Genetic Aspects of Necrobiotic Xanthogranuloma.

This genetic association study examines the genetic aspects of necrobiotic xanthogranuloma in 3 patients in China.

Confinement controls the directional cell responses to fluid forces.

Our understanding of how fluid forces influence cell migration in confining environments remains limited. By integrating microfluidics with live-cell imaging, we demonstrate that cells in tightly-but not moderately-confined spaces reverse direction and move upstream upon exposure to fluid forces. This fluid force-induced directional change occurs less frequently when cells display diminished mechanosensitivity, experience elevated hydraulic resistance, or sense a chemical gradient. Cell reversal requires actin polymerization to the new cell front, as shown mathematically and experimentally. Actin polymerization is necessary for the fluid force-induced activation of NHE1, which cooperates with calcium to induce upstream migration. Calcium levels increase downstream, mirroring the subcellular distribution of myosin IIA, whose activation enhances upstream migration. Reduced lamin A/C levels promote downstream migration of metastatic tumor cells by preventing cell polarity establishment and intracellular calcium rise. This mechanism could allow cancer cells to evade high-pressure environments, such as the primary tumor.

SOS1 gene family in mangrove (Kandelia obovata): Genome-wide identification, characterization, and expression analyses under salt and copper stress.

BACKGROUND: Salt Overly Sensitive 1 (SOS1), a plasma membrane Na+/H+ exchanger, is essential for plant salt tolerance. Salt damage is a significant abiotic stress that impacts plant species globally. All living organisms require copper (Cu), a necessary micronutrient and a protein cofactor for many biological and physiological processes. High Cu concentrations, however, may result in pollution that inhibits the growth and development of plants. The function and production of mangrove ecosystems are significantly impacted by rising salinity and copper contamination. RESULTS: A genome-wide analysis and bioinformatics techniques were used in this study to identify 20 SOS1 genes in the genome of Kandelia obovata. Most of the SOS1 genes were found on the plasma membrane and dispersed over 11 of the 18 chromosomes. Based on phylogenetic analysis, KoSOS1s can be categorized into four groups, similar to Solanum tuberosum. Kandelia obovata's SOS1 gene family expanded due to tandem and segmental duplication. These SOS1 homologs shared similar protein structures, according to the results of the conserved motif analysis. The coding regions of 20 KoSOS1 genes consist of amino acids ranging from 466 to 1221, while the exons include amino acids ranging from 3 to 23. In addition, we found that the 2.0 kb upstream promoter region of the KoSOS1s gene contains several cis-elements associated with phytohormones and stress responses. According to the expression experiments, seven randomly chosen genes experienced up- and down-regulation of their expression levels in response to copper (CuCl2) and salt stressors. CONCLUSIONS: For the first time, this work systematically identified SOS1 genes in Kandelia obovata. Our investigations also encompassed physicochemical properties, evolution, and expression patterns, thereby furnishing a theoretical framework for subsequent research endeavours aimed at functionally characterizing the Kandelia obovata SOS1 genes throughout the life cycle of plants.

Bioorthogonal conjugation and responsive nanocoating of probiotics for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is closely associated with dysregulated immune response, gut mucosal barrier, and microbiota. Conventional treatments suffer from inferior bioavailability and inadequate efficiency. Herein, we present a synergistic therapeutic strategy based on multifunctionalized probiotics to mitigate IBD through single oral administration. The probiotic (Escherichia coli Nissle 1917) is bioorthogonally conjugated with immunomodulators and subsequently encapsulated by an enteric coating. The viability and bioactivity of probiotics are not affected by the modifications. And the armored probiotics are able to resist the harsh environment of the stomach and shed their enteric coating in the intestinal tract, exposing immunomodulators to polarize pro-inflammatory M1-type macrophages into anti-inflammatory M2-type. In a mouse colitis model, orally administered multifunctionalized probiotics cooperatively alleviate IBD with increased body weight to 1.13 folds and decreased disease activity index to 0.43 folds, through downregulating the pro-inflammatory cytokines expression, upregulating the epithelial tight junction-associated proteins levels to restore the intestinal barrier, and increasing the microbiota richness and abundance. This work exhibits a feasible approach to construct functionalized orally administered probiotics for enhanced synergistic therapy of IBD.

Production Allocation Optimization of Gas Reservoirs with Edge and Bottom Aquifer Based on a Parallel-Structured Genetic Algorithm.

As gas reservoir pressure decreases, edge and bottom water irregularly flow into the reservoir through storage and permeability spaces. Water influx poses a significant challenge for the development of gas reservoirs, impacting development efficiency and the ultimate recovery rate. Therefore, exploring rational optimization methods for gas well allocation is essential. This study utilizes the vertical well productivity equation considering two-phase flow and employs the net present value (NPV) to evaluate the economic benefits of gas well production. A parallel-structured genetic algorithm (GA) is developed to account for dynamic reservoir inflow, wellbore conditions, and surface facilities engineering. The new model is applied to investigate the optimal allocation of the B-21 well in the Amu Darya right bank gas reservoirs in Turkmenistan. Results indicate a match of over 90% between the cumulative gas production and water/gas ratio calculated by the proposed method and those calculated by a numerical simulation model. Compared with the traditional genetic algorithm, the new approach reduces the number of iterations to approximately 2100 (a 72.4% decrease) and significantly improves the convergence rate.

Unlocking policy effects: Water resources management plans and urban water pollution.

Water resource management, as a foundation for supporting sustainable urban development, has garnered increasing attention from scholars. Developing effective water resource management plans is a major challenge faced by countries worldwide. This study uses the 2015 Water Pollution Control and Prevention Action Plan (WPCAP) in China as a natural experiment and employs a Difference-in-Differences (DID) model to estimate the relationship between WPCAP and urban water pollution from 2010 to 2021. The findings are as follows: 1) WPCAP reduces water pollution. 2) WPCAP decreases water pollution in high-policy-pressure cities but increases water pollution in low-policy-pressure cities within a 60 km radius, particularly having a significantly negative impact on water pollution in low-policy-pressure cities with low altitude. 3) optimizing industrial and domestic water use, as well as enhancing sewage treatment capabilities, are crucial pathways through which WPCAP reduces water pollution. Additionally, WPCAP significantly improves water pollution control capabilities in cities with abundant water resources, large cities, and industrialized cities. 4) although WPCAP's ability to control water pollution increases management costs, it also raises residential income and promotes population growth. These findings have important implications for the sustainable development of water resources in emerging countries, including China.

Overexpression of miR-20a-5p in mesenchymal stem cell derived-exosomes from systemic lupus erythematosus patients restored therapeutic effect and Treg immune regulation.

We and other groups have documented that bone marrow-mesenchymal stem cells (BM-MSCs) from Systemic lupus erythematosus (SLE) patients demonstrated signs of senescence, including reduced ability of regulating Treg. Treg cell defects or Treg cell deficiency are regarded as significant factors in the progression of SLE. Exosomes, nanoscale vesicles, abound in molecular and genetic contents, play a critical role in intercellular communications. The purpose of this research is to investigate the mechanism of MSCs-exosomes regulating Tregs cells in SLE, further elucidate the mechanism of immune dysregulation of aging BM-MSCs, and provide theoretical basis and data support for new targets of SLE treatment. In the study, BM-MSCs and exosomes were isolated successfully. Exosomes could be up-taken by naïve CD4+T cells. MSCs-exosomes attenuated SLE clinical manifestation in vivo, but MSCs-exosomes from SLE patients were ineffective. MSCs-exosomes from SLE patients dysregulated Treg cells differentiation in vivo and in vitro. Exosomal miR-20a-5p contributed to the effect of MSCs-exosomes regulating Treg cells. Up-regulating the expression of miR-20a-5p in SLE MSCs-exosomes can restore their ability to promote Treg differentiation and treatment effect. This study further elucidated the role of in the immunomodulatory mechanism of BM-MSCs-exosomes and provided new ideas for the non-cellular autologous transplantation therapy of SLE.

Unpaired fundus image enhancement based on constrained generative adversarial networks.

Fundus photography (FP) is a crucial technique for diagnosing the progression of ocular and systemic diseases in clinical studies, with wide applications in early clinical screening and diagnosis. However, due to the nonuniform illumination and imbalanced intensity caused by various reasons, the quality of fundus images is often severely weakened, brings challenges for automated screening, analysis, and diagnosis of diseases. To resolve this problem, we developed strongly constrained generative adversarial networks (SCGAN). The results demonstrate that the quality of various datasets were more significantly enhanced based on SCGAN, simultaneously more effectively retaining tissue and vascular information under various experimental conditions. Furthermore, the clinical effectiveness and robustness of this model were validated by showing its improved ability in vascular segmentation as well as disease diagnosis. Our study provides a new comprehensive approach for FP and also possesses the potential capacity to advance artificial intelligence-assisted ophthalmic examination.

Adsorption of metals on aged microplastics in intensive mariculture areas: Aggravating the potential ecological risks to marine organisms.

Field determination of the metal adsorption capacity of microplastics (MPs) by using a passive sampler had been done in typical subtropical mariculture area in China. The adsorption of eight metals (Fe, Mn, Cu, Zn, As, Pb, Cr and Cd) by five types of MPs (low-density polyethylene, polypropylene, polystyrene, poly(ethylene terephthalate) and poly(vinyl chloride) (PVC) was compared, including metal types, mariculture types (cage and longline culture), metal residue content in ambient environment, polymer types and particle sizes of MPs. The results showed that Cu, Zn, As, Cd, Pb and Cr in the mariculture environment were contaminated compared with the quality criteria. The concentrations of these six metals adsorbed on five MPs increased linearly with those in seawater. More enriched Cu and As in MPs in marine cage culture than in longline culture, due to the obvious endogenous pollution emissions for the artificial diets, fish medicine and disinfectants. Aged PVC with more cracks and pores showed higher metal adsorption capacity than any other polymers. MPs with a smaller size range of 50-74 µm tended to accumulate higher amounts of metals than those with a larger size range of 74-178 µm, consisting with the surface characteristics of MPs. The significant positive relationship between the concentrations of nutrients in seawater and the adsorption amounts of Cu, Zn and As on MPs implies that the eutrophication would promote their pollution. Based on the ecological risk assessment, the occurrence of MPs could aggravate the potential risk of metals to marine organisms in intensive mariculture areas. This is the first time to reveal the impacts of the adsorption of metals on aged MPs on the potential ecological risks of metals to organisms under the realistic environmental condition.

Biological functions and biomedical applications of extracellular vesicles derived from blood cells.

There is a growing interest in using extracellular vesicles (EVs) for therapeutic applications. EVs are composed of cytoplasmic proteins and nucleic acids and an external lipid bilayer containing transmembrane proteins on their surfaces. EVs can alter the state of the target cells by interacting with the receptor ligand of the target cell or by being internalised by the target cell. Blood cells are the primary source of EVs, and 1 µL of plasma contains approximately 1.5 × 107 EVs. Owing to their easy acquisition and the avoidance of cell amplification in vitro, using blood cells as a source of therapeutic EVs has promising clinical application prospects. This review summarises the characteristics and biological functions of EVs derived from different blood cell types (platelets, erythrocytes, and leukocytes) and analyses the prospects and challenges of using them for clinical therapeutic applications. In summary, blood cell-derived EVs can regulate different cell types such as immune cells (macrophages, T cells, and dendritic cells), stem cells, and somatic cells, and play a role in intercellular communication, immune regulation, and cell proliferation. Overall, blood cell-derived EVs have the potential for use in vascular diseases, inflammatory diseases, degenerative diseases, and injuries. To promote the clinical translation of blood cell-derived EVs, researchers need to perform further studies on EVs in terms of scalable and reproducible isolation technology, quality control, safety, stability and storage, regulatory issues, cost-effectiveness, and long-term efficacy.

Perspectives for capillary refill time in clinical practice for sepsis.

BACKGROUND: Capillary refill time (CRT) is defined as the time taken for color to return to an external capillary bed after pressure is applied to cause blanching. Recent studies demonstrated the benefits of CRT in guiding fluid therapy for sepsis. However, lack of consistency among physicians in how to perform and interpret CRT has led to a low interobserver agreement for this assessment tool, which prevents its availability in sepsis clinical settings. OBJECTIVE: To give physicians a concise overview of CRT and explore recent evidence on its reliability and value in the management of sepsis. RESEARCH DESIGN: A narrative review. RESULTS: This narrative review summarizes the factors affecting CRT values, for example, age, sex, temperature, light, observation techniques, work experience, training level and differences in CRT measurement methods. The methods of reducing the variability of CRT are synthesized. Based on studies with highly reproducible CRT measurements and an excellent inter-rater concordance, we recommend the standardized CRT assessment method. The threshold of normal CRT values is discussed. The application of CRT in different phases of sepsis management is summarized. CONCLUSIONS: Recent data confirm the value of CRT in critically ill patients. CRT should be detected by trained physicians using standardized methods and reducing the effect of ambient-related factors. Its association with severe infection, microcirculation, tissue perfusion response, organ dysfunction and adverse outcomes makes this approach a very attractive tool in sepsis. Further studies should confirm its value in the management of sepsis. IMPLICATIONS FOR CLINICAL PRACTICE: As a simple assessment, CRT deserves more attention even though it has not been widely applied at the bedside. CRT could provide nursing staff with patient's microcirculatory status, which may help to develop individualized nursing plans and improve the patient's care quality and treatment outcomes.

Association Between Atopic Dermatitis and Aging: Clinical Observations and Underlying Mechanisms.

As one of the most prevalent chronic inflammatory skin diseases, atopic dermatitis (AD) increasingly affects the aging population. Amid the ongoing global aging trend, it's essential to recognize the intricate relationship between AD and aging. This paper reviews existing knowledge, summarizing clinical observations of associations between AD and aging-related diseases in various systems, including endocrine, cardiovascular, and neurological. Additionally, it discusses major theories explaining the correlation, encompassing skin-mucosal barriers, systemic inflammation and stress, genes, signal transduction, and environmental and behavioral factors. The association between AD and aging holds significant importance, both in population and basic perspectives. While further research is warranted, this paper aims to inspire deeper exploration of inflammation/allergy-aging dynamics and the timely management of elderly patients with AD.

Leading with purpose: Unraveling the impact of responsible leadership on employee green behavior in the workplace.

Although sustainability has been a priority for organizations, there is still a lack of research on how leaders with a stakeholder perspective can motivate employees to adopt green behavior for sustainability in a complex and changing environment. This paper introduced social cognitive theory to describe two mechanisms by which responsible leadership predicts employee green behavior. Our research considers felt obligation for constructive change and stakeholder value as mediations with cognitive perspective in this process. Additionally, we consider the moderating effects of positive emotion and the superior-subordinate relationship. Our model received support from the investigation and research. By emphasizing the significance of perceived responsible leadership and proposing a new way of perceiving employee green behavior that ensures guidance from responsible leadership along the cognition perspective, the present research contributes to our understanding of the incentive effect of responsible leadership on employee green behavior.

A Pseudo-Surfactant Chemical Permeation Enhancer to Treat Otitis Media via Sustained Transtympanic Delivery of Antibiotics.

Chemical permeation enhancers (CPEs) represent a prevalent and safe strategy to enable noninvasive drug delivery across skin-like biological barriers such as the tympanic membrane (TM). While most existing CPEs interact strongly with the lipid bilayers in the stratum corneum to create defects as diffusion paths, their interactions with the delivery system, such as polymers forming a hydrogel, can compromise gelation, formulation stability, and drug diffusion. To overcome this challenge, differing interactions between CPEs and the hydrogel system are explored, especially those with sodium dodecyl sulfate (SDS), an ionic surfactant and a common CPE, and those with methyl laurate (ML), a nonionic counterpart with a similar length alkyl chain. Notably, the use of ML effectively decouples permeation enhancement from gelation, enabling sustained delivery across TMs to treat acute otitis media (AOM), which is not possible with the use of SDS. Ciprofloxacin and ML are shown to form a pseudo-surfactant that significantly boosts transtympanic permeation. The middle ear ciprofloxacin concentration is increased by 70-fold in vivo in a chinchilla AOM model, yielding superior efficacy and biocompatibility than the previous highest-performing formulation. Beyond improved efficacy and biocompatibility, this single-CPE formulation significantly accelerates its progression toward clinical deployment.

Construction and validation of a novel tumor morphology immune inflammatory nutritional score (TIIN score) for intrahepatic cholangiocarcinoma: a multicenter study.

BACKGROUND: Tumor morphology, immune function, inflammatory levels, and nutritional status play critical roles in the progression of intrahepatic cholangiocarcinoma (ICC). This multicenter study aimed to investigate the association between markers related to tumor morphology, immune function, inflammatory levels, and nutritional status with the prognosis of ICC patients. Additionally, a novel tumor morphology immune inflammatory nutritional score (TIIN score), integrating these factors was constructed. METHODS: A retrospective analysis was performed on 418 patients who underwent radical surgical resection and had postoperative pathological confirmation of ICC between January 2016 and January 2020 at three medical centers. The cohort was divided into a training set (n = 272) and a validation set (n = 146). The prognostic significance of 16 relevant markers was assessed, and the TIIN score was derived using LASSO regression. Subsequently, the TIIN-nomogram models for OS and RFS were developed based on the TIIN score and the results of multivariate analysis. The predictive performance of the TIIN-nomogram models was evaluated using ROC survival curves, calibration curves, and clinical decision curve analysis (DCA). RESULTS: The TIIN score, derived from albumin-to-alkaline phosphatase ratio (AAPR), albumin-globulin ratio (AGR), monocyte-to-lymphocyte ratio (MLR), and tumor burden score (TBS), effectively categorized patients into high-risk and low-risk groups using the optimal cutoff value. Compared to individual metrics, the TIIN score demonstrated superior predictive value for both OS and RFS. Furthermore, the TIIN score exhibited strong associations with clinical indicators including obstructive jaundice, CEA, CA19-9, Child-pugh grade, perineural invasion, and 8th edition AJCC N stage. Univariate and multivariate analysis confirmed the TIIN score as an independent risk factor for postoperative OS and RFS in ICC patients (p < 0.05). Notably, the TIIN-nomogram models for OS and RFS, constructed based on the multivariate analysis and incorporating the TIIN score, demonstrated excellent predictive ability for postoperative survival in ICC patients. CONCLUSION: The development and validation of the TIIN score, a comprehensive composite index incorporating tumor morphology, immune function, inflammatory level, and nutritional status, significantly contribute to the prognostic assessment of ICC patients. Furthermore, the successful application of the TIIN-nomogram prediction model underscores its potential as a valuable tool in guiding individualized treatment strategies for ICC patients. These findings emphasize the importance of personalized approaches in improving the clinical management and outcomes of ICC.

Forensic efficiency and population genetic construction of Guizhou Gelao minority from Southwest China revealed by a panel of 23 autosomal STR loci.

Short tandem repeats (STRs) are the most common genetic markers in forensic and human population genetics due to their high polymorphism, rapid detection, and reliable genotyping. To adapt the rapid growth of forensic DNA database and solve problems in disputed cases, a panel of 23 autosomal STR loci with high discriminating ability was constructed recently. The Tai-Kadai-speaking Gelao is the most ancient indigenous minority in Guizhou province, however, the forensic efficiency and population genetic structure remain poorly explored. Here, 490 Guizhou Gelao individuals from Southwest China were genotyped with the panel of 23 STRs using the Huaxia Platinum Kit. A total of 265 alleles were screened. The combined discrimination power and the combined probability of paternity were 0.9999 and 0.9999, respectively. This indicated the 23 loci had higher discrimination power in Guizhou Gelao and could be applied to forensic practice. Comprehensive population structures with reference populations from China and abroad using the neighbour-joining phylogenetic tree (N-J tree), multidimensional scaling, principal component analysis and heatmap demonstrated that Guizhou Gelao was genetically closer to Guizhou Han than other populations. Moreover, our results showed that a complex phylogenetic model was influenced by ethnic, geographic, and linguistic factors. Key points: The first batch of genetic data for 23 autosomal STRs in 490 Geolao individuals from Guizhou was provided.The 23 STR panel can afford high genetic polymorphisms and discrimination power and can be efficiently applied to forensic practice in Guizhou Gelao population.A complex phylogenetic model influenced by ethnic, geographic, and linguistic factors was uncovered.

Revolutionizing energy practices: Unleashing the power of artificial intelligence in corporate energy transition.

Corporate energy transition is crucial for long-term sustainable development. The widely discussed Artificial Intelligence (AI), as a disruptive technological innovation, is highly potential for enhancing environment performance. However, the specific impact of AI on the process of corporate energy transition and its underlying mechanisms have not been fully explored. This study focuses on A-share listed corporates in Shanghai and Shenzhen stock markets in China spanning from 2011 to 2021. Based on corporate annual report information and information from over 200,000 patent application texts, we innovatively construct indicators for corporate energy transition and AI technology application. Furthermore, we empirically investigate the impact of AI technology on corporate energy transition and its potential mechanisms through combining information asymmetry theory and institutional theory. The empirical results indicate that: 1) AI can drive corporate energy transition and the promoting effect of AI collaborative innovation on corporate energy transition should not be ignored. 2) AI can help corporates achieve energy transition through pathways such as mitigating information asymmetry, reducing financing constraints, adjusting sustainable development concepts and practices. 3) The driving effect of AI on corporate energy transition varies depending on the characteristics of different types of corporates, industries, and regions. This study provides strategic guidance and decision support for business managers and policymakers, assisting both corporates and governments in better utilizing AI technology during the social energy transition process to achieve a dual optimization of environmental and economic goals.

Development and Application of a Multidimensional Database for the Detection of Quaternary Ammonium Compounds and Their Phase I Hepatic Metabolites in Humans.

The COVID-19 pandemic has led to significantly increased human exposure to the widely used disinfectants quaternary ammonium compounds (QACs). Xenobiotic metabolism serves a critical role in the clearance of environmental molecules, yet limited data are available on the routes of QAC metabolism or metabolite levels in humans. To address this gap and to advance QAC biomonitoring capabilities, we analyzed 19 commonly used QACs and their phase I metabolites by liquid chromatography-ion mobility-tandem mass spectrometry (LC-IM-MS/MS). In vitro generation of QAC metabolites by human liver microsomes produced a series of oxidized metabolites, with metabolism generally occurring on the alkyl chain group, as supported by MS/MS fragmentation. Discernible trends were observed in the gas-phase IM behavior of QAC metabolites, which, despite their increased mass, displayed smaller collision cross-section (CCS) values than those of their respective parent compounds. We then constructed a multidimensional reference SQLite database consisting of m/z, CCS, retention time (rt), and MS/MS spectra for 19 parent QACs and 81 QAC metabolites. Using this database, we confidently identified 13 parent QACs and 35 metabolites in de-identified human fecal samples. This is the first study to integrate in vitro metabolite biosynthesis with LC-IM-MS/MS for the simultaneous monitoring of parent QACs and their metabolites in humans.