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Abstract Ferroelectric tunnel junctions are promising towards high-reliability and low-power non-volatile memories and computing devices. Yet it is challenging to maintain a high tunnelling electroresistance when the ferroelectric layer is thinned down towards atomic scale because of the ferroelectric structural instability and large depolarization field. Here we report ferroelectric tunnel junctions based on samarium-substituted layered bismuth oxide, which can maintain tunnelling electroresistance of 7 × 105 with the samarium-substituted bismuth oxide film down to one nanometer, three orders of magnitude higher than previous reports with such thickness, owing to efficient barrier modulation by the large ferroelectric polarization. These ferroelectric tunnel junctions demonstrate up to 32 resistance states without any write-verify technique, high endurance (over 5 × 109), high linearity of conductance modulation, and long retention time (10 years). Furthermore, tunnelling electroresistance over 109 is achieved in ferroelectric tunnel junctions with 4.6-nanometer samarium-substituted bismuth oxide layer, which is higher than commercial flash memories. The results show high potential towards multi-level and reliable non-volatile memories.

Abstract Objective Traditional observational research has suggested a connection between socioeconomic position, mental health, and sleep apnea (SA), but the specifics of this connection are still unclear. Using the Mendelian randomization approach, we intended to evaluate the potential causal link between mental health, socioeconomic status, and SA. Methods Our research employed summary statistics data from large-scale genome-wide association studies (GWAS) on mental health, socioeconomic status, and SA. In the main study, the connection between mental health, socioeconomic status, and SA was examined using the inverse variance weighted approach. In addition, as a supplement, we also used other Mendelian randomization methods, including MR Egger, weighted median, simple mode, and weighted mode. Results The primary analysis showed that educational attainment, including longer years of schooling, college or university degree, and higher intelligence was associated with a lower risk of SA (OR = 0.750, 95%CI = 0.653–0.862; OR = 0.558, 95%CI = 0.423–0.735; OR = 0.871, 95%CI = 0.760–0.999, respectively), while social deprivation was associated with a higher risk of SA (OR = 1.821, 95%CI = 1.075–3.085). And the income was not associated with the risk of sleep apnea (OR = 0.877, 95%CI = 0.682–1.129). In mental health exposure, major depressive disorder was associated with a higher risk of sleep apnea (OR = 1.196, 95%CI = 1.015–1.409), while attention-deficit hyperactivity disorder, bipolar disorder, and schizophrenia were not associated with the risk of sleep apnea (OR = 1.064, 95%CI = 0.958–1.181; OR = 1.030, 95%CI = 0.942–1.127; OR = 0.990, 95%CI = 0.957–1.025, respectively). Reverse MR analysis failed to find a causal effect from SA on mental health and socioeconomic status. Conclusions This MR investigation offers proof of a possible causal relationship between SA, socioeconomic level, and mental health.

Localization quality assessment in the Chinese context has largely focused on software systems and technical handbooks (Cui, 2013). The explosion of e-commerce underscores the need for culturally adapted websites (Liu et al., 2022). Yet very few systematic studies have been conducted on the commercial localization of Spanish product descriptions and instructions genres for the Chinese market. This paper presents the preliminary results of the first stage in a study aimed at developing and testing a set of criteria to assess the quality of localized cosmetic instructions on Chinese third-party platforms. Specifically, we focus on the genre characteristics of B2C websites in three subcorpora: original Spanish, original Chinese and translated Chinese. We have applied models of analysis of functional moves in digital genres from Swalesian genre theory (Swales, 1990; Bhatia, 1993), and found that localized Chinese descriptions show more freedom in the functional structure than their Spanish source texts. The results are expected to provide guidance for translators in order to better attract Chinese consumers.

BackgroundFollowing COVID-19, reports suggest Long COVID and autoimmune diseases (AIDs) in infected individuals. However, bidirectional causal effects between Long COVID and AIDs, which may help to prevent diseases, have not been fully investigated.MethodsSummary-level data from genome-wide association studies (GWAS) of Long COVID (N = 52615) and AIDs including inflammatory bowel disease (IBD) (N = 377277), Crohn’s disease (CD) (N = 361508), ulcerative colitis (UC) (N = 376564), etc. were employed. Bidirectional causal effects were gauged between AIDs and Long COVID by exploiting Mendelian randomization (MR) and Bayesian model averaging (BMA).ResultsThe evidence of causal effects of IBD (OR = 1.06, 95% CI = 1.00–1.11, p = 3.13E-02), CD (OR = 1.10, 95% CI = 1.01–1.19, p = 2.21E-02) and UC (OR = 1.08, 95% CI = 1.03–1.13, p = 2.35E-03) on Long COVID was found. In MR-BMA, UC was estimated as the highest-ranked causal factor (MIP = 0.488, MACE = 0.035), followed by IBD and CD.ConclusionThis MR study found that IBD, CD and UC had causal effects on Long COVID, which suggests a necessity to screen high-risk populations.

This study proposes a novel colorimetric method based on the ultraviolet/visible spectrophotometry-colorimetric method (UV/Vis-CM) for detecting and quantifying total triterpenoids in traditional Chinese medicine. By incorporating the colourants 2-hydroxy-5-methylbenzaldehyde and concentrated sulfuric acid, triterpenoid compounds colour development became more sensitive, and the detection accuracy was significantly improved. 2-hydroxy-5-methylbenzaldehyde and concentrated sulfuric acid were incorporated in a 1:3 vol ratio at room temperature to react with the total triterpenes for 25 min, incorporated to an ice bath for 5 min, and then detected at the optimal absorption wavelength. The accuracy and reliability of this method were verified by comparison with high-performance liquid chromatography and four other colorimetric methods. Additionally, this approach has the advantages of not requiring heating during operation, high sensitivity, short usage time, low solvent usage, and low equipment costs. This study not only offers a reliable method for detecting total triterpenes in traditional Chinese medicine but also offers a rapid detection tool for on-site testing and large-scale screening, laying a foundation for the modernization of traditional Chinese medicine research, quality control, and drug development.

Tactile feedback can effectively improve the controllability of an interactive intelligent robot, and enable users to distinguish the sizes/shapes/compliance of grasped objects. However, it is difficult to recognize object roughness/textures through tactile feedback due to the surface features cannot be acquired with equipped sensors. The purpose of this study is to investigate whether different object roughness/textures can be classified using machine vision and utilized for human-machine haptic interaction. Based on practical application, two classes of specialized datasets, the roughness dataset consisted of different spacing/shapes/height distributions of the surface bulges and the texture dataset included eight types of representative surface textures, were separately established to train the respective classification models. Four kinds of typical deep learning models (YOLOv5l, SSD300, ResNet18, ResNet34) were employed to verify the identification accuracies of surface features corresponding to different roughness/textures. The human fingers' ability to objects roughness recognition also was quantified through a psychophysical experiment with 3D-printed test objects, as a reference benchmark. The computation results showed that the average roughness recognition accuracies based on SSD300, ResNet18, ResNet34 were higher than 95%, which were superior to those of the human fingers (94% and 91% for 2 and 3 levels of object roughness, respectively). The texture recognition accuracies with all models were higher than 84%. Outcomes indicate that object roughness/textures can be effectively classified using machine vision and exploited for human-machine haptic interaction, providing the feasibility of functional sensory restoration of intelligent robots equipped with visual capture and tactile stimulation devices.

BackgroundLong COVID is a major challenge facing the public. Gut microbiota is closely related to Long COVID. However, the causal effects between gut microbiota and Long COVID remains unclear.MethodsUsing summary statistics from Genome-Wide Association Studies (GWAS), Mendelian randomization (MR) analyses were performed to investigate the relationship between gut microbiota and Long COVID. The primary statistical method employed was Inverse Variance Weighted (IVW). Sensitivity analyses were then conducted to evaluate the reliability of the findings and account for potential confounding variables. Finally, a reverse MR analysis was conducted to examine potential associations between Long COVID and genetically predicted gut microbiota compositions.ResultsThere were 2 positive and 1 negative causal effect between gut microbiota and Long COVID. Meta-analysis results show that genus Parasutterella (OR = 1.145, 95%CI = 1.035 ∼ 1.266, P = 0.008) and genus Oscillospira (OR = 1.425, 95%CI = 1.235 ∼ 1.645, P < 0.001) significantly increased the risk of Long COVID. And genus Eisenbergiella (OR = 0.861, 95%CI = 0.785 ∼ 0.943, P = 0.001) significantly decreased the risk of Long COVID. Neither the pleiotropy nor the heterogeneity was observed. Reverse causal effect does not hold.ConclusionOur research has provided genetic evidence that establishes multiple causal relationships between the gut microbiota and Long COVID, supporting the role of the gut microbiota in Long COVID. It is possible that different taxa play a role in the development of Long COVID. The causal relationships identified in this study require further investigation.

Abstract The proteasome inhibitor bortezomib (BTZ) is the first‐line therapy for multiple myeloma (MM). BTZ resistance largely limits its clinical application in MM. Interleukin‐33 (IL‐33) exerts antitumor effects through various mechanisms, including enhancing antitumor immunity and promoting the apoptosis of cancer cells. Here, the synergistic anti‐MM effect of IL‐33 and BTZ was verified, and the underlying mechanisms were elucidated. Bioinformatic analysis indicated that IL‐33 expression levels were downregulated in MM, and that BTZ‐treated MM patients with high IL‐33 levels had better prognosis than those with low IL‐33 levels. Moreover, the patients with high IL‐33 levels had a better treatment response to BTZ. Further immune analysis suggested that IL‐33 can enhance the anti‐MM immunity. IL‐33 and BTZ synergistically inhibited proliferation and induced apoptosis of MM cells, which was mediated by the excessive accumulation of cellular reactive oxygen species (ROS). Furthermore, increased ROS hindered the nuclear translocation of NF‐κB‐p65, thereby decreasing the transcription of target stemness‐related genes (SOX2, MYC, and OCT3/4). These effects induced by the combination therapy could be reversed by eliminating ROS by N‐acetylcysteine. In conclusion, our results indicated that IL‐33 enhanced the sensitivity of MM to BTZ through ROS‐mediated inhibition of nuclear factor kappa‐B (NF‐κB) signal and stemness properties.

Entomopathogenic fungi (EPF) are economical and environmentally friendly, forming an essential part of integrated pest management strategies. We screened six strains of Beauveria bassiana (B1–B6) (Hypocreales: Cordycipitaceae), of which B4 was the most virulent to Bactrocera dorsalis (Hendel) (Diptera: Tephritidae). We further assessed the biological characteristics of strain B4 and the environmental factors influencing its ability to infect B. dorsalis. We also evaluated the effects of B4 on two of the natural predators of B. dorsalis. We found that strain B4 was the most virulent to 3rd instar larvae, pupae, and adult B. dorsalis, causing mortality rates of 52.67, 61.33, and 90.67%, respectively. B4 was not toxic to B. dorsalis eggs. The optimum B4 effects on B. dorsalis were achieved at a relative humidity of 91–100% and a temperature of 25°C. Among the six insecticides commonly used for B. dorsalis control, 1.8% abamectin emulsifiable concentrate had the strongest inhibitory effect on B4 strain germination. B4 spraying affected both natural enemies (Amblyseius cucumeris and Anastatus japonicus), reducing the number of A. cucumeris and killing A. japonicus adults. We found a valuable strain of EPF (B4) that is virulent against many life stages of B. dorsalis and has great potential for the biological control of B. dorsalis. We also provide an important theoretical and practical base for developing a potential fungicide to control B. dorsalis.

Purpose: The occurrence of hyponatremia is a prevalent complication following transnasal transsphenoidal surgery for pituitary adenoma surgery, which adversely affects patient prognosis, hospitalization duration, and rehospitalization risk. The primary objective of this study is to strengthen the correlation between clinical factors associated with pituitary adenoma and postoperative hyponatremia. Additionally, the study aims to develop a predictive model for postoperative hyponatremia in patients with pituitary adenoma, with the ultimate goal of establishing a basis for reducing the occurrence of postoperative hyponatremia following surgical interventions. Methods: The chi-square test or Fisher test was employed for nominal data, while the t-test or Mann-Whitney test was utilized for continuous data analysis. In cases where the data exhibited statistical differences, binary logistic analysis was conducted to examine the risk and protective factors associated with postoperative hyponatremia. XGBoost was employed to construct predictive models for hyponatremia in this study. The patients were partitioned into training and test sets, and the most suitable parameters were determined through five-fold cross-validation and subsequently utilized for training on the training set. The discriminatory capability was assessed on the internal validation set. Results and conclusions: Out of the total 280 patients included in this investigation, 82 patients experienced early postoperative hyponatremia. Among these individuals, male gender (P = 0.02, odds ratio = 1.98) was identified as a risk factor for early postoperative hyponatremia, while preoperative chloride levels (P = 0.021, odds ratio = 0.866) and surgery time (P = 0.039, odds ratio = 0.990) were identified as protective factors against postoperative hyponatremia. The XGBoost model exhibited a sensitivity of 94.2%, a specificity of 61.5%, a positive predictive value of 51.6%, a negative predictive value of 96%, and identified male gender, preoperative sodium, and preoperative cortisol as the most significant predictors. Our findings indicate that gender may have influence in the development of early postoperative hyponatremia in patients with pituitary adenomas.

【Objective】The bHLH transcription factor family is an important family of transcription factors in eukaryotes, which plays an important role in plant growth and development, secondary metabolism and stress response. Analysis of the response pattern of bHLH transcription factor gene OsbHLH109 (LOC_Os01g67480) to stress and hormones in rice (Oryza sativa L.) could provide a theoretical basis for further researches on the functions of OsbHLH109 in stress and hormone responses.【Method】The bioinformatics of OsbHLH109 was analyzed, and the expression patterns of OsbHLH109 in different tissues of Rice Zhonghua 11 under different hormone and abiotic stresses were analyzed by quantitative PCR (qRT-PCR).【Result】The encoding region of OsbHLH109 was 1 164 bp in length, containing 6 exons and encoding 388 amino acids, which was a bHLH transcription factor containing a conserved domain of HLH. Phylogenetic analysis showed that OsbHLH109 was closely related to the homologous proteins in monocots and Dicotyledones. The analysis of cis-acting elements showed that the promoter region of OsbHLH109 contained 24 plant hormone response cis-elements and 25 environmental stress response cis-elements. The qRT-PCR analysis showed that OsbHLH109 was expressed in roots, stems, leaves and young panicles of rice, but the expression level was the highest in leaves. The results of hormone treatment response expression profile analysis showed that the response expression differences of OsbHLH109 in leaves to 6-Benzylaminopurine (6-BA), indole acetic acid (IAA), gibberellic acid (GA3) and abscisic acid (ABA) treatments all reached significant levels. The results of stress treatment response expression profile analysis showed that the response of OsbHLH109 to low temperature stress, drought stress, high temperature stress and salt stress were significantly different in leaves, indicating that the expression of OsbHLH109 was induced by 6-BA, GA3, IAA, ABA, high temperature, low temperature, PEG6000 and NaCl, which suggested that OsbHLH109 was essential for the abiotic stress responses in rice.【Conclusion】Rice OsbHLH109 is a member of the bHLH transcription factor family and is highly expressed in leaves. The expression of OsbHLH109 gene is regulated by high temperature, low temperature and salt stress, and responds to hormone signals such as 6-BA, IAA, GA3 and ABA. It is predicted that it may be involved in abiotic stress response of rice through ABA and other hormone signal transduction pathways.

AbstractContext Vitiligo is a common skin disease with a complex pathogenesis, and so far, no effective treatment is available. Lycium barbarum L. (Solanaceae) polysaccharide (LBP), the main active ingredient of goji berries, has been demonstrated to protect keratinocytes and fibroblasts against oxidative stress.Objective This study explored the effects and mechanism of LBP on monobenzone-induced vitiligo in mice.Materials and methods C57BL/6 mice were randomly divided into five groups (n = 6): negative control that received vaseline, vitiligo model group induced by monobenzone that treated with vaseline, positive control that received tacrolimus (TAC), LBP groups that received 0.3 and 0.6 g/kg LBP, respectively. We quantified the depigmentation by visual examination and scores, detected the expression of CD8+ T cells, pro-inflammatory cytokines and analysed the STAT3-Hsp70-CXCL9/CXCL10 pathway.Results LBP 0.3 and 0.6 g/kg groups can significantly reduce depigmentation scores and the infiltration of local inflammatory cells in the skin lesions. Moreover, the expression of CXCL9, CXCL3, CXCL10 and HSP70 decreased by 54.3, 20.3, 48.5 and 27.2% in 0.3 g/kg LBP group, which decreased by 62.1, 26.6, 58.2 and 34.5% in 0.6 g/kg LBP group. In addition, 0.3 and 0.6 g/kg LBP decreased the release of IL-8 (9.7%, 22.8%), IL-6 (40.8%, 42.5%), TNF-α (25.7%, 35%), IFN-γ (25.1%, 27.6%) and IL-1β (23.7%, 33.7%) and inhibited the phosphorylation expression of STAT3 by 63.2 and 67.9%, respectively.Conclusion These findings indicated LBP might be recommended as a new approach for vitiligo which provide a theoretical basis for the clinical application of LBP in treating vitiligo patients.

In this paper, the theoretical innovation is made on the traditional fire distribution problem. Considering the actual situation of the ship’s fault, based on the principle of multi-objective optimization, the improved distributed genetic algorithm is used for preliminary solution. And the corresponding fault-tolerant control law is formulated to correct the fault-tolerant strategy, so as to ensure the better fire strike effect and maintain a high fault tolerance. Finally, through simulation experiments, it is verified that this method can converge to the optimal solution quickly, and can reduce the loss to the maximum extent when compensating. It has certain research value for combat.

In the context of rapid urbanization in third-world countries, many cities adopt high-density development, effectively using land but limiting open space, especially for children, impacting their spatial rights. This study focused on the Dongcheng and Xicheng districts of Beijing. It employed methods such as variance inflation factor, multiple linear regression, spatial autocorrelation, and spatial econometric models to investigate the impact of various configuration factors on children’s satisfaction with outdoor activity space. The study also revealed the spillover effects of outdoor activity space configuration for children in high-density urban environments. The results showed that (1) children’s satisfaction was significantly influenced by the configuration elements. The variables that had the most significant impact on satisfaction were the number of outdoor spaces, facilities’ amusement, advertisements, and service management levels. (2) Using spatial econometric models, we determined that spatial dependency significantly enhances the model’s explanatory power. The quantity of outdoor space had the greatest effect on children’s outdoor activity space satisfaction, followed by facilities’ amusement and advertisement impact, and service management had the least impact, though all categories positively affected satisfaction. This study held significant value and importance in improving the rights of children in mega-cities in developing countries and promoting the physical and mental well-being of children.

Avian pathogenic E. coli (APEC), a widespread bacterium, results in serious economic losses to the poultry industry annually, and it poses a threat to human health due to the contaminated retail poultry meat and eggs. Recently, it has been demonstrated that long non-coding RNAs played important roles in regulating gene expression and the animal immune response. This study aimed to systematically explore the function of the novel long intergenic non-coding transcript, lincRNA-73240, upon APEC infection. A bioinformatics analysis indicated that lincRNA-73240 had no coding ability and a relative stable secondary structure with multiple hairpin rings. Moreover, the RT-qPCR results showed that lincRNA-73240 was highly expressed in lungs, heart, liver, spleen, cecum tonsils, thymus, ileum, bursa of Fabricius, harderian gland, and muscles in comparison to the cerebrum. Additionally, overexpression of lincRNA-73240 can promote the expression levels of inflammation, apoptosis, autophagy, and oxidative stress-related genes, as well as the production of reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO) upon APEC infection, which lead to cellular injury and apoptosis. These findings collectively establish a foundation for the study of the biological function of chicken lincRNA-73240 and provide a theoretical basis for further research on the molecular mechanisms of the chicken immune response.

Assisted reproduction technology (ART) procedures are often impacted by post-ovulatory aging (POA), which can lead to reduced fertilization rates and impaired embryo development. This study used RNA sequencing analysis and experimental validation to study the similarities and differences between in vivo- and vitro-matured porcine oocytes before and after POA. Differentially expressed genes (DEGs) between fresh in vivo-matured oocyte (F_vivo) and aged in vivo-matured oocyte (A_vivo) and DEGs between fresh in vitro-matured oocyte (F_vitro) and aged in vitro-matured oocyte (A_vitro) were intersected to explore the co-effects of POA. It was found that “organelles”, especially “mitochondria”, were significantly enriched Gene Ontology (GO) terms. The expression of genes related to the “electron transport chain” and “cell redox homeostasis” pathways related to mitochondrial function significantly showed low expression patterns in both A_vivo and A_vitro groups. Weighted correlation network analysis was carried out to explore gene expression modules specific to A_vivo. Trait–module association analysis showed that the red modules were most associated with in vivo aging. There are 959 genes in the red module, mainly enriched in “RNA binding”, “mRNA metabolic process”, etc., as well as in GO terms, and “spliceosome” and “nucleotide excision repair” pathways. DNAJC7, IK, and DDX18 were at the hub of the gene regulatory network. Subsequently, the functions of DDX18 and DNAJC7 were verified by knocking down their expression at the germinal vesicle (GV) and Metaphase II (MII) stages, respectively. Knockdown at the GV stage caused cell cycle disorders and increase the rate of abnormal spindle. Knockdown at the MII stage resulted in the inefficiency of the antioxidant melatonin, increasing the level of intracellular oxidative stress, and in mitochondrial dysfunction. In summary, POA affects the organelle function of oocytes. A_vivo oocytes have some unique gene expression patterns. These genes may be potential anti-aging targets. This study provides a better understanding of the detailed mechanism of POA and potential strategies for improving the success rates of assisted reproductive technologies in pigs and other mammalian species.

Abstract The role of de novo evolved genes from non-coding sequences in regulating morphological differentiation between species/subspecies remains largely unknown. Here, we show that a rice de novo gene GSE9 contributes to grain shape difference between indica/xian and japonica/geng varieties. GSE9 evolves from a previous non-coding region of wild rice Oryza rufipogon through the acquisition of start codon. This gene is inherited by most japonica varieties, while the original sequence (absence of start codon, gse9) is present in majority of indica varieties. Knockout of GSE9 in japonica varieties leads to slender grains, whereas introgression to indica background results in round grains. Population evolutionary analyses reveal that gse9 and GSE9 are derived from wild rice Or-I and Or-III groups, respectively. Our findings uncover that the de novo GSE9 gene contributes to the genetic and morphological divergence between indica and japonica subspecies, and provide a target for precise manipulation of rice grain shape.

The objective of this study was to optimize the extraction process of total flavonoids from Haloragis micrantha (Thunb.) R. Brown. and explore its antioxidant activity. With the yield of total flavonoids as an evaluation index, single factor tests were used to investigate the effects of ethanol volume fraction, solid-liquid ratio, ultrasonic temperature and extraction time on the total flavonoids content of Haloragis micrantha (Thunb.) R. Brown., and the Box-Behnken method was used to optimize the extraction process. The scavenging ability and total reducing power of total flavonoids of Haloragis micrantha (Thunb.) R. Brown. to DPPH and ABTS+ free radicals were detected. The results showed that optimum extraction process was ethanol volume fraction of 76.15%, liquid to material ratio of 1:39.66 g/mL, ultrasonic time of 41.14 min. The yield of total flavonoids from Haloragis micrantha (Thunb.) R. Brown. was 28.61±0.05 mg/g. The total flavonoids of Haloragis micrantha (Thunb.) R. Brown. could effectively scavenge DPPH and ABTS+ free radicals. Within a certain range, the scavenging ability increased with the increasing of mass concentration, and the total flavonoids of Haloragis micrantha (Thunb.) R. Brown. had high reducing power and better antioxidant activity. The total flavonoids of Haloragis micrantha (Thunb.) R. Brown. had the strongest ability to scavenge ABTS+ free radicals. When the concentration of total flavonoids was 3 mg/mL, the clearance rate of ABTS+ were 98.28%, which was equivalent to 3 mg/mL vitamin C (clearance rate was 99.81%). This process would be simple and feasible, and the extracted total flavonoids have good antioxidant activity.

Abstract The tumor microenvironment (TME) is a highly intricate milieu, comprising a multitude of components, including immune cells and stromal cells, that exert a profound influence on tumor initiation and progression. Within the TME, angiogenesis is predominantly orchestrated by endothelial cells (ECs), which foster the proliferation and metastasis of malignant cells. The interplay between tumor and immune cells with ECs is complex and can either bolster or hinder the immune system. Thus, a comprehensive understanding of the intricate crosstalk between ECs and immune cells is essential to advance the development of immunotherapeutic interventions. Despite recent progress, the underlying molecular mechanisms that govern the interplay between ECs and immune cells remain elusive. Nevertheless, the immunomodulatory function of ECs has emerged as a pivotal determinant of the immune response. In light of this, the study of the relationship between ECs and immune checkpoints has garnered considerable attention in the field of immunotherapy. By targeting specific molecular pathways and signaling molecules associated with ECs in the TME, novel immunotherapeutic strategies may be devised to enhance the efficacy of current treatments. In this vein, we sought to elucidate the relationship between ECs, immune cells, and immune checkpoints in the TME, with the ultimate goal of identifying novel therapeutic targets and charting new avenues for immunotherapy.

To study the effect of Annulohypoxylon stygium fermented tea aqueous extracts (ASTAE) on blood lipids and liver protection in mice, 80 male KM mice were established hyperlipidemic model by high-fat diet induction, and then randomly divided into eight groups: blank control group (CK), model group (HF), positive control group (UA, 200 mg/kg), green tea group (GT, 400 mg/kg), Annulohypoxylon stygium group (AS, 400 mg/kg), and high (HA, 400 mg/kg), medium (MA, 200 mg/kg) and low (LA, 100 mg/kg) dose Annulohypoxylon stygium fermented tea aqueous extracts groups. After 5 weeks, serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (Scr), blood urea nitrogen (BUN) and adiponectin (ADPN) levels were detected. Detect the organ index, and liver fat lesions and distribution were observed by HE and oil red O staining. The results showed that compared with the HF group, the HA group could extremely significantly reduce the levels of TC, TG, LDL-C, AST, ALT, BUN and Scr in hyperlipidemia mice (P

Abstract Mitochondrial RNA splicing 2 (Mrs2), a eukaryotic CorA ortholog, enables Mg2+ to permeate the inner mitochondrial membrane and plays an important role in mitochondrial metabolic function. However, the mechanism by which Mrs2 permeates Mg2+ remains unclear. Here, we report four cryo-electron microscopy (cryo-EM) reconstructions of Homo sapiens Mrs2 (hMrs2) under various conditions. All of these hMrs2 structures form symmetrical pentamers with very similar pentamer and protomer conformations. A special structural feature of Cl−-bound R-ring, which consists of five Arg332 residues, was found in the hMrs2 structure. Molecular dynamics simulations and mitochondrial Mg2+ uptake assays show that the R-ring may function as a charge repulsion barrier, and Cl− may function as a ferry to jointly gate Mg2+ permeation in hMrs2. In addition, the membrane potential is likely to be the driving force for Mg2+ permeation. Our results provide insights into the channel assembly and Mg2+ permeation of hMrs2.

Abstract The SWI/SNF ATP-dependent chromatin remodeler is a master regulator of the epigenome, controlling pluripotency and differentiation. Towards the C-terminus of the catalytic subunit of SWI/SNF is a motif called the AT-hook that is evolutionary conserved. The AT-hook is present in many chromatin modifiers and generally thought to help anchor them to DNA. We observe however that the AT-hook regulates the intrinsic DNA-stimulated ATPase activity aside from promoting SWI/SNF recruitment to DNA or nucleosomes by increasing the reaction velocity a factor of 13 with no accompanying change in substrate affinity (KM). The changes in ATP hydrolysis causes an equivalent change in nucleosome movement, confirming they are tightly coupled. The catalytic subunit’s AT-hook is required in vivo for SWI/SNF remodeling activity in yeast and mouse embryonic stem cells. The AT-hook in SWI/SNF is required for transcription regulation and activation of stage-specific enhancers critical in cell lineage priming. Similarly, growth assays suggest the AT-hook is required in yeast SWI/SNF for activation of genes involved in amino acid biosynthesis and metabolizing ethanol. Our findings highlight the importance of studying SWI/SNF attenuation versus eliminating the catalytic subunit or completely shutting down its enzymatic activity.

Protein is an important nutrient required by the human body. The change of protein structure during processing will lead to changes in its functional properties, in turn affecting the quality of foods. There are many physical methods available to alter the structure of proteins to expand their application in the food industry. The new electrophysical processing technology has become a hot spot in the field of food processing due to its advantages of high efficiency, low energy consumption, and slight loss of nutrients. Therefore, this paper reviews the effects of electric field technology (ohmic heating and electrostatic field) and electromagnetic field technology (microwave, radio frequency and magnetic field) on the change of protein structure at multiscales (macroscopic, molecular and microscopic levels), in order provide a theoretical basis for the development and utilization of electromagnetic field processed protein products.

Abstract Background The phagocytosis and homeostasis of microglia play an important role in promoting blood clearance and improving prognosis after subarachnoid hemorrhage (SAH). LC3-assocaited phagocytosis (LAP) contributes to the microglial phagocytosis and homeostasis via autophagy-related components. With RNA-seq sequencing, we found potential signal pathways and genes which were important for the LAP of microglia. Methods We used an in vitro model of oxyhemoglobin exposure as SAH model in the study. RNA-seq sequencing was performed to seek critical signal pathways and genes in regulating LAP. Bioparticles were used to access the phagocytic ability of microglia. Western blot (WB), immunoprecipitation, quantitative polymerase chain reaction (qPCR) and immunofluorescence were performed to detect the expression change of LAP-related components and investigate the potential mechanisms. Results In vitro SAH model, there were increased inflammation and decreased phagocytosis in microglia. At the same time, we found that the LAP of microglia was inhibited in all stages. RNA-seq sequencing revealed the importance of P38 MAPK signal pathway and DAPK1 in regulating microglial LAP. P38 was found to regulate the expression of DAPK1, and P38-DAPK1 axis was identified to regulate the LAP and homeostasis of microglia after SAH. Finally, we found that P38-DAPK1 axis regulated expression of BECN1, which indicated the potential mechanism of P38-DAPK1 axis regulating microglial LAP. Conclusion P38-DAPK1 axis regulated the LAP of microglia via BECN1, affecting the phagocytosis and homeostasis of microglia in vitro SAH model. Video Abstract

BackgroundObesity and dyslipidemia, major global health concerns, have been linked to psoriasis, but previous studies faced methodological limitations and their shared genetic basis remains unclear. This study examines various obesity-related and lipidemic traits as potential contributors to psoriasis development, aiming to clarify their genetic associations and potential causal links.MethodsSummary statistics from genome-wide association studies (GWAS) conducted for obesity-related traits (body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for the body mass index (WHRadjBMI)) and lipidemic traits (high-density lipoprotein (HDL), LDL, triglyceride (TG), total Cholesterol (TC), apolipoprotein A1 (apoA1), apolipoprotein B (apoB), and apolipoprotein E (apoE)) and psoriasis, all in populations of European ancestry, were used. We quantified genetic correlations, identified shared loci and explored causal relationship across traits.ResultsWe found positive genetic correlation between BMI and psoriasis (rg=0.22, p=2.44×10-18), and between WHR and psoriasis (rg=0.19, p=1.41×10-12). We further found the positive genetic correlation between psoriasis and WHRadjBMI(rg=0.07, p=1.81×10-2) the genetic correlation, in while the effect of BMI was controlled for. We identified 14 shared loci underlying psoriasis and obesity-related traits and 43 shared loci between psoriasis and lipidemic traits via cross-trait meta-analysis. Mendelian randomization (MR) supported the causal roles of BMI (IVW OR=1.483, 95%CI=1.333-1.649), WHR (IVW OR=1.393, 95%CI=1.207-1.608) and WHRadjBMI (IVW OR=1.18, 95%CI=1.047-1.329) in psoriasis, but not observe any significant association between lipidemic traits and the risk of psoriasis. Genetic predisposition to psoriasis did not appear to affect the risk of obesity and lipidemic traits.ConclusionsAn intrinsic link between obesity-related traits and psoriasis has been demonstrated. The genetic correlation and causal role of obesity-related traits in psoriasis highlight the significance of weight management in both the prevention and treatment of this condition.

BackgroundParkinson’s disease (PD) symptoms deteriorate with disease progression. Although deep brain stimulation (DBS) can effectively improve the motor signs of PD patients, it is not yet known whether DBS surgery, which is an invasive treatment modality, may change the progression of PD.ObjectiveThe aim of this work was to compare the effect of DBS with that of drug treatment on the progression of PD.MethodsA total of 77 patients with PD with the Hoehn and Yahr scale (HY) stage of 2.5 or 3 were included, and were divided into 34 in the drug therapy alone group (Drug-G) and 43 in the DBS therapy group (DBS-G). All patients were subjected to a follow-up of 2 years, and disease severity was assessed by the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III), the Montreal Cognitive Assessment (MOCA), the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD) scores. In addition, the quality of life of patients and the burden on their family were assessed by the 39-item PD questionnaire (PDQ-39) scores, daily levodopa equivalent dose (LED), patient’s annual treatment-related costs, and the Zarit Caregiver Burden Scale (ZCBS) score. The changes in relevant scale scores between the two groups were compared at each follow-up stage.ResultsThe UPDRS-III score of the patients in the “off” state increased from year to year in both groups, and the degree of increase of this score was greater in the DBS-G than in the Drug-G group. The MOCA score in both groups began to decline in the 2nd year of follow-up, and the decline was greater in the Drug-G than in the DBS-G group. DBS treatment did not affect patients’ psychiatric disorders. The PDQ39, LED, costs, and ZCBS were negatively correlated with the follow-up time in patients in the DBS-G group, and positively correlated with the follow-up time in patients in the Drug-G.ConclusionPD is progressive regardless of treatment. The findings from this follow-up study suggest that the disease progression of patients in DBS-G may be slightly faster compared to the drug-G, but the advantages of DBS are also evident. Indeed, DBS better improves patient’s motor signs and quality of life and reduces the family burden. In addition, DBS has less impact on patients in terms of cognitive and mental effects.

Epidemics are dangerous and difficult to prevent and control, especially in urban areas. Clarifying the correlation between the COVID-19 Outbreak Frequency and the urban spatial environment may help improve cities’ ability to respond to such public health emergencies. In this study, we firstly analyzed the spatial distribution characteristics of COVID-19 Outbreak Frequency by correlating the geographic locations of COVID-19 epidemic-affected neighborhoods in the city of Beijing with the time point of onset. Secondly, we created a geographically weighted regression model combining the COVID-19 Outbreak Frequency with the external spatial environmental elements of the city. Thirdly, different grades of epidemic-affected neighborhoods in the study area were classified according to the clustering analysis results. Finally, the correlation between the COVID-19 Outbreak Frequency and the internal spatial environmental elements of different grades of neighborhoods was investigated using a binomial logistic regression model. The study yielded the following results. (i) Epidemic outbreak frequency was evidently correlated with the urban external spatial environment, among building density, volume ratio, density of commercial facilities, density of service facilities, and density of transportation facilities were positively correlated with COVID-19 Outbreak Frequency, while water and greenery coverage was negatively correlated with it. (ii) The correlation between COVID-19 Outbreak Frequency and the internal spatial environmental elements of neighborhoods of different grades differed. House price and the number of households were positively correlated with the COVID-19 Outbreak Frequency in low-end neighborhoods, while the number of households was positively correlated with the COVID-19 Outbreak Frequency in mid-end neighborhoods. In order to achieve spatial justice, society should strive to address the inequality phenomena of income gaps and residential differentiation, and promote fair distribution of spatial environments.

Introduction: Surgical training traditionally adheres to the apprenticeship paradigm, potentially exposing trainees to an increased risk of complications stemming from their limited experience. To mitigate this risk, augmented and virtual reality have been considered, though their effectiveness is difficult to assess. Research question: The PASSION study seeks to investigate the improvement of manual dexterity following intensive training with neurosurgical simulators and to discern how surgeons' psychometric characteristics may influence their learning process and surgical performance. Material and methods: Seventy-two residents were randomized into the simulation group (SG) and control group (CG). The course spanned five days, commencing with assessment of technical skills in basic procedures within a wet-lab setting on day 1. Over the subsequent core days, the SG engaged in simulated procedures, while the CG carried out routine activities in an OR. On day 5, all residents' technical competencies were evaluated. Psychometric measures of all participants were subjected to analysis. Results: The SG demonstrated superior performance (p

Abstract Background Colorectal cancer (CRC), known as prevalent cancer, has risen to be the leading cause of cancer‐related death. Engineered exosomes had attracted much attention since they acted as carriers to deliver small molecule drugs, therapeutic nucleic acids, and polypeptides to treat a series of cancers. Methods and Results Here, we found that the PKH‐26 labeled exosomes, which were derived from the CRC cells, could be efficiently absorbed by SW1116 cells and had an abundant fluorescence distribution in tumors, compared with the exosomes derived from mesenchymal stem cells (MSC) and HepG2 cells. This Research demonstrated that engineered CRC‐exosomes loaded with functional miR‐1270 (Exo‐miR‐1270) enriched in miR‐1270 strongly inhibited the proliferation by CCK‐8 and EdU assays, migration by wound‐healing and transwell assays, and promoted the apoptosis for CRC cells through flow cytometry. MiR‐1270 overexpression delivered by CRC exosomes contributed to inhibiting the tumor growth potential of CRC in vivo and increasing the overall survival of the mice. Moreover, the safety evaluation results showed that CRC‐exosomes loaded with functional miR‐1270‐mimics had no toxicity for other organs by histopathological analysis and no influence on the vital chemistry and hematology parameters for mice in vivo safety evaluation. Conclusion These results indicate that Exo‐miR‐1270 can effectively treat CRC tumors by intravenous administration. Our work provided a foundation that the homologous tumor‐derived exosomes mediated miRNA delivery for the treatment of CRC.

The rapid advancement of the internationalization process has led to the gradual labeling and commoditization of commercial space, which is detached from the connotation of regional culture. This paper establishes a commercial space layout model and a commercial space layout optimization design process based on Bayesian network, combined with the geometric characteristics and layout attributes of commercial space layout. It also utilizes Simpson’s index and kernel density analysis to explore the influencing factors of regional culture integration into commercial space design and finally takes the design of comprehensive commercial space with regional characteristics of culture in the Central Plains as a research case to specifically explore the feasibility of integrating regional cultural characteristics into commercial space design. The results show that in the process of designing the commercial space of regional culture in the Central Plains, the audiovisual comfort reaches its best when the space aspect ratio is about 1.42 and the color saturation is about 25.05. The layout effect is the best with a visual exposure degree of 995 for the row and column layout. The integration of regional culture into commercial space design can be referenced by this study.

Restoring bone defects caused by conditions such as tumors, trauma, or inflammation is a significant clinical challenge. Currently, there is a need for the development of bone tissue engineering scaffolds that meet clinical standards to promote bone regeneration in these defects. In this study, we combined the porous Ti6Al4V scaffold in bone tissue engineering with advanced bone grafting techniques to create a novel “metal-bone” scaffold for enhanced bone regeneration. Utilizing 3D printing technology, we fabricated a porous Ti6Al4V scaffold with an average pore size of 789 ± 22.69 μm. The characterization and biocompatibility of the scaffold were validated through in vitro experiments. Subsequently, the scaffold was implanted into the distal femurs of experimental animals, removed after 3 months, and transformed into a “metal-bone” scaffold. When this “metal-bone” scaffold was re-implanted into bone defects in the animals, the results demonstrated that, in comparison to a plain porous Ti6Al4V scaffold, the scaffold containing bone tissue achieved accelerated early-stage bone regeneration. The experimental group exhibited more bone tissue generation in the early stages at the defect site, resulting in superior bone integration. In conclusion, the “metal-bone” scaffold, containing bone tissue, proves to be an effective bone-promoting scaffold with promising clinical applications.

This study aimed to investigate the impacts of vegetables with different textures on food oral processing behavior, food intake and satiety. Broccoli cooked by microwave for different periods of time were tested in this study. The oral processing behavior of simultaneous and sequential consumption of cooked broccoli and rice, ad libitum food intake and postprandial satiety were measured in healthy subjects. Results showed that compared with co-ingestion of soft broccoli and seasoned rice (SSR), sequential ingestion of hard broccoli followed by seasoned rice (H + SR) increased the number of chews, the oral sensory exposure time and the number of chews per gram by 44%, 34% and 57%, respectively, and reduced the eating rate by 25% and the rice intake by 20%. Moreover, compared with SSR, H + SR effectively suppressed the perception of postprandial hunger. In conclusion, hard-cooked broccoli helped to reduce food intake and inhibit subjective hunger by enhancing oral processing, and this effect was more significant when the vegetable was first consumed cooked by cooked.