High-intensity interval training alleviates exhaustive exercise-induced HSP70-assisted selective autophagy in skeletal muscle.

This study was designed to probe the effect of chaperone-assisted selective autophagy (CASA) on the maintenance of proteostasis during exhaustive exercise and uncover the alteration of CASA in muscle fibers with pre-high-intensity interval training (HIIT) intervention-induced muscle adaptation in response to exhaustive exercise. Rats were randomly divided into a control group; an exhaustive exercise group; and an HIIT + exhaustive exercise group. Results show myofibril damage and BiP levels were increased after exhaustive exercise, and the levels of the HSP70, BAG3, ubiquitin, autophagy-related proteins, and their interactions were increased. HIIT intervention before exhaustive exercise could decrease myofibril injury and BiP levels, accompanied by down-regulation of HSP70/BAG3 complex and selective autophagy. In conclusion, exhaustive exercise promotes CASA to clear protein aggregation for keeping proteostasis in muscle fibers; pre-HIIT intervention improves myofibril injury and unfold protein response caused by exhaustive exercise, which might contribute to inhibit the augmentation of CASA.

The role of comprehensive geriatric assessment in the identification of different nutritional status in geriatric patients: a real-world, cross-sectional study.

Background: Malnutrition is an often unrecognized problem, but it is common in older patients and leads to adverse outcomes. Aims: The purpose of this study is to analyze the prevalence of the risk of undernutrition in elderly patients and the correlation between CGA and nutritional status, and to determine the nutritional status of elderly patients. Methods: This is a real-world cross-sectional study of continuously enrolled elderly patients aged 65 years or older with a complete CGA database. CGA inventory was prepared by compiling and screening general information, body composition and blood biochemical results. MNA was also conducted for each elderly patient to screen for malnutrition. A multivariable logistic regression analysis was used to determine the association between the CGA and nutritional assessment. Result: The average age of the 211 selected elderly patients (160 men and 51 women) was 79.60 ± 9.24 years, and their ages ranged from 65 to 96 years. After controlling for confounders, patients with a history of PUD (OR = 2.353, p = 0.044), increased ADLs & IADLs scores (OR = 1.051, p = 0.042) or GDS scores (OR = 6.078, p < 0.001) may increase the incidence of the risk of undernutrition respectively, while an increase in BMI (OR = 0.858, p = 0.032) may lower the incidence of malnutrition risk. In addition, increased ADLs & IADLs scores (OR = 1.096, p = 0.002) or GDS scores (OR = 11.228, p < 0.001) may increase the incidence of undernutrition. However, increased MMSE (OR = 0.705, p < 0.001), BMI (OR = 0.762, p = 0.034), UAC (OR = 0.765, p = 0.048) and CC (OR = 0.721, p = 0.003) may decrease the incidence of undernutrition, respectively. Conclusion: The study found that the prevalence of risk of undernutrition in elderly patients was the highest. Risk of undernutrition was independently associated with peptic ulcer disease, ADLs & IADLs, GDS and BMI. However, we found that when the nutritional status reached the level of undernutrition, it was related to more factors, including ADLs & IADLs, MMSE, GDS, BMI, UAC and CC. Determining the level of malnutrition through CGA may help to prevent and intervene malnutrition as early as possible.

The relationship between Comprehensive Geriatric Assessment parameters and depression in elderly patients.

Background: Depression is common and serious among elderly patients. The treatment of elderly depression is often delayed owing to insufficient diagnosis, which eventually leads to adverse consequences. Aims: To explore the association between the parameters of the Comprehensive Geriatric Assessment and depression in elderly patients. Methods: A cross-sectional study of 211 outpatients and inpatients aged ≥ 65 years from the Comprehensive Geriatric Assessment database was conducted. A Comprehensive Geriatric Assessment inventory was prepared by compiling and screening general characteristics, chronic diseases (cardiovascular disease, diabetes, and peptic ulcer disease), nutritional status, daily living ability, anthropometric measurements (body mass index (BMI), upper arm circumference, and calf circumference), and blood biochemical indicators (hemoglobin, albumin, prealbumin, triglycerides, and low-density lipoprotein cholesterol). The Geriatric Depression Scale was also conducted for each elderly patient to screen for depression. A multivariable logistic regression analysis was used to determine the association between the parameters of the Comprehensive Geriatric Assessment and geriatric depression. Results: There were 63 patients in the depression group with a median age of 84.00 years, and 148 patients in the non-depression group with a median age of 78.50 years. After controlling for confounders, the risk of depression in elderly patients with cardiovascular diseases was 6.011 times higher than that in those without cardiovascular diseases (p < 0.001); and the risk of depression in elderly patients with peptic ulcer diseases was 4.352 times higher than that in those without peptic ulcer diseases (p < 0.001); the risk of depression in elderly patients decreased by 22.6% for each 1-point increase in the Mini Nutritional Assessment (p < 0.001). The risk of depression in elderly patients decreased by 19.9% for each 1-point increase in calf circumference (p = 0.002), and by 13.0% for each 1-point increase in albumin (p = 0.014). Conclusion: Our findings suggest that Comprehensive Geriatric Assessment parameters, such as cardiovascular disease, peptic ulcer disease, Mini Nutritional Assessment score, calf circumference, and albumin, were associated with depression. The Comprehensive Geriatric Assessment can assist in the early identification of depression in the elderly population.

Single-Cell Digital Microfluidic Mass Spectrometry Platform for Efficient and Multiplex Genotyping of Circulating Tumor Cells.

Gene mutation profiling of heterogeneous circulating tumor cells (CTCs) offers comprehensive and real-time molecular information of tumors for targeted therapy guidance, but the lack of efficient and multiplex genotyping techniques for single-CTC analysis greatly hinders its development and clinical application. This paper reports a single-CTC mass spectrometry analysis method for efficient and multiplex mutation profiling based on digital microfluidics. Digital microfluidics affords integrated single-CTC manipulation, from single-CTC isolation to high-performance whole genome amplification, via nanoliter droplet-based wettability trapping and hydrodynamic adjustment of cell distribution. Coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, multiplex mutation information of individual CTCs can be efficiently and accurately identified by the inherent mass differences of different DNA sequences. This platform achieves Kirsten rat sarcoma viral oncogene mutation profiling of heterogeneous CTCs at the single-cell level from cancer patient samples, offering new avenues for genotype profiling of single CTCs and cancer therapy guidance.

The correlation between nutrition and frailty and the receiver operating characteristic curve of different nutritional indexes for frailty.

BACKGROUND: Frailty is a kind of geriatric syndrome, which is very common in the elderly. Patients with malnutrition are at higher risk of frailty. This study explored the correlation between nutrition and frailty and compared the receiver operating characteristic curve of different nutritional indexes for frailty. METHODS: This cross-sectional study included 179 inpatients aged ≥65 years old. Frailty was measured using Fried Frailty Phenotype, handgrip strength was measured using JAMAR@Plus and the 4.57 m usual gait speed was measured using a stopwatch. Comprehensive nutritional assessment refers to the application of Mini Nutritional Assessment (MNA) to assess the nutritional status of patients. RESULTS: Compared with the non-frailty group, the upper arm circumference, calf circumference, hemoglobin, albumin, prealbumin, cholesterol and low density lipoprotein in the frailty group were lower (P < 0.05). Comprehensive nutritional assessment, whether as a categorical variable or a continuous variable, was significantly correlated with frailty (P < 0.05). Model1 showed that the risk of frailty in malnourished patients was 3.381 times higher than that in well nourished patients (P = 0.036). Model2 showed that the risk of frailty decreased by 13.8% for every 1 point increase in MNA score (P = 0.009). The area under the curves of albumin, prealbumin and hemoglobin was larger (AUC > 0.65), AUC was 0.718, 0.693 and 0.743, respectively. CONCLUSIONS: Our results suggest that malnutrition is closely related to frailty. As for single nutritional indexes, albumin, prealbumin and hemoglobin were found to be associated with frailty. Further cohort studies are needed to verify their ability to screen for frailty.

Sensitive, Rapid, and Automated Detection of DNA Methylation Based on Digital Microfluidics.

Biomarkers based on DNA methylation have attracted wide attention in biomedical research due to their potential clinical value. Therefore, a sensitive and accurate method for DNA methylation detection is highly desirable for the discovery and diagnostics of human diseases, especially cancers. Here, an integrated, low-cost, and portable point-of-care (POC) device is presented to analyze DNA methylation, which integrates the process of pyrosequencing in a digital microfluidic chip. Without additional equipment and complicated operation, droplets are manipulated by patterned electrodes with individually programmed control. The system exhibited an excellent sensitivity with a limit of detection (LOD) of 10 pg and a comparable checkout down to 5% methylation level within 30 min, which offered a potential substitute for the detection of DNA methylation. With the advantages of portability, ease of use, high accuracy, and low cost, the POC platform shows great potential for the analysis of tumor-specific circulating DNA.

Digital-WGS: Automated, highly efficient whole-genome sequencing of single cells by digital microfluidics.

Single-cell whole-genome sequencing (WGS) is critical for characterizing dynamic intercellular changes in DNA. Current sample preparation technologies for single-cell WGS are complex, expensive, and suffer from high amplification bias and errors. Here, we describe Digital-WGS, a sample preparation platform that streamlines high-performance single-cell WGS with automatic processing based on digital microfluidics. Using the method, we provide high single-cell capture efficiency for any amount and types of cells by a wetted hydrodynamic structure. The digital control of droplets in a closed hydrophobic interface enables the complete removal of exogenous DNA, sufficient cell lysis, and lossless amplicon recovery, achieving the low coefficient of variation and high coverage at multiple scales. The single-cell genomic variations profiling performs the excellent detection of copy number variants with the smallest bin of 150 kb and single-nucleotide variants with allele dropout rate of 5.2%, holding great promise for broader applications of single-cell genomics.

Rapid, real-time chemiluminescent detection of DNA mutation based on digital microfluidics and pyrosequencing.

To explore genome mutation meaningfully, it is in urgent need to develop an automated and inexpensive platform for DNA mutation analysis. Digital microfluidics is a powerful platform for a broad range of applications due to the advantages of high automatization and low reagent consumption. Pyrosequencing enables DNA sequencing based on non-electrophoresis bioluminescence, which is suitable for rapid and sensitive analysis of short sequences. Herein, we describe a palmtop sequencing platform for automatic, real-time and portable analysis of DNA mutations, which is based on the pyrosequencing principle and implemented by digital microfluidics. The portable system can sequence a DNA template with up to 53 bp with 100% accuracy within 2 h. Mutation in the KRAS gene can be detected within 30 min with a LOD as low as 5% mutant level. Portable and accurate gender identification was further demonstrated by sequencing a short amelogenin fragment. With the advantages of portability, ease of use, high accuracy, and low cost, the palmtop sequencing platform shows great potential for portable genetic testing in a variety of circumstances.

MicroRNA-210 alleviates oxidative stress-associated cardiomyocyte apoptosis by regulating BNIP3.

Oxidative stress-induced myocardial apoptosis and necrosis are involved in ischemia/reperfusion (I/R) injury. This study was performed to investigate microRNA (miR)-210's role in oxidative stress-related myocardial damage. The expression of miR-210 was upregulated in myocardial tissues of I/R rats, while that of Bcl-2 adenovirus E1B 19kDa-interacting protein 3 (BNIP3) was downregulated. To simulate in vivo oxidative stress, H9c2 cells were treated with H2O2 for 48 h. MiR-210 level was increased upon H2O2 stimulation, peaked at 8 h, and then decreased. An opposite expression pattern of BNIP3 was observed. BNIP3 was demonstrated as a direct target of miR-210 via luciferase reporter assay. H2O2-induced cell apoptosis was attenuated by miR-210 mimics, whereas aggravated by miR-210 inhibitor. MiR-210 knockdown-induced cell apoptosis in presence of H2O2 was attenuated by BNIP3 siRNA. Our work demonstrates that miR-210 plays a protective role in H2O2-induced cardiomyocyte apoptosis at least by regulating the pro-apoptotic BNIP3.

Directional Selection from Host Plants Is a Major Force Driving Host Specificity in Magnaporthe Species.

One major threat to global food security that requires immediate attention, is the increasing incidence of host shift and host expansion in growing number of pathogenic fungi and emergence of new pathogens. The threat is more alarming because, yield quality and quantity improvement efforts are encouraging the cultivation of uniform plants with low genetic diversity that are increasingly susceptible to emerging pathogens. However, the influence of host genome differentiation on pathogen genome differentiation and its contribution to emergence and adaptability is still obscure. Here, we compared genome sequence of 6 isolates of Magnaporthe species obtained from three different host plants. We demonstrated the evolutionary relationship between Magnaporthe species and the influence of host differentiation on pathogens. Phylogenetic analysis showed that evolution of pathogen directly corresponds with host divergence, suggesting that host-pathogen interaction has led to co-evolution. Furthermore, we identified an asymmetric selection pressure on Magnaporthe species. Oryza sativa-infecting isolates showed higher directional selection from host and subsequently tends to lower the genetic diversity in its genome. We concluded that, frequent gene loss or gain, new transposon acquisition and sequence divergence are host adaptability mechanisms for Magnaporthe species, and this coevolution processes is greatly driven by directional selection from host plants.