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Abstract Arable land is the lifeblood of food production, it is of great significance to promote the protection of arable land and ensure national food security by accurately understanding the change law of cultivated land and its driving mechanism. This study takes the Weibei dry plateau region of China as an example, explores its spatial and temporal change characteristics through the center of gravity shift and land use shift matrix, and couples the geographic probe model to reveal the driving mechanisms affecting arable land change. The results show that in the past 25 years, the total arable land area in the Weibei Dry Plateau Region of China has decreased by 5.58%, and the stability of arable land resources in the whole region has weakened. The center of gravity of arable land shifts to the northeast, and the standard deviation ellipse of arable land mainly undergoes the change process of "increase (1995–2015)-decrease (2015–2020)", and the spatial distribution of arable land tends to be dispersed. In the LISA frequency mapping, the proportion of stable constant and low-frequency areas is as high as 89.58%, and the spatial pattern of cultivated land is relatively stable. Medium and high frequency areas. The transformation mode is mainly "low-low" aggregation, "low–high" aggregation is not significant, and the decline of cultivated land in the study area is more obvious. In the past 25 years, a total of 1017.26 km2 of arable land was converted to construction land. The explanatory power of the influencing factors varies in each period (0.299 to 0.731), with total agricultural machinery power has the strongest explanatory power of 0.694, 0.592, and 0.731, respectively. The interaction between slope and annual average temperature and other factors being the highest, both greater than 0.8. Through the construction of LISA frequency mapping, combined with the center of gravity model and standard deviation ellipse, the spatial evolution trend of regional arable land is more comprehensively and dynamically grasped. By using the geodetector model, the driving mechanism of the changes of arable land is revealed comprehensively, which provides a theoretical basis for the scientific management and effective protection of arable land resources and a basis for decision-making.

The effects of whole egg powder, cake oil and sugar additive amount on the specific volume, texture characteristics and sensory scores of the cake were evaluated using single factor experiment. Based on the single factor experiment, response surface methodology was used to optimize the formula of the cake premixed powder with the sensory score as the response value. The results showed that the cake had the highest sensory score of 87.12 when the formula of the premixed powder was 65% whole egg powder, 20% cake oil and 57.5% of white granulated sugar. The specific volume and texture characteristics of the cake under the optimal formula were determined as follows: Specific volume was 3.69 mL/g, hardness was 438.54±19.31 g, elasticity was 0.91±0.02, and cohesiveness was 0.69±0.01, which were all better than those before response surface optimization. The cakes prepared with the optimal formula were bright yellow and had small internal pores, soft and elastic taste, and a unique cake aroma, sweet but not greasy. The electronic nose was used to analyze the flavor of the optimal cake, and the results found that ethanol, amine, fluorine and hydrocarbon were the main flavor substances in the cake. Further flavor analysis indicated that the optimal cake contained nine pleasant flavor substances, among which 1-nonanal and (E,E)-2,4-decadien-1-al were at relatively high levels in the optimal cake, thus presenting a pleasant aroma as a whole.

Abstract The development of high-performance oxide-based transistors is critical to enable very large-scale integration (VLSI) of monolithic 3-D integrated circuit (IC) in complementary metal oxide semiconductor (CMOS) backend-of-line (BEOL). Atomic layer deposition (ALD) deposited ZnO is an attractive candidate due to its excellent electrical properties, low processing temperature below copper interconnect thermal budget, and conformal sidewall deposition for novel 3D architecture. An optimized ALD deposited ZnO thin-film transistor achieving a record field-effect and intrinsic mobility (µ FE /µ o ) of 85/140 cm2/V·s is presented here. The ZnO TFT was integrated with HfO2 RRAM in a 1 kbit (32 × 32) 1T1R array, demonstrating functionalities in RRAM switching. In order to co-design for future technology requiring high performance BEOL circuitries implementation, a spice-compatible model of the ZnO TFTs was developed. We then present designs of various ZnO TFT-based inverters, and 5-stage ring oscillators through simulations and experiments with working frequency exceeding 10’s of MHz.

Abstract The “eat me” signal, phosphatidylserine is exposed on the surface of dying cells by phospholipid scrambling. Previously, we showed that the Xkr family protein Xkr4 is activated by caspase-mediated cleavage and binding of the XRCC4 fragment. Here, we show that extracellular calcium is an additional factor needed to activate Xkr4. The constitutively active mutant of Xkr4 is found to induce phospholipid scrambling in an extracellular, but not intracellular, calcium-dependent manner. Importantly, other Xkr family members also require extracellular calcium for activation. Alanine scanning shows that D123 and D127 of TM1 and E310 of TM3 coordinate calcium binding. Moreover, lysine scanning demonstrates that the E310K mutation-mediated salt bridge between TM1 and TM3 bypasses the requirement of calcium. Cysteine scanning proves that disulfide bond formation between TM1 and TM3 also activates phospholipid scrambling without calcium. Collectively, this study shows that extracellular calcium functions as a molecular glue for TM1 and TM3 of Xkr proteins for activation, thus demonstrating a regulatory mechanism for multi-transmembrane region-containing proteins.

α-Conotoxins are disulfide-rich peptides obtained from the venom of cone snails, which are considered potential molecular probes and drug leads for nAChR-related disorders. However, low specificity towards different nAChR subtypes restricts the further application of many α-conotoxins. In this work, a series of loop1 amino acid-substituted mutants of α-conotoxin RegIIA were synthesized, whose potency and selectivity were evaluated by an electrophysiological approach. The results showed that loop1 alanine scanning mutants [H5A]RegIIA and [P6A]RegIIA blocked rα7 nAChR with IC50s of 446 nM and 459 nM, respectively, while their inhibition against rα3β2 and rα3β4 subtypes was negligible, indicating the importance of the fifth and sixth amino acid residues for RegIIA’s potency and selectivity. Then, second-generation mutants were designed and synthesized, among which the analogues [H5V]RegIIA and [H5S]RegIIA showed significantly improved selectivity and comparable potency towards rα7 nAChR compared with the native RegIIA. Overall, these findings provide deep insights into the structure–activity relationship of RegIIA, as well as revealing a unique perspective for the further modification and optimization of α-conotoxins and other active peptides.

Teaching satisfaction and resilience play important roles in the education field, but most research focuses on higher education, with few scholars studying their impact on language teaching within the context of middle school education. In this sense, this study employs a mixed-methods research design, selecting 375 Chinese middle school English teachers to investigate the roles of teaching satisfaction and resilience in the relationship between self-efficacy and teachers’ well-being. A structural equation modeling approach and NVivo were utilized to analyze quantitative data and qualitative data, respectively. Quantitative results reveal that both teaching satisfaction and resilience mediate the relationship between self-efficacy and teachers’ well-being. Qualitative interviews reveal that teaching satisfaction primarily enhances job commitment, reduces job stress, improves student relationships, and increases professional growth. Meanwhile, resilience plays a crucial role in stress management, positive adaptation, and emotional regulation. This research offers insightful implications for improving teachers’ well-being and contributes significantly to the broader discourse on foreign language teacher education.

With the rapid development of industry, the discharge of heavy metal-containing wastewater poses a significant threat to aquatic and terrestrial environments as well as human health. This paper provides a brief introduction to the basic principles of ion-imprinted polymer preparation and focuses on the interaction between template ions and functional monomers. We summarized the current research status on typical heavy metal ions, such as Cu(II), Ni(II), Cd(II), Hg(II), Pb(II), and Cr(VI), as well as metalloid metal ions of the As and Sb classes. Furthermore, it discusses recent advances in multi-ion-imprinted polymers. Finally, the paper addresses the challenges faced by ion-imprinted technology and explores its prospects for application.

Proso millet (Panicum miliaceum L.) is resilient to abiotic stress, especially to drought. However, the mechanisms by which its roots adapt and tolerate salt stress are obscure. In this study, to clarify the molecular mechanism of proso millet in response to drought stress, the physiological indexes and transcriptome in the root of seedlings of the proso millet cultivar ‘Yumi 2’ were analyzed at 0, 0.5, 1.0, 1.5, and 3.0 h of stimulated drought stress by using 20% PEG-6000 and after 24 h of rehydration. The results showed that the SOD activity, POD activity, soluble protein content, MDA, and O2−· content of ‘Yumi 2’ increased with the time of drought stress, but rapidly decreased after rehydration. Here, 130.46 Gb of clean data from 18 samples were obtained, and the Q30 value of each sample exceeded 92%. Compared with 0 h, the number of differentially expressed genes (DEGs) reached the maximum of 16,105 after 3 h of drought, including 9153 upregulated DEGs and 6952 downregulated DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that upregulated DEGs were mainly involved in ATP binding, nucleus, protein serine/threonine phosphatase activity, MAPK signaling pathway–plant, plant–pathogen interactions, and plant hormone signal transduction under drought stress, while downregulated DEGs were mainly involved in metal ion binding, transmembrane transporter activity, and phenylpropanoid biosynthesis. Additionally, 1441 TFs screened from DEGs were clustered into 64 TF families, such as AP2/ERF-ERF, bHLH, WRKY, NAC, MYB, and bZIP TF families. Genes related to physiological traits were closely related to starch and sucrose metabolism, phenylpropanoid biosynthesis, glutathione metabolism, and plant hormone signal transduction. In conclusion, the active oxygen metabolism system and the soluble protein of proso millet root could be regulated by the activity of protein serine/threonine phosphatase. AP2/ERF-ERF, bHLH, WRKY, NAC, MYB, and bZIP TF families were found to be closely associated with drought tolerance in proso millet root. This study will provide data to support a subsequent study on the function of the drought tolerance gene in proso millet.

Abstract Abundant extrachromosomal circular DNA (eccDNA) is associated with transposable element (TE) activity. However, how the eccDNA compartment is controlled by epigenetic regulations and what is its impact on the genome is understudied. Here, using long reads, we sequence both the eccDNA compartment and the genome of Arabidopsis thaliana mutant plants affected in DNA methylation and post-transcriptional gene silencing. We detect a high load of TE-derived eccDNA with truncated and chimeric forms. On the genomic side, on top of truncated and full length TE neo-insertions, we detect complex structural variations (SVs) notably at a disease resistance cluster being a natural hotspot of SV. Finally, we serendipitously identify large tandem duplications in hypomethylated plants, suggesting that SVs could have been overlooked in epigenetic mutants. We propose that a high eccDNA load may alter DNA repair pathways leading to genome instability and the accumulation of SVs, at least in plants.

Abstract Background This study aimed to investigate the expression profile of immune response-related proteins of Behcet’s disease (BD) patients and identify potential biomarkers for this disease. Methods Plasma was collected from BD patients and healthy controls (HC). Immune response-related proteins were measured using the Olink Immune Response Panel. Differentially expressed proteins (DEPs) were used to construct prediction models via five machine learning algorithms: naive Bayes, support vector machine, extreme gradient boosting, random forest, and neural network. The prediction performance of the five models was assessed using the area under the curve (AUC) value, recall (sensitivity), specificity, precision, accuracy, F1 score, and residual distribution. Subtype analysis of BD was performed using the consensus clustering method. Results Proteomics results showed 43 DEPs between BD patients and HC (P

Purpose: The purpose of this study is to investigate the efficacy and safety of immune checkpoint inhibitors (ICIs) or plus with chemotherapy in older patients. Methods: We enrolled 110 older patients with non-small cell lung cancer (NSCLC ≥75 years) who received either chemotherapy alone (chemo), ICI plus chemotherapy (ICI + chemo), or ICI alone and ICI plus other therapies, which included anti-angiogenesis drugs or other novel ICI (ICIs). Patient characteristics, treatment response, survival, and toxicity were evaluated. Results: In total population, the ICIs group has the highest disease control rate (DCR 75%). There were no significant differences in progression-free survival (PFS) and overall survival (OS) among older patients between ICI + chemo and ICIs groups (PFS: 5.3 months vs. 5.5 months, p = 0.70, OS: 10.7 months vs. 20.3 months, p = 0.995). Meanwhile, we observed ICIs had a longer PFS and OS than chemo group (PFS: 3.9 months vs. 5.5 months, p = 0.01, OS: 10.9 months vs. 20.3 months, p = 0.05). Subgroup analysis showed that patients with programmed death ligand-1 (PD-L1) ≥ 1% had a distinct longer trend toward OS in ICIs group compared to ICI + chemo group (22.4 months vs. 10.7 months, p = 0.605), even though there was no significant difference. In terms of safety, ICIs was more tolerable and had a lower discontinuation rate than ICI + chemo group. Conclusion: In the real world, ICI + chemo is more likely to be discontinued due to adverse effects and does not significantly improve patient survival compared with ICIs treatment in total population and subgroup. Therefore, ICI alone or ICIs plus other therapies, such as anti-angiogenesis drugs or other novel ICI (ICIs) could be recommended for older cases with PD-L1 positive NSCLC.

In this paper, we investigate the crossover behaviors of entanglement and return probability at the critical point in one-dimensional XXZ model by quantum renormalization group method. Two types of quench protocols (A) adding the interaction term in z spin direction suddenly and (B) rotating all the even spins by π about the z spin direction suddenly are considered to drive the dynamics of the system, respectively. The dynamical behaviors are closely related to the initial state under two types of quench protocols, especially at N→∞. For the left of critical point, return probabilities eventually approach one under both types of quench protocols. For the right of critical point, return probability oscillates between the maximum value and zero for quench A and tends to one for quench B, respectively. In addition, we discuss the evolution period of entanglement (return probability), find that it is positively and negatively correlated with N in the spin-fluid and Néel phases, respectively. By further analyzing the behaviors of entanglement, return probability and evolution period under both types of quench protocols near the critical point, we observe that they exist the same scaling behaviors, in which the exponents are identical to entanglement exponent of the stationary system, which is related to the results of renormalization group.

Atopic dermatitis is one of the most common dermatologic problems, especially in children. Given the ability of symbiotic microorganisms in modulating the immune system, probiotics administration has been studied in previous research in the management of atopic dermatitis. However, there are conflicting results between studies. In this study, we aimed to assess the effectiveness of mixed probiotics as a treatment option for atopic dermatitis induced by ovalbumin. BALB/c juvenile mice were classified and divided into the ovalbumin group, mixed probiotic group (ovalbumin + LK), and control group. Except for the control group, all mice were sensitized with ovalbumin to establish a model of atopic dermatitis. The mixed probiotics were given by gavage for 14 days. Mice body weight, skin lesions, skin inflammation, ovalbumin-specific Ig, the number of Treg and CD103+DC, and the expression level of PD-1/PD-L1 were examined. The results showed that mixed probiotics can improve body weight and alleviate skin symptoms. Mixed probiotics reduced serum Th2 inflammatory factors, eosinophils, mast cell degranulation, mast cell count, and the expression of ovalbumin-specific immunoglobulin E/G1 and increased the anti-inflammatory cytokine interleukin-10, Treg cells, CD103+DC cells, and the expression level of PD-1/PD-L1. These findings suggest that mixed probiotics could be a viable treatment option for atopic dermatitis and provide insight into the underlying mechanisms involved.

To cope with the emissions permit trading program, industrial firms have to change production decisions, which may affect their pollution discharge, labor demand, and workers’ wage earnings. Using a time-varying difference-in-differences framework together with robustness checks, this research explores the impacts of the SO2 emissions trading scheme (SETS) on SO2 emissions, employment, and wages of industrial firms in China. It was noted that the program resulted in a remarkable decline not only in SO2 emissions but also in labor demands and wages. The mechanism analyses further show that emissions reduction is mainly driven by fossil energy input decrease rather than by desulfurization technology. The negative effects of employment and wages are driven by the negative output effect and insufficient technology rather than by the environmental substitute effect. Our findings contribute to the improvement of the market-oriented environmental permit trading program and development of regulated firms in developing countries.

At present, medications containing inhaled corticosteroids (ICS-containing) are the keystones of asthma treatment. The majority of asthmatic children can significantly improve clinical outcomes with little worsening by standardized inhaled glucocorticoid treatment, but there is still a small proportion of children who are unable to achieve good symptom control even after the maximum standardized treatment, known as ‘children with difficult-to-treat asthma (DA)’. The high heterogeneity of DA makes therapy challenging and expensive, which poses a serious risk to children’s health and makes it extremely difficult for clinical physicians to accurately identify and treat children with DA. This article reviews the definition, evaluation, and treatment of this asthma in order to provide a reference for optimal clinical decision-making.

The application of mycorrhizal fungi as a bioaugmentation technology for phytoremediation of heavy metal (HM) contaminated soil has attracted widespread attention. In order to explore whether the adaptation of Pinus massoniana (P. massoniana) to metal polluted soil depends on the metal adaptation potential of their associated ectomycorrhizal fungi (ECMF), we evaluated the cadmium (Cd) tolerance of 10 ecotypes of Cenococcum geophilum (C. geophilum) through a membership function method, and P. massoniana seedlings were not (NM) or inoculated by Cd non-tolerant type (JaCg144), low-tolerant (JaCg32, JaCg151) and high-tolerant (JaCg205) isolates of C. geophilum were exposed to 0 and 100 mg·kg-1 for 3 months. The result showed that, each ecotype of C. geophilum significantly promoted the growth, photosynthesis and chlorophyll content, proline (Pro) content and the activity of peroxidase (POD) of P. massoniana seedlings, and decreased malonaldehyde (MDA) content and catalase (CAT) and superoxide dismutase (SOD) activity. The comprehensive evaluation D value of the tolerance to Cd stress showed that the order of the displaced Cd resistance of the four ecotypic mycorrhizal P. massoniana was: JaCg144 > JaCg151 > JaCg32 > JaCg205. Pearson correlation analysis showed that the Sig. value of the comprehensive evaluation (D) values of the strains and mycorrhizal seedlings was 0.077 > 0.05, indicating that the Cd tolerance of the the C. geophilum isolates did not affect its regulatory effect on the Cd tolerance of the host plant. JaCg144 and JaCg151 which are non-tolerant and low-tolerant ecotype significantly increased the Cd content in the shoots and roots by about 136.64-181.75% and 153.75-162.35%, indicating that JaCg144 and JaCg151 were able to effectively increase the enrichment of Cd from the soil to the root. Transcriptome results confirmed that C. geophilum increased the P. massoniana tolerance to Cd stress through promoting antioxidant enzyme activity, photosynthesis, and lipid and carbohydrate synthesis metabolism. The present study suggests that mental-non-tolerant ecotypes of ECMF can protect plants from Cd pollution, providing more feasible strategies for ectomycorrhizal-assisted phytoremediation.

Abstract Hearing loss is one of the most common neurosensory disorders in humans, and above half of hearing loss is caused by gene mutations. Among more than 100 genes that cause non-syndromic hearing loss, myosin VI (MYO6) is typical in terms of the complexity of underlying mechanisms, which are not well understood. In this study, we used both knock-out (Myo6 −/−) and point mutation (Myo6 C442Y ) mice as animal models, performed whole-cell patch-clamp recording and capacitance measurement in the inner hair cells (IHCs) in the cochlea, and sought to reveal potential functional and developmental changes in their ribbon synapses. In Myo6 −/− cochleae of both before (P8-10) and after hearing onset (P18-20), exocytosis from IHCs, measured in whole-cell capacitance change (ΔCm), was significantly reduced, Ca2+ current amplitude (ICa) was unchanged, but Ca2+ voltage dependency was differently altered, causing significant increase in Ca2+ influx in mature IHCs but not in immature IHCs. In immature IHCs of Myo6 C442Y/C442Y cochleae, neither ΔCm nor ICa was altered, but both were reduced in mature IHCs of the same animal model. Furthermore, while the reduction of exocytosis was caused by a combination of the slower rate of depleting readily releasable (RRP) pool of synaptic vesicles and slower sustained release rate (SRR) in Myo6 −/− immature IHCs, it was likely due to smaller RRP and slower SRR in mature IHCs of both animal models. These results expand our understanding of the mechanisms of deafness caused by MYO6 mutations, and provide a solid theoretical and scientific basis for the diagnosis and treatment of deafness.

Autophagy, as a special programmed cell death, is a critical degradative process that eliminates intracellular abnormal proteins or damage organelles to balance cell energy and favor cell metabolism with autophagy-related (ATG) proteins. Autophagy activation is being increasingly recognized as an essential hallmark in tumorigenesis through influencing the metabolism of stromal cells in the tumor microenvironment (TME) which comprises of tumor cells, cancer-associated fibroblasts (CAFs), cancer-associated endothelial cells (CAEs), immune cells and adipocytes. Tumor cells can reuse autophagy-involved recycling to maintain mitochondrial function and energy supply to meet the metabolic demand of their growth and proliferation. However, the mechanism through which autophagy can promote a crosstalk between tumor and stroma cells is not clear. Reprogramed metabolism is one of the main characteristics of TME leading to higher adaptability of tumor cells with diverse mechanisms. The activation of autophagy has expanded our understanding on the interaction between tumor metabolism and TME. The aim of this review is to report recent advances on the metabolic cross-talk between stromal cells and solid tumor cells induced by autophagy in TME and revealed potential therapeutic targets.

Neuroendocrine neoplasms (NENs) include well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Somatostatin receptors (SSTRs) are highly expressed on NETs cells, and somatostatin analogs (SSAs) could bind to SSTRs with high affinities, regulating cell proliferation and hormone secretion. As many clinical trials have demonstrated the antiproliferative efficacy and safety of SSAs in metastatic gastroenteropancreatic NETs (GEP-NETs), SSAs have been recommended by multiple NEN guidelines as the first-line therapy of GEP-NETs. In recent years, more and more researches have been exploring new therapeutic possibilities of SSA in GEP-NETs, such as high-dose SSA as second-line therapy, SSA in metastatic GEP-NETs with Ki-67 > 10%, SSA as adjuvant therapy for postoperative pancreatic NETs patients, and combinations of SSA with chemotherapy or targeted therapy. In this review, we summarized the latest published or released researches and discussed new application attempts of SSA in GEP-NETs.

China is the world’s largest producer and exporter of concentrated apple juice (CAJ). However, traditional concentration methods such as vacuum evaporation (VE) and freeze concentration cause the loss of essential nutrients and heat-sensitive components with high energy consumption. A green and effective technique is thus desired for juice concentration to improve product quality and sustainability. In this study, a hybrid forward osmosis–membrane distillation (FO–MD) process was explored for the concentration of apple juice using sodium lactate (L-NaLa) as a renewable draw solute. As a result, commercial apple juice could be concentrated up to 65 °Brix by the FO process with an average flux of 2.5 L·m−2·h−1. Most of the nutritional and volatile compounds were well retained in this process, while a significant deterioration in product quality was observed in products obtained by VE concentration. It was also found that membrane fouling in the FO concentration process was reversible, and a periodical UP water flush could remove most of the contaminants on the membrane surface to achieve a flux restoration of more than 95%. In addition, the L-NaLa draw solution could be regenerated by a vacuum membrane distillation (VMD) process with an average flux of around 7.87 L∙m−2∙h−1 for multiple reuse, which further enhanced the long-term sustainability of the hybrid process.

Three types of Co3O4 catalyst, namely Co3O4 nanoparticles (denoted as Co3O4-NPs, ∼12 nm in diameter), Co3O4 nanoparticles encapsulated in mesoporou s SiO2 (denoted as Co3O4@SiO2), and Co3O4 nanoparticles inside microporous SiO2 hollow sub-microspheres (denoted as Co3O4-in-SiO2), were explored to catalyze the combustion of lean methane. It was found that the methane conversion over the three catalysts has the order of Co3O4-NPs ≈ Co3O4@SiO2 > Co3O4-in-SiO2 due to the different catalyst structure. The comparison experiments at high temperatures indicate the Co3O4@SiO2 has a significantly improved anti-sintering performance. Combined with the TEM and BET measurements, the results prove that the presence of the mesoporous SiO2 layer can maintain the catalytical activity and significantly improve the anti-sintering performance of Co3O4@SiO2. In contrast, the microporous SiO2 layer reduces the catalytical activity of Co3O4-in-SiO2 possibly due to its less effective diffusion path of combustion product. Thus, the paper demonstrates the pore size of SiO2 layer and catalyst structure are both crucial for the catalytical activity and stability.

ObjectiveAssociations between plasma homocysteine (Hcy), vitamin B12, and folate and the risk of all-cause mortality are unclear. This study aimed to examine whether plasma Hcy, vitamin B12, and folate levels independently predict the risk of all-cause mortality in American adults with stroke.MethodsData from the United States National Health and Examination Survey (NHANES; 1999–2006) were used and linked with the latest (2019) National Death Index (NDI). Cox proportional hazards models and restricted cubic splines were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of all-cause mortality for Hcy, folate, and B12 levels in adults with stroke. Sample weights were calculated to ensure the generalizability of the results.ResultsA total of 431 participants were included (average age: 64.8 years). During a median follow-up of 10.4 years, 316 deaths occurred. Hcy was positively associated with all-cause mortality in adults with stroke (HR, 1.053; 95% CI: 1.026–1.080). Stroke patients with plasma Hcy levels in the fourth quartile had a 1.631-fold higher risk of all-cause mortality (HR, 1.631; 95% CI: 1.160–2.291) than those in the first quartile. The association between plasma Hcy and all-cause mortality was strong significant in older patients (p for interaction = 0.020). Plasma folate and vitamin B12 concentrations were inversely correlated with Hcy concentrations [B-value (95% CI): −0.032 (−0.056– −0.008), −0.004 (−0.007– −0.002), respectively]. No significant associations were observed between folate, vitamin B12 levels, and all-cause mortality in adults with stroke.ConclusionPlasma Hcy levels were positively associated with all-cause mortality in older adults with stroke. Folate and vitamin B12 levels were inversely correlated with Hcy. Plasma Hcy may serve as a useful predictor in mortality risk assessment and targeted intervention in adults with stroke.

Objective This study examined knowledge and practice of breakthrough cancer pain (BTcP) management among general practitioners (GPs) providing palliative care in Shanghai.Design Cross-sectional study using a self-administered questionnaire.Setting and participants A total of 393 GPs providing palliative care in 32 community health service centres in Shanghai were recruited by stratified cluster random sampling between 1 May and 30 June 2022.Outcome measures Knowledge and practice concerning BTcP management.Results A total of 375 questionnaires were collected and declared valid. The median knowledge score was 11 out of 21 points. Only 36.3% (n=136) of the participating GPs scored 11 points or more, which was categorised as good knowledge. Only 24.8% (n=93) of the GPs used Davies’ adapted diagnostic algorithm as the gold standard for diagnosis. All of the GPs assessed the intensity of BTcP; however, less than a quarter of the GPs evaluated the relationship between background pain and BTcP (22.1%, n=83), the impact of BTcP on activities of daily living (24.0%, n=90), the impact of BTcP on social relationships (14.4%, n=54) and the impact of BTcP on mood (10.1%, n=38). 56.5% (n=212) of the GPs reported that they used pain tools in the assessment of BTcP. All of the GPs prescribed immediate-release morphine as rescue medication for relieving BTcP; however, 60.5% (n=227) prescribed the dose based on their personal experiences, irrespective of the basal opioid dose, and 57.3% (n=215) did not conduct dose titration after providing the initial dose. No GPs reported that they ever administered interventional treatment to their patients.Conclusions Insufficient knowledge and inappropriate behaviours in BTcP diagnosis, assessment and treatment were identified. There is an urgent need to improve BTcP management among GPs providing palliative care in Shanghai.

Abstract The effects of chronic occupational noise exposure on hypertension are debated. We aimed to investigate the association between occupational noise exposure and the prevalence of hypertension. The cross‐sectional data were collected from 2017 to 2018 using occupational physical examination data from a local aircraft manufacturing enterprise in Xi'an. We categorized occupational noise exposure as high (≥85 dBA) and low noise exposure (

Phytoestrogens and cold negatively influence male fertility. However, the combined effects of these two factors on male reproduction remain unknown. Herein, we studied the changes of sperm parameters and identify potential biomarkers involved in testis of rats, which were intervened by phytoestrogens combined with cold stress. Male Sprague–Dawley rats were randomly divided into control and model groups. The rats in the model group were fed an estrogen diet and placed in a climate chamber [10 ± 2°C; humidity of 75 ± 5%] for 12 h/daily. When compared with the control group after 24 weeks, the rats in the model group showed increased food intake, urine and stool outputs, and higher estradiol and follicle-stimulating hormone levels. However, lower sperm concentration, motility, and viability, and reduced testosterone levels were detected. The epithelial cells of the seminiferous tubules and epididymal ducts presented morphological abnormalities. Proteomic analysis showed that 24 testicular proteins were upregulated and 15 were downregulated. The identified proteins were involved in reticulophagy and stress response. Our findings suggest that the phytoestrogens combined with cold stress had negative effects on the reproductive function of male rats and provide the basis for the establishment of “course simulation” type of oligospermia animal model.

Background: The relationship between genetic polymorphism and postoperative pain and the prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is not fully understood. Objective: To examine whether lncRNA-GAS5 and its promoter region rs145204276 polymorphism can predict postoperative pain and prognosis of the patients with HCC undergoing hepatectomy. Methods: Seventy patients with HCC undergoing hepatectomy were enrolled. The lncRNA-GAS5 levels in CD4+ T cells from peripheral blood mononuclear cells (PBMC-CD4+ T cells) and tumor tissues were measured by qRT-PCR. Genotyping analysis of rs145204276 was performed using the TaqMan platform. PBMC-CD4+ T cells were isolated and the cytokine levels in helper T (Th) cells were determined by flow cytometry. Patients with Ins/Ins genotype carrying the rs145204276 polymorphism were allocated into the Ins group, and others were allocated into the Del group. Results: The lncRNA-GAS5 level decreased significantly in PBMC-CD4+ T cells and tumor tissues compared with the healthy controls and corresponding adjacent non-tumor tissues. The patients with Del/Del genotype showed significantly higher lncRNA-GAS5 expression in PBMC-CD4+ T cells, lower postoperative pain scores, and better overall survival. LncRNA-GAS5 expression in PBMC-CD4+ T cells was negatively associated with IL-6, IL-17, and the RORγT/CD3 ratio (an indicator of TH17 polarization). Conclusion: LncRNA-GAS5 expression and its promoter region rs145204276 polymorphism are prognostic biomarkers that can predict postoperative pain of patients with HCC undergoing hepatectomy.

Natural Gas Hydrate (NGH) and Hydrate-bearing Sediments (HBS) are emerging as an important potential energy resource. Radial Jet Drilling (RJD) technology, turning sharply in the casing and drilling laterals by using water jet, is a valid approach to solve problems of high cost, low efficiency during the exploitation of NGHs. The performance of water jet drilling remains unclear, and traditional finite element methods cannot accurately depict the water jet drilling ability due to mesh distortion. This paper analyzes the water jet erosion process of NGH and HBS. Experiments on the erosion of reconstituted gas hydrates are conducted and visualized in both submerged and submerged confining pressure conditions. Subsequently, two coupled nozzle–target models are solved by Arbitrary Lagrangian Eulerian (ALE) and Smooth Particle Hydrodynamics (SPH) methods. The flow field, the deformation and erosion of the hydrates induced by water jet are simulated. The experimental results show that there are specific shapes of cylindrical erosion pits for NGH and HBS. The numerical results are consistent with the experiments, which proves the effectiveness of water jet exploring hydrate resources. The submerged condition and the confining pressure condition will hinder the erosion efficiency, and the critical erosion velocities for both HBS and NGH are obtained. ALE method has superior accuracy in modeling the damaged area and erosion pit characteristics; while SPH method, has advantages in showing the motion state of the single particles and unstable and discontinuous flow field. This paper provides a good guidance for understanding the water jet drilling performance and selecting the appropriate simulation method in NGH reservoirs development.

Abstract Background Elongases of very long chain fatty acids (ELOVLs), a family of first rate-limiting enzymes in the synthesis of long-chain fatty acids, play an essential role in the biosynthesis of complex lipids. Disrupting any of ELOVLs affects normal growth and development in mammals. Genetic variations in ELOVLs are associated with backfat or intramuscular fatty acid composition in livestock. However, the effects of ELOVL gene family on breeding selection and lipid deposition in different tissues are still unknown in chickens. Results Genetic variation patterns and genetic associations analysis showed that the genetic variations of ELOVL genes were contributed to breeding selection of commercial varieties in chicken, and 14 SNPs in ELOVL2-6 were associated with body weight, carcass or fat deposition traits. Especially, one SNP rs17631638T > C in the promoter of ELOVL3 was associated with intramuscular fat content (IMF), and its allele frequency was significantly higher in native and layer breeds compared to that in commercial broiler breeds. Quantitative real-time PCR (qRT-PCR) determined that the ELOVL3 expressions in pectoralis were affected by the genotypes of rs17631638T > C. In addition, the transcription levels of ELOVL genes except ELOVL5 were regulated by estrogen in chicken liver and hypothalamus with different regulatory pathways. The expression levels of ELOVL1-6 in hypothalamus, liver, abdominal fat and pectoralis were correlated with abdominal fat weight, abdominal fat percentage, liver lipid content and IMF. Noteworthily, expression of ELOVL3 in pectoralis was highly positively correlated with IMF and glycerophospholipid molecules, including phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl glycerol and phospholipids inositol, rich in ω-3 and ω-6 long-chain unsaturated fatty acids, suggesting ELOVL3 could contribute to intramuscular fat deposition by increasing the proportion of long-chain unsaturated glycerophospholipid molecules in pectoralis. Conclusions In summary, we demonstrated the genetic contribution of ELOVL gene family to breeding selection for specialized varieties, and revealed the expression regulation of ELOVL genes and their potential roles in regulating lipid deposition in different tissues. This study provides new insights into understanding the functions of ELOVL family on avian growth and lipid deposition in different tissues and the genetic variation in ELOVL3 may aid the marker-assisted selection of meat quality in chicken.

IntroductionPrevious studies have found that unique patterns of gut microbial colonization in infancy associated with the development of allergic diseases. However, there is no research on the gut microbiota characteristics of AR children in Chinese Mainland.ObjectiveTo investigate the changes of gut microbial of AR children in Chinese Mainland and evaluate the correlation between gut microbial and clinical indexes.MethodsIn this clinical study, fecal samples from 24 AR children and 25 healthy control children (HCs) were comparative via next generation sequencing of the V3-V4 regions of the 16S rRNA gene. Analyzed the relationship between clinical features and gut microbial using Spearman correlation.ResultsCompared to HCs, AR children showed significant decreases in Shannon index and significant increases in Simpson index at both the family and genera levels (all p

Aminoglycoside antibiotics (AGAs) are widely used in life-threatening infections, but they accumulate in cochlear hair cells (HCs) and result in hearing loss. Increases in adenosine triphosphate (ATP) concentrations and P2X7 receptor expression were observed after neomycin treatment. Here, we demonstrated that P2X7 receptor, which is a non-selective cation channel that is activated by high ATP concentrations, may participate in the process through which AGAs enter hair cells. Using transgenic knockout mice, we found that P2X7 receptor deficiency protects HCs against neomycin-induced injury in vitro and in vivo. Subsequently, we used fluorescent gentamicin–Fluor 594 to study the uptake of AGAs and found fluorescence labeling in wild-type mice but not in P2rx7−/− mice in vitro. In addition, knocking-out P2rx7 did not significantly alter the HC count and auditory signal transduction, but it did inhibit mitochondria-dependent oxidative stress and apoptosis in the cochlea after neomycin exposure. We thus conclude that the P2X7 receptor may be linked to the entry of AGAs into HCs and is likely to be a therapeutic target for auditory HC protection.

ObjectiveHomocysteine (Hcy) is a predictor for stroke. B vitamins are required for the metabolism of Hcy. We designed a study to investigate the associations of plasma Hcy and B vitamins with the prevalence of stroke in adults.MethodsA total of 8,371 adults were included in the National Health and Examination Survey (NHANES) between 2003–2006 in the United States. Multivariate regression analysis and smooth curve fitting were conducted to evaluate the associations of stroke prevalence with Hcy, folate, vitamin B6, and B12. A segmented regression model was used to analyze the threshold effects. Sample weights were calculated to ensure the results’ generalizability.ResultsThe mean age of all participants was 46.43 years (51.8% women), and the prevalence of stroke was 2.72%. A nonlinear and positive association was found between plasma Hcy levels and the prevalence of stroke. Furthermore, L-shaped associations were found between plasma vitamin B6 and folate levels and stroke, with the turning point at 65.2 nmol/L for vitamin B6 and 26 nmol/L for folate, respectively. Vitamin B12 revealed a U-shaped relationship with stroke, with the turning points at 492.98 pmol/L for vitamin B12.ConclusionNon-linear associations of plasma Hcy and B vitamins levels with stroke prevalence were found in American adults. These associations may have an implication that higher plasma Hcy levels should be reduced, and plasma vitamin B6, vitamin B12 and folate levels should be moderately improved in stroke prevention. Future studies are needed to verify the causality of these associations and elucidate the underlying mechanisms.

Cement-emulsified asphalt (CEA) has been widely used in slab ballastless track and asphalt pavement cold recycling projects because of its high stiffness and toughness. In CEA material, emulsifiers and asphalt affect the cement’s hydration process and microstructure. Thus, to further investigate the effects of anionic emulsifiers (AEs) and anionic emulsified asphalt (AEA) with different demulsification rates on the hydration process and microstructure of cement, two types of AE (rapid-setting and slow-setting) and their corresponding AEA were used to prepare modified cement pastes. First, it was confirmed that the AEs and AEA delayed cement hydration by measuring the setting time, X-ray diffraction (XRD) patterns, and electrical resistivity of the cement paste. Then, the microstructure of the cement paste was determined with mercury intrusion porosimetry (MIP) and a scanning electron microscope (SEM), and it was found that AEs and AEA have varying degrees of inhibitory effects on the formation of the cement paste microstructure. Finally, based on the energy dispersive spectrometer (EDS) element content of the cement paste and Fourier transform infrared spectroscopy (FTIR) on the two AEs, the inhibition mechanism of AE and AEA with different demulsifier rates on the cement hydration process was analyzed. The experimental results showed that both AEs and AEA delayed the hydration process of cement to varying degrees and altered the microstructure of cement, and slow setting anionic emulsified asphalt (SAEA) had the greatest impact on the hydration process and microstructure of cement. Compared to pure cement paste, the initial setting time of cement paste mixed with SAEA was delayed by 73.9%, and the final setting time was delayed by 66.7%. After adding SAEA, the most probable aperture of the cement paste increased from 62.50 nm to 71.19 nm after one day of hydration. Due to the fact that there were more carboxyl groups with negative charges, more -COO− was adsorbed onto the surface of cement particles in the slow-cracking anionic emulsifier (SAE); compared with the rapid-setting anionic emulsifier (RAE) and the rapid-setting anionic emulsified asphalt (RAEA), the SAE and the SAEA had a stronger delaying effect on the hydration reaction of cement.

Abstract Background The ideal neural interface or scaffold for stem cell therapy shall have good biocompatibility promoting survival, maturation and integration of neural stem cells (NSCs) in targeted brain regions. The unique electrical, hydrophilic and surface-modifiable properties of Ti3C2Tx MXene make it an attractive substrate, but little is known about how it interacts with NSCs during development and maturation. Results In this study, we cultured NSCs on Ti3C2Tx MXene and examined its effects on morphological and electrophysiological properties of NSC-derived neurons. With a combination of immunostaining and patch-clamp recording, we found that Ti3C2Tx MXene promotes NSCs differentiation and neurite growth, increases voltage-gated current of Ca2+ but not Na+ or K+ in matured neurons, boosts their spiking without changing their passive membrane properties, and enhances synaptic transmission between them. Conclusions These results expand our understanding of interaction between Ti3C2Tx MXene and NSCs and provide a critical line of evidence for using Ti3C2Tx MXene in neural interface or scaffold in stem cell therapy.