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IntroductionThe gut microbiota, T cell subsets, and cytokines participate in tuberculosis (TB) pathogenesis. To date, the mechanisms by which these factors interactively promote TB development at different time points remain largely unclear. In the context of this study, We looked into the microorganisms in the digestive tract, T cell types, and cytokines related to tuberculosis.MethodsAccording to QIIME2, we analyzed 16SrDNA sequencing of the gut microbiome on the Illumina MiSeq. Enzyme-linked immunosorbent assay was used to measure the concentrations of cytokines.ResultsWe showed the presence of 26 identifiable differential microbiomes in the gut and 44 metabolic pathways between healthy controls and the different time points in the development of TB in patients. Five bacterial genera (Bacteroides, Bifidobacterium, Faecalibacterium, Collinsella, and Clostridium) were most closely associated with CD4/CD8, whereas three bacterial taxa (Faecalibacterium, Collinsella, and Clostridium) were most closely associated with CD4. Three bacterial taxa (Faecalibacterium, Ruminococcus, and Dorea) were most closely associated with IL-4. Ruminococcus was most closely associated with IL-2 and IL-10.ConclusionDiverse microorganisms, subsets of T cells, and cytokines, exhibiting varying relative abundances and structural compositions, were observed in both healthy controls and patients throughout distinct phases of tuberculosis. Gaining insight into the function of the gut microbiome, T cell subsets, and cytokines may help modulate therapeutic strategies for TB.

Previous studies have shown that early-life exposure to fine particulate matter (PM2.5) is associated with an increasing risk of autism spectrum disorder (ASD), however, the specific sensitive period of ASD is unknown. Here, a model of dynamic whole-body concentrated PM2.5 exposure in pre- and early-postnatal male offspring rats (MORs) was established. And we found that early postnatal PM2.5 exposed rats showed more typical ASD behavioral characteristics than maternal pregnancy exposure rats, including poor social interaction, novelty avoidance and anxiety disorder. And more severe oxidative stress and inflammatory responses were observed in early postnatal PM2.5 exposed rats. Moreover, the expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN) was down-regulated and the ratios of p-PI3K/PI3K and p-AKT/AKT were up-regulated in early postnatal PM2.5 exposed rats. This study suggests that early postnatal exposure to PM2.5 is more susceptible to ASD-like phenotype in offspring than maternal pregnancy exposure and the activation of PI3K-AKT signaling pathway may represent underlying mechanisms.

Objective: Deltamethrin (DLM) is a commonly used insecticide, which is harmful to many organs. Here, we explored the effects of chronic low-dose DLM residues on colon tissue and its potential mechanism. Methods: The mice were given long-term low-dose DLM by intragastric administration, and the body weights and disease activity index (DAI) scores of the mice were regularly recorded. The colon tissues were then collected for hematoxylin-eosin, immunofluorescence and immunohistochemistry staining. Besides, the RNA sequencing was performed to explore the potential mechanism. Results: Our results showed that long-term exposure to low-dose DLM could cause inflammation in mice colon tissue, manifested as weight loss, increased DAI score, increased apoptosis of colonic epithelial cells, and increased infiltration of inflammatory cells. However, we observed that after long-term exposure to DLM and withdrawal for a period of time, although apoptosis was restored, the recovery of colon inflammation was not ideal. Subsequently, we performed RNA sequencing and found that long-term DLM exposure could lead to the senescence of some cells in mice colon tissue. The results of staining of cellular senescence markers in colon tissue showed that the level of cellular senescence in the DLM group was significantly increased, and the p53 signalling related to senescence was also significantly activated, indicating that cellular senescence played a key role in DLM-induced colitis. We further treated mice with quercetin (QUE) after long-term DLM exposure, and found that QUE could indeed alleviate DLM-induced colitis. In addition, we observed that long-term accumulation of DLM could aggravate DSS-induced colitis in mice, and QUE treatment could reverse this scenario. Conclusion: Continuous intake of DLM caused chronic colitis in mice, and the inflammation persisted even after discontinuation of DLM intake. This was attributed to the induction of cellular senescence in colon tissue. Treatment with QUE alleviated DLM-induced colitis by reducing cellular senescence. Long-term DLM exposure also aggravated DSS-induced colitis, which could be mitigated by QUE treatment.

Chinese coal reservoirs are characterized by “Three High and One Low”, and the pore structure of coal is an important factor affecting the permeability, the degree of drainage difficulty and the subsequent drainage mode. In order to accurately characterize the full scale pore size structure of coal, three methods of high pressure mercury injection, low temperature liquid nitrogen and carbon dioxide adsorption are used. Based on the compressibility correction of the high pressure mercury injection experimental data, combined with the fractal theory, the dominant pore size characterization sections of different experimental methods are analyzed, and the full scale joint characterization of 10 groups of coal samples in Yunnan Laochang mining area is realized. The results show that: The compression coefficient of coal matrix ranges from 7.06179×10−11 to 1.23531×10−10 m2/N, and the cumulative mercury intake after correction is reduced by 15.89% ～ 27.82% compared with that before correction, with an average of 21.65%. The coal matrix begins to be compressed when the mercury injection pressure reaches 0.7 MPa. Irreversible damage occurs when the mercury injection pressure reaches 14.3 MPa. In the liquid nitrogen adsorption experiment, the pore volume increases gradually with the increase of the pore size on the whole, the pore area tends to be stable and the adsorption volume is small, and the pore adsorption rate is the fastest. The overall rate decreases with the increase of the pore size. The adsorption volume curve and differential curve of carbon dioxide adsorption experiment stage are basically consistent, and the pore volume decreases with the increase of pore size. The mercury injection fractal curve can be divided into three sections. When lgPi > 1.1, the fractal dimension reaches the maximum, and the coal matrix suffers irreversible compression failure. The low temperature liquid nitrogen adsorption fractal curve takes Pj/Ps =0.5 as the boundary line. The fractal dimension of 2−5 nm pore size is between 1.93−2.92, with an average value of 2.57. The fractal dimension of 5−100 nm pore diameter is 2.16−2.76, with an average value of 2.49, indicating strong heterogeneity. Based on the three experimental results, with 1.5nm and 100nm as the splicing points, the coal samples are dominated by micropores with pore sizes ranging from 0.41nm to 0.86nm, with the largest proportion of pore volume.

Objective Syringomyelia is a common central nervous system disease characterized by the dilation of the central canal (CC). Regarding the pathogenesis of syringomyelia, cerebrospinal fluid (CSF) circulation obstruction in the subarachnoid space (SAS) of the spinal cord has been widely accepted. However, clinical and animal studies on obstructing the CSF in SAS failed to form syringomyelia, challenging the theory of SAS obstruction. The precise pathogenesis remains unknown. Methods We utilized an extradural compression rat model to investigate the pathogenesis underlying syringomyelia. Magnetic resonance imaging enabled detection of syringomyelia formation. To assess CSF flow within the SAS, Evans blue was infused into the cisterna magna. Histological analysis allowed morphological examination of the CC. Furthermore, CSF flow through the CC was traced using Ovalbumin Alexa-Flour 647 conjugate (OAF-647). Scanning electron microscopy (SEM) enabled visualization of ependymal cilia. Results The findings showed that the dura mater below the compression segment exhibited lighter coloration relative to the region above the compression, indicative of partial obstruction within the SAS. However, the degree of SAS occlusion did not significantly differ between syringomyelia (SM-Y group) and those without (SM-N group). Intriguingly, hematoxylin and eosin staining and CSF tracing revealed occlusion of the CC accompanied by reduced CSF flow in the SM-Y group compared to SM-N and control groups. SEM images uncovered impairment of ependymal cilia inside the syringomyelia. Conclusion CC occlusion may represent a physiological prerequisite for syringomyelia formation, while SAS obstruction serves to initiate disease onset. The impairment of ependymal cilia appears to facilitate progression of syringomyelia.

The skin, being the largest organ in the human body, plays a vital role in shielding internal organs from external physical and chemical factors. However, skin damage caused by various factors such as injuries, surgeries, diabetes, or burns can lead to wounds that diminish the skin's protective function. Monitoring essential physiological parameters like temperature, moisture, and pH is crucial to facilitate antibiotic treatment, remote physician monitoring, patient comfort, cost reduction, and prevention of hospital-acquired infections. To this end, innovative wound coverings made of biological materials like gelatin, carboxymethyl chitosan, and titanium nanoparticles have been developed, mainly for hospital and pediatric applications. These wound coverings come equipped with sensors to monitor temperature, pH, and moisture and are suitable for pediatric hospitals where children experience difficulty in wound healing due to their sensitive skin. The temperature monitoring feature allows physicians to accurately assess the wound's temperature, detect potential infections, and take prompt actions. These wound coverings can significantly enhance wound treatment for patients, as real-time monitoring of physiological parameters enables informed decision-making by physicians, leading to better therapeutic outcomes. Furthermore, the use of these wound coverings can minimize the risk of hospital-acquired infections. Their adaptability and flexibility make them ideal for various wound types and sizes, ensuring patient comfort and compliance with the treatment plan. In conclusion, the development of innovative and flexible wound coverings using biological materials and equipped with sensors represents a significant breakthrough in wound management. The use of these wound coverings has the potential to revolutionize wound care and improve patient outcomes, particularly in pediatric hospitals where wound healing is often challenging.

Abstract The relationship between Needle Track Bleeding (NTB) and the occurrence of postoperative immediate pneumothorax remains unclear. In our cross-sectional study, we conducted a retrospective collected of data from 674 consecutive patients who underwent CT-guided percutaneous transthoracic lung biopsies between 2019 and 2022. A logistic regression model was employed to explore the association between NTB and postoperative immediate pneumothorax, and restricted cubic spline curves was used to investigate the link and its explicit curve shape. A sensitivity analysis was performed by transforming the continuous NTB into categorical variable and calculated an E-value. A total of 453 participants (47.90% male) were included in our analysis. The postoperative immediate pneumothorax rate was 41.05% (186/453). We found a negative correlation between NTB and postoperative immediate pneumothorax (OR = 0.91, 95%CI 0.88–0.95) after adjusting for confounding factors. This relationship was nonlinear, with a key inflection point at NTB of 8 mm. No significant link was noted for NTB > 8 mm (OR = 0.98, 95%CI 0.95–1.02), while a protective association was observed for NTB ≤ 8 mm (OR = 0.74, 95%CI 0.66–0.81). NTB showed a nonlinear, protective correlation with postoperative immediate pneumothorax. However, when NTB exceeded 8 mm, the protective association was not observed.

Abstract Injection-production operation parameters, the minimum injection gas pressure (IGP: operation pressure), IGP interval, minimum IGP residence time, and injection-production cycle of the underground salt rock gas storage under long-term operation, affect not only the capacity and working ability of a salt cavern but also be crucial to the safety and stability of the surrounding rock. A 3D geo-mechanical model of the salt cavern is established to study the stability of the storage in the operation period. The deformation, expansion safety factor, volume shrinkage, and plastic zone are comprehensively considered for predicting the feasibility and stability of the salt cavern. The stability of the surrounding rock of the cavern with different injection-production parameters and the impact of each parameter on the stability of the cavern during operating are systematically investigated. The results indicate that the displacement, the expansion coefficient of the surrounding rock, and the volume shrinkage rate of the salt cavern reduces significantly with the increment of IGP interval and minimum IGP, while they increases with raising the minimum IGP residence time and injection-production cycle. With the continuous operation of the cavity, the displacement and the volume shrinkage rate enhances significantly year by year with the augment of operation parameters, moreover, their value show a fluctuating upward trend with the alternation of the gas injection and the production. The volume of the plastic zone is enlarged with the increment of the IGP interval, minimum IGP, and injection-production cycle, while it reduces with the extension of the minimum IGP residence time. The variation becomes remarkably with the augment of parameters. The sensitivity coefficients of each injection-production operation parameter are ranked, from large to small, as follows: IGP interval, minimum IGP, minimum IGP residence time, injection-production cycle. The results can offer beneficial reference for effectively optimize the injection-production parameters, so as to provide technical guidance for ensuring the stability of the storage and meeting requirements for the storage capacity.

Abstract Objective The aim of the present study was to explore the prognostic role of γδ T cells in colorectal cancer, and establish a nomogram for predicting the survival of the patients. Methods Immunohistochemistry was performed to analyze the infiltration degree of γδ T cells in tumor and normal tissues of colorectal cancer. The relationship between γδ T cells infiltration in tumor tissues and the prognosis of patients with colorectal cancer were determined by Cox regression analysis and survival analysis. R software was used to establish and verify a nomogram for predicting the prognosis of patients with colorectal cancer. Results The degree of γδ T cell infiltration in tumor tissues and normal tissues of CRC was not different (t = 0.35, P = 0.73). However, the infiltration of γδ T cell was related to the survival status of the patients (x 2 = 4.88, P = 0.03). Besides, the infiltrating degree of γδ T cells in tumor tissue was obviously related to the prognostic improvement of the patients with colorectal cancer (log-rank P = 0.02) and could reflect the benefit of adjuvant chemotherapy. The nomogram based on tumor diameter, tumor location, AJCC stage, chemotherapy, serum CEA level and γδ T cell infiltration was established and could provide a reference for predicting the survival of colorectal cancer patients. Conclusion γδ T cell infiltration degree in tumor tissue was an important factor to improve the outcome of patients with colorectal cancer, and can predict the benefit of adjuvant chemotherapy.

Abstract Background About 10% of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations are harbored as uncommon mutations. This study aimed to explore the efficacy and safety of dacomitinib, a second-generation EGFR tyrosine kinase inhibitor (EGFR-TKIs), in treating uncommon EGFR-mutated advanced NSCLC. Methods Treatment-naïve advanced NSCLC patients treated with dacomitinib at Hunan Cancer Hospital with uncommon EGFR mutations were evaluated. The primary endpoint was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Result Between December 2019 and December 2021, a total of 16 patients was included. Median PFS was 14.0 (95% CI 4.32–23.7) months, and median OS was not reached. ORR was 68.8% (95% CI 41.3 to 89.0%) and DCR was 93.8% (95%CI 69.8 to 99.8%), including three achieving complete remission (CR) and eight achieving partial remission (PR). Median PFS for patients with brain metastasis was 9.0 (95%CI 6.9 to 11.1) months. Intracranial ORR was 100%, including 2 CR and 4 PR. Major treatment-related adverse events (TRAEs) included rash (87.5%), paronychia (62.5%), oral ulcers (50.0%), and diarrhea (50.0%), none of which were ≥ grade 3 TRAEs. Conclusions Dacomitinib showed good activity and manageable toxicity in NSCLC patients with uncommon EGFR mutations.

During field surveys and culture procedures, large growth disparities in Anguilla japonica have been observed. However, the potential causes are unknown. This study explored differences in digestive ability, metabolic levels, and transcriptomic profiles of appetite-related genes between growth-retarded eel (GRE) and normal-growing eel (NGE) under the same rearing conditions. The results showed that growth hormone (gh) mRNA expression in GREs was considerably lower than NGEs. The levels of total protein (TP), total cholesterol (T-CHO), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood ammonia (BA), blood urea nitrogen (BUN), and alkaline phosphatase (ALP) in GREs were significantly lower than in NGEs. Conversely, levels of glucose (GLU), alanine aminotransferase (ALT), and aspartate transaminase (AST) were higher in GREs. The activities of SOD, CAT, and T-AOC levels were also significantly lower in GREs, as were the activities of glucose-related enzymes including hexokinase (HK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6PASE). Additionally, orexigenic genes (npy and ghrelin) were dramatically downregulated, whereas anorexigenic genes (crh and pyy) were significantly upregulated in GREs. These findings suggested that variances in growth hormone, metabolic activities, and appetite level could be associated with the different growth rates of A. japonica. The present research not only revealed the characteristics of the growth, metabolism, and appetite of GREs but also offered new perspectives into the substantial growth discrepancies in A. japonica, providing novel ideas for enhancing fish growth.

Self-supervised learning has made significant progress in point cloud processing. Currently, the primary tasks of self-supervised learning, which include point cloud reconstruction and representation learning, are trained separately due to their structural differences. This separation inevitably leads to increased training costs and neglects the potential for mutual assistance between tasks. In this paper, a self-supervised method named PointUR-RL is introduced, which integrates point cloud reconstruction and representation learning. The method features two key components: a variable masked autoencoder (VMAE) and contrastive learning (CL). The VMAE is capable of processing input point cloud blocks with varying masking ratios, ensuring seamless adaptation to both tasks. Furthermore, CL is utilized to enhance the representation learning capabilities and improve the separability of the learned representations. Experimental results confirm the effectiveness of the method in training and its strong generalization ability for downstream tasks. Notably, high-accuracy classification and high-quality reconstruction have been achieved with the public datasets ModelNet and ShapeNet, with competitive results also obtained with the ScanObjectNN real-world dataset.

Flexible thermoelectric materials have drawn significant attention from researchers due to their potential applications in wearable electronics and the Internet of Things. Despite many reports on these materials, it remains a significant challenge to develop cost-effective methods for large-scale, patterned fabrication of materials that exhibit both excellent thermoelectric performance and remarkable flexibility. In this study, we have developed an Ag2Se-based ink with excellent printability that can be used to fabricate flexible thermoelectric films by screen printing and low-temperature sintering. The printed films exhibit a Seebeck coefficient of −161 μV/K and a power factor of 3250.9 μW/m·K2 at 400 K. Moreover, the films demonstrate remarkable flexibility, showing minimal changes in resistance after being bent 5000 times at a radius of 5 mm. Overall, this research offers a new opportunity for the large-scale patterned production of flexible thermoelectric films.

Voltage source inverters are extensively used in the grid connection of renewable energy-sourced generators, and multilevel converters, in particular, have attracted a great deal of attention in recent years. This paper investigates the application of a novel passivity-based sliding mode (PSM) control scheme on three-level grid-tie active Neutral-Point-Clamped (ANPC) inverters that yield fast and stable responses to grid impedance variations. Simulation studies confirm that this control scheme can produce high tracking performance and is also robust against grid load variations. Furthermore, to enhance ANPC efficiency, the loss distribution of switching devices controlled by the proposed strategy is evaluated. An optimal scheme is finally proposed for allocating silicon and Wide-Band-Gap switching devices, resulting in a hybrid ANPC inverter capable of achieving a desirable trade-off between the power losses and the device cost.

Potential inconsistencies between the goals of unsupervised representation learning and clustering within multi-stage deep clustering can diminish the effectiveness of these techniques. However, because the goal of unsupervised representation learning is inherently flexible and can be tailored to clustering, we introduce PointStaClu, a novel single-stage point cloud clustering method. This method employs stable cluster discrimination (StaClu) to tackle the inherent instability present in single-stage deep clustering training. It achieves this by constraining the gradient descent updates for negative instances within the cross-entropy loss function, and by updating the cluster centers using the same loss function. Furthermore, we integrate entropy constraints to regulate the distribution entropy of the dataset, thereby enhancing the cluster allocation. Our framework simplifies the process, employing a single loss function and an encoder for deep point cloud clustering. Extensive experiments on the ModelNet40 and ShapeNet dataset demonstrate that PointStaClu significantly narrows the performance gap between unsupervised point cloud clustering and supervised point cloud classification, presenting a novel approach to point cloud classification tasks.

Male infertility has emerged as a global issue, partly attributed to psychological stress. However, the cellular and molecular mechanisms underlying the adverse effects of psychological stress on male reproductive function remain elusive. We created a psychologically stressed model using terrified-sound and profiled the testes from stressed and control rats using single-cell RNA sequencing. Comparative and comprehensive transcriptome analyses of 11,744 testicular cells depicted the cellular landscape of spermatogenesis and revealed significant molecular alterations of spermatogenesis suffering from psychological stress. At the cellular level, stressed rats exhibited delayed spermatogenesis at the spermatogonia and pachytene phases, resulting in reduced sperm production. Additionally, psychological stress rewired cellular interactions among germ cells, negatively impacting reproductive development. Molecularly, we observed the down-regulation of anti-oxidation-related genes and up-regulation of genes promoting reactive oxygen species (ROS) generation in the stress group. These alterations led to elevated ROS levels in testes, affecting the expression of key regulators such as ATF2 and STAR, which caused reproductive damage through apoptosis or inhibition of testosterone synthesis. Overall, our study aimed to uncover the cellular and molecular mechanisms by which psychological stress disrupts spermatogenesis, offering insights into the mechanisms of psychological stress-induced male infertility in other species and promises in potential therapeutic targets.

BackgroundHepatitis B surface antigen (HBsAg) clearance is associated with improved long-term outcomes and reduced risk of complications. The aim of our study was to identify the effects of levels of HBsAg in HCC patients undergoing TACE and sequential ablation. In addition, we created a nomogram to predict the prognosis of HCC patients with high levels of HBsAg (≥1000U/L) after local treatment.MethodThis study retrospectively evaluated 1008 HBV-HCC patients who underwent TACE combined with ablation at Beijing Youan Hospital and Beijing Ditan Hospital from January 2014 to December 2021, including 334 patients with low HBsAg levels and 674 patients with high HBsAg levels. The high HBsAg group was divided into the training cohort (N=385), internal validation cohort (N=168), and external validation cohort (N=121). The clinical and pathological features of patients were collected, and independent risk factors were identified using Lasso-Cox regression analysis for developing a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves in the training and validation cohorts. Patients were classified into high-risk and low-risk groups based on the risk scores of the nomogram.ResultAfter PSM, mRFS was 28.4 months (22.1-34.7 months) and 21.9 months (18.5-25.4 months) in the low HBsAg level and high HBsAg level groups (P

IntroductionThere are three main types of culture in human society, namely, individual-oriented, relationship-oriented and social-oriented cultures. In history, there are two main positions on the relationship between culture and self-construal: the cultural determinist position and the interaction position. After analyzing literature critically, we propose that the interaction position is more persuasive than the cultural determinist position. A self-construal model was constructed from an interactionist and polycultural perspective, pointing out the relationship between three cultures and self-construal. We argue that individuals interacting with cultures in the context of globalization can develop a more integrated self-construal. The present study proposes the existence of polycultural self-construal, and aimed to explore how self-construal factors relate to cultures.MethodsThree approaches—psychological tests, priming with cultural icons and content analysis—were used to explore mechanisms between cultures (individual-oriented, relationship-oriented, and social-oriented cultures) and self-construal. In Study 1, we recruited 460 undergraduate students as participants through campus advertising to complete three psychological tests, namely, the Cultural Identity Scale (CIS), the Marlowe-Crowne Social Approval Scale (MC-SDS), and the Polycultural Self-construal Scale (PSCS). In Study 2, we created icon materials that could prime the three cultures. The experimental process was divided into two stages: priming and measurement. First, 165 participants were presented with icon materials on the computer screen to activate the corresponding culture, and then they were asked to complete the PSCS. In Study 3, the experimental procedures were followed as for Study 2. Then the Ten Statements Test (TST) was used. Each of the 178 participants gave 10 different responses to the question of “Who am I?.” Each participant’s “I am …” narratives were qualitatively processed using content analysis.ResultsThe individual-oriented culture mainly affects the individuality and equality factor of self-construal. The relationship-oriented culture mainly impacts the relationality factor of self-construal, while the social-oriented culture mainly affects the collectivity and equality factors of self-construal. There were no significant differences in the effects of the three cultures on the autonomy factor of self-construal. The multi-components of the polycultural self-construal are difficult to interpret based on one culture type. All three cultures have specific and shared effects on human self-construal.

ABSTRACT CRF01_AE strains have been shown to form multiple transmission clusters in China, and some clusters have disparate pathogenicity in Chinese men who have sex with men. This study focused on other CRF01_AE clusters prevalent in heterosexual populations. The CD4+ T-cell counts from both cross-section data in National HIV Molecular Epidemiology Survey and seropositive cohort data were used to evaluate the pathogenicity of the CRF01_AE clusters and other HIV-1 sub-types. Their mechanisms of pathogenicity were evaluated by co-receptor tropisms, predicted by genotyping and confirmed with virus isolate phenotyping, as well as inflammation parameters. Our research elucidated that individuals infected with CRF01_AE clusters 1 and 2 exhibited significantly lower baseline CD4+ T-cell counts and greater CD4+ T-cell loss in cohort follow-up, compared with other HIV-1 sub-types and CRF01_AE clusters. The increased pathogenesis of cluster 1 or 2 was associated with higher CXCR4 tropisms, higher inflammation/immune activation, and increased pyroptosis. The protein structure modeling analysis revealed that the envelope V3 loop of clusters 1 and 2 viruses is favorable for CXCR4 co-receptor usage. Imbedded with the most mutating reverse transcriptase, HIV-1 is one of the most variable viruses. CRF01_AE clusters 1 and 2 have been found to have evolved into more virulent strains in regions with predominant heterosexual infections. The virulent strains increased the pressure for early diagnosis and treatment in HIV patients. To save more lives, HIV-1 surveillance systems should be upgraded from serology and genotyping to phenotyping, which could support precision interventions for those infected by virulent viruses.IMPORTANCERetroviruses swiftly adapt, employing error-prone enzymes for genetic and phenotypic evolution, optimizing survival strategies, and enhancing virulence levels. HIV-1 CRF01_AE has persistently undergone adaptive selection, and cluster 1 and 2 infections display lower counts and fast loss of CD4+ T cells than other HIV-1 sub-types and CRF01_AE clusters. Its mechanisms are associated with increased CXCR4 tropism due to an envelope structure change favoring a tropism shift from CCR5 to CXCR4, thereby shaping viral phenotype features and impacting pathogenicity. This underscores the significance of consistently monitoring HIV-1 genetic evolution and phenotypic transfer to see whether selection bias across risk groups alters the delicate balance of transmissible versus toxic trade-offs, since virulent strains such as CRF01_AE clusters 1 and 2 could seriously compromise the efficacy of antiviral treatment. Only through such early warning and diagnostic services can precise antiviral treatments be administered to those infected with more virulent HIV-1 strains.

Purpose: To investigate whether erythropoietin (EPO) can treat pulmonary arterial hypertension (PAH) in rats by regulating the differentiation and homing of bone marrow mesenchymal stem cells (BMSCs) through Notch1/Jagged signaling pathway. Materials & methods: BMSCs were isolated from the bone marrow of 6-week-old male SD rats by whole bone marrow method and identified. BMSCs were treated with 500 IU/mL EPO, and the proliferation, migration, invasion and differentiation ability, and the expression of MMP-2 and MMP-9 protein of BMSCs were detected in vitro. After the establishment of the pulmonary hypertension model in rats, BMSCs were intervened with different concentrations of EPO and injected into the rats through intravenous injection. The levels of TNF-α, IL-1β and IL-6 in lung tissue, the expression of SRY CXCR4, CCR2, Notch1 and Jagged protein in lung tissue, and the levels of TGF-α, vascular endothelial factor (VEGF), IGF-1 and HGF in serum were detected. Immunofluorescence (IF) staining was used to detect the co-localization of CD34. Results: EPO promoted the proliferation, migration, and invasion of BMSCs by inhibiting Notch1/Jagged pathway in vitro, and induced BMSCs to differentiate into vascular smooth muscle cells and vascular endothelial cells. EPO inhibited Notch1/Jagged pathway in PAH rats, induced BMSCs homing and differentiation, increased the levels of TGF-α, VEGF, IGF-1 and HGF, and decreased the levels of TNF-α, IL-1β and IL-6. Discussion & conclusion: EPO can inhibit the Notch1/Jagged pathway and promote the proliferation, migration, invasion, homing and differentiation of BMSCs to treat pulmonary hypertension in rats in vitro and in vivo.

BackgroundPeritoneal dialysis (PD) is a common treatment method for patients with renal failure. While peritonitis and tube floating migration are commonly observed complications, visceral perforation caused by PD is relatively rare. We present a case report of a patient undergoing PD due to renal failure, who encountered two instances of visceral perforation. In both occurrences, Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) played a pivotal role in providing accurate diagnoses and precise localization of the perforation sites. This report underscores the paramount significance of SPECT/CT in diagnosing visceral perforations in the context of PD.Case presentationA 73-year-old elderly male has been undergoing PD for 1 year due to renal failure. Recently, there has been impaired drainage of the PD catheter. The clinical team suspected the occurrence of peritonitis. The patient underwent a 99mTc Sodium Pertechnetate (99mTc-NaTcO4) SPECT/CT examination, which identified intestinal perforation. After 20 days of conservative treatment, a SPECT/CT follow-up examination revealed the resolution of the intestinal perforation, but a new bladder perforation emerged. The dialysis catheter was methodically and gradually withdrawn in stages while simultaneously performing bladder decompression. Following these interventions, the patient remained free from peritonitis and cystitis.ConclusionThe utilization of SPECT/CT proved to be highly valuable in the accurate diagnosis of visceral perforation, a relatively rare complication observed in PD patients.

The performance of on-orbit GaAs-based solar cells is susceptible to the displacement damage effect. The proton-induced primary displacement damage in GaAs on a geosynchronous equatorial orbit (GEO) was simulated and analyzed by combining the Monte Carlo (MC) and molecular dynamics (MD) methods. The MC simulation provided the distribution of primary knock-on atoms (PKAs) in GaAs induced by GEO-related protons to the MD simulation. In MD simulations, the effects of radiation fluence and ambient temperature on the displacement damage were considered. The simulation results showed that GEO-related protons generated a significant number of PKAs within an energy range of below 10 keV in GaAs. The high-fluence radiation emulated by the binary PKA could generate more point defects and cluster defects in GaAs than the low-fluence radiation emulated by single PKAs. As compared to room temperature (300 K), both a low (100 K) and high (500 K) ambient temperature could deteriorate the displacement damage. In addition, a high ambient temperature of 500 K could induce widespread thermal spikes in GaAs as compared to 100 and 300 K. This work can provide useful insight into the proton-induced displacement damage in GaAs and the radiation hardening of GaAs-based photoelectric devices in space.

BackgroundCrohn’s disease (CD) is a non-specific chronic inflammatory disease of the gastrointestinal tract and is a phenotype of inflammatory bowel disease (IBD). The current study sought to compile the resting-state functional differences in the brain between CD patients and healthy controls.MethodsThe online databases PubMed, Web of Science Core, and EMBASE were used to find the published neuroimage studies. The search period was from the beginning through December 15, 2023. The predetermined inclusion and exclusion criteria allowed for the identification of the studies. The studies were assembled by two impartial reviewers, who also assessed their quality and bias.ResultsThis review comprised 16 resting-state fMRI studies in total. The included studies generally had modest levels of bias. According to the research, emotional processing and pain processing were largely linked to increased or decreased brain activity in patients with CD. The DMN, CEN, and limbic systems may have abnormalities in patients with CD, according to research on brain networks. Several brain regions showed functional changes in the active CD group compared to the inactive CD group and the healthy control group, respectively. The abnormalities in brain areas were linked to changes in mood fluctuations (anxiety, melancholy) in patients with CD.ConclusionFunctional neuroimaging helps provide a better understanding of the underlying neuropathological processes in patients with CD. In this review, we summarize as follows: First, these findings indicate alterations in brain function in patients with CD, specifically affecting brain regions associated with pain, emotion, cognition, and visceral sensation; second, disease activity may have an impact on brain functions in patients with CD; and third, psychological factors may be associated with altered brain functions in patients with CD.

PurposeTo evaluate the characteristic of blood supply of liver portal vein tumor thrombus (PVTT) using perfusion indexes and spectral parameters.MethodsBetween July 2020 and December 2022, the study enrolled 25 liver cancer patients completed with PVTT (male=20, female=5; age 41-74 years (59.48 ± 9.12)) from the Interventional Department of Jiangsu Cancer Hospital. There were 11 cases of type III PVTT, 12 of type II PVTT, and 2 of type I PVTT (Cheng’s classification). All patients underwent spectral perfusion scans through dual-layer spectral detector computed tomography. The PVTTs were divided into proximal and distal groups based on the distance between the tumor thrombus and the main portal vein. The perfusion analysis was performed on the 120-kVp conventional images to generate hepatic perfusion index (HPI). The spectral based images (SBIs) during the artery and venous peak phases were extracted from the perfusion data. The iodine map and 40&100-keV virtual monoenergetic image (VMI) were generated from SBI data. HPI, iodine concentration (IC), CT value at 40 and 100-keV, and spectral slope (40-100keV) of the primary lesion, proximal and distal PVTT, and liver parenchyma were measured and compared. The correlation between the primary lesion and proximal and distal PVTT was analyzed.ResultsThe IC and spectral slope during the arterial and venous peak phases and HPI of the primary lesion, proximal PVTT, and distal PVTT were highly correlated (P

Summary: Background: Platinum-doublet chemotherapy plus immunotherapy has been the standard of care for the first-line treatment of advanced non-small cell lung cancer lacking actional driver mutations. However, optimization of drug combinations is still needed to find a better balance between therapeutic efficacy and safety in the immunotherapy era. We aimed to investigate the efficacy and safety of platinum-free albumin bound paclitaxel (nab-paclitaxel) combined with camrelizumab and apatinib as first-line treatment for patients with advanced lung adenocarcinoma. Methods: In this multicenter open-label, single-arm phase II trial, patients with systemic treatment-naïve advanced lung adenocarcinoma without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations received a rational-based combination of camrelizumab (200 mg intravenously, day one), apatinib (250 mg, q.d., five continuous days per week), and nab-paclitaxel (135 mg/m2 intravenously, days one and eight) every three weeks for four to six cycles in China. Patients with controlled disease were maintained with camrelizumab and apatinib. The primary end point was progression-free survival (PFS). This trial is registered with ClinicalTrials.gov (No. NCT04459078). Findings: Between August 26, 2020 and May 20, 2022, 64 patients were enrolled. The median PFS was 14.3 (95% CI: 9.9, not reached) months. The confirmed objective response rate was 64.1% (95% CI: 51.1, 75.7). The grade 3–4 hematologic treatment-related adverse events (TRAEs) were decreased neutrophil count (14.1%), decreased white blood cell count (7.8%), and anemia (3.1%). The most common non-hematologic TRAEs of grade 3–4 were increased alanine transaminase (18.8%) and aspartate transaminase (15.6%). No treatment-related death occurred. The quality of life was on average not clinically meaningful worse through treatment cycle 14. Interpretation: Nab-paclitaxel plus camrelizumab and apatinib showed clinically meaningful anti-tumor activity and manageable safety, with few hematologic toxicities, and might be a potential treatment option in patients with advanced lung adenocarcinoma lacking EGFR/ALK mutations. Funding: Heath Research Foundation of Chinese Society of Clinical Oncology, Hunan Provincial Natural Science Foundation of China, Hunan Cancer Hospital Climb Plan, Sister Institution Network Fund of The University of Texas MD Anderson Cancer Center, The Science and Technology Innovation Program of Hunan Province, and Suzhou Sheng Diya Biomedical Co., Ltd, a subsidiary of Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Shanghai, China).

Geosmin is an environmental pollutant that causes off-flavor in water and aquatic products. The high occurrence of geosmin contamination in aquatic systems and aquaculture raises public awareness, however, few studies have investigated the response pathways of geosmin stress on freshwater fish. In this research, grass carp were exposed to 50 μg/L geosmin for 96 h, liver tissue was sequenced and validated using real-time qPCR. In total of 528 up-regulated genes and 488 down-regulated genes were observed, includes cytochrome P450 and uridine diphosphate (UDP)-glucuronosyltransferase related genes. KEGG analysis showed that chemical carcinogenesis-DNA adducts, metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450 pathway was enriched. Common genes from the target genes of microRNAs and differential expression genes are enriched in metabolism of xenobiotics cytochrome P450 pathway. Two miRNAs (dre-miR-146a and miR-212–3p) down regulated their target genes (LOC127510138 and adh5, respectively) which are enriched cytochrome P450 related pathway. The results present that geosmin is genetoxic to grass carp and indicate that cytochrome P450 system and UDP-glucuronosyltransferase play essential roles in biotransformation of geosmin. MicroRNAs regulate the biotransformation of geosmin by targeting specific genes, which contributes to the development of strategies to manage its negative impacts in both natural and artificial environments.

Abstract Foundation models, often pre-trained with large-scale data, have achieved paramount success in jump-starting various vision and language applications. Recent advances further enable adapting foundation models in downstream tasks efficiently using only a few training samples, e.g., in-context learning. Yet, the application of such learning paradigms in medical image analysis remains scarce due to the shortage of publicly accessible data and benchmarks. In this paper, we aim at approaches adapting the foundation models for medical image classification and present a novel dataset and benchmark for the evaluation, i.e., examining the overall performance of accommodating the large-scale foundation models downstream on a set of diverse real-world clinical tasks. We collect five sets of medical imaging data from multiple institutes targeting a variety of real-world clinical tasks (22,349 images in total), i.e., thoracic diseases screening in X-rays, pathological lesion tissue screening, lesion detection in endoscopy images, neonatal jaundice evaluation, and diabetic retinopathy grading. Results of multiple baseline methods are demonstrated using the proposed dataset from both accuracy and cost-effective perspectives.

Graphene quantum dots (GQDs) have attracted great research interest due to their remarkable quantum confinement and edge effects. In addition to exhibiting stable photoluminescence, it also has many advantages such as low cytotoxicity, good solubility and chemical inertness, making it widely used in bioimaging, photocatalysts and sensors. The industrial development of GQDs has been seriously hampered by the expensive raw materials and tedious operation of traditional preparation methods. Coal and its derivatives not only possess the characteristics of low price and abundant reserves, but also show greater advantages than graphite, graphene, graphite oxide and other carbon materials in the preparation of GQDs due to its inherent internal disorder structure and small crystal domain. GQDs can be prepared by simply stripping the aromatic ring clusters inside the coal and its derivatives through physical, chemical or electrochemical methods. This review first summarizes the “top-down” synthesis method of coal-based graphene quantum dots (C-GQDs) and its pros and cons. Then the structural morphology, chemical composition, fluorescence properties of C-GQDs and their influencing factors are analyzed. Further, we describe the progress in applications of C-GQDs in fields such as sensors, bioimaging and energy Finally, the future development of C-GQDs is discussed from the perspectives of preparation methods, carbon source selection and research directions, and the following experimental schemes are proposed: (1) Experiment with H2O2 as oxidizer and thermally altered coals as carbon sources； (2) Experiments other than oxidation with sulfuric acid and nitric acid using superhigh organic sulfur coals as carbon sources； (3) Experiment on coal macerals as a carbon sources. In addition, the combination of experimentally derived basic data and computer simulation technology can solve the problems of current research such as single fluorescence color and low quantum yield. The goals of clean utilization of coal resources and green development of GQDs have been achieved.

Abstract Background Large-scale medical equipment, which is extensively implemented in medical services, is of vital importance for diagnosis but vulnerable to various anomalies and failures. Most hospitals that conduct regular maintenance have been suffering from medical equipment-related incidents for years. Currently, the Internet of Medical Things (IoMT) has emerged as a crucial tool in monitoring the real-time status of the medical equipment. In this paper, we develop an IoMT system of Computed Tomography (CT) equipment in the West China Hospital, Sichuan University and collected the system status time-series data. Novel multivariate time-series classification models and frameworks are proposed to predict the anomalies of CT equipment. The important features that are closely related to the equipment anomalies are identified with the model. Methods We extracted the real-time CT equipment status time-series data of 11 equipment between May 19, 2020 and May 19, 2021 from the IoMT, which includes the equipment oil temperature, anode voltage, etc. The arcs are identified as labels of anomalies due to their relationship with decreased imaging quality and CT equipment failures. To improve prediction accuracy, the statistics and transformations of the raw historical time-series data segment in the sliding time window are used to construct new features. Due to the particularity of time-series data, two frameworks are proposed for splitting the training and test sets. Then the Decision Tree, Support Vector Machine, Logistic Regression, Naive Bayesian, and K-Nearest Neighbor classification models are used to classify the system status. We also compare our model to state-of-the-art models. Results The results show that the anomaly prediction accuracy and recall of our method are 79% and 77%, respectively. The oil temperature and anode voltage are identified as the decisive features that may lead to anomalies. The proposed model outperforms the others when predicting the anomalies of the CT equipment based on our dataset. Conclusions The proposed method could predict the state of CT equipment and be used as a reference for practical maintenance, where unexpected anomalies of medical equipment could be reduced. It also brings new insights into how to handle non-uniform and imbalanced time series data in practical cases.

The effective surgical treatments of localized prostate cancer patients were explored. 90 prostate cancer patients admitted to our hospital were selected as study subjects. They were divided into research (treated by modified extraperitoneal total intrafascial laparoscopic radical prostatectomy) and control (treated by extraperitoneal laparoscopic radical prostatectomy) groups by random number table method, having 45 cases each. The operation time, bleeding volume, drainage time, hospitalization time, vascular endothelial stimulation index, urinary control function, erectile function, complications, and recurrence were monitored and compared. No significant difference was found between the two groups in clinical operation related indexes. On 3rd and 7th days after operation, VEGF (Vascular Endothelial Growth Factor) and IGF-I (Insulin-like Growth Factor 1) in research group were lower than those in control (p < 0.005). The urine control rate and erectile function normal rate in research group were higher than those in control (p < 0.005). Modified extraperitoneal laparoscopic total intrafascial radical prostatectomy reduced the degrees of trauma and irritation in the operation of prostate cancer patients. Moreover, during the observation period, it improved the postoperative urinary control and erectile function of patients and reduced the complications. Thus, this method has the worth of clinical promotion and application.

Abstract This paper presents the stability-evaluation outcomes of a multimachine power system (MMPS) connected with a large-scale hybrid wind farm (WF) and photovoltaic (PV) farm or hybrid wind/PV farm (HWPF) and a hybrid energy-storage system (HESS) consisting of a vanadium redox flow battery (VRFB) and a supercapacitor (SC). A probability scheme is used to determine the rated power of the proposed HESS, where the capacities of the VRFB-ESS and the SC-ESS are designed to effectively utilize their operating features. The control strategy of the HESS is proposed to reduce the pressure of the VRFB-ESS and smooth the output power fluctuations of the HWPF. The steady-state stability, small-signal stability, dynamic performances, and transient simulations of the studied grid-tied HWPF fed to the MMPS with and without the HESS are achieved. The simulation outcomes show that the proposed HESS can enhance the stability and power-smoothing performance of the HWPF fed to the MMPS.

Abstract Myocardial ischemia–reperfusion injury (MIRI) was often observed after surgeries, causing a lot of suffering to patients. Inflammation and apoptosis were critical determinants during MIRI. We conveyed experiments to reveal the regulatory functions of circHECTD1 in MIRI development. The Rat MIRI model was established and determined by 2,3,5‐triphenyl tetrazolium chloride (TTC) staining. We analyzed cell apoptosis using TUNEL and flow cytometry. Proteins expression was evaluated by western blot. The RNA level was determined by qRT‐PCR. Secreted inflammatory factors were analyzed by ELISA assay. To predict the interaction sequences on circHECTD1, miR‐138‐5p, and ROCK2, bioinformatics analysis was performed. Dual‐luciferase assay was used to confirm these interaction sequences. CircHECTD1 and ROCK2 were upregulated in the rat MIRI model, while miR‐138‐5p was decreased. CircHECTD1 knockdown alleviated H/R‐induced inflammation in H9c2 cells. Direct interaction and regulation of circHECTD1/miR‐138‐5p and miR‐138‐5p/ROCK2 were confirmed by dual‐luciferase assay. CircHECTD1 promoted H/R‐induced inflammation and cell apoptosis by inhibiting miR‐138‐5p. miR‐138‐5p alleviated H/R‐induced inflammation, while ectopic ROCK2 antagonized such effect of miR‐138‐5p. Our research suggested that the circHECTD1‐modulated miR‐138‐5p suppressing is responsible for ROCK2 activation during H/R‐induced inflammatory response, providing a novel insight into MIRI‐associated inflammation.

Accurate and robust 3D human modeling from a single image presents significant challenges. Existing methods have shown potential, but they often fail to generate reconstructions that match the level of detail in the input image. These methods particularly struggle with loose clothing. They typically employ parameterized human models to constrain the reconstruction process, ensuring the results do not deviate too far from the model and produce anomalies. However, this also limits the recovery of loose clothing. To address this issue, we propose an end-to-end method called IHRPN for reconstructing clothed humans from a single 2D human image. This method includes a feature extraction module for semantic extraction of image features. We propose an image semantic feature extraction aimed at achieving pixel model space consistency and enhancing the robustness of loose clothing. We extract features from the input image to infer and recover the SMPL-X mesh, and then combine it with a normal map to guide the implicit function to reconstruct the complete clothed human. Unlike traditional methods, we use local features for implicit surface regression. Our experimental results show that our IHRPN method performs excellently on the CAPE and AGORA datasets, achieving good performance, and the reconstruction of loose clothing is noticeably more accurate and robust.

Photocatalysis performs excellently when degrading organic pollutants, but the photocatalytic degradation rate is not high for most photocatalysts due to their narrow sunlight adsorption range and high recombination rate of electron hole pairs. Herein, we use V2C-MXene with a wide sunlight adsorption range to couple ZnO porous nanosheets and form ZnO/MXene hybrids using a facile electrostatic self-assembly method. The ZnO/MXene hybrids acquired demonstrated improved photochemical efficiency in breaking down methylene blue (MB) when contrasted with porous ZnO nanosheets. The degradation rate of MB reached 99.8% under UV irradiation for 120 min after the ZnO/MXene hybrid formation, while 38.6% was attained by the ZnO porous nanosheets. Moreover, photodegradation rate constants (k) were calculated as 3.05 × 10−3 and 5.42 × 10−2 min−1 for ZnO porous nanosheets and ZnO/MXene hybrids, respectively, indicating that the photodegradation performance was enhanced by 17.8 times after the modification of V2C. This was probably because the modification of V2C can increase the specific surface area to provide more sites for MB adsorption, widen the sunlight adsorption range to produce good photothermal effect, and facilitate the transfer of photogenerated carriers in ZnO to promote the reaction of more photogenerated carriers with MB. Hence, this work offers a simple approach to creating effective photocatalysts for breaking down organic contaminants.

Plant factories offer a promising solution to some of the challenges facing traditional agriculture, allowing for year-round rapid production of plant-derived foods. However, the effects of conditions in plant factories on metabolic nutrients remain to be explored. In this study, we used three rice accessions (KongYu131, HuangHuaZhan, and Kam Sweet Rice) as objectives, which were planted in a plant factory with strict photoperiods that are long-day (12 h light/12 h dark) or short-day (8 h light/16 h dark). A total of 438 metabolites were detected in the harvested rice grains. The difference in photoperiod leads to a different accumulation of metabolites in rice grains. Most metabolites accumulated significantly higher levels under the short-day condition than the long-day condition. Differentially accumulated metabolites were enriched in the amino acids and vitamin B6 pathway. Asparagine, pyridoxamine, and pyridoxine are key metabolites that accumulate at higher levels in rice grains harvested from the short-day photoperiod. This study reveals the photoperiod-dependent metabolomic differences in rice cultivated in plant factories, especially the metabolic profiling of taste- and nutrition-related compounds.

(1) Background: HBV-DNA is an essential clinical indicator of primary hepatocellular carcinoma (HCC) prognosis. Our study aimed to investigate the prognostic implication of a low load of HBV-DNA in HCC patients who underwent local treatment. Additionally, we developed and validated a nomogram to predict the recurrence of patients with low (20–100 IU/mL) viral loads (L-VL). (2) Methods: A total of 475 HBV-HCC patients were enrolled, including 403 L-VL patients and 72 patients with very low (p = 0.024). The content of the nomogram included gender, BCLC stage, Glob, and MLR. The C-index (0.682 vs. 0.609); 1-, 3-, and 5-year AUCs (0.729, 0.784, and 0.783, vs. 0.631, 0.634, the 0.665); calibration curves; and decision curve analysis (DCA) curves of the training and validation cohorts proved the excellent predictive performance of the nomogram. There was a statistically significant difference in RFS between the low-, immediate-, and high-risk groups both in the training and validation cohorts (p < 0.001); (4) Conclusions: Patients with L-VL had a worse prognosis. The nomogram developed and validated in this study has the advantage of predicting patients with L-VL.

Background: The morphology and internal composition, particularly the nucleus-to-cross sectional area (NP-to-CSA) ratio of the lumbar intervertebral discs (IVDs), is important information for finite element models (FEMs) of spinal loadings and biomechanical behaviors, and, yet, this has not been well investigated and reported. Methods: Anonymized MRI scans were retrieved from a previously established database, including a total of 400 lumbar IVDs from 123 subjects (58 F and 65 M). Measurements were conducted manually by a spine surgeon and using two computer-assisted segmentation algorithms, i.e., fuzzy C-means (FCM) and region growing (RG). The respective results were compared. The influence of gender and spinal level was also investigated. Results: Ratios derived from manual measurements and the two computer-assisted algorithms (FCM and RG) were 46%, 39%, and 38%, respectively. Ratios derived manually were significantly larger. Conclusions: Computer-assisted methods provide reliable outcomes that are traditionally difficult for the manual measurement of internal composition. FEMs should consider the variability of NP-to-CSA ratios when studying the biomechanical behavior of the spine.

Currently, the visual detection of a target’s shock flow field through background schlieren technology is a novel detection system. However, there are very few studies on the long-distance background schlieren imaging mechanism and its application in system design in the field of target detection. This paper proposes a design optimization method for space-based BOS detection system metrics. By establishing sensitivity evaluation models and image signal-to-noise ratio evaluation models for BOS detection systems, the influence of the different flight parameters and key parameters of BOS systems (detection spectral bands and spatial resolution) on target detection efficiency is explored. Furthermore, an optimization method based on the image signal-to-noise ratio of the BOS system and the overall metrics for specific scenarios are provided. The simulation results demonstrate that under satellite background images and speckle background images, the system metrics can detect and identify the schlieren of high-speed targets, with better applicability to disordered and complex real background images. This research contributes to advancing the development of high-speed target detection technology based on BOS.

Internal discharge and overheating faults in sulfur hexafluoride (SF6) gas-insulated electrical equipment will generate a series of characteristic gas products. Hydrogen fluoride (HF) is one of the main decomposition gases under discharge failure. Because of its extremely corrosive nature, it can react with other materials in gas-insulated switchgear (GIS), resulting in a short existence time, so it needs to be detected online. Resonant gas photoacoustic spectroscopy has the advantage of high sensitivity, fast response, and no sample gas consumption, and can be used for the online detection of flowing gas. In this paper, a simulated GIS corona discharge experimental platform was built, and the HF generated in the discharge was detected online by gas photoacoustic spectroscopy. The absorption peak of HF molecule near 1312.59 nm was selected as the absorption spectral line, and a resonant photoacoustic cell was designed. To improve the detection sensitivity of HF, wavelength modulation and second-harmonic detection technology were used. The online monitoring of HF in the simulated GIS corona discharge fault was successfully realized. The experimental results show that the sensitivity of the designed photoacoustic spectroscopy detection system for HF is 0.445 μV/(μL/L), and the limit of detection (LOD) is 0.611 μL/L.

Detecting the unintended adverse reactions of drugs (ADRs) is a crucial concern in pharmacological research. The experimental validation of drug–ADR associations often entails expensive and time-consuming investigations. Thus, a computational model to predict ADRs from known associations is essential for enhanced efficiency and cost-effectiveness. Here, we propose BiMPADR, a novel model that integrates drug gene expression into adverse reaction features using a message passing neural network on a bipartite graph of drugs and adverse reactions, leveraging publicly available data. By combining the computed adverse reaction features with the structural fingerprints of drugs, we predict the association between drugs and adverse reactions. Our models obtained high AUC (area under the receiver operating characteristic curve) values ranging from 0.861 to 0.907 in an external drug validation dataset under differential experiment conditions. The case study on multiple BET inhibitors also demonstrated the high accuracy of our predictions, and our model’s exploration of potential adverse reactions for HWD-870 has contributed to its research and development for market approval. In summary, our method would provide a promising tool for ADR prediction and drug safety assessment in drug discovery and development.

Pyrolysis is the basis of clean coal technologies such as coal liquefaction and gasification, especially for the low-rank coal. To further investigate the pyrolysis characteristics of low-rank coals, a series of different vitrinite/inertinite ratio ZJZ, MTH, and DT coals (V/I: 0.1, 0.76, and 1.76 respectively) are used as the research objects. The chemical structure of the sample was analyzed with Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction technology (XRD). The pyrolysis process and gas release behavior of coal samples at 30−900 °C was checked by TG-MS. The results show that the chemical structure content of low-rank coals with different V/I is quite different. Compared with the inertinite-rich ZJZ coals, the vitrinite-rich coals have relatively rich aliphatic structures, long aliphatic chains, and oxygen functional groups. Especially for DT coal, it has more C—O content. The corresponding aromatic structure content decreases with the increase of the mirror-inert ratio. With the increase of V/I in the coal, the aromatic layer spacing d002, the ratio of the aromatic layer size to the aromatic layer stacking height (La/Lc) increase, and Lc, La and the number of stacking layers (N) decrease. The weight loss ratio of DT, MTH, and ZJZ coal during pyrolysis is 36.4%, 32.2%, and 28.9% respectively. As the V/I decreases, the final pyrolysis gaseous product yield and the maximum pyrolysis rate decrease accordingly. During the pyrolysis process, the small molecular gas, such as H2, H2O, CH4, CO, CO2, are released; In addition, the content of released gas is closely related to the maceral composition. The mass of small molecules produced by inertinite-rich coal is almost lower than that produced by vitrinite-rich coal. Because the vitrinite in coal contains more aliphatic structures, and the polycondensation capacity between the aromatic layers is stronger, the free radicals fragment are easily formed during the thermal process and then combined into gas.

Abstract The emergence of dynamic optical switching has opened up new perspectives for lightening the ever growing load on the electrical switches and routers, to meet the increasing demand on high-speed and flexible data processing and management in fiber-optic communications. Despite diversity schemes of optical switching in the single-mode regime, multi-mode switching of the hybrid fiber and chip system enabled by photonic integrated circuits, especially for the fiber-chip-fiber system, is still an outstanding challenge. Here, we propose and demonstrate the mode and polarization transmission and switching fiber-chip-fiber system with few-mode fibers (FMFs), including the FMF links for mode- and polarization-division multiplexing data transmission, the femtosecond (fs)-laser inscribed 3-dimensional (3D) photonic lantern silica chip for (de)multiplexing and coupling between FMFs and chip, and the topology-optimized N × N non-blocking 2-dimensional (2D) silicon switch array chip for switching and routing. Using 30-Gbaud quadrature phase-shift keying signals on wavelength-division multiplexing (WDM) channels, the WDM-compatible hybrid mode/polarization transmission, switching and routing system with FMFs, fs-laser inscribed silica (de)multiplexing chip and silicon switch array chip are demonstrated in the experiment with favorable operation performance. The demonstration may open the door for developing robust multi-dimensional optical data processing in fiber-optic communication systems with versatile fibers and chips.

Objective Knee osteoarthritis (OA) patients exhibit greater gait asymmetry than healthy controls. However, gait asymmetry in kinematics, kinetics and muscle forces across patients with different severity levels of knee OA is still unknown. The study aimed to investigate the changes of gait asymmetry in lower limb kinematics, kinetics, and muscle force across patients with different severity levels of knee OA. Methods This is a cross‐sectional study. From January 2020 to January 2021, 118 patients with symptomatic and radiographic medial knee OA were categorized into three groups using the Kellgren and Lawrence scale (mild: grade 1 and 2, n = 37; moderate: grade 3, n = 31; severe: grade 4, n = 50). During self‐paced walking, marker trajectories and ground reaction forces data were recorded. Musculoskeletal simulations were used to determine gait kinematics, kinetics, and muscle force. One‐way analysis of variance with Tukey's post‐hoc test was used to evaluate group difference. Paired‐sample t‐test was used to compared the between‐limb difference. Results In the Severe group, significantly greater asymmetry index in knee flexion/extension range of motion (45%) was observed with a greater value on the contralateral side (p

Murray cod (Maccullochella peelii) is a freshwater percichthyid fish that has a high market value and potential for culture in recirculating aquaculture systems (RASs). Illumination is an important environmental factor that affects the growth and physiological condition of fishes. A comprehensive understanding of the relationship between the light factors and the growth, nutrient composition and stress response of juvenile Murray cod in RAS is important to achieve satisfactory theoretical and practical aquaculture performance. Juvenile Murray cod were randomly assigned to nine RAS tanks with a volume of 1.5 m3, with each tank containing 120 fishes (3.5 ± 0.5g). The fish were cultured for 120 days under different light intensities (1200, 2400, and 3600 lx) and photoperiods (12L: 12D, 18L: 6D and 24L: 0D). The results showed that the final weight and feed conversion ratio of Murray cod under a light intensity of 1200 lx were significantly better than those under 3600 lx (P

Objective To investigate the effect of the SMAC gene on paclitaxel sensitivity and cellular activity in lung adenocarcinoma cells based on the caspase-3/Bcl-2/Bax signaling pathway. Methods A paclitaxel-resistant cell line A549/Taxol was established for lung adenocarcinoma, and the cells were divided into four following groups: pcDNA-NC (transfected with pcDNA-NC blank vector), pcDNA-SMAC (transfected with pcDNA-SMAC vector), siRNA-NC (transfected with siRNA-NC empty virus vector), and siRNA-SMAC groups (transfected with siRNA-SMAC lentiviral vector). The SMAC mRNA expression in cells was detected by qRT-PCR; cell sensitivity was detected by MTT; cell proliferation ability was detected by cloning assay; cell invasion ability was detected by Transwell; apoptosis ability was detected by flow cytometry assay; and caspase-3, Bcl-2 and Bax protein expression in cells were detected by Western blot analysis. Results The SMAC mRNA expression was significantly lower in A549 cells compared with BEAS-2B cells (P < 0.05). The SMAC mRNA expression was significantly higher in the pcDNA-SMAC group than that in the pcDNA-NC group cells (P < 0.05). The SMAC mRNA expression was significantly lower in the cells of the siRNA-SMAC group (P < 0.05) than that in the siRNA-NC group. The SMAC mRNA expression was significantly lower in the cells of the siRNA-SMAC group (P < 0.05) than in the siRNA-NC group. Compared with the pcDNA-NC group, the cell IC50, cell clone number, cell invasion ability, and Bcl-2 protein and Bcl-2/Bax ratio were significantly lower in the pcDNA-SMAC group, the cell resistance index reversal was 2.51-fold, and the apoptosis ability and caspase-3, as well as Bax protein expression, were significantly higher (P < 0.05). Compared with the siRNA-NC group, cell IC50, cell clone number, cell invasion ability, and Bcl-2 protein and Bcl-2/Bax ratio were significantly higher in the siRNA-SMAC group, and apoptosis ability and caspase-3 and Bax protein expression were significantly lower (P < 0.05). Conclusion High expression of SMAC increases paclitaxel sensitivity, inhibits cell growth and invasion, promotes apoptosis in lung adenocarcinoma cells, and has a regulatory effect on the caspase-3/Bcl-2/Bax signaling pathway.

Abstract Background To develop a fully automatic framework for the diagnosis of cause for left ventricular hypertrophy (LVH) via cardiac cine images. Methods A total of 302 LVH patients with cine MRI images were recruited as the primary cohort. Another 53 LVH patients prospectively collected or from multi-centers were used as the external test dataset. Different models based on the cardiac regions (Model 1), segmented ventricle (Model 2) and ventricle mask (Model 3) were constructed. The diagnostic performance was accessed by the confusion matrix with respect to overall accuracy. The capability of the predictive models for binary classification of cardiac amyloidosis (CA), hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD) were also evaluated. Additionally, the diagnostic performance of best Model was compared with that of 7 radiologists/cardiologists. Results Model 3 showed the best performance with an overall classification accuracy up to 77.4% in the external test datasets. On the subtasks for identifying CA, HCM or HHD only, Model 3 also achieved the best performance with AUCs yielding 0.895–0.980, 0.879–0.984 and 0.848–0.983 in the validation, internal test and external test datasets, respectively. The deep learning model showed non-inferior diagnostic capability to the cardiovascular imaging expert and outperformed other radiologists/cardiologists. Conclusion The combined model based on the mask of left ventricular segmented from multi-sequences cine MR images shows favorable and robust performance in diagnosing the cause of left ventricular hypertrophy, which could be served as a noninvasive tool and help clinical decision.

Abstract Background Clinical evidence of immune checkpoint inhibitors combined with antiangiogenic drugs in patients with advanced non‐small cell lung cancer (NSCLC) was limited. Recombinant human endostatin (rh‐endostatin), an antiangiogenic drug, and camrelizumab, an anti‐PD‐1 antibody, have been approved for the treatment of advanced NSCLC in China. This study aimed to investigate the efficacy and safety of rh‐endostatin plus camrelizumab and chemotherapy in the treatment of advanced NSCLC. Methods Eligible patients were enrolled and received camrelizumab (200 mg, day 1) every 3 weeks and continuous intravenous infusion of rh‐endostatin (70 mg/day, days 1–3) and cisplatin combined with pemetrexed (for adenocarcinoma) or paclitaxel (for NSCLC other than adenocarcinoma) every 3 weeks. Primary endpoint was progression‐free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. Results Overall, 27 patients were included, and 25 patients were eligible for efficacy evaluation. For these 25 patients, ORR was 48.15% (13/27) and DCR was 85.19% (23/27). With a median follow‐up of 10.37 months, the median PFS was 8.9 (95% CI: 4.23–13.57) months. Median OS was not reached. Overall, 96.3% of patients experienced at least one treatment‐related adverse event, and grade 3 TRAEs occurred in 9 (33.3%) patients. No unexpected AEs were observed. Conclusion Rh‐endostatin plus camrelizumab and chemotherapy showed favorable efficacy and safety profile in patients with advanced NSCLC, representing a promising treatment regimen for these patients.

Abstract The aim of this study is to evaluate the factors affecting the objective response rate (ORR) after neoadjuvant therapy of taxol plus platinum (TP) regimen combined with programmed cell death protein-1 (PD-1) inhibitors for esophageal cancer, and establish a predictive model for forecasting ORR. According to the inclusion and exclusion criteria, consecutive esophageal cancer patients who were treated in the First Affiliated Hospital of Xi’an Jiaotong University from January 2020 to February 2022 were enrolled in this study as a training cohort, while patients who were treated in the Shaanxi Provincial Cancer Hospital Affiliated to Medical College of Xi’an Jiaotong University from January 2020 to December 2021 were enrolled as a validation cohort. All patients were treated with resectable locally advanced esophageal cancer and received neoadjuvant chemotherapy combined with immunotherapy. The ORR was defined as the sum of complete pathological response, major pathological response and partial pathological response. Logistic regression analysis was performed to determine the factors that might be related to the ORR of the patients after neoadjuvant therapy. The nomogram based on the result of regression analysis was established and verified to predict the ORR. In this study, 42 patients were included as training cohort and 53 patients were included as validation cohort. Chi-square analysis showed that neutrophil, platelet, platelet-to-lymphocytes ratio (PLR), systemic immune-inflammation index (SII), D-dimer and carcinoembryonic antigen (CEA) between ORR group and non-ORR group were significantly different. Logistic regression analysis showed that aspartate aminotransferase (AST), D-dimer and CEA were independent predictors of ORR after neoadjuvant immunotherapy. Finally, a nomogram was established based on AST, D-dimer and CEA. Internal validation and external validation revealed that the nomogram had a good ability to predict ORR after neoadjuvant immunotherapy. In conclusion, AST, D-dimer and CEA were the independent predictors of ORR after neoadjuvant immunotherapy. The nomogram based on these three indicators showed a good predictive ability.

In this study, to screen for candidate markers of temozolomide (TMZ) resistance in glioblastoma, we artificially established TMZ drug-resistant glioblastoma (GBM) cell lines, U251-TMZ and U87-TMZ. In the U251-TMZ and U87-TMZ cell lines, we screened and analyzed differentially expressed proteins using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) differential proteomics. Compared with the U251 and U87 control cell lines, 95 differential proteins were screened in the U251-TMZ and U87-TMZ cell lines, of which 28 proteins were upregulated and 67 proteins were down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the co-upregulated proteins showed that most of the differentially expressed proteins were located in the cytoplasm and were significantly upregulated in the biological processes related to vesicular transport in the intimal system and inflammatory response mediated by myeloid leukocytes. Seven candidates were identified as potential GBM markers of TMZ resistance. Combined with existing research findings, our study supports that UAP1L1 and BCKDK are promising potential markers of TMZ resistance in GBM. This is important for further understanding the molecular mechanisms that drive the development and enhancement of TMZ resistance.

In this study, we explored the impact of ionic liquid gating on YBa2Cu3O7−x superconductivity. We observed that direct contact of YBa2Cu3O7−x and the ionic liquid N-diethyl-N-methyl-N-(2methoxyethyl)ammonium bis(trifluoromethanesulfonyl)imide (DEME-TFSI) results in irreversible electrochemical reactions, despite the application of a relatively low gate voltage at 220 K. Capping a thin layer of boron nitride (BN) on YBa2Cu3O7−x enabled a reversible modulation of carrier density at 300 K. Benefiting from the higher ion mobility of ionic liquid at 300 K, this modification led to more than a one-time increase in carrier density, a 3-time improvement in voltage modulation efficiency, and a reversible tuning of the superconducting temperature. These findings suggest that using a BN capping layer holds promise for enhancing the stability and efficiency of devices using ionic liquid gating.