Dysfunctional natural killer cells can be reprogrammed to regain anti-tumor activity.

Natural killer (NK) cells are critical to the innate immune system, as they recognize antigens without prior sensitization, and contribute to the control and clearance of viral infections and cancer. However, a significant proportion of NK cells in mice and humans do not express classical inhibitory receptors during their education process and are rendered naturally "anergic", i.e., exhibiting reduced effector functions. The molecular events leading to NK cell anergy as well as their relation to those underlying NK cell exhaustion that arises from overstimulation in chronic conditions, remain unknown. Here, we characterize the "anergic" phenotype and demonstrate functional, transcriptional, and phenotypic similarities to the "exhausted" state in tumor-infiltrating NK cells. Furthermore, we identify zinc finger transcription factor Egr2 and diacylglycerol kinase DGKα as common negative regulators controlling NK cell dysfunction. Finally, experiments in a 3D organotypic spheroid culture model and an in vivo tumor model suggest that a nanoparticle-based delivery platform can reprogram these dysfunctional natural killer cell populations in their native microenvironment. This approach may become clinically relevant for the development of novel anti-tumor immunotherapeutic strategies.

The elementary reactions for incorporation into crystals.

The growth rates of crystals are largely dictated by the chemical reaction between solute and kinks, in which a solute molecule severs its bonds with the solvent and establishes new bonds with the kink. Details on this sequence of bond breaking and rebuilding remain poorly understood. To elucidate the reaction at the kinks we employ four solvents with distinct functionalities as reporters on the microscopic structures and their dynamics along the pathway into a kink. We combine time-resolved in situ atomic force microscopy and x-ray and optical methods with molecular dynamics simulations. We demonstrate that in all four solvents the solute, etioporphyrin I, molecules reach the steps directly from the solution; this finding identifies the measured rate constant for step growth as the rate constant of the reaction between a solute molecule and a kink. We show that the binding of a solute molecule to a kink divides into two elementary reactions. First, the incoming solute molecule sheds a fraction of its solvent shell and attaches to molecules from the kink by bonds distinct from those in its fully incorporated state. In the second step, the solute breaks these initial bonds and relocates to the kink. The strength of the preliminary bonds with the kink determines the free energy barrier for incorporation into a kink. The presence of an intermediate state, whose stability is controlled by solvents and additives, may illuminate how minor solution components guide the construction of elaborate crystal architectures in nature and the search for solution compositions that suppress undesirable or accelerate favored crystallization in industry.

Insights into the role of glycerophospholipids on the iron export function of SLC40A1 and the molecular mechanisms of ferroportin disease.

SLC40A1 is the sole iron export protein reported in mammals. In humans, its dysfunction is responsible for ferroportin disease, an inborn error of iron metabolism transmitted as an autosomal dominant trait and observed in different ethnic groups. As a member of the major facilitator superfamily, SLC40A1 requires a series of conformational changes to enable iron translocation across the plasma membrane. The influence of lipids on protein stability and its conformational changes has been little investigated to date. Here, we combine molecular dynamics simulations of SLC40A1 embedded in membrane bilayers with experimental alanine scanning mutagenesis to analyze the specific role of glycerophospholipids. We identify four basic residues (Lys90, Arg365, Lys366, and Arg371) that are located at the membrane-cytosol interface and consistently interact with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) molecules. These residues surround a network of salt bridges and hydrogens bonds that play a critical role in stabilizing SLC40A1 in its basal outward-facing conformation. More deeply embedded in the plasma membrane, we identify Arg179 as a charged amino acid residue also tightly interacting with lipid polar heads. This results in a local deformation of the lipid bilayer. Interestingly, Arg179 is adjacent to Arg178, which forms a functionally important salt-bridge with Asp473 and is a recurrently associated with ferroportin disease when mutated to glutamine. We demonstrate that the two p.Arg178Gln and p.Arg179Thr missense variants have similar functional behaviors. These observations provide insights into the role of phospholipids in the formation/disruption of the SLC40A1 inner gate, and give a better understanding of the diversity of molecular mechanisms of ferroportin disease.

Activin E is a transforming growth factor ß ligand that signals specifically through activin receptor-like kinase 7.

Activins are one of the three distinct subclasses within the greater Transforming growth factor ß (TGFß) superfamily. First discovered for their critical roles in reproductive biology, activins have since been shown to alter cellular differentiation and proliferation. At present, members of the activin subclass include activin A (ActA), ActB, ActC, ActE, and the more distant members myostatin and GDF11. While the biological roles and signaling mechanisms of most activins class members have been well-studied, the signaling potential of ActE has remained largely unknown. Here, we characterized the signaling capacity of homodimeric ActE. Molecular modeling of the ligand:receptor complexes showed that ActC and ActE shared high similarity in both the type I and type II receptor binding epitopes. ActE signaled specifically through ALK7, utilized the canonical activin type II receptors, ActRIIA and ActRIIB, and was resistant to the extracellular antagonists follistatin and WFIKKN. In mature murine adipocytes, ActE invoked a SMAD2/3 response via ALK7, like ActC. Collectively, our results establish ActE as a specific signaling ligand which activates the type I receptor, ALK7.

Plexin-B1 and Plexin-B2 play non-redundant roles in GABAergic synapse formation.

Synapse formation in the mammalian brain is a complex and dynamic process requiring coordinated function of dozens of molecular families such as cell adhesion molecules (CAMs) and ligand-receptor pairs (Ephs/Ephrins, Neuroligins/Neurexins, Semaphorins/Plexins). Due to the large number of molecular players and possible functional redundancies within gene families, it is challenging to determine the precise synaptogenic roles of individual molecules, which is key to understanding the consequences of mutations in these genes for brain function. Furthermore, few molecules are known to exclusively regulate either GABAergic or glutamatergic synapses, and cell and molecular mechanisms underlying GABAergic synapse formation in particular are not thoroughly understood. We previously demonstrated that Semaphorin-4D (Sema4D) regulates GABAergic synapse development in the mammalian hippocampus while having no effect on glutamatergic synapse development, and this effect occurs through binding to its high affinity receptor, Plexin-B1. In addition, we demonstrated that RNAi-mediated Plexin-B2 knock-down decreases GABAergic synapse density suggesting that both receptors function in this process. Here, we perform a structure-function study of the Plexin-B1 and Plexin-B2 receptors to identify the protein domains in each receptor which are required for its synaptogenic function. Further, we examine whether Plexin-B2 is required in the presynaptic neuron, the postsynaptic neuron, or both to regulate GABAergic synapse formation. Our data reveal that Plexin-B1 and Plexin-B2 function non-redundantly to regulate GABAergic synapse formation and suggest that the transmembrane domain may underlie functional distinctions. We also provide evidence that Plexin-B2 expression in presynaptic GABAergic interneurons, as well as postsynaptic pyramidal cells, regulates GABAergic synapse formation in hippocampus. These findings lay the groundwork for future investigations into the precise signaling pathways required for synapse formation downstream of Plexin-B receptor signaling.

Mechanisms of the septic heart: From inflammatory response to myocardial edema.

Sepsis-induced myocardial dysfunction (SIMD), also known as sepsis-induced cardiomyopathy (SICM), is linked to significantly increased mortality. Despite its clinical importance, effective therapies for SIMD remain elusive, largely due to an incomplete understanding of its pathogenesis. Over the past five decades, research involving both animal models and human studies has highlighted several pathogenic mechanisms of SICM, yet many aspects remain unexplored. Initially thought to be primarily driven by inflammatory cytokines, current research indicates that these alone are insufficient for the development of cardiac dysfunction. Recent studies have brought attention to additional mechanisms, including excessive nitric oxide production, mitochondrial dysfunction, and disturbances in calcium homeostasis, as contributing factors in SICM. Emerging clinical evidence has highlighted the significant role of myocardial edema in the pathogenesis of SICM, particularly its association with cardiac remodeling in septic shock patients. This review synthesizes our current understanding of SIMD/SICM, focusing on myocardial edema's contribution to cardiac dysfunction and the critical role of the bradykinin receptor B1 (B1R) in altering myocardial microvascular permeability, a potential key player in myocardial edema development during sepsis. Additionally, this review briefly summarizes existing therapeutic strategies and their challenges and explores future research directions. It emphasizes the need for a deeper understanding of SICM to develop more effective treatments.

Drugs/agents for the treatment of ischemic stroke: Advances and perspectives.

Ischemic stroke (IS) poses a significant threat to global human health and life. In recent decades, we have witnessed unprecedented progresses against IS, including thrombolysis, thrombectomy, and a few medicines that can assist in reopening the blocked brain vessels or serve as standalone treatments for patients who are not eligible for thrombolysis/thrombectomy therapies. However, the narrow time windows of thrombolysis/thrombectomy, coupled with the risk of hemorrhagic transformation, as well as the lack of highly effective and safe medications, continue to present big challenges in the acute treatment and long-term recovery of IS. In the past 3 years, several excellent articles have reviewed pathophysiology of IS and therapeutic medicines for the treatment of IS based on the pathophysiology. Regretfully, there is no comprehensive overview to summarize all categories of anti-IS drugs/agents designed and synthesized based on molecular mechanisms of IS pathophysiology. From medicinal chemistry view of point, this article reviews a multitude of anti-IS drugs/agents, including small molecule compounds, natural products, peptides, and others, which have been developed based on the molecular mechanism of IS pathophysiology, such as excitotoxicity, oxidative/nitrosative stresses, cell death pathways, and neuroinflammation, and so forth. In addition, several emerging medicines and strategies, including nanomedicines, stem cell therapy and noncoding RNAs, which recently appeared for the treatment of IS, are shortly introduced. Finally, the perspectives on the associated challenges and future directions of anti-IS drugs/agents are briefly provided to move the field forward.

Exploring the Molecular Therapeutic Mechanisms of Gemcitabine through Quantitative Proteomics.

Gemcitabine (GEM) is widely employed in the treatment of various cancers, including pancreatic cancer. Despite their clinical success, challenges related to GEM resistance and toxicity persist. Therefore, a deeper understanding of its intracellular mechanisms and potential targets is urgently needed. In this study, through mass spectrometry analysis in data-dependent acquisition mode, we carried out quantitative proteomics (three independent replications) and thermal proteome profiling (TPP, two independent replications) on MIA PaCa-2 cells to explore the effects of GEM. Our proteomic analysis revealed that GEM led to the upregulation of the cell cycle and DNA replication proteins. Notably, we observed the upregulation of S-phase kinase-associated protein 2 (SKP2), a cell cycle and chemoresistance regulator. Combining SKP2 inhibition with GEM showed synergistic effects, suggesting SKP2 as a potential target for enhancing the GEM sensitivity. Through TPP, we pinpointed four potential GEM binding targets implicated in tumor development, including in breast and liver cancers, underscoring GEM's broad-spectrum antitumor capabilities. These findings provide valuable insights into GEM's molecular mechanisms and offer potential targets for improving treatment efficacy.

Comparative transcriptomic analysis of the different developmental stages of ovary in the cuttlefish Sepia pharaonis.

The cuttlefish, Sepia pharaonis, is characterized by rapid growth and strong disease resistance, making it an important commercially farmed cephalopod species in the southeastern coastal regions of China. However, in the reproductive process of S. pharaonis, there are challenges such as a low output of eggs, poor quality, and low survival rates of newly hatched juveniles. Therefore, there is an urgent need to study the molecular mechanisms underlying ovarian development in this species. In this study, we conducted the first transcriptomic analysis of the ovary at four developmental stages: the undeveloped stage, developing stage, nearly-ripe stage, and ripe stage, and compared the transcriptomics among these four stages using Illumina sequencing technology. The total numbers of clean reads of the four stages ranged from 40,890,772 to 52,055,714 reads. A total of 136,829 DEGs were obtained, GC base ratios of raw data were between 38.44 and 44.59%, and the number of uniquely mapped reads spanned from 88.08 to 95.90%. The Pearson correlation coefficient demonstrated a strong correlation among different samples within the same group, PCA and Anosim analysis also revealed that the grouping of these four stages was feasible, and each stage could be distinguished from the others. GO enrichment analysis demonstrated that ovarian follicle growth, sex differentiation, and transforming growth factor beta receptor, played a foreshadowing role at the early ovarian development stage, and the terms of small molecule metabolic process, peptide metabolic process, and catalytic activity were prominent at the mature stage. Meanwhile, KEGG analysis showed that the early ovarian development of S. pharaonis was mainly associated with the cell cycle, DNA replication, and carbon metabolism, while the mid-late ovarian development was involved with the signal transduction, endocrine system, and reproduction pathway. RT-qPCR further confirmed the consistent expression patterns of genes such as 17ß-HSD, GH, VGS, NFR, and NYR in the ovaries of S. pharaonis, exhibiting elevated levels of expression during the maturation stage. Conversely, ER and OM exhibited high expression levels during the early stages of ovarian development. These transcriptomic data provide insights into the molecular mechanisms of S. pharaonis ovarian development. The findings of this study will contribute to improving the reproduction and development of cuttlefish and enriching the bioinformatics knowledge of cephalopods.

Decoding HiPSC-CM's Response to SARS-CoV-2: mapping the molecular landscape of cardiac injury.

BACKGROUND: Acute cardiac injury caused by coronavirus disease 2019 (COVID-19) increases mortality. Acute cardiac injury caused by COVID-19 requires understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly infects cardiomyocytes. This study provides a solid foundation for related studies by using a model of SARS-CoV-2 infection in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) at the transcriptome level, highlighting the relevance of this study to related studies. SARS-CoV-2 infection in hiPSC-CMs has previously been studied by bioinformatics without presenting the full molecular biological process. We present a unique bioinformatics view of the complete molecular biological process of SARS-CoV-2 infection in hiPSC-CMs. METHODS: To validate the RNA-seq datasets, we used GSE184715 and GSE150392 for the analytical studies, GSE193722 for validation at the cellular level, and GSE169241 for validation in heart tissue samples. GeneCards and MsigDB databases were used to find genes associated with the phenotype. In addition to differential expression analysis and principal component analysis (PCA), we also performed protein-protein interaction (PPI) analysis, functional enrichment analysis, hub gene analysis, upstream transcription factor prediction, and drug prediction. RESULTS: Differentially expressed genes (DEGs) were classified into four categories: cardiomyocyte cytoskeletal protein inhibition, proto-oncogene activation and inflammation, mitochondrial dysfunction, and intracellular cytoplasmic physiological function. Each of the hub genes showed good diagnostic prediction, which was well validated in other datasets. Inhibited biological functions included cardiomyocyte cytoskeletal proteins, adenosine triphosphate (ATP) synthesis and electron transport chain (ETC), glucose metabolism, amino acid metabolism, fatty acid metabolism, pyruvate metabolism, citric acid cycle, nucleic acid metabolism, replication, transcription, translation, ubiquitination, autophagy, and cellular transport. Proto-oncogenes, inflammation, nuclear factor-kappaB (NF-κB) pathways, and interferon signaling were activated, as well as inflammatory factors. Viral infection activates multiple pathways, including the interferon pathway, proto-oncogenes and mitochondrial oxidative stress, while inhibiting cardiomyocyte backbone proteins and energy metabolism. Infection limits intracellular synthesis and metabolism, as well as the raw materials for mitochondrial energy synthesis. Mitochondrial dysfunction and energy abnormalities are ultimately caused by proto-oncogene activation and SARS-CoV-2 infection. Activation of the interferon pathway, proto-oncogene up-regulation, and mitochondrial oxidative stress cause the inflammatory response and lead to diminished cardiomyocyte contraction. Replication, transcription, translation, ubiquitination, autophagy, and cellular transport are among the functions that decline physiologically. CONCLUSION: SARS-CoV-2 infection in hiPSC-CMs is fundamentally mediated via mitochondrial dysfunction. Therapeutic interventions targeting mitochondrial dysfunction may alleviate the cardiovascular complications associated with SARS-CoV-2 infection.

Effects of super-enhancers in cancer metastasis: mechanisms and therapeutic targets.

Metastasis remains the principal cause of cancer-related lethality despite advancements in cancer treatment. Dysfunctional epigenetic alterations are crucial in the metastatic cascade. Among these, super-enhancers (SEs), emerging as new epigenetic regulators, consist of large clusters of regulatory elements that drive the high-level expression of genes essential for the oncogenic process, upon which cancer cells develop a profound dependency. These SE-driven oncogenes play an important role in regulating various facets of metastasis, including the promotion of tumor proliferation in primary and distal metastatic organs, facilitating cellular migration and invasion into the vasculature, triggering epithelial-mesenchymal transition, enhancing cancer stem cell-like properties, circumventing immune detection, and adapting to the heterogeneity of metastatic niches. This heavy reliance on SE-mediated transcription delineates a vulnerable target for therapeutic intervention in cancer cells. In this article, we review current insights into the characteristics, identification methodologies, formation, and activation mechanisms of SEs. We also elaborate the oncogenic roles and regulatory functions of SEs in the context of cancer metastasis. Ultimately, we discuss the potential of SEs as novel therapeutic targets and their implications in clinical oncology, offering insights into future directions for innovative cancer treatment strategies.

Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.

Ubiquitination, a pivotal posttranslational modification of proteins, plays a fundamental role in regulating protein stability. The dysregulation of ubiquitinating and deubiquitinating enzymes is a common feature in various cancers, underscoring the imperative to investigate ubiquitin ligases and deubiquitinases (DUBs) for insights into oncogenic processes and the development of therapeutic interventions. In this review, we discuss the contributions of the ubiquitin-proteasome system (UPS) in all hallmarks of cancer and progress in drug discovery. We delve into the multiple functions of the UPS in oncology, including its regulation of multiple cancer-associated pathways, its role in metabolic reprogramming, its engagement with tumor immune responses, its function in phenotypic plasticity and polymorphic microbiomes, and other essential cellular functions. Furthermore, we provide a comprehensive overview of novel anticancer strategies that leverage the UPS, including the development and application of proteolysis targeting chimeras (PROTACs) and molecular glues.

Potential Application of MicroRNAs and Some Other Molecular Biomarkers in Alzheimer's Disease.

Alzheimer's disease (AD) is the world's most common neurodegenerative disease, expected to affect up to one-third of the elderly population in the near future. Among the major challenges in combating AD are the inability to reverse the damage caused by the disease, expensive diagnostic tools, and the lack of specific markers for the early detection of AD. This paper highlights promising research directions for molecular markers in AD diagnosis, including the diagnostic potential of microRNAs. The latest molecular methods for diagnosing AD are discussed, with particular emphasis on diagnostic techniques prior to the appearance of full AD symptoms and markers detectable in human body fluids. A collection of recent studies demonstrates the promising potential of molecular methods in AD diagnosis, using miRNAs as biomarkers. Up- or downregulation in neurodegenerative diseases may not only provide a new diagnostic tool but also serve as a marker for differentiating neurodegenerative diseases. However, further research in this direction is needed.

Molecular Mechanisms in the Design of Novel Targeted Therapies for Neurodegenerative Diseases.

Neurodegenerative diseases are a diverse group of diseases characterized by a progressive loss of neurological function due to damage to nerve cells in the central nervous system. In recent years, there has been a worldwide increase in the expanding associated with increasing human life expectancy. Molecular mechanisms control many of the essential life processes of cells, such as replication, transcription, translation, protein synthesis and gene regulation. These are complex interactions that form the basis for understanding numerous processes in the organism and developing new diagnostic and therapeutic approaches. In the context of neurodegenerative diseases, molecular basis refers to changes at the molecular level that cause damage to or degeneration of nerve cells. These may include protein aggregates leading to pathological structures in brain cells, impaired protein transport in nerve cells, mitochondrial dysfunction, inflammatory processes or genetic mutations that impair nerve cell function. New medical therapies are based on these mechanisms and include gene therapies, reduction in inflammation and oxidative stress, and the use of miRNAs and regenerative medicine. The aim of this study was to bring together the current state of knowledge regarding selected neurodegenerative diseases, presenting the underlying molecular mechanisms involved, which could be potential targets for new forms of treatment.

Upregulation of hsa-miR-141-3p promotes uterine cervical carcinoma progression via targeting dual-specificity protein phosphatase 1.

We aimed to explore the aberrant expression status of hsa-miR-141-3p and dual-specificity protein phosphatase 1 (DUSP1) and their relative mechanisms in uterine cervical carcinoma (UCC).Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was conducted to detect the expression of hsa-miR-141-3p. Immunohistochemical (IHC) staining was performed to examine the expression of DUSP1 in UCC. Gene chips and RNA-seq datasets were also obtained to assess the expression level. Integrated standardized mean difference (SMD) was calculated to evaluate the expression status of hsa-miR-141-3p in UCC tissues comprehensively. DUSP1-overexpression and hsa-miR-141-3p-inhibition HeLa cells were established, and CCK-8, transwell, wound healing, cell cycle, and apoptosis assays were implemented. The targets of hsa-miR-141-3p were obtained with online tools, and the combination of hsa-miR-141-3p and DUSP1 was validated via dual-luciferase reporter assay. Single-cell RNA-seq data were analyzed to explore hsa-miR-141-3p and DUSP1 in different cells. An integrated SMD of 1.41 (95% CI[0.45, 2.38], p = 0.0041) with 558 samples revealed the overexpression of hsa-miR-141-3p in UCC tissues. And the pooled SMD of -1.06 (95% CI[-1.45, -0.66], p < 0.0001) with 1,268 samples indicated the downregulation of DUSP1. Inhibition of hsa-miR-141-3p could upregulate DUSP1 expression and suppress invasiveness and metastasis of HeLa cells. Overexpression of DUSP1 could hamper proliferation, invasion, and migration and boost apoptosis and distribution of G1 phase. The dual-luciferase reporter assay validated the combination of hsa-miR-141-3p and DUSP1. Moreover, the targets of hsa-miR-141-3p were mainly enriched in the MAPK signaling pathway and activated in fibroblasts and endothelial cells. The current study illustrated the upregulation of hsa-miR-141-3p and the downregulation of DUSP1 in UCC tissues. Hsa-miR-141-3p could promote UCC progression by targeting DUSP1.

An update on chronic complications of diabetes mellitus: from molecular mechanisms to therapeutic strategies with a focus on metabolic memory.

Diabetes mellitus, a chronic metabolic disease, often leads to numerous chronic complications, significantly contributing to global morbidity and mortality rates. High glucose levels trigger epigenetic modifications linked to pathophysiological processes like inflammation, immunity, oxidative stress, mitochondrial dysfunction, senescence and various kinds of cell death. Despite glycemic control, transient hyperglycemia can persistently harm organs, tissues, and cells, a latent effect termed "metabolic memory" that contributes to chronic diabetic complications. Understanding metabolic memory's mechanisms could offer a new approach to mitigating these complications. However, key molecules and networks underlying metabolic memory remain incompletely understood. This review traces the history of metabolic memory research, highlights its key features, discusses recent molecules involved in its mechanisms, and summarizes confirmed and potential therapeutic compounds. Additionally, we outline in vitro and in vivo models of metabolic memory. We hope this work will inform future research on metabolic memory's regulatory mechanisms and facilitate the development of effective therapeutic compounds to prevent diabetic complications.

Integrated analysis of the transcriptome and metabolome reveals the molecular mechanism regulating cotton boll abscission under low light intensity.

BACKGROUND: Cotton boll shedding is one of the main factors adversely affecting the cotton yield. During the cotton plant growth period, low light conditions can cause cotton bolls to fall off prematurely. In this study, we clarified the regulatory effects of low light intensity on cotton boll abscission by comprehensively analyzing the transcriptome and metabolome. RESULTS: When the fruiting branch leaves were shaded after pollination, all of the cotton bolls fell off within 5 days. Additionally, H2O2 accumulated during the formation of the abscission zone. Moreover, 10,172 differentially expressed genes (DEGs) and 81 differentially accumulated metabolites (DAMs) were identified. A KEGG pathway enrichment analysis revealed that the identified DEGs and DAMs were associated with plant hormone signal transduction and flavonoid biosynthesis pathways. The results of the transcriptome analysis suggested that the expression of ethylene (ETH) and abscisic acid (ABA) signaling-related genes was induced, which was in contrast to the decrease in the expression of most of the IAA signaling-related genes. A combined transcriptomics and metabolomics analysis revealed that flavonoids may help regulate plant organ abscission. A weighted gene co-expression network analysis detected two gene modules significantly related to abscission. The genes in these modules were mainly related to exosome, flavonoid biosynthesis, ubiquitin-mediated proteolysis, plant hormone signal transduction, photosynthesis, and cytoskeleton proteins. Furthermore, TIP1;1, UGT71C4, KMD3, TRFL6, REV, and FRA1 were identified as the hub genes in these two modules. CONCLUSIONS: In this study, we elucidated the mechanisms underlying cotton boll abscission induced by shading on the basis of comprehensive transcriptomics and metabolomics analyses of the boll abscission process. The study findings have clarified the molecular basis of cotton boll abscission under low light intensity, and suggested that H2O2, phytohormone, and flavonoid have the potential to affect the shedding process of cotton bolls under low light stress.

Highlight of 2023: Tregs in the lungs.

In this article for the Highlights of the 2023 Series, we discuss recent discoveries on regulatory T cells in the lungs and their multifaceted roles in various contexts. Key advancements in Treg immunology have broadened our understanding of lung tissue homeostasis and the potential role of Tregs in pathological processes.

Comparative transcriptomics revealed parallel evolution and innovation of photosymbiosis molecular mechanisms in a marine bivalve.

Photosymbioses between heterotrophic hosts and autotrophic symbionts are evolutionarily prevalent and ecologically significant. However, the molecular mechanisms behind such symbioses remain less elucidated, which hinders our understanding of their origin and adaptive evolution. This study compared gene expression patterns in a photosymbiotic bivalve (Fragum sueziense) and a closely related non-symbiotic species (Trigoniocardia granifera) under different light conditions to detect potential molecular pathways involved in mollusc photosymbiosis. We discovered that the presence of algal symbionts greatly impacted host gene expression in symbiont-containing tissues. We found that the host immune functions were suppressed under normal light compared with those in the dark. In addition, we found that cilia in the symbiont-containing tissues play important roles in symbiont regulation or photoreception. Interestingly, many potential photosymbiosis genes could not be annotated or do not exhibit orthologues in T. granifera transcriptomes, indicating unique molecular functions in photosymbiotic bivalves. Overall, we found both novel and known molecular mechanisms involved in animal-algal photosymbiosis within bivalves. Given that many of the molecular pathways are shared among distantly related host lineages, such as molluscs and cnidarians, it indicates that parallel and/or convergent evolution is instrumental in shaping host-symbiont interactions and responses in these organisms.

Exploring silique number in Brassica napus L.: Genetic and molecular advances for improving yield.

Silique number is a crucial yield-related trait for the genetic enhancement of rapeseed (Brassica napus L.). The intricate molecular process governing the regulation of silique number involves various factors. Despite advancements in understanding the mechanisms regulating silique number in Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa), the molecular processes involved in controlling silique number in rapeseed remain largely unexplored. In this review, we identify candidate genes and review the roles of genes and environmental factors in regulating rapeseed silique number. We use genetic regulatory networks for silique number in Arabidopsis and grain number in rice to uncover possible regulatory pathways and molecular mechanisms involved in regulating genes associated with rapeseed silique number. A better understanding of the genetic network regulating silique number in rapeseed will provide a theoretical basis for the genetic improvement of this trait and genetic resources for the molecular breeding of high-yielding rapeseed.