Search

Abstract Obesity is an important risk factor for breast cancer in women before and after menopause. Adipocytes, key mediators in the tumor microenvironment, play a pivotal role in the relationship between obesity with cancer. However, the potential of dietary components in modulating this relationship remains underexplored. Genistein, a soy-derived isoflavone, has shown promise in reducing breast cancer risk, attenuating obesity-associated inflammation, and improving insulin resistance. However, there are no reports examining whether genistein has the ability to reduce the effects of obesity on breast tumor development. In this study, we constructed a mammary tumor model in ovariectomized obese mice and examined the effects of genistein on body condition and tumor growth. Moreover, the effects of genistein on the tumor microenvironment were examined via experimental observation of peritumoral adipocytes and macrophages. In addition, we further investigated the effect of genistein on adipocyte and breast cancer cell crosstalk via coculture experiments. Our findings indicate that dietary genistein significantly alleviates obesity, systemic inflammation, and metabolic disorders induced by a high-fat diet in ovariectomized mice. Notably, it also inhibits tumor growth in vivo. The impact of genistein extends to the tumor microenvironment, where it reduces the production of cancer-associated adipocytes (CAAs) and the recruitment of M2d-subtype macrophages. In vitro, genistein mitigates the transition of adipocytes into CAAs and inhibits the expression of inflammatory factors by activating PPAR-γ pathway and degrading nuclear NF-κB. Furthermore, it impedes the acquisition of invasive properties and epithelial‒mesenchymal transition in breast cancer cells under CAA-induced inflammation, disrupting the Wnt3a/β-catenin pathway. Intriguingly, the PPAR-γ inhibitor T0070907 counteracted the effects of genistein in the coculture system, underscoring the specificity of its action. Our study revealed that genistein can mitigate the adverse effects of obesity on breast cancer by modulating the tumor microenvironment. These findings provide new insights into how genistein intake and a soy-based diet can reduce breast cancer risk.

Abstract Background iPSC reprogramming technology exhibits significant promise in the realms of clinical therapeutics, disease modeling, pharmaceutical drug discovery, and various other applications. However, the extensive utilization of this technology has encountered impediments in the form of inefficiency, prolonged procedures, and ambiguous biological processes. Consequently, in order to improve this technology, it is of great significance to delve into the underlying mechanisms involved in iPSC reprogramming. The BET protein BRD4 plays a crucial role in the late stage of reprogramming; however, its precise function in the early stage remains unclear. Results Our study aims to investigate BRD4’s role in the early stages of iPSC reprogramming. Our investigation reveals that early inhibition of BRD4 substantially enhances iPSC reprogramming, whereas its implementation during the middle-late stage impedes the process. During the reprogramming, ribosome DNA expression initially increases before decreasing and then gradually recovers. Early inhibition of BRD4 improved the decline and restoration of rDNA expression in the early and middle-late stages, respectively. Additionally, we uncovered the mechanism of BRD4’s regulation of rDNA transcription throughout reprogramming. Specifically, BRD4 interacts with UBF and co-localizes to both the rDNA promoter and enhancer regions. Ultimately, BRD4 facilitates rDNA transcription by promoting the enrichment of histone H3 lysine 27 acetylation in the surrounding chromatin. Moreover, we also discovered that early inhibition of BRD4 facilitates cells’ transition out of the somatic cell state and activate pluripotent genes. Conclusions In conclusion, our results demonstrate that early inhibition of BRD4 promotes sequential dynamic expression of rDNA, which improves iPSC reprogramming efficiency.

Abstract To investigate the extent of damage and seepage characteristics of water-saturated coal samples after subjecting them to microwave cycling. The microwave equipment was used to process the coal samples by microwave cycling. The non-contact digital image processing technology and acoustic emission system were used to carry out the triaxial loading experimental study of the coal samples to obtain the mechanical parameter characteristics, energy evolution pattern, acoustic emission information and permeability characteristics of coal samples under different microwave cycle times. The results of the study show that: With the increase in the number of microwave cycles, dense grid-loaded cracks gradually appeared on the surface of the coal samples, the triaxial partial stresses of the coal samples decreased, and the strains also decreased, and the modulus of elasticity and Poisson’s ratio also decreased; In the densification stage stage, the dissipated energy is higher than the elastic energy, and as the elastic stage proceeds, the elastic energy gradually reverses to exceed the dissipated energy, and the total energy and elastic energy of the coal samples decrease with the increase in the number of cycles, and the dissipated energy rises; Coal samples produce a large number of fissures due to the increase in the number of microwave cycles, the more frequent the fissure activity during the loading process, the acoustic emission amplitude and ringing count scattering points all become dense with the increase in the number of cycles, and the data increase; Initial permeability, destructive permeability and average permeability were all increased, microwave treatment has a better effect of permeability enhancement, the permeability of the treated coal samples was changed from low permeability to medium permeability, and the permeability enhancement was the largest in 6 cycles, and the permeability was increased by 7.18 times. This article explores the damage condition of water-saturated coal samples under microwave cycling treatment. Then, it explores the effect of microwave cycling on the permeability enhancement of the coal body, which provides a new method for exploring the gas permeability enhancement and extraction of low-permeability coal samples underground.

Abstract Pu'er crude tea (PCT), the initial raw material for making Pu'er tea, is favored because of unique flavor and health effects. Emotional response is helpful to explain consumers’ choice of different flavors of tea. This study aims to clarify the key floral volatiles of PCT and their emotional impact on people. Twenty‐nine compounds were identified as the key volatiles from 237 volatiles, which formed the flowery aroma of PCT. Linalool, geraniol, nonanal, and methyl salicylate were more abundant in the PCT, they evoked the top five emotions (mild, wild, aggressive, tame, bored). Methyl salicylate contributed most to the wild emotion in the two mixed samples (B10 and B14), and it may contribute positively to the health effects of tea, such as refreshing and anti‐inflammatory. This study provided a preliminary research idea for exploring the relationship between tea aroma and human emotions and its potential role in human health.

Abstract Osteoarthritis (OA) is the most common degenerative joint disorder that causes disability in aged individuals, caused by functional and structural alterations of the knee joint. To investigate whether metabolic drivers might be harnessed to promote cartilage repair, a liquid chromatography–mass spectrometry (LC–MS) untargeted metabolomics approach was carried out to screen serum biomarkers in osteoarthritic rats. Based on the correlation analyses, α-ketoglutarate (α-KG) has been demonstrated to have antioxidant and anti-inflammatory properties in various diseases. These properties make α-KG a prime candidate for further investigation of OA. Experimental results indicate that α-KG significantly inhibited H2O2-induced cartilage cell matrix degradation and apoptosis, reduced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), increased superoxide dismutase (SOD) and glutathione (GSH)/glutathione disulfide (GSSG) levels, and upregulated the expression of ETV4, SLC7A11 and GPX4. Further mechanistic studies observed that α-KG, like Ferrostatin-1 (Fer-1), effectively alleviated Erastin-induced apoptosis and ECM degradation. α-KG and Fer-1 upregulated ETV4, SLC7A11, and GPX4 at the mRNA and protein levels, decreased ferrous ion (Fe2+) accumulation, and preserved mitochondrial membrane potential (MMP) in ATDC5 cells. In vivo, α-KG treatment inhibited ferroptosis in OA rats by activating the ETV4/SLC7A11/GPX4 pathway. Thus, these findings indicate that α-KG inhibits ferroptosis via the ETV4/SLC7A11/GPX4 signaling pathway, thereby alleviating OA. These observations suggest that α-KG exhibits potential therapeutic properties for the treatment and prevention of OA, thereby having potential clinical applications in the future.

Abstract Objective High low-density-lipoprotein (LDL) cholesterol has been associated with an increased risk of coronary artery diseases (CAD) including acute myocardial infarction (AMI). However, whether lipids lowering drug treatment is causally associated with decreased risk of AMI remains largely unknown. We used Mendelian randomization (MR) to evaluate the influence of genetic variation affecting the function of lipid-lowering drug targets on AMI. Methods Single-nucleotide polymorphisms (SNPs) associated with lipids as instruments were extracted from the Global Lipids Genetics Consortium (GLGC). The genome-wide association study (GWAS) data for AMI were obtained from UK Biobank. Two sample MR analysis was used to study the associations between high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TG) with AMI (n = 3,927). Genetic variants associated with LDL cholesterol at or near drug target gene were used to mimic drug effects on the AMI events in drug target MR. Results Genetically predicted higher LDL-C (per one SD increase in LDL-C of 38.67 mg/dL, OR 1.006, 95% CI 1.004–1.007) and TG (per one SD increase in TG of 90.72 mg/dL, 1.004, 1.002–1.006) was associated with increased risk of AMI, but decreased risk for higher HDL-C (per one SD increase in HDL-C of 15.51 mg/dL, 0.997, 0.995–0.999) in univariable MR. Association remained significant for LDL-C, but attenuated toward the null for HDL-C and TG in multivariable MR. Genetically proxied lower LDL-C with genetic variants at or near the PCSK9 region (drug target of evolocumab) and NPC1L1 (drug target of ezetimibe) were associated with decreased risk of AMI (0.997, 0.994–0.999 and 0.986, 0.975–0.998, respectively), whereas genetic variants at HMGCR region (drug target of statin) showed marginal association with AMI (0.995, 0.990-1.000). After excluding drug target-related SNPs, LDL-C related SNPs outside the drug target region remained a causal effect on AMI (0.994, 0.993–0.996). Conclusions The findings suggest that genetically predicted LDL-C may play a predominant role in the development of AMI. The drug MR results imply that ezetimibe and evolocumab may decrease the risk of AMI due to their LDL-C lowering effect, and there are other non-drug related lipid lowering pathways that may be causally linked to AMI.

Significant differences exist in aroma and taste of different grades of large-leaf black tea. In this study, sensory histology combined with metabolomics were used to investigate the sensory characteristics and phytochemical profiles of different grades of Huangpu black tea (HPBT). Sensory evaluation showed that high grade HPBT had high intensity of pekoe, fresh aroma and umami, with aroma and taste scores declining with decreasing grades. 173 non-volatiles were identified, of which 23 marker metabolites could be used as discrimination of different grades HPBT taste. In addition, 154 volatile compounds were identified in the different grades of HPBT, with 15 compounds as key odorants for distinguishing the aroma of different grades of HPBT. Furthermore, correlation analysis revealed that linalool, geraniol and nonanal contributed to the aroma quality score of HPBT. This study will provide a more comprehensive understanding for processing, quality evaluation and grade evaluation system of large-leaf black tea.

Abstract Antimicrobial peptides (AMPs), ancient scavengers of bacteria, are very poorly induced in macrophages infected by Mycobacterium tuberculosis (M. tuberculosis), but the underlying mechanism remains unknown. Here, we report that L-alanine interacts with PRSS1 and unfreezes the inhibitory effect of PRSS1 on the activation of NF-κB pathway to induce the expression of AMPs, but mycobacterial alanine dehydrogenase (Ald) Rv2780 hydrolyzes L-alanine and reduces the level of L-alanine in macrophages, thereby suppressing the expression of AMPs to facilitate survival of mycobacteria. Mechanistically, PRSS1 associates with TAK1 and disruptes the formation of TAK1/TAB1 complex to inhibit TAK1-mediated activation of NF-κB pathway, but interaction of L-alanine with PRSS1, disables PRSS1-mediated impairment on TAK1/TAB1 complex formation, thereby triggering the activation of NF-κB pathway to induce expression of AMPs. Moreover, deletion of antimicrobial peptide gene β-defensin 4 (Defb4) impairs the virulence by Rv2780 during infection in mice. Both L-alanine and the Rv2780 inhibitor, GWP-042, exhibits excellent inhibitory activity against M. tuberculosis infection in vivo. Our findings identify a previously unrecognized mechanism that M. tuberculosis uses its own alanine dehydrogenase to suppress host immunity, and provide insights relevant to the development of effective immunomodulators that target M. tuberculosis.

Objective The maglev train of Beijing Subway Line S1 had a brake release failure during operation, impacting line normal operation. Therefore, it is necessary to find out the exact cause of the fault and put forward improvement measures. Method The working principle of the train brake control system of Beijing Subway Line S1 is briefly described. By using fishbone diagram analysis method, eight main causes of train brake release failure are identified , and the triggers of each cause are listed. Considering the actual situation of train fault, the cause set of train brake release on this line is further sorted out, and the root cause of train breaking failure on this line is determined using investigation method. The characteristics of solenoid valve are analyzed and corresponding improvement measures are taken. Result & Conclusion The solenoid valve stuck in EP (electro-pneumatic solenoid valve) module of train PBCU (pneumatic brake control unit) on this line is the root cause for train brake release failure. After replacing the balanced solenoid valve produced by MAC Valves, Inc.in the United States with the stop solenoid valve produced by German NASS Magnet GmbH, the train brake release failure on this line is effectively tackled.

Abstract An important concern for tea consumers is whether appropriate storage can effectively improve the ability of oolong tea to alleviate type 2 diabetes mellitus (T2DM). In this study, the antidiabetic effects of three aged oolong tea (2001, 2011, and 2020) extracts (aged TEs) in db/db T2DM mice were investigated and compared for the first time. The results showed that aged oolong tea extracts (aged TEs) alleviated the abnormal fasting blood glucose levels, lipid profiles, insulin resistance, and reduced ectopic fat deposition in liver. Moreover, aged TEs alleviated T2DM‐related tissue damage and activated insulin receptor (INSR)/insulin receptor substrate (IRS)/phosphatidylinositol‐3 kinase (PI3K)/phosphatidylinositol‐3 kinase (AKT)/glycogen synthase kinase 3 beta (GSK‐3β)/glycogen synthase (GYS)‐mediated hepatic glycogen synthesis signaling pathway. In addition, aged TEs altered gut microbiota composition and gut metabolite profiles associated with T2DM. Together, all three aged TEs (400 mg/kg/day in mice, a human equivalent dose of 7 g/60 kg/day), especially 2011, can effectively alleviate T2DM, and proper storage can effectively improve the ability of oolong tea to alleviate T2DM.

Abstract Kuding Tea (Ilex latifolia) is a bitter‐tasting herbal tea that was used for the treatment of symptoms related with diabetes mellitus, hypertension, and hyperlipidemia. However, Kuding Tea is also difficultly accepted by people in daily life because of its poor palatability. In this study, Kuding Tea, green tea (GT) (Camellia sinensis L.), and Luohan (Siraitia grosvenorii) fruits were formulated into a compound Kuding Tea (CKT) to improve the taste and health benefits of this beverage. High‐fat diet‐fed male C57BL/6J mice were used as animal models to explore the effects of CKT (6 or 12 mg/mL, water ad libitum) on body weight, food intake, liver function, blood glucose and lipids, and gene expression. L02 and 3T3‐L1 cells were used to further demonstrate the effects of CKT on fat accumulation and hepatic lipid deposition. Our results suggest that CKT can regulate glucose and lipid metabolism by decreasing body weight, reducing white adipose deposition, improving glucose tolerance, increasing the expression of brown adipose genes, and reducing fat accumulation in the liver, and CKT inhibited fat accumulation better than GT. In addition, a low dose (6 mg/mL) of CKT reduced the abundance of Desulfovibrio bacteria, positively associated with obesity, and increased that of norank_f__Muribaculaceae, Lachnospiraceae_NK4A136_group, and Alloprevotella, which are beneficial to glucose and lipid metabolism. This study suggests that CKT not only has a better palatability but also has potential preventive effects on high‐fat diet‐induced glucose–lipid metabolic diseases.

Min pigs exhibit remarkable cold tolerance, where vitamin B1 synthesis by gut microbiota is crucial for the host's energy metabolism. However, the role of this synthesis in cold adaptation of Min pigs are not yet fully understood. This study utilized 16S rRNA amplicon and metagenomic sequencing to examine seasonal variations in the gut microbiota of Min pigs. Results indicated a significant rise in microbial diversity in winter, with the Bacteroidetes group being the most notably increased. The vitamin B1 biosynthetic pathway was significantly enriched during winter, with six significantly upregulated genes (ThiC, ThiD, ThiE, ThiG, ThiH, and ThiL) showing strong evidence of purifying selection. Among the six vitamin B1 synthesis genes significantly upregulated during winter, the increase was mainly due to a marked elevation in several sequences from specific microbial species. Binding energy analysis revealed that, except for ThiL, the average substrate binding energy of the top 10 sequences with the largest seasonal differences was significantly lower than those of the 10 sequences with the smallest differences. Furthermore, most of these sequences were uniquely prevalent in Min pigs and were not found in the homologous sequences of Duroc pigs. Bacteroidetes and Bacteroidales were identified as the primary contributors to these gene sequences. This research provides valuable insights for developing innovative cold-resistant feed and probiotics.

Abstract Anti‐cancer peptides (ACPs) represent a promising potential for cancer treatment, although their mechanisms need to be further elucidated to improve their application in cancer therapy. Lycosin‐I, a linear amphipathic peptide isolated from the venom of Lycosa singorensis, shows significant anticancer potential. Herein, it is found that Lycosin‐I, which can self‐assemble into a nanosphere structure, has a multimodal mechanism of action involving lipid binding for the selective and effective treatment of leukemia. Mechanistically, Lycosin‐I selectively binds to the K562 cell membrane, likely due to its preferential interaction with negatively charged phosphatidylserine, and rapidly triggers membrane lysis, particularly at high concentrations. In addition, Lycosin‐I induces apoptosis, cell cycle arrest in the G1 phase and ferroptosis in K562 cells by suppressing the PI3K‐AKT‐mTOR signaling pathway and activating cell autophagy at low concentrations. Furthermore, intraperitoneal injection of Lycosin‐I inhibits tumor growth of K562 cells in a nude mouse xenograft model without causing side effects. Collectively, the multimodal effect of Lycosin‐I can provide new insights into the mechanism of ACPs, and Lycosin‐I, which is characterized by high potency and specificity, can be a promising lead for the development of anti‐leukemia drugs.

Summary: Background: Severe burn wounds face two primary challenges: dysregulated cellular impairment functions following infection and an unbalanced wound hydration microenvironment leading to excessive inflammation and collagen deposition. These results in hypertrophic scar contraction, causing significant deformity and disability in survivors. Methods: A three-dimensional (3D) printed double-layer hydrogel (DLH) was designed and fabricated to address the problem of scar formation after burn injury. DLH was developed using methacrylated silk fibroin (SFMA) and gelatin methacryloyl (GelMA) for the upper layer, and GelMA and hyaluronic acid methacryloyl (HAMA) for the lower layer. To combat infection, copper-epigallocatechin gallate (Cu-EGCG) was incorporated into the lower layer bioink, collectively referred to as DLS. To balance wound hydration levels, HaCaT cells were additionally encapsulated in the upper layer, designed as DLS/c. Findings: DLH demonstrated suitable porosity, appropriate mechanical properties, and excellent biocompatibility. DLS exhibited potent antimicrobial properties, exerted anti-inflammatory effects by regulating macrophage polarisation, and may enhance angiogenesis through the HIF-1α/VEGF pathway. In the DLS/c group, animal studies showed significant improvements in epidermal formation, barrier function, and epidermal hydration, accompanied by reduced inflammation. In addition, Masson’s trichrome and Sirius red staining revealed that the structure and ratio of dermal collagen in DLS/c resembled that of normal skin, indicating considerable potential for scarless wound healing. Interpretation: This biomimetic matrix shows promise in addressing the challenges of burn wounds and aiming for scarless repair, with benefits such as anti-infection, epidermal hydration, biological induction, and optimised topological properties. Funding: Shown in Acknowledgements.

African swine fever (ASF) is a highly contagious, fatal disease of pigs caused by African swine fever virus (ASFV). The complexity of ASFV and our limited understanding of its interactions with the host have constrained the development of ASFV vaccines and antiviral strategies. To identify host factors required for ASFV replication, we developed a genome-wide CRISPR knockout (GeCKO) screen that contains 186,510 specific single guide RNAs (sgRNAs) targeting 20,580 pig genes and used genotype II ASFV to perform the GeCKO screen in wild boar lung (WSL) cells. We found that knockout of transmembrane protein 239 (TMEM239) significantly reduced ASFV replication. Further studies showed that TMEM239 interacted with the early endosomal marker Rab5A, and that TMEM239 deletion affected the co-localization of viral capsid p72 and Rab5A shortly after viral infection. An ex vivo study showed that ASFV replication was significantly reduced in TMEM239-/- peripheral blood mononuclear cells from TMEM239 knockout piglets. Our study identifies a novel host factor required for ASFV replication by facilitating ASFV entry into early endosomes and provides insights for the development of ASF-resistant breeding.

Liquid chromatography-mass spectrometry (LC-MS) combined with multivariate analysis were used to characterize the nonvolatile compounds of broken green tea and explore the effect of isolated scenting on metabolic profile and taste quality of broken green tea in this research. A total of 236 nonvolatile compounds were identified and 13 compounds were believed to be the key characteristic taste compounds of scented broken green tea. Meanwhile, the optimal isolated scenting time of broken green tea was determined to be 10 h based on the sensory evaluation and PLS results. The contents and types of flavonoids, organic acids and catechins lead to the difference of taste quality at different scenting times. Overall, these findings provided a theoretical basis for scenting to improve the taste of broken green tea, and provide a new idea for improving the taste of broken green tea.

‘Baimmaocha’ is a distinctive resource for production of high-quality black tea, and its processed black tea has unique aroma characteristics. 190 volatile compounds were identified by comprehensive two-dimensional gas chromatography–olfactometry-quadrupole-time-of-flight mass spectrometry(GC × GC-O-Q-TOMS), and among them 23 compounds were recognized as key odorants contributing to forming different aroma characteristics in ‘Baimaocha’ black teas of Rucheng, Renhua, and Lingyun (RCBT, RHBT, LYBT). The odor activity value coupled with GC-O showed that methyl salicylate (RCBT), geraniol (RHBT), trans-β-ionone and benzeneacetaldehyde (LYBT) might be the most definitive aroma compounds identified from their respective regions. Furthermore, PLS analysis revealed three odorants as significant contributors to floral characteristic, four odorants related to fruity attribute, four odorants linked to fresh attribute, and three odorants associated with roasted attribute. These results provide novel insights into sensory evaluation and chemical substances of ‘Baimaocha’ black tea and provide a theoretical basis for controlling and enhancement tea aroma quality.

Hyperglycemia can cause early damage to human bady and develop into diabates that will severely threaten human healthy. The effectively clinical treatment of hyperglycemiais is by inhibiting the activity of α-amylase. Black tea has been reported to show inhibitory effect on α-amylase and can be used for hyperglycemia treatment. However, the mechanism underlying is unclear. In this study, in vivo experiment showed that black tea theaflavins extract (BTE) effectively alleviated hyperglycemia. In vitro experiment showed that the effects may be caused by the interation between theaflavins and α-amylase. While TF1 and TF3 were mixed type inhibitors of α-amylase, TF2A and TF2B were competitive inhibitors of α-amylase. Molecular docking analysis showed that theaflavins monomers interacted with the hydrophobic region of α-amylase. Further study verified that monomer-α-amylase complex was spontaneously formed depending on hydrophobic interactions. Taken together, theaflavins showed potential anti-hyperglycemia effect via inhibiting α-amylase activity. Our results suggested that theaflavins might be utilized as a new type of α-amylase inhibitor to prevent and cure hyperglycemia.

Based on the measurements of petrological, petrophysical and elastic properties of the samples of different sedimentary facies in the fourth member of Sinian Dengying Formation (Deng 4 Member) in the Sichuan Basin, the diagenetic processes of reservoirs of different sedimentary facies and their controls on the petrophysical properties were discussed. The results show that cracks and mineral composition jointly control the petrophysical properties, and both are significantly influenced by sedimentary environment and diagenesis. The microbial dolomite of mound-shoal facies mainly experienced multi-stage dolomitization, penecontemporaneous dissolution, tectonic rupture and hydrothermal/organic acid dissolution processes, giving rise to cracks and dissolved pores. The grannular dolomite of inter-mound-shoal bottomland or dolomitic lagoon facies mainly underwent mechanical compaction, burial dolomitization and tectonic-hydrothermal action, creating cracks and intercrystalline pores. The diagenesis related to crack development increases the pressure- and saturation-dependent effects of samples, leading to significant decrease in the compressional wave impedance and Poisson's ratio. Dolomitization changes the properties of mineral particles, resulting in a Poisson's ratio close to dolomite. The muddy, siliceous and calcareous sediments in the low-energy environment lead to the decrease of impedance and the differential change of Poisson's ratio (significantly increased or decreased). The samples with both cracks and dissolved pores show high P-wave velocity dispersion characteristics, and the P-wave velocity dispersion of samples with only fractures or pores is the lowest.

The construction costs and operational challenges of rural microgrids have garnered widespread attention. This study focuses on grid-connected rural microgrids incorporating wind, solar, hydro, and storage systems, and proposes a two-tier optimization configuration model that considers both enterprise costs and user satisfaction. The upper-tier model aims to minimize enterprise costs, covering construction, operation and maintenance, as well as penalties for a curtailment of wind, solar, and hydro power. The lower-tier model evaluates power reliability and cost-effectiveness to maximize user satisfaction. Using the particle swarm optimization algorithm, this study analyzes a case in Yudaokou, Hebei Province, and proposes three optimization schemes: minimizing enterprise costs, maximizing user satisfaction, and a compromise between the two. The optimal scheme, which employs 17 photovoltaic panels, 12 wind turbines, and 15 energy storage units, achieved a user satisfaction score of 0.90. This two-tier planning model provides practical insights for the rational configuration of rural microgrids and reveals the nonlinear relationship between costs and user experience.

To solve the problem of large residual deformation and high repair cost of traditional frame structures after an earthquake, a new type of assembled shuttle-shaped self-centering mild steel energy dissipation brace (ASSSEDB) with stable stiffness, material saving, and easy replacement was proposed. The plastic deformation of mild steel is used to dissipate energy, and the disc spring system provides a reset function. Based on the working mechanism of energy dissipation brace, a restoring force model for the ASSSEDB was established, and then the numerical analysis was carried out by ANSYS to verify the accuracy of the proposed model. The results confirm that the ASSSEDB has stable energy dissipation ability and a resetting function, with a full hysteresis curve. The finite element analysis results align well with the developed restoring force model, and the maximum deviations of initial stiffness and ultimate capacity are, respectively, 1.4% and 2.3%, which indicates that the established restoring force model can provide a theoretical basis for design of the ASSSEDB. Furthermore, the time history analysis was carried out to assess the seismic performance of a six-story steel frame structure using the proposed ASSSEDB. The results show that compared with the steel frame structure with BRBs, the proposed ASSSEDB can decrease the residual deformation of structures by up to 93.41%. The self-centering ratio of the ASSSEDB is crucial in controlling residual deformation of structures, and it is recommended to be greater than 1.0.

ABSTRACT A sunken solar greenhouse is a unique structure used in China that has good thermal performance and a low cost. To explore the thermal environment and the marginal effect area under the trellis membrane in a sunken solar greenhouse, daytime heat absorption and nighttime exothermic models of the greenhouse were established based on existing theories and hypotheses. An experimental study of the three-dimensional thermal environment of a solar greenhouse was also conducted in the Jinzhong Basin of Shanxi Province. The daytime heat absorption model described how the internal thermal environment of the greenhouse changes in three dimensions, while the nighttime model calculated the amount of heat released at night. The results showed that the rate of change in the maximum temperature difference along the height direction in the greenhouse was 13 times that along the vertical direction, and three times that along the horizontal direction. We also observed that the marginal effect area under the membrane varied over time and by month. The minimum value of the marginal effect area occurred at the middle cross-section, spanning the middle position of the greenhouse, and the maximum height was 2.7 m. The results of this study can provide theoretical guidance and experimental data for the thermal environment of greenhouses of the same type in the Jinzhong Basin of Shanxi Province, thus providing a basis for environmental regulation and low-temperature margins in greenhouses.

Yellow tea is a lightly fermented tea with unique sensory qualities and health benefits. However, chemical composition and sensory quality of yellow tea products have rarely been studied. 12 representative yellow teas, which were basically covered the main products of yellow tea, were chosen in this study. Combined analysis of non-targeted/targeted metabolomics and electronic sensor technologies (E-eye, E-nose, E-tongue) revealed the chemical and sensor variation. The results showed that yellow big tea differed greatly from yellow bud teas and yellow little teas, but yellow bud teas could not be effectively distinguished from yellow little teas based on chemical constituents and electronic sensory characteristics. Sensor variation of yellow teas might be attributed to some compounds related to bitterness and aftertaste-bitterness (4′-dehydroxylated gallocatechin-3-O-gallate, dehydrotheasinensin C, myricitin 3-O-galactoside, phloroglucinol), aftertaste-astringency (methyl gallate, 1,5-digalloylglucose, 2,6-digalloylglucose), and sweetness (maltotriose). This study provided a comprehensive understanding of yellow tea on chemical composition and sensory quality.

Abstract Background Doxorubicin (DOX)-induced cardiotoxicity (DIC) is a major impediment to its clinical application. It is indispensable to explore alternative treatment molecules or drugs for mitigating DIC. WGX50, an organic extract derived from Zanthoxylum bungeanum Maxim, has anti-inflammatory and antioxidant biological activity, however, its function and mechanism in DIC remain unclear. Methods We established DOX-induced cardiotoxicity models both in vitro and in vivo. Echocardiography and histological analyses were used to determine the severity of cardiac injury in mice. The myocardial damage markers cTnT, CK-MB, ANP, BNP, and ferroptosis associated indicators Fe2+, MDA, and GPX4 were measured using ELISA, RT-qPCR, and western blot assays. The morphology of mitochondria was investigated with a transmission electron microscope. The levels of mitochondrial membrane potential, mitochondrial ROS, and lipid ROS were detected using JC-1, MitoSOX™, and C11-BODIPY 581/591 probes. Results Our findings demonstrate that WGX50 protects DOX-induced cardiotoxicity via restraining mitochondrial ROS and ferroptosis. In vivo, WGX50 effectively relieves doxorubicin-induced cardiac dysfunction, cardiac injury, fibrosis, mitochondrial damage, and redox imbalance. In vitro, WGX50 preserves mitochondrial function by reducing the level of mitochondrial membrane potential and increasing mitochondrial ATP production. Furthermore, WGX50 reduces iron accumulation and mitochondrial ROS, increases GPX4 expression, and regulates lipid metabolism to inhibit DOX-induced ferroptosis. Conclusion Taken together, WGX50 protects DOX-induced cardiotoxicity via mitochondrial ROS and the ferroptosis pathway, which provides novel insights for WGX50 as a promising drug candidate for cardioprotection. Graphic abstract

Objectives Anterior cervical decompression and fusion (ACF) has become a widely accepted surgical treatment for degenerative cervical diseases, but occasionally, significant intraoperative blood loss (SIBL), which is defined as IBL of 500 mL or more, will occur. We aimed to investigate the independent risk factors for SIBL during ACF for degenerative cervical diseases. Methods We enrolled 1150 patients who underwent ACF for degenerative cervical diseases at our hospital between 2013 and 2019. The patients were divided into two groups: the SIBL group (n = 38) and the non‐SIBL group (n = 1112). Demographic, surgical and radiographic data were recorded prospectively to investigate the independent risk factors for SIBL. For counting data, the chi‐square test or Fisher's exact probability test was used. Student's t‐test or the Mann–Whitney rank sum test was used for comparisons between groups of measurement data. Univariate analysis and multivariate logistic regression analysis were further used to analyze the significance of potential risk factors. Results The incidence of SIBL during ACF was 3.3% (38/1150). A multivariate analysis revealed that female sex (odds ratio [OR], 6.285; 95% confidence interval [CI], 2.707–14.595; p

Fuzhuan brick-tea (FZT) has long been consumed for its supposed weight loss and lipid-lowering benefits. In this study, we show that the regulation of fat storage in Caenorhabditis elegans from a water extract of FZT was affected by cholesterol levels. We found that FZT significantly decreased fat storage under normal cholesterol levels or in a cholesterol-free diet, while lipid accumulation was increased for a high cholesterol diet. Moreover, this mechanism may involve the conserved sterol regulatory element-binding protein (SREBP)/mediator-15 (MDT-15) signaling pathway and the nuclear hormone receptor NHR-80. In addition, lipid synthesis-related genes inhibited by FZT were partially affected by a cholesterol-free diet. Thus, our findings suggested that the potential lipid-lowering effects of FZT may depend on the cholesterol level, which may help to improve the consumption of FZT.

Theasinensin A (TSA), a dimer of epigallocatechin gallate, has been preliminarily demonstrated to have hypoglycemia and anti-inflammatory effects. However, little information is available on its potential mechanisms of anti-diabetes. Therefore, the present study aimed to investigate the influence of TSA on glucose and lipid metabolism and gut microbiota in high-fat-diet/streptozotocin-induced diabetic mice. As result, TSA improved polydipsia, polyphagia and impaired glucose tolerance of diabetic mice, declined the fasting blood glucose and hepatic triglyceride level, and enhanced the expression at mRNA level of insulin receptor substrate, phosphoinositide 3-kinase, protein kinase B and glucagon-like peptide 1 receptor (GLP-1R) in the diabetic liver. Moreover, TSA could restore the disorder of gut microbiota of diabetic mice. High-dose (100 mg/kg) TSA showed better beneficial effects from the blood biochemical parameters, hepatic function and gut microbiota. In general, high-dose TSA significantly modulated gut microbiota by increasing the relative abundance of Akkermansia and decreasing the relative abundances of Acetatifactor, Anaerotruncus, Pseudoflavonifactor, Oscillibacter and Clostridium clusters. The results indicated that TSA could exert an anti-diabetes effect in diabetic mice through restoring glucose homeostasis, declining hepatic steatosis, activating insulin and GLP-1 signaling pathways, and ameliorating gut microbiota dysbiosis.

As one of the common garden shrub species in Beijing, Jasminum nudiflorum is very popular among citizens for its unique ornamental properties in early spring. Copper (Cu) pollution is one of the most serious heavy metal pollution types in Beijing. To explore the remediation effect of J. nudiflorum on urban copper pollution. By simulating the soil and atmospheric copper pollution conditions in Beijing, pot experiments were conducted to set up nine different concentrations of soil and atmosphere Cu treatments to verify the Cu enrichment ability and physiological growth characteristics of J. nudiflorum. The results were as follows: (1) Soil treatment and atmospheric deposition treatment and were able to significantly increase Cu content in root, stem and leaf of J. nudiflorum, among them, the contribution of soil ranged from 63.48% to 96.99%. The Cu content in each treatment showed the order of root>stem>leaf. (2) Under atmospheric treatment, photochemical conversion efficiency (Fv/Fm) and relative chlorophyll content (SPAD value) were increased, initial fluorescence (F0) was decreased, and photosynthetic capacity was promoted. The photosynthesis of J. nudiflorum was inhibited by soil treatment and co-treatment with soil and atmosphere. (3) Compared with atmospheric single factor treatment, soil single factor treatment and co-treatment with soil and atmosphere resulted in increased accumulation of reactive oxygen species (ROS), increased membrane lipid peroxidation, increased malondialdehyde (MDA) content, and decreased antioxidant enzyme activity and proline (PRO) content, and finally led to damage of the biofilm system. (4) The low-concentration Cu treatment promoted the growth of J. nudiflorum, while the high-concentration copper treatments (SHAL, SHAH) inhibited the growth of J. nudiflorum. The minimum value of the root tolerance index (TI) of J. nudiflorum was 69.19%, which indicated that J. nudiflorum belonged to a highly tolerant plant. In conclusion, under the simulated treatment of soil and atmosphere Cu pollution in Beijing, J. nudiflorum can effectively absorb and enrich Cu in soil and atmosphere while maintaining its own normal physiological and growth activities. This conclusion provides a certain theoretical basis for the prevention and control of Cu pollution and the maintenance and restoration of the ecological environment in Beijing.

In recent years, the energy consumption structure has been accelerating towards clean and low-carbon globally, and China has also set positive goals for new energy development, vigorously promoting the development and utilization of renewable energy, accelerating the implementation of renewable energy substitution actions, and focusing on improving the consumption capacity of new energy. However, due to the intermittent and unstable characteristics of renewable energy, it is difficult to meet the demands of the power load side in practical applications. Energy storage is an important link for the grid to efficiently accept new energy, which can significantly improve the consumption of new energy electricity such as wind and photovoltaics by the power grid, ensuring the safe and reliable operation of the grid system, but energy storage is a high-cost resource. Therefore, this paper focuses on the energy storage scenarios for a big data industrial park and studies the energy storage capacity allocation plan and business model of big data industrial park. Firstly, based on the characteristics of the big data industrial park, three energy storage application scenarios were designed, which are grid center, user center, and market center. On this basis, an optimal energy storage configuration model that maximizes total profits was established, and financial evaluation methods were used to analyze the corresponding business models. Finally, taking an actual big data industrial park as an example, the economic viability of energy storage configuration schemes under two scenarios was discussed, and an energy storage system construction plan was proposed to promote the zero-carbon target of the big data industrial park.

The joints of buffer material composite blocks as potential weak parts in the engineering barrier system of a high-level radioactive waste (HLW) repository must be studied in depth. Therefore, a laboratory experiment device suitable for unsaturated composite bentonite samples was developed. The evolution of temperature and volumetric water content at different locations of Gaomiaozi (GMZ) composite bentonite samples with time before and after simulated water inflow was measured by the experiment device. According to the experimental results, the thermal conductivity and hydraulic conductivity of the joint location after healing of the composite bentonite samples were obtained. The experimental results show that the change in the internal temperature of the composite bentonite samples is mainly affected by the temperature boundary and that the change in the internal water has little effect on it. In a short period of time, the loading of hydraulic boundary conditions only makes the volumetric water content of the soil near the hydraulic boundary increase significantly but has little effect on other locations. And, affected by the temperature boundary, the volumetric water content of the soil near the temperature boundary gradually decreases with time. The process of hydration swelling of the composite bentonite sample is accompanied by the adjustment of stress. The composite bentonite samples are continuously squeezed to the joint area after hydration swelling, the whole composite samples are generally homogenized, and the joints between the composite bentonite samples tend to heal. The thermal conductivity and permeability of the joint location after healing can meet the requirements of the engineering barrier of the HLW repository.

Recently, research has confirmed that jasmine tea may help improve the depressive symptoms that are associated with psychiatric disorders. Our team previously found that jasmine tea improved the depressive-like behavior that is induced by chronic unpredictable mild stress (CUMS) in Sprague Dawley (SD) rats. We hypothesized that the metabolic disorder component of depression may be related to the gut microbiota, which may be reflected in the metabolome in plasma. The influence of jasmine tea on gut microbiota composition and the association with depressive-related indexes were explored. Furthermore, the metabolites in plasma that are related to the gut microbiota were identified. SD rats were treated with control or CUMS and administrated jasmine tea for 8 weeks. The 16S rRNA gene amplicon sequencing was used to analyze the gut microbiota in feces samples, and untargeted metabolomics was used to analyze the metabolites in plasma. The results found that jasmine tea significantly ameliorated the depressive behavior induced by CUMS, significantly improved the neurotransmitter concentration (BDNF and 5-HT), and decreased the pro-inflammation levels (TNF-α and NF-κB). The intervention of jasmine tea also alleviated the dysbiosis caused by CUMS; increased the relative abundance of Bacteroides, Blautia, Clostridium, and Lactobacillus; and decreased Ruminococcus and Butyrivibrio in the CUMS-treated rats. Furthermore, the serum metabolites of the CUMS-treated rats were reversed after the jasmine tea intervention, i.e., 22 were up-regulated and 18 were down-regulated, which may have a close relationship with glycerophospholipid metabolism pathways, glycine serine and threonine metabolism pathways, and nicotinate and nicotinamide metabolism pathways. Finally, there were 30 genera of gut microbiota related to the depressive-related indexes, and 30 metabolites in the plasma had a strong predictive ability for depressive behavior. Potentially, our research implies that the intervention of jasmine tea can ameliorate the depression induced by CUMS via controlling the gut flora and the host’s metabolism, which is an innovative approach for the prevention and management of depression.

In the development and progression of cervical cancer, oxidative stress plays an important role within the cells. Among them, Solute Carrier Family 7 Member 11 (SLC7A11/xCT) is crucial for maintaining the synthesis of glutathione and the antioxidant system in cervical cancer cells. In various tumor cells, studies have shown that SLC7A11 inhibits ferroptosis, a form of cell death, by mediating cystine uptake and maintaining glutathione synthesis. Additionally, SLC7A11 is also involved in promoting tumor metastasis and immune evasion. Therefore, inhibiting the SLC7A11/xCT axis has become a potential therapeutic strategy for cervical cancer. In this study, through structure-based high-throughput virtual screening, a compound targeting the SLC7A11/xCT axis named compound 1 (PubChem CID: 3492258) was discovered. In vitro experiments using HeLa cervical cancer cells as the experimental cell model showed that compound 1 could reduce intracellular glutathione levels, increase glutamate and reactive oxygen species (ROS) levels, disrupt the oxidative balance within HeLa cells, and induce cell death. Furthermore, molecular dynamics simulation results showed that compound 1 has a stronger binding affinity with SLC7A11 compared to the positive control erastin. Overall, all the results mentioned above indicate the potential of compound 1 in targeting the SLC7A11/xCT axis and treating cervical cancer both in vitro and in silico.

The food crisis has increased demand for agricultural resources due to various factors such as extreme weather, energy crises, and conflicts. A solar greenhouse enables counter-seasonal winter cultivation due to its thermal insulation, thus alleviating the food crisis. The root temperature is of critical importance, although the mechanism of soil thermal environment change remains uncertain. This paper presents a comprehensive study of the soil thermal environment of a solar greenhouse in Jinzhong City, Shanxi Province, employing a variety of analytical techniques, including theoretical, experimental, and numerical simulation, and deep learning modelling. The results of this study demonstrate the following: During the overwintering period, the thermal environment of the solar greenhouse floor was divided into a low-temperature zone, a constant-temperature zone, and a high-temperature zone; the distance between the low-temperature boundary and the southern foot was 2.6 m. The lowest temperature in the low-temperature zone was 11.06 °C and the highest was 19.05 °C. The floor in the low-temperature zone had to be heated; the lowest value of the constant-temperature zone was 18.29 °C, without heating. The minimum distance between the area of high temperature and the southern foot of the solar greenhouse was 8 m and the lowest temperature reading was 19.29 °C. The indoor soil temperature tended to stabilise at a depth of 45 cm, and the lowest temperature reading at a horizontal distance of 1400 mm from the south foot was 19.5 °C. The Fluent and LSTM models fitted well and the models can be used to help control soil temperature during overwintering in extreme climates. The research can provide theoretical and data support for the crop areas and the heating of pipelines in the solar greenhouse.

The solar greenhouse is a significant agricultural facility in China. It enables the cultivation of crops during periods that do not coincide with the natural growing season, thus alleviating the pressure on the supply of fruits and vegetables during the winter months. The primary rationale behind the necessity of greenhouse cultivation lies in the fact that the temperature conditions conducive to optimal crop growth can be precisely replicated within this controlled environment. However, it is important to acknowledge that a distinct low-temperature area persists under the film during the overwintering period, with the precise delineation of its boundaries and distribution patterns remaining uncertain. In order to investigate the characteristics of the temperature distribution within the marginal region under the solar greenhouse film, experimental studies, CFD simulations, and LSTM prediction models were employed. The results of these studies indicate that, during the overwintering period, a low-temperature region was observed with approximately equal temperatures near the film membrane. The maximum horizontal distance from the south-side bottom corner was 6130 mm, while the minimum height from the ground was 600 mm. The lowest temperature in the low-temperature region was 4 °C, and the maximum observed temperature difference within the same period in different months was 1 °C. Additionally, a region of elevated temperatures was observed under the film. The lowest temperature in this region was 36.7 °C, and the highest temperature point was within the optimal range for crop growth. The CFD numerical simulation results were consistent with the actual observations, and the LSTM prediction model demonstrated high reliability. The findings of this study offer a theoretical foundation for the distribution of high and low temperatures in solar greenhouses. Furthermore, the developed prediction model provides the necessary buffer time for control, thus enhancing the efficiency of greenhouse cultivation.

Introduction: Fluoride is widely presented in drinking water and foods. A strong relation between fluoride exposure and obesity has been reported. However, the potential mechanisms on fluoride-induced obesity remain unexplored.Objectives and methodsThe effects of fluoride on the obesity were investigated using mice model. Furthermore, the role of gut homeostasis in exacerbation of the obesity induced by fluoride was evaluated.ResultsThe results showed that fluoride alone did not induce obesity in normal diet (ND) fed mice, whereas, it could trigger exacerbation of obesity in high-fat diet (HFD) fed mice. Fluoride impaired intestinal barrier and activated Toll-like receptor 4 (TLR4) signaling to induce obesity, which was further verified in TLR4−/− mice. Furthermore, fluoride could deteriorate the gut microbiota in HFD mice. The fecal microbiota transplantation from fluoride-induced mice was sufficient to induce obesity, while the exacerbation of obesity by fluoride was blocked upon gut microbiota depletion. The fluoride-induced bloom of Erysipelatoclostridium ramosum was responsible for exacerbation of obesity. In addition, a potential strategy for prevention of fluoride-induced obesity was proposed by intervention with polysaccharides from Fuzhuan brick tea.ConclusionOverall, these results provide the first evidence of a comprehensive cross-talk mechanism between fluoride and obesity in HFD fed mice, which is mediated by gut microbiota and intestinal barrier. E. ramosum was identified as a crucial mediator of fluoride induced obesity, which could be explored as potential target for prevention and treatment of obesity with exciting translational value.

Abstract Long-term consumption of tea with high fluoride (F) content has a potential threat to human health. The application of different amounts of biochar to reduce F accumulation in tea leaves has been little studied. In this study, a pot experiment was conducted to investigate the effect of biochar amounts (0, 0.5%, 2.5%, 5.0%, 8.0%, and 10.0%, w/w) on tea F content during the tea plant growth. Changes in tea quality, soil F fraction, and soil properties caused by biochar and the relationship with tea F accumulation were also considered. The results showed that the application of biochar amendment significantly reduced water-soluble F contents in tea leaves compared to CK (without biochar), especially in the 8.0% treatment (72.55%). Overall, biochar contributed to improving tea polyphenols and caffeine, but had no significant impact on free amino acids and water leachate. Compared with CK, 5.0–10.0% biochar significantly increased soil water-soluble F content due to the substitution of F− with OH− under high pH. Additionally, biochar applied to tea garden soil was effective in decreasing the soil exchangeable aluminum (Ex-Al) content (46.37–91.90%) and increasing the soil exchangeable calcium (Ca2+) content (12.02–129.74%) compared to CK, and correlation analysis showed that this may help reduce F enrichment of tea leaves. In general, the application of 5.0–8.0% biochar can be suggested as an optimal application dose to decrease tea F contents while simultaneously improving tea quality. Graphical Abstract

How PD-L1 expression is regulated in cancer is poorly understood. Here, we report that the ATP-binding activity of ERBB3 pseudokinase regulates PD-L1 gene expression in colorectal cancers (CRCs). ERBB3 is one of the four members of the EGF receptor family, all with protein tyrosine kinase domains. ERBB3 is a pseudokinase with a high binding affinity to ATP. We showed that ERBB3 ATP-binding inactivation mutant reduces tumorigenicity in genetically engineered mouse models and impairs xenograft tumor growth of CRC cell lines. The ERBB3 ATP-binding mutant cells dramatically reduce IFN-γ-induced PD-L1 expression. Mechanistically, ERBB3 regulates IFN-γ-induced PD-L1 expression through the IRS1-PI3K-PDK1-RSK-CREB signaling axis. CREB is the transcription factor that regulates PD-L1 gene expression in CRC cells. Knockin of a tumor-derived ERBB3 mutation located in the kinase domain sensitizes mouse colon cancers to anti-PD1 antibody therapy, suggesting that ERBB3 mutations could be predictive biomarkers for tumors amenable to immune checkpoint therapy.

Lipid deposition has emerged as a looming challenge worldwide. Previous studies have confirmed the fat-lowering effect of tea polyphenols (TP) in mice, but the underlying mechanism remains elusive. Furthermore, it remains unclear whether TP has the same effect in larger animals. Herein, we simultaneously investigated the regulatory effects of TP on lipid deposition in rats and Ningxiang pigs. The results showed that TP could effectively reduce fat accumulation in rats on a high-fat diet (HFD). As expected, TP supplementation led to a reduction in backfat thickness, fat rate, and subcutaneous fat cell size in Ningxiang pigs. Additionally, TP attenuated gut microbiota dysbiosis by enhancing microbial diversity and increasing the relative abundance of Bacteroides and Akkermansia in both models. Collectively, our results suggest that TP may reduce fat accumulation in rats and Ningxiang pigs by regulating gut microbiota. Therefore, TP could potentially serve as a functional agent for improving fat deposition in humans and Ningxiang pigs.

Abstract In mice, retrotransposon‐associated long noncoding RNAs (lncRNA) play important regulatory roles in pre‐implantation development; however, it is largely unknown whether they function in the pre‐implantation development in pigs. The current study aims to screen for retrotransposon‐associated lncRNA in porcine early embryos and identifies a porcine 8‐cell embryo‐specific SINE‐associated nuclear long noncoding RNA named SAWPA. SAWPA is essential for porcine embryonic development as depletion of SAWPA results in a developmental arrest at the 8‐cell stage, accompanied by the inhibition of the JNK‐MAPK signaling pathway. Mechanistically, SAWPA works in trans as a transcription factor for JNK through the formation of an RNA‐protein complex with HNRNPA1 and MED8 binding the SINE elements upstream of JNK. Therefore, as the first functional SINE‐associated long noncoding RNAs in pigs, SAWPA provides novel insights for the mechanism research on retrotransposons in mammalian pre‐implantation development.

Abstract Background Large-scale multi-ethnic DNA sequencing data is increasingly available owing to decreasing cost of modern sequencing technologies. Inference of the population structure with such sequencing data is fundamentally important. However, the ultra-dimensionality and complicated linkage disequilibrium patterns across the whole genome make it challenging to infer population structure using traditional principal component analysis based methods and software. Results We present the ERStruct Python Package, which enables the inference of population structure using whole-genome sequencing data. By leveraging parallel computing and GPU acceleration, our package achieves significant improvements in the speed of matrix operations for large-scale data. Additionally, our package features adaptive data splitting capabilities to facilitate computation on GPUs with limited memory. Conclusion Our Python package ERStruct is an efficient and user-friendly tool for estimating the number of top informative principal components that capture population structure from whole genome sequencing data.

Abstract Venous thromboembolism occurs in up to one-third of patients with COVID-19. Venous thromboembolism and COVID-19 may share a common genetic architecture, which has not been clarified. To fill this gap, we leverage summary-level genetic data from the latest COVID‐19 host genetics consortium and UK Biobank and examine the shared genetic etiology and causal relationship between COVID-19 and venous thromboembolism. The cross-trait and co-localization analyses identify 2, 3, and 4 shared loci between venous thromboembolism and severe COVID-19, COVID-19 hospitalization, SARS-CoV-2 infection respectively, which are mapped to ABO, ADAMTS13, FUT2 genes involved in coagulation functions. Enrichment analysis supports shared biological processes between COVID-19 and venous thromboembolism related to coagulation and immunity. Bi-directional Mendelian randomization suggests that venous thromboembolism was associated with higher risk of three COVID-19 traits, and SARS-CoV-2 infection was associated with a higher risk of venous thromboembolism. Our study provides timely evidence for the genetic etiology between COVID-19 and venous thromboembolism (VTE). Our findings contribute to the understanding of COVID-19 and VTE etiology and provide insights into the prevention and comorbidity management of COVID-19.

This paper aims to discuss the implementation of data analysis and information management for elderly nursing care from a data-driven perspective. It addresses the current challenges of in-home caregivers, providing a basis for decision making in analyzing nursing service content and evaluating job performance. The characteristics of caregivers’ activities were analyzed during the design of a wearable device-wearing scheme and a sensor data collection system. XGBoost, SVM, and Random Forest models were used in the experiments, with the Cuckoo search algorithm employed to optimize the XGBoost model parameters. Based on the control group experiment, it was confirmed that the XGBoost model, after adjusting the parameters using the Cuckoo search algorithm, exhibited better recognition performance than the SVM and RandomForest models, and the accuracy reached 0.9438. Wearable devices present high recognition accuracy in caregiver activity recognition research, which greatly improves the inspection of caregivers’ work and further promotes the completion of services. This study actively explores the applications of information technology and artificial intelligence theory to address practical problems and effectively promote the digitalization and intelligent development of the elderly nursing care industry.

The interplay patterns of amino acid residues are pivotal in determining the tertiary structure and flexibility of proteins, which in turn are intricately linked to their functionality and interactions with other molecules. Here, we introduce ARIP, a novel tool designed to identify contact residues within proteins. ARIP employs a modified version of the dr_sasa algorithm and an atomic overlap weighted algorithm to directly calculate the contact area and volume between atoms based on their van der Waals radius. It also allows for the selection of solvent radii, recognizing that not every atom in proteins can interact with water molecules. The solvent parameters were derived from the analysis of approximately 5000 protein and nucleic acid structures with water molecules determined using X-ray crystallography. One advantage of the modified algorithm is its capability to analyze multiple models within a single PDB file, making it suitable for molecular dynamic capture. The contact volume is symmetrically distributed between the interacting atoms, providing more informative results than contact area for the analysis of intra- and intermolecular interactions and the development of scoring functions. Furthermore, ARIP has been applied to four distinct cases: capturing key residue–residue contacts in NMR structures of P4HB, protein–drug binding of CYP17A1, protein–DNA binding of SPI1, and molecular dynamic simulations of BRD4.

Epigallocatechin-3-gallate (EGCG) is a main bioactive constituent in green tea. Being a redox-active polyphenol, high-dose EGCG exhibits pro-oxidative activity and could cause liver injury. L-theanine is a unique non-protein amino acid in green tea and could provide liver-protective effects. The purpose of this study was to investigate the hepatoprotective effects of L-theanine on EGCG-induced liver injury and the underlying mechanisms. A total of 300 mg/kg L-theanine was administrated to ICR mice for 7 days. Then, the acute liver injury model was established through intragastric administration of 1000 mg/kg EGCG. Pretreatment with L-theanine significantly alleviated the oxidative stress and inflammatory response caused by high-dose EGCG through modulation of Nrf2 signaling and glutathione homeostasis. Furthermore, metabolomic results revealed that L-theanine protects mice from EGCG-induced liver injury mainly through the regulation of amino acid metabolism, especially tryptophan metabolism. These findings could provide valuable insights into the potential therapeutic applications of L-theanine and highlight the importance of the interactions between dietary components.

The rehabilitation of wind turbine foundations after damage is increasingly common. However, limited research exists on the deformation of wind turbine foundations after rehabilitation. Artificial intelligence methods can be used to analyze future deformation state and predict post-rehabilitation deformation of foundations. This paper focuses on analyzing the stability of damaged wind turbine foundations after rehabilitation, as well as establishing and evaluating machine learning models. Specifically, Decision Tree (DT), Extreme Gradient Boosting (XGB), Support Vector Regression (SVR), and Long Short-Term Memory Network (LSTM) models are utilized to predict the vertical displacement of the rehabilitated foundation. Hence, the stability of the rehabilitated foundation is discussed in correlation with the measured wind speed, based on the foundation vertical displacement data. During the development of the machine learning model, the most suitable combination of hyperparameters is determined. The prediction performance of the SVR and LSTM models, which exhibit good performance, is compared to further evaluate their effectiveness. Furthermore, the models are analyzed and validated. The results indicate that the vertical displacements of the rehabilitated foundations gradually get close to a state of steady fluctuation over time. The SVR model is identified as the most effective in predicting the vertical displacements of wind turbine foundations after rehabilitation. This study aims to analyze and predict the vertical displacement of wind turbine foundations after rehabilitation based on extensive field monitoring data and powerful machine learning models.

Arsenic (As) and copper (Cu) are two common contaminants in the environment. When organisms are exposed to As or/ and Cu in large quantities or for sustained periods, oxidative stress is induced, adversely affecting kidney function. However, the molecular mechanisms involved in As or/ and Cu-induced nephrotoxicity remain elusive. In this experiment, wild-type C57BL/6 and Nrf2-knockout mice (n = 24 each) were exposed to arsenic trioxide and copper chloride alone or in combination. Our research findings indicate that exposure to As or/ and Cu can activate the Nrf2 antioxidant pathway by upregulating the levels of Nrf2, HO-1, CAT, and downregulating the level of Keap1, thereby reducing As or/ and Cu-induced oxidative stress. Meanwhile, exposure induced kidney cell pyroptosis and apoptosis by promoting the expression of NLRP3 inflammasomes and Caspase-3, which peaked in mice co-treated with As and Cu. Subsequently, we investigated its role in As or/ and Cu-induced kidney injury by knocking out Nrf2. Our results show that after knocking out Nrf2, the expression of antioxidant factors CAT and HO-1 significantly decreased. Based on the low antioxidant capacity after Nrf2 knockout, the levels of NLRP3 inflammasome, GSDMD, and Caspase1 were significantly upregulated after exposure to As and Cu, indicating more severe cellular pyroptosis. In addition, the level of Caspase3-mediated apoptosis was also more severe. Taken together, there is crosstalk between Nrf2-mediated antioxidant capacity and apoptosis/ pyroptosis induced by exposure to As or/ and Cu. Depletion of Nrf2 alters its antioxidant capacity, ultimately leading to more severe apoptosis, pyroptosis, and nephrotoxicity.

The quality of jasmine tea is related to the volatiles of its infusion. In this study, the volatiles of jasmine tea infusion were extracted under the optimal conditions with a 50/30 μm DVB/CAR/PDMS fiber, tea/water ratio of 1:25 and extraction time of 5 min. A total of 204 volatiles were analyzed by comprehensive two-dimensional gas chromatography-quadrupole time-of-flight mass spectrometry (GC × GC-Q-TOF-MS). Twenty-five compounds were identified as the key volatile compounds by fold change (FC), orthogonal partial least squares discriminant analysis (OPLS-DA), and two-way orthogonal partial least squares analysis (O2PLS). Then optimal amount of flowers (80%–120%) was obtained by the equation describing key volatiles and quality of jasmine tea infusion. And 80% amount of flowers was more appropriate considering the production cost and more pleasant taste. This study laid a foundation for the extraction and research of volatiles of tea infusion and guided the reasonable amount of flowers to produce jasmine tea.

Obesity is regarded to be correlated with disorders of lipid metabolism, bile acid metabolism and dysbiosis of the gut microbiota. Moringa-Fu brick tea (MFBT), a functional food, has a significant anti-obesity effect. However, the effectiveness and mechanisms of MFBT in preventing obesity require further investigation. Here, our results show that moringa-Fu brick tea extract (MFTE) displays anti-obesity effects by reducing high-fat diet-induced weight gain and adipose tissue accumulation in rats, and attenuating visceral adiposity index, oxidative stress and inflammation. In addition, MFTE could regulate gut microbiota diversity, reduce the relative abundance of microbioa associated with bile salt hydrolase (BSH) activity, such as Blautia, Ruminococcaceae, Coprococcus and Roseburia. Moreover, MFTE could improve the expression of the main rate-limiting enzymes CYP7A1 and CYP27A1 in the process of bile acid synthesis, downregulate the expression of intestinal FXR protein, promote the serum bile acid level, and reduce the accumulation of cholesterol in serum and liver. Taken together, these results suggested that MFBT could serve as a functional food for prevention of obesity and hyperlipidemia in association with regulating bile acid metabolism and gut microbiota.

In this study, the solid-state fermentation (SSF) of dark tea was carried out using Bacillus subtilis LK-1, which was isolated from Fu brick tea (FBT). The effects of SSF with B. subtilis on volatile organic compounds (VOCs), non-volatile metabolites, and antioxidant activities of dark tea was investigated. A total of 45 VOCs were identified, primarily consisting of ketones (18), hydrocarbons (8), aldehydes (7), and alcohols (6). Following fermentation, the content of key odor active substances such as linalool, β-ionone, and 3,5-octadiene-2-one significantly increased, resulting in an enhanced floral and fruity aroma of dark tea. Furthermore, new flavor substances like geranyl isovalerate and decanal were produced during SSF, enriching the aroma profile of dark tea. Non-ester catechins demonstrated a drastic increase, while ester catechins remarkably decreased after SSF. Furthermore, SSF led to a slight decrease in the total polyphenols content and antioxidant activity of dark tea. There is a close relationship between VOCs and the main non-volatile metabolites during SSF. Overall, this study highlighted the great impact of SSF with B. subtilis on the metabolites of dark tea and provided valuable insights into the role of bacteria in shaping the metabolite profile of FBT.

The proton-activated chloride (PAC) channel plays critical roles in ischemic neuron death, but its activation mechanisms remain elusive. Here, we investigated the gating of PAC channels using its novel bifunctional modulator C77304. C77304 acted as a weak activator of the PAC channel, causing moderate activation by acting on its proton gating. However, at higher concentrations, C77304 acted as a weak inhibitor, suppressing channel activity. This dual function was achieved by interacting with 2 modulatory sites of the channel, each with different affinities and dependencies on the channel's state. Moreover, we discovered a protonation-independent voltage activation of the PAC channel that appears to operate through an ion-flux gating mechanism. Through scanning-mutagenesis and molecular dynamics simulation, we confirmed that E181, E257, and E261 in the human PAC channel serve as primary proton sensors, as their alanine mutations eliminated the channel's proton gating while sparing the voltage-dependent gating. This proton-sensing mechanism was conserved among orthologous PAC channels from different species. Collectively, our data unveils the polymodal gating and proton-sensing mechanisms in the PAC channel that may inspire potential drug development.