Uncovering the genomic bases of phenotypic adaptation is a major goal in biology, but this has been hard to achieve for complex behavioural traits. Here we leverage the repeated, independent evolution of obligate cavity nesting in birds to test the hypothesis that pressure to compete for a limited breeding resource has facilitated convergent evolution in behaviour, hormones and gene expression. We used an integrative approach, combining aggression assays in the field, testosterone measures and transcriptome-wide analyses of the brain in wild-captured females and males. Our experimental design compared species pairs across five avian families, each including one obligate cavity-nesting species and a related species with a more flexible nest strategy. We find behavioural convergence, with higher levels of territorial aggression in obligate cavity nesters, particularly among females. Across species, levels of testosterone in circulation were not associated with nest strategy nor aggression. Phylogenetic analyses of individual genes and co-regulated gene networks revealed more shared patterns of brain gene expression than expected by drift, although the scope of convergent gene expression evolution was limited to a small percentage of the genome. When comparing our results to other studies that did not use phylogenetic methods, we suggest that accounting for shared evolutionary history may reduce the number of genes inferred as convergently evolving. Altogether, we find that behavioural convergence in response to shared ecological pressures is associated with largely independent evolution of gene expression across different avian families, punctuated by a narrow set of convergently evolving genes.

Exercise combats obesity and metabolic disorders, but the underlying mechanism is incompletely understood. KLF10, a transcription factor involved in various biological processes, has an undefined role in adipose tissue and obesity. Here, we show that exercise facilitates adipocyte-derived KLF10 expression via SIRT1/FOXO1 pathway. Adipocyte-specific knockout of KLF10 blunts exercise-promoted white adipose browning, energy expenditure, fat loss, glucose tolerance in diet-induced obese male mice. Conversely, adipocyte-specific transgenic expression of KLF10 in male mice enhanced the above metabolic profits induced by exercise. Mechanistically, KLF10 interacts with FOXO1 and facilitates the recruitment of KDM4A to form a ternary complex on the promoter regions of Pnpla2 and Lipe genes to promote these key lipolytic genes expression by demethylating H3K9me3 on their promoters, which facilitates lipolysis to defend against obesity in male mice. As a downstream effector responding to exercise, adipose KLF10 could act as a potential target in the fight against obesity.

Lumbar spinal stenosis (LSS) is a degenerative condition characterized by the narrowing of the spinal canal, resulting in chronic pain and impaired mobility. However, the molecular mechanisms underlying LSS remain unclear. In this study, we performed RNA sequencing (RNA-seq) to investigate differential gene expression in a rat LSS model and identify the key genes and pathways involved in its pathogenesis.

We used bioinformatics analysis to identify significant alterations in gene expression between the LSS-induced and sham groups.

Pearson's correlation analysis demonstrated strongly consistent intragroup expression (r > 0.9), with distinct gene expression between the LSS and sham groups. A total of 113 differentially expressed genes (DEGs) were identified, including upregulated genes such as Slc47a1 and Prg4 and downregulated genes such as Higd1c and Mln. Functional enrichment analysis revealed that these DEGs included those involved in key biological processes, including synaptic plasticity, extracellular matrix organization, and hormonal regulation. Gene ontology analysis highlighted critical molecular functions such as mRNA binding and integrin binding, as well as cellular components such as contractile fibers and the extracellular matrix, which were significantly affected by LSS.

Our findings provide novel insights into the molecular mechanisms underlying LSS and offer potential avenues for the development of targeted therapies aimed at mitigating disease progression and improving patient outcomes.

Clear cell renal cell carcinoma (ccRCC) is resistant to radiotherapy and chemotherapy. Thus, it is necessary to find new diagnostic markers and therapeutic targets to increase the overall outcomes of ccRCC. Recent studies have shown that therapeutic methods that interfere with the energy transfer system can also positively affect the treatment process.

The present study is focused on finding markers associated with mitochondrial metabolic pathways that affect the outcome of ccRCC. For this purpose, we investigated various aspects of the relationship between mitochondrial metabolism and ccRCC based on analysis of gene network connections and differentially expressed genes, through assessment of protein-protein interaction, mutations, and promoter methylation on the related genes. We also investigated gene interaction with miRNAs and immune infiltration analysis.

Through these steps, we provided a list of possible diagnostic markers and therapeutic targets for ccRCC.

The current study further proved the importance of mitochondrial metabolic pathways in the pathogenesis of ccRCC and provided a list of possible diagnostic markers and therapeutic targets from these pathways that can be used in ccRCC.

Cancer cell dormancy (CCD) in colorectal cancer (CRC) poses a significant challenge to effective treatment. In CRC, CCD contributes to tumour recurrence, drug resistance, and amplifying the disease's burden. The molecular mechanisms governing CCD and strategies for eliminating dormant cancer cells remain largely unexplored. Therefore, understanding the molecular mechanisms governing dormancy is crucial for improving patient outcomes and developing targeted therapies. This editorial highlights the complex interplay of signalling pathways and factors involved in colorectal CCD, emphasizing the roles of Hippo/YAP, pluripotent transcription factors such as NANOG, HIF-1α signalling, and Notch signalling pathways. Additionally, ERK/p38α/β/MAPK pathways, AKT signalling pathway, and Extracellular Matrix Metalloproteinase Inducer, along with some potential less explored pathways such as STAT/p53 switch and canonical and non-canonical Wnt and SMAD signalling, are also involved in promoting colorectal CCD. Highlighting their clinical significance, these findings may offer the potential for identifying key dormancy regulator pathways, improving treatment strategies, surmounting drug resistance, and advancing personalized medicine approaches. Moreover, insights into dormancy mechanisms could lead to the development of predictive biomarkers for identifying patients at risk of recurrence and the tailoring of targeted therapies based on individual dormancy profiles. It is essential to conduct further research into these pathways and their modulation to fully comprehend CRC dormancy mechanisms and enhance patient outcomes.

Colorectal cancer (CRC) is the third-most prevalent cancer globally. The biological significance of telomeres in CRC carcinogenesis and progression is underscored by accumulating data. Nevertheless, not much is known about how telomere-related genes (TRGs) affect CRC prognosis. Therefore, the aim of this study was to investigate the role of TRGs in CRC prognosis.

We retrospectively obtained the expression profiles and clinical data of CRC patients from public databases. Utilizing least absolute shrinkage and selection operator (LASSO) regression analysis, we created a telomere-related risk model to predict survival outcomes, identifying ten telomere-related differentially expressed genes (TRDEGs). Based on TRDEGs, we stratified patients from The Cancer Genome Atlas (TCGA) into low- and high-risk subsets. Subsequently, we conducted comprehensive analyses, including survival assessment, immune cell infiltration, drug sensitivity, and prediction of molecular interactions using Kaplan-Meier curves, ESTIMATE, CIBERSORT, OncoPredict, and other approaches.

The model showed exceptional predictive accuracy for survival. Significant differences in survival were observed between the two groups of participants grouped according to the model (P<0.001), and this difference was further confirmed in the external validation set (GSE39582) (P=0.004). Additionally, compared to the low-risk group, the high-risk group exhibited significantly advanced tumor node metastasis (TNM) stages, lower proportions of activated CD4+ T cells, effector memory CD4+ T cells, and memory B cells, but increased ratios of M2 macrophages and regulatory T cells (Tregs), elevated tumor immune dysfunction and exclusion (TIDE) scores, and diminished sensitivity to dabrafenib, lapatinib, camptothecin, docetaxel, and telomerase inhibitor IX, reflecting the signature's capacity to distinguish clinical pathological characteristics, immune environment, and drug efficacy. Finally, we validated the expression of the ten TRDEGs (ACACB, TPX2, SRPX, PPARGC1A, CD36, MMP3, NAT2, MMP10, HIGD1A, and MMP1) through quantitative real-time polymerase chain reaction (qRT-PCR) and found that compared to normal cells, the expression levels of ACACB, HIGD1A, NAT2, PPARGC1A, and TPX2 in CRC cells were elevated, whereas those of CD36, SRPX, MMP1, MMP3, and MMP10 were reduced.

Overall, we constructed a telomere-related biomarker capable of predicting prognosis and treatment response in CRC individuals, offering potential guidance for drug therapy selection and prognosis prediction.

HIGD1B (HIG1 Hypoxia Inducible Domain Family Member 1B) is a protein-coding gene linked to the occurrence and progression of various illnesses. However, its precise function in gastric cancer (GC) remains unclear.

The expression of HIGD1B is determined through the TCGA and GEO databases and verified using experiments. The association between HIGD1B and GC patients' prognosis was analyzed via the Kaplan-Meier (K-M) curve. Subsequently, the researchers utilized ROC curves to assess the diagnostic capacity of HIGD1B and employed COX analysis to investigate risk factors for GC. The differentially expressed genes (DEGs) were then subjected to functional enrichment analysis, and a nomogram was generated to forecast the survival outcome and probability of GC patients. Additionally, we evaluated the interaction between HIGD1B and the immune cell infiltration and predicted the susceptibility of GC patients to therapy.

HIGD1B is markedly elevated in GC tissue and cell lines, and patients with high HIGD1B expression have a poorer outcome. In addition, HIGD1B is related to distinct grades, stages, and T stages. The survival ROC curves of HIGD1B and nomogram for five years were 0.741 and 0.735, suggesting appropriate levels of diagnostic efficacy. According to Cox regression analysis, HIGD1B represents a separate risk factor for the prognosis of gastric cancer (p<0.01). GSEA analysis demonstrated that the HIGD1B is closely related to cancer formation and advanced pathways. Moreover, patients with high HIGD1B expression exhibited a higher level of Tumor-infiltration immune cells (TIICs) and were more likely to experience immune escape and drug resistance after chemotherapy and immunotherapy.

This study explored the potential mechanisms and diagnostic and prognostic utility of HIGD1B in GC, as well as identified HIGD1B as a valuable biomarker and possible therapeutic target for GC.

Neuregulin 4 (Nrg4), an epidermal growth factor (EGF) family member, can bind to and activate the ErbB4 receptor tyrosine kinase. Nrg4 has five different isoforms by alternative splicing and performs a wide variety of functions. Nrg4 is involved in a spectrum of physiological processes including neurobiogenesis, lipid metabolism, glucose metabolism, thermogenesis, and angiogenesis. In pathological processes, Nrg4 inhibits inflammatory factor levels and suppresses apoptosis in inflammatory diseases. In addition, Nrg4 could ameliorate obesity, insulin resistance, and cardiovascular diseases. Furthermore, Nrg4 improves non-alcoholic fatty liver disease (NAFLD) by promoting autophagy, improving lipid metabolism, and inhibiting cell death of hepatocytes. Besides, Nrg4 is closely related to the development of cancer, hyperthyroidism, and some other diseases. Therefore, elucidation of the functional role and mechanisms of Nrg4 will provide a clearer view of the therapeutic potential and possible risks of Nrg4.

Liver disease has become one of the main causes of health issue worldwide. Sirtuin (Sirt) 2 is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, and is expressed in multiple organs including liver, which plays important and complex roles by interacting with various substrates. Physiologically, Sirt2 can improve metabolic homeostasis. Pathologically, Sirt2 can alleviate inflammation, endoplasmic reticulum (ER) stress, promote liver regeneration, maintain iron homeostasis, aggravate fibrogenesis and regulate oxidative stress in liver. In liver diseases, Sirt2 can mitigate fatty liver disease (FLD) including non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD), but aggravate hepatitis B (HBV) and liver ischemia-reperfusion injury (LIRI). The role of Sirt2 in liver cancer and aging-related liver diseases, however, has not been fully elucidated. In this review, these biological processes regulated by Sirt2 in liver are summarized, which aims to update the function of Sirt2 in liver and to explore the potential role of Sirt2 as a therapeutic target for liver diseases.

Exercise is an effective non-pharmacological strategy for ameliorating nonalcoholic fatty liver disease (NAFLD), but the underlying mechanism needs further investigation. Cysteine dioxygenase type 1 (Cdo1) is a key enzyme for cysteine catabolism that is enriched in liver, whose role in NAFLD remains poorly understood. Here, we show that exercise induces the expression of hepatic Cdo1 via the cAMP/PKA/CREB signaling pathway. Hepatocyte-specific knockout of Cdo1 (Cdo1LKO) decreases basal metabolic rate of the mice and impairs the effect of exercise against NAFLD, whereas hepatocyte-specific overexpression of Cdo1 (Cdo1LTG) increases basal metabolic rate of the mice and synergizes with exercise to ameliorate NAFLD. Mechanistically, Cdo1 tethers Camkk2 to AMPK by interacting with both of them, thereby activating AMPK signaling. This promotes fatty acid oxidation and mitochondrial biogenesis in hepatocytes to attenuate hepatosteatosis. Therefore, by promoting hepatic Camkk2-AMPK signaling pathway, Cdo1 acts as an important downstream effector of exercise to combat against NAFLD.

Extracellular vesicles (EVs) are membrane-bound particles released from cells, and their cargo can alter the function of recipient cells. EVs from X-irradiated cells have been shown to play a likely role in non-targeted effects. However, EVs derived from proton irradiated cells have not yet been studied. We aimed to investigate the proteome of EVs and their cell of origin after proton or X-irradiation. The EVs were derived from a human oral squamous cell carcinoma (OSCC) cell line exposed to 0, 4, or 8 Gy from either protons or X-rays. The EVs and irradiated OSCC cells underwent liquid chromatography-mass spectrometry for protein identification. Interestingly, we found different protein profiles both in the EVs and in the OSCC cells after proton irradiation compared to X-irradiation. In the EVs, we found that protons cause a downregulation of proteins involved in cell growth and DNA damage response compared to X-rays. In the OSCC cells, proton and X-irradiation induced dissimilar cell death pathways and distinct DNA damage repair systems. These results are of potential importance for understanding how non-targeted effects in normal tissue can be limited and for future implementation of proton therapy in the clinic.

White adipocytes play a key role in the regulation of fat mass amount and energy balance. An appropriate level of white adipocyte differentiation is important for maintaining metabolic homeostasis. Exercise, an important way to improve metabolic health, can regulate white adipocyte differentiation. In this review, the effect of exercise on the differentiation of white adipocytes is summarized. Exercise could regulate adipocyte differentiation in multiple ways, such as exerkines, metabolites, microRNAs, and so on. The potential mechanism underlying the role of exercise in adipocyte differentiation is also reviewed and discussed. In-depth investigation of the role and mechanism of exercise in white adipocyte differentiation would provide new insights into exercise-mediated improvement of metabolism and facilitate the application of exercise-based strategy against obesity.

Energy-dissipating adipocytes have the potential to improve metabolic health. Here, we identify hypoxia-induced gene domain protein-1a (HIGD1A), a mitochondrial inner membrane protein, as a positive regulator of adipose browning. HIGD1A is induced in thermogenic fats by cold exposure. Peroxisome proliferator-activated receptor gamma (PPARγ) transactivates HIGD1A expression synergistically with peroxisome proliferators-activated receptor γ coactivator α (PGC1α). HIGD1A knockdown inhibits adipocyte browning, whereas HIGD1A upregulation promotes the browning process. Mechanistically, HIGD1A deficiency impairs mitochondrial respiration to increase reactive oxygen species (ROS) level. This increases NAD⁺ consumption for DNA damage repair and curtails the NAD⁺/NADH ratio, which inhibits sirtuin1 (SIRT1) activity, thereby compromising adipocyte browning. Conversely, overexpression of HIGD1A blunts the above process to promote adaptive thermogenesis. Furthermore, mice with HIGD1A knockdown in inguinal and brown fat have impaired thermogenesis and are prone to diet-induced obesity (DIO). Overexpression of HIGD1A favors adipose tissue browning, ultimately preventing DIO and metabolic disorders. Thus, the mitochondrial protein HIGD1A links SIRT1 activity to adipocyte browning by inhibiting ROS levels.

Krüppel-like factor 10 (KLF10), also known as TGFβ-inducible early gene-1 (TIEG1), was first found in human osteoblasts. Early studies show that KLF10 plays an important role in osteogenic differentiation. Through decades of research, KLF10 has been found to have complex functions in many different cell types, and its expression and function is regulated in multiple ways. As a downstream factor of transforming growth factor β (TGFβ)/SMAD signaling, KLF10 is involved in various biological functions, including glucose and lipid metabolism in liver and adipose tissue, the maintenance of mitochondrial structure and function of the skeletal muscle, cell proliferation and apoptosis, and plays roles in multiple disease processes, such as nonalcoholic steatohepatitis (NASH) and tumor. Besides, KLF10 shows gender-dependent difference of regulation and function in many aspects. In this review, the biological functions of KLF10 and its roles in disease states is updated and discussed, which would provide new insights into the functional roles of KLF10 and a clearer view of potential therapeutic strategies by targeting KLF10.