Mitochondrial Dysfunction-Molecular Mechanisms and Potential Treatment approaches of Hepatocellular Carcinoma.

Primary liver cancer (PLC), also known as hepatocellular carcinoma (HCC), is a common type of malignant tumor of the digestive system. Its pathological form has a significant negative impact on the patients' quality of life and ability to work, as well as a significant financial burden on society. Current researches had identified chronic hepatitis B virus infection, aflatoxin B1 exposure, and metabolic dysfunction-associated steatotic liver disease (MASLD) as the main causative factors of HCC. Numerous variables, including inflammatory ones, oxidative stress, apoptosis, autophagy, and others, have been linked to the pathophysiology of HCC. On the other hand, autoimmune regulation, inflammatory response, senescence of the hepatocytes, and mitochondrial dysfunction are all closely related to the pathogenesis of HCC. In fact, a growing number of studies have suggested that mitochondrial dysfunction in hepatocytes may be a key factor in the pathogenesis of HCC. In disorders linked to cancer, mitochondrial dysfunction has gained attention in recent 10 years. As the primary producer of adenosine triphosphate (ATP) in liver cells, mitochondria are essential for preserving cell viability and physiological processes. By influencing multiple pathological processes, including mitochondrial fission/fusion, mitophagy, cellular senescence, and cell death, mitochondrial dysfunction contributes to the development of HCC. We review the molecular mechanisms of HCC-associated mitochondrial dysfunction and discuss new directions for quality control of mitochondrial disorders as a treatment for HCC.

The JA-to-ABA signaling relay promotes lignin deposition for wound healing in Arabidopsis.

Plants are frequently exposed to herbivory and mechanical damage that result in wounding. Two fundamental strategies, regeneration and healing, are employed by plants upon wounding. How plants make different decisions and how wound healing is sustained until the damaged tissues recover are not fully understood. In this study, we found that local auxin accumulation patterns, determined by wounding modes, may activate different recovery programs in wounded tissues. Wounding triggers transient jasmonic acid (JA) signaling that promotes lignin deposition in the first few hours after wounding occurs. This early response is subsequently relayed to ABA signaling via MYC2. The induced JA signaling promotes ABA biosynthesis to maintain the expression of RAP2.6, a key factor for sustained lignin biosynthesis and the later wound-healing process. Our findings provide mechanistic insights into how plants heal from wounding and clarify the molecular mechanisms that underlie the prolonged healing process following wounding.

Sleep duration and heart failure risk: Insights from a Mendelian Randomization Study.

To investigate the causal relationship between sleep duration and heart failure (HF) in a European population. We focused on the continuous sleep duration of 460,099 European individuals as our primary exposure. Genome-wide significant single nucleotide polymorphisms (SNPs, n = 9851,867) linked to continuous sleep duration were adopted as instrumental variables. The outcome of interest was based on HF events in a European cohort (n = 977,323; with 930,014 controls and 47,309 cases). We employed a two-sample Mendelian randomization (MR) approach to infer causality between sleep duration and the incidence of HF. For validation purposes, an additional cohort of 336,965 European individuals diagnosed with insomnia was selected as a secondary exposure group. Using its SNPs, a subsequent two-sample MR analysis was conducted with the HF cohort to further corroborate our initial findings. Employing the MR methodology, we selected 57 SNPs that are associated with sleep duration, and 24 SNPs that are associated with insomnia as instrumental variables. We discerned a substantial association between genetically inferred sleep duration and HF risk (odds ratio: 0.61; 95% confidence interval: 0.47-0.78, P < .0001). Our subsequent analysis highlighted a pronounced increased HF risk associated with insomnia (odds ratio: 1.54; 95% confidence interval: 1.08-2.17, P < .02). These conclusions were further bolstered by consistent results from sensitivity analyses. Our study suggests a causal linkage between sleep duration and the onset risk of HF in the European population. Notably, shorter sleep durations were associated with a heightened risk of HF.

Effectiveness and feasibility of continuous positive airway pressure in patients with stroke and sleep apnea: a meta-analysis of randomized trials.

STUDY OBJECTIVES: This meta-analysis aimed to investigate the feasibility and effectiveness of continuous positive airway pressure (CPAP) treatment in stroke patients with sleep apnea. METHODS: PubMed, EMBASE, and the Cochrane Library were searched from inception until July 28, 2022, for randomized controlled trials comparing the use of CPAP and usual treatment in patients with stroke or transient ischemic attack and sleep apnea. The primary outcome measures were the feasibility of CPAP therapy, neurological function, and functional status. RESULTS: After screening 5,747 studies, 14 studies with 1,065 patients were included in this meta-analysis. Overall, 8 of the 14 studies recorded CPAP use, and the mean CPAP use was 4.47 hours per night (95% confidence interval [CI]: 3.85-5.09). The risk ratio of discontinuing CPAP was 1.50 (95% CI: 0.76-2.94; P = .24). Analysis of the neurofunctional scales showed that CPAP treatment improved neurological function (standardized mean difference: 0.28; 95% CI: 0.02-0.53), but there was substantial heterogeneity (I2 = 57%, P = .03) across the studies. CPAP treatment had no significant effect on functional status vs the control (standardized mean difference: 0.25; 95% CI: -0.01 to 0.51), but the studies also had substantial heterogeneity (I2 = 55%, P = .06). CONCLUSIONS: CPAP treatment is feasible in patients with stroke and sleep apnea and may improve neurological outcomes in these patients. However, this finding should be interpreted with caution because of the substantial heterogeneity of current trials. CITATION: Fu S, Peng X, Li Y, Yang L, Yu H. Effectiveness and feasibility of continuous positive airway pressure in patients with stroke and sleep apnea: a meta-analysis of randomized trials. J Clin Sleep Med. 2023;19(9):1685-1696.

CRISPR/Cas9 Based Cell-Type Specific Gene Knock-Out in Arabidopsis Roots.

CRISPR/Cas9 (hereafter Cas9)-mediated gene knockout is one of the most important tools for studying gene function. However, many genes in plants play distinct roles in different cell types. Engineering the currently used Cas9 system to achieve cell-type-specific knockout of functional genes is useful for addressing the cell-specific functions of genes. Here we employed the cell-specific promoters of the WUSCHEL RELATED HOMEOBOX 5 (WOX5), CYCLIND6;1 (CYCD6;1), and ENDODERMIS7 (EN7) genes to drive the Cas9 element, allowing tissue-specific targeting of the genes of interest. We designed the reporters to verify the tissue-specific gene knockout in vivo. Our observation of the developmental phenotypes provides strong evidence for the involvement of SCARECROW (SCR) and GIBBERELLIC ACID INSENSITIVE (GAI) in the development of quiescent center (QC) and endodermal cells. This system overcomes the limitations of traditional plant mutagenesis techniques, which often result in embryonic lethality or pleiotropic phenotypes. By allowing cell-type-specific manipulation, this system has great potential to help us better understand the spatiotemporal functions of genes during plant development.

First Detection of blaNDM-1-Haboring IncHI2 Plasmid in Escherichia coli Strain Isolated from Goose in China.

Carbapenem-resistant Enterobacteriaceae infections are among the most serious threats to human and animal health worldwide. Of the 1013 strains of Escherichia coli isolated and identified in 14 regions of China from 2007 to 2018, seven strains were resistant to meropenem and all were positive for blaNDM. The seven New Delhi metallo-ß-lactamase (NDM)-positive strains belonged to five different sequence types, indicating that most of the NDM-positive strains were nonclonal. An IncHI2 plasmid carrying the blaNDM-1 element was identified in the C1147 strain from a goose source and reported for the first time, showing a specific structure. Conjugation experiments revealed that the IncHI2 plasmid was conjugatable, and the horizontal propagation of the plasmid led to the rapid propagation of NDM in the same and different strains. This study revealed that waterfowl, as a potential transmission factor for carbapenem-resistant blaNDM-1, poses a threat to human health.

An Adaptive Fuzzy Approach to Fault Estimation Observer Design With Actuator Fault and Digital Communication.

This article investigates the fault estimation (FE) problem for a class of nonlinear systems via an adaptive fuzzy approach. Considering the limited communication capacity of networks, the quantized measurement signals are used to construct adaptive laws instead of the real measurements in the designed fuzzy observer. By injecting the quantizer parameter into the observer inputs, the quantization effects on the convergence of estimation errors can be compensated. It is also shown that nondifferentiable actuator faults can be reconstructed by the developed FE approach. Finally, two simulation examples are provided to illustrate the validity of the presented scheme.

Application and challenge of bacteriophage in the food protection.

In recent years, foodborne diseases caused by pathogens have been increasing. Therefore, it is essential to control the growth and transmission of pathogens. Bacteriophages (phages) have the potential to play an important role in the biological prevention, control, and treatment of these foodborne diseases due to their favorable advantages. Phages not only effectively inhibit pathogenic bacteria and prolong the shelf life of food, but also possess the advantages of specificity and an absence of chemical residues. Currently, there are many cases of phage applications in agriculture, animal disease prevention and control, food safety, and the treatment of drug-resistant disease. In this review, we summarize the recent research progress on phages against foodborne pathogenic bacteria, including Escherichia coli, Salmonella, Campylobacter, Listeria monocytogenes, Shigella, Vibrio parahaemolyticus, and Staphylococcus aureus. We also discuss the main issues and their corresponding solutions in the application of phages in the food industry. In recent years, although researchers have discovered more phages with potential applications in the food industry, most researchers use these phages based on their host spectrum, and the application environment is mostly in the laboratory. Therefore, the practical application of these phages in different aspects of the food industry may be unsatisfactory and even have some negative effects. Thus, we suggest that before using these phages, it is necessary to identify their specific receptors. Using their specific receptors as the selection basis for their application and combining phages with other phages or phages with traditional antibacterial agents may further improve their safety and application efficiency. Collectively, this review provides a theoretical reference for the basic research and application of phages in the food industry.

Development and evaluation of a Mycobacterium bovis interferon-γ enzyme-linked immunospot (ELISpot) assay for detection of bovine tuberculosis.

Bovine tuberculosis (bTB) caused by Mycobacterium bovis is an important zoonotic disease. This infection is difficult to control because of the limited ability of the tuberculin skin test (TST) and ancillary IFN-γ release assay to detect all infected animals. In this study, we aimed to develop an efficient assay based on the enzyme-linked immunospot (ELISpot) technique for the diagnosis of bTB, with IFN-γ monoclonal antibodies 3E9 and Bio-labeled 6F8 used as capture and detection antibodies, respectively. As expected, there were significantly more M. bovis-specific spot-forming units (SFU) in bTB-infected cattle than in healthy cattle when an M. bovis-specific antigen, CFP-10-ESAT-6 fusion protein (CE protein), was used. The M. bovis IFN-γ ELISpot assay demonstrated a high level of agreement (90.83%) with the BOVIGAM ELISA test (Thermo Fisher Scientific) for detecting bTB. Furthermore, 3 of 109 cattle tested negative by both the TST and the BOVIGAM ELISA tests, but positive by the ELISpot assay (TST- ELISA- ELISpot+). During subsequent long-term monitoring, these 3 cattle became TST+ ELISA+ ELISpot+. These results suggest that the M. bovis IFN-γ ELISpot assay we established could detect infected cattle earlier than the BOVIGAM ELISA test.

Relationship between plasma angiogenic growth factors and diabetic foot ulcers.

BACKGROUND: Angiogenic growth factors play an important role in wound healing. However, their associations with diabetic foot ulcers (DFUs) in humans have rarely been investigated. We examined the relationships between circulating concentrations of vascular endothelial growth factor (VEGF)-A and placenta growth factor (PlGF), and DFU risk. METHODS: We recruited 447 participants, including 169 DFU patients, 182 diabetes patients without DFUs, and 96 diabetes-free individuals. Plasma VEGF-A and PlGF concentrations were measured using commercial enzyme immunoassay kits. RESULTS: Concentrations of VEGF-A and PlGF in DFU patients were higher than those in diabetes-free controls (P < 0.05), but lower than those in the diabetic controls (P < 0.05). Increased concentrations of VEGF-A and PlGF were associated with a reduced risk of DFUs. The odds ratios (95% confidence intervals) were 0.93 (0.88, 0.97) for every 10 pg/ml increase in VEGF-A concentrations, and 0.96 (0.94, 0.99) for every 5 pg/ml increase in PlGF concentrations. VEGF-A concentrations were positively related to BMI, glycated hemoglobin (HbA1c), hypertension, and neuropathy, and PlGF was positively correlated to age, HbA1c, and hypertension, among DFU patients. CONCLUSION: VEGF-A and PlGF play important roles in the development of DFU but need to be confirmed in prospective studies.

Aqueous synthesis and characterization of TGA-capped CdSe quantum dots at freezing temperature.

CdSe quantum dots (QDs) have traditionally been synthesized in organic phase and then transferred to aqueous solution by functionalizing their surface with silica, polymers, short-chain thiol ligands, or phospholipid micelles. However, a drastic increase in the hydrodynamic size and biotoxicity of QDs may hinder their biomedical applications. In this paper, the TGA-capped CdSe QDs are directly synthesized in aqueous phase at freezing temperature, and they prove to possess high QY (up to 14%).