Search

Abstract Background Diabetes-associated cognitive dysfunction, characterized by hippocampal synaptic loss as an early pathological feature, seriously threatens patients’ quality of life. Synapses are dynamic structures, and hormones play important roles in modulating the formation and elimination of synapses. The pituitary, the master gland of the body, releases several hormones with multiple roles in hippocampal synaptic regulation. In this study, we aimed to explore the relationship between pituitary hormones and cognitive decline in diabetes. Methods A total of 744 patients with type 2 diabetes (T2DM) (445 men and 299 postmenopausal women) who underwent serum pituitary hormone level assessments, comprehensive cognitive evaluations and MRI scans were enrolled. Dynamic diet interventions were applied in both chow diet-fed mice and high-fat diet (HFD)-fed diabetic mice. The cognitive performance and hippocampal pathology of prolactin (PRL)-knockout mice, neuronal prolactin receptor (PRLR)-specific knockout mice and microglial PRLR-specific knockout mice were assessed. Microglial PRLR-specific knockout mice were fed an HFD to model diabetes. Diabetic mice received an intracerebroventricular infusion of recombinant PRL protein or vehicle. Results This clinical study revealed that decreased PRL levels were associated with cognitive impairment and hippocampal damage in T2DM patients. In diabetic mice, PRL levels diminished before hippocampal synaptic loss and cognitive decline occurred. PRL loss could directly cause cognitive dysfunction and decreased hippocampal synaptic density. Knockout of PRLR in microglia, rather than neurons, induced hippocampal synaptic loss and cognitive impairment. Furthermore, blockade of PRL/PRLR signaling in microglia exacerbated abnormal microglial phagocytosis of synapses, further aggravating hippocampal synaptic loss and cognitive impairment in diabetic mice. Moreover, PRL infusion reduced microglia-mediated synaptic loss, thereby alleviating cognitive impairment in diabetic mice. Conclusion PRL is associated with cognitive dysfunction and hippocampal damage in T2DM patients. In diabetes, a decrease in PRL level drives hippocampal synaptic loss and cognitive impairment by increasing microglia-mediated synapse engulfment. Restoration of PRL levels ameliorates cognitive dysfunction and hippocampal synaptic loss in diabetic mice.

Abstract With the progress of micro electromechanical system (MEMS) technology, the performance of MEMS inertial measurement unit (IMU) composed of gyroscopes and accelerometers has been improved. Among the inertial sensors, MEMS triaxial gyroscope plays an important role in attitude estimation, navigation and positioning of intelligent mobile terminals such as unmanned aerial vehicles and unmanned vehicles. However, the measured values of low and medium cost MEMS triaxial gyroscopes are mainly affected by temperature (or thermal effect) and random errors. As results, the drift errors correlated with temperature will reduce application accuracy of MEMS triaxial gyroscope. The traditional calibration method for thermal drift errors relies on the expensive equipment, such as turntable and the temperature control system, which increases the cost of calibration. Therefore, an effective thermal calibration method that is available when using low- or high-cost tools for MEMS triaxial gyroscope will be meaningful for majority users. Hence, this paper analyzed and established the thermal drift model of MEMS triaxial gyroscope, and proposed a segmented systematic calibration method based on 24 states according to this model. Simulation shows that the proposed method can obtain the results approaching the real parameter thermal drift curves. Calibration experiments and parameters test show that the max errors of attitude calculation are reduced to 10% of the results using the original parameters, which indicates that the effectiveness of the proposed method.

Based on 778 earthquakes (2009—2022) and their observation reports recorded by the Hunan Seismic Network, through the analysis of the cross-correlation of the waveforms, 149 repeated earthquake pairs were identified which were recorded at least 3 stations with cross-correlation coefficients no less than 0.8. After obtaining these data, the location errors and phase picking errors of the Hunan Seismic Network were statistically analyzed. The results show that the horizontal location error is around 3.5 km, and the vertical location error is around 3 km. The Pg and Sg phase picking errors are about 0.4 s and 0.7 s, respectively. There is no significant difference in location error in Hunan region, except for the Changde area, where the error is basically within 4 km.

Abstract Background Previous studies have revealed the effects of different physical activity (PA) types on visceral adipose tissue (VAT) accumulation in individuals with overweight/obesity. However, the independent association (especially the dose–response relationship) between PA and VAT in individuals with and without overweight/obesity remains less explored. Visceral adiposity index (VAI), calculated from waist circumference, body mass index (BMI), triglyceride and high-density lipoprotein cholesterol, is a novel indicator of VAT. This study aims to elucidate the association between PA and VAI in participants with and without overweight/obesity. Methods Participants who are overweight or obese and with complete data on VAI, PA, and other essential covariates from the National Health and Nutrition Examination Survey (NHANES) database (2015–2018) were included in this study. PA was evaluated by the PA questionnaire and converted into metabolic equivalent task (MET) hours per week (MET-h/wk) based on the suggested MET scores. Multivariate linear regression models were used to identify the association between PA and VAI. Subgroup analyses, combined with interaction tests and restricted cubic spline (RCS) regression analyses, were utilized to explore the stability and nonlinearity of PA-VAI association, respectively. Results A total of 4, 312 participants with complete data on PA and VAI was included in this study, with 3, 441 of them being overweight or obese. After adjusting for all potential covariates, increased PA was found to be significantly associated with remarkable lower level of VAI in all participants (β = -0.0004, P = 0.003), participants with (β = -0.0013, P = 0.012) and without (β = -0.0004, P = 0.003) overweight/obesity. Subgroup analyses and interaction tests revealed that the PA-VAI association was not modified by other covariates in individuals with overweight/obesity. Furthermore, RCS analyses revealed that PA was significantly, linearly and negatively associated with VAI in all participants, participants with and without overweight/obesity (all P 0.05). Noteworthily, as opposed to individuals without overweight/obesity, PA was significantly associated with lower VAI in participants with overweight/obesity after exceeding the threshold of 150 MET-h/wk. Conclusion Increased PA was significantly associated with lower level of VAI, but a higher level of PA (> 150 MET-h/wk) was needed to obtain significantly lower level of VAI in individuals with overweight/obesity.

Two types of poly-porphyrin-based heterogeneous photocatalysts including insoluble polymer and water-soluble nanoparticles exhibited excellent photocatalytic activity in visible-light-induced dehydrogenation in water. The extremely low catalyst loading (0.01 ​mol%) of water-soluble nanoparticles provided so far the highest turnover frequency (TOF) value (333 h-1) for such transformation among reported records.

Abstract Background Both atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases. If the two exist together, the risk of stroke, hospitalization for HF and all-cause death is increased. Currently, research on left atrial appendage closure (LAAC) in patients with AF and HF is limited and controversial. This study was designed to investigate the safety and effectiveness of LAAC in AF patients with different types of HF. Methods Patients with non-valvular atrial fibrillation (NVAF) and HF who underwent LAAC in the First Affiliated Hospital of Army Medical University from August 2014 to July 2021 were enrolled. According to left ventricular ejection fraction (LVEF), the study divided into HF with reduced ejection fraction (LVEF

Abstract Urbanization has led to homogenizing heritage site landscapes, and the protective measures have become disconnected from public needs. Additionally, the complex and diverse overall characteristics of heritage sites and the uneven distribution of values across different areas are related to the lack of landscape experience assessment. The “subjective + objective” cognitive evaluation and visual perception framework that adopts the Scenic Beauty Estimation Procedure-Semantic Differential (SBE–SD) method and eye-tracking analysis can compensate for the limitations of a single evaluation method by integrating quantitative and qualitative analysis. This research takes the Yi’an Fortress in Zhangpu County, Fujian Province, as the object and examines the visual experiences of different areas and types of landscapes within the Yi’an Fortress. The findings reveal several key insights: (1) Significant differences were found in the landscape experiences of different areas within the heritage site. The visual experience score of the core building area of Yi’an Fortress is (1.01) > the heritage entrance area (0.897) > the residential area (0.841) > the natural ecological area (0.784), indicating that the natural ecological area should be the focus of future protection and development efforts, with a particular emphasis on enhancing the ‘landscape aesthetic’ and ‘landscape cultural’ aspects. (2) The landscape experience scores can be used to understand the reasons for the differences in participants’ experiences of different landscapes. The architectural heritage landscape of the Yi’an Fortress scored highest in the experience evaluation due to its superior performance in terms of ‘landscape form’ factors. The cultural decorative landscape scored next, while the garden greening landscape scored the lowest, due to their poorer performance in terms of ‘landscape form’ and ‘landscape aesthetics’. (3) The eye-tracking data was consistent with the results of the subjective evaluation, validating the “subjective + objective” cognitive evaluation and visual perception framework, employing the SBE–SD method and eye-tracking analysis is a scientific and effective method for assessing the visual experience of heritage landscapes. These results provide a scientific basis for the heritage planners and managers of the Yi’an fortress to improve the landscape environment, better meet public needs, and preserve the unique character of this vital cultural resource. Furthermore, this study offers a new research method and approach for the protection of other heritage landscapes.

Abstract Background The burgeoning field of research on the dual-factor model of mental health (DFM) has highlighted its significance, yet the applicability of the DFM in military personnel and its longitudinal relationships with different dimensions of meaning in life remains unclear. This study aimed to clarify the applicability of the DFM for military personnel and to investigate longitudinal relationships between the dual factors of mental health (negative factor, positive factor) and the two dimensions of meaning in life (presence of meaning, search for meaning) in military personnel. Methods In this study, data were collected in two waves (April and August 2023) from 227 Chinese military personnel. We constructed a dual-factor model with depression as the negative factor and subjective well-being as the positive factor, and we compared it with a single-factor model to determine if DFM could be applied to military personnel. We also constructed a cross-lagged model to investigate longitudinal relationships between depression, subjective well-being, presence of meaning, and search for meaning. Results According to the findings, military personnel fit better with the DFM than with the single-factor model. Cross-lagged analysis results revealed that both the presence of meaning and the search for meaning negatively predicted depression and positively predicted subjective well-being. Conclusions The DFM had good applicability among military personnel. Both the presence of meaning and the search for meaning could improve military mental health, suggesting that both dimensions of meaning in life may be potential targets for improving military mental health.

Abstract Background Huangkui Lianchang Decoction (HLD) is a traditional Chinese herbal formula for treating ulcerative colitis (UC). However, its mechanism of action remains poorly understood. The Study aims to validate the therapeutic effect of HLD on UC and its mechanism by integrating network pharmacology, bioinformatics, and experimental validation. Methods UC targets were collected by databases and GSE19101. The active ingredients in HLD were detected by ultra-performance liquid chromatography-tandem mass spectrometry. PubChem collected targets of active ingredients. Protein–protein interaction (PPI) networks were established with UC-related targets. Gene Ontology and Kyoto Encyclopedia (KEGG) of Genes and Genomes enrichment were analyzed for the mechanism of HLD treatment of UC and validated by the signaling pathways of HLD. Effects of HLD on UC were verified using dextran sulfate sodium (DDS)-induced UC mice experiments. Results A total of 1883 UC-related targets were obtained from the GSE10191 dataset, 1589 from the database, and 1313 matching HLD-related targets, for a total of 94 key targets. Combined with PPI, GO, and KEGG network analyses, the signaling pathways were enriched to obtain IL-17, Toll-like receptor, NF-κB, and tumor necrosis factor signaling pathways. In animal experiments, HLD improved the inflammatory response of UC and reduced UC-induced pro-inflammatory factors such as Tumor Necrosis Factor Alpha (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6). HLD suppressed proteins TLR4, MyD88, and NF-κB expression. Conclusions This study systematically dissected the molecular mechanism of HLD for the treatment of UC using a network pharmacology approach. Further animal verification experiments revealed that HLD inhibited inflammatory responses and improved intestinal barrier function through the TLR4/MyD88/NF-κB pathway.

Abstract Cancer is rarely the straightforward consequence of an abnormality in a single gene, but rather reflects a complex interplay of many genes, represented as gene modules. Here, we leverage the recent advances of model-agnostic interpretation approach and develop CGMega, an explainable and graph attention-based deep learning framework to perform cancer gene module dissection. CGMega outperforms current approaches in cancer gene prediction, and it provides a promising approach to integrate multi-omics information. We apply CGMega to breast cancer cell line and acute myeloid leukemia (AML) patients, and we uncover the high-order gene module formed by ErbB family and tumor factors NRG1, PPM1A and DLG2. We identify 396 candidate AML genes, and observe the enrichment of either known AML genes or candidate AML genes in a single gene module. We also identify patient-specific AML genes and associated gene modules. Together, these results indicate that CGMega can be used to dissect cancer gene modules, and provide high-order mechanistic insights into cancer development and heterogeneity.

In order to understand the types, biological characteristics, and metabolites types of pathogenic fungi in carambola, the typical diseased parts of carambola fruit were collected for fungal isolation by tissue isolation methods. The fungi were identified by morphological and molecular identification methods based on ITS sequencing analysis. The biological characteristics of pathogenic fungi were explored, and metabolites were isolated and purified using liquid chromatography. Their structures were established on the basis of 1H NMR and 13C NMR. The results were as follows: The four strains were identified as Fusarium equiseti, Neopestalotiopsis sp., Schizophyllum commune and Cladosporium cladosporioides. All four strains could cause disease in carambola fruit. The fermentation products of Fusarium equiseti were chemically investigated, leading to the discovery of four compounds, 3,7,9-trihydroxy-1-methyl-6H-dibenzo[b,d]pyran-6-on, 1,4,7-trihydroxy-3,9-dimethoxy-6H-benzo[c]chromen-6-one, lecanoric acid and 7-hydroxy-4-methyl-1(3H)-isobenzofuranone. The results of biological characteristics indicated that the optimal growth temperature for the four pathogenic fungi was 25~28 ℃, and they could all grow within the pH range of 4~10.

Coastal wetlands are hotspots for nitrogen (N) cycling, and crab burrowing is known to transform N in intertidal marsh soils. However, the underlying mechanisms remain unclear. This study conducted field experiments and used indoor control test devices to investigate the seasonal response of nitrogen to crab disturbance at the sediment–water interface in coastal tidal flat wetlands. The results showed that crab disturbance exhibited significant seasonality with large seasonal differences in cave density and depth. Due to crab disturbance, nitrogen fluxes at the sediment–water interface were much greater in the box with crabs than in the box without crabs. In summer, NH4+-N showed a positive flux from the sediment to the overlying water, but NO2−-N and NO3−-N showed positive fluxes from the sediment to the overlying water only in early stages. In winter, NH4+-N showed a positive flux from the sediment to the overlying water, but NO2−-N and NO3−-N both exhibited positive and negative fluxes. These results indicated that the presence of crab burrows can cause the aerobic layer to move downward by approximately 8–15 cm in summer and directly promote nitrification at the sediment surface.

Three new species of Meotipa Simon, 1895 are described based on specimens collected from Guangxi Zhuang Autonomous Region, China: Meotipa lingulata sp. nov. (female), M. pseudomultuma sp. nov. (both male and female) and M. tortuosa sp. nov. (both male and female). Detailed descriptions, photographs, line drawings, sequences of histone H3, and a distribution map of the three new species are provided.

Circulating tumor cells (CTCs) are cancer cells that detach from the primary tumor and enter the bloodstream, where they can seed new metastatic lesions in distant organs. CTCs are often associated with white blood cells (WBCs), especially neutrophils, the most abundant and versatile immune cells in the blood. Neutrophils can interact with CTCs through various mechanisms, such as cell-cell adhesion, cytokine secretion, protease release, and neutrophil extracellular traps (NETs) formation. These interactions can promote the survival, proliferation, invasion, and extravasation of CTCs, as well as modulate the pre-metastatic niche and the tumor microenvironment. Therefore, inhibiting CTC-neutrophils interaction could be a potential strategy to reduce tumor metastasis and improve the prognosis of cancer patients. In this review, we summarize the current literature on CTC-neutrophils interaction’ role in tumor metastasis and discuss the possible therapeutic approaches to target this interaction.

This study offers a comprehensive evaluation of urban renewal efforts in Shandong Province, China, by employing the entropy method combined with the Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS). An evaluation index system was constructed to assess the weights of key factors influencing urban renewal, including the renovation of old residential areas, improvement in sewage treatment quality, development of sponge cities, adoption of clean heating, and enhancement of air quality. Analysis of 16 prefecture-level cities in 2019 reveals significant disparities in performance, with Jinan achieving the highest ranking due to notable improvements in infrastructure and environmental management. Meanwhile, other cities displayed varying levels of success, reflecting different developmental stages and capacities. The findings underscore the necessity for tailored strategies to optimize urban renewal outcomes, focusing on high-weight factors such as sewage treatment, clean heating, and residential renovation. This study provides actionable insights for policymakers, advocating adaptive renewal strategies that align with local contexts and encourage continuous innovation. The results highlight the importance of targeted policy interventions to enhance urban renewal quality across Shandong Province, promoting sustainable urban development and better living standards.

Preeclampsia (PE) is a pregnancy-related disease characterized by vascular endothelial cell injury. This study aimed to investigate the role of methyltransferase-like protein 14 (METTL14) in vascular endothelial cell injury in PE. The PE cell model was established by treating human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-alpha (TNF-α) in vitro. METTL14 and forkhead box protein 1 (FOXP1) were silenced, and miR-34a-5p was overexpressed in HUVECs to evaluate their effects. HUVEC viability, apoptosis, and the levels of intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and endothelin-1 were measured. The N6-methyladenosine (m6A) modification of pri-miR-34a-5p was quantified. The interactions between miR-34a-5p, DiGeorge syndrome critical region 8, and m6A enrichment in miR-34a-5p were analyzed. The relationship between miR-34a-5p and FOXP1 was also verified. The results showed that the expressions of METTL14, FOXP1, and miR-34a-5p were determined. METTL14 expression was elevated in the TNF-α-induced HUVEC injury model. Silencing METTL14 improved HUVEC viability, inhibited apoptosis, and reduced endothelial inflammation. METTL14 promoted miR-34a-5p expression through m6A modification. Overexpression of miR-34a-5p or silencing of FOXP1 reversed the protective effects of METTL14 silencing on cell injury in the PE model. In conclusion, METTL14 mediated m6A modification to promote miR-34a-5p expression, leading to the inhibition of FOXP1 expression, which aggravated endothelial cell damage in the PE cell model.

[ Objective ] VQ proteins are plant-specific proteins with the conserved VQ motifs ( Fxxh- VQxhTG ), which play an important role in plant growth and development as well as in response to abiotic stresses. The role of the VQ gene family in litchi ( Litchi chinensis ) had not been systematically studied. We identified the LcVQ gene family members as well as their expression patterns in different tissues of ly- chee and their responses to abiotic stresses. This laid a foundation for studying its stress-resistant mecha- nism. [ Methods ] The sequences of LcVQ genes were obtained from the L . chinensis genome using bioin- formatics methods , and their physicochemical properties , subcellular localizations , gene structures , and conserved motifs were analyzed ; a phylogenetic tree was constructed using MEGA 6.0 to analyze the phy- logenetic relationships of the VQ proteins in L . chinensis , Arabidopsis , and Oryza sativa ; the responses to various abiotic stresses were verified by the quantitative real-time PCR ( qRT-PCR ) . [ Results ] A total of 18 LcVQ genes were identified from L . chinensis genome , named as LcVQ1 - 18 , which were clustered into 9 subgroups. They were widely distributed on 11 of 15 chromosomes of lychee. The amino acid num- bers of LcVQ proteins were ranged from 111 to 427 , and molecular weights from 12.48 kD to 45.49 kD. Subcellular localizations showed that except for LcVQ15 and LcVQ17 were localized at the cytoplasm , all other LcVQ proteins were localized at the nucleus. The LcVQ promoters contained a large number of growth and development , plant hormone , and stress-responsiveness related response elements. The LcVQ genes expression was varied at different tissues , which was divided into universal expression and specific expression. Under the treatment of low temperature , high temperature , drought , and salt stress , we found that 4 , 3 , 3 , and 4 LcVQ genes were significantly up-regulated at 3 hours of treatment , respective- ly , indicating that these genes could respond to the abiotic stresses. [ Conclusion ] There are 18 VQ mem- bers in the L . chinensis genome with typical VQ binding domains and participate in different stress re- sponses.

Abstract Two-dimensional (2D) AMX2 compounds are a family of mixed ionic and electronic conductors (where A is a monovalent metal ion, M is a trivalent metal, and X is a chalcogen) that offer a fascinating platform to explore intrinsic coupled ionic-electronic properties. However, the synthesis of 2D AMX2 compounds remains challenging due to their multielement characteristics and various by-products. Here, we report a separated-precursor-supply chemical vapor deposition strategy to manipulate the chemical reactions and evaporation of precursors, facilitating the successful fabrication of 20 types of 2D AMX2 flakes. Notably, a 10.4 nm-thick AgCrS2 flake shows superionic behavior at room temperature, with an ionic conductivity of 192.8 mS/cm. Room temperature ferroelectricity and reconfigurable positive/negative photovoltaic currents have been observed in CuScS2 flakes. This study not only provides an effective approach for the synthesis of multielement 2D materials with unique properties, but also lays the foundation for the exploration of 2D AMX2 compounds in electronic, optoelectronic, and neuromorphic devices.

Abstract Topologically associating domains (TADs), megabase-scale features of chromatin spatial architecture, are organized in a domain-within-domain TAD hierarchy. Within TADs, the inner and smaller subTADs not only manifest cell-to-cell variability, but also precisely regulate transcription and differentiation. Although over 20 TAD callers are able to detect TAD, their usability in biomedicine is confined by a disagreement of outputs and a limit in understanding TAD hierarchy. We compare 13 computational tools across various conditions and develop a metric to evaluate the similarity of TAD hierarchy. Although outputs of TAD hierarchy at each level vary among callers, data resolutions, sequencing depths, and matrices normalization, they are more consistent when they have a higher similarity of larger TADs. We present comprehensive benchmarking of TAD hierarchy callers and operational guidance to researchers of life science researchers. Moreover, by simulating the mixing of different types of cells, we confirm that TAD hierarchy is generated not simply from stacking Hi-C heatmaps of heterogeneous cells. Finally, we propose an air conditioner model to decipher the role of TAD hierarchy in transcription.

In the process of high-speed additive manufacturing, machining defects such as low surface accuracy, high surface roughness, residual stresses and micro-cracks have a serious impact on the performance and life of the product. These machining defects need to be removed by post-treatment in order to promote the use of additive manufactured parts in industrial production. This article provides a systematic review of existing post-treatment technologies for additive manufactured parts, divided into surface post-treatment technologies and overall post-treatment technologies. The processing cost expenditure of the most common post-processing methods is analyzed. The core values and key metrics of post-processing are explored. The prospects for post-processing technology for additive manufactured parts in six key development directions are discussed. The present review systematically discusses the process capabilities and research developments of post-processing technologies for high-speed additive manufacturing, taking into account knowledge from both basic and applied research areas.

In response to problems of poor sampling quality, low sensitivity, and high demand for medical personnel regarding the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) oropharyngeal (OP) swab sampling used in China, we aimed to evaluate the diagnostic performance and acceptability of saliva-based nucleic acid amplification tests (NAATs) in China. The results showed that, using nasopharyngeal (NP) swab results as the gold standard, the overall sensitivities for saliva specimens and OP swabs were 93.3 % and 85.0 %, the specificities were 92.6 % and 93.8 %, respectively. The results of an acceptability survey showed that the scores for saliva, OP, and NP samples were 9.46 ± 1.69, 8.11 ± 2.42, and 4.58 ± 3.82 out of 10, respectively, with significant differences among the three groups (P

Abstract Triglyceride (TAG) deposition in the liver is associated with metabolic disorders. In lower vertebrate, the propensity to accumulate hepatic TAG varies widely among fish species. Diacylglycerol acyltransferases (DGAT1 and DGAT2) are major enzymes for TAG synthesis. Here we show that large yellow croaker (Larimichthys crocea) has significantly higher hepatic TAG level than that in rainbow trout (Oncorhynchus mykiss) fed with same diet. Hepatic expression of DGATs genes in croaker is markedly higher compared with trout under physiological condition. Meanwhile, DGAT1 and DGAT2 in both croaker and trout are required for TAG synthesis and lipid droplet formation in vitro. Furthermore, oleic acid treatment increases DGAT1 expression in croaker hepatocytes rather than in trout and has no significant difference in DGAT2 expression in two fish species. Finally, effects of various transcription factors on croaker and trout DGAT1 promoter are studied. We find that DGAT1 is a target gene of the transcription factor CREBH in croaker rather than in trout. Overall, hepatic expression and transcriptional regulation of DGATs display significant species differences between croaker and trout with distinct hepatic triglyceride deposition, which bring new perspectives on the use of fish models for studying hepatic TAG deposition.

Abstract Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6–18.0) for the immunotherapy group compared with 9.9 months (8.0–11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40–0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3–32.8) for the control group (HR, 0.57 [95% CI, 0.33–0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

Abstract Mesenchymal stem cells (MSCs) are widely distributed pluripotent stem cells with powerful immunomodulatory capacity. MSCs transplantation therapy (MSCT) is widely used in the fields of tissue regeneration and repair, and treatment of inflammatory diseases. Apoptosis is an important way for tissues to maintain cell renewal, but it also plays an important role in various diseases. And many studies have shown that MSCs improves the diseases by regulating cell apoptosis. The regulation of MSCs on apoptosis is double-sided. On the one hand, MSCs significantly inhibit the apoptosis of diseased cells. On the other hand, MSCs also promote the apoptosis of tumor cells and excessive immune cells. Furthermore, MSCs regulate apoptosis through multiple molecules and pathways, including three classical apoptotic signaling pathways and other pathways. In this review, we summarize the current evidence on the regulation of apoptosis by MSCs.

Lipid metabolism disorders lead to lipotoxicity. The hyperlipidemia-induced early stage of renal injury mainly manifests as podocyte damage. CD36 mediates fatty acid uptake and the subsequent accumulation of toxic lipid metabolites, resulting in podocyte lipotoxicity.

Cuproptosis is a newly identified form of copper-dependent cell death that differs from other known pathways. This discovery provides a new way to explore copper-based nanomaterial applications in cancer therapy. This study used a layer-by-layer self-assembling method to load Cu2-xS nanoparticle (NP) cores with the siRNA of the PD-L1 immune escape-related gene and wrap a silk fibroin (SF) shell to form a multifunctional copper-based SF nanoplatform, denoted as CuS-PEI-siRNA-SFNs. CuS-PEI-siRNA-SFNs induced cuproptosis and exerted an antitumor effect via multiple mechanisms, including photothermal therapy (PTT), chemodynamic therapy (CDT), and immune activation. The presence of significant dihydrolipoamide S-acetyltransferase (DLAT) oligomers in 4T1 cells treated with CuS-PEI-siRNA-SFNs indicated the triggering of cuproptosis. Furthermore, in vivo experimental results showed that CuS-PEI-siRNA-SFNs efficiently accumulated in the tumor tissues of 4T1 tumor-bearing mice inhibited primary tumor and lung metastasis, and displayed excellent biosafety and antitumor activity. This study demonstrated that the synergistic effect of cuproptosis, PTT, CDT, and immune activation showed promise for treating metastatic breast cancer.

Introduction: Ovarian cancer is the most malignant gynecological tumor. Previous studies have demonstrated that chimeric antigen receptor (CAR)-engineered NK-92 cells targeting folate receptor α (αFR) (NK-92-αFR-CAR) can specifically kill αFR-positive ovarian cancer cells. However, the migration barrier restricts antitumor effects of CAR-engineered cells. Objectives: To elucidate the mechanism by which NK-92-αFR-CAR cells induce the secretion of chemokine CXCL10 during killing ovarian cancer cells. It is speculated that NK-92-αFR-CAR-CXCR3A can target αFR and have chemotaxis of CXCL10, and they may have stronger killing effect of ovarian cancer. Methods: Study the mechanism of CXCL10 expression strongly induced by TNF-α and IFN-γ combined stimulation in ovarian cancer cells. Construct the fourth generation of NK-92-αFR-CAR-CXCR3A cells, which were co-expressed CXCR3A and αFR-CAR. Evaluate the killing and migration effects of NK-92-αFR-CAR-CXCR3A in vitro and in vivo. Results: RNA sequencing (RNA-seq) first revealed that the expression level of the chemokine CXCL10 was most significantly increased in ovarian cancer cells co-cultured with NK-92-αFR-CAR. Secondly, cytokine stimulation experiments confirmed that IFN-γ and TNF-α secreted by NK-92-αFR-CAR synergistically induced high CXCL10 expression in ovarian cancer cells. Further signaling pathway experiments showed that IFN-γ and TNF-α enhanced the activation level of the IFN-γ-IFNGR-JAK1/2-STAT1-CXCL10 signaling axis. Cytotoxicity experiments showed that NK-92-αFR-CAR-CXCR3A cells could not only efficiently kill αFR-positive ovarian cancer cells in vitro but also secrete IFN-γ and TNF-α. Higher migration than that of NK-92-αFR-CAR was detected in NK-92-αFR-CAR-CXCR3A using transwell assay. NK-92-αFR-CAR-CXCR3A effectively killed tumor cells in different mouse xenograft models of ovarian cancer and increased infiltration into tumor tissue. Conclusion: This study confirmed that IFN-γ and TNF-α secreted by αFR-CAR-engineered NK cells can synergistically induce high expression of CXCL10 in ovarian cancer cells and constructed self-driving αFR-CAR-engineered NK cells that can break through migration barriers based on CXCL10, which may provide a new therapeutic weapon for ovarian cancer.

Objective To elucidate the underlying mechanism by which the proliferation and migration abilities of human umbilical cord mesenchymal stem cells (hUC-MSCs) determine their therapeutic efficacy in rheumatoid arthritis treatment.Methods The DBA/1J mice were utilized to establish a collagen-induced RA (CIA) mouse model and to validate the therapeutic efficacy of hUC-MSCs transfected with CD151 siRNA. RNA-seq, QT-PCR and western blotting were utilized to evaluate the mRNA and protein levels of the PI3K/AKT pathway, respectively.Results IFN-γ significantly enhanced the proliferation and migration abilities of hUC-MSCs, up-regulating the expression of CD151, a gene related to cell proliferation and migration. Effective inhibition of this effect was achieved through CD151 siRNA treatment. However, IFN-γ did not affect hUC-MSCs differentiation or changes in cell surface markers. Additionally, transplantation of CD151-interfered hUC-MSCs (siRNA-CD151-hUC-MSCs) resulted in decreased colonization in the toes of CIA mice and worse therapeutic effects compared to empty vector treatment (siRNA-NC-hUC-MSCs).Conclusion IFN-γ facilitates the proliferation and migration of hUC-MSCs through the CD151/PI3K/AKT pathway. The therapeutic efficacy of siRNA-CD151-hUC-MSCs was found to be inferior to that of siRNA-NC-hUC-MSCs.

ABSTRACTObjectives Diabetic gastrointestinal dysfunction (DGD) is a serious complication of diabetic mellitus (DM), affecting the enteric nervous system (ENS), particular enteric glial cells (EGCs). This study aimed to elucidate the effects and underlying molecular mechanisms of hyperglycemic stress on EGCs in in vitro and in vivo models of DM.Methods In in vitro studies, enteric glial cell line CRL-2690 was exposed to hyperglycemia stress, and cell viability, cell apoptosis and oxidative damage were assessed. In in vivo studies, STZ-induced diabetic mice were constructed, and cell apoptosis and oxidative damage of EGCs in the duodenum of DM mice were assessed.Results The results showed that hyperglycemic stress markedly induced oxidative damage of EGCs in in vitro and in vivo models of DM. This damage was found to be dependent on the activation of redoxosomes, which involved the phosphorylation of SRC and Vav2, the up-regulation of active RAC1-GTP, and the activation of NADPH oxidase (NOX). Moreover, inhibitors of redoxosomes, such as the RAC1 inhibitor NSC23766 and the NOX inhibitor VAS2870, effectively mitigated the hyperglycemic stress-induced oxidative damage of EGCs. Additionally, inhibition of p66SHC, a downstream target of redoxosomes, attenuated oxidative damage of EGCs under hyperglycemic stress.Discussion Our findings suggest that the redoxosomes/p66SHC signaling is involved in the oxidative damage of EGCs during the pathological process of DGD. This signaling cascade may represent a potential therapeutic target for the treatment of DGD.

IntroductionDeglycosylated azithromycin (Deg-AZM), a newly developed Class I drug with good therapeutic effects on slow transit constipation, is a small-molecule transgelin agonist that has been approved for clinical trials in 2024. The preclinical pharmacokinetic profile of Deg-AZM was investigated to support further development.MethodsA LC-MS/MS method was established and validated to detected the concentration of Deg-AZM in various biological samples. In vivo tests such as pharmacokinetic studies in rats and dogs, tissue distribution studies in rats, and extraction studies in rats were conducted to investigated the preclinical pharmacokinetic behaviors of Deg-AZM comprehensively. The plasma protein rate of Deg-AZM was determined by rapid equilibrium dialysis method in vitro. The metabolic stability and metabolite profile of Deg-AZM was assessed using pooled mice, rats, dogs, monkeys and humans microsomes in vitro. The PK profiles of Deg-AZM in human was predicted based on physiologically based pharmacokinetic (PBPK) models.ResultsThe plasma protein binding rates of Deg-AZM were lower in mice and rats, higher in dogs, and moderate in humans. The metabolic process of Deg-AZM was similar in rat and human liver microsomes. From Pharmacokinetic studies in rats and dogs, Deg-AZM was rapidly absorbed into the blood and then quickly eliminated. Plasma exposure of Deg-AZM was dose dependent with no accumulation after continuous gavage administration. In addition, there is no significant gender difference in the pharmacokinetic behavior of Deg-AZM. Deg-AZM was widely distributed in the tissues without obvious accumulation, and mainly excreted from the urinary excretion pathway. Furthermore, the pharmacokinetic profiles of Deg-AZM in humans showed dose dependency.ConclusionThe pharmacokinetic profiles of Deg-AZM was fully explored, these results could provide valuable information to support the first-in-human dosage prediction and phase I clinical design.

BackgroundMetabolically associated fatty liver disease (MAFLD) insidiously affects people's health, and many models have been proposed for the evaluation of liver fibrosis. However, there is still a lack of noninvasive and sensitive models to screen MAFLD in high-risk populations. ObjectiveThe purpose of this study was to explore a new method for early screening of the public and establish a home-based tool for regular self-assessment and monitoring of MAFLD. MethodsIn this cross-sectional study, there were 1758 eligible participants in the training set and 200 eligible participants in the testing set. Routine blood, blood biochemistry, and FibroScan tests were performed, and body composition was analyzed using a body composition instrument. Additionally, we recorded multiple factors including disease-related risk factors, the Forns index score, the hepatic steatosis index (HSI), the triglyceride glucose index, total body water (TBW), body fat mass (BFM), visceral fat area, waist-height ratio (WHtR), and basal metabolic rate. Binary logistic regression analysis was performed to explore the potential anthropometric indicators that have a predictive ability to screen for MAFLD. A new model, named the MAFLD Screening Index (MFSI), was established using binary logistic regression analysis, and BFM, WHtR, and TBW were included. A simple rating table, named the MAFLD Rating Table (MRT), was also established using these indicators. ResultsThe performance of the HSI (area under the curve [AUC]=0.873, specificity=76.8%, sensitivity=81.4%), WHtR (AUC=0.866, specificity=79.8%, sensitivity=80.8%), and BFM (AUC=0.842, specificity=76.9%, sensitivity=76.2%) in discriminating between the MAFLD group and non-fatty liver group was evaluated (P

Abstract Considerable progress has been made in the development of drug delivery systems for diabetic wounds. However, underlying drawbacks, such as low delivery efficiency and poor tissue permeability, have rarely been addressed. In this study, a multifunctional biohybrid nanorobot platform comprising an artificial unit and several biological components is constructed. The artificial unit is a magnetically driven nanorobot surface modified with antibacterial 2‐hydroxypropyltrimethyl ammonium chloride chitosan, which enables the entire platform to move and has excellent tissue penetration capacity. The biological components are two‐step engineered extracellular vesicles that are first loaded with mangiferin, a natural polyphenolic compound with antioxidant properties, and then glycoengineered on the surface to enhance cellular uptake efficiency. As expected, the platform is more easily absorbed by endothelial cells and fibroblasts and exhibits outstanding dermal penetration performance and antioxidant properties. Encouraging results are also observed in infected diabetic wound models, showing improved wound re‐epithelialization, collagen deposition, angiogenesis, and accelerated wound healing. Collectively, a biohybrid nanorobot platform that possesses the functionalities of both artificial units and biological components serves as an efficient delivery system to promote diabetic wound repair through dual‐enhanced cell and tissue penetration and multistep interventions.

This study develops a system simulation model based on the megawatt-class supercritical carbon dioxide Brayton cycle unit in Hengshui, China, to examine the effect of pipe section resistance on system performance. The results indicate that increased pressure loss in pipe sections significantly reduces power generation efficiency and power supply efficiency. Specifically, a 100 % increase in pressure loss results in 3.290 % and 4.377 % decreases in power generation efficiency and power supply efficiency, respectively. Moreover, higher pressure loss leads to increased CO2 mass flow rate at design power generation load. When the pressure loss is doubled, it requires a 17.593 % increase in CO2 mass flow rate to achieve the design power. Pressure loss in high-pressure section has minimal impact on system performance, while resistance in low-pressure section significantly affects it. For instance, a 100 % increase in pressure loss from the compressor outlet to the low temperature regenerator inlet causes a 0.37 % decrease in system power supply efficiency, and a similar increase from the high temperature regenerator outlet to the low temperature regenerator inlet leads to a 0.76 % decrease. These findings provide meaningful guidance for component design and piping layout optimization for similar systems.

BackgroundLymph node metastasis is the major cause of increased recurrence and death in patients with papillary thyroid carcinoma (PTC). We evaluate the clinicopathologic factors affecting excellent response (ER) in patients with PTC with lymph node metastasis following operation and 131I ablation therapy.MethodsA total of 423 patients with PTC with lymph node metastasis who underwent thyroidectomy and postoperative 131I ablation therapy were enrolled. The relationship between clinicopathological factors affecting ER achievement was analyzed.ResultsMultivariate analysis showed that the foci diameter (≤1 cm), unifocal, combination with Hashimoto’s thyroiditis (HT), lymph node metastases rate (LR) (≤40%), no postoperative lymph node metastasis, low preablative stimulated thyroglobulin (ps-Tg) level (≤3.87 ng/mL), and the time of 131I ablation therapy (one time) were positively correlated with the ER achievement [odds ratio (OR): 1.744, 3.114, 3.920, 4.018, 2.074, 9.767, and 49.491, respectively; all p < 0.05]. The receiver operating characteristic (ROC) curves showed that the cutoff values of ps-Tg and LR were 4.625 ng/mL and 50.50%, respectively. The AUC of ROC of ps-Tg and LR for predicting ER achievement was 0.821 and 0.746, respectively. The Tg and the cumulative risk of non-ER elevated with the increase of LR, especially for the high-level ps-Tg (>4.625 ng/mL) group.ConclusionThe foci diameter and number, combination with HT, LR, and ps-Tg level are independent factors for ER. Ps-Tg level and LR are valid predictive factors for the efficacy of 131I therapy in patients with PTC. The predictive value of the cumulative risk of non-ER can be improved by the combination of ps-Tg and LR.

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

Taxonomic notes on the Talaus species from China are provided. Two new species, T. yuyang Yao & Liu, sp. nov. and T. zhangjiangkou Yao & Liu, sp. nov. are described and illustrated, and a further three species are redescribed based on their genitalic characters: T. dulongjiang Tang, Yin, Ubick & Peng, 2008, T. niger Tang, Yin, Ubick & Peng, 2008, and T. sulcus Tang & Li, 2010. The species T. xiphosus Zhu & Ono, 2007 is considered a junior synonym of T. triangulifer Simon, 1886 based on an examination of many recently collected female and male specimens from Guangxi Province, China. Diagnoses, detailed illustrations and a map of distributional records of the six treated species of Talaus in China are provided.

Abstract To reliably assess the condition of concrete structures, a surface wave-based comprehensive index has been developed. Considering various factors (e.g., aggregate types) influencing the surface wave-based characteristics, a relative index for concrete condition assessment has presented. To address the conflicts between individual indexes, the weight for each index is determined in accordance with its credibility. The effectiveness of the proposed methodology is verified by using test results from six concrete beams with different void volume ratios. Hereby three characteristics of surface waves (i.e., P- and R-wave velocities, and attenuation coefficient) are used to diagnose the concrete beams. It is found that the comprehensive index has the advantage in handling abnormal measurements of the individual indexes by reducing their weights to lower their influence on the final diagnosis. Comparison of the diagnoses based on the comprehensive index and individual indexes reveals that the comprehensive index performs much better than any other individual index. It matches greatly with the compressive strength of the concrete beams obtained from the destructive test. In conclusion, the proposed methodology presents a single comprehensive diagnostic feature with improved reliability on the fitness of the concrete structures for decision-makers.

To achieve the goals of carbon peaking and carbon neutrality, the retrofitting of existing coal-fired power plants is crucial to achieving energy-saving and emission reduction goals. A conventional recovery system of waste heat typically occurs downstream of the air preheater, where the energy quality in flue gas is low, resulting in limited coal-saving benefits. This study proposes a scheme involving a flue gas exchanger bypassing the air preheater and low-temperature economizers, which is used to transfer the waste heat from flue gas to primary and secondary air (System I). Additionally, a heat pump can be introduced to provide supplementary energy for primary and secondary air, as well as the condensate from the steam turbine (System II). The coal consumption rate and exergy efficiency are used to evaluate the two schemes. The results show that both waste heat recovery systems can increase the power output of the coal-fired unit by recovering waste heat. System II can boost power output by approximately 13.98 MW. The power increase in both waste heat recovery systems show a declining trend as the unit load decreases. This increased power is primarily attributed to the medium- and low-pressure cylinders, while the contributions from ultra-high-pressure and high-pressure cylinders are negligible. The increased power output for the medium-pressure cylinder ranges from approximately 3.49 to 3.58 MW, while the low-pressure cylinder has an increased power output of around 10.10 to 10.19 MW. The coal consumption rate is decreased from 250.3 g/(kW·h) to 247.5 g/(kW·h) under a full load condition for both systems, which can be augmented at lower load conditions. System II outperforms System I at 30% load condition, achieving a reduced coal consumption rate of 3.36 g/(kW·h). System I has an exergy efficiency of 40%, while System II shows a higher efficiency of 44%.

Bacterial damage has significantly impacted humanity, prompting the control of harmful microorganisms and infectious diseases. In this study, antibacterial bio-based PA56 fibres were prepared with high-speed spinning using ethylene-methyl acrylate-glycidyl methacrylate terpolymer (EMA) as the compatibiliser and polypentamethylene guanidine sulphate (PPGS) as the antibacterial agent. The effects of PPGS content on the properties of PA56 draw-textured yarns (DTYs) were investigated. The compatibility between PPGS and PA greatly improved with EMA incorporation. Compared with PA56 fibres, the elongation at break of the sample containing 2.0 wt% EMA and PPGS increased by 25.93%. The inhibition rates of the fibres with 1.0 wt% PPGS against Escherichia coli and Staphylococcus aureus reached over 99.99%. Samples were easily coloured with dyes, exhibiting good colour fastness, regardless of the EMA content. However, the antibacterial performances of dyed DTYs decreased to varying degrees. the inhibition rates of samples of 0.5wt% addition of PPGS against E. coli were reduced from 99.99% to 28.50% and 25.36% after dyeing with Acid Blue 80 and Dispersible Blue 2BLN, respectively. The EMA-modified fibres exhibited the best antibacterial activity after dyeing with neutral gray 2BL. These findings are expected to promote the wider use of biobased PA56 in practical applications that require antibacterial performance and to guide the dyeing process of antimicrobial fibres.

Finger vein (FV) biometrics have garnered considerable attention due to their inherent non-contact nature and high security, exhibiting tremendous potential in identity authentication and beyond. Nevertheless, challenges pertaining to the scarcity of training data and inconsistent image quality continue to impede the effectiveness of finger vein recognition (FVR) systems. To tackle these challenges, we introduce the visual feature-guided diamond convolutional network (dubbed ‘VF-DCN’), a uniquely configured multi-scale and multi-orientation convolutional neural network. The VF-DCN showcases three pivotal innovations: Firstly, it meticulously tunes the convolutional kernels through multi-scale Log-Gabor filters. Secondly, it implements a distinctive diamond-shaped convolutional kernel architecture inspired by human visual perception. This design intelligently allocates more orientational filters to medium scales, which inherently carry richer information. In contrast, at extreme scales, the use of orientational filters is minimized to simulate the natural blurring of objects at extreme focal lengths. Thirdly, the network boasts a deliberate three-layer configuration and fully unsupervised training process, prioritizing simplicity and optimal performance. Extensive experiments are conducted on four FV databases, including MMCBNU_6000, FV_USM, HKPU, and ZSC_FV. The experimental results reveal that VF-DCN achieves remarkable improvement with equal error rates (EERs) of 0.17%, 0.19%, 2.11%, and 0.65%, respectively, and Accuracy Rates (ACC) of 100%, 99.97%, 98.92%, and 99.36%, respectively. These results indicate that, compared with some existing FVR approaches, the proposed VF-DCN not only achieves notable recognition accuracy but also shows fewer number of parameters and lower model complexity. Moreover, VF-DCN exhibits superior robustness across diverse FV databases.

Summary: Allergic asthma is a chronic non-communicable disease characterized by lung tissue inflammation. Current treatments can alleviate the clinical symptoms to some extent, but there is still no cure. Recently, the transplantation of mesenchymal stem cells (MSCs) has emerged as a potential approach for treating allergic asthma. Gingival-derived mesenchymal stem cells (GMSCs), a type of MSC recently studied, have shown significant therapeutic effects in various experimental models of autoimmune diseases. However, their application in allergic diseases has yet to be fully elucidated. In this study, using an OVA-induced allergic asthma model, we demonstrated that GMSCs decrease CD11b+CD11c+ proinflammatory dendritic cells (DCs), reduce Th2 cells differentiation, and thus effectively diminish eosinophils infiltration. We also identified that the core functional factor, hepatocyte growth factor (HGF) secreted by GMSCs, mediated its effects in relieving airway inflammation. Taken together, our findings indicate GMSCs as a potential therapy for allergic asthma and other related diseases.

Summary: Wax gland complex (WGC) serves as the primary generator of beeswax; however, the dynamic biological function in wax secretion remains unclear. To elucidate the developmental mechanism of WGC, we conducted a comprehensive analysis to reveal the variations in proteins and metabolites among the newly emerged bee (NEB), wax-secreting bee (WSB), and overaged bee (OAB). We identified 3,295 proteins and 159 metabolites in WGC. Specifically, NEB elevated the expression of ribosomal proteins for preparing the glandular organ. While WSB promoted the size of epidermal cells and oenocytes, the enrichment of fatty acids and energy metabolism in WSB suggested a strong ability in wax synthesis. In OAB, disorganized wax tubules, and up-regulated cysteine proteases reflected the gland degeneration. These findings highlight the dynamic changes in the level of molecule and morphological structure in WGC, offering valuable insights into the development and mechanism of wax secretion in honeybees and other wax insects.

Peptide YY (PYY3-36) is a post-prandially released gut hormone with potent appetite-reducing activity, the mechanism of action of which is not fully understood. Unravelling how this system physiologically regulates food intake may help unlock its therapeutic potential, whilst minimising unwanted effects. Here we demonstrate that germline and post-natal targeted knockdown of the PYY3-36 preferring receptor (neuropeptide Y (NPY) Y2 receptor (Y2R)) in the afferent vagus nerve is required for the appetite inhibitory effects of physiologically-released PYY3-36, but not peripherally administered pharmacological doses. Post-natal knockdown of the Y2R results in a transient body weight phenotype that is not evident in the germline model. Loss of vagal Y2R signalling also results in altered meal patterning associated with accelerated gastric emptying. These results are important for the design of PYY-based anti-obesity agents.

Abstract Background Patients with urosepsis associated with upper urinary tract stones require further stone management after emergency drainage. Objective To evaluate the safety and efficacy of elective flexible ureteroscopic lithotripsy (F-URSL) for upper urinary tract stones in patients with prior urosepsis who have undergone emergency drainage using retrograde ureteral stent(RUS) or percutaneous nephrostomy (PCN). Method Between January 2017 and December 2021, clinical data were collected for 102 patients who underwent elective F-URSL following emergency drainage for urosepsis caused by upper ureteral or renal stones. The patients were categorized into two groups based on the drainage method used: the RUS group and the PCN group. The collected data included patient demographics, stone parameters, infection recovery after emergency drainage, and clinical outcomes post F-URSL. Subsequently, the data underwent statistical analysis. Results A total of 102 patients were included in the statistical analysis, with 58 (56.86%) in the RUS group and 44 (43.14%) in the PCN group. Among the patients, 84 (82.35%) were female and 18 (17.65%) were male, with an average age of 59.36 years. Positive urine cultures were observed in 71 (69.61%) patients. Successful drainage was achieved in all patients in both groups, and there were no significant differences in the time required for normalization of white blood cell count (WBC) and body temperature following drainage. Additionally, all patients underwent F-URSL successfully, and no statistically significant differences were observed between the two groups in terms of operative time, stone-free rates, postoperative fever, and postoperative hospital stay. Conclusion Both RUS and PCN have been established as effective approaches for managing urosepsis caused by upper urinary tract stones. Furthermore, the impact of these two drainage methods on the subsequent management of stones through elective F-URSL has shown consistent outcomes.

Abstract Background Group 2 innate lymphoid cells (ILC2s) are critical sources of type 2 cytokines and represent one of the major tissue-resident lymphoid cells in the mouse lung. However, the molecular mechanisms underlying ILC2 activation under challenges are not fully understood. Results Here, using single-cell transcriptomics, genetic reporters, and gene knockouts, we identify four ILC2 subsets, including two non-activation subsets and two activation subsets, in the mouse acute inflammatory lung. Of note, a distinct activation subset, marked by the transcription factor Nr4a1, paradoxically expresses both tissue-resident memory T cell (Trm), and effector/central memory T cell (Tem/Tcm) signature genes, as well as higher scores of proliferation, activation, and wound healing, all driven by its particular regulons. Furthermore, we demonstrate that the Nr4a1+ILC2s are restrained from activating by the programmed cell death protein-1 (PD-1), which negatively modulates their activation-related regulons. PD-1 deficiency places the non-activation ILC2s in a state that is prone to activation, resulting in Nr4a1+ILC2 differentiation through different activation trajectories. Loss of PD-1 also leads to the expansion of Nr4a1+ILC2s by the increase of their proliferation ability. Conclusions The findings show that activated ILC2s are a heterogenous population encompassing distinct subsets that have different propensities, and therefore provide an opportunity to explore PD-1's role in modulating the activity of ILC2s for disease prevention and therapy.

Metallic glasses have received a lot of interest because of their excellent mechanical, physical, and chemical qualities. For example, they have a stronger resistivity than crystalline metals composed of the same elements and a lower viscosity coefficient. However, the difficulty in creating alloy compositions has been a concern for researchers. Traditional amorphous alloy systems design approaches, such as empirical trial-and-error methods and methods based on density functional theory (DFT), have assisted researchers in exploring numerous amorphous alloy systems during the growth of materials science over the last few decades. However, with the continuous development of materials science, these methods have been difficult to meet the needs of researchers due to their long development cycles and low efficiency. Additionally, the complex and long-range disordered structure of metallic glasses makes it difficult to understand their structure and nature in a comprehensive and clear way by conventional methods. Amorphous alloy composition design and property analysis are now often conducted using machine learning techniques because of their low experimental cost, short development cycle, strong data processing capability, and high predictive performance, among other advantages. They present new approaches and chances to address significant key bottlenecks in the field of metallic glass. In this study, the main processes of machine learning model building were introduced. Subsequently, the related studies on data pre-processing, model construction, and model validation were presented. For data pre-processing, data selection, feature engineering, and advanced data balancing methods were primarily described. In the feature engineering part, the model performance with various input features was examined, and it was shown that either employing physical properties or directly using the alloy compositions as the model input might result in high performance. Four machine learning algorithms were used to generate the machine learning model: artificial neural networks (ANN), support vector machines (SVM), random forest (RF), and extreme gradient boosting (XGBoost). A comparison indicates that SVM models work best with small data sets, whereas the performance of all other models tends to get better as the amount of training data increases. Generally, the XGBoost method outperforms several other methods and is, therefore, often used in machine learning competitions. Model validation approaches: K-fold cross-validation and leave-one-out cross-validation methods were presented. A good metallic glass performance prediction method needs to perform well in both validation methods. Finally, this study provides several possible future research directions on feature engineering, dataset construction, validation, and machine learning models.

Objective: CAR-T/NK cells have had limited success in the treatment of solid tumors, such as colorectal cancer (CRC), in part because of the heterogeneous nature of tumor-associated antigens that lead to antigen-negative relapse after the initial response. This barrier might be overcome by enhancing the recruitment and durability of endogenous immune cells. Methods: Immunohistochemistry and flow cytometry were used to assess the expression of CD133 antigen in tissue microarrays and cell lines, respectively. Retroviral vector transduction was used to generate CBLB502-secreting CAR133-NK92 cells (CAR133-i502-NK92). The tumor killing capacity of CAR133-NK92 cells in vitro and in vivo were quantified via LDH release, the RTCA assay, and the degranulation test, as well as measuring tumor bioluminescence signal intensity in mice xenografts. Results: We engineered CAR133-i502-NK92 cells and demonstrated that those cells displayed enhanced proliferation (9.0 × 104 cells vs. 7.0 × 104 cells) and specific anti-tumor activities in vitro and in a xenogeneic mouse model, and were well-tolerated. Notably, CBLB502 secreted by CAR133-i502-NK92 cells effectively activated endogenous immune cells. Furthermore, in hCD133+/hCD133− mixed cancer xenograft models, CAR133-i502-NK92 cells suppressed cancer growth better than the counterparts (n = 5, P = 0.0297). Greater T-cell infiltration was associated with greater anti-tumor potency (P < 0.0001). Conclusions: Armed with a CBLB502 TLR5 agonist, CAR133-NK92 cells were shown to be capable of specifically eliminating CD133-positive colon cancer cells in a CAR133-dependent manner and indirectly eradicating CD133-negative colon cancer cells in a CBLB502-specific endogenous immune response manner. This study describes a novel technique for optimizing CAR-T/NK cells for the treatment of antigenically-diverse solid tumors.

Three new Otacilia species were collected from Jiangxi Provinces, China during a survey of the spider fauna of the region: Otacilia anfu Liu, sp. nov. (♂♀), O. guanshan Liu, sp. nov. (♂♀), and O. mingyueshan Liu, sp. nov. (♂♀). All species are described and illustrated with photographs and SEM micrographs, and their distribution is also mapped.