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Abstract Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-β1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-β1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8+ T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8+ T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC.

Abstract This paper is based on the proximity engineering project of the Baishiyi tunnel group passing under the Chongqing West Station track group. Considering the train load and the spatial relationship of the tunnel and track groups, the settlement patterns, horizontal displacement, and differential settlement of the tunnel–strata–tracks system during the excavation process are studied through theoretical calculations and numerical simulation methods. The results indicate that the tunnel vault, strata, and track settlement deformation patterns are similar. Throughout the tunnel construction process, the tracks underwent uplift, settlement, and eventually stabilized. The settlement trough formed by the excavation of the three tunnels below the track group has an impact range of 25–145 m. Between 35 and 75 m, the differential settlement of the double track gradually increases with excavation. As the tunnel face reaches 75 m, the track differential settlement gradually converges and tends to stabilize. To minimize the impact of underpass tunnel construction on track groups, it is recommended to use a combination of full-section hole grouting and surface reinforcement grouting for ground reinforcement. Additionally, optimizing the construction parameters, including the step length and primary support closure time, and strengthening the locking anchor can further reduce the impact.

Abstract Adipose tissues in the hypodermis, the crucial stem cell reservoir in the skin and the endocrine organ for the maintenance of skin homeostasis undergo significant changes during skin aging. Dermal white adipose tissue (dWAT) has recently been recognized as an important organ for both non-metabolic and metabolic health in skin regeneration and rejuvenation. Defective differentiation, adipogenesis, improper adipocytokine production, and immunological dissonance dysfunction in dWAT lead to age-associated clinical changes. Here, we review age-related alterations in dWAT across levels, emphasizing the mechanisms underlying the regulation of aging. We also discuss the pathogenic changes involved in age-related fat dysfunction and the unfavorable consequences of accelerated skin aging, such as chronic inflammaging, immunosenescence, delayed wound healing, and fibrosis. Research has shown that adipose aging is an early initiation event and a potential target for extending longevity. We believe that adipose tissues play an essential role in aging and form a potential therapeutic target for the treatment of age-related skin diseases. Further research is needed to improve our understanding of this phenomenon.

Abstract Background The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. Methods Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. Results A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022–3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259–4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184–3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519–4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. Conclusions NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.

Six species of the ant-eating spider of the family Zodariidae are described from Xizang, China, including five new species: Asceua chayu sp. nov. (♀), A. dawai sp. nov. (♂♀), Mallinella migu sp. nov. (♂), M. mеdog sp. nov. (♂♀), and M. yadong sp. nov. (♂♀). The female of Cydrela linzhiensis (Hu, 2001) is described here for the first time. Descriptions and photographs of all the species are provided.

Abstract Background Adipose-derived stem cells (ASCs) represent the most advantageous choice for soft tissue regeneration. Studies proved the recruitment of ASCs post tissue injury was mediated by chemokine CXCL12, but the mechanism by which CXCL12 is generated after tissue injury remains unclear. Migrasomes are newly discovered membrane-bound organelles that could deliver CXCL12 spatially and temporally in vivo. In this study, we sought to investigate whether migrasomes participate ASC-mediated tissue regeneration. Methods Discrepant and asymmetrical soft tissue regeneration mice model were established, in which HE staining, immunofluorescent staining, western blot and qPCR were conducted to confirm the role of CXCL12 and migrasomes in ASC-mediated tissue regeneration. Characterization of ASC-derived migrasomes were carried out by confocal microscopy, scanning electron microscopy, transmission electron microscopy as well as western blot analysis. The function and mechanism of migrasomes were further testified by assisting tissue regeneration with isolated migrasomes in vivo and by in vitro transwell combined with co-culture system. Results Here, we show for the first time that migrasomes participate in soft tissue regeneration. ASCs generate migrasomes enriched with CXCL12 to mediate tissue regeneration. Migrasomes from ASCs could promote stem cells migration by activating CXCR4/RhoA signaling in vivo and in vitro. Chemoattracted ASCs facilitate regeneration, as demonstrated by the upregulation of an adipogenesis-associated protein. This positive feed-back-loop creates a favorable microenvironment for soft tissue regeneration. Thus, migrasomes represent a new therapeutic target for ASC-mediated tissue regeneration. Conclusions Our findings reveal a previously unknown function of ASCs in mediating tissue regeneration by generating migrasomes. The ASC-derived migrasomes can restore tissue regeneration by recruiting stem cells, which highlighting the potential application of ASC-derived migrasomes in regenerative medicine.

In this paper, we will conclude the results of Bufeng-1 (BF-1) A/B data processing, calibration workflow, and validation of the calibrated sea surface winds, land surface soil moisture, and sea surface height measurements. Since 2019, the BF-1 mission has operated in-orbit for over 4 years. The Earth reflected delay Doppler maps (DDMs) are continuously collected to perform global sea surface and land observations. At the same time, the intermediate frequency (IF) raw data are also obtained for 12 seconds every pass in diagnostic mode. To begin with, a brief description of the spaceborne Global Navigation Satellite System Reflectometry (GNSS-R) technique will be provided in the introduction. Next, we will present the overview of Chinese BF-1 mission and the data specifications used in our research. In the next section, the BF-1 mission-related spaceborne power calibration and validation are presented to show the support to power DDM observable production for sea surface and land surface applications. Then, the status of Chinese Beidou System (BDS) Equivalent Isotropic Radiated Power (EIRP) acquisition programme is then introduced. Furthermore, the latest sea surface height (SSH) measurements results including two modes (group delay and carrier phase) and wind speed derivation based on machine learning (ML) method will be spatial-temporal aligned and validated with auxiliary datasets including Denmark Technology University (DTU) mean sea surface (MSS) products and European Centre for Medium-Range Weather Forecasts (ECMWF) ERA5 reanalysis. The previous published results of sea surface winds retrieval under Hurricane conditions and soil moisture retrieval are also reviewed for the BF-1 mission applications. Finally, the conclusion of BF-1 derived results will be discussed to draw out ongoing/future works.

Abstract While many studies have sought to explore the degree to which sarcopenia-related traits are associated with cognitive performance, these studies have yielded contradictory results without any clear indication of the causality of such relationships. In efforts to better understand associations between sarcopenia-related traits and cognitive ability, a series of multivariate linear regression assessments were carried out upon datasets derived through the National Health and Nutrition Examination Survey (NHANES). Of these, cognitive performance was assessed by the Digit Symbol Substitution Test (DDST), the Consortium to Establish a Registry for Alzheimer’s Disease Immediate Recall Test (CERAD-IR), Delayed Recall Test (CERAD-DR) and Animal Fluency Test (AFT). Causal relationships between the two were further inferred via a two-sample Mendelian randomization (MR) analysis approach. Sarcopenia-related traits considered in these assessments included walking speed, appendicular skeletal muscle mass (ASM), and hand grip strength (HGS). Walking speed, ASM, and HGS were all significantly independently related to cognitive scores following adjustment for covariates. MR assessments also identified that each 1-SD higher walking speed and appendicular lean mass were causally and respectively associated with a 0.34 [standard error (SE) = 0.09; p

Abstract Background Modifying diet is crucial for diabetes and complication management. Numerous studies have shown that adjusting eating habits to align with the circadian rhythm may positively affect metabolic health. However, eating midpoint, eating duration, and their associations with diabetic kidney disease (DKD) are poorly understood. Methods The National Health and Nutrition Examination Survey (2013–2020) was examined for information on diabetes and dietary habits. From the beginning and ending times of each meal, we calculated the eating midpoint and eating duration. Urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g and/or estimated glomerular filtration rate (eGFR)

Abstract 2,5-Dimethylpyrazine (2,5-DMP) is important pharmaceutical raw material and food flavoring agent. Recently, engineering microbes to produce 2,5-DMP has become an attractive alternative to chemical synthesis approach. In this study, metabolic engineering strategies were used to optimize the modified Escherichia coli BL21 (DE3) strain for efficient synthesis of 2,5-DMP using L-threonine dehydrogenase (EcTDH) from Escherichia coli BL21, NADH oxidase (EhNOX) from Enterococcus hirae, aminoacetone oxidase (ScAAO) from Streptococcus cristatus and L-threonine transporter protein (EcSstT) from Escherichia coli BL21, respectively. We further optimized the reaction conditions for synthesizing 2,5-DMP. In optimized conditions, the modified strain can convert L-threonine to obtain 2,5-DMP with a yield of 2897.30 mg/L. Therefore, the strategies used in this study contribute to the development of high-level cell factories for 2,5-DMP. Graphical Abstract

The registration of laser point clouds in complex conditions in wilderness scenes is an important aspect in the research field of autonomous vehicle navigation. It serves as the foundation for solving problems such as environment reconstruction, map construction, navigation and positioning, and pose estimation during the motion process of autonomous vehicles using laser radar sensors. Due to the sparse structured features, uneven point cloud density, and high noise levels in wilderness scenes, achieving reliable and accurate point cloud registration is challenging. In this paper, we propose a semantic-supervised sparse point cloud registration network (S3PCRNet) aiming to achieve effective registration of laser point clouds in wilderness large-scale scenes. Firstly, a local feature aggregation module is designed to extract the local structural features of the point cloud. Then, based on rotation position encoding, a randomly grouped self-attention mechanism is proposed to obtain the global features of the point cloud through learning. A semantic information weight matrix is calculated to filter out negligible points. Subsequently, a semantic fusion feature module is utilised to find reliable correspondences between point clouds. Finally, the proposed method is trained and evaluated on both the RELLIS-3D dataset and a self-made Off-road-3D dataset.

Abstract CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining immune homeostasis in multiple sclerosis (MS). Hence, we aimed to explore the therapeutic efficacy and safety of adoptive cell therapy (ACT) utilizing induced antigen-specific Tregs in an animal model of MS, that is, in an experimental autoimmune encephalomyelitis (EAE) model. B cells from EAE model that were activated with soluble CD40L were used as antigen-presenting cells (APCs) to induce the differentiation of antigen-specific Tregs from naïve CD4 precursors, and then, a stepwise isolation of CD4+CD25highCD127low Tregs was performed using a flow sorter. All EAE mice were divided into Treg-treated group (2 × 104 cells in 0.2 mL per mouse, n = 14) and sham-treated group (0.2 mL normal saline (NS), n = 20), which were observed daily for clinical assessment, and for abnormal appearance for 6 weeks. Afterward, histological analysis, immunofluorescence and real-time PCR were performed. Compared to sham-treated mice, Treg-treated mice exhibited a significant decrease in disease severity scores and reduced inflammatory infiltration and demyelination in the spinal cord. Additionally, Tregs-treated mice demonstrated higher CCN3 protein and mRNA levels than sham-treated mice. The results of this preclinical study further support the therapeutic potential of this ACT approach in the treatment of MS.

Abstract Antimicrobial peptides, such as bacteriocin, produced by probiotics have become a promising novel class of therapeutic agents for treating infectious diseases. Selected lactic acid bacteria (LAB) isolated from fermented foods with probiotic potential were evaluated for various tests, including exopolysaccharide production, antibiotic susceptibility, acid and bile tolerance, antibacterial activity, and cell adhesion and cytotoxicity to gastric cell lines. Six selected LAB strains maintained their high viability under gastrointestinal conditions, produced high exopolysaccharides, showed no or less cytotoxicity, and adhered successfully to gastric cells. Furthermore, three strains, Weissella confusa CYLB30, Lactiplantibacillus plantarum CYLB47, and Limosilactobacillus fermentum CYLB55, demonstrated a strong antibacterial effect against drug-resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella enterica serovar Choleraesuis, Enterococcus faecium, and Staphylococcus aureus. Whole genome sequencing was performed on these three strains using the Nanopore platform; then, the results showed that all three strains did not harbor genes related to toxins, superantigens, and acquired antimicrobial resistance, in their genome. The bacteriocin gene cluster was found in CYLB47 genome, but not in CYLB30 and CYLB55 genomes. In SDS-PAGE, the extract of CYLB30 and CYLB47 bacteriocin-like inhibitory substance (BLIS) yielded a single band with a size of less than 10 kDa. These BLIS inhibited the growth and biofilm formation of drug-resistant P. aeruginosa and methicillin-resistant S. aureus (MRSA), causing membrane disruption and inhibiting adhesion ability to human skin HaCaT cells. Moreover, CYLB30 and CYLB47 BLIS rescued the larvae after being infected with P. aeruginosa and MRSA infections. In conclusion, CYLB30 and CYLB47 BLIS may be potential alternative treatment for multidrug-resistant bacteria infections.

Abstract Liver injury is a core pathological process in the majority of liver diseases, yet the genetic factors predisposing individuals to its initiation and progression remain poorly understood. Here we show that asialoglycoprotein receptor 1 (ASGR1), a lectin specifically expressed in the liver, is downregulated in patients with liver fibrosis or cirrhosis and male mice with liver injury. ASGR1 deficiency exacerbates while its overexpression mitigates acetaminophen-induced acute and CCl4-induced chronic liver injuries in male mice. Mechanistically, ASGR1 binds to an endoplasmic reticulum stress mediator GP73 and facilitates its lysosomal degradation. ASGR1 depletion increases circulating GP73 levels and promotes the interaction between GP73 and BIP to activate endoplasmic reticulum stress, leading to liver injury. Neutralization of GP73 not only attenuates ASGR1 deficiency-induced liver injuries but also improves survival in mice received a lethal dose of acetaminophen. Collectively, these findings identify ASGR1 as a potential genetic determinant of susceptibility to liver injury and propose it as a therapeutic target for the treatment of liver injury.

Characterization of the mechanical properties plays an essential role in the post-processing and evaluation of the functionality of the additively manufactured metallic parts. A number of studies have been focused on the tensile properties of additively manufactured metals. However, the quasi-static compression test of the additively manufactured 316L blocks with different heat-treatment conditions and scanning strategies seems to be overlooked in the literature. This paper aims to provide a comprehensive study of compressive mechanical response in plastic deformation of SS316L fabricated by selective laser melting (SLM). The mechanical response and microstructures in compressive deformation is analyzed for three printing strategies with 0°-, 90°- and 67.5°- scanning and three heat treatment conditions (450 °C for 3 h, 1100 °C for 1 h with furnace cool and 1100 °C for 1 h with water quenching) for selective laser melted (SLMed) stainless steel 316L in comparison with wrought stainless steel 316L in this work. Alteration of mechanical properties, microstructure evolution and compressive deformation mechanism is studied. Melt pool features are not significantly affected by low-temperature heat treatment (450 °C for 3 h) but fully dissolved through high-temperature heat treatment (1100 °C for 1 h). High-temperature heat treatment provides a higher resistance to compressive plastic deformation for SLMed 316L compared with the low-temperature heat-treated and as-built samples where more twinnings are observed. The compressive plastic deformation mechanism of 90°- and 67.5°-scanning samples is similar, which mainly results from twinning-induced plasticity. For 0°-scanning samples, the strong crystallographic texture is the main cause of anisotropic deformation. Modelling and simulation have been conducted to explain the anisotropic deformation mechanism of the 0°-scanning strategy. Simulation results suggest that the morphology difference of laser-scanning tracks and melt pools, which leads to material flow along the laser scanning direction, explains the anisotropic deformation mechanism.

AIM: To investigate a pioneering framework for the segmentation of meibomian glands (MGs), using limited annotations to reduce the workload on ophthalmologists and enhance the efficiency of clinical diagnosis. METHODS: Totally 203 infrared meibomian images from 138 patients with dry eye disease, accompanied by corresponding annotations, were gathered for the study. A rectified scribble-supervised gland segmentation (RSSGS) model, incorporating temporal ensemble prediction, uncertainty estimation, and a transformation equivariance constraint, was introduced to address constraints imposed by limited supervision information inherent in scribble annotations. The viability and efficacy of the proposed model were assessed based on accuracy, intersection over union (IoU), and dice coefficient. RESULTS: Using manual labels as the gold standard, RSSGS demonstrated outcomes with an accuracy of 93.54%, a dice coefficient of 78.02%, and an IoU of 64.18%. Notably, these performance metrics exceed the current weakly supervised state-of-the-art methods by 0.76%, 2.06%, and 2.69%, respectively. Furthermore, despite achieving a substantial 80% reduction in annotation costs, it only lags behind fully annotated methods by 0.72%, 1.51%, and 2.04%. CONCLUSION: An innovative automatic segmentation model is developed for MGs in infrared eyelid images, using scribble annotation for training. This model maintains an exceptionally high level of segmentation accuracy while substantially reducing training costs. It holds substantial utility for calculating clinical parameters, thereby greatly enhancing the diagnostic efficiency of ophthalmologists in evaluating meibomian gland dysfunction.

Abstract Adipose-derived stem cells (ASCs) are a critical adult stem cell subpopulation and are widely utilized in the fields of regenerative medicine and stem cell research due to their abundance, ease of harvest, and low immunogenicity. ASCs, which are homologous with skin by nature, can treat immune-related skin diseases by promoting skin regeneration and conferring immunosuppressive effects, with the latter being the most important therapeutic mechanism. ASCs regulate the immune response by direct cell–cell communication with immune cells, such as T cells, macrophages, and B cells. In addition to cell–cell interactions, ASCs modulate the immune response indirectly by secreting cytokines, interleukins, growth factors, and extracellular vesicles. The immunomodulatory effects of ASCs have been exploited to treat many immune-related skin diseases with good therapeutic outcomes. This article reviews the mechanisms underlying the immunomodulatory effects of ASCs, as well as progress in research on immune-related skin diseases.