Targeted desialylation and cytolysis of tumour cells by fusing a sialidase to a bispecific T-cell engager.

Bispecific T-cell engagers (BiTEs) bring together tumour cells and cytotoxic T cells by binding to specific cell-surface tumour antigens and T-cell receptors, and have been clinically successful for the treatment of B-cell malignancies. Here we show that a BiTE-sialidase fusion protein enhances the susceptibility of solid tumours to BiTE-mediated cytolysis of tumour cells via targeted desialylation-that is, the removal of terminal sialic acid residues on glycans-at the BiTE-induced T-cell-tumour-cell interface. In xenograft and syngeneic mouse models of leukaemia and of melanoma and breast cancer, and compared with the parental BiTE molecules, targeted desialylation via the BiTE-sialidase fusion proteins enhanced the formation of immunological synapses, T-cell activation and T-cell-mediated tumour-cell cytolysis in the presence of the target antigen. The targeted desialylation of tumour cells may enhance the potency of therapies relying on T-cell engagers.

Effects of Tirofiban on Neurological Deterioration in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial.

Importance: Evidence supports using antiplatelet therapy in patients with acute ischemic stroke. However, neurological deterioration remains common under the currently recommended antiplatelet regimen, leading to poor clinical outcomes. Objective: To determine whether intravenous tirofiban administered within 24 hours of stroke onset prevents early neurological deterioration in patients with acute noncardioembolic stroke compared with oral aspirin. Design, Setting, and Participants: This investigator-initiated, multicenter, open-label, randomized clinical trial with blinded end-point assessment was conducted at 10 comprehensive stroke centers in China between September 2020 and March 2023. Eligible patients were aged 18 to 80 years with acute noncardioembolic stroke within 24 hours of onset and had a National Institutes of Health Stroke Scale (NIHSS) score of 4 to 20. Intervention: Patients were assigned randomly (1:1) to receive intravenous tirofiban or oral aspirin for 72 hours using a central, web-based, computer-generated randomization schedule; all patients then received oral aspirin. Main Outcome: The primary efficacy outcome was early neurological deterioration (increase in NIHSS score ≥4 points) within 72 hours after randomization. The primary safety outcome was symptomatic intracerebral hemorrhage within 72 hours after randomization. Results: A total of 425 patients were included in the intravenous tirofiban (n = 213) or oral aspirin (n = 212) groups. Median (IQR) age was 64.0 years (56.0-71.0); 124 patients (29.2%) were female, and 301 (70.8%) were male. Early neurological deterioration occurred in 9 patients (4.2%) in the tirofiban group and 28 patients (13.2%) in the aspirin group (adjusted relative risk, 0.32; 95% CI, 0.16-0.65; P = .002). No patients in the tirofiban group experienced intracerebral hemorrhage. At 90-day follow-up, 3 patients (1.3%) in the tirofiban group and 3 (1.5%) in the aspirin group died (adjusted RR, 1.15; 95% CI, 0.27-8.54; P = .63), and the median (IQR) modified Rankin scale scores were 1.0 (0-1.25) and 1.0 (0-2), respectively (adjusted odds ratio, 1.28; 95% CI, 0.90-1.83; P = .17). Conclusions and Relevance: In patients with noncardioembolic stroke who were seen within 24 hours of symptom onset, tirofiban decreased the risk of early neurological deterioration but did not increase the risk of symptomatic intracerebral hemorrhage or systematic bleeding. Trial Registration: ClinicalTrials.gov Identifier: NCT04491695.

Design and Characterization of a New Formulation for the Delivery of COVID-19-mRNA Vaccine to the Nasal Mucosa.

Chitosan, a natural polysaccharide derived from chitin, possesses biocompatibility, biodegradability, and mucoadhesive characteristics, making it an attractive material for the delivery of mRNA payloads to the nasal mucosa and promoting their uptake by target cells such as epithelial and immune cells (e.g., dendritic cells and macrophages). In this project, we aimed at developing novel lipid-based nanoformulations for mRNA delivery to counteract the pandemic caused by SARS-CoV-2 virus. The formulations achieved a mRNA encapsulation efficiency of ~80.2% with chitosan-lipid nanoparticles, as measured by the RiboGreen assay. Furthermore, the evaluation of SARS-CoV-2 Spike (S) receptor-binding domain (RBD) expression via ELISA for our vaccine formulations showed transfection levels in human embryonic kidney cells (HEK 293), lung carcinoma cells (A549), and dendritic cells (DC 2.4) equal to 9.9 ± 0.1 ng/mL (174.7 ± 1.1 fold change from untreated cells (UT)), 7.0 ± 0.2 ng/mL (128.1 ± 4.9 fold change from UT), and 0.9 ± 0.0 ng/mL (18.0 ± 0.1 fold change from UT), respectively. Our most promising vaccine formulation was also demonstrated to be amenable to lyophilization with minimal degradation of loaded mRNA, paving the way towards a more accessible and stable vaccine. Preliminary in vivo studies in mice were performed to assess the systemic and local immune responses. Nasal bronchoalveolar lavage fluid (BALF) wash showed that utilizing the optimized formulation resulted in local antibody concentrations and did not trigger any systemic antibody response. However, if further improved and developed, it could potentially contribute to the management of COVID-19 through nasopharyngeal immunization strategies.

RNA structure profiling at single-cell resolution reveals new determinants of cell identity.

RNA structure is critical for multiple steps in gene regulation. However, how the structures of transcripts differ both within and between individual cells is unknown. Here we develop a SHAPE-inspired method called single-cell structure probing of RNA transcripts that enables simultaneous determination of transcript secondary structure and abundance at single-cell resolution. We apply single-cell structure probing of RNA transcripts to human embryonic stem cells and differentiating neurons. Remarkably, RNA structure is more homogeneous in human embryonic stem cells compared with neurons, with the greatest homogeneity found in coding regions. More extensive heterogeneity is found within 3' untranslated regions and is determined by specific RNA-binding proteins. Overall RNA structure profiles better discriminate cell type identity and differentiation stage than gene expression profiles alone. We further discover a cell-type variable region of 18S ribosomal RNA that is associated with cell cycle and translation control. Our method opens the door to the systematic characterization of RNA structure-function relationships at single-cell resolution.

Endovascular Therapy for Basilar Artery Occlusion in Sudden Onset to Maximal Deficit Ischemic Events.

BACKGROUND: The presence of sudden onset to maximal deficit (SOTMD) in patients with acute basilar artery occlusion often results in more severe outcomes. However, the effect of endovascular therapy on SOTMD and whether the outcome is affected by onset-to-puncture time remain unclear. METHODS AND RESULTS: This retrospective analysis was conducted using data from the prospective BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry). Consecutive patients with basilar artery occlusion receiving endovascular therapy were dichotomized into SOTMD and non-SOTMD cohorts. The primary outcomes included a favorable outcome (modified Rankin scale 0-3), recanalization, and mortality at 90 days. The outcomes of patients with SOTMD were analyzed using multivariable logistic regression. In the multivariate analysis, a favorable outcome was similar between the two cohorts (odds ratio [OR], 0.88 [95% CI, 0.58-1.34]; P=0.5), although the mortality of patients with SOTMD was higher than that of patients with non-SOTMD (OR, 1.67 [95% CI, 1.14-2.44]; P=0.008). The probability of mortality increased from 40.0% at 1 hour to 70.0% at 6 hours in the SOTMD cohort, and favorable outcomes of patients with non-SOTMD declined from 38.0% at 1 hour to 18.0% at 8 hours. CONCLUSIONS: No significant difference was observed in favorable outcomes between the SOTMD and non-SOTMD groups, although mortality was higher in the SOTMD cohort. The patients with SOTMD had a stronger time dependence for endovascular therapy in terms of mortality, while the time dependency regarding favorable outcome in the NSOTMD group was even higher. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800014759.

Direct RNA sequencing coupled with adaptive sampling enriches RNAs of interest in the transcriptome.

Abundant cellular transcripts occupy most of the sequencing reads in the transcriptome, making it challenging to assay for low-abundant transcripts. Here, we utilize the adaptive sampling function of Oxford Nanopore sequencing to selectively deplete and enrich RNAs of interest without biochemical manipulation before sequencing. Adaptive sampling performed on a pool of in vitro transcribed RNAs resulted in a net increase of 22-30% in the proportion of transcripts of interest in the population. Enriching and depleting different proportions of the Candida albicans transcriptome also resulted in a 11-13.5% increase in the number of reads on target transcripts, with longer and more abundant transcripts being more efficiently depleted. Depleting all currently annotated Candida albicans transcripts did not result in an absolute enrichment of remaining transcripts, although we identified 26 previously unknown transcripts and isoforms, 17 of which are antisense to existing transcripts. Further improvements in the adaptive sampling of RNAs will allow the technology to be widely applied to study RNAs of interest in diverse transcriptomes.

Barriers to uptake of cataract surgery among elderly patients in rural China: a cross-sectional study.

OBJECTIVE: To investigate factors that differentiate elderly adults in rural China who accept free vision screening and cataract surgery from those who could benefit from vision care but refuse it when offered. DESIGN: We conducted a population-based, cross-sectional study between October and December 2016. Logistic regression models were used to examine the predictors of accepting free vision screening and cataract surgery. SETTING: Rural communities in Handan, China. PARTICIPANTS: Adults aged 50 years or older, with presenting visual acuity ≤6/18 in the better seeing eye, suspected by examining ophthalmologist to be due to cataract. RESULTS: Among 613 persons with cataract identified on a population basis, 596 (97.2%) completed the household survey (mean (SD) age, 71.5 (10.0) years; 79.8% female). A total of 214 persons (35.9%) refused participation, while 382 (64.1%) took part in the vision screening. A total of 193 (50.5%) participants were found eligible for surgery, while 189 (49.5%) were not. Among 99 randomly selected participants who were offered immediate free surgery, surgery was accepted by 77 participants (77.8%) and refused by 22 (22.2%). In the multivariate model, being engaged in income-generating activities (p<0.01), self-reported better physical capacity (p<0.001) and having had a recent physical examination (p=0.01) were significantly associated with acceptance of vision screening. The only variable significantly associated with acceptance of surgery was presenting visual acuity, with better vision inversely associated with acceptance of surgery (p<0.05) models. CONCLUSION: Our results suggest that refusal of basic eye examinations may be at least as important a determinant of low surgical rates in rural China as lack of acceptance of surgery itself.

Self-Adaptive Liquid Film: Dynamic Realization of Dendrite-Free Zn Deposition Toward Ultralong-Life Aqueous Zn Battery.

The poor reversibility and stability of Zn metal anode (ZMA) caused by uncontrolled Zn deposition behaviors and serious side reactions severely impeded the practical application of aqueous Zn metal battery. Herein, a liquid-dynamic and self-adaptive protective layer (LSPL) was constructed on the ZMA surface for inhibiting dendrites and by-products formation. Interestingly, the outer LSPL consists of liquid perfluoropolyether (PFPE), which can dynamically adapt volume change during repeat cycling and inhibit side reactions. Moreover, it can also decrease the de-solvation energy barrier of Zn2+ by strong interaction between C-F bond and foreign Zn2+ , improving Zn2+ transport kinetics. For the LSPL inner region, in-situ formed ZnF2 through the spontaneous chemical reaction between metallic Zn and part PFPE can establish an unimpeded Zn2+ migration pathway for accelerating ion transfer, thereby restricting Zn dendrites formation. Consequently, the LSPL-modified ZMA enables reversible Zn deposition/dissolution up to 2000 h at 1 mA cm-2 and high coulombic efficiency of 99.8% at 4 mA cm-2 . Meanwhile, LSPL@Zn||NH4 V4 O10 full cells deliver an ultralong cycling lifespan of 100 00 cycles with 0.0056% per cycle decay rate at 10 A g-1 . This self-adaptive layer provides a new strategy to improve the interface stability for next-generation aqueous Zn battery.

Versatile Structural Engineering of Metal-Organic Frameworks Enabling Switchable Catalytic Selectivity.

The structure engineering of metal-organic frameworks (MOFs) forms the cornerstone of their applications. Nonetheless, realizing the simultaneous versatile structure engineering of MOFs remains a significant challenge. Herein, a dynamically mediated synthesis strategy to simultaneously engineer the crystal structure, defect structure, and nanostructure of MOFs is proposed. These include amorphous Zr-ODB nanoparticles, crystalline Zr-ODB-hz (ODB = 4,4'-oxalyldibenzoate, hz = hydrazine) nanosheets, and defective d-Zr-ODB-hz nanosheets. Aberration-corrected scanning transmission electron microscopy combined with low-dose high-angle annular dark-field imaging technique vividly portrays these engineered structures. Concurrently, the introduced hydrazine moieties confer self-reduction properties to the respective MOF structures, allowing the in situ installation of catalytic Pd nanoparticles. Remarkably, in the hydrogenation of vanillin-like biomass derivatives, Pd/Zr-ODB-hz yields partially hydrogenated alcohols as the primary products, whereas Pd/d-Zr-ODB-hz exclusively produces fully hydrogenated alkanes. Density functional theory calculations, coupled with experimental evidence, uncover the catalytic selectivity switch triggered by the change in structure type. The proposed strategy of versatile structure engineering of MOFs introduces an innovative pathway for the development of high-performance MOF-based catalysts for various reactions.

Spatial-temporal evolution of soil gas Rn before two Ms ≥ 5.0 earthquakes in the mid-eastern of the Qilian fault zone (QLF).

The mid-eastern segment of the Qilianshan fault zone (QLF) on the northeastern margin of the Qinghai-Tibet Plateau is considered one of the key seismic hazard areas. The Zhangye Ms5.0 earthquake and Menyuan Ms6.9 earthquake are the two Ms ≥ 5.0 earthquakes in recent years. The spatio-temporal evolution of Rn across the fault before the two Ms ≥ 5.0 earthquakes were explored by combining a solid seismogenic model and numerical simulation results in this study. The results demonstrates the spatial distribution of Rn concentration intensity varies over time, indicating the evolving characteristics of fracture zone activity. The time-series variation characteristics are closely related the Zhangye Ms5.0 earthquake and Menyuan Ms6.9 earthquake. Overall, in the seismic source area and surrounding medium area of Zhangye Ms5.0 earthquake, the soil gas Rn anomaly across faults characterized by a turning upward trend after continuous decline. The closer to the source area, the more obvious the upward trend. For Menyuan Ms6.9 earthquake, the survey line (HT1) located in the main fracture zone of the earthquake and the survey line (HT7,30km from the epicenter) closer to the epicenter also showed a similar trend, while the other measurement lines in far-field exhibit declining trend before the Menyuan Ms6.9 earthquake. Therefore, the continuous decline trend of soil gas may be crucial information for medium-term earthquake preparation in the seismogenic zone, and the trend of turning upward after continuous decline is a significant signal of short-term seismogenic event in far-field. This research could improve the understanding of the anomalous features of soil gas precursors and tracking the active sections of the fault. According to the model, the earthquake area canseismic source area, the surrounding medium area be divided into three sections: the seismic source area, the surrounding medium area, and the fracture fragmentation area.

Dengue and Zika RNA-RNA interactomes reveal pro- and anti-viral RNA in human cells.

BACKGROUND: Identifying host factors is key to understanding RNA virus pathogenicity. Besides proteins, RNAs can interact with virus genomes to impact replication. RESULTS: Here, we use proximity ligation sequencing to identify virus-host RNA interactions for four strains of Zika virus (ZIKV) and one strain of dengue virus (DENV-1) in human cells. We find hundreds of coding and non-coding RNAs that bind to DENV and ZIKV viruses. Host RNAs tend to bind to single-stranded regions along the virus genomes according to hybridization energetics. Compared to SARS-CoV-2 interactors, ZIKV-interacting host RNAs tend to be downregulated upon virus infection. Knockdown of several short non-coding RNAs, including miR19a-3p, and 7SK RNA results in a decrease in viral replication, suggesting that they act as virus-permissive factors. In addition, the 3'UTR of DYNLT1 mRNA acts as a virus-restrictive factor by binding to the conserved dumbbell region on DENV and ZIKV 3'UTR to decrease virus replication. We also identify a conserved set of host RNAs that interacts with DENV, ZIKV, and SARS-CoV-2, suggesting that these RNAs are broadly important for RNA virus infection. CONCLUSIONS: This study demonstrates that host RNAs can impact virus replication in permissive and restrictive ways, expanding our understanding of host factors and RNA-based gene regulation during viral pathogenesis.

Establishment and validation of nomogram models for overall survival and cancer-specific survival in spindle cell sarcoma patients.

Spindle cell sarcoma (SCS) is rare in clinical practice. The objective of this study was to establish nomograms to predict the OS and CSS prognosis of patients with SCS based on the Surveillance, Epidemiology, and End Results (SEER) database. The data of patients with SCS between 2004 and 2020 were extracted from the SEER database and randomly allocated to a training cohort and a validation cohort. Univariate and multivariate Cox regression analyses were used to screen for independent risk factors for both overall survival (OS) and cancer-specific survival (CSS). Nomograms for OS and CSS were established for patients with SCS based on the results of multivariate Cox analysis. Then, we validated the nomograms by the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Finally, Kaplan‒Meier curves and log-rank tests were applied to compare patients with SCS at three different levels and in different treatment groups. A total of 1369 patients with SCS were included and randomly allocated to a training cohort (n = 1008, 70%) and a validation cohort (n = 430, 30%). Age, stage, grade, tumour location, surgery, radiation and diagnosis year were found to be independent prognostic factors for OS by Cox regression analysis, while age, stage, grade, tumour location and surgery were found to be independent prognostic factors for CSS. The nomogram models were established based on the results of multivariate Cox analysis for both OS and CSS. The C-indices of the OS model were 0.76 and 0.77 in the training and validation groups, respectively, while they were 0.76 and 0.78 for CSS, respectively. For OS, the 3- and 5-year AUCs were 0.801 and 0.798, respectively, in the training cohort and 0.827 and 0.799, respectively, in the validation cohort; for CSS, they were 0.809 and 0.786, respectively, in the training cohort and 0.831 and 0.801, respectively, in the validation cohort. Calibration curves revealed high consistency in both OS and CSS between the observed survival and the predicted survival. In addition, DCA was used to analyse the clinical practicality of the OS and CSS nomogram models and revealed that they had good net benefits. Surgery remains the main treatment method for SCS patients. The two nomograms we established are expected to accurately predict the personalized prognosis of SCS patients and may be useful for clinical decision-making.

SynCluster: Reaction Type Clustering and Recommendation Framework for Synthesis Planning.

AI-assisted synthesis planning has emerged as a valuable tool in accelerating synthetic chemistry for the discovery of new drugs and materials. The template-free approach, which showcases superior generalization capabilities, is seen as the mainstream direction in this field. However, it remains unclear whether such an end-to-end approach can achieve problem-solving performance on par with experienced chemists without fully revealing insights into the chemical mechanisms involved. Moreover, there is a lack of unified and chemically inspired frameworks for improving multitask reaction predictions in this area. In this study, we have addressed these challenges by investigating the impact of fine-grained reaction-type labels on multiple downstream tasks and propose a novel framework named SynCluster. This framework incorporates unsupervised clustering cues into the baseline models and identifies plausible chemical subspaces which is compatible with multitask extensions and can serve as model-independent indicators to effectively enhance the performance of multiple downstream tasks. In retrosynthesis prediction, SynCluster achieves significant improvements of 4.1 and 11.0% in top-1 and top-10 prediction accuracy, respectively, compared to the baseline Molecular Transformer, and achieves a notable enhancement of 13.9% in top-10 accuracy when combined with Retroformer. By incorporating simplified molecular-input line-entry system augmentation, our framework achieves higher top-10 accuracy compared to state-of-the-art sequence-based retrosynthesis models and improves over the baseline on the diversity and validity of reactants. SynCluster also achieves 94.9% top-10 accuracy in forward synthesis prediction and 51.5% top-10 Maxfrag accuracy in reagent prediction. Overall, SynCluster provides a fresh perspective with chemical interpretability and reinforcement of domain knowledge in the synthesis design. It offers a promising solution for improving the accuracy and efficiency of AI-assisted synthesis planning and bridges the gap between template-free approaches and the problem-solving abilities of experienced chemists.

Translational control of furina by an RNA regulon is important for left-right patterning, heart morphogenesis and cardiac valve function.

Heart development is a complex process that requires asymmetric positioning of the heart, cardiac growth and valve morphogenesis. The mechanisms controlling heart morphogenesis and valve formation are not fully understood. The pro-convertase FurinA functions in heart development across vertebrates. How FurinA activity is regulated during heart development is unknown. Through computational analysis of the zebrafish transcriptome, we identified an RNA motif in a variant FurinA transcript harbouring a long 3' untranslated region (3'UTR). The alternative 3'UTR furina isoform is expressed prior to organ positioning. Somatic deletions in the furina 3'UTR lead to embryonic left-right patterning defects. Reporter localisation and RNA-binding assays show that the furina 3'UTR forms complexes with the conserved RNA-binding translational repressor, Ybx1. Conditional ybx1 mutant embryos show premature and increased Furin reporter expression, abnormal cardiac morphogenesis and looping defects. Mutant ybx1 hearts have an expanded atrioventricular canal, abnormal sino-atrial valves and retrograde blood flow from the ventricle to the atrium. This is similar to observations in humans with heart valve regurgitation. Thus, the furina 3'UTR element/Ybx1 regulon is important for translational repression of FurinA and regulation of heart development.

Flavivirus genome recoding by codon optimisation confers genetically stable in vivo attenuation in both mice and mosquitoes.

Virus genome recoding is an attenuation method that confers genetically stable attenuation by rewriting a virus genome with numerous silent mutations. Prior flavivirus genome recoding attempts utilised codon deoptimisation approaches. However, these codon deoptimisation approaches act in a species dependent manner and were unable to confer flavivirus attenuation in mosquito cells or in mosquito animal models. To overcome these limitations, we performed flavivirus genome recoding using the contrary approach of codon optimisation. The genomes of flaviviruses such as dengue virus type 2 (DENV2) and Zika virus (ZIKV) contain functional RNA elements that regulate viral replication. We hypothesised that flavivirus genome recoding by codon optimisation would introduce silent mutations that disrupt these RNA elements, leading to decreased replication efficiency and attenuation. We chose DENV2 and ZIKV as representative flaviviruses and recoded them by codon optimising their genomes for human expression. Our study confirms that this recoding approach of codon optimisation does translate into reduced replication efficiency in mammalian, human, and mosquito cells as well as in vivo attenuation in both mice and mosquitoes. In silico modelling and RNA SHAPE analysis confirmed that DENV2 recoding resulted in the extensive disruption of genomic structural elements. Serial passaging of recoded DENV2 resulted in the emergence of rescue or adaptation mutations, but no reversion mutations. These rescue mutations were unable to rescue the delayed replication kinetics and in vivo attenuation of recoded DENV2, demonstrating that recoding confers genetically stable attenuation. Therefore, our recoding approach is a reliable attenuation method with potential applications for developing flavivirus vaccines.

Update and latest advances in mechanisms and management of colitis-associated colorectal cancer.

Colitis-associated colorectal cancer (CAC) is defined as a specific cluster of colorectal cancers that develop as a result of prolonged colitis in patients with inflammatory bowel disease (IBD). Patients with IBD, including ulcerative colitis and Crohn's disease, are known to have an increased risk of developing CAC. Although the incidence of CAC has significantly decreased over the past few decades, individuals with CAC have increased mortality compared to individuals with sporadic colorectal cancer, and the incidence of CAC increases with duration. Chronic inflammation is generally recognized as a major contributor to the pathogenesis of CAC. CAC has been shown to progress from colitis to dysplasia and finally to carcinoma. Accumulating evidence suggests that multiple immune-mediated pathways, DNA damage pathways, and pathogens are involved in the pathogenesis of CAC. Over the past decade, there has been an increasing effort to develop clinical approaches that could help improve outcomes for CAC patients. Colonoscopic surveillance plays an important role in reducing the risk of advanced and interval cancers. It is generally recommended that CAC patients undergo endoscopic removal or colectomy. This review summarizes the current understanding of CAC, particularly its epidemiology, mechanisms, and management. It focuses on the mechanisms that contribute to the development of CAC, covering advances in genomics, immunology, and the microbiome; presents evidence for management strategies, including endoscopy and colectomy; and discusses new strategies to interfere with the process and development of CAC. These scientific findings will pave the way for the management of CAC in the near future.

Dysregulated microRNAs as a biomarker for diagnosis and prognosis of hepatitis B virus-associated hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignancy with a high incidence and fatality rate worldwide. Hepatitis B virus (HBV) infection is one of the most important risk factors for its occurrence and development. Early detection of HBV-associated HCC (HBV-HCC) can improve clinical decision-making and patient outcomes. Biomarkers are extremely helpful, not only for early diagnosis, but also for the development of therapeutics. MicroRNAs (miRNAs), a subset of non-coding RNAs approximately 22 nucleotides in length, have increasingly attracted scientists' attention due to their potential utility as biomarkers for cancer detection and therapy. HBV profoundly impacts the expression of miRNAs potentially involved in the development of hepatocarcinogenesis. In this review, we summarize the current progress on the role of miRNAs in the diagnosis and treatment of HBV-HCC. From a molecular standpoint, we discuss the mechanism by which HBV regulates miRNAs and investigate the exact effect of miRNAs on the promotion of HCC. In the near future, miRNA-based diagnostic, prognostic, and therapeutic applications will make their way into the clinical routine.

Noncovalent composites of meso-substituted A2B2-porphyrins and carbon nanotubes for enhanced electrocatalytic oxygen reduction.

Exploring highly active oxygen reduction electrocatalysts with low precious metals content is imperative but remains a considerable challenge. Herein, a series of heterobimetallic multi-walled carbon nanotubes (MWCNTs) electrocatalysts based on metal complexes are presented. These electrocatalysts feature diverse transition metals (M=Mn, Fe, Co, Ni) 5,15-bromophenyl-10, 20-methoxyphenyl porphyrin (MBMP) and tetrakis(triphenylphosphine)palladium (0) (Pd[P(Ph3)4]) anchored non-covalently on its surface. The resulting NiBMP-based MWCNTs with Pd[P(Ph3)4] (PdNiN4/MWCNTs) display outstanding electrocatalytic oxygen reduction activity (onset potential, 0.941 V; half wave potential, 0.830 V) and robust long-term durability in alkaline electrolyte. While in neutral condition, the MnBMP-based MWCNTs with Pd[P(Ph3)4] (PdMnN4/MWCNTs) are the most active heterobimetallic ORR catalyst and produce ultra-low concentration hydrogen peroxide (H2O2yield, 1.2%-1.3%). Synergistically tuning the ORR electrocatalytic activity and electron transfer pathway is achieved by the formation of NiBMP/MnBMP-Pd[P(Ph3)4] active sites. This work indicates such metalloporphyrin-Pd[P(Ph3)4] active sites on MWCNTs have significantly positive influence on electrocatalytic ORR systems and provides facile and mild strategy for designing highly efficient ORR electrocatalysts with ultra-low loading precious metal.

Unintended consequences: Disrupting microbial communities of Nilaparvata lugens with non-target pesticides.

Insects are frequently exposed to a range of insecticides that can alter the structure of the commensal microbiome. However, the effects of exposure to non-target pesticides (including non-target insecticides and fungicides) on insect pest microbiomes are still unclear. In the present study, we exposed Nilaparvata lugens to three target insecticides (nitenpyram, pymetrozine, and avermectin), a non-target insecticide (chlorantraniliprole), and two fungicides (propiconazole and tebuconazole), and observed changes in the microbiome's structure and function. Our results showed that both non-target insecticide and fungicides can disrupt the microbiome's structure. Specifically, symbiotic bacteria of N. lugens were more sensitive to non-target insecticide compared to target insecticide, while the symbiotic fungi were more sensitive to fungicides. We also found that the microbiome in the field strain was more stable under pesticides exposure than the laboratory strain (a susceptible strain), and core microbial species g_Pseudomonas, s_Acinetobacter soli, g_Lactobacillus, s_Metarhizium minus, and s_Penicillium citrinum were significantly affected by specifically pesticides. Furthermore, the functions of symbiotic bacteria in nutrient synthesis were predicted to be significantly reduced by non-target insecticide. Our findings contribute to a better understanding of the impact of non-target pesticides on insect microbial communities and highlight the need for scientific and rational use of pesticides.