Deterministic positioning and alignment of a single-molecule exciton in plasmonic nanodimer for strong coupling.

Experimental realization of strong coupling between a single exciton and plasmons remains challenging as it requires deterministic positioning of the single exciton and alignment of its dipole moment with the plasmonic fields. This study aims to combine the host-guest chemistry approach with the cucurbit[7]uril-mediated active self-assembly to precisely integrate a single methylene blue molecule in an Au nanodimer at the deterministic position (gap center of the nanodimer) with the maximum electric field (EFmax) and perfectly align its transition dipole moment with the EFmax, yielding a large spectral Rabi splitting of 116 meV for a single-molecule exciton-matching the analytical model and numerical simulations. Statistical analysis of vibrational spectroscopy and dark-field scattering spectra confirm the realization of the single exciton strong coupling at room temperature. Our work may suggest an approach for achieving the strong coupling between a deterministic single exciton and plasmons, contributing to the development of room-temperature single-qubit quantum devices.

Complete Mitogenome sequencing of the fish louse Argulus japonicus (Crustacea: Branchiura): Comparative analyses and phylogenetic implications.

The fish louse Argulus japonicus, a branchiuran crustacean of the Argulidae family, is attracting increasing attention because of its parasitic tendencies and significant health threats to global fish farming. The mitogenomes can yield a foundation for studying epidemiology, genetic diversity, and molecular ecology and therefore may be used to assist in the surveillance and control of A. japonicus. In this study, we sequenced and assembled the complete mitogenome of A. japonicus to shed light on its genetic and evolutionary blueprint. Our investigation indicated that the 15,045-bp circular genome of A. japonicus encodes 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), and 2 ribosomal RNAs (rRNAs) with significant AT and GC skews. Comparative genomics provided an evolutionary scenario for the genetic diversity of 13 PCGs: all were under purifying selection, with cox1 and nad6 having the lowest and highest evolutionary rates, respectively. Genome-wide phylogenetic trees established a close relationship between species of the families Argulidae (Arguloida) and Armilliferidae (Porocephalida) within Crustacea, and further, A. japonicus and Argulus americanus were determined to be more closely related to each other than to others within the family Argulidae. Single PCG-based phylogenies supported nad1 and nad6 as the best genetic markers for evolutionary and phylogenetic studies for branchiuran crustaceans due to their similar phylogenetic topologies with those of genome-based phylogenetic analyses. To sum up, these comprehensive mitogenomic data of A. japonicus and related species refine valuable marker resources and should contribute to molecular diagnostic methods, epidemiological investigations, and ecological studies of the fish ectoparasites in Crustacea.

Clinical Characteristics and Pathogen Spectrum of Male Genital Fungal Infections in Nanchang Area, South China.

The cutaneous fungal infections in male genitalia are relatively rare, and often present with various atypical clinical symptoms. It was mainly reported in a small number of case reports, while data with large number of patients were rarely reported. In this study, we reported 79 male patients with cutaneous fungal infections on scrotum or penis. The fungal infections were confirmed by microscopic examination directly and fungus culture. Clinical characteristics and predisposing factors were also collected. Of these 79 patients, 72 has lesions on scrotum, 5 on penis and 2 on both scrotum and penis. Trichophyton (T.) rubrum is the most common pathogen, found in 50 (67.6%) patients, which presented diverse clinical manifestation such as majorly erythematous, dry diffused scaly lesions without a clear border, slightly powdery and scutular scalings. Candida (C.) albicans is the secondly common pathogen, found in 21 (28.4%) patients, which also presented diverse lesions such as erythematous with dry whitish scaly lesions and erythematous erosion. The predisposing factors mainly included concomitant fungal infections on sites other than genitalia, especially inguinal region (tinea cruris), application of corticosteroid and high moisture. In conclusion, cutaneous fungal infections in male genitalia could be caused by different fungi, showed atypical or mild clinical appearances in most cases and might be a fungus reservoir, emphasizing the necessity to timely perform the fungi examinations and corresponding therapy.

Alcohol-Processable All-Polymer n-Type Thermoelectrics.

The general strategy for n-type organic thermoelectric is to blend n-type conjugated polymer hosts with small molecule dopants. In this work, all-polymer n-type thermoelectric is reported by dissolving a novel n-type conjugated polymer and a polymer dopant, poly(ethyleneimine) (PEI), in alcohol solution, followed by spin-coating to give polymer host/polymer dopant blend film. To this end, an alcohol-soluble n-type conjugated polymer is developed by attaching polar and branched oligo (ethylene glycol) (OEG) side chains to a cyano-substituted poly(thiophene-alt-co-thiazole) main chain. The main chain results in the n-type property and the OEG side chain leads to the solubility in hexafluorineisopropanol (HFIP). In the polymer host/polymer dopant blend film, the Coulombic interaction between the dopant counterions and the negatively charged polymer chains is reduced and the ordered stacking of the polymer host is preserved. As a result, the polymer host/polymer dopant blend exhibits the power factor of 36.9 µW m-1 K-1, which is one time higher than that of the control polymer host/small molecule dopant blend. Moreover, the polymer host/polymer dopant blend shows much better thermal stability than the control polymer host/small molecule dopant blend. This research demonstrates the high performance and excellent stability of all-polymer n-type thermoelectric.

Nanoconfinement Enables Photoelectrochemical Selective Oxidation of Glycerol via the Microscale Fluid Effect.

The glycerol oxidation reaction (GOR) run with photoelectrochemical cells (PECs) is one of the most promising ways to upgrade biomass because it is thermodynamically favorable, while irreversible overoxidation leads to unsatisfactory product selectivities. Herein, a tunable one-dimensional nanoconfined environment was introduced into the GOR process, which accelerated mass transfer of glycerol via the microscale fluid effect and changed the main oxidation product from formic acid (FA) to glyceraldehyde (GLD), which led to retention of the heavier multicarbon products. The rate of glycerol diffusion in the nanochannels increased by a factor of 4.92 with decreasing inner diameters. The main product from the PEC-selective oxidation of glycerol changed from the C1 product FA to the C3 product GLD with a great selectivity of 60.7%. This work provides a favorable approach for inhibiting further oxidation of multicarbon products and illustrates the importance of microenvironmental regulation in biomass oxidation.

Synthesis of ß-Cyclodextrin@gold Nanoparticles and Its Application on Colorimetric Assays for Ascorbic Acid and Salmonella Based on Peroxidase-like Activities.

The peroxidase-like behaviors of gold nanoparticles (AuNPs) have the potential to the development of rapid and sensitive colorimetric assays for specific food ingredients and contaminants. Here, using NaBH4 as a reducing agent, AuNPs with a supramolecular macrocyclic compound ß-cyclodextrin (ß-CD) capped were synthesized under alkaline conditions. Monodispersal of ß-CD@AuNPs possessed a reduction in diameter size and performed great peroxidase-like activities toward both substrates, H2O2 and TMB. In the presence of H2O2, the color change of TMB oxidization to oxTMB was well-achieved using ß-CD@AuNPs as the catalyst, which was further employed to develop colorimetric assays for ascorbic acid, with a limit of detection as low as 0.2 µM in ddH2O. With the help of the host-guest interaction between ß-CD and adamantane, AuNPs conjugated with nanobodies to exhibit peroxidase-like activities and specific recognition against Salmonella Typhimurium simultaneously. Based on this bifunctional bioprobe, a selective and sensitive one-step colorimetric assay for S. Typhimurium was developed with a linear detection from 8.3 × 104 to 2.6 × 108 CFU/mL and can be provided to spiked lettuce with acceptable recoveries of 97.31% to 103.29%. The results demonstrated that the excellent peroxidase-like behaviors of ß-CD@AuNPs can be applied to develop a colorimetric sensing platform in the food industry.

Returning to Work Following Hematopoietic Cell Transplantation: The Survivor's Perspective.

While curing a patient's underlying disease is the primary goal of physicians performing hematopoietic cell transplantation (HCT), the ultimate objective is to provide patients with optimal post-HCT quality of life. For many survivors, this includes returning to work (RTW). We conducted a survey of 1- to 5-yr post-HCT survivors at our center to evaluate their perspective on facilitators and barriers to RTW as well as to gauge interest in potentially useful RTW support interventions. Survivors aged 18 to 65 yrs (n = 994) were sent an annual survey that included 36 supplementary questions about post-HCT RTW. Survey questions were selected from published national cancer survivor surveys and then modified specifically for HCT survivors. Three hundred forty-four (35%) survivors with a mean age of 53 yrs completed the survey, of whom 272 (79%) had worked prior to their diagnosis. Of those 272 patients, 145 (53%) were working currently and another 22 (8%) had attempted to go back to work following HCT but were not presently working. We found that having had an allogeneic versus autologous HCT (P = .006) was associated with a decreased likelihood of currently working, whereas frequent employer communication (>once a month) (P = .070) and having a more supportive employer (P = .036) were associated with a greater chance of currently working. Of survivors currently working, 45% reported that they had made one or more changes to their work schedule (e.g., flexible schedule or part-time work) or environment (e.g., work from home) upon RTW. Ninety-five percent of responders reported that they could have benefited from RTW support provided by the transplant center, but only 13% indicated that they had received it. Education on RTW challenges, information on disability benefits, and access to physical therapy were among the most requested support interventions. To improve post-HCT quality of life for survivors open to assistance, providers should address work status and goals, recognize barriers to successful return, and offer RTW support including working directly with employers. Allogeneic HCT survivors are particularly vulnerable to failing attempts to RTW and should be the target of retention interventions. A previously published manuscript on RTW guidance for providers of stem cell transplant patients endorsed by the American Society of Transplant and Cellular Therapy is available in Open Access and can be used as a tool to counsel and support these patients.

High performance artificial visual perception and recognition with a plasmon-enhanced 2D material neural network.

The development of neuromorphic visual systems has recently gained momentum due to their potential in areas such as autonomous vehicles and robotics. However, current machine visual systems based on silicon technology usually contain photosensor arrays, format conversion, memory and processing modules. As a result, the redundant data shuttling between each unit, resulting in large latency and high-power consumption, seriously limits the performance of neuromorphic vision chips. Here, we demonstrate an artificial neural network (ANN) architecture based on an integrated 2D MoS2/Ag nanograting phototransistor array, which can simultaneously sense, pre-process and recognize optical images without latency. The pre-processing function of the device under photoelectric synergy ensures considerable improvement of efficiency and accuracy of subsequent image recognition. The comprehensive performance of the proof-of-concept device demonstrates great potential for machine vision applications in terms of large dynamic range (180 dB), high speed (500 ns) and low energy consumption per spike (2.4 × 10-17 J).

Effect of high NEFA concentration on lipid metabolism disorders in hepatocytes based on lipidomics.

Introduction: High concentrations of nonesterified fatty acids (NEFA) is the key of characteristic of fatty liver in dairy cows. Therefore, the aim of this study was to investigate the effect of high concentration of NEFA on lipid metabolism in hepatocytes through the lipidomic approach and molecular biology techniques. Methods: Stimulate AML-12 cells with different concentrations of NEFA, observe the cellular lipid accumulation, and select 0.6 mM NEFA stimulation concentration for subsequent experiments. Collect cells for lipidomics analysis. Results: High concentration of NEFA (0.6-2.4 mM) significantly reduced the cell viability in a concentration-dependent manner, indicating that high concentrations of NEFA have lipotoxicity on hepatocytes. In addition, NEFA promoted triglycerides (TAG) accumulation, increased the mRNA expression of the lipogenic molecules SREBP1c and FASN, and decreased the mRNA expression of lipolytic molecules CPT1A and HSL in hepatocytes. Mechanistically, high concentration of NEFA induced lipid metabolism disorders in hepatocytes by regulating metabolic pathways such as glycerol phospholipid metabolism, glycosyl phosphatidylinositol anchored biosynthesis, triglyceride metabolism, sphingolipid metabolism, and inositol phosphate metabolism. Discussion: High concentration of NEFA is lipotoxic to cells, promoting lipid accumulation. LPE (18:2), LPE (18:3), LPE (18:1) via glycerophospholipid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, glycerolipid metabolism, sphingolipid metabolism, and inositol phosphate metabolism, indicating their potential regulation role in the pathogenesis of fatty liver.

Activated CD4 T cells/Tregs derived immune-metabolism signature provide precise prognosis assessment for gastric cancer and beneficial for treatment option.

Background: The prognostic significance of the ratio of activated CD4 T cells to Tregs infiltrating tumor tissues in gastric cancer (GC) remains unknown. Materials and methods: For the quantification of infiltration of immune cells, the ssGSEA algorithm, which is a single sample gene set enrichment analysis, was utilized. Group A was defined as having activated CD4 T cells/Tregs >1, while group B was defined as having activated CD4 T cells/Tregs <1. To compare the overall survival (OS) of the two groups, the Kaplan-Meier survival analysis was employed. The R package 'limma' was used to identify the immune and metabolism related genes that were expressed differentially between the two groups, with a false discovery rate (FDR) less than 0.05. The risk score (RS) was constructed by combining univariate Cox regression analysis, LASSO penalized Cox regression analysis, and multivariate Cox regression analysis. The median RS was used to classify high-risk (HR) and low-risk (LR) groups. Results: A predicted unfavorable outcome of GC was observed when the ratio of activated CD4 T cells to Tregs was less than 1. Our proposed RS was utilized for prognostic risk categorization in ten distinct independent cohorts (TCGA-STAD, n = 371; GSE84437, n = 433; GSE26253, n = 432; GSE13861, n = 65; GSE15459, n = 192; GSE26899, n = 93; GSE26901, n = 109; GSE28541, n = 40; GSE34942, n = 56; GSE62254, n = 300) and exhibited exceptional precision. In terms of tumor microenvironment (TME) and treatment strategies, compared to the LR group, the HR group was characterized by a higher infiltration levels of stromal cells, Tregs, macrophages, Tfh, mast cells, and NK cells, inclined to activated CD4 T cells/Tregs <1, and exhibited insensitivity to immunotherapy and multiple chemotherapy drugs. In relation to the potential molecular mechanism, the excessive activation of oncogenic pathways such as MAPK, hedgehog, WNT, calcium, and TGF-ß signaling pathways may accelerate the malignant progression of GC by stimulating angiogenesis, promoting EMT, and altering ECM. Conversely, the overactivation of the P53 pathway is likely to inhibit tumor proliferation by regulating the cell cycle. Conclusion: The immune-metabolism signature associated with the ratio of activated CD4 T cells and Tregs could be used to assess prognosis, TME, and treatment strategies in GC patients.

Characterization of Immunosuppressive Myeloid Cells in Merkel Cell Carcinoma: Correlation with Resistance to PD-1 Pathway Blockade.

PURPOSE: Merkel cell carcinoma (MCC) is a highly immunogenic skin cancer. Although essentially all MCCs are antigenic through viral antigens or high tumor mutation burden, MCC has a response rate of only approximately 50% to PD-(L)1 blockade suggesting barriers to T-cell responses. Prior studies of MCC immunobiology have focused on CD8 T-cell infiltration and their exhaustion status, while the role of innate immunity, particularly myeloid cells, in MCC remains underexplored. EXPERIMENTAL DESIGN: We utilized single-cell transcriptomics from 9 patients with MCC and multiplex IHC staining of 54 patients' preimmunotherapy tumors, to identify myeloid cells and evaluate association with immunotherapy response. RESULTS: Single-cell transcriptomics identified tumor-associated macrophages (TAM) as the dominant myeloid component within MCC tumors. These TAMs express an immunosuppressive gene signature characteristic of monocytic myeloid-derived suppressor cells and importantly express several targetable immune checkpoint molecules, including PD-L1 and LILRB receptors, that are not present on tumor cells. Analysis of 54 preimmunotherapy tumor samples showed that a subset of TAMs (CD163+, CD14+, S100A8+) selectively infiltrated tumors that had significant CD8 T cells. Indeed, higher TAM prevalence was associated with resistance to PD-1 blockade. While spatial interactions between TAMs and CD8 T cells were not associated with response, myeloid transcriptomic data showed evidence for cytokine signaling and expression of LILRB receptors, suggesting potential immunosuppressive mechanisms. CONCLUSIONS: This study further characterizes TAMs in MCC tumors and provides insights into their possible immunosuppressive mechanism. TAMs may reduce the likelihood of treatment response in MCC by counteracting the benefit of CD8 T-cell infiltration. See related commentary by Silk and Davar, p. 1076.

[Effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction].

Jiming Powder is a traditional ancient prescription with good therapeutic effect in the treatment of heart failure, but its mechanism lacks further exploration. In this study, a mouse model of coronary artery ligation was used to evaluate the effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction. The study constructed a mouse model of heart failure after myocardial infarction using the method of left anterior descending coronary artery ligation. The efficacy of Jiming Powder was evaluated from multiple angles, including ultrasound imaging, hematoxylin-eosin(HE) staining, Masson staining, Sirius Red staining, and serum myocardial enzyme spectrum detection. Western blot analysis was performed to detect key proteins involved in ventricular remodeling, including transforming growth factor-ß1(TGF-ß1), α-smooth muscle actin(α-SMA), wingless-type MMTV integration site family member 3a(Wnt3a), ß-catenin, matrix metallopeptidase 2(MMP2), matrix metallopeptidase 3(MMP3), TIMP metallopeptidase inhibitor 1(TIMP1), and TIMP metallopeptidase inhibitor 2(TIMP2). The results showed that compared with the model group, the high and low-dose Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVID;s) and diastole(LVID;d), increased the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improved cardiac function in mice after myocardial infarction, and effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactic dehydrogenase(LDH), thus protecting ischemic myocardium. HE staining showed that Jiming Powder could attenuate myocardial inflammatory cell infiltration after myocardial infarction. Masson and Sirius Red staining demonstrated that Jiming Powder effectively inhibited myocardial fibrosis, reduced the collagen Ⅰ/Ⅲ ratio in myocardial tissues, and improved collagen remodeling after myocardial infarction. Western blot results showed that Jiming Powder reduced the expression of TGF-ß1, α-SMA, Wnt3a, and ß-catenin, decreased the levels of MMP2, MMP3, and TIMP2, and increased the level of TIMP1, suggesting its role in inhibiting cardiac fibroblast transformation, reducing extracellular matrix metabolism in myocardial cells, and lowering collagen Ⅰ and α-SMA content, thus exerting an anti-myocardial fibrosis effect after myocardial infarction. This study revealed the role of Jiming Powder in improving ventricular remodeling and treating myocardial infarction, laying the foundation for further research on the pharmacological effect of Jiming Powder.

[Mechanism of Jiming Powder in ameliorating heart failure with preserved ejection fraction based on metabolomics].

In this study, untargeted metabolomics was conducted using the liquid chromatography-tandem mass spectrometry(LC-MS/MS) technique to analyze the potential biomarkers in the plasma of mice with heart failure with preserved ejection fraction(HFpEF) induced by a high-fat diet(HFD) and nitric oxide synthase inhibitor(Nω-nitro-L-arginine methyl ester hydrochloride, L-NAME) and explore the pharmacological effects and mechanism of Jiming Powder in improving HFpEF. Male C57BL/6N mice aged eight weeks were randomly assigned to a control group, a model group, an empagliflozin(10 mg·kg~(-1)·d~(-1)) group, and high-and low-dose Jiming Powder(14.3 and 7.15 g·kg~(-1)·d~(-1)) groups. Mice in the control group were fed on a low-fat diet, and mice in the model group and groups with drug intervention were fed on a high-fat diet. All mice had free access to water, with water in the model group and Jiming Powder groups being supplemented with L-NAME(0.5 g·L~(-1)). Drugs were administered on the first day of modeling, and 15 weeks later, blood pressure and cardiac function of the mice in each group were measured. Heart tissues were collected for hematoxylin-eosin(HE) staining to observe pathological changes and Masson's staining to observe myocardial collagen deposition. Untargeted metabolomics analysis was performed on the plasma collected from mice in each group, and metabolic pathway analysis was conducted using MetaboAnalyst 5.0. The results showed that the blood pressure was significantly lower and the myocardial concentric hypertrophy and left ventricular diastolic dysfunction were significantly improved in both the high-dose and low-dose Jiming Powder groups as compared with those in the model group. HE and Masson staining showed that both high-dose and low-dose Jiming Powder significantly alleviated myocardial fibrosis. In the metabolomics experiment, 23 potential biomarkers were identified and eight strongly correlated metabolic pathways were enriched, including linoleic acid metabolism, histidine metabolism, alpha-linolenic acid metabolism, glycerophospholipid metabolism, purine metabolism, porphyrin and chlorophyll metabolism, arachidonic acid metabolism, and pyrimidine metabolism. The study confirmed the pharmacological effects of Jiming Powder in lowering blood pressure and ameliorating HFpEF and revealed the mechanism of Jiming Powder using the metabolomics technique, providing experimental evidence for the clinical application of Jiming Powder in treating HFpEF and a new perspective for advancing and developing TCM therapy for HFpEF.

Effects of Stigmasterol on 3-Chloropropane-1,2-diol Fatty Acid Esters and Aldehydes Formation in Heated Soybean Oil.

In this study, we investigated the inhibitory effects of three soybean isoflavones and two soybean phytosterols on the formation of 3-chloropropane-1,2-diol fatty acid esters (3-MCPDE) and aldehydes in heated soybean oil model. 0.4 mM of genistin, genistein, daidzein, stigmasterol, and ß-sitosterol significantly reduced 3-MCPDE formation by 25.7, 51.4, 21.4, 61.6, and 55.7%, and total aldehydes formation by 42.03, 43.94, 28.36, 54.74, and 39.23%, respectively. Further study showed that stigmasterol reduced the content of glycidyl esters (GEs) and glycidol, two key intermediates of 3-MCPDE, and prevented fatty acids degradation in the oils. Moreover, the effects of continuous frying time on the content of stigmasterol and the migration of stigmasterol were evaluated in the fried dough sticks model system. The content of stigmasterol in soybean oil was found to be significantly decreased with prolonged heating time. The concentrations of stigmasterol in fried dough sticks and the migration rates of stigmasterol from soybean oil to fried dough sticks decreased with repeated frying sessions. In addition, stigmasterol undergoes oxidative changes during heat treatment, and the oxidation products including 5,6α-epoxystigmasterol, 5,6ß-epoxystigmasterol, 7α-hydroxystigmasterol, 7ß-hydroxystigmasterol, stigmasterlol-3ß,5α,6ß-triol, and 7-ketostigmasterol were identified in the frying oils but not in the fried dough sticks. Overall, stigmasterol could be added to soybean oil to reduce 3-MCPDE and aldehydes formation, and reacting with GEs/glycidol and protection of lipid acids from oxidation may be the mechanism of action of stigmasterol.

Functional Diversity of Mammalian Small Heat Shock Proteins: A Review.

The small heat shock proteins (sHSPs), whose molecular weight ranges from 12∼43 kDa, are members of the heat shock protein (HSP) family that are widely found in all organisms. As intracellular stress resistance molecules, sHSPs play an important role in maintaining the homeostasis of the intracellular environment under various stressful conditions. A total of 10 sHSPs have been identified in mammals, sharing conserved α-crystal domains combined with variable N-terminal and C-terminal regions. Unlike large-molecular-weight HSP, sHSPs prevent substrate protein aggregation through an ATP-independent mechanism. In addition to chaperone activity, sHSPs were also shown to suppress apoptosis, ferroptosis, and senescence, promote autophagy, regulate cytoskeletal dynamics, maintain membrane stability, control the direction of cellular differentiation, modulate angiogenesis, and spermatogenesis, as well as attenuate the inflammatory response and reduce oxidative damage. Phosphorylation is the most significant post-translational modification of sHSPs and is usually an indicator of their activation. Furthermore, abnormalities in sHSPs often lead to aggregation of substrate proteins and dysfunction of client proteins, resulting in disease. This paper reviews the various biological functions of sHSPs in mammals, emphasizing the roles of different sHSPs in specific cellular activities. In addition, we discuss the effect of phosphorylation on the function of sHSPs and the association between sHSPs and disease.

Chitooligosaccharide reconstitutes intestinal mucus layer to improve oral absorption of water-soluble drugs.

Intestinal mucus is a complex natural hydrogel barrier with unique physical properties that impede the absorption of various oral drugs. Both washout from the upper water layer and the physical resistance of the mucus layer particularly affect bioavailability of, especially, highly water-soluble molecules. One potential strategy for designing pharmaceutical formulations is to add absorption enhancers (AEs). However, there are few reports of AEs that work on mucus and their underlying mechanisms, leading to imprecise application. In this study, we investigated chitooligosaccharide (COS) as a safe, low-cost, and effective oral drug AE. We revealed the hydrodynamic law of interaction between COS and the intestinal mucus layer, which was associated with absorption benefiting mucus structural reconstruction. Based on this, we designed a translational strategy to improve the bioavailability of a group of soluble oral drugs by drinking COS solution before administration. Moreover, this research is expected to expand its application scenario by reducing drug dosage such as avoiding gastro-intestinal irritation and slowing veterinary antibiotic resistance.

Immunotherapy Efficacy-related Risk Classifier Differentiate Prognostic Characteristics of Gastric Cancer-A Large-scale Retrospective Study.

Prognostic signatures related to the efficacy of immunotherapy have not been determined in gastric cancer (GC). We identified the differentially expressed genes between the CR/PR and SD/PD groups with the R package "limma" (false discovery rate <0.05) in the IMvigor210 data set. The GSE13861 (n=65), GSE15459 (n=192), GSE26899 (n=93), GSE26901 (n=109), GSE28541 (n=40), GSE34942 (n=56), and GSE62254 (n=300) cohorts were merged into a training cohort (n=855). Univariate Cox regression analysis, LASSO penalized Cox regression analysis, and multivariate Cox regression analysis were jointly applied to construct the prognostic model. The Cancer Genome Atlas (TCGA)-STAD (n=371), GSE84437 (n=433), GSE26253 (n=432), and IMvigor210 (n=348) cohorts were utilized for external validation. The GC patients were divided into 16 subgroups according to clinical features for universal applicability validation. Repeated validation confirmed that the overall survival of the high-risk (HR) group was significantly reduced compared with that of the low-risk (LR) group. The HR group showed a higher infiltration abundance of regulatory T cells, macrophages, T follicular helper cells, and natural killer T cells, whereas the infiltration levels of activated CD4 T cells and monocytes were upregulated in the LR group. The calcium, TGF-ß, MAPK, Hedgehog, and KRAS signaling pathways were overactivated in the HR group, while the hallmarks related to DNA damage repair and metabolism were enriched in the LR group. In addition, the LR group had high tumor mutation burden, FLG, and OBSCN mutations. A prognostic risk classifier for GC patients was identified and validated by carrying out a multicenter retrospective study.

Neglected Adult Tinea Capitis in South China: A Retrospective Study in Nanchang, Jiangxi Province, from 2007 to 2021.

Tinea capitis (TC) in adults is much less frequently diagnosed in comparison to TC in children. In this study, we explored retrospectively adult TC in a specialized dermatology hospital, located in South China, during the years 2007-2021. Among 1037 TC cases, 168 (16.2%) patients were older than 18 years. The majority of adults with TC, 77.38% (130/168), were older than 40, with a peak in the age of 51-60 years (40/168, 23.81%). Before presenting at our hospital, many of patients did not got proper treatment due to misdiagnosis or simply did not consulted an appropriate clinic. 60.71% (102/168) of the patients reported symptoms lasting for more than 1 year and 29.76% (50/168) reported chronic scalp problems of at least 10 years. And 27.38% (46/168) of the patients had an immunocompromised status, including long-term use of corticosteroids shampoo, type 2 diabetes mellitus (DM), psoriasis vulgaris, rheumatoid arthritis, systemic lupus erythematosus or bullous pemphigoid. As for clinical presentation, 87.5% (147/168) of the cases presented as black dot type of TC and anthropophilic dermatophytes were the predominant etiology, with Trichophyton violaceum (126), T. tonsurans (15), T. rubrum (8) and T. shoenleinii (6). Grey patch type of TC (3.57%, 6/168) was seldom in Jiangxi Province and zoophilic/geophilic dermatophytes were rare. Our study indicates that anthropophilic Trichophyton species can cause long-lasting TC in adults. Not in all cases, the manifestation had symptom clearly indicating a dermatophyte-related TC. Thus, patients with long-lasting scalp inflammation, also older ones, should be examined for the presence of dermatophyte-related TC.

Highly Tunable Lateral Homojunction Formed in Two-Dimensional Layered CuInP2S6 via In-Plane Ionic Migration.

As basic building blocks for next-generation information technologies devices, high-quality p-n junctions based on van der Waals (vdW) materials have attracted widespread interest. Compared to traditional two-dimensional (2D) heterojunction diodes, the emerging homojunctions are more attractive owing to their intrinsic advantages, such as continuous band alignments and smaller carrier trapping. Here, utilizing the long-range migration of Cu+ ions under an in-plane electric field, a lateral p-n homojunction was constructed in the 2D layered copper indium thiophosphate (CIPS). The symmetric Au/CIPS/Au devices demonstrate an electric-field-driven resistance switching (RS) accompanied by a rectification behavior without any gate control. Moreover, such rectification behavior can be continuously modulated by poling voltage. We deduce that the reversable rectifying RS behavior is governed by the effective lateral build-in potential and the change of the interfacial barrier during the poling process. Furthermore, the CIPS p-n homojuction is evidenced by the photovoltaic effect, with the spectral response extending up to the visible region due to the better photogenerated carrier separation efficiency. Therefore, this work provides a facile route to fabricate homojunctions through electric-field-driven ionic migration.