Cell death shapes cancer immunity: spotlighting PANoptosis.

PANoptosis represents a novel type of programmed cell death (PCD) with distinctive features that incorporate elements of pyroptosis, apoptosis, and necroptosis. PANoptosis is governed by a newly discovered cytoplasmic multimeric protein complex known as the PANoptosome. Unlike each of these PCD types individually, PANoptosis is still in the early stages of research and warrants further exploration of its specific regulatory mechanisms and primary targets. In this review, we provide a brief overview of the conceptual framework and molecular components of PANoptosis. In addition, we highlight recent advances in the understanding of the molecular mechanisms and therapeutic applications of PANoptosis. By elucidating the complex crosstalk between pyroptosis, apoptosis and necroptosis and summarizing the functional consequences of PANoptosis with a special focus on the tumor immune microenvironment, this review aims to provide a theoretical basis for the potential application of PANoptosis in cancer therapy.

Progress in the Study of Temporomandibular Joint Lavage in Temporomandibular Joint Disorder.

With the continuous development and progress of medicine, there are many methods for the treatment of temporomandibular disorders, among which temporomandibular joint lavage is also constantly developed. In the past century, through the efforts of some scholars and clinical summary, the understanding of this disease has been deepened and broadened. At present, through continuous exploration of the treatment methods, the lavage is relatively mature, and has achieved good clinical results. In this paper, the application of temporomandibular joint lavage in the treatment of temporomandibular joint disorders, its treatment methods, treatment mechanism, the auxiliary of other drugs, indications, complications and so on were discussed.

The influence of spheroid maturity on fusion dynamics and micro-tissue assembly in 3D tumor models.

Three-dimensional (3D) cell culture has been used in many fields of biology because of its unique advantages. As a representative of the 3D systems, 3D spheroids are used as building blocks for tissue construction. Larger tumor aggregates can be assembled by manipulating or stacking the tumor spheroids. The motivation of this study is to investigate the behavior of the cells distributed at different locations of the spheroids in the fusion process and the mechanism behind it. To this aim, spheroids with varying grades of maturity or age were generated for fusion to assemble micro-tumor tissues. The dynamics of the fusion process, the motility of the cells distributed in different heterogeneous architecture sites, and their reactive oxygen species profiles were studied. We found that the larger the spheroid necrotic core, the slower the fusion rate of the spheroid. The cells that move were mainly distributed on the spheroid's surface during fusion. In addition to dense microfilament distribution and low microtubule content, the reactive oxygen content was high in the fusion site, while the non-fusion site was the opposite. Last, multi-spheroids with different maturities were fused to complex micro-tissues to mimic solid tumors and evaluate Doxorubicin's anti-tumor efficacy.

Transcriptomics of Leaf Development in the Endangered Dioecious Magnolia kwangsiensis: Molecular Basis Underpinning Specialized Metabolism Genes.

Magnolia kwangsiensis, a dioecious tree native to China, is recognized not only for its status as an at-risk species but also for its potential in therapeutic applications courtesy of its bioactive compounds. However, the genetic underpinnings of its leaf development and compound biosynthesis are not well documented. Our study aims to bridge this knowledge gap through comparative transcriptomics, analyzing gene expression through different leaf maturation stages. We studied the transcriptome of M. kwangsiensis leaves by applying RNA sequencing at juvenile, tender, and mature phases. We identified differentially expressed genes (DEGs) to explore transcriptional changes accompanying the developmental trajectory. Our analysis delineates the transcriptional landscape of over 20,000 genes with over 6000 DEGs highlighting significant transcriptional shifts throughout leaf maturation. Mature leaves demonstrated upregulation in pathways related to photosynthesis, cell wall formation, and polysaccharide production, affirming their structural integrity and specialized metabolic functions. Our GO and KEGG enrichment analyses underpin these findings. Furthermore, we unveiled coordinated gene activity correlating development with synthesizing therapeutically relevant polysaccharides. We identified four novel glycosyltransferases potentially pivotal in this synergistic mechanism. Our study uncovers the complementary evolutionary forces that concurrently sculpt structural and chemical defenses. These genetic mechanisms calibrate leaf tissue resilience and biochemical efficacy.

Comparative efficacy of anti-vascular endothelial growth factor on diabetic macular edema diagnosed with different patterns of optical coherence tomography: A network meta-analysis.

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have emerged as the most common therapeutic approach for the management of diabetic macular edema (DME). Despite their proven superiority over other interventions, there is a paucity of data regarding the relative effectiveness of anti-VEGF agents in treating DME diagnosed with different patterns of optical coherence tomography (OCT). In this regard, we conducted a systematic review and comparative analysis of the therapeutic efficacy of intravitreal bevacizumab, ranibizumab, aflibercept, and conbercept in the management of DME with diffuse retinal thickening (DRT), cystoid macular edema (CME), and serous retinal detachment (SRD) patterns identified using OCT. Our study encompassed a comprehensive search of PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang Data from their inception until January 25, 2023. The network meta-analysis involved the inclusion of 1606 patients from 20 retrospective studies with a moderate risk of bias but no evidence of publication bias. The DRT group had the highest increase in best-corrected visual acuity (BCVA) with anti-VEGF, while the SRD group had the greatest reduction in Central Macular Thickness (CMT). Furthermore, conbercept, ranibizumab, and bevacizumab, respectively, showed the best treatment outcomes for patients with DRT, CME, and SRD in terms of improvement in BCVA. And, conbercept exhibited the highest reduction in CMT in the DRT, CME, and SRD groups. In conclusion, our study highlights the efficacy of anti-VEGF agents in the management of DME and provides valuable insights into the selection of anti-VEGF agents tailored to the individual needs of patients.

A high-quality chromosome-level genome assembly of the endangered tree Kmeria septentrionalis.

Kmeria septentrionalis is a critically endangered tree endemic to Guangxi, China, and is listed on the International Union for Conservation of Nature's Red List. The lack of genetic information and high-quality genome data has hindered conservation efforts and studies on this species. In this study, we present a chromosome-level genome assembly of K. septentrionalis. The genome was initially assembled to be 2.57 Gb, with a contig N50 of 11.93 Mb. Hi-C guided genome assembly allowed us to anchor 98.83% of the total length of the initial contigs onto 19 pseudochromosomes, resulting in a scaffold N50 of 135.08 Mb. The final chromosome-level genome, spaning 2.54 Gb, achieved a BUSCO completeness of 98.9% and contained 1.67 Gb repetitive elements and 35,927 coding genes. This high-quality genome assembly provides a valuable resource for understanding the genetic basis of conservation-related traits and biological properties of this endangered tree species. Furthermore, it lays a critical foundation for evolutionary studies within the Magnoliaceae family.

Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN) for cross-modal individual analysis of the whole brain.

Cross-modal analysis of the same whole brain is an ideal strategy to uncover brain function and dysfunction. However, it remains challenging due to the slow speed and destructiveness of traditional whole-brain optical imaging techniques. Here we develop a new platform, termed Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN), for non-destructive, high-speed, 3D imaging of ex vivo rodent, ferret, and non-human primate brains. Using an optimally designed image acquisition scheme and an accompanying machine-learning algorithm, PATTERN extracts signals of genetically-encoded probes from photobleaching-based temporal modulation and enables reliable visualization of neural projection in the whole central nervous system with 3D isotropic resolution. Without structural and biological perturbation to the sample, PATTERN can be combined with other whole-brain imaging modalities to acquire the whole-brain image with both high resolution and morphological fidelity. Furthermore, cross-modal transcriptome analysis of an individual brain is achieved by PATTERN imaging. Together, PATTERN provides a compatible and versatile strategy for brain-wide cross-modal analysis at the individual level.

Peptide S4 is an entry inhibitor of SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant socioeconomic burden, and combating COVID-19 is imperative. Blocking the SARS-CoV-2 RBD-ACE2 interaction is a promising therapeutic approach for viral infections, as SARS-CoV-2 binds to the ACE2 receptors of host cells via the RBD of spike proteins to infiltrate these cells. We used computer-aided drug design technology and cellular experiments to screen for peptide S4 with high affinity and specificity for the human ACE2 receptor through structural analysis of SARS-CoV-2 and ACE2 interactions. Cellular experiments revealed that peptide S4 effectively inhibited SARS-CoV-2 and HCoV-NL63 viruses from infecting host cells and was safe for cells at effective concentrations. Based on these findings, peptide S4 may be a potential pharmaceutical agent for clinical application in the treatment of the ongoing SARS-CoV-2 pandemic.

Demethylzeylasteral (T-96) initiates extrinsic apoptosis against prostate cancer cells by inducing ROS-mediated ER stress and suppressing autophagic flux

BACKGROUND: Demethylzeylasteral (T-96) is a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF) that has been reported to exhibit anti-neoplastic effects against several types of cancer cells. However, the potential anti-tumour effects of T-96 against human Prostate cancer (CaP) cells and the possible underlying mechanisms have not been well studied. RESULTS: In the current study, T-96 exerted significant cytotoxicity to CaP cells in vitro and induced cell cycle arrest at S-phase in a dose-dependent manner. Mechanistically, T-96 promoted the initiation of autophagy but inhibited autophagic flux by inducing ROS-mediated endoplasmic reticulum (ER) stress which subsequently activated the extrinsic apoptosis pathway in CaP cells. These findings implied that T-96-induced ER stress activated the caspase-dependent apoptosis pathway to inhibit proliferation of CaP cells. Moreover, we observed that T-96 enhances the sensitivity of CaP cells to the chemotherapeutic drug, cisplatin. CONCLUSIONS: Taken together, our data demonstrated that T-96 is a novel modulator of ER stress and autophagy, and has potential therapeutic applications against CaP in the clinic.