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Abstract Background Chronic kidney disease (CKD) and its associated end-stage renal disease (ESRD) are significant health problems that pose a threat to human well-being. Renal fibrosis is a common feature and ultimate pathological outcome of various CKD leading to ESRD. The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) is a refined compound formulated by our research group, which has been clinically administered for over a decade and has demonstrated the ability to improve the inflammatory state of various acute or chronic kidney diseases. However, the underlying mechanism by which A&P ameliorates renal fibrosis remains unclear. Methods We established a mouse model by surgically ligating the unilateral ureter to induce renal injury in vivo. And we utilized renal in situ electroporation of a plasmid with low LncRNA A33 expression to establish the unilateral ureteral obstruction(UUO)mouse model. In vitro, we stimulated primary tubular epithelial cells(pTEC) injury using TGF-β1, siRNA-A33, and pcDNA3.1-A33 plasmids were transfected into pTECs to respectively knockdown and overexpress LncRNA A33, and both in vitro and in vivo models were intervened with A&P. Results The results demonstrated that A&P effectively alleviated renal fibrosis in mice. Subsequent findings indicated high expression of LncRNA A33 in the kidneys of UUO mice and TGF-β1-induced renal tubular cells. In situ, renal electroporation of a plasmid with reduced LncRNA A33 expression revealed that inhibiting LncRNA A33 significantly improved renal fibrosis in UUO mice. Moreover, A&P effectively suppressed LncRNA A33 expression both in vitro and in vivo. Subsequent downregulation of LncRNA A33 in renal tubular epithelial cells resulted in the downregulation of numerous fibrotic markers, a significant inhibition of LncRNA A33, and a notable reduction in downstream ferroptosis signaling. Cell experiments demonstrated that A&P improved renal fibrosis in UUO mice by inhibiting LncRNA A33 and downregulating ferroptosis signaling. Conclusion Through the inhibition of LncRNA A33 and subsequent downregulation of ferroptosis signaling, A&P showed potential as a therapeutic approach for improving renal fibrosis in UUO mice, providing a potential treatment avenue for CKD.

Abstract Objective The aim of this study was to explore the effects of vitamin D supplementation on metabolic parameters in women with polycystic ovary syndrome (PCOS). Methods A total of 60 PCOS women with vitamin D deficiency or insufficiency were enrolled in this randomized controlled trial. Participants were randomized to vitamin D group (2000 IU/day) or control group. The observational parameters were measured at baseline and after treatment, including body mass index (BMI), waist to hip ratio (WHR), oral glucose tolerance test (OGTT) and insulin release test, and lipid metabolism parameters. Results The serum 25(OH)D concentrations at different time points after vitamin D supplementation were significantly higher than that in control group (P 0.05), and these differences of metabolic parameters were also not observed between vitamin D group (non-IR) and control group (non-IR) (P > 0.05). Conclusion Vitamin D supplementation had beneficial effects on metabolic parameters in PCOS women, especially in women with obesity or insulin resistance.

Abstract To accurately detect the early deterioration of electrical insulation in power cables, an energizing system is required for offline partial discharge (PD) measurements. The damped alternating current (DAC) testing system has emerged as an effective tool for inducing PD events. However, the existing systems often suffer from limitations such as signal interference, low sensitivity, and high costs. To address these issues, this study proposes a novel dual‐resonance DAC testing system that is simple in structure and cost‐effective. The prototype was built for testing 10‐kV distribution cables, and its effectiveness was validated through experimental tests on a cable sample. The results show that this approach significantly improves PD detection sensitivity and successfully completes PD localization. This research contributes to the development of more efficient and affordable DAC generation technology for power cable testing applications.

Abstract. Background:. Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons. Methods:. We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT. Results:. Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9–34.5%) and 43.8% (95% CI, 28.3–59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death. Conclusion:. The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons. Trial Registration:. ClinicalTrials.gov, NCT02879526.

Abstract Background Atherogenic index of plasma (AIP) is a non-traditional lipid parameter that can reflect the burden of atherosclerosis. A lipid profile resembling atherosclerosis emerged during pregnancy. Although lipid metabolism is pivotal in diabetes pathogenesis, there is no evidence linking AIP to gestational diabetes mellitus (GDM). Therefore, our objective was to explore the relationship between AIP and GDM and assess AIP's predictive capability for GDM. Methods This was a secondary analysis based on data from a prospective cohort study in Korea involving 585 single pregnant women. AIP was calculated as log10 (TG/HDL). We examined the relationship between AIP and GDM using logistic regression models, curve fitting, sensitivity analyses, and subgroup analyses. Receiver operating characteristic (ROC) analysis was also used to determine the ability of AIP to predict GDM. Results The average age of the participants was 32.06 ± 3.76 years. The AIP was 0.24 ± 0.20 on average. The GDM incidence was 6.15%. After adjustment for potentially confounding variables, AIP showed a positive linear relationship with GDM (P for non-linearity: 0.801, OR 1.58, 95% CI 1.27–1.97). The robustness of the connection between AIP and GDM was demonstrated by sensitivity analyses and subgroup analyses. An area under the ROC curve of 0.7879 (95% CI 0.7087–0.8671) indicates that AIP is an excellent predictor of GDM. With a specificity of 75.41% and sensitivity of 72.22%, the ideal AIP cut-off value for identifying GDM was 0.3557. Conclusions This study revealed that the AIP at 10–14 weeks of gestation was independently and positively correlated with GDM risk. AIP could serve as an early screening and monitoring tool for pregnant women at high risk of GDM, thereby optimizing GDM prevention strategies. Trial registration ClinicalTrials.gov registration no. NCT02276144. Graphical abstract

Highlights Derived from silica photonic crystals, inverse opal microspheres have a regularly connected porous structure and inherit structural color properties. Combined with the stable scaffold and the photothermal phase-transition of the secondary filling material, the inverse opal composite microspheres are endowed with self-healing properties and the ability for controllable drug release. Inverse opal microspheres were significantly treated for diabetic wound, via promoting tissue regeneration, collagen deposition and angiogenesis. Meanwhile, the release of drugs could be monitored by the structural color characteristic.

Abstract Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), remains a highly lethal malignancy with limited therapeutic options and a dismal prognosis. By targeting the underlying molecular abnormalities responsible for PDAC development and progression, gene therapy offers a promising strategy to overcome the challenges posed by conventional radiotherapy and chemotherapy. This study sought to explore the therapeutic potential of small activating RNAs (saRNAs) specifically targeting the CCAAT/enhancer-binding protein alpha (CEBPA) gene in PDAC. To overcome the challenges associated with saRNA delivery, tetrahedral framework nucleic acids (tFNAs) were rationally engineered as nanocarriers. These tFNAs were further functionalized with a truncated transferrin receptor aptamer (tTR14) to enhance targeting specificity for PDAC cells. The constructed tFNA-based saRNA formulation demonstrated exceptional stability, efficient saRNA release ability, substantial cellular uptake, biocompatibility, and nontoxicity. In vitro experiments revealed successful intracellular delivery of CEBPA-saRNA utilizing tTR14-decorated tFNA nanocarriers, resulting in significant activation of tumor suppressor genes, namely, CEBPA and its downstream effector P21, leading to notable inhibition of PDAC cell proliferation. Moreover, in a mouse model of PDAC, the tTR14-decorated tFNA-mediated delivery of CEBPA-saRNA effectively upregulated the expression of the CEBPA and P21 genes, consequently suppressing tumor growth. These compelling findings highlight the potential utility of saRNA delivered via a designed tFNA nanocarrier to induce the activation of tumor suppressor genes as an innovative therapeutic approach for PDAC.

Abstract Leukemia stem cells (LSCs) are recognized as the root cause of leukemia initiation, relapse, and drug resistance. Lipid species are highly abundant and essential component of human cells, which often changed in tumor microenvironment. LSCs remodel lipid metabolism to sustain the stemness. However, there is no useful lipid related biomarker has been approved for clinical practice in AML prediction and treatment. Here, we constructed and verified fatty acid metabolism-related risk score (LFMRS) model based on TCGA database via a series of bioinformatics analysis, univariate COX regression analysis, and multivariate COX regression analysis, and found that the LFMRS model could be an independent risk factor and predict the survival time of AML patients combined with age. Moreover, we revealed that Galectin-1 (LGALS1, the key gene of LFMRS) was highly expressed in LSCs and associated with poor prognosis of AML patients, and LGALS1 repression inhibited AML cell and LSC proliferation, enhanced cell apoptosis, and decreased lipid accumulation in vitro. LGALS1 repression curbed AML progression, lipid accumulation, and CD8+ T and NK cell counts in vivo. Our study sheds light on the roles of LFMRS (especially LGALS1) model in AML, and provides information that may help clinicians improve patient prognosis and develop personalized treatment regimens for AML.

Abstract Objectives This study aims to describe the differences in body composition among different body parts of the elderly in the community and its relationship with sarcopenia. Methods Elderly people aged ≥65 underwent bioelectric impedance analysis testing and were categorized into a sarcopenia group, possible sarcopenia group, and control group. The characteristics of body composition indicators in different parts and their relationship with different stages of sarcopenia were analyzed. Results The sarcopenia group illustrated the lowest values of FFM, FFM%, BFM, BFM%, ICW, and limb PhA, along with higher ECW/TBW in the trunk and left leg compared to the control group. The possible sarcopenia group showed lower FFM% in limbs and trunk, and higher BFM% compared to the control group. Gender differences in elderly body composition were observed, with an increase in BFM% in various body parts posing a risk factor for possible sarcopenia in elderly males, whereas an increase in BFM% except in the left arm was a protective factor for sarcopenia in elderly females. Conclusion The body composition of the elderly in the community varied significantly in different stages of sarcopenia and genders, which correlated with sarcopenia.

Abstract Our main objective was to use machine learning methods to identify significant structural factors associated with pain severity in knee osteoarthritis patients. Additionally, we assessed the potential of various classes of imaging data using machine learning techniques to gauge knee pain severity. The data of semi-quantitative assessments of knee radiographs, semi-quantitative assessments of knee magnetic resonance imaging (MRI), and MRI images from 567 individuals in the Osteoarthritis Initiative (OAI) were utilized to train a series of machine learning models. Models were constructed using five machine learning methods: random forests (RF), support vector machines (SVM), logistic regression (LR), decision tree (DT), and Bayesian (Bayes). Employing tenfold cross-validation, we selected the best-performing models based on the area under the curve (AUC). The study results indicate no significant difference in performance among models using different imaging data. Subsequently, we employed a convolutional neural network (CNN) to extract features from magnetic resonance imaging (MRI), and class activation mapping (CAM) was utilized to generate saliency maps, highlighting regions associated with knee pain severity. A radiologist reviewed the images, identifying specific lesions colocalized with the CAM. The review of 421 knees revealed that effusion/synovitis (30.9%) and cartilage loss (30.6%) were the most frequent abnormalities associated with pain severity. Our study suggests cartilage loss and synovitis/effusion lesions as significant structural factors affecting pain severity in patients with knee osteoarthritis. Furthermore, our study highlights the potential of machine learning for assessing knee pain severity using radiographs.

This is an article in the field of ceramics and composites. The performance of asphalt mixtures with different iron tailings content was analyzed. The rutting resistance, water stability and crack resistance of the asphalt mixture were analyzed. This verified the feasibility of iron tailings applied to the middle surface of low-grade roads. The results showed that the flexural strength decreased the most when the dosage was from 20% to 40%. The increase rate of immersion residue stability began to decrease after the dosage was 20%. As the content of iron tailings continued to increase, the FT-IR spectrum of iron tailings asphalt concrete showed a small, new absorption peak locally and an enhancement to the original absorption peak. This showed that after the addition of iron tailings, the asphalt concrete chemically reacted with it, and the internal structure of the original asphalt was changed and new functional groups were generated. With the increasing content of iron tailings, the proportion of the area of cycloalkane and alkane C-H functional groups in the asphalt concrete of iron tailings asphalt concrete showed a trend of first increasing and then decreasing. And when the iron tailings content was 20%, the area ratio of asphalt naphthenic and alkane C-H functional groups reached the maximum.

Abstract Previous research has produced inconsistent findings concerning the connection between metabolic syndrome and prostate cancer. It is challenging for observational studies to establish a conclusive causal relationship between the two. However, Mendelian randomization can provide stronger evidence of causality in this context. To examine the causal link between a metabolic composite and its components with prostate cancer, we performed a two-sample Mendelian randomization (MR) study utilizing aggregated data from genome-wide association studies, followed by meta-analyses. In our study, we employed inverse variance weighting as the primary method for MR analysis. Additionally, we assessed potential sources of heterogeneity and horizontal pleiotropy through the Cochran’s Q test and MR-Egger regression. Moreover, we used multivariate MR to determine whether smoking versus alcohol consumption had an effect on the outcomes. We found no causal relationship between metabolic syndrome and its components and prostate cancer(MetS, odds ratio [OR] = 0.95, 95% confidence interval [CI] = 0.738–1.223, p = 0.691; TG, [OR] = 1.02, 95%[CI] = 0.96–1.08, p = 0.59); HDL, [OR] = 1.02, 95% [CI] = 0.97–1.07, p = 0.47; DBP, [OR] = 1.00, 95%[CI] = 0.99–1.01, p = 0.87; SBP, [OR] = 1.00, 95%[CI] = 0.99–1.00, p = 0.26; FBG [OR] = 0.92, 95%[CI] = 0.81–1.05, p = 0.23; WC, [OR] = 0.93, 95%[CI] = 0.84–1.03, p = 0.16). Finally, the MVMR confirms that the metabolic syndrome and its components are independent of smoking and alcohol consumption in prostate cancer. We didn’t find significant evidence to determine a causal relationship between the metabolic syndrome and its components and prostate cancer through MR analysis. Further research is necessary to explore the potential pathogenesis between the two diseases.

Abstract To analyze the current status of "pseudo" unplanned endotracheal extubation in ICU patients in China's tertiary hospitals and to provide a reference for improving the quality of medical care. Through the National Nursing Quality Data Platform, unplanned endotracheal extubation data reported by ICUs in China's tertiary hospitals from 2019 to 2022 were analyzed. The situation of reported hospitals, causes, and the current status of "pseudo" unplanned endotracheal extubation in ICU patients was analyzed. The indicator of unplanned endotracheal extubation in ICUs of China’s tertiary hospitals is mainly from first-class tertiary hospitals (74.9%), most of which are self-extractions by patients (74.6%). The proportion of "pseudo" unplanned endotracheal extubation is 45.1%. "Pseudo" unplanned endotracheal extubation is common in the ICUs of China's tertiary hospitals. As such, management blind spots deserve attention from managers and clinical staff.

Abstract Background Healthy eating is one of the most important nonpharmacologic treatments for patients with atherosclerosis(AS). However, it is unclear how elderly AS patients in western China perceive their dietary status and which type of nutritional assistance they would be willing to receive. Therefore, the primary purpose of this study was to understand the level of knowledge about current dietary habits and healthy eating habits among elderly AS patients in western China, and the secondary purpose was to identify acceptable nutritional assistance measures or pathways for those patients to help them manage disease progression. Methods An implementation study approach was used to recruit elderly patients with AS-related diseases in western China for semistructured interviews. Results 14 participants were included in the study, and the following three themes were identified from the interviews:(1) the diet with regional characteristics; (2) low nutrition-related health literacy; (3) complex attitudes towards nutritional assistance. Most participants had misconceptions about healthy eating, and the sources of their knowledge might not be trustworthy. Participants expressed a preference for personalized nutritional assistance, especially that provided by medical-nursing combined institutions. Conclusion Patients in western China need nutritional assistance for their regional dietary habits; therefore, healthy dietary patterns consistent with the regional culture are proposed to improve the prevailing lack of knowledge about healthy diets, improve the dietary structure of patients, and control the development of the disease.

Abstract Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated promising efficacy in early trials for relapsed/refractory diffuse large B cell lymphoma (DLBCL). However, its efficacy in treating primary refractory DLBCL has not been comprehensively investigated, and the underlying resistance mechanisms remain unclear. Here, we report the outcomes of a phase I, open-label, single-arm clinical trial of relmacabtagene autoleucel (relma-cel), a CD19-targeted CAR-T cell product, with safety and efficacy as primary endpoints. Among the 12 enrolled patients, 8 experienced grade 4 hematologic toxicity of treatment-emergent adverse event. No grade ≥3 cytokine release syndrome or neurotoxicity occurred. Single-cell RNA sequencing revealed an increase proportion of C1QB-expressing macrophages in patients with progressive disease before CAR-T cell therapy. Cholesterol efflux from M2 macrophages was found to inhibit CAR-T cells cytotoxicity by inducing an immunosuppressive state in CD8+ T cells, leading to their exhaustion. Possible interactions between macrophages and CD8+ T cells, mediating lipid metabolism (AFR1-FAS), immune checkpoint activation, and T cell exhaustion (LGALS9-HAVCR2, CD86-CTLA4, and NECTIN2-TIGIT) were enhanced during disease progression. These findings suggest that cholesterol efflux from macrophages may trigger CD8+ T cell exhaustion, providing a rationale for metabolic reprogramming to counteract CAR-T treatment failure. Chinadrugtrials.org.cn identifier: CTR20200376.

Abstract Security is a crucial concern in the Internet of Things (IoT) ecosystem. Due to IoT devices' constrained processing and storage resources, providing reliable security solutions is challenging. Encryption is one of the most commonly used techniques to secure user data against unauthorized access. Therefore, it is essential to develop encryption solutions that have minimal impact on the performance of IoT devices. This study introduces a hybrid encryption approach that combines symmetric blowfish encryption with asymmetric elliptic curves. Blowfish encryption is used to encrypt large volumes of data, which could otherwise affect the execution time. In contrast, elliptic curve cryptography is utilized to ensure the security of the private key, which has a small size and does not increase the execution time significantly. The suggested approach provides advantages of both asymmetric and symmetric encryption methods, leading to an improvement in throughput and a reduction in execution time. The proposed approach was evaluated, yielding promising results in comparison to other cryptographic algorithms. The results show the optimization of more than 15% in the execution time and the efficiency increase by the proposed solution. This improvement represents security with the least impact on processing resources.

Abstract Background Job burnout is a prevalent and emerging challenge in the primary medical system, causing mass turnover, especially of primary medical staff. Little attention has been paid to the different dimensions of job burnout (emotional exhaustion, personality disintegration, and reduced sense of achievement), which may hinder efforts to tackle high turnover intention among primary medical staff. From the perspective of conservation of resources theory, social support and psychological capital are basic resources with potential to diminish job burnout and thus lower turnover intention. However, there is insufficient research evidence on the relationships between social support, psychological capital, and the three dimensions of job burnout within the primary medical system. Objectives Focusing on primary medical staff, this study conducts a path analysis to examine the correlations between two types of resources (social support and psychological capital) and the three dimensions of job burnout, and to test the impact of the latter on turnover intention. Based on the results, effective management strategies to improve the work stability of primary medical staff are proposed. Methods Multi-stage cluster random sampling was used to select participants in Anhui Province, China. Data were collected using a self-administered questionnaire containing measures of the main variables and demographic questions. In total, 1132 valid questionnaires were returned by primary medical staff. Structural equation modeling was used for path analysis of the data. Results Social support was negatively associated with emotional exhaustion (β = − 0.088, P = 0.020), personality disintegration (β = − 0.235, P

Abstract This phase II trial aimed to determine the efficacy and safety of induction chemoimmunotherapy of camrelizumab plus modified TPF in locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) (NCT04156698). The primary endpoint was objective response rate (ORR), and secondary endpoints were 3-year overall survival (OS), progression-free survival (PFS), larynx preservation rate (LPR), and metastasis-free survival (MFS). Patients (cT3-4aN0-2M0), regardless of sex, received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg d1, docetaxel 75 mg/m2 d1, cisplatin 25 mg/m2 d1-3, and capecitabine 800 mg/m2 bid d1-14, q21d. Patients were assigned to radioimmunotherapy if they had a complete or partial response, those with stable or progressive disease underwent surgery and adjuvant (chemo)radiotherapy. Camrelizumab was maintained post-radioimmunotherapy. Fifty-one patients were enrolled with a median follow-up duration of 23.7 months. After induction therapy, the ORR was 82.4% (42/51), meeting the prespecified endpoint. Grade 3/4 adverse events occurred in 26 patients, and no treatment-related death occurred. As three-year outcomes were immature, two-year OS, PFS and LPR were reported. As no distant metastatic event had occurred, MFS was not reported here. The two-year OS, PFS, and LPR rates were 83.0%, 77.1%, and 70.0%, respectively. The induction chemoimmunotherapy of camrelizumab plus TPF showed a high ORR rate with an acceptable safety profile in LA HSCC.

Abstract Light intensity is a key factor affecting the synthesis of secondary metabolites in plants. However, the response mechanisms of metabolites and genes in Gentiana macrophylla under different light intensities have not been determined. In the present study, G. macrophylla seedlings were treated with LED light intensities of 15 µmol/m2/s (low light, LL), 90 µmol/m2/s (medium light, ML), and 200 µmol/m2/s (high light, HL), and leaves were collected on the 5th day for further investigation. A total of 2162 metabolites were detected, in which, the most abundant metabolites were identified as flavonoids, carbohydrates, terpenoids and amino acids. A total of 3313 and 613 differentially expressed genes (DEGs) were identified in the LL and HL groups compared with the ML group, respectively, mainly enriched in KEGG pathways such as carotenoid biosynthesis, carbon metabolism, glycolysis/gluconeogenesis, amino acids biosynthesis, plant MAPK pathway and plant hormone signaling. Besides, the transcription factors of GmMYB5 and GmbHLH20 were determined to be significantly correlated with loganic acid biosynthesis; the expression of photosystem-related enzyme genes was altered under different light intensities, regulating the expression of enzyme genes involved in the carotenoid, chlorophyll, glycolysis and amino acids pathway, then affecting their metabolic biosynthesis. As a result, low light inhibited photosynthesis, delayed glycolysis, thus, increased certain amino acids and decreased loganic acid production, while high light got an opposite trend. Our research contributed significantly to understand the molecular mechanism of light intensity in controlling metabolic accumulation in G. macrophylla.

Abstract Loess areas, such as the Loess Plateau, are characterized by a fragile ecological environment, high soil erosion, and frequent geological disasters due to the unique hydrological properties of loess (e.g., collapsibility and permeability). Therefore, the loess must be stabilized for use in engineering construction. Traditional stabilizers (lime, cement, and fly ash) cause environmental problems, such as soil salinization and greenhouse gas emissions. Therefore, this study investigated the effect of nanosilica on the hydrological properties of loess and the microscopic mechanism. Different nanosilica contents (0.2%, 0.4%, 0.8%, 1%, and 3%) were added to loess sample, and the particle size distribution, Atterberg limits, collapsibility, and soil water characteristics were analyzed. The results revealed the following. The addition of nanosilica changed the particle size distribution, liquid limit, plastic limit, and plasticity index of loess. After the addition of nanosilica with different contents, the loess collapsibility coefficient curve shifted downward, the soil water retention curve shifted upward, and the unsaturated permeability coefficient curve shifted downward. The pores between particles were filled, and the number of large and medium pores and the pore connectivity were lower after the nanosilica addition. The surface of the coarse particles adsorbed more fine particles, and a large number of micro-aggregates or clay aggregates were present in the pores between particles. In conclusion, the environmentally friendly material nanosilica can be used to improve the hydrological properties of loess, which is applicable to alleviating soil erosion and preventing geological disasters on the Loess Plateau.

Abstract Waste activated sludge (WAS) is attracting attention for its energy and resource potential. Anaerobic digestion (AD) can be used to efficiently recover energy resources and stabilize pollutants in WAS, with biochar emerging as an ideal additive to boost this process. However, the low abundance of surface functional groups and small pore structure of raw biochar may limit its performance in the AD of WAS. These limitations can be overcome by using functional biochar. In this review, the preparation and modification methods for functional biochar and its role in the AD of WAS are systematically summarized and discussed. Notably, the role of functional biochar in electron transfer, buffering effects, microbial immobilization, alleviation of inhibitory effects, and functional microbial modulation are analyzed. Additionally, the impacts of biochar on digestate utilization, pollutant removal, and carbon fixation are discussed. Special attention is given to functional biochar for its ability to promote circular economy and carbon neutrality. Finally, future perspectives on the use of functional biochar in the AD of WAS are presented. The aim of this review is to provide insights into the application of functional biochar in the AD of WAS from the perspective of performance improvement, resource utilization, and circular economy. Graphical Abstract

Abstract The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain. Graphical Abstract

Abstract Implantable neural probes, essential for brain electrophysiological research, have advanced with ultra-flexible designs to mitigate immune responses and postoperative complications. Strategies of shuttle-assisted implantation and temporary stiffening address issues in penetrating these probes into the target region, avoiding undesired bending. However, the risk of intraoperative bleeding remains due to these implants’ necessary rigidity during insertion. Here, we describe a neural probe with mechanical compliance accompanying self-implantation along the principal axis in the absence of bleeding. Crucial to the behavior is its anisotropic relaxation, which is dominated by the cross-sectional in-plane deformation inhibition due to interchain interactions between the parallel backbones in the globally aligned polymer system. We observed the ensured upright insertion of the probe into the brain while avoiding angiorrhexis with a two-photon microscope and a high-speed camera. The probes permit electrophysiological studies with minimal foreign body responses and imageological compatibility, underscoring their clinical potential.

Abstract Background Early and appropriate antibiotic treatment improves the clinical outcome of patients with sepsis. There is an urgent need for rapid identification (ID) and antimicrobial susceptibility testing (AST) of bacteria that cause bloodstream infection (BSI). Rapid ID and AST can be achieved by short-term incubation on solid medium of positive blood cultures using MALDI-TOF mass spectrometry (MS) and the BD M50 system. The purpose of this study is to evaluate the performance of rapid method compared to traditional method. Methods A total of 124 mono-microbial samples were collected. Positive blood culture samples were short-term incubated on blood agar plates and chocolate agar plates for 5 ∼ 7 h, and the rapid ID and AST were achieved through Zybio EXS2000 MS and BD M50 System, respectively. Results Compared with the traditional 24 h culture for ID, this rapid method can shorten the cultivation time to 5 ∼ 7 h. Accurate organism ID was achieved in 90.6% of Gram-positive bacteria (GP), 98.5% of Gram-negative bacteria (GN), and 100% of fungi. The AST resulted in the 98.5% essential agreement (EA) and 97.1% category agreements (CA) in NMIC-413, 99.4% EA and 98.9% CA in PMIC-92, 100% both EA and CA in SMIC-2. Besides, this method can be used for 67.2% (264/393) of culture bottles during routine work. The mean turn-around time (TAT) for obtaining final results by conventional method is approximately 72.6 ± 10.5 h, which is nearly 24 h longer than the rapid method. Conclusions The newly described method is expected to provide faster and reliable ID and AST results, making it an important tool for rapid management of blood cultures (BCs). In addition, this rapid method can be used to process most positive blood cultures, enabling patients to receive rapid and effective treatment.

Abstract Objective Meteorin-like (Metrnl), a secreted myokine, is a newly discovered neurotrophic factor. The aim of this study was to determine if there is a correlation between the Metrnl level and diabetic peripheral neuropathy (DPN). Methods The investigation was conducted on a sample of 80 patients with type 2 diabetes mellitus (T2DM) and 60 healthy controls. The T2DM patients were categorized into two subgroups based on skin biopsy: the DPN subgroup (n = 20) and the diabetes without neuropathy subgroup (n = 60). Results The T2DM groups had higher serum Metrnl concentrations compared with the controls. The serum Metrnl concentration was significantly lower in the DPN group than in T2DM patients without neuropathy. Logistic regression analysis demonstrated a notable correlation between serum Metrnl and DPN (OR: 0.997, 95% CI: 0.995–1.000, P

This study was to evaluate the effect of supplementing the diet of broilers with Neolamarckia cadamba leaf extract (NCLE) on meat quality by evaluating antioxidant parameters and the expression of genes in the p38 mitogen-activated protein kinase/nuclear factor-erythroid 2-related factor 2/antioxidant responsive element (p38 MAPK/Nrf2/ARE) signaling pathway, coupled with LC–MS-based metabolomic analysis. A total of 480 one-day-old male broilers were randomly allocated to four treatment groups—a control (CON) group, which was fed a basal diet, and three NCLE treatment groups, which were fed the basal diet supplemented with 100, 200, or 400 mg/kg NCLE (N1, N2, and N3 groups, respectively) for 42 d. Compared with the CON group, meat quality was improved in the N2 and N3 groups, as evidenced by the higher pH45min (P

As a key component of lithium-ion batteries, a separator with excellent electrolyte wettability and good thermal stability has an important impact on the overall performance of lithium-ion batteries. Herein, a PVDF/sepiolite electrospun layer was coated on one side of the PP separator via electrospinning technology to prepare the composite separator (xMS-PVDF@PP) with sepiolite nanofibers modified with vinyltriethoxysilane (VTES) to ameliorate their dispersibility and compatibility with PVDF polymer matrix. The effect of modified sepiolite addition amounts on the physical and electrochemical properties of composite separator was intensively studied. It is found that the as-prepared xMS-PVDF@PP composite separator displays enhanced porosity, electrolyte uptake, thermal stability and Li+ ion transport kinetics than pristine PP separator. Specifically, Li|LiFePO4 battery with 20MS-PVDF@PP as separator shows the best rate and cycling performance, with a specific discharge capacity of 115.3 mAh·g–1 at 10C rate and a capacity retention rate of 97.06% after 200 cycles at 1C rate. The sepiolite in the electrospun layer can immobilize PF6– anion to facilitate the uniform distribution of Li+ ions and then inhibit the lithium dendrite growth, as well as absorb HF to alleviate Fe2+ dissolution from LiFePO4 cathode, thereby further improving the electrochemical performance of LiFePO4 battery.

Previous studies have shown that maternal resveratrol improved growth performance and altered the microbial composition of suckling piglets under hot summer conditions. However, it remains unclear how maternal resveratrol improves growth performance of suckling piglets during high summer temperatures. A total of 20 sows (Landrace × Large White; three parity) were randomly assigned to 2 groups (with or without 300 mg/kg resveratrol) from d 75 of gestation to d 21 of lactation during high ambient temperatures (from 27 to 30 °C). The results showed that maternal resveratrol supplementation increased total daily weight gain of piglets under hot summer conditions, which is consistent with previous studies. Furthermore, we found that maternal resveratrol improved the intestinal morphology and intestinal epithelial proliferation in suckling piglets. Dietary resveratrol supplementation affected the characteristics of exosome-derived microRNAs (miRNAs) in sow colostrum, as well as the genes targeted by differentially produced miRNAs. MiRNAs are concentrated in the tight junction pathway. As a result, the expression of intestinal tight junction proteins was increased in suckling piglets (P

【Objective】The experiment was carried out to study the effects of potassium magnesium sulfate (PMS) on sow performance, plasma biochemical indicators, antioxidant capacity and immune function in late pregnancy.【Method】By using simple factor design of the experiment, sixty sows (Landrace×Yorkshire) with 3-4 parity, good health and similar expected delivery in the third trimester of pregnancy (85th day of pregnancy) were randomly divided into 4 groups (15 replicates in each group and 1 sow in each replicate). The experimental groups during gestation were supplemented with PMS 0 (CK), 5, 10 and 15 g/d for each sow, respectively. After delivery, all sows during lactation were fed the same commercial lactation feed. The experiment ended on the 18th day of lactation.【Result】(1) Supplemental PMS had no significant effects on litter size, healthy litter size, back fat thickness, labor, body weight, feed intake in sows during lactation, and newborn weight of piglets, number of weaned piglets and number of deaths of lactating piglets. Compared with the control group, the fecal score of sows during late pregnancy after PMS supplementation showed a linear increase (Plinear < 0.05) and 10 g/d group had significant effects (PANOVA < 0.05); After supplementation with PMS, it showed a linear increase (Plinear < 0.05) in newborn litter weight, litter weight of weaned piglets, average litter gain of lactating piglets and daily gain of lactating piglets (PANOVA < 0.05). Compared with the control group, the newborn litter weight, litter weight of weaned piglets, average litter gain of lactating piglets and daily gain of lactating piglets in the 10 g/d group were increased by 16.27%, 24.42%, 35.14% and 31.64%. Except for newborn litter weight, all other indicators showed quadratic effect (PQuadratic < 0.05) and significant differences were found between groups (PANOVA < 0.05); (2) It showed a linear increase in the contents of triglyceride (TG), cholesterol (CHO), low-density lipoprotein (LDL) and insulin (INS) in plasma of sows supplemented with PMS (Plinear < 0.05). The contents of TG, CHO, LDL and INS in the 10 g/d group increased by 50.00%, 28.35%, 25.00% and 31.98% compared with the control group; TG and LDL had a quadratic effect (PQuadratic < 0.05). (3) Linear changes were found in contents of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM) and glutathione peroxidase (GSH-Px) (Plinear < 0.05) in the plasma of sows after supplementation with PMS, and they were increased by 17.10%, 20.34%, 8.00% and 15.04% in the 10 g/d group, compared with the control group. (4) It showed a linear increase (PANOVA < 0.05) in fat content of colostrum of sow with PMS supplementation (Plinear < 0.05), with significant increase. Non-fat milk solids, lactose and protein were linearly increased (Plinear < 0.05) and had an increasing trend (0.05 < PANOVA < 0.1). The fat content of colostrum supplemented with 10 g/d were increased by 51.42% compared with the control group.【Conclusion】PMS supplementation in late preganancy can significantly improve the fecal scores of sows, relieve sow constipation, and improve sow performance and body health, with 10 g/d supplementation as the optimal dose.

Objective: Accurate infant brain parcellation is crucial for understanding early brain development; however, it is challenging due to the inherent low tissue contrast, high noise, and severe partial volume effects in infant magnetic resonance images (MRIs). The aim of this study was to develop an end-to-end pipeline that enabled accurate parcellation of infant brain MRIs. Methods: We proposed an end-to-end pipeline that employs a two-stage global-to-local approach for accurate parcellation of infant brain MRIs. Specifically, in the global regions of interest (ROIs) localization stage, a combination of transformer and convolution operations was employed to capture both global spatial features and fine texture features, enabling an approximate localization of the ROIs across the whole brain. In the local ROIs refinement stage, leveraging the position priors from the first stage along with the raw MRIs, the boundaries of the ROIs are refined for a more accurate parcellation. Results: We utilized the Dice ratio to evaluate the accuracy of parcellation results. Results on 263 subjects from National Database for Autism Research (NDAR), Baby Connectome Project (BCP) and Cross-site datasets demonstrated the better accuracy and robustness of our method than other competing methods. Conclusion: Our end-to-end pipeline may be capable of accurately parcellating 6-month-old infant brain MRIs.

This work investigates the effect of Ru on the precipitation of the topologically close-packed (TCP) phase from the γ-γʹ microstructural degradation analysis. The addition of Ru is found to delay the precipitation time of the TCP phase from 100 h to 1000 h after thermal exposure at 950 °C. The effect of Ru on the γ-γʹ microstructural degradation is also investigated. Adding Ru slightly decreases the coarsening rate of the γʹ size and promotes the reduction of the volume fraction of γʹ phase. The reduction of the volume fraction of γʹ phase causes the ''inverse partitioning'' effect and increases the solution limit of the TCP forming element in the matrix. These help inhibit the precipitation of the TCP phases in Ni-based single crystal superalloys during thermal exposure.

In this paper, the fourth power mean values of the generalized quadratic Gauss sums associated with the $ 3 $-order and $ 4 $-order Dirichlet characters are given by using the properties of the Dirichlet characters and Gauss sums.

Abstract Understanding water saturation levels in tight gas carbonate reservoirs is vital for optimizing hydrocarbon production and mitigating challenges such as reduced permeability due to water saturation (Sw) and pore throat blockages, given its critical role in managing capillary pressure in water drive mechanisms reservoirs. Traditional sediment characterization methods such as core analysis, are often costly, invasive, and lack comprehensive spatial information. In recent years, several classical machine learning models have been developed to address these shortcomings. Traditional machine learning methods utilized in reservoir characterization encounter various challenges, including the ability to capture intricate relationships, potential overfitting, and handling extensive, multi-dimensional datasets. Moreover, these methods often face difficulties in dealing with temporal dependencies and subtle patterns within geological formations, particularly evident in heterogeneous carbonate reservoirs. Consequently, despite technological advancements, enhancing the reliability, interpretability, and applicability of predictive models remains imperative for effectively characterizing tight gas carbonate reservoirs. This study employs a novel data-driven strategy to prediction of water saturation in tight gas reservoir powered by three recurrent neural network type deep/shallow learning algorithms—Gated Recurrent Unit (GRU), Recurrent Neural Networks (RNN), Long Short-Term Memory (LSTM), Support Vector Machine (SVM), K-nearest neighbor (KNN) and Decision tree (DT)—customized to accurately forecast sequential sedimentary structure data. These models, optimized using Adam's optimizer algorithm, demonstrated impressive performance in predicting water saturation levels using conventional petrophysical data. Particularly, the GRU model stood out, achieving remarkable accuracy (an R-squared value of 0.9973) with minimal errors (RMSE of 0.0198) compared to LSTM, RNN, SVM, KNN and, DT algorithms, thus showcasing its proficiency in processing extensive datasets and effectively identifying patterns. By achieving unprecedented accuracy levels, this study not only enhances the understanding of sediment properties and fluid saturation dynamics but also offers practical implications for reservoir management and hydrocarbon exploration in complex geological settings. These insights pave the way for more reliable and efficient decision-making processes, thereby advancing the forefront of reservoir engineering and petroleum geoscience.

Abstract Background This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with nasopharyngeal carcinoma (NPC). Methods Clinical data of 415 patients with NPC treated with intensity-modulated radiotherapy between December 2014 and October 2018 were retrospectively analysed. The patients were categorised into modified and comparison groups. Late xerostomia and dysphagia were evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer scoring. Survival analysis was performed using the Kaplan–Meier method. Differences in late toxicity and dose parameters between both groups were compared. Prognostic factors for survival and late toxicity were assessed using regression analyses. Results Patients in the modified group developed late xerostomia and dysphagia less frequently than those in the comparison group did (P

Abstract Despite recent technological advancements in cell tumor DNA (ctDNA) mutation detection, challenges persist in identifying low-frequency mutations due to inadequate sensitivity and coverage of current procedures. Herein, we introduce a super-sensitivity and specificity technique for detecting ctDNA mutations, named HiCASE. The method utilizes PCR-based CRISPR, coupled with the restriction enzyme. In this work, HiCASE focuses on testing a series of EGFR mutations to provide enhanced detection technology for non–small cell lung cancer (NSCLC), enabling a detection sensitivity of 0.01% with 40 ng cell free DNA standard. When applied to a panel of 140 plasma samples from 120 NSCLC patients, HiCASE exhibits 88.1% clinical sensitivity and 100% specificity with 40 μL of plasma, higher than ddPCR and Super-ARMS assay. In addition, HiCASE can also clearly distinguish T790M/C797S mutations in different positions at a 1% variant allele frequency, offering valuable guidance for drug utilization. Indeed, the established HiCASE assay shows potential for clinical applications.

Abstract The aging process of the kidneys is accompanied with several structural diseases. Abnormal fiber formation disrupts the balance of kidney structure and function, causing to end-stage renal disease and subsequent renal failure. Despite this, the precise mechanism underlying renal damage in aging remains elusive. In this study, ABI3BP gene knockout mice were used to investigate the role of ABI3BP in renal aging induced by irradiation. The results revealed a significant increase in ABI3BP expression in HK2 cells and kidney tissue of aging mice, with ABI3BP gene knockout demonstrating a mitigating effect on radiation-induced cell aging. Furthermore, the study observed a marked decrease in Klotho levels and an increase in ferroptosis in renal tissue and HK2 cells following irradiation. Notably, ABI3BP gene knockout not only elevated Klotho expression but also reduced ferroptosis levels. A significant negative correlation between ABI3BP and Klotho was established. Further experiments demonstrated that Klotho knockdown alleviated the aging inhibition caused by ABI3BP downregulation. This study identifies the upregulation of ABI3BP in aged renal tubular epithelial cells, indicating a role in promoting ferroptosis and inducing renal aging by inhibiting Klotho expression.

Abstract Background Dengue fever stands as one of the most extensively disseminated mosquito-borne infectious diseases worldwide. While numerous studies have investigated its influencing factors, a gap remains in long-term analysis, impeding the identification of temporal patterns, periodicity in transmission, and the development of effective prevention and control strategies. Thus, we aim to analyze the periodicity of dengue fever incidence and explore the association between various climate factors and the disease over an extended time series. Methods By utilizing monthly dengue fever cases and climate data spanning four decades (1978–2018) in Guangdong province, China, we employed wavelet analysis to detect dengue fever periodicity and analyze the time-lag relationship with climate factors. Additionally, Geodetector q statistic was employed to quantify the explanatory power of each climate factor and assess interaction effects. Results Our findings revealed a prolonged transmission period of dengue fever over the 40-year period, transitioning from August to November in the 1970s to nearly year-round in the 2010s. Moreover, we observed lags of 1.5, 3.5, and 3 months between dengue fever and temperature, relative humidity, and precipitation, respectively. The explanatory power of precipitation, temperature, relative humidity, and the Oceanic Niño Index (ONI) on dengue fever was determined to be 18.19%, 12.04%, 11.37%, and 5.17%, respectively. Dengue fever exhibited susceptibility to various climate factors, with notable nonlinear enhancement arising from the interaction of any two variables. Notably, the interaction between precipitation and humidity yielded the most significant effect, accounting for an explanatory power of 75.32%. Conclusions Consequently, future prevention and control strategies for dengue fever should take into account these climate changes and formulate corresponding measures accordingly. In regions experiencing the onset of high temperatures, humidity, and precipitation, it is imperative to initiate mosquito prevention and control measures within a specific window period of 1.5 months.

BackgroundStudies on the relationships of environmental noise exposure with negative emotions and sleep quality have long been reported. Self-perceived noise intensity is not only related to environmental noise exposure, but also reflects an individual's susceptibility to noise; however, few studies on self-perceived noise intensity, negative emotions, and sleep quality have been reported, and it is not clear whether negative emotions play a mediating role in the relationship between self-perceived noise intensity and sleep quality. ObjectiveTo analyze the mediating role of negative emotions (anxiety, depression, and stress) in the relationship between self-perceived noise intensity and sleep quality in noise-exposed workers, and to provide a scientific basis for addressing psychological problems and sleep quality induced by noise exposure. MethodsStratified cluster sampling was used to select noise-exposed workers from a large equipment manufacturing plant in Chengdu from May to June 2023, and demographic characteristics were investigated using a self-designed general information questionnaire; self-perceived noise intensity was reported by the study subjects as the noise intensity of their workplaces; sleep quality was synthesized from three indicators: night sleep duration, self-perceived sleep quality, and sleep-related symptoms; the Anxiety-Depression-Stress Scale (DASS-21 scale) was used to evaluate anxiety, depression, and stress of a worker. Structural equation modeling was used to analyze the pathways of negative emotions (anxiety, depression, and stress) between self-perceived noise intensity and sleep quality. ResultsThe positive rates of negative emotions were 33.1% (anxiety symptoms, 215/649), 26.0% (depression symptoms, 169/649), and 14.0% (stress symptoms, 91/649), respectively in a total of 649 noise-exposed workers. Self-perceived noise intensity was positively correlated with sleep quality score (r=0.218, P

Abstract The emergence of convolutional neural network (CNN) and transformer has recently facilitated significant advances in image super-resolution (SR) tasks. However, these networks commonly construct complex structures, having huge model parameters and high computational costs, to boost reconstruction performance. In addition, they do not consider the structural prior well, which is not conducive to high-quality image reconstruction. In this work, we devise a lightweight interactive feature inference network (IFIN), complementing the strengths of CNN and Transformer, for effective image SR reconstruction. Specifically, the interactive feature aggregation module (IFAM), implemented by structure-aware attention block (SAAB), Swin Transformer block (SWTB), and enhanced spatial adaptive block (ESAB), serves as the network backbone, progressively extracts more dedicated features to facilitate the reconstruction of high-frequency details in the image. SAAB adaptively recalibrates local salient structural information, and SWTB effectively captures rich global information. Further, ESAB synergetically complements local and global priors to ensure the consistent fusion of diverse features, achieving high-quality reconstruction of images. Comprehensive experiments reveal that our proposed networks attain state-of-the-art reconstruction accuracy on benchmark datasets while maintaining low computational demands. Our code and results are available at: https://github.com/wwaannggllii/IFIN .

Abstract Background Marfan syndrome (MFS) is an autosomal dominant connective tissue disease with wide clinical heterogeneity, and mainly caused by pathogenic variants in fibrillin-1 (FBN1). Methods A Chinese 4-generation MFS pedigree with 16 family members was recruited and exome sequencing (ES) was performed in the proband. Transcript analysis (patient RNA and minigene assays) and in silico structural analysis were used to determine the pathogenicity of the variant. In addition, germline mosaicism in family member (Ι:1) was assessed using quantitative fluorescent polymerase chain reaction (QF-PCR) and short tandem repeat PCR (STR) analyses. Results Two cis-compound benign intronic variants of FBN1 (c.3464–4 A > G and c.3464-5G > A) were identified in the proband by ES. As a compound variant, c.3464-5_3464-4delGAinsAG was found to be pathogenic and co-segregated with MFS. RNA studies indicated that aberrant transcripts were found only in patients and mutant-type clones. The variant c.3464-5_3464-4delGAinsAG caused erroneous integration of a 3 bp sequence into intron 28 and resulted in the insertion of one amino acid in the protein sequence (p.Ile1154_Asp1155insAla). Structural analyses suggested that p.Ile1154_Asp1155insAla affected the protein’s secondary structure by interfering with one disulfide bond between Cys1140 and Cys1153 and causing the extension of an anti-parallel β sheet in the calcium-binding epidermal growth factor-like (cbEGF)13 domain. In addition, the asymptomatic family member Ι:1 was deduced to be a gonadal mosaic as assessed by inconsistent results of sequencing and STR analysis. Conclusions To our knowledge, FBN1 c.3464-5_3464-4delGAinsAG is the first identified pathogenic intronic indel variant affecting non-canonical splice sites in this gene. Our study reinforces the importance of assessing the pathogenic role of intronic variants at the mRNA level, with structural analysis, and the occurrence of mosaicism.

In this work, a two-stage rolling method with varied temperature and strain rate was proposed for powder metallurgy (PM) Ti–47Al–2Cr–2Nb-0.2W alloy sheets based on the guidance of processing map and microstructure evolution. Compared with conventional rolling at a high temperature and a low strain rate, the TiAl alloy exhibited enhanced plastic deformability through the implementation of the two-stage rolling method, resulting in a higher cumulative true strain. Microstructure analysis revealed significant grain refinement in the rolled sheet. During the first stage of hot rolling with high temperatures and low strain rates, the softening behavior caused by dynamic recovery (DRV) and dynamic recrystallization (DRX) is conducive to the plastic deformation in the second stage rolling (low temperatures and high strain rates). In addition, the formation of mechanical twins further promotes DRX behavior. The softening mechanism of α2 phase is DRV, and that of γ phase is continuous dynamic recrystallization (CDRX) and discontinuous dynamic recrystallization (DDRX).

Abstract Interactions of tumor cells with immune cells in the tumor microenvironment play an important role during malignancy progression. We previously identified that GAS5 inhibited tumor development by suppressing proliferation of tumor cells in non-small cell lung cancer (NSCLC). Herein, we discovered a tumor-suppressing role for tumor cell-derived GAS5 in regulating tumor microenvironment. GAS5 positively coordinated with the infiltration of macrophages and T cells in NSCLC clinically, and overexpression of GAS5 promoted macrophages and T cells recruitment both in vitro and in vivo. Mechanistically, GAS5 stabilized p53 by directly binding to MYBBP1A and facilitating MYBBP1A-p53 interaction, and enhanced p53-mediated transcription of IRF1, which activated type I interferon signaling and increased the production of downstream CXCL10 and CCL5. We also found that activation of type I interferon signaling was associated with better immunotherapy efficacy in NSCLC. Furthermore, the stability of GAS5 was regulated by NAT10, the key enzyme responsible for N4-acetylcytidine (ac4C) modification, which bound to GAS5 and mediated its ac4C modification. Collectively, tumor cell-derived GAS5 could activate type I interferon signaling via the MYBBP1A-p53/IRF1 axis, promoting immune cell infiltration and potentially correlating with immunotherapy efficacy, which suppressed NSCLC progression. Our results suggested GAS5 as a promising predictive marker and potential therapeutic target for combination therapy in NSCLC. A schematic diagram demonstrating the regulatory effect of GAS5 on immune cell infiltration by activating type I interferon signaling via MYBBP1A-p53/IRF1 axis in non-small cell lung cancer. IFN, interferon.

Abstract Background The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. Methods HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan–Meier method was utilised to analyse progression-free survival (PFS). Results This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5–22.1) versus 9.2 months (95% CI: 7.5–13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4–18.2) versus 22.2 months (95% CI: 18.3–NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9–NA) versus 8.3 months (95% CI: 6.7–13.8)]. Conclusions HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. Trial registration NCT03534453. Registered at May 23, 2018.

Abstract Background Esophageal cancer brings emotional changes, especially anxiety to patients. Co-existing anxiety makes the surgery difficult and may cause complications. This study aims to evaluate effects of anxiety in postoperative complications of esophageal cancer patients with chronic obstructive pulmonary disease (COPD). Methods Patients with esophageal cancer and co-existing COPD underwent tumor excision. Anxiety was measured using Hospital Anxiety and Depression Scale (HAD) before surgery. Clavien-Dindo criteria were used to grade surgical complications. A multiple regression model was used to analyze the relationship between anxiety and postoperative complications. The chi-square test was used to compare the differences in various types of complications between the anxiety group and the non-anxiety group. A multinomial logistic regression model was used to analyze the influencing factors of mild and severe complications. Results This study included a total of 270 eligible patients, of which 20.7% had anxiety symptoms and 56.6% experienced postoperative complications. After evaluation by univariate analysis and multivariate logistic regression models, the risk of developing complications in anxious patients was 4.1 times than non-anxious patients. Anxious patients were more likely to develop pneumonia, pyloric obstruction, and arrhythmia. The presence of anxiety, surgical method, higher body mass index (BMI), and lower preoperative oxygen pressure may increase the incidence of minor complications. The use of surgical methods, higher COPD assessment test (CAT) scores, and higher BMI may increase the incidence of major complications, while anxiety does not affect the occurrence of major complications (P = 0.054). Conclusion Preoperative anxiety is associated with postoperative complications in esophageal cancer patients with co-existing COPD. Anxiety may increase the incidence of postoperative complications, especially minor complications in patient with COPD and esophageal cancer.

Abstract Background Lung adenocarcinoma metastasizing to the brain results in a notable increase in patient mortality. The high incidence and its impact on survival presents a critical unmet need to develop an improved understanding of its mechanisms. Methods To identify genes that drive brain metastasis of tumor cells, we collected cerebrospinal fluid samples and paired plasma samples from 114 lung adenocarcinoma patients with brain metastasis and performed 168 panel-targeted gene sequencing. We examined the biological behavior of PMS2 (PMS1 Homolog 2)-amplified lung cancer cell lines through wound healing assays and migration assays. In vivo imaging techniques are used to detect fluorescent signals that colonize the mouse brain. RNA sequencing was used to compare differentially expressed genes between PMS2 amplification and wild-type lung cancer cell lines. Results We discovered that PMS2 amplification was a plausible candidate driver of brain metastasis. Via in vivo and in vitro assays, we validated that PMS2 amplified PC-9 and LLC lung cancer cells had strong migration and invasion capabilities. The functional pathway of PMS2 amplification of lung cancer cells is mainly enriched in thiamine, butanoate, glutathione metabolism. Conclusion Tumor cells elevated expression of PMS2 possess the capacity to augment the metastatic potential of lung cancer and establish colonies within the brain through metabolism pathways.

Abstract Background Metabolic disorders (MetDs) have been demonstrated to be closely linked to numerous diseases. However, the precise association between MetDs and pulmonary tuberculosis (PTB) remains poorly understood. Method Summary statistics for exposure and outcomes from genome-wide association studies (GWASs) for exposures and outcomes were obtained from the BioBank Japan Project (BBJ) Gene–exposure dataset. The 14 clinical factors were categorized into three groups: metabolic laboratory markers, blood pressure, and the MetS diagnostic factors. The causal relationship between metabolic factors and PTB were analyzed using two-sample Mendelian Randomization (MR). Additionally, the direct effects on the risk of PTB were investigated through multivariable MR. The primary method employed was the inverse variance-weighted (IVW) model. The sensitivity of this MR analysis was evaluated using MR-Egger regression and the MR-PRESSO global test. Results According to the two-sample MR, HDL-C, HbA1c, TP, and DM were positively correlated with the incidence of active TB. According to the multivariable MR, HDL-C (IVW: OR 2.798, 95% CI 1.484–5.274, P = 0.001), LDL (IVW: OR 4.027, 95% CI 1.140–14.219, P = 0.03) and TG (IVW: OR 2.548, 95% CI 1.269–5.115, P = 0.009) were positively correlated with the occurrence of PTB. TC (OR 0.131, 95% CI 0.028–0.607, P = 0.009) was negatively correlated with the occurrence of PTB. We selected BMI, DM, HDL-C, SBP, and TG as the diagnostic factors for metabolic syndrome. DM (IVW, OR 1.219, 95% CI 1.040–1.429 P = 0.014) and HDL-C (IVW, OR 1.380, 95% CI 1.035–1.841, P = 0.028) were directly correlated with the occurrence of PTB. Conclusions This MR study demonstrated that metabolic disorders, mainly hyperglycemia, and dyslipidemia, are associated with the incidence of active pulmonary tuberculosis.

Abstract Tunnel cracks are thin and narrow linear targets, and their pixel proportions in images are usually very low, less than 6%; therefore, a method is needed to better detect small crack targets. In this study, a crack detection method based on crack characteristics and an anchor-free framework is investigated. First, the characteristics of cracks are analyzed to obtain the real crack texture, interference noise texture, and targets appearing near each crack as the context information for the model to filter and remove noise. We discuss the crack detection performance of anchor-based and anchor-free algorithms. Then, an optimized anchor-free algorithm is proposed in this paper for crack detection. Based on the advantages of YOLOX-x, we add a semantic enhancement module to better use contextual information. The experimental results show that the anchor-free algorithm performs slightly better than other algorithms in crack detection situations. In addition, the proposed method displays better detection performance for slender and inconspicuous cracks, with an average precision of 0.858.