ALDH2 dysfunction and alcohol cooperate in cancer stem cell enrichment.

The alcohol metabolite acetaldehyde is a potent human carcinogen linked to esophageal squamous cell carcinoma (ESCC) initiation and development. Aldehyde dehydrogenase 2 (ALDH2) is the primary enzyme that detoxifies acetaldehyde in the mitochondria. Acetaldehyde accumulation causes genotoxic stress in cells expressing the dysfunctional ALDH2E487K dominant negative mutant protein linked to ALDH2*2, the single nucleotide polymorphism highly prevalent among East Asians. Heterozygous ALDH2*2 increases the risk for the development of ESCC and other alcohol-related cancers. Despite its prevalence and link to malignant transformation, how ALDH2 dysfunction influences ESCC pathobiology is incompletely understood. Herein, we characterize how ESCC and preneoplastic cells respond to alcohol exposure using cell lines, three-dimensional organoids and xenograft models. We find that alcohol exposure and ALDH2*2 cooperate to increase putative ESCC cancer stem cells with high CD44 expression (CD44H cells) linked to tumor initiation, repopulation and therapy resistance. Concurrently, ALHD2*2 augmented alcohol-induced reactive oxygen species and DNA damage to promote apoptosis in the non-CD44H cell population. Pharmacological activation of ALDH2 by Alda-1 inhibits this phenotype, suggesting that acetaldehyde is the primary driver of these changes. Additionally, we find that Aldh2 dysfunction affects the response to cisplatin, a chemotherapeutic commonly used for the treatment of ESCC. Aldh2 dysfunction facilitated enrichment of CD44H cells following cisplatin-induced oxidative stress and cell death in murine organoids, highlighting a potential mechanism driving cisplatin resistance. Together, these data provide evidence that ALDH2 dysfunction accelerates ESCC pathogenesis through enrichment of CD44H cells in response to genotoxic stressors such as environmental carcinogens and chemotherapeutic agents.

Transcriptomics and gut microbiome analysis of the edible herb Bidens pilosa as a functional feed additive to promote growth and metabolism in tilapia (Oreochromis spp.).

To reduce the use of antibiotics and chemicals in aquaculture, an edible herb, Bidens pilosa, has been selected as a multifunctional feed additive. Although there has been considerable research into the effects of B. pilosa on poultry, the wider effects of B. pilosa, particularly on the growth and gut microbiota of fish, remain largely unexplored. We aimed to investigate the interactive effects between the host on growth and the gut microbiota using transcriptomics and the gut microbiota in B. pilosa-fed tilapia. In this study, we added 0.5% and 1% B. pilosa to the diet and observed that the growth performance of tilapia significantly increased over 8 weeks of feeding. Comparative transcriptome analysis was performed on RNA sequence profiles obtained from liver and muscle tissues. Functional enrichment analysis revealed that B. pilosa regulates several pathways and genes involved in amino acid metabolism, lipid metabolism, carbohydrate metabolism, endocrine system, signal transduction, and metabolism of other amino acids. The expression of the selected growth-associated genes was validated by qRT-PCR. The qRT-PCR results indicated that B. pilosa may enhance growth performance by activating the expression of the liver igf1 and muscle igf1rb genes and inhibiting the expression of the muscle negative regulator mstnb. Both the enhancement of liver endocrine IGF1/IGF1Rb signaling and the suppression of muscle autocrine/paracrine MSTN signaling induced the expression of myogenic regulatory factors (MRFs), myod1, myog and mrf4 in muscle to promote muscle growth in tilapia. The predicted function of the gut microbiota showed several significantly different pathways that overlapped with the KEGG enrichment results of differentially expressed genes in the liver transcriptomes. This finding suggested that the gut microbiota may influence liver metabolism through the gut-liver axis in B. pilosa-fed tilapia. In conclusion, dietary B. pilosa can regulate endocrine IGF1 signaling and autocrine/paracrine MSTN signaling to activate the expression of MRFs to promote muscle growth and alter the composition of gut bacteria, which can then affect liver amino acid metabolism, carbohydrate metabolism, endocrine system, lipid metabolism, metabolism of other amino acids, and signal transduction in the host, ultimately enhancing growth performance. Our results suggest that B. pilosa has the potential to be a functional additive that can be used as an alternative to reduce antibiotic use as a growth promoter in aquaculture.

Novel ectopic expression of zona pellucida 3 glycoprotein in lung cancer promotes tumor growth.

Zona pellucida 3 (ZP3) expression is classically found in the ZP-layer of the oocytes, lately shown in ovarian and prostate cancer. A successful ZP3 ovarian cancer immunotherapy in transgenic mice suggested its use as an attractive therapeutic target. The biological role of ZP3 in cancer growth and progression is still unknown. We found that ~88% of the analyzed adenocarcinoma, squamous and small cell lung carcinomas to express ZP3. Knockout of ZP3 in a ZP3-expressing lung adenocarcinoma cell line, significantly decreased cell viability, proliferation, and migration rates in vitro. Zona pellucida 3 knock out (ZP3-KO) cell tumors inoculated in vivo in immunodeficient non-obese diabetic, severe combined immunodeficient mice showed significant inhibition of tumor growth and mitigation of the malignant phenotype. RNA sequencing revealed the deregulation of cell migration/adhesion signaling pathways in ZP3-KO cells. This novel functional relevance of ZP3 in lung cancer emphasized the suitability of ZP3 as a target in cancer immunotherapy and as a potential cancer biomarker.

Suppression of aldehyde dehydrogenase 2 in kidney proximal tubules contributes to kidney fibrosis through Transforming Growth Factor-ß signaling.

Chronic kidney disease (CKD) is an increasingly prevalent disorder that poses a significant global health and socioeconomic burden. East Asian countries such as China, Taiwan, Japan, and South Korea have a higher incidence and prevalence of kidney failure when compared to Western nations, and the reasons for this discrepancy remain unclear. Aldehyde dehydrogenase 2 (ALDH2) is an essential detoxifying enzyme for exogenous and endogenous aldehyde metabolism in mitochondria. Inactivating mutations at E504K and E487K are found in 35-45% of East Asian populations and has been linked to a higher risk of various disorders, including cardiovascular diseases and cancer. However, little is known about the role of ALDH2 in CKD. Here, we characterized the expression pattern of ALDH2 in normal and CKD human and mouse kidneys and demonstrated that ALDH2 expression was significantly reduced, and that the protein level was inversely correlated with the degree of CKD and fibrosis. Further, we treated ALDH2*2 knock-in mice, a loss of ALDH2 function model, with aristolochic acid and found that these mice showed enhanced fibrosis. Moreover, ALDH2 deficiency was associated with kidney fibrosis involving epithelial cell differentiation process in vivo and in vitro. However, ALDH2 overexpression protected proximal tubule epithelial cells from transforming growth factor-ß-induced dedifferentiation or partial epithelial-mesenchymal transdifferentiation in vitro. Thus, our findings yield important clinical information regarding the development and progression of CKD involving ALDH2, especially among East Asian populations.

Uncovering newly identified aldehyde dehydrogenase 2 genetic variants that lead to acetaldehyde accumulation after an alcohol challenge.

BACKGROUND: Aldehyde dehydrogenase 2 (ALDH2) is critical for alcohol metabolism by converting acetaldehyde to acetic acid. In East Asian descendants, an inactive genetic variant in ALDH2, rs671, triggers an alcohol flushing response due to acetaldehyde accumulation. As alcohol flushing is not exclusive to those of East Asian descent, we questioned whether additional ALDH2 genetic variants can drive facial flushing and inefficient acetaldehyde metabolism using human testing and biochemical assays. METHODS: After IRB approval, human subjects were given an alcohol challenge (0.25 g/kg) while quantifying acetaldehyde levels and the physiological response (heart rate and skin temperature) to alcohol. Further, by employing biochemical techniques including human purified ALDH2 proteins and transiently transfected NIH 3T3 cells, we characterized two newly identified ALDH2 variants for ALDH2 enzymatic activity, ALDH2 dimer/tetramer formation, and reactive oxygen species production after alcohol treatment. RESULTS: Humans heterozygous for rs747096195 (R101G) or rs190764869 (R114W) had facial flushing and a 2-fold increase in acetaldehyde levels, while rs671 (E504K) had facial flushing and a 6-fold increase in acetaldehyde levels relative to wild type ALDH2 carriers. In vitro studies with recombinant R101G and R114W ALDH2 enzyme showed a reduced efficiency in acetaldehyde metabolism that is unique when compared to E504K or wild-type ALDH2. The effect is caused by a lack of functional dimer/tetramer formation for R101G and decreased Vmax for both R101G and R114W. Transiently transfected NIH-3T3 cells with R101G and R114W also had a reduced enzymatic activity by ~ 50% relative to transfected wild-type ALDH2 and when subjected to alcohol, the R101G and R114W variants had a 2-3-fold increase in reactive oxygen species formation with respect to wild type ALDH2. CONCLUSIONS: We identified two additional ALDH2 variants in humans causing facial flushing and acetaldehyde accumulation after alcohol consumption. As alcohol use is associated with a several-fold higher risk for esophageal cancer for the E504K variant, the methodology developed here to characterize ALDH2 genetic variant response to alcohol can lead the way precision medicine strategies to further understand the interplay of alcohol consumption, ALDH2 genetics, and cancer.

Targeting colorectal cancer with small-molecule inhibitors of ALDH1B1.

Aldehyde dehydrogenases (ALDHs) are promising cancer drug targets, as certain isoforms are required for the survival of stem-like tumor cells. We have discovered selective inhibitors of ALDH1B1, a mitochondrial enzyme that promotes colorectal and pancreatic cancer. We describe bicyclic imidazoliums and guanidines that target the ALDH1B1 active site with comparable molecular interactions and potencies. Both pharmacophores abrogate ALDH1B1 function in cells; however, the guanidines circumvent an off-target mitochondrial toxicity exhibited by the imidazoliums. Our lead isoform-selective guanidinyl antagonists of ALDHs exhibit proteome-wide target specificity, and they selectively block the growth of colon cancer spheroids and organoids. Finally, we have used genetic and chemical perturbations to elucidate the ALDH1B1-dependent transcriptome, which includes genes that regulate mitochondrial metabolism and ribosomal function. Our findings support an essential role for ALDH1B1 in colorectal cancer, provide molecular probes for studying ALDH1B1 functions and yield leads for developing ALDH1B1-targeting therapies.

Changes of neurofilament light chain in patients with alcohol dependence following withdrawal and the genetic effect from ALDH2 Polymorphism.

Neurofilament light chain (NFL), as a measure of neuroaxonal injury, has recently gained attention in alcohol dependence (AD). Aldehyde dehydrogenase 2 (ALDH2) is the major enzyme which metabolizes the alcohol breakdown product acetaldehyde. An ALDH2 single nucleotide polymorphism (rs671) is associated with less ALDH2 enzyme activity and increased neurotoxicity. We examined the blood NFL levels in 147 patients with AD and 114 healthy controls using enzyme-linked immunosorbent assay and genotyped rs671. We also followed NFL level, alcohol craving and psychological symptoms in patients with AD after 1 and 2 weeks of detoxification. We found the baseline NFL level was significantly higher in patients with AD than in controls (mean ± SD: 264.2 ± 261.8 vs. 72.1 ± 35.6 pg/mL, p < 0.001). The receiver operating characteristic curve revealed that NFL concentration could discriminate patients with AD from controls (area under the curve: 0.85; p < 0.001). The NFL levels were significantly reduced following 1 and 2 weeks of detoxification, with the extent of reduction correlated with the improvement of craving, depression, and anxiety (p < 0.001). Carriers with the rs671 GA genotype, which is associated with less ALDH2 activity, had higher NLF levels either at baseline or after detoxification compared with GG carriers. In conclusion, plasma NFL level was increased in patients with AD and reduced after early abstinence. Reduction in NFL level corroborated well with the improvement of clinical symptoms. The ALDH2 rs671 polymorphism may play a role in modulating the extent of neuroaxonal injury and its recovery.

Collaborative Human-Computer Vision Operative Video Analysis Algorithm for Analyzing Surgical Fluency and Surgical Interruptions in Endonasal Endoscopic Pituitary Surgery: Cohort Study.

BACKGROUND: The endonasal endoscopic approach (EEA) is effective for pituitary adenoma resection. However, manual review of operative videos is time-consuming. The application of a computer vision (CV) algorithm could potentially reduce the time required for operative video review and facilitate the training of surgeons to overcome the learning curve of EEA. OBJECTIVE: This study aimed to evaluate the performance of a CV-based video analysis system, based on OpenCV algorithm, to detect surgical interruptions and analyze surgical fluency in EEA. The accuracy of the CV-based video analysis was investigated, and the time required for operative video review using CV-based analysis was compared to that of manual review. METHODS: The dominant color of each frame in the EEA video was determined using OpenCV. We developed an algorithm to identify events of surgical interruption if the alterations in the dominant color pixels reached certain thresholds. The thresholds were determined by training the current algorithm using EEA videos. The accuracy of the CV analysis was determined by manual review, and the time spent was reported. RESULTS: A total of 46 EEA operative videos were analyzed, with 93.6%, 95.1%, and 93.3% accuracies in the training, test 1, and test 2 data sets, respectively. Compared with manual review, CV-based analysis reduced the time required for operative video review by 86% (manual review: 166.8 and CV analysis: 22.6 minutes; P<.001). The application of a human-computer collaborative strategy increased the overall accuracy to 98.5%, with a 74% reduction in the review time (manual review: 166.8 and human-CV collaboration: 43.4 minutes; P<.001). Analysis of the different surgical phases showed that the sellar phase had the lowest frequency (nasal phase: 14.9, sphenoidal phase: 15.9, and sellar phase: 4.9 interruptions/10 minutes; P<.001) and duration (nasal phase: 67.4, sphenoidal phase: 77.9, and sellar phase: 31.1 seconds/10 minutes; P<.001) of surgical interruptions. A comparison of the early and late EEA videos showed that increased surgical experience was associated with a decreased number (early: 4.9 and late: 2.9 interruptions/10 minutes; P=.03) and duration (early: 41.1 and late: 19.8 seconds/10 minutes; P=.02) of surgical interruptions during the sellar phase. CONCLUSIONS: CV-based analysis had a 93% to 98% accuracy in detecting the number, frequency, and duration of surgical interruptions occurring during EEA. Moreover, CV-based analysis reduced the time required to analyze the surgical fluency in EEA videos compared to manual review. The application of CV can facilitate the training of surgeons to overcome the learning curve of endoscopic skull base surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT06156020; https://clinicaltrials.gov/study/NCT06156020.

4-Hydroxynonenal impairs miRNA maturation in heart failure via Dicer post-translational modification.

BACKGROUND AND AIMS: Developing novel therapies to battle the global public health burden of heart failure remains challenging. This study investigates the underlying mechanisms and potential treatment for 4-hydroxynonenal (4-HNE) deleterious effects in heart failure. METHODS: Biochemical, functional, and histochemical measurements were applied to identify 4-HNE adducts in rat and human failing hearts. In vitro studies were performed to validate 4-HNE targets. RESULTS: 4-HNE, a reactive aldehyde by-product of mitochondrial dysfunction in heart failure, covalently inhibits Dicer, an RNase III endonuclease essential for microRNA (miRNA) biogenesis. 4-HNE inhibition of Dicer impairs miRNA processing. Mechanistically, 4-HNE binds to recombinant human Dicer through an intermolecular interaction that disrupts both activity and stability of Dicer in a concentration- and time-dependent manner. Dithiothreitol neutralization of 4-HNE or replacing 4-HNE-targeted residues in Dicer prevents 4-HNE inhibition of Dicer in vitro. Interestingly, end-stage human failing hearts from three different heart failure aetiologies display defective 4-HNE clearance, decreased Dicer activity, and miRNA biogenesis impairment. Notably, boosting 4-HNE clearance through pharmacological re-activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) using Alda-1 or its improved orally bioavailable derivative AD-9308 restores Dicer activity. ALDH2 is a major enzyme responsible for 4-HNE removal. Importantly, this response is accompanied by improved miRNA maturation and cardiac function/remodelling in a pre-clinical model of heart failure. CONCLUSIONS: 4-HNE inhibition of Dicer directly impairs miRNA biogenesis in heart failure. Strikingly, decreasing cardiac 4-HNE levels through pharmacological ALDH2 activation is sufficient to re-establish Dicer activity and miRNA biogenesis; thereby representing potential treatment for patients with heart failure.

A non-genetic engineering platform for rapidly generating and expanding cancer-specific armed T cells.

BACKGROUND: Cancer-specific adoptive T cell therapy has achieved successful milestones in multiple clinical treatments. However, the commercial production of cancer-specific T cells is often hampered by laborious cell culture procedures, the concern of retrovirus-based gene transfection, or insufficient T cell purity. METHODS: In this study, we developed a non-genetic engineering technology for rapidly manufacturing a large amount of cancer-specific T cells by utilizing a unique anti-cancer/anti-CD3 bispecific antibody (BsAb) to directly culture human peripheral blood mononuclear cells (PBMCs). The anti-CD3 moiety of the BsAb bound to the T cell surface and stimulated the differentiation and proliferation of T cells in PBMCs. The anti-cancer moiety of the BsAb provided these BsAb-armed T cells with the cancer-targeting ability, which transformed the naïve T cells into cancer-specific BsAb-armed T cells. RESULTS: With this technology, a large amount of cancer-specific BsAb-armed T cells can be rapidly generated with a purity of over 90% in 7 days. These BsAb-armed T cells efficiently accumulated at the tumor site both in vitro and in vivo. Cytotoxins (perforin and granzyme) and cytokines (TNF-α and IFN-γ) were dramatically released from the BsAb-armed T cells after engaging cancer cells, resulting in a remarkable anti-cancer efficacy. Notably, the BsAb-armed T cells did not cause obvious cytokine release syndrome or tissue toxicity in SCID mice bearing human tumors. CONCLUSIONS: Collectively, the BsAb-armed T cell technology represents a simple, time-saving, and highly safe method to generate highly pure cancer-specific effector T cells, thereby providing an affordable T cell immunotherapy to patients.

Deep Reinforcement Learning for Joint Trajectory Planning, Transmission Scheduling, and Access Control in UAV-Assisted Wireless Sensor Networks.

Unmanned aerial vehicles (UAVs) can be used to relay sensing information and computational workloads from ground users (GUs) to a remote base station (RBS) for further processing. In this paper, we employ multiple UAVs to assist with the collection of sensing information in a terrestrial wireless sensor network. All of the information collected by the UAVs can be forwarded to the RBS. We aim to improve the energy efficiency for sensing-data collection and transmission by optimizing UAV trajectory, scheduling, and access-control strategies. Considering a time-slotted frame structure, UAV flight, sensing, and information-forwarding sub-slots are confined to each time slot. This motivates the trade-off study between UAV access-control and trajectory planning. More sensing data in one time slot will take up more UAV buffer space and require a longer transmission time for information forwarding. We solve this problem by a multi-agent deep reinforcement learning approach that takes into consideration a dynamic network environment with uncertain information about the GU spatial distribution and traffic demands. We further devise a hierarchical learning framework with reduced action and state spaces to improve the learning efficiency by exploiting the distributed structure of the UAV-assisted wireless sensor network. Simulation results show that UAV trajectory planning with access control can significantly improve UAV energy efficiency. The hierarchical learning method is more stable in learning and can also achieve higher sensing performance.

DHCR24, a Key Enzyme of Cholesterol Synthesis, Serves as a Marker Gene of the Mouse Adrenal Gland Inner Cortex.

Steroid hormones are synthesized through enzymatic reactions using cholesterol as the substrate. In steroidogenic cells, the required cholesterol for steroidogenesis can be obtained from blood circulation or synthesized de novo from acetate. One of the key enzymes that control cholesterol synthesis is 24-dehydrocholesterol reductase (encoded by DHCR24). In humans and rats, DHCR24 is highly expressed in the adrenal gland, especially in the zona fasciculata. We recently reported that DHCR24 was expressed in the mouse adrenal gland's inner cortex and also found that thyroid hormone treatment significantly upregulated the expression of Dhcr24 in the mouse adrenal gland. In the present study, we showed the cellular expression of DHCR24 in mouse adrenal glands in early postnatal stages. We found that the expression pattern of DHCR24 was similar to the X-zone marker gene 20αHSD in most developmental stages. This finding indicates that most steroidogenic adrenocortical cells in the mouse adrenal gland do not synthesize cholesterol locally. Unlike the 20αHSD-positive X-zone regresses during pregnancy, some DHCR24-positive cells remain present in parous females. Conditional knockout mice showed that the removal of Dhcr24 in steroidogenic cells did not affect the overall development of the adrenal gland or the secretion of corticosterone under acute stress. Whether DHCR24 plays a role in conditions where a continuous high amount of corticosterone production is needed requires further investigation.

Acute Effects of Combining Dynamic Stretching and Vibration Foam Rolling Warm-up on Lower-Limb Muscle Performance and Functions in Female Handball Players.

ABSTRACT: Chen, CH, Chiu, CH, Tseng, WC, Wu, CY, Su, HH, Chang, CK, and Ye, X. Acute effects of combining dynamic stretching and vibration foam rolling warm-up on lower-limb muscle performance and functions in female handball players. J Strength Cond Res 37(6): 1277-1283, 2023-The purpose of this study was to compare the acute effects of 3 warm-up protocols on knee flexor and extensor muscles performance in elite female collegiate handball players. Ten female handball players with poor hamstring flexibility completed 3 randomly sequenced experimental visits. During each visit, a different warm-up protocol (general running warm-up [GW], dynamic stretching [DS], or DS combined with vibration foam rolling [DS + VR]) was delivered before the subsequent tests: quadriceps and hamstring muscle stiffness, knee extension and flexion range of motion (ROM), knee joint position sense, knee extension and flexion isokinetic strength with hamstring-quadriceps strength ratio, and muscle endurance during fatiguing exercise. Relative to the GW, the DS + VR protocol resulted in significantly greater knee flexion ROM (mean ± SD : DS + VR = 79.4° ± 7.7°; GW = 69.3° ± 9.6°) and lower hamstring muscle stiffness (DS + VR = 253.33 ± 36.20 N·m -1 ; GW = 292.89 ± 24.28 N·m -1 ). In addition, the DS + VR protocol also yielded greater hamstring muscle endurance than the other 2 protocols did (fatigue percentage: DS + VR = 30.24% ± 10.84%; GW = 41.40% ± 8.98%; DS = 42.22% ± 9.42%). Therefore, the results of this experiment suggest that it can be more beneficial for the female handball players to warm-up with the DS + VR, rather than the GW and DS protocols.

Enterovirus A71 Induces Neurological Diseases and Dynamic Variants in Oral Infection of Human SCARB2-Transgenic Weaned Mice.

Enterovirus A71 (EV-A71) and many members of the Picornaviridae family are neurotropic pathogens of global concern. These viruses are primarily transmitted through the fecal-oral route, and thus suitable animal models of oral infection are needed to investigate viral pathogenesis. An animal model of oral infection was developed using transgenic mice expressing human SCARB2 (hSCARB2 Tg), murine-adapted EV-A71/MP4 virus, and EV-A71/MP4 virus with an engineered nanoluciferase gene that allows imaging of viral replication and spread in infected mice. Next-generation sequencing of EV-A71 genomes in the tissues and organs of infected mice was also performed. Oral inoculation of EV-A71/MP4 or nanoluciferase-carrying MP4 virus stably induced neurological symptoms and death in infected 21-day-old weaned mice. In vivo bioluminescence imaging of infected mice and tissue immunostaining of viral antigens indicated that orally inoculated virus can spread to the central nervous system (CNS) and other tissues. Next-generating sequencing further identified diverse mutations in viral genomes that can potentially contribute to viral pathogenesis. This study presents an EV-A71 oral infection murine model that efficiently infects weaned mice and allows tracking of viral spread, features that can facilitate research into viral pathogenesis and neuroinvasion via the natural route of infection. IMPORTANCE Enterovirus A71 (EV-A71), a positive-strand RNA virus of the Picornaviridae, poses a persistent global public health problem. EV-A71 is primarily transmitted through the fecal-oral route, and thus suitable animal models of oral infection are needed to investigate viral pathogenesis. We present an animal model of EV-A71 infection that enables the natural route of oral infection in weaned and nonimmunocompromised 21-day-old hSCARB2 transgenic mice. Our results demonstrate that severe disease and death could be stably induced, and viral invasion of the CNS could be replicated in this model, similar to severe real-world EV-A71 infections. We also developed a nanoluciferase-containing EV-A71 virus that can be used with this animal model to track viral spread after oral infection in real time. Such a model offers several advantages over existing animal models and can facilitate future research into viral spread, tissue tropism, and viral pathogenesis, all pressing issues that remain unaddressed for EV-A71 infections.

ALDH2 Expression, Alcohol Intake and Semen Parameters among East Asian Men.

PURPOSE: Inactivating mutations in mitochondrial aldehyde dehydrogenase 2 (ALDH2) are highly prevalent. The most common variant allele, ALDH2*2, is present in 40%-50% of East Asians, and causes acetaldehyde accumulation, flushing and tachycardia after alcohol intake. The relationship between alcohol intake and ALDH2 genotype on semen parameters remains unknown. MATERIALS AND METHODS: We conducted a cross-sectional study to determine the association between ALDH2 genotype, alcohol consumption and semen parameters among East Asian men. Volunteers completed a survey and submitted a semen sample for analysis. Participants were genotyped to determine ALDH2 status (ALDH2*1/*1, ALDH2*1/*2, ALDH2*2/*2), and immunohistochemical staining was used to determine protein expression of ALDH2 in spermatozoa. RESULTS: Of 112 men 45 (40.2%) were ALDH2*2 carriers. Among ALDH2*2 carriers, alcohol consumption was associated with significantly lower total sperm motility (median 20% [interquartile range 11%-42%] vs 43% [IQR 31%-57%], p=0.005) and progressive sperm motility (19% [IQR 11%-37%] vs 36% [IQR 25%-53%], p=0.008). Among alcohol consumers, ALDH2*2 carriers had significantly lower total sperm motility (20% [IQR 11%--42%] vs 41% [IQR 19%-57%], p=0.02), progressive sperm motility (19% [IQR 11%-37%] vs 37% [IQR 17%-50%], p=0.02) and total motile sperm count (28 million [M; IQR 9-79M] vs 71M [IQR 23-150M], p=0.05) compared to ALDH2*1/*1 individuals. Secondly, ALDH2 expression in human spermatozoa was significantly lower in ALDH2*2 carriers (ALDH2*1/*1 vs ALDH2*1/*2, p=0.01; ALDH2*1/*1 vs ALDH2*2/*2, p <0.001). CONCLUSIONS: Our findings suggest genotyping ALDH2, coupled with alcohol cessation counseling, may improve semen parameters among men.

Patients' Perspective of the Impacts of Group Psychoeducation for Bipolar Disorder: A Qualitative Study.

ABSTRACT: Little is known regarding the mechanisms involved in the clinical improvement of patients with bipolar disorder (BD) after group psychoeducation. We aimed at investigating these mechanisms by focusing on their subjective experience. Thirteen patients with BD aged 35.54 (SD, 12.06) were recruited. Interviews were analyzed using thematic analysis. Four high-order themes were identified: a) relationship among patients, b) effect of the facilitation style, c) program-related factors, and d) subjective impacts. "Relationships among patients" included a lower-ordered theme evoked by all participants, that is, "shared experiences." Shared experiences included acknowledging that BD has a neurobiological substrate and that its manifestations are similar in BD; the social support and empowering message of those who have managed to exert control over the illness were also highlighted. Our results shed some light on the mechanisms underlying the effectiveness of group psychoeducation. The shared experience of patients seems to play an important role, probably through destigmatization.

Carbohydrate mouth rinsing decreases fatigue index of taekwondo frequency speed of kick test.

Carbohydrate mouth rinsing (CMR) potentially affects the interval training performance of taekwondo athletes. This study explored the effect of CMR on vertical jump, kicking speed, and fatigue index before and after simulated taekwondo competition. In a crossover experimental design, 13 trained taekwondo athletes were randomly divided into the CMR and control trials. After warming up, the participants used 6.6% maltodextrin (CMR trial) or mineral water (control trial) to rinse their mouth. Next, the participants underwent tests of vertical jump, kicking speed, and maximum number of kicks. After the tests, the participants rinsed their mouth again, followed by using Wingate testing bikes for 5-s sprint and 25-s rest to simulate taekwondo competitions. Four repetitions were performed in each round for 2 min for a total of three rounds. The results revealed that the fatigue index of the participants in the CMR trial before and after the simulated competition was significantly lower than that of the control trial. However, the two trials differed nonsignificantly in their performance in vertical jump, kicking speed, and the simulated competition. Overall, the study results indicated that CMR reduces the fatigue index but no change was observed in performance for vertical jump, kicking speed, and the simulated competition of trained taekwondo athletes.

Fungal diversity notes 1512-1610: taxonomic and phylogenetic contributions on genera and species of fungal taxa.

This article is the 14th in the Fungal Diversity Notes series, wherein we report 98 taxa distributed in two phyla, seven classes, 26 orders and 50 families which are described and illustrated. Taxa in this study were collected from Australia, Brazil, Burkina Faso, Chile, China, Cyprus, Egypt, France, French Guiana, India, Indonesia, Italy, Laos, Mexico, Russia, Sri Lanka, Thailand, and Vietnam. There are 59 new taxa, 39 new hosts and new geographical distributions with one new combination. The 59 new species comprise Angustimassarina kunmingense, Asterina lopi, Asterina brigadeirensis, Bartalinia bidenticola, Bartalinia caryotae, Buellia pruinocalcarea, Coltricia insularis, Colletotrichum flexuosum, Colletotrichum thasutense, Coniochaeta caraganae, Coniothyrium yuccicola, Dematipyriforma aquatic, Dematipyriforma globispora, Dematipyriforma nilotica, Distoseptispora bambusicola, Fulvifomes jawadhuvensis, Fulvifomes malaiyanurensis, Fulvifomes thiruvannamalaiensis, Fusarium purpurea, Gerronema atrovirens, Gerronema flavum, Gerronema keralense, Gerronema kuruvense, Grammothele taiwanensis, Hongkongmyces changchunensis, Hypoxylon inaequale, Kirschsteiniothelia acutisporum, Kirschsteiniothelia crustaceum, Kirschsteiniothelia extensum, Kirschsteiniothelia septemseptatum, Kirschsteiniothelia spatiosum, Lecanora immersocalcarea, Lepiota subthailandica, Lindgomyces guizhouensis, Marthe asmius pallidoaurantiacus, Marasmius tangerinus, Neovaginatispora mangiferae, Pararamichloridium aquisubtropicum, Pestalotiopsis piraubensis, Phacidium chinaum, Phaeoisaria goiasensis, Phaeoseptum thailandicum, Pleurothecium aquisubtropicum, Pseudocercospora vernoniae, Pyrenophora verruculosa, Rhachomyces cruralis, Rhachomyces hyperommae, Rhachomyces magrinii, Rhachomyces platyprosophi, Rhizomarasmius cunninghamietorum, Skeletocutis cangshanensis, Skeletocutis subchrysella, Sporisorium anadelphiae-leptocomae, Tetraploa dashaoensis, Tomentella exiguelata, Tomentella fuscoaraneosa, Tricholomopsis lechatii, Vaginatispora flavispora and Wetmoreana blastidiocalcarea. The new combination is Torula sundara. The 39 new records on hosts and geographical distribution comprise Apiospora guiyangensis, Aplosporella artocarpi, Ascochyta medicaginicola, Astrocystis bambusicola, Athelia rolfsii, Bambusicola bambusae, Bipolaris luttrellii, Botryosphaeria dothidea, Chlorophyllum squamulosum, Colletotrichum aeschynomenes, Colletotrichum pandanicola, Coprinopsis cinerea, Corylicola italica, Curvularia alcornii, Curvularia senegalensis, Diaporthe foeniculina, Diaporthe longicolla, Diaporthe phaseolorum, Diatrypella quercina, Fusarium brachygibbosum, Helicoma aquaticum, Lepiota metulispora, Lepiota pongduadensis, Lepiota subvenenata, Melanconiella meridionalis, Monotosporella erecta, Nodulosphaeria digitalis, Palmiascoma gregariascomum, Periconia byssoides, Periconia cortaderiae, Pleopunctum ellipsoideum, Psilocybe keralensis, Scedosporium apiospermum, Scedosporium dehoogii, Scedosporium marina, Spegazzinia deightonii, Torula fici, Wiesneriomyces laurinus and Xylaria venosula. All these taxa are supported by morphological and multigene phylogenetic analyses. This article allows the researchers to publish fungal collections which are important for future studies. An updated, accurate and timely report of fungus-host and fungus-geography is important. We also provide an updated list of fungal taxa published in the previous fungal diversity notes. In this list, erroneous taxa and synonyms are marked and corrected accordingly.

Acute Effects of Different Warm-up Protocols on Sports Performance in Elite Male Collegiate Handball Players.

ABSTRACT: Chen, CH, Chang, CK, Tseng, WC, Chiu, CH, Dai, X, and Ye, X. Acute effects of different warm-up protocols on sports performance in elite male collegiate handball players. J Strength Cond Res 36(8): 2262-2267, 2022-This study aimed to examine the effects of 3 different warm-up protocols on subsequent sports performance in elite male collegiate handball players. Fifteen handball players (19.0 ± 2.4 years) completed 3 separated randomly sequenced experimental visits. During each visit, they started with different warm-up protocols (traditional warm-up [TRAD] vs. warm-up with core stability exercises [CORE] vs. warm-up with elastic band exercises [ELAS]) and completed with a series of randomly ordered sport-specific performance testing measurements: 30-m sprint, countermovement jump, medicine ball overhead forward throw, and standing and jump handball throw tests. Both CORE and ELAS protocols induced statistically significant differences (p < 0.05) on overall sports performance (sprint time, jump height, medicine ball throwing peak velocity and power, and handball throwing velocities), as compared to the TRAD. In addition, the ELAS protocol imposed small-to-medium effects (effect size range: 0.45-0.82), enhancing handball throwing velocity and medicine ball throwing performance comparing with the CORE. Sport-specific warm-up protocols that contain core stability or elastic band-based exercises likely induced subsequent performance enhancements (sprint, jump, and throw) in elite male collegiate handball players when compared with TRAD. Furthermore, including elastic band exercises in the warm-up protocol even induced superior upper-body performance enhancement (explosive power and handball throwing velocity) than other protocols. Therefore, preconditioning warm-up activities using elastic band-based exercises can be integrated into a traditional sport-specific warm-up protocol for elite collegiate handball players before competition or training.

Targeting aldehyde dehydrogenase 2: new therapeutic opportunities.

A family of detoxifying enzymes called aldehyde dehydrogenases (ALDHs) has been a subject of recent interest, as its role in detoxifying aldehydes that accumulate through metabolism and to which we are exposed from the environment has been elucidated. Although the human genome has 19 ALDH genes, one ALDH emerges as a particularly important enzyme in a variety of human pathologies. This ALDH, ALDH2, is located in the mitochondrial matrix with much known about its role in ethanol metabolism. Less known is a new body of research to be discussed in this review, suggesting that ALDH2 dysfunction may contribute to a variety of human diseases including cardiovascular diseases, diabetes, neurodegenerative diseases, stroke, and cancer. Recent studies suggest that ALDH2 dysfunction is also associated with Fanconi anemia, pain, osteoporosis, and the process of aging. Furthermore, an ALDH2 inactivating mutation (termed ALDH2*2) is the most common single point mutation in humans, and epidemiological studies suggest a correlation between this inactivating mutation and increased propensity for common human pathologies. These data together with studies in animal models and the use of new pharmacological tools that activate ALDH2 depict a new picture related to ALDH2 as a critical health-promoting enzyme.