Berberine sensitizes immune checkpoint blockade therapy in melanoma by NQO1 inhibition and ROS activation.

Unprecedented progress in immune checkpoint blockade (ICB) therapy has been made in cancer treatment. However, the response to ICB therapy is limited to a small subset of patients. The development of ICB sensitizers to improve cancer immunotherapy outcomes is urgently needed. Berberine (BBR), a well-known phytochemical compound isolated from many kinds of medicinal plants such as Berberis aristata, Coptis chinensis, and Phellondendron chinense Schneid, has shown the ability to inhibit the proliferation, invasion and metastasis of cancer cells. In this study, we investigated whether BBR can enhance the therapeutic benefit of ICB for melanoma, and explored the underlying mechanisms involved. The results showed that BBR could sensitize ICB to inhibit tumor growth and increased the survival rate of mice. Moreover, BBR stimulated intracellular ROS production partially by inhibiting NQO1 activity, which induced immunogenic cell death (ICD) in melanoma, elevated the levels of damage-associated molecular patterns (DAMPs), and subsequently activated DC cells and CD8 + T cells in vitro and in vivo. In conclusion, BBR is a novel ICD inducer. BBR could enhance the therapeutic benefit of ICB for melanoma. These effects were partially mediated through the inhibition of NQO1 and ROS activation.

Machine learning models for daily net radiation prediction across different climatic zones of China.

Net radiation (Rn), a critical component in land surface energy cycling, is calculated as the difference between net shortwave radiation and longwave radiation at the Earth's surface and holds significant importance in crop models for precision agriculture management. In this study, we examined the performance of four machine learning models, including extreme learning machine (ELM), hybrid artificial neural networks with genetic algorithm models (GANN), generalized regression neural networks (GRNN), and random forests (RF), in estimating daily Rn at four representative sites across different climatic zones of China. The input variables included common meteorological factors such as minimum and maximum temperature, relative humidity, sunshine duration, and shortwave solar radiation. Model performance was assessed and compared using statistical parameters such as the correlation coefficient (R2), root mean square errors (RMSE), mean absolute errors (MAE), and Nash-Sutcliffe coefficient (NS). The results indicated that all models slightly underestimated actual Rn, with linear regression slopes ranging from 0.810 to 0.870 across different zones. The estimated Rn was found to be comparable to observed values in terms of data distribution characteristics. Among the models, the ELM and GANN demonstrated higher consistency with observed values, exhibiting R2 values ranging from 0.838 to 0.963 and 0.836 to 0.963, respectively, across varying climatic zones. These values surpassed those of the RF (0.809-0.959) and GRNN (0.812-0.949) models. Additionally, the ELM and GANN models showed smaller simulation errors in terms of RMSE, MAE, and NS across the four climatic zones compared to the RF and GRNN models. Overall, the ELM and GANN models outperformed the RF and GRNN models. Notably, the ELM model's faster computational speed makes it a strong recommendation for Rn estimates across different climatic zones of China.

The impact of the nursing work environment on compassion fatigue: The mediating role of general self-efficacy.

AIM: To explore the interplay between the perceived nursing work environment, general self-efficacy, and compassion fatigue among registered nurses in Chinese hospitals. BACKGROUND: Compassion fatigue emerges as a significant occupational stress response globally, with the nursing work environment being a pivotal influencer. There is a knowledge gap in understanding how the nursing work environment and general self-efficacy interrelate to affect compassion fatigue, particularly among Chinese nurses. METHODS: Employing a cross-sectional, descriptive design, this study utilized validated questionnaires to gather data from 7085 nurses across public and private hospitals in China. The analysis focused on assessing the interrelations among the perceived nursing work environment, general self-efficacy, and different dimensions of compassion fatigue. FINDING: More than half (65.67%) of the participants experienced moderate or high burnout levels, with 76.43% experiencing secondary traumatic stress. The lowest rating in the nursing work environment was for nurse/physician collaboration (10 ± 2.07), while general self-efficacy scored higher (27.54 ± 6.26). A positive relationship existed between the work environment and both general self-efficacy and compassion satisfaction, with a negative correlation to burnout and traumatic stress. General self-efficacy was a partial mediator in the link between work environment and compassion fatigue, suggesting that improving the work environment can decrease compassion fatigue by boosting nurses' self-efficacy. CONCLUSION: This study underscores the profound impact of the nursing work environment on compassion fatigue, mediated by general self-efficacy. It highlights the necessity of fostering a supportive work environment to enhance nurses' self-efficacy and overall well-being. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Healthcare managers and institutions must create supportive work environments to reduce compassion fatigue among nurses. This includes professional development programs to enhance self-efficacy and job satisfaction. Policies should address high workloads and inadequate support. Nurse leaders should foster environments that promote psychological well-being, improving outcomes for both nurses and patients. Regular assessments and adjustments of work conditions are essential to maintain a healthy work environment.

Immunogenicity and safety of Vero cell culture-derived Japanese encephalitis vaccine: a phase 3 study in Chinese infants.

BACKGROUND: Japanese encephalitis (JE) is a severe infectious disease of the central nervous system. Vaccination with Vero cell culture-derived vaccines may effectively reduce JE incidence. RESEARCH DESIGN AND METHODS: In this single-center, randomized, blinded, positive-controlled clinical trial in China involving 600 healthy infants aged 6-11 months, participants were divided into experimental and control groups administered JEV-PI and JEV-LI, respectively. Antibody titers were determined after 0- and 7-day immunization schedules. A booster dose followed 12 months later. RESULTS: After primary vaccination and before booster vaccination, the positive conversion rate, geometric mean titer (GMT), and geometric mean increase (GMI) of JEV-PI-neutralizing antibodies exceeded those of JEV-LI. After booster immunization, the GMT and GMI of JEV-PI were higher than those of JEV-LI. After primary immunization, the local, systemic, and overall adverse reactions were of grades 1 and 2, with a low incidence of grade 3. After booster immunization, these differences were mainly grades 1 and 2, with no differences between JEV-PI and JEV-LI. CONCLUSION: JEV-PI is a promising vaccine as infants acquired long-lasting and highly neutralizing immune antibodies after inoculation with JEV-PI. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry (https://www.chictr.org.cn/showproj.html?proj = 203130; registration number: ChiCTR2300074692; registration date: 14/08/2023).

Low-dose abiraterone plus Olaparib as a late-line treatment for mCRPC patients without BRCA1/2 mutations: a multicenter retrospective pilot study.

Although overall survival data are still premature, the PROpel study found radiological progression-free survival (PFS) benefits of abiraterone and olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC). However, for patients who have not been genetically tested or lack BRCA1/2 mutations (BRCAm), this combination therapy has been questioned as a first-line conventional treatment for mCRPC, mainly due to significant health economics and side effects. In our retrospective study, we found that treatment with low-dose abiraterone plus olaparib as a late-line treatment for mCRPC could lead to prostate-specific antigen (PSA) and symptom PFS in selective cases even without BRCAm. The median PSA-PFS was 8 months (IQR: 6.5-11.5), with a median follow-up duration of 39.0 months (IQR: 27.5-64.5). Gene tests were conducted in all patients, identifying non-BRCA mutations through ctDNA testing (24%), tumor tissue testing (12%), or both (64%). Adverse events occurred in 72% of patients, with 16% experiencing Grade ≥ 3 events. Common adverse events included anemia (64%), decreased appetite (48%), and fatigue (25%). Our findings support low-dose abiraterone plus olaparib as a potential option for mCRPC patients without BRCAm, offering manageable safety and efficacy profiles.

The introgression of BjMYB113 from Brassica juncea leads to purple leaf trait in Brassica napus.

The purple leaves of Brassica napus are abundant in anthocyanins, which are renowned for their role in conferring distinct colors, stress tolerance, and health benefits, however the genetic basis of this trait in B. napus remains largely unelucidated. Herein, the purple leaf B. napus (PL) exhibited purple pigments in the upper epidermis and a substantial increase in anthocyanin accumulation, particularly of cyanidin, compared to green leaf B. napus (GL). The genetic control of the purple leaf trait was attributed to a semi-dominant gene, pl, which was mapped to the end of chromosome A03. However, sequencing of the fragments amplified by the markers linked to pl indicated that they were all mapped to chromosome B05 from B. juncea. Within this B05 chromosomal segment, the BjMYB113 gene-specific marker showed perfect co-segregation with the purple leaf trait in the F2 population, suggesting that the BjMYB113 introgression from B. juncea was the candidate gene for the purple leaf trait in B. napus. To further verify the function of candidate gene, CRISPR/Cas9 was performed to knock out the BjMYB113 gene in PL. The three myb113 mutants exhibited evident green leaf phenotype, absence of purple pigments in the adaxial epidermis, and a significantly reduced accumulation of anthocyanin compared to PL. Additionally, the genes involved in positive regulatory (TT8), late anthocyanin biosynthesis (DFR, ANS, UFGT), as well as transport genes (TT19) were significantly suppressed in the myb113 mutants, further confirming that BjMYB113 was response for the anthocyanin accumulation in purple leaf B. napus. This study contributes to an advanced understanding of the regulation mechanism of anthocyanin accumulation in B. napus.

Fe Single Atoms Anchored on N-doped Mesoporous Carbon Microspheres for Promoted Oxygen Reduction Reaction.

Fe single atoms (Fe SAs) based catalysts have received much attention in electrocatalytic oxygen reduction reaction (ORR) due to its low-cost and high activity. Yet, the facile synthesis of efficient and stable Fe SAs catalysts are still challenging. Here, we reported a Fe SAs anchored on N-doped mesoporous carbon microspheres (NC) catalyst via spraying drying and pyrolysis processes. The highly active Fe SAs are uniformly distributed on the NC matrix, which prevented the aggregation benefiting from the enhanced Fe-N bonds. Also, the mesoporous carbon structure is favorable for fast electron and mass transfer. The optimized Fe@NC-2-900 catalyst shows positive half wave potential (E1/2 = 0.86 V vs reversible hydrogen electrodes (RHE)) and starting potential (Eonset = 0.98 V vs RHE) in ORR, which is comparable to the commercial Pt/C catalyst (E1/2= 0.87 V, Eonset = 1.08 V). Outstanding stability with a current retention rate of 92.5% for 9 hours and good methanol tolerance are achieved. The assembled zinc-air batteries showed good stability up to 500 hours at a current density of 5 mA cm-2. This work shows potentials of Fe SAs based catalysts for the practical application in ORR and pave a new avenue for promoting their catalytic performances.

Exploring factors influencing awareness and knowledge of human papillomavirus in Chinese college students: A cross-sectional study.

Cervical cancer remains a significant health burden in China, characterized by high incidence and mortality rates, which are exacerbated by low Human Papillomavirus (HPV) vaccination coverage, leading to substantial loss of productivity, emotional suffering, and family strain. Understanding factors that influence HPV awareness and knowledge is crucial for developing effective educational strategies. This cross-sectional study, conducted from September to October 2022, involved 2,679 college students from various educational institutions in Jiangsu Province, China. Data were collected via an online questionnaire covering demographics, HPV knowledge, and vaccination behaviors. Statistical analyses, including Chi-square tests and multifactorial logistic regression, were used to identify factors influencing HPV knowledge. The study revealed that while over 90% of students correctly identified HPV's transmission and risks, significant knowledge gaps and misconceptions persist, particularly regarding HPV's association with HIV/AIDS and its treatment. Factors significantly associated with better HPV knowledge included age (22-24 years), female gender, being a medical major, being in a relationship, familiarity with HPV, and participation in sexual education programs. Despite a high willingness to receive the HPV vaccine (91.64%), actual vaccination rates remained low. These findings suggest that while Chinese college students were generally aware of HPV, targeted educational interventions are essential to address knowledge gaps and promote HPV vaccination effectively.

A case report of recurrent testicular germ cell tumor in a patient with a history of primary pulmonary germ cell tumor and a review of the literature.

Background: Compared to testicular germ cell tumors, the incidence of extragonadal germ cell tumors (EGCTs) is relatively low. While the lungs are a common site for metastasis of malignant germ cell tumors, primary pulmonary germ cell tumors are extremely rare. Objective: To enhance the understanding of the diagnosis and treatment of germ cell tumors, particularly extragonadal germ cell tumors (EGCTs). Methods: A Case Report of Recurrent Testicular Germ Cell Tumor in a Patient with Primary Pulmonary Germ Cell Tumor and a Review of the Literature. Clinical data: The patient was initially diagnosed with primary pulmonary germ cell tumor and received standard treatment. Five years later, the patient developed a recurrent testicular germ cell tumor. The pathological results from the two surgeries were different, indicating embryonal carcinoma in the first instance and seminoma in the second. Conclusion: For cases with a high suspicion of extragonadal germ cell tumors (EGCTs), early pathological biopsy is essential to confirm the histological subtype and to guide the selection of the most appropriate and sensitive treatment regimen.

Enhancing Early Diagnosis of Bipolar Disorder in Adolescents Through Multimodal Neuroimaging.

BACKGROUND: Bipolar disorder (BD), a severe neuropsychiatric condition, often appears during adolescence. Traditional diagnostic methods, which primarily rely on clinical interviews and single-modal magnetic resonance imaging (MRI) techniques, may have limitations in accuracy. This study aimed to improve adolescent BD diagnosis by integrating behavioral assessments with multimodal MRI. We hypothesized that this combination would enhance diagnostic accuracy for at-risk adolescents. METHODS: A retrospective cohort of 309 participants, including patients with BD, offspring of patients with BD (with and without subthreshold symptoms), non-BD offspring with subthreshold symptoms, and healthy control participants, was analyzed. Behavioral attributes were integrated with MRI features from T1-weighted, resting-state functional MRI, and diffusion tensor imaging. Three diagnostic models were developed using GLMNET multinomial regression: a clinical diagnosis model based on behavioral attributes, an MRI-based model, and a comprehensive model integrating both datasets. RESULTS: The comprehensive model achieved a prediction accuracy of 0.83 (95% CI, 0.72-0.92), significantly higher than the clinical (0.75) and MRI-based (0.65) models. Validation with an external cohort showed high accuracy (0.89, area under the curve = 0.95). Structural equation modeling revealed that clinical diagnosis (ß = 0.487, p < .0001), parental BD history (ß = -0.380, p < .0001), and global function (ß = 0.578, p < .0001) significantly affected brain health, while psychiatric symptoms showed only a marginal influence (ß = -0.112, p = .056). CONCLUSIONS: This study highlights the value of integrating multimodal MRI with behavioral assessments for early diagnosis in at-risk adolescents. Combining neuroimaging enables more accurate patient subgroup distinctions, facilitating timely interventions and improving health outcomes. Our findings suggest a paradigm shift in BD diagnostics, advocating for incorporating advanced imaging techniques in routine evaluations.

Comparative analysis of drought indices in the tropical zones of China.

The intensity and frequency of drought are increasing in the tropical zone of China under global warming, and accurate assessment of drought severity and duration is critical for sustainable ecosystem management. Previous studies usually rely on one or more drought indices calculated from meteorological station or reanalysis data. However, the assessment results based on these drought indices are not consistent, which can be due to the differences in data sources and index parameters. In this study, we aim to identify the optimal dataset and drought index, and accurately evaluate the drought severity and drought duration in the tropical zone of China. We assessed the accuracy of five drought indices, namely Precipitation Anomaly in Percentage (PA), Relative Moisture Index (MI), Standardized Precipitation Index (SPI), Standardized Precipitation Evapotranspiration Index (SPEI) and Meteorological Drought Composite Index (MCI), calculated from meteorological station data and the China Meteorological Forcing Dataset (CMFD) with respect to drought records compiled by local government. Results indicate that the drought index calculated based on meteorological station data can better match the government-compiled drought records than CMFD. MI is the optimal index for drought severity and duration assessment in study area, especially for winter-spring drought and severe drought, followed by PA. The normalized bell-shaped line of fitted precipitation in winter and spring is biased towards the less rainy side in SPI calculations, which leads to more underestimation even for officially recommended MCI, and actual water supply are also misrepresented in SPEI calculations. This study offers valuable insights for policymakers to use optimal dataset and drought index to accurately assess the drought events, and take effective measures to alleviate its impact on tropical ecosystems in China.

Psoralen attenuates cigarette smoke extract-induced inflammation by modulating CD8+ T lymphocyte recruitment and chemokines via the JAK2/STAT1 signaling pathway.

Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory disease. Psoralen (PSO) is the main pharmacological component identified from Bu-Shen-Fang-Chuan formula which has been traditionally used in treatment of COPD, yet its efficacy in COPD inflammation were unreported. In this study, we aimed to elucidate the anti-inflammatory potential of PSO in COPD and unravel the underlying mechanisms, focusing on T lymphocyte recruitment and the modulation of chemokines, namely monokine induced by interferon-gamma (CXCL9), interferon inducible protein 10 (CXCL10), and interferon inducible T-Cell alpha chemoattractant (CXCL11). In vitro, RAW264.7 was stimulated by interferon (IFN)-γ + cigarette smoke extract (CSE) and were treated with PSO (2.5, 5, 10 µM), then the levels of chemokines and the activation of Janus kinase (JAK)/Signal transducer and activator of transcription 1 (STAT1) pathway were analyzed by real time PCR and western blot. In vivo, a murine model was established by intraperitoneal injection of CSE on day 1, 8, 15, and 22, then treated with PSO (10 mg/kg). Our experiments in vitro illustrated that PSO reduced the levels of CXCL9, CXCL10, and CXCL11, and decreased the protein phosphorylation levels of JAK2 and STAT1. Additionally, PSO effectively improved inflammatory infiltration and decreased the proportion of CD8+ T cells in CSE-exposed mice. Furthermore, PSO reduced the levels of CXCL9, CXCL10, and CXCL11 in bronchoalveolar lavage fluid (BALF) and lung tissue, and decreased the protein phosphorylation levels of JAK2 and STAT1. In conclusion, our results revealed the therapeutic potential of PSO for COPD inflammation, possibly mediated through the regulation of CD8+ T cell recruitment and chemokines via the JAK2/STAT1 signaling pathway.

BMP1 Promotes Keloid by Inducing Fibroblast Inflammation and Fibrogenesis.

Keloid is a typical fibrotic and inflammatory skin disease with unclear mechanisms and few therapeutic targets. In this study, we found that BMP1 was significantly increased in a collagen high-expressing subtype of fibroblast by reanalyzing a public single-cell RNA-sequence data set of keloid. The number of BMP1-positive fibroblast cells was increased in keloid fibrotic loci. Increased levels of BMP1 were further validated in the skin tissues and fibroblasts from keloid patients. Additionally, a positive correlation between BMP1 and the Keloid Area and Severity Index was found in keloid patients. In vitro analysis revealed collagen production, the phosphorylation levels of p65, and the IL-1ß secretion decreased in BMP1 interfered keloid fibroblasts. Besides, the knockdown of BMP1 inhibited the growth and migration of keloid fibroblast cells. Mechanistically, BMP1 inhibition downregulated the noncanonical TGF-ß pathways, including p-p38 and p-ERK1/2 signaling. Furthermore, we found the delivery of BMP1 siRNAs could significantly alleviate keloid in human keloid-bearing nude mice. Collectively, our results indicated that BMP1 exhibited various pathogenic effects on keloids as promoting cell proliferation, migration, inflammation, and ECM deposition of fibroblast cells by regulating the noncanonical TGF-ß/p38 MAPK, and TGF-ß/ERK pathways. BMP1-lowing strategies may appear as a potential new therapeutic target for keloid.

Nutrient-delivery and metabolism reactivation therapy for melanoma.

To fulfil the demands of rapid proliferation, tumour cells undergo significant metabolic alterations. Suppression of hyperactivated metabolism has been proven to counteract tumour growth. However, whether the reactivation of downregulated metabolic pathways has therapeutic effects remains unexplored. Here we report a nutrient-based metabolic reactivation strategy for effective melanoma treatment. L-Tyrosine-oleylamine nanomicelles (MTyr-OANPs) were constructed for targeted supplementation of tyrosine to reactivate melanogenesis in melanoma cells. We found that reactivation of melanogenesis using MTyr-OANPs significantly impeded the proliferation of melanoma cells, primarily through the inhibition of glycolysis. Furthermore, leveraging melanin as a natural photothermal reagent for photothermal therapy, we demonstrated the complete eradication of tumours in B16F10 melanoma-bearing mice through treatment with MTyr-OANPs and photothermal therapy. Our strategy for metabolism activation-based tumour treatment suggests specific nutrients as potent activators of metabolic pathways.

FOXS1 acts as an oncogene and induces EMT through FAK/PI3K/AKT pathway by upregulating HILPDA in prostate cancer.

Prostate cancer (PCa) is a widespread global health concern characterized by elevated rates of occurrence, and there is a need for novel therapeutic targets to enhance patient outcomes. FOXS1 is closely linked to different cancers, but its function in PCa is still unknown. The expression of FOXS1, its prognostic role, clinical significance in PCa, and the potential mechanism by which FOXS1 affects PCa progression were investigated through bioinformatics analysis utilizing public data. The levels of FOXS1 and HILPDA were evaluated in clinical PCa samples using various methods, such as western blotting, immunohistochemistry, and qRT-PCR. To examine the function and molecular mechanisms of FOXS1 in PCa, a combination of experimental techniques including CCK-8 assay, flow cytometry, wound-healing assay, Transwell assay, and Co-IP assay were employed. The FOXS1 expression levels were significantly raised in PCa, correlating strongly with tumor aggressiveness and an unfavorable prognosis. Regulating FOXS1 expression, whether upregulating or downregulating it, correspondingly enhanced or inhibited the growth, migration, and invasion capabilities of PCa cells. Mechanistically, we detected a direct interaction between FOXS1 and HILPDA, resulting in the pathway activation of FAK/PI3K/AKT and facilitation EMT in PCa cells. FOXS1 collaborates with HILPDA to initiate EMT, thereby facilitating the PCa progression through the FAK/PI3K/AKT pathway activation.

Evaluating the causal association between bronchiectasis and different types of inflammatory bowel disease: a two-sample Mendelian randomization study.

Background and objectives: Previous observational studies have established a connection between bronchiectasis and inflammatory bowel disease (IBD), but none of these studies have provided a clear explanation for the underlying cause of this relationship. The present study thus implemented Mendelian randomization (MR) design to explore possible bidirectional relationships between IBD and bronchiectasis risk, with an additional focus on Crohn's disease (CD) and ulcerative colitis (UC) as IBD subtypes. Materials and methods: A large genome-wide association study (GWAS)-derived data pool was leveraged to examine the relationships between bronchiectasis and IBD, CD, and UC. Two-sample MR analyses were performed with an inverse variance weighted (IVW) approach supplemented with the MR-Egger and weighted median methods. Sensitivity analyses were used to further assess the reliability of the main MR study findings. The possibility of reverse causation was also evaluated using a reverse MR approach. Results: The IVW MR analytical approach revealed that IBD (p = 0.074), UC (p = 0.094), and CD (p = 0.644) had no significant impact on the incidence of bronchiectasis, with the converse also being true (p = 0.471, p = 0.700, and p = 0.099, respectively). Conclusion: This MR analysis demonstrated that the higher occurrence of bronchiectasis in patients with IBD is not caused by genetic predisposition.

Huang Lian Jie Du Decoction enhances the anti-tumor efficacy of immune checkpoint inhibitors by activating TLR7/8 signalling in melanoma.

BACKGROUND: The clinical application of immune checkpoint inhibitors (ICIs) is limited by their drug resistance, necessitating the development of ICI sensitizers to improve cancer immunotherapy outcomes. Huang Lian Jie Du Decoction (HLJD, Oren-gedoku-to in Japanese, Hwangryunhaedok-tang in Korean), a famous traditional Chinese medicinal prescription, has exhibited potential in the field of cancer treatment. This study aims to investigate the impact of HLJD on the efficacy of ICIs in melanoma and elucidate the underlying mechanisms. METHODS: The potential synergistic effects of HLJD and ICIs were investigated on the tumor-bearing mice model of B16F10 melanoma, and the tumor infiltration of immune cells was tested by flow cytometry. The differential gene expression in tumors between HLJD and ICIs group and ICIs alone group were analyzed by RNA-seq. The effects of HLJD on oxidative stress, TLR7/8, and type I interferons (IFN-Is) signaling were further validated by immunofluorescence, PCR array, and immunochemistry in tumor tissue. RESULTS: HLJD enhanced the anti-tumor effect of ICIs, significantly inhibited tumor growth, and prolonged the survival duration in melanoma. HLJD increased the tumor infiltration of anti-tumor immune cells, especially DCs, CD4+ T cells and CD8+T cells. Mechanically, HLJD activated the oxidative stress and TLR7/8 signaling pathway and IFN-Is-related genes in tumors. CONCLUSIONS: HLJD enhanced the therapeutic benefits of ICIs in melanoma, through increasing reactive oxygen species (ROS), promoting the TLR7/8 pathway, and activating IFN-Is signaling, which in turn activated DCs and T cells.

Metabolome and transcriptome analyses reveal changes of rapeseed in response to ABA signal during early seedling development.

Seed germination is an important development process in plant growth. The phytohormone abscisic acid (ABA) plays a critical role during seed germination. However, the mechanism of rapeseed in response to ABA is still elusive. In order to understand changes of rapeseed under exogenous ABA treatment, we explored differentially expressed metabolites (DEMs) and the differentially expressed genes (DEGs) between mock- and ABA-treated seedlings. A widely targeted LC-MS/MS based metabolomics were used to identify and quantify metabolic changes in response to ABA during seed germination, and a total of 186 significantly DEMs were identified. There are many compounds which are involved in ABA stimuli, especially some specific ABA transportation-related metabolites such as starches and lipids were screened out. Meanwhile, a total of 4440 significantly DEGs were identified by transcriptomic analyses. There was a significant enrichment of DEGs related to phenylpropanoid and cell wall organization. It suggests that exogenous ABA mainly affects seed germination by regulating cell wall loosening. Finally, the correlation analysis of the key DEMs and DEGs indicates that many DEGs play a direct or indirect regulatory role in DEMs metabolism. The integrative analysis between DEGs and DEMs suggests that the starch and sucrose pathways were the key pathway in ABA responses. The two metabolites from starch and sucrose pathways, levan and cellobiose, both were found significantly down-regulated in ABA-treated seedlings. These comprehensive metabolic and transcript analyses provide useful information for the subsequent post-transcriptional modification and post germination growth of rapeseed in response to ABA signals and stresses.

Unraveling lipid metabolism reprogramming for overcoming drug resistance in melanoma.

Cutaneous melanoma is the deadliest form of skin cancer, and its incidence is continuing to increase worldwide in the last decades. Traditional therapies for melanoma can easily cause drug resistance, thus the treatment of melanoma remains a challenge. Various studies have focused on reversing the drug resistance. As tumors grow and progress, cancer cells face a constantly changing microenvironment made up of different nutrients, metabolites, and cell types. Multiple studies have shown that metabolic reprogramming of cancer is not static, but a highly dynamic process. There is a growing interest in exploring the relationship between melanoma andmetabolic reprogramming, one of which may belipid metabolism. This review frames the recent research progresses on lipid metabolism in melanoma.In addition, we emphasize the dynamic ability of metabolism during tumorigenesis as a target for improving response to different therapies and for overcoming drug resistance in melanoma.

The Treatment of Refractory Vitiligo With Autologous Cultured Epithelium Grafting: A Real-World Retrospective Cohort Study.

BACKGROUND: Surgical intervention is the main therapy for refractory vitiligo. We developed a modified autologous cultured epithelial grafting (ACEG) technique for vitiligo treatment. Between January 2015 and June 2019, a total of 726 patients with vitiligo underwent ACEG in China, with patient characteristics and clinical factors being meticulously documented. Using a generalized linear mixed model, we were able to assess the association between these characteristics and the repigmentation rate. RESULTS: ACEG demonstrated a total efficacy rate of 82.81% (1754/2118) in treating 726 patients, with a higher repigmentation rate of 64.87% compared to conventional surgery at 52.69%. Notably, ACEG showed a better response in treating segmental vitiligo, lesions on lower limbs, age ≤ 18, and stable period > 3 years. A keratinocyte:melanocyte ratio below 25 was found to be advantageous too. Single-cell RNA sequencing analysis revealed an increase in melanocyte count and 2 subclusters of keratinocytes after ACEG, which remained higher in repigmented sites even after 1 year. CONCLUSIONS: ACEG is a promising therapy for refractory vitiligo. Patient age, clinical type, lesion site, and stability before surgery influence repigmentation in ACEG. The mechanism of repigmentation after ACEG treatment is likely not confined to the restoration of melanocyte populations. It may also involve an increase in the number of keratinocytes that support melanocyte function within the affected area. These keratinocytes may aid the post-transplant survival and function of melanocytes by secreting cytokines and extracellular matrix components. TRIAL REGISTRATION: registered with Chictr.org.cn (ChiCTR2100051405).