Although new developments of surgery, chemotherapy, radiotherapy, and immunotherapy treatments for cancer have improved patient survival, the emergence of chemoresistance in cancer has significant impacts on treatment effects. The development of chemoresistance involves several polygenic, progressive mechanisms at the molecular and cellular levels, as well as both genetic and epigenetic heterogeneities. Chemotherapeutics induce epigenetic reprogramming in cancer cells, converting a transient transcriptional state into a stably resistant one. Super-enhancers (SEs) are central to the maintenance of identity of cancer cells and promote SE-driven-oncogenic transcriptions to which cancer cells become highly addicted. This dependence on SE-driven transcription to maintain chemoresistance offers an Achilles’ heel for chemoresistance. Indeed, the inhibition of SE components dampens oncogenic transcription and inhibits tumor growth to ultimately achieve combined sensitization and reverse the effects of drug resistance. No reviews have been published on SE-related mechanisms in the cancer chemoresistance. In this review, we investigated the structure, function, and regulation of chemoresistance-related SEs and their contributions to the chemotherapy via regulation of the formation of cancer stem cells, cellular plasticity, the microenvironment, genes associated with chemoresistance, noncoding RNAs, and tumor immunity. The discovery of these mechanisms may aid in the development of new drugs to improve the sensitivity and specificity of cancer cells to chemotherapy drugs.

Tumor immune microenvironment (TIME) consists of intra-tumor immunological components and plays a significant role in tumor initiation, progression, metastasis, and response to therapy. Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the cancer treatment paradigm. Although CAR-T cell immunotherapy has emerged as a successful treatment for hematologic malignancies, it remains a conundrum for solid tumors. The heterogeneity of TIME is responsible for poor outcomes in CAR-T cell immunotherapy against solid tumors. The advancement of highly sophisticated technology enhances our exploration in TIME from a multi-omics perspective. In the era of machine learning, multi-omics studies could reveal the characteristics of TIME and its immune resistance mechanism. Therefore, the clinical efficacy of CAR-T cell immunotherapy in solid tumors could be further improved with strategies that target unfavorable conditions in TIME. Herein, this review seeks to investigate the factors influencing TIME formation and propose strategies for improving the effectiveness of CAR-T cell immunotherapy through a multi-omics perspective, with the ultimate goal of developing personalized therapeutic approaches.

LncRNAs play a pivotal role in the regulation of epigenetic modification, cell cycle, differentiation, proliferation, migration and other physiological activities. In particular, considerable studies have shown that the aberrant expression and dysregulation of lncRNAs are widely implicated in cancer initiation and progression by acting as tumour promoters or suppressors. Hippo signalling pathway has attracted researchers’ attention as one of the critical cancer‐related pathways in recent years. Increasing evidences have demonstrated that lncRNAs could interact with Hippo cascade and thereby contribute to acquisition of multiple malignant hallmarks, including proliferation, metastasis, relapse and resistance to anti‐cancer treatment. Specifically, Hippo signalling pathway is reported to modulate or be regulated by widespread lncRNAs. Intriguingly, certain lncRNAs could form a reciprocal feedback loop with Hippo signalling. More speculatively, lncRNAs related to Hippo pathway have been poised to become important putative biomarkers and therapeutic targets in human cancers. Herein, this review focuses on the crosstalk between lncRNAs and Hippo pathway in carcinogenesis, summarizes the comprehensive role of Hippo‐related lncRNAs in tumour progression and depicts their clinical diagnostic, prognostic or therapeutic potentials in tumours.

Introduction: Chlamydia psittaci infection is a zoonotic infectious disease, which mainly inhaled through the lungs when exposed to the secretions of poultry that carry pathogenic bacteria. The traditional respiratory specimens or serological antibody testing is slow, and the false-negative rate is high. Metagenomic next-generation sequencing (mNGS) gives a promising rapid diagnosis tool. Methods: We retrospectively summarized the clinical characteristics of five C. psittaci pneumonia patients diagnosed by mNGS, conducted a literature review summarizing the clinical characteristics of patients with C. psittaci pneumonia reported since 2010. Results: Five C. psittaci pneumonia patients confirmed by mNGS aged from 36 to 66 years with three males. About 60% of patients had a history of contact with avian or poultry. All patients had a high fever over 38.5 °C, cough, hypodynamia, hypoxemia, and dyspnea on admission. Two patients had invasive ventilator support and extracorporeal membrane oxygenation support. Inflammatory index levels on admission and follow-up were all higher than normal values. Doxycycline or moxifloxacin and their combination therapy were used in patients. Four patients improved and were discharged, and one patient died due to multiple organ failures and disseminated intravascular coagulation. We summarized 19 articles including 69 C. psittaci pneumonia patients and patients in 11 publications were identified by mNGS, and most patients are treated with tetracycline and quinolone with good outcomes. Conclusion: mNGS is a promising rapid diagnosis tool, which may increase the detection rate and shorten the diagnosis time of C. psittaci pneumonia. Further case-control studies are needed to confirm.

Objectives: Dendrobium officinale polysaccharide (DOP) is the main active ingredient in a valuable traditional Chinese medicine, which exerts several pharmacological activities including hepatoprotection and hypoglycemic effects. However, the effects of DOP on obesity-associated insulin resistance (IR) and lipid metabolism remain unknown. This study aimed to investigate the role of DOP in IR and abnormal lipid metabolism in obese mice.Methods: IR models were established using 3T3-L1 adipocytes, C2C12 myocytes, and primary cultured hepatocytes exposed to palmitate acid. After treatment with DOP, insulin-stimulated glucose uptake, glucose release, and AKT phosphorylation was detected. Fasting blood glucose, fasting serum insulin, the glucose tolerance test (GTT), and the insulin tolerance test (ITT) were measured to evaluate IR of obese mice. Lipid analysis was conducted to evaluate the effects of DOP on lipid metabolism in obese mice.Results:In vitro, DOP treatment ameliorated palmitic acid-induced IR in adipocytes, myocytes, and hepatocytes. DOP regulated cellular insulin sensitivity via the peroxisome proliferator-activated receptor-γ (PPAR-γ). Furthermore, administration of DOP significantly reduced the IR and visceral adipose tissue (VAT) inflammation of diet-induced obese (DIO) and the genetically-induced obesity mice (ob/ob) mouse models. In addition, DOP treatment attenuated the high-fat diet (HFD)-induced liver lipid accumulation by reducing liver triglycerides (TG), plasma free fatty acid (FFA), serum cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels, while increasing HDL-C levels.Conclusion: DOP could improve obesity-associated IR and abnormal lipid metabolism through its activities on PPAR-γ, and may serve as a potential therapeutic agent for obesity-associated insulin resistance and lipid metabolism disorder.

Immunotherapy has revolutionized the oncology treatment paradigm, and CAR-T cell therapy in particular represents a significant milestone in treating hematological malignancies. Nevertheless, tumor resistance due to target heterogeneity or mutation remains a Gordian knot for immunotherapy. This review elucidates molecular mechanisms and therapeutic potential of next-generation immunotherapeutic tools spanning genetically engineered immune cells, multi-specific antibodies, and cell engagers, emphasizing multi-targeting strategies to enhance personalized immunotherapy efficacy. Development of logic gate modulation-based circuits, adapter-mediated CARs, multi-specific antibodies, and cell engagers could minimize adverse effects while recognizing tumor signals. Ultimately, we highlight gene delivery, gene editing, and other technologies facilitating tailored immunotherapy, and discuss the promising prospects of artificial intelligence in gene-edited immune cells.