Chemical modification, structure elucidation and antifungal mechanism studies of a peptide extracted from garlic (Allium sativum L.).

BACKGROUND: Garlic is a promising source of antimicrobial peptide separation, and chemical modification is an effective method for activity improvement. The present study aimed to improve the antifungal activity of a peptide extracted from garlic. Chemical modifications were conducted, and the structure-activity relationship and antifungal mechanism were investigated. RESULTS: The results indicated that the cationic charge induced by Lys residue at the N-terminal was important for the antimicrobial activity, and the modified sequence exhibited significant antifungal activity with low mammalian toxicity and a low tendency of drug resistance (p < 0.05). The structure-activity relationship analysis revealed that the modified active peptide had a predominant α-helical structure and an inner cyclic correlation. Transcriptomic analysis showed that peptide KMLKKLFR (Lys-Met-Leu-Lys-Lyse-Leu-Phe-Arg) affected the rRNA processing and carbon metabolism process of Candida albicans. In addition, the membrane potential study indicated a non-membrane destruction mechanism, and molecular docking analysis and a DNA interaction assay suggested promising inner targets. CONCLUSION: The results of the present study indicate that chemical modification by amino acid substitution was effective for antimicrobial activity improvement. The present study would benefit future antimicrobial peptide development and suggests that garlic is a great source of antibacterial peptides and peptide template separations for coping with antibiotic resistance. © 2024 Society of Chemical Industry.

Association between green space and multiple ambient air pollutants with depressive and anxiety symptoms among Chinese adolescents: The role of physical activity.

OBJECTIVE: To explore the association between green space, multiple ambient air pollutants and depressive/anxiety symptoms and the mediating role of physical activity (PA) in Chinese adolescents. METHOD: A school-based health survey was conducted in eight provinces in China in 2021. 22,868 students aged 14.64 (±1.77) years completed standard questionnaires to record details of depressive, anxiety symptoms and PA. We calculated the average normalized difference vegetation index (NDVI) in circular buffers of 200 m, 500 m and 1000 m and estimated the concentrations of PM10, PM2.5, CO, NO2, O3, SO2 around the adolescents' school addresses. RESULTS: The exposure-response curves showed that the lower the NDVI value, the higher the risk of depressive and anxiety symptoms. CO, PM2.5 and SO2 and air pollution score were associated with increased risk of depressive and anxiety symptoms. NDVI in all circular buffers decreased the risk of depressive and anxiety symptoms at low levels of PA, but the associations were not significant at high levels of PA. In the subgroup analysis, PM10, PM2.5, CO, NO2, SO2, AQI and air pollution score increased the risk of depressive and anxiety symptoms at low PA levels, but the associations were not significant at high levels of PA. Mediation analysis indicated that the mediating effect of PA on the association between NDVI, NDVI-200 m NDVI-500 m, CO, PM10, PM2.5, SO2, AQI and depressive/anxiety symptoms was statistically significant（p < 0.05）. CONCLUSION: Middle-high level PA could reduce the strength of association between air pollution and depressive and anxiety symptoms. Meanwhile, the association between green space/air pollution and depressive/anxiety symptoms was partly mediated by PA.

Steam explosion-assisted grinding improves the functional properties and antioxidant activity of Java tea-leaf powders (Clerodendranthus spicatus).

BACKGROUND: Java tea is widely consumed and has multiple health effects. This study established a steam explosion (SE) pretreatment method to prepare Java tea-leaf powders. The physicochemical, functional properties, phenolic extraction, and antioxidant activity of Java tea-leaf powders produced by simple and SE-assisted milling methods were investigated. RESULTS: In comparison with simple milling, SE pretreatment broke the cell wall effectively and reduced the particle size of Java tea-leaf powders. Steam explosion-treated powders showed higher values for sensory signals, bulk and tap density, and for the water solubility index. After SE treatment, the adsorption capacities to glucose, soybean oil, and cholesterol of leaf powders were increased by up to 55, 95, and 80% respectively. The extracts from SE-treated powders also showed higher total polyphenol content and antioxidant activity. CONCLUSION: Steam explosion treatment is helpful for the improvement of functional properties and antioxidant activity, which can benefit the development and application of Java tea-leaf powders. © 2024 Society of Chemical Industry.

Does environmental pollution reduce residents' income? Evidence from CFPS in China.

Understanding the relationship between environmental pollution and residents' income is extremely important for promoting sustained progress and high-quality economic growth. This research examines the impact, mechanism, and heterogeneity of environmental contamination on residents' earnings by fusing the micro data from China Family Panel Survey with the macro data of government statistics. The results reveal that environmental degradation has a significantly negative impact on residents' individual income. Further research on the intermediary mechanism finds that environmental pollution plays a harmful role in residents' income by reducing residents' subjective well-being and labor employment. Besides, the income effect of environmental pollution is significantly heterogeneous among different regions and differentiated groups. The deteriorating environmental quality widens urban-rural income gap and increases wage inequality of inhabitants in eastern, central, and western regions of China. The gender income gap and the income disparity between different income brackets also expand with environmental deterioration. These findings not only prove that long-term development at the cost of the ecological environment is undesirable, but also demonstrate the important role of the improvement of ecological environmental quality in promoting human well-being.

Effects of myricetin and its derivatives on nonenzymatic glycation: A mechanism study based on proteomic modification and fluorescence spectroscopy analysis.

Myricetin and its derivatives, myricitrin and dihydromyricetin, are flavonoids widely presented in foods and phytomedicine that possess tremendous health potential. In this study, we compared the antiglycation activity of myricetin and its derivatives, then investigated the underlying mechanism using proteomic modification and fluorescence spectroscopy analysis. All three compounds exhibited thorough inhibition on nonenzymatic glycation process, with the inhibitory effects on AGEs reaching 85% at 40 µmol/L. They effectively protected bovine serum albumin (BSA) structure by inhibiting protein oxidation, preventing the conversion from α-helix to ß-sheet, and reducing amyloid-like cross-ß structure formation. Among the three compounds, myricetin showed a predominant antiglycation activity. Proteomic analysis identified the early glycated sites that were protected by myricetin, including lysine K235, 256, 336, 421, 420, 489, etc. Additionally, fluorescence spectroscopy revealed spontaneous interactions between BSA and myricetin. Overall, myricetin holds promise as an antiglycation agent in both the food and drug industries.

Effects of social-ecological risk factors and resilience on the relationship between metabolic metrics and mental health among young adults.

The correlation between metabolic metrics and mental health remains underexplored, with few in-depth studies examining whether this association exists among college students and whether it might be moderated by socio-ecological risk factors (SERFs) and mediated by resilience. A follow-up study design investigated the association between baseline metabolic metrics, SERFs and resilience and mental health. A multivariable linear regression model using the PROCESS method established the relationship of SERFs, resilience and metabolic metrics with mental health. Participants were 794 adolescents (mean age: 18.64 [±0.90] years). In multivariable linear regression, the high-level SERFs (ß = 0.124), resilience (ß = -0.042), LCI (ß = 0.072), and RFM (ß = 0.145) were associated with higher depression symptoms, while CVH (ß = 0.602), TyG (ß = 0.295), TyG-BMI (ß = 0.004), and RC (ß = -0.041) were not. An association was also observed between SERFs, resilience, RFM and anxiety. Resilience mediated the relationship between metabolic metrics and depression and anxiety, and SERFs moderated this relationship, demonstrating the relationship between resilience, metabolic metrics, SERFs and mental health. By revealing the potential sociological mechanism underlying the relationship between metabolic metrics and adolescents' mental health, this study provides a theoretical basis for further exploration of the biological foundations of mental health.

Adsorption Potential, Speciation Transformation, and Risk Assessment of Hg-, Cd-, and Pb-Contaminated Soils Using Biochar in Combination with Potassium Dihydrogen Phosphate.

The objective of this study is to develop a remediation technology for composited heavy metal-contaminated soil. Biochars (BC300, BC400, and BC500) derived from corn were combined with potassium dihydrogen phosphate (KH2PO4) to immobilize and remove heavy metal ions, including mercury (Hg2+), cadmium (Cd2+), and lead (Pb2+). The adsorption kinetics of metal ions in aqueous solutions with different concentrations was tested, and the fitting effects of the two models were compared. The findings demonstrate that the joint application of biochar and KH2PO4 could markedly enhance the immobilization efficacy of Pb2+, whereas the utilization of KH2PO4 on its own exhibited a more pronounced immobilization impact on Cd2+. Furthermore, the present study underscores the shortcomings of various remediation techniques that must be taken into account when addressing heavy metal-contaminated soils. It also emphasizes the value of comprehensive remediation techniques that integrate multiple remediation agents. This study offers a novel approach and methodology for addressing the intricate and evolving challenges posed by heavy metal contamination in soil. Its practical value and potential for application are significant.

Updated Progress on Polysaccharides with Anti-Diabetic Effects through the Regulation of Gut Microbiota: Sources, Mechanisms, and Structure-Activity Relationships.

Diabetes mellitus (DM) is a common chronic metabolic disease worldwide. The disturbance of the gut microbiota has a complex influence on the development of DM. Polysaccharides are one type of the most important natural components with anti-diabetic effects. Gut microbiota can participate in the fermentation of polysaccharides, and through this, polysaccharides regulate the gut microbiota and improve DM. This review begins by a summary of the sources, anti-diabetic effects and the gut microbiota regulation functions of natural polysaccharides. Then, the mechanisms of polysaccharides in regulating the gut microbiota to exert anti-diabetic effects and the structure-activity relationship are summarized. It is found that polysaccharides from plants, fungi, and marine organisms show great hypoglycemic activities and the gut microbiota regulation functions. The mechanisms mainly include repairing the gut burrier, reshaping gut microbiota composition, changing the metabolites, regulating anti-inflammatory activity and immune function, and regulating the signal pathways. Structural characteristics of polysaccharides, such as monosaccharide composition, molecular weight, and type of glycosidic linkage, show great influence on the anti-diabetic activity of polysaccharides. This review provides a reference for the exploration and development of the anti-diabetic effects of polysaccharides.

Novel ethylenediamine-ß-cyclodextrin grafted membranes for the chiral separation of mandelic acid and its derivatives.

In the present study, flat cellulose acetate ultrafiltration membranes were prepared first by nonsolvent induced phase separation method. Then chiral membranes for separating the enantiomers were prepared by grafting the ultrafiltration membranes using ethylenediamine-ß-cyclodextrin as the chiral selector and epichlorohydrin as the spacer arm. The pure water permeability of the ultrafiltration membrane was around 115 L·m-2·h-1·bar-1. The properties of the chiral membranes were characterized using infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). The chiral membrane performance in enantiomer separation was evaluated with racemates, such as mandelic acid (MA), 2-chloromandelic acid (2-ClMA), 4-chloromandelic acid (4-ClMA), and methyl mandelate (MM). The influence of feed concentration on the separation efficiency was also investigated. The results indicated that the enantiomeric excess percentages (e.e%) of the racemic mixtures for these four chiral compounds were up to 31.8%, 25.4%, 17.8%, and 32.6%, respectively. The binding free energy of the chiral selector with the (S)-enantiomer calculated by molecular dynamics simulations was stronger than that with the (R)-enantiomer, which was consistent with the experimental results (higher concentration of (R)-enantiomer in the permeate). This supports the affinity absorption-separation mechanism.

Reaction Process of Solid Waste Composite-Based Cementitious Materials for Immobilizing and Characterizing Heavy Metals in Lead and Zinc Tailings: Based on XRD, SEM-EDS and Compressive Strength Characterization.

This study investigates the synergistic effect and mechanism of gelling materials with blast furnace slag (BFS), steel slag (SS) and desulphurization gypsum (DG) as the main components on the hardening of heavy metal ions by lead and zinc tailings. It is found that lead and zinc tailing (LZT) is mainly composed of dolomite and quartz and contain small amounts of calcium, aluminum, iron, magnesium and other elements as well as heavy metals such as lead and zinc. By the mechanical activation method, it is found that the lead and zinc tailings powder has the largest specific surface area and the highest activity index when the ball milling time is 2 h. At a hardening timepoint of 28 d, the calcite crystals in the samples are intertwined with the amorphous C-S-H gel (C-S-H gels are mainly composed of 3CaO∙SiO2 and 2CaO∙SiO2), which enhances the structural strength of the samples. The chemical reaction analysis confirmed that the formation of calcite is a major driver for the hydration reaction of the steel slag-desulphurization gypsum (SSSDG) system. Overall, the slag, steel slag and desulphurization gypsum solid waste-based gelling materials have synergistic effects in hardening heavy metals by limiting the leaching of metal ions, adsorbing metal ions and hardening heavy metals, and facilitating the hydration process through the formation of compound salt precipitates.

Substitutions of physical activity and sedentary behavior with negative emotions and sex difference among college students.

BACKGROUND: A growing number of studies have found that physical activity (PA) benefits mental health, and sedentary behavior (SB) increases the risk of psychological symptoms, but it remains unclear whether substituting the duration of different activities may affect the association, and whether sex difference exists among college students. METHODS: A longitudinal survey was conducted in three colleges in Anhui province, China. A total of 8049 participants validly answered the questionnaire, which included demographic variables, PA, SB and negative emotions (depressive, anxiety, and stress symptoms). RESULTS: Substituting 30 min per day of SB with equivalent walking was associated with lower scores of depressive symptoms. Stress symptoms were reduced when SB was substituted by moderate intensity PA (MPA) and walking. Substituting 30 min per day of MPA in place of walking and SB was associated with an amelioration of depressive and stress symptoms in females, and a reallocation of 30 min walking was associated with lower depressive and stress symptom scores when SB was replaced in males. CONCLUSIONS: Replacing SB with walking and MPA ameliorates the depressive and stress symptoms in young adults. The results suggest a reallocation of time from SB or walking to MPA in females while from SB to walking in males may markedly reduce the depressive and stress symptoms in college population.

Engineered Bacterial Biomimetic Vesicles Reprogram Tumor-Associated Macrophages and Remodel Tumor Microenvironment to Promote Innate and Adaptive Antitumor Immune Responses.

Tumor-associated macrophages (TAMs) are among the most abundant infiltrating leukocytes in the tumor microenvironment (TME). Reprogramming TAMs from protumor M2 to antitumor M1 phenotype is a promising strategy for remodeling the TME and promoting antitumor immunity; however, the development of an efficient strategy remains challenging. Here, a genetically modified bacterial biomimetic vesicle (BBV) with IFN-γ exposed on the surface in a nanoassembling membrane pore structure was constructed. The engineered IFN-γ BBV featured a nanoscale structure of protein and lipid vesicle, the existence of rich pattern-associated molecular patterns (PAMPs), and the costimulation of introduced IFN-γ molecules. In vitro, IFN-γ BBV reprogrammed M2 macrophages to M1, possibly through NF-κB and JAK-STAT signaling pathways, releasing nitric oxide (NO) and inflammatory cytokines IL-1ß, IL-6, and TNF-α and increasing the expression of IL-12 and iNOS. In tumor-bearing mice, IFN-γ BBV demonstrated a targeted enrichment in tumors and successfully reprogrammed TAMs into the M1 phenotype; notably, the response of antigen-specific cytotoxic T lymphocyte (CTL) in TME was promoted while the immunosuppressive myeloid-derived suppressor cell (MDSC) was suppressed. The tumor growth was found to be significantly inhibited in both a TC-1 tumor and a CT26 tumor. It was indicated that the antitumor effects of IFN-γ BBV were macrophage-dependent. Further, the modulation of TME by IFN-γ BBV produced synergistic effects against tumor growth and metastasis with an immune checkpoint inhibitor in an orthotopic 4T1 breast cancer model which was insensitive to anti-PD-1 mAb alone. In conclusion, IFN-γ-modified BBV demonstrated a strong capability of efficiently targeting tumor and tuning a cold tumor hot through reprogramming TAMs, providing a potent approach for tumor immunotherapy.

De-Epithelialized Viable Tracheal Allotransplantation Without Immunosuppressants: 5-Year Follow-Up.

OBJECTIVE: Tracheal transplantation could be a better option for patients with long segmental laryngotracheal stenosis or defects, but the need for immunosuppressants limits its widespread use due to the antigenicity of the tracheal epithelium. Chemically treated or cryopreserved nonviable tracheal allografts have no immunogenicity but lead to necrosis and stenosis in long-term outcomes. The present report describes the 5-year outcomes of de-epithelialized viable tracheal allotransplantation without immunosuppressants in a patient with severe laryngotracheal stenosis. METHODS: The recipient was a 47-year-old female with relapsing polychondritis affecting the larynx and cervical trachea and producing a 5 cm long stenosis that could not be repaired using resection and anastomosis. A tracheal allograft was obtained from a 45-year-old male donor and treated with a combination of 3% sodium dodecyl sulfate (SDS) and organ preservation solution for 138 hours. The allograft was revascularized by heterotopical implantation in the infrahyoid muscles of the recipient for 3 months and then transplantation to the laryngotracheal defect with a split-thickness skin graft sutured to the lumen and a silicon T-tube. No immunosuppressants were used postoperatively. RESULTS: The allograft was de-epithelialized, and most of the cartilage rings remained viable after the treatment. The allograft was revascularized, viable, and mechanically stable after 3 months of heterotopic implantation. No apparent signs of rejection or destruction were observed. The T-tube was removed, and the internal lining of the allograft was repopulated 4 months after orthotopic transplantation, despite the skin graft necrotizing at 2 weeks. Endoscopy and computed tomography showed a patent airway 5 years after orthotopic transplantation. The patient was able to resume her usual quality of life. CONCLUSION: The present study demonstrates that transplantation of the de-epithelialized viable tracheal allograft without immunosuppressants is safe and promising for patients with long laryngotracheal stenosis or defects, especially for those with malignant tumor resections.

Physical properties, phenolic profile and antioxidant capacity of Java tea (Clerodendranthus spicatus) stems as affected by steam explosion treatment.

Java tea (Clerodendranthus spicatus) has been favored for its various health benefits and abundance of phenolic substances. Steam explosion (SE) treatment was performed in the pretreatment of Java tea stems and the physical properties, phenolic profile and antioxidant capacity were investigated. Extraction kinetics study showed that the phenolics yields of Java tea stems treated at 2.4 MPa for 10 min reached the maximum in 40 min, which was approximately 3 times the yields of raw stems in 180 min. The antioxidant activities of the extracts of Java tea stems were also significantly increased after SE treatment (P < 0.05). In addition, 19 phenolics were detected in Java tea stems by HPLC/QTOF-MS/MS, and rosmarinic acid was found to be hydrolyzed to danshensu during the SE process. SE could be an efficient pretreatment technology to improve the extraction rates of phenolics and conversions of their high-value hydrolyzed products, which could facilitate further research of Java tea products.

Role of polygenic risk scores in the association between chronotype and health risk behaviors.

BACKGROUND: This study explores the association between chronotypes and adolescent health risk behaviors (HRBs) by testing how genetic background moderates these associations and clarifies the influence of chronotypes and polygenic risk score (PRS) on adolescent HRBs. METHODS: Using VOS-viewer software to select the corresponding data, this study used knowledge domain mapping to identify and develop the research direction with respect to adolescent risk factor type. Next, DNA samples from 264 students were collected for low-depth whole-genome sequencing. The sequencing detected HRB risk loci, 49 single nucleotide polymorphisms based to significant SNP. Subsequently, PRSs were assessed and divided into low, moderate, and high genetic risk according to the tertiles and chronotypes and interaction models were constructed to evaluate the association of interaction effect and clustering of adolescent HRBs. The chronotypes and the association between CLOCK-PRS and HRBs were examined to explore the association between chronotypes and mental health and circadian CLOCK-PRS and HRBs. RESULTS: Four prominent areas were displayed by clustering information fields in network and density visualization modes in VOS-viewer. The total score of evening chronotypes correlated with high-level clustering of HRBs in adolescents, co-occurrence, and mental health, and the difference was statistically significant. After controlling covariates, the results remained consistent. Three-way interactions between chronotype, age, and mental health were observed, and the differences were statistically significant. CLOCK-PRS was constructed to identify genetic susceptibility to the clustering of HRBs. The interaction of evening chronotypes and high genetic risk CLOCK-PRS was positively correlated with high-level clustering of HRBs and HRB co-occurrence in adolescents, and the difference was statistically significant. The interaction between the sub-dimensions of evening chronotypes and the high genetic CLOCK-PRS risk correlated with the outcome of the clustering of HRBs and HRB co-occurrence. CONCLUSIONS: The interaction of PRS and chronotype and the HRBs in adolescents appear to have an association, and the three-way interaction between the CLOCK-PRS, chronotype, and mental health plays important roles for HRBs in adolescents.

X3DFast model for classifying dairy cow behaviors based on a two-pathway architecture.

Behavior is one of the important factors reflecting the health status of dairy cows, and when dairy cows encounter health problems, they exhibit different behavioral characteristics. Therefore, identifying dairy cow behavior not only helps in assessing their physiological health and disease treatment but also improves cow welfare, which is very important for the development of animal husbandry. The method of relying on human eyes to observe the behavior of dairy cows has problems such as high labor costs, high labor intensity, and high fatigue rates. Therefore, it is necessary to explore more effective technical means to identify cow behaviors more quickly and accurately and improve the intelligence level of dairy cow farming. Automatic recognition of dairy cow behavior has become a key technology for diagnosing dairy cow diseases, improving farm economic benefits and reducing animal elimination rates. Recently, deep learning for automated dairy cow behavior identification has become a research focus. However, in complex farming environments, dairy cow behaviors are characterized by multiscale features due to large scenes and long data collection distances. Traditional behavior recognition models cannot accurately recognize similar behavior features of dairy cows, such as those with similar visual characteristics, i.e., standing and walking. The behavior recognition method based on 3D convolution solves the problem of small visual feature differences in behavior recognition. However, due to the large number of model parameters, long inference time, and simple data background, it cannot meet the demand for real-time recognition of dairy cow behaviors in complex breeding environments. To address this, we developed an effective yet lightweight model for fast and accurate dairy cow behavior feature learning from video data. We focused on four common behaviors: standing, walking, lying, and mounting. We recorded videos of dairy cow behaviors at a dairy farm containing over one hundred cows using surveillance cameras. A robust model was built using a complex background dataset. We proposed a two-pathway X3DFast model based on spatiotemporal behavior features. The X3D and fast pathways were laterally connected to integrate spatial and temporal features. The X3D pathway extracted spatial features. The fast pathway with R(2 + 1)D convolution decomposed spatiotemporal features and transferred effective spatial features to the X3D pathway. An action model further enhanced X3D spatial modeling. Experiments showed that X3DFast achieved 98.49% top-1 accuracy, outperforming similar methods in identifying the four behaviors. The method we proposed can effectively identify similar dairy cow behaviors while improving inference speed, providing technical support for subsequent dairy cow behavior recognition and daily behavior statistics.

Fabrication and characterization of a novel zein/pectin/pumpkin seed oil Pickering emulsion and the effects of myricetin on oxidation stability.

In this study, zein/pectin/pumpkin seed oil (PSO) Pickering emulsions (ZPPEs) were fabricated loading with myricetin (MYT), and the quality control methods of oxidation stability were innovatively investigated. The microstructure and particle properties of zein-pectin particles were determined. The zein to pectin ratio of 5:3 and oil phase fraction (φ = 50 %) turned out as the most optimal conditions for the stabilization of myricetin-loaded ZPPEs. The expected oil-in-water emulsion-type structure was confirmed by confocal laser scanning microscopy (CLSM). The internal 3D structure of Pickering emulsions (Lugol's solution improved the water-phase contrast) was imaged by micro-computed tomography (Micro-CT) for the first time. Results showed a sponge like structure of water phase in emulsion with 42 µm as mean droplet size. Light-induced oxidation was evaluated with the PetroOxy method and malondialdehyde (MDA) assays. Encapsuling ZPPEs with MYT could prevent the light induced oxidation, especially, loading of MYT at the core of the emulsion. The analysis of Electronic nose (E-nose) was used to analyze the odor before and after UV-induced oxidation, and showed a good discrimination. This study provided a new approach to prepare ZPPEs with high oxidation stability. Micro-CT, PetroOxy and E-nose could be new methods for characterization and quality assessment of Pickering emulsions.

Single-cell transcriptome analysis indicates fatty acid metabolism-mediated metastasis and immunosuppression in male breast cancer.

Male breast cancer (MBC) is a rare but aggressive malignancy with cellular and immunological characteristics that remain unclear. Here, we perform transcriptomic analysis for 111,038 single cells from tumor tissues of six MBC and thirteen female breast cancer (FBC) patients. We find that that MBC has significantly lower infiltration of T cells relative to FBC. Metastasis-related programs are more active in cancer cells from MBC. The activated fatty acid metabolism involved with FASN is related to cancer cell metastasis and low immune infiltration of MBC. T cells in MBC show activation of p38 MAPK and lipid oxidation pathways, indicating a dysfunctional state. In contrast, T cells in FBC exhibit higher expression of cytotoxic markers and immune activation pathways mediated by immune-modulatory cytokines. Moreover, we identify the inhibitory interactions between cancer cells and T cells in MBC. Our study provides important information for understanding the tumor immunology and metabolism of MBC.

Learning how to detect: A deep reinforcement learning method for whole-slide melanoma histopathology images.

Cutaneous melanoma represents one of the most life-threatening malignancies. Histopathological image analysis serves as a vital tool for early melanoma detection. Deep neural network (DNN) models are frequently employed to aid pathologists in enhancing the efficiency and accuracy of diagnoses. However, due to the paucity of well-annotated, high-resolution, whole-slide histopathology image (WSI) datasets, WSIs are typically fragmented into numerous patches during the model training and testing stages. This process disregards the inherent interconnectedness among patches, potentially impeding the models' performance. Additionally, the presence of excess, non-contributing patches extends processing times and introduces substantial computational burdens. To mitigate these issues, we draw inspiration from the clinical decision-making processes of dermatopathologists to propose an innovative, weakly supervised deep reinforcement learning framework, titled Fast medical decision-making in melanoma histopathology images (FastMDP-RL). This framework expedites model inference by reducing the number of irrelevant patches identified within WSIs. FastMDP-RL integrates two DNN-based agents: the search agent (SeAgent) and the decision agent (DeAgent). The SeAgent initiates actions, steered by the image features observed in the current viewing field at various magnifications. Simultaneously, the DeAgent provides labeling probabilities for each patch. We utilize multi-instance learning (MIL) to construct a teacher-guided model (MILTG), serving a dual purpose: rewarding the SeAgent and guiding the DeAgent. Our evaluations were conducted using two melanoma datasets: the publicly accessible TCIA-CM dataset and the proprietary MELSC dataset. Our experimental findings affirm FastMDP-RL's ability to expedite inference and accurately predict WSIs, even in the absence of pixel-level annotations. Moreover, our research investigates the WSI-based interactive environment, encompassing the design of agents, state and reward functions, and feature extractors suitable for melanoma tissue images. This investigation offers valuable insights and references for researchers engaged in related studies. The code is available at: https://github.com/titizheng/FastMDP-RL.

Relationship between chronotype and mental behavioural health among adolescents: a cross-sectional study based on the social ecological system.

BACKGROUND: Health risk behaviors (HRBs) is a kind of phenomenon behavior that often occurs in adolescence, and also often appears in clusters. Previous studies suggested an association between social ecological risk factors (SERFs) and HRBs. This study explored 1) whether chronotype moderates the risk of HRBs associated with SERFs and 2) whether mental health is a mediator in this relationship. METHODS: Adolescents were recruited from 39 junior or senior schools (three cities, 13 schools per city) using a multistage cluster sampling method conducted between October, 2020 and June, 2021. The Social Ecological System, Morningness-Eveningness Questionnaire, Brief Instrument on Psychological Health Youths, and Youth Risk Behavior Surveillance questionnaires were used to measure the SERFs, chronotype, mental health and HRBs. Latent category analysis was used to explore the clustering mode of HRBs. The primary exposure was SERFs, and the primary outcome was HRBs; chronotype was a moderator, and mental health was a mediator. The multivariable logistic regression model was used to determine the relationship between SERFs and chronotype and mental behavioral health status. Mediation moderate analysis using the PROCESS method was used to explore the relationship between these variables. Sensitivity analysis was conducted to evaluate the robustness of the model. RESULTS: In total, 17,800 individuals were initially enrolled. After excluding 947 individuals with invalid questionnaires, 16,853 participants were finally included in the analysis. The mean age of participants was 15.33 ± 1.08 years. After adjusting for covariates, multivariable logistic regression found that high levels of SERFs (odds ratio [OR] = 10.10, 95% confidence interval [CI]: 8.88-11.43, P < 0.01), intermediate chronotype (OR = 5.24, 95% CI: 4.57-6.01, P < 0.01), and eveningness (OR = 1.83, 95% CI: 1.64-2.05, P < 0.01) were associated with higher HRBs frequency. This study also assessed the interaction between chronotype, SERFs and HRBs (OR = 27.84, 95% CI: 22.03-35.19, P < 0.01) and mental health (OR = 18.46, 95% CI: 13.16-25.88, P < 0.01). The moderated mediation analyses examined the relationship between chronotype, SERFs, mental health and HRBs. CONCLUSIONS: SERFs may be important variables in measuring the effect of the adolescent psychosocial environment on HRBs; this effect is mediated by mental health and moderated by chronotype.