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AbstractContext Rheumatoid arthritis (RA) is an autoimmune disease with aberrant Th17 cell differentiation. Panax notoginseng (Burk.) F. H. Chen (Araliaceae) saponins (PNS) have an anti-inflammatory effect and can suppress Th17 cell differentiation.Objective To investigate mechanisms of PNS on Th17 cell differentiation in RA, and the role of pyruvate kinase M2 (PKM2).Materials and methods Naive CD4+T cells were treated with IL-6, IL-23 and TGF-β to induce Th17 cell differentiation. Apart from the Control group, other cells were treated with PNS (5, 10, 20 μg/mL). After the treatment, Th17 cell differentiation, PKM2 expression, and STAT3 phosphorylation were measured via flow cytometry, western blots, or immunofluorescence. PKM2-specific allosteric activator (Tepp-46, 50, 100, 150 μM) and inhibitor (SAICAR, 2, 4, 8 μM) were used to verify the mechanisms. A CIA mouse model was established and divided into control, model, and PNS (100 mg/kg) groups to assess an anti-arthritis effect, Th17 cell differentiation, and PKM2/STAT3 expression.Results PKM2 expression, dimerization, and nuclear accumulation were upregulated upon Th17 cell differentiation. PNS inhibited the Th17 cells, RORγt expression, IL-17A levels, PKM2 dimerization, and nuclear accumulation and Y705-STAT3 phosphorylation in Th17 cells. Using Tepp-46 (100 μM) and SAICAR (4 μM), we demonstrated that PNS (10 μg/mL) inhibited STAT3 phosphorylation and Th17 cell differentiation by suppressing nuclear PKM2 accumulation. In CIA mice, PNS attenuated CIA symptoms, reduced the number of splenic Th17 cells and nuclear PKM2/STAT3 signaling.Discussion and conclusions PNS inhibited Th17 cell differentiation through the inhibition of nuclear PKM2-mediated STAT3 phosphorylation. PNS may be useful for treating RA.

IntroductionEmbryo implantation requires synchronous communication between the embryo and maternal endometrium. Inadequate maternal endometrial receptivity is one of the principal causes for embryo implantation failure [especially repeated implantation failure (RIF)] when biopsied good-quality euploid embryos are transferred. An RNA-seq-based endometrial receptivity test (rsERT) was previously established to precisely guide successful embryo implantation. In this study, we aimed to evaluate the effect of personalized embryo transfer (pET) via rsERT on the clinical outcomes in patients with RIF.MethodsA total of 155 patients with RIF were included in the present retrospective study and were divided into two groups: 60 patients who underwent rsERT and pET (Group rsERT) and 95 patients who underwent standard frozen embryo transfer (FET) without rsERT (Group FET). Reproductive outcomes were compared for patients who underwent rsERT-guided pET and standard FET.ResultsForty percent (24/60) of the patients who underwent rsERT were receptive, and the remaining 60% (36/60) were non-receptive. The positive human chorionic gonadotropin (β-hCG) rate (56.3% vs. 30.5%, P = 0.003) and clinical pregnancy rate (43.8% vs. 24.2%, P = 0.017) were significantly higher in Group rsERT patients than in FET group patients. Additionally, Group rsERT patients also showed a higher implantation rate (32.1% vs. 22.1%, P = 0.104) and live birth rate (35.4% vs. 21.1%, P = 0.064) when compared with FET patients, although without significance. For subpopulation analysis, the positive β-hCG rate, clinical pregnancy rate, implantation rate, and live birth rate of receptive patients were not statistically significant different from those of non-receptive patients.ConclusionsThe rsERT can significantly improve the pregnancy outcomes of RIF patients, indicating the clinical potential of rsERT-guided pET.

IntroductionChronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence and mortality. In some acute exacerbations of COPD (AECOPD) in patients with no obvious signs of infection, early antibiotic treatment seems to clinically improve the disease, but more studies are needed to determine the prognostic impact of antibiotic treatment in AECOPD patients with no obvious signs of infection.PurposeTo clarify the impact of antibiotic treatment on the short-term and long-term prognoses of AECOPD patients without obvious signs of infection.MethodsThe impact of the two treatment methods on the prognosis of patients was compared at 30, 90, 180, and 360 days after discharge. A multicenter, randomized, parallel-controlled clinical trial was conducted in a department of respiratory and critical care medicine in Central China. All patients met the inclusion criteria for AECOPD, and the patients were randomly assigned to the antibiotic group or the nonantibiotic group at a 1:1 ratio. Patients in the antibiotic group were given moxifloxacin 400 mg/day intravenously for 7 days. Patients in the nonantibiotic group were intravenously injected with the same amount of normal saline as the amount of moxifloxacin given to those in the antibiotic group for 7 days.ResultsThere were 406 patients in the antibiotic group and 410 patients in the nonantibiotic group. During the short-term and long-term follow-ups, the acute exacerbation frequency, intensive care unit (ICU) treatment rate, mortality, and mMRC and CAT scores were not significantly different between the two groups (p > 0.05). At the 180- and 360-day follow-ups, the forced expiratory volume in 1 s (FEV1%) and peak expiratory flow (PEF) were not significantly different between the two groups (p > 0.05). The 30-day readmission rate was significantly lower in the antibiotic group than in the nonantibiotic group (p < 0.05). The time from discharge to the first acute exacerbation was not significantly different between the two groups (p > 0.05). The length of the first hospital stay after discharge was significantly lower in the antibiotic group (5.84 days) than in the nonantibiotic group (6.75 days) (p < 0.05). At the 30-day follow-up, the acute exacerbation frequency, age, C-reactive protein (CRP) level, and sputum viscosity were significantly greater in the nonantibiotic group than in the antibiotic group (p < 0.05). In addition, according to the receiver operating characteristic (ROC) analysis, the frequency of acute exacerbations at the 30-day follow-up was significantly greater in COPD patients aged >62.5 years, with a CRP level >12.56 mg/L or with a sputum viscosity >III, in the nonantibiotic group than in those in the antibiotic group, suggesting that the short-term prognosis was poor.ConclusionPatients who are >62.5 years of age, have a CRP concentration >12.56 mg/L, or have a sputum viscosity >III without obvious signs of infection should be treated with antibiotics to improve their short-term prognosis.Clinical Trial Registration:(https://www.chictr.org.cn), (ChiCTR1800018921)

As one of the core pieces of equipment in the multiphase mixing system, the helical axial-flow multiphase pump plays a vital role in the process of offshore oil extraction. In order to explore the influence of the impeller blade outlet setting angle on the internal flow of the helical axial-flow multiphase pump, this paper increases the outlet setting angle of the flow surface by −3°, −1.5°, and 1.5°, respectively, based on the original multiphase pump. It calculates the flow characteristics of the impeller with four different outlet setting angles (including the original impeller) under the design condition with different inlet gas volume fractions (GVFs = 0, 10%, 30%, 50%, and 70%) by adopting the Euler–Euler non-homogeneous flow model and SST k-ω turbulence model. Furthermore, it compares its external characteristic curve and the internal pressure, velocity, gas distribution, and other rules of change of the impeller and guide vane under higher inlet GVF conditions (50%). The results show that in the pure water state, increasing the outlet setting angle appropriately can enhance both the pressure pressurization capability and efficiency of the helical axial-flow multiphase pump; the pressure pressurization capability and efficiency of each scheme decrease with an increase in inlet GVF, and at 50%–70% inlet GVF, the option of increasing the outlet setting angle by −1.5° is better; as the blade outlet setting angle decreases, the axial cross-sectional pressure after gas–liquid mixing increases, the overall velocity distribution is more uniform, and the vortex formed due to the counter-pressure flow in the secondary guide vane is reduced; the accumulation of gas phase on the backside of the impeller and guide vanes improves, leading to a reduction in flow losses.

Abstract Bioconversion of CO2 into liquid fuels or chemicals, preferred medium chain carboxylic acids (caproic and caprylic acid), is an attractive CO2 utilization technology. The present study aims to investigate the effects of different ratios of H2/CO2 on regulating the distribution of C2‐C8 carboxylic acid products, while the headspace pressure of 1.5 bar was set to amplify the effect of different ratios. The H2/CO2 ratio of 4:1 was more suitable for preparing acetic acid, where the highest acetic acid yield was 17.5 g/L. And the H2/CO2 ratio of 2:1 showed excellent chain elongation ability with the highest n‐caprylic yield of 2.4 g/L. Additionally, the actual H2/CO2 ratios of 4:1 reactors were higher than that in 2:1 may be course chain elongation often accompanied by H2 production. The 16S rRNA genes analysis shows that the genus Terrisporobacter and Coriobacteriales may be related to acetic acid production enriched in H2/CO2 ratio 4:1 reactors, and the genus Clostridium and Paenibacillaceae may associate with the chain elongation pathway were enriched in H2/CO2 ratio 2:1 reactors.

Background and aimsHypertensive disorders of pregnancy (HDP) is a significant cause of maternal and neonatal mortality. This study aims to identify risk factors for new-onset HDP and to develop a prediction model for assessing the risk of new-onset hypertension during pregnancy.MethodsWe included 446 pregnant women without baseline hypertension from Liyang People's Hospital at the first inspection, and they were followed up until delivery. We collected maternal clinical parameters and biomarkers between 16th and 20th weeks of gestation. Logistic regression was used to determine the effect of the risk factors on HDP. For model development, a backward selection algorithm was applied to choose pertinent biomarkers, and predictive models were created based on multiple machine learning methods (generalised linear model, multivariate adaptive regression splines, random forest, and k-nearest neighbours). Model performance was evaluated using the area under the curve.ResultsOut of the 446 participants, 153 developed new-onset HDP. The HDP group exhibited significantly higher baseline body mass index (BMI), weight change, baseline systolic/diastolic blood pressure, and platelet counts than the control group. The increase in baseline BMI, weight change, and baseline systolic and diastolic blood pressure significantly elevated the risk of HDP, with odds ratios and 95% confidence intervals of 1.10 (1.03–1.17), 1.10 (1.05–1.16), 1.04 (1.01–1.08), and 1.10 (1.05–1.14) respectively. Restricted cubic spline showed a linear dose-dependent association of baseline BMI and weight change with the risk of HDP. The random forest-based prediction model showed robust performance with the area under the curve of 0.85 in the training set.ConclusionThis study establishes a prediction model to evaluate the risk of new-onset HDP, which might facilitate the early diagnosis and management of HDP.

BackgroundMeasuring the development of Chinese centers for disease control and prevention only by analyzing human resources for health seems incomplete. Moreover, previous studies have focused more on the quantitative changes in healthcare resources and ignored its determinants. Therefore, this study aimed to analyze the allocation of healthcare resources in Chinese centers for disease control and prevention from the perspective of population and spatial distribution, and to further explore the characteristics and influencing factors of the spatial distribution of healthcare resources.MethodsDisease control personnel density, disease control and prevention centers density, and health expenditures density were used to represent human, physical, and financial resources for health, respectively. First, health resources were analyzed descriptively. Then, spatial autocorrelation was used to analyze the spatial distribution characteristics of healthcare resources. Finally, we used spatial econometric modeling to explore the influencing factors of healthcare resources.ResultsThe global Moran index for disease control and prevention centers density decreased from 1.3164 to 0.2662 (p

Diabetic kidney disease (DKD), a metabolic related syndrome characterized by abnormal glomerular filtration rate (GFR), proteinuria and renal microangiopathy, is one of the most common form of chronic kidney diseases (CKD), whereas extracellular vesicles (EVs) have been recently evidenced as a novel cell communication player in DKD occurrence and progress via releasing various of bioactive molecules, including proteins, lipids and especially RNA, among which noncoding RNAs (including miRNAs, lncRNAs and circRNAs) are the major regulators. In current review, we summarized the mechanistic role of EVs in DKD according to biology function classifications, including inflammation and oxidative stress, epithelial–mesenchymal transition (EMT), cell death and extracellular matrix (ECM) deposition. Furthermore, potential clinical applications based on these non-coding RNA have also been reviewed, thereby expecting possible therapeutic insights in clinical practice.

The energy-consuming right trading system (ECRTS) is a significant institutional innovation in China to address the increasingly severe energy crisis and environmental issues. Identifying the policy effects of energy consumption rights on corporate environmental performance (CEP) is conducive to achieving a win-win situation for China's economic growth and carbon neutrality. This study aims to analyze the impact of energy-consuming right trading system on corporate environmental performance and provide empirical evidence and policy implications for the full implementation of future policies. Using data from Chinese listed industrial enterprises from 2012 to 2019 and adopting the difference-in-differences method and mediation analysis, we empirically analyze the policy effects of energy-consuming right trading system. We find that the energy-consuming right trading system significantly promotes the improvement of corporate environmental performance, and the conclusion remains valid after a series of robustness tests. Further mechanism examinations indicate that the system mainly enhances environmental performance by affecting corporate green technological innovation. Heterogeneity tests suggest that the energy-consuming right trading system has a stronger impact on companies in economically developed regions, non-state-owned enterprises, and those with higher asset flexibility. Our research results can aid in the green transformation of enterprises and provide practical evidence for China to accelerate the comprehensive construction of the energy consumption rights trading market.

Corn seeds are an essential element in agricultural production, and accurate identification of their varieties and quality is crucial for planting management, variety improvement, and agricultural product quality control. However, more than traditional manual classification methods are needed to meet the needs of intelligent agriculture. With the rapid development of deep learning methods in the computer field, we propose an efficient residual network named ERNet to identify hyperspectral corn seeds. First, we use linear discriminant analysis to perform dimensionality reduction processing on hyperspectral corn seed images so that the images can be smoothly input into the network. Second, we use effective residual blocks to extract fine-grained features from images. Lastly, we detect and categorize the hyperspectral corn seed images using the classifier softmax. ERNet performs exceptionally well compared to other deep learning techniques and conventional methods. With 98.36% accuracy rate, the result is a valuable reference for classification studies, including hyperspectral corn seed pictures.

Thrombocytopenia caused by long-term radiotherapy and chemotherapy exists in cancer treatment. Previous research demonstrates that 5-Hydroxtrayptamine (5-HT) and its receptors induce the formation of megakaryocytes (MKs) and platelets. However, the relationships between 5-HT1A receptor (5-HTR1A) and MKs is unclear so far. We screened and investigated the mechanism of vilazodone as a 5-HTR1A partial agonist in promoting MK differentiation and evaluated its therapeutic effect in thrombocytopenia. We employed a drug screening model based on machine learning (ML) to screen the megakaryocytopoiesis activity of Vilazodone (VLZ). The effects of VLZ on megakaryocytopoiesis were verified in HEL and Meg-01 cells. Tg (itga2b: eGFP) zebrafish was performed to analyze the alterations in thrombopoiesis. Moreover, we established a thrombocytopenia mice model to investigate how VLZ administration accelerates platelet recovery and function. We carried out network pharmacology, Western blot, and immunofluorescence to demonstrate the potential targets and pathway of VLZ. VLZ has been predicted to have a potential biological action. Meanwhile, VLZ administration promotes MK differentiation and thrombopoiesis in cells and zebrafish models. Progressive experiments showed that VLZ has a potential therapeutic effect on radiation-induced thrombocytopenia in vivo. The network pharmacology and associated mechanism study indicated that SRC and MAPK signaling are both involved in the processes of megakaryopoiesis facilitated by VLZ. Furthermore, the expression of 5-HTR1A during megakaryocyte differentiation is closely related to the activation of SRC and MAPK. Our findings demonstrated that the expression of 5-HTR1A on MK, VLZ could bind to the 5-HTR1A receptor and further regulate the SRC/MAPK signaling pathway to facilitate megakaryocyte differentiation and platelet production, which provides new insights into the alternative therapeutic options for thrombocytopenia.

Eye deformity, a noteworthy embryopathy, is intricately linked with maternal diabetes, frequently resulting in embryonic malformation or even death. In this investigation, a hyperglycemic chick embryo model was established to delve into the protective potential of tamarind shell extract (TSE) on eye development. Chick embryos were administered with TSE (at dosages of 1, 2, and 4 µg/egg) through air sac injection on embryo development day 0 (EDD0) and later exposed to D-glucose (0.4 mmol/egg) on EDD1. To validate our findings, we replicated hyperglycemic environment using D-glucose in ARPE-19 cell model. Our research unveiled that TSE proficiently counters O-GlcNAcylation of proteins in the presence of D-glucose, thereby reinstating levels of key proteins involved in eye development, including Pax6, Daam1, mTOR, and Cdc42. Furthermore, TSE was pinpointed to curtail the D-glucose concentration within the embryo eye, considerably decreasing the accumulation of reactive oxygen species and malondialdehyde accumulation in both the ARPE-19 cells and chick embryos. Beyond its fundamental role in boosting the cellular antioxidative activity, the improved expression of apoptosis-related proteins like Caspase-3, BAX, BCL-2 and other like PI3K and AKT were observed. This suggests a probable activation of the PI3K-AKT-mTOR pathway on ARPE-19 cells by TSE, thereby downregulating apoptotic proteins in ARPE-19 cells during oxidative stress. TSE may become a potent natural countermeasure against D-glucose-induced eye malformation.

NAD(P)HX dehydratase (NAXD) gene is one of the key enzymes encoding the nicotinamide nucleotide repair system, reportedly associated with Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2 (PEBEL2). Here, we generated an induced pluripotent stem cell (iPSC) line from the dermal fibroblasts (HDFs) of a PEBEL2 patient who carried biallelic mutations, c.101_102delTA(p.Thr35Phefs*63) and c.318C > G (p.Ile160Met) in NAXD. These iPSCs showed stable amplification in vitro, expressed pluripotent markers, and differentiated spontaneously into three germ layers, as well as NAXD mutations with normal karyotype.

Rational fertilization is the main measure to improve crop yield, but there are differences in the optimal effects of nitrogen (N), phosphorus (P) and potassium (K) rationing exhibited by the same crop species in different regions and soil conditions. In order to determine the optimum fertilization ratio for high yield of Sapindus mukorossi in western Fujian to provide scientific basis. We carried out the experimental design with different ratios of N, P and K to investigate the effects of fertilization on the yield. and leaf physiology of Sapindus mukorossiand soil properties. Results showed that the yield of Sapindus mukorossi reached the highest value (1464.58 kg ha-1) at N2P2K2 treatment, which increased to 1056.25 kg ha-1 compared with the control. There were significant differences in the responses of soil properties and leaf physiological factors to fertilization treatments. Factor analysis showed that the integrated scores of soil factors and leaf physiological characteristic factors of Sapindus mukorossi under N2P2K2 fertilization treatment were the highest, which effectively improved the soil fertility and leaf physiological traits. The yield of Sapindus mukorossi showed a highly significant linear positive correlation with the integrated scores (r=0.70, p

Summary: Motivation-driven mating is a basic affair for the maintenance of species. However, the underlying molecular mechanisms that control mating motivation are not fully understood. Here, we report that NRG1-ErbB4 signaling in the medial amygdala (MeA) is pivotal in regulating mating motivation. NRG1 expression in the MeA negatively correlates with the mating motivation levels in adult male mice. Local injection and knockdown of MeA NRG1 reduce and promote mating motivation, respectively. Consistently, knockdown of MeA ErbB4, a major receptor for NRG1, and genetic inactivation of its kinase both promote mating motivation. ErbB4 deletion decreases neuronal excitability, whereas chemogenetic manipulations of ErbB4-positive neuronal activities bidirectionally modulate mating motivation. We also identify that the effects of NRG1-ErbB4 signaling on neuronal excitability and mating motivation rely on hyperpolarization-activated cyclic nucleotide-gated channel 3. This study reveals a critical molecular mechanism for regulating mating motivation in adult male mice.

Bicyclo[1.1.0]butanes (BCBs) and [1.1.1]propellanes (tricyclo[1.1.1.01,3]pentanes, TCPs) are structurally unique compounds with different chemical properties. Strain-release driven reactions have emerged as an atom- and step-economic strategy for the organic synthesis. Using this strategy, a variety of functional ring molecules have been efficiently synthesized, including various cyclobutane molecules, bicyclo[2.1.1]hexanes, bicyclo[1.1.1]pentanes, and others. More specifically, these strain release-driven reactions include aspects of nucleophilic addition, radical addition, electrophilic or transition metal catalysis. This review will discuss the recent developments in the strain-release transformations of bicyclo[1.1.0]butanes and [1.1.1]propellanes.

Summary: Ovarian endometriosis is characterized by the growth of endometrial tissue within the ovary, causing infertility and chronic pain. However, its pathophysiology remains unclear. Utilizing high-precision single-cell RNA sequencing, we profile the normal, eutopic, and ectopic endometrium from 34 individuals across proliferative and secretory phases. We observe an increased proportion of ciliated cells in both eutopic and ectopic endometrium, characterized by a diminished expression of estrogen sulfotransferase, which likely confers apoptosis resistance. After translocating to ectopic lesions, endometrial epithelium upregulates nicotinamide N-methyltransferase expression that inhibits apoptosis by promoting deacetylation and subsequent nuclear exclusion of transcription factor forkhead box protein O1, thereby leading to the downregulation of the apoptotic gene BIM. Moreover, epithelial cells in ectopic lesions elevate HLA class II complex expression, which stimulates CD4+ T cells and consequently contributes to chronic inflammation. Altogether, our study provides a comprehensive atlas of ovarian endometriosis and highlights potential therapeutic targets for modulating apoptosis and inflammation.

Abstract Mesenchymal stem cells (MSCs) have been applied in transplantation to treat intracerebral hemorrhage (ICH) but with limited efficacy. Accumulated evidence has shown that glial cell-derived neurotrophic factor (GDNF) plays a crucial part in neuronal protection and functional recovery of the brain after ICH; however, GDNF has difficulty crossing the blood–brain barrier, which limits its application. In this study, we investigated the influences of MSCs overexpressing GDNF (MSCs/GDNF) on the brain structure as well as gait of rats after ICH and explored the possible mechanisms. We found that cell transplantation could reverse the neurological dysfunction and brain damage caused by ICH to a certain extent, and MSCs/GDNF transplantation was superior to MSCs transplantation. Moreover, Transplantation of MSCs overexpressing GDNF effectively reduced the volume of bleeding foci and increased the level of glucose uptake in rats with ICH, which could be related to improving mitochondrial quality. Furthermore, GDNF produced by transplanted MSCs/GDNF further inhibited neuroinflammation, improved mitochondrial quality and function, promoted angiogenesis and the survival of neurons and oligodendrocytes, and enhanced synaptic plasticity in ICH rats when compared with simple MSC transplantation. Overall, our data indicate that GDNF overexpression heightens the curative effect of MSC implantation in treating rats following ICH.

Abstract Background Treatment options for pregnant women with immune thrombocytopenia (ITP) who do not respond to first-line treatment are limited. Few studies have reported the use of recombinant human thrombopoietin (rhTPO) for this subset of patients. Aims To investigate the efficacy and safety of rhTPO in ITP during pregnancy and determine obstetric outcomes and predictors of treatment response. Methods From July 2013 to October 2022, the data of 81 pregnant women with ITP and a platelet count 0.05, both). Compared with controls, rhTPO patients had higher platelet counts (median [interquartile range]: 42 [21.5–67.5] vs. 25 [19–29] × 109/L, P = 0.002), lower bleeding rate (6.1% vs. 25%, P = 0.027), and lower platelet transfusion rate before delivery (57.6% vs. 97.9%, P 0.05). No liver or renal function impairment or thrombosis cases were observed in the rhTPO group. GEE analysis revealed that the baseline mean platelet volume (MPV) (odds ratio [OR]: 0.522, P = 0.002) and platelet-to-lymphocyte ratio (PLR) (OR: 1.214, P = 0.025) were predictors of response to rhTPO treatment. Conclusion rhTPO may be an effective and safe treatment option for pregnancies with ITP that do not respond to first-line treatment; it may have slightly prolonged the gestational age of delivery. Patients with a low baseline MPV and high baseline PLR may be more responsive to rhTPO treatment. The present study serves as a foundation for future research.

Introduction Thirdhand smoke is an emerging threat to global public health. There is no research on young people's exposure to thirdhand smoke in China. This study aims to investigate the exposure status and beliefs of thirdhand smoke among young Chinese people and provide a reference for policy regarding thirdhand smoke. Methods Data from the 2022 Chinese Resident Psychological and Behavioral Survey were used to select young people aged 15–24 years. A total of 11781 subjects were included in this study. Demographic information, beliefs about thirdhand smoke, and exposure status to thirdhand smoke were investigated. Results Among the participants, 47.8% reported being exposed to thirdhand smoke (males: 49.1%, females: 47.0%). Young people living in urban areas (AOR=0.84, 95% CI: 0.77–0.91, p 12000 RMB (AOR=0.81, 95% CI: 0.71–0.92, p=0.001) were less likely to be exposed to thirdhand smoke. Young people with junior high school education or higher, and current or former smokers, were more likely to be exposed to thirdhand smoke. There is room for improvement in the beliefs about thirdhand smoke among young people. Conclusions Thirdhand smoke exposure is an issue that should be addressed in public health policy. Young people with low income and current or former smokers are populations that should be mainly focused on in public education and prevention work on thirdhand smoke.

In this paper, we study a $ p\, $-Laplacian ($ p > 2 $) reaction-diffusion system based on weighted graphs that is used to describe a network mutualistic model of population ecology. After overcoming difficulties caused by the nonlinear $ p\, $-Laplacian, we develop a new strong mutualistic condition, and the blow-up properties of the solution for any nontrivial initial data are proved under this condition. In this sense, we extend the blow-up results of models with a graph Laplacian ($ p = 2 $) to a general graph $ p\, $-Laplacian.

Abstract Background Neutrophilic airway inflammation is a challenge in asthma management and is associated with poor patient prognosis. Mucin 1 (MUC1), which contains a cytoplasmic tail (MUC1-CT), has been found to mediate glucocorticoid sensitivity in asthma; however, its role in modulating neutrophilic airway inflammation in asthma remains unknown. Methods Human-induced sputum cells were collected from healthy participants (n = 12), patients with mild-to-moderate asthma (n = 34), and those with severe asthma (n = 18). In vitro human lung bronchial 1 epithelial cell line (BEAS-2B) was transfected with small interfering RNA against MUC1 (MUC1-siRNA) and then stimulated by lipopolysaccharide (LPS), where some cells were pretreated with a TLR4 inhibitor (TAK-242). In vivo mouse model of asthmatic neutrophil airway inflammation was induced by ovalbumin (OVA)/LPS. Some groups were intraperitoneally injected with MUC1-CT inhibitor (GO-203) and/or TAK-242 . Results The mRNA expression of MUC1 was downregulated in the induced sputum of patients with asthma and correlated with asthmatic neutrophilic airway inflammation. The mRNA expressions of TLR4, MyD88, nucleotide-binding oligomerization domain-like pyrin domain-containing protein 3 (NLRP3), caspase-1, interleukin (IL)-18, and IL-1β in induced sputum cells of patients with asthma were upregulated and related to the mRNA expression of MUC1. LPS activated the TLR4 pathway and NLRP3-mediated pyroptosis in BEAS-2B cells in vitro, which were significantly aggravated after MUC1-siRNA transfection. Furthermore, MUCl-CT interacted with TLR4, and the interaction between TLR4 and MyD88 was significantly increased after MUCl-siRNA transfection. Moreover, TAK-242 ameliorated TLR4/MyD88/nuclear factor kappa B (NF-κB) pathway activation, NLRP3 inflammasome-mediated pyroptosis, and neutrophilic inflammation exacerbated by MUC1 downregulation. GO-203 exacerbated TLR4/MyD88/NF-κB pathway activation in vivo, and NLRP3 inflammasome-mediated pyroptosis reduced in a mouse model of asthmatic neutrophil airway inflammation induced by OVA/LPS; these pathological changes were partially alleviated after TAK-242 application. Conclusion This study revealed that MUC1 downregulation plays an important role in asthmatic neutrophilic airway inflammation. MUC1-CT reduces NLRP3 inflammasome-mediated pyroptosis by inhibiting the activation of the TLR4/MyD88/NF-κB pathway, thereby attenuating neutrophil airway inflammation in patients with asthma.

Abstract According to the latest epidemiological investigation, lung adenocarcinoma (LUAD) is one of the most fatal cancer among both men and women. Despite continuous advancements in treatment approaches in recent years, the prognosis for LUAD remains relatively poor. Given the crucial role of the solute carrier (SLC) family in maintaining cellular energy metabolism stability, we conducted a comprehensive analysis of the association between SLC genes and LUAD prognosis. In the present study, we identified 71 genes among the SLC family members, of which 32 were downregulated and 39 were upregulated in LUAD samples. Based on these differentially expressed genes, a prognostic risk scoring model was established that was composed of five genes (SLC16A7, SLC16A4, SLC16A3, SLC12A8, and SLC25A15) and clinical characteristics; this model could effectively predict the survival and prognosis of patients in the cohort. Notably, SLC2A1, SLC25A29, and SLC27A4 were identified as key genes associated with survival and tumor stage. Further analysis revealed that SLC25A29 was underexpressed in LUAD tissue and regulated the phenotype of endothelial cells. Endothelial cell proliferation and migration increased and apoptosis decreased with a decrease in SLC25A29 expression. Investigation of the upstream regulatory mechanisms of SLC25A29 revealed that SLC25A29 expression gradually decreased as the lactate concentration increased. This phenomenon suggested that the expression of SLC25A29 may be related to lactylation modification. ChIP-qPCR experiments confirmed the critical regulatory role played by H3K14la and H3K18la modifications in the promoter region of SLC25A29. In conclusion, this study confirmed the role of SLC family genes in LUAD prognosis and revealed the role of SLC25A29 in regulating endothelial cell phenotypes. These study results provided important clues to further understand LUAD pathogenesis and develop appropriate therapeutic strategies.

Abstract Purpose Accurately segmenting the hippocampus is an essential step in brain tumor radiotherapy planning. Some patients undergo brain tumor resection beforehand, which can significantly alter the postoperative regions’ appearances and intensity of the 3D MR images. However, there are limited tumor resection patient images for deep neural networks to be effective. Methods We propose a novel automatic hippocampus segmentation framework via postoperative image synthesis. The variational generative adversarial network consists of intensity alignment and a weight-map-guided feature fusion module, which transfers the postoperative regions to the preoperative images. In addition, to further boost the performance of hippocampus segmentation, We design a joint training strategy to optimize the image synthesis network and the segmentation task simultaneously. Results Comprehensive experiments demonstrate that our proposed method on the dataset with 48 nasopharyngeal carcinoma patients and 67 brain tumor patients observes consistent improvements over state-of-the-art methods. Conclusion The proposed postoperative image synthesis method act as a novel and powerful scheme to generate additional training data. Compared with existing deep learning methods, it achieves better accuracy for hippocampus segmentation of brain tumor patients who have undergone brain tumor resection. It can be used as an automatic contouring tool for hippocampus delineation in hippocampus-sparing radiotherapy.

Abstract Van der Waals dielectrics are fundamental materials for condensed matter physics and advanced electronic applications. Most dielectrics host isotropic structures in crystalline or amorphous forms, and only a few studies have considered the role of anisotropic crystal symmetry in dielectrics as a delicate way to tune electronic properties of channel materials. Here, we demonstrate a layered anisotropic dielectric, SiP2, with non-symmorphic twofold-rotational C 2 symmetry as a gate medium which can break the original threefold-rotational C 3 symmetry of MoS2 to achieve unexpected linearly-polarized photoluminescence and anisotropic second harmonic generation at SiP2/MoS2 interfaces. In contrast to the isotropic behavior of pristine MoS2, a large conductance anisotropy with an anisotropy index up to 1000 can be achieved and modulated in SiP2-gated MoS2 transistors. Theoretical calculations reveal that the anisotropic moiré potential at such interfaces is responsible for the giant anisotropic conductance and optical response. Our results provide a strategy for generating exotic functionalities at dielectric/semiconductor interfaces via symmetry engineering.

Analyzing heart sound signals presents a novel approach for early diagnosis of pediatric congenital heart disease. The existing segmentation algorithms have limitations in accurately distinguishing the first (S1) and second (S2) heart sounds, limiting the diagnostic utility of cardiac cycle data for pediatric pathology assessment. This study proposes a time bidirectional long short-term memory network (TBLSTM) based on multi-scale analysis to segment pediatric heart sound signals according to different cardiac cycles. Mel frequency cepstral coefficients and dynamic characteristics of the heart sound fragments were extracted and input into random forest for multi-classification of congenital heart disease. The segmentation model achieved an overall F1 score of 94.15% on the verification set, with specific F1 scores of 90.25% for S1 and 86.04% for S2. In a situation where the number of cardiac cycles in the heart sound fragments was set to six, the results for multi-classification achieved stabilization. The performance metrics for this configuration were as follows: accuracy of 94.43%, sensitivity of 95.58%, and an F1 score of 94.51%. Furthermore, the segmentation model demonstrates robustness in accurately segmenting pediatric heart sound signals across different heart rates and in the presence of noise. Notably, the number of cardiac cycles in heart sound fragments directly impacts the multi-classification of these heart sound signals.

Developing reusable and easy-to-operate biocatalysts is of significant interest in biodiesel production. Here, magnetic whole-cell catalysts constructed through immobilizing recombinant Escherichia coli cells (containing MAS1 lipase) into Fe3O4–chitosan magnetic microspheres (termed MWCC@MAS1) were used for fatty acid methyl ester (FAME) production from waste cooking oil (WCO). During the preparation process of immobilized cells, the effects of chitosan concentration and cell concentration on their activity and activity recovery were investigated. Optimal immobilization was achieved with 3% (w/v) chitosan solution and 10 mg wet cell/mL cell suspension. Magnetic immobilization endowed the whole-cell catalysts with superparamagnetism and improved their methanol tolerance, enhancing the recyclability of the biocatalysts. Additionally, we studied the effects of catalyst loading, water content, methanol content, and reaction temperature on FAME yield, optimizing these parameters using response surface methodology and Box–Behnken design. An experimental FAME yield of 89.19% was gained under the optimized conditions (3.9 wt% catalyst loading, 22.3% (v/w) water content, 23.0% (v/w) methanol content, and 32 °C) for 48 h. MWCC@MAS1 demonstrated superior recyclability compared to its whole-cell form, maintaining about 86% of its initial productivity after 10 cycles, whereas the whole-cell form lost nearly half after just five cycles. These results suggest that MWCC@MAS1 has great potential for the industrial production of biodiesel.

Amid the escalating global demand for raw materials, the gradual exhaustion of terrestrial mineral resources, and the rise in extraction costs and energy consumption, the development of deep-sea mineral resources has become a focal point of international interest. The pipeline lifting mining system, distinguished by its superior mining efficiency and minimized environmental impact, now accounts for over 50% of the total energy consumption in mining operations. Serving as the “heart” of this system, the deep-sea lifting pump’s comprehensive performance (high pressure tolerance, non-clogging features, elevated lift capacity, wear resistance, corrosion resistance, and high reliability, etc.), is critical to transport efficiency, operational stability, and lifespan of the mining system. As a mixed transport pump for solid and liquid media under extreme conditions, its internal flow structure is exceedingly complex, incorporating gas–liquid–solid multiphase flow. A precise understanding of its internal flow mechanisms is essential for breaking through the design limitations of deep-sea lifting pumps and enhancing their operational stability and reliability under various working conditions and multiphase media, thereby providing technical support for advancing global marine resource development and offshore equipment upgrades. This paper comprehensively reviews the design theory, optimization methods, numerical simulations, and experimental studies of deep-sea lifting pumps. It discusses the application of various design optimization techniques in hydraulic lifting pumps, details the multiphase flow numerical algorithms commonly used in deep-sea lifting pumps along with their modified models, and summarizes some experimental methodologies in this field. Lastly, it outlines the forthcoming challenges in deep-sea lifting pump research and proposes potential directions to promote the commercial development of deep-sea mining, thereby offering theoretical and engineering support for the development of deep-sea mining slurry pumps.

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Axial clearance is a critical parameter affecting the performance of vortex pumps. In this study, numerical simulation and experimental validation methods are employed to establish four different clearance schemes. The analysis focuses on multiple aspects, including the internal flow field, clearance flow field, leakage flow, and recirculation flow, to investigate the impact of axial clearance on the internal flow field and the external characteristics of the vortex pump. The results indicate that under the pressure difference between the inlet and outlet, the main flow leaks from the high-pressure region at the outlet to the clearance flow channel, and the clearance flow returns to the main flow channel at the low-pressure region of the inlet. As the axial clearance increases, the intensity of the vortices inside the pump gradually decreases. This leads to a reduction in intensity of the momentum exchange between the fluid inside and outside the impeller, causing a decline in the pump performance curve. Simultaneously, the increase in clearance reduces the flow resistance in the clearance region, and the clearance flow gradually stabilizes. The interaction between the clearance flow and the main flow intensifies, causing the leakage flow and recirculation flow to increase rapidly, which results in significant energy loss.

Branch prediction is a momentous technology guarantee for processor performance, especially for the widely used superscalar processor. The properties of the branch predictor significantly affect the overall performance, power consumption, and area of the processor. To obtain a more cost-effective branch predictor in the superscalar processor, an attempt is made to use a single TAGE (tagged geometric history length) predictor to predict the branches within the fetch width. The championship branch prediction platform is used to evaluate the performance of the predictor, and its prediction ability is sufficient to meet the prediction conditions. However, in practice, conflicts in both the predictor and branch target buffer affect its performance. To solve the above problem, this paper adds additional prediction paths based on a single TAGE branch predictor and independently saves and predicts additional branch instruction information. This predictor is implemented in the processor using hardware description language and compared with a single TAGE branch predictor to perform standard benchmark programs for embedded processors, dhrystone, coremark and embench. Experimental results show that the performance of the optimized branch predictor is improved by 14.1 percentage points, while the storage overhead is only increased by 9.06%. Finally, through the analysis of the experimental data, it is found that this scheme is not only conducive to the prediction of additional branch instructions, but also can achieve more accurate prediction of single branch instruction through more accurate acquisition of branch history information.

Objective: To explore the conditions of embedding diacylglycerol (DAG) with sodium casein (SC) and nano cellulose cellulose (NCC) as wall materials and improve the quality of functional fermented dairy products.Methods: Using milk fat as raw material, DAG was prepared by enzymolysis reaction. Using SC and NCC as wall materials, oil in water DAG emulsion was prepared. The addition amount of SC and NCC, particle size and homogeneous pressure of the emulsion under optimal preparation conditions were screened, and rheological analysis, texture analysis and sensory analysis were conducted on soft cheese with DAG nano-emulsion added. The stability difference between them was investigated and soft cheese was prepared as a fat substitute. Results: The optimum conditions for preparing sodium caseinate cellulose DAG lotion by the high-pressure homogenization method were as follows: NCC content 1.5%, SC content 5%, core wall ratio 1:1, homogenization pressure 100 MPa. All lotions are oils in water with particle sizes between 100~240 nm. By analyzing the characteristics of soft cheese, with the addition of DAG lotion, the elasticity of soft cheese increased, and the hardness, consistency, and cohesiveness all increased at first and then decreased. When the addition of lotion was 2%, the sensory quality was significantly higher than in other groups. Conclusion: In the NCC content of 1.5%, SC content of 5%, core wall ratio of 1:1, under the conditions of homogenization pressure of 100 MPa, DAG could be effectively embedded, and the embedding rate could reach 77.9%. When 2% DAG lotion was added to soft cheese, the sensory quality of the soft cheese could be significantly improved.

Abstract Background Endothelial-mesenchymal transition (EndoMT) is an emerging adaptive process that modulates lymphatic endothelial function to drive aberrant lymphatic vascularization in the tumour microenvironment (TME); however, the molecular determinants that govern the functional role of EndoMT remain unclear. Here, we show that cancer-associated fibroblast (CAF)-derived PAI-1 promoted the EndoMT of lymphatic endothelial cells (LECs) in cervical squamous cell carcinoma (CSCC). Methods Immunofluorescent staining of α-SMA, LYVE-1 and DAPI were examined in primary tumour samples obtained from 57 CSCC patients. Assessment of cytokines secreted by CAFs and normal fibroblasts (NFs) was performed using human cytokine antibody arrays. The phenotype of EndoMT in lymphatic endothelial cells (LECs), gene expression levels, protein secretion and activity of signaling pathways were measured by real-time RT-PCR, ELISA or western blotting. The function of lymphatic endothelial monolayers was examined by transwell, tube formation assay, transendothelial migration assay in vitro. Lymphatic metastasis was measured using popliteal lymph node metastasis model. Furthermore, association between PAI-1 expression and EndoMT in CSCC was analyzed by immunohistochemistry. The Cancer Genome Atlas (TCGA) databases was used to assess the association of PAI-1 with survival rate in CSCC. Results CAF-derived PAI-1 promoted the EndoMT of LECs in CSCC. LECs undergoing EndoMT could initiate tumour neolymphangiogenesis that facilitated cancer cell intravasation/extravasation, which in turn promoted lymphatic metastasis in CSCC. Mechanistically, PAI-1 activated the AKT/ERK1/2 pathways by directly interacting with low-density lipoprotein receptor-related protein (LRP1), thereby leading to elevated EndoMT activity in LECs. Blockade of PAI-1 or inhibition of LRP1/AKT/ERK1/2 abrogated EndoMT and consequently attenuated CAF-induced tumour neolymphangiogenesis. Furthermore, clinical data revealed that increased PAI-1 levels positively correlated with EndoMT activity and poor prognosis in CSCC patients. Conclusion Our data indicate that CAF-derived PAI-1 acts as an important neolymphangiogenesis-initiating molecular during CSCC progression through modulating the EndoMT of LECs, resulting in promotion of metastasis ability in primary site. PAI-1 could serve as an effective prognostic biomarker and therapeutic target for CSCC metastasis.

Objective: Our preliminary research indicates that acacetin modulates the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome, providing protection against Alzheimer’s Disease (AD) and cerebral ischemic reperfusion injury. The mechanisms of acacetin to inhibit the activation of the NLRP3 inflammasome remain fully elucidated. This study aims to investigate the effects and potential mechanisms of acacetin on various agonists induced NLRP3 inflammasome activation.Methods: A model for the NLRP3 inflammasome activation was established in mouse bone marrow-derived macrophages (BMDMs) using Monosodium Urate (MSU), Nigericin, Adenosine Triphosphate (ATP), and Pam3CSK4, separately. Western blot analysis (WB) was employed to detect Pro-caspase-1, Pro-Interleukin-1β (Pro-IL-1β) in cell lysates, and caspase-1, IL-1β in supernatants. Enzyme-Linked Immunosorbent Assay (ELISA) was used to measured the release of IL-1β, IL-18, and Tumor Necrosis Factor-alpha (TNF-α) in cell supernatants to assess the impact of acacetin on NLRP3 inflammasome activation. The lactate dehydrogenase (LDH) release was also assessed. The Nuclear Factor Kappa B (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways related proteins were evaluated by WB, and NF-κB nuclear translocation was observed via laser scanning confocal microscopy (LSCM). Disuccinimidyl Suberate (DSS) cross-linking was employed to detect oligomerization of Apoptosis-associated Speck-like protein containing a Caspase Recruitment Domain (ASC), and LSCM was also used to observe Reactive Oxygen Species (ROS) production. Inductively Coupled Plasma (ICP) and N-(6-methoxyquinolyl) acetoethyl ester (MQAE) assays were utilized to determined the effects of acacetin on the efflux of potassium (K+) and chloride (Cl-) ions.Results: Acacetin inhibited NLRP3 inflammasome activation induced by various agonists, reducing the release of TNF-α, IL-1β, IL-18, and LDH. It suppressed the expression of Lipopolysaccharides (LPS)-activated Phosphorylated ERK (p-ERK), p-JNK, and p-p38, inhibited NF-κB p65 phosphorylation and nuclear translocation. Acacetin also reduced ROS production and inhibited ASC aggregation, thus suppressing NLRP3 inflammasome activation. Notably, acacetin did not affect K+ and Cl-ions efflux during the activation process.Conclusion: Acacetin shows inhibitory effects on both the priming and assembly processes of the NLRP3 inflammasome, positioning it as a promising new candidate for the treatment of NLRP3 inflammasome-related diseases.

The surface water and groundwater in the mountainous area are vulnerable to contamination from the mining and transportation construction in Sichuan Province, China. Pollutants produced by anthropogenic activities transport within the groundwater from mountains to rivers on the plain, transferring contamination to the surface water. This study investigates the process of groundwater flow and contaminant transport from mountains to the lowlands based on synthetic numerical models. Two key factors are considered: precipitation and the slope of the mountain. Based on the real situation in Sichuan Province, four rainfall recharge rates are defined as 600, 800, 1,000, and 1,200 mm/yr, and five slope angles are considered: 20°, 25°, 30°, 35°, and 40°. The simulation results reveal that the groundwater level and solute transport are strongly influenced by the precipitation amounts and slope angles. The mountains with lower slopes maintain a relatively higher groundwater level under steady-state rainfall conditions; for example, groundwater levels decrease from 340 m to 300 m as slope angles increase at a 1,200 mm/yr precipitation level. Contaminant transport from the source in the mountain to the surface river is faster with increasing precipitations and decreasing slope angles. The model with 20° slope angle and 1,200 mm/yr precipitation exhibits the fastest solute migration, with the contaminant arrival time of 65 years. Furthermore, the models with 35° and 40° slope angles at a 600 mm/yr precipitation level show the slow transport speed with the contaminant arrival time of more than 75 years. In addition, higher precipitation may lead to more contaminant transport to the river. The analysis and findings of this study offer valuable insights into groundwater protection at the boundaries of mountains and plains.

Tumor immunotherapy, an innovative anti-cancer therapy, has showcased encouraging outcomes across diverse tumor types. Among these, the PD-1/PD-L1 signaling pathway is a well-known immunological checkpoint, which is significant in the regulation of immune evasion by tumors. Nevertheless, a considerable number of patients develop resistance to anti-PD-1/PD-L1 immunotherapy, rendering it ineffective in the long run. This research focuses on exploring the factors of PD-1/PD-L1-mediated resistance in tumor immunotherapy. Initially, the PD-1/PD-L1 pathway is characterized by its role in facilitating tumor immune evasion, emphasizing its role in autoimmune homeostasis. Next, the primary mechanisms of resistance to PD-1/PD-L1-based immunotherapy are analyzed, including tumor antigen deletion, T cell dysfunction, increased immunosuppressive cells, and alterations in the expression of PD-L1 within tumor cells. The possible ramifications of altered metabolism, microbiota, and DNA methylation on resistance is also described. Finally, possible resolution strategies for dealing with anti-PD-1/PD-L1 immunotherapy resistance are discussed, placing particular emphasis on personalized therapeutic approaches and the exploration of more potent immunotherapy regimens.

Injured articular cartilage is a leading cause for osteoarthritis. We recently discovered that endogenous stem/progenitor cells not only reside in the superficial zone of mouse articular cartilage, but also regenerated heterotopic bone and cartilage in vivo. However, whether critical-size osteochondral defects can be repaired by pure induced chemotatic cell homing of these endogenous stem/progenitor cells remains elusive. Here, we first found that cells in the superficial zone of articular cartilage surrounding surgically created 3 × 1 mm defects in explant culture of adult goat and rabbit knee joints migrated into defect-filled fibrin/hylaro1nate gel, and this migration was significantly more robust upon delivery of exogenous granulocyte-colony stimulating factor (G-CSF). Remarkably, G–CSF–recruited chondrogenic progenitor cells (CPCs) showed significantly stronger migration ability than donor-matched chondrocytes and osteoblasts. G–CSF–recruited CPCs robustly differentiated into chondrocytes, modestly into osteoblasts, and barely into adipocytes. In vivo, critical-size osteochondral defects were repaired by G–CSF–recruited endogenous cells postoperatively at 6 and 12 weeks in comparison to poor healing by gel-only group or defect-only group. ICRS and O'Driscoll scores of articular cartilage were significantly higher for both 6- and 12-week G-CSF samples than corresponding gel-only and defect-only groups. Thus, endogenous stem/progenitor cells may be activated by G-CSF, a Food and Drug Administration (FDA)-cleared bone-marrow stimulating factor, to repair osteochondral defects.

Previous studies have demonstrated that carbohydrate sulfotransferase family proteins (CHSTs) play a crucial role in the extracellular matrix structural constituent and cancer progression, however, the effect of CHSTs on gastric cancer is still superficial. To investigate these, our study seeks to provide a comprehensive understanding of CHSTs' expression, immune infiltration, and prognostic implications in gastric cancer, utilizing data from the TCGA, GEO and GTEx databases. Furthermore, we conducted experimental validation to elucidate the role of CHST14 specifically in gastric cancer. Our findings suggest that most CHSTs were highly expressed in gastric cancer. Gene copy number variations further indicated prevalent CHSTs amplification in gastric cancer, pointing to its potential relevance in disease progression. Intriguingly, we noted strong positive correlations between most CHSTs and immune cell infiltration. Importantly, most members of CHSTs were related to OS and PFI with gastric cancer, with particular emphasis on CHST14 and CHST9. Multifactorial regression analysis indicates that CHST14 is an independent prognostic factor influencing the overall survival of gastric cancer patients. In further experimental validation, our results demonstrate elevated expression of CHST14 in gastric cancer, and knocking down CHST14 inhibits gastric cancer cell proliferation, invasion, migration and EMT. Additionally, CHST14 may exert its function through the regulation of the Wnt pathway. In summary, our study comprehensively analyzes the hitherto undescribed role of CHSTs in gastric cancer through the analysis of multi-omics data. Importantly, we identify CHST14 as a pivotal promoter in the malignant progression of gastric cancer, offering potential targets for gastric cancer therapy.

The formulation of science and technology financial policies directly influences the direction of national economic development. Quantitative evaluation of these policies is an important method to reflect the consistency and strengths and weaknesses of policy interrelations. This paper analyzes 16 science and technology financial policy documents issued by the Chinese central government from 2016 to 2022, using text analysis and content analysis to extract keyword frequencies, and constructs 9 primary variables and 34 secondary variables. For the first time, a PMC-AE index model for science and technology financial policies is established, and a quantitative evaluation is conducted on 5 significant policy documents out of the 16. The results show that, from an overall analysis, Policy 1 and Policy 4 are at a good level, while the other three policies are at an excellent level. From the analysis of individual policy PMC-AE indexes, the rankings in descending order are: P2 > P5 > P3 > P4 > P1. Overall, the policies effectively meet the needs of China's science and technology financial development, with P2, P3, and P5 being at an excellent level, P4 at a good level, and P1 at an acceptable level, mainly reflecting the need for improvement in aspects such as policy synchronization with the current stage, targeted entities, guiding fields, and policy content. It is recommended that Chinese government departments should focus on five aspects in policy formulation: building a talent system for science and technology finance, improving the quality of financial services, coordinating central and local financial policies, protecting intellectual property rights in science and technology finance, and strengthening financial supervision. This will be conducive to the effective implementation of science and technology financial policies.

Background: Tousled-like kinase 2 (TLK2) is integral to DNA repair, replication, and cell cycle regulation, crucial for maintaining genome stability and integrity. However, the expression and prognostic value of TLK2 in hepatitis B viral (HBV) -related hepatocellular carcinoma (HCC) remains unclear.Methods: We examined TLK2 expression and prognostic implications in pan-cancer by using diverse databases. Subsequently, TLK2 expression in HBV-related HCC tissues and adjacent tissues was assessed using quantitative real-time PCR and immunohistochemistry. The prognostic value of TLK2 was assessed through ROC curves, time-dependent ROC curves, Cox regression, Kaplan-Meier curve, and decision curve analysis. Additionally, analyses of immune infiltration, protein-protein interactions, key molecules of tumor-related signaling pathways, molecular subtypes, and TLK2-associated differentially expressed genes (DEGs) were conducted, along with GO/KEGG and GSEA enrichment analyses.Results: TLK2 expression was significantly higher in HCC tissues compared to adjacent tissues and correlated with gender, AFP levels, albumin-bilirubin (ALBI) grade, microvascular invasion (MVI), maximum tumor diameter, tumor number, and TNM stage. TLK2 overexpression emerged as an independent risk factor for overall survival (OS) and recurrence-free survival (RFS) in HBV-related HCC patients. An integrated OS nomogram model, incorporating TLK2, age, ALBI grade, MVI, and tumor number, displayed enhanced prognostic capability (C-index: 0.765, 95% CI: 0.732–0.798) in predicting OS and has a higher net benefit than the TNM stage. Moreover, TLK2 expression correlated closely with immune cell infiltration and key molecules of signaling pathways. Functional enrichment analyses highlighted significant associations with DNA duplex unwinding, double-strand break repair, DNA replication, cell cycle, E2F targets, G2M checkpoint, and MYC targets V1.Conclusion: TLK2 is notably overexpressed in HBV-related HCC and emerges as a promising prognostic biomarker, necessitating further validation.

BackgroundHealth workers play a central role in global tuberculosis (TB) elimination efforts. If medical students have prejudiced attitudes toward TB patients, this may make it difficult for them to provide effective health care to TB patients in their future roles as health workers. There is currently no research on prejudice toward TB patients among medical students in China. This study aimed to explore the current status of medical students’ prejudice against patients with TB and its associated predictors.MethodsWe conducted a cross-sectional questionnaire survey among medical students at a medical university in Dalian, Liaoning Province, Northeast China. Multiple logistic regression analysis was employed to determine the predictive factors of medical students’ prejudice against patients with TB.ResultsMore than half (57.23%) of the medical students held prejudices against individuals with TB. Multivariate logistic regression analysis revealed that not receiving TB health education (OR: 2.12, 95% CI: 1.35–3.32), not knowing a person with TB (OR: 2.52, 95% CI: 1.39–4.56), and fear of TB/TB patients (OR: 6.79, 95% CI: 4.36–10.56) were identified as risk factors for medical students’ prejudice against TB patients. Conversely, residing in rural areas (OR: 0.60, 95% CI: 0.38–0.95), agreeableness (OR: 0.82, 95% CI: 0.73–0.92) and emotional stability (OR: 0.90, 95% CI: 0.81–1.00) in the Big Five personality traits, and a better understanding of TB knowledge (OR: 0.58, 95% CI: 0.38–0.89) were identified as protective factors.ConclusionIn China, a considerable number of medical students still exhibit prejudice against patients with TB. Targeted interventions, such as incorporating TB health education into the core curriculum of medical students, and enhance their agreeableness and emotional stability, are still needed. Furthermore, greater focus should be placed on medical students from urban backgrounds or those who harbor fear or do not know a person with TB.