Search

With China's aging population on the rise, the incidence of senile dementia, particularly neurodegenerative diseases Alzheimer's disease ( AD), is also increasing, leading to significant economic and emotional burdens for patients and their families. Consequently, research on brain senescence and AD has become imperative. This review delves into recent advancements in understanding the pathogenesis of AD, offering crucial insights into the neurodegenerative processes associated with brain senescence and informing strategies for managing and treating AD and related conditions.

Abstract Background The purpose of this study was to improve the deep learning (DL) model performance in predicting and classifying IMRT gamma passing rate (GPR) by using input features related to machine parameters and a class balancing technique. Methods A total of 2348 fields from 204 IMRT plans for patients with nasopharyngeal carcinoma were retrospectively collected to form a dataset. Input feature maps, including fluence, leaf gap, leaf speed of both banks, and corresponding errors, were constructed from the dynamic log files. The SHAP framework was employed to compute the impact of each feature on the model output for recursive feature elimination. A series of UNet++ based models were trained on the obtained eight feature sets with three fine-tuning methods including the standard mean squared error (MSE) loss, a re-sampling technique, and a proposed weighted MSE loss (WMSE). Differences in mean absolute error, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were compared between the different models. Results The models trained with feature sets including leaf speed and leaf gap features predicted GPR for failed fields more accurately than the other models (F(7, 147) = 5.378, p

In China, the energy consumption in the building sector has increased tremendously in the past decades. It is important to investigate advanced passive energy-saving technologies for buildings. By applying phase-change materials in walls, the peak cooling/heating load can be significantly reduced. In the present study, a numerical model of one-dimensional heat transfer within a phase-change wall was developed and solved by Matlab, which was successfully validated with published data. Subsequently, the model was used to simulate the thermal performance of a phase-change wall in a hotel building in Shanghai, China. Simulation results demonstrate that the performance of the phase-change wall is optimized when the phase-change material is applied to both sides of the wall. Year-round heat transfer is minimized using layers of paraffin (C16-C28) and capric acid (2 cm), with phase-change temperatures of 43℃ and 16.3℃, respectively. The PCM wall reduces inwardthe inward heat transfer by 26.9% compared with a common wall without phase-change material. The outward heat loss is also reduced by 15.7% during the heating season. This study demonstrates that the PCM wall can effectively reduce indoor heat gain in summerin the summer and heat loss in winterin the winter. The numerical model has proven to be feasible for optimizing construction design.

Abstract Background Boron (B) is an essential micronutrient for plants. Inappropriate B supply detrimentally affects the productivity of numerous crops. Understanding of the molecular responses of plants to different B supply levels would be of significance in crop improvement and cultivation practices to deal with the problem. Results We conducted a comprehensive analysis of the transcriptome and proteome of tobacco seedlings to investigate the expression changes of genes/proteins in response to different B supply levels, with a particular focus on B deficiency. The global gene and protein expression profiles revealed the potential mechanisms involved in the responses of tobacco to B deficiency, including up-regulation of the NIP5;1-BORs module, complex regulation of genes/proteins related to cell wall metabolism, and up-regulation of the antioxidant machinery. Conclusion Our results demonstrated that B deficiency caused severe morphological and physiological disorders in tobacco seedlings, and revealed dynamic expression changes of tobacco genes/proteins in response to different B supply levels, especially to B deficiency, thus offering valuable insights into the molecular responses of tobacco to B deficiency.

Abstract Background This hemodialysis center experienced the pandemic from December 2022 to January 2023. Therefore, we sought to describe the clinical characteristics and mortality outcomes in hemodialysis patients during this Omicron surge. Methods According to whether they are infected, they are divided into two groups: SARS-CoV-2-positive and SARS-CoV-2-negative. The SARS-CoV-2-positive group was divided into a survival group and a non-survival group for comparison. Results 366 of 457 hemodialysis patients were infected with SARS-CoV-2. The most common symptoms observed were fever (43.2%) and cough (29.8%), Followed by diarrhea (1.4%). Hemodialysis patients with hypertension were more susceptible to SARS-CoV-2 infection. The lymphocyte count, serum creatinine, serum potassium, and serum phosphorus in the SARS-CoV-2-positive group were significantly lower than those in the SARS-CoV-2-negative group. The all-cause mortality rate for infection with SARS-CoV-2 was 5.2%. Only 7 of 366 SARS-CoV-2-positive patients were admitted to the intensive care unit, but 6 of them died. Intensive care unit hospitalization rates were significantly higher in the non-survival group compared with the survival group. White blood cells count, neutrophil count, C-reactive protein, AST, and D-dimer in the non-survival group were higher than those in the survival group. The lymphocyte count, hemoglobin concentration, serum creatinine, serum albumin, serum phosphorus and parathyroid hormone in the non-survival group were lower than those in the survival group. Age > 65 years, elevated C-reactive protein and AST are independent risk factors for death. Finally, no significant difference in vaccination status was found between the SARS-CoV-2-positive group and the negative group. Conclusions Hemodialysis patients are at high risk for SARS-CoV-2 infection. Ensuring the adequacy of hemodialysis treatment and maintaining good physical condition of patients are the top priorities.

Abstract BackgroundIn recent years, the number of HIV/AIDS cases among youth has increased year by year around the world. A spatial and temporal analysis of these AIDS cases is necessary for the development of youth AIDS prevention and control policies. ObjectiveThis study aimed to analyze the spatial and temporal distribution and associated factors of HIV/AIDS among youth in Guangxi as an example. MethodsThe reported HIV/AIDS cases of youths aged 15‐24 years in Guangxi from January 2014 to December 2021 were extracted from the Chinese Comprehensive Response Information Management System of HIV/AIDS. Data on population, economy, and health resources were obtained from the Guangxi Statistical Yearbook. The ArcGIS (version 10.8; ESRI Inc) software was used to describe the spatial distribution of AIDS incidence among youths in Guangxi. A Bayesian spatiotemporal model was used to analyze the distribution and associated factors of HIV/AIDS, such as gross domestic product per capita, population density, number of health technicians, and road mileage per unit area. ResultsFrom 2014 to 2021, a total of 4638 cases of HIV/AIDS infection among youths were reported in Guangxi. The reported incidence of HIV/AIDS cases among youths in Guangxi increased from 9.13/100,000 in 2014 to 11.15/100,000 in 2019 and then plummeted to a low of 8.37/100,000 in 2020, followed by a small increase to 9.66/100,000 in 2021. The districts (counties) with relatively high HIV/AIDS prevalence among youths were Xixiangtang, Xingning, Qingxiu, Chengzhong, and Diecai. The reported incidence of HIV/AIDS among youths was negatively significantly associated with road mileage per unit area (km) at a posterior mean of −0.510 (95% CI −0.818 to 0.209). It was positively associated with population density (100 persons) at a posterior mean of 0.025 (95% CI 0.012‐0.038), with the number of health technicians (100 persons) having a posterior mean of 0.007 (95% CI 0.004‐0.009). ConclusionsIn Guangxi, current HIV and AIDS prevention and control among young people should focus on areas with a high risk of disease. It is suggested to strengthen the allocation of AIDS health resources and balance urban development and AIDS prevention. In addition, AIDS awareness, detection, and intervention among Guangxi youths need to be strengthened.

Abstract Background Immune‐checkpoint inhibitors are now used more commonly in combination than monotherapy as the first‐line choice in patients with unresectable advanced melanoma. Nevertheless, for cases that progressed after the initial combination therapy, the subsequent regimen option can be very difficult. Herein, we reported the efficacy and safety of a triple combination regimen in Chinese unresectable advanced melanoma patients who had poor responses to the first‐line immune therapy. Methods We reviewed the clinical profiles of patients diagnosed with stage IIIC‐IV melanoma between June 1, 2020, and September 30, 2023. The patients who failed the prior immune therapies and received anti‐PD‐1 mono antibody plus interferon(IFN)‐alpha 1b and anlotinib hydrochloride as the second‐line therapy were enrolled in the retrospective analysis. Additionally, we examined the exhaustion of T‐cells using mIHC staining in available tumor samples. Results Fifty‐five patients were included in this study. The median follow‐up period was 13.6 months. The objective response rate evaluated by the investigators was 9.1%(1CR, 4PR). The disease control rate was 47.3%. The median overall survival was 17.6 months, and the median progression‐free survival was 2.8 months. The adverse events rate of any grade was 100%. Grade 3 or 4 irAEs were observed in 29.1% of cases. Multiplex immunohistochemical staining revealed an increased trend of TIM3 expression on tumor‐infiltrating T cells in patients without objective response. Conclusion PD‐1 monoclonal antibody plus interferon‐alpha 1b plus anlotinib showed acceptable tolerability and anticancer benefits in Chinese metastatic melanoma patients as a second‐line therapy.

Abstract Vitiligo is an autoimmune disease characterized by epidermal melanocyte destruction, with abnormal autoimmune responses and excessive oxidative stress as two cardinal mechanisms. Human umbilical mesenchymal stem cells‐derived exosomes (hUMSCs‐Exos) are regarded as promising therapeutic choice for autoimmune diseases due to potent immunosuppressive and anti‐oxidative properties, which can be potentiated under 3D cell culture condition. Nevertheless, whether exosomes derived from 3D spheroids of hUMSCs (3D‐Exos) exhibit considerable therapeutic effect on vitiligo and the underlying mechanism remain elusive. In this study, systemic administration of 3D‐Exos showed a remarkable effect in treating mice with vitiligo, as revealed by ameliorated skin depigmentation, less CD8+T cells infiltration, and expanded Treg cells in skin, and 3D‐Exos exerted a better effect than 2D‐Exos. Mechanistically, 3D‐Exos can prominently facilitate the expansion of Treg cells in vitiligo lesion and suppress H2O2‐induced melanocytes apoptosis. Forward miRNA profile analysis and molecular experiments have demonstrated that miR‐132‐3p and miR‐125b‐5p enriched in 3D‐Exos greatly contributed to these biological effects by targeting Sirt1 and Bak1 respectively. In aggregate, 3D‐Exos can efficiently ameliorate vitiligo by simultaneously potentiating Treg cells‐mediated immunosuppression and suppressing oxidative stress‐induced melanocyte damage via the delivery of miR‐132‐3p and miR‐125b‐5p. The employment of 3D‐Exos will be a promising treament for vitiligo.

Abstract is missing (Short communication)

Abstract Vitiligo is a hypopigmented skin disease characterized by the loss of melanin. The progressive nature and widespread incidence of vitiligo necessitate timely and accurate detection. Usually, a single diagnostic test often falls short of providing definitive confirmation of the condition, necessitating the assessment by dermatologists who specialize in vitiligo. However, the current scarcity of such specialized medical professionals presents a significant challenge. To mitigate this issue and enhance diagnostic accuracy, it is essential to build deep learning models that can support and expedite the detection process. This study endeavors to establish a deep learning framework to enhance the diagnostic accuracy of vitiligo. To this end, a comparative analysis of five models including ResNet (ResNet34, ResNet50, and ResNet101 models) and Swin Transformer series (Swin Transformer Base, and Swin Transformer Large models), were conducted under the uniform condition to identify the model with superior classification capabilities. Moreover, the study sought to augment the interpretability of these models by selecting one that not only provides accurate diagnostic outcomes but also offers visual cues highlighting the regions pertinent to vitiligo. The empirical findings reveal that the Swin Transformer Large model achieved the best performance in classification, whose AUC, accuracy, sensitivity, and specificity are 0.94, 93.82%, 94.02%, and 93.5%, respectively. In terms of interpretability, the highlighted regions in the class activation map correspond to the lesion regions of the vitiligo images, which shows that it effectively indicates the specific category regions associated with the decision-making of dermatological diagnosis. Additionally, the visualization of feature maps generated in the middle layer of the deep learning model provides insights into the internal mechanisms of the model, which is valuable for improving the interpretability of the model, tuning performance, and enhancing clinical applicability. The outcomes of this study underscore the significant potential of deep learning models to revolutionize medical diagnosis by improving diagnostic accuracy and operational efficiency. The research highlights the necessity for ongoing exploration in this domain to fully leverage the capabilities of deep learning technologies in medical diagnostics.

Abstract Background The elimination of schistosomiasis remains a challenging task, with current measures primarily focused on the monitoring and control of Oncomelania hupensis (O. hupensis) snail, the sole intermediate host of Schistosome japonicum. Given the emerging, re-emerging, and persistent habitats of snails, understanding their genetic diversity might be essential for their successful monitoring and control. The aims of this study were to analyze the genetic diversity of Oncomelania hupensis robertsoni (O. h. robertsoni) using microsatellite DNA markers; and validate the applicability of previously identified microsatellite loci for O. hupensis in hilly regions. Methods A total of 17 populations of O. h. robertsoni from Yunnan Province in China were selected for analysis of genetic diversity using six microsatellite DNA polymorphic loci (P82, P84, T4-22, T5-11, T5-13, and T6-27). Results The number of alleles among populations ranged from 0 to 19, with an average of 5. The average ranges of expected (He) and observed (Ho) heterozygosity within populations were 0.506 to 0.761 and 0.443 to 0.792, respectively. The average fixation index within the population ranged from – 0.801 to 0.211. The average polymorphic information content (PIC) within the population ranged from 0.411 to 0.757, appearing to be polymorphic for all loci (all PIC > 0.5), except for P28 and P48. A total of 68 loci showed significant deviations from Hardy-Weinberg equilibrium (P < 0.05), and pairwise Fst values ranged from 0.051 to 0.379. The analysis of molecular variance indicated that 88% of the variation occurred within snail populations, whereas 12% occurred among snail populations. Phylogenetic trees and principal coordinate analysis revealed two distinct clusters within the snail population, corresponding to “Yunnan North” and “Yunnan South”. Conclusions O. h. robertsoni exhibited a relatively high level of genetic differentiation, with variation chiefly existing within snail populations. All snail in this region could be separated into two clusters. The microsatellite loci P82 and P84 might not be suitable for classification studies of O. hupensis in hilly regions. These findings provided important information for the monitoring and control of snail, and for further genetic diversity studies on snail populations. Graphical Abstract

BackgroundGlobally, gallstones represented a prevalent condition of the digestive system, heavily affected by metabolic dysfunctions such as obesity, dyslipidemia, insulin resistance, and diabetes. The triglyceride-glucose (TyG) index served as an accessible novel indicator for evaluating insulin resistance, offering a precise reflection of metabolic conditions. However, no studies have yet explored their relationship. The link between the TyG and gallstone risk was the primary purpose of this study.MethodsUtilized data from the public database, the National Health and Nutrition Examination Survey, for the years 2017-2020. The logit model was utilized to elucidate the connection between the TyG and the gallstones risk. The restricted cubic spline (RCS) analysis served to verify any non-linear relationships existing between them. Sensitivity analyses, encompassing both stratified and interaction analyses, were conducted to identify populations of particular interest and assess potential interactions between covariates and the TyG index.ResultsA total of 4544 individuals were included. The risk of gallstones in high group was 1.6 times that of the low group. The potential cut-off value for the TyG index was 6.19. Above this threshold, there was a 40% heightened risk of gallstones with each one-unit increment in the TyG. The RCS analysis revealed the absence of a non-linear association between them. The populations warranting particular focus included those over 60 years, non-White people, individuals with a body mass index ≥25, smokers, drinkers, those with hypertension, and diabetes. Apart from smoking history, alcohol consumption, and history of diabetes, there were no interactions between other variables and the TyG index.ConclusionThe current study represented the inaugural investigation into the link between TyG index and the risk of gallstones. A positive correlation existed between them, signifying that an increase in TyG paralleled an elevated risk of gallstones. No non-linear relationship has been found between them. Besides, a 40% increase in gallstone risk accompanied each unit rise in TyG. Considering the convenience and accessibility of TyG in clinical settings, it has a promising potential for clinical application.

Abstract Melanocyte stem cells (MSCs), melanocyte lineage‐specific skin stem cells derived from the neural crest, are observed in the mammalian hair follicle, the epidermis or the sweat gland. MSCs differentiate into mature melanin‐producing melanocytes, which confer skin and hair pigmentation and uphold vital skin functions. In controlling and coordinating the homeostasis, repair and regeneration of skin tissue, MSCs play a vital role. Decreased numbers or impaired functions of MSCs are closely associated with the development and therapy of many skin conditions, such as hair graying, vitiligo, wound healing and melanoma. With the advancement of stem cell technology, the relevant features of MSCs have been further elaborated. In this review, we provide an exhaustive overview of cutaneous MSCs and highlight the latest advances in MSC research. A better understanding of the biological characteristics and micro‐environmental regulatory mechanisms of MSCs will help to improve clinical applications in regenerative medicine, skin pigmentation disorders and cancer therapy. Key points This review provides a concise summary of the origin, biological characteristics, homeostatic maintenance and therapeutic potential of cutaneous MSCs. The role and potential application value of MSCs in skin pigmentation disorders are discussed. The significance of single‐cell RNA sequencing, CRISPR‐Cas9 technology and practical models in MSCs research is highlighted.

Abstract Background Tumor cells frequently suffer from endoplasmic reticulum (ER) stress. Previous studies have extensively elucidated the role of tumorous unfolded protein response in melanoma cells, whereas the effect on tumor immunology and the underlying mechanism remain elusive. Methods Bioinformatics, biochemical assays and pre-clinical mice model were employed to demonstrate the role of tumorous inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) in anti-tumor immunity and the underlying mechanism. Results We firstly found that IRE1α signaling activation was positively associated with the feature of tumor-infiltrating lymphocytes. Then, pharmacological ER stress induction by HA15 exerted prominent anti-tumor effect in immunocompetent mice and was highly dependent on CD8+T cells, paralleled with the reshape of immune cells in tumor microenvironment via tumorous IRE1α-XBP1 signal. Subsequently, tumorous IRE1α facilitated the expression and secretion of multiple chemokines and cytokines via XBP1-NF-κB axis, leading to increased infiltration and anti-tumor capacity of CD8+T cells. Ultimately, pharmacological induction of tumorous ER stress by HA15 brought potentiated therapeutic effect along with anti-PD-1 antibody on melanoma in vivo. Conclusions Tumorous IRE1α facilitates CD8+T cells-dependent anti-tumor immunity and improves immunotherapy efficacy by regulating chemokines and cytokines via XBP1-NF-κB axis. The combination of ER stress inducer and anti-PD-1 antibody could be promising for increasing the efficacy of melanoma immunotherapy.

Psoriasis is a common inflammatory skin disease, in which epidermal keratinocytes play a vital role in its pathogenesis by acting both as the responder and as the accelerator to the cutaneous psoriatic immune response. Advanced glycation end products (AGEs) are a class of proinflammatory metabolites that are commonly accumulating in cardiometabolic disorders. Recent studies have also observed the increased level of AGEs in the serum and skin of psoriasis patients, but the role of AGEs in psoriatic inflammation has not been well investigated. In the present study, we initially detected abnormal accumulation of AGEs in epidermal keratinocytes of psoriatic lesions collected from psoriasis patients. Furthermore, AGEs promoted the proliferation of keratinocytes via upregulated Keratin 17 (K17)-mediated p27KIP1 inhibition followed by accelerated cell cycle progression. More importantly, AGEs facilitated the production of interleukin-36 alpha (IL-36α) in keratinocytes, which could enhance T helper 17 (Th17) immune response. In addition, the induction of both K17 and IL-36α by AGEs in keratinocytes was dependent on the activation of signal transducer and activator of transcription 1/3 (STAT1/3) signaling pathways. At last, the effects of AGEs on keratinocytes were mediated by the receptor for AGEs (RAGE). Taken together, these findings support that AGEs potentiate the innate immune function of keratinocytes, which contributes to the formation of psoriatic inflammation. Our study implicates AGEs as a potential pathogenic link between psoriasis and cardiometabolic comorbidities.

There is a competitive and coordinated relationship among organisms which depends on their chemical connections [...]

IntroductionPhosphorus (P), which plays a vital role in plant growth, is continually added to soil to maximize biomass production, leading to excessive P accumulation and water eutrophication.ResultsIn this study, a pot experiment using a subtropical tobacco-growing soil fertilized with four P levels—no P, low P, medium P, and high P—was conducted and rhizosphere and bulk soils were analyzed.ResultsP addition significantly increased tobacco biomass production (except under low P input) and total soil P and available P content (P0.05). Moreover, a significant difference was found between rhizosphere soils with low (LR) and high (HR) P inputs (P0.05). Functional prediction revealed that P application significantly decreased the total P and N metabolism of microorganisms in rhizosphere soils (P

Abstract Excessive and prolonged ultraviolet radiation (UVR) exposure causes photodamage, photoaging, and photocarcinogenesis in human skin. Therefore, safe and effective sun protection is one of the most fundamental requirements. Living organisms tend to evolve various natural photoprotective mechanisms to avoid photodamage. Among them, melanin is the main functional component of the photoprotective system of human skin. Polydopamine (PDA) is synthesized as a mimic of natural melanin, however, its photoprotective efficiency and mechanism in protecting against skin damage and photoaging remain unclear. In this study, the novel sunscreen products based on melanin-inspired PDA nanoparticles (NPs) are rationally designed and prepared. We validate that PDA NPs sunscreen exhibits superior effects on photoprotection, which is achieved by the obstruction of epidermal hyperplasia, protection of the skin barrier, and resolution of inflammation. In addition, we find that PDA NPs are efficiently intake by keratinocytes, exhibiting robust ROS scavenging and DNA protection ability with minimal cytotoxicity. Intriguingly, PDA sunscreen has an influence on maintaining homeostasis of the dermis, displaying an anti-photoaging property. Taken together, the biocompatibility and full photoprotective properties of PDA sunscreen display superior performance to those of commercial sunscreen. This work provides new insights into the development of a melanin-mimicking material for sunscreens.

With the improvement of people's living standards and health awareness, the safety of animal-derived food has attracted worldwide attention. Chemical contamination (melamine, veterinary drug residues, food additive residues, etc.) and pathogenic microorganisms are the primary causes of food safety issues in animal-derived food products, potentially threatening human health and socioeconomic development. Therefore, it is essential to establish rapid detection methods for animal-derived food safety. Surface-enhanced Raman spectroscopy (SERS) has the advantages of rapid detection, good selectivity, and high sensitivity. It has shown great application potential in food safety, which has become one of the research hotspots. This paper reviews the application of SERS in the safety of animal-derived food detection and comprehensively introduces the use of SERS to detect melamine, foodborne pathogens, pesticide and veterinary drug residues, and food additives. Furthermore, it prospects the application of SERS technology in rapid residue detection, which would be believed to provide valuable insights into the field of SERS-based food safety evaluation.

Abstract Background The activation of CD8+ T cells and their trafficking to the skin through JAK-STAT signaling play a central role in the development of vitiligo. Thus, targeting this key disease pathway with innovative drugs is an effective strategy for treating vitiligo. Natural products isolated from medicinal herbs are a useful source of novel therapeutics. Demethylzeylasteral (T-96), extracted from Tripterygium wilfordii Hook F, possesses immunosuppressive and anti-inflammatory properties. Methods The efficacy of T-96 was tested in our mouse model of vitiligo, and the numbers of CD8+ T cells infiltration and melanocytes remaining in the epidermis were quantified using whole-mount tail staining. Immune regulation of T-96 in CD8+ T cells was evaluated using flow cytometry. Pull-down assay, mass spectrum analysis, molecular docking, knockdown and overexpression approaches were utilized to identify the target proteins of T-96 in CD8+ T cells and keratinocytes. Results Here, we found that T-96 reduced CD8+ T cell infiltration in the epidermis using whole-mount tail staining and alleviated the extent of depigmentation to a comparable degree of tofacitinib (Tofa) in our vitiligo mouse model. In vitro, T-96 decreased the proliferation, CD69 membrane expression, and IFN-γ, granzyme B, (GzmB), and perforin (PRF) levels in CD8+ T cells isolated from patients with vitiligo. Pull-down assays combined with mass spectrum analysis and molecular docking showed that T-96 interacted with JAK3 in CD8+ T cell lysates. Furthermore, T-96 reduced JAK3 and STAT5 phosphorylation following IL-2 treatment. T-96 could not further reduce IFN-γ, GzmB and PRF expression following JAK3 knockdown or inhibit increased immune effectors expression upon JAK3 overexpression. Additionally, T-96 interacted with JAK2 in IFN-γ-stimulated keratinocytes, inhibiting the activation of JAK2, decreasing the total and phosphorylated protein levels of STAT1, and reducing the production and secretion of CXCL9 and CXCL10. T-96 did not significantly inhibit STAT1 and CXCL9/10 expression following JAK2 knockdown, nor did it suppress upregulated STAT1-CXCL9/10 signaling upon JAK2 overexpression. Finally, T-96 reduced the membrane expression of CXCR3, and the culture supernatants pretreated with T-96 under IFN-γ stressed keratinocytes markedly blocked the migration of CXCR3+CD8+ T cells, similarly to Tofa in vitro. Conclusion Our findings demonstrated that T-96 might have positive therapeutic responses to vitiligo by pharmacologically inhibiting the effector functions and skin trafficking of CD8+ T cells through JAK-STAT signaling.

Abstract Background Diagnosis and treatment of diffuse malignant peritoneal mesothelioma (DMPM) are still challenging. The aim of the present study was to explore the correlation between CD74, CD10, Ki-67 and clinicopathological parameters, and identify independent prognostic factors of DMPM. Methods Seventy patients with pathologically proven DMPM were retrospectively reviewed. The expression of CD74, CD10 and Ki-67 in peritoneal tissues was detected by immunohistochemical analysis using standard avidin biotin complex (ABC) immunostaining technique. Kaplan-Meier survival analysis and multivariate Cox regression analyses were performed to assess prognostic factors. The nomogram based on the Cox hazards regression model was established. C-index and calibration curve were performed to evaluate the accuracy of nomogram models. Results The median age of DMPM was 62.34 years, and the male-to-female ratio was 1: 1.80. CD74 expression was identified in 52 (74.29%) of 70 specimens, CD10 in 34 (48.57%) specimens, and higher Ki-67 in 33(47.14%) specimens. CD74 was negatively associated with asbestos exposure(r = -0.278), Ki-67(r = -0.251) and TNM stage(r = -0.313). All patients were effectively followed up in the survival analysis. Univariate analysis revealed that PCI, TNM stage, treatment, Ki-67, CD74 and ECOG PS were associated with DMPM prognosis. CD74 (HR = 0.65, 95%Cl:0.46–0.91, P = 0.014), Ki-67(HR = 2.09, 95%Cl:1.18–3.73, P = 0.012),TNM stage (HR = 1.89, 95%Cl:1.16–3.09, P = 0.011), ECOG PS(HR = 2.12, 95%Cl:1.06–4.25, P = 0.034), systemic chemotherapy (HR = 0.41, 95%Cl:0.21–0.82, P = 0.011) and intraperitoneal chemotherapy (HR = 0.34, 95%Cl:0.16–0.71, P = 0.004) were independent predictors by multivariate Cox analysis. The C‑index of the nomogram for predicting overall survival (OS) was 0.81. The OS calibration curve showed good agreement between nomogram-predicted and observed survival. Conclusions CD74, Ki-67, TNM stage, ECOG PS and treatment were independent factors affecting prognosis of DMPM. Reasonable chemotherapy treatment might improve the prognosis of patients. The proposed nomogram was a visual tool to effectively predict the OS of DMPM patients.

Vitiligo is an autoimmune disease that leads to disfiguring depigmented lesions of skin and mucosa. Although effective treatments are available for vitiligo, there are still some patients with poor responses to conventional treatment. Refractory vitiligo lesions are mostly located on exposed sites such as acral sites and lips, leading to significant life stress. Understanding the causes of refractory vitiligo and developing targeted treatments are essential to enhance vitiligo outcomes. In this review, we summarized recent treatment approaches and some potential methods for refractory vitiligo. Janus kinase inhibitors have shown efficacy in refractory vitiligo. A variety of surgical interventions and fractional carbon dioxide laser have been widely applied to combination therapies. Furthermore, melanocyte regeneration and activation therapies are potentially effective strategies. Patients with refractory vitiligo should be referred to psychological monitoring and interventions to reduce the potential pathogenic effects of chronic stress. Finally, methods for depigmentation and camouflage may be beneficial in achieving uniform skin color and improved quality of life. Our ultimate focus is to provide alternative options for refractory vitiligo and to bring inspiration to future research.

Abstract Melanoma is the most lethal type of skin cancer, originating from the malignant transformation of melanocyte. While the development of targeted therapy and immunotherapy has gained revolutionary advances in potentiating the therapeutic effect, the prognosis of patients with melanoma is still suboptimal. During tumor progression, melanoma frequently encounters stress from both endogenous and exogenous sources in tumor microenvironment. SIRT7 is a nuclear-localized deacetylase of which the activity is highly dependent on intracellular nicotinamide adenine dinucleotide (NAD+), with versatile biological functions in maintaining cell homeostasis. Nevertheless, whether SIRT7 regulates tumor cell biology and tumor immunology in melanoma under stressful tumor microenvironment remains elusive. Herein, we reported that SIRT7 orchestrates melanoma progression by simultaneously promoting tumor cell survival and immune evasion via the activation of unfolded protein response. We first identified that SIRT7 expression was the most significantly increased one in sirtuins family upon stress. Then, we proved that the deficiency of SIRT7 potentiated tumor cell death under stress in vitro and suppressed melanoma growth in vivo. Mechanistically, SIRT7 selectively activated the IRE1α-XBP1 axis to potentiate the pro-survival ERK signal pathway and the secretion of tumor-promoting cytokines. SIRT7 directly de-acetylated SMAD4 to antagonize the TGF-β-SMAD4 signal, which relieved the transcriptional repression on IRE1α and induced the activation of the IRE1α-XBP1 axis. Moreover, SIRT7 up-regulation eradicated anti-tumor immunity by promoting PD-L1 expression via the IRE1α-XBP1 axis. Additionally, the synergized therapeutic effect of SIRT7 suppression and anti-PD-1 immune checkpoint blockade was also investigated. Taken together, SIRT7 can be employed as a promising target to restrain tumor growth and increase the effect of melanoma immunotherapy.

In China, Fusarium pseudograminearum has emerged as a major pathogen causing Fusarium crown rot (FCR) and caused significant losses. Studies on the pathogen’s properties, especially its mating type and trichothecene chemotypes, are critical with respect to disease epidemiology and food/feed safety. There are currently few available reports on these issues. This study investigated the species composition, mating type idiomorphs, and trichothecene genotypes of Fusarium spp. causing FCR in Henan, China. A significant shift in F. pseudograminearum-induced FCR was found in the present study. Of the 144 purified strains, 143 were F. pseudograminearum, whereas only 1 Fusarium graminearum was identified. Moreover, a significant trichothecene-producing capability of F. pseudograminearum strains from Henan was observed in this work. Among the 143 F. pseudograminearum strains identified, F. pseudograminearum with a 15ADON genotype was found to be predominant (133 isolates), accounting for 92.36% of all strains, followed by F. pseudograminearum with a 3ADON genotype, whereas only one NIV genotype strain was detected. Overall, a relatively well-balanced 1:1 ratio of the F. pseudograminearum population was found in Henan. To the best of our knowledge, this is the first study that has examined the Fusarium populations responsible for FCR across the Henan wheat-growing region.

Plant–soil feedback (PSF) was initially developed in the field of agricultural practices. In recent years, PSF has been extended to various ecosystems. Root exudates, essential for the exchange of materials, energy, and information at the plant–soil interface, significantly influence PSF. However, how PSF is driven by root secretions and the role of these secretions in different PSF pathways still needs to be further explored, particularly in forest ecosystems. Soil nutrients, microbial communities, and nematodes are important research topics in the process of PSF driven by root exudates. Investigating these aspects driven by root exudates provides valuable insights into the complex interactions both above ground and below the surface. This research can offer theoretical support and guidance for building stable, healthy, and sustainable forest ecosystems in the future.

The bi-facial photovoltaic sunshade (BiPVS) is an innovative solution that utilizes vertically mounted bi-facial photovoltaic modules to provide shading. The BiPVS is capable of converting incident solar radiation into electricity on both the front and rear sides of the module, resulting in higher electrical efficiency compared to traditional mono-facial PV sunshades. The BiPVS has great potential as a sustainable solution for building shading and energy generation, which allows for improved indoor light/thermal environment and building energy efficiency. In this study, the bi-facial photovoltaic sunshade (BiPVS) was implemented in an office under typical hot summer and warm winter climate of Shenzhen, China. The energy performance of the BiPVS was analyzed using Energyplus. The comprehensive building energy saving was evaluated by comparing the energy consumption of the office with and without the BiPVS. Results showed that the total annual photovoltaic power generation was 133.19 kWh, while the comprehensive building energy savings were 159.65 kWh. Additionally, carbon dioxide emissions were reduced by 83.29 kgCO2 per year. The proposed method can help optimize the design parameters of BiPVS according to specific climate conditions, building types, and orientation, and contribute to the development of high-efficiency BIPV technology and support efforts towards carbon neutrality.

The pollution of cadmium (Cd) to environment is becoming increasingly serious. In this study, the ability of the continuous flow bioreactor with sulfate as the electron acceptor to remove pollutants from Cd-containing wastewater was investigated. The results show that Cd2+ could be effectively removed and the concentration of Cd2+ in the anaerobic effluent is less than 0.01 ​mg/L. Cd can affect the decomposition of urea by anaerobic sludge. In addition, ammonia nitrogen could be also effectively removed with the removal rate was approximately 72.4%. The activated sludge mainly removed Cd through the precipitation of cadmium sulfide outside the bacteria after sulfide was generated by bacterial sulfate metabolism, facilitated continuous biological removal of Cd from wastewater. Microbial community structure analysis revealed Trichococcus and Hyphomicrobium mainly occurred in anaerobic and anoxic reaction, and Sulfurovum was unique to the sulfur oxidation reaction, with a content of 10.20% and the ability to oxidize sulfide. The content of Nitrosomonas in aerobic reaction zone reached 36.75%, but no nitrifying bacteria were detected. The technology in this study, which used sulfate as the electron acceptor for the continuous biological removal of Cd2+, has future engineering application value for the treatment of wastewater containing low concentrations of Cd.

Abstract With the rapid development of social networks, academic social networks have attracted increasing attention. In particular, providing personalized recommendations for learners considering data sparseness and cold-start scenarios is a challenging task. An important research topic is to accurately discover potential friends of learners to build implicit learning groups and obtain personalized collaborative recommendations of similar learners according to the learning content. This paper proposes a personalized explainable learner implicit friend recommendation method (PELIRM). Methodologically, PELIRM utilizes the learner's multidimensional interaction behavior in social networks to calculate the degrees of trust between learners and applies the three-degree influence theory to mine the implicit friends of learners. The similarity of research interests between learners is calculated by cosine and term frequency–inverse document frequency. To solve the recommendation problem for cold-start learners, the learner's common check-in IP is used to obtain the learner's location information. Finally, the degree of trust, similarity of research interests, and geographic distance between learners are combined as ranking indicators to recommend potential friends for learners and give multiple interpretations of the recommendation results. By verifying and evaluating the proposed method on real data from Scholar.com, the experimental results show that the proposed method is reliable and effective in terms of personalized recommendation and explainability.

The root extracts and root exudates from the Taxus chinensis var. mairei had significant promote effects on growth of Camptoteca acuminata seedlings. Four taxane chemicals, cephalomannine, 10-deacetylbacatin III, paclitaxel and 7-Epi-10-deacetyl-paclitaxel, were isolated from T. chinensis var. mairei root extracts and their structures were identified by spectroscopic analysis. The chemicals were detected in T. chinensis var. mairei root exudates, rhizosphere soils, and their concentrations ranged from 0.01 to 5.90 μg/g. At an approximate concentration determined in T. chinensis var. mairei root exudates, all four chemicals significantly promoted the growth of C. acuminata seedlings. Therefore, four chemicals from T. chinensis var. mairei root exudates may act as allelochemicals accelerating growth of C. acuminata seedling. There were significant relationships between growth of C. acuminata seedlings, soil properties, enzyme activities and microbial community under allelochemicals’ application. The results provide a reference for in-depth understanding of C. acuminata and T. chinensis var. mairei interactions.

This paper proposes a special disconnector for surge protector (SPD) with the ability to pass large pulse currents under multiple pulses, which has been verified to solve the problem of SPD fire and combustion under multiple pulses in engineering applications. The safety problem caused by the lightning strike failure of SPD has always been a difficult research point in low-voltage power distribution systems, especially the failure mechanism under multi-pulse lightning strike is still unclear. In this paper, the multi-pulse lightning generator is used to simulate the multi-pulse lightning current to carry out the SPD lightning impulse test. The results show that the SPD will have short-circuit breakdown and fire and combustion under multi-pulse lightning strikes, mainly because the continuous pulses will generate energy superposition, and the built-in disconnector and external disconnector fuses and circuit breakers cannot effectively cooperate with the SPD, and there is a protection blind spot. As a result, the SPD cannot be quickly detached at the moment of a short circuit. Based on the thermal effect of multi-pulse lightning strikes, a multi-pulse SPD special disconnector is designed, which can effectively solve the problem of lightning strike ignition of SPD under multi-pulse lightning strikes, and is of great significance to the lightning protection safety of low-voltage power distribution systems.

The endothermic hydrocarbon fuel is used as a coolant to realize active cooling for the high-heat-flux components of air-breathing hypersonic vehicles. Because of its complex composition and severe thermal boundary conditions, the unstable heat transfer and coking are usually the major problems. Flow boiling heat transfer of a kind of endothermic hydrocarbon fuel named EHF-204 and its visualization were experimentally investigated in mini-channels with 2.0 mm internal diameter at heat flux of 250 kW/m2 and 500 kW/m2. It is found that the heat transfer enhancement and heat transfer deterioration would occur obviously during the flow boiling heat transfer process at subcritical and near-critical pressures of 1.0 MPa and 2.5 MPa. After the fuel was completely vaporized, the heat transfer coefficient would slowly increase again with the increasing fuel temperature. The heat transfer enhancement and heat transfer deterioration process at subcritical temperatures were not existed at the supercritical pressure of 4.0 MPa. The flow patterns of bubbly flow, slug flow, and churn flow were clearly observed at the subcritical pressures. Flow pattern visualization proved that the constant wall temperature heat transfer processes at subcritical pressures were subcooled boiling and saturation boiling flow. The bigger bubbles were formed at lower pressures, which caused higher heat transfer coefficient. The bubbly flow, slug flow caused the heat transfer enhancement, and the appearance of churn flow was a feather that made the boiling heat transfer transition from heat transfer enhancement to heat transfer deterioration. Some interesting visualization phenomena were observed in this study including the twice vaporization during flow boiling.

This study was conducted to investigate the effects of nitrogen application on growth, photosynthetic performance, nitrogen metabolism activities, and fruit quality of tomato plants under high-temperature (HT) stress. Three levels of daily minimum/daily maximum temperature were adopted during the flowering and fruiting stage, namely control (CK; 18°C/28°C), sub-high temperature (SHT; 25°C/35°C), and high-temperature (HT; 30°C/40°C) stress. The levels of nitrogen (urea, 46% N) were set as 0 (N1), 125 (N2), 187.5 (N3), 250 (N4), and 312.5 (N5) kg hm2, respectively, and the duration lasted for 5 days (short-term). HT stress inhibited the growth, yield, and fruit quality of tomato plants. Interestingly, short-term SHT stress improved growth and yield via higher photosynthetic efficiency and nitrogen metabolism whereas fruit quality was reduced. Appropriate nitrogen application can enhance the high-temperature stress tolerance of tomato plants. The maximum net photosynthetic rate (PNmax), stomatal conductance (gs), stomatal limit value (LS), water-use efficiency (WUE), nitrate reductase (NR), glutamine synthetase (GS), soluble protein, and free amino acids were the highest in N3, N3, and N2, respectively, for CK, SHT, and HT stress, whereas carbon dioxide concentration (Ci), was the lowest. In addition, maximum SPAD value, plant morphology, yield, Vitamin C, soluble sugar, lycopene, and soluble solids occurred at N3-N4, N3-N4, and N2-N3, respectively, for CK, SHT, and HT stress. Based on the principal component analysis and comprehensive evaluation, we found that the optimum nitrogen application for tomato growth, yield, and fruit quality was 230.23 kg hm2 (N3-N4), 230.02 kg hm2 (N3-N4), and 115.32 kg hm2 (N2), respectively, at CK, SHT, and HT stress. Results revealed that the high yield and good fruit quality of tomato plants at high temperatures can be maintained by higher photosynthesis, nitrogen efficiency, and nutrients with moderate nitrogen.

Strong alkali alkali-surfactant-polymer (ASP) flooding produced water is a by-product of oil recovery, and it is a stable system composed of petroleum, polyacrylamide, surfactant, and inorganic salts. Efficient, green, and safe ASP produced water treatment technology is essential for oilfield exploitation and environmental protection. In this study, an anaerobic/anoxic/moving bed biofilm reactor with a microfiltration membrane was established and assessed for the real strong alkali ASP flooding produced water (pH 10.1–10.4) treatment. The results show that the average removal rates of COD, petroleum, suspended solids, polymers and surfactants in this process are 57, 99, 66, 40, and 44%, respectively. GC-MS results show that most of the organic compounds such as alkanes and olefins in the strong alkali ASP produced water are degraded. Microfiltration membrane can significantly improve the efficiency and stability of sewage treatment system. Paracoccus (AN), Synergistaceae (ANO) and Trichococcus (MBBR) are the main microorganisms involved in the degradation of pollutants. This study reveals the potential and adaptability of composite biofilm system in treating the produced water of strong alkali ASP produced water.

To study the impact of nitrogen application on the photosynthetic structure and photosystem activity of tomato (Lycopersicon esculentum Mill.) leaves during the recovery stage after heat stress, the OJIP curve and JIP parameters were determined through a control experiment in an artificial climate chamber. The tomato variety was “Jinfen No. 1”. Four day/night temperature levels (25 °C/15 °C as control CKT; 30 °C/20 °C, lightly high-temperature LHT; 35 °C/25 °C, moderate high-temperature MHT; 40 °C/30 °C, severe high-temperature SHT) were set for a duration of 7 days. Five nitrogen supply levels (N1–N5: 0, 1.3, 1.95, 2.6 and 3.75 g/plant, respectively; 2.6 g/plant is the recommended nitrogen application rate, CKTN4) were applied. The results showed that the O, K, J, I and P phases on the chlorophyll a fluorescence curve were significantly affected by different nitrogen treatments in heat stress recovery. Compared with CKT, with the increase in nitrogen supply, the fluorescence intensity of SHTN2-SHTN5 treatment increased significantly at P, I and J phases, while that of MHTN1-MHTN4 treatment decreased. The fluorescence intensity of SHTN5 and SHTN3 increased by 13.27% and 10.10% in the P phase, 13.52% and 12.1% in the I phase and 20.16% and 26.18% in the J phase, respectively. There were highly significant differences (p < 0.01) in the impact of high temperatures and nitrogen levels on the fluorescence parameters. On the 1st day after short-term heat stress, N had no significant effect on Fv/FM, Fv, Fo and FM; however, their interaction was significant (p < 0.05). On the 8th day, there were no significant interaction effects between HT and N for Fv/Fo, ABS/RC and DIo/RC. Fv/Fo proved to be sensitive to the application of both high temperatures and nitrogen. Under all five nitrogen applications, temperature played a significant role in increasing DIo/RC, especially for N2 and N3. The results indicated that decreasing the nitrogen application under SHT resulted in a higher number of active RCs and an increased value of specific energy flux (ABS/RC, TRo/RC and DIo/RC), indicating the enhanced ability of RC to reduce plastoquinone. The study provides a reference for the diagnosis of nitrogen nutrition under high-temperature stress using chlorophyll fluorescence methods.

Objective: Skin diseases constitute a widespread health concern, and the application of machine learning and deep learning algorithms has been instrumental in improving diagnostic accuracy and treatment effectiveness. This paper aims to provide a comprehensive review of the existing research on the utilization of machine learning and deep learning in the field of skin disease diagnosis, with a particular focus on recent widely used methods of deep learning. The present challenges and constraints were also analyzed and possible solutions were proposed. Methods: We collected comprehensive works from the literature, sourced from distinguished databases including IEEE, Springer, Web of Science, and PubMed, with a particular emphasis on the most recent 5-year advancements. From the extensive corpus of available research, twenty-nine articles relevant to the segmentation of dermatological images and forty-five articles about the classification of dermatological images were incorporated into this review. These articles were systematically categorized into two classes based on the computational algorithms utilized: traditional machine learning algorithms and deep learning algorithms. An in-depth comparative analysis was carried out, based on the employed methodologies and their corresponding outcomes. Conclusions: Present outcomes of research highlight the enhanced effectiveness of deep learning methods over traditional machine learning techniques in the field of dermatological diagnosis. Nevertheless, there remains significant scope for improvement, especially in improving the accuracy of algorithms. The challenges associated with the availability of diverse datasets, the generalizability of segmentation and classification models, and the interpretability of models also continue to be pressing issues. Moreover, the focus of future research should be appropriately shifted. A significant amount of existing research is primarily focused on melanoma, and consequently there is a need to broaden the field of pigmented dermatology research in the future. These insights not only emphasize the potential of deep learning in dermatological diagnosis but also highlight directions that should be focused on.

Cheqianzi Decoction (CQD) is a Traditional Chinese Medicine (TCM) formula comprising four herbs and is recorded in the Ancient Materia Medica “Shengji Zonglu”. Individually, these four herbs have been shown to reduce uric acid (UA) levels, to treat hyperuricemia (HUA), and alleviate kidney damage. However, the therapeutic efficacy of the CQD and related mechanism are not yet clear.In this study, high performance liquid chromatography (HPLC) analysis confirmed that the contents of the chemical components of the four herbal medicines were in accordance with the provisions of the Chinese Pharmacopoeia. A total of 99 potential targets were identified in the network pharmacology analysis of CQD, indicating its involvement in the regulation of inflammatory and apoptotic signaling pathways, and potential value for treating HUA and alleviating kidney injury. In vivo pharmacodynamic studies showed that compared with the Model group, significantly decreased levels of serum uric acid (SUA), serum creatinine (SCr), blood urea nitrogen (BUN) (all P < 0.05), and inflammatory factors (P < 0.01) were detected in the CQD group. Quantitative real-time PCR and Western blot analyses showed that compared with the Model group, adenosine triphosphate (ATP)-binding cassette efflux transporter G2 (ABCG2) expression in the CQD group was significantly upregulated (P

ABSTRACT The rhizosphere of invasive plants presumably develops different soil microbial assemblages compared with native plants, which may hinder or promote their invasion. However, to date, no studies have clearly explored rhizosphere microbial community assemblages during invasion. The invasive species Ambrosia artemisiifolia L. and Bidens pilosa L. are widely distributed in China and are known to reduce local biodiversity and cause agricultural losses. Monoculture of A. artemisiifolia or B. pilosa, a mixture of each invasive and native species, and monoculture of native species were established to simulate different degrees of invasion. Metagenomic sequencing techniques were used to test microbial community structure and function. The aim was to explore the drivers of the assembly of peculiar functional microbes in the rhizosphere soil of invasive species during the long-term invasive-native species interaction. Compared with the native species, the relative abundance of 34 microbial genera was higher in the rhizosphere soil of the invasive species. The NO3-N concentration in the rhizosphere soil from the A. artemisiifolia and B. pilosa monocultures was lower than that from monocultures of the three native plants, whereas pH followed the opposite trend. The NO3-N concentration was significantly and negatively correlated with Sporichthya, Afipia, Actinokineospora, and Pseudolabrys. pH was positively correlated with Bradyrhizobium, Actinoplanes, Micromonospora, Steroidobacter, Burkholderia, and Labilithrix. The differences in soil microbes, NO3-N concentrations, and pH between native and invasive species suggest that the rhizosphere soil microbial assemblages may vary. The reduced NO3-N concentration and increased pH corelated with changes in rhizosphere microbial community during A. artemisiifolia and B. pilosa invasion. IMPORTANCE Soil microbial communities play a vital role in the growth of invasive plants. Invasive species may shape peculiar functional microbes in the rhizosphere soil of an invasive species to benefit its growth. However, the drivers of the assembly of soil microbial communities in the rhizosphere soil of invasive species remain unclear. Our study established the relationship between soil microbial communities and soil chemical properties during invasion by A. artemisiifolia and B. pilosa. Additionally, it showed that the presence of the invasive plants correlated with changes in NO3-N and pH, as well as in rhizosphere microbial community assemblage. Furthermore, the study provided important insights into the difference in the microbial community assembly between native and invasive plant species.

Abstract Vitiligo is a cutaneous depigmenting autoimmune disease caused by the extensive destruction of epidermal melanocytes. Convincing data has defined a critical role for oxidative stress in the pathogenesis of vitiligo. Oxeiptosis is a caspase-independent cell death modality that was reportedly triggered by oxidative stress and operative in pathogen clearance. However, whether oxeiptosis exists in oxidative stress-induced melanocytes demise in vitiligo remains undetermined. In the present study, we initially found that other cell death modalities might exist in addition to the well-recognized apoptosis and necroptosis in H2O2-treated melanocytes. Furthermore, AIFM1 was found to be dephosphorylated at Ser116 in oxidative stress-induced melanocytes death, which was specific to oxeiptosis. Moreover, KEAP1 and PGAM5, upstream of the AIFM1 in oxeiptosis, were found to operate in melanocytic death. Subsequently, the KEAP1-PGAM5-AIFM1 signaling pathway was proved to be involved in oxidative stress-triggered melanocytes demise through the depletion of KEAP1 and PGAM5. Altogether, our study indicated that oxeiptosis might occur in melanocytes death under oxidative stress and contribute to the pathogenesis of vitiligo.

Abstract. Interleukins (ILs) and associated cytokines serve as the means of communication for immune cells and non-immune cells. The use of ILs in harnessing the immune system to cancer treatment has been a promising approach. ILs not only nurture an environment enabling cancer growth but also simultaneously trigger a productive tumor-directed immune response. These properties of ILs are increasingly being explored as a strategy to improve the outcomes of cancer. Here, we describe recently innovative technological approaches that have been developed to improve the pharmacokinetics, safety, and efficacies of IL-2, 15, 10, and 18 in the treatment of melanoma. Furthermore, the combination of ILs and immune checkpoint inhibition may synergize to reshape the tumor environment, thus yielding better clinical benefits in the future.

The treatment efficiency of Chromium (Cr)-containing Printed Circuit Board (PCB) wastewater is significantly hampered by the limited physiological activity of microorganisms when activated sludge is applied. In this study, the biodegradation and electron transfer based on sulfur metabolism in the integrated (BESI®) process use sulfur as the electron acceptor to achieve sulfate reduction and sulfide oxidation, leading to efficient removal of Cr. The concentrations of total Cr and Cr(VI) in the effluent were reduced to 0.5 mg/L and 0.1 mg/L, respectively, from an initial range of 25–32 mg/L in the influent. The removal of Cr (ΔC(Cr(VI))) mainly occurred in the Sulfate Reduction (SR) reactor, which was significantly correlated with the generation of sulphide (

Bacillus can help plants to acquire nutrients either directly or indirectly. However, the role of Bacillus community on the competitive growth of invasive Ambrosia artemisiifolia is poorly understood. Native Setaria viridis is often found in areas that have been invaded by A. artemisiifolia. We sought to determine whether the quantitative and/or qualitative differences in the Bacillus community present on the invasive A. artemisiifolia and native S.viridis provide a competitive advantage to the invasive over native species. A field experiment was established to imitate the invasion of A. artemisiifolia. The 16S rRNA gene was commercially sequenced to identify the bacilli isolated from the rhizosphere soil of field-grown A. artemisiifolia and S. viridis. The Bacillus communities in their rhizosphere were compared, and their effects on the competitive growth of A. artemisiifolia and S. viridis were tested in the pot experiments. Bacillus in the rhizosphere soil of A. artemisiifolia significantly enhanced its intra-specific competitive ability. The relative abundance of B. megaterium in the rhizosphere soil of A. artemisiifolia was significantly higher than that of S. viridis. Inoculation with B. megaterium that was isolated from the rhizosphere soil of both A. artemisiifolia and S. viridis significantly enhanced the relative competitiveness of A. artemisiifolia and inhibited that of S. viridis. The higher abundance of B. megaterium in the rhizosphere of A. artemisiifolia creates higher levels of available nutrients than that in the native S. viridis, which enhance the competitive growth of A. artemisiifolia. The result helps to discover the mechanism of Bacillus community in the invasion of A. artemisiifolia.

Abstract Melanoma is the most lethal skin cancer that originates from the malignant transformation of melanocytes. Although melanoma has long been regarded as a cancerous malignancy with few therapeutic options, increased biological understanding and unprecedented innovations in therapies targeting mutated driver genes and immune checkpoints have substantially improved the prognosis of patients. However, the low response rate and inevitable occurrence of resistance to currently available targeted therapies have posed the obstacle in the path of melanoma management to obtain further amelioration. Therefore, it is necessary to understand the mechanisms underlying melanoma pathogenesis more comprehensively, which might lead to more substantial progress in therapeutic approaches and expand clinical options for melanoma therapy. In this review, we firstly make a brief introduction to melanoma epidemiology, clinical subtypes, risk factors, and current therapies. Then, the signal pathways orchestrating melanoma pathogenesis, including genetic mutations, key transcriptional regulators, epigenetic dysregulations, metabolic reprogramming, crucial metastasis-related signals, tumor-promoting inflammatory pathways, and pro-angiogenic factors, have been systemically reviewed and discussed. Subsequently, we outline current progresses in therapies targeting mutated driver genes and immune checkpoints, as well as the mechanisms underlying the treatment resistance. Finally, the prospects and challenges in the development of melanoma therapy, especially immunotherapy and related ongoing clinical trials, are summarized and discussed.

BackgroundNon-segmental vitiligo (NSV) is an autoimmune skin disorder that is difficult to determine disease activity/severity and thus to treat. Alarmins have emerged as promising biomarkers in various diseases, so further confirmation of their potential roles in NSV would be of considerable value. With the present work, we aimed to determine the serum levels of alarmins in patients with NSV, correlate these alarmins with disease activity and severity, and analyze the predictive value of the combination of these markers.Methods104 NSV patients and 56 healthy controls were enrolled at the Xijing Hospital of Fourth Military Medical University between September 1, 2018, and June 30, 2019. The serum levels of alarmins (including IL-33, IL-1α, S100A9, S100A12, S100B, and HMGB1) were measured with enzyme-linked immunosorbent assays. The predictive performance of these biomarkers was evaluated with the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and other representative statistics.ResultsA total of 104 patients with NSV (mean [SD] age, 34.2 [13.0] years; 62 [59.6%] male) and 56 healthy controls (mean [SD] age, 34.8 [13.5] years; 34 [60.7%] male) were enrolled. For vitiligo diagnosis, S100B had the highest sensitivity (92.31%), whereas HMGB1 had the highest specificity (85.71%); the combination of IL-1α, S100B, S100A9, and HMGB1 increased the AUC value to 0.925, with a sensitivity of 87.50% and a specificity of 85.71%. Multivariate logistic regression analysis showed S100B (OR, 1.019; 95% CI, 1.002-1.038; P =0.03), S100A9 (OR, 1.002; 95% CI, 1.001-1.003; P

Abstract Objective To develop high-quality synthetic CT (sCT) generation method from low-dose cone-beam CT (CBCT) images by using attention-guided generative adversarial networks (AGGAN) and apply these images to dose calculations in radiotherapy. Methods The CBCT/planning CT images of 170 patients undergoing thoracic radiotherapy were used for training and testing. The CBCT images were scanned under a fast protocol with 50% less clinical projection frames compared with standard chest M20 protocol. Training with aligned paired images was performed using conditional adversarial networks (so-called pix2pix), and training with unpaired images was carried out with cycle-consistent adversarial networks (cycleGAN) and AGGAN, through which sCT images were generated. The image quality and Hounsfield unit (HU) value of the sCT images generated by the three neural networks were compared. The treatment plan was designed on CT and copied to sCT images to calculated dose distribution. Results The image quality of sCT images by all the three methods are significantly improved compared with original CBCT images. The AGGAN achieves the best image quality in the testing patients with the smallest mean absolute error (MAE, 43.5 ± 6.69), largest structural similarity (SSIM, 93.7 ± 3.88) and peak signal-to-noise ratio (PSNR, 29.5 ± 2.36). The sCT images generated by all the three methods showed superior dose calculation accuracy with higher gamma passing rates compared with original CBCT image. The AGGAN offered the highest gamma passing rates (91.4 ± 3.26) under the strictest criteria of 1 mm/1% compared with other methods. In the phantom study, the sCT images generated by AGGAN demonstrated the best image quality and the highest dose calculation accuracy. Conclusions High-quality sCT images were generated from low-dose thoracic CBCT images by using the proposed AGGAN through unpaired CBCT and CT images. The dose distribution could be calculated accurately based on sCT images in radiotherapy.

Objective: To explore treatment planning approaches using volumetric modulated arc therapy (VMAT) for head and neck cancer patients with metallic dental fillings. Methods: Fifty-six patients with metallic dental fillings treated with radiotherapy were selected, and three VMAT plans, the jaw-tracking plan, fixed-jaw plan, and non-coplanar plan, were designed for each patient. In the jaw-tracking plan, two coplanar partial arc fields that avoid the metal area were set, and the jaw was automatically tracked. In the fixed-jaw plan, different fields were set in three sections according to the fixed-jaw method. The fields were the same as those in the jaw-tracking plan for the section containing metal implants, while full arc fields were set in the nonmetal sections. In the non-coplanar plan, a non-coplanar arc field was added based on the jaw-tracking plan. The treatment plan in the jaw-tracking plan was optimized, and the constraints on the planning target volume (PTV) or organs at risk (OARs) in the jaw-tracking plan were copied to the other two plans. The dose distribution in PTV and OARs of the patients in the three treatment plans was compared. Results: There were no significant differences in the maximum doses to the spinal cord or optic nerves among the three treatment plans. However, compared with the jaw-tracking plan, the fixed-jaw plan showed lower mean doses to the pharynx [(42.9 ​± ​7.1) Gy vs. (44.1 ​± ​7.1) Gy, P ​

Objectives This study aims to explore the spatial and spatiotemporal distribution of pertussis in Hunan Province, and provide a scientific basis for targeting preventive measures in areas with a high incidence of pertussis.Design In this retrospective spatial and spatiotemporal (ecological) study, the surveillance and population data of Hunan Province from 2009 to 2019 were analysed. The ArcGIS V.10.3 software was used for spatial autocorrelation analysis and visual display, and SaTScan V.9.6 software was used for statistical analysis of spatiotemporal scan data.Settings Confirmed and suspected pertussis cases with current addresses in Hunan Province and onset dates between 1 January 2009 and 31 December 2019 were included in the study.Participants The study used aggregated data, including 6796 confirmed and suspected pertussis cases.Results The seasonal peak occurred between March and September, and scattered children were at high risk. The global Moran’s I was between 0.107 and 0.341 (p

Melanoma results from the malignant transformation of melanocytes and accounts for the most lethal type of skin cancers. In the pathogenesis of melanoma, disordered metabolism is a hallmark characteristic with multiple metabolic paradigms involved in, e.g., glycolysis, lipid metabolism, amino acid metabolism, oxidative phosphorylation, and autophagy. Under the driving forces of oncogenic mutations, melanoma metabolism is rewired to provide not only building bricks for macromolecule synthesis and sufficient energy for rapid proliferation and metastasis but also various metabolic intermediates for signal pathway transduction. Of note, metabolic alterations in tumor orchestrate tumor immunology by affecting the functions of surrounding immune cells, thereby interfering with their antitumor capacity, in addition to the direct influence on tumor cell intrinsic biological activities. In this review, we first introduced the epidemiology, clinical characteristics, and treatment proceedings of melanoma. Then, the components of the tumor microenvironment, especially different populations of immune cells and their roles in antitumor immunity, were reviewed. Sequentially, how metabolic rewiring contributes to tumor cell malignant behaviors in melanoma pathogenesis was discussed. Following this, the proceedings of metabolism- and metabolic intermediate-regulated tumor immunology were comprehensively dissertated. Finally, we summarized currently available drugs that can be employed to target metabolism to intervene tumor immunology and modulate immunotherapy.

Metabolites/impurities (MIs) of penicillin are normally considered to be the main substances inducing immediate hypersensitivity reactions in penicillin treatment. Our previous research found that penicillin can cause non-allergic hypersensitivity reactions (NAHRs) by directly triggering vascular hyperpermeability and exudative inflammation. However, the chief culprits and underlying mechanisms involved in penicillin-induced NAHRs have not yet been fully elucidated. In this study, we used a combination of approaches including a mouse non-allergic hypersensitivity reaction model, UPLC-MS/MS analyses of arachidonic acid metabolites (AAMs), immunoblotting technique, and molecular docking, etc to investigate the culprits involved in penicillin-induced hypersensitivity reactions. We found penilloic acid, one of the main MIs of penicillin, could trigger NAHRs via inducing increased vascular permeability, while the other MIs did no exhibit similar effect. Penilloic acid-induced reactions were not IgE-dependent. Significantly increased arachidonic acids and cascade metabolites in lungs, and activation of RhoA/ROCK signaling pathway in the ears and lungs of mice were noticed after once administration of penilloic acid. This study revealed that penilloic acid was the chief culprit involved in penicillin-induced immediate NAHRs in mice, which mainly associated with direct stimulation of vascular hyperpermeability and exudative inflammation. The activations of AAMs and RhoA/ROCK signaling pathway played important roles in these reactions.

Our research group successfully designed the F. carica and Taxus cuspidata Sieb. et Zucc mixed forest, and confirmed that their interspecific relationship was stable and F. carica has a promoting effect on neighboring T. cuspidata growth. However, the promoting mechanism has not been elucidated. In this study, F. carica was used as the donor plant and T. cuspidata was used as the recipient plant. T. cuspidata seedlings were irrigated with F. carica root extracts of different concentrations (10.0, 20.0, 40.0 g·L−1), and the plant height, base diameter, photosynthetic parameters, photosynthetic pigments, MDA contents, and antioxidant enzyme activities were measured. Soil physical and chemical properties, enzyme activities, and microbial diversity were measured. The results showed that the abundance of growth-promoting bacteria increased and the number of pathogenic bacteria decreased in the rhizosphere of T. cuspidata soil. It was speculated that the chemicals secreted by F. carica roots interacted with soil microorganisms of T. cuspidata soil after enrichment, changed soil microbial diversity, and indirectly promoted the growth of T. cuspidata. UPLC-QTOF-MS/MS was used to analyze F. carica root water extract and F. carica root exudates, respectively, and it was found that the main components were similar. Therefore, the promoting effect of F. carica on T. cuspidata is mainly caused by the accumulation of potential chemicals in F. carica root exudates in the soil through interaction with soil microorganisms. Furthermore, the allelopathic-promoting mechanism of F. carica on T. cuspidata was discussed from various aspects, to provide a theoretical basis for the protection, breeding, and sustainable management of T. cuspidata resources.