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Low-temperature pretreatment methods such as hydrothermal carbonization and dry terrefaction can effectively improve the fuel characteristics of biomass, achieving an efficient biomass utilization. Empty fruit bunch (EFB) was selected as the experimental raw material, and was pretreated by hydrothermal carbonization and dry terrefaction in the temperature range of 180−220 ℃, to study the effect of carbonization pretreatment on the physicochemical properties of biomass. The results showed that both hydrothermal carbonization and dry terrefaction could increase the carbon content and heating value of the biomass, reduce the H/C and O/C, and the quality enhancement effect of hydrothermal carbonization was more obvious at the same reaction temperature. A study on the CO2 gasification reaction characteristics of carbonization product pellets was carried out at 800−950 ℃ using large pellet thermogravimetry, and the experimental results showed that the carbon conversion rate of EFB feedstock pellets was only 30% at 800 ℃ for 60 min, but could be up to 100% at 850−950 ℃, and the peak gasification reaction rate of the pellets increased from 0.007%/min at 800 ℃ to 0.042%/min at 950 ℃. When the gasification temperature was 950 ℃, the gasification reactivity of hydrothermal carbon particles, R0.5 (reactivity corresponding to 50% carbon conversion), decreased from 0.034 min−1 for raw material particles to 0.023 min−1 for HT-180, and decreased to 0.011 min−1 when the hydrothermal temperature was increased from 180 ℃ to 220 ℃; the R0.5 of 200 ℃ terrefaction particles was the highest at 0.039 min−1. The analysis of the surface morphology and specific surface area of the granular gasification char at different gasification stages at 950 ℃ proved that the pellets formed by the melting of ash during the gasification process of EFB feedstock and terrefaction pellets adhered to their surfaces, and the pellet pores were clogged in the process of increasing the carbon conversion from 50% to 80%, and the specific surface areas were reduced by 502.40 m2/g and 452.44 m2/g respectively. During the process of increasing carbon conversion from 80% to 98%, the ash pellets gradually fused and coated the surface of the gasification char, resulting in the specific surface area of the pellets to reduce to about 1 m2/g, and the R0.98 (reactivity corresponding to 98% carbon conversion) to reduce to 0.017 min−1 and 0.018 min−1, respectively. The specific surface area of hydrothermal carbon pellets increased by 126.98 m2/g during the increase of carbon conversion from 80% to 98%, which was attributed to the fact that the removal of AAEMs by hydrothermal carbonization alleviated the slagging phenomenon during the gasification of pellets, resulting in no significant change in the reactivity of the pellets for gasification.

Abstract Background Usage of immune checkpoint inhibitors (ICIs) has prolonged the overall survival (OS) of patients with extensive‐stage small‐cell lung cancer (ES‐SCLC). In clinical trials, males accounted for a large proportion, leading to the uncertainty of its efficacy in female patients. We therefore conducted this study to explore the efficacy and safety of using ICIs in female patients with ES‐SCLC. Methods We retrospectively enrolled female SCLC patients and subdivided them into two groups. Group A (n = 40) was defined as ES‐SCLC patients who received first‐line standard chemotherapy with or without ICIs. Group B (n = 47) included relapsed SCLC patients who were administered with second‐line therapies. Kaplan–Meier methodology was used to calculate survival analysis. Chi‐squared tests were used to analyze the incidence of adverse events (AEs). Results Median progression‐free survival (PFS) and median OS favored the ICI‐contained cohorts (Group A PFS: 8.3 vs. 6.1 months; OS: not reached vs. 11.3 months; Group B PFS: 15.1 vs. 3.3 months; OS: 35.3 vs. 8.3 months), especially in those patients who received second‐line immunotherapies. Patients who received immunotherapy had a slightly higher incidence rate of grade ≥3 AEs (Group A: 71.4% vs. 46.2%; Group B: 44.5% vs. 13.2%). Those who developed grade ≥3 AEs in first‐line ICIs cohort had a more favorable survival (PFS: 8.3 vs. 3.2 months; OS: not reached vs. 5.1 months). Conclusions Our study suggested that female ES‐SCLC patients treated with immunotherapy tended to achieve a relatively longer survival. The incidence of AEs (grade ≥3) was higher in women patients receiving ICIs, which requires monitoring more closely.

As a concrete achievement of sharing economy, sharing intermediate bulk containers (IBCs) have emerged and developed in recent years. Meanwhile, high temperature is one of the essential factors in routing optimal problems for vehicles with hazardous material (hazmat). Therefore, to address the above issue, a variant of the hazmat vehicle routing problem of sharing IBCs is proposed. Correspondingly, a mixed non-linear integer programming model is refined considering temperature-based time windows. Specifically, the given problem is solved by using a novel adaptive large neighborhood search (ALNS) algorithm. The main innovation points are as follows. Firstly, temperature-based time windows are quantified and integrated into the proposed hazmat vehicle routing optimal model. Secondly, novel heuristic operators are introduced in the ALNS algorithm. Finally, 18 numerical examples for the Solomon set demonstrate that the proposed algorithm is suitable to solve this kind of hazmat vehicle routing optimal problem.

Ferroptosis is a unique modality of regulated cell death that is driven by iron-dependent phospholipid peroxidation. N6-methyladenosine (m6A) RNA modification participates in varieties of cellular processes. However, it remains elusive whether m6A reader Fragile X Mental Retardation Protein (FMRP) are involved in the modulation of ferroptosis in breast cancer (BC). In this study, we found that FMRP expression was elevated and associated with poor prognosis and pathological stage in BC patients. Overexpression of FMRP induced ferroptosis resistance and exerted oncogenic roles by positively regulating a critical ferroptosis defense gene SLC7A11. Mechanistically, upregulated FMRP catalyzes m6A modification of SLC7A11 mRNA and further influences the SLC7A11 translation through METTL3-dependent manner. Further studies revealed that FMRP interacts with splicing factor hnRNPM to recognize the splice site and then modulated the exon skip splicing event of SLC7A11 transcript. Interestingly, SLC7A11-S splicing variant can effectively promote FMRP overexpression-induced ferroptosis resistance in BC cells. Moreover, our clinical data suggested that FMRP/hnRNPM/SLC7A11 expression were significantly increased in the tumor tissues, and this signal axis was important evaluation factors closely related to the worse survival and prognosis of BC patients. Overall, our results uncovered a novel regulatory mechanism by which high FMRP expression protects BC cells from undergoing ferroptosis. Targeting the FMRP–SLC7A11 axis has a dual effect of inhibiting ferroptosis resistance and tumor growth, which could be a promising therapeutic target for treating BC.

Abstract Osteosarcoma is an aggressive form of bone cancer and affects the health in children and adolescents. Although conventional treatment improves the osteosarcoma survival, some patients have metastasis and drug resistance, leading to a worse prognosis. Therefore, it is necessary to explore the molecular mechanism of osteosarcoma occurrence and progression, which could discover the novel treatment for osteosarcoma. Long noncoding RNAs (lncRNAs) have been reported to regulate osteosarcoma occurrence and malignant progression. LncRNA HOXA-AS3 facilitates the tumorigenesis and progression in a variety of human cancers. However, the underlying mechanism of lncRNA HOXA-AS3-induced oncogenesis is poorly determined in osteosarcoma. To address this point, we utilized several cellular biological strategies and molecular approaches to explore the biological functions and mechanisms of lncRNA HOXA-AS3 in osteosarcoma cells. We found that lncRNA HOXA-AS3 facilitates cell proliferation and invasion via targeting miR-218-5p/FOXP1 axis in osteosarcoma. In conclusion, lncRNA HOXA-AS3 could be a promising target for osteosarcoma treatment.

ObjectiveTo explore the risk factors of delivery room (DR) resuscitation and assess the association of DR resuscitation with neonatal outcomes in very preterm infants (VPIs).MethodsA multicenter retrospective cross-sectional study included VPIs with gestational age (GA)

BackgroundCockayne syndrome (CS) is a rare, multisystem, autosomal recessive disorder characterized by cachectic dwarfism, nervous system abnormalities, and premature aging. Mutations in the ERCC6 and ERCC8 genes are the predominant causes of Cockayne syndrome, with ERCC6 gene mutations present in approximately 75% of cases.MethodsTrio-based whole-exome sequencing (trio-WES) was employed to identify potential pathogenic variants associated with CS. Preimplantation genetic testing for monogenic disorders (PGT-M) was conducted to prevent the transmission of the pathogenic variant.ResultsTwo compound heterozygous mutations were identified in ERCC6—c.1297G>T (p. Glu433*) and c.1607T>G (p. Leu536Trp)—with c.1297G>T representing a novel mutation. Four blastocysts resulting from intracytoplasmic sperm injection were subjected to biopsy. Genetic analyses revealed that E1 harbored maternal mutations in diploid embryos, E2 and E3 carried both paternal and maternal mutations in non-diploid embryos, and E4 did not carry paternal or maternal mutations in diploid embryos. Following the transfer of the E4 embryos, a single successful pregnancy was achieved.ConclusionThe successful application of PGT-M in this family offers a potential approach for addressing other monogenic diseases. The findings of this study broaden the variant spectrum of ERCC6 and will contribute to the molecular diagnosis and genetic counseling of CS. This case highlights the feasibility and effectiveness of PGT-M in preventing CS and provides valuable insights for similarly affected families.

BackgroundPulmonary fibrosis (PF) emerges as a significant pulmonary sequelae in the convalescent phase of coronavirus disease 2019 (COVID-19), with current strategies neither specifically preventive nor therapeutic. Licoricesaponin G2 (LG2) displays a spectrum of natural activities, including antibacterial, anti-inflammatory, and antioxidant properties, and has been effectively used in treating various respiratory conditions. However, the potential protective effects of LG2 against PF remain underexplored.MethodsNetwork analysis and molecular docking were conducted in combination to identify the core targets and pathways through which LG2 acts against PF. In the model of bleomycin (BLM)-induced C57 mice and transforming growth factor-β1 (TGF-β1)-induced A549 and MRC5 cells, techniques such as western blot (WB), quantitative Real-Time PCR (qPCR), Immunohistochemistry (IHC), Immunofluorescence (IF), and Transwell migration assays were utilized to analyze the expression of Epithelial-mesenchymal transition (EMT) and inflammation proteins. Based on the analysis above, we identified targets and potential mechanisms underlying LG2’s effects against PF.ResultsNetwork analysis has suggested that the mechanism by which LG2 combats PF may involve the TNF-α pathway. Molecular docking studies have demonstrated a high binding affinity of LG2 to TNF-α and MMP9. Observations from the study indicated that LG2 may mitigate PF by modulating EMT and extracellular matrix (ECM) remodeling. It is proposed that the therapeutic effect is likely arises from the inhibition of inflammatory expression through regulation of the TNF-α pathway.ConclusionLG2 mitigates PF by suppressing TNF-α signaling pathway activation, modulating EMT, and remodeling the ECM. These results provide compelling evidence supporting the use of LG2 as a potential natural therapeutic agent for PF in clinical trials.

Abstract Background Previous studies have reported inconsistent results regarding blastocyst selection with a high day 3 (D3) cell number and the eventual pregnancy outcomes. Thus, in this study, the relationship between the D3 cell number and clinical outcomes of day 5 single blastocyst transfer (SBT) in vitrified-warmed transfer cycles was investigated. Methods Our retrospective study included 1144 day 5 SBT in vitrified-warmed cycles between February 2016 and February 2021. All cycles were the first vitrified-warmed cycles, and the female patients were less than 35 years of age. Based on the D3 cell number, the cycles were divided into four groups, as follows: group A (3–7 cells, n = 130); group B (8–9 cells, n = 621); group C (10–12 cells, n = 328); and group D (13–16 cells, n = 65). The differences in the live birth rate (LBR), clinical pregnancy rate, and miscarriage rate were examined among the four groups. Results The LBR and clinical pregnancy rate increased with the D3 cell number (P 9 cells) was associated with a high LBR in the vitrified-warmed day 5 SBT cycles of patients 9 cells on D3 can be preferentially selected for transplantation.

Abstract Respiratory diseases, marked by structural changes in the airways and lung tissues, can lead to reduced respiratory function and, in severe cases, respiratory failure. The side effects of current treatments, such as hormone therapy, drugs, and radiotherapy, highlight the need for new therapeutic strategies. Traditional Chinese Medicine (TCM) offers a promising alternative, leveraging its ability to target multiple pathways and mechanisms. Active compounds from Chinese herbs and other natural sources exhibit anti-inflammatory, antioxidant, antitumor, and immunomodulatory effects, making them valuable in preventing and treating respiratory conditions. Ferroptosis, a unique form of programmed cell death (PCD) distinct from apoptosis, necrosis, and others, has emerged as a key area of interest. However, comprehensive reviews on how natural products influence ferroptosis in respiratory diseases are lacking. This review will explore the therapeutic potential and mechanisms of natural products from TCM in modulating ferroptosis for respiratory diseases like acute lung injury (ALI), asthma, pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD), lung ischemia–reperfusion injury (LIRI), pulmonary hypertension (PH), and lung cancer, aiming to provide new insights for research and clinical application in TCM for respiratory health.

Abstract The article presents the results of experimental studies on the gasification of mixtures of brown coal and polyethylene (up to 20 wt% fraction) in a laboratory reactor. The work aims to study the agglomeration process during the heating and oxidation of the mixtures. The measurement results (gas composition, pressure drop) provide indirect information on the dynamics of thermal decomposition and structural changes in the fuel bed. We have shown that the interaction between polyethylene and a coal surface leads to the formation of dense agglomerates, in which the molten polymer acts as a binder. Clinkers form as a result of interfacial interactions between components and filtration flow rearranging. The hydrogen/carbon ratio in the solid residue of coal-polyethylene co-gasification increases from 0.07–0.2 to 1.11, indicating the formation of stable hydrocarbon compounds on the carbon surface. The conducted research makes it possible to identify possible interactions between chemical reactions and transfer processes that lead to agglomeration in mixtures of coal with polyethylene.

Summary: Maternal obesity has long-term effects on offspring metabolic health. Among the potential mechanisms, prior research has indicated potential disruptions in circadian rhythms and gut microbiota in the offspring. To challenge this hypothesis, we implemented a maternal high fat diet regimen before and during pregnancy, followed by a standard diet after birth. Our findings confirm that maternal obesity impacts offspring birth weight and glucose and lipid metabolisms. However, we found minimal impact on circadian rhythms and microbiota that are predominantly driven by the feeding/fasting cycle. Notably, maternal obesity altered rhythmic liver gene expression, affecting mitochondrial function and inflammatory response without disrupting the hepatic circadian clock. These changes could be explained by a masculinization of liver gene expression similar to the changes observed in polycystic ovarian syndrome. Intriguingly, such alterations seem to provide the first-generation offspring with a degree of protection against obesity when exposed to a high fat diet.

Introduction Preterm birth complications and neonatal asphyxia are the leading causes of neonatal mortality worldwide. Surviving preterm and asphyxiated newborns can develop neurological sequelae; therefore, timely and appropriate neonatal resuscitation is important to decrease neonatal mortality and disability rates. There are very few systematic studies on neonatal resuscitation in China, and its prognosis remains unclear. We established an online registry for neonatal resuscitation in Shenzhen based on Utstein’s model and designed a prospective, multicentre, open, observational cohort study to address many of the limitations of existing studies. The aim of this study is to explore the implementation and management, risk factors and outcomes of neonatal resuscitation in Shenzhen.Methods and analysis This prospective, multicentre, open, observational cohort study will be conducted between January 2024 and December 2026 and will include >1500 newborns resuscitated at birth by positive pressure ventilation at five hospitals in Shenzhen, located in the south-central coastal area of Guangdong province, China. Maternal and infant information, resuscitation information, hospitalisation information and follow-up information will be collected. Maternal and infant information, resuscitation information and hospitalisation information will be collected from the clinical records of the patients. Follow-up information will include the results of follow-up examinations and outcomes, which will be recorded using the WeChat applet ‘Resuscitation Follow-up’. These data will be provided by the neonatal guardians through the applet on their mobile phones. This study will provide a more comprehensive understanding of the implementation and management, risk factors and outcomes of neonatal resuscitation in Shenzhen; the findings will ultimately contribute to the reduction of neonatal mortality and disability rates in Shenzhen.Ethics and dissemination Our protocol has been approved by the Medical Ethics Committee of Shenzhen Luohu People’s Hospital (2023-LHQRMYY-KYLL-048). We will present the study results at academic conferences and peer-reviewed paediatrics journals.Trial registration number ChiCTR2300077368.

Glycyrrhiza glabra L. is a common heritage herbal medicine rich in antioxidant compounds such as flavonoids and triterpenoids. Non-alcoholic fatty liver disease has been the global prevalent chronic liver disorder. To investigate the curative role and mechanism of the Glycyrrhiza glabra L. crude extract on NAFLD, in vitro, we used oleic acid, palmitic acid, ML-385 and 3-MA to stimulate HepG2 cells. In vivo, we used Tyloxapol to inject mice intraperitoneally to establish an acute model, and high-fat diet to feed wild-type, Nrf2-/- and ATG5flox/flox mice to establish a chronic model. We used high performance liquid chromatography to analyse the content of major bioactive components in the Glycyrrhiza glabra L. crude extract. Our study found the Glycyrrhiza glabra L. crude extract could effectively alleviate lipid accumulation in non-alcoholic fatty liver disease, activate Nrf2 and promote autophagy. However, this alleviating effect disappeared when the Nrf2 and autophagy were inhibited separately. Our study demonstrates that crude extraction of active ingredients from traditional herbal medicines may be a potentially inexpensive, rapid and safe approach to alleviate lipid accumulation in non-alcoholic fatty liver disease.

Abstract According to the latest evidence, the microbial metabolite Urolithin A (UA), known for its role in promoting cellular health, modulates CD8+ T cell‐mediated antitumor activity. However, the direct target protein of UA and its underlying mechanism remains unclear. Here, this research identifies ERK1/2 as the specific target crucial for UA‐mediated CD8+ T cell activation. Even at low doses, UA markedly enhances the persistence and effector functions of primary CD8+ cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells both in vitro and in vivo. Mechanistically, UA interacts directly with ERK1/2 kinases, enhancing their activation and subsequently facilitating T cell activation by engaging ULK1. The UA‐ERK1/2‐ULK1 axis promotes autophagic flux in CD8+ CTLs, enhancing cellular metabolism and maintaining reactive oxygen species (ROS) levels, as evidenced by increased oxygen consumption and extracellular acidification rates. UA‐treated CD8+ CTLs also display elevated ATP levels and enhanced spare respiratory capacity. Overall, UA activates ERK1/2, inducing autophagy and metabolic adaptation, showcasing its potential in tumor immunotherapy and interventions for diseases involving ERKs.

Abstract Background Abnormal blood potassium levels are associated with an increased risk of cardiometabolic diseases and mortality in the general population; however, evidence regarding the association between dyskalemia and mortality among patients with cardiovascular disease (CVD) remains inconclusive. This study aimed to evaluate the association of potassium levels with all-cause and cardiovascular mortality among patients with CVD. Methods PubMed, Embase, Web of Science, and Cochrane Library databases were searched up to August 2023 to identify relevant cohort studies among patients with CVD, such as myocardial infarction, stroke, and heart failure. Abnormal potassium levels were considered as hypokalemia or hyperkalemia. The primary outcomes were all-cause mortality based on follow-up length (including in-hospital, short-term and long-term mortality) and cardiovascular mortality. The methodological quality of included studies was assessed by using the Newcastle-Ottawa Scale. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Restricted cubic splines were applied to explore the dose-response relationship. Results Thirty-one cohort studies involving 227,645 participants with an average age of 68.3 years were included in the meta-analysis, all of which achieved moderate to high quality. Hyperkalemia was significantly associated with an approximately 3.0-fold increased risk of all-cause in-hospital mortality (RR:2.78,95CI%:1.92,4.03), 1.8-fold of all-cause short-term mortality (RR:1.80, 95CI%:1.44,2.27), 1.3-fold of all-cause long-term mortality (RR:1.33, 95CI%:1.19,1.48) and 1.2-fold of cardiovascular mortality (RR:1.19, 95CI%:1.04,1.36). Similar positive associations were also observed between hypokalemia and risk of all-cause mortality and cardiovascular mortality. The RRs of all-cause in-hospital, short-term, long-term mortality and cardiovascular mortality with hyperkalemia were attenuated to 2.21 (95CI%:1.60,3.06), 1.46(95CI%:1.25,1.71), 1.23 (95CI%:1.09,1.39) and 1.13 (95CI%:1.00,1.27) when treating hypokalemia together with normokalemia as the reference group. A U-shaped association was observed between potassium levels and mortality, with the lowest risk at around 4.2 mmol/L. Conclusions Both hypokalemia and hyperkalemia were positively associated with the risk of mortality in patients with CVD. Our results support the importance of potassium homeostasis for improving the CVD management. Registration PROSPERO, CRD42022324337.

Abstract The latest development of Generative Artificial Intelligence (GenAI), particularly ChatGPT, has drawn the attention of educational researchers and practitioners. We have witnessed many innovative uses of ChatGPT in STEM classrooms. However, studies regarding students’ perceptions of ChatGPT as a virtual tutoring tool in STEM education are rare. The current study investigated undergraduate students’ perceptions of using ChatGPT in a physics class as an assistant tool for addressing physics questions. Specifically, the study examined the accuracy of ChatGPT in answering physics questions, the relationship between students’ ChatGPT trust levels and answer accuracy, and the influence of trust on students’ perceptions of ChatGPT. Our finding indicates that despite the inaccuracy of GenAI in question answering, most students trust its ability to provide correct answers. Trust in GenAI is also associated with students’ perceptions of GenAI. In addition, this study sheds light on students’ misconceptions toward GenAI and provides suggestions for future considerations in AI literacy teaching and research.

BackgroundThere is a lack of research evidence on the association between sugar-sweetened beverage (SSB) consumption and gestational diabetes mellitus (GDM) in China. ObjectiveTo explore the association between frequency of SSB consumption before pregnancy and risk of GDM in pregnant women in Shaanxi Province, and to provide a scientific basis for targeted interventions to control maternal blood glucose. MethodsThe recruitment to the China Birth Cohort study started in October 2020. Pregnant women at 6-16 weeks who had their first prenatal examination at five hospitals in Shaanxi Province were recruited. A maternal health questionnaire was used to collect basic information about pregnant women. A semi-quantitative food frequency questionnaire was used to collect the consumption of carbonated beverages, fruit and vegetable juice beverages, coffee beverages, and milk tea beverages in one year before pregnancy, which were summed to obtain the SSB consumption. Pregnant women were divided into three groups according to SSB consumption, namely 0.05) between SSB consumption and maternal age, pre-pregnancy BMI, or first labor or not. For each additional SSB consumption per day, the risk of GDM increased by 94% (OR=1.94, 95%CI: 1.37, 2.75); and the maternal OGTT 1-hour glucose and 2-hour glucose increased by 0.33 mmol·L−1 and 0.18 mmol·L−1, respectively (P0.05). ConclusionHigher SSB consumption before pregnancy increases the risk of GDM in pregnant women.

Abstract Background Human leucocyte antigen (HLA)-DR plays a crucial role in the immune response against hepatitis B virus (HBV). We aimed to investigate the associations of HLA-DR single nucleotide polymorphisms (SNPs) with the generation of hepatocellular carcinoma (HCC)-related HBV mutations. The effects of HLA-DR SNPs and their interactions with HBV mutations on HCC risks were also determined. Methods Five HLA-DR SNPs (rs3135363, rs9268644, rs35445101, rs24755213, and rs984778) were genotyped in 792 healthy controls, 586 chronic hepatitis B (CHB) patients, 536 liver cirrhosis (LC) patients, and 1500 HCC patients using quantitative PCR. Sanger sequencing was used to identify the HBV mutations. Logistic regression model was performed to evaluate the association of HLA-DR SNPs with HCC risk and the frequencies of HCC-related HBV mutations. Results The variant genotypes at rs3135363, rs9268644, rs35445101, rs24755213, and rs984778 were associated with decreased HCC risks. In genotype C HBV-infected subjects, variant genotypes of these SNPs were associated with decreased frequencies of HCC-related HBV mutations such as C1653T, T1674C/G, G1719T, T1753A/C, A1762T/G1764A, A1846T, G1896A, G1899A, and preS deletion. AG genotype at rs3135363, CA genotype at rs9268644, and AG genotype at rs24755213 reduced the generation of T1753A/C and G1896A in genotype B HBV-infected subjects, respectively. In addition, the interactions of rs3135363, rs9268644, rs24755213 with C1653T, T1753A/C, A1846T, and G1896A decreased the risks of HCC. Conclusions HLA-DR genetic polymorphisms might predispose the host to immunoselection of HCC-related HBV mutations and affect the HCC risks possibly through interacting with HBV mutations.

Reinforcement learning (RL) has been shown to be effective in path planning. However, it usually requires exploring a sufficient number of state–action pairs, some of which may be unsafe when deployed in practical obstacle environments. To this end, this paper proposes an end-to-end planning method based model-free RL framework with optimization, which can achieve better learning performance with a safety guarantee. Firstly, for second-order drone systems, a differentiable high-order control barrier function (HOCBF) is introduced to ensure the output of the planning algorithm falls in a safe range. Then, a safety layer based on the HOCBF is proposed, which projects RL actions into a feasible solution set to guarantee safe exploration. Finally, we conducted a simulation for drone obstacle avoidance and validated the proposed method in the simulation environment. The experimental results demonstrate a significant enhancement over the baseline approach. Specifically, the proposed method achieved a substantial reduction in the average cumulative number of collisions per drone during training compared to the baseline. Additionally, in the testing phase, the proposed method realized a 43% improvement in the task success rate relative to the MADDPG.

Abstract Soot generation is a major challenge in industries. The elimination of soot is particularly crucial to reduce pollutant emissions and boost carbon conversion. The mechanisms for soot oxidation are complex, with quantified models obtained under in situ conditions still missing. We prepare soot samples via noncatalytic partial oxidation of methane. Various oxidation models are established based on the results of in situ transmission electron microscopy experiments. A quantified maturity parameter is proposed and used to categorize the soot particles according to the nanostructure at various maturity levels, which in turn lead to different oxidation mechanisms. To tackle the challenges in the kinetic analysis of soot aggregates, a simplification model is proposed and soot oxidation rates are quantified. In addition, a special core-shell separation model is revealed through in situ analysis and kinetic studies. In this study, we obtain important quantified models for soot oxidation under in situ conditions.

Abstract Background Maturity-onset diabetes of the young type 2 (MODY2) is a rare genetic disorder characterized as mild fasting hyperglycemia with low risk of vascular complications caused by glucokinase gene mutation. This study aims to investigate metabolites alteration associated with MODY2, exploring possible mechanism underlying characteristic clinical manifestations and low cardiovascular risks of MODY2 and providing serum metabolite biomarkers to facilitating MODY2 diagnosis. Methods Fasting serum samples from MODY2, type 1 diabetes (T1DM) and healthy individuals were collected. By using targeted metabolomics via liquid chromatography–tandem mass spectrometry platform, we quantified the metabolites involved in tricarboxylic acid (TCA) cycle and one-carbon metabolism. Results Metabolomic profiling revealed significant difference of intermediates from central metabolism cycle, methionine cycle and several amino acids between MODY2 and T1DM groups. Among these, serum citrate, α-ketoglutaric acid, serine, glycine, glutamine and homocysteine were significantly elevated in MODY2 patients compared with T1DM patients; and compared with healthy subjects, malate and methionine levels were significantly increased in the two groups of diabetic patients. The correlation analysis with clinical indexes showed that α- ketoglutarate, serine, glycine, and glutamine were negatively correlated with blood glucose indicators including fasting blood glucose, HbA1c, and GA, while citrate was positively correlated with C-peptide. And homocysteine displayed positive correlation with HDL and negative with C-reactive protein, which shed light on the mechanism of mild symptoms and low risk of cardiovascular complications in MODY2 patients. A panel of 4 metabolites differentiated MODY2 from T1DM with AUC of 0.924, and a combination of clinical indices and metabolite also gained good diagnostic value with AUC 0.948. Conclusion In this research, we characterized the metabolite profiles of TCA cycle and one-carbon metabolism in MODY2 and T1DM and identified promising diagnostic biomarkers for MODY2. This study may provide novel insights into the pathogenesis and clinical manifestations of MODY2.

Abstract Inadequate β‐cell mass and insulin secretion are essential for the development of type 2 diabetes (T2D). TNF‐α‐induced protein 8‐like 1 (Tipe1) plays a crucial role in multiple diseases, however, a specific role in T2D pathogenesis remains largely unexplored. Herein, Tipe1 as a key regulator in T2D, contributing to the maintenance of β cell homeostasis is identified. The results show that the β‐cell‐specific knockout of Tipe1 (termed Ins2‐Tipe1BKO) aggravated diabetic phenotypes in db/db mice or in mice with high‐fat diet‐induced diabetes. Notably, Tipe1 improves β cell mass and function, a process that depends on Gαs, the α subunit of the G‐stimulating protein. Mechanistically, Tipe1 inhibited the K48‐linked ubiquitination degradation of Gαs by recruiting the deubiquitinase USP5. Consequently, Gαs or cAMP agonists almost completely restored the dysfunction of β cells observed in Ins2‐Tipe1BKO mice. The findings characterize Tipe1 as a regulator of β cell function through the Gαs/cAMP pathway, suggesting that Tipe1 may emerge as a novel target for T2D intervention.

Objective This study aimed to compare the pregnancy outcomes of Day 2 (D2) fresh embryo transfer and D3 fresh embryo transfer in women with only one zygote with two pronuclei (2PN). Methods Data on 432 in vitro fertilization-embryo transfer cycles with only one 2PN zygote from January 2016 to January 2022 were retrospectively collected. A total of 302 fresh embryo transfers on D2 (n = 193) and D3 (n = 109) were analyzed, and pregnancy outcomes were compared. Results The patients’ characteristics were not different between D2 and D3 embryo transfer. There were no significant differences in the rates of clinical pregnancy, early abortion, or live birth between D2 and D3 embryo transfer. A multivariate logistic regression model controlling for age, the fertilization method, the number of oocytes harvested, and the number of high-quality embryos transferred showed that the live birth rate was similar between D2 and D3 embryo transfer. Conclusion In in vitro fertilization-embryo transfer cycles with only one 2PN zygote, D2 fresh embryo transfer may provide similar pregnancy outcomes to those of D3 embryo transfer. D2 embryo transfer may be an option because of the risk of cycle cancellation due to the absence of viable embryos on D3.

Abstract Activation of endogenous neural stem cells (NSCs) is greatly significant for the adult neurogenesis; however, it is extremely limited in the spinal cord after injury. Recent evidence suggests that accumulation of protein aggregates impairs the ability of quiescent NSCs to activate. Ubiquitin c-terminal hydrolase l-1 (UCHL1), an important deubiquitinating enzyme, plays critical roles in protein aggregations clearance, but its effects on NSC activation remains unknown. Here, we show that UCHL1 promotes NSC activation by clearing protein aggregates through ubiquitin-proteasome approach. Upregulation of UCHL1 facilitated the proliferation of spinal cord NSCs after spinal cord injury (SCI). Based on protein microarray analysis of SCI cerebrospinal fluid, it is further revealed that C3+ neurotoxic reactive astrocytes negatively regulated UCHL1 and proteasome activity via C3/C3aR signaling, led to increased abundances of protein aggregations and decreased NSC proliferation. Furthermore, blockade of reactive astrocytes or C3/C3aR pathway enhanced NSC activation post-SCI by reserving UCHL1 and proteasome functions. Together, this study elucidated a mechanism regulating NSC activation in the adult spinal cord involving the UCHL1-proteasome approach, which may provide potential molecular targets and new insights for NSC fate regulation.

Abstract Using a newly developed experimental setup, the features and advantages of an autothermal single-casing atmospheric subbituminous coal fluidized bed air-blown gasifier, combining a combustion and gasification section, and mixing the dispersed phase (inert material, char) and heat exchange between them through an annular transfer device, have been revealed. To increase the efficiency of the gasifier, an experimental-computational method was developed find the conditions for optimal operation, combining changing the annular flow’s geometry and regulating the primary air for gasification. A simple and reliable multizone thermodynamic calculation model makes it possible to predict the composition of char and syngas in the gasification section with acceptable accuracy. This method confirmed that a two-section fluidized bed gasifier can provide efficient gasification of solid fuels and is suitable for use in small-scale cogeneration plants. Syngas with a heating value of 3.6–4.5 MJ/m3 and CGE of 38.2%–42.3% was obtained in the experimental setup without optimizing the primary air flow rate. With optimization, the indicators increased to the heating value of syngas of 5.20–5.34 MJ/m3 and CGE of 42.5%–50.0%. With heat regeneration of 0.8, CGE increases to 70%.

Objective: To perform a bibliometric analysis of published research on acupuncture for neurodevelopmental disorders and to provide new insights for future studies. Methods: Web of Science Core Collection was used to search for articles on acupuncture for neurodevelopmental disorders in children, from inception to Dec 4, 2022. VOSviewer and CiteSpace software were used for bibliometric analyses. VOSviewer was used to analyze and visualize the knowledge maps of the articles’ countries, authors, and institutions of origin, the journals and keywords. CiteSpace was used to visualize the dual-map overlay of the journals in which the articles were published and those publishing the articles they cited. Results: A total of 119 papers were retrieved. The highest number of publications came from China, followed by the United States and South Korea. The most frequently cited article was from the United States, followed by China. The most publications were from KyungHee University, followed by Sichuan University. Author Cho, Seung-hun from KyungHee University published the most articles. The Journal of Alternative and Complementary Medicine and Medicine published the most articles. The top three most frequently used keywords were “acupuncture”, “children”, and “complementary”. Conclusion: Research intensity and recognition, as well as collaboration within the field of acupuncture for treating neurodevelopmental disorders in children has increased. Research is generally diverse and comprehensive, and the neuro–endocrine–immune mechanism should be a new direction for further development. More basic research is also needed, to elucidate the therapeutic mechanisms, to standardize and validate the use of acupuncture for neurodevelopmental disorders.

Background: Acupuncture has promising effects on diabetes, but there is limited evidence on prediabetes. The purpose of this study was to evaluate the effect and safety of Zuo's warming Yang acupuncture therapy on prediabetic patients. Methods: Fifty five individuals with prediabetes were recruited for the study. Participants in the non-acupuncture group received a 12-week lifestyle intervention, while those in the acupuncture group received the same lifestyle intervention in addition to two 50-minute sessions of Zuo's warming Yang acupuncture therapy per week. The primary outcomes measure fasting plasma glucose (FPG), 2-hour postprandial glucose (2hPG), and Glycated hemoglobin determination (HbA1c) after 12 weeks of treatment. Results: Both acupuncture group and non-acupuncture group showed significant reductions in FPG and 2hPG levels after treatment, with a statistically significant difference between them (FPG:6.25 ± 0.48 vs 5.73 ± 0.50, P

Increasing evidence shows that metabolic factors are involved in the pathological process of osteoarthritis (OA). Lactate has been shown to contribute to the onset and progression of diseases. While whether lactate is involved in the pathogenesis of OA through impaired chondrocyte function and its mechanism remains unclear. This study confirmed that serum lactate levels were elevated in OA patients compared to healthy controls and were positively correlated with synovial fluid lactate levels, which were also correlated with fasting blood glucose, high-density lipoprotein, triglyceride. Lactate treatment could up-regulate expressions of the lactate receptor hydroxy-carboxylic acid receptor 1 (HCAR1) and lactate transporters in human chondrocytes. We demonstrated the dual role of lactate, which as a metabolite increased NADPH levels by shunting glucose metabolism to the pentose phosphate pathway, and as a signaling molecule up-regulated NADPH oxidase 4 (NOX4) via activating PI3K/Akt signaling pathway through receptor HCAR1. Particularly, lactate could promote reactive oxygen species (ROS) generation and chondrocyte damage, which was attenuated by pre-treatment with the NOX4 inhibitor GLX351322. We also confirmed that lactate could increase expression of catabolic enzymes (MMP-3/13, ADAMTS-4), reduce the synthesis of type II collagen, promote expression of inflammatory cytokines (IL-6, CCL-3/4), and induce cellular hypertrophy and aging in chondrocytes. Subsequently, we showed that chondrocyte damage mediated by lactate could be reversed by pre-treatment with N-Acetyl-l-cysteine (NAC, ROS scavenger). Finally, we further verified in vivo that intra-articular injection of lactate in Sprague Dawley (SD) rat models could damage cartilage and exacerbate the progression of OA models that could be countered by the NOX4 inhibitor GLX351322. Our study highlights the involvement of lactate as a metabolic factor in the OA process, providing a theoretical basis for potential metabolic therapies of OA in the future.

Abstract Mitochondrial function and homeostasis are critical to the proliferation of lung cancer cells. T-cell immunoglobulin and mucin domain-containing molecule 4 (TIM-4) promotes the development and progression of lung cancer. However, the role of TIM-4 in mitochondria homeostasis in tumor cells remains completely unknown. In this study, we found that TIM-4 promoted growth and proliferation of lung cancer cells by the oxidative phosphorylation (OXPHOS) pathway. Consistently, inhibition of OXPHOS reversed TIM-4-induced proliferation of lung cancer cells. Notably, TIM-4 promoted mitochondrial fusion via enhancing L-OPA1 protein expression. Mechanistically, TIM-4 regulated protein of L-OPA1 through the PI3K/AKT pathway, and TIM-4 interacted with ANXA2 to promote the activation of PI3K/AKT signaling. Collectively, TIM-4 promotes oxidative phosphorylation of lung cancer cells to accelerate tumor progress via ANXA2/PI3K/AKT/OPA1 axis, which sheds significant new lights on the potential role of TIM-4 in regulating tumor cell metabolism.

The insulator defect targets in Unmanned Aerial Vehicle (UAV) images are often small and set against complex backgrounds. Consequently, traditional object detection algorithms commonly struggle to identify these minor defects. To enhance precision and recall in detecting insulator defects, a novel model, GC-YOLO (ghost convolution and centralized feature pyramid -You Only Look Once), based on YOLOv5s, has been introduced. GC-YOLO incorporates the Ghost convolution module in the backbone network, reducing feature redundancy and improving the inference speed of the feature extraction network. Moreover, an attention mechanism based on Coordinate Attention (CA) is integrated at the terminal of the backbone network, aimed at emphasizing the extraction of crucial information from target features. The Explicit Visual Center Block (EVCBlock) module from Centralized Feature Pyramid Network (CFPNet) is introduced in the neck layer to effectively fuse multi-scale features and enhance the feature map’s characterization capability. Furthermore, in order to enhance the precision in detecting small-sized defects, a small object detection head is also added to the detection layer based on CFPNet. Experimental results demonstrate that GC-YOLO achieves a recall of 89.7% and mAP@0.5 of 94.2%, surpassing YOLOv5s by 7% and 6.5%, respectively. The proposed algorithm exhibits superior detection precision in complex scenes, providing a theoretical basis for intelligent and mechanized railway monitoring systems.

Ensuring the promptly removal of foreign objects from transmission lines is crucial for electricity safety. However, the existing object detection algorithms exhibit low precision and recall due to factors such as uncertainty in the type of foreign objects, imbalance of positive and negative samples, and the complexity of aerial photography backgrounds. Therefore, in this paper, an algorithm called DF-YOLO (Deformable Faster-You Only Look Once) for transmission line foreign object detection is proposed to resolve these problems. The algorithm is based on YOLOv7-Tiny and tailored to the dataset’s characteristics to achieve high precision along with excellent recall. The Focal-DIoU loss function is utilized to balance positive and negative sample proportions during training. Additionally, the algorithm incorporates the deformable convolution (DCN) module and the SimAM attention mechanism to enhance model performance, particularly in terms of foreign object recall and detection accuracy. Moreover, we optimized the network inference speed with the improved SPPCSPC_S-F module. Experimental results demonstrate that the improved DF-YOLO network achieves a 2.04% increase in mAP@.5 compared to the original YOLOv7-Tiny network. The recall rate also improves from 89% to 91.51%. Additionally, the inference speed of the network rises from 130 to 140 FPS, which enhances detection effectiveness and reduces the frequency of transmission line leaks triggered by foreign object incursion.

Overdosage of antibiotics used to prevent bacterial infections in the human and animal gastrointestinal tract would result in disturbing of intestinal barrier, significant misbalancing effects of intestinal microflora and persuading bacterial resistance. The main objective of the present investigation is to design and develop novel combinations of organic curcumin (Cur) and antimicrobial peptide (Amp) loaded chitosan nanoformulations (Cur/Amp@CS NPs) to improve significant effects on antibacterial action, immune response, intestine morphology, and intentional microflora. The antibacterial efficiency of the prepared nanoformulations was evaluated using Escherichia coli (E. coli) induced bacterial infections in GUT of Rat models. Further, we studied the cytocompatibility, inflammatory responses, α-diversity, intestinal morphology, and immune responses of treated nanoformulations in rat GUT models. The results indicated that Cur/Amp@CS NPs are greatly beneficial for intestinal microflora and could be a prodigious alternative of antibiotics.

Background: An increasing amount of clinical evidence of acupuncture's effect on protracted opioid abstinence syndrome (POAS) has emerged in recent years. The aim of this study was to evaluating the evidence of efficacy of acupuncture for POAS. clinical and scientific research work. Methods: Four English-language databases (PubMed, Medline, Embase, Cochrane Libraries) and three Chinese-language databases (CNKI, WanFang and VIP Libraries) were searched, with coverage from database inception to March 31, 2022. Randomized clinical trials (RCTs) evaluating the effects of acupuncture and acupuncture-related therapies for prophylaxis or treatment of POAS were included. Data were screened and extracted independently according to pre-set tabular formats. RCT quality was assessed using risk of bias tool in the Cochrane Collaboration. The primary outcome was opiate withdrawal scale. The secondary outcomes are depression, anxiety for assessing protracted symptoms. The scores on the above scales are proportional to the severity of the symptoms. Results: Twenty-eight trials met the inclusion criteria and provided data for the meta-analysis. A total of only 3 studies (11%) were judged to be low-risk overall due to various biases in them. Acupuncture-related therapy showed statistical differences in improving protracted withdrawal symptom scores compared with sham acupuncture (5 studies, Standard mean difference (SMD), -1.85, 95% CI [-3.21, -0.50], P = 0.007), western medicine (7 studies, SMD, -0.72, 95% CI [-1.22, -0.21], P = 0.005) and no treatment (3 studies, SMD,-2.26, 95% CI [-3.82, -0.69], P = 0.005) with high heterogeneity. Conclusions: Acupuncture maybe safe and effective in relieving POAS individuals’ protracted withdrawal symptoms. However, the results of our review should be interpreted with caution because of the high risk of bias of the included trials. Study registration: The protocol of this review has been registered at PROSPERO (CRD42022335505).

BackgroundExcessive neutrophil extracellular traps (NETs) is involved in the progression of acute pancreatitis (AP) but the mechanisms controlling NETs formation in AP are not fully understood. Therefore, our study sought to investigate the mechanism of the highly expressed P-selectin stimulating the formation of NETs in AP.MethodsNETs formation was detected by flow cytometry, immunofluorescence staining, and cf-DNA and MPO-DNA complexes were measured as biomarkers of NETs formation. Neutrophils treated with P-selectin and pharmacological inhibitors were examined by western blot, immunofluorescence staining and flow cytometry. Mouse model of AP was established by caerulein and the effect of inhibiting P-selectin by PSI-697 on the level of NETs and PAD4 in pancreatic tissue was observed. The severity of AP was evaluated by histopathological score and the detection of serum amylase and lipase.ResultsPatients with AP had elevated levels of NETs and P-selectin compared with healthy volunteers. Stimulation of P-selectin up-regulated the expression of PSGL-1, increased the phosphorylation of Syk, mediated intracellular calcium signal and led to the activation and expression of PAD4, which modulated NETs formation in neutrophils. Pretreament with PSI-697 blunted NETs formation and PAD4 expression in the pancreatic tissue, and ameliorated the severity of AP in mice.ConclusionTaken together, these results suggest that P-selectin induces NETs through PSGL-1 and its downstream Syk/Ca2+/PAD4 signaling pathway, and that targeting this pathway might be a promising strategy for the treatment of AP.

Global warming may increase potential evapotranspiration (ETp), reducing the water resources in Yangzi River Delta. Therefore, it is important to investigate the trend of ETp there under the background of climate change. To this purpose, the systematic biases in temperature outputs of 24 global climate models (GCMs) under 3 shared socioeconomic pathways—representative concentration pathways (SSPs) emission scenarios (SSP1-2.6, SSP2-4.5, and SSP5-8.5)—are first corrected by using 8 bias correction methods. Then, the trend of ETp in Yangtze River Delta is projected by using 4 ETp calculation formulas (Blaney–Criddle, Hargreaves–Samani, Makkink, and Priestley–Taylor). The uncertainty of the projections is estimated and decomposed by using multi-way analysis of variance frameworks. The influence of uncertainty on the projected change signal is quantified by using the signal-to-noise ratio. The results show that all emission scenarios indicate robust increments of ETp. Specifically, relative to 1971~2000, ETp will increase by 0.14~0.17 mm d−1 (5.7~6.8%) during 2021~2050 and by 0.21~0.41 mm d−1 (8.5~16.7%) during 2061~2090, respectively. During 2021~2050, the uncertainty of ETp projections is dominantly contributed by the main effects of GCM (63%) and the ETp calculation formula (24%). During 2061~2090, it is mainly contributed by the main effect of GCM (36%), followed by the main effects of the emission scenario (34%) and the ETp calculation formula (18%). The ETp projections are generally reliable and robust during the two projection periods.

The aim of this study was to investigate the correlation between spiciness and saliva flow rate by measuring the saliva flow rate of subjects after consuming different concentrations of capsaicin solutions, and to establish a rapid method for determining the spiciness of foods. The physiological change caused by the increasing of saliva secretion after eating spicy food was used as the influential indicators of spicy taste intensity. The salivary flow rate was calculated by the salivary secretion of the subjects, and the relationship between the spicy intensity and salivary flow rate was fitted. Based on the fitting model, a new grading system for rapid and accurate calibration of spiciness was constructed, and the model grading results were verified by sensory evaluation method. The results showed that the intensity of spiciness significantly affects salivary flow rate (P3000): Saliva flow rate (g/min)>3.569. By collecting the saliva secretion of 5~10 people after eating spicy food, the spiciness of the food tasted by the testers could be rated quickly by combining the quantitative relationship between spicy taste intensity and saliva flow rate. The saliva flow rate spiciness rating result was in the same spicy taste measurement level as the sensory rating result, which could basically reflect the real spiciness feeling of people after eating spicy food.

Summary: Emerging evidence shows that pancreatic β-cell function and quality are key determinants in the progression of type 2 diabetes (T2D). The transcription factor zinc finger homeobox 2 (Zhx2) is involved in proliferation and development of multiple cells. However, the exact role of Zhx2 in β-cells and T2D remains completely unknown. Here, we report that Zhx2 orchestrates β-cell mass and function by regulating paired box protein pax-6 (Pax6). We found that β-cell-specific knockout Zhx2 (Zhx2BKO) mice showed a decrease in β-cell proliferation and glucose homeostasis. Under prediabetic and diabetic conditions, we discovered glucose intolerance in both Zhx2BKO-HFD mice and Zhx2BKO-db/db mice, with reduced β-cell mass and insulin secretion. Mechanistically, we demonstrated that Zhx2 targeted the Pax6 promoter region (−1740∼-1563; −862∼-559; −251∼+75), enhanced promoter activity. Overall, Zhx2 maintains β-cell function by transcriptionally regulating Pax6, which provides a therapeutic target for diabetes intervention.

Abstract With the increase in extremely low birth weight (ELBW) infants, their outcome attracted worldwide attention. However, in China, the related studies are rare. The hospitalized records of ELBW infants discharged from twenty-six neonatal intensive care units in Guangdong Province of China during 2008–2017 were analyzed. A total of 2575 ELBW infants were enrolled and the overall survival rate was 55.11%. From 2008 to 2017, the number of ELBW infants increased rapidly from 91 to 466, and the survival rate improved steadily from 41.76% to 62.02%. Increased survival is closely related to birth weight (BW), regional economic development, and specialized hospital. The incidence of complications was neonatal respiratory distress syndrome (85.2%), oxygen dependency at 28 days (63.7%), retinopathy of prematurity (39.3%), intraventricular hemorrhage (29.4%), necrotizing enterocolitis (12.0%), and periventricular leukomalacia (8.0%). Among the 1156 nonsurvivors, 90.0% of infants died during the neonatal period (≤ 28 days). A total of 768 ELBW infants died after treatment withdrawal, for reasons of economic and/or poor outcome. The number of ELBW infants is increasing in Guangdong Province of China, and the overall survival rate is improving steadily.

Abstract Traumatic brain injury (TBI) is a cause of disability and death worldwide, but there are currently no specific treatments for this condition. Release of excess reactive oxygen species (ROS) in the injured brain leads to a series of pathological changes; thus, eliminating ROS could be a potential therapeutic strategy. Herein, we synthesized insulin-incubated ultrasmall palladium (Pd@insulin) clusters via green biomimetic chemistry. The Pd@insulin clusters, which were 3.2 nm in diameter, exhibited marked multiple ROS-scavenging ability testified by the theoretical calculation. Pd@insulin could be rapidly excreted via kidney-urine metabolism and induce negligible adverse effects after a long-time treatment in vivo. In a TBI mouse model, intravenously injected Pd@insulin clusters aggregated in the injured cortex, effectively suppressed excessive ROS production, and significantly rescued motor function, cognition and spatial memory. We found that the positive therapeutic effects of the Pd@insulin clusters were mainly attributed to their ROS-scavenging ability, as they inhibited excessive neuroinflammation, reduced cell apoptosis, and prevented neuronal loss. Therefore, the ability of Pd@insulin clusters to effectively eliminate ROS, as well as their simple structure, easy synthesis, low toxicity, and rapid metabolism may facilitate their clinical translation for TBI treatment.

Abstract Disaster-hit and/or un-electrified remote areas usually have electricity accessibility issues and an abundance of plant-derived debris and wood from destroyed wooden structures; this can be potentially addressed by employing a decentralized ultra-small biomass-fed gasification power generating system. This paper presents an assessment of the technical viability of an ultra-small gasification system that utilizes densified carbonized wood pellets/briquettes. The setup was run continuously for 100 h. A variety of biomass was densified and carbonized by harnessing fugitive heat sources before charging into the reactor. Carbonized briquettes and furnished blends exhibited inferior gasification performance compared to the carbonized pellets. In the absence of tar blockage problems, steady-state conditions were achieved when pre-treated feedstock was used. Under steady-state conditions for carbonized pellets gasification operated at an equivalence ratio of 0.32, cold gas efficiency and carbon conversion achieved 49.2% and 70.5%, respectively. Overall efficiency and maximum power output of 20.3% and 21 kW were realised, respectively. It was found that the system could keep stable while the low heating valve of syngas was over 4 MJ/m3 on condition that avoiding tar blocking issues. The results indicate that the proposed compact ultra-small power generation system is a technically feasible approach to remedy power shortage challenge. In addition, process simulation considering carbonized wood gasification combined power generation was formulated to produce syngas and electricity. Woody pellets with the flow rate of 20 kg/h could generate a 15.18 kW power at the air flow rate of 40 Nm3/h, which is in a good agreement with 15 kW in the 100 h operation. It is indicated that the gasification combined power generation cycle simulated by Aspen simulator could achieve reliable data to assist the complicated experiment operation.

With the gradual decline in freshwater resources, the space available for freshwater aquaculture is diminishing and the need to maximize saline water for aquaculture is increasing. This study aimed to elucidate the impact mechanisms of the disruption of the glutamate pathway on serum metabolism and ammonia excretion in crucian carp (Carassius auratus) under carbonate alkaline stress. A freshwater control group (C group), a 20 mmol/L NaHCO3 stress group (L group), and a 40 mmol/L NaHCO3 stress group (H group) were established. After 30 days of exposure, methionine sulfoximine (MSO) was injected to block the glutamate pathway metabolism, and the groups post-blocking were labeled as MC, ML, and MH. Ultra-high-performance liquid chromatography coupled with the quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomics technique was employed to detect changes in the composition and content of crucian carp serum metabolites. Significant differential metabolites were identified, and related metabolic pathways were analyzed. The results revealed that, following the glutamate pathway blockade, a total of 228 differential metabolites (DMs) were identified in the three treatment groups. An enrichment analysis indicated significant involvement in glycerophospholipid metabolism, arachidonic acid metabolism, sphingolipid metabolism, purine metabolism, arginine and proline biosynthesis, pantothenate and CoA biosynthesis, glutathione metabolism, and fatty acid degradation, among other metabolic pathways. The results showed that ROS imbalances and L-arginine accumulation in crucian carp after the glutamate pathway blockade led to an increase in oxidative stress and inflammatory responses in vivo, which may cause damage to the structure and function of cell membranes. Crucian carp improves the body’s antioxidant capacity and regulates cellular homeostasis by activating glutathione metabolism and increasing the concentration of phosphatidylcholine (PC) analogs. Additionally, challenges such as aggravated ammonia excretion obstruction and disrupted energy metabolism were observed in crucian carp, with the upregulation of purine metabolism alleviating ammonia toxicity and maintaining energy homeostasis through pantothenate and CoA biosynthesis as well as fatty acid degradation. This study elucidated the metabolic changes in crucian carp under carbonate alkaline stress after a glutamate pathway blockade at the cellular metabolism level and screened out the key metabolic pathways, which provide a scientific basis for further in-depth studies on the ammonia excretion of freshwater scleractinian fishes under saline and alkaline habitats at a later stage.

As the core components of electric vehicles, the safety of the electric system, including motors, batteries, and electronic control systems, has always been of great concern. To provide early warning of electric-system failure and troubleshoot the problem in time, this study proposes a novel energy-vehicle electric-system failure-classification method, which is named Pearson-ShuffleDarkNet37-SE-Fully Connected-Net (PSDSEF). Firstly, the raw data were preprocessed and dimensionality reduction was performed after the Pearson correlation coefficient; then, data features were extracted utilizing ShuffleNet and an improved DarkNet37-SE network based on DarkNet53; secondly, the inserted squeeze-and-excitation networks (SE-Net) channel attention were able to obtain more fault-related target information; finally, the prediction results of the ShuffleNet and DarkNet37-SE networks were aggregated with a fully connected neural network to output the classification results. The experimental results showed that the proposed PSDSEF-based electric vehicles electric-system fault-classification method achieved an accuracy of 97.22%, which is better than other classical convolutional neural networks with the highest accuracy of 92.19% (ResNet101); the training time is faster than the average training time of the comparative networks. The proposed PSDSEF has the advantage of high classification accuracy and small number of parameters.

BackgroundOccupational stress and depressive symptoms of disease prevention and control personnel are serious.ObjectiveTo investigate the relationship between occupational stress, psychological capital, and depressive symptoms of disease prevention and control personnel, and analyze the potential mediating effect of psychological capital on the relationship between occupational stress and depressive symptoms.MethodsFrom July to September 2020, a cluster random sampling method was used to select 2201 employees from 21 centers for disease control and prevention as study subjects covering all levels of administrative divisions in Jiangsu Province. A total of 2036 valid questionnaires were collected with a recovery rate of 92.5%. The Core Occupational Stress Scale, Patient Health Questionnaire, and Psychological Capital Questionnaire were used to investigate their occupational stress, depressive symptoms, and psychological capital. Stratified regression analysis was used to explore the effects of occupational stress and psychological capital on depressive symptoms. A mediating effect model was used to analyze and verify the potential mediating effect of psychological capital on the relationship between occupational stress and depressive symptoms.ResultsThe total scores in M (P25, P75) of occupational stress, depressive symptoms, and psychological capital in the target population were 42.0 (37.0, 48.0), 8.0 (4.0, 9.0), and 4.6 (4.0, 5.0) respectively. The positive rate of occupational stress was 31.0% (631/2036), and the positive rate of depressive symptoms was 22.0% (448/2036). The dimensional scores of organization and reward, and demand and effort of occupational stress were positively correlated with the total score of depressive symptoms [Spearman correlation coefficients (rs) were 0.371 and 0.269, P

Summary: Background: Some observational studies found that dyslipidaemia is a risk factor for non-alcoholic fatty liver disease (NAFLD), and lipid-lowering drugs may lower NAFLD risk. However, it remains unclear whether dyslipidaemia is causative for NAFLD. This Mendelian randomisation (MR) study aimed to explore the causal role of lipid traits in NAFLD and evaluate the potential effect of lipid-lowering drug targets on NAFLD. Methods: Genetic variants associated with lipid traits and variants of genes encoding lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium genome-wide association study (GWAS). Summary statistics for NAFLD were obtained from two independent GWAS datasets. Lipid-lowering drug targets that reached significance were further tested using expression quantitative trait loci data in relevant tissues. Colocalisation and mediation analyses were performed to validate the robustness of the results and explore potential mediators. Findings: No significant effect of lipid traits and eight lipid-lowering drug targets on NAFLD risk was found. Genetic mimicry of lipoprotein lipase (LPL) enhancement was associated with lower NAFLD risks in two independent datasets (OR1 = 0.60 [95% CI 0.50–0.72], p1 = 2.07 × 10−8; OR2 = 0.57 [95% CI 0.39–0.82], p2 = 3.00 × 10−3). A significant MR association (OR = 0.71 [95% CI, 0.58–0.87], p = 1.20 × 10−3) and strong colocalisation association (PP.H4 = 0.85) with NAFLD were observed for LPL expression in subcutaneous adipose tissue. Fasting insulin and type 2 diabetes mediated 7.40% and 9.15%, respectively, of the total effect of LPL on NAFLD risk. Interpretation: Our findings do not support dyslipidaemia as a causal factor for NAFLD. Among nine lipid-lowering drug targets, LPL is a promising candidate drug target in NAFLD. The mechanism of action of LPL in NAFLD may be independent of its lipid-lowering effects. Funding: Capital’s Funds for Health Improvement and Research (2022-4-4037). CAMS Innovation Fund for Medical Sciences (CIFMS, grant number: 2021-I2M-C&T-A-010).

Background: Respiratory diseases are common and frequent diseases. Due to the high pathogenicity and side effects of respiratory diseases, the discovery of new strategies for drug treatment is a hot area of research. Scutellaria baicalensis Georgi (SBG) has been used as a medicinal herb in China for over 2000 years. Baicalin (BA) is a flavonoid active ingredient extracted from SBG that BA has been found to exert various pharmacological effects against respiratory diseases. However, there is no comprehensive review of the mechanism of the effects of BA in treating respiratory diseases. This review aims to summarize the current pharmacokinetics of BA, baicalin-loaded nano-delivery system, and its molecular mechanisms and therapeutical effects for treating respiratory diseases.Method: This review reviewed databases such as PubMed, NCBI, and Web of Science from their inception to 13 December 2022, in which literature was related to “baicalin”, “Scutellaria baicalensis Georgi”, “COVID-19”, “acute lung injury”, “pulmonary arterial hypertension”, “asthma”, “chronic obstructive pulmonary disease”, “pulmonary fibrosis”, “lung cancer”, “pharmacokinetics”, “liposomes”, “nano-emulsions”, “micelles”, “phospholipid complexes”, “solid dispersions”, “inclusion complexes”, and other terms.Result: The pharmacokinetics of BA involves mainly gastrointestinal hydrolysis, the enteroglycoside cycle, multiple metabolic pathways, and excretion in bile and urine. Due to the poor bioavailability and solubility of BA, liposomes, nano-emulsions, micelles, phospholipid complexes, solid dispersions, and inclusion complexes of BA have been developed to improve its bioavailability, lung targeting, and solubility. BA exerts potent effects mainly by mediating upstream oxidative stress, inflammation, apoptosis, and immune response pathways. It regulates are the NF-κB, PI3K/AKT, TGF-β/Smad, Nrf2/HO-1, and ERK/GSK3β pathways.Conclusion: This review presents comprehensive information on BA about pharmacokinetics, baicalin-loaded nano-delivery system, and its therapeutic effects and potential pharmacological mechanisms in respiratory diseases. The available studies suggest that BA has excellent possible treatment of respiratory diseases and is worthy of further investigation and development.

The development and utilization of saline-alkaline water, an important backup resource, has received widespread attention. However, the underuse of saline-alkaline water, threatened by the single species of saline-alkaline aquaculture, seriously affects the development of the fishery economy. In this work, a 30-day NaHCO3 stress experimental study combined with analyses of untargeted metabolomics, transcriptome, and biochemical approaches was conducted on crucian carp to provide a better understanding of the saline-alkaline stress response mechanism in freshwater fish. This work revealed the relationships among the biochemical parameters, endogenous differentially expressed metabolites (DEMs), and differentially expressed genes (DEGs) in the crucian carp livers. The biochemical analysis showed that NaHCO3 exposure changed the levels of several physiological parameters associated with the liver, including antioxidant enzymes (SOD, CAT, GSH-Px), MDA, AKP, and CPS. According to the metabolomics study, 90 DEMs are involved in various metabolic pathways such as ketone synthesis and degradation metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, and linoleic acid metabolism. In addition, transcriptomics data analysis showed that a total of 301 DEGs were screened between the control group and the high NaHCO3 concentration group, of which 129 up-regulated genes and 172 down-regulated genes. Overall, NaHCO3 exposure could cause lipid metabolism disorders and induce energy metabolism imbalance in the crucian carp liver. Simultaneously, crucian carp might regulate its saline-alkaline resistance mechanism by enhancing the synthesis of glycerophospholipid metabolism, ketone bodies, and degradation metabolism, at the same time increasing the vitality of antioxidant enzymes (SOD, CAT, GSH-Px) and nonspecific immune enzyme (AKP). Herein, all results will provide new insights into the molecular mechanisms underlying the stress responses and tolerance to saline-alkaline exposure in crucian carp.

Elatostema stewardii is an important medicinal plant endemic to China. In this study, the complete chloroplast genome of E. stewardii was sequenced and assembled using next-generation sequencing technology. The complete chloroplast genome length of E. stewardii was 150,263 bp, including two inverted repeats (IRs) of 24,681 bp, which are separated by LSC and SSC of 83,791 bp and 17,110 bp, respectively. A total of 129 genes were included in the genome, consisting 85 protein-coding genes, eight rRNA genes, and 36 tRNA genes, the overall GC content of this genome was 36.3%. There are few studies on the genus Elatostema of Urticaceae, this chloroplast genome sequence will provide useful data for further research on solving the generic and familial relationships in Urticaceae.