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Abstract Rice is highly sensitive to low temperatures, making cold stress a significant factor limiting its growth, especially during the bud bursting stage. To address this, an RIL population derived from a cross between cold-tolerant and cold-sensitive rice varieties was used to identify nine QTLs linked to cold tolerance under temperatures of 4 ℃, 5 °C, and 6 ℃ using a high-density genetic map. One candidate gene, LOC_Os07g44410, was identified through gene function annotation, haplotype analysis, and qRT-PCR, with two main haplotypes (Hap1 and Hap2) showing distinct phenotypic differences. qRT-PCR analysis showed that the expression level of LOC_Os07g44410 in cold tolerant lines carrying Hap1 was significantly higher than that in cold sensitive lines carrying Hap2. Hap1, associated with greater cold tolerance, was predominant in japonica rice, while Hap2 related to cold sensitive was majority in indica rice. This study offers valuable genetic resources for further research on cold tolerance mechanisms and breeding applications at the bud bursting stage in rice.

Abstract We investigate the motion of particles in the spacetime of a Kerr black hole immersed in swirling universes. Using the Poincaré section, fast Lyapunov exponent indicator, bifurcation diagram, and basins of attraction, we present the effects of the swirling parameter and the spin parameter on the dynamical behaviors of the motion of particles, and confirm the presence of chaos in the motion of particles in this background spacetime. We find that the swirling parameter can change the range of the spin parameter where the chaos occurs, and vice versa. Moreover, we observe clearly that, regardless of the spin parameter, there exist some self-similar fractal fine structures in the basins boundaries of attractors for the spacetime of a black hole immersed in swirling universes. The combination of the swirling parameter and the spin parameter provides richer physics in the motion of particles.

Laser powder bed fusion (L-PBF) produced NiTi alloys have significant potential in biomedical applications. Varying the parameters of the L-PBF process may result in the NiTi alloys with different ratios of B2 and B19′ phases, thereby, the different corrosion performance in the human body. However, a dearth of research efforts remains dedicated to resolving this issue. This work employed three different but comparable sets of parameters in the L-PBF process to produce NiTi alloys with different ratios of B2 and B19′ phases. The corrosion behavior of samples in Hank's solutions with the addition of lactic acid and their evolution of passive films were investigated. The sample with the dominant B2 phase has a slower passive film formation rate and a higher corrosion rate than those with mixed B2/B19′ phases at the early film formation stage. As corrosion progresses, the passive films rapidly form within 24 h, followed by gradual degradation, represented by their varied charge transfer resistance. The degradation of passive films is attributed to the dissolution of NiO on the film surfaces, resulting from the hydration reaction. Such a phenomenon leads to imperfections in the passive films, diminishing their protective effectiveness for the underlying substrate. The sample with a faster film formation rate would also maintain a considerable corrosion resistance after film degradation. The presence of lactic acid accelerates the degradation of passive film and decreases the corrosion resistance of samples. This work advances the understanding of the relationship between the evolution of passive films and the processing parameters of L-PBF-produced NiTi alloys.

Abstract This study aimed to identify the correlation of serum 25(OH)D level with sarcopenia and its components in Chinese elderly aged 65 years and above from rural areas. A total of 368 Chinese elderly aged 65 years and above in rural areas were enrolled. Indicators of muscle mass and strength, including the appendicular skeletal muscle mass (ASM), skeletal muscle index (SMI) and hand grip strength (HGS) were measured. Physical performance was assessed by the Short Physical Performance Battery (SPPB). Serum 25(OH)D levels were measured using the liquid chromatography with tandem mass spectrometry. Correlations of serum 25(OH)D level with sarcopenia and its components in Chinese elderly were identified by the binary logistic regression and linear regression analyses. The median serum 25(OH)D level was 34.80 ng/ml, and significantly higher in men than in women (40.70 ng/ml vs. 27.30 ng/ml). The prevalence of sarcopenia in our cohort was 21.5%, and higher in men than in women (29.4% vs. 10.8%). The serum 25(OH)D level was not correlated with sarcopenia, HGS and SPPB score in either male or female elderly. Positive correlations of age with sarcopenia, low HGS and low SPPB score were observed in male elderly, while significant correlations were not observed in females. Correlation analyses of sarcopenia components revealed that age was negatively correlated with SMI and gait speed in male elderly, but negatively correlated with the gait speed and positively correlated with the time to complete 5 sit-to-stand movements in female elderly. In conclusion, rural Chinese elderly have relatively high vitamin D level and prevalence of sarcopenia. Age but not serum 25(OH)D level is significantly correlated with sarcopenia in vitamin D sufficient male elderly.

Background: Small cell lung cancer (SCLC) is a highly aggressive disease characterized by early metastasis. Aneuploid CD31- disseminated tumor cells (DTCs) and CD31+ disseminated tumor endothelial cells (DTECs) residing in the bone marrow are generally considered as the initiators of metastatic process. However, the clinical significance of DTCs and DTECs in SCLC remains poorly understood. The aim of this study is to investigate the clinical implications of diverse subtypes of highly heterogeneous DTCs and DTECs in SCLC patients. Methods: Subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) was applied to enrich and perform comprehensive morphologic, karyotypic, and phenotypic characterization of aneuploid DTCs and DTECs in 30 patients. Additionally, co-detection of circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) was conducted on 24 of the enrolled patients. Proof-of-concept of the whole exon sequencings (WES) on precisely selected different subtypes of CTCs or DTCs, longitudinally detected from a representative case with pathologically confirmed bone marrow metastasis, was validated to feasibly reveal genetic mutations in these cells. Results: DTCs, DTECs and their subtypes were readily detectable in SCLC patients. Comparative analysis revealed that the number of DTCs and DTECs was significantly higher than that of their corresponding CTCs and CTECs (P < 0.001 for both). Positive detection of disseminated tumor microemboli (DTM) or disseminated tumor endothelial microemboli (DTEM) was associated with inferior survival outcomes (P = 0.046 and P = 0.048). Patients with EpCAM+ DTCs detectable displayed significantly lower disease control rate (DCR) (16.67% vs 73.33%, P = 0.019), reduced median progression-free survival (mPFS) and median overall survival (mOS) compared with those with EpCAM- DTCs (P = 0.028 and P = 0.002, respectively). WES analysis indicated that post-treatment DTCs isolated from bone marrow at the time of disease progression shared more homologous somatic gene mutations with pre-treatment CTCs compared with post-treatment CTCs. Conclusions: Our findings suggest that bone marrow sampling and characterization of DTC subtypes provided a valuable tool for predicting treatment response and the prognosis in SCLC. Moreover, DTCs inherit a greater amount of homologous somatic information from pre-treatment CTCs, indicating their potential role in disease progression and treatment resistance.

Livestock behavior is related to the healthy breeding and welfare level. Therefore, monitoring the behavior of sheep is helpful to predict the health status of sheep and thus safeguard the production performance of sheep. Taking semi-housed sheep as the research object, a behavior identification method for housed sheep based on spatio-temporal information is proposed. Firstly, video acquisition of housed sheep is carried out, and sheep detection and tracking is implemented based on the YOLOv5 coupled with a Deep-SORT algorithm, which detects sheep from the flock and labels their identity information; then, sheep posture estimation is done based on the Alphapose algorithm, which estimates the keypoints in the skeleton; finally, the detected keypoints are inputted into the trained spatio-temporal graph convolutional network model, and the spatio-temporal graph constructed from the keypoints and edge information is used for sheep behavior recognition. In the study, two keypoints selection proposals were made to implement sheep behavior recognition for non-contacted detection of ruminating, lying down and other behaviors. The results show the feasibility of sheep behavior recognition based on spatio-temporal information in semi-housed farming. The method provides a new solution idea for intelligent monitoring of sheep behavior and health assessment.

Circular RNAs (circRNAs) play crucial roles in the immune and inflammatory responses of many diseases by acting as competing endogenous RNAs (ceRNAs). However, the role of circRNAs as ceRNAs in the immune and inflammatory processes of coronary atherosclerosis heart disease (CHD) remains unclear. This study aimed to identify and validate the potential immune-related circRNAs as biomarkers for CHD. Firstly, we constructed a ceRNA regulatory network including 14 circRNAs, 24 miRNAs, and 15 genes through bioinformatics analysis. Four hub genes were identified and five candidate immune-related circRNAs were screened. Subsequently, the expression levels of these candidate circRNAs were detected by qRT-PCR. Notably, hsa_circRNA_101069 and hsa_circRNA_406053 showed significant up-regulation in CHD patients (p < 0.001). The value of these circRNAs as biomarkers for CHD was evaluated by the area under the ROC curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) indexes. Adding circRNAs to a traditional CHD model significantly enhanced classification performance, with an IDI of 0.058 and an NRI of 0.280 for hsa_circRNA_101069 and an IDI of 0.051 and an NRI of 0.480 for hsa_circRNA_406053. Furthermore, hsa_circRNA_101069 was up-regulated in ox-LDL-induced THP-1 macrophages, and silencing hsa_circRNA_101069 significantly inhibited the apoptosis rates and the inflammatory cytokines levels. This study constructed an immune-related circRNA-miRNA-mRNA network and identified two circRNAs as biomarkers for CHD, with hsa_circRNA_101069 potentially contributing to the pathological basis of CHD.

Abstract Glycolysis-derived lactate was identified as substrate for histone lactylation, which has been regarded as a significant role in transcriptional regulation in many tissues. However, the role of histone lactylation in the metabolic center, the hypothalamus, is still unknown. Here, we show that hypothalamic pro-opiomelanocortin (POMC) neuron-specific deletion of family with sequence similarity 172, member A (Fam172a) can increase histone lactylation and protect mice against diet-induced obesity (DIO) and related metabolic disorders. Conversely, overexpression of Fam172a in POMC neurons led to an obesity-like phenotype. Using RNA-seq and CUT&Tag chromatin profiling analyzes, we find that knockdown of Fam172a activates the glycolytic process and increases peptidylglycine α-amidating monooxygenase (PAM), which affects the synthesis of α-MSH, via H4K12la (histone lactylation). In addition, pharmacological inhibition of lactate production clearly abrogates the anti-obesity effect of PFKO (POMC-Cre, Fam172a loxP/loxP , POMC neurons Fam172a knockout). These findings highlight the importance of Fam172a and lactate in the development of obesity and our results mainly concern male mice.

Abstract The Whale Optimization Algorithm (WOA) is regarded as a classic metaheuristic algorithm, yet it suffers from limited population diversity, imbalance between exploitation and exploration, and low solution accuracy. In this paper, we propose the Spiral-Enhanced Whale Optimization Algorithm (SEWOA), which incorporates a nonlinear time-varying self-adaptive perturbation strategy and an Archimedean spiral structure into the original WOA. The Archimedean spiral structure enhances the diversity of the solution space, aiding the algorithm in escaping local optima. The nonlinear time-varying self-adaptive optimization dynamic perturbation strategy improves the algorithm’s local search capability and enhances solution accuracy. The effectiveness of the proposed algorithm is validated from multiple perspectives using CEC2014 test functions, CEC2017 test functions, and 23 benchmark test functions. The experimental results demonstrate that the enhanced Whale Optimization Algorithm significantly improves population diversity, balances global and local search, and enhances solution accuracy. Additionally, SEWOA exhibits excellent performance in solving three engineering design problems, showcasing its value and wide range of potential applications.

Abstract Cardiac arrest (CA) is a serious health concern that often results in mortality or severe neurological dysfunction in the case of survival. Our aim was to explore the neurological prognostic factors in patients with CA. This retrospective observational study included adult patients with CA. We investigated serum neuron-specific enolase (NSE), S100 calcium-binding protein β (S100β), and indices and parameters at 1, 3, 5, 7 and intensive care unit (ICU) discharge days after CA. The primary study endpoint was the Cerebral Performance Category (CPC) scale score at ICU discharge, which was dichotomized as good neurological outcome (CPC 1–2: full recovery or moderate disability) and poor neurological outcome (CPC 3–5: severe disability, vegetative state, or death). Of the 191 adult patients with CA, 42 (22%) had good neurological outcomes, and 149 (78%) had poor neurological outcomes. NSE at 1,3,5,7 and ICU discharge days showed excellent predictive accuracy for neurological outcomes (area under the curve [AUC]: 0.666, 0.716, 0.870, 0.739, and 0.901, respectively). However, S100β exhibited general predictive power (AUC: 0.666, 0.573, 0.607, 0.594, 0.727). Finally, the early warning model, which combined day 1 NSE, day 1 S100β, cardiac arrest time, SOFA scores, APACHE II scores, and age, was used to screen CA patients with poor neurological prognosis at early stages and had an AUC of 0.792. Serum concentrations of NSE and S100β were significantly elevated in CA patients and could be prognostic biomarkers to predict neurological outcomes. Day 1 NSE and S100β combined with multiple indicators could be a decent early warning model for poor neurological prognosis in patients with CA.

Abstract It is generally believed that Carbapenem-resistant Enterobacterales (CRE) colonization is primarily responsible for systemic infection in humans. However, there is no consensus on whether decolonization should be recommended in clinical practice. In China, the specific situation of CRE colonization and consequent systemic infection in hospitalized patients necessitates further exploration. We conducted a cohort study and analyzed various clinical characteristics of inpatients with intestinal CRE colonization. A risk prediction model for consequent CRE infection was established and externally validated. Our prediction model is freely available online at https://creinfection.shinyapps.io/dynnomapp/ . 839 intestinal CRE colonization samples from inpatients were included. 317 cases of intestinal CRE colonization were enrolled, 25.9% of whom developed systemic infections. The consequent CRE infection rates of Klebsiella pneumoniae and Escherichia coli were 27.0% and 32.3%. The departments at high risk for subsequent CRE infection were respiratory medicine, hematology, and intensive care unit. Secondary infection after intestinal CRE colonization in inpatients can significantly prolong the length of hospital stay (26 days vs. 33 days, P < 0.001), increase the total medical cost (144735.34￥ vs. 281852.34￥, P < 0.001), and has poor (85.11% vs. 52.44%, P < 0.001) efficacy and high mortality (5.96% vs. 18.29%, P = 0.001). Our study makes a significant contribution to comprehensively specify CRE infection, because these results can facilitate early identification of high-risk hospitalized patients, timely implementation to decolonize treatment interventions, ultimately achieve the goal of CRE nosocomial infection prevention and control.

Abstract The identification and classification of various phenotypic features of Auricularia cornea fruit bodies are crucial for quality grading and breeding efforts. The phenotypic features of Auricularia cornea fruit bodies encompass size, number, shape, color, pigmentation, and damage. These phenotypic features are distributed across various views of the fruit bodies, making the task of achieving both rapid and accurate identification and classification challenging. This paper proposes a novel multi-view multi-label fast network that integrates two different views of the Auricularia cornea fruiting body, enabling rapid and precise identification and classification of six phenotypic features simultaneously. Initially, a multi-view feature extraction model based on partial convolution was constructed. This model incorporates channel attention mechanisms to achieve rapid phenotypic feature extraction of the Auricularia cornea fruiting body. Subsequently, an efficient multi-task classifier was designed, based on class-specific residual attention, to ensure accurate classification of phenotypic features. Finally, task weights were dynamically adjusted based on heteroscedastic uncertainty, reducing the training complexity of the multi-task classification. The proposed network achieved a classification accuracy of 94.66% and an inference speed of 11.9 ms on an image dataset of dried Auricularia cornea fruiting bodies with three views and six labels. The results demonstrate that the proposed network can efficiently and accurately identify and classify all phenotypic features of Auricularia cornea.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic necrotizing vasculitis that predominantly affects small vessels. In this report, we present a typical case of granulomatosis with polyangiitis (GPA) complicated by spontaneous renal hemorrhage (SRH), a rare but potentially severe condition. The patient developed SRH during immunosuppressive therapy but recovered following conservative treatment. We then conducted a systematic literature review on SRH in the context of AAV, and analyzed clinical features, management strategies, and patient prognosis. A total of 15 patients were enrolled for statistical analysis, comprising the one case reported in the current study and 14 from the literature. Of these patients, nine presented with GPA and six showed microscopic polyangiitis (MPA), with a sex distribution of 3:2 males to females. The average patient age was 54.5 years, and ranged from 25 to 82 years. Acute flank pain was the most common clinical manifestation, and was occasionally accompanied by anemia and shock. Treatment varied for the different patients. Eight patients received glucocorticoid and immunosuppressive agents that included rituximab, cyclophosphamide, and azathioprine; five patients underwent transcatheter arterial embolization (TAE); and one patient underwent nephrectomy. Our findings indicate that SRH typically occurs early in the course of AAV and correlates with disease activity, with renal aneurysm rupture as the primary cause. More than half of the patients respond well to corticosteroids and immunosuppressants. Timely TAE is essential for patients showing persistent deterioration despite conservative management.

To enhance the personal immunity to COVID-19, a third booster dose of inactivated COVID-19 vaccines program campaign was implemented in China. Our study endeavored to compare the dynamics of neutralizing antibodies generated by four distinct booster vaccines against three kinds of live SARS-CoV-2 virus (wild-type, Delta AY.23, and Omicron BA5.2). This cohort study involved 320 healthy individuals, who were randomly assigned to four groups, to receive boosters with inactivated vaccine (COVac and BIBP), the adenovirus type-5-vectored vaccine (Convidecia), and the recombinant protein-based vaccine (Zifivax), respectively, all the vaccines studied had the Wuhan variant as their parental variant. Participants were recruited from December 2021 to June 2022, with a follow-up period of 180 days. We evaluated humoral immune responses and their longevity by measuring the geometric mean titers (GMTs) of neutralizing antibodies against the SARS-CoV-2 virus at various time points post-boost. After 180 days of follow-up, 310 participants completed the study. Across all booster groups, neutralizing antibodies against the wild-type virus declined sharply within the first 90 days, accounting for an 81.24 to 92.34% reduction, then slowed down with gradually decreasing decay rates. By day 14 of post-boost, the ability to neutralize the Delta variant slightly diminished compared to the wild-type, whereas neutralizing antibodies against the Omicron variant exhibited a more pronounced decline, ranging from 10.78 to 19.88 times lower than those against the wild-type. Notably, heterologous boosting with the Convidecia vaccine maintained higher GMTs of neutralizing antibodies against both Delta and Omicron variants compared to the other boosters. At 180 days of post-boost, GMTs of neutralizing antibodies against SARS-CoV-2 had substantially decreased, yet individuals who received the Convidecia vaccine still exhibited higher titers than those who received other boosters. In summary, neutralizing antibody levels significantly waned 180 days after the third vaccine dose, with the most pronounced decline occurring within the initial 90 days. Heterologous boosting with Convidecia demonstrated a more robust, durable, and broad humoral immune response compared to boosting with inactivated vaccines or Zifivax, suggesting that adenovirus vector vaccines possess a special advantage in the realm of vaccine development for preventing infectious diseases.

ObjectiveOsteosarcoma is the most common primary bone cancer with a high propensity for local invasion and metastasis. An increasing number of research studies show that telomeres play an important role in the occurrence and development of cancer. Thus, we established a telomere-related signature in osteosarcoma to comprehensively evaluate the pathogenic roles of telomeres in this disease.MethodsThe data on osteosarcoma were collected from the TARGET and Gene Expression Omnibus databases. First, we constructed a telomere-related signature using univariate and LASSO Cox regression analyses. Subsequently, we analyzed the prognostic value, functional annotation, immune microenvironment, and cell communication patterns of the telomere-related signature in osteosarcoma via comprehensive bioinformatics analyses. Cell proliferation was analyzed using the CCK-8 assay, and cell migration and invasion capabilities were evaluated using the Transwell assay.ResultsBased on the SP110, HHAT, TUBB, MORC4, TERT, PPARG, MAP3K5, PAGE5, MAP7, and CAMK1G, a telomere-related signature was built in osteosarcoma patients. The telomere-related signature could effectively predict the prognosis of osteosarcoma patients. The osteosarcoma patients in the high TELscore group exhibited poor prognosis. In addition, the telomere-related signature demonstrated predictive value for the immune microenvironment and drug sensitivity in osteosarcoma. Finally, we discovered significant reduction in MAP7 expression in osteosarcoma cells, and patients with low MAP7 expression had poor prognosis. Moreover, the overexpression of MAP7 significantly reduced cell proliferation, the ability of cell migration, and invasion in osteosarcoma cells.ConclusionA telomere-related signature was constructed in osteosarcoma patients, offering predictive values into prognosis, the immune microenvironment, and drug sensitivity. Moreover, MAP7 might serve as a prognostic marker for osteosarcoma patients.

Parathyroid hormone (PTH) is a pivotal hormone that regulates serum calcium and phosphate and is closely associated with higher risk of cardiovascular disease and mortality in patients with chronic kidney disease (CKD). PTH can undergo oxidation at methionine 8 and methionine 18 of the molecule. This oxidation process leads to a lower binding affinity to the PTH receptor due to molecular refolding, particularly for PTH oxidized at methionine 8. Although, the oxidation of PTH has been reported for several decades, it is only recently that a method has been developed to detect non-oxidized PTH (n-oxPTH) levels. The utilization of this assay enables the precise detection of n-oxPTH levels and facilitates the evaluation of their correlation with poor prognosis in patients with CKD. However, the current available clinical research findings indicate that n-oxPTH does not demonstrate clinical superiority over iPTH. Here, we provide a comprehensive review on the mechanism of PTH oxidation, the n-oxPTH assay method, and its correlation with iPTH and clinical outcomes.

This article describes a case of successful management of late-onset CLS occurring after allo-HSCT, employing bevacizumab as the therapeutic agent. Capillary leak syndrome (CLS) represents a critical complication arising from allogeneic hematopoietic stem cell transplantation (allo-HSCT). The prognosis for CLS remains considerably constrained. A targeted therapeutic approach targeting vascular endothelial growth factor (VEGF) offers a novel strategy for the management of CLS.

Abstract Objective To develop a reproducible survival rabbit model for laryngotracheal stenosis (LTS). Methods Seventy New Zealand white (NZW) rabbits were randomly divided into experimental groups (n = 30) and a control group (n = 40). In experimental groups, a nylon brush was inserted retrograde from the tracheotomy through the subglottis and rotated until a full layer circumferential mucosal injury to cartilage exposure, assisted by fiberoptic laryngoscopy (FOL) visualization. Experimental group 1 (n = 10), rotated 10 times; group 2 (n = 20), rotated 20 times. The control group underwent tracheotomy only without nylon brush scraping. The rabbits underwent FOL at 1st, 4th, 8th, and 12th week postinjury respectively to observe the formation of LTS. They were euthanized and the larynxes and tracheas were subjected to gross and histopathological examination at 12 weeks postinjury. Results The control group all survived, while five cases in experimental groups died from LTS and/or mucous plug. Histological observation showed that the control group had intact laryngotracheal mucosal epithelium without any stenosis; the experimental groups showed proliferation of fibroblasts and thickening of collagen fibers. The mean stenosis in control group was 9.31 ± 0.98%, while that in experimental group 1 was 32.78 ± 7.07% and 58.25 ± 8.96% in experimental group 2. The difference between the three groups was statistically significant (χ2 = 47.98, p

Precisely estimating the carbonate’s porosity is essential for subsurface reservoir characterization. However, conventional methods for obtaining porosity using either core measurements or logging interpretation are expensive and inefficient. Considering the sequence data feature of logging curves and the booming development of intelligent networks in geoscience, this study proposes a reliable and low-cost intelligent Porosity Prediction Transformer (PPTransformer) framework for reservoir porosity prediction using logging curves as inputs. PPTransformer network not only extracts global features through convolutional layers but also captures local features using Encoders and self-attention mechanisms. This proposed network is a data-driven supervised learning framework with a superior accuracy and robustness. The testing results demonstrate that compared to the Transformer network, Long Short-Term time series network, and support vector machine method, the PPTransformer framework exhibits the highest average correlation coefficient and determination coefficient indicators and the lowest root mean square error and absolute error indicators. Moreover, adding stratigraphic lithology as geological constraints to the PPTransformer framework further improves the prediction performance. This indicates that geological constraints will enhance network performance.

Summary: Tank-binding kinase 1 (TBK1) is a critical signal transducer in the nuclear factor κB (NF-κB) and interferon regulatory factor (IRF) pathways, essential for innate immunity. However, its negative regulation mechanisms remain unclear. This study demonstrates that TBK1 succinylation, regulated by desuccinylase SIRT5, inhibits lipopolysaccharide (LPS)/Toll-like receptor 4 (TLR4)-mediated NF-κB and IRF signaling activation. We identified three key succinylation sites on TBK1: K38, K154, and K692. In endotoxemia and sepsis models, reduced SIRT5 levels in macrophages increased TBK1 succinylation, inhibiting its binding to IRF3 and TRAF2 and suppressing the inflammatory response. In vivo, adoptive transfer of macrophages expressing the succinylation-resistant TBK1-2KR (K154/692R) mutant reversed the inflammatory cytokine suppression caused by SIRT5 deficiency, exacerbating sepsis-induced lung injury. These findings reveal a novel mechanism by which SIRT5 modulates TBK1 activity and macrophage-mediated inflammation during sepsis.

Objective This study aimed to investigate the role of RAB32 in glioblastomas and its molecular mechanisms that regulate gliomas. Methods The expression and prognostic value of RAB32 were evaluated using western blotting and the Gene Expression Profiling Interactive, Chinese Glioma Genome Atlas, and The Cancer Genome Atlas databases. Lentivirus containing sh-RAB32 or OE-RAB32 was used to manipulate RAB32 expression in glioma cells. The effects of RAB32 on cell proliferation, migration, and invasion were determined by western blotting, cell counting kit-8, plate cloning, wound healing, and transwell assays. Gene set enrichment analysis was used to screen for associations between the JAK/STAT3 signaling pathway and RAB32. The role of this pathway was verified using JAK/STAT3 inhibitors. Results RAB32 expression was significantly upregulated in patients with glioma and in glioma cell lines. The expression level was positively correlated with the glioma grade and served as an independent prognostic factor. In vitro experiments revealed that RAB32 knockdown inhibited glioblastoma cell proliferation, migration, and invasion, while the opposite effects were observed with overexpression and could be inhibited by the JAK/STAT3 inhibitor BP-1-102. Conclusion RAB32 promotes malignant progression of glioblastoma cells through the JAK/STAT signaling pathway, providing new possibilities for therapeutic targets for glioblastoma.

Nucleotides and β-glucan have demonstrated positive effects on the growth and health of aquaculture species. However, little research has been done on the combined effects of using both supplements on the intestinal health and flesh quality of fish. In the present study, we evaluated the impact of nucleotides (0.01 %) or/and β-glucan (0.10 %) on parameters related to intestinal health and flesh quality in grass carp (69.97 ± 0.05 g) over a 60-day feeding period. The results showed that both nucleotides and β-glucan significantly increased catalase activity, enhanced mRNA expression level of zonula occludens-3, downregulated interleukin-1β, interferon, Toll-like receptor-4, and Toll-like receptor-7 expression in the intestine (P < 0.05). Additionally, they also resulted in enhanced springiness and increased percentage of total unsaturated fatty acids, while reducing Myostatin 1 expression and total saturated fatty acids content in the muscle (P < 0.05). This indicates that these supplements have similar effects in promoting oxidation resistance, suppressing inflammation, and improving intestinal barrier integrity and flesh quality in grass carp. Besides, the combination of nucleotides and β-glucan led to a decrease in Firmicutes abundance and an increase in Actinobacteria compared to the control group. We further observed the synergistic effects of nucleotides and β-glucan in decreasing the expression of inflammation related genes (interleukin-1β, interferon, Toll-like receptor-4, and Toll-like receptor-7) and improving parameters associated with intestinal morphology (villus height, villus width and gut wall thickness) and flesh quality (chewiness, springiness, total tasty free amino acids, total saturated fatty acids and total unsaturated fatty acids). Overall, our results suggest that the combined application of nucleotides and β-glucan is more effective in promoting intestinal health and improving flesh quality in grass carp compared to using either supplement alone.

AbstractWith the development of the manufacturing industry and the continuous progress of science and technology, as one of the core equipment of the high-end manufacturing industry, CNC lathe is also developed and improved. After searching a large amount of literature, through the elaboration of the current domestic and foreign research institutions for the CNC lathe research history, development level and development status, comparative analysis of different types of CNC lathe structure, characteristics and applications, concluded that the CNC lathe is the best choice for the current rotary parts machining manufacturing tools. On this basis, it analyzes and summarizes the tool path planning, cutting process optimization, high-speed cutting technology and other key technical issues to be solved in the future development of CNC lathe, and finally looks forward to the development trend of CNC lathe, in order to provide references for related research.

Background: When resuscitating patients with septic shock, cerebrovascular reactivity parameters are calculated by monitoring regional cerebral oxygen saturation (rSO2) using near-infrared spectroscopy to determine the optimal blood pressure. Here, we aimed to analyze the impact of cerebral autoregulation-directed optimal blood pressure management on the incidence of delirium and the prognosis of patients with septic shock. Methods: This prospective randomized controlled clinical study was conducted in the Xiangya Hospital of Central South University, China. Fifty-one patients with septic shock (December 2020–May 2022) were enrolled and randomly allocated to the experimental (n=26) or control group (n=25). Using the ICM+ software, we monitored the dynamic changes in rSO2 and mean arterial pressure (MAP) and calculated the cerebrovascular reactivity parameter tissue oxygen reactivity index to determine the optimal blood pressure to maintain normal cerebral autoregulation function during resuscitation in the experimental group. The control group was treated according to the Surviving Sepsis Campaign Guidelines. Differences in the incidence of delirium and 28-day mortality between the two groups were compared, and the risk factors were analyzed. Results: The 51 patients, including 39 male and 12 female, had a mean age of (57.0±14.9) years. The incidence of delirium was 40.1% (23/51), and the 28-day mortality rate was 29.4% (15/51). The mean MAP during the first 24 h of intensive care unit (ICU) admission was higher ([84.5±12.2] mmHg vs. [77.4±11.8] mmHg, P=0.040), and the incidence of delirium was lower (30.8% vs. 60.0%, P=0.036) in the experimental group than in the control group. The use of cerebral autoregulation-directed optimal blood pressure (odds ratio [OR]=0.090, 95% confidence interval [CI]: 0.009 to 0.923, P=0.043) and length of ICU stay (OR=1.473, 95% CI: 1.093 to 1.985, P=0.011) were risk factors for delirium during septic shock. Vasoactive drug dose (OR=8.445, 95% CI: 1.26 to 56.576, P=0.028) and partial pressure of oxygen (PaO2) (OR=0.958, 95% CI: 0.921 to 0.996, P=0.032) were the risk factors for 28-day mortality. Conclusions: The use of cerebral autoregulation-directed optimal blood pressure management during shock resuscitation reduces the incidence of delirium in patients with septic shock. Trial Registration: ClinicalTrials.gov ldentifer: NCT03879317

Abstract Purpose Glycolysis and immune metabolism play important roles in acute myocardial infarction (AMI). Therefore, this study aimed to identify and experimentally validate the glycolysis-related hub genes in AMI as diagnostic biomarkers, and further explore the association between hub genes and immune infiltration. Methods Differentially expressed genes (DEGs) from AMI peripheral blood mononuclear cells (PBMCs) were analyzed using R software. Glycolysis-related DEGs (GRDEGs) were identified and analyzed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) for functional enrichment. A protein–protein interaction network was constructed using the STRING database and visualized using Cytoscape software. Immune infiltration analysis between patients with AMI and stable coronary artery disease (SCAD) controls was performed using CIBERSORT, and correlation analysis between GRDEGs and immune cell infiltration was performed. We also plotted nomograms and receiver operating characteristic (ROC) curves to assess the predictive accuracy of GRDEGs for AMI occurrence. Finally, key genes were experimentally validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting using PBMCs. Results A total of 132 GRDEGs and 56 GRDEGs were identified on the first day and 4–6 days after AMI, respectively. Enrichment analysis indicated that these GRDEGs were mainly clustered in the glycolysis/gluconeogenesis and metabolic pathways. Five hub genes (HK2, PFKL, PKM, G6PD, and ALDOA) were selected using the cytoHubba plugin. The link between immune cells and hub genes indicated that HK2, PFKL, PKM, and ALDOA were significantly positively correlated with monocytes and neutrophils, whereas G6PD was significantly positively correlated with neutrophils. The calibration curve, decision curve analysis, and ROC curves indicated that the five hub GRDEGs exhibited high predictive value for AMI. Furthermore, the five hub GRDEGs were validated by RT-qPCR and western blotting. Conclusion We concluded that HK2, PFKL, PKM, G6PD, and ALDOA are hub GRDEGs in AMI and play important roles in AMI progression. This study provides a novel potential immunotherapeutic method for the treatment of AMI.

Abstract Background The role of circular RNAs (circRNAs) as biomarkers of coronary artery disease (CAD) remains poorly explored. This study aimed to identify and validate potential circulating circRNAs as biomarkers for the diagnosis of CAD. Methods The expression profile of circRNAs associated with CAD was obtained from Gene Expression Omnibus (GEO) database. Differential expression analysis, weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operation (LASSO) were employed to identify CAD-related hub circRNAs. The expression levels of these hub circRNAs were validated using qRT-PCR in blood samples from 100 CAD patients and 100 controls. The diagnostic performance of these circRNAs was evaluated through logistic regression analysis, receiver operator characteristic (ROC) analysis, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Functional enrichment analyses were performed to predict the possible mechanisms of circRNAs in CAD. Results A total of ten CAD-related hub circRNAs were identified through WGCNA and LASSO analysis. Among them, hsa_circ_0069972 and hsa_circ_0021509 were highly expressed in blood samples of CAD patients, and they were identified as independent predictors after adjustment for relevant confounders. The area under the ROC curve for hsa_circ_0069972 and hsa_circ_0021509 was 0.760 and 0.717, respectively. The classification of patients was improved with the incorporation of circRNAs into the clinical model composed of conventional cardiovascular risk factors, showing an IDI of 0.131 and NRI of 0.170 for hsa_circ_0069972, and an IDI of 0.111 and NRI of 0.150 for hsa_circ_0021509. Functional enrichment analyses revealed that the hsa_circ_0069972-miRNA-mRNA network was enriched in TGF-β、FoxO and Hippo signaling pathways, while the hsa_circ_0021509-miRNA-mRNA network was enriched in PI3K/Akt and MAPK signaling pathways. Conclusion Hsa_circ_0069972 and hsa_circ_0021509 were identified by integrated analysis, and they are highly expressed in CAD patients. They may serve as novel biomarkers for CAD.

Abstract Objective Exploring the predictive value of NLR, PLR, MLR, and SII for the severity of cervical cancer screening abnormalities in patients. Methods A retrospective analysis was conducted on the data of 324 patients suspected of cervical lesions due to abnormal TCT and/or HPV in our hospital from January 2023 to December 2023, who underwent colposcopy. The pathological results of colposcopic biopsy confirmed that there were 140 cases of chronic cervicitis, which classified as the group without cervical lesions. The cervical lesion group included 184 cases, including 91 cases of LSIL, 71 cases of HSIL, and 22 cases of cervical cancer. Compared the differences in preoperative peripheral blood NLR, PLR, MLR, and SII among different groups of patients, and evaluated their predictive value for the severity of cervical lesions using Receiver Operating Characteristic (ROC) curves. Results The levels of NLR, PLR, and SII in the group without cervical lesions were lower than those in the group with cervical lesions (p 0.05). The comparison of NLR among LSIL, HSIL, and cervical cancer groups showed statistically significant differences (p 0.05). The AUC of peripheral blood NLR, PLR, and SII for predicting cervical lesions were 0.569, 0.582, and 0.572, respectively. The optimal cutoff values were 2.3,176.48, and 603.56. The sensitivity and specificity were 38.6% and 73.6%, 28.8% and 85.7%, 37.5% and 76.4%, respectively. At the same time, the joint testing of the three had the highest efficiency, with sensitivity of 69% and specificity of 45%. Conclusion Although the peripheral blood NLR, PLR, and SII of the cervical lesions patients were higher than those without cervical lesions in cervical cancer screening abnormal patients, the predictive ROC curve discrimination was low. Therefore, it is not recommended to use preoperative peripheral blood inflammatory markers as markers for cervical cancer screening abnormal patient diversion.

Abstract Fine particulate matter (PM2.5) is suggested to pose a severe risk to the kidneys by inducing functional degradation and chronic kidney diseases (CKD). This study aims to explore the nephrotoxicity of PM2.5 exposure and the underlying mechanism. Herein, based on the UK Biobank, it is found that per interquartile range (IQR) increase in PM2.5 is associated with a 6% (95% CI: 1%–11%), 7% (95% CI: 3%–11%), 9% (95% CI: 4%–13%), 11% (95% CI: 9%–13%), and 10% (95% CI: 8%–12%) increase in the risk of nephritis, hydronephrosis, kidney stone, acute renal failure, and CKD, respectively. In experimental study, noticeable kidney injury, which is the initiation of kidney diseases, is observed with PM2.5 exposure in C57BL/6N mice (n = 8), accompanied with oxidative stress, autophagy and pyroptosis. In vitro, HK‐2 cells with PM2.5‐stimulation exhibit tubulopathy, increased reactive oxygen species (ROS) generation and activated pyroptosis and autophagy. All changes are abolished by ROS scavenger of N‐acetyl‐L‐cysteine (NAC) both in vivo and in vitro. In conclusion, the study provides evidence showing that PM2.5 exposure is associated with 5 kinds of kidney diseases by directly inducing nephrotoxicity, in which ROS may be the potential target by triggering autophagy and pyroptosis.

Functional diversity refers to the value, range, and distribution of functional traits within a community, such as the morphological, physiological and behavioral characteristics of species that determine the role a species plays in an ecosystem. Assessing the drivers of elevational pattern of functional diversity is crucial to predict the effects of global change on functional diversity and community structure. In our research, we collected mosses species data from 65 sampling sites and measured 11 functional traits that are related to their ecological functions. We applied double canonical correspondence analysis (DCCA) to analyze species responses to environmental conditions based on their traits. We applied generalized additive models with a Gaussian function of variance to determine the elevational patterns of functional trait composition, diversity and community structure. We applied and compared boosted regression trees (BRT) without considering functional traits and piecewise structural equation modelling (SEM) mediated with functional traits to relate environmental variables with functional diversity and functional community structure, respectively. We found the first DCCA axis accounted for the largest dissimilarities between the two groups of species and correlated mainly with the water-utilization traits. Although both functional diversity and community structure displayed negatively skewed pattern along the elevational gradient, habitat complexity and climatic variables contributed differently to their respective patterns. The SEM approach consistently outperformed the BRT approach in explaining the variations in both functional diversity and community structure. Our findings highlight the important role of functional traits in mediating the relationship between the environment and functional diversity metrics. Both biotic and abiotic processes play a significant role in shaping the community assemblages, with environmental variables having distinct impacts. Traits related to structure maintenance, water absorption, cell hydration, and nutrient acquisition were found to be key drivers of functional diversity, while water-utilization traits were mainly responsible for regulating functional community structure.

Background: Higher greenness was associated with a lower risk of adult mortality. However, the effects of greenness on the mortality of infant and child under-5 have not been fully examined. Objectives: The association of greenness on the infant mortality rate (IMR) and child under-5 mortality rate (U5MR) in 147 Chinese cities from 2009 to 2020 was evaluated. Methods: Average and maximum annual population-weighted greenness, IMR (per 1000 live births), and U5MR (per 1000 live births) in 147 cities from 2009 to 2020 were collected, and a longitudinal panel study was conducted. Greenness exposure was evaluated using satellite-derived data at a spatial resolution of 250 m ×250 m in urban regions, and linear mixed-effect models were applied to assess the associations between greenness and IMR or U5MR in China. Results: This national study showed that long-term exposure to greenness was associated with lower IMR and U5MR, respectively. Specifically, a 0.1 increase of Normalized Difference Vegetation Index (NDVI) in greenness was statistically significant with a decrease in IMR (-1.05 ‰, 95 % CI: −1.48, −0.63 ‰) and U5MR (-1.82 ‰, 95 % CI: −2.39, −1.25 ‰) in fully-adjusted model, respectively. In the stratified analyses, greenness effects on U5MR in the western (-2.33 ‰, 95 % CI: −3.43, −1.23 ‰) and central regions (-2.06 ‰, 95 % CI: −3.01, −1.10 ‰) were stronger than that in the eastern region (-0.86 ‰, 95 % CI: −1.66, −0.07 ‰). Conclusions: This nationwide study indicated that exposure to higher greenness was associated with lower mortality rates in infant and child under-5 in China.

The aim of this study is to optimize the extraction process of oat saponins (Os) and to evaluate their antioxidant potential. Single factor experiment, response surface optimization design, and orthogonal test were employed to optimize the process of ultrasonic-assisted extraction of Os, and the optimal extraction conditions were as followed: ethanol volume fraction of 80 %, material-solvent ratio of 1:14, ultrasonic power of 400 W, ultrasonic time of 25 min, extraction temperature of 60℃, extraction time of 180 min, and the extraction rate of Os was 0.317 %±0.105 %. Using the method, the crude extract of Os was prepared and its abilities of scavenging radicals in vitro and inhibiting protein oxidation in pork were determined, with ascorbic acid (Vc) as the control. Results revealed that the scavenging ability of Os against DPPH radical, hydroxyl radical (·OH) and superoxide anion (O2–) increased with the concentration of Os. Interestingly, the scavenging abilities of Os against DPPH and O2– were far lower than that of Vc, but its scavenging ability against ·OH was very close to that of Vc, reaching 84.59 % and 96.33 %, respectively. Furthermore, the experiments of pork storage and Fenton oxidation system showed that Os with 0.09–0.72 mg/mL could reduce the production of carbonyl (8.49 %-50.05 %) and the oxidation of total sulfhydryl (1.29 %-25.86 %), and effectively inhibit the oxidation of protein in pork by 7.82 %–22.53 %. The results of this study will provide a theoretical basis for the application of oat saponins as a natural anti-protein oxidant in meat processing and storage.

Motivated by high interest in Lorentz invariant massive gravity models known as the dRGT massive gravity, we discuss the dRGT massive gravity including the coupling term between dilaton scalar field and massive graviton, and present static and spherically symmetric solutions of dilatonic black holes in four and higher dimensional spacetime. Later, we investigate phase structure of these black hole solutions, and discover that the dilatonic black hole could possess two horizons, extreme and naked singularity black holes for the suitably parameters values. Calculating the conserved and thermodynamic quantities, we check the validity of the first law of thermodynamics.

Aristolochic acid (AA) exposure is a severe public health concern worldwide. AAs damage the kidney with an inevitable acute phase that is similar to acute kidney injury (AKI). Gasdermin E (GSDME) is abundant in the kidney; thus; it-mediated pyroptosis might be essential in connecting cell death and inflammation and promoting AAs-AKI. However, the role and exact mechanism of pyroptosis in AAs-AKI have not been investigated. In this study, aristolochic acid I (AAI) was used to establish AKI models. The expression and translocation results showed GSDME-mediated pyroptosis in AAI-AKI. Knocking down GSDME attenuated AAI-induced cell death and transcription of proinflammatory cytokines. Mechanistic research inhibiting caspase (casp) 3, casp 8, and casp 9 with specific chemical antagonists demonstrated that GSDME was activated by cleaved casp 3. Furthermore, the kinase activity of upstream receptor-interacting protein kinase 1 (RIPK1) was significantly elevated, and inhibiting RIPK1 with specific inhibitors markedly improved AAI-induced cell damage. In addition, the level of autophagy was obviously increased. Pretreatment with a specific autophagic inhibitor (3-methyladenine) or knockdown of autophagic genes (Atg5 or Atg7) evidently reduced the activity of RIPK1 and downstream apoptosis and pyroptosis, thus attenuating AA-induced cell injury, which suggested that RIPK1 was a novel link conferring autophagic promotion of pyroptosis. These findings reveal GSDME-mediated pyroptosis for the first time in AAI-induced AKI, propose its novel role in the transcription of cytokines, and demonstrate that autophagy promotes pyroptosis via the RIPK1-dependent apoptotic pathway. This study promotes the understanding of the toxic effects and exact mechanisms of AAs. This will contribute to evaluating the environmental risk of AA exposure and might provide potential therapeutic targets for AA-AKI.

Abstract While COVID-19 becomes periodical, old individuals remain vulnerable to severe disease with high mortality. Although there have been some studies on revealing different risk factors affecting the death of COVID-19 patients, researchers rarely provide a comprehensive analysis to reveal the relationships and interactive effects of the risk factors of COVID-19 mortality, especially in the elderly. Through retrospectively including 1917 COVID-19 patients (102 were dead) admitted to Xiangya Hospital from December 2022 to March 2023, we used the association rule mining method to identify the risk factors leading causes of death among the elderly. Firstly, we used the Affinity Propagation clustering to extract key features from the dataset. Then, we applied the Apriori Algorithm to obtain 6 groups of abnormal feature combinations with significant increments in mortality rate. The results showed a relationship between the number of abnormal feature combinations and mortality rates within different groups. Patients with “C-reactive protein > 8 mg/L”, “neutrophils percentage > 75.0 %”, “lymphocytes percentage < 20%”, and “albumin < 40 g/L” have a 2 $$\times$$ × mortality rate than the basic one. When the characteristics of “D-dimer > 0.5 mg/L” and “WBC > $$9.5 \times 10^9$$ 9.5 × 10 9 /L” are continuously included in this foundation, the mortality rate can be increased to 3 $$\times$$ × or 4 $$\times$$ × . In addition, we also found that liver and kidney diseases significantly affect patient mortality, and the mortality rate can be as high as 100%. These findings can support auxiliary diagnosis and treatment to facilitate early intervention in patients, thereby reducing patient mortality.

Abstract Background Nowadays, moderate gaming behaviors can be a pleasant and relaxing experiences among adolescents. However, excessive gaming behavior may lead to gaming disorder (GD) that disruption of normal daily life. Understanding the possible risk factors of this emerging problem would help to suggest effective at preventing and intervening. This study aimed to investigate the prevalence of GD and analyze its possible risk factors that adolescents with GD. Methods Data were collected between October 2020 and January 2021. In total, a sample of 7901 students (4080 (52%) boys, 3742 (48%) girls; aged 12–18 years) completed questionnaires regarding the Gaming-Related Behaviors Survey, Gaming Disorder Symptom Questionnaire-21 (GDSQ-21); Behavioral Inhibition System and Behavioral Activation System Scale (BIS/BAS Scale); Emotion Regulation Questionnaire (ERQ); Short-form Egna Minnenav Barndoms Uppfostran for Chinese (s-EMBU-C); and Adolescent Self-Rating Life Events Checklist (ASLEC). Results The prevalence of GD was 2.27% in this adolescent sample. The GD gamers were a little bit older (i.e., a higher proportion of senior grades), more boys, with more gaming hours per week in the last 12 months, with more reward responsiveness, maternal rejecting and occurrence of negative life events (e.g., interpersonal relationships, being punished and bereavement factors). Conclusion These possible risk factors may influence the onset of GD. Future research in clinical, public health, education and other fields should focus on these aspects for provide target prevention and early intervention strategies.

Abstract Objectives To compare the diagnostic performance of intratumoral and peritumoral features from different contrast phases of breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) by building radiomics models for differentiating molecular subtypes of breast cancer. Methods This retrospective study included 377 patients with pathologically confirmed breast cancer. Patients were divided into training set (n = 202), validation set (n = 87) and test set (n = 88). The intratumoral volume of interest (VOI) and peritumoral VOI were delineated on primary breast cancers at three different DCE-MRI contrast phases: early, peak, and delayed. Radiomics features were extracted from each phase. After feature standardization, the training set was filtered by variance analysis, correlation analysis, and least absolute shrinkage and selection (LASSO). Using the extracted features, a logistic regression model based on each tumor subtype (Luminal A, Luminal B, HER2-enriched, triple-negative) was established. Ten models based on intratumoral or/plus peritumoral features from three different phases were developed for each differentiation. Results Radiomics features extracted from delayed phase DCE-MRI demonstrated dominant diagnostic performance over features from other phases. However, the differences were not statistically significant. In the full fusion model for differentiating different molecular subtypes, the most frequently screened features were those from the delayed phase. According to the Shapley additive explanation (SHAP) method, the most important features were also identified from the delayed phase. Conclusions The intratumoral and peritumoral radiomics features from the delayed phase of DCE-MRI can provide additional information for preoperative molecular typing. The delayed phase of DCE-MRI cannot be ignored. Critical relevance statement Radiomics features extracted and radiomics models constructed from the delayed phase of DCE-MRI played a crucial role in molecular subtype classification, although no significant difference was observed in the test cohort. Key Points The molecular subtype of breast cancer provides a basis for setting treatment strategy and prognosis. The delayed-phase radiomics model outperformed that of early-/peak-phases, but no differently than other phases or combinations. Both intra- and peritumoral radiomics features offer valuable insights for molecular typing. Graphical Abstract

Background: The cartilage stem/progenitor cells (CSPC) play a critical role in maintaining cartilage homeostasis. However, the effects of phenotypic fluctuations of CSPC on cartilage degeneration and the role of CSPC in the pathogenesis of OA is largely unknown. Methods: The cartilage samples of 3 non-OA and 10 OA patients were collected. Human CSPC (hCSPC) derived from these patients were isolated, identified, and evaluated for cellular functions. Additionally, chondrocytes derived from OA patients were isolated. The effect of Yes-associated protein (YAP) expression on hCSPC was investigated in vitro. The OA rat model was established by Hulth's method. Lentivirus-mediated YAP (Lv-YAP) or lentivirus-mediated YAP RNAi (Lv-YAP-RNAi) was injected intra-articularly to modulate YAP expression in rat joints. In addition, allogeneic rat CSPC (rCSPC) overexpressing or silencing YAP were transplanted by intra-articularly injection. We also evaluated the functions of rCSPC and the OA-related cartilage phenotype in the rat model. Finally, the transcriptome of OA rCSPC overexpressing YAP was examined to explore the potential downstream targets of YAP in rCSPC. Results: hCSPC derived from OA patients exhibited differential chondrogenesis capacity. Among them, a subset of hCSPC showed pronounced dysfunction, including impaired chondrogenic differentiation, inhibition of proliferation and migration, and downregulation of lubricin. Additionally, YAP was lowly expressed in quiescent non-OA hCSPC, upregulated in activated OA hCSPC, but significantly downregulated in dysfunctional OA hCSPC. Notably, the overexpression of YAP in OA hCSPC improved the proliferation, lubricin production, cell migration, and senescence, while silencing YAP had the opposite effect. In vivo, upregulation of YAP in the joint delayed OA progression and improved the cartilage regeneration capacity of rCSPC. Using transcriptomic analysis, we found that YAP may regulate rCSPC function by upregulating Baculoviral IAP repeat-containing 2 (BIRC2). Importantly, the knockdown of BIRC2 partly blocked the regulation of YAP on the CSPC function. Conclusion: Dysfunction of CSPC compromises the intrinsic repair capacity of cartilage and impairs cartilage homeostasis in OA. Notably, the transcriptional co-activator YAP plays a critical role in maintaining CSPC function through potential target gene BIRC2. The Translational Potential of this Article: In this study, we observed targeting the YAP-BIRC2 axis improved the CSPC function and restored the cartilage homeostasis in OA. This study provides a potential stem cell-modifying OA therapy.

To better meet the requirements in loss-of-coolant accidents (LOCA) and conventional operating conditions in nuclear applications, this work prepared Cr, FeCrAl, and Cr/FeCrAl composite coatings on Zr alloys using plasma spraying technology. The microstructures, hardness, and high-temperature oxidation resistance of coatings are examined. The high-temperature oxidation of coatings was conducted at 1200 °C in air for 20, 40, and 60 min. All coatings exhibited characteristic lamellar microstructures accompanied by small pores. The inner layers of the coatings, benefiting from the “compacting effect” of subsequently deposited particles, displayed lower porosity and higher hardness. The order of high-temperature oxidation resistance among the coatings was determined as follows: Cr/FeCrAl coating > Cr coating > FeCrAl coating. Notably, the Cr/FeCrAl composite coating demonstrated exceptional durability even after a 60-min exposure, with no ZrO2 formation and negligible Fe and Cr diffusion. However, oxygen could still reach the Zr substrate due to inherent pores and the lamellar structure in the as-sprayed coatings. Therefore, post-treatments are suggested to mitigate or eliminate these pores, thereby improving high-temperature oxidation resistance.

Abstract Background The molecular mechanism of fetal cystic hygroma (CH) is still unclear, and no study has previously reported the transcriptome changes of single cells in CH. In this study, single-cell transcriptome sequencing (scRNA-seq) was used to investigate the characteristics of cell subsets in the lesion tissues of CH patients. Methods Lymphoid tissue collected from CH patients and control donors for scRNA-seq analysis. Differentially expressed gene enrichment in major cell subpopulations as well as cell-cell communication were analyzed. At the same time, the expression and interactions of important VEGF signaling pathway molecules were analyzed, and potential transcription factors that could bind to KDR (VEGFR2) were predicted. Results The results of scRNA-seq showed that fibroblasts accounted for the largest proportion in the lymphatic lesions of CH patients. There was a significant increase in the proportion of lymphatic endothelial cell subsets between the cases and controls. The VEGF signaling pathway is enriched in lymphatic endothelial cells and participates in the regulation of cell-cell communication between lymphatic endothelial cells and other cells. The key regulatory gene KDR in the VEGF signaling pathway is highly expressed in CH patients and interacts with other differentially expressed EDN1, TAGLN, and CLDN5 Finally, we found that STAT1 could bind to the KDR promoter region, which may play an important role in promoting KDR up-regulation. Conclusion Our comprehensive delineation of the cellular composition in tumor tissues of CH patients using single-cell RNA-sequencing identified the enrichment of lymphatic endothelial cells in CH and highlighted the activation of the VEGF signaling pathway in lymphoid endothelial cells as a potential modulator. Simple summary The molecular and cellular pathogenesis of fetal cystic hygroma (CH) remains largely unknown. This study examined the distribution and gene expression signature of each cell subpopulation and the possible role of VEGF signaling in lymphatic endothelial cells in regulating the progression of CH by single-cell transcriptome sequencing. The enrichment of lymphatic endothelial cells in CH and the activation of the VEGF signaling pathway in lymphatic endothelial cells provide some clues to the pathogenesis of CH from the perspective of cell subpopulations.

Abstract Background Triptolide is a widely utilized natural anti-inflammatory drug in clinical practice. Aim of this study was to evaluate effects of triptolide on hPDLSCs osteogenesis in an inflammatory setting and to investigate underlying mechanisms. Methods Using the tissue block method to obtain hPDLSCs from extracted premolar or third molar. Flow cytometry, osteogenic and adipogenic induction were carried out in order to characterise the features of the cells acquired. hPDLSC proliferative activity was assessed by CCK-8 assay to determine the effect of TNF-α and/or triptolide. The impact of triptolide on the osteogenic differentiation of hPDLSCs was investigated by ALP staining and quantification. Osteogenesis-associated genes and proteins expression level were assessed through PCR and Western blotting assay. Finally, BAY-117,082 was used to study the NF-κB pathway. Results In the group treated with TNF-α, there was an elevation in inflammation levels while osteogenic ability and the expression of both osteogenesis-associated genes and proteins decreased. In the group co-treated with TNF-α and triptolide, inflammation levels were reduced and osteogenic ability as well as the expression of both osteogenesis-associated genes and proteins were enhanced. At the end of the experiment, both triptolide and BAY-117,082 exerted similar inhibitory effects on the NF-κB pathway. Conclusion The osteogenic inhibition of hPDLSCs by TNF-α can be alleviated through triptolide, with the involvement of the p-IκBα/NF-κB pathway in this mechanism.

Abstract Background Ralstonia pickettii is a low virulent, gram-negative bacillus that is rarely associated with human infections and may cause bacteremia. Microbacterium species are gram-positive coryneforms that are generally considered as a contaminant in Gram staining of blood cultures, especially when the time to positivity is longer than 48 h. Both these bacterial species are emerging opportunistic pathogens that may occasionally cause serious infections and even life-threatening health conditions. Case presentation Here, we report the case of a patient with bacteremia caused by both R. pickettii and Microbacterium. We advocate for providers to order rapid antibiotic susceptibility testing, since our patient’s suffered two kinds of rare pathogens with the opposite of drug sensitivity results to imipenem. Conclusions Our case present a patient suffered septic shock caused by R. pickettii and Microbacterium. Improving the antibiotic management based on the result of antimicrobial susceptibility tests is the key of successful treatment.

The effects of P addition on the microstructure and properties of a Cu-Ni-Ti alloy were investigated. The relationship between evolution of precipitates and hardness, electrical conductivity and softening temperature was established. The results showed that P addition increases the hardness and electrical conductivity, while also possessing good softening resistance. After 90% hot rolling and 500 °C aging, the Cu-Ni-Ti-P alloy reaches its maximum hardness and electrical conductivity of 165 HV and 57.2%IACS. Furthermore, the softening temperature of Cu-Ni-Ti-P alloy reaches 720 °C. The addition of P promotes the precipitation of Ni atoms from the Cu matrix, reduces the concentration of solute atoms, and as a result, increases the electrical conductivity of the alloy. Furthermore, the formation of the Ni _3 P phase further enhances the hardness of the alloy. The P solute atoms dissolved in the matrix and the nano-scale Ni _3 P phase form, which may be one reason for the increase in hardness due to precipitation strengthening.

Background: Tanshinone IIA (Tan IIA) is a lipophilic active constituent derived from the rhizomes and roots of Salvia miltiorrhiza Bunge (Danshen), a common Chinese medicinal herb. However, clinical applications of Tan IIA are limited due to its poor solubility in water. Methods: To overcome this limitation, we developed a calcium alginate hydrogel (CA) as a hydrophilic carrier for Tan IIA, which significantly improved its solubility. We also prepared nanoparticles with pH-responsive properties to explore their potential for controlled drug delivery. The physicochemical properties of Tan IIA/CA nanoparticles were evaluated, including their size, stability, and release profile. We also utilized RNA sequencing to further investigate the underlying anticancer mechanisms of Tan IIA/CA nanoparticles. Results: The Tan IIA/CA nanoparticles demonstrated enhanced solubility and exhibited potent anticancer activity in vitro. Additionally, the nanoparticles showed promising pH-responsive behavior, which is beneficial for controlled release applications. Further investigation into the molecular mechanisms revealed that the anticancer effects of Tan IIA/CA were mediated through apoptosis, ferroptosis, and autophagy pathways. Conclusions: This study confirms the anticancer potential and mechanisms of Tan IIA, while also presenting an innovative approach to enhance the solubility of this poorly soluble compound. The use of CA-based nanoparticles could be a valuable strategy for improving the therapeutic efficacy of Tan IIA in cancer treatment.

In response to the structural changes of tomato seedlings, traditional image techniques are difficult to accurately quantify key morphological parameters, such as leaf area, internode length, and mutual occlusion between organs. Therefore, this paper proposes a tomato point cloud stem and leaf segmentation framework based on Elite Strategy-based Improved Red-billed Blue Magpie Optimization (ES-RBMO) Algorithm. The framework uses a four-layer Convolutional Neural Network (CNN) for stem and leaf segmentation by incorporating an improved swarm intelligence algorithm with an accuracy of 0.965. Four key phenotypic parameters of the plant were extracted. The phenotypic parameters of plant height, stem thickness, leaf area and leaf inclination were analyzed by comparing the values extracted by manual measurements with the values extracted by the 3D point cloud technique. The results showed that the coefficients of determination (R2) for these parameters were 0.932, 0.741, 0.938 and 0.935, respectively, indicating high correlation. The root mean square error (RMSE) was 0.511, 0.135, 0.989 and 3.628, reflecting the level of error between the measured and extracted values. The absolute percentage errors (APE) were 1.970, 4.299, 4.365 and 5.531, which further quantified the measurement accuracy. In this study, an efficient and adaptive intelligent optimization framework was constructed, which is capable of optimizing data processing strategies to achieve efficient and accurate processing of tomato point cloud data. This study provides a new technical tool for plant phenotyping and helps to improve the intelligent management in agricultural production.

Rice blast disease, caused by Magnaporthe oryzae (M. oryzae), is a significant threat to global rice production. Conventional methods for disease management face limitations, emphasizing the importance of sustainable alternatives. In this study, two rice cultivars with different blast resistant abilities, the susceptible variety CO39 and the resistant variety Pi4b, were used as materials to study the effects of Piriformospora indica (Pi) on the resistance to M. oryzae infection and rice growth. The in vitro tests revealed no direct antagonistic interaction between Pi and M. oryzae. However, the in vivo experiments showed that Pi promoted plant growth by increasing root and shoot length, chlorophyll content, and nitrogen uptake, particularly in CO39 during pathogen infection. Pi inoculation also significantly reduced disease severity, which was indicated by smaller lesion areas and shorter lesion lengths in both cultivars but a more pronounced effect in CO39. This occurred due to the decreasing levels of MDA and the modulating activity of antioxidant enzymes in Pi-inoculated rice plants. At the early stage of M. oryzae infection, the expression of the ethylene signaling gene OsEIN2 and the gibberellin biosynthesis gene OsGA20ox1 in Pi-inoculated CO39 decreased but significantly increased in both rice cultivars at the later stage. The reverse was found for the pathogenesis-related (PR) genes OsPR10 and OsPBZ1 and the blast-resistant genes OsBRG1, OsBRG2, and OsBRW1, suggesting early growth suppression for rice resilience to blast followed by a later shift back to growth. Meanwhile, Pi inoculation increased OsCesA9 expression in rice to strengthen cell walls and establish the primary defense barrier against M. oryzae and upregulated the expression of OsNPR1 without a significant difference in CO39 but downregulated it in Pi4b to activate PR genes to enhance plant resistance. In summary, these results underscore the potential of Pi as a sustainable biological control agent for rice blast disease, which is particularly beneficial for blast-susceptible rice cultivars.