Effects of heat-killed Lactiplantibacillus plantarum TWK10 on exercise performance, fatigue, and muscle growth in healthy male adults.

Consumption of Lactiplantibacillus plantarum TWK10 (TWK10) has beneficial probiotic effects, improves exercise endurance performance, regulates body composition, and mitigates aging-related problems in mice and humans. Here, we investigated the effects of heat-killed TWK10 on exercise endurance performance, muscle weight and strength, fatigue, and body composition in a double-blind, placebo-controlled clinical trial. Thirty healthy males aged 20-40 years were assigned to the Control group or heat-killed TWK10 group (TWK10-HK) in a balanced order according to each individual's initial maximal oxygen uptake. After 6-week administration, the exercise endurance time in the TWK10-HK was significantly increased (p = 0.0028) compared with that in the Control group. The grip strength on the right and left hands of the subjects was significantly increased (p = 0.0002 and p = 0.0140, respectively) in the TWK10-HK compared with that in the Control group. Administration of heat-killed TWK10 resulted in a significant increase (p = 0.0275) in muscle weight. After 6-week administration, serum lactate, and ammonia levels were significantly lower in the TWK10-HK group than in the Control group during the exercise and recovery periods. These findings demonstrate that heat-killed TWK10 has significant potential to be used as a postbiotic for humans.

Examining Physical Wellness as the Fundamental Element for Achieving Holistic Well-Being in Older Persons: Review of Literature and Practical Application in Daily Life.

This review examines the impact of physical activity, nutrition, and sleep evaluations on the physical wellness (PW) and overall well-being of older individuals. A comprehensive search was conducted in databases like PubMed, Google Scholar, and EBSCO Information Services. The search spanned from January 2000 to December 2022, resulting in 19,400 articles, out of which 98 review articles met the inclusion criteria. Through the analysis of these articles, key characteristics of the literature were summarized, and opportunities to enhance the practical application of physical activity (PA), nutrition, and sleep evaluations in the daily lives of older persons were identified. Regular physical activity is crucial for older persons to maintain their physical, mental, and emotional well-being and prevent age-related health issues. Older persons have specific nutritional needs, including increased protein, vitamin D, calcium, and vitamin B12 intake. Poor sleep quality in older persons is associated with negative health outcomes such as cognitive decline, physical disability, and mortality. This review emphasizes the significance of considering physical wellness as a fundamental element for achieving holistic well-being in older persons and highlights the importance of physical activity, nutrition, and sleep evaluations in improving their overall health and well-being. By understanding and implementing these findings, we can enhance the quality of life and promote healthy aging in older persons.

Different Impacts of Heat-Killed and Viable Lactiplantibacillus plantarum TWK10 on Exercise Performance, Fatigue, Body Composition, and Gut Microbiota in Humans.

Lactiplantibacillus plantarum TWK10, a probiotic strain, has been demonstrated to improve exercise performance, regulate body composition, and ameliorate age-related declines. Here, we performed a comparative analysis of viable and heat-killed TWK10 in the regulation of exercise performance, body composition, and gut microbiota in humans. Healthy adults (n = 53) were randomly divided into three groups: Control, TWK10 (viable TWK10, 3 × 1011 colony forming units/day), and TWK10-hk (heat-killed TWK10, 3 × 1011 cells/day) groups. After six-week administration, both the TWK10 and TWK10-hk groups had significantly improved exercise performance and fatigue-associated features and reduced exercise-induced inflammation, compared with controls. Viable TWK10 significantly promoted improved body composition, by increasing muscle mass proportion and reducing fat mass. Gut microbiota analysis demonstrated significantly increasing trends in the relative abundances of Akkermansiaceae and Prevotellaceae in subjects receiving viable TWK10. Predictive metagenomic profiling revealed that heat-killed TWK10 administration significantly enhanced the signaling pathways involved in amino acid metabolisms, while glutathione metabolism, and ubiquinone and other terpenoid-quinone biosynthesis pathways were enriched by viable TWK10. In conclusion, viable and heat-killed TWK10 had similar effects in improving exercise performance and attenuating exercise-induced inflammatory responses as probiotics and postbiotics, respectively. Viable TWK10 was also highly effective in regulating body composition. The differences in efficacy between viable and heat-killed TWK10 may be due to differential impacts in shaping gut microbiota.

Persistent TLR4 Activation Promotes Hepatocellular Carcinoma Growth through Positive Feedback Regulation by LIN28A/Let-7g miRNA.

Chronic inflammation caused by liver damage or infection plays an important role in the development and progression of hepatocellular carcinoma (HCC). The activation of Toll-like receptors 4 (TLR4) is involved in HCC tumorigenesis. Moreover, high TLR4 expression in HCC has been linked to poor prognosis. Although the expression of TLR4 in HCC is relatively low compared to hematopoietic cells, it is important to explore the molecular mechanism leading to the elevation of TLR4 in HCC. In this study, we aimed to investigate the positive regulating loop for TLR4 expression in HCC in response to chronic inflammation. Our results confirm that the mRNA expression of TLR4 and proinflammatory cytokines, including interleukin 6 (IL6) and C-C motif chemokine ligand 2 (CCL2), positively correlate in human HCC samples. High TLR4 expression in HCC is more susceptible to lipopolysaccharide (LPS); TLR4 activation in HCC provides growth and survival advantages and thus promotes tumorigenesis. It has been shown that the LIN28/let-7 microRNA (miRNA) axis is a downstream effector of the TLR4 signal pathway, and let-7 miRNA is a potential post-transcriptional regulator for TLR4. Thus, we investigated the correlation between TLR4 and LIN28A mRNA and let-7g miRNA in HCC clinical samples and found that the expression of TLR4 was positively correlated with LIN28A and negatively correlated with let-7g miRNA. Moreover, by culturing PLC/PRF5 (PLC5) HCC cells in low-dose LPS-containing medium to mimic chronic inflammation for persistent TLR4 activation, the mRNA and protein levels of TLR4 and LIN28A were elevated, and let-7g miRNA was decreased. Furthermore, the 3' untranslated region (3'UTR) of TLR4 mRNA was shown to be the target of let-7g miRNA, suggesting that inhibition of let-7g miRNA is able to increase TLR4 mRNA. While parental PLC5 cells have a low susceptibility to LPS-induced cell growth, long-term LPS exposure for PLC5 cells leads to increased proliferation, cytokine expression and stemness properties. In conclusion, our studies demonstrate positive feedback regulation for chronic TLR4 activation in the modulation of TLR4 expression level through the LIN28A/let-7g pathway in HCC and suggest a connection between chronic inflammation and TLR4 expression level in HCC for promoting tumorigenesis.

Exercise Dosage in Reducing the Risk of Dementia Development: Mode, Duration, and Intensity-A Narrative Review.

Senile dementia, also known as dementia, is the mental deterioration which is associated with aging. It is characterized by a decrease in cognitive abilities, inability to concentrate, and especially the loss of higher cerebral cortex function, including memory, judgment, abstract thinking, and other loss of personality, even behavior changes. As a matter of fact, dementia is the deterioration of mental and intellectual functions caused by brain diseases in adults when they are mature, which affects the comprehensive performance of life and work ability. Most dementia cases are caused by Alzheimer's disease (AD) and multiple infarct dementia (vascular dementia, multi-infarct dementia). Alzheimer's disease is characterized by atrophy, shedding, and degenerative alterations in brain cells, and its occurrence is linked to age. The fraction of the population with dementia is smaller before the age of 65, and it increases after the age of 65. Since women live longer than men, the proportion of women with Alzheimer's disease is higher. Multiple infarct dementia is caused by a cerebral infarction, which disrupts blood supply in multiple locations and impairs cerebral cortex function. Researchers worldwide are investigating ways to prevent Alzheimer's disease; however, currently, there are no definitive answers for Alzheimer's prevention. Even so, research has shown that we can take steps to reduce the risk of developing it. Prospective studies have found that even light to moderate physical activity can lower the risk of dementia and Alzheimer's disease. Exercise has been proposed as a potential lifestyle intervention to help reduce the occurrence of dementia and Alzheimer's disease. Various workout modes will be introduced based on various physical conditions. In general, frequent exercise for 6-8 weeks lessens the risk of dementia development.

Verification and dissection of one quantitative trait locus for grain size and weight on chromosome 1 in rice.

Grain size and weight are the key traits determining rice quality and yield and are mainly controlled by quantitative trait loci (QTL). In this study, one minor QTL that was previously mapped in the marker interval of JD1009-JD1019 using the Huanghuazhan/Jizi1560 (HHZ/JZ1560) recombinant inbred line (RIL) population, qTGW1-2, was validated to regulate grain size and weight across four rice-growing seasons using twenty-one near isogenic line (NIL)-F2 populations. The twenty-one populations were in two types of genetic background that were derived from the same parents HHZ and JZ1560. Twelve F9, F10 or F11 NIL-F2 populations with the sequential residual heterozygous regions covering JD1009-RM6840 were developed from one residual heterozygote (RH) in the HHZ/JZ1560 RIL population, and the remaining nine BC3F3, BC3F4 or BC3F5 NIL-F2 populations with the sequential residual heterozygous regions covering JD1009-RM6840 were constructed through consecutive backcrosses to the recurrent parent HHZ followed with marker assistant selection in each generation. Based on the QTL analysis of these genetic populations, qTGW1-2 was successfully confirmed to control grain length, width and weight and further dissected into two QTLs, qTGW1-2a and qTGW1-2b, which were respectively narrowed down to the marker intervals of JD1139-JD1127 (~ 978.2-kb) and JD1121-JD1102 (~ 54.8-kb). Furthermore, the two types of NIL-F2 populations were proved to be able to decrease the genetic background noise and increase the detection power of minor QTL. These results provided an important basis for further map-based cloning and molecular design breeding with the two QTLs in rice.

Posttranslational Modification of Waxy to Genetically Improve Starch Quality in Rice Grain.

The waxy (Wx) gene, encoding the granule-bound starch synthase (GBSS), is responsible for amylose biosynthesis and plays a crucial role in defining eating and cooking quality. The waxy locus controls both the non-waxy and waxy rice phenotypes. Rice starch can be altered into various forms by either reducing or increasing the amylose content, depending on consumer preference and region. Low-amylose rice is preferred by consumers because of its softness and sticky appearance. A better way of improving crops other than downregulation and overexpression of a gene or genes may be achieved through the posttranslational modification of sites or regulatory enzymes that regulate them because of their significance. The impact of posttranslational GBSSI modifications on extra-long unit chains (ELCs) remains largely unknown. Numerous studies have been reported on different crops, such as wheat, maize, and barley, but the rice starch granule proteome remains largely unknown. There is a need to improve the yield of low-amylose rice by employing posttranslational modification of Wx, since the market demand is increasing every day in order to meet the market demand for low-amylose rice in the regional area that prefers low-amylose rice, particularly in China. In this review, we have conducted an in-depth review of waxy rice, starch properties, starch biosynthesis, and posttranslational modification of waxy protein to genetically improve starch quality in rice grains.

COVID-19 Pandemic Is Associated with an Adverse Impact on Burnout and Mood Disorder in Healthcare Professionals.

The coronavirus disease 2019 (COVID-19) pandemic results in a profound physical and mental burden on healthcare professionals. This study aims to evaluate burnout status and mood disorder of healthcare workers during this period. An online questionnaire was voluntarily answered by eligible adult employees in a COVID-19 specialized medical center. The major analysis included the burnout status and mood disorder. Factors related to more severe mood disorder were also identified. A total of 2029 participants completed the questionnaire. There were 901 (44.4%) and 923 (45.5%) participants with moderate to severe personal and work-related burnout status, respectively. Nurses working in the emergency room (ER), intensive care unit (ICU)/isolation wards, and general wards, as well as those with patient contact, had significantly higher scores for personal burnout, work-related burnout, and mood disorder. This investigation identified 271 participants (13.35%) with moderate to severe mood disorder linked to higher personal/work-related burnout scores and a more advanced burnout status. Univariate analysis revealed that nurses working in the ER and ICU/isolation wards were associated with moderate to severe mood disorder risk factors. Multivariate analysis demonstrated that working in the ER (OR, 2.81; 95% CI, 1.14-6.90) was the only independent risk factor. More rest, perquisites, and an adequate supply of personal protection equipment were the most desired assistance from the hospital. Compared with the non-pandemic period (2019), employees working during the COVID-19 pandemic (2020) have higher burnout scores and percentages of severe burnout. In conclusion, this study suggests that the COVID-19 pandemic has had an adverse impact on healthcare professionals. Adequate measures should be adopted as early as possible to support the healthcare system.

The Effect of Kefir Supplementation on Improving Human Endurance Exercise Performance and Antifatigue.

Kefir is an acidic, carbonated, and fermented dairy product produced by fermenting milk with kefir grains. The Lactobacillus species constitutes an important part of kefir grains. In a previous animal study, kefir effectively improved exercise performance and had anti-fatigue effects. The purpose of this research was to explore the benefits of applying kefir to improve exercise performance, reduce fatigue, and improve physiological adaptability in humans. The test used a double-blind crossover design and supplementation for 28 days. Sixteen 20-30 year-old subjects were divided into two groups in a balanced order according to each individual's initial maximal oxygen uptake and were assigned to receive a placebo (equal flavor, equal calories, 20 g/day) or SYNKEFIR™ (20 g/day) every morning. After the intervention, there were 28 days of wash-out, during which time the subjects did not receive further interventions. After supplementation with SYNKEFIR™, the exercise time to exhaustion was significantly greater than that before ingestion (p = 0.0001) and higher than that in the Placebo group by 1.29-fold (p = 0.0004). In addition, compared with the Placebo group, the SYNKEFIR™ administration group had significantly lower lactate levels in the exercise and recovery (p < 0.05). However, no significant difference was observed in the changes in the gut microbiota. Although no significant changes in body composition were found, SYNKEFIR™ did not cause adverse reactions or harm to the participants' bodies. In summary, 28 days of supplementation with SYNKEFIR™ significantly improved exercise performance, reduced the production of lactic acid after exercise, and accelerated recovery while also not causing any adverse reactions.

Erratum: Cheng, Y.-C., et al. Evidence Supports PA Prescription for Parkinson's Disease: Motor Symptoms and Non-Motor Features: A Scoping Review. Int. J. Environ. Res. Public Health 2020, 17, 2894.

The authors wish to make the following corrections to their paper published in IJERPH [1]: authors' affiliation [...].

Evidence Supports PA Prescription for Parkinson's Disease: Motor Symptoms and Non-Motor Features: A Scoping Review.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder, which relates to not only motor symptoms, but also cognitive, autonomic, and mood impairments. The literature suggests that pharmacological or surgical treatment has a limited effect on providing relief of the symptoms and also restricting its progression. Recently, research on non-pharmacological interventions for people living with PD (pwPD) that alleviate their motor and non-motor features has shown a new aspect in treating this complex disease. Numerous studies are supporting exercise intervention as being effective in both motor and non-motor facets of PD, such as physical functioning, strength, balance, gait speed, and cognitive impairment. Via the lens of the physical profession, this paper strives to provide another perspective for PD treatment by presenting exercise modes categorized by motor and non-motor PD symptoms, along with its effects and mechanisms. Acknowledging that there is no "one size fits all" exercise prescription for such a variable and progressive disease, this review is to outline tailored physical activities as a credible approach in treating pwPD, conceivably enhancing overall physical capacity, ameliorating the symptoms, reducing the risk of falls and injuries, and, eventually, elevating the quality of life. It also provides references and practical prescription applications for the clinician.

Genome-Wide Identification of QTLs for Grain Protein Content Based on Genotyping-by-Resequencing and Verification of qGPC1-1 in Rice.

To clarify the genetic mechanism underlying grain protein content (GPC) and to improve rice grain qualities, the mapping and cloning of quantitative trait loci (QTLs) controlling the natural variation of GPC are very important. Based on genotyping-by-resequencing, a total of 14 QTLs were detected with the Huanghuazhan/Jizi1560 (HHZ/JZ1560) recombinant inbred line (RIL) population in 2016 and 2017. Seven of the fourteen QTLs were repeatedly identified across two years. Using three residual heterozygote-derived populations, a stably inherited QTL named as qGPC1-1 was validated and delimited to a ~862 kb marker interval JD1006-JD1075 on the short arm of chromosome 1. Comparing the GPC values of the RIL population determined by near infrared reflectance spectroscopy (NIRS) and Kjeldahl nitrogen determination (KND) methods, high correlation coefficients (0.966 and 0.983) were observed in 2016 and 2017. Furthermore, 12 of the 14 QTLs were identically identified with the GPC measured by the two methods. These results indicated that instead of the traditional KND method, the rapid and easy-to-operate NIRS was suitable for analyzing a massive number of samples in mapping and cloning QTLs for GPC. Using the gel-based low-density map consisted of 208 simple sequence repeat (SSR) and insert/deletion (InDel) markers, the same number of QTLs (fourteen) were identified in the same HHZ/JZ1560 RIL population, and three QTLs were repeatedly detected across two years. More stably expressed QTLs were identified based on the genome resequencing, which might be attributed to the high-density map, increasing the detection power of minor QTLs. Our results are helpful in dissecting the genetic basis of GPC and improving rice grain qualities through molecular assisted selection.

Cobalt salt-catalyzed carbocyclization reactions of α-bromo-N-phenylacetamide derivatives.

An efficient and low-cost method for the synthesis of 4-substituted quinolin-2-(1H)-ones has been developed. In the presence of TBHP, the cobalt(ii)-catalyzed carbocyclization reactions of arylethenyl substituted α-bromo-N-phenylacetamides, involving sequential 6-exo-trig radical cyclization, t-butylperoxy radical cross-coupling reaction and the base-promoted ionic Kornblum-DeLaMare reaction, produced 4-benzoylquinolin-2-(1H)-ones. A variety of useful functional groups such as methoxy, fluoro, chloro, bromo, methoxycarbonyl, and cyano groups, are compatible with the reaction conditions. This strategy was further applied to arylethynyl substituted α-bromo-N-phenylacetamides, and 4-benzylquinolin-2-(1H)-ones were formed effectively.

Aberrant expression of annexin A10 is closely related to gastric phenotype in serrated pathway to colorectal carcinoma.

Annexin A10 (ANXA10) is a member of the ANX family that is normally expressed in gastric mucosa. ANXA10 was recently observed to be upregulated in sessile serrated adenoma, a precursor to microsatellite-unstable colorectal cancer. We investigated the use of ANXA10 in diagnosing colorectal carcinoma. In an immunohistochemical analysis, the intensity and quantity of ANXA10, MUC5AC, MUC6 and CDX2 in 123 colorectal carcinomas were graded. We determined the molecular status of BRAF and KRAS mutations, as well as the microsatellite instability status and the CpG island methylator phenotype in all colorectal carcinomas, and subcategorized into four molecular subgroups according to the molecular derangements. Nuclear ANXA10 staining was present in 36 colorectal carcinomas, exhibiting a strong significant association with the BRAF mutation status (P<0.0001) and positive CpG island methylator phenotype (P<0.0001), and a borderline significant association with high levels of microsatellite instability (P=0.072). The ANXA10-positive colorectal carcinomas were frequently positive for MUC5AC and MUC6, and were associated with absent or reduced CDX2 expression (all P<0.0001). According to a classification and regression tree analysis, ANXA10 is a superior marker for the molecular subtyping of colorectal carcinomas and represents a specific marker for colorectal cancers of the serrated pathway. Our results indicated that ANXA10 expression is implicated in gastric programming in serrated-pathway-associated colorectal carcinoma. ANXA10-positive colorectal carcinoma is highly associated with the molecular features of the serrated neoplasia pathway.

Traditional serrated adenoma has two pathways of neoplastic progression that are distinct from the sessile serrated pathway of colorectal carcinogenesis.

Traditional serrated adenoma is one type of colorectal serrated neoplasm and a precursor of colorectal cancer. We evaluated the pathologic and molecular features of 60 traditional serrated adenomas with cytologic dysplasia and/or invasive carcinoma. On the basis of morphological features, 16 cases (27%) were categorized as traditional serrated adenoma with serrated dysplasia and 25 cases (42%) as traditional serrated adenoma with conventional adenomatous dysplasia. In addition, 19 cases (31%) showed an overall tubulovillous adenomatous structure but with focal serrated feature. Traditional serrated adenoma with serrated dysplasia had a significantly higher frequency of BRAF mutation than traditional serrated adenoma with conventional adenomatous dysplasia and tubulovillous adenoma with serrated feature (P=0.006), whereas traditional serrated adenoma with conventional adenomatous dysplasia and tubulovillous adenoma with serrated feature had higher frequencies of KRAS mutation than traditional serrated adenoma with serrated dysplasia (P<0.0001). Only traditional serrated adenoma with serrated dysplasia showed sessile serrated adenoma-like lesions at the periphery (n=3) and developed invasive carcinomas when the lesions were <15 mm in size. Abnormal nuclear accumulation of ß-catenin was detected in traditional serrated adenoma with conventional adenomatous dysplasia and tubulovillous adenoma with serrated feature but not in traditional serrated adenoma with serrated dysplasia. The frequency of the positive CpG island methylator phenotype was similar among the three dysplastic subtypes, and immunostaining of four mismatch repair proteins in the nucleus was retained in all traditional serrated adenomas and associated invasive malignancies. Traditional serrated adenoma-associated adenocarcinomas (n=28) displayed distinctive morphological features: oval cell nuclei, serrated glands, infiltrating borders, rare occurrences of necrosis and mucinous differentiation. Overexpression of p53 was detected only in high-grade dysplasia and invasive adenocarcinoma. Our findings indicate that traditional serrated adenoma is a heterogeneous neoplasm with two pathways of neoplastic progression, which are distinct from the sessile serrated pathway of colorectal carcinogenesis.

Characterization of Aß aggregation mechanism probed by congo red.

ß-Amyloid peptide (1) (Aß) aggregates are toxic to neuron and the main cause of Alzheimer's disease (AD). The role of congo red (CR) on Aß aggregation is controversial in aqueous solution. Both prevention and promotion of Aß aggregation have been proposed, suggesting that CR may interact with Aß of different structural conformations resulting in different effects on Aß aggregation behavior. CR with these characteristics can be applied to probe the molecular mechanism of Aß aggregation. Therefore, in the present study, we used CR as a probe to study the Aß aggregation behavior in sodium dodecyl sulfate (SDS) condition. Our results show that Aß(40) adopts two short helices at Q15-S26 and K28-L34 in the SDS environment. CR can interact with the helical form of Aß(40), and the main interaction site is located at the first helical and hydrophobic core region, residues 17-25, which is assigned as a discordant helix region. Furthermore, CR may prevent Aß(40) undergoing α-helix to ß-strand conversion, and therefore aggregation through stabilizing the helical conformation of discordant helix in SDS environment, suggesting that the discordant helix plays a key role on the conformational stabilization of Aß. Our present study implies that any factors or molecules that can stabilize the discordant helical conformation may also prevent the Aß aggregation in membrane associated state. This leads to a new therapeutic strategy for the development of lead compounds to AD.

Ozone exposure in the culture medium inhibits enterovirus 71 virus replication and modulates cytokine production in rhabdomyosarcoma cells.

In the present study, the effects of ozone exposure on enterovirus 71 (EV71) replication and related cytokine production were investigated. Rhabdomyosarcoma cells (RD) were exposed to 0.5, 1, 1.5 and 2 ppm ozone or filtered air under different exposure regimens before or after infection for 1 or 2 h. The results revealed that at a proper concentration of ozone, e.g., 1.5 or 2 ppm, ozone exposure restricted virus production, prolonged survival time of cells and modulated cytokine production related to EV71 infection. Upon exposure of non-infected cells to ozone at 1.5 or 2 ppm for 1h, the production of IL-1beta, IL-6 and TNF-alpha was primed and boosted by the subsequent EV71 infection, generating an inhibitory effect on EV71 replication during the post-infection period of 48 h. While infected cells were exposed to ozone for 2 h at 1.5 or 2 ppm, ozone did not affect cytokine production by RD cells in response to EV71 infection. The data showed that ozone effect on induction of cytokine was only found in uninfected cells. The ozone-induced cytokines produced prior to the onset of EV71 infection generated antiviral effects, which proved beneficial in suppressing the subsequent EV71 infection.