Household Environments and Functional Decline Among Middle-Aged and Older Adults in China: Variations by Gender, Age, and Residence.

This study examined the associations between household social, economic, and physical environments and the trajectory of functional limitations over time among middle-aged and older adults in China, and how this relationship differs by gender, age, and residence. Linear growth curve models were applied to a sample of 13,564 respondents aged 45 years and older from four waves of the China Health and Retirement Longitudinal Study (CHARLS 2011-2018). Living alone, particularly for rural, female, and older respondents, was associated with a faster functional decline when compared to living with a spouse and without children. Improved housing quality was associated with a slower functional decline. Living with young descendants and without adult children for urban residents and a lower expenditure per capita for younger respondents were associated with a faster functional decline. These findings suggest that policies aimed at enhancing living conditions have the potential to improve physical functioning of older adults.

Idebenone ameliorates statin-induced myotoxicity in atherosclerotic ApoE-/- mice by reducing oxidative stress and improving mitochondrial function.

Statins are the first line of choice for the treatment for atherosclerosis, but their use can cause myotoxicity, a common side effect that may require dosage reduction or discontinuation. The exact mechanism of statin-induced myotoxicity is unknown. Previous research has demonstrated that the combination of idebenone and statin yielded superior anti-atherosclerotic outcomes. Here, we investigated the mechanism of statin-induced myotoxicity in atherosclerotic ApoE-/- mice and whether idebenone could counteract it. After administering simvastatin to ApoE-/- mice, we observed a reduction in plaque formation as well as a decrease in their exercise capacity. We observed elevated levels of lactic acid and creatine kinase, along with a reduction in the cross-sectional area of muscle fibers, an increased presence of ragged red fibers, heightened mitochondrial crista lysis, impaired mitochondrial complex activity, and decreased levels of CoQ9 and CoQ10. Two-photon fluorescence imaging revealed elevated H2O2 levels in the quadriceps, indicating increased oxidative stress. Proteomic analysis indicated that simvastatin inhibited the tricarboxylic acid cycle. Idebenone treatment not only further reduced plaque formation but also ameliorated the impaired exercise capacity caused by simvastatin. Our study represents the inaugural comprehensive investigation into the mechanisms underlying statin-induced myotoxicity. We have demonstrated that statins inhibit CoQ synthesis, impair mitochondrial complex functionality, and elevate oxidative stress, ultimately resulting in myotoxic effects. Furthermore, our research marks the pioneering identification of idebenone's capability to mitigate statin-induced myotoxicity by attenuating oxidative stress, thereby safeguarding mitochondrial complex functionality. The synergistic use of idebenone and statin not only enhances the effectiveness against atherosclerosis but also mitigates statin-induced myotoxicity.

[Correlation Analysis of Peripheral Blood B Cell Count with Clinical Features and Prognosis in Patients Newly Diagnosed with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To explore the correlation between peripheral blood B cell count and clinical features and prognosis of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS: The relationship of peripheral blood B cell count with clinical features, laboratory indexes and prognosis in 67 patients with newly diagnosed DLBCL was retrospectively analyzed. RESULTS: Patients were divided into low B-cell count group (B cell＜0.1×109/L, n=34) and high B-cell count group (B cell≥0.1×109/L, n=33) according to the median B cell count values. Compared with the high B cell count group, the low B cell count group had a higher proportion of patients with Lugano stage III-IV, elevated LDH, elevated ß2-MG and IPI score 3-5 and increased CRP (P =0.033, 0.000, 0.023, 0.001, 0.033). The peripheral CD3+ and CD4+ cell counts of patients in the low B cell count group were significantly lower than those in the high B cell count group (P =0.010, 0.017). After initial treatment, overall response rate (ORR) and complete remission (CR) rate in high B cell count group were significantly higher than those in low B cell count group (P =0.032, 0.013). The median follow-up time of patients was 23(2-77) months, progression-free survival (PFS) and overall survival (OS) of patients in the high B cell count group were significantly better than those in the low B cell count group (P =0.001, 0.002). Univariate analysis showed that pretreatment low B cell count in the peripheral blood was associated with shortened PFS and OS (HR=4.108, P =0.002; HR=8.218, P =0.006). Multivariate analysis showed that low B cell count was an independent prognostic factor for shortened PFS (HR=3.116, P =0.037). CONCLUSION: Decreased peripheral blood B cell count in newly diagnosed DLBCL patients is associated with high-risk clinical features and may affect the efficacy of immunochemotherapy, which is associated with poor clinical prognosis.

Enhancing water retention and mechanisms of citrus and soya bean dietary fibres in pre-fermented frozen dough.

In recent years, the production of prepared and frozen foods has increased with economic development. However, during freezing, moisture migration forms ice crystals that damage food structure and reduce quality. This study investigates moisture migration changes in pre-fermented dough during frozen storage and effectiveness of Citrus fibre (CF) and Soya dietary fibre (SDF) on quality improvement. Pre-fermented frozen dough properties were evaluated at different freezing storage days with CF and SDF. Results showed frozen storage reduced water retention, converting deeply bound water to weakly bound and free water. Freezable water content increased significantly from 53% (fresh) to 56.95% (60d-control), forming disruptive ice crystals in gluten protein structure. SDF had superior water flow restriction compared to CF, preventing large ice crystal accumulation, enhancing water-holding capacity, and maintaining gluten protein structure. These findings lay a theoretical foundation for improving quality and industrial applications of pre-fermented frozen dough.

Cnidii Fructus: A traditional Chinese medicine herb and source of antiosteoporotic drugs.

BACKGROUND: Osteoporosis (OP) is a prevalent chronic metabolic bone disease for which limited countermeasures are available. Cnidii Fructus (CF), primarily derived from Cnidium monnieri (L.) Cusson., has been tested in clinical trials of traditional Chinese medicine for the management of OP. Accumulating preclinical studies indicate that CF may be used against OP. MATERIALS AND METHODS: Comprehensive documentation and analysis were conducted to retrieve CF studies related to its main phytochemical components as well as its pharmacokinetics, safety and pharmacological properties. We also retrieved information on the mode of action of CF and, in particular, preclinical and clinical studies related to bone remodeling. This search was performed from the inception of databases up to the end of 2022 and included PubMed, China National Knowledge Infrastructure, the National Science and Technology Library, the China Science and Technology Journal Database, Weipu, Wanfang, the Web of Science and the China National Patent Database. RESULTS: CF contains a wide range of natural active compounds, including osthole, bergapten, imperatorin and xanthotoxin, which may underlie its beneficial effects on improving bone metabolism and quality. CF action appears to be mediated via multiple processes, including the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK), Wnt/ß-catenin and bone morphogenetic protein (BMP)/Smad signaling pathways. CONCLUSION: CF and its ingredients may provide novel compounds for developing anti-OP drugs.

BMSC Alleviates Dry Eye by Inhibiting the ROS-NLRP3-IL-1ß Signaling Axis by Reducing Inflammation Levels.

PURPOSE: Bone marrow mesenchymal stem cells (BMSC) have multiple biological functions and are widely involved in regulating inflammatory diseases, tissue repair and regeneration. However, the mechanism of their action in dry eye disease (DED) is currently unclear. The purpose of this study was to investigate the effect of BMSCs in the treatment of dry eye mice and to explore its specific therapeutic mechanism. METHODS: Mouse corneal epithelial cells (MCECs) were treated with 500 mOsM sodium chloride hypertonic solution to induce a DED cell model. The dry eye animal model was constructed by adding 5 µL 0.2% benzalkonium chloride solution to mouse eyes. Western blotting was used to detect the expression of related proteins, and flow cytometry, enzyme-linked immunosorbent assay (ELISA), terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, hematoxylin-eosin (HE) staining, and periodic acid schiff (PAS) staining were used to detect cell and eye tissue damage. RESULTS: The experimental results showed that BMSCs can reduce the levels of reactive oxygen species (ROS) and inflammatory factors in MCECs, promote cell proliferation, inhibit cell apoptosis, improve the integrity of the corneal epithelial layer in vivo, promote an increase in the number of goblet cells, and alleviate DED. Further exploration of the molecular mechanism of BMSCs treatment revealed that BMSCs alleviate the progression of DED by inhibiting the ROS-NLRP3-IL-1ß signaling pathway. CONCLUSION: BMSCs inhibit ROS-NLRP3-IL-1ß signaling axis, reducing inflammation levels and alleviating dry eye symptoms. These findings provide new ideas and a basis for the treatment of DED and provide an experimental basis for further research on the application value of BMSCs in alleviating DED.

Generation of human vascularized and chambered cardiac organoids for cardiac disease modelling and drug evaluation.

Human induced pluripotent stem cell (hiPSC)-derived cardiac organoids (COs) have shown great potential in modelling human heart development and cardiovascular diseases, a leading cause of global death. However, several limitations such as low reproducibility, limited vascularization and difficulty in formation of cardiac chamber were yet to be overcome. We established a new method for robust generation of COs, via combination of methodologies of hiPSC-derived vascular spheres and directly differentiated cardiomyocytes from hiPSCs, and investigated the potential application of human COs in cardiac injury modelling and drug evaluation. The human COs we built displayed a vascularized and chamber-like structure, and hence were named vaschamcardioids (vcCOs). These vcCOs exhibited approximately 90% spontaneous beating ratio. Single-cell transcriptomics identified a total of six cell types in the vcCOs, including cardiomyocytes, cardiac precursor cells, endothelial cells, fibroblasts, etc. We successfully recaptured the processes of cardiac injury and fibrosis in vivo on vcCOs, and showed that the FDA-approved medication captopril significantly attenuated cardiac injury-induced fibrosis and functional disorders. In addition, the human vcCOs exhibited an obvious drug toxicity reaction to doxorubicin in a dose-dependent manner. We developed a three-step method for robust generation of chamber-like and vascularized complex vcCOs, and our data suggested that vcCOs might become a useful model for understanding pathophysiological mechanisms of cardiovascular diseases, developing intervention strategies and screening drugs.

Targeting PRMT9-mediated arginine methylation suppresses cancer stem cell maintenance and elicits cGAS-mediated anticancer immunity.

Current anticancer therapies cannot eliminate all cancer cells, which hijack normal arginine methylation as a means to promote their maintenance via unknown mechanisms. Here we show that targeting protein arginine N-methyltransferase 9 (PRMT9), whose activities are elevated in blasts and leukemia stem cells (LSCs) from patients with acute myeloid leukemia (AML), eliminates disease via cancer-intrinsic mechanisms and cancer-extrinsic type I interferon (IFN)-associated immunity. PRMT9 ablation in AML cells decreased the arginine methylation of regulators of RNA translation and the DNA damage response, suppressing cell survival. Notably, PRMT9 inhibition promoted DNA damage and activated cyclic GMP-AMP synthase, which underlies the type I IFN response. Genetically activating cyclic GMP-AMP synthase in AML cells blocked leukemogenesis. We also report synergy of a PRMT9 inhibitor with anti-programmed cell death protein 1 in eradicating AML. Overall, we conclude that PRMT9 functions in survival and immune evasion of both LSCs and non-LSCs; targeting PRMT9 may represent a potential anticancer strategy.

State-transition modeling of blood transcriptome predicts disease evolution and treatment response in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is initiated and maintained by BCR::ABL which is clinically targeted using tyrosine kinase inhibitors (TKIs). TKIs can induce long-term remission but are also not curative. Thus, CML is an ideal system to test our hypothesis that transcriptome-based state-transition models accurately predict cancer evolution and treatment response. We collected time-sequential blood samples from tetracycline-off (Tet-Off) BCR::ABL-inducible transgenic mice and wild-type controls. From the transcriptome, we constructed a CML state-space and a three-well leukemogenic potential landscape. The potential's stable critical points defined observable disease states. Early states were characterized by anti-CML genes opposing leukemia; late states were characterized by pro-CML genes. Genes with expression patterns shaped similarly to the potential landscape were identified as drivers of disease transition. Re-introduction of tetracycline to silence the BCR::ABL gene returned diseased mice transcriptomes to a near healthy state, without reaching it, suggesting parts of the transition are irreversible. TKI only reverted the transcriptome to an intermediate disease state, without approaching a state of health; disease relapse occurred soon after treatment. Using only the earliest time-point as initial conditions, our state-transition models accurately predicted both disease progression and treatment response, supporting this as a potentially valuable approach to time clinical intervention, before phenotypic changes become detectable.

Early life exposure to Chinese famine and risk of digestive system cancer in midlife.

To investigate whether early-life exposure to the Great Famine of 1959-1961 in China was associated with the risk of digestive system cancer. The prospective cohort study involved 17 997 participants from the Kailuan Study (Tangshan, China) that began in 2006. All participants were divided into three groups based on their date of birth. The unexposed group (born from 1 October 1962 to 30 September 1964), fetal-exposed group (born from 1 October 1959 to 30 December 1961), and early-childhood-exposed group (born from 1 October 1956 to 30 December 1958). The Cox proportional hazards model was used to analyze the association between early famine exposure and digestive system cancer. During the mean follow-up period of (10.4 ± 2.2) years, a total of 223 digestive system cancer events occurred. Including 54 cases in the unexposed group (62.14/100 000 person-years), 57 cases in the fetal-exposed group (114.8/100 000 person-years), and 112 cases in the early-childhood-exposure group (122.2/100 000 person-years). After adjusting covariates, compared with the unexposed group, the HR and 95% CI were 1.85 (1.28, 2.69) for participants in the fetal-exposed group and 1.92 (1.38, 2.66) for participants in the early-childhood-exposed group. No interactions were observed in our study. After classifying digestive system cancers, the HR and 95% CI were 2.02 (1.03, 3.97) for colorectal cancer for participants in the fetal-exposed group and 2.55 (1.43, 4.55) for participants in the early-childhood-exposed group. The HR and 95% CI were (1.13, 3.83) of liver cancer for participants in the fetal-exposed group and 1.15 (0.63, 2.10) for participants in the early-childhood-exposed group. Early-life famine exposure was associated with a higher risk of digestive system cancer in adulthood. Fetal-exposed individuals might increase the risk of colorectal cancer and liver cancer, and early childhood-exposed might increase the risk of colorectal cancer.

Characteristics and phylogenetic analysis of the complete mitochondrial genome of Erasmia pulchella Hope, 1840 (lepidoptera: zygaenidae).

Erasmia pulchella has brightly colored wings and releases toxic cyanide as a defense against predation. At present, the molecular phylogenetic status of this species is still unclear. Here, we presented the first complete mitochondrial genome of the genus Erasmia, which was assembled from data generated using a genome skimming method. The assembled mitogenome was 15,197 bp in length and consists of 37 genes, including 13 protein-coding genes, two rRNAs, 22 tRNAs, and a control region. Phylogenetic analysis based on both maximum likelihood (ML) and Bayesian inference (BI) revealed that E. pulchella was most closely related to Amesia sanguiflua.

A comparative study on riboflavin responsive multiple acyl-CoA dehydrogenation deficiency due to variants in FLAD1 and ETFDH gene.

Lipid storage myopathy (LSM) is a heterogeneous group of lipid metabolism disorders predominantly affecting skeletal muscle by triglyceride accumulation in muscle fibers. Riboflavin therapy has been shown to ameliorate symptoms in some LSM patients who are essentially concerned with multiple acyl-CoA dehydrogenation deficiency (MADD). It is proved that riboflavin responsive LSM caused by MADD is mainly due to ETFDH gene variant (ETFDH-RRMADD). We described here a case with riboflavin responsive LSM and MADD resulting from FLAD1 gene variants (c.1588 C > T p.Arg530Cys and c.1589 G > C p.Arg530Pro, FLAD1-RRMADD). And we compared our patient together with 9 FLAD1-RRMADD cases from literature to 106 ETFDH-RRMADD cases in our neuromuscular center on clinical history, laboratory investigations and pathological features. Furthermore, the transcriptomics study on FLAD1-RRMADD and ETFDH-RRMADD were carried out. On muscle pathology, both FLAD1-RRMADD and ETFDH-RRMADD were proved with lipid storage myopathy in which atypical ragged red fibers were more frequent in ETFDH-RRMADD, while fibers with faint COX staining were more common in FLAD1-RRMADD. Molecular study revealed that the expression of GDF15 gene in muscle and GDF15 protein in both serum and muscle was significantly increased in FLAD1-RRMADD and ETFDH-RRMADD groups. Our data revealed that FLAD1-RRMADD (p.Arg530) has similar clinical, biochemical, and fatty acid metabolism changes to ETFDH-RRMADD except for muscle pathological features.

Effects of restoration years on soil nitrogen and phosphorus in inland salt marshes.

Inland salt marsh wetlands have very important ecological functions in semi-arid areas. However, degradation and soil desertification have impacted these areas, making it necessary to study the impact of wetland restoration years on the soil quality of salt marsh wetland. We used remote sensing methods, field surveys, and inquiries to examine the seasonal profile effects of two-, four-, and six-year restoration periods on total nitrogen (TN), total phosphorus (TP) and the ratio of nitrogen to phosphorus (N:P) in P. australis and S. triqueter wetland natural states. Our results showed that soil TN in P. australis wetland in restored conditions was higher than that in natural conditions. The average soil TP of the S. triqueter wetlands at 0-10 cm, 10-20 cm, 20-30 cm, and 30-40 cm layers was 0.36 g/kg, 0.31 g/kg, 0.21 g/kg, and 0.17 g/kg s in September, respectively. The soil TP of the S. triqueter wetland increased slightly over the entire growing season. The restoration years had a great influence on the soil TP of the S. triqueter wetland from May to July. The soil TN in the P. australis wetland was almost restored to its natural condition in each layer during the six-year restoration period. The soil TP of the S. triqueter wetland was higher in the restored two-year period and showed a decreasing trend with an increased soil depth. Our conclusions can significantly guide the restoration of inland salt marsh wetlands.

End-stage renal disease in a critical patient with superior vena cava syndrome with central vein catheters inserted via the superficial femoral vein: A case study.

Superior vena cava syndrome (SVCS) is caused by obstruction to the blood flow through this vein. Indwelling central venous devices, such as cardiac pacemakers and haemodialysis catheters have emerged as the most common benign aetiology of SVCS. SVCS is particularly severe in patients with end-stage renal disease who require continuous renal replacement therapy plus infusion therapy. The presence of SVCS results in a reduction of available venous access for affected patients. Therefore, venous access plays a crucial role in the management of these patients. The importance of dealing with vascular access (VA) in critical patients with these conditions cannot be overstated. This case describes an 81-year-old man with respiratory failure who had end-stage renal disease complicated with SVCS. Using ultrasound-guided puncture, we inserted a peripherally inserted central catheter (PICC) into the superficial femoral vein to meet his infusion requirements in intensive care. After successful placement, the catheter tip position was adjusted using imaging to position the tip relative to the haemodialysis catheter. Whenever patients with severe renal dysfunction are treated, central veins should be preserved. Safe PICC access is possible via the superficial femoral vein to protect the last central VA for rational use. This meets urgent needs for infusion and deserves promotion.

Doping strategies for inorganic lead-free halide perovskite solar cells: progress and challenges.

In recent years, remarkable advancements have been achieved in the field of halide perovskite solar cells (PSCs). However, the commercialization of PSCs has been impeded by challenges such as Pb leakage and the instability of hybrid organic-inorganic perovskites (HOIPs). Hence, the future lies in the development of environmentally friendly inorganic lead-free halide perovskites (LFHPs) based on elements like Sn, Ge, Bi, Sb, and Cu, which show great promise for photovoltaic applications. However, LFHP photovoltaic cells still face challenges such as low efficiency, poor film quality, and stability in comparison to HOIPs. These limitations significantly hinder their further development. To address these issues, element doping strategies, including cationic and anionic doping, as well as the use of additives, are frequently employed. These strategies aim to improve film quality, passivate defects, reduce the band gap, and enhance device performance and stability. In this paper, we aim to provide a comprehensive review of the recent research progress in doping strategies for LFHPs.

Preparation of pectin-coated and chitosan-coated phenylethanoside liposomes: Studies on characterization, stability, digestion and release behavior.

In this paper, the effects of extrusion, ultrasound on physicochemical properties of liposomes were studied, and the liposomes were prepared by ethanol injection combined with extrusion-ultrasound. In addition, the quality of PhGs lips, pectin-coated PhGs lips (P-lips) and chitosan-coated PhGs lips (C-lips) was evaluated by the average particle size, encapsulation efficiency (EE) and other indicators, which indicated that the nanoparticles had been successfully prepared. Compared with extrusion or ultrasonic operation alone, the EEs of ethanol injection combined with extrusion-ultrasonic increased by 8 % and 18 % respectively. Subsequently, transmission electron microscopy, Fourier transform infrared spectroscopy and DSC thermal analysis showed that PhGs in PhGs lips may produce hydrogen bonding forces with phospholipids, and pectin and chitosan in P-lips and C-lips were not only coated on the surface of PhGs lips, but also might have some interaction between them. Cell experiments showed that PhGs lips, P-lips and C-lips can effectively improve the bioavailability of PhGs. In addition, the storage stability of P-lips and C-lips was not significantly improved compared to PhGs lips, but their digestive stability was significantly improved, and the final retention rate in simulated intestinal fluid was about 25 % higher than that of PhGs lips.

The antiviral effects of TRIM23 and TRIM32 proteins in rainbow trout (Oncorhynchus mykiss).

TRIM proteins play a crucial antiviral effector role in the innate immune system of vertebrates. In this study, we found that TRIM proteins exhibited the highest expression levels in immune organs such as spleen and kidney during IHNV infection in rainbow trout, meanwhile, we successfully amplified TRIM23 and TRIM32 from diseased rainbow trout and analyzed their gene sequences, revealing that rainbow trout TRIM23 and TRIM32 proteins are closely related to Atlantic salmon and Chinook salmon; In this experiment, the TRIM23 and TRIM32 protein genes were resoundingly constructed as a recombinant plasmids and expressed in CHSE-214 cells. Upon transfected with the recombinant plasmid, followed by viral infection, significant decreasion in the copy numbers of the virus was observed, indicating that the TRIM23 and TRIM32 proteins of rainbow trout play an important role in inhibiting virus replication, with the TRIM32 role being the most pronounced. These results provide a basis for subsequent in-depth study of the antiviral effects of TRIM proteins, and provide new ideas for immune enhancers.

Geographical region traceability of wild topmouth culter (Culter alburnus) from Xingkai Lake based on muscle quality and aroma profiles.

The wild topmouth culter (Culter alburnus) from Xingkai Lake (XKL) is highly regarded for its delicious taste and unique flavor. In this study, based on muscle quality and aroma analysis, we first differentiated the XKL population from three wild populations in Heilongjiang Province and one artificially cultured population (from Xingkai Lake). Compared with the other populations, the XKL population has a significantly higher crude protein content, essential amino acid content, delicious amino acid content, and n-3/n-6 PUFA ratio. Additionally, it exhibits superior hardness, elasticity, chewiness, recoverability, and viscosity. E-nose detection analysis revealed that W1S, W2S, and W3S were the potential sensors contributing the most to the differences among the five populations. HS-SPME-GC-MS and multivariate regression analysis showed that 21 volatile flavor compounds were identified as key markers for geographical identification of the Xingkai Lake region. These findings will provide guidance for the geographical traceability and identification of the XKL population.

A novel benzothiazole-based mononuclear platinum(II) complex displaying potent antiproliferative activity in HepG-2 cells via mitochondrial-mediated apoptosis.

A novel mononuclear platinum(II) complex, [Pt(L-H)Cl] (1, where L= N-(4-(benzo[d]thiazol-2-yl)phenyl)-2-((2-pyridylmethyl)(2-hydroxyethyl)-amino)acetamide), was obtained by covalently tethering a benzothiazole derivative 2-(4-aminophenyl)benzothiazole to the 2-pyridylmethyl-2-hydroxyethylamine chelating PtII center. In vitro tests indicated that complex 1 displayed excellent antiproliferative activity against the tested cancer cell lines, especially liver cancer HepG-2 and SMMC-7221 cells. Importantly, the complex possessed 4.33-fold higher antiproliferative activity as compared with cisplatin against HepG-2 cells, but was less toxic to the normal cell line L02 with the selectivity index (SI = IC50(L02)/IC50(HepG-2)) value of 8.36 compared to cisplatin (SI, 1.40). The results suggested that 1 might have the potential to act as a candidate for the treatment of hepatocellular carcinoma (HCC). Cellular uptake and distribution studies showed that 1 could effectively pass through the membrane of cells, enter the nuclei and mitochondria, induce the platination of cellular DNA. The interaction of 1 with CT-DNA demonstrated that 1 could effectively bind to DNA in a dual binding mode, i.e., the intercalation of the 2-(4-aminophenyl)benzothiazole unit plus monofunctional platination of the platinum(II) moiety. In addition, Hoechst 33342 staining and flow cytometry analysis illustrated that 1 arrested the cell cycle in HepG-2 cancer cells at G2/M phases, induced mitochondrial membrane depolarization, increased ROS generation, and caused obvious cell apoptosis. Further cellular mechanism studies elucidated that 1 triggered HepG-2 cell apoptosis via the mitochondrial-mediated pathway by upregulating the gene and protein expression levels of Bax, downregulating the gene and protein expression levels of Bcl-2, and activating the caspase cascade.

Mitochondrial myopathy without extraocular muscle involvement: a unique clinicopathologic profile.

OBJECTIVE: Mitochondrial myopathy without extraocular muscles involvement (MiMy) represents a distinct form of mitochondrial disorder predominantly affecting proximal/distal or axial muscles, with its phenotypic, genotypic features, and long-term prognosis poorly understood. METHODS: A cross-sectional study conducted at a national diagnostic center for mitochondrial disease involved 47 MiMy patients, from a cohort of 643 mitochondrial disease cases followed up at Qilu Hospital from January 1, 2000, to January 1, 2021. We compared the clinical, pathological, and genetic features of MiMy to progressive external ophthalmoplegia (PEO) and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) patients. RESULTS: MiMy patients demonstrated a more pronounced muscle involvement syndrome, with lower 6MWT scores, higher FSS, and lower BMI compared to PEO and MELAS patients. Serum levels of creatinine kinase (CK), lactate, and growth and differentiation factor 15 (GDF15) were substantially elevated in MiMy patients. Nearly a third (31.9%) displayed signs of subclinical peripheral neuropathy, mostly axonal neuropathy. Muscle biopsies revealed that cytochrome c oxidase strong (COX-s) ragged-red fibers (RRFs) were a typical pathological feature in MiMy patients. Genetic analysis predominantly revealed mtDNA point pathogenic variants (59.6%) and less frequently single (12.8%) or multiple (4.2%) mtDNA deletions. During the follow-up, a majority (76.1%) of MiMy patients experienced stabilization or improvement after therapeutic intervention. CONCLUSIONS: This study provides a comprehensive profile of MiMy through a large patient cohort, elucidating its unique clinical, genetic, and pathological features. These findings offer significant insights into the diagnostic and therapeutic management of MiMy, ultimately aiming to ameliorate patient outcomes and enhance the quality of life.