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A spanning subgraph H of a graph G is called a [Formula: see text]-factor of G if every component of H is isomorphic to a path of order at least k, where [Formula: see text] is an integer. A graph G is called a [Formula: see text]-factor-critical graph if [Formula: see text] contains a [Formula: see text]-factor for any [Formula: see text] with [Formula: see text]. A graph G is called a [Formula: see text]-factor-deleted graph if [Formula: see text] has a [Formula: see text]-factor for any [Formula: see text] with [Formula: see text]. Intuitively, if a graph is dense enough, it will have a [Formula: see text]-factor. In this paper, we give some sufficient conditions for a graph to be a [Formula: see text]-factor-critical graph or a [Formula: see text]-factor-deleted graph. In this paper, we demonstrate that (i) G is a [Formula: see text]-factor-critical graph if its sun toughness [Formula: see text] and [Formula: see text]. (ii) G is a [Formula: see text]-factor-critical graph if its degree sum [Formula: see text] and [Formula: see text]. (iii) G is a [Formula: see text]-factor-deleted graph if its sun toughness [Formula: see text] and [Formula: see text]. (iv) G is a [Formula: see text]-factor-deleted graph if its degree sum [Formula: see text] and [Formula: see text].

Abstract Colorectal cancer (CRC) is a prevalent malignant tumor that presents significant challenges to both public health and healthcare systems. The aim of this study was to develop a machine learning model based on five years of clinical follow-up data from CRC patients to accurately identify individuals at risk of poor prognosis. This study included 411 CRC patients who underwent surgery at Yixing Hospital and completed the follow-up process. A modeling dataset containing 73 characteristic variables was established by collecting demographic information, clinical blood test indicators, histopathological results, and additional treatment-related information. Decision tree, random forest, support vector machine, and extreme gradient boosting (XGBoost) models were selected for modeling based on the features identified through recursive feature elimination (RFE). The Cox proportional hazards model was used as the baseline for model comparison. During the model training process, hyperparameters were optimized using a grid search method. The model performance was comprehensively assessed using multiple metrics, including accuracy, F1 score, Brier score, sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristic curve, calibration curve, and decision curve analysis curve. For the selected optimal model, the decision-making process was interpreted using the SHapley Additive exPlanations (SHAP) method. The results show that the optimal RFE-XGBoost model achieved an accuracy of 0.83 (95% CI 0.76–0.90), an F1 score of 0.81 (95% CI 0.72–0.88), and an area under the receiver operating characteristic curve of 0.89 (95% CI 0.82–0.94). Furthermore, the model exhibited superior calibration and clinical utility. SHAP analysis revealed that increased perioperative transfusion quantity, higher tumor AJCC stage, elevated carcinoembryonic antigen level, elevated carbohydrate antigen 19–9 (CA19-9) level, advanced age, and elevated carbohydrate antigen 125 (CA125) level were correlated with increased individual mortality risk. The RFE-XGBoost model demonstrated excellent performance in predicting CRC patient prognosis, and the application of the SHAP method bolstered the model’s credibility and utility.

Abstract Background Besides tumorous information, synergistic liver parenchyma assessments may provide additional insights into the prognosis of hepatocellular carcinoma (HCC). This study aimed to investigate whether 3D synergistic tumor-liver analysis could improve the prediction accuracy for HCC prognosis. Methods A total of 422 HCC patients from six centers were included. Datasets were divided into training and external validation datasets. Besides tumor, we also performed automatic 3D assessment of liver parenchyma by extracting morphological and high-dimensional data, respectively. Subsequently, we constructed a tumor model, a tumor-liver model, a clinical model and an integrated model combining information from clinical factors, tumor and liver parenchyma. Their discrimination and calibration were compared to determine the optimal model. Subgroup analysis was conducted to test the robustness, and survival analysis was conducted to identify high- and low-risk populations. Results The tumor-liver model was superior to the tumor model in terms of both discrimination (training dataset: 0.747 vs. 0.722; validation dataset: 0.719 vs. 0.683) and calibration. Moreover, the integrated model was superior to the clinical model and tumor-liver model, particularly in discrimination (training dataset: 0.765 vs. 0.695 vs. 0.747; validation dataset: 0.739 vs. 0.628 vs. 0.719). The AUC of the integrated model was not influenced by AFP level, BCLC stage, Child–Pugh grade, and treatment style in training (6 months p value: 0.245–0.452; 12 months p value: 0.357–0.845) and validation (6 months p value: 0.294–0.638; 12 months p value: 0.365–0.937) datasets. With a risk score of 1.06, high- and low-risk populations demonstrated significant difference for progression-free survival (p

Abstract Objective Summaries of the relationships between the microbiota and liver cirrhosis and their conclusions are not consistent. This study describes microbial differences in patients with liver cirrhosis by performing a meta-analysis. Methods We searched PubMed, Embase, Web of Science, and the Cochrane Library and collected related articles published before March 10, 2024. Ratio of autochthonous to non-autochthonous taxa was calculated as the cirrhosis dysbiosis ratio (CDR). Using a random-effects model, the standard mean deviation (SMD) and 95% confidence interval (CI) were calculated. We subsequently performed subgroup, sensitivity, and publication bias analyses. cirrhosis dysbiosis ratio. Results A total of 53 eligible papers including 5076 participants were included. The pooled estimates revealed a moderately significant reduction in gut microbiome richness in patients with liver cirrhosis compared with controls, including the Shannon, Chao1, observed species, ACE, and PD indices, but no significant difference was observed for the Simpson index. Over 80% of the studies reported significant differences in β diversity. Families Enterobacteriaceae and Pasteurellaceae, belonging to the phylum Proteobacteria, along with the family Streptococcaceae and the genera Haemophilus, Streptococcus, and Veillonella, were significantly associated with liver cirrhosis compared to the control group. In contrast, the healthy group exhibited a higher abundance of the class Clostridia, particularly the families Lachnospiraceae and Ruminococcaceae, which are known for their diversity and role as common gut commensals. Furthermore, the class Bacilli, predominantly represented by the genus Streptococcus, was markedly enriched in the cirrhosis group. Conclusions The microbiota richness of liver cirrhosis patients was lower than that of healthy controls. Alterations in gut microbiota linked to liver cirrhosis were characterized by a decrease in Lachnospiraceae, Ruminococcaceae, and Clostridia and an enrichment of Enterobacteriaceae, Pasteurellaceae, Streptococcaceae, Bacilli, and Streptococcus.

It is of great significance to search for advanced glycation end products (AGEs) inhibitors with high activity and low side effects from food-borne natural products for the prevention and improvement of related diseases. To elucidate the inhibitory effect of tectoridin on the generation of advanced glycation end products (AGEs), the glycation system of bovine serum protein (BSA)-methylglyoxal (MGO) was established, the effects of tectoridin on the AGEs inhibition, glycation degree, protein oxidation products, protein cross-linking and MGO trapping were investigated by spectroscopy, SDS-PAGE, HPLC, LTQ-Orbitrap MS, and molecular docking. The results showed that tectoridin increased the content of lysine and thiol, reduced the contents of protein carbonylation and protein oxidation products, alleviated the cross-linking structure of BSA. The mono-MGO adduct of tectoridin was identified in the incubation of MGO with tectoridin. Molecular docking results showed that hydrogen bonding and hydrophobic interactions were the major driving forces for stabilizing tectoridin-BSA complexes. Tectoridin was a promising natural AGEs inhibitor. Mechanism analysis revealed that tectoridin alleviated AGEs formation by trapping MGO to form mono-tectoridin-MGO complexes and forming stable tectoridin-BSA complexes. These findings would provide the theoretical basis for the development of tectoridin as a novel, natural and effective inhibitor of AGEs.

Despite advances in treatment, prostate cancer remains a leading cause of cancer-related deaths among men, highlighting the urgent need for innovative therapeutic strategies. MicroRNAs (miRNAs) have emerged as key regulatory molecules in cancer biology. In this research, we investigated the tumor-suppressive role of miR-5100 in PCa and its underlying molecular mechanism. By using RT-qPCR, we observed lower miR-5100 expression in PCa cell lines than in benign prostate cells. Functional assays demonstrated that miR-5100 overexpression significantly suppressed PCa cell proliferation, migration, and invasion. By using RNA-sequencing, we identified 446 down-regulated and 806 upregulated candidate miR-5100 target genes overrepresenting cell cycle terms. Mechanistically, E2F7 was confirmed as a direct target of miR-5100 using the reporter gene assay and RIP assay. By conducting flow cytometry analysis, cell cycle progression was blocked at the S phase. E2F7 overexpression partially mitigated the suppressive impact of miR-5100 in PCa cells. In conclusion, miR-5100 is a tumor suppressor in PCa by blocking cell cycle and targeting E2F7.

Abstract Point defects in crystalline solids behave as optically addressable individual quantum systems when present in sufficiently low concentrations. In two-dimensional (2D) semiconductors, such quantum defects hold potential as versatile single photon sources. Here, we report the synthesis and optical properties of Nb-doped monolayer WS2 in the dilute limit where the average spacing between individual dopants exceeds the optical diffraction limit, allowing the emission spectrum to be studied at the single-dopant level. We show that these individual dopants exhibit common features of quantum emitters, including narrow emission lines (with linewidths

Abstract Large-scale regular nucleic acid testing (NAT) such as Regular-1/7, played a crucial role in the successful and sustained containment of COVID-19 in China, enabling rapid case detection in low-risk areas. However, Regular-1/7 strategies are extremely costly and time-consuming. To address these challenges and facilitate the broader implementation of large-scale NAT during outbreaks of highly contagious diseases with long incubation periods, we propose a novel sampling strategy called Weighted Hub and Time Sampling (WHTS). This strategy considers the intensity of social activity, the degree of social overlap, and the time interval since the last NAT for each individual. Based on a scale-free contact network model, we simulated the spread of scenario in a community and compared the performance of the WHTS strategy to the Regular-1/7 strategy in terms of cost reduction and shorter alert time. The results show that WHTS-1/14 strategy can save half of the cost, and WHTS-1/7 strategy can alert 1.0 days in advance, compared to Regular-1/7 strategy. Additionally, The WHTS-1/14 strategy also achieves promising results under various scenarios, even though it samples half as many people as the Regular-1/7 strategy. Our study offers a valuable reference for large-scale testing in future efforts to manage emerging infectious diseases.

During the boll formation stage, cotton bolls exhibit the lowest expression of Bacillus thuringiensis (Bt) insecticidal proteins. Resistance to insects varies notably among different organs, which poses challenges for controlling cotton bollworms. Consequently, an experimental strategy was designed in the 2020–2021 cotton growing season to coordinate the enhancement of protein synthesis and the attenuation of degradation. Two Bt cultivars of Gossypium hirsutum, namely the hybrid Sikang 3 and the conventional Sikang 1, were used as test materials. Three treatments were applied at the peak flowering period: CK (the control), T1 (amino acids), and T2 (amino acids and EDTA). The results show that, in comparison to the CK group, the Bt protein contents were significantly increased in both cotton bolls and their subtending leaves under the T1 and T2 treatments. The maximum levels of increase observed were 67.5% in cotton bolls and 21.7% in leaves. Moreover, the disparity in Bt protein content between cotton bolls and their subtending leaves notably decreased by 31.2%. Correlation analysis suggested that the primary physiological mechanisms for augmenting Bt protein content involve increased protein synthesis and reduced protein catabolism, which are independent of Bt gene expression levels. Stepwise regression and path analysis revealed that elevating the soluble protein content and transaminase activity, while reducing the catabolic enzyme activities, are instrumental in enhancing the Bt protein content. Consequently, the coordinated application of amino acids and EDTA emerges as a strategy that can improve the overall resistance of Bt cotton and mitigate the spatiotemporal variations in Bt toxin concentrations in both cotton bolls and leaves.

Abstract The Cape hare (Lepus capensis) is among the most widely distributed hare species globally, inhabiting extensive regions across Africa, the Middle East, and Central Asia. However, evolutionary and genetic research on L. capensis was seriously impeded by the absence of a reference genome. Here, we assembled and constructed a chromosome-level genome of L. capensis (with scaffolds anchored to 25 chromosomes and a total assembled length of 2.9 Gb, achieving a contig N50 length of 124.44 Mb) using PacBio HiFi sequencing and Hi-C assembly technology. Evaluation using BUSCO indicated the genome assembly to be 98.2% complete. The de novo prediction revealed that repetitive sequences constitute 46.13% of the entire genome, and long interspersed nuclear elements (LINEs) constituted the largest portion. We annotated a total of 13, 868 protein-coding genes using transcriptomes from two tissues (muscle and skin). This high-quality reference genome serves as a valuable genomic resource for advancing genetic studies in this species.

Abstract Background Aberrant activation of mesenchymal epithelial transition (MET) has been considered to mediate primary and acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC). However, mechanisms underlying this process are not wholly clear and the effective therapeutic strategy remains to be determined. Methods The gefitinib-resistant NSCLC cell lines were induced by concentration increase method in vitro. Western blot and qPCR were used to investigate the relationship between MET and vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling pathway. Double luciferase reporter gene and co-immunoprecipitation were used to further reveal the regulation mechanism between MET and VEGF/VEGFR2. The effect of combined inhibition of MET and VEGF/VEGFR2 signaling pathway on the therapeutic sensitivity of EGFR-TKI in gefitinib resistant cell lines with MET aberration was verified ex vivo and in vivo. Results We successfully obtained two gefitinib-resistant NSCLC cell lines with EGFR mutation and abnormal activation of MET. We observed that MET formed a positive feedback loop with the VEGF/VEGFR2 signaling, leading to persistent downstream signaling activation. Specifically, MET up-regulated VEGFR2 expression in a MAPK/ERK/ETS1-dependent manner, while VEGF promoted physical interaction between VEGFR2 and MET, thereby facilitating MET phosphorylation. A MET inhibitor, crizotinib, combined with an anti-VEGF antibody, bevacizumab, enhanced the sensitivity of NSCLC cells to gefitinib and synergistically inhibited the activation of downstream signaling in vitro. Dual inhibition of MET and VEGF combined with EGFR TKIs markedly restrained tumor growth in both human NSCLC xenograft models and in an EGFR/MET co-altered case. Conclusions Our work reveals a positive feedback loop between MET and VEGF/VEGFR2, resulting in continuous downstream signal activation. Combined inhibition of MET and VEGF/VEGFR2 signaling pathway may be beneficial for reversing EGFR TKIs resistance.

Abstract The role of the compromised immune microenvironment, including immune checkpoints, in myelodysplastic syndromes (MDS) has been identified as critical This study aimed to investigate the expression patterns of immune checkpoints, particularly soluble PD-1/PD-L1 (sPD-1/sPD-L1) as well as PD-1 on effector T cell subsets, and assess their prognostic value and potential regulatory roles in MDS. 161 MDS patients were enrolled, including 129 patients were primarily diagnosed with de novo MDS, together with 59 MDS patients who underwent hypomethylating agents (HMAs) therapy. Plasma sPD-L1 level was elevated in newly diagnosed MDS patients, which was also found to be associated with MDS disease progression that further increase in higher IPSS-R score group. Patients with increased sPD-L1 expression at diagnosis exhibited notably poorer overall survival, and multivariate Cox analysis indicated that elevated sPD-L1 was an independent risk factor. Furthermore, the levels of multiple cytokines and membrane-bound PD-1 on T cells were found to correlate with sPD-1/sPD-L1 levels in plasma. Importantly, we also found sPD-L1 levels significantly increased in MDS patients who showed progression of disease following HMAs therapy. In conclusion, we found elevated plasma sPD-L1 levels in MDS patients are associated with disease progression and poorer overall survival. This study showed that sPD-L1 is a potential biomarker for prognosis and a target for immunotherapy in MDS.

Abstract After disease progression on endocrine therapy (ET) plus a CDK4/6 inhibitor, there is no standardized sequence for subsequent treatment lines for estrogen receptor positive (ER+) metastatic breast cancer (MBC). CDK4/6i retrial as a treatment strategy is commonplace in modern clinical practice; however, the available prospective data investigating this strategy have had inconclusive results. To frame this data in a real-world context, we performed a retrospective analysis assessing the efficacy of CDK4/6is in 195 patients who had previous exposure to CDK4/6i in a prior treatment line at our institution. Among patients who had stopped a CDK4/6i due to toxicity, CDK4/6i retrial either immediately after with a different CDK4/6i or in a further treatment line with the same initial CDK4/6i was both safe and effective, with a median time to treatment failure (TTF) of 10.1 months (95%CI, 4.8–16.9). For patients whose disease progressed on a prior CDK4/6i, we demonstrated comparable median TTFs for patients rechallenged with the same CDK4/6i (4.3 months, 95%CI 3.2–5.5) and with a different CDK4/6i (4.7 months, 95%CI 3.7–6.0) when compared to the recent PACE, PALMIRA, and MAINTAIN trials. Exploratory genomic analysis suggested that the presence of mutations known to confer CDK4/6i resistance, such as TP53 mutations, CDK4 amplifications, and RB1 or FAT1 loss of function mutations may be molecular biomarkers predictive of CDK4/6i retrial failure.

Abstract This study aimed to evaluate the bioequivalence between test and reference insulin degludec (IDeg) and the effects of body composition on pharmacokinetics and pharmacodynamics of IDeg in Chinese healthy volunteers. In this randomized, open-label, crossover trial, 30 healthy Chinese males were assigned to receive a single subcutaneous dose (0.4 IU/kg) of each formulation under 24-h euglycemic hyperinsulinaemic clamp. Body compositions were analysed prior to administration and blood samples were collected at specific times. The 90% of primary pharmacokinetic parameters and 95% of primary pharmacodynamic parameters confidence intervals for the ratio of the least-squares geometric means were all in the range of 80–125%. As the fat content level increases, C max , AUC0−12 and GIR-AUC0−24 decreased whereas AUC24−96 increased sequentially. Therefore, the equivalence was demonstrated between test and reference, and in healthy Chinese volunteers, higher levels of adiposity are associated with slower rates of insulin absorption and distribution and the poorer glucose-lowering effect.

Abstract This research was intended to compare the clinical efficacy of hepatic arterial infusion chemotherapy (HAIC) in conjunction with lenvatinib and PD-1 inhibitors to first-line systemic chemotherapy for advanced intrahepatic cholangiocarcinoma(ICC). The research enrolled advanced ICC patients who underwent HAIC plus lenvatinib and PD-1 inhibitor(n = 51) or first-line systemic chemotherapy(cisplatin + gemcitabine, n = 39) between July 2020 to January 2023 in Zhongshan People’s Hospital.Their clinical outcomes were assessed through measurement of parameters encompassing objective response rate (ORR), disease control rate (DCR), median overall survival (mOS), median progression-free survival (mPFS), median duration of response (mDOR), and treatment-related adverse events (TRAEs). In accordance with the RECIST1.1, the ORR in the HAIC + L + P and SC groups was 43.1% and 20.5%, while the DCR was 90.2% and 69.2%, respectively (P = 0.04 and = 0.02, respectively). The change in the maximum diameter of intrahepatic target lesions in patients before and after treatment and the diameter of intrahepatic tumors in the HAIC + L + P group were sharply smaller versus the SC group ( P

The advent of 3D printing (3DP) has garnered significant interest from both academia and industry due to its potential to revolutionize engineering, manufacturing, and through its utilization of advanced materials. Even though the application of 3D printing in footwear design and manufacture is quite appreciated, academic discourse on the subject relative to footwear design and manufacture is rather scarce compared to other fields such as pharmaceuticals, electronics and food. The purpose of this review is to explore the techniques, the application trends and the impact of 3D printing technology concerning footwear design and manufacture. Using relevant data from many relevant sources, this study uncovered that 3D printing has significantly impacted shoe design and manufacture by enhancing production efficiency, environmental sustainability, material innovation and Inter-Industry Collaborative Projects among others. Most of the major players in the footwear industry such as Nike, Adidas, Reebok and New Balance already have many footwear releases based on 3D printing. Also discussed are some specific areas in which 3D printing is being applied in footwear design and manufacture. These areas include but are not limited to the design of smart shoes, shoe lasts, complex shoe geometries, avant-garde concept shoes and so on. This study is of particular importance to stakeholders in the footwear research and design industry as it provides important information about the current trends as well as the impact of 3D printing technology on the sector.

Abstract Background Drug-induced liver injury (DILI) is gradually becoming a common global problem that causes acute liver failure, especially in acute hepatic damage caused by acetaminophen (APAP). Paeoniflorin (PF) has a wide range of therapeutic effects to alleviate a variety of hepatic diseases. However, the relationship between them is still poorly investigated in current studies. Purpose This work aimed to explore the protective effects of PF on APAP-induced hepatic damage and researched the potential molecular mechanisms. Methods C57BL/6J male mice were injected with APAP to establish DILI model and were given PF for five consecutive days for treatment. Aiming to clarify the pharmacological effects, the molecular mechanisms of PF in APAP-induced DILI was elucidated by high-throughput and other techniques. Results The results demonstrated that serum levels of ALP, γ-GT, AST, TBIL, and ALT were decreased in APAP mice by the preventive effects of PF. Moreover, PF notably alleviated hepatic tissue inflammation and edema. Meanwhile, the results of TUNEL staining and related apoptotic factors coincided with the results of transcriptomics, suggesting that PF inhibited hepatocyte apoptosis by regulated MAPK signaling. Besides, PF also acted on reactive oxygen species (ROS) to regulate the oxidative stress for recovery the damaged mitochondria. More importantly, transmission electron microscopy showed the generation of autophagosomes after PF treatment, and PF was also downregulated mTOR and upregulated the expression of autophagy markers such as ATG5, ATG7, and BECN1 at the mRNA level and LC3, p62, ATG5, and ATG7 at the protein level, implying that the process by which PF exerted its effects was accompanied by the occurrence of autophagy. In addition, combinined with molecular dynamics simulations and western blotting of MAPK, the results suggested p38 as a direct target for PF on APAP. Specifically, PF-activated autophagy through the downregulation of MAPK/mTOR signaling, which in turn reduced APAP injury. Conclusions Paeoniflorin mitigated liver injury by activating autophagy to suppress oxidative stress and apoptosis via the MAPK/mTOR signaling pathway. Taken together, our findings elucidate the role and mechanism of paeoniflorin in DILI, which is expected to provide a new therapeutic strategy for the development of paeoniflorin. Graphical abstract

Abstract Conventional magnetic biosensing technologies have reduced analytical capacity for magnetic field dimensionality and require extensive sample processing. To address these challenges, we spatially engineer 3D magnetic response gradients for direct and programmable molecular detection in native biofluids. Named magnetic augmentation through triple-gradient coupling for high-performance detection (MATCH), the technology comprises gradient-distributed magnetic nanoparticles encapsulated within responsive hydrogel pillars and suspended above a magnetic sensor array. This configuration enables multi-gradient matching to achieve optimal magnetic activation, response and transduction, respectively. Through focused activation by target biomarkers, the platform preferentially releases sensor-proximal nanoparticles, generating response gradients that complement the sensor’s intrinsic detection capability. By implementing an upstream module that recognizes different biomarkers and releases universal activation molecules, the technology achieves programmable detection of various circulating biomarkers in native plasma. It bypasses conventional magnetic labeling, completes in

Abstract Background The initial randomized, double‐blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first‐line therapy in epidermal growth factor receptor (EGFR)‐mutated advanced non‐small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study. Methods Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double‐blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow‐up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological‐BICR). The primary endpoint for this subgroup analysis was CNS progression‐free survival (PFS). Results Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological‐BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17‐0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11‐0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non‐CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed. Conclusions These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR‐mutated advanced NSCLC with baseline CNS metastases. Trial registration ClinicalTrials.gov number, NCT03849768

Abstract The bride price, as an informal institution originated from traditional culture, is pervasive in many areas of the developing world in a form of a payment from the family of the groom to that of the bride at marriage. We study the effects of bride price on parents' health in China. Using information on bride price payment and various health measures from the China Health and Retirement Longitudinal Study, we find that the bride price significantly reduces self‐reported health among the grooms' parents after addressing the endogeneity issue with average sex ratio within a family computed as an instrumental variable. The reductions are heterogenous across urban and rural areas. Mechanism analysis suggests the negative health outcomes are driven by family debt, heavier psychological stress and longer work hours caused by bride price payments.

We studied the case of a 22-year-old Pregnant woman who self-administered about 200 ml of diquat solution (200 g/L) during a suicide attempt. She developed vomiting, and was admitted to the emergency department of our hospital 5 h later. Based on symptoms, and elevated levels of myoglobin and creatine kinase, the patient was diagnosed with rhabdomyolysis, acute renal failure and toxic encephalopathy caused by diquat poisoning. Undergoing hemoperfusion and hemofiltration were administered immediately. Rhabdomyolysis, toxic encephalopathy, and abortion occurred successively in the pregnant woman. The patient was discharged from the hospital after 37 days of treatment with a Glasgow–Pittsburgh Cerebral Classification (CPC) score of grade 2.this was a case of diquat poisoning complicated with renal failure, rhabdomyolysis, and toxic encephalopathy in a pregnant, which would enrich the experience of diquat poisoning treatment.

Barnyard grass, a pernicious weed thriving in rice fields, poses a significant challenge to agricultural productivity. Detection of barnyard grass before the four-leaf stage is critical for effective control measures. However, due to their striking visual similarity, separating them from rice seedlings at early growth stages is daunting using traditional visible light imaging models. To explore the feasibility of hyperspectral identification of barnyard grass and rice in the seedling stage, we have pioneered the DeepBGS hyperspectral feature parsing framework. This approach harnesses the power of deep convolutional networks to automate the extraction of pertinent information. Initially, a sliding window-based technique is employed to transform the one-dimensional spectral band sequence into a more interpretable two-dimensional matrix. Subsequently, a deep convolutional feature extraction module, ensembled with a bilayer LSTM module, is deployed to capture both global and local correlations inherent within hyperspectral bands. The efficacy of DeepBGS was underscored by its unparalleled performance in discriminating barnyard grass from rice during the critical 2-3 leaf stage, achieving a 98.18% accuracy rate. Notably, this surpasses the capabilities of other models that rely on amalgamations of machine learning algorithms and feature dimensionality reduction methods. By seamlessly integrating deep convolutional networks, DeepBGS independently extracts salient features, indicating that hyperspectral imaging technology can be used to effectively identify barnyard grass in the early stages, and pave the way for the development of advanced early detection systems.

In this study, the post-curing kinetic, molecular mobility and mechanical behavior of polymethylacrylimide (PMI), synthesized from methacrylic acid and methacrylonitrile, were systematically investigated. Differential scanning calorimetry results identified three distinct temperature zones during the post-curing process, which represented different types of curing reactions. Model-free kinetic methods were used to evaluate the post-curing kinetics of PMI materials. Fourier transform infrared spectroscopy demonstrated that the cyclization of anhydride groups predominantly occurred at lower post-curing temperatures, while the decomposition and transformation were observed at higher temperatures. Meanwhile, there was a progressive formation of imide rings with the increase of post-curing temperature. In addition, the molecular segment mobility of PMI materials was investigated via dielectric relaxation spectroscopy, and molecular segment mobility was gradually restricted during the post-curing process, indicated the formation of crosslinked network structure. Those changes of microstructures agreed well with the evolution of compressive properties. This study provides insights into the curing kinetics and structural evolution of PMI during post-curing process, offering guidance for optimizing post-curing conditions to achieve superior mechanical performance.

Engineering structures are expected to steadily sustain a load with minimal deformation when subjected to thermal variation. In this study, we propose a multiphase structure with high thermal stiffness invariability (HTSI) and develop a method to topologically design such a structure using discrete material optimization (DMO). First, a series of quasi-static characterization tests under different temperatures was performed to assess the thermo-elastic properties of the multiphase material candidates. Second, an HTSI design method was proposed based on the multiphase material properties and DMO for acquiring both 2D and 3D multiphase structures. Last, a 3D multiphase structure was manufactured using additive manufacturing and corresponding experiments were performed to validate the effectiveness of the proposed method in the design of multiphase structures with HTSI. The results for 2D multiphase structures show that the HTSI design can ameliorate the fluctuation of structural compliance or stiffness when the temperature changes from 30 ℃ to 70 ℃. The fluctuations were reduced by 5.13 % and 20.3 % in the 2D cantilever and MBB beam, respectively, when compared to those produced via the general thermo-elastic (GTE) design. These results for designing 3D multiphase structures demonstrate that using the HTSI design can reduce thermally induced stiffness fluctuation by 24.4% when compared to the GTE design by experiments. The numerical accuracy was also validated with an error of only 7.7%.

ObjectivesThe present study aim to systematically review the prevalence and influencing factors of oral frailty in older people.MethodsA search strategy was developed and implemented to systematically review literature across PubMed, Embase, Web of Science, MEDLINE (via EBSCOhost), CINAHL, the Cochrane Library, Scopus, China Knowledge Resource Integrated Database (CNKI), Wanfang Data, Chinese Biomedical Database (CBM), and Weipu Database (VIP), in accordance with the PRISMA 2020 guidelines. Our search encompassed studies published up to June 28, 2024, that investigated the prevalence or risk factors of oral frailty among older adults. Literature screening, data extraction, and quality assessment were independently performed by two researchers, followed by data analysis using Stata 17 software. This study has been registered with PROSPERO.ResultsA total of 35 studies involving 202,864 participants were analyzed. The overall prevalence of oral frailty among older adults was 34.0% (95% CI: 27.9–40.1%, I2 = 99.7%, p

Green sea turtles are listed on the International Union for Conservation of Nature’s Red List of Threatened Species. Thus, conservation efforts, including investigation of factors affecting the health of green sea turtles, are critical. Viral communities play vital roles in maintaining animal health. In the present study, shotgun metagenomics was used for the first time to survey viruses in the feces of green sea turtles. Most viral contigs were DNA viruses that mainly belonged to Caudoviricetes, followed by Crassvirales. Additionally, most of the viral contigs were not assigned to any known family or genus, implying a large knowledge gap in the taxonomy of green sea turtle gut viruses. Host prediction showed that most viruses were connected to two phyla: Bacteroidetes and Firmicutes. Furthermore, KEGG enrichment analysis showed that the viral genes were mainly involved in phage-associated and metabolic pathways. Phylogenetic tree reconstruction of Caudovirales terminase large-subunit (TerL) protein showed that most of the sequences were phylogenetically distant. This study expands our understanding of the viral diversity in green sea turtles. In particular, analysis of the virome RNA fraction is exceedingly important for investigating intestinal viromes; therefore, future studies could use metatranscriptomics to study RNA viruses.

ObjectivesTo analyzed the clinical characteristics and treatment modalities of heat stroke (HS) and to identify risk factors for a poor prognosis of HS and provide reference suggestions for its treatment and prevention.Measurements and main resultsWe enrolled a total of 247 patients, with hypertension, diabetes, and psychosis being the top three comorbidities associated with HS. The incidence of HS was higher among males and older individuals. Compared to the control group, the poor prognosis group experienced higher temperatures, a higher incidence of cerebral edema, and gastrointestinal bleeding (all p

Objectives This study aimed to evaluate the knowledge, attitudes and practices (KAP) of patients with chronic respiratory diseases towards pulmonary rehabilitation.Design Cross-sectional, web-based questionnaire study.Setting Tertiary healthcare hospital in Taiyuan, Shanxi Province, China.Participants A total of 511 patients with chronic respiratory diseases were recruited from the hospital’s outpatient and inpatient departments. After data cleaning, 501 valid responses (98.04% valid response rate) were analysed. Participants were aged 18 or older, able to complete the questionnaire independently or with assistance and included individuals from diverse demographic backgrounds.Primary and secondary outcome measures Primary outcomes included KAP scores related to pulmonary rehabilitation. The secondary outcome assessed the association between demographic factors (age, gender, income, education, smoking status) and KAP scores using structural equation modelling (SEM).Results The mean KAP scores were 1.26±2.85 for knowledge, 30.46±3.63 for attitudes and 34.58±5.55 for practices. SEM analysis showed that knowledge directly influenced attitudes (β=−0.538, p

Chongqing Old Rose is an ancient edible rose variety native to Chongqing, China, but is under-reported. Further evidence is required to fully establish its potential benefits. The complete metabolic profiles were examined for comparative analysis between the Old Rose and three rose cultivars. The results showed that the pathways of flavonoid biosynthesis, monoterpenoid biosynthesis, and phenylalanine metabolism were significantly enriched in Old Rose. The predominant anthocyanins in Old Rose were cyanidin and peonidin, which may contribute to flower coloration and indicate the antioxidant potential of this plant. Additionally, this plant was rich in aromatic compounds and terpenoids such as 2-phenylethanol, linalool, geraniol, and caryophyllene α-oxide, indicating that it has a natural basis for extracting essential oil. Moreover, the presence of some active phytoconstituents, such as phenols, steroids, and alkaloids, also suggests its potential for edible and medicinal applications besides flavonoids and terpenoids.

ABSTRACT Background This study compares the efficacy and safety of single autologous stem cell transplantation (ASCT) versus tandem ASCT for multiple myeloma (MM) patients in the era of novel agents. Methods A total of 112 high‐risk MM patients were included (single ASCT, (n = 57) or tandem ASCT(n = 55) in this retrospective multicenter study. Responses and outcomes were evaluated. Results At 100 days after ASCT1 and ASCT2, 36 (63.2%) versus 45 (81.8%) patients achieved sCR/CR, 16 (28.1%) versus 7 (12.7%) patients achieved VGPR, and 5 (8.8%) versus 1 (1.8%) patient achieved PR, respectively, in the single and tandem ASCT cohorts. The 3‐year cumulative incidence of non‐relapse mortality and disease progression was 0% versus 7.3% (p = 0.083), and 45.8% versus 25.8% (p = 0.039), respectively, for the single and tandem ASCT cohort. The tandem ASCT cohort showed a trend of better 3‐year probability of PFS (58.1% vs. 64.7%, p = 0.064) compared with the single ASCT cohort. In multivariate analysis, ultra high‐risk and achieving

Abstract Zinc ion hybrid capacitors (ZIHCs) with Zn metal faradic and carbon capacitive electrodes have potential applications in grid‐scale energy storage systems and wearable devices. However, the high specific energy density reported in many recent studies is based on the mass of active carbon materials alone, with deficient device energy density. This perspective article discusses how four crucial parameters influence the device energy density of ZIHCs, including areal mass loading (mc) and specific capacity (Qg,c) of active carbon materials in cathodes, negative‐to‐positive electrode capacity ratio (N/P), and electrolyte‐to‐active carbon materials mass ratio (E/C). Using a representative device model, how the device energy density varies when these four parameters change is shown. Detailed analysis indicates that specific parameter windows with the four parameters within narrow ranges (e.g., mc = 10–20 mg cm−2, Qg,c > 100 mAh g−1, N/P < 20, and E/C < 5) need to be achieved simultaneously to deliver application‐relevant energy density (e.g., >30 Wh kg−1) in ZIHCs. It is hoped that these findings assist in objectively evaluating reported performance data and identifying essential issues for future research development to realize practical applications.

Background Hypoxia‐induced pulmonary hypertension (HPH) is a severe vascular disorder that is characterized by the involvement of endothelial‐to‐mesenchymal transition (EndMT) in its pathogenesis. Our previous research has suggested that the gene versican may have a crucial role in the development of HPH. However, the exact function of versican in HPH requires further investigation. Methods and Results The expression of versican and markers of EndMT was assessed using Western blot, immunohistochemistry, and immunofluorescence. Vascular remodeling and right ventricular hypertrophy in patients with HPH and mice were evaluated through hematoxylin and eosin staining, Masson's staining, and hemodynamic measurements. Protein interactions were validated using co‐immunoprecipitation, and the DNA methylation level of versican was examined using methylation‐specific polymerase chain reaction. Compared with the control, EndMT was observed in patients with HPH, HPH mouse models, and hypoxia‐treated human pulmonary artery endothelial cells, accompanied by a significant increase of versican. Endothelium‐specific knockdown of versican reversed HPH progression and effectively prevented EndMT in mouse models and human pulmonary artery endothelial cells. We further confirmed that versican participated in EndMT by targeting the key transcription factor Twist1. Additionally, the upregulation of versican may be attributed to promoter hypomethylation, which was mediated by reduced DNA methyltransferases activity under hypoxic conditions. Conclusions This study provides the initial evidence showcasing the role of promoter hypomethylation‐mediated versican upregulation in promoting EndMT by targeting Twist1, which facilitates vascular remodeling and the progression of HPH. These findings offer a promising new target for the treatment of HPH.

Although authoritarian leadership (AL) behaviour is critical to organisational performance, its impact in different cultural contexts has received scant academic attention especially for managing bespoke projects which require temporary organisations to be formed. Drawing from self-determination and expectancy theories, this present research develops an integrated model to interpret the underlying impacts that the two dichotomous groups of ALs (i.e. discipline- and dominance-focused) have on project team members' task and innovative performance in China. The model developed was tested using the data collected from 316 Chinese project team members. Empirical evidence indicates that psychological empowerment acts as a ‘mediator’ via which the discipline- and dominance-focused ALs can positively and negatively affect the team members' task and innovative performance respectively. Additionally, the aforementioned indirect relationships are moderated by outcome expectancy, implying a positive interdependency between them. This research enriches an understanding of ALs and project team in terms of task completion and innovation and is useful for developing interventions to improve project team performance.

H5N1 avian influenza viruses bearing the clade 2.3.2.1 hemagglutinin (HA) gene have been widely detected in birds and poultry in several countries. During our routine surveillance, we isolated 28 H5N1 viruses between January 2017 and October 2020. To investigate the genetic relationship of the globally circulating H5N1 viruses and the biological properties of those detected in China, we performed a detailed phylogenic analysis of 274 representative H5N1 strains and analyzed the antigenic properties, receptor-binding preference, and virulence in mice of the H5N1 viruses isolated in China. The phylogenic analysis indicated that the HA genes of the 274 viruses belonged to six subclades, namely clades 2.3.2.1a to 2.3.2.1f; these viruses acquired gene mutations and underwent complicated reassortment to form 58 genotypes, with G43 being the dominant genotype detected in eight Asian and African countries. The 28 H5N1 viruses detected in this study carried the HA of clade 2.3.2.1c (two strains), 2.3.2.1d (three strains), or 2.3.2.1f (23 strains), and formed eight genotypes. These viruses were antigenically well-matched with the H5-Re12 vaccine strain used in China. Animal studies showed that the pathogenicity of the H5N1 viruses ranged from non-lethal to highly lethal in mice. Moreover, the viruses exclusively bound to avian-type receptors and have not acquired the ability to bind to human-type receptors. Our study reveals the overall picture of the evolution of clade 2.3.2.1 H5N1 viruses and provides insights into the control of these viruses.

Pancreatic ductal adenocarcinoma (PDAC) is currently difficult to treat, even when therapies are combined with immune checkpoint blockade (ICB). A novel strategy for immunotherapy would be to maximize the therapeutic potential of oncolytic viruses (OVs), which have been proven to engage the regulation of tumor microenvironment (TME) and cause-specific T-cell responses. To boost tumor sensitivity to ICB therapy, this study aimed to investigate how glutathione peroxide 4 (GPX4)-loaded OVs affect CD8+ T cells and repair the immunosuppressive environment. Here, we successfully constructed a novel recombinant oncolytic vaccinia virus (OVV) encoding the mouse GPX4 gene. We found the OVV-GPX4 effectively replicated in tumor cells and prompted the expression of GPX4 in T cells. Our research indicated that OVV-GPX4 could reshape the TME, rectify the depletion of CD8+T cells, and enhance the antitumor effects of ICB therapy.

Mycobacterium chelonae and Sporothrix globosa, both of which are opportunistic pathogens, have been proved to be possible multidrug resistant. However, are all recurring symptoms in chronic infections related to decreasing susceptibility? Here we report a case of sporotrichosis secondary to M. chelonae infection. In addition, we find that the blackish-red spots under the dermoscopic view can be employed as a signal for the early identification and regression of subcutaneous fungal infection.

Abstract Background Sudden temperature drops, resulting from extreme weather events, often occur during the boll-setting period of cotton in Xinjiang, China, causing decreased expression of Bacillus thuringiensis (Bt) insecticidal proteins in cotton bolls. The precise threshold temperatures and durations that lead to significant changes in Cry1Ac endotoxin levels under low temperatures remain unclear. To address this, we investigated the effects of different temperatures and stress durations on Cry1Ac endotoxin levels in cotton bolls. In 2020–2021, two Bt transgenic cotton varieties, conventional Sikang1 and hybrid Sikang3, were selected as experimental materials. Various low temperatures (ranging from 16 to 20 °C) with different durations (12 h, 24 h and 48 h) were applied during the peak boll-setting period. Results As the temperature decreased, the Cry1Ac endotoxin content in the boll shell, fiber, and seed exhibited a declining trend. Moreover, the threshold temperature which caused a significant reduction in Cry1Ac endotoxin content increased with the prolonged duration of low-temperature stress. Among the components of cotton bolls, seeds were most affected by low-temperature stress, with the threshold temperature for a significant reduction in Cry1Ac endotoxin content ranging from 17 °C to 19 °C. Correlation analysis indicated that low temperatures led to a decrease in protein synthesis capacity and an increase in degradation ability, resulting in reduced Cry1Ac endotoxin content. Pathway analysis revealed that both free amino acid and peptidase had significant negative effects on Cry1Ac endotoxin content. Conclusion In summary, when the daily average temperature was ≤ 19 °C, implementing cultural practices to reduce free amino acid content and peptidase activity could serve as effective cold defense strategies for Bt cotton production.

Abstract Endometrial cancer (EC) is associated with significant risk factors such as polycystic ovarian syndrome (PCOS) and sedentary behavior. In our study, we aim to employ machine learning algorithms to investigate the potential molecular processes that underlie their interaction and explore their respective roles in the diagnosis and immunotherapy of EC. The GEO database provides access to microarray data, which was utilized in this study to identify gene expression modules associated with PCOS and sedentary behavior, using weighted gene expression network analysis (WGCNA). Cluego software was then employed to investigate the energy enrichment of shared pathways in both PCOS and sedentary individuals, and differential gene analysis was used to confirm another two databases. The miRNAs–mRNAs controlled network was constructed to verify the pathway. The immune-related factors of the shared pathway in EC were then analyzed. Finally, to validate our findings, we conducted cell experiments using EC cell lines (AN3CA, KLE, Ishikawa, RL95-2, and HEC-1A). We found that increased intracellular aromatic compound anabolism is a common feature of both PCOS and sedentary individuals. We then developed a disease pathway model that was based on the common genetic characteristics of PCOS and sedentary behavior. We utilized pathway typing in EC samples and found a significant survival difference between the two subgroups, with the upregulated expression type exhibiting an immune-hot phenotype. Finally, the experimental results confirmed the expression of the hub gene (NAA15) in EC. The findings of our study suggest that genes related to the intracellular aromatic compound metabolic pathway can be used for immunotherapy of EC.

Abstract The global spread of H5 clade 2.3.4.4 highly pathogenic avian influenza (HPAI) viruses threatens poultry and public health. The continuous circulation of these viruses has led to their considerable genetic and antigenic evolution, resulting in the formation of eight subclades (2.3.4.4a–h). Here, we examined the antigenic sites that determine the antigenic differences between two H5 vaccine strains, H5-Re8 (clade 2.3.4.4g) and H5-Re11 (clade 2.3.4.4h). Epitope mapping data revealed that all eight identified antigenic sites were located within two classical antigenic regions, with five sites in region A (positions 115, 120, 124, 126, and 140) and three in region B (positions 151, 156, and 185). Through antigenic cartography analysis of mutants with varying numbers of substitutions, we confirmed that a combination of mutations in these eight sites reverses the antigenicity of H5-Re11 to that of H5-Re8, and vice versa. More importantly, our analyses identified H5-Re11_Q115L/R120S/A156T (H5-Re11 + 3) as a promising candidate for a broad-spectrum vaccine, positioned centrally in the antigenic map, and offering potential universal protection against all variants within the clade 2.3.4.4. H5-Re11 + 3 serum has better cross-reactivity than sera generated with other 2.3.4.4 vaccines, and H5-Re11 + 3 vaccine provided 100% protection of chickens against antigenically drifted H5 viruses from various 2.3.4.4 antigenic groups. Our findings suggest that antigenic regions A and B are immunodominant in H5 viruses, and that antigenic cartography-guided vaccine design is a promising strategy for selecting a broad-spectrum vaccine.

Abstract The existing diagnostic methods of epilepsy have great limitations, and more reliable and less difficult diagnostic methods are needed. We collected serum samples of adult patients with first-diagnosed epilepsy (EPs) and seizure control patients (EPRs) for non-targeted metabolomics detection and found that they were both significantly altered, with increased expression of nicotine addiction, linoleic acid metabolism, purine metabolism, and other metabolic pathways. The diagnostic model based on 4 differential metabolites achieved a diagnostic efficiency of 99.4% in the training cohort and 100% in the validation cohort. In addition, the association analysis of oral flora, serum metabolism, and clinical indicators also provided a new angle to analyze the mechanism of epilepsy. In conclusion, this study characterized the serum metabolic characteristics of EPs and EPRs and the changes before and after epilepsy control based on a large cohort, demonstrating the potential of metabolites as non-invasive diagnostic tools for epilepsy.

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a type of pulmonary hypertension with a low incidence. Despite pulmonary endarterectomy(PEA) being the preferred treatment for CTEPH, for patients who failed medical therapy and who are not suitable candidates for PEA, lung transplantation (LT) is still the only effective treatment for end-stage CTEPH; however, there are currently very few reports on the efficacy of LT for CTEPH. Methods We retrospectively analyzed the clinical data of seven patients diagnosed with CTEPH between July 2019 and July 2021. The follow-up deadline was March, 2022. Results The mean age at admission was 54 ± 12 years. The average value of mean pulmonary artery pressure (mPAP) was 40 ± 5 mmHg. The mean preoperative oxygenation index(PaO2/FiO2) was 203 ± 56 mm Hg. After evaluation, one patient underwent left LT and the rest underwent bilateral LT. Three patients received intraoperative veno-venous extracorporeal membrane oxygenation (ECMO) support, and four patients received intraoperative veno-arterial ECMO support. The average postoperative mPAP was 19 ± 4 mmHg. The mean postoperative oxygenation index(PaO2/FiO2) was 388 ± 83 mmHg. There was a significant difference between the preoperative and postoperative mPAP and oxygenation index(PaO2/FiO2). All patients recovered well and were discharged 37 ± 19 days postoperatively. The mean follow-up duration was 19 ± 8 months. There was no recurrence of CTEPH. Conclusions LT is an effective treatment for end-stage CTEPH, which can improve cardiopulmonary function and quality of life and prolong survival. Patients who are unable to tolerate PEA should be considered for LT as early as possible when internal medicine failed.

Magnesium-based biomaterials (MBMs) are one of the most promising materials for tissue engineering due to their unique mechanical properties and excellent functional properties. This review describes the development, advantages, and challenges of MBMs for biomedical applications, especially for tissue repair and regeneration. The history of the use of MBMs from the beginning of the 20th century is traced, and the transformative advances in contemporary applications of MBMs in areas such as orthopedics and cardiovascular surgery are emphasized. The review also provides insight into the signaling pathways affected by MBMs, such as the PI3K/Akt and RANKL/RANK/OPG pathways, which are critical for osteogenesis and angiogenesis. The review advocates that future research should focus on optimizing alloy compositions, surface modification and exploring innovative technologies such as 3D printing to improve the efficacy of MBMs in complex tissue repair. The potential of MBMs to tissue engineering and regenerative medicine is significant, urging further exploration and interdisciplinary collaboration to maximize their therapeutic effects.

Abstract The study aims to explore the central genes that Kawasaki disease (KD) and Obesity (OB) may jointly contribute to coronary artery disease. Investigating single-cell datasets (GSE168732 and GSE163830) from a comprehensive gene expression database, we identified characteristic immune cell subpopulations in KD and OB. B cells emerged as the common immune cell characteristic subgroup in both conditions. Subsequently, we analyzed RNA sequencing datasets (GSE18606 and GSE87493) to identify genes associated with B-cell subpopulations in KD and OB. Lastly, a genome-wide association study and Mendelian randomization were conducted to substantiate the causal impact of these core genes on myocardial infarction. Quantitative real-time PCR (qRT-PCR) to validate the expression levels of hub genes in KD and OB. The overlapping characteristic genes of B cell clusters in both KD and OB yielded 70 shared characteristic genes. PPI analysis led to the discovery of eleven key genes that significantly contribute to the crosstalk. Employing receiver operating characteristic analysis, we evaluated the specificity and sensitivity of these core genes and scored them using Cytoscape software. The inverse variance weighting analysis suggested an association between TNFRSF17 and myocardial infarction risk, with an odds ratio of 0.9995 (95% CI = 0.9990–1.0000, p = 0.049). By employing a single-cell combined transcriptome data analysis, we successfully pinpointed central genes associated with both KD and OB. The implications of these findings extend to shedding light on the increased risk of coronary artery disease resulting from the co-occurrence of OB and KD.

Abstract In order to predict the damage behaviours of 3D-printed continuous carbon fibre (CCF) reinforced composites, when additional short carbon fibre (SCF) composite components are employed for continuous printing or special functionality, a novel path-dependent progressive failure (PDPF) numerical approach is developed. First, a progressive failure model using Hashin failure criteria with continuum damage mechanics to account for the damage initiation and evaluation of 3D-printed CCF reinforced polyamide (PA) composites is developed, based on actual fibre placement trajectories with physical measurements of 3D-printed CCF/PA constituents. Meanwhile, an elastic-plastic model is employed to predict the plastic damage behaviours of SCF/PA parts. Then, the accuracy of the PDPF model was validated so as to study 3D-printed CCF/PA composites with either negative Poisson’s ratio or high stiffness. The results demonstrate that the proposed PDPF model can achieve higher prediction accuracies in mechanical properties of these 3D-printed CCF/PA composites. Mechanism analyses show that the stress distribution is generally aggregated in the CCF areas along the fibre placement paths, and the shear damage and matrix tensile/compressive damage are the key damage modes. This study provides a new approach with valuable information for characterising complex 3D-printed continuous fibre-matrix composites with variable mechanical properties and multiple constituents.

Abstract Background In recent years, global climate change in tandem with increased human activity has resulted in habitat degradation or the migration of rare medicinal plants, potentially impacting the quality of medicinal herbs. Astragalus membranaceus var. mongholicus is a valuable bulk medicinal material in Northwest China. As the demand for this medicinal herb continues to increase in both domestic and international markets, ensuring the sustainable development of high-quality Astragali Radix is important. In this study, the maximum entropy (Maxent) model was applied, thereby incorporating 136 distribution records, along with 39 environmental factors of A. membranaceus var. mongholicus, to assess the quality zonation and potential distribution of this species in China under climate change. Results The results showed that the elevation, annual mean temperature, precipitation of wettest month, solar radiation in June, and mean temperature of warmest quarter were the critical environmental factors influencing the accumulation of astragaloside IV and Astragalus polysaccharide in A. membranaceus var. mongholicus. Among the twelve main environmental variables, annual mean temperature, elevation, precipitation of the wettest month, and solar radiation in November were the four most important factors influencing the distribution of A. membranaceus var. mongholicus. In addition, ecological niche modelling revealed that highly suitable habitats were mainly located in central and western Gansu, eastern Qinghai, northern Shaanxi, southern Ningxia, central Inner Mongolia, central Shanxi, and northern Hebei. However, the future projections under climate change suggested a contraction of these suitable areas, shifting towards northeastern high-latitude and high-elevation mountains. Conclusions The findings provide essential insights for developing adaptive strategies for A. membranaceus var. mongholicus cultivation in response to climate change and can inform future research on this species. By considering the identified environmental factors and the potential impacts of the predicted climate changes, we can visualize the regional distribution of high-quality Radix Astragali and develop conservation strategies to protect and restore its suitable habitats.

In order to obtain a green and efficient preparation process for carboxymethyl porous starch, carboxymethyl porous starch was prepared by mechanical activation solid phase etherification method, where enzymatically hydrolyzed porous cassava starch was used as raw material, sodium chloroacetate as etherifying agent, and sodium hydroxide as catalyst. Single-factor experiments were conducted to explore the effects of various factors on the degree of substitution (DS) of carboxymethyl porous starch, and the application of carboxymethyl porous starch in soy sauce was discussed. The results showed that the optimal process conditions for the preparation of carboxymethyl porous starch by mechanical activation and solid phase synthesis method were as follows: The molar ratio of porous starch to sodium chloroacetate was 1:1, the mass fraction of sodium hydroxide was 18.8%, the ball milling time was 1.5 h, and the reaction temperature was 50℃. Under these conditions, the highest DS of carboxymethyl porous starch obtained was up to 0.2532. Furthermore, the carboxymethylation reaction of porous starch was confirmed by infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM). With the increase of DS of carboxymethyl porous starch, its cold water solubility, water absorption, and adsorption of lemon yellow increased. When DS was 0.2532, the cold water solubility of carboxymethyl porous starch reached 64.94%, the water absorption rate reached 180.73%, and the adsorption amount of lemon yellow reached 2.5086 mg·g−1. The powder soy sauce prepared by carboxymethyl porous starch has better solubility, lower moisture absorption, and higher content of amino acid nitrogen, and is closer to the original soy sauce compared to those prepared by cassava starch and porous starch. Therefore, the mechanical activation and solid phase etherification method can effectively prepare carboxymethyl porous starch, which is simple to operate, environmentally friendly, and highly substitutive, providing a scientific basis for the development and utilization of porous starch.

Abstract The KEYNOTE-522 (KN522) regimen for neoadjuvant treatment of triple negative breast cancer (TNBC) utilized q3week dosing for doxorubicin plus cyclophosphamide (AC); however, dose-dense AC (ddAC) has demonstrated superior overall survival (OS) compared to q3week AC in anthracycline and taxane-based regimens. We performed a retrospective analysis assessing the use of ddAC in KN522 and the impact of sequencing ddAC before or after carboplatin/paclitaxel (CbT) plus pembrolizumab on multiple outcomes. 128 patients with TNBC were included. Overall pathologic complete response (pCR) rate of 56%. Sequencing of ddAC vs CbT first showed no difference in pCR rate (ddAC 55% vs. CbT 58%, p = 0.77). However, ddAC first compared to CbT first correlated with a significant increase in the incidence of overall treatment delays (ddAC 70% vs. CbT 51%, p = 0.03), with cytopenias most frequent (ddAC 59% vs. CbT 31%, p = 0.001). ddAC in a modified KN522 regimen is safe, tolerable, and effective. Efficacy is comparable regardless of chemotherapy sequencing, but ddAC first is significantly associated with higher rates of treatment delays and cytopenias.