Pd-catalyzed asymmetric Larock reaction for the atroposelective synthesis of N─N chiral indoles.

Atropisomeric indoles defined by a N─N axis are an important class of heterocycles in synthetic and medicinal chemistry and material sciences. However, they remain heavily underexplored due to limited synthetic methods and challenging stereocontrol over the short N─N bonds. Here, we report highly atroposelective access to N─N axially chiral indoles via the asymmetric Larock reaction. This protocol leveraged the powerful role of chiral phosphoramidite ligand to attenuate the common ligand dissociation in the original Larock reaction, forming N─N chiral indoles with excellent functional group tolerance and high enantioselectivity via palladium-catalyzed intermolecular annulation between readily available o-iodoaniline and alkynes. The multifunctionality in the prepared chiral indoles allowed diverse post-coupling synthetic transformations, affording a broad array of functionalized chiral indoles. Experimental and computational studies have been conducted to explore the reaction mechanism, elucidating the enantio-determining and rate-limiting steps.

Flagellimonas halotolerans sp. nov., a novel bacterium isolated from the South China Sea.

Two Gram-stain-negative strains, designed SYSU M86414T and SYSU M84420, were isolated from marine sediment samples of the South China Sea (Sansha City, Hainan Province, PR China). These strains were aerobic and could grow at pH 6.0-8.0 (optimum, pH 7.0), 4-37 °C (optimum, 28 °C), and in the presence of 0-10 % NaCl (w/v; optimum 3 %). The predominant respiratory menaquinone of strains SYSU M86414T and SYSU M84420 was MK-6. The primary cellular polar lipid was phosphatidylethanolamine. The major cellular fatty acids (>10 %) in both strains were iso-C15 : 0, iso-C15 : 1 G, and iso-C17 : 0 3-OH. The DNA G+C content of strains SYSU M86414T and SYSU M84420 were both 42.10 mol%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that these novel strains belonged to the genus Flagellimonas and strain SYSU M86414T showed the highest 16S rRNA gene sequence similarity to Flagellimonas marinaquae JCM 11811T (98.83 %), followed by Flagellimonas aurea BC31-1-A7T (98.62 %), while strain SYSU M84420 had highest 16S rRNA gene sequence similarity to F. marinaquae JCM 11811T (98.76 %) and F. aurea BC31-1-A7T (98.55 %). Based on the results of polyphasic analyses, strains SYSU M86414T and SYSU M84420 should be considered to represent a novel species of the genus Flagellimonas, for which the name Flagellimonas halotolerans sp. nov. is proposed. The type strain of the proposed novel isolate is SYSU M86414T (=GDMCC 1.3806T=KCTC 102040T).

Global Burden and Trends of Primary Liver Cancer Attributable to Comorbid Type 2 Diabetes Mellitus Among People Living with Hepatitis B: An Observational Trend Study from 1990 to 2019.

BACKGROUND: Type 2 diabetes mellitus (T2DM) increases the risk of liver cancer among people living with hepatitis B virus (HBV). Our study aimed to estimate the global burden and trends of liver cancer attributable to comorbid T2DM among people living with HBV from 1990 to 2019. METHODS: We calculated the population attributable fractions (PAFs) of liver cancer attributable to comorbid T2DM among the burden of HBV-related liver cancer. We applied the PAFs to the burden of HBV-related liver cancer derived from the Global Burden of Disease (GBD) 2019 database to obtain the burden of liver cancer attributable to HBV-T2DM comorbidity. The prevalence, disability-adjusted life year (DALY), and deaths of liver cancer attributable to the comorbidity were assessed at the global, regional, and country levels and then stratified by the sociodemographic index (SDI), sex, and age group. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends. RESULTS: In 2019, the global age-standardized prevalence and DALY rates of liver cancer attributable to HBV-T2DM comorbidity were 9.9 (8.4-11.5) and 182.4 (154.9-212.7) per 10,000,000 individuals, respectively. High-income Asia Pacific and East Asia had the highest age-standardized prevalence and DALY rates of liver cancer attributable to HBV-T2DM comorbidity, respectively. From 1990 to 2019, age-standardized prevalence and DALY rates increased in 16 out of 21 GBD regions. High-income North America had the largest annual increases in both age-standardized prevalence rates (EAPC = 6.07; 95% UI, 5.59 to 6.56) and DALY rates (EAPC = 4.77; 95% UI, 4.35 to 5.20), followed by Australasia and Central Asia. Across all SDI regions, the high SDI region exhibited the most rapid increase in age-standardized prevalence and DALY rates from 1990 to 2019. Additionally, men had consistently higher disease burdens than women across all age groups. The patterns of mortality burden and trends are similar to those of DALYs. CONCLUSIONS: The burden of liver cancer attributable to comorbid T2DM among people living with HBV has exhibited an increasing trend across most regions over the last three decades. Tailored prevention strategies targeting T2DM should be implemented among individuals living with HBV.

MultiModRLBP: A Deep Learning Approach for Multi-Modal RNA-Small Molecule Ligand Binding Sites Prediction.

This study aims to tackle the intricate challenge of predicting RNA-small molecule binding sites to explore the potential value in the field of RNA drug targets. To address this challenge, we propose the MultiModRLBP method, which integrates multi-modal features using deep learning algorithms. These features include 3D structural properties at the nucleotide base level of the RNA molecule, relational graphs based on overall RNA structure, and rich RNA semantic information. In our investigation, we gathered 851 interactions between RNA and small molecule ligand from the RNAglib dataset and RLBind training set. Unlike conventional training sets, this collection broadened its scope by including RNA complexes that have the same RNA sequence but change their respective binding sites due to structural differences or the presence of different ligands. This enhancement enables the MultiModRLBP model to more accurately capture subtle changes at the structural level, ultimately improving its ability to discern nuances among similar RNA conformations. Furthermore, we evaluated MultiModRLBP on two classic test sets, Test18 and Test3, highlighting its performance disparities on small molecules based on metal and non-metal ions. Additionally, we conducted a structural sensitivity analysis on specific complex categories, considering RNA instances with varying degrees of structural changes and whether they share the same ligands. The research results indicate that MultiModRLBP outperforms the current state-of-the-art methods on multiple classic test sets, particularly excelling in predicting binding sites for non-metal ions and instances where the binding sites are widely distributed along the sequence. MultiModRLBP also can be used as a potential tool when the RNA structure is perturbed or the RNA experimental tertiary structure is not available. Most importantly, MultiModRLBP exhibits the capability to distinguish binding characteristics of RNA that are structurally diverse yet exhibit sequence similarity. These advancements hold promise in reducing the costs associated with the development of RNA-targeted drugs.

Associations between remnant cholesterol levels and mortality in patients with diabetes.

BACKGROUND: Dyslipidemia is frequently present in patients with diabetes. The associations of remnant cholesterol and mortality remains unclear in patients with diabetes. AIM: To explore the associations of remnant cholesterol with all-cause and cardiovascular mortality in patients with diabetes. METHODS: This prospective cohort study included 4740 patients with diabetes who participated in the National Health and Nutrition Examination Survey from 1999 through 2018. Remnant cholesterol was used as the exposure variable, and all-cause and cardiovascular mortality were considered outcome events. Outcome data were obtained from the National Death Index, and all participants were followed from the interview date until death or December 31, 2019. Multivariate proportional Cox regression models were used to explore the associations between exposure and outcomes, in which remnant cholesterol was modeled as both a categorical and a continuous variable. Restricted cubic splines (RCSs) were calculated to assess the nonlinearity of associations. Subgroup (stratified by sex, age, body mass index, and duration of diabetes) and a series of sensitivity analyses were performed to evaluate the robustness of the associations. RESULTS: During a median follow-up duration of 83 months, 1370 all-cause deaths and 389 cardiovascular deaths were documented. Patients with remnant cholesterol levels in the third quartile had a reduced risk of all-cause mortality [hazard ratio (HR) 95% confidence interval (CI): 0.66 (0.52-0.85)]; however, when remnant cholesterol was modeled as a continuous variable, it was associated with increased risks of all-cause [HR (95%CI): 1.12 (1.02-1.21) per SD] and cardiovascular [HR (95%CI): 1.16 (1.01-1.32), per SD] mortality. The RCS demonstrated nonlinear associations of remnant cholesterol with all-cause and cardiovascular mortality. Subgroup and sensitivity analyses did not reveal significant differences from the above results. CONCLUSION: In patients with diabetes, higher remnant cholesterol was associated with increased risks of all-cause and cardiovascular mortality, and diabetes patients with slightly higher remnant cholesterol (0.68-1.04 mmol/L) had a lower risk of all-cause mortality.

Distinct experiences and care needs of advanced cancer patients with good ECOG performance status: a qualitative phenomenological study.

BACKGROUND: Advanced cancer patients with good Eastern Cooperative Oncology Group (ECOG) performance status (score 0-1) are underrepresented in current qualitative reports compared with their dying counterparts. AIM: To explore the experiences and care needs of advanced cancer patients with good ECOG. DESIGN: A qualitative phenomenological approach using semi-structured interview was employed. Data was analyzed using the Colaizzi's method. SETTING/PARTICIPANTS: Purposive sample of terminal solid cancer patients on palliative care aged 18-70 years with a 0-1 ECOG score were recruited from a tertiary general hospital. RESULTS: Sixteen participants were interviewed. Seven themes were generated from the transcripts, including experiencing no or mild symptoms; independence in self-care, decision-making, and financial capacity; prioritization of cancer growth suppression over symptom management; financial concerns; hope for prognosis and life; reluctance to discuss death and after-death arrangements; and use of complementary and alternative medicine (CAM) and religious coping. CONCLUSIONS: Advanced cancer patients with good ECOG have distinct experiences and care needs from their dying counterparts. They tend to experience no or mild symptoms, demonstrate a strong sense of independence, and prioritize cancer suppression over symptom management. Financial concerns were common and impact their care-related decision-making. Though being hopeful for their prognosis and life, many are reluctant to discuss death and after-death arrangements. Many Chinese patients use herbal medicine as a CAM modality but need improved awareness of and accessibility to treatment options. Healthcare professionals and policy-makers should recognize their unique experiences and needs when tailoring care strategies and policies.

Efficacy and safety of Panax notoginseng saponin injection in the treatment of acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.

Purpose: This study aimed to assess the efficacy and safety of Panax notoginseng saponin (PNS) injection, when combined with conventional treatment (CT), for acute myocardial infarction (AMI). Methods: Comprehensive searches were conducted in seven databases from inception until 28 September 2023. The search aimed to identify relevant randomized controlled trials (RCTs) focusing on PNS injection in the context of AMI. This meta-analysis adhered to the PRISMA 2020 guidelines, and its protocol was registered with PROSPERO (number: CRD42023480131). Result: Twenty RCTs involving 1,881 patients were included. The meta-analysis revealed that PNS injection, used adjunctively with CT, significantly improved treatment outcomes compared to CT alone, as evidenced by the following points: (1) enhanced total effective rate [OR = 3.09, p < 0.05]; (2) decreased incidence of major adverse cardiac events [OR = 0.32, p < 0.05]; (3) reduction in myocardial infarct size [MD = -6.53, p < 0.05]; (4) lower ST segment elevation amplitude [MD = -0.48, p < 0.05]; (5) mitigated myocardial injury as indicated by decreased levels of creatine kinase isoenzymes [MD = -11.19, p < 0.05], cardiac troponin T [MD = -3.01, p < 0.05], and cardiac troponin I [MD = -10.72, p < 0.05]; (6) enhanced cardiac function, reflected in improved brain natriuretic peptide [MD = -91.57, p < 0.05], left ventricular ejection fraction [MD = 5.91, p < 0.05], left ventricular end-diastolic dimension [MD = -3.08, p < 0.05], and cardiac output [MD = 0.53, p < 0.05]; (7) reduced inflammatory response, as shown by lower levels of C-reactive protein [MD = -2.99, p < 0.05], tumor necrosis factor-α [MD = -6.47, p < 0.05], interleukin-6 [MD = -24.46, p < 0.05], and pentraxin-3 [MD = -2.26, p < 0.05]; (8) improved vascular endothelial function, demonstrated by decreased endothelin-1 [MD = -20.56, p < 0.05] and increased nitric oxide [MD = 1.33, p < 0.05]; (9) alleviated oxidative stress, evidenced by increased superoxide dismutase levels [MD = 25.84, p < 0.05]; (10) no significant difference in adverse events [OR = 1.00, p = 1.00]. Conclusion: This study highlighted the efficacy and safety of adjunctive PNS injections in enhancing AMI patient outcomes beyond CT alone. Future RCTs need to solidify these findings through rigorous methods. Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/), identifier (CRD42023480131).

Kaempferol Improves Exercise Performance by Regulating Glucose Uptake, Mitochondrial Biogenesis, and Protein Synthesis via PI3K/AKT and MAPK Signaling Pathways.

Kaempferol is a natural flavonoid with reported bioactivities found in many fruits, vegetables, and medicinal herbs. However, its effects on exercise performance and muscle metabolism remain inconclusive. The present study investigated kaempferol's effects on improving exercise performance and potential mechanisms in vivo and in vitro. The grip strength, exhaustive running time, and distance of mice were increased in the high-dose kaempferol group (p < 0.01). Also, kaempferol reduced fatigue-related biochemical markers and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) related to antioxidant capacity. Kaempferol also increased the glycogen and adenosine triphosphate (ATP) content in the liver and skeletal muscle, as well as glucose in the blood. In vitro, kaempferol promoted glucose uptake, protein synthesis, and mitochondrial function and decreased oxidative stress in both 2D and 3D C2C12 myotube cultures. Moreover, kaempferol activated the PI3K/AKT and MAPK signaling pathways in the C2C12 cells. It also upregulated the key targets of glucose uptake, mitochondrial function, and protein synthesis. These findings suggest that kaempferol improves exercise performance and alleviates physical fatigue by increasing glucose uptake, mitochondrial biogenesis, and protein synthesis and by decreasing ROS. Kaempferol's molecular mechanism may be related to the regulation of the PI3K/AKT and MAPK signaling pathways.

Prognostic value of PAX8 in small cell lung cancer.

Objectives: Small cell lung cancer (SCLC) shows poor prognosis since it metastasizes widely at early stage. Paired box gene (PAX) 8 is a transcriptional factor of PAX family, of which the expression in lung cancer is a controversial issue, and its prognostic value of PAX8 in SCLC is still unclear. Materials and methods: Overall, 184 subjects who were pathologically diagnosed with SCLC were enrolled in the study. Immunohistochemical analysis of PAX8 and Ki-67 were performed. The correlations between PAX8 expression and clinical features or Ki-67 index were further analyzed. Subsequently, an analysis of the association between PAX8, stage, Ki-67 status, and overall survival (OS) were performed in 169 subjects with follow-up information. Results: PAX8 was positive in 53.8% (99/184) SCLC specimens. The positive rate is significantly higher in extensive-stage specimens (61.0%) than in limited-stage specimens (45.24%). PAX8 expression is positively correlated with Ki-67 index (P = 0.001) while negatively correlated with OS (HR = 3.725, 95% CI 1.943-7.139, P＜0.001). In combination groups, the PAX8 negative and limited stage group had the most promising OS. Conclusion: PAX8 expression rate in SCLC specimens is not low. It has prognostic value in small cell lung cancer.

An Odorant Receptor Expressed in Both Antennae and Ovipositors Regulates Benzothiazole-Induced Oviposition Behavior in Bactrocera dorsalis.

The oriental fruit fly,Bactrocera dorsalis (Hendel), is a notorious pest of fruit crops, causing severe damage to fleshy fruits during oviposition and larval feeding. Gravid females locate suitable oviposition sites by detecting the host volatiles. Here, the oviposition preference of antenna-removed females and the electrophysiological response of ovipositors to benzothiazole indicated that both antennae and ovipositors are involved in perceiving benzothiazole. Subsequently, odorant receptors (ORs) expressed in both antennae and ovipositors were screened, and BdorOR43a-1 was further identified to respond to benzothiazole using voltage-clamp recording. Furthermore, BdorOR43a-1-/- mutants were obtained using the CRISPR/Cas9 system and their oviposition preference to benzothiazole was found to be significantly altered compared to WT females, suggesting that BdorOR43a-1 is one of the important ORs for benzothiazole perception. Our results not only demonstrate the important role of antennae and ovipositors in benzothiazole-induced oviposition but also elucidate on the OR responsible for benzothiazole perception in B. dorsalis.

Correction to "Engineering of CuMOF-SWCNTs@AuNPs-Based Electrochemical Sensors for Ultrasensitive and Selective Monitoring of Imatinib in Human Serum".

[This corrects the article DOI: 10.1021/acsomega.3c08002.].

Femtosecond Laser Fabrication of Three-Dimensional Bubble-Propelled Microrotors for Multicomponent Mechanical Transmission.

Inspired by the reverse thrust generated by fuel injection, micromachines that are self-propelled by bubble ejection are developed, such as microrods, microtubes, and microspheres. However, controlling bubble ejection sites to build micromachines with programmable actuation and further enabling mechanical transmission remain challenging. Here, bubble-propelled mechanical microsystems are constructed by proposing a multimaterial femtosecond laser processing method, consisting of direct laser writing and selective laser metal reduction. The polymer frame of the microsystems is first printed, followed by the deposition of catalytic platinum into the desired local site of the microsystems by laser reduction. With this method, a variety of designable microrotors with selective bubble ejection sites are realized, which enable excellent mechanical transmission systems composed of single and multiple mechanical components, including a coupler, a crank slider, and a crank rocker system. We believe the presented bubble-propelled mechanical microsystems could be extended to applications in microrobotics, microfluidics, and microsensors.

Stomatohabitans albus gen. nov., sp. nov., an oral living facultative anaerobic actinobacteria isolated form Steller sea lion, and proposal of Stomatohabitantaceae fam. nov. and Stomatohabitantales ord. nov.

Two novel actinobacteria, designated as SYSU M7M538T and SYSU M7M531, were isolated from oral of Eumetopias jubatus in Zhuhai Chimelong Ocean Kingdom, China. The cells of these microorganisms stained Gram-positive and were rod shaped. These strains were facultative anaerobic, and catalase-positive. Optimal growth occurred at 37 °C and pH 7.0 over 7 days of cultivation. Both strains possessed diphosphatidylglycerol, phosphatidylglycerol and phosphocholine as the major polar lipids. The main menaquinone was MK-9(H4). The major fatty acids were C16:0, C17:1w8c, C17:0, C18:1w9c and C18:0. Analyses of genome sequences revealed that the genome size of SYSU M7M538T was 2.1 Mbp with G + C content of 52.5 %, while the genome size of SYSU M7M531 was 2.3 Mbp with G + C content of 52.7 %. The ANI and 16S rRNA gene analysis results showed that the pairwise similarities between the two strains and other recognized Nitriliruptoria species were less than 64.9 % and 89.0 %, respectively. Phylogenetic analysis of the 16S rRNA gene sequences indicated that strains SYSU M7M538T and SYSU M7M531 formed a well-separated phylogenetic branch distinct from other orders of Nitriliruptoria. Based on the data presented here, these two strains are considered to represent a novel species of a novel genus, for which the name Stomatohabitans albus gen. nov., sp. nov., with the type strain SYSU M7M538T (=KCTC 59113T = GDMCC 1.4286T), are proposed. We also propose that these organisms represent a novel family named Stomatohabitantaceae fam. nov. of a novel order Stomatohabitantales ord. nov.

Engineering of CuMOF-SWCNTs@AuNPs-Based Electrochemical Sensors for Ultrasensitive and Selective Monitoring of Imatinib in Human Serum.

Imatinib (IMA) is a common chemotherapy drug for the treatment of leukemia and can potentially lead to drug resistance and toxicity during the course of treatment. Monitoring IMA concentrations in body fluids is necessary to optimize therapeutic schedules and avoid overdosage. In this paper, a novel ultrasensitive electrochemical sensor based on CuMOF and SWCNTs@AuNPs was developed to determine this antileukemic drug. Herein, AuNPs were supported on carboxylic single-walled carbon nanotubes (SWCNT-COOH), and then poly(diallyldimethylammonium chloride) (PDDA) was used as a dispersant to overcome the internal van der Waals interactions among the CNTs, further increasing the AuNP loading. Moreover, the morphology, structure, composition, and electrochemical properties of the CuMOF-SWCNTs@AuNPs composite film were characterized using SEM, TEM, FT-IR, UV-vis, XRD, XPS, CV, and EIS. Due to the advantage of the superior electrocatalytic and conductive properties of SWCNTs@AuNPs and their preferable adsorptivity and affinity to IMA of CuMOF, the fabricated glassy carbon electrode significantly improved the determination performance via their synergetic amplified effect. Under optimal conditions, a wide linear response was exhibited in the range from 0.05 to 20.0 µM and the low detection limit of 5.2 nM. In addition, our prepared sensor has been applied to the analysis of IMA in blood serum samples with acceptable results. Therefore, our CuMOF-SWCNTs@AuNPs-based electrochemical sensor possessed prominent sensing responses for IMA, which could be used as a prospective approach in clinical application.

Suppressing the expression of glutathione S-transferase gene GSTd10 increases the sensitivity of Zeugodacus cucurbitae against ß-cypermethrin.

Zeugodacus cucurbitae Coquillett (Diptera: Tephritidae) is an agriculturally and economically important pest worldwide that has developed resistance to ß-cypermethrin. Glutathione S-transferases (GSTs) have been reported to be involved in the detoxification of insecticides in insects. We have found that both ZcGSTd6 and ZcGSTd10 were up-regulated by ß-cypermethrin induction in our previous study, so we aimed to explore their potential relationship with ß-cypermethrin tolerance in this study. The heterologous expression of ZcGSTd6 and ZcGSTd10 in Escherichia coli showed significantly high activities against 1-chloro-2,4-dinitrobenzene (CDNB). The kinetic parameters of ZcGSTd6 and ZcGSTd10 were determined by Lineweaver-Burk. The Vmax and Km of ZcGSTd6 were 0.50 µmol/min·mg and 0.3 mM, respectively. The Vmax and Km of ZcGSTd10 were 1.82 µmol/min·mg and 0.53 mM. The 3D modelling and molecular docking results revealed that ß-cypermethrin exhibited a stronger bounding to the active site SER-9 of ZcGSTd10. The sensitivity to ß-cypermethrin was significantly increased by 18.73% and 27.21%, respectively, after the knockdown of ZcGSTd6 and ZcGSTd10 by using RNA interference. In addition, the inhibition of CDNB at 50% (IC50) and the inhibition constants (Ki) of ß-cypermethrin against ZcGSTd10 were determined as 0.41 and 0.33 mM, respectively. The Ki and IC50 of ß-cypermethrin against ZcSGTd6 were not analysed. These results suggested that ZcGSTd10 could be an essential regulator involved in the tolerance of Z. cucurbitae to ß-cypermethrin.

Extracellular Matrix Orchestration of Tissue Remodeling in the Chronically Inflamed Mouse Colon.

BACKGROUND & AIMS: Chronic inflammatory illnesses are debilitating and recurrent conditions associated with significant comorbidities, including an increased risk of developing cancer. Extensive tissue remodeling is a hallmark of such illnesses, and is both a consequence and a mediator of disease progression. Despite previous characterization of epithelial and stromal remodeling during inflammatory bowel disease, a complete understanding of its impact on disease progression is lacking. METHODS: A comprehensive proteomic pipeline using data-independent acquisition was applied to decellularized colon samples from the Muc2 knockout (Muc2KO) mouse model of colitis for an in-depth characterization of extracellular matrix remodeling. Unique proteomic profiles of the matrisomal landscape were extracted from prepathologic and overt colitis. Integration of proteomics and transcriptomics data sets extracted from the same murine model produced network maps describing the orchestrating role of matrisomal proteins in tissue remodeling during the progression of colitis. RESULTS: The in-depth proteomic workflow used here allowed the addition of 34 proteins to the known colon matrisomal signature. Protein signatures of prepathologic and pathologic colitic states were extracted, differentiating the 2 states by expression of small leucine-rich proteoglycans. We outlined the role of this class and other matrisomal proteins in tissue remodeling during colitis, as well as the potential for coordinated regulation of cell types by matrisomal ligands. CONCLUSIONS: Our work highlights a central role for matrisomal proteins in tissue remodeling during colitis and defines orchestrating nodes that can be exploited in the selection of therapeutic targets.

RPEMHC: improved prediction of MHC-peptide binding affinity by a deep learning approach based on residue-residue pair encoding.

MOTIVATION: Binding of peptides to major histocompatibility complex (MHC) molecules plays a crucial role in triggering T cell recognition mechanisms essential for immune response. Accurate prediction of MHC-peptide binding is vital for the development of cancer therapeutic vaccines. While recent deep learning-based methods have achieved significant performance in predicting MHC-peptide binding affinity, most of them separately encode MHC molecules and peptides as inputs, potentially overlooking critical interaction information between the two. RESULTS: In this work, we propose RPEMHC, a new deep learning approach based on residue-residue pair encoding to predict the binding affinity between peptides and MHC, which encode an MHC molecule and a peptide as a residue-residue pair map. We evaluate the performance of RPEMHC on various MHC-II-related datasets for MHC-peptide binding prediction, demonstrating that RPEMHC achieves better or comparable performance against other state-of-the-art baselines. Moreover, we further construct experiments on MHC-I-related datasets, and experimental results demonstrate that our method can work on both two MHC classes. These extensive validations have manifested that RPEMHC is an effective tool for studying MHC-peptide interactions and can potentially facilitate the vaccine development. AVAILABILITY: The source code of the method along with trained models is freely available at https://github.com/lennylv/RPEMHC.

Acceleration or retardation by a magnetic field of the anodic processes of iron in molybdate-bearing chloride solutions.

The modulation by a horizontal magnetic field of the anodic processes of iron in molybdate-bearing chloride solutions is determined. The magnetic field can accelerate or retard the anodic reaction depending on the rate-controlling steps at specified electrode potentials. The anodic current density arising from uniform dissolution from open or semi-open pits is increased by the magnetic field. The current density originating from occluded pits can be decreased by the magnetic field, where autocatalysis has a dominant effect on the pitting rate. The effect of the magnetic field on the pitting corrosion is a combination of the influence on electrochemical reactions at the interfaces of the pits and the disturbance of the autocatalysis process inside the pit enclave through the magnetohydrodynamic (MHD) effect. Micro-MHD effects for specific locations and macro-MHD effects for pitting systems are recommended to illustrate the magnetic effect on localized corrosion phenomena at various combinations of potentials and solution compositions.

The subgenomic flaviviral RNA suppresses RNA interference through competing with siRNAs for binding RISC components.

During the life cycle of mosquito-borne flaviviruses, substantial subgenomic flaviviral RNA (sfRNA) is produced via incomplete degradation of viral genomic RNA by host XRN1. Zika virus (ZIKV) sfRNA has been detected in mosquito and mammalian somatic cells. Human neural progenitor cells (hNPCs) in the developing brain are the major target cells of ZIKV, and antiviral RNA interference (RNAi) plays a critical role in hNPCs. However, whether ZIKV sfRNA was produced in ZIKV-infected hNPCs as well as its function remains not known. In this study, we demonstrate that abundant sfRNA was produced in ZIKV-infected hNPCs. RNA pulldown and mass spectrum assays showed ZIKV sfRNA interacted with host proteins RHA and PACT, both of which are RNA-induced silencing complex (RISC) components. Functionally, ZIKV sfRNA can antagonize RNAi by outcompeting small interfering RNAs (siRNAs) in binding to RHA and PACT. Furthermore, the 3' stem loop (3'SL) of sfRNA was responsible for RISC components binding and RNAi inhibition, and 3'SL can enhance the replication of a viral suppressor of RNAi (VSR)-deficient virus in a RHA- and PACT-dependent manner. More importantly, the ability of binding to RISC components is conversed among multiple flaviviral 3'SLs. Together, our results identified flavivirus 3'SL as a potent VSR in RNA format, highlighting the complexity in virus-host interaction during flavivirus infection.IMPORTANCEZika virus (ZIKV) infection mainly targets human neural progenitor cells (hNPCs) and induces cell death and dysregulated cell-cycle progression, leading to microcephaly and other central nervous system abnormalities. RNA interference (RNAi) plays critical roles during ZIKV infections in hNPCs, and ZIKV has evolved to encode specific viral proteins to antagonize RNAi. Herein, we first show that abundant sfRNA was produced in ZIKV-infected hNPCs in a similar pattern to that in other cells. Importantly, ZIKV sfRNA acts as a potent viral suppressor of RNAi (VSR) by competing with siRNAs for binding RISC components, RHA and PACT. The 3'SL of sfRNA is responsible for binding RISC components, which is a conserved feature among mosquito-borne flaviviruses. As most known VSRs are viral proteins, our findings highlight the importance of viral non-coding RNAs during the antagonism of host RNAi-based antiviral innate immunity.

Sublethal and transgenerational effects of lufenuron on the biological traits of Panonychus citri (McGregor) (Acari: Tetranychidae).

The citrus red mite, Panonychus citri (McGregor), is a globally important pest that has developed severe resistance to various pesticides. Lufenuron has been widely used in the control of the related pests in citrus orchard ecosystem. In this study, the susceptibilities of egg, larva, deutonymph and female adult of P. citri to lufenuron was determined, and the LC50 values were 161.354 mg/L, 49.595 mg/L, 81.580 mg/L, and 147.006 mg/L, respectively. Life-table analysis indicated that the fecundities were significantly increased by 11.86% and 26.84% after the mites were treated with LC20 concentrations of lufenuron at the egg or deutonymph stages, respectively. After eggs were treated with lufenuron, the immature stage and longevity were also affected, and resulted in a significant increase in r, R0 and λ. After exposure of female adults to LC20 of lufenuron, the fecundity and longevity of F0 generation significantly decreased by 31.99% and 10.94%, respectively. Furthermore, the expression level of EcR and Vg was significantly inhibited upon mites was treated with lufenuron. However, lufenuron exposure has a positive effect on fecundity and R0 in F1 generation, the expression of all reproduction-related genes was significantly up-regulated. In conclusion, there was a stimulating effect on the offspring population. Our results will contribute to the assessment of the resurgence of P. citri in the field after the application of lufenuron and the development of integrated pest control strategies in citrus orchards.