In recent years, the roles of mitochondrial RNA and its associated human diseases have been reported to increase significantly. Treatments based on mtRNA metabolic processes and nuclear gene mutations are thus discussed. The mitochondrial oxidative phosphorylation process is affected by mtRNA metabolism, including mtRNA production, maturation, stabilization, and degradation, which leads to a variety of inherited human mitochondrial diseases. Moreover, mitochondrial diseases are caused by mitochondrial messenger RNA, mitochondrial transfer RNA, and mitochondrial ribosomal RNA gene mutations. This review presents the molecular mechanisms of human mtRNA metabolism and pathological mutations in mtRNA metabolism-related nuclear-encoded/nonencoded genes and mitochondrial DNA mutations to highlight the importance of mitochondrial RNA-related diseases and treatments.
Humans ; Mitochondrial Diseases/therapy* ; RNA, Mitochondrial ; RNA/genetics* ; Mitochondria/genetics* ; Mutation/genetics* ; RNA, Transfer/genetics* ; DNA, Mitochondrial/genetics*

Acute kidney injury (AKI) is a critical clinical condition characterized by rapid renal function decline, with high morbidity, mortality, and healthcare costs. Traditional Chinese medicine (TCM) has shown potential effects on mitigating oxidative stress and programmed cell death in AKI models. Scutellaria barbata D. Don (SB) and Scleromitrion diffusum (Willd.) R. J. Wang (SD), a classic TCM herbal pair exhibited anti-inflammatory and antioxidant activities. Using advanced chromatographic separation technology, we enriched the effective fractions of water extracts from SB-SD, obtaining self-assembled herbal nanoparticles (SB and SD nanoparticles, SSNPs) rich in flavonoids and terpenoids. These SSNPs demonstrated robust antioxidant properties in vitro and mitigated AKI progression in vivo by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Oral administration of SSNPs in mice resulted in absorption into the bloodstream, formation of a protein corona, reduced macrophage phagocytosis, and enhanced bioavailability and renal targeting. Furthermore, we investigated the self-assembly principle of SSNPs using representative flavonoids and terpenoids. Kinetic studies and in situ transmission electron microscopy (in situ TEM) revealed that these compounds self-assemble via supramolecular forces like hydrogen bonding and π-π interactions, forming stable nanostructures. This study elucidates the renoprotective effects and mechanisms of SB and SD, and provides a novel approach for the development of TCM-based nanomedicines, highlighting the potential of nano-TCM in AKI treatment.

Objective:To study the risk factors and the molecular epidemiology characteristics for Carbapenem-resistant Enterobacteriaceae(CRE) colonization in neonatal inpatients in Shenzhen region, China, which provide reference for the prevention and control of clinical CRE infection.Methods:This study is a prospective case-control study.Anal samples from inpatients between January 2023 and December 2023 at Longgang Maternity and Child Institute of Shantou University Medical College and Shenzhen Children's Hospital were collected for screening CRE strain. Drug susceptibility test, modified Carbapenem Inactivation Method (mCIM) test, drug resistance-related gene sequencing and multilocus sequence typing (MLST) were performed for isolated CRE strains.Meanwhile, the clinical data were collected for analyzing the risk factors of CRE intestinal colonization by multivariate regression analysis.Results:A total of 1 517 patients were screened, 26 CRE(1.7%, 26/1 517) were identified which including 14 Escherichia coli(53.8%, 14/26), 11 Klebsiella pneumoniae(42.3%, 11/26), 1 Enterobacter cloacae(3.9%, 1/26). The predominant carbapenemase gene was New Delhi Metallo(NDM) (92.4%, 24/26), followed by Imipenem (IMP) (3.8%, 1/26) and Guiana extended spectrum gene (GES) (3.8%, 1/26).Among the carried NDM resistance genes, New Delhi Metallo 5 (NDM5) was the main one, accounting for 84.6% (22/26).The MLST typing of Escherichia coli was mainly Sequence Type 48 (ST48) (6/14), while that of Klebsiella pneumoniae was mainly Sequence Type 35 (ST35) (10/11). All CRE isolates were resistant to penicillin, penicillinase inhibitors, cephalosporins, ertapenem and imipenem.The resistance rates of Escherichia coli to amikacin, levofloxacin was 1/14, 4/14, respectively. All isolates of Klebsiella pneumoniae were sensitive to amikacin, and the resistance rate to levofloxacin is 1/11. Risk factors for CRE colonization include the older age, length of hospital stay, tracheal intubation, invasive respiration, lumbar puncture, Apgar <7 score, and exposure to antibiotics.Conclusions:NDM5 is the predominant resistant gene in CRE isolated from neonatal patients feces in Shenzhen region.It is necessary to strengthen the screening of CRE colonization in neonate for prevention and control of CRE infection.

Purpose To investigate the changes of free water(FW)values in the key basal ganglia of dopamine system in the brain of early Parkinson's disease(PD)by free water imaging,and to reveal the potential relationship between the changes and early PD.Materials and Methods From February to December 2023,62 patients with early PD and 27 healthy controls were enrolled in the Parkinson's Disease Progression Markers Project database,and 25 age-and sex-matched healthy controls were self-recruited from Henan Provincial People's Hospital.All subjects underwent clinical scale assessment and MRI data collection.Free water imaging was used to calculate the FW values of key nuclei in dopamine system,and the difference of FW values between PD group and healthy controls group,the correlation between FW values of PD group and clinical scale scores were analyzed.Results The FW values of compact part of substantia nigra(SNc)and ventral tegmental area(VTA)in PD group were significantly higher than those in healthy controls group(Z=2.458-3.914,all P<0.05).Regression analysis showed that FW values of SNc were correlated with the movement disorder society-sponsored revision unified Parkinson′s disease rating scale(MDS-UPDRS)Ⅲ scores and state-trait anxiety inventory(STAI)scores on both sides(r2=0.223,P<0.001;r2=0.125,P=0.018;r2=0.151,P=0.003;r2=0.128,P=0.017),the FW value of VTA on the left was significantly correlated with MDSUPDRS Ⅲ score(r2=0.143,P=0.004)and the FW value of the right VTA was significantly correlated with the STAI score(r2=0.125,P=0.019).Conclusion The FW values of SNc and VTA in PD patients are significantly increased in the early stage,and are correlated with motor and non-motor symptoms in PD patients.FW values may reflect brain degeneration,and this change may be related to the decline of motor and non-motor function in patients.

Objective:To study the risk factors and the molecular epidemiology characteristics for Carbapenem-resistant Enterobacteriaceae(CRE) colonization in neonatal inpatients in Shenzhen region, China, which provide reference for the prevention and control of clinical CRE infection.Methods:This study is a prospective case-control study.Anal samples from inpatients between January 2023 and December 2023 at Longgang Maternity and Child Institute of Shantou University Medical College and Shenzhen Children's Hospital were collected for screening CRE strain. Drug susceptibility test, modified Carbapenem Inactivation Method (mCIM) test, drug resistance-related gene sequencing and multilocus sequence typing (MLST) were performed for isolated CRE strains.Meanwhile, the clinical data were collected for analyzing the risk factors of CRE intestinal colonization by multivariate regression analysis.Results:A total of 1 517 patients were screened, 26 CRE(1.7%, 26/1 517) were identified which including 14 Escherichia coli(53.8%, 14/26), 11 Klebsiella pneumoniae(42.3%, 11/26), 1 Enterobacter cloacae(3.9%, 1/26). The predominant carbapenemase gene was New Delhi Metallo(NDM) (92.4%, 24/26), followed by Imipenem (IMP) (3.8%, 1/26) and Guiana extended spectrum gene (GES) (3.8%, 1/26).Among the carried NDM resistance genes, New Delhi Metallo 5 (NDM5) was the main one, accounting for 84.6% (22/26).The MLST typing of Escherichia coli was mainly Sequence Type 48 (ST48) (6/14), while that of Klebsiella pneumoniae was mainly Sequence Type 35 (ST35) (10/11). All CRE isolates were resistant to penicillin, penicillinase inhibitors, cephalosporins, ertapenem and imipenem.The resistance rates of Escherichia coli to amikacin, levofloxacin was 1/14, 4/14, respectively. All isolates of Klebsiella pneumoniae were sensitive to amikacin, and the resistance rate to levofloxacin is 1/11. Risk factors for CRE colonization include the older age, length of hospital stay, tracheal intubation, invasive respiration, lumbar puncture, Apgar <7 score, and exposure to antibiotics.Conclusions:NDM5 is the predominant resistant gene in CRE isolated from neonatal patients feces in Shenzhen region.It is necessary to strengthen the screening of CRE colonization in neonate for prevention and control of CRE infection.

Purpose To investigate the changes of free water(FW)values in the key basal ganglia of dopamine system in the brain of early Parkinson's disease(PD)by free water imaging,and to reveal the potential relationship between the changes and early PD.Materials and Methods From February to December 2023,62 patients with early PD and 27 healthy controls were enrolled in the Parkinson's Disease Progression Markers Project database,and 25 age-and sex-matched healthy controls were self-recruited from Henan Provincial People's Hospital.All subjects underwent clinical scale assessment and MRI data collection.Free water imaging was used to calculate the FW values of key nuclei in dopamine system,and the difference of FW values between PD group and healthy controls group,the correlation between FW values of PD group and clinical scale scores were analyzed.Results The FW values of compact part of substantia nigra(SNc)and ventral tegmental area(VTA)in PD group were significantly higher than those in healthy controls group(Z=2.458-3.914,all P<0.05).Regression analysis showed that FW values of SNc were correlated with the movement disorder society-sponsored revision unified Parkinson′s disease rating scale(MDS-UPDRS)Ⅲ scores and state-trait anxiety inventory(STAI)scores on both sides(r2=0.223,P<0.001;r2=0.125,P=0.018;r2=0.151,P=0.003;r2=0.128,P=0.017),the FW value of VTA on the left was significantly correlated with MDSUPDRS Ⅲ score(r2=0.143,P=0.004)and the FW value of the right VTA was significantly correlated with the STAI score(r2=0.125,P=0.019).Conclusion The FW values of SNc and VTA in PD patients are significantly increased in the early stage,and are correlated with motor and non-motor symptoms in PD patients.FW values may reflect brain degeneration,and this change may be related to the decline of motor and non-motor function in patients.

Objective To evaluate the application of three deep learning algorithms in automatic segmentation of clinical target volumes (CTVs) in high-dose-rate brachytherapy after surgery for endometrial carcinoma. Methods A dataset comprising computed tomography scans from 306 post-surgery patients with endometrial carcinoma was divided into three subsets: 246 cases for training, 30 cases for validation, and 30 cases for testing. Three deep convolutional neural network models, 3D U-Net, 3D Res U-Net, and V-Net, were compared for CTV segmentation. Several commonly used quantitative metrics were employed, i.e., Dice similarity coefficient, Hausdorff distance, 95th percentile of Hausdorff distance, and Intersection over Union. Results During the testing phase, CTV segmentation with 3D U-Net, 3D Res U-Net, and V-Net showed a mean Dice similarity coefficient of 0.90 ± 0.07, 0.95 ± 0.06, and 0.95 ± 0.06, a mean Hausdorff distance of 2.51 ± 1.70, 0.96 ± 1.01, and 0.98 ± 0.95 mm, a mean 95th percentile of Hausdorff distance of 1.33 ± 1.02, 0.65 ± 0.91, and 0.40 ± 0.72 mm, and a mean Intersection over Union of 0.85 ± 0.11, 0.91 ± 0.09, and 0.92 ± 0.09, respectively. Segmentation based on V-Net was similarly to that performed by experienced radiation oncologists. The CTV segmentation time was < 3.2 s, which could save the work time of clinicians. Conclusion V-Net is better than other models in CTV segmentation as indicated by quantitative metrics and clinician assessment. Additionally, the method is highly consistent with the ground truth, reducing inter-doctor variability and treatment time.

Long-chain acyl-coenzyme A (CoA) synthase 4 (ACSL4) is an enzyme that esterifies CoA into specific polyunsaturated fatty acids, such as arachidonic acid and adrenic acid. Based on accumulated evidence, the ACSL4-catalyzed biosynthesis of arachidonoyl-CoA contributes to the execution of ferroptosis by triggering phospholipid peroxidation. Ferroptosis is a type of programmed cell death caused by iron-dependent peroxidation of lipids; ACSL4 and glutathione peroxidase 4 positively and negatively regulate ferroptosis, respectively. In addition, ACSL4 is an essential regulator of fatty acid (FA) metabolism. ACSL4 remodels the phospholipid composition of cell membranes, regulates steroidogenesis, and balances eicosanoid biosynthesis. In addition, ACSL4-mediated metabolic reprogramming and antitumor immunity have attracted much attention in cancer biology. Because it facilitates the cross-talk between ferroptosis and FA metabolism, ACSL4 is also a research hotspot in metabolic diseases and ischemia/reperfusion injuries. In this review, we focus on the structure, biological function, and unique role of ASCL4 in various human diseases. Finally, we propose that ACSL4 might be a potential therapeutic target.
Humans ; Ferroptosis ; Apoptosis ; Phospholipids/metabolism* ; Nitric Oxide Synthase

Objective:To investigate the changes of biventricular myocardial strain in amateur marathon runners using the cardiac MR feature tracking (CMR-FT) technique.Methods:Forty-one amateur marathon runners (marathon exercise group) and 20 age-matched healthy volunteers (control group) were recruited according to the inclusion criteria. After the kinematic parameters were obtained, all subjects underwent a CMR cine sequence imaging. The CMR images were post-processed using CVI42 software. The biventricular function parameters including end-diastole/end-systolic volume (EDV/ESV), end-diastole/end-systolic volume index (EDVI/ESVI), end-diastole/end-systolic myocardial mass (MMD/MMS), end-diastole/end-systolic myocardial mass index (MMDI/MMSI), stroke volume and index (SV/SVI), cardiac index (CI) and ejection fraction (EF), as well as the biventricular myocardial strain parameters including global radial/circumferential/longitudinal strain (GRS/GCS/GLS), global radial/circumferential/longitudinal diastolic strain rate (GRSDr/GCSDr/GLSDr) were measured and calculated. Demographic data, kinematic index, cardiac function and myocardial strain parameters were compared between the two groups.Results:Compared with the control group, the exercise group showed significant decrease heart rates ( P<0.001). It was found that the left ventricular function parameters (ESVI, MMD, MMDI, MMS, MMSI) and the right ventricular function parameters (EDVI, ESVI) of the exercise group were significantly higher than those of control group (all P<0.05); while the left ventricular strain parameters (GCS, GRSDr, GCSDr, GLSDr) and the right ventricular strain parameters (GRSDr, GLSDr) were of the exercise group were significantly lower than those of control group (all P<0.05). Conclusions:Amateur marathon runners have lower myocardial strain capacity and higher left ventricular myocardial mass. The ventricular diastolic strain rate may sensitively reflect the compensatory changes of ventricular function with the normal ejection fraction.

Objective:To screen the differentially expressed exosomal miRNAs derived from liver cancer stem cells (LCSCs) and its effect on the malignant biological characteristics of liver cancer cells.Methods:miRNA expression profile chip was used to analyze the differentially expressed exosomal miRNA derived from LCSCs. The effects of miRNA on malignant phenotypes of LCSCs were identified. The cells were further treated with doxorubicin at different concentrations (0, 150, 300 μmol/L), and the expression level of miR-196a was detected by quantitative real-time PCR (qRT-PCR). The apoptosis of liver cancer cells cultured by exosomes derived from LCSCs (Exo-NC group) and exosomes derived from miR-196a inhibited LCSCs (Exo-Inhibitor group) and the activity of caspase3/7 under the action of exosomes from LCSCs were detected. Nude mice were randomly divided into Do-PBS group, Do-Exo-Inhibitor group and Do-Exo-NC group using random number table method, with 5 mice in each group, and the effect of miR-196a on nude mice xenograft tumor model with liver cancer cells was analyzed.Results:In this study, exosomes were isolated and purified from CD133 + Huh7 stem cell culture supernatant. miR-7162-3p, miR-1910-5, miR-3613-3p, miR-196a and miR-155-5p were up-regulated, while miR-1246 and miR-3613-5p were down-regulated. miR-7162-3p, miR-196a and miR-155-5p in exosomes had important effects on the self-renewal ability of LCSCs. miR-1910-5p, miR-196a and miR-155-5p had important effects on the invasion ability of liver cancer stem cells, among which miR-196a had the most significant inhibitory effect. Treatment for 24 h, the miR-196a expression level of the 0, 150 and 300 μmol/L doxorubicin was 0.96±0.05, 1.23±0.05 and 2.33±0.03 respectively, with a statistically significant difference ( F=996.90, P<0.001). Treatment for 48 h, the miR-196a expression level of the 0, 150 and 300 μmol/L doxorubicin were 1.02±0.07, 2.35±0.05 and 2.89±0.55 respectively, with a statistically significant difference ( F=303.00, P<0.001). When the concentration of doxorubicin was 0 and 300 μmol/L, the apoptosis rates of the Exo-NC group were 9.37%±0.19% and 11.64%±0.27%, and those of the Exo-Inhibitor group were were 18.80%±1.91% and 22.79%±1.57%, with statistically significant differences ( t=4.41, P=0.048; t=4.96, P=0.038). When doxorubicin was not used, the ratios of caspase3/7 in the Exo-NC group at 24 h and 48 h were 0.94±0.08 and 0.97±0.09, and those in the Exo-Inhibitor group were 1.56±0.01 and 1.58±0.01, with statistically significant differences ( t=11.41, P=0.008; t=6.07, P=0.026). Under 300 μmol/L doxorubicin, the ratios of caspase3/7 in the Exo-NC group at 24 h and 48 h were 0.95±0.07 and 1.36±0.08, and those in the Exo-Inhibitor group were 2.84±0.08 and 3.20±0.14, with statistically significant differences ( t=24.20, P=0.002; t=15.78, P=0.004). The results of xenograft tumor in nude mice showed that the tumor volumes of Do-PBS, Do-Exo-Inhibitor and Do-Exo-NC groups increased successively, which were (1 051.86±89.90) mm 3, (1 310.91±86.66) mm 3 and (2 185.14± 352.34) mm 3 respectively, with a statistically significant difference ( F=30.28, P<0.001). The weights of the transplanted tumors in the 3 groups increased successively, which were (0.36±0.10) g, (0.39±0.12) g and (0.76±0.16) g respectively, with a statistically significant difference ( F=11.81, P=0.002). The expression of miR-196a in tumors was significantly decreased after miR-196a inhibitor transfection. The expression levels of the 3 groups were 1.05±0.16, 0.38±0.08 and 2.17±0.26, with a statistically significant difference ( F=48.93, P<0.001). Conclusion:The exosomal secreted by LCSCs can enhance the resistance of liver cancer cells to doxorubicin by miR-196a.