Association of CirAEs and Efficacy in NSCLC Patients Treated with PD-1/PD-L1: A Meta-analysis of Cohort Studies.

PURPOSE: To systematically evaluate the relationship between cutaneous immunerelated adverse events (cirAEs) and the efficacy of PD-1/PD-L1 in the treatment of non-small cell lung cancer (NSCLC) and to provide an evidence-based reference for the clinical application of PD-1/PD-L1 and safety evaluation. METHODS: Electronic databases (PubMed, Embase, Medline, Web of Science, and the Cochrane Library) were screened systematically to collect prospective or retrospective cohort studies on the correlation between cirAEs and efficacy of PD-1/PD-L1 in the treatment of NSCLC. RESULTS: A total of 3514 participants were included in 13 cohort studies (enclosing an ambidirectional cohort study). Outcomes revealed that compared with those patients with non cirAEs, patients suffering cirAEs were associated with significantly higher objective response rate (ORR) [risk ratio (RR): 1.74, 95% confidence interval (CI): 1.42-2.14, P<0.00001], longer progressionfree survival (PFS) [RR: 0.52, 95% CI: 0.45-0.60, P<0.00001], and longer overall survival (OS) [RR:0.46, 95% CI: 0.38-0.56]. Sensitivity analyses through the exclusion of one study at a time did not significantly influence the outcomes, indicating that the meta-analysis results were relatively robust. Furthermore, subgroup analyses revealed consistent results in the study design (prospective or retrospective cohort studies), as well as in the endpoint results (PFS and OS) of Kaplan-Meier curves or Cox proportional hazards regression for evaluable patients. CONCLUSION: Currently, evidence reveals that cirAEs development may be associated with a good prognosis and can be an early predictor of the efficacy of PD-1/PD-L1 in the treatment of NSCLC patients.

Parasitism of Hirsutella rhossiliensis on Different Nematodes and Its Endophytism Promoting Plant Growth and Resistance against Root-Knot Nematodes.

The endoparasitic fungus Hirsutella rhossiliensis is an important biocontrol agent of cyst nematodes in nature. To determine the potential parasitism of the fungus on a non-natural host, the pinewood nematode (Bursaphelenchus xylophilus) living in pine trees and the endophytic ability of the fungus on plants, in this paper, we first constructed and utilized a green fluorescent protein (GFP)-tagged H. rhossiliensis HR02 transformant to observe the fungal infection process on B. xylophilus and its colonization on Arabidopsis roots. Then, we compared the fungal parasitism on three species of nematodes with different lifestyles, and we found that the fungal parasitism is correlated with nematode species and stages. The parasitic effect of H. rhossiliensis on adults of B. xylophilus is similar to that on second-stage juveniles (J2) of the root-knot nematode Meloidogyne incognita after 24 h of inoculation, although the virulence of the fungus to second-stage juveniles of M. incognita is stronger than that to those of B. xylophilus and Caenorhabditis elegans. Moreover, the endophytism of H. rhossiliensis was confirmed. By applying an appropriate concentration of H. rhossiliensis conidial suspension (5 × 106 spores/mL) in rhizosphere soil, it was found that the endophytic fungus can promote A. thaliana growth and reproduction, as well as improve host resistance against M. incognita. Our results provide a deeper understanding of the fungus H. rhossiliensis as a promising biocontrol agent against plant-parasitic nematodes.

Guarding skin under PPE: Mechanistic insights and technological innovations.

In the presence of diseases transmitted through respiratory droplets and direct contact, healthcare workers (HCWs) necessitate the use of personal protective equipment (PPE). For optimal safety, PPE should securely conform to the skin during extended wear. However, conventional PPE often lacks adequate air permeability and hygroscopicity, trapping heat and moisture emitted by the body within the enclosure. Such a hot and humid internal environment can induce skin damage, such as erythema, rash, pruritus, and itching among others, leading to microbial growth on the skin surface, the production of inflammatory mediators at the wound site and an increased risk of infection. This review strives to comprehensively elucidate the fundamental mechanisms triggering adverse skin reactions and their resultant manifestations. Furthermore, we explore recent advancements aimed at inhibiting these mechanisms to effectively mitigate the occurrence of skin lesions.

Single-cell multi-omics sequencing and its application in tumor heterogeneity.

In recent years, the emergence and development of single-cell sequencing technologies have provided unprecedented opportunities to analyze deoxyribonucleic acid, ribonucleic acid and proteins at single-cell resolution. The advancements and reduced costs of high-throughput technologies allow for parallel sequencing of multiple molecular layers from a single cell, providing a comprehensive insight into the biological state and behavioral mechanisms of cells through the integration of genomics, transcriptomics, epigenomics and proteomics information. Researchers are actively working to further improve the cost-effectiveness, stability and high-throughput capabilities of single-cell multi-omics sequencing technologies and exploring their potential in precision medicine through clinical diagnostics. This review aims to survey the cutting-edge advancements in single-cell multi-omics sequencing, summarizing the representative technologies and their applications in profiling complex diseases, with a particular focus on tumors.

scRNA-seq data analysis method to improve analysis performance.

With the development of single-cell RNA sequencing technology (scRNA-seq), we have the ability to study biological questions at the level of the individual cell transcriptome. Nowadays, many analysis tools, specifically suitable for single-cell RNA sequencing data, have been developed. In this review, the currently commonly used scRNA-seq protocols are discussed. The upstream processing flow pipeline of scRNA-seq data, including goals and popular tools for reads mapping and expression quantification, quality control, normalization, imputation, and batch effect removal is also introduced. Finally, methods to evaluate these tools in both cellular and genetic dimensions, clustering and differential expression analysis are presented.

URA3 as a Selectable Marker for Disruption and Functional Assessment of PacC Gene in the Entomopathogenic Fungus Isaria javanica.

An effective selection marker is necessary for genetic engineering and functional genomics research in the post-genomic era. Isaria javanica is an important entomopathogenic fungus with a broad host range and prospective biocontrol potentials. Given that no antibiotic marker is available currently in this fungus, developing an effective selection marker is necessary. In this study, by applying overlap PCR and split-marker deletion strategy, combining PEG-mediated protoplasm transformation method, the uridine auxotrophy gene (ura3) in the I. javanica genome was knocked out. Then, using this transformation system, the pH response transcription factor gene (IjpacC) was disrupted successfully. Loss of IjpacC gene results in an obvious decrease in conidial production, but little impact on mycelial growth. The virulence of the ΔIjpacC mutant on caterpillars is similar to that of the wild-type strain. RT-qPCR detection shows that expression level of an acidic-expressed S53 gene (IF1G_06234) in ΔIjpacC mutant is more significantly upregulated than in the wild-type strain during the fungal infection on caterpillars. Our results indicate that a markerless transformation system based upon complementation of uridine auxotrophy is successfully developed in I. javanica, which is useful for exploring gene function and for genetic engineering to enhance biological control potential of the fungus.

Analysis approaches for the identification and prediction of N6-methyladenosine sites.

The global dynamics in a variety of biological processes can be revealed by mapping transcriptional m6A sites, in particular full-transcriptome m6A. And individual m6A sites have contributed to biological function, which can be evaluated by stoichiometric information obtained from the single nucleotide resolution. Currently, the identification of m6A sites is mainly carried out by experiment and prediction methods, based on high-throughput sequencing and machine learning model respectively. This review summarizes the recent topics and progress made in bioinformatics methods of deciphering the m6A methylation, including the experimental detection of m6A methylation sites, techniques of data analysis, the way of predicting m6A methylation sites, m6A methylation databases, and detection of m6A modification in circRNA. At the end, the essay makes a brief discussion for the development perspective in this area.

The journey of CAR-T therapy in hematological malignancies.

Chimeric antigen receptor T (CAR-T) cells therapy has revolutionized the treatment paradigms for hematological malignancies, with multi-line therapy-refractory patients achieving durable complete remissions (CR) and relatively high objective response rate (ORR). So far, many CAR-T products, such as Kymriah, Yescarta and Tecartus, have been developed and got the unprecedented results. However, some patients may relapse afterwards, driving intense investigations into promoting the development of novel strategies to overcome resistance and mechanisms of relapse. Notable technical progress, such as nanobodies and CRISPR-Case9, has also taken place to ensure CAR-T cell therapy fully satisfies its medical potential. In this review, we outline the basic principles for the development and manufacturing processes of CAR-T cell therapy, summarize the similarities and differences in efficacy of different products as well as their corresponding clinical results, and discuss CAR-T immunotherapy combined with other clinical effects of drug therapy.

Roles of Species-Specific Legumains in Pathogenicity of the Pinewood Nematode Bursaphelenchus xylophilus.

Peptidases are very important to parasites, which have central roles in parasite biology and pathogenesis. In this study, by comparative genome analysis, genome-wide peptidase diversities among plant-parasitic nematodes are estimated. We find that genes encoding cysteine peptidases in family C13 (legumain) are significantly abundant in pine wood nematodes Bursaphelenchus genomes, compared to those in other plant-parasitic nematodes. By phylogenetic analysis, a clade of B. xylophilus-specific legumain is identified. RT-qPCR detection shows that these genes are highly expressed at early stage during the nematode infection process. Utilizing transgene technology, cDNAs of three species-specific legumain were introduced into the Arabidopsis γvpe mutant. Functional complementation assay shows that these B. xylophilus legumains can fully complement the activity of Arabidopsis γVPE to mediate plant cell death triggered by the fungal toxin FB1. Secretory activities of these legumains are experimentally validated. By comparative transcriptome analysis, genes involved in plant cell death mediated by legumains are identified, which enrich in GO terms related to ubiquitin protein transferase activity in category molecular function, and response to stimuli in category biological process. Our results suggest that B. xylophilu-specific legumains have potential as effectors to be involved in nematode-plant interaction and can be related to host cell death.