tRNA-derived small RNAs in human cancers: roles, mechanisms, and clinical application.

Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are a new type of non-coding RNAs (ncRNAs) produced by the specific cleavage of precursor or mature tRNAs. tsRNAs are involved in various basic biological processes such as epigenetic, transcriptional, post-transcriptional, and translation regulation, thereby affecting the occurrence and development of various human diseases, including cancers. Recent studies have shown that tsRNAs play an important role in tumorigenesis by regulating biological behaviors such as malignant proliferation, invasion and metastasis, angiogenesis, immune response, tumor resistance, and tumor metabolism reprogramming. These may be new potential targets for tumor treatment. Furthermore, tsRNAs can exist abundantly and stably in various bodily fluids (e.g., blood, serum, and urine) in the form of free or encapsulated extracellular vesicles, thereby affecting intercellular communication in the tumor microenvironment (TME). Meanwhile, their abnormal expression is closely related to the clinicopathological features of tumor patients, such as tumor staging, lymph node metastasis, and poor prognosis of tumor patients; thus, tsRNAs can be served as a novel type of liquid biopsy biomarker. This review summarizes the discovery, production, and expression of tsRNAs and analyzes their molecular mechanisms in tumor development and potential applications in tumor therapy, which may provide new strategies for early diagnosis and targeted therapy of tumors.

Exosome derived from tumor-associated macrophages: biogenesis, functions, and therapeutic implications in human cancers.

Tumor-associated macrophages (TAMs), one of the most abundant immune cell types in the tumor microenvironment (TME), account for approximately 50% of the local hematopoietic cells. TAMs play an important role in tumorigenesis and tumor development through crosstalk between various immune cells and cytokines in the TME. Exosomes are small extracellular vesicles with a diameter of 50-150 nm, that can transfer biological information (e.g., proteins, nucleic acids, and lipids) from secretory cells to recipient cells through the circulatory system, thereby influencing the progression of various human diseases, including cancer. Recent studies have suggested that TAMs-derived exosomes play crucial roles in malignant cell proliferation, invasion, metastasis, angiogenesis, immune responses, drug resistance, and tumor metabolic reprogramming. TAMs-derived exosomes have the potential to be targeted for tumor therapy. In addition, the abnormal expression of non-coding RNAs and proteins in TAMs-derived exosomes is closely related to the clinicopathological features of patients with cancer, and these exosomes are expected to become new liquid biopsy markers for the early diagnosis, prognosis, and monitoring of tumors. In this review, we explored the role of TAMs-derived exosomes in tumorigenesis to provide new diagnostic biomarkers and therapeutic targets for cancer prevention.

Optimal dose of tirzepatide for type 2 diabetes mellitus: A meta-analysis and trial sequential analysis.

Objective: The purpose of this study is to evaluate the optimal dose of tirzepatide (TZP) for the treatment of type 2 diabetes mellitus (T2DM) by meta-analysis and trial sequential analysis (TSA). Methods: Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022. Mean differences (MD) and 95% confidence intervals (95%CI) were used for continuous variables, and relative risk (RR) and 95%CI were used for dichotomous variables. Results: Compared with TZP 5 mg, meta-analysis showed that TZP 10 mg significantly reduced glycosylated hemoglobin type A1c (HbA1c) (MD -0.24, 95%CI -0.31~-0.17, P < 0.00001), fasting serum glucose (FSG) (MD -5.82, 95%CI -8.35~-3.28, P < 0.00001) and weight (MD -2.47, 95%CI -2.95~-1.98, P < 0.00001), and TZP 15 mg significantly reduced HbA1c (MD -0.37, 95%CI -0.44~-0.29, P < 0.00001), FSG (MD -8.52, 95%CI -11.07~-5.98, P < 0.00001) and weight (MD -4.63, 95%CI -5.45~-3.81, P < 0.00001). Compared with TZP 10 mg, TZP 15 mg dramatically reduced HbA1c (MD -0.12, 95%CI -0.19~-0.05, P = 0.001), FSG (MD -2.73, 95%CI -5.29~-0.17, P = 0.04) and weight (MD -2.18, 95%CI -2.67~-1.70, P < 0.00001). The TSA indicated that the benefits observed in the current information set were conclusive, except for the FSG of "TZP 15 mg vs. TZP 10 mg". In terms of safety endpoints, meta-analysis revealed that there was no significant difference in the serious adverse events (AEs), major adverse cardiovascular events-4 (MACE-4), cardiovascular death, hypertension, cancer and hypoglycemic of the three dose groups of TZP. Compared with TZP 5 mg, TZP 10 mg increased total adverse events (RR 1.06, 95%CI 1.01~1.11, P = 0.03) and gastrointestinal (GI) AEs (RR 1.17, 95%CI 1.03~1.33, P = 0.02), and TZP 15 mg increased total AEs (RR 1.10, 95%CI 1.05~1.15, P = 0.0001). There were no significant differences in total AEs and GI AEs for TZP 15 mg compared to TZP 10 mg. The TSA demonstrated that the total AEs of "TZP 15 mg vs. TZP 5 mg" were conclusive. Conclusions: TZP 15 mg >TZP 10 mg > TZP 5 mg in terms of lowering glycemia and reducing weight. TZP 5 mg > TZP 10 mg = TZP 15 mg in terms of safety. On this basis, we recommend TZP 5 mg as the first-choice dose for patients with T2DM to minimize AEs while reducing glycemia and weight. If patients cannot effectively control their glycemia after taking TZP 5 mg, it is recommended to take TZP 15 mg directly to achieve the best effect of glycemic reduction. However, most of the included studies have the background of basic medication, the independent efficacy and safety of different doses of TZP still need to be tested. Systematic review registration: Unique Identifier: CRD42022341966.

Myocardial Ischemia-Reperfusion Injury: Therapeutics from a Mitochondria-Centric Perspective.

Coronary arterial disease is the most common cardiovascular disease. Myocardial ischemia-reperfusion injury caused by the initial interruption of organ blood flow and subsequent restoration of organ blood flow is an important clinical problem with various cardiac reperfusion strategies after acute myocardial infarction. Even though blood flow recovery is necessary for oxygen and nutrient supply, reperfusion causes pathological sequelae that lead to the aggravation of ischemic injury. At present, although it is known that injury will occur after reperfusion, clinical treatment always focuses on immediate recanalization. Mitochondrial fusion, fission, biogenesis, autophagy, and their intricate interaction constitute an effective mitochondrial quality control system. The mitochondrial quality control system plays an important role in maintaining cell homeostasis and cell survival. The removal of damaged, aging, and dysfunctional mitochondria is mediated by mitochondrial autophagy. With the help of appropriate changes in mitochondrial dynamics, new mitochondria are produced through mitochondrial biogenesis to meet the energy needs of cells. Mitochondrial dysfunction and the resulting oxidative stress have been associated with the pathogenesis of ischemia/reperfusion (I/R) injury, which play a crucial role in the pathophysiological process of myocardial injury. This review aimed at elucidating the mitochondrial quality control system and establishing the possibility of using mitochondria as a potential therapeutic target in the treatment of I/R injuries.

Nitrogen-doped porous carbon encapsulating iron nanoparticles for enhanced sulfathiazole removal via peroxymonosulfate activation.

Developing novel catalyst with both high efficiency and stability presents an enticing prospect for peroxymonosulfate (PMS) activation. In this paper, nitrogen-doped porous carbon encapsulating iron nanoparticles (CN-Fe) was fabricated by a facile carbothermal reduction process using polyaniline (PANI) and α-Fe2O3 as the precursors. The stubborn antibiotics, sulfathiazole (STZ), was employed as a target pollutant, demonstrating that CN-Fe coupled with PMS could achieve 96% removal efficiency and even 57% mineralization rate of STZ within 40 min. More importantly, the rate constant of CN-Fe was calculated to be 0.07665 min-1, which was 6 times higher than that of the commercial α-Fe2O3 catalyst. Furthermore, CN-Fe also presented a favorable catalytic performance for removing other organic pollutants including phenolic compounds and organic dyes. Interestingly, the catalytic activity of the used CN-Fe catalyst could be regenerated after thermal treatment (600 °C) and the as-synthesized CN-Fe catalyst exhibited excellent long-term stability with almost no loss of activity after storage for three months. The catalytic mechanism in the CN-Fe/PMS system was elucidated by electron paramagnetic resonance (EPR), linear sweep voltammetry (LSV), radical and electron trapping tests, which confirmed that sulfate radicals (SO4-), hydroxyl radicals (OH), superoxide radicals (O2-) and singlet oxygen (1O2) were generated in the oxidation process with the assistance of electron transfer between PMS and catalyst. To our knowledge, this was the first attempt for the application of PANI-derived CN-Fe hybrid materials as PMS activators and the findings would provide a simple and promising strategy to fabricate highly efficient and environment-benign catalysts for wastewater remediation.

Verrucosispora rhizosphaerae sp. nov., isolated from mangrove rhizosphere soil.

An actinomycete strain, 2603PH03T, was isolated from a mangrove rhizosphere soil sample collected in Wenchang, China. Phylogenetic analysis of the 16S rRNA gene sequence of strain 2603PH03T indicated high similarity to Verrucosispora gifthornensis DSM 44337T (99.4%), Verrucosispora andamanensis (99.4%), Verrucosispora fiedleri MG-37T (99.4%) and Verrucosispora maris AB18-032T (99.4%). The cell wall was found to contain meso-diaminopimelic acid and glycine. The major menaquinones were identified as MK-9(H4), MK-9(H6) and MK-9(H8), with MK-9(H2), MK-10(H2), MK-9(H10) and MK-10(H6) as minor components. The characteristic whole cell sugars were found to be xylose and mannose. The phospholipid profile was found to contain phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol mannoside, phosphatidylinositol, phosphatidylserine and an unidentified phospholipid. The DNA G+C content was determined to be 70.1 mol%. The results of physiological and biochemical tests and low DNA-DNA relatedness readily distinguished the isolate from the closely related species. On the basis of these phenotypic and genotypic data, strain 2603PH03T is concluded to represent a novel species of the genus Verrucosispora, for which the name Verrucosispora rhizosphaerae sp. nov. is proposed. The type strain is 2603PH03T (=CCTCC AA 2016023T = DSM 45673T).