Current Advances in the Functional Genes of Edible and Medicinal Fungi: Research Techniques, Functional Analysis, and Prospects.

Functional genes encode various biological functions required for the life activities of organisms. By analyzing the functional genes of edible and medicinal fungi, varieties of edible and medicinal fungi can be improved to enhance their agronomic traits, growth rates, and ability to withstand adversity, thereby increasing yield and quality and promoting industrial development. With the rapid development of functional gene research technology and the publication of many whole-genome sequences of edible and medicinal fungi, genes related to important biological traits have been mined, located, and functionally analyzed. This paper summarizes the advantages and disadvantages of different functional gene research techniques and application examples for edible and medicinal fungi; systematically reviews the research progress of functional genes of edible and medicinal fungi in biological processes such as mating type, mycelium and fruit growth and development, substrate utilization and nutrient transport, environmental response, and the synthesis and regulation of important active substances; and proposes future research directions for functional gene research for edible and medicinal fungi. The overall aim of this study was to provide a valuable reference for further promoting the molecular breeding of edible and medicinal fungi with high yield and quality and to promote the wide application of edible and medicinal fungi products in food, medicine, and industry.

The Effect of 14-Day Consumption of Hydrogen-Rich Water Alleviates Fatigue but Does Not Ameliorate Dyspnea in Long-COVID Patients: A Pilot, Single-Blind, and Randomized, Controlled Trial.

(1) Background: Hydrogen (H2) may be a potential therapeutic agent for managing Long COVID symptoms due to its antioxidant and anti-inflammatory properties. However, more scientific literature is needed to describe the effects of H2 administration on treating symptoms. A study aimed to investigate the impact of hydrogen-rich water (HRW) administration on the fatigue and dyspnea of Long-COVID patients for 14 consecutive days. (2) Methods: In this randomized, single-blind, placebo-controlled study, 55 participants were recruited, and 23 of them were excluded. A total of 32 eligible participants were randomized into a hydrogen-rich water (HRW) group (n = 16) and a placebo water (PW) group (n = 16) in which they were instructed to consume hydrogen-rich water or placebo water for 14 days, respectively. The participants completed the Fatigue Severity Scale (FSS), Six-Minute Walk Test (6MWT), 30 s Chair Stand Test (30s-CST), Modified Medical Research Council Dyspnea Rating Scale (mMRC), Pittsburgh Sleep Quality Index (PSQI), and depression anxiety stress scale (DASS-21) before and after the intervention. A linear mixed-effects model was used to analyze the effects of HRW. Cohen's d values were used to assess the effect size when significance was observed. The mean change with 95% confidence intervals (95% CI) was also reported. (3) Results: The effects of HRW on lowering FSS scores (p = 0.046, [95% CI = -20.607, -0.198, d = 0.696] and improving total distance in the 6WMT (p < 0.001, [95% CI = 41.972, 61.891], d = 1.010), total time for the 30s-CST (p = 0.002, [95% CI = 1.570, 6.314], d = 1.190), and PSQI scores (p = 0.012, [95% CI = -5.169, 0.742], d = 1.274) compared to PW were of a significantly moderate effect size, while there was no significant difference in mMRC score (p = 0.556) or DASS-21 score (p > 0.143). (4) Conclusions: This study demonstrates that HRW might be an effective strategy for alleviating fatigue and improving cardiorespiratory endurance, musculoskeletal function, and sleep quality. Still, it does not ameliorate dyspnea among Long-COVID patients.

Inhalation of hydrogen-rich gas before acute exercise alleviates exercise fatigue.

Hydrogen, as an antioxidant, may have the potential to mitigate fatigue and improve selected oxidative stress markers induced by strenuous exercise. This study focused on previously unexplored approach of pre-exercise inhalation of hydrogen-rich gas (HRG). Twenty-four healthy adult men first completed prelaboratories to determine maximum cycling power (Wmax) and maximum cycling time (Tmax). Then they were subjected to ride Tmax at 80% Wmax on cycle ergometers after inhaled HRG or placebo gas (air) for 60-minute in a double-blind, counterbalanced, randomized, and crossover design. The cycling frequency in the fatigue modelling process and the rating of perceived exertion (RPE) at the beginning and end of the ride were recorded. Before gas inhalation and after fatigue modeling, visual analog scale (VAS) for fatigue and counter-movement jump (CMJ) were tested, and blood samples were obtained. The results showed that compared to placebo, HRG inhalation induced significant improvement in VAS, RPE, the cycling frequency in the last 30 seconds, the ability to inhibit hydroxyl radicals, and serum lactate after exercise (p < 0.028), but not in CMJ height and glutathione peroxidase activit. In conclusions, HRG inhalation prior to acute exercise can alleviate exercise-induced fatigue, maintain functional performance, and improve hydroxyl radical and lactate levels.

Can molecular hydrogen supplementation reduce exercise-induced oxidative stress in healthy adults? A systematic review and meta-analysis.

Objective: Exercise-induced oxidative stress affects multiple neurophysiological processes, diminishing the exercise performance. Hydrogen (H2) can selectively reduce excessive free radicals, but studies observed its "dual effects" on exercise-induced oxidative stress, that is, increasing or decreasing the oxidative stress. Therefore, we here conducted a systematic review and meta-analysis to quantitatively assess the influence of H2 on exercise-induced oxidative stress in healthy adults. Methods: We conducted a systematic review of publications across five databases. The following keywords were used for search strategy: ["hydrogen"[Mesh] or "molecular hydrogen" or "hydrogen rich water" or "hydrogen-rich water" or "hydrogen rich saline"] and ["Oxidative Stress"[Mesh] or "Antioxidative Stress" or "Oxidative Damage" or "Oxidative Injury" or "Oxidative Cleavage"] and ["randomized controlled trial"[Mesh] or "randomized" or "RCT"]. We included trials reporting the effects of H2 on exercise-induced oxidative stress and potential antioxidant capacity post-exercise in healthy adults. Additionally, subgroup analyses were conducted to explore how various elements of the intervention design affected those outcomes. Results: Six studies, encompassing seven experiments with a total of 76 participants, were included in our analysis. Among these studies, hydrogen-rich water, hydrogen bathing, and hydrogen-rich gas were three forms used in H2 administration. The H2 was applied in different timing, including before, during, or after exercise only, both before and after exercise, and repeatedly over days. Single-dose, multi-dose within 1 day and/or multiple-dose over days were implemented. It was observed that compared to placebo, the effects of H2 on oxidative stress (diacron-reactive oxygen metabolites, d-ROMs) was not significant (SMD = -0.01, 95%CI-0.42 to 0.39, p = 0.94). However, H2 induced greater improvement in antioxidant potential capacity (Biological Antioxidant Potential, BAP) (SMD = 0.29, 95% CI 0.04 to 0.54, p = 0.03) as compared to placebo. Subgroup analyses revealed that H2 supplementation showed greater improvement (SMD = 0.52, 95%CI 0.16 to 0.87, p = 0.02) in the antioxidant potential capacity of intermittent exercises than continuous exercise. Conclusion: H2 supplementation can help enhance antioxidant potential capacity in healthy adults, especially in intermittent exercise, but not directly diminish the levels of exercise-induced oxidative stress. Future studies with more rigorous design are needed to examine and confirm these findings. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=364123, Identifier CRD42022364123.

Effects of endurance exercise on physiologic complexity of the hemodynamics in prefrontal cortex.

Significance: Prefrontal cortex (PFC) hemodynamics are regulated by numerous underlying neurophysiological components over multiple temporal scales. The pattern of output signals, such as functional near-infrared spectroscopy fluctuations (i.e., fNIRS), is thus complex. We demonstrate first-of-its-kind evidence that this fNIRS complexity is a marker that captures the influence of endurance capacity and the effects of hydrogen gas (H2) on PFC regulation. Aim: We aim to explore the effects of different physical loads of exercise as well as the intaking of hydrogen gas on the fNIRS complexity of the PFC. Approach: Twenty-four healthy young men completed endurance cycling exercise from 0 (i.e., baseline) to 100% of their physical loads after intaking 20 min of either H2 or placebo gas (i.e., control) on each of two separate visits. The fNIRS measuring the PFC hemodynamics and heart rate (HR) was continuously recorded throughout the exercise. The fNIRS complexity was quantified using multiscale entropy. Results: The fNIRS complexity was significantly greater in the conditions from 25% to 100% of the physical load (p<0.0005) compared with the baseline and after intaking H2 before exercise; this increase of fNIRS complexity was significantly greater compared with the control (p=0.001∼0.01). At the baseline, participants with a greater fNIRS complexity had a lower HR (ß=-0.35∼-0.33, p=0.008∼0.02). Those with a greater increase of complexity had a lower increase of the HR (ß=-0.30∼-0.28, p=0.001∼0.002) during exercise. Conclusions: These observations suggest that fNIRS complexity would be a marker that captures the adaptive capacity of PFC to endurance exercise and to the effects of interventions on PFC hemodynamics.

Characterizing the supraspinal sensorimotor control of walking using MRI-compatible system: a systematic review.

BACKGROUND: The regulation of gait is critical to many activities of everyday life. When walking, somatosensory information obtained from mechanoreceptors throughout body is delivered to numerous supraspinal networks and used to execute the appropriate motion to meet ever-changing environmental and task demands. Aging and age-related conditions oftentimes alter the supraspinal sensorimotor control of walking, including the responsiveness of the cortical brain regions to the sensorimotor inputs obtained from the peripheral nervous system, resulting in diminished mobility in the older adult population. It is thus important to explicitly characterize such supraspinal sensorimotor elements of walking, providing knowledge informing novel rehabilitative targets. The past efforts majorly relied upon mental imagery or virtual reality to study the supraspinal control of walking. Recent efforts have been made to develop magnetic resonance imaging (MRI)-compatible devices simulating specific somatosensory and/or motor aspects of walking. However, there exists large variance in the design and functionality of these devices, and as such inconsistent functional MRI (fMRI) observations. METHODS: We have therefore completed a systematic review to summarize current achievements in the development of these MRI-compatible devices and synthesize available imaging results emanating from studies that have utilized these devices. RESULTS: The device design, study protocol and neuroimaging observations of 26 studies using 13 types of devices were extracted. Three of these devices can provide somatosensory stimuli, eight motor stimuli, and two both types of stimuli. Our review demonstrated that using these devices, fMRI data of brain activation can be successfully obtained when participants remain motionless and experience sensorimotor stimulation during fMRI acquisition. The activation in multiple cortical (e.g., primary sensorimotor cortex) and subcortical (e.g., cerebellum) regions has been each linked to these types of walking-related sensorimotor stimuli. CONCLUSION: The observations of these publications suggest the promise of implementing these devices to characterize the supraspinal sensorimotor control of walking. Still, the evidence level of these neuroimaging observations was still low due to small sample size and varied study protocols, which thus needs to be confirmed via studies with more rigorous design.

Exogenous γ-Aminobutyric Acid (GABA) Enhanced Response to Abiotic Stress in Hypsizygus marmoreus by Improving Mycelial Growth and Antioxidant Capacity.

γ-Aminobutyric (GABA) acid is a nutrient and signaling molecule existing in many plants, participating in the regulation of metabolism and various physiological activities. Two strains of Hypsizygus marmoreus (a white variety and a brown variety) were investigated to study the impact of exogenous GABA on mycelial growth and the response to stress. Mycelial growth, microscopic morphology, antioxidant profile, and gad2 expression in H. marmoreu were investigated under salt, dehydration, or cold stress. The results indicated that 5 mM GABA stimulated mycelial growth under standard cultivation conditions, whereas GABA addition over 10 mM hindered the growth. Under salt, dehydration, or cold stress, treatment with 5 mM GABA significantly enhanced the mycelial growth rate and density of both H. marmoreus strains by promoting front hyphae branching. Meanwhile, the activities of key antioxidant enzymes such as peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) were enhanced by GABA, thereby augmenting the defensive network against abiotic stress. Additionally, gad2 expression and GABA concentration were increased under abiotic stresses as a resistance regulation response. The exogenous addition of GABA strengthened the upregulation of gad2 expression and GABA production. These findings indicated that exogenously adding low concentrations of GABA effectively enhanced the mycelial growth and antioxidant profile of H. marmoreus, thereby improving its resistance against stresses.

Intravoxel incoherent motion imaging to assess the acute effects of moderate-intensity continuous training and high-intensity interval training on thigh muscles.

This study investigated the use of intravoxel incoherent motion imaging (IVIM) to compare skeletal muscle perfusion during and after high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) to determine the impact on fat oxidation outcomes. Twenty overweight volunteers were recruited for the study. Each participant received one HIIT intervention and one MICT intervention using a cycling ergometer. Participants underwent a magnetic resonance imaging scan before, immediately after, and 1 and 2 h after each intervention. The IVIM parameters (D, fD*) of the rectus femoris, vastus lateralis, and biceps femoris long head were obtained. Changes in IVIM parameters of these muscles after both exercise interventions were compared using a two-factor repeated measures analysis of variance. In the rectus femoris, the fD* increased immediately after exercise intervention (d = 0.69 × 10-3  mm2 /s, p < 0.0083) and 2 h after exercise intervention (d = 0.64 × 10-3  mm2 /s, p < 0.0083) compared with before exercise. The increase in the fD* in the HIIT group was greater than that in the MICT group (d = 0.32, p = 0.023). In the vastus lateralis, the fD* increased immediately after the exercise intervention (d = 0.53 × 10-3  mm2 /s, p < 0.001) and returned to the pre-exercise level 1 h after exercising. The increase in the fD* in the HIIT group was lower than that in the MICT group (d = -0.21, p = 0.015). For the biceps femoris long head, the fD* was not significantly different between the two exercise interventions before and after exercise. Furthermore, the fD* 60 min after the HIIT intervention correlated with maximal oxygen consumption (VO2max), whereas fD* immediately after the MICT intervention correlated with VO2max. In summary, IVIM parameters can be used to evaluate differences in muscle perfusion between HIIT and MICT, and show a correlation with VO2max.

Acute Effects of Fatigue on Cardiac Autonomic Nervous Activity.

The onset of fatigue disrupts the functioning of the autonomic nervous system (ANS), potentially elevating the risk of life-threatening incidents and impairing daily performance. Previous studies mainly focused on physical fatigue (PF) and mental fatigue (MF) effects on the ANS, with limited knowledge concerning the influence of physical-mental fatigue (PMF) on ANS functionality. This study aimed to assess the immediate impact of PMF on ANS function and to compare its effects with those of PF and MF on ANS function. Thirty-six physically active college students (17 females) without burnout performed 60-min cycling exercises, AX-Continuous Performance Task (AX-CPT), and cycling combined with AX-CPT to induce PF, MF, and PMF respectively. Subjective fatigue levels were measured using the Rating of Perceived Exertion scale and the Visual Analog Scale-Fatigue. Heart rate variability was measured before and after each protocol to assess cardiac autonomic function. The proposed tasks successfully induced PF, MF, and PMF, demonstrated by significant changes in subjective fatigue levels. Compared with baseline, PMF decreased the root mean square of successive differences (RMSSD) between normal heartbeats (P < 0.001, d = 0.50), the standard deviation of normal-to-normal RR intervals (SDNN) (P < 0.01, d = 0.33), and the normalized high-frequency (nHF) power (P < 0.001, d = 0.32) while increased the normalized low-frequency (nLF) power (P < 0.001, d = 0.35) and the nLF/nHF ratio (P < 0.001, d = 0.40). Compared with MF, PMF significantly decreased RMSSD (P < 0.001, η2 = 0.431), SDNN (P < 0.001, η2 = 0.327), nLF (P < 0.01, η2 = 0.201), and nHF (P < 0.001, η2 = 0.377) but not the nLF/nHF ratio. There were no significant differences in ΔHRV (i.e., ΔRMSSD, ΔSDNN, ΔnLF/nHF, ΔnLF, and ΔnHF), heart rate, and training impulse between PF- and PMF-inducing protocols. Cognitive performance (i.e., accuracy) in AX-CPT during the PMF-inducing protocol was significantly lower than that during the MF-inducing protocol (P < 0.001, η2 = 0.101). PF and PMF increased sympathetic activity and decreased parasympathetic activity, while MF enhanced parasympathetic activity.

Selection and validation of internal control genes for quantitative real-time RT‒qPCR normalization of Phlebopus portentosus gene expression under different conditions.

Phlebopus portentosus (Berk. and Broome) Boedijn is an attractive edible mushroom and is considered the only bolete for which artificial cultivation in vitro has been achieved. Gene expression analysis has become widely used in research on edible fungi and is important for elucidating the functions of genes involved in complex biological processes. Selecting appropriate reference genes is crucial to ensuring reliable RT‒qPCR gene expression analysis results. In our study, a total of 12 candidate control genes were selected from 25 traditional housekeeping genes based on their expression stability in 9 transcriptomes of 3 developmental stages. These genes were further evaluated using geNorm, NormFinder, and RefFinder under different conditions and developmental stages. The results revealed that MSF1 domain-containing protein (MSF1), synaptobrevin (SYB), mitogen-activated protein kinase genes (MAPK), TATA-binding protein 1 (TBP1), and SPRY domain protein (SPRY) were the most stable reference genes in all sample treatments, while elongation factor 1-alpha (EF1), actin and ubiquitin-conjugating enzyme (UBCE) were the most unstably expressed. The gene SYB was selected based on the transcriptome results and was identified as a novel reference gene in P. portentosus. This is the first detailed study on the identification of reference genes in this fungus and may provide new insights into selecting genes and quantifying gene expression.

A meta-analysis of the criterion-related validity of Session-RPE scales in adolescent athletes.

BACKGROUND: The objective of this study was to establish the criterion-related validity of the session-rating of perceived exertion (s-RPE) method in adolescent athletes. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines, a meta-analysis (PROSPERO ID: CRD42022373126) was performed using Stata 15.1 software. Eight databases using the following terms: ('s-RPE' OR 'Rating Perceived Exertion session' OR 'RPE session' OR 'RPE' OR 'Rate of Perceived Exertion' OR 'Rated of Perceived Exertion') AND ('Adolescen*' OR 'Youth*' OR 'Teen*') AND ('validity' OR 'correlation' OR 'concurrent validity') were searched up to 2022. Articles meeting the inclusion criteria were screened and adopted the "Methodological Index for Non-Randomized Studies (MINORS)" to evaluate the risk of bias. RESULTS: An initial 1798 studies using the s-RPE method were identified and finally, a total of 16 studies were included for further analysis. The relationship between assessment instruments CR-10 or CR-100 modified methods of s-RPE and the heart rate measures of these selected studies were calculated using correlation coefficient (r values) and Fisher's z-score. A strong to very strong correlation between s-RPE and HR was observed (overall: r = 0.74; CR-10: r = 0.69; CR-100: r = 0.80). CR-100 scale (Fisher's z = 1.09) was shown to have a higher criterion validity than that of the CR-10 scale (Fisher's z = 0.85). CONCLUSION: Preliminary findings showed that s-RPE using either CR-10 or CR-100 scales can be used "stand-alone" for monitoring internal training load for children and adolescent athletes. Future studies should focus on whether CR-100 could better perform than CR-10 for junior and children athletes in different age groups and sports as well as the causes leading to potential scoring biases.

LC/MS- and GC/MS-based metabolomic profiling to determine changes in flavor quality and bioactive components of Phlebopus portentosus under low-temperature storage.

Introduction: Low temperature is the most common method used to maintain the freshness of Phlebopus portentosus during long-distance transportation. However, there is no information regarding the nutritional changes that occur in P. portentosus preserved postharvest in low temperature. Methods: In this study, the changes in flavor quality and bioactive components in fruiting bodies stored at 4 °C for different storage periods were determined through LC/MS and GC/MS analyses. Sampling was performed at 0, 3, 5, 7, and 13 days storage. Results and Discussion: Based on the results, the metabolites present in caps and stipes were different at the same period and significantly different after 7 days of storage. A total of 583 and 500 different metabolites were detected in caps and stipes, respectively, and were mainly lipids and lipid-like molecules, organic acids and derivatives, organic oxygen compounds and others. Except for prenol lipids and nucleotides, the expression levels of most metabolites increased with longer storage time. In addition, geosmin was identified as the major contributor to earthy-musty odors, and the level of geosmin was increased when the storage time was short. Conclusion: The variations in these metabolites might cause changes in flavor quality and bioactive components in P. portentosus. Variations in these metabolites were thoroughly analyzed, and the results revealed how storage processes affect the postharvest quality of P. portentosus for the first time.

Characterization, Recombinant Production, and Bioactivity of a Novel Immunomodulatory Protein from Hypsizygus marmoreus.

A novel fungal immunomodulatory protein (FIP), identified as FIP-hma, was discovered in the genome of an edible mushroom Hypsizygus marmoreus. Bioinformatics analysis suggested FIP-hma contained the cerato-platanin (CP) conserved domain and was categorized into Cerato-type FIP. In phylogenetic analysis, FIP-hma was clustered into a new branch of the FIP family, displaying large system divergence from most of the other FIPs. The higher gene expression of FIP-hma was observed during the vegetative growth stages than that during the reproductive growth stages. In addition, the cDNA sequence of FIP-hma was cloned and successfully expressed in Escherichia coli (E. coli) BL21(DE3). The recombinant protein of FIP-hma (rFIP-hma) was neatly purified and isolated by Ni-NTA and SUMO-Protease. The iNOS, IL-6, IL-1ß, and TNF-α levels of RAW 264.7 macrophages were upregulated by rFIP-hma, indicating its activation of an immune response by regulating central cytokines. No cytotoxic effects were observed in an MTT test. The findings of this work discovered a novel immunoregulatory protein from H. marmoreus, provided a systematic bioinformatic profile, suggested an effective approach for its heterologous recombinant production, and reported its potent immunoregulatory activity in macrophages. This study sheds light on the physiological function research of FIPs and their further industrial utilization.

Potential Role of Lysine Acetylation and Autophagy in Brown Film Formation and Postripening of Lentinula edodes Mycelium.

Lentinula edodes is one of the most widely cultivated edible mushrooms in the world. When cultivated in sawdust, the surface mycelium of L. edodes needs a long postripening stage wherein it forms a brown film (BF) by secreting and accumulating pigments. BF formation is critical for the high quality and yield of fruiting bodies. Protein lysine acetylation (KAC) is an important post-translational modification that regulates growth and development. Previous studies have shown that deacetylase levels are significantly increased during BF formation in the postripening stage of L. edodes. The aim of this study was to assess the role of protein acetylation during BF formation. To this end, we compared the acetylome of L. edodes mycelia before and after BF formation using anti-acetyl antibody-based label-free quantitative proteomics. We identified 5,613 acetylation sites in 1,991 proteins, and quantitative information was available for 4,848 of these sites in 1,815 proteins. Comparative acetylome analysis showed that the modification of 699 sites increased and that of 562 sites decreased during BF formation. Bioinformatics analysis of the differentially acetylated proteins showed significant enrichment in the tricarboxylic acid (TCA) cycle and proteasome pathways. Furthermore, functional assays showed that BF formation is associated with significant changes in the activities of proteasome, citrate synthase, and isocitrate dehydrogenase. Consistent with this hypothesis, the lysine deacetylase inhibitor trichostatin (TSA) delayed autophagy and BF formation in L. edodes. Taken together, KAC and autophagy play important roles in the mycelial BF formation and postripening stage of L. edodes. IMPORTANCE Mycelial BF formation and postripening of L. edodes affects the quality and quantity of its edible fruiting bodies. In this study, we explored the role of protein KAC in this biological process, with the aim of optimizing the cultivation and yield of L. edodes.

Genotype-Phenotype Models Predicting V̇O 2max Response to High-Intensity Interval Training in Physically Inactive Chinese.

PURPOSE: This study aimed to analyze the interindividual differences of the maximal oxygen uptake (V̇O 2max ) response to 12 wk of high-intensity interval training (HIIT), and the genotype-phenotype models were constructed to predict the effect of HIIT on V̇O 2max . METHODS: A total of 228 physically inactive adults who completed a 12-wk HIIT were analyzed. A genome-wide association study (GWAS) was conducted to identify genetic variants associated with the V̇O 2max response. Nonresponders, responders, and the highest training responders were defined as the effect sizes (ES) <0.2, ≥0.2, and ≥0.8, respectively. We generated polygenic predictor score (PPS) using lead variants and constructed a predictive model for V̇O 2max response based on a linear stepwise regression analysis. RESULTS: The V̇O 2max increased significantly after HIIT (~14%, P < 0.001), but with interindividual differences (-7.8 to 17.9 mL·kg -1 ·min -1 ). In 27% of participants, the V̇O 2max showed no improvement. We identified one genetic locus near the γ-aminobutyric acid type A receptor subunit beta 3 gene ( GABRB3 , rs17116985) associated with V̇O 2max response at the genome-wide significance level ( P < 5 × 10 -8 ), and an additional nine single nucleotide polymorphisms (SNPs) at the suggestive significance level ( P < 1 × 10 -5 ). The SNPs rs474377, rs9365605, and rs17116985, respectively, explained 11%, 9%, and 6.2% of variance in V̇O 2max response. The 13 SNPs ( P < 1 × 10 -5 ) were found on chromosome 6 (position: 148209316-148223568). Individuals with a PPS greater than 1.757 had the highest response, and those with a PPS lower than -3.712 were nonresponders. The PPS, baseline V̇O 2max , sex, and body mass explained 56.4% of the variance in the V̇O 2max response; the major predictor was the PPS, which explained 39.4% of the variance. CONCLUSIONS: The PPS, baseline V̇O 2max , sex, and body mass could explain the variance in V̇O 2max response. Individuals who had a PPS greater than 1.757 had the highest training response after 12 wk of HIIT. Genetic variants in a region on chromosome 6, especially the sterile alpha motif domain containing 5 gene ( SAMD5 ), which had been explored influencing angiogenesis, might have a potential role in the V̇O 2max response.

Transformation of Compatible Mating-Type Genes in Monokaryons Triggers Fruiting Body Development by Activating Mating Pathways in Pleurotus eryngii.

Fruiting body formation is the most important developmental event in the edible mushroom life cycle; however, the genetic regulation of this process is not well understood. Pleurotus eryngii is a widely cultivated mushroom with high economic value. The mating of two monokaryons carrying compatible A and B mating-type genes is required for the development of fruiting bodies in P. eryngii. In this study, we showed that the monokaryons of P. eryngii transformed with compatible homeodomain (A mating type) and pheromone (B mating type) genes can complete fruiting body development but cannot form basidiospores. Transcriptional analyses revealed that expression of endogenous homeodomain and pheromone receptor genes and mating signaling pathways were activated by transferred homeodomain and pheromone genes in the transformants. Our findings provide a novel model for studying fruiting body development, which may accelerate the genetic breeding of edible mushrooms in the future. IMPORTANCE Fruiting bodies of edible mushrooms have high nutritional value. However, the fruiting body development of mushrooms is not well understood, and thus, many wild edible mushrooms of economic importance cannot be cultivated artificially. Moreover, variety among cultivatable mushrooms has improved marginally. Under natural conditions, fruiting body development can be initiated only in a dikaryon, the sexual mycelium obtained from mating two compatible monokaryons. The present work showed induction of fruiting body development in Pleurotus eryngii monokaryons by genetic manipulation. Gene expression analyses revealed key genes and signaling pathways involved in the fruiting body development of P. eryngii.

Improving cold-adaptability of mesophilic cellulase complex with a novel mushroom cellobiohydrolase for efficient low-temperature ensiling.

Low ambient temperature poses a challenge for rice straw-silage processing in cold climate regions, as cold limits enzyme and microbial activity in silages. Here, a novel cold-active cellobiohydrolase (VvCBHI-I) was isolated from Volvariella volvacea, which exhibited outstanding cellobiohydrolase activity at 10-30 °C. The crude cellulase complex in the VvCBHI-I-expressing transformant T1 retained 50% relative activity at 10 °C, while the wildtype Trichoderma reesei showed <5% of the activity. VvCBHI-I greatly improved the saccharification efficiency of the cellulase complex with pretreated rice straw as substrate at 10 °C. In rice straw silage, pH (<4.5) and lactic acid content (>4.6%) remained stable after 15-day ensiling with the cellulase complex from T1 and Lactobacillus plantarum. Moreover, the proportions of cellulose and hemicellulose decreased to 29.84% ± 0.15% and 21.25% ± 0.26% of the dried material. This demonstrates the crucial potential of mushroom-derived cold-active cellobiohydrolases in successful ensiling in cold regions.

The lignin-degrading abilities of Gelatoporia subvermispora gat1 and pex1 mutants generated via CRISPR/Cas9.

White-rot fungi efficiently degrade wood lignin; however, the mechanisms involved remain largely unknown. Recently, a forward genetics approach to identify several genes in Pleurotus ostreatus (Agaricales) in which mutations cause defects in wood lignin degradation was used. For example, pex1 encodes a peroxisome biogenesis factor and gat1 encodes a putative Agaricomycetes-specific DNA-binding transcription factor. In this study, we examined the effects of single-gene mutations in pex1 or gat1 on wood lignin degradation in another white-rot fungus, Gelatoporia (Ceriporiopsis) subvermispora (Polyporales), to investigate conserved and derived degradation mechanisms in white-rot fungi. G. subvermispora pex1 and gat1 single-gene mutant strains were generated from a monokaryotic wild-type strain, FP-90031-Sp/1, using plasmid-based CRISPR/Cas9. As in P. ostreatus, Gsgat1 mutants were nearly unable to degrade lignin sourced from beech wood sawdust medium (BWS), while Gspex1 mutants exhibited a delay in lignin degradation. We also found that the transcripts of lignin-modifying enzyme-encoding genes, mnp4, mnp5, mnp6, mnp7, and mnp11, which predominantly accumulate in FP-90031-Sp/1 cultured with BWS, were greatly downregulated in Gsgat1 mutants. Taken together, the results suggest that Gat1 may be a conserved regulator of the ligninolytic system of white-rot fungi and that the contribution of peroxisomes to the ligninolytic system may differ among species.

Effects of molecular hydrogen supplementation on fatigue and aerobic capacity in healthy adults: A systematic review and meta-analysis.

Background: Fatigue is oftentimes induced by high-intensity exercise potentially via the exceeded amount of reactive oxygen species, leading to diminished functions (e.g., aerobic capacity) and increased risk of injuries. Studies indicate that molecular hydrogen (H2), with antioxidant and anti-inflammatory properties, may be a promising strategy to alleviate fatigue and improve aerobic capacity. However, such effects have not been comprehensively characterized. Objective: To systematically assess the effects of in taking H2 on fatigue and aerobic capacity in healthy adults. Methods: The search was conducted in August 2022 in five databases. Studies with randomized controlled or crossover designs that investigated the rating of perceived exertion (RPE), maximal oxygen uptake (VO2max), peak oxygen uptake (VO2peak), and endurance performance were selected. The data (mean ± standard deviation and sample size) were extracted from the included studies and were converted into the standardized mean difference (SMD). Random-effects meta-analyses were performed. Subgroup analysis was used to analyze potential sources of heterogeneity due to intervention period, training status, and type of exercise. Results: Seventeen publications (19 studies) consisting of 402 participants were included. The pooled effect sizes of H2 on RPE (SMDpooled = -0.38, 95%CI -0.65 to -0.11, p = 0.006, I 2 = 33.6%, p = 0.149) and blood lactate (SMDpooled = -0.42, 95% CI -0.72 to -0.12, p = 0.006, I 2 = 35.6%, p = 0.114) were small yet significant with low heterogeneity. The pooled effect sizes of H2 on VO2max and VO2peak (SMDpooled = 0.09, 95% CI -0.10 to 0.29, p = 0.333, I 2 = 0%, p = 0.998) and endurance performance (SMDpooled = 0.01, 95% CI -0.23 to 0.25, p = 0.946, I 2 = 0%, p > 0.999) were not significant and trivial without heterogeneity. Subgroup analysis revealed that the effects of H2 on fatigue were impacted significantly by the training status (i.e., untrained and trained), period of H2 implementation, and exercise types (i.e., continuous and intermittent exercises). Conclusions: This meta-analysis provides moderate evidence that H2 supplementation alleviates fatigue but does not enhance aerobic capacity in healthy adults. Systematic review registration: www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022351559.

The Effects of Repetitive Transcranial Magnetic Stimulation on Standing Balance and Walking in Older Adults with Age-related Neurological Disorders: A Systematic Review and Meta-analysis.

BACKGROUND: Considerable evidence showed that repetitive transcranial magnetic stimulation (rTMS) can improve standing balance and walking performance in older adults with age-related neurological disorders. We here thus completed a systematic review and meta-analysis to quantitatively examine such benefits of rTMS. METHODS: A search strategy based on the PICOS principle was used to obtain the literature in 4 databases. The screening and assessments of quality and risk of bias in the included studies were independently completed by 2 researchers. Outcomes included scales related to standing balance, Timed Up and Go (TUG) time, and walking speed/time/distance. RESULTS: Twenty-three studies consisting of 532 participants were included, and the meta-analysis was completed on 21 of these studies. The study quality was good. Compared to control, rTMS induced both short-term (≤3 days after last intervention session) and long-term (≥1 month following last intervention session) significant improvements in balance scales (eg, Berg Balance Scale), TUG time, and walking speed/time/distance (short-term: standardized mean difference [SMD] = 0.26-0.34, 95% confidence interval [CI] = 0.05-0.62; long-term: SMD = 0.40-0.47, 95% CI = 0.04-0.79) for both PD and stroke cohorts. Subgroup analyses suggested that greater than 9 sessions of high-frequency rTMS targeting primary motor cortex with greater than 3 000 pulses/wk can maximize such benefits. Only a few mild-to-moderate adverse events/side effects were reported, which were similar between rTMS and control group. CONCLUSION: The results suggest that rTMS holds promise to improve balance and walking performance in older adults with age-related neurological disorders. Future studies with more rigorous design are needed to confirm the observations in this work.