Skin organoid transplantation promotes tissue repair with scarless in frostbite.

Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells and fibroblasts during frostbite. Most importantly, human-induced pluripotent stem cell (hiPSC) -derived skin organoids combining with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment significantly accelerated wound healing by reducing early inflammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fibroblasts, significantly reduced fibroblast-to-myofibroblast transition by regulating the integrin α5ß1-FAK pathway, and remodeled the extracellular matrix (ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfigurement and skin dysfunction caused by frostbite.

NAD+-boosting agent nicotinamide mononucleotide potently improves mitochondria stress response in Alzheimer's disease via ATF4-dependent mitochondrial UPR.

Extensive studies indicate that mitochondria dysfunction is pivotal for Alzheimer's disease (AD) pathogenesis; while cumulative evidence suggests that increased mitochondrial stress response (MSR) may mitigate neurodegeneration in AD, explorations to develop a MSR-targeted therapeutic strategy against AD are scarce. We combined cell biology, molecular biology, and pharmacological approaches to unravel a novel molecular pathway by which NAD+-boosting agent nicotinamide mononucleotide (NMN) regulates MSR in AD models. Here, we report dyshomeostasis plasma UPRmt-mitophagy-mediated MSR profiles in AD patient samples. NMN restores NAD+ metabolic profiles and improves MSR through the ATF4-dependent UPRmt pathway in AD-related cross-species models. At the organismal level, NAD+ repletion with NMN supplementation ameliorates mitochondrial proteotoxicity, decreases hippocampal synaptic disruption, decreases neuronal loss, and brain atrophy in mice model of AD. Remarkably, omics features of the hippocampus with NMN show that NMN leads to transcriptional changes of genes and proteins involved in MSR characteristics, principally within the astrocyte unit rather than microglia and oligodendrocytes. In brief, our work provides evidence that MSR has an active role in the pathogenesis of AD, as reducing mitochondrial homeostasis via atf4 depletion in AD mice aggravates the hallmarks of the disease; conversely, bolstering mitochondrial proteostasis by NMN decreases protein aggregation, restores memory performance, and delays disease progression, ultimately translating to increased healthspan.

Partially Amorphous Ru-Doped CoSe Nanoparticles with Optimized Intermediates Adsorption for Highly Efficient Sulfur Oxidation Reaction.

The application of thermodynamically more favorable sulfur oxidation reaction (SOR) to replace oxygen evolution reaction (OER) in electrocatalytic water electrolysis is an appealing strategy to achieve low-energy hydrogen production while removing toxic sulfur ions from wastewater. However, the study of SOR catalysts with both activity and stability still faces great challenges. Herein, this study prepares partially amorphous Ru-doped CoSe (pa-Ru-CoSe) nanoparticles for SOR. The doping of Ru keeps Co in an electron-deficient state, which enhances the adsorption of SOR intermediates and improves the catalytic activity. Meanwhile, the partially amorphous selenide possesses great corrosion resistance to sulfur species, thus ensuring stability in long-term SOR. In addition, the pa-Ru-CoSe requires only 0.566 V to reach a current density of 100 mA cm-2 in the SOR-HER coupled system and remains stable for 200 h. This work provides a promising partially amorphous strategy for SOR catalysts with both catalytic activity and long-term stability, enabling hydrogen production with low energy consumption and simultaneous sulfur production.

miR­1343­3p inhibits autophagy by directly targeting ATG7 in multiple myeloma cells.

Multiple myeloma (MM) is the second most common type of hematological malignancy globally. Despite application of several new drugs, such as daratumumab, bortezomib/lenalidomide/dexamethasone, in combination with hematopoietic stem cell transplantation, overall prognosis remains poor and the pathological mechanism of MM is still unknown. The present study used TargetScan to predict autophagy-related 7 (ATG7) as a candidate target gene of microRNA (miR)-1343-3p and confirmed the interaction between miR-1343-3p and the ATG7 3' untranslated region (3'UTR) using a dual-luciferase reporter assay. In U266 and RPMI-8226 MM cell lines, miR-1343-3p mimic transfection decreased mRNA and protein levels of ATG7, while miR-1343-3p inhibition increased ATG7 expression levels using reverse transcription-qPCR and western blot analysis. miR-1343-3p mimic transfection inhibited U266 and RPMI-8226 cell survival. Finally, miR-1343-3p regulated ATG7 and autophagy in MM cells using western blot analysis. The present findings suggested that miR-1343-3p may regulate ATG7 and autophagy by directly targeting the 3'UTR of ATG7. To the best of our knowledge, there are no direct data showing the roles of miR-1343-3p in development of MM; however, miR-1343-3p may be considered a potential target for MM treatment.

Diffusion behavior and environmental impact of odorants and TVOCs detected in a wastewater treatment plant for collaborative leachate treatment in Northwest China.

Wastewater treatment plants (WWTPs) are major sources of volatile gaseous compounds, especially in mixed-source systems such as domestic wastewater and landfill leachate. This study aimed to investigate the emission behavior and environmental impact of gaseous substances, such as hydrogen sulfide (H2S), ammonia (NH3), carbon sulfide (CS2), and phosphine (PH3), at a WWTP in Northwest China. Odorants were detected in the air surrounding the grid room (XGS), biochemical treatment tank (SHC), secondary sedimentation tank (ECC), and sludge dewatering room (NTS). For comparison, the upwind boundary (O-SF) and downwind boundaries (O-XF) monitoring points were used, with odor concentrations ranging from 3.95 to 725.27 odor units. The concentration ranges of the odorant substances were 5.27-88.69, 5.61-71.96, 5.70-32.63, and 0.12-5.87 mg/m3 for H2S, NH3, CS2, and PH3, respectively. Meteorological factors such as temperature, relative humidity, and wind speed and direction substantially influence odorant emissions. The concentrations of various odorants and volatile organic compounds (VOCs) detected at the O-XF monitoring point were higher than those detected at the O-SF monitoring point, indicating that the wind intensified their diffusion toward the downwind plant boundary. The average odor intensities of odorant substances emitted from wastewater or sludge treatment equipment were 3.37, 5.09, 4.42, 2.00, and 3.82 for total VOCs, H2S, NH3, CS2, and PH3, respectively. Among them four, with downwind diffusion, only H2S presented olfactory and chronic toxicity risks based on Gaussian plume model calculations. The hazard index ranking across monitoring sites was XGS > NTS > SHC > ECC > O-XF > O-SF. These findings emphasize the urgent need for effective measures to control and mitigate gaseous pollutants emitted by collaborative WWTPS, thereby protecting environmental quality and public health.

Precise Electrocatalysis on Fe-Porphyrin Conjugated Networks Achieves Energy-Efficient Extraction of Uranium.

Electrochemical extraction has the potential to enhance uranium (U) extraction capacity and rates, but thus far, high selectivity and energy efficiency have not been achieved through the design of electrode materials. Herein, a precise electrocatalysis strategy is developed using a Ferrum (Fe) porphyrin-phenanthroline conjugated network (Fe@PDACN) for energy-efficient uranium extraction. The phenanthroline provides specific binding sites for selective enrichment of U(VI) at active sites (Kd = 2.79 × 105 mL g-1 in multi-ion solution). The Fe(II) sites have strong trap-redox activity for U(VI) and act as dynamic electron donors to rapidly mediate electrocatalytic U(VI) extraction through the redox reaction of Fe(0/II)/Fe(III). Moreover, the Fe-porphyrin blocks support sustained electron donation for U(VI) electrocatalysis by pre-storing electrons. These features enable selective uranium capture and a high electroextraction capacity of 24 646.3 mg g-1 from simulated nuclear wastewater in 280 h at a low voltage of -1.5 V. An ultra-high Faraday efficiency of 90.1% is achieved, and the energy cost is 3.22 × 10-2 $ kg-1 U, significantly lower than the previously reported materials. This work provides a highly efficient strategy for uranium extraction from water.

Pollution Characteristics and Ecological Impact of Screening Analysis of Fishing Port Sediments from Dalian, North China.

Environmental pollution from synthetic chemical mixtures has significant adverse impacts on marine ecosystems. However, identifying the main constituents of chemical mixtures that pose ecological threats is challenging due to the necessity of an integrated workflow for comprehensive identification and toxicological prioritization of pollutants. Here, an all-in-one mass spectrometric strategy integrating target, suspect, and nontarget analysis was used to investigate organic pollutants of concern in fishing port sediments, with 355 pollutants (32 from target analysis, 118 from suspect screening and 205 from nontarget analysis) identified in 11 categories. The chemical classes of polycyclic aromatic hydrocarbons (PAHs), pesticides, and intermediates were the extensively detected chemical classes. The ecological risks of absolutely quantified pollutants (i.e., 16 parent PAHs, 7 organophosphate esters (OPEs), 10 pesticides and 4 benzotriazole ultraviolet absorbers) were assessed using toxicity-weighted concentration ranking, with o,p'-DDT being the major contributor. Under the toxicological priority index (ToxPi) framework, an extended ranking of all identified pollutants was achieved by combining instrument response and detection frequency, with a priority control list of 15 pollutants obtained, of which benzo[ghi]perylene (BghiP) and p,p'-DDE had the highest risk priority. Due to frequent detection rates and significant environmental risks, routine monitoring of petroleum pollutants is considered essential. This study presents a general workflow that includes comprehensive identification and prioritization of pollutants, facilitating chemical management and ecological risk assessment.

RNF39 facilitates antiviral immune responses by promoting K63-linked ubiquitination of STING.

The cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS)-dependent pathway is a key DNA-sensing pathway that recognizes cytosolic DNA and plays a crucial role in initiating innate immune responses against pathogenic microbes and cancer. Various molecules have been identified as regulators of the cGAS-dependent pathway that controls innate immune responses. However, despite the important roles of Stimulator-of-interferon genes (STING) in the cGAS-dependent pathway, the regulation of its activation has not been elucidated. Here, we show that the E3 ubiquitin ligase, RING finger protein 39 (RNF39), interacts with STING in macrophages and HERK293T cells. Moreover, RNF39 accelerates DNA-sensing pathways by promoting lysine (K)63-linked ubiquitination of STING, and then facilitating the formation of STING-TBK1 complex. Concordantly, Rnf39 deficiency inhibits innate immune responses triggered by DNA viral infection and accelerates viral replication. Furthermore, herpes simplex virus-1 (HSV-1) infection induces RNF39 expression in an IFN-I-dependent manner. Thus, we outline a novel mechanism for controlling STING activation and a feedback mechanism for controlling antiviral immune responses. RNF39 could be a priming intervention target for the prevention and treatment of viral diseases, especially DNA viral infections.

A knowledge-transfer-based approach for combining ordinal regression and medical scoring system in the early prediction of sepsis with electronic health records.

OBJECTIVE: The prediction of sepsis, especially early diagnosis, has received a significant attention in biomedical research. In order to improve current medical scoring system and overcome the limitations of class imbalance and sample size of local EHR (electronic health records), we propose a novel knowledge-transfer-based approach, which combines a medical scoring system and an ordinal logistic regression model. MATERIALS AND METHODS: Medical scoring systems (i.e. NEWS, SIRS and QSOFA) are generally robust and useful for sepsis diagnosis. With local EHR, machine-learning-based methods have been widely used for building prediction models/methods, but they are often impacted by class imbalance and sample size. Knowledge distillation and knowledge transfer have recently been proposed as a combination approach for improving the prediction performance and model generalization. In this study, we developed a novel knowledge-transfer-based method for combining a medical scoring system (after a proposed score transformation) and an ordinal logistic regression model. We mathematically confirmed that it was equivalent to a specific form of the weighted regression. Furthermore, we theoretically explored its effectiveness in the scenario of class imbalance. RESULTS: For the local dataset and the MIMIC-IV dataset, the VUS (the volume under the multi-dimensional ROC surface, a generalization measure of AUC-ROC for ordinal categories) of the knowledge-transfer-based model (ORNEWS) based on the NEWS scoring system were 0.384 and 0.339, respectively, while the VUS of the traditional ordinal regression model (OR) were 0.352 and 0.322, respectively. Consistent analysis results were also observed for the knowledge-transfer-based models based on the SIRS/QSOFA scoring systems in the ordinal scenarios. Additionally, the predicted probabilities and the binary classification ROC curves of the knowledge-transfer-based models indicated that this approach enhanced the predicted probabilities for the minority classes while reducing the predicted probabilities for the majority classes, which improved AUCs/VUSs on imbalanced data. DISCUSSION: Knowledge transfer, which combines a medical scoring system and a machine-learning-based model, improves the prediction performance for early diagnosis of sepsis, especially in the scenarios of class imbalance and limited sample size.

Electric-field assisted cascade reactions to create alginate/carboxymethyl chitosan composite hydrogels with gradient architecture and reconfigurable mechanical properties.

Rational designs of polysaccharide-based hydrogels with organ-like three-dimensional architecture provide a great possibility for addressing the shortages of allograft tissues and organs. However, spatial-temporal control over structure in bulk hydrogel and acquire satisfied mechanical properties remain an intrinsic challenge to achieve. Here, we show how electric-field assisted molecular self-assembly can be coupled to a directional reaction-diffusion (RD) process to produce macroscopic hydrogel in a controllable manner. The electrical energy input was not only to generate complex molecule gradients and initiate the molecular self-assembly, but also to guide/facilitate the RD processes for the gel rapid growth via a cascade construction interaction. The hydrogel mechanical properties can be tuned and enhanced by using an interpenetrating biopolymer network and multiple ionic crosslinkers, leading to a wide-range of mechanical modulus to match with biological organs or tissues. We demonstrate diverse 3D macroscopic hydrogels can be easily prepared via field-assisted directional reaction-diffusion and specific joint interactions. The humility-triggered dissipation of functional gradients and antibacterial performance confirm that the hydrogels can serve as an optically variable soft device for wound management. Therefore, this work provides a general approach toward the rational fabrication of soft hydrogels with controlled architectures and functionality for advanced biomedical systems.

Recent advances in pharmaceutical cocrystals of theophylline.

Currently, cocrystallization is a promising strategy for tailoring the physicochemical properties of active pharmaceutical ingredients. Theophylline, an alkaloid and the most primary metabolite of caffeine, is a readily available compound found in tea and coffee. It functions primarily as a bronchodilator and respiratory stimulant, making it a mainstay treatment for lung diseases like asthma. Theophylline's additional potential benefits, including anti-inflammatory and anticancer properties, and its possible role in neurological disorders, have garnered significant research interest. Cocrystal formation presents a viable approach to improve the physicochemical properties of theophylline and potentially mitigate its toxic effects. This review comprehensively explores several successful studies that utilized cocrystallization to favorably alter the physicochemical properties of theophylline or its CCF. Notably, cocrystals can not only enhance the solubility and bioavailability of theophylline but also exhibit synergistic effects with other APIs. The review further delves into the hydrogen bonding sites within the theophylline structure and the hydrogen bonding networks observed in cocrystal structures.

A novel approach to the analysis of Overall Survival (OS) as response with Progression-Free Interval (PFI) as condition based on the RNA-seq expression data in The Cancer Genome Atlas (TCGA).

BACKGROUND: Overall Survival (OS) and Progression-Free Interval (PFI) as survival times have been collected in The Cancer Genome Atlas (TCGA). It is of biomedical interest to consider their dependence in pathway detection and survival prediction. We intend to develop novel methods for integrating PFI as condition based on parametric survival models for identifying pathways associated with OS and predicting OS. RESULTS: Based on the framework of conditional probability, we developed a family of frailty-based parametric-models for this purpose, with exponential or Weibull distribution as baseline. We also considered two classes of existing methods with PFI as a covariate. We evaluated the performance of three approaches by analyzing RNA-seq expression data from TCGA for lung squamous cell carcinoma and lung adenocarcinoma (LUNG), brain lower grade glioma and glioblastoma multiforme (GBMLGG), as well as skin cutaneous melanoma (SKCM). Our focus was on fourteen general cancer-related pathways. The 10-fold cross-validation was employed for the evaluation of predictive accuracy. For LUNG, p53 signaling and cell cycle pathways were detected by all approaches. Furthermore, three approaches with the consideration of PFI demonstrated significantly better predictive performance compared to the approaches without the consideration of PFI. For GBMLGG, ten pathways (e.g., Wnt signaling, JAK-STAT signaling, ECM-receptor interaction, etc.) were detected by all approaches. Furthermore, three approaches with the consideration of PFI demonstrated better predictive performance compared to the approaches without the consideration of PFI. For SKCM, p53 signaling pathway was detected only by our Weibull-baseline-based model. And three approaches with the consideration of PFI demonstrated significantly better predictive performance compared to the approaches without the consideration of PFI. CONCLUSIONS: Based on our study, it is necessary to incorporate PFI into the survival analysis of OS. Furthermore, PFI is a survival-type time, and improved results can be achieved by our conditional-probability-based approach.

QTL Mapping of Fiber- and Seed-Related Traits in Chromosome Segment Substitution Lines Derived from Gossypium hirsutum × Gossypium darwinii.

A narrow genetic basis limits further the improvement of modern Gossypium hirsutum cultivar. The abundant genetic diversity of wild species provides available resources to solve this dilemma. In the present study, a chromosome segment substitution line (CSSL) population including 553 individuals was established using G. darwinii accession 5-7 as the donor parent and G. hirsutum cultivar CCRI35 as the recipient parent. After constructing a high-density genetic map with the BC1 population, the genotype and phenotype of the CSSL population were investigated. A total of 235 QTLs, including 104 QTLs for fiber-related traits and 132 QTLs for seed-related traits, were identified from four environments. Among these QTLs, twenty-seven QTLs were identified in two or more environments, and twenty-five QTL clusters consisted of 114 QTLs. Moreover, we identified three candidate genes for three stable QTLs, including GH_A01G1096 (ARF5) and GH_A10G0141 (PDF2) for lint percentage, and GH_D01G0047 (KCS4) for seed index or oil content. These results pave way for understanding the molecular regulatory mechanism of fiber and seed development and would provide valuable information for marker-assisted genetic improvement in cotton.

[Genetic analysis and prenatal diagnosis for a Chinese pedigree affected with Autosomal dominant polycystic kidney disease].

OBJECTIVE: To explore the clinical phenotype and genetic etiology for a Chinese pedigree affected with Autosomal dominant polycystic kidney disease (ADPKD). METHODS: A pedigree with ADPKD diagnosed at the Department of Gynaecology of the First Affiliated Hospital of Zhengzhou University in December 2020 was selected as the study subject. Clinical data of the pedigree was collected, and whole exome sequencing (WES) was carried out for the proband. Candidate variants were verified by Sanger sequencing of the proband and her relatives. RESULTS: Fetal ultrasonography showed increased volume and parenchymal echogenicity in both kidneys. The fetus was found to harbor c.11098C>T (p.R3700C) and c.11039T>C (p.F3680S) compound heterozygous variants of the PKD1 gene, which were respectively inherited from its mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PM1+PM2_supporting+PP3). CONCLUSION: The c.11098C>T (p.R3700C) and c.11039T>C (p.F3680S) compound heterozygous variants of the PKD1 gene probably underlay the ADPKD in the fetus. Above finding has provided guidance for the genetic counseling and prenatal diagnosis for this pedigree.

SEPT9: From pan-cancer to lung squamous cell carcinoma.

BACKGROUND: SEPT9 is a pivotal cytoskeletal GTPase that regulates diverse biological processes encompassing mitosis and cytokinesis. While previous studies have implicated SEPT9 in tumorigenesis and development; comprehensive pan-cancer analyses have not been performed. This study aims to systematically explore its role in cancer screening, prognosis, and treatment, addressing this critical gap. METHODS: Gene and protein expression data containing clinical information were obtained from public databases for pan-cancer analyses. Additionally, clinical samples from 90 patients with lung squamous cell carcinoma (LUSC) were used to further experimentally validate the clinical significance of SEPT9. In addition, the molecular docking tool was used to analyze the affinities between SEPT9 protein and drugs. RESULTS: SEPT9 is highly expressed in various cancers, and its aberrant expression correlates with genetic alternations and epigenetic modifications, leading to adverse clinical outcomes. Take LUSC as an example, additional dataset analyses and immunohistochemical experiments further confirm the diagnostic and prognostic values as well as the clinical relevance of the SEPT9 gene and protein. Functional enrichment, single-cell expression, and immune infiltration analyses revealed that SEPT9 promotes malignant tumor progression and modulates the immune microenvironments, enabling patients to benefit from immunotherapy. Moreover, drug sensitivity and molecular docking analyses showed that SEPT9 is associated with the sensitivity and resistance of multiple drugs and has stable binding activity with them, including Vorinostat and OTS-964. To harness its prognostic and therapeutic potential in LUSC, a mitotic spindle-associated prognostic model including SEPT9, HSF1, ARAP3, KIF20B, FAM83D, TUBB8, and several clinical characteristics, was developed. This model not only improves clinical outcome predictions but also reshapes the immune microenvironment, making immunotherapy more effective for LUSC patients. CONCLUSION: This is the first study to systematically analyze the role of SEPT9 in cancers and innovatively apply the mitotic spindle-associated model to LUSC, fully demonstrating its potential as a valuable biomarker for cancer screening and prognosis, and highlighting its application value in promoting immunotherapy and chemotherapy, particularly for LUSC.

Endothelial Cells Mediated by STING Regulate Oligodendrogenesis and Myelination During Brain Development.

Oligodendrocyte precursor cells (OPCs) migrate extensively using blood vessels as physical scaffolds in the developing central nervous system. Although the association of OPCs with the vasculature is critical for migration, the regulatory mechanisms important for OPCs proliferative and oligodendrocyte development are unknown. Here, a correlation is demonstrated between the developing vasculature and OPCs response during brain development. Deletion of endothelial stimulator of interferon genes (STING) disrupts angiogenesis by inhibiting farnesyl-diphosphate farnesyltransferase 1 (FDFT1) and thereby reducing cholesterol synthesis. Furthermore, the perturbation of metabolic homeostasis in endothelial cells increases interleukin 17D production which mediates the signal transduction from endothelial cells to OPCs, which inhibits oligodendrocyte development and myelination and causes behavioral abnormalities in adult mice. Overall, these findings indicate how the endothelial STING maintains metabolic homeostasis and contributes to oligodendrocyte precursor cells response in the developing neocortex.

Diffusion behavior and transport risk of bioaerosol particles in a domestic waste landfill site in an arid and cold region of northwestern China.

Bioaerosols have attracted increasing attention as novel contaminants because of their potential role in the spread of disease. In this study, sampling sites were established in a landfill in northwestern China with the aim of investigating the emission and diffusion characteristics of bioaerosols. The results revealed that the counts of airborne bacteria released by landfill cover area (LCA) and waste dumping area (WDA) located in the landfill area reached 18 193 ± 30 CFU/m3 and 10 948 ± 105 CFU/m3, respectively. These two aeras were the main sources of bioaerosol generation. Meanwhile, Corynebacterium spp., Bacteroidetes spp., and Pseudomonas spp. were identified as potential pathogens. A Gaussian model was applied to simulate the diffusion of the bioaerosols; the influence distance was calculated as 12 km from the boundary of the landfill site. The potential health risks of bioaerosol exposure to on-site workers and nearby residents were calculated and evaluated in terms of aerosol concentration, particle size, and pathogenic bacteria. The present study promotes the recognition of the emission behavior of microorganisms in aerosol particles and provides a basis for controlling bioaerosol contamination from landfill sites, particularly those located in cold and arid northwestern regions of China.

Establishment of a CD8+ T cells-related prognostic risk model for acral melanoma based on single-cell and bulk RNA sequencing.

BACKGROUND: CD8+ T cells have been recognized as crucial factors in the prognosis of melanoma. However, there is currently a lack of gene markers that accurately describe their characteristics and functions in acral melanoma (AM), which hinders the development of personalized medicine. METHODS: Firstly, we explored the composition differences of immune cells in AM using single-cell RNA sequencing (scRNA-seq) data and comprehensively characterized the immune microenvironment of AM in terms of composition, developmental differentiation, function, and cell communication. Subsequently, we constructed and validated a prognostic risk scoring model based on differentially expressed genes (DEGs) of CD8+ T cells using the TCGA-SKCM cohort through Lasso-Cox method. Lastly, immunofluorescence staining was performed to validate the expression of four genes (ISG20, CCL4, LPAR6, DDIT3) in AM and healthy skin tissues as included in the prognostic model. RESULTS: The scRNA-seq data revealed that memory CD8+ T cells accounted for the highest proportion in the immune microenvironment of AM, reaching 70.5%. Cell-cell communication analysis showed extensive communication relationships among effector CD8+ T cells. Subsequently, we constructed a prognostic scoring model based on DEGs derived from CD8+ T cell sources. Four CD8+ T cell-related genes were included in the construction and validation of the prognostic model. Additionally, immunofluorescence results demonstrated that ISG20 and CCL4 were downregulated, while LPAR6 and DDIT3 were upregulated in AM tissues compared to normal skin tissues. CONCLUSION: Identifying biomarkers based on the expression levels of CD8+ T cell-related genes may be an effective approach for establishing prognostic models in AM patients. The independently prognostic risk evaluation model we constructed provides new insights and theoretical support for immunotherapy in AM.

Competitive coordination assisted scalable fabrication of FITC­nickel frameworks anchored nanofiber paper for colorimetric/fluorescent monitoring of shrimp freshness.

A novel type of colorimetric/fluorescent nanopaper indicator has been developed from the melt-extruded poly (vinyl alcohol-co-ethylene) nanofibers with surface anchored metal-organic frameworks (MOFs) by an interfacial coordination strategy. Specifically, the fluorescein isothiocyanate molecules could be anchored to the nanofiber surface by nickel ions and co-assembled into a hydrophilic nanocoating via a dynamic water/alcohol solvent evaporation method. Interestingly, this hydrophilic surface enables fast adsorption of moistures and interaction with biological amine vapors, resulting a saffron cake-layer of MOF nanocrystals with ultra-sensitive colorimetric/fluorescent responses based on an alkaline pH/ammonia induced competitive coordination mechanism. Finally, these porous nanofibrous matrix and active nanocoating make the nano-paper an ultra-sensitive optical platform for in-situ monitoring of the shrimp freshness from mins to weeks. Therefore, this composite film shows great potential into advanced paper-based indicators for food quality control and safety in processing industry.

Sulfonylation of Pyridyl Phosphonium Salts with Sulfinate Salts in Aqueous Media for the Synthesis of 4-Pyridyl Sulfones via C-P Bond Cleavage.

A Na2S2O8-initiated sulfonylation of pyridyl phosphonium salts with sulfinate salts in aqueous media has been developed for facile access to 4-pyridyl sulfones. The reactions, which employed pyridyl phosphonium salts as efficient pyridylation agents via C-P bond activation, showed both broad substrate generality and good functional group compatibility. In addition, the scale-up synthesis and the late-stage modification of pharmaceutically active complex molecules (e.g., loratadine, bisacodyl) could also be successfully realized.