An attractor state zone precedes neural crest fate in melanoma initiation.

The field cancerization theory suggests that a group of cells containing oncogenic mutations are predisposed to transformation 1, 2 . We previously identified single cells in BRAF V600E ;p53 -/- zebrafish that reactivate an embryonic neural crest state before initiating melanoma 3-5 . Here we show that single cells reactivate the neural crest fate from within large fields of adjacent abnormal melanocytes, which we term the "cancer precursor zone." These cancer precursor zone melanocytes have an aberrant morphology, dysplastic nuclei, and altered gene expression. Using single cell RNA-seq and ATAC-seq, we defined a distinct transcriptional cell attractor state for cancer precursor zones and validated the stage-specific gene expression initiation signatures in human melanoma. We identify the cancer precursor zone driver, ID1, which binds to TCF12 and inhibits downstream targets important for the maintenance of melanocyte morphology and cell cycle control. Examination of patient samples revealed precursor melanocytes expressing ID1, often surrounding invasive melanoma, indicating a role for ID1 in early melanomagenesis. This work reveals a surprising field effect of melanoma initiation in vivo in which tumors arise from within a zone of morphologically distinct, but clinically covert, precursors with altered transcriptional fate. Our studies identify novel targets that could improve early diagnosis and prevention of melanoma.

Assessment of the Incidence and Risk Factors of Stress Urinary Incontinence in Women after Cervical Cancer Surgery: A Single-Centre Retrospective Study.

BACKGROUND: Stress urinary incontinence (SUI) is a common postoperative complication that significantly affects the quality of life in women who have undergone radical hysterectomy for cervical cancer. This study evaluates the incidence and risk factors associated with SUI in women after cervical cancer surgery. METHODS: This case-control study included women diagnosed with cervical cancer who underwent radical hysterectomy at our hospital between May 2020 and May 2023. Participants were divided into two groups based on the presence of postoperative SUI, namely the SUI group and the SUI-free group. Inclusion criteria required the absence of preoperative urinary incontinence and stable vital signs. Data were collected on demographic characteristics, tumour histology and staging, urodynamic parameters, and intraoperative and postoperative factors. RESULTS: Ninety-seven patients with cervical cancer who underwent radical hysterectomy were divided into two groups: The SUI group (n = 27) and the SUI-free group (n = 70), with an SUI incidence of 27.8% in the study population. Significant differences between the SUI and SUI-free groups were observed in menopausal status (p = 0.026), chronic constipation (p = 0.011), and tumour diameter (p < 0.001). Urodynamic assessments revealed a higher maximum urinary flow rate (Qmax) in the SUI group compared to the SUI-free group (21.36 ± 6.41 vs. 17.38 ± 5.18 mL/s; p = 0.002). Logistic regression analysis identified menopause (odds ratio (OR) = 7.700, 95% confidence interval (CI) = 1.256-47.192), chronic constipation (OR = 9.918, 95% CI = 1.387-70.911), Qmax (OR = 1.302, 95% CI = 1.061-1.598), and surgery duration (OR = 1.040, 95% CI = 1.001-1.081) as independent protective factors. CONCLUSIONS: SUI is a significant postoperative complication in women undergoing cervical cancer surgery. Menopause, chronic constipation, tumour diameter, Qmax, and surgery duration were independent risk factors.

Engineering the novel azobenzene-based molecular photoswitches for suppressing bacterial infection through dynamic regulation of biofilm formation.

BACKGROUND: Bacterial biofilm is a strong fortress for bacteria to resist harsh external environments, which can enhance their tolerance and exacerbate the drug/pesticide resistance risk. Currently, photopharmacology provides an advanced approach via precise spatiotemporal control for regulating biological activities by light-controlling the molecular configurations, thereby having enormous potential in the development of drug/pesticides. RESULTS: To further expand the photopharmacology application for discovering new antibiofilm agents, we prepared a series of light-controlled azo-active molecules and explored their photo isomerization, fatigue resistance, and anti-biofilm performance. Furthermore, their mechanisms of inhibiting biofilm formation were systematically investigated. Overall, designed azo-derivative A11 featured excellent anti-Xoo activity with an half-maximal effective concentration (EC50) value of 5.45 µg mL-1, and the EC50 value could be further elevated to 2.19 µg mL-1 after ultraviolet irradiation (converted as cis-configuration). The photo-switching behavior showed that A11 had outstanding anti-fatigue properties. An in-depth analysis of the action mechanism showed that A11 could effectively inhibit biofilm formation and the expression of relevant virulence factors. This performance could be dynamically regulated via loading with private light-switch property. CONCLUSION: In this work, designed light-controlled azo molecules provide a new model for resisting bacterial infection via dynamic regulation of bacterial biofilm formation. © 2024 Society of Chemical Industry.

Activity-based protein profiling guided new target identification of quinazoline derivatives for expediting bactericide discovery: Activity-based protein profiling derived new target discovery of antibacterial quinazolines.

INTRODUCTION: The looming antibiotic-resistance problem has imposed an enormous crisis on global public health and agricultural development. Even worse, the evolution and widespread distribution of antibiotic-resistance elements in bacterial pathogens have made the resurgence of diseases that were once easily treatable deadly again. The development of antibiotics with novel mechanisms of action is urgently required. OBJECTIVES: Inspired by charming activity-based protein profiling (ABPP) technology and increasing attention to quinazolines in the development of antibacterial agents, this study engineered a series of new quinazoline derivatives, assessed their antibacterial profiles, and first identified the possible target. METHODS: The target identification and their possible binding sites were verified by ABPP technology, molecular docking, and molecular dynamic simulations. The fatty acid synthesis process was analyzed by gas chromatography, propidium iodide staining, and scanning electron microscopy. The physicochemical properties and fungicide-likeness were evaluated using the Fungicide Physicochemical-properties Analysis Database. RESULTS: Compound 7a, an acrylamide-functionalized quinazoline derivative, exhibited excellent antibacterial potency against Xanthomonas oryzae pv. oryzae with an EC50 value of 13.20 µM. More importantly, ABPP technology showed that ß-ketoacyl-ACP-synthase Ⅱ (FabF) was the first identified quinazolines' potential target. Compound 7a could selectively bind to the Cys151 residue of FabF through covalent interaction, suppress fatty acid biosynthesis, and damage the cell membrane integrity, thereby killing the bacteria. The pot experiment results showed that compound 7a demonstrated protective and curative values of 49.55 % and 47.46 %, surpassing controls bismerthiazol and thiodiazole copper. Finally, compound 7a exhibited low toxicity towards non-target organisms. These unprecedented performances contributed to excavating new quinazoline-based bactericidal agents. CONCLUSION: Our research highlights the superiority of ABPP technology, for the first time, identifies the target of engineered quinazolines in pathogenic bacteria, and their potential target fished by ABPP tools holds great promise for the development of quinazoline-based and/or FabF-targeted bactericides.

Exploring the gut microbiota of healthy captive Asian elephants from various locations in Yunnan, China.

Introduction: The Asian elephant (Elephas maximus) is a giant herbivore classified as an endangered wildlife species by the International Union for Conservation of Threatened Species.This study aims to investigate and compare the core gut microbiota of captive Asian elephants from three different locations in Yunnan Province, China, to explore the impact of environmental and husbandry factors on microbial diversity. Methods: We collected fecal samples from 29 captive Asian elephants from three locations and performed full-length 16S rRNA gene sequencing. Microbial diversity was assessed using alpha diversity (Chao1 and Shannon indexes) and beta diversity (Bray-Curtis and Euclidean distance metrics). Principal coordinate analysis (PCoA) was used to visualize microbial variation among groups. Results: Alpha diversity analysis showed that the microbial diversity in the Yexianggu group was higher than that in the other groups. Bray-Curtis and Euclidean metrics revealed significant differences among the microbial communities. Bacteroidetes and Firmicutes, which are key cellulose-degrading bacteria, were the dominant phyla in all groups. Synergistaceae was the most abundant family in the Menghai group, while Lachnospiraceae and Pirellulaceae were more abundant in the Yexianggu and Yuantongshan groups, respectively. Genus p-1008-a5-gut-group was more abundant in Yexianggu, and Prevotella was predominant in Menghai. Discussion: These results indicate that habitat and husbandry practices significantly influence the gut microbiota of captive Asian elephants. The identification of bacterial species such as Lactobacillus fermentum, Clostridium neonatale, Enterococcus mundtii, Klebsiella huaxiensis, Corynebacterium nasicanis, and Streptococcus equinus highlights the potential role of specific microbes in maintaining host-microbial interactions. Promoting microbial diversity through improved captive conditions could enhance the health of these endangered animals.

The Value of lncRNAs as a Biomarker for the Diagnosis of Gestational Diabetes: A Meta-Analysis.

Gestational diabetes mellitus (GDM) is a common metabolic disorder in pregnancy and leads to serious harm to the mother and the fetus. A variety of lncRNAs play a key role in GDM. This meta-analysis was performed to explore the potential value of lncRNAs in GDM diagnosis. Articles correlated with lncRNA and GDM were screened from Embase, Medline, EBSCO, PubMed, Chinese National Knowledge Infrastructure, and WanFang databases. Summary receiver operator characteristic (SROC) was performed to evaluate the pooled area under curve (AUC). Forest plot was conducted to calculate the sensitivity, specificity, diagnostic likelihood ratio (LR), diagnostic score, and diagnostic odds ratio (DOR). Deeks' funnel plot was utilized to evaluate the publication bias. Eleven articles containing 12 tests (1060 GDM patients and 1066 controls) were included in this meta-analysis. AUC (0.89, 95%CI=0.86-0.92), sensitivity (0.84, 95%CI=0.80-0.87), and specificity (0.81, 95%CI=0.77-0.85)of the SROC curve showed a high diagnostic value of lncRNA for GDM. Positive LR (PLR 4.40, 95%CI=3.45-5.60) and negative LR (NLR 0.20, 95%CI=0.15-0.26) results indicated that the diagnosis of lncRNA for GDM had low clinical utility. Diagnostic score (3.09, 95%CI=2.62-3.57) and DOR (22.04, 95%CI=13.68-35.51) results suggested lncRNAs have good discriminative effect on GDM. Heterogeneity was significantly higher, but not induced by the subgroups. LncRNAs had high diagnostic value and good discriminative effect for GDM, but the clinical utility was not high. This meta-analysis study offers a potential target for GDM diagnosis.

2D g-C3N5 p-Doping of Donor Material for High-Efficiency Organic Solar Cells.

Molecular doping of organic semiconductor is a great strategy for significantly regulating the electronic band structure of organic semiconductor while increasing charge mobility and carrier concentration. Here, a facile strategy is presented by introducing 2D g-C3N5 as a p-dopant into PM6, improving the charge mobility and hole carrier concentration of PM6. Moreover, the electron transfer between PM6 and g-C3N5 can effectively downshift the Fermi energy level and highest occupied molecular orbital (HOMO) energy level of PM6, which leads to the increase the built-in electric field of organic solar cells (OSCs). The addition of g-C3N5 also effectively enhances the crystallization of active layer, thereby improving the stability of OSCs. As a result, a champion bulk-heterojunction (BHJ) and layer-by-layer (LbL) structure OSCs are successfully achieved featuring a high-power conversion efficiency of 18.10%/18.25%, simultaneously having excellent device stability. This work shows that introducing a low concentration dopant into organic donor is an effective method for improving the electrical performance of organic donor and the efficiency of OSCs.

[Characteristics of Phytoplankton Community Structure in Lakes of Wetlands Dominated by Different Aquatic Plants and Its Driving Factors].

In wetland ecosystems, small shallow lakes are critical transition zones of land and water, which are usually dominated by aquatic plants with different growth forms. However, the differences and key influencing factors of phytoplankton communities in shallow lakes dominated by different aquatic plants are unclear. On this basis, nine surveys were conducted at five sampling sites of three lakes in Zhangye National Wetland Park from June to November in 2022, which were respectively dominated by the emergent Phragmites australis （LL）, the submerged Potamogeton perfoliatus （CL）, and the floating-leaved Nymphaea tetragona （SL）. During the study period, the three lakes showed obvious habitat differences. A total of 237 species of phytoplankton in seven phyla and 93 genera were identified in the three lakes, including 189 species, 151 species, and 147 species in the LL, CL, and SL lakes, respectively. Among them, Ulnaria acus, Scenedesmus quadricauda, Achnanthidium minutissimum, Nitzschia stagnorum, Navicula radiosa, and Gymnodinium aeruginosum were shared dominant species of all three lakes, indicating that they had strong environmental adaptability, whereas Navicula lanceolala, Encyonopsis cesatii, and Eunotia diodon and Cymbella aequalis were only dominant in the CL, LL, and SL lakes, respectively. Simultaneously, these dominant algae appeared with obviously distinct statuses of niche width, niche overlap, and interspecific correlation among the three lakes. Using principal coordinate analysis （PCoA） and permutational multivariate analysis of variance （PERMANOVA）, significant differences were found in algal community composition among the three lakes （P<0.001）. Multiple regression on （dis）similarity matrices analysis （MRM） showed that the heterogeneity of phytoplankton communities among the three lakes was positively affected by NO3--N and pH and negatively affected by dissolved oxygen （DO） and was closely positively correlated with the abundance of six dominant species, namely, S. quadricauda, U. acus, N. stagnorum, Pseudoanabaena sp., Merismopedia punctata, and A. minutissimum. These results indicate that aquatic plants with different growth types could affect the composition, structure, and stability of phytoplankton communities in the same habitat with them by shaping their habitat heterogeneity. Therefore, selecting specific growth types of aquatic plants for aquatic ecosystem restoration in wetland construction and management will be conducive to regulate the state of water habitat and phytoplankton community structure effectively.

CYLD Maintains Retinal Homeostasis by Deubiquitinating ENKD1 and Promoting the Phagocytosis of Photoreceptor Outer Segments.

Phagocytosis of shed photoreceptor outer segments by the retinal pigment epithelium (RPE) is essential for retinal homeostasis. Dysregulation of the phagocytotic process is associated with irreversible retinal degenerative diseases. However, the molecular mechanisms underlying the phagocytic activity of RPE cells remain elusive. In an effort to uncover proteins orchestrating retinal function, the cylindromatosis (CYLD) deubiquitinase is identified as a critical regulator of photoreceptor outer segment phagocytosis. CYLD-deficient mice exhibit abnormal retinal structure and function. Mechanistically, CYLD interacts with enkurin domain containing protein 1 (ENKD1) and deubiquitinates ENKD1 at lysine residues K141 and K242. Deubiquitinated ENKD1 interacts with Ezrin, a membrane-cytoskeleton linker, and stimulates the microvillar localization of Ezrin, which is essential for the phagocytic activity of RPE cells. These findings thus reveal a crucial role for the CYLD-ENKD1-Ezrin axis in regulating retinal homeostasis and may have important implications for the prevention and treatment of retinal degenerative diseases.

An update review on biopolymer Xanthan gum: Properties, modifications, nanoagrochemicals, and its versatile applications in sustainable agriculture.

During the development of green agriculture and pesticide use, "reducing pesticides use and improving control efficiency" is imperative. To date, new pesticide formulations created by nanotechnology can be expected to overcome the difficulties that cannot be solved by the traditional pesticide processes and make pesticide formulations close to the needs of green agricultural production. As natural polysaccharides, Xanthan gum (XG) charactered by a repeated units and side chain of d-glucose, d-mannose, and d-glucuronic acid, and thereby having the unprecedented features in response to wide practice in various fields. This review introduces the properties of the natural polymer XG and its current status of application in agriculture, focusing on the pesticide adjuvant and preparation of novel pesticide and fertilizer delivery systems (such as core-shell and hydrogel), and combined with the applications in mulch film and soil engineering. Furthermore, the properties of Xantho-oligosaccharides suitable for agriculture were discussed. Finally, the potential of XG for the creation of nanopesticides and its future prospects are highlighted. Taken together, XG's excellent performance endows it with a wide range of applications in the agriculture field, and result in strong stimulating the sustainable development of agriculture and evolution of agricultural industry.

Clinical significance of circulating long non-coding RNA SNHG1 in type 2 diabetes mellitus and its association with cell proliferation of pancreatic ß-cell.

BACKGROUND: To explore the association of long non-coding RNA (lncRNA) SNHG1/ miR-195 axis with type 2 diabetes mellitus (T2DM) and islet function. METHODS: The expression of SNHG1 and miR-195 was measured in T2DM patients and in healthy subjects. Correlation between indciators was evaluated using Pearson correlation analysis. INS-1 cells were used to perform the cell function assays. Insulin secretion by INS-1 was detected using ELISA. Cell counting kit-8 (CCK-8) and flow cytometry was used to detect cell proliferation and apoptosis. Luciferase report assay was to used to verify the target of SNHG1. RESULTS: The expression of SNHG1 was increased and miR-195 level was decreased in the serum of T2DM patients. Both SNHG1 and miR-195 could be biomarkers for T2DM diagnosis. The fasting plasma glucose (FPG) and HbA1c were positively related to SNHG1 and negatively related to miR-195. SNHG1 inhibited insulin secretion, and cell proliferation and promoted apoptosis of INS-1 cells via binding to miR-195. CONCLUSIONS: Detection of SNHG1 and miR-195 might predict T2DM. SNHG1 could suppress proliferation and insulin secretion, but promote apoptosis of INS-1 cells via sponging miR-195.

Performance of the Flash10 COVID-19 point-of-care molecular test.

After the COVID-19 pandemic, fever clinics urgently require rapid nucleic acid tests to enhance their capacity for timely pathogen detection. This study evaluated the analytical performance and clinical utility of the Flash10 SARS-CoV-2 point-of-care test (Flash10 POCT) for detecting SARS-CoV-2 in patients with fever in the adult fever clinic in Beijing Tsinghua Changgung Hospital from August 1 to August 30, 2023. The analytical performance and clinical utility of the Flash10 POCT for detecting SARS-CoV-2 were assessed in 125 patients with fever syndrome in the adult fever clinic. The Flash10 POCT demonstrated an analytical precision of 3.1% for the Ct values of the ORF1ab gene and 2.9% for the Ct values of the N gene in SARS-CoV-2 nucleic acid testing. Furthermore, the Flash10 POCT demonstrated a lower limit of detection (LoD) of 100 copies/mL, with no detected aerosol contamination leakage. Of the 125 patients (median age 61.9 years, 52% male and 48% female), both the Flash10 POCT and RT-PCR tests yielded positive results for 100 patients and negative results for 25 patients (Fisher's exact test, p < 0.0001). The median turn-around-time for the Flash10 POCT was significantly shorter, at 1.05 h, compared to 16.15 h required for RT-PCR tests (Wilcoxon signed rank test, p < 0.0001). The Flash10 POCT showed high analytical performance, achieving a 100% detection rate for SARS-CoV-2 compared to RT-PCR tests, while also exhibiting a significantly shorter turn-around-time. Implementing the Flash10 POCT had the potential to expedite the care of adults presenting with fever.

Mode-Locked Characteristic of L-Band All-Fiber Laser with Different 2D and Quasi-2D Perovskite Saturable Absorbers.

In recent years, the quasi-2D perovskite material ((PEA)2(CsPbBr3)n-1PbBr4) has exhibited outstanding optoelectronic performance and environmental stability due to its unique structure, presenting a broad range of potential applications. However, structural differences arising from varying values of "n" result in distinct nonlinear effects in perovskite materials, which have not been thoroughly investigated to date. We conducted a comparative analysis of the mode-locked characteristics of 2D and n = 3, 4, 5, and 6 quasi-2D perovskite materials within an Erbium-doped fiber laser (EDFL). All materials exhibited excellent saturable absorption effects. Besides, the superior performance of the n = 5 quasi-2D perovskite material, with an SNR of 72.59 dB, performed best in terms of the average power and single pulse energy. The five-layer quasi-2D perovskites offer a suitable bandgap, exciton binding energy, and moderate quantum confinement, leading to effective laser operation. Additionally, the optimal nonlinear absorption, refractive index, and thermal stability contribute to stable and high-power laser performance, while suppressing surface states and interface effects. Experimental results indicate that quasi-2D perovskite materials hold significant potential for applications in the realm of ultrafast optics.

Predictors of early and interim culture un-conversion in multidrug-resistant/rifampicin-resistant tuberculosis: a retrospective multi-center cohort study in China.

BACKGROUND: We aimed to evaluate the predictors for early and interim culture conversion within 2 months and 6 months of treatment in multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) patients in China. METHODS: This study included adult MDR/RR-TB patients with a positive baseline sputum culture from 8 institutions located in different cities in China from May 2018 to January 2022. We mainly used logistic regression model to derive possible predictors of early and interim culture conversion. RESULTS: A total of 813 patients were enrolled and 28.5% of them received multidrug-resistant treatment regimens containing bedaquiline. Of these, 362 (44.5%) patients experienced culture conversion within 2 months of treatment, and 649 (79.8%) within 6 months. The results of the multivariable logistic regression analysis revealed that acid-fast bacilli smear positive (adjusted odds ratio [aOR] = 1.637, 95% confidence interval [CI] = 1.197-2.238), cavities (aOR = 1.539, 95% CI = 1.132-2.092), bilateral disease (aOR = 1.638, 95% CI = 1.183-2.269), and viral hepatitis (aOR = 2.585, 95% CI = 1.189-5.622) were identified as risk factors for early culture un-conversion within 2 months of treatment. Additionally, smoking history (aOR = 2.197, 95% CI = 1.475-3.273), previous treatment for tuberculosis (aOR = 1.909, 95% CI = 1.282-2.844), bilateral disease (aOR = 2.201, 95% CI = 1.369-3.537), viral hepatitis (aOR = 2.329, 95% CI = 1.094-4.962) were identified as risk factors for interim culture un-conversion within 6 months of treatment, while patients with regimen containing bedaquiline (aOR = 0.310, 95% CI = 0.191-0.502) was a protective factor. CONCLUSIONS: A history of smoking, a baseline sputum AFB smear positive, lung cavities, bilateral disease, previous anti-tuberculosis treatment, or a comorbidity of viral hepatitis can be used as the predictors for early and interim culture un-conversion in MDR/RR-TB patients, while bedaquiline was a protective factor .

Visual impairment as the initial presentation in multiple myeloma: a case report and literature review.

Background: Multiple myeloma (MM) is a type of blood cancer, which rarely infiltrates the central nervous system (CNS) and lacks specific neurological symptoms. The prognosis is often poor, as the disease progresses rapidly. Herein, we present a rare case of MM with CNS involvement. Case Description: A 53-year-old man was admitted to the Neurosurgery Department, Jinhua Hospital Affiliated to Zhejiang University with initial symptoms of "blurred vision for 3 months accompanied by numbness on the right side of the face for 7 days". Enhanced cranial magnetic resonance imaging revealed a tumor deep in the right temporal bone. During exploratory surgery, the "fleshy" mass was completely removed. Postoperative pathology confirmed a diagnosis of "plasmacytoma with intermediate features". The patient received multiple systematic chemotherapy treatments after surgery in the department of hematology of Jinhua Hospital Affiliated to Zhejiang University. During a 10-month follow-up period, the patient's neurological symptoms improved, and his general condition was considered good. Conclusions: This report summarizes the clinical features, diagnosis, treatment, and prognosis of a patient with MM involving the CNS and examines the relevant literature. This case may serve as a reference for future clinical treatment and diagnosis. Further research on the pathophysiology of such cases is warranted.

Sketching the spatial disparities in heatwave trends by changing atmospheric teleconnections in the Northern Hemisphere.

Pronounced spatial disparities in heatwave trends are bound up with a diversity of atmospheric signals with complex variations, including different phases and wavenumbers. However, assessing their relationships quantitatively remains a challenging problem. Here, we use a network-searching approach to identify the strengths of heatwave-related atmospheric teleconnections (AT) with ERA5 reanalysis data. This way, we quantify the close links between heatwave intensity and AT in the Northern Hemisphere. Approximately half of the interannual variability of heatwaves is explained and nearly 80% of the zonally asymmetric trend signs are estimated correctly by the AT changes in the mid-latitudes. We also uncover that the likelihood of extremely hot summers has increased sharply by a factor of 4.5 after 2000 over areas with enhanced AT, but remained almost unchanged over the areas with attenuated AT. Furthermore, reproducing Eastern European heatwave trends among various models of the Coupled Model Intercomparison Project Phase 6 largely depends on the simulated Eurasian AT changes, highlighting the potentially significant impact of AT shifts on the simulation and projection of heatwaves.

Coupling is key for the tropical Indian and Atlantic oceans to boost super El Niño.

The influences of the tropical Indian and Atlantic oceans on the development of El Niño Southern Oscillation (ENSO), especially regarding super El Niño events, have been a subject of debate. In particular, several studies argue that these cross-basin influences may be mere statistical artifacts resulting from the high auto-correlation of ENSO. To clarify this issue, we conduct a series of perfect model hindcast experiments to untangle the individual and synergistic effects of the tropical Indian and Atlantic oceans. Our results clearly demonstrate that without these cross-basin effects, the Pacific warming would rarely reach super El Niño level. Specifically, the individual effect of the Indian Ocean efficiently enhances the development of super El Niño events. In contrast, the Atlantic's effect is initially limited because it fails to establish the Bjerknes feedback in the Pacific. However, when coupled with the Indian Ocean, the Atlantic's effect becomes more pronounced as it is amplified by the Bjerknes feedback established by the Indian Ocean.

Chronic bisphenol A induced neurotoxicity: Exposure risk, molecular fate within carp and its potential phytoremediation.

Bisphenol A (BPA) is an endocrine-disrupting toxicant commonly used in the plastics industry, as a result, it is present in large quantities in the environment. Therefore, current study was designed to assess BPA induced neurotoxicity and molecular fate within common carp (Cyprinus carpio), largely used edible fish. Following 6 weeks exposure to BPA 1/5th of 96 h LC50 (1.31 mg/L), brain exhibited oxidative damage, which was evidenced by compromised antioxidant system (CAT, SOD, GSH) and increased level of biomacromolecule peroxidation (MDA and 8-OHDG). Functional damage to the brain observed in the form of blood-brain barrier disruption (decreased tight junction gene expression) and nerve conduction impairment (reduced acetylcholinesterase activity). Mechanistically, apoptotic cell death indicated by characteristic alteration in key biomarkers (bcl-2, caspase, and p53-related gene family). Whereas, coadministration of powdered PP (pomegranate peel) (8 %) with BPA effectively mitigated the BPA toxicity, as evidenced by the restoration of the above-mentioned bioindicators. Thereby, BPA-induced neurotoxicity could be potentially detoxified by applying PP dietary enrichment.

Craters on the melanoma surface facilitate tumor-immune interactions and demonstrate pathologic response to checkpoint blockade in humans.

Immunotherapy leads to cancer eradication despite the tumor's immunosuppressive environment. Here, we used extended long-term in-vivo imaging and high-resolution spatial transcriptomics of endogenous melanoma in zebrafish, and multiplex imaging of human melanoma, to identify domains that facilitate immune response during immunotherapy. We identified crater-shaped pockets at the margins of zebrafish and human melanoma, rich with beta-2 microglobulin (B2M) and antigen recognition molecules. The craters harbor the highest density of CD8+ T cells in the tumor. In zebrafish, CD8+ T cells formed prolonged interactions with melanoma cells within craters, characteristic of antigen recognition. Following immunostimulatory treatment, the craters enlarged and became the major site of activated CD8+ T cell accumulation and tumor killing that was B2M dependent. In humans, craters predicted immune response to ICB therapy, showing response better than high T cell infiltration. This marks craters as potential new diagnostic tool for immunotherapy success and targets to enhance ICB response.

Treatment Outcomes and Associated Influencing Factors Among Patients with Rifampicin-Resistant Tuberculosis: A Multicenter, Retrospective, Cohort Study in China.

Objective: Rifampin-resistant tuberculosis (RR-TB) remains a serious global public health concern. We assessed treatment outcomes and associated influencing factors among RR-TB patients in China. Methods: This research enrolled 1339 patients who started RR-TB treatment between May 2018 and April 2020 in China retrospectively. Data were collected from the electronic medical records. Multivariable logistic regression analysis was used to identify the influencing factors related to unfavorable outcomes. Results: Of the 1339 RR-TB patients, 78.8% (1055/1339) achieved treatment success (cured or treatment completed), 5.1% (68/1339) experienced treatment failure, 1.1% (15/1339) died during treatment, 10.1% (135/1339) were lost to follow-up, and 4.9% (66/1339) were not evaluated. About 67.7% (907/1339) of patients experienced at least one adverse event (AE). The most common AE was hypohepatia (507/1339, 37.9%), followed by hyperuricemia (429/1339, 32.0%), anemia (368/1339, 27.5%), electrolyte disturbance (318/1339, 23.7%), peripheral neuritis (245/1339, 18.3%), and gastrointestinal reactions (203/1339, 15.2%). Multivariate analysis showed that age ≥60 years [adjusted odds ratio (aOR): 1.96, 95% confidence interval (CI): 1.39-2.77], national minority (aOR: 2.36, 95% CI: 1.42-3.93), smoking (aOR: 1.50, 95% CI: 1.10-2.04), cardiopathy (aOR: 2.90, 95% CI: 1.33-6.31), tumors (aOR: 9.84, 95% CI: 2.27-42.67), immunocompromise (aOR: 2.17, 95% CI: 1.21-3.91), re-treated TB (aOR: 1.46, 95% CI: 1.08-1.97), and experienced gastrointestinal reactions (aOR: 2.27, 95% CI: 1.52-3.40) were associated with unfavorable outcomes. Body mass index (BMI) ≥18.5 kg/m2, regimens containing bedaquiline and experienced adverse events (AEs) such as hypohepatia, leukopenia, peripheral neuritis, and optic neuritis were associated with favorable outcomes. Conclusion: High rates of treatment success were achieved for RR-TB patients at tertiary tuberculosis hospitals in China. Age ≥60 years, national minority, smoking status, comorbidities, re-treated TB, and experienced gastrointestinal reactions were independent prognostic factors for unfavorable treatment outcomes.