Priority sources identification and risks assessment of heavy metal(loid)s in agricultural soils of a typical antimony mining watershed.

Heavy metal(loid) (HM) pollution in agricultural soils has become an environmental concern in antimony (Sb) mining areas. However, priority pollution sources identification and deep understanding of environmental risks of HMs face great challenges due to multiple and complex pollution sources coexist. Herein, an integrated approach was conducted to distinguish pollution sources and assess human health risk (HHR) and ecological risk (ER) in a typical Sb mining watershed in Southern China. This approach combines absolute principal component score-multiple linear regression (APCS-MLR) and positive matrix factorization (PMF) models with ER and HHR assessments. Four pollution sources were distinguished for both models, and APCS-MLR model was more accurate and plausible. Predominant HM concentration source was natural source (39.1%), followed by industrial and agricultural activities (23.0%), unknown sources (21.5%) and Sb mining and smelting activities (16.4%). Although natural source contributed the most to HM concentrations, it did not pose a significant ER. Industrial and agricultural activities predominantly contributed to ER, and attention should be paid to Cd and Sb. Sb mining and smelting activities were primary anthropogenic sources of HHR, particularly Sb and As contaminations. Considering ER and HHR assessments, Sb mining and smelting, and industrial and agricultural activities are critical sources, causing serious ecological and health threats. This study showed the advantages of multiple receptor model application in obtaining reliable source identification and providing better source-oriented risk assessments. HM pollution management, such as regulating mining and smelting and implementing soil remediation in polluted agricultural soils, is strongly recommended for protecting ecosystems and humans.

Whole genome sequences of 135 "Candidatus Liberibacter asiaticus" strains from China.

"Candidatus Liberibacter asiaticus" (CLas) is a phloem-limited alpha-proteobacteria causing Citrus Huanglongbing, the destructive disease currently threatening global citrus industry. Genomic analyses of CLas provide insights into its evolution and biology. Here, we sequenced and assembled whole genomes of 135 CLas strains originally from 20 citrus cultivars collected at ten citrus-growing provinces in China. The resulting dataset comprised 135 CLas genomes ranging from 1,221,309 bp to 1,308,521 bp, with an average coverage of 675X. Prophage typing showed that 44 strains contained Type 1 prophage, 89 strains contained Type 2 prophage, 44 strains contained Type 3 prophage, and 34 of them contained more than one type of prophage/phage. The SNP calling identified a total of 5,090 SNPs. Genome-based phylogenetic analysis revealed two major clades among CLas strains, with Clade I dominated by CLas strains containing Type 1 prophage (79/95) and Clade II dominated by CLas strains containing Type 1 or Type 3 prophage (80/95). This CLas genome dataset provides valuable resources for studying genetic diversity and evolutionary pattern of CLas strains.

The Lian-Dou-Qing-Mai Formula activates the PPARγ-LXRα-ABCA1/ABCG1 pathway by regulating IL-10, leading to the promotion of cholesterol efflux and a reduction in atherosclerotic plaques.

BACKGROUND: To observe the effect of the Lian-Dou-Qing-Mai (LDQM) formula on lipid metabolism in mice and explore its mechanism from the perspective of regulating the PPARγ/LXRα/ABCA1 signaling pathway. METHODS: THP-1 cells were induced to transform into foam cells with ox-LDL. Atherosclerosis (AS) models were constructed using a high-fat diet in ApoE-/- mice. Detection kits were used to evaluate triglyceride (TG) and total cholesterol (TC) content; TNF-α, MCP-1, MMP-9, TMP-1, PPARγ, LXRα, ABCA1, and ABCG1 mRNA and protein expression were identified using real-time PCR and western blot. Interleukin-10 (IL-10) blood levels were measured using an enzyme-linked immunosorbent assay (ELISA), and aortic plaque development and lipid deposition were seen using hematoxylin and eosin (HE) and oil red O staining, respectively. RESULTS: In the cell model, LDQM could inhibit the formation of THP-1 macrophage-derived foam cells and the expression of inflammatory factors, promote macrophage cholesterol efflux, increase the expression of IL-10, and activate the PPARγ-LXRα-ABCA1/ABCG1 pathway. Additional IL-10 treatment further promotes LDQM-induced cholesterol efflux in THP-1 cells; in In vivo models, LDQM inhibited the area of atherosclerotic lesions, aortic lipid deposition, and inflammation levels in ApoE-/- mice through IL-10, and activated the expression level of the PPARγ-LXRα-ABCA1/ABCG1 pathway. CONCLUSION: LDQM may affect the PPARγ/LXRα/ABCA1 signaling pathway through IL-10, regulate lipid metabolism, reduce serum inflammatory expression and lipid deposition, and improve the formation of atheroplaques.

Prognostic value of baseline clinicopathological characteristics in first-line chemotherapy ± immunotherapy for extensive-stage small cell lung cancer: a retrospective cohort study.

Background: The integration of chemotherapy and immunotherapy as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC) has been adopted in clinical practice, yet the response to immune checkpoint inhibitors (ICIs) is variable, benefiting only a fraction of patients. The current absence of reliable biomarkers for predicting treatment response and prognosis represents a significant gap in knowledge, hindering the optimization of patient stratification and treatment planning. This retrospective cohort study aims to assess the potential predictive and prognostic significance of clinicopathological baseline features in ES-SCLC patients. Methods: Our study retrospectively analyzed the data of consecutive patients with ES-SCLC treated with first-line etoposide plus platinum chemotherapy ± immunotherapy at The Affiliated Lihuili Hospital of Ningbo University from April 2017 to April 2023. Data on clinical information, serum laboratory indicators, pathological immunohistochemical markers, and progression-free survival (PFS) times were collected. Univariate and multivariate Cox regression analyses were employed to determine whether these indicators could serve as independent prognostic factors for PFS. Further, potential predictive markers for treatment efficacy were identified using a Cox regression model that incorporated an interaction term between treatment modality and the indicator. Results: A total of 121 patients with ES-SCLC were enrolled in the study, of whom 62 received chemotherapy alone, and 59 received chemotherapy in combination with immunotherapy. Compared to chemotherapy alone, the addition of immunotherapy to first-line chemotherapy significantly extended the PFS time [P<0.001; hazard ratio (HR) =0.42; 95% confidence interval (CI): 0.28, 0.64] of the ES-SCLC patients. The multivariate analysis revealed that an immunochemotherapy regimen (P<0.001, HR =0.40; 95% CI: 0.24, 0.68), a low-density lipoprotein (LDL) level of >1.8 mmol/L (P=0.02; HR =0.41; 95% CI: 0.20, 0.85) were independent prognostic factors of favorable PFS in the first-line treatment of all ES-SCLC, while a lactate dehydrogenase (LDH) level of >273 U/L (P=0.04; HR =1.78; 95% CI: 1.03, 3.07), a neuron-specific enolase (NSE) concentration of >102.6 ng/mL (P=0.009; HR =6.49; 95% CI: 1.60, 26.32), an apolipoprotein A1 (ApoA1) concentration of >0.9 g/L (P<0.001; HR =4.15; 95% CI: 1.98, 8.71), and an apolipoprotein B (ApoB) concentration of >0.8 g/L (P=0.002; HR =2.24; 95% CI: 1.34, 3.75) were independent prognostic factors of poorer PFS. Further, the interaction effect analysis demonstrated that an LDL level of >1.8 mmol/L and the absence of bone metastasis were potential predictors of an improved response to ICI therapy compared to chemotherapy alone. Conclusions: This study showed the survival benefit of receiving a chemoimmunotherapy regimen as the first-line treatment in a real-world scenario. It also suggests the prognostic significance of pre-treatment LDL, LDH, NSE, ApoA1, and ApoB with optimal cut-off values in the first-line treatment of all ES-SCLC, and the potential utility of baseline LDL level or the presence of bone metastasis in guiding first-line treatment strategies.

The respiratory syncytial virus vaccine and monoclonal antibody landscape: the road to global access.

Respiratory syncytial virus (RSV) is the second most common pathogen causing infant mortality. Additionally, RSV is a major cause of morbidity and mortality in older adults (age ≥60 years) similar to influenza. A protein-based maternal vaccine and monoclonal antibody (mAb) are now market-approved to protect infants, while an mRNA and two protein-based vaccines are approved for older adults. First-year experience protecting infants with nirsevimab in high-income countries shows a major public health benefit. It is expected that the RSV vaccine landscape will continue to develop in the coming years to protect all people globally. The vaccine and mAb landscape remain active with 30 candidates in clinical development using four approaches: protein-based, live-attenuated and chimeric vector, mRNA, and mAbs. Candidates in late-phase trials aim to protect young infants using mAbs, older infants and toddlers with live-attenuated vaccines, and children and adults using protein-based and mRNA vaccines. This Review provides an overview of RSV vaccines highlighting different target populations, antigens, and trial results. As RSV vaccines have not yet reached low-income and middle-income countries, we outline urgent next steps to minimise the vaccine delay.

Abnormal phenotypic defects detection of jujube using explainable machine learning enhanced computer vision.

Jujube is susceptible to biotic and abiotic adversity stresses resulting in abnormal phenotypic defects. Therefore, abnormal phenotype fruits should be removed during postharvest sorting to increase added value. An improved maximum horizontal diameter linear regression (MHD-LR) method for size grading of jujube prior to detection of abnormal phenotypic defects was developed. The accuracy of the MHD-LR model is 95%, with an error of only 0.95 mm. In addition, a method for detecting abnormal phenotypic defects in jujube was established. It can effectively and accurately classify seven kinds of jujube phenotypes (regular, irregular, wrinkled, moldy, hole-broken, skin-broken, and scarred). The data augmentation method based on linear interpolation can effectively expand the dataset with a variance of only 0.0006. Support vector machine-decision tree (SVMDT), logistic regression, back propagation neural network, and long short-term memory network models were established to classify jujube samples with different phenotypes, with accuracies of 99.57%, 99.00%, 99.14%, and 99.29%, respectively. The results showed that the SVMDT model had higher accuracy and explainability. This research is expected to provide a new method to improve the precise classification of abnormal phenotypic defects in postharvest jujube.

Gut microbiome pattern impacts treatment response in primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease. An inadequate response to ursodeoxycholic acid (UDCA) poses a high risk of progression toward end-stage liver disease. Gut dysbiosis has been implicated in PBC. Here, we aimed to investigate microbial signatures that permit risk stratification and provide mechanistic insights into novel therapies for PBC. METHODS: We prospectively recruited UDCA treatment-naive patients with PBC and performed metagenomic sequencing and metabolomic profiling using stool and serum samples obtained before (n = 132) and after (n = 59) treatment. PBC microbiome subtypes were identified using unsupervised machine learning methods and validated in two independent cohorts. FINDINGS: PBC baseline metagenomes clustered into two community subtypes characterized by varying abundances of Clostridia taxa. Compared with Clostridialow microbiomes, Clostridiahigh microbiomes were more similar to healthy controls. Notably, patients in the Clostridialow subtype exhibited a 2-fold higher UDCA non-response rate compared to those in the Clostridiahigh subtype (41% vs. 20%, p = 0.015). Integrative analysis of metagenomic and metabolomic data revealed divergent functional modules and metabolic activities between the two metacommunities. In particular, anaerobic fermentation and the production of bioactive metabolites, including tryptophan derivatives and secondary bile acids, crucial for immune regulation and gut barrier maintenance, were markedly diminished in the Clostridialow subtype. Moreover, UDCA administration reconfigured the fecal microbial and metabolic profiles only in the Clostridiahigh group. Importantly, the microbiome subtypes and their associations with UDCA response were reproducible in two independent treatment-naive PBC cohorts. CONCLUSIONS: Characterizing baseline microbiota patterns may enable the prediction of treatment outcomes in PBC and facilitate personalized treatment strategies. FUNDING: This research was mainly supported by the National Natural Science Foundation of China.

Inhibition of CCL7 improves endothelial dysfunction and vasculopathy in mouse models of diabetes mellitus.

Diabetic vascular disease is a major complication of diabetes mellitus (DM). Chemokine C-C motif ligand 7 (CCL7) attracts macrophages and monocytes, amplifying inflammatory processes in the vasculature. We hypothesized a causal role for CCL7 in diabetic vasculopathy. CCL7 concentrations were higher in the plasma of patients with type 2 DM, as well as in supernatants from their endothelial progenitor cells (EPCs). High-glucose stimulation increased the secretion of CCL7 from human dermal microvascular endothelial cells (HDMECs) through the c-Fos and c-Jun signaling pathways. CCL7 inhibition using knockdown or neutralization antibody treatment reversed the high glucose-induced impaired tube formation and migration abilities of EPCs, human aortic endothelial cells, human coronary artery endothelial cells, and HDMECs. Administration of recombinant human CCL7 protein impaired tube formation and migration abilities by down-regulating the AKT-endothelial nitric oxide synthase and AKT/nuclear factor erythroid 2-related factor 2/heme oxygenase-1/vascular endothelial growth factor/stromal cell-derived factor-1 pathways and by up-regulating ERK/phosphorylated p65/interleukin-1ß/interleukin-6/tumor necrosis factor-α pathways through CC chemokine receptor 3 in endothelial cells. Ccl7 knockout in streptozotocin-treated mice showed improved neovasculogenesis in ischemic limbs and accelerated wound repair, with increased circulating EPCs and capillary density. CCL7 antibody treatment in db/db mice and high-fat diet-induced hyperglycemia mice showed improved neovasculogenesis in ischemic limbs and wound areas, accompanied by up-regulation of angiogenic proteins and down-regulation of inflammatory proteins. Endothelial cell-specific Ccl7-knockout mice showed ameliorated diabetic vasculopathy in streptozotocin-induced DM. This study highlights the potential of CCL7 as a therapeutic target for diabetic vasculopathy.

Analysis of long-term outcome of modified gastric bypass for type 2 diabetes mellitus in Chinese patients.

BACKGROUND: Bariatric and metabolic surgery have been routinely performed following the rapid increase in obesity and metabolic diseases worldwide. Of all evolving procedures, Roux-en-Y gastric bypass (RYGB) is considered the gold standard for surgical treatment of patients with type 2 diabetes mellitus (T2DM) and obesity. RYGB was introduced in China nearly 20 years ago, but the number of RYGB surgeries only accounts for 3.1% of the total number of weight loss and metabolic surgeries in China, it's effect on Chinese people still needs further study. AIM: To investigate the effect and safety of a modified gastric bypass performed in Chinese patients with T2DM. METHODS: Patients with obesity and T2DM who underwent modified gastric bypass, with > 5-year follow-up data, were analyzed. RESULTS: All 37 patients underwent uneventful laparoscopic surgery, no patient was switched to laparotomy during the surgery, and no severe complications were reported. Average weight and body mass index of the patients reduced from 84.6 ± 17.3 (60.0-140.0) kg and 30.9 ± 5.0 (24.7-46.2) kg/m2 to 67.1 ± 12.2 (24.7-46.2) kg and 24.6 ± 3.9 (17.7-36.5) kg/m2, respectively, and fasting plasma glucose and glycated hemoglobin decreased from 7.4 ± 3.4 mmol/L and 8.2% ± 1.7% preoperatively to 6.5 ± 1.3 mmol/L and 6.5% ± 0.9% 5-years postoperatively, respectively. Only 29.7% (11/37) of the patients used hypoglycemic drugs 5-years postoperatively, and the complete remission rate of T2DM was 29.7% (11/37). Triglyceride level reduced significantly but high-density lipoprotein increased significantly (both P < 0.05) compared with those during the preoperative period. Liver and renal function improved significantly postoperatively, and binary logistic regression analysis revealed that the patients' preoperative history of T2DM and fasting C-peptide were significant prognostic factors influencing complete T2DM remission after RYGB (P = 0.006 and 0.012, respectively). CONCLUSION: The modified gastric bypass is a safe and feasible procedure for Chinese patients with obesity and T2DM, exhibiting satisfactory amelioration of weight problems, hyperglycemia, and combination disease.

IL-1ß-induced mesenchymal stem cell-derived exosomes inhibit neuronal ferroptosis in intracerebral hemorrhage through the HSPA5/GPX4 axis.

BACKGROUND: Neuronal cell ferroptosis following intracerebral hemorrhage (ICH) is a crucial factor contributing to the poor prognosis of ICH patients. The objective of this investigation was to investigate the molecular mechanism of IL-1ß-induced mesenchymal stem cell-derived exosomes (IL-1ß-Exo) in mitigating ICH injury. METHODS: Exo and IL-1ß-Exo were obtained and identified. Hemin was used to induce an ICH model, and an ICH mouse model was established using Collagenase. Exo and IL-1ß-Exo interventions were conducted to study their impact and molecular mechanisms on neuronal ferroptosis in ICH. RESULTS: Vesicular structure Exo and IL-1ß-Exo, with an average particle size of 141.7 ± 38.8 nm and 138.8 ± 37.5 nm, respectively, showed high expression of CD63, CD9 and CD81 could be taken up by SH-SY5Y cells. These Exos reversed Hemin-induced abnormalities in neuronal cells, including elevated iron, Fe2+, ROS, MDA, 4-HNE, and decreased SOD, GSH-Px, GSH, FTH1 levels, and cell vitality. The RNA content of IL-1ß-Exo was linked to its ability to reduce iron accumulation. There was an interaction between HSPA5 and GPX4. Exo and IL-1ß-Exo reversed Hemin-induced downregulation of HSPA5 and GPX4 expression. Overexpression and knockdown of HSPA5 respectively potentiate or counteract the impacts of Exo and IL-1ß-Exo. IL-1ß-Exo was more effective than Exo. These findings were further validated in ICH mice. Moreover, both Exo and IL-1ß-Exo reduced the modified neurological severity score and brain water content, as well as alleviated pathological damage in ICH mice. CONCLUSION: IL-1ß-Exo inhibited neuronal ferroptosis in ICH through the HSPA5/GPX4 axis.

Paeonol potentiates colistin efficacy against K. pneumoniae by promoting membrane disruption and oxidative damage.

BACKGROUND: Although colistin is widely recognized as the last line of antibiotics against gram-negative bacteria, the emergence and spread of colistin resistance severely diminish its clinical efficacy and application. An alternative strategy to alleviate this crisis is to identify promising colistin adjuvants with enhanced antibacterial activity. PURPOSE: In this study, the adjuvant effects of paeonol on colistin and the underlying mechanisms were investigated. METHOD: Minimum Inhibitory Concentration (MIC) and checkerboard assays were used to investigate the adjuvant activity and structure-activity relationship of paeonol on the antibacterial effect of colistin in vitro. Time-dependent killing and resistance development assays were used to investigate the bactericidal effects and emergence of colistin resistance. Different fluorescent probes and competitive inhibition tests were used to investigate bacterial membrane functions and potential targets. Skin infection and peritonitis-sepsis models were used to evaluate the combined in vivo effects of colistin and paeonol in vivo. RESULT: Paeonol enhanced the antibacterial effects of colistin against gram-negative bacteria, particularly Klebsiella pneumoniae. Structure-activity relationship analysis showed that the hydroxyl, 4-methoxy and ketone carbonyl side chains of the benzene ring contributed to the adjuvant effect of paeonol. Paeonol enhances the bactericidal effects of colistin and minimizes the emergence of colistin resistance. Notably, mechanistic studies demonstrated that the combination of colistin and paeonol enhances membrane disruption and oxidative damage, possibly via interactions with phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CAL). Importantly, paeonol enhanced the efficacy of colistin in both the skin and peritonitis infection models. CONCLUSION: This is the first report on the adjuvant potential of paeonol in colistin to combat K. pneumoniae by promoting membrane disruption and oxidative damage via targeting membrane phospholipids. Notably, the verified target, PE, provides an additional avenue for screening new colistin adjuvants.The combination therapy of paeonol and colistin is a promising strategy for treating infections caused by gram-negative pathogens to address antibiotic resistance issues.

Novel circular RNA hsa_circ_0036683 suppresses proliferation and migration by mediating the miR-4664-3p/CDK2AP2 axis in non-small cell lung cancer.

BACKGROUND: The aim of the present study was to investigate the function of novel circular RNA hsa_circ_0036683 (circ-36683) in non-small cell lung cancer (NSCLC). METHODS: RNA sequencing was used to screen out differentially expressed miRNAs. Expression levels of miR-4664-3p and circ-36683 were evaluated in lung carcinoma cells and tissues by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The effects of miR-4664-3p and circ-36683 on proliferation and migration were assessed using cell counting kit-8 (CCK-8), wound healing and transwell migration assays and xenograft experiments. The targeting relationship of circ-36683/miR-4664-3p/CDK2AP2 was assessed by luciferase reporter assays, western blot, qRT-PCR and argonaute2-RNA immunoprecipitation (AGO2 RIP). Co-immunoprecipitation (Co-IP), 5-ethynyl-2'-deoxyuridine (EdU) staining and CCK-8 were used to validate the indispensable role of CDK2AP2 in suppressing cell proliferation as a result of CDK2AP1 overexpression. RESULTS: By RNA sequencing, miR-4664-3p was screened out as an abnormally elevated miRNA in NSCLC tissues. Transfection of miR-4664-3p could promote cell proliferation, migration and xenograft tumor growth. As a target of miR-4664-3p, CDK2AP2 expression was downregulated by miR-4664-3p transfection and CDK2AP2 overexpression could abolish the proliferation promotion resulting from miR-4664-3p elevation. Circ-36683, derived from back splicing of ABHD2 pre-mRNA, was attenuated in NSCLC tissue and identified as a sponge of miR-4664-3p. The functional study revealed that circ-36683 overexpression suppressed cell proliferation, migration and resulted in G0/G1 phase arrest. More importantly, the antioncogenic function of circ-36683 was largely dependent on the miR-4664-3p/CDK2AP2 axis, through which circ-36683 could upregulate the expression of p53/p21/p27 and downregulate the expression of CDK2/cyclin E1. CONCLUSION: The present study revealed the antioncogenic role of circ-36683 in suppressing cell proliferation and migration and highlighted that targeting the circ-36683/miR-4664-3p/CDK2AP2 axis is a promising strategy for the intervention of NSCLC.

A Comparative Evaluation of Three Diagnostic Assays for the Detection of Human Monkeypox.

Accurate and early diagnosis of monkeypox virus (MPXV) is crucial for controlling epidemics and treating affected individuals promptly. This study aimed to assess the analytical and clinical performance of the MolecisionTM Monkeypox Virus qPCR Assay, Biorain Monkeypox Virus ddPCR Assay, and MAGLUMI® Monkeypox Virus Ag (chemiluminescence immunoassay, CLIA) Assay. Additionally, it aimed to compare the clinical application of antigen and nucleic acid assays to offer insights into using commercial monkeypox assay kits. Specimens from 117 clinical patients, serial diluted virus cell culture supernatant, and artificially created positive samples were tested to evaluate the performance of these assay kits for MPXV diagnostics. The Biorain Monkeypox Virus ddPCR Assay had a limit of detection (LoD) of 3.89 CCID50/mL, while the MolecisionTM Monkeypox Virus qPCR Assay had an LoD of 15.55 CCID50/mL. The MAGLUMI® Monkeypox Virus Ag (CLIA) Assay had an LoD of 0.500 pg/mL. The accuracy of the MolecisionTM Monkeypox Virus qPCR Assay was comparable to the Biorain Monkeypox Virus ddPCR Assay, and the MAGLUMI® Monkeypox Virus Ag (CLIA) Assay demonstrated high sensitivity. The specificity of all three MPXV diagnostic assays for clinical specimens with potential cross-reacting substances was 100%. In conclusion, this study provides valuable insights into the clinical application of monkeypox assays, supporting efforts to mitigate and control the spread of monkeypox.

Hb A2-Guangxi [δ79 (EF3) Asp→Asn, HBD: C.238G > A] and polyA + 70 (HBD: C.*200G > A): Two Novel δ-Globin Gene Mutations Identified in a Chinese Family.

We report the molecular and hematological identifications of two novel δ-globin gene mutations found in Guangxi Zhuang Autonomous Region, China. Capillary electrophoresis of the proband showed 1.3% Hb A2, accompanied by a minor unknown peak (0.7%) within the Z1 zone. High-performance liquid chromatography also revealed the presence of 1.5% Hb A2 and a 0.6% unknown peak. Routine genetic testing (Gap-PCR and reverse dot-blot hybridization) for common α-thalassemia was performed, and no mutations were observed. Sanger sequencing identified a heterozygous mutation for GAC > AAC at codon 79 (HBD:c.238G > A) and G > A at polyA + 70 (HBD:c.*200G > A) of the δ-globin gene. This variant was named Hb A2-Guangxi [δ79 (EF3) Asp→Asn, HBD:c.238G > A] after the geographic origin of the proband.

Controlled Synthesis of 2D Ferromagnetic/Antiferromagnetic Cr7Te8/MnTe Vertical Heterostructures for High-Tunable Coercivity.

Two-dimensional ferromagnetic/antiferromagnetic (2D-FM/AFM) heterostructures are of great significance to realize the application of spintronic devices such as miniaturization, low power consumption, and high-density information storage. However, traditional mechanical stacking can easily damage the crystal quality or cause chemical contamination residues for 2D materials, which can result in weak interface coupling and difficulty in device regulation. Chemical vapor deposition (CVD) is an effective way to achieve a high-quality heterostructure interface. Herein, high-quality interface 2D-FM/AFM Cr7Te8/MnTe vertical heterostructures were successfully synthesized via a one-pot CVD method. Moreover, the atomic-scale structural scanning transmission electron microscope (STEM) characterization shows that the interface of the vertical heterostructure is clear and flat without an excess interface layer. Compared to the parent Cr7Te8, the coercivity (HC) of the high-quality interface Cr7Te8/MnTe heterostructure is significantly reduced as the thickness of MnTe increases, with a maximum decrease of 74.5% when the thickness of the MnTe nanosheet is around 30 nm. Additionally, the HC of the Cr7Te8/MnTe heterostructure can also be regulated by applying a gate voltage, and the HC increases or decreases with increasing positive or negative gate voltages. Thus, the effective regulation of HC is essential to improving the performance of advanced spintronic devices (e.g., MRAM and magnetic sensors). Our work will provide ideas for spin controlling and device application of 2D-FM/AFM heterostructures.

Identification of Isoliensinine as a Ferroptosis Suppressor with Iron-Chelating Activity.

Ferroptosis is a type of regulated cell death driven by the iron-dependent accumulation of lipid peroxides. The high involvement of ferroptosis in diverse human diseases highlights the need for the identification of new chemotypes with anti-ferroptotic activity. Here, we performed a natural product library screening in HT1080 fibrosarcoma cells and identified licochalcone A (LA), isoeugenyl acetate (ISA), and isoliensinine (ISL) as suppressors of either RSL3- or IKE-induced ferroptosis. Mechanistically, ferroptosis resistance conferred by these compounds is mainly through GPX4/NRF2-independent mechanisms. Among them, only ISL could effectively rescue ferroptosis induced by FINO2, which is a stable oxidant of ferrous iron, suggesting that ISL may have the properties of an iron chelator. Consistent with the hypothesis, both computational tools and X-ray photoelectron spectroscopy supported the binding between ISL and iron ions. And ISL greatly inhibited excessive iron-dependent ferroptotic cell death through limiting intracellular iron accumulation. Furthermore, its iron chelator activity also protected mice from organ injury in an acute iron overload model. In conclusion, this study provided valuable insights for developing effective anti-ferroptosis agents from natural products, which represent a potential therapeutic strategy for treating ferroptosis-associated organ damage.

New species, new records, and common species of Diderma (Physarales, Didymiaceae) from China.

Myxomycetes are fungus-like organisms that play a significant role in ecological processes, however, their taxonomic diversity and distribution in China are poorly understood. Diderma is an important genus within the Class Myxogastria that has received little attention in China. This study provides new insights into the geographic range of Diderma species in China and identifies previously unreported and newly recorded species. Our results reveal that the geographic distribution of Diderma species in China is more diverse than previously thought, with four previously unreported species found in Liaoning, Hubei, Sichuan, and Gansu provinces. In addition, we describe five new Diderma species that are distinct from previously known species, namely Diderma annuliferum, Diderma gansuense, Diderma roseum, Diderma jilinense, and Diderma flexocapillitium. We identified these species using a combination of morphological characterization, DNA sequencing, and phylogenetic analysis. Our findings have important implications for understanding Myxomycete biodiversity in China and can inform future research on the ecology, biogeography, and evolution of these fascinating organisms. Specifically, our study highlights the need for continued exploration of underrepresented areas to gain a more comprehensive understanding of the diversity and distribution of Myxomycetes in China. IMPORTANCE: The discovery of five new Diderma species and the revelation of their diverse distribution expand our understanding of Myxomycete diversity and provide a foundation for future studies on the ecology and biogeography of these organisms. These findings contribute to our knowledge of microbial diversity and have practical implications for conserving underrepresented areas and maintaining healthy ecosystems.

ß-Caryophyllene Confers Cardioprotection by Scavenging Radicals and Blocking Ferroptosis.

Ferroptosis is a form of regulated cell death triggered by iron-dependent lipid peroxidation and has been associated with heart diseases. However, there are currently no approved drugs that specifically inhibit ferroptosis in clinical practice, which largely limits the translational potential of this novel target. Here, we demonstrated that ß-caryophyllene (BCP; 150 µM), a natural dietary cannabinoid, protects cardiomyocytes against ferroptotic cell death induced by cysteine deprivation or glutathione peroxidase 4 (GPX4) inactivation. Moreover, BCP preserved the mitochondrial morphology and function during ferroptosis induction. Unexpectedly, BCP supported ferroptosis resistance independent of canonical antiferroptotic pathways. Our results further suggested that BCP may terminate radical chain reactions through interactions with molecular oxygen, which also explains why its oxidation derivative failed to suppress ferroptosis. Finally, oral BCP administration (50 mg/kg, daily) significantly alleviated doxorubicin (15 mg/kg, single i.p. injection)-induced cardiac ferroptosis and cardiomyopathy in mice. In conclusion, our data revealed the role of BCP as a natural antiferroptotic compound and suggest pharmacological modification based on BCP as a promising therapeutic strategy for treating ferroptosis-associated heart disorders.

Insect ribosome-rescuer Pelo-Hbs1 complex on sperm surface mediates paternal arbovirus transmission.

Arboviruses can be paternally transmitted by male insects to offspring for long-term persistence, but the mechanism remains largely unknown. Here, we use a model system of a destructive rice reovirus and its leafhopper vector to find that insect ribosome-rescuer Pelo-Hbs1 complex expressed on the sperm surface mediates paternal arbovirus transmission. This occurs through targeting virus-containing tubules constituted by viral nonstructural protein Pns11 to sperm surface via Pns11-Pelo interaction. Tubule assembly is dependent on Hsp70 activity, while Pelo-Hbs1 complex inhibits tubule assembly via suppressing Hsp70 activity. However, virus-activated ubiquitin ligase E3 mediates Pelo ubiquitinated degradation, synergistically causing Hbs1 degradation. Importantly, Pns11 effectively competes with Pelo for binding to E3, thus antagonizing E3-mediated Pelo-Hbs1 degradation. These processes cause a slight reduction of Pelo-Hbs1 complex in infected testes, promoting effective tubule assembly. Our findings provide insight into how insect sperm-specific Pelo-Hbs1 complex is modulated to promote paternal virus transmission without disrupting sperm function.

Two New Species of the Genus Diderma (Physarales, Didymiaceae) in China with an Addition to the Distribution.

Myxomycetes are an important component of terrestrial ecosystems, and in order to understand their diversity and phylogenetic relationships, taxonomic issues need to be addressed. In our 1985-2021 biodiversity investigations in Shaanxi Province, Jilin Province, the Inner Mongolia Autonomous Region, Hubei Province, and Henan Province, China, Diderma samples were observed on rotten leaves, rotten branches, and dead wood. The samples were studied, based on morphological features coupled with multigene phylogenetic analyses of nSSU, EF-1α, and COI sequence data, which revealed two new species (Diderma shaanxiense sp. nov. and D. clavatocolumellum sp. nov.) and two known species (D. radiatum and D. globosum). In addition, D. radiatum and D. globosum were newly recorded in Henan Province and the Inner Mongolia Autonomous Region, respectively. The paper includes comprehensive descriptions, detailed micrographs, and the outcomes of phylogenetic analyses for both the newly discovered and known species. Additionally, it offers morpho-logical comparisons between the new species and similar ones.