Explore the vast range of titles available.

The advent of 5’ single-cell RNA sequencing (scRNA-seq) technologies offers unique opportunities to identify and analyze transcription start sites (TSSs) at a single-cell resolution. These technologies have the potential to uncover the complexities of transcription initiation and alternative TSS usage across different cell types and conditions. Despite the emergence of computational methods designed to analyze 5’ RNA sequencing data, current methods often lack comparative evaluations in single-cell contexts and are predominantly tailored for paired-end data, neglecting the potential of single-end data. This study introduces scTSS, a computational pipeline developed to bridge this gap by accommodating both paired-end and single-end 5’ scRNA-seq data. scTSS enables joint analysis of multiple single-cell samples, starting with TSS cluster prediction and quantification, followed by differential TSS usage analysis. It employs a Binomial generalized linear mixed model to accurately and efficiently detect differential TSS usage. We demonstrate the utility of scTSS through its application in analyzing transcriptional initiation from single-cell data of two distinct diseases. The results illustrate scTSS’s ability to discern alternative TSS usage between different cell types or biological conditions and to identify cell subpopulations characterized by unique TSS-level expression profiles.

The increasing number of scRNA-seq data emphasizes the need for integrative analysis to interpret similarities and differences between single-cell samples. Although different batch effect removal methods have been developed, none are suitable for heterogeneous single-cell samples coming from multiple biological conditions. We propose a method, scINSIGHT, to learn coordinated gene expression patterns that are common among, or specific to, different biological conditions, and identify cellular identities and processes across single-cell samples. We compare scINSIGHT with state-of-the-art methods using simulated and real data, which demonstrate its improved performance. Our results show the applicability of scINSIGHT in diverse biomedical and clinical problems.

Immune checkpoint blockade (ICB) has significantly advanced cancer immunotherapy, yet its patient response rates are generally low. Vaccines, including immunostimulant‐adjuvanted peptide antigens, can improve ICB. The emerging neoantigens generated by cancer somatic mutations elicit cancer‐specific immunity for personalized immunotherapy; the novel cyclic dinucleotide (CDN) adjuvants activate stimulator of interferon genes (STING) for antitumor type I interferon (IFN‐I) responses. However, CDN/neoantigen vaccine development has been limited by the poor antigen/adjuvant codelivery. Here, pH‐responsive CDN/neoantigen codelivering nanovaccines (NVs) for ICB combination tumor immunotherapy are reported. pH‐responsive polymers are synthesized to be self‐assembled into multivesicular nanoparticles (NPs) at physiological pH and disassembled at acidic conditions. NPs with high CDN/antigen coloading are selected as NVs for CDN/antigen codelivery to antigen presenting cells (APCs) in immunomodulatory lymph nodes (LNs). In the acidic endosome of APCs, pH‐responsive NVs facilitate the vaccine release and escape into cytosol, where CDNs activate STING for IFN‐I responses and antigens are presented by major histocompatibility complex (MHC) for T‐cell priming. In mice, NVs elicit potent antigen‐specific CD8+ T‐cell responses with immune memory, and reduce multifaceted tumor immunosuppression. In syngeneic murine tumors, NVs show robust ICB combination therapeutic efficacy. Overall, these CDN/neoantigen‐codelivering NVs hold the potential for ICB combination tumor immunotherapy. Cancer neoantigens and cyclic dinucleotide (CDN) vaccines can improve immune checkpoint blockade (ICB) immunotherapy, but have poor codelivery. Here, pH‐responsive nanovaccines are reported that efficiently codeliver CDNs/antigens to the cytosol of lymph nodal antigen presenting cells, resulting in efficient STING activation, durable antigen presentation, potent CD8+ T‐cell responses with memory, reduced tumor immunosuppression, and robust ICB combination tumor therapy.

The regulation of emission color, emission efficiency, and asymmetry factor is of great significance for the real applications of circularly polarized luminescent (CPL) materials. Herein, we develop a modular synthetic strategy toward full‐color‐tunable CPL materials based on chiral macrocyclic aggregation‐induced emission (AIE) luminogens via delicate molecular engineering. Modular synthesis of chiral AIEgens with different acceptor moieties has afforded a series of bright solid emitters with tunable emission colors. These chiral cyclic AIEgens have retained high solid‐state emission quantum yield and displayed CPL emission from blue to red as nano‐aggregates, in liquid crystal matrix and polymer film. The strong acceptor units in the red‐emitting chiral AIEgens RBTPE‐2CN and SBTPE‐2CN have rendered them twisted intramolecular charge transfer properties and solvatochromic luminescence. And polymer matrix with different polarity further facilitates the tuning of CPL emission color from green to red emission. These results have paved a reliable approach toward constructing full‐spectra solid‐state CPL material. Modular synthesis toward chiral macrocyclic AIEgens with tailored propeller chirality and customized emission color was well established, whereas full‐spectra‐tunable circularly polarized luminescent emission could be realized via donor‐acceptor engineering on AIEgens or matrix engineering with a diverse polymer film.

Marine antimicrobial peptides (AMPs) represent a promising source for combating infections, especially against antibiotic-resistant pathogens and traditionally challenging infections. However, traditional drug discovery methods face challenges such as time-consuming processes and high costs. Therefore, leveraging machine learning techniques to expedite the discovery of marine AMPs holds significant promise. Our study applies machine learning to develop marine AMPs, focusing on Crassostrea gigas mucus rich in antimicrobial components. We conducted proteome sequencing of C. gigas mucous proteins, used the iAMPCN model for peptide activity prediction, and evaluated the antimicrobial, hemolytic, and cytotoxic capabilities of six peptides. Proteomic analysis identified 4490 proteins, yielding about 43,000 peptides (8–50 amino acids). Peptide ranking based on length, hydrophobicity, and charge assessed antimicrobial potential, predicting 23 biological activities. Six peptides, distinguished by their high relative scores and promising biological activities, were chosen for bactericidal assay. Peptides P1 to P4 showed antimicrobial activity against E. coli, with P2 and P4 being particularly effective. All peptides inhibited S. aureus growth. P2 and P4 also exhibited significant anti-V. parahaemolyticus effects, while P1 and P3 were non-cytotoxic to HEK293T cells at detectable concentrations. Minimal hemolytic activity was observed for all peptides even at high concentrations. This study highlights the potent antimicrobial properties of naturally occurring oyster mucus peptides, emphasizing their low cytotoxicity and lack of hemolytic effects. Machine learning accurately predicted biological activity, showcasing its potential in peptide drug discovery.

Whole-brain radiotherapy (WBRT) is the mainstay of therapy in treating cancer patients with brain metastases, but unfortunately, it might also lead to decline in neurocognitive function. This study aims to investigate the preservation of long-term neurocognitive function in patients after hippocampal avoidance whole-brain radiotherapy (HA-WBRT). Retrospectively, 47 patients diagnosed with brain metastases of non-small cell lung cancer (NSCLC) between 2015-01-01 and 2017-12-31 at the Department of Oncology, XXX Hospital were selected and divided into 2 groups. Group A (n = 27) received HA-WBRT, whereas group B (n = 20) received WBRT. Neurocognitive function was analyzed at baseline and at 3, 6, 9, 12 and 24 months after radiotherapy, using Mine-Mental State Examination (MMSE) scales and Montreal Cognitive Assessment (MoCA) scales. The OS, PFS and tumor recurrence sites were also analyzed. When evaluated at 12 and 24 months after radiotherapy, the cognitive function scores of the hippocampal avoidance group were significantly higher than those of the non-hippocampal avoidance group (P < 0.001). In terms of patient survival, there was no significant difference in OS (P = 0.2) and PFS (P = 0.18) between these 2 groups. Fourteen patients in group A and 12 patients in group B had brain tumor recurrence after radiation, only one patient in group A occurred within 5 mm from the edge of the hippocampus (P > 0.05). In conclusion, HA-WBRT might have a protective effect on long-term neurocognitive function and did not affect patient survival.

The Hippo signaling pathway is an evolutionarily conserved signaling cascade that plays a crucial role in regulating cell proliferation, differentiation, and apoptosis. It has been shown to be a key regulator of cell fate and cellular homeostasis in various immune processes. Despite its well-established functions in vertebrate immunity, its roles in marine invertebrate immunity remain poorly understood. Therefore, our present work provides fresh mechanistic insights into how the Hippo pathway orchestrates hemocytic functions in Crassostrea hongkongensis, with implications for studies on its major forms and modifications in animal evolution. The complete set of Hippo pathway genes, including SAV1, MOB1, LATS, YAP/TAZ, TEAD, and MST, were identified from the C. hongkongensis genome. Quantitative PCR assays were conducted to examine the mRNA expression levels of these genes in different tissues and the levels of these genes in hemocytes before and after bacterial challenges. The study also examined the crosstalk between the Hippo pathway and other immune pathways, such as the AP-1 and p53-dependent p21 signaling cascades. RNA interference was used to knock down MST and TEAD, and MST is a core orchestrator of non-canonical Hippo signaling, to investigate its impact on phagocytosis and bacterial clearance in hemocytes. The results demonstrated that members of the Hippo pathway were highly expressed in hemocytes, with their expression levels significantly increasing following bacterial challenges. Crosstalk between the Hippo pathway and other immune pathways triggered hemocytic apoptosis, which functioned similarly to the canonical Mst-Lats-Yap signaling pathway in Drosophila and mammals. Knocking down MST resulted in increased phagocytosis and boosted the efficiency of bacterial clearance in hemocytes, presumably due to mobilized antioxidant transcription by Nrf for maintaining immune homeostasis. This study provides novel insights into the regulatory mechanisms underlying the Hippo pathway in immune responses of C. hongkongensis hemocytes. The study highlights the importance of the Hippo pathway in maintaining immune homeostasis and orchestrating hemocytic functions in oysters. Moreover, this study demonstrates the divergence of the Hippo pathway's roles in marine invertebrate immunity from mammalian observations, indicating the need for further comparative studies across species. These findings have significant implications for future research aimed at elucidating the evolutionary trajectory and functional diversity of the Hippo signaling pathway in animal evolution.

Chronic postsurgical pain is a challenging problem after breast cancer surgery. This prospective, randomized, double-blinded, parallel-group, placebo-controlled trial was conducted to evaluate the influence of preoperative ultrasound-guided multilevel paravertebral blocks (PVBs) on chronic pain following mastectomy. One hundred eighty-four women were randomized to receive ultrasound-guided multilevel (T1-T5) PVBs with 5 mL of ropivacaine 0.5% or normal saline per level. The primary end point was the incidence of chronic pain at 3 months following mastectomy assessed by the brief pain inventory (BPI), while the secondary end points were the acute postoperative pain, the number of patients requiring rescue analgesia, postoperative nausea and vomiting (PONV), side effects, and chronic pain at 6 months after surgery assessed by the BPI. A total of 172 patients completed the study. Ultrasound-guided multilevel PVBs significantly decreased immediate postoperative pain for the first 12 hours ( <0.001). Additionally, fewer patients in the PVB group required rescue analgesia in the first 48 hours post-operatively compared to the control group (5/86 vs 28/86, OR =0.128, 95% CI: 0.047-0.351, <0.001). No statistically significant difference was tested between the two groups (9.3% vs 17.4%, OR =0.419, 95% CI: 0.162-1.087, =0.068) in the incidence of PONV. At 3 months, the incidence of chronic pain (BPI average pain score ≥3) was 34.5% and 51.2% (OR =0.511, 95% CI: 0.277-0.944, =0.031) in the PVB and control groups, respectively, and at 6 months, the incidence was 22.1% and 37.2% (OR =0.479, 95% CI: 0.245-0.936, =0.03), respectively. No complications occurred during the study. This study indicated that perioperative ultrasound-guided multilevel PVBs with ropivacaine improved acute postoperative pain and decreased postmastectomy chronic pain at 3 and 6 months postoperatively.

In this study, the whole mitochondrial genome of Silurus grahami was reported to be 16,518 bp in length, including 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs, and one control region. The phylogenetic analysis based on 13 protein-coding genes showed that S. grahami was sister to clade of S. meridionalis and S. lanzhouensis. A total of 81 bases differences were identified in COI barcoding region, which could be used for species identification in catfish.