curves and an advanced deep learning algorithm to construct a T2lm prediction model, offering a robust data foundation for irreducible water saturation evaluation. The results show that the new method is applicable to wells with and without specialized NMR logging data. For the Mishrif Formation, the predicted irreducible water saturation achieved a coefficient of determination of 0.943 compared to core results, with a mean absolute error of 2.37% and a mean relative error of 8.46%. Despite introducing additional errors with inverted T2lm curves, it remains within acceptable limits. Compared to traditional methods, this approach provides enhanced predictive accuracy and broader applicability.

ObjectivesElectromagnetic pulse can seriously affect and even destroy naval shipborne electronic information systems, weapons, equipment and so on. Due to the complexity of the antenna port load circuit, it is necessary to formulate a numerical method which can easily obtain the antenna load current.MethodsThe induced current of the terminal is obtained on the basis of the finite-difference time-domain (FDTD) and Holland model. According to the Thévenin equivalent circuit, the conductor is equivalent to the voltage source to realize decoupling between the conductor and load end, and the load circuit is solved using Simulink software.ResultsCompared with the traditional terminal model, this method is simple and feasible for high-order circuit processing. The effectiveness of the model is verified using non-linear elements and parallel capacitors and resistors as the load respectively. The results show that the calculation results of this method are consistent with those of the traditional methods. Finally, the antenna of the end-connected protector is calculated. The results show that the lead inductance caused by the installation of the protector is an important factor affecting the protection performance.ConclusionsThe method proposed in this paper can greatly reduce the simulation complexity of the coupling current of an antenna with a complex load, giving it useful reference value for the field of ship electromagnetic pulse protection design.

Abstract Background NRG1 fusions are rare oncogenic drivers in solid tumors, and the incidence of NRG1 fusions in non-small cell lung cancer (NSCLC) was 0.26%. It is essential to explore potential therapeutic strategies and efficacy predictors for NRG1 fusion-positive cancers. Case presentation We report an advanced lung adenocarcinoma patient harboring a novel NPTN-NRG1 fusion identified by RNA-based next-generation sequencing (NGS), which was not detected by DNA-based NGS at initial diagnosis. Transcriptomics data of the tissue biopsy showed NRG1α isoform accounted for 30% of total NRG1 reads, and NRG1β isoform was undetectable. The patient received afatinib as fourth-line treatment and received a progression-free survival (PFS) of 14 months. Conclusions This report supports afatinib can provide potential benefit for NRG1 fusion patients, and RNA-based NGS is an accurate and cost-effective strategy for fusion detection and isoform identification.

In order to test the effects of the crude extracts from Rhodobacter sphaeroides (CCRS) on the volatile flavor substances and flavor amino acids of sausages during storage, the sausages were respectively processed with addition of CCRS at higher, medium and lower concentrations. Sausage processed without addition of CCRS was used as control. The volatile flavor substances and free amino acids were respectively analyzed using headspace solid-phase micro-extraction gas chromatography mass spectrometry (HS-SPME-GC-MS) and amino acid analyzer. The experimental results showed that a total of 36 volatile flavor substances were detected by GC-MS, including 17 alcohols, 1 ester, 10 aldehydes, 2 acids, 3 alkanes and 3 other components, among which 8 substances were considered the main flavor substances. Multivariate statistical analysis showed that the content and types of alcohols in sausages added CCRS were lower than those in control after 3 months storage. After 6 months storage, the alcohol content in the sausages with CCRS was higher than that of the control. However, the aldehyde content of the sausages with CCRS was lower than that of the control. Moreover, the CCRS promoted the production of ethenyl hexanoate, which was the only one ester in the sausages. On the other hand, the addition of low concentration of CCRS reduced the content of heptaldehyde, octanoic acid and other odor substances. Amino acid analysis suggested that the CCRS increased the proportion of delicate and sweet amino acids. The taste activity value (TAV) analysis indicated that the histidine TAV value was the strongest and had the greatest impact on sausage taste. The present study would provide a theoretical basis and technical support for enhancing the flavor quality of Chinese traditional sausages based on the metabolites of Rhodobacter sphaeroides.

PurposeIn patients with resectable esophageal squamous cell carcinoma (ESCC), neoadjuvant therapy increased the curative resection rate, disease-free survival, and overall survival for patients with resectable ESCC. However, the efficacy of neoadjuvant therapy varies among different patients. We aim to compare the differences in the characteristics of peripheral blood T lymphocyte subsets before and after neoadjuvant therapy in patients with different curative efficacy.MethodThis study enrolled 266 ESCC patients who received neoadjuvant therapy and esophagectomy from August 2018 to August 2022. The postoperative pathological results divided patients into the major pathological response (MPR) and non-MPR groups. Compare the differences in peripheral blood T lymphocyte subsets and analyze the trend of changes in T lymphocyte subsets at different phases of treatment. Propensity score matching was used to reduce the influence of potential confounding factors.ResultsPrior to the neoadjuvant therapy, particularly before the second cycle, the MPR group exhibited significantly higher ratios of CD4/CD8 (P=0.009) and helper T cells (TH ratio, P=0.030) compared to the non-MPR group. In contrast, the suppressor T cell ratio (TS ratio) was lower (P=0.016) in the MPR group. The difference in peripheral blood lymphocyte subsets between the two groups of patients who underwent neoadjuvant chemoradiotherapy is significant.ConclusionIn peripheral blood, T lymphocyte subsets varied significantly based on the effectiveness of neoadjuvant treatment. Prior to the second cycle of neoadjuvant therapy, a higher CD4/CD8 and TH ratio, coupled with a decreased TS ratio, might suggest enhanced treatment outcomes.

PurposeThe aim of this study was to explore parental preferences for the procedural sedation of children in dentistry through a discrete choice experiment (DCE) to inform clinical decisions and oral health management.MethodsBased on literature reviews, interviews with parents of pediatric dental patients, and expert consultation, six attributes, including fasting time, recovery time, sedative administration routes, adverse reactions, sedation depth and procedure cost, were incorporated into the DCE questionnaire. The DCE questionnaire collected data on parental preferences for pediatric dental sedation treatment from June to August 2022. A conditional logit model was used to analyze preference and willingness to pay (WTP) for each attribute and its level. Subgroup analyses assessing the impact of parents' dental anxiety on procedural sedation preferences were also conducted using conditional logit models.ResultsA total of 186 valid questionnaires were gathered. Parents' preferences for fewer adverse reactions, a milder sedation depth, lower out-of-pocket cost, shorter fasting and recovery times and administration by inhalation were significantly associated with their choice of sedation model. The conditional logit model showed that parents were most interested in treatments with no adverse reactions (0% vs. 15%) (Coef, 1.033; 95% CI, 0.833–1.233), followed by those providing minimal sedation (vs. deep sedation) (Coef, 0.609; 95% CI, 0.448–0.769). Moreover, the relative importance of adverse reactions and fasting time was higher among anxious than nonanxious parents. The study found a WTP threshold of ¥1,538 for reducing adverse reactions (15% to 0%). The WTP threshold for the best sedation procedure scenario (no fasting requirement, 10 min recovery time, administration by inhalation, 0% adverse reaction incidence and minimal sedation) was ¥3,830.ConclusionReducing the adverse reactions and depth of sedation are predominant considerations for parents regarding procedural sedation in pediatric dentistry, followed by lower cost, shorter fasting and recovery times and inhalation sedation. Parents with dental anxiety had a stronger preference for options with a lower incidence of adverse reactions and shorter fasting time than parents without dental anxiety. This discovery is helpful for doctors and can promote collaborative decision-making among parents and doctors.

Abstract Intangible cultural heritage (ICH) of traditional Chinese medicine is a vivid testimony to the continuous inheritance of Chinese civilization. The study of ICH of traditional Chinese medicine from the perspective of the geographical environment, spatial relationships and diachronic development is of great significance for understanding objectively the reasons for the formation of spatial distribution patterns of ICH and the pathways and extent of its spread; as a consequence, such information can help us improve our understanding of the integrity and historical continuity of culture. From a geography perspective, this study seeks to explore the spatial patterns of traditional Chinese medicine ICH based on knowledge concerning the extent of spreading of traditional Chinese medicine ICH. At the same time, the spatial analysis technique ArcGIS is used to express the spatiotemporal development of traditional Chinese medicine ICH in a simple, clear and visual way. Also, the factors influencing the spatial distribution of traditional Chinese medicine ICH are analyzed. The main findings are as follows: (1) The spatial distribution of traditional Chinese medicine ICH practices is cohesive as a whole, with a tendency to aggregate and strong imbalance in distribution. (2) There are significant differences in the classification and number of traditional Chinese medicine ICH. (3) Traditional Chinese medicine ICH practices have obvious differentiation in time and space distribution when factoring in their announcement in batches. (4) Traditional medicine practices have significant spatial autocorrelation. Appreciation of the aforementioned features allows us to gain consensus on the development and evolution of traditional Chinese medicine ICH, and hence can justify how we allocate funds to promote traditional Chinese medicine ICH projects, paying particular attention to researching the historical context, and preserving the extraction of the local characteristics of traditional Chinese medicine ICH.

In order to investigate the effect of natural air-drying on the quality and flavor of raw mustard roots, the moisture content, water activity, hardness, crispness, protein content, amino acid nitrogen content, total plate count and total lactic acid bacteria were measured and compared before and after air-drying of the raw mustard roots. The changes of volatile flavor substances were analyzed by solid-phase microextraction gas chromatography-mass spectrometry (SPME-GC-MS). The results showed that the hardness of mustard roots after natural air-drying was significantly enhanced and the crispness was reduced (P1, P

To solve the wear problem of stamping dies in high-speed machining，cathodic multi-arc ion plating is often used to improve surface properties，and the surface quality of cathode multi-arc ion plated coating is one of main factors affecting the life of stamping dies.In this paper，the effects of the DC bias voltage，flow rate of nitrogen and arc current on the surface quality of CrAlN coating were studied by the orthogonal experiments.The significance of the effects of DC bias voltage，flow rate of nitrogen and arc current on the surface quality of the CrAlN coating was analyzed by the extreme-range method and variance method.Results showed that the surface quality of the CrAlN coating was affected most significantly by the flow rate of nitrogen，and the DC bias voltage also influenced the number of large particles on the surface of the CrAlN coating.When the DC bias voltage was 160 V，the nitrogen flow rate was 1 600 mL/min，and the arc source current was 120 A，the as-prepared coating possessed the minimum number of large particles on the surface (42.5 per 10，000 μm2) and the optimal surface quality.

Kiwi wine (KW) is tipically made by fermenting juice from peeled kiwifruit, resulting in the disposal of peel and pomace as by-products. However, the peel contains various beneficial compounds, like phenols and flavonoids. Since the peel is edible and rich in these compounds, incorporating it into the fermentation process of KW presents a potential solution to minimize by-product waste. This study compared the aroma and taste profiles of KW from peeled (PKW) and unpeeled (UKW) kiwifruits by combining intelligent sensory technology, GC-MS, and 1H-NMR. Focusing on aroma profiles, 75 volatile organic compounds (VOCs) were identified in KW fermented with peel, and 73 VOCs in KW without peel, with 62 VOCs common to both. Among these compounds, rose oxide, D-citronellol, and bornylene were more abundant in UKW, while hexyl acetate, isoamyl acetate, and 2,4,5-trichlorobenzene were significantly higher in PKW. For taste profiles, E-tongue analysis revealed differences in the taste profiles of KW from the two sources. A total of 74 molecules were characterized using 1H-NMR. UKW exhibited significantly higher levels of tartrate, galactarate, N-acetylserotonin, 4-hydroxy-3-methoxymandelate, fumarate, and N-acetylglycine, along with a significantly lower level of oxypurinol compared to PKW. This study seeks to develop the theoretical understanding of the fermentation of kiwifruit with peel in sight of the utilization of the whole fruit for KW production, to increase the economic value of kiwifruit production.

To investigate the diversity and dynamics of microorganisms in Chinese fresh beef (CFB) without acid discharge treatment during cold storage, high-throughput sequencing was employed to analyze the CFB refrigerated for 0, 3, 7, and 10 days. The results showed that the community richness of the fungi and bacteria decreased significantly. However, the diversity decreased in the early stage and increased in the later stage. At the phylum level, Ascomycota (74.1–94.1%) and Firmicutes (77.3–96.8%) were the absolutely dominant fungal and bacterial phyla. The relative abundance of both fungal and bacterial phyla displayed a trend of increasing and then decreasing. At the genus level, Candida (29.3–52.5%) and Lactococcus (19.8–59.3%) were, respectively, the dominant fungal and bacterial genera. The relative abundance of Candida showed a trend of increasing and then decreasing, while Lactococcus possessed the opposite trend. KEGG metabolic pathways analysis suggested that carbohydrate metabolism, membrane transport, and amino acid metabolism were the major metabolic pathways of bacteria. Bugbase prediction indicated the major microbial phenotype of bacteria in CFB during cold storage was Gram-positive (17.2–31.6%). Correlation analysis suggested that Lactococcus, Citrobacter, Proteus, and Rhodotorula might be the main microorganisms promoting the production of off-flavor substances in CFB. This study provides a theoretical basis for the preservation of Chinese fresh beef.

Energy distribution justice is of primary concern within the energy justice framework and it is crucial to increase public acceptance of offshore wind energy and further advance its development. The rapid development of offshore wind energy in China has inevitably impacted the livelihoods of coastal vulnerable groups (CVGs) engaged in fisheries and tourism in the coastal zone. While current policies often compensate for livelihood losses through cash payments, the fiscal strain caused by COVID-19 renders this approach unsustainable. Consequently, this research pioneers the exploration of Chinese tourist groups’ landscape preferences towards offshore wind farms (OWFs). This study proposes a new approach to enhance OWF landscapes for tourism development, thereby balancing the distribution of costs and benefits between CVGs and tourists. The research focuses on Beihai City in the Beibu Gulf Economic Region, utilizing a combination of Q-methodology and choice experiments that incorporates cut-offs. Answers to eighty Q-methodology questionnaires and 1324 choice experiment questionnaires are obtained. The findings indicate that this region can achieve energy distribution justice by compensating for the livelihood losses of CVGs through tourism. Contrary to traditional assumptions about wind farm noise preferences, Chinese tourists prefer proximity to OWFs, as an appropriate coastal acoustics landscape can enhance their tourism experience. In light of these findings, this paper presents policy recommendations towards energy distribution justice.

The direct discharge of rare earth wastewater causes the waste of resources and heavy metal pollution. This paper compared the adsorption behaviors of lanthanide ions on bentonite under sulfate and nitrate systems by examining the factors affecting the adsorption, such as adsorption time, pH, background electrolyte concentration, and initial rare earth ion concentration. It was shown that the sulfate system was more favorable for the adsorption of rare earth ions on the bentonite surface. The maximum adsorption capacity in the sulfate system was about 1.7 times that in the nitrate system. In contrast, the adsorption under the nitrate system was more sensitive to the changes in pH and background electrolyte concentration. The adsorption processes under both systems are spontaneous physical adsorption processes (ΔGθ are from −27.64 to −31.48 kJ/mol), and both are endothermic (ΔHθ are 10.38 kJ/mol for the nitrate and 7.53 kJ/mol for the sulfate) and entropy-increasing (ΔSθ are 61.54 J/mol for the nitrate and 76.24 J∙mol−1 for the sulfate) processes. This study helps to provide information about the optimizing process parameters for the adsorption treatment of rare earth wastewater using bentonite.

In order to improve the utilization rate of coal measure kaolinite gangue resources, this paper takes coal measure kaolinite in Heidaigou area of Inner Mongolia as the research object, and studies the iron and titanium removal of coal measure hard kaolinite contained in it. The process mineralogy of coal gangue was analyzed by X-ray diffraction (XRD), X-ray fluorescence (XRF), scanning electron microscope (SEM) and microscope test from the aspects of chemical composition, microstructure and mineral composition. Different magnetic species were used to conduct high-gradient magnetic separation of iron-bearing and titanium-bearing minerals, and the single-factor experiment showed that magnetite powder was superior to artificial ferrite. The orthogonal experiment shows that magnetic separation current 6 A, ore timing 20 s and slurry concentration 45% are the best experimental conditions, and the iron removal rate is 35.63% and the titanium removal rate is 39.29%. The whiteness of the final product is 80.96% after calcination, which meets the whiteness requirement of calcined kaolin used in rubber and plastic industry.

Background: Accumulating studies demonstrated that patients with coronavirus disease 2019(COVID-19) could develop a variety of neurological manifestations and long-term neurological sequelae, which may be different from the strains. At the peak of the Omicron variant outbreak in Shanghai, China, no relevant epidemiological data about neurological manifestations associated with this strain was reported. Objective: To investigate neurological manifestations and related clinical features in patients with mild to moderate COVID-19 patients with Omicron variant. Methods: A self-designed clinical information registration form was used to gather the neurological manifestations of mild to moderate COVID-19 patients admitted to a designated hospital in Shanghai from April 18, 2022 to June 1, 2022. Demographics, clinical presentations, laboratory findings, treatments and clinical outcomes were compared between patients with and without neurological manifestations. Results: One hundred sixty-nine(48.1 %) of 351 patients diagnosed with mild to moderate COVID-19 exhibited neurological manifestations, the most common of which were fatigue/weakness(25.1 %) and myalgia(20.7 %), whereas acute cerebrovascular disease(0.9 %), impaired consciousness(0.6 %) and seizure(0.6 %) were rare. Younger age(p = 0.001), female gender(p = 0.026) and without anticoagulant medication(p = 0.042) were associated with increasing proportions of neurological manifestations as revealed by multivariate logistic regressions. Patients with neurological manifestations had lower creatine kinase and myoglobin levels, as well as higher proportion of patchy shadowing on chest scan. Vaccination status, clinical classification of COVID-19 and clinical outcomes were similar between the two groups. Conclusions: Nearly half of the involved patients have neurological manifestations which were relatively subjective and closely associated with younger age, female gender and without anticoagulation. Patients with neurologic manifestations may be accompanied by increased lung patchy shadowing.

Abstract HERPUD1 is an important early marker of endoplasmic reticulum stress (ERS) and is involved in the ubiquitination and degradation of several unfolded proteins. However, its role in tumorigenesis is seldom studied, and its role in ovarian cancer is unclear. Lewis y antigen is a tumor-associated sugar antigen that acts as an ‘antenna’ on the cell surface to receive signals from both inside and outside the cell. We previously reported that Lewis y can promote ovarian cancer by promoting autophagy and inhibiting apoptosis. In this study, we detect the expression of HERPUD1 and Lewis y antigens in 119 different ovarian cancer tissues, determine their relationship with clinicopathological parameters, analyze the correlation between these two proteins, and explore the related cancer-promoting mechanisms through MTT, flow cytometry, western blotting, and bioinformatics. HERPUD1 is highly expressed in ovarian cancer, especially in the early stage, and the expression of HERPUD1 and Lewis y antigen was positively correlated. After overexpression of Lewis y antigen, the expression level of HERPUD1 increased. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) analysis showed that HERPUD1 and its related genes are enriched in regulating immunity, endoplasmic reticulum stress, ubiquitin-dependent degradation, ERS-induced apoptosis, and other key signaling pathways. We also clarified the HERPUD1 network of kinases, microRNA and transcription factor targets, and the impact of HERPUD1 mutations on prognosis. In addition, HERPUD1 promotes the proliferation of ovarian cancer cells, inhibits apoptosis, affects the cell cycle, promotes the occurrence of autophagy, and inhibits EMT and PI3K/AKT/mTOR and p38MAPK pathways. Overall, HERPUD1, regulated by the expression of tumor-associated protein Lewis y, promotes cell survival in the early stages of tumors, suggesting that HERPUD1 may play an important role in the development of ovarian cancer.

Anaplastic lymphoma kinase (ALK) fusion gene is an important tumor driver gene of non-small cell lung cancer, accounting for about 5% of patients with non-small cell lung cancer, of which 97% are patients with lung adenocarcinoma. Since the first discovery of echinoderm microtubule associated protein-like 4 (EML4)-ALK fusion in patients with lung adenocarcinoma in 2007, a variety of ALK fusion partners have been detected. CLIP1-ALK fusion gene was detected by next generation sequencing (NGS) in this patient with advanced lung squamous cell carcinoma, and Alectinib and Ensartinib were taken orally on May 5, 2021. Aletinib was effective for this patient but the patients died on September 30, 2021. This is a report of lung squamous cell carcinoma patients with CLIP1-ALK fusion gene treated with ALK inhibitors.