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Abstract Heat stress has become one of the abiotic stresses that pose an increasing threat to maize production due to global warming. The Hsp20 gene family confers tolerance to various abiotic stresses in plants. However, very few Hsp20s have been identified in relation to maize thermotolerance. In this study, we conducted a comprehensive study of Hsp20s involved in thermotolerance in maize. A total of 33 maize Hsp20 genes (ZmHsp20s) were identified through scanning for a conserved α-crystalline domain (ACD), and they were categorized into 14 subfamilies based on phylogenetic analysis. These genes are distributed across all maize chromosomes and nine of them are in regions previously identified as heat-tolerance quantitative trait loci (hrQTL). These hrQTL-associated ZmHsp20s show variation in tissue-specific expression profiles under normal conditions, and seven of them possess 1–5 heat stress elements in their promoters. The integration of RNA-seq data with real-time RT-PCR analysis indicated that ZmHsp23.4, ZmHsp22.8B and ZmHsp18 were dramatically induced under heat stress. Additionally, these genes exhibited co-expression patterns with key ZmHsfs, which are crucial in the heat tolerance pathway. When a null mutant carrying a frame-shifted ZmHsp18 gene was subjected to heat stress, its survival rate decreased significantly, indicating a critical role of ZmHsp18 in maize thermotolerance. Our study lays the groundwork for further research into the roles of ZmHsp20s in enhancing maize’s thermotolerance.

As a fundamental tool in synthetic biology, promoters are pivotal in regulating gene expression, enabling precise genetic control and spurring innovation across diverse biotechnological applications. However, most advances in engineered genetic systems rely on host-specific regulation of the genetic portion. With the burgeoning diversity of synthetic biology chassis cells, there emerges a pressing necessity to broaden the universal promoter toolkit spectrum, ensuring adaptability across various microbial chassis cells for enhanced applicability and customization in the evolving landscape of synthetic biology. In this study, we analyzed and validated the primary structures of natural endogenous promoters from Escherichia coli, Bacillus subtilis, Corynebacterium glutamicum, Saccharomyces cerevisiae, and Pichia pastoris, and through strategic integration and rational modification of promoter motifs, we developed a series of cross-species promoters (Psh) with transcriptional activity in five strains (prokaryotic and eukaryotic). This series of cross species promoters can significantly expand the synthetic biology promoter toolkit while providing a foundation and inspiration for standardized development of universal components The combinatorial use of key elements from prokaryotic and eukaryotic promoters presented in this study represents a novel strategy that may offer new insights and methods for future advancements in promoter engineering.

Abstract Background Microbes in the cold polar and alpine environments play a critical role in feedbacks that amplify the effects of climate change. Defining the cold adapted ecotype is one of the prerequisites for understanding the response of polar and alpine microbes to climate change. Results Here, we analysed 85 high-quality, de-duplicated genomes of Deinococcus, which can survive in a variety of harsh environments. By leveraging genomic and phenotypic traits with reverse ecology, we defined a cold adapted clade from eight Deinococcus strains isolated from Arctic, Antarctic and high alpine environments. Genome-wide optimization in amino acid composition and regulation and signalling enable the cold adapted clade to produce CO2 from organic matter and boost the bioavailability of mineral nitrogen. Conclusions Based primarily on in silico genomic analysis, we defined a potential cold adapted clade in Deinococcus and provided an updated view of the genomic traits and metabolic potential of Deinococcus. Our study would facilitate the understanding of microbial processes in the cold polar and alpine environments.

Serine/arginine-rich splicing factor 3 (SRSF3), the smallest member of the SR protein family, serves multiple roles in RNA processing, including splicing, translation, and stability. Recent studies have shown that SRSF3 is implicated in several inflammatory diseases. However, its impact on macrophage inflammation remains unclear. Herein, we determined the expression of SRSF3 in inflammatory macrophages and found that the level of SRSF3 was increased in macrophages within atherosclerotic plaques, as well as in RAW-264.7 macrophages stimulated by lipopolysaccharides. Moreover, the downregulation of SRSF3 suppressed the levels of inflammatory cytokines by deactivating the nuclear factor κB (NFκB) pathway. Furthermore, the alternative splicing of myeloid differentiation protein 2 (MD2), a co-receptor of toll-like receptor 4 (TLR4), is regulated by SRSF3. The depletion of SRSF3 increased the level of the shorter MD2B splicing variants, which contributed to inflammatory inhibition in macrophages. In conclusion, our findings imply that SRSF3 regulates lipopolysaccharide-stimulated inflammation, in part by controlling the alternative splicing of MD2 mRNA in macrophages.

Bacteria exhibit a rich repertoire of RNA molecules that intricately regulate gene expression at multiple hierarchical levels, including small RNAs (sRNAs), riboswitches, and antisense RNAs. Notably, the majority of these regulatory RNAs lack or have limited protein-coding capacity but play pivotal roles in orchestrating gene expression by modulating transcription, post-transcription or translation processes. Leveraging and redesigning these regulatory RNA elements have emerged as pivotal strategies in the domains of metabolic engineering and synthetic biology. While previous investigations predominantly focused on delineating the roles of regulatory RNA in Gram-negative bacterial models such as Escherichia coli and Salmonella enterica, this review aims to summarize the mechanisms and functionalities of endogenous regulatory RNAs inherent to typical Gram-positive bacteria, notably Bacillus subtilis. Furthermore, we explore the engineering and practical applications of these regulatory RNA elements in the arena of synthetic biology, employing B. subtilis as a foundational chassis.

BackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder posing challenges to patients, caregivers, and society. Accessible and accurate information is crucial for effective AD management. ObjectiveThis study aimed to evaluate the accuracy, comprehensibility, clarity, and usefulness of the Generative Pretrained Transformer’s (GPT) answers concerning the management and caregiving of patients with AD. MethodsIn total, 14 questions related to the prevention, treatment, and care of AD were identified and posed to GPT-3.5 and GPT-4 in Chinese and English, respectively, and 4 respondent neurologists were asked to answer them. We generated 8 sets of responses (total 112) and randomly coded them in answer sheets. Next, 5 evaluator neurologists and 5 family members of patients were asked to rate the 112 responses using separate 5-point Likert scales. We evaluated the quality of the responses using a set of 8 questions rated on a 5-point Likert scale. To gauge comprehensibility and participant satisfaction, we included 3 questions dedicated to each aspect within the same set of 8 questions. ResultsAs of April 10, 2023, the 5 evaluator neurologists and 5 family members of patients with AD rated the 112 responses: GPT-3.5: n=28, 25%, responses; GPT-4: n=28, 25%, responses; respondent neurologists: 56 (50%) responses. The top 5 (4.5%) responses rated by evaluator neurologists had 4 (80%) GPT (GPT-3.5+GPT-4) responses and 1 (20%) respondent neurologist’s response. For the top 5 (4.5%) responses rated by patients’ family members, all but the third response were GPT responses. Based on the evaluation by neurologists, the neurologist-generated responses achieved a mean score of 3.9 (SD 0.7), while the GPT-generated responses scored significantly higher (mean 4.4, SD 0.6; P

Quasi-Zero Stiffness (QZS) is essential for low-frequency passive vibration isolation, with the negative stiffness mechanism (NSM) being pivotal for achieving QZS. Mechanical spring-based NSMs often face issues like contact friction, parasitic high-frequency modes, and stiffness nonlinearity. This paper presents a new magnetic NSM designed to overcome these challenges effectively. The mechanism is applied to a Fast Steering Mirror (FSM) as a case study, enhancing its vibration isolation performance. Initially, a torque model for the magnetic NSM is established, exploring the impact of various structural dimensions on torque and nonlinear issues. The magnetic NSM features adjustable negative stiffness and a large, adjustable linear working range. Experiments were designed to validate the principle of the magnetic NSM and its effect on the QZS FSM’s vibration isolation performance. The experimental results confirm the accuracy of the magnetic NSM principle. The QZS FSM stiffness is significantly reduced to quasi-zero stiffness, resulting in a decrease of the resonance peak from 20.1 to −12.8 dB and lowering the minimum suppressible vibration frequency from 54.63 to 3.44 Hz, thereby enhancing the vibration isolation performance of the QZS FSM.

We present a rare case of a large parathyroid carcinoma (PC) characterized by severe hyperparathyroidism, hypercalcemia, and osteoporosis. Long-standing calcium loss resulted in thoracic and facial deformities, initially misdiagnosed as oral malignancy.

Deep-fried breaded tilapia nuggets (DFBTNs) have good market prospects as a tilapia deep-processed product. In this study, we used pre-optimized DFBTNs to simulate the mass change from storage to consumption and investigated the changes in storage shelf-life and frying mass transfer kinetics of DFBTNs. Microbial growth trend and shelf-life prediction models at different storage temperatures were developed using a modified Gompertz equation. The R2 of the fitted equations were all greater than 0.98, and the predicted shelf-life of the products was close to the actual measurement time. The ability of the electronic nose and tongue to differentiate between odor and taste can be used as a secondary indicator to determine whether a product is spoiled or not. During the reheating process of deep-frying, the batter shell moisture decreased (18.69 %→6.89 %), and the oil content increased (2.76 %→27.35 %). The mass transfer coefficient k fitted by Fick's second law for moisture evaporation was 0.0086, and the mass transfer coefficient k fitted by the first-order kinetic equation for oil absorption was 0.1137. This study is informative for storing and consuming DFBTNs, which can provide a basis for the deep processing and high-value utilization of tilapia.

Abstract Toll-like receptor 9 (TLR9) recognizes bacterial, viral and self DNA and play an important role in immunity and inflammation. However, the role of TLR9 in obesity is less well-studied. Here, we generate B-cell-specific Tlr9-deficient (Tlr9 fl/fl /Cd19Cre +/- , KO) B6 mice and model obesity using a high-fat diet. Compared with control mice, B-cell-specific-Tlr9-deficient mice exhibited increased fat tissue inflammation, weight gain, and impaired glucose and insulin tolerance. Furthermore, the frequencies of IL-10-producing-B cells and marginal zone B cells were reduced, and those of follicular and germinal center B cells were increased. This was associated with increased frequencies of IFNγ-producing-T cells and increased follicular helper cells. In addition, gut microbiota from the KO mice induced a pro-inflammatory state leading to immunological and metabolic dysregulation when transferred to germ-free mice. Using 16 S rRNA gene sequencing, we identify altered gut microbial communities including reduced Lachnospiraceae, which may play a role in altered metabolism in KO mice. We identify an important network involving Tlr9, Irf4 and Il-10 interconnecting metabolic homeostasis, with the function of B and T cells, and gut microbiota in obesity.

Abstract Object This study aimed to investigate the changes in the translucency and color of four different multi-layered zirconia materials when the sintering temperature were inaccurate. Materials and methods Two hundred zirconia samples (11 × 11 × 1.0 mm) of four multi-layered zirconia, Upcera TT-GT (UG), Upcera TT-ML (UM), Cercon xt ML (CX), and Lava Esthetic (LE), were divided into five subgroups according to the sintering temperature: L1 (5% lower temperature), L2 (2.5% lower temperature), R (recommended sintering temperature), H2 (2.5% higher temperature), H1 (5% higher temperature). After sintering, color coordinates were measured. Then the translucency parameter (TP) values, and the color differences (between the inaccurate sintering temperature and the recommended temperature) of each zirconia specimen were calculated. Statistical analysis was performed by using three-way ANOVA tests, the one-way ANOVA, and Tukey’s post hoc test. Results Three-way ANOVA results showed that material type, sintering temperature, specimen section, and their interactions significantly influenced the TP values (except for the interactions of specimen section and sintering temperature) (P .05). Compared with recommended sintering temperature, higher sintering temperature caused higher TP values for CX, but lower for LE. Three-way ANOVA results showed that material type, sintering temperature, and their interactions significantly influenced the ∆E 00 values (P

Objective This study aimed to explore the efficacy and safety of high-intensity focused ultrasound (HIFU) ablation for treating fumarate hydratase (FH)-deficient uterine leiomyomas.Method Ten patients with FH-deficient uterine leiomyomas treated with HIFU ablation at the Third Xiangya Hospital from July 2017 to January 2023 were enrolled in this study. The effectiveness and adverse effects of HIFU were analyzed.Results The median age of the patients who received HIFU was 32.0 years (range: 28–41 years). Only 2 patients had solitary uterine leiomyomas, whereas the remaining 8 patients had multiple uterine leiomyomas. The median diameter of the largest myoma was 56 mm (range: 41–99 mm). Magnetic resonance imaging showed that the FH-deficient uterine leiomyomas of 8 patients presented as mixed intensity on T2WI, that of one patient was hypointense, and that of another patient was hyperintense on T2WI. All patients successfully underwent HIFU ablation in one session without severe adverse effects. The median nonperfusion volume ratio (NPVR) was 40% (30.0%–78.0%) after HIFU treatment. Four patients had NPVR ≥70%. At 3-month follow-up after HIFU ablation, the clinical symptoms of 5 of the 8 patients with symptoms before treatment were relieved. Six months after treatment, 4 of the 8 patients with symptoms were still in remission. All patients received reintervention by March 2024. The reintervention rates were 20%, 70%, and 90% at 12, 24, and 36 months, respectively, after HIFU ablation.Conclusion HIFU is a safe and feasible treatment for FH-deficient uterine leiomyomas, and most patients show effective results in the short term after treatment. However, the reintervention rates are high, and the long-term effects are limited.

AimTo examine the prevalence and potential risk factors of multimorbidity among older adult in China. In addition, we investigated the pattern of multimorbidity.MethodsThis study is based on data from the fourth Sample Survey of the Aged Population in Urban and Rural China (SSAPUR) in 2015, a comprehensive survey of individuals aged 60 years or older in China. We calculated baseline data and prevalence rates for comorbidities, stratified by household registration, age, sex, education, exercise, and health insurance. Univariate and multivariate logistic regression analyses were conducted to identify potential risk factors for comorbidities. Furthermore, we determined the prevalence rates for the three most frequent disease combinations.ResultsA total of 215,040 participants were included in our analysis. The prevalence of multimorbidity was 50.5% among the older adult in China. The prevalence rate was slightly higher in rural areas than in urban areas, with rates of 51.5 and 49.6%, respectively (p

Objectives: Antibodies to gp210 and sp100 are specific and unique anti-nuclear autoantibodies (ANAs) associated with primary biliary cholangitis (PBC). Importantly the presence of anti-gp210 and anti-sp100 responses is indicative of poor clinical outcomes. However, the utility of measuring titers of these antibodies remains unclear. Materials and methods: Using the in-house purified gp210 (HSA108-C18) and sp100 (amino acid position 296–386), we quantitatively measured serum autoantibodies to gp210 and sp100 using chemiluminescence immunoassay (CLIA) in a very large cohort of 390 patients with PBC, including 259 cases with no prior ursodesoxycholic acid (UDCA) treatment and 131 cases with UDCA treatment. We also analyzed serial changes in anti-gp210 and anti-sp100 levels in 245 sequential samples from 88 patients. Results: In our cross-sectional analysis, we detected anti-gp210 immunoglobulin G (IgG) and anti-sp100 IgG autoantibodies in 129 out of 390 (33.1%) and 80 out of 390 (20.5%) PBC patients, respectively. Multivariate analysis revealed that serum IgG (st.β = 0.35, P = 0.003) and gamma-glutamyltransferase (GGT) (st.β = 0.23, P = 0.042) levels at baseline were independently associated with anti-gp210 concentrations. In serial testing, we observed significant fluctuations in anti-gp210 antibody levels. These fluctuations reflected responsiveness to UDCA therapy, particularly in anti-gp210-positive patients with initially lower concentrations in the stages of disease. Conclusions: Our study reflects that quantitative changes of anti-gp210 antibody are indicative of UDCA responses. There is a great need for newer metrics in PBC and we suggest that a more detailed and longer study of these unique ANAs is warranted.

Abstract Wind energy, as a renewable energy source, offers the advantage of clean and pollution-free power generation. Its abundant resources have positioned wind power as the fastest-growing and most widely adopted method of electricity generation. Wind speed stands as a key characteristic when studying wind energy resources. This study primarily focuses on predictive models for wind speed in wind energy generation. The intense intermittency, randomness, and uncontrollability of wind speeds in wind power generation present challenges, leading to high development costs and posing stability challenges to power systems. Consequently, scientifically forecasting wind speed variations becomes imperative to ensure the safety of wind power equipment, maintain grid integration of wind power, and ensure the secure and stable operation of power systems. This holds significant guiding value and significance for power production scheduling institutions. Due to the complexity of wind speed, scientifically predicting its fluctuations is crucial for ensuring the safety of wind power equipment, maintaining wind power integration systems, and ensuring the secure and stable operation of power systems. This research aims to enhance the accuracy and stability of wind speed prediction, thereby reducing the costs associated with wind power generation and promoting the sustainable development of renewable energy. This paper utilizes an improved Hilbert–Huang transform (HHT) using complementary ensemble empirical mode decomposition (CEEMD) to overcome issues in the traditional empirical mode decomposition (EMD) method, such as component mode mixing and white noise interference. Such an approach not only enhances the efficiency of wind speed data processing but also better accommodates strong stochastic and nonlinear characteristics. Furthermore, by employing mathematical analytical methods to compute weights for each component, a dynamic neural network model is constructed to optimize wind speed time series modeling, aiming for a more accurate prediction of wind speed fluctuations. Finally, the optimized HHT-NAR model is applied in wind speed forecasting within the Xinjiang region, demonstrating significant improvements in reducing root mean square errors and enhancing coefficient of determination. This model not only showcases theoretical innovation but also exhibits superior performance in practical applications, providing an effective predictive tool within the field of wind energy generation.

Modern Multi-Function Radars (MFRs) are sophisticated sensors that are capable of flexibly adapting their control parameters in transmitted pulse sequences. In complex electromagnetic environments, efficiently and accurately recognizing the inter-pulse modulations of non-cooperative radar pulse sequences is a key step for modern Electronic Support (ES) systems. Existing recognition methods focus more on algorithmic designs, such as neural network structure designs, to improve recognition performance. However, in open electromagnetic environments with increased flexibility in radar transmission, these methods would suffer performance degradation due to domain shifts between training and testing datasets. To address this issue, this study proposes a robust radar inter-pulse modulation feature extraction and recognition method based on disentangled representation learning. At first, inspired by the Representation Learning Theory (RLT), the received radar pulse sequences can be disentangled into three explanatory factors related to (i) modulation types, (ii) modulation parameters, and (iii) measurement characteristics, such as measurement noise. Then, an explainable radar pulse sequence disentanglement network is proposed based on auto-encoding variational Bayes. The features extracted through the proposed method can effectively represent the key latent factors related to recognition tasks and maintain performance under domain shift conditions. Experiments on both ideal and non-ideal situations demonstrate the effectiveness, robustness, and superiority of the proposed method in comparison with other methods.

Objective: The Asian Working Group for Sarcopenia 2019 consensus emphasized nutritional assessment and intervention for community-dwelling older people with sarcopenia status. This study aimed to examine the association of serum albumin and dietary protein intake (DPI) with all-cause mortality among older adults at risk of sarcopenia. Methods: We enrolled 1763 older adults at risk of sarcopenia in the Chinese Longitudinal Healthy Longevity Survey (2012–2018) using calf circumference and handgrip strength. Serum albumin concentrations were measured using bromocresol green methods, and DPI frequency was evaluated using a semi-quantitative questionnaire at baseline. Cox proportional hazards models were used to explore the association of serum albumin and DPI with all-cause mortality. Results: During 5606.3 person-years of follow-up (median: 3.28 years), 802 older people died. After adjusting for socio-demographics, health behaviors, and clinical characteristics, we observed an inverse linear association between serum albumin and all-cause mortality (Pnon-linear = 0.429). Participants with low albumin levels ( 0.05). Moreover, the association between low albumin and all-cause mortality remained significant in the lower DPI subgroup (HR = 1.47, 95 % CI = 1.18–1.85), but was not significant in the high DPI subgroup (HR = 1.15, 95 % CI = 0.92–1.39). Conclusions: Serum albumin levels are inversely associated with all-cause mortality in community-based older adults at risk of sarcopenia. Sufficient dietary protein consumption may attenuate the effect of low serum albumin on increased mortality and potential mechanisms for the interaction warrant further exploration.

There has been a major increase in Type 2 diabetes and obesity in many countries, and this will lead to a global public health crisis, which not only impacts on the quality of life of individuals well but also places a substantial burden on healthcare systems and economies. Obesity is linked to not only to type 2 diabetes but also cardiovascular diseases, musculoskeletal disorders, and certain cancers, also resulting in increased medical costs and diminished quality of life. A number of studies have linked changes in gut in obesity development. Dysbiosis, a deleterious change in gut microbiota composition, leads to altered intestinal permeability, associated with obesity and Type 2 diabetes. Many factors affect the homeostasis of gut microbiota, including diet, genetics, circadian rhythms, medication, probiotics, and antibiotics. In addition, bariatric surgery induces changes in gut microbiota that contributes to the metabolic benefits observed post-surgery. Current obesity management strategies encompass dietary interventions, exercise, pharmacotherapy, and bariatric surgery, with emerging treatments including microbiota-altering approaches showing promising efficacy. While pharmacotherapy has demonstrated significant advancements in recent years, bariatric surgery remains one of the most effective treatments for sustainable weight loss. However, access to this is generally limited to those living with severe obesity. This underscores the need for non-surgical interventions, particularly for adolescents and mildly obese patients. In this comprehensive review, we assess longitudinal alterations in gut microbiota composition and functionality resulting from the two currently most effective anti-obesity treatments: pharmacotherapy and bariatric surgery. Additionally, we highlight the functions of gut microbiota, focusing on specific bacteria, their metabolites, and strategies for modulating gut microbiota to prevent and treat obesity. This review aims to provide insights into the evolving landscape of obesity management and the potential of microbiota-based approaches in addressing this pressing global health challenge.

Background: Sarcopenia, characterised by an ongoing loss of skeletal muscle mass and reduced strength and function, is frequently observed in patients with non-small cell lung cancer (NSCLC). However, the relationship between sarcopenia and the prognosis of NSCLC treated with immune checkpoint inhibitors (ICIs) remains unclear. This aimed to assess whether sarcopenia is an independent prognostic factor for survival in patients with advanced NSCLC receiving ICIs. Methods: For this retrospective cohort study, we analysed the medical records of patients attending our hospital aged 18–75 years who were newly diagnosed with stage IIIB to stage IV NSCLC, and who had received ICIs as first- or second-line therapy between May 2019 and April 2022. The skeletal muscle index (SMI) was calculated from computed tomography (CT) images and relevant clinical characteristics within 4 weeks of initiating treatment and used to diagnose sarcopenia status. The Kaplan-Meier method and log-rank test were used to calculate and compare patients' progression-free survival (PFS). Cox proportional hazard regression was used to examine the associations between sarcopenia and survival outcomes. The chi-square test was used to compare treatment response outcomes, such as the objective response rate (ORR), disease control rate (DCR), and immunotherapy-related adverse events (irAEs), between individuals with and without sarcopenia. Additionally, the Student's t-test was utilised to compare SMI values between patients by their objective response (OR) and disease control (DC). Finally, the Mann-Whitney U test was used to compare nutritional and inflammatory indicators between the sarcopenia groups. Results: The study enrolled 70 patients, of whom 34 (48.6%) were diagnosed with sarcopenia. The median PFS of patients with and without sarcopenia was 7.5 vs. 13.4 months, respectively (p = 0.006). The proportional hazards regression analysis showed sarcopenia to be an independent prognostic factor for shorter PFS (hazard ratio (HR): 0.504, 95% CI: 0.265–0.962, p = 0.038). Using chi square tests, we found significant differences in the ORR (20.59% vs. 58.33%, p = 0.001) and occurrence of any irAEs (44.1% vs. 22.2%, p = 0.028) between the sarcopenia and the non-sarcopenia groups, respectively. The Student's t-test showed a significant difference in SMI between the ORR group and the non-ORR group (49.99 ± 7.00 vs. 42.98 ± 2.18 cm2/m2, p = 0.0015). While the sarcopenia group were with significantly a lower CD4+/CD8+ ratios and a higher C-reactive protein (CRP) level (p = 0.026, p = 0.011, respectively). Conclusions: This study found that sarcopenia is a significant predictor of a poor prognosis for patients with advanced NSCLC receiving ICIs. Multiple inflammatory and immune functions related to prognosis also differ by sarcopenia status.

Abstract Background Thyroid cancer (THCA) is the most common type of endocrine cancers, and the disease recurrences were usually associated with the risks of metastasis and fatality. Butyrophilin-like protein 9 (BTNL9) is a member of the immunoglobulin families. This study investigated the prognostic role of BTNL9 in THCA. Methods Gene enhancers of BTNL9 were identified by interrogating H3K27ac ChIP-seq and RNA-seq data of papillary thyroid cancer (PTC) and benign thyroid nodule (BTN) tissues. Meanwhile, BTNL9 expression level was verified by qRT-PCR in 30 pairs of primary THCA and adjacent normal tissues. Clinicopathological and RNA sequencing data were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) to analyze the relations between BTNL9 expression and immune cell infiltration, chemokines/cytokines, immune checkpoint genes, clinical parameters and prognosis values. Besides, survival analysis combining BTNL9 expression and immune cell infiltration scores was conducted. Functional enrichment analysis was performed to investigate the potential biological mechanisms. Cox regression analyses were used to explore independent clinical indicators, and a nomogram model incorporating BTNL9 expression with clinical parameters was established. Results BTNL9 showed significantly stronger H3K27ac modifications in BTN than PTC tissues at the promoter region (chr5: 181,035,673–181,047,436) and gene body (chr5: 181,051,544–181,054,849). The expression levels of BTNL9 were significantly down-regulated in THCA samples compared to normal tissues, and were strongly associated with different tumor stages, immune cell infiltrations, chemokines/cytokines and immune checkpoint genes in THCA. Functional enrichment analyses indicated that BTNL9 was involved in immune-related and cancer-related pathways. The Kaplan–Meier analysis showed lower BTNL9 expression was associated with poorer progression-free interval (PFI). BTNL9 expression and pathologic stages were independent prognostic indicators of PFI in THCA. Conclusions The results implied an important role of BTNL9 in the tumor progression, with the possibility of serving as a novel prognostic biomarker and a potential therapeutic target for THCA.

Abstract Background When prepubertal lambs are superovulated, the ovarian response to gonadotropin stimulation has great individual difference and the collected oocytes have lower developmental ability than that of adult ewes. Over the years, growth hormone (GH) has been used in assisted reproduction because it can improve the reproductive performance in humans and animals. However, the effect of GH on ovaries and oocytes of prepubertal lambs remains unclear. Methods Before and during follicle-stimulating hormone (FSH) superovulation of prepubertal lambs (4‒6-week-old), the lambs were treated with high (50 mg) or low dose (25 mg) of ovine GH in a long (5 days) or short (2 days) period. The recovered oocytes were used for in vitro maturation and fertilization, and several parameters of oocyte quality and development capacity were evaluated. The possible underlying mechanisms of GH action were explored by analysis of granulosa cell (GC) transcriptome, ovarian proteome and follicular fluid metabolome. Results Treatment of lambs with 50 mg GH over 5 days (long treatment) potentially promoted the response of lambs to superovulation and improved the development capacity of retrieved oocytes, consequently increasing the high quality embryo yield from lambs. A number of differently expressed genes or proteins were found in ovaries between GH-treated and untreated lambs. Cellular experiments revealed that GH reduced the oxidative stress of GCs and promoted the GC proliferation probably through activation of the PI3K/Akt signaling pathway. Finally, analysis of follicular fluid metabolome indicated that GH treatment altered the abundance of many metabolites in follicular fluid, such as antioxidants and fatty acids. Conclusions GH treatment has a beneficial role on function of lamb ovaries, which supports the development of follicles and oocytes and improves the efficiency of embryo production from prepubertal lambs.

BackgroundAdverse psychosocial factors play an important role in cardio-cerebral vascular disease (CCVD). The aim of this study was to evaluate the impact of the cumulative burden of loneliness on the risk of CCVD in the Chinese older adult.MethodsA total of 6,181 Chinese older adult over the age of 62 in the monitoring survey of the fourth Sample Survey of the Aged Population in Urban and Rural China (SSAPUR) were included in this study. The loneliness cumulative burden (scored by cumulative degree) was weighted by the loneliness score for two consecutive years (2017–2018) and divided into low- and high-burden groups. The outcome was defined as the incidence of CCVD 1 year later (2018–2019). A multivariate logistic regression model was used to examine the relationship between the cumulative burden of loneliness and the new onset of CCVD.ResultsAmong participants, 18.9% had a higher cumulative burden of loneliness, and 11.5% had a CCVD incidence within 1 year. After multivariate adjustment, the risk of developing CCVD in the high-burden group was approximately 37% higher than that in the low-burden group (OR 1.373, 95%CI 1.096–1.721; p = 0.006). Similar results were obtained when calculating the burden based on cumulative time. Longitudinal change in loneliness was not significantly associated with an increased risk of CCVD. A higher cumulative burden of loneliness may predict a higher risk of developing CCVD in older adult individuals aged 62–72 years or in those with diabetes.ConclusionThe cumulative burden of loneliness can be used to assess the risk of new-onset CCVD in the older adult in the short term.

Background: Lung cancer is the malignant tumor with the highest morbidity and mortality rate in China. Although chemotherapy is effective in improving clinical symptoms, it causes a variety of acute and chronic side effects, seriously aggravating the psychological stress of patients. Laughter Yoga as a new type of aerobic exercise can effectively reduce stress levels and increase positive mood in patients. This study aimed to examine the effects of laughter yoga on perceived stress, positive psychological capital, and exercise capacity in lung cancer patients. Methods: This study was a randomized, single-blind, parallel-group trial. The study enrolled 84 lung cancer chemotherapy patients from a general hospital in central China. These patients were randomly allocated to control and intervention groups (n = 42 per group) after baseline assessments. Patients in the control group received routine care and those in the intervention group received laughter yoga intervention. Perceived stress, positive psychological capital, and exercise capacity were assessed at baseline, immediately post-intervention. Results: During the implementation of the study, there were 2 dropouts in each of the intervention and control groups. Ultimately, 80 patients in the control and intervention groups completed the trial. Patients who received laughter yoga intervention had significantly higher scores in positive psychological capital ( P

The dynamic and temporal changes of host genome architecture during Epstein-Barr virus (EBV) transformation are not well known. Here the authors transform human primary B lymphocyte into lymphoblastoid cell lines (LCLs) with EBV and show that the host 3D genome is rewired to facilitate expression of key oncogenes.

Background: Studies have shown that vagus nerve-mediated inflammatory reflex could inhibit cytokine production and inflammation in sepsis animals. Objectives: This study aimed to explore the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) on inflammation and disease severity of sepsis patients. Methods: A randomized, double-blind, sham-controlled pilot study was performed. Twenty sepsis patients were randomly assigned to receive taVNS or sham stimulation for five consecutive days. Stimulation effect was assessed with serum cytokine levels, Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score, and Sequential Organ Failure Assessment (SOFA) score at baseline and on Day 3, Day 5, and Day 7. Results: TaVNS was well tolerated in the study population. Patients receiving taVNS experienced significant reductions in serum TNF-α and IL-1β levels and increases in IL-4 and IL-10 levels. SOFA scores decreased on Day 5 and Day 7 compared with baseline in the taVNS group. However, no changes were found in sham stimulation group. The changes of cytokine from Day 7 to Day 1 were greater with taVNS than sham stimulation. No differences in the APACHE Ⅱ score and SOFA score were observed between the two groups. Conclusions: TaVNS resulted in significantly lower serum pro-inflammatory cytokines and higher serum anti-inflammatory cytokines in sepsis patients.

Gene regulation by trans-acting small RNAs (sRNAs) has considerable advantages over other gene regulation strategies. However, synthetic sRNAs mainly take natural sRNAs (MicC or SgrS) as backbones and comprise three functional elements folding into two or more stem-loop structures: an mRNA base pairing region, an Hfq-binding structure, and a rho-independent terminator. Due to limited numbers of natural sRNAs and complicated backbone structures, synthetic sRNAs suffer from low activity programmability and poor structural modularity. Moreover, natural sRNA backbone sequences may increase the possibility of unwanted recombination. Here, we present a bottom-up approach for creating structure defined single-stem loop small non-coding RNAs (ssl-sRNAs), which contain a standardized scaffold of a 7 bp-stem-4 nt-loop-polyU-tail and a 24 nt basing pairing region covering the first eight codons. Particularly, ssl-sRNA requires no independent Hfq-binding structure, as the polyU tail fulfills the roles of binding Hfq. A thermodynamic-based scoring model and a web server sslRNAD (http://www.kangzlab.cn/) were developed for automated design of ssl-sRNAs with well-defined structures and programmable activities. ssl-sRNAs displayed weak polar effects when regulating polycistronic mRNAs. The ssl-sRNA designed by sslRNAD showed regulatory activities in both Escherichia coli and Bacillus subtilis. A streamlined workflow was developed for the construction of customized ssl-sRNA and ssl-sRNA libraries. As examples, the E. coli cell morphology was easily modified and new target genes of ergothioneine biosynthesis were quickly identified with ssl-sRNAs. ssl-sRNA and its designer sslRNAD enable researchers to rapidly design sRNAs for knocking down target genes.

Bacillus subtilis as the Gram-positive model bacterium has been widely used in synthetic biology and biotechnology while the regulatory RNA tools for B. subtilis are still not fully explored. Here, a bottom-up approach is proposed for designing artificial trans-acting sRNAs. By engineering the intrinsic sRNA SR6, a minimized core scaffold structure consisting of an 8 bp stem, a 4 nt loop, and a 9 nt polyU tail was generated and proven to be sufficient for constructing sRNAs with strong repression activity (83%). Moreover, we demonstrate this artificial sRNA system functions well in an hfq-independent manner and also achieves strong repression efficiency in Escherichia coli (above 80%). A structure-based sRNA design principle was further developed for the automatic generation of custom sRNAs with this core scaffold but various sequences, which facilitates the manipulation and avoids structure disruption when fusing any base-pairing sequence. By applying these auto-designed sRNAs, we rapidly modified the cell morphology and biofilm formation, and regulated metabolic flux toward acetoin biosynthesis. This sRNA system with cross-species regulatory activities not only enriched the gene regulation toolkit in synthetic biology for B. subtilis and E. coli but also enhanced our understanding of trans-acting sRNAs.

As a major coal country, China faces the issue of significant gas emissions during the coal mining process. This study aims to improve the utilization efficiency of mine gas, reduce greenhouse gas emissions, and promote the low-carbon and green transformation of the coal industry. A 10 kW gas regenerative thermal oxidizer (RTO) experimental system was constructed. The effects of initial methane concentration, low-temperature flue gas proportion, and operating load on combustion temperature, methane oxidation rate, high-temperature flue gas energy, and system thermal efficiency were studied. The results show that when the combustion temperature is below 600 °C, the CH4 combustion reaction cannot proceed effectively, and the system temperature continuously decreases and cannot be maintained stably. The experiment determines the stable operating methane concentration range of the RTO. In this experimental system, the lower limit of the initial methane concentration is 0.28%, corresponding to an 86% methane oxidation rate. As the initial methane concentration decreases, the combustion temperature also decreases, and the methane oxidation rate follows suit. The higher the low-temperature flue gas proportion, the higher the combustion temperature, and the system’s thermal efficiency and output heat decrease with the increase in the low-temperature flue gas proportion. This experiment explores multiple factors affecting regenerative thermal oxidation, providing a basis for ensuring the safe and stable operation of the system and its optimization. Improving the thermal insulation and heat exchange performance of the storage body can expand the lower limit of the initial methane concentration, thereby increasing the stability and thermal efficiency of the system.

Antifreeze peptides have become effective antifreeze agents for frozen products, but their low quantity of active ingredients and high cost limit large-scale application. This study used the glycosylation of fish collagen peptides with glucosamine hydrochloride catalyzed by transglutaminase to obtain a transglutaminase-catalyzed glycosylation product (TGP) and investigate its antifreeze effect on tilapia. Compared with the blank group, the freshness (pH value of 6.31, TVB-N value of 21.7 mg/100 g, whiteness of 46.28), textural properties (especially hardness and elasticity), and rheological properties of the TGP groups were significantly improved. In addition, the protein structures of the samples were investigated using UV absorption and fluorescence spectroscopy. The results showed that the tertiary structure of the TGP groups changed to form a dense polymer. Therefore, this approach can reduce the denaturation and decomposition of muscle fibers and proteins in fish meat more effectively and has a better protective effect on muscle structure and protein aggregation, improving the stability of fish meat. This study reveals an innovative method for generating antifreeze peptides by enzymatic glycosylation, and glycosylated fish collagen peptide products can be used as new and effective green antifreeze agents in frozen foods.

Poor wind conditions in metropolitan areas can result in inadequate ventilation and degradation of the thermal environment. Several researches have demonstrated that the building ground floor elevation (BGFE) enhances the wind conditions surrounding buildings. Further investigation is required to thoroughly examine the BGFE’s impact on the wind conditions in the courtyard area. We researched how the various overhead placements affect the ventilation of a U-shaped school building’s courtyard space in different wind directions. We performed Computational Fluid Dynamics (CFD) numerical simulation experiments on 93 overhead scenarios based on field measurements and validation. The statistical analysis of the experimental data revealed that the BGFE had significant effects on reducing the mean air age (p < 0.001), standard deviation of air age (p < 0.01), standard deviation of wind speed (p < 0.001), and mean wind speed (p < 0.01) in the courtyard space. The BGFE in the northeastern zone of the U-shaped school building significantly increased the mean air age (p < 0.05), while the BGFE in the middle and southwestern zones significantly decreased the mean air age (p < 0.001), and the BGFE in the southeastern zone significantly decreased the mean wind speed (p < 0.05). The BGFE facilitates the entry of fresh air and offers even ventilation while significantly reducing wind speed. Choose sites C and D to enhance the U-shaped courtyard’s ventilation and avoid locations B and E. This paper’s findings provide theoretical guidance for designing the elevation of courtyard space from a ventilation perspective and for the green rehabilitation of existing buildings.

Larix principis-rupprechtii Mayr, a coniferous species indigenous to Northern China, possesses significant ecological and economic value. Somatic embryogenesis offers a pathway with significant potential for large-scale propagation, long-term germplasm conservation, and genetic transformation in L. principis-rupprechtii Mayr. However, it remains unclear whether significant variations occur in embryogenic tissues during long-term successive subculturing, which could impact the productivity of somatic embryos. This is a pivotal concern that lacks comprehensive understanding. In this study, three embryogenic cell lines were used to explore the dynamics and relationships among proliferation rate, pre-treatment proliferation rate, and embryogenic capabilities across a series of 32 subculturing cycles. Proliferation rate, pre-treatment proliferation rate, and somatic embryo maturation rate showed no significant correlation with subculturing cycles. However, there was a positive correlation between subculturing cycles and pre-treatment proliferation rate and a negative correlation with somatic embryo maturation rate in the BFU1 cell line. In addition, we utilized ten SSR molecular markers to investigate the genetic stability in embryogenic tissues during long-term subculturing. No genomic variations were detected in any of the three embryogenic cell lines, which suggests that the observed phenotypic dynamics during subculturing may not be primarily driven by genomic alterations. This study provides novel insights into the dynamics of the long-term culture of embryogenic tissues, laying a foundation for the optimization and application of somatic embryogenesis techniques in L. principis-rupprechtii Mayr and potentially other coniferous species.

A modified Extended State Kalman Filter (ESKF)-based Model Predictive Control (MPC) algorithm is introduced to tailor the enhanced disturbance suppression in electro-optical tracking systems. Traditional control techniques, although robust, often struggle in scenarios with concurrent internal, external disturbances, and sensor noise. The proposed algorithm effectively overcomes these limitations by precisely estimating system states and actively mitigating disturbances, thus significantly boosting noise and perturbation control resilience. The primary contributions of this study include the integration of ESKF for accurate system state and disturbance estimation in noisy environments, the embedding of an ESKF estimation-compensation loop to simulate an improved disturbance-free system, and a simplified modeling approach for the controlled device. This designed structure minimizes the reliance on extensive system identification, easing the predictive control model-based constraints. Moreover, the approach incorporates total disturbance estimation into the optimization problem, safeguarding against actuator damage and ensuring high tracking accuracy. Through rigorous simulations and experiments, the ESKF-based MPC has demonstrated enhanced model error tolerance and superior disturbance suppression capabilities. Comparative analyses under varying model parameters and external disturbances highlight its exceptional trajectory tracking performance, even in the presence of model uncertainties and external noise.

Abstract Dual targeting to immune checkpoints has achieved a better therapeutic efficacy than single targeting due to synergistic extrication of tumour immunity. However, most dual targeting strategies are usually antibody dependent which facing drawbacks of antibodies, such as poor solid tumour penetration and unsatisfied affinity. To meet the challenges, we engineered a cell membrane displaying a fusion protein composed of SIRPα and PD‐1 variants, the high‐affinity consensus (HAC) of wild‐type molecules, and with which prepared nanovesicles (NVs). Through disabling both SIRPα/CD47 and PD‐1/PD‐L1 signalling, HAC NVs significantly preserved the phagocytosis and antitumour effect of macrophages and T cells, respectively. In vivo study revealed that HAC NVs had better tumour penetration than monoclonal antibodies and higher binding affinity to CD47 and PD‐L1 on tumour cells compared with the NVs expressing wild‐type fusion protein. Exhilaratingly, dual‐blockade of CD47 and PD‐L1 with HAC NVs exhibited excellent therapeutic efficacy and biosafety. This study provided a novel biomaterial against tumoural immune escape and more importantly an attractive biomimetic technology of protein delivery for multi‐targeting therapies.

BackgroundSince the application of Immune checkpoint inhibitors (ICI), the clinical outcome for metastatic cancer has been greatly improved. Nevertheless, treatment response varies in patients, making it urgent to identify patients who will receive clinical benefits after ICI therapy. Adipose body composition has proved to be associated with tumor response. In this systematic review, we aimed to summarize the current evidence on imaging adipose biomarkers that predict clinical outcomes in patients treated with ICI in various cancer types.MethodsEmbase and PubMed were searched from database inception to 1st February 2023. Articles included investigated the association between imaging-based adipose biomarkers and the clinical outcomes of patients treated with ICI. The methodological quality of included studies was evaluated through Newcastle- Ottawa Quality Assessment Scale and Radiomics Quality Score tools. ResultsTotally, 22 studies including 2256 patients were selected. Non-small cell lung cancer (NSCLC) had the most articles (6 studies), followed by melanoma (5 studies), renal cell carcinoma (RCC) (3 studies), urothelial carcinoma (UC) (2 studies), head and neck squamous cell carcinoma (HNSCC) (1 study), gastric cancer (1 study) and liver cancer (1 study). The remaining 3 studies investigated metastatic solid tumors including various types of cancers. Adipose biomarkers can be summarized into 5 categories, including total fat, visceral fat, subcutaneous fat, intramuscular fat and others, which exerted diverse correlations with patients’ prognosis after being treated with ICI in different cancers. Most biomarkers of body fat were positively associated with survival benefits. Nevertheless, more total fat was predictable of worse outcomes in NSCLC, while inter-muscular fat was associated with poor clinical benefits in UC. ConclusionThere is relatively well-supported evidence for imaging-based adipose biomarkers to predict the clinical outcome of ICI. In general, most of the studies show that adipose tissue is positively correlated with clinical outcomes. This review summarizes the significant biomarkers proven by researches for each cancer type. Further validation and large independent prospective cohorts are needed in the future. The protocol of this systematic review has been registered at the International Prospective Register of Systematic Reviews (http://www.crd.york.ac.uk/PROSPERO, registration no: CRD42023401986).

A large number of uncertainties such as external excitement, model parameter perturbation, complex boundary conditions, time delays, seriously impact the operation of the piezoelectric plate structure. Therefore, an active disturbance rejection controller is designed and implemented based on an extended state observer to address such issues. The controller designed is analyzed in frequency-domain to address the time delays introduced by the sensors, actuators, communicational networks, computational delays, etc. Knowing that the accurate models are difficult to build, the Lissajous graphics and frequency test methods, hence, are implemented to estimate the delay and model parameters of the system. The stability characteristics and performance are verified via two intuitive frequency response methods, the small gain theorem and the Nyquist diagram. Bedsides, the relationship between time delays and control parameters is quantified, which enables controller parameters to be adjusted according to frequency index. This is the first attempt to use the small-gain theorem, which is favored for its numerical precision and computational efficiency, to analyze the active disturbance rejection control of time-delay systems. A case of a disturbed all-clamped piezoelectric plate with delays is, in particular, tested under a hardware-in-the-loop benchmark. Theoretical and experimental results show the effectiveness of the proposed approach to suppress the structure vibration in the presence of delays and disturbances.

Abstract Aging is always accompanied by chronic diseases which probably attribute to long‐term chronic inflammation in the aging body. Whereas, the mechanism of chronic inflammation in aging body is still obscure. Mesenchymal stem cells (MSCs) are capable of local chemotaxis to sites of inflammation and play a powerful role in immune regulation. Whether degeneration of MSCs in the aging body is associated with unbalanced inflammation is still not clear. In this study, immunosuppressive properties of aged MSCs are found to be repressed. The impaired immunosuppressive function of aged MSCs is associated with lower expression of the Hippo effector Yes‐associated protein 1 (YAP1) and its target gene signal transducer and activator of transcription 1 (STAT1). YAP1 regulates the transcription of STAT1 through binding with its promoter. In conclusion, a novel YAP1/STAT1 axis maintaining immunosuppressive function of MSCs is revealed and impairment of this signal pathway in aged MSCs probably resulted in higher inflammation in aged mice liver.

Mitogen-activated protein kinases (MAPKs, also known as MPKs) regulate diverse cellular and physiological functions, and dual-specificity MAPK phosphatases (MKPs) modulate MAPK signalling through MAPK dephosphorylation and inactivation. Due to lacking of overall understanding for the regulatory networks between Chrysanthemum morifolium MKPs (CmMKPs) and C. morifolium MAPKs (CmMPKs), we systematically studied the interactions between four groups of CmMPKs and eight identified CmMKPs in chrysanthemum and found that the interaction between the specific CmMKP and the specific CmMPK differed from those in other plants. Furthermore, the expression of CmMKP1 and CmMKP1-LIKE1 showed opposite trends during the development of chrysanthemum flower buds under salt treatment and Alternaria alternata inoculation, but these genes could interact with the same CmMPKs, providing insight into the subfunctionalization of paralogues. Amino acid variations (M87V, T277P and V6L) in dual-specificity protein phosphatases (DsPTP1)-LIKE1/2/3 changed the interactions of these proteins with the four CmMPK groups in chrysanthemum, providing evidence for the de/neofunctionalization of paralogues in polyploids, suggesting that we can identify the key functional sites of proteins by studying polyploid paralogues.

The existence of speckles in synthetic aperture radar (SAR) images affects its subsequent application in computer vision tasks, so the research of speckle suppression plays a very important role. Convolutional neural networks based speckle suppression algorithms cannot reach a good balance between despeckling effect and structure detail preservation. Considering these issues, a multiscale feature adaptive enhance network for suppressing speckle is proposed. Specifically, an encoder–decoder architecture embedded with multiscale operations is constructed to capture rich contextual information and remove speckles from coarse to fine. Then, deformable convolution is introduced to flexibly adapt changes in ground objects’ complex and diverse image features. Also, the constructed feature adaptive mixup module mitigates shallow feature degradation in deep networks by establishing connections between shallow image texture features and deep image semantic features with learnable weights. Experiments on synthetic and real SAR images show that the proposed method produces advanced results regarding visual quality and objective metrics.

Artemisia sphaerocephala Krasch gum (ASKG) can be carboxymethylated and greasy-based emulsified to improve its water solubility and emulsifying property, while the effect of modified ASKG on wheat flour processing as a gluten enhancer remains largely unknown. In this study, we investigated the gluten-increasing effect of ASKG in the formation of wheat flour dough and the production of greasy dough through its carboxymethylation and emulsification modification. The results showed that the carboxymethylation could reduce the optimum addition amount of ASKG from 1.0% to 0.4% in wheat flour. Carboxymethyl ASKG (C-ASKG) increased the wet gluten content, gluten index, water absorption, dough development time, dough stability time, and reduced the weakening degree. However, C-ASKG did not show better reinforcement in greasy dough than ASKG. In comparison, ASKG emulsified (E-ASKG) by wheat germ oil and palm stearin fat was shown to be more suitable for greasy dough modulation. The addition of 1.0% of ASKG and 5% of oil or fat in flour by emulsification manner reduced the difference between the oil and fat during the formation of gluten and improve the evaluation indexes of dough texture. This study demonstrated that carboxymethylation could reduce the dosage of ASKG used in wheat flour as a gluten enhancer, while emulsive ASKG was suitable for the gluten reinforcement of water-oiled dough.

Abstract Background Non-small cell lung cancer (NSCLC) is the most common lung cancer with high mortality across the world, but it is challenging to develop an effective therapy for NSCLC. Celastrol is a natural bioactive compound, which has been found to possess potential antitumor activity. However, the underlying molecular mechanisms of celastrol activity in NSCLC remain elusive. Methods Cellular function assays were performed to study the suppressive role of celastrol in human NSCLC cells (H460, PC-9, and H520) and human bronchial epithelial cells BEAS-2B. Cell apoptosis levels were analyzed by flow cytometry, Hoechst 33342, caspase-3 activity analysis, and western blot analysis. Intracellular reactive oxygen species (ROS) were analyzed by flow cytometry and fluorescence microscope. Expression levels of endoplasmic reticulum (ER) stress-related proteins and phosphorylated signal transducer and activator of transcription 3 (P-STAT3) were identified via western blot analysis. A heterograft model in nude mice was employed to evaluate the effect of celastrol in vivo. Results Celastrol suppressed the growth, proliferation, and metastasis of NSCLC cells. Celastrol significantly increased the level of intracellular ROS; thus, triggering the activation of the ER stress pathway and inhibition of the P-STAT3 pathway, and eventually leading to cell apoptosis, and the effects were reversed by the pre-treatment with N-Acetyl-l-cysteine (NAC). Celastrol also suppressed tumor growth in vivo. Conclusion The outcomes revealed that celastrol plays a potent suppressive role in NSCLC in vitro and in vivo. Celastrol induces apoptosis via causing mitochondrial ROS accumulation to suppress the STAT3 pathway. Celastrol may have potential application prospects in the therapy of NSCLC.

Abstract Head and neck squamous cell carcinomas (HNSCCs) are characterized by an abundance of monocytes and macrophages recruited from the peripheral blood. However, it has not been determined whether these infiltrated cells can be released back into circulation with a tumor‐associated neobiosignature. This study reports that Bestrophin1 (BEST1), a component protein of Ca2+‐activated Cl− channels (CaCCs), is highly expressed on classical monocytes in the peripheral blood of HNSCC patients. This is due to monocyte education by tumor cells, in which tumoral VEGF‐A upregulates BEST1 expression on monocytes through the MEK‐ERK‐ELK1 pathway. This leads to improved secretion of IL‐6 and IL‐8, which promotes tumor cell proliferation. This work also finds that BEST1 facilitates the motility of monocytes, contributing to the migration of these cells back into circulation. These results suggest that the expression of BEST1 on peripheral monocytes may be a potential tool for monitoring tumor progression, and opens up the possibility of searching for cancer biomarkers on monocytes rather than on the tumor or its products.

Purpose: Previous studies proved the benefits of electroacupuncture (EA) on heart in ischemia reperfusion injury and chronic heart failure. However, the role of EA on sepsis-induced cardiac dysfunction has rarely been elucidated before. In this study, we aimed to investigate the effects of EA on cardiac dysfunction in a rat model of sepsis and to speculate the underlying mechanisms. Methods: Sepsis was induced by cecum ligation and puncture in anesthetized rats. EA at the acupoint “Neiguan (PC6)” was applied 0.5 h after the induction of sepsis for 20 min. Heart rate variability was obtained immediately after EA to evaluate autonomic balance. Echocardiography was performed at 6 h and 24 h after sepsis induction in vivo. Measurements of hemodynamics, blood gases, cytokines and biochemistry were collected at 24 h. Cardiac tissue underwent immunofluorescence staining to determine the expression of α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages. Results: EA increased vagus nerve activity, prevented the development of hyperlactatemia, attenuated the decline of left ventricle ejection fraction, suppressed systemic and cardiac inflammation and alleviated the histopathological manifestations of heart in sepsis rats. Furthermore, the cardiac tissue from EA treated rats showed increased expressions of α7nAChR on macrophages. The cardio-protective and anti-inflammatory effects of EA were partly or completely prevented in rats with vagotomy. Conclusion: EA at PC6 attenuates left ventricle dysfunction and decreases inflammation in sepsis-induced cardiac dysfunction. The cardio-protective effects of EA are mediated through vagus nerve mediated cholinergic pathway.

This study concerns the problem of integrated optimization of structure and control based on a fast steering mirror, aiming to achieve simultaneous optimization of the mechanical structure and control system. The traditional research and development path of the fast steering mirror involves a lengthy process from the initial design to the final physical manufacture. In the prior process, it was necessary to produce physical prototypes for repeated debugging and iterative optimization to achieve design requirements, but this approach consumes a significant amount of time and cost. To expedite this process and reduce unnecessary experimental costs, this study proposes an integrated optimization of structure and control (IOSC) method. With the use of IOSC, it is possible to achieve simultaneous optimization of structure and control. Specifically, the use of non-dominated sorting genetic algorithm II (NSGA-II) obtains globally optimal controller parameters and mechanical structure parameters under certain performance indices. This achieves an effective balance between the resonance frequency generated by the system and the working bandwidth, providing a high-precision reference for the research and development of fast steering mirrors.

Postovulatory aging is known to impair the oocyte quality and embryo development due to oxidative stress in many different animal models, which reduces the success rate or pregnancy rate in human assisted reproductive technology (ART) and livestock timed artificial insemination (TAI), respectively. Salidroside (SAL), a phenylpropanoid glycoside, has been shown to exert antioxidant and antitumor effects. This study aimed to investigate whether SAL supplementation could delay the postovulatory oocyte aging process by alleviating oxidative stress. Here, we show that SAL supplementation decreases the malformation rate and recovers mitochondrial dysfunction including mitochondrial distribution, mitochondrial membrane potential (ΔΨ) and ATP content in aged oocytes. In addition, SAL treatment alleviates postovulatory aging-caused oxidative stress such as higher reactive oxygen species (ROS) level, lower glutathione (GSH) content and a reduced expression of antioxidant-related genes. Moreover, the cytoplasmic calcium ([Ca2+]c) and mitochondrial calcium ([Ca2+]mt) of SAL-treated oocytes return to normal levels. Notably, SAL suppresses the aging-induced DNA damage, early apoptosis and improves spindle assembly in aged oocytes, ultimately elevating the embryo developmental rates and embryo quality. Finally, the RNA-seq and confirmatory experience showed that SAL promotes protective autophagy in aged oocytes by activating the MAPK pathway. Taken together, our research suggests that supplementing SAL is an effective and feasible method for preventing postovulatory aging and preserving the oocyte quality, which potentially contributes to improving the successful rate of ART or TAI.

Vehicle emissions have become a significant contributor to urban air pollution. However, studies specific to city-level vehicle emission inventories are still scarce and tend to be outdated. This study introduces a methodology for developing high-resolution monthly vehicle emission inventories. We applied this methodology to Changzhou in 2022 to analyze emission characteristics and generate gridded emission data with a resolution of 0.01° × 0.01°. The results show that the total vehicle emissions of carbon monoxide (CO), volatile organic compounds (VOCs), nitrogen oxides (NOx), and fine particulate matters (PM2.5) in Changzhou are 39.69, 8.68, 18.6, and 0.56 Gg, respectively. Light-duty passenger vehicles are the main contributors to CO (74.3%) and VOCs (86.1%) emissions, while heavy-duty trucks play a significant role in NOx (50.7%) and PM2.5 (34.7%) emissions. Gasoline vehicles are mainly responsible for CO (78.6%) and VOCs (91.4%) emissions, while diesel vehicles are the primary source of NOx (81.1%) and PM2.5 (70.6%) emissions. Notably, China IV vehicles have the highest emission contribution rates (ranging from 32.5% to 44.9%). Seasonally, emissions peak in winter and are lowest in April. Spatially, emission intensity is higher in the northeast of Changzhou compared to the west and south. The methodology presented in this study offers a valuable tool for developing comprehensive city-level emission inventories, and the results provide critical insights that can inform the formulation of effective environmental policies.

Vitrification is a crucial method for preserving animal germ cells. Considering the increased oxidative stress and organelle damage incurred, it is still necessary to make the process more efficient for oocytes. As the energy source of oocytes, mitochondria are the most abundant organelle in oocytes and play a crucial role in their maturation. Here, we found that Mito-TEMPO, a mitochondria-targeted antioxidant, could efficaciously improve the oxidative stress injury of vitrified oocytes by recovering mitochondrial function via the mitochondrial respiratory chain. It was observed that Mito-TEMPO not only improves oocyte viability and meiosis but also maintains spindle structure. A subsequent study indicated that Mito-TEMPO effectively rescued mitochondrial dysfunction and attenuated vitrification-induced oxidative stress. Further investigation revealed that Mito-TEMPO regulates vitrified oocytes’ intracellular Ca2+ homeostasis and ATP content and provides strong antioxidant properties. Additionally, an analysis of the transcriptome at the single-cell level revealed that the respiratory chain mediates the beneficial effect of Mito-TEMPO on vitrified oocytes. Overall, our findings indicate that supplementing oocytes with Mito-TEMPO is an effective method to shield them from the damage caused by vitrification. In addition, the beneficial effects of Mito-TEMPO on vitrified sheep oocytes could inspire further investigations of the principles underlying oocyte cryobiology in other animals.

The effect of temperature fluctuations on the freshness of shrimp in simulated trays was investigated by setting a freeze–thaw (F-T) cycle of 12 h after freezing at −20 °C and thawing at 1 °C under refrigeration. The results showed that the shrimp’s physicochemical properties deteriorated to different extents with the increase in F-T cycles. The total colony count of shrimp was 6.07 lg CFU/g after 21 cycles, and the volatile saline nitrogen content reached 30.36 mg/100 g, which exceeded the edible standard. In addition, the sensory quality and textural properties (hardness, elasticity, chewiness, and adhesion) declined to different degrees with increased F-T cycles. LF-NMR and protein property measurements showed that F-T cycles resulted in reduced water holding capacity and protein denaturation, which were the main factors leading to the deterioration of shrimp quality. Furthermore, flavor changes were analyzed using an electronic nose sensor to establish a freshness model. The W1W, W1S, W2S, and W5S sensors were correlated with the quality changes in shrimp and used as the main sensors for detecting the freshness of Penaeus vannamei. As a result, to better maintain the overall freshness, temperature fluctuations should be minimized in sales and storage, and fewer than 8 F-T cycles should be performed.

To improve the identification accuracy of pressure fluctuation signals in the draft tube of hydraulic turbines, this study proposes an improved manta ray foraging optimization (ITMRFO) algorithm to optimize the identification method of a probabilistic neural network (PNN). Specifically, first, discrete wavelet transform was used to extract features from vibration signals, and then, fuzzy c-means algorithm (FCM) clustering was used to automatically classify the collected information. In order to solve the local optimization problem of the manta ray foraging optimization (MRFO) algorithm, four optimization strategies were proposed. These included optimizing the initial population of the MRFO algorithm based on the elite opposition learning algorithm and using adaptive t distribution to replace its chain factor to optimize individual update strategies and other improvement strategies. The ITMRFO algorithm was compared with three algorithms on 23 test functions to verify its superiority. In order to improve the classification accuracy of the probabilistic neural network (PNN) affected by smoothing factors, an improved manta ray foraging optimization (ITMRFO) algorithm was used to optimize them. An ITMRFO-PNN model was established and compared with the PNN and MRFO-PNN models to evaluate their performance in identifying pressure fluctuation signals in turbine draft tubes. The evaluation indicators include confusion matrix, accuracy, precision, recall rate, F1-score, and accuracy and error rate. The experimental results confirm the correctness and effectiveness of the ITMRFO-PNN model, providing a solid theoretical foundation for identifying pressure fluctuation signals in hydraulic turbine draft tubes.

Forestry’s high-quality development is crucial for China’s sustainable ecological, economic, and social progress. To elevate the efficiency of carbon sequestration in forestry, continuously improve the increment of carbon sinks, and contribute to achieving carbon neutrality, it is crucial to accurately assess the level of carbon sequestration efficiency in China’s forestry and explore its long-term evolution trend. In this paper, a super-efficiency SBM model, which combines the SBM model with the super-efficiency method and considers the relaxation variables, was selected to evaluate the forestry carbon sequestration efficiency of 31 provinces in China; likewise, the temporal development features of the efficacy of Chinese forests in sequestering carbon were examined using the nuclear density estimation method. Secondly, the study constructed traditional and spatial Markov probability transfer matrices to further explore the spatiotemporal evolution of carbon sequestration efficiency within Chinese forestry. Finally, combined with the Markov chain infinite distribution matrix, the future trajectory of carbon sequestration efficiency in China’s forestry was scientifically forecasted. The findings indicate that: (1) The average carbon sequestration efficiency of forestry in China showed a stable increase with fluctuations and reached the optimal state in 2018. The carbon sequestration efficiency level of various forest regions was always portrayed as southwest forest region > southern forest region > northeast forest region > northern forest region. From 2003 to 2018, there were significant differences in forestry carbon sequestration efficiency among provinces. The distribution of forestry carbon sequestration efficiency exhibited a “three-pillar” distribution pattern with Xizang, Zhejiang, and Heilongjiang as the core, and the marginal regions continuously promoted the carbon sequestration efficiency to the inland. (2) The type of transfer of forestry carbon sequestration efficiency in China is stable, and it is difficult to achieve cross-stage transfer in the short term. Moreover, the forestry carbon sequestration efficiency of each province tended to converge to a high (low) level over time, showing a “bimodal distribution” of low efficiency and high efficiency, indicating the existence of the obvious “club convergence phenomenon”. (3) Forecasting from a long-term evolution trend perspective, the outlook for the future evolution of forestry carbon sequestration efficiency in China is optimistic, and the overall trend was concentrated in the high-value area. Therefore, future forestry development in China should contemplate both internal structure optimization and coordinated regional development. Attention should be placed on forestry carbon sequestration’s role while considering the distinctive endowments of each region and developing reasonable, differentiated, and collaborative forestry management strategies.