Key processes required for the different stages of fungal carnivory by a nematode-trapping fungus.

Nutritional deprivation triggers a switch from a saprotrophic to predatory lifestyle in soil-dwelling nematode-trapping fungi (NTF). In particular, the NTF Arthrobotrys oligospora secretes food and sex cues to lure nematodes to its mycelium and is triggered to develop specialized trapping devices. Captured nematodes are then invaded and digested by the fungus, thus serving as a food source. In this study, we examined the transcriptomic response of A. oligospora across the stages of sensing, trap development, and digestion upon exposure to the model nematode Caenorhabditis elegans. A. oligospora enacts a dynamic transcriptomic response, especially of protein secretion-related genes, in the presence of prey. Two-thirds of the predicted secretome of A. oligospora was up-regulated in the presence of C. elegans at all time points examined, and among these secreted proteins, 38.5% are predicted to be effector proteins. Furthermore, functional studies disrupting the t-SNARE protein Sso2 resulted in impaired ability to capture nematodes. Additionally, genes of the DUF3129 family, which are expanded in the genomes of several NTF, were highly up-regulated upon nematode exposure. We observed the accumulation of highly expressed DUF3129 proteins in trap cells, leading us to name members of this gene family as Trap Enriched Proteins (TEPs). Gene deletion of the most highly expressed TEP gene, TEP1, impairs the function of traps and prevents the fungus from capturing prey efficiently. In late stages of predation, we observed up-regulation of a variety of proteases, including metalloproteases. Following penetration of nematodes, these metalloproteases facilitate hyphal growth required for colonization of prey. These findings provide insights into the biology of the predatory lifestyle switch in a carnivorous fungus and provide frameworks for other fungal-nematode predator-prey systems.

Increased risk of psychiatric disorder in patients with hearing loss: a nationwide population-based cohort study.

BACKGROUND: Hearing loss has been shown to be a risk factor for psychiatric disorders. In addition, long-term hearing loss is associated with increased hospitalization and mortality rates; however, the increased risk and duration of effect of hearing loss in combination with other chronic diseases on each psychiatric disorder are still not clearly defined. The purpose of this article is to clarify the risk of hearing loss for each disorder over time. METHODS: This was a retrospective cohort study, and a national health insurance research database in Taiwan was utilized. All (n = 1,949,101) Taiwanese residents who had a medical visit between 2000 and 2015 were included. Patients with hearing loss and a comparative retrospective cohort were analyzed. Every subject was tracked individually from their index date to identify the subjects who later received a diagnosis of a psychiatric disorder. The Kaplan‒Meier method was used to analyze the cumulative incidence of psychiatric disorders. Cox regression analysis was performed to identify the risk of psychiatric disorders. RESULTS: A total of 13,341 (15.42%) and 31,250 (9.03%) patients with and without hearing loss, respectively, were diagnosed with psychiatric disorders (P < 0.001). Multivariate analysis indicated that hearing loss significantly elevated the risk of psychiatric disorders (adjusted HR = 2.587, 95% CI 1.723-3.346, p < 0.001). CONCLUSION: Our findings indicate that patients with hearing loss are more likely to develop psychiatric disorders. Furthermore, the various psychiatric disorders are more likely to occur at different times. Our findings have important clinical implications, including a need for clinicians to implement early intervention for hearing loss and to pay close attention to patients' psychological status. Trial registration TSGHIRB No. E202216036.

C-Phycocyanin Attenuates Noise-Induced Cochlear Synaptopathy via the Inhibition of Oxidative Stress and Intercellular Adhesion Molecule-1 in the Cochlea.

The synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are the most vulnerable structures in the noise-exposed cochlea. Cochlear synaptopathy results from the disruption of these synapses following noise exposure and is considered the main cause of poor speech understanding in noisy environments, even when audiogram results are normal. Cochlear synaptopathy leads to the degeneration of SGNs if damaged IHC-SGN synapses are not promptly recovered. Oxidative stress plays a central role in the pathogenesis of cochlear synaptopathy. C-Phycocyanin (C-PC) has antioxidant and anti-inflammatory activities and is widely utilized in the food and drug industry. However, the effect of the C-PC on noise-induced cochlear damage is unknown. We first investigated the therapeutic effect of C-PC on noise-induced cochlear synaptopathy. In vitro experiments revealed that C-PC reduced the H2O2-induced generation of reactive oxygen species in HEI-OC1 auditory cells. H2O2-induced cytotoxicity in HEI-OC1 cells was reduced with C-PC treatment. After white noise exposure for 3 h at a sound pressure of 118 dB, the guinea pigs intratympanically administered 5 µg/mL C-PC exhibited greater wave I amplitudes in the auditory brainstem response, more IHC synaptic ribbons and more IHC-SGN synapses according to microscopic analysis than the saline-treated guinea pigs. Furthermore, the group treated with C-PC had less intense 4-hydroxynonenal and intercellular adhesion molecule-1 staining in the cochlea compared with the saline group. Our results suggest that C-PC improves cochlear synaptopathy by inhibiting noise-induced oxidative stress and the inflammatory response in the cochlea.

Natural diversity in the predatory behavior facilitates the establishment of a robust model strain for nematode-trapping fungi.

Nematode-trapping fungi (NTF) are a group of specialized microbial predators that consume nematodes when food sources are limited. Predation is initiated when conserved nematode ascaroside pheromones are sensed, followed by the development of complex trapping devices. To gain insights into the coevolution of this interkingdom predator-prey relationship, we investigated natural populations of nematodes and NTF that we found to be ubiquitous in soils. Arthrobotrys species were sympatric with various nematode species and behaved as generalist predators. The ability to sense prey among wild isolates of Arthrobotrys oligospora varied greatly, as determined by the number of traps after exposure to Caenorhabditis elegans While some strains were highly sensitive to C. elegans and the nematode pheromone ascarosides, others responded only weakly. Furthermore, strains that were highly sensitive to the nematode prey also developed traps faster. The polymorphic nature of trap formation correlated with competency in prey killing, as well as with the phylogeny of A. oligospora natural strains, calculated after assembly and annotation of the genomes of 20 isolates. A chromosome-level genome assembly and annotation were established for one of the most sensitive wild isolates, and deletion of the only G-protein ß-subunit-encoding gene of A. oligospora nearly abolished trap formation. In summary, our study establishes a highly responsive A. oligospora wild isolate as a model strain for the study of fungus-nematode interactions and demonstrates that trap formation is a fitness character in generalist predators of the nematode-trapping fungus family.

Genome-wide association study reveals ethnicity-specific SNPs associated with ankylosing spondylitis in the Taiwanese population.

BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune disease affecting mainly spine and sacroiliac joints and adjacent soft tissues. Genome-wide association studies (GWASs) are used to evaluate genetic associations and to predict genetic risk factors that determine the biological basis of disease susceptibility. We aimed to explore the race-specific SNP susceptibility of AS in Taiwanese individuals and to investigate the association between HLA-B27 and AS susceptibility SNPs in Taiwan. METHODS: Genotyping data were collected from a medical center participating in the Taiwan Precision Medicine Initiative (TPMI) in the northern district of Taiwan. We designed a case-control study to identify AS susceptibility SNPs through GWAS. We searched the genome browser to find the corresponding susceptibility genes and used the GTEx database to confirm the regulation of gene expression. A polygenic risk score approach was also applied to evaluate the genetic variants in the prediction of developing AS. RESULTS: The results showed that the SNPs located on the sixth chromosome were related to higher susceptibility in the AS group. There was no overlap between our results and the susceptibility SNPs found in other races. The 12 tag SNPs located in the MHC region that were found through the linkage disequilibrium method had higher gene expression. Furthermore, Taiwanese people with HLA-B27 positivity had a higher proportion of minor alleles. This might be the reason that the AS prevalence is higher in Taiwan than in other countries. We developed AS polygenic risk score models with six different methods in which those with the top 10% polygenic risk had a fivefold increased risk of developing AS compared to the remaining group with low risk. CONCLUSION: A total of 147 SNPs in the Taiwanese population were found to be statistically significantly associated with AS on the sixth pair of chromosomes and did not overlap with previously published sites in the GWAS Catalog. Whether those genes mapped by AS-associated SNPs are involved in AS and what the pathogenic mechanism of the mapped genes is remain to be further studied.

Lysosomal Dysfunction and Autophagy Blockade Contribute to MDMA-Induced Neurotoxicity in SH-SY5Y Neuroblastoma Cells.

Methylenedioxymethamphetamine (MDMA) is a psychostimulant with high abuse potential and severe neurotoxicity. According to our previous study, MDMA promotes autophagosome accumulation and contributes to cell death in cultured cortical and serotonergic neurons. However, the detailed mechanism underlying autophagy dysfunction remains unclear. Lysosomes play an important role in autophagic degradation. The present study aimed to examine the role of lysosomal function in autophagic flux in neuronal cultures exposed to MDMA. We showed that MDMA induced enlarged vesicles that accumulate in SH-SY5Y neuroblastoma cells. In addition, we demonstrated that MDMA stimulated dynamin-dependent but clathrin-independent endocytosis, which might contribute to vacuole expansion. Morphological and Western blot analyses revealed that MDMA induced lysosomal swelling, whereas the activity of the lysosomal hydrolytic enzymes cathepsin B and cathepsin D was decreased in SH-SY5Y and cultured cortical neurons, which might lead to autophagosome accumulation and autophagic degradation blockage. Intriguingly, inactivation of cathepsins B and D led to cell death and autophagy-lysosomal dysregulation, which mimicked MDMA-induced neurotoxicity. Consequently, impairment of lysosomal proteolysis and blockage of autophagy degradation contributed to MDMA-induced neurotoxicity in neuronal cultures.

Fungal feature tracker (FFT): A tool for quantitatively characterizing the morphology and growth of filamentous fungi.

Filamentous fungi are ubiquitous in nature and serve as important biological models in various scientific fields including genetics, cell biology, ecology, evolution, and chemistry. A significant obstacle in studying filamentous fungi is the lack of tools for characterizing their growth and morphology in an efficient and quantitative manner. Consequently, assessments of the growth of filamentous fungi are often subjective and imprecise. In order to remedy this problem, we developed Fungal Feature Tracker (FFT), a user-friendly software comprised of different image analysis tools to automatically quantify different fungal characteristics, such as spore number, spore morphology, and measurements of total length, number of hyphal tips and the area covered by the mycelium. In addition, FFT can recognize and quantify specialized structures such as the traps generated by nematode-trapping fungi, which could be tuned to quantify other distinctive fungal structures in different fungi. We present a detailed characterization and comparison of a few fungal species as a case study to demonstrate the capabilities and potential of our software. Using FFT, we were able to quantify various features at strain and species level, such as mycelial growth over time and the length and width of spores, which would be difficult to track using classical approaches. In summary, FFT is a powerful tool that enables quantitative measurements of fungal features and growth, allowing objective and precise characterization of fungal phenotypes.

Correction to: Risk reduction of long-term major adverse cardiovascular events after endoscopic thoracic sympathectomy in palmar hyperhidrosis.

There is a typographical error in the International Classification of Disease Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic code used for palmar hyperhidrosis. The published manuscript wrongly reports that the ICD-9-CM code used for palmar hyperhidrosis was 708.8 (which indicates a diagnosis of "Other specified urticaria"), when, in actuality, the correct code 780.8 ("Hyperhidrosis") was applied. The authors regret this typographical error.

Risk reduction of long-term major adverse cardiovascular events after endoscopic thoracic sympathectomy in palmar hyperhidrosis.

PURPOSE: Palmar hyperhidrosis (PH) is excessive sweating of the palms resulting from sympathetic overactivity, and patients who undergo endoscopic thoracic sympathectomy (ETS) show reduced cardiac demand after 1 year and improved cerebral perfusion within 2-4 weeks. However, the long-term risks of major adverse cardiovascular events (MACE) following ETS remain unclear. METHODS: We searched the Longitudinal National Health Insurance Database in Taiwan and identified PH patients (International Classification of Disease, Ninth Revision, Clinical Modification diagnostic code 708.8) from the outpatient database and patients who underwent ETS (procedure code 05.29) from the inpatient database between 2000 and 2010; furthermore, we excluded patients younger than 18 years of age or older than 65 years of age. We defined MACE as stroke (diagnostic codes 430-437), myocardial infarction (diagnostic code 410), or death. Patients followed until the first cardiac event or December 31, 2010. Risk factors were identified using a multivariable Cox proportional hazards regression. RESULTS: The incidence of MACE was significantly lower in patients with ETS (0.76%) than without (1.67%). In PH patients, ETS significantly reduced the risk of MACE (adjusted hazard ratio 0.473; 95% confidence interval 0.277-0.808). CONCLUSION: PH patients who underwent ETS showed a reduced risk of MACE over a long-term follow-up period. This result could provide support for patients with PH who are considering undergoing ETS because of its additional cardiovascular benefits.

Clinical assessment of diode laser-assisted endoscopic intrasphenoidal vidian neurectomy in the treatment of refractory rhinitis.

For chronic rhinitis that is refractory to medical therapy, surgical intervention such as endoscopic vidian neurectomy (VN) can be used to control the intractable symptoms. Lasers can contribute to minimizing the invasiveness of ENT surgery. The aim of this retrospective study is to compare in patients who underwent diode laser-assisted versus traditional VN in terms of operative time, surgical field, quality of life, and postoperative complications. All patients had refractory rhinitis with a poor treatment response to a 6-month trial of corticosteroid nasal sprays and underwent endoscopic VN between November 2006 and September 2015. They were non-randomly allocated into either a cold instrument group or a diode laser-assisted group. Vidian nerve was excised with a 940-nm continuous wave diode laser through a 600-µm silica optical fiber, utilizing a contact mode with the power set at 5 W. A visual analog scale (VAS) was used to grade the severity of the rhinitis symptoms for quality of life assessment before the surgery and 6 months after. Of the 118 patients enrolled in the study, 75 patients underwent cold instrument VN and 43 patients underwent diode laser-assisted VN. Patients in the laser-assisted group had a significantly lower surgical field score and a lower postoperative bleeding rate than those in the cold instrument group. Changes in the VAS were significant in preoperative and postoperative nasal symptoms in each group. The application of diode lasers for vidian nerve transection showed a better surgical field and a lower incidence of postoperative hemorrhage. Recent advancements in laser application and endoscopic technique has made VN safer and more effective. We recommend this surgical approach as a reliable and effective treatment for patients with refractory rhinitis.

An Analysis of Long-Term Ischemic Stroke Risk in Survivors of Septicemia.

INTRODUCTION: Sepsis increases the long-term incidence of ischemic stroke (IS). The chances for long-term IS in patients who are discharged after sepsis are unclear. Our aim was to demonstrate long-term risk chances of IS after septicemia discharge. We used a nomogram to identify those septicemia survivors with the higher risk of developing IS. METHODS: Inpatient data were used from the Taiwan Longitudinal Health Insurance Database, from 2001 to 2003. The event was IS rehospitalization after discharge of septicemia. We used multivariate Cox proportional regression of the risk factors for IS in septicemia survivors to create a nomogram. RESULTS: There were 642 IS incidents in this study. The risk factors for IS in survivors of septicemia were advanced age (hazard ratio [HR] 1.035 [95% confidence interval (CI) 1.029-1.042]), new-onset atrial fibrillation (HR 1.875 [95% CI 1.327-2.651]), hypertension (HR 2.042 [95% CI 1.687-2.471]), diabetes mellitus (HR 1.735 [95% CI 1.469-2.05]), coronary artery disease (HR 1.661 [95% CI 1.408-1.96]), chronic kidney disease (HR 1.264 [95% CI 1.071-1.49]), chronic obstructive pulmonary disease (HR 1.201 [95% CI 1.016-1.421]), and local hospital admission (HR 1.414 [95% CI 1.155-1.731]). The model showed good calibration and discrimination, with a bootstrap-corrected concordance index of .785. CONCLUSION: With this prognostic nomogram, we found age with the strongest factor for IS. There was increased IS incidence with more comorbid conditions in advance-aged septicemia survivors. Physicians must identify high IS-risk patients and control risk factors to prevent adverse events in the clinical setting.

Dried salted plum consumption ameliorates hyperbaric oxygen therapy-induced otalgia severity at the first chamber session: a prospective randomized controlled study.

PURPOSE: One of the most common complications of hyperbaric oxygen (HBO2) therapy is middle ear barotrauma (MEB), occasionally causing otalgia. The objective of this study was to evaluate the effect of dried salted plum consumption on MEB and otalgia associated with HBO2 therapy. MATERIALS AND METHODS: Patients undergoing the first chamber session of HBO2 therapy were included in the present prospective randomized controlled trial. The Valsalva maneuver was administered to all patients before HBO2. The patients were randomly divided into two groups: one that ate a dried salted plum during HBO2 treatment and the other that did not. An otoscopic examination was performed after HBO2 therapy. The MEB was graded according to Teed scores. The degree of otalgia was recorded using the Visual Analog Scale (VAS). RESULTS: Ninety patients were enrolled. The overall incidence of MEB (Teed score grade 1~4) was 39.6% (21 of 53) for patients administered a dried salted plum versus 37.8% (14 of 37) for the control group (P=1.000). The incidence of mild MEB (Teed score grade 1~2) and severe MEB (Teed score Grade 3~4) between the two groups was not significantly different. Otalgia was present in 5.7% (3 of 53) of patients administered a dried salted plum versus 18.9% (7 of 37) for the control group (P=.085). No patients administered a dried salted plum had a VAS score ≥4 for otalgia versus 10.8% (4 of 37) for the control group (P=.026). CONCLUSIONS: Dried salted plum consumption does not decrease the incidence of MEB, but may ameliorate the severity of first chamber session HBO2-induced otalgia.

Potential Treatments for Epiglottic Collapse in Obstructive Sleep Apnea: How Modified Drug-Induced Sleep Endoscopy Help?

OBJECTIVE: In patients with obstructive sleep apnea (OSA), epiglottic collapse (EC) constitutes a major factor in the failure of continuous positive airway pressure therapy and uvulopalatopharyngoplasty. This study explored treatments that can improve EC in patients with OSA through drug-induced sleep endoscopy with target-controlled infusion (TCI-DISE). STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary center. METHODS: This study screened 352 OSA patients who underwent TCI-DISE between 2016 and 2022. Fifty-four patients with EC were included in the final analysis. EC severity was assessed multiple times through TCI-DISE with different interventions. RESULTS: The application of these interventions in patients with anteroposterior epiglottic collapse (apEC) led to a significant decrease in apEC severity from total to partial or no obstruction in 60.0% of patients by head rotation, in 53.6% by mouth closure, in 47.4% who received oral appliances (OA), and in 28.0% who received intermittent negative airway pressure (iNAP). With simultaneous head rotation, apEC severity decreased more significantly from total to partial or no obstruction in 77.8% of patients by mouth closure, in 70.3% who received OA, and in 68.0% who received iNAP. Lateral epiglottic collapse (latEC) severity decreased in 53.8% of patients after OA use and in 61.5% of patients with OA use and head rotation. CONCLUSION: This study identified head rotation with mouth closure as the most effective treatment for apEC through TCI-DISE. Patients with latEC had higher weight, apnea-hypopnea index, and body mass index compared with patients with apEC. OA use with head rotation appeared more effective in latEC through TCI-DISE.

The nematode-trapping fungus Arthrobotrys oligospora detects prey pheromones via G protein-coupled receptors.

The ability to sense prey-derived cues is essential for predatory lifestyles. Under low-nutrient conditions, Arthrobotrys oligospora and other nematode-trapping fungi develop dedicated structures for nematode capture when exposed to nematode-derived cues, including a conserved family of pheromones, the ascarosides. A. oligospora senses ascarosides via conserved MAPK and cAMP-PKA pathways; however, the upstream receptors remain unknown. Here, using genomic, transcriptomic and functional analyses, we identified two families of G protein-coupled receptors (GPCRs) involved in sensing distinct nematode-derived cues. GPCRs homologous to yeast glucose receptors are required for ascaroside sensing, whereas Pth11-like GPCRs contribute to ascaroside-independent nematode sensing. Both GPCR classes activate conserved cAMP-PKA signalling to trigger trap development. This work demonstrates that predatory fungi use multiple GPCRs to sense several distinct nematode-derived cues for prey recognition and to enable a switch to a predatory lifestyle. Identification of these receptors reveals the molecular mechanisms of cross-kingdom communication via conserved pheromones also sensed by plants and animals.

Increased Risk of Injury in Ménière's Disease and Effects of Treatment: Population-Based Retrospective Cohort Study.

OBJECTIVE: To investigate the risk of injury in patients with Ménière's disease (MD) and the effects of treatment. STUDY DESIGN: Population-based retrospective cohort study. SETTING: Data were collected from the Longitudinal Health Insurance Database 2005, containing the information of 2 million randomly selected individuals in Taiwan. METHODS: We enrolled 90,481 patients with newly diagnosed MD between 2000 and 2017 and 361,924 matched individuals without MD. The study outcomes were diagnoses of all-cause injuries. The Kaplan-Meier method was used to determine the cumulative incidence rates of injury in the MD and non-MD cohorts, and a log-rank test was used to analyze the differences between the cohorts. Cox proportional hazards models were used to calculate the 18-year hazard ratios of each cohort. RESULTS: A total of 80,151 patients were diagnosed with injuries during the follow-up period: 24,031 and 56,120 from the MD and non-MD cohorts, respectively. The adjusted hazard ratio (aHR) was 2.19 (95% CI, 2.16-2.35) after adjusting for demographic characteristics and comorbidities. Subgroup analysis revealed that MD was associated with an increased incidence of unintentional and intentional injuries (aHR, 2.24 [95% CI, 2.21-2.41] and 2.05 [95% CI, 2.01-2.19], respectively). Treatment with diuretics, antivertigo medications, or surgery did not reduce the risk of injury (aHR, 0.98 [95% CI, 0.59-1.54], 0.94 [95% CI, 0.58-1.50], and 0.99 [95% CI, 0.61-1.54]). CONCLUSION: MD is independently associated with an increased risk of injuries. Medical or surgical treatment for MD does not reduce the risk of injury in patients with MD. Physicians should counsel patients with MD regarding preventive measures for avoiding subsequent injuries.

Upper Airway Surgery or Weight Control? Modified Drug-Induced Sleep Endoscopy for Obstructive Sleep Apnea.

OBJECTIVE: To identify the value of head rotation in the supine position and oral appliance (OA) use in drug-induced sleep endoscopy (DISE). STUDY DESIGN: Eighty-three sleep apnea adults undergoing target-controlled infusion-DISE (TCI-DISE) were recruited from a tertiary academic medical center. SETTING: During DISE, 4 positions were utilized: supine position (position 1), head rotation (position 2), mandibular advancement using an OA (position 3), and head rotation with an OA (position 4). METHODS: Polysomnography (PSG) data and anthropometric variables during DISE were analyzed. RESULTS: Eighty-three patients (65 men and 18 women; mean [standard deviation, SD], 48.5 [11.0] years) who underwent PSG and TCI-DISE were included. The mean (SD) apnea-hypopnea index (AHI) was 35.5 (22.4) events/h. Twenty-three patients had persistent complete concentric velopharyngeal collapse in the supine position, even with concurrent head rotation and OA (position 4). Their mean (SD) AHI was 54.7 (24.6) events/h, significantly higher than that of the 60 patients without such collapse in position 4 (p < .001). Their mean (SD) body mass index (BMI) was 29.0 (4.1) kg/m2 , also significantly higher (p = .005). After adjustment for age, BMI, tonsil size, and tongue position, the degree of velum and tongue base obstruction was significantly associated with sleep apnea severity in positions 2, 3, and 4. CONCLUSION: We showed the feasibility, safety, and usefulness of using simple edge-to-edge, reusable OA in DISE. Patients who are not responsive to head rotation and OA during TCI-DISE may need upper airway surgery and/or weight control.

The cAMP-PKA pathway regulates prey sensing and trap morphogenesis in the nematode-trapping fungus Arthrobotrys oligospora.

Sensing environmental factors and responding swiftly to them is essential for all living organisms. For instance, predators must act rapidly once prey is sensed. Nematode-trapping fungi (NTF) are predators that use "traps" differentiated from vegetative hyphae to capture, kill, and consume nematodes. These traps undergo drastic and rapid morphological changes upon nematode induction. Multiple signaling hubs have been shown to regulate this remarkable process. Here, we demonstrate that the conserved cAMP-PKA signaling pathway exerts a crucial role in trap morphogenesis of the nematode-trapping fungi Arthrobotrys oligospora. A gene deletion mutant of the PKA catalytic subunit TPK2 proved insensitive toward nematode presence. Moreover, we show that the G protein alpha subunit GPA2 acts upstream of adenylate cyclase, with GPA2 deletion resulting in substantially reduced trap formation, whereas exogenous provision of cAMP rescued the prey-sensing and trap morphogenesis defects of a gpa2 mutant. Thus, we show that cAMP production triggered by G protein signaling and downstream PKA activity are vital for prey-sensing and trap development in A. oligospora, demonstrating that this highly conserved signaling pathway is critical for nematode-trapping fungi and nematode predator-prey interactions.

Air Pollution Exposure and the Relative Risk of Sudden Sensorineural Hearing Loss in Taipei.

(1) Background: The etiologies of sudden sensorineural hearing loss (SSHL) remain unclear. The level of mean particulate matter with a diameter of 2.5 µm or less (PM2.5) was not associated with SSHL, but the maximum PM2.5 level exhibited a negative association with SSHL in Korea. Exposure to nitrogen dioxide (NO2) for 2 weeks increased the risk of SSHL. The lag effects of SSHL after air pollution exposure were limited. We aimed to evaluate the association of SSHL with air pollution exposure to determine whether air pollution exposure caused delayed effects. (2) Methods: This observational study used inpatient data obtained from electronic health records at the Tri-Service General Hospital from 2011 to 2019. The data of all SSHL patients were retrieved. The air quality dataset from Songshan station from 2011 to 2019 was used. The main outcomes were the relative risks (RRs) of SSHL associated with PM2.5, O3, and NO2 exposures within 1 month. The relationships between these factors were examined using distributed lag nonlinear time series models. (3) Results: The RR of SSHL associated with PM2.5 exposure was 1.195 (95% confidence interval (C.I.: 1.047-1.363) for a 10 unit increase at a lag of 7 days. The RR of SSHL associated with O3 exposure was 1.14 (95% C.I.: 1.003-1.3) for a 10 unit increase at a lag of 9 days. The RR of SSHL associated with NO2 exposure was 1.284 (95% C.I.: 1.05-1.57) for a 10 unit increase at a lag of 23 days. (4) Conclusions: In our study, SSHL was confirmed to be associated with air pollution exposure with a lag effect. We discussed possible mechanisms to explore possible biological hypotheses and support further research. Large-scale studies including participants with other ethnicities and causal relationships are needed to confirm our findings.

Innovative Hybrid-Alignment Annotation Method for Bioinformatics Identification and Functional Verification of a Novel Nitric Oxide Synthase in Trichomonas vaginalis.

Both the annotation and identification of genes in pathogenic parasites are still challenging. Although, as a survival factor, nitric oxide (NO) has been proven to be synthesized in Trichomonas vaginalis (TV), nitric oxide synthase (NOS) has not yet been annotated in the TV genome. We developed a witness-to-suspect strategy to identify incorrectly annotated genes in TV via the Smith-Waterman and Needleman-Wunsch algorithms through in-depth and repeated alignment of whole coding sequences of TV against thousands of sequences of known proteins from other organisms. A novel NOS of TV (TV NOS), which was annotated as hydrogenase in the NCBI database, was successfully identified; this TV NOS had a high witness-to-suspect ratio and contained all the NOS cofactor-binding motifs (NADPH, tetrahydrobiopterin (BH4), heme and flavin adenine dinucleotide (FAD) motifs). To confirm this identification, we performed in silico modeling of the protein structure and cofactor docking, cloned the gene, expressed and purified the protein, performed mass spectrometry analysis, and ultimately performed an assay to measure enzymatic activity. Our data showed that although the predicted structure of the TV NOS protein was not similar to the structure of NOSs of other species, all cofactor-binding motifs could interact with their ligands with high affinities. We clearly showed that the purified protein had high enzymatic activity for generating NO in vitro. This study provides an innovative approach to identify incorrectly annotated genes in TV and highlights a novel NOS that might serve as a virulence factor of TV.

Effect of the Nintendo Ring Fit Adventure Exergame on Running Completion Time and Psychological Factors Among University Students Engaging in Distance Learning During the COVID-19 Pandemic: Randomized Controlled Trial.

BACKGROUND: The COVID-19 outbreak has not only changed the lifestyles of people globally but has also resulted in other challenges, such as the requirement of self-isolation and distance learning. Moreover, people are unable to venture out to exercise, leading to reduced movement, and therefore, the demand for exercise at home has increased. OBJECTIVE: We intended to investigate the relationships between a Nintendo Ring Fit Adventure (RFA) intervention and improvements in running time, cardiac force index (CFI), sleep quality (Chinese version of the Pittsburgh Sleep Quality Index score), and mood disorders (5-item Brief Symptom Rating Scale score). METHODS: This was a randomized prospective study and included 80 students who were required to complete a 1600-meter outdoor run before and after the intervention, the completion times of which were recorded in seconds. They were also required to fill out a lifestyle questionnaire. During the study, 40 participants (16 males and 24 females, with an average age of 23.75 years) were assigned to the RFA group and were required to exercise for 30 minutes 3 times per week (in the adventure mode) over 4 weeks. The exercise intensity was set according to the instructions given by the virtual coach during the first game. The remaining 40 participants (30 males and 10 females, with an average age of 22.65 years) were assigned to the control group and maintained their regular habits during the study period. RESULTS: The study was completed by 80 participants aged 20 to 36 years (mean 23.20, SD 2.96 years). The results showed that the running time in the RFA group was significantly reduced. After 4 weeks of physical training, it took females in the RFA group 19.79 seconds (P=.03) and males 22.56 seconds (P=.03) less than the baseline to complete the 1600-meter run. In contrast, there were no significant differences in the performance of the control group in the run before and after the fourth week of intervention. In terms of mood disorders, the average score of the RFA group increased from 1.81 to 3.31 for males (difference=1.50, P=.04) and from 3.17 to 4.54 for females (difference=1.38, P=.06). In addition, no significant differences between the RFA and control groups were observed for the CFI peak acceleration (CFIPA)_walk, CFIPA_run, or sleep quality. CONCLUSIONS: RFA could either maintain or improve an individual's physical fitness, thereby providing a good solution for people involved in distance learning or those who have not exercised for an extended period. TRIAL REGISTRATION: ClinicalTrials.gov NCT05227040; https://clinicaltrials.gov/ct2/show/NCT05227040.