Characterization of the complete mitochondrial genome of Paecilomyces variotii and comparative evolutionary mitochondriomics of 36 fungi.

BACKGROUD: Paecilomyces variotii has important economic value in stimulating crop growth, biodegradation, and other aspects. Up to now, there are no research reports on its mitochondrial genome. METHODS AND RESULTS: The mitochondrial genome of Paecilomyces variotii was determined with the next-generation sequencing method (Illumina, NovaSeq), and its characteristics were analyzed using various bioinformatics approaches. The length of complete mitochondrial genome sequence of P. variotii is 40,965 bp and consists of 14 protein-coding genes, 2 ribosomal RNA genes, 1 ribosomal protein S3 gene, 26 transport RNA genes. The results of phylogenetics analysis using Bayesian inference and Maximum likelihood methods showed that P. variotii belongs to the Eurotiales order in the Thermoascaceae family, and 9 genera within the Eurotiomycetes class were effectively distinguished with high support rates (bootstrap value > 92% and posterior probabilities > 99%). The analysis of synonymous substitution rates and nonsynonymous substitution rates indicated that the Ka/Ks values of the 14 PCGs in the mitochondrial genomes of the two orders in the Eurotiomycetes class ranged from 0 to 0.4333. CONCLUSIONS: This study revealed the structural and sequence information characteristics of the mitochondrial genome of P. variotii, and the phylogenetic results strongly support its classification within the family Thermoascaceae, consistent with traditional morphological taxonomy studies. The 14 PCGs in the mitochondrial genomes of the two orders in the Eurotiomycetes class are subject to strong purifying (negative) selection. The results of this research provides an important molecular basis for the development of genomics, evolutionary genetics and molecular markers of P. variotii in the future.

Profile of cough triggers and their relationship with capsaicin cough sensitivity in chronic cough.

BACKGROUND: Cough hypersensitivity is an important part of the neurophysiology of cough, which presents with increased cough response to a lower level of stimuli or triggers. Classification of stimuli might bring about additional insight into the underlying mechanisms and management. OBJECTIVES: This study investigated the profile of cough triggers in chronic cough patients and their relationship with capsaicin cough sensitivity. DESIGN: This was a cross-sectional observational study. METHODS: We enrolled patients with different causes of chronic cough from 2006 to 2021. Cough triggers were defined as cough response to chemical triggers, mechanical triggers, meal triggers, or thermal trigger. Cough sensitivity to capsaicin was evaluated by the capsaicin challenge test, which was expressed as the lowest concentration of capsaicin inducing 5 or more coughing (C5). RESULTS: Among 1211 patients with chronic cough, 1107 (91.4%) patients reported at least one cough trigger. Chemical triggers (66.9%) were the most common cough triggers, followed by thermal exposure (50.6%), mechanical triggers (48.2%), and meal triggers (21.2%). There was no difference in the proportion of chemical triggers among different etiologies. Patients with refractory chronic cough reported the highest prevalence of cough triggers (97.1%). A higher number of meal triggers (34.9%) was associated with gastroesophageal reflux-related cough, and meal triggers and mechanical triggers were more common in refractory chronic cough. Among 254 patients who completed capsaicin challenge test, both the number of total triggers and the number of chemical triggers had a significant but mild correlation with capsaicin cough sensitivity. CONCLUSION: Cough hypersensitivity as reflected by a variety of cough triggers is a common feature in chronic cough patients, but different etiologies present specific profiles of cough triggers, which could not be evaluated comprehensively by capsaicin cough sensitivity.

High-Dose Deltamethrin Induces Developmental Toxicity in Caenorhabditis elegans via IRE-1.

Deltamethrin (DM), a Type II pyrethroid, is widely used worldwide in agriculture, household applications, and medicine. Recent studies have shown that DM exerts a variety of toxic effects on organs such as the kidney, heart muscle, and nerves in animals. However, little is known about the effects of high-dose DM on growth and development, and the mechanism of toxicity remains unclear. Using the Caenorhabditis elegans model, we found that high-dose DM caused a delay in nematode development. Our results showed that high-dose DM reduced the activation of the endoplasmic reticulum unfolded protein response (UPRER). Further studies revealed that high-dose DM-induced developmental toxicity and reduced capacity for UPRER activation were associated with the IRE-1/XBP-1 pathway. Our results provide new evidence for the developmental toxicity of DM and new insights into the mechanism of DM toxicity.

Complete chloroplast genome sequence of Camellia sinensis: genome structure, adaptive evolution, and phylogenetic relationships.

The chloroplast (cp) genome holds immense potential for a variety of applications including species identification, phylogenetic analysis, and evolutionary studies. In this study, we utilized Illumina NovaSeq 6000 to sequence the DNA of Camellia sinensis L. cultivar 'Zhuyeqi', followed by the assembly of its chloroplast genome using SPAdes v3.10.1, with subsequent analysis of its features and phylogenetic placement. The results showed that the cp genome of 'Zhuyeqi' was 157,072 bp, with a large single-copy region (LSC, 86,628 bp), a small single-copy region (SSC,18,282 bp), and two inverted repeat regions (IR, 26,081 bp). The total AT and GC contents of the cp genome of 'Zhuyeqi' were observed to be 62.21% and 37.29%, respectively. The cp genome encoded 135 unique genes, including 90 protein-coding genes (CDS), 37 tRNA genes, and 8 rRNA genes. Moreover, 31 codons and 247 simple sequence repeats (SSRs) were identified. The cp genomes of 'Zhuyeqi' were found to be relatively conserved, with conservation observed in the IR region, which showed no evidence of inversions or rearrangements. The five regions with the largest variations were identified, with four regions (rps12, rps19, rps16, and rpl33) located in the LSC region and one divergent region (trnI-GAU) in the IR region. Phylogenetic analysis revealed that Camellia sinensis (KJ996106.1) was closely related to 'Zhuyeqi', indicating a close phylogenetic relationship between these two species. These findings could provide important genetic information for further research into breeding of tea tree, phylogeny, and evolution of Camellia sinensis.

Predictive value of clinical features for anti-reflux therapy response in suspected gastroesophageal reflux-induced chronic cough.

Background: Not all gastroesophageal reflux-induced cough (GERC) patients respond to anti-reflux treatment. It is not certain whether reflux-related symptoms or other clinical characteristics could indicate a successful response to anti-reflux treatment. In this study, we aimed to investigate the relationship between clinical features and anti-reflux response. Methods: We retrospectively analyzed the clinical characteristics of suspected GERC who had reflux-related symptoms or reflux evidence based on abnormal 24-hour esophageal pH value monitoring, or who had no evidence of other common causes of chronic cough in our chronic cough database with a standard case report form. All patients experienced anti-reflux treatment with proton pump inhibitors (PPIs) plus prokinetic agents for at least 2 weeks and were divided into responders and non-responders based on the treatment response. Results: Among 241 patients with suspected GERC, 146 (60.6%) showed a successful response. There was no significant difference in regard to the proportion of reflux-related symptoms, and results of 24-hour esophageal pH value monitoring between responders and non-responders. Compared with non-responders, responders had higher proportions of nasal itching (21.2% vs. 8.4%; P=0.014), tickle in the throat (51.4% vs. 35.8%; P=0.025) and lower proportion of pharyngeal foreign body sensation (32.9% vs. 54.7%; P=0.001). Multivariate analysis showed that nasal itching [hazard ratio (HR): 1.593, 95% confidence interval (CI): 1.025-2.476, P=0.039], tickle in the throat (HR: 1.605, 95% CI: 1.152-2.238, P=0.005), pharyngeal foreign body sensation (HR: 0.499, 95% CI: 0.346-0.720, P<0.001) and sensitivity to at least one cough trigger (HR: 0.480, 95% CI: 0.237-0.973, P=0.042) were associated with the therapeutic response. Conclusions: Over half of suspected GERC patients benefited from anti-reflux therapy. A few clinical features rather than reflux-related symptoms might indicate a response to anti-reflux treatment. Further study is needed for the predictive value.

Nano-calcium alleviates the cracking of nectarine fruit and improves fruit quality.

To explore the use of L-aspartic acid nano-calcium (nano-Ca) to reduce nectarine fruit-cracking, we sprayed the crack-susceptible nectarine cultivar 'Huaguang' [Prunus persica (L.) Batsch var. nectarina (Ait.) Maxim.] with nano-Ca. The results showed that nano-Ca could reduce the fruit-cracking percentage of nectarine by more than 20%. Nano-Ca was effective because it increased the calcium pectinate content of the peel, reduced the activity of cell-wall metabolic enzymes, and changed the peel structure and enhanced its toughness. We also found that nano-Ca enhanced calmodulin activity in leaves, upregulated key genes of sucrose synthesis in leaves and sucrose transport in stem phloem, and significantly increased the soluble sugar content in the fruit by more than 2%. In addition, Nano-Ca also enhanced calmodulin activity in peel and up-regulated key genes related to anthocyanin-synthesis, promoting anthocyanin accumulation in the peel. The result will lay a theoretical foundation for the physiological and molecular mechanisms of nectarine-cracking and its prevention.

Epidermal growth factor receptor promotes high-fructose nonalcoholic fatty liver disease by inducing mitochondrial fission in zebrafish.

Mitochondrial function has a pivotal role in the pathogenesis of NAFLD. Mitochondrial dynamics is a foundational activity underlying the maintenance of mitochondrial function in bioenergetics, the maintenance of MtDNA, calcium homeostasis, reactive oxygen species metabolism, and quality control. Loss of mitochondrial plasticity in terms of functions, morphology and dynamics may also be the critical switch from NAFLD/NASH to HCC. However, the cause of mitochondrial fission in NAFLD remains unclear. Recent studies have reported that EGFR can bind to Mfn1 and interfere with its polymerization. In this study, we investigated whether EGFR binds to Mfn1 in NAFLD, and whether reducing their binding can improve NAFLD in zebrafish model. Our results demonstrated that EGFR was activated in hepatocytes from high fructose (HF)-induced NAFLD zebrafish and interfered with Mfn1 polymerization, leading to reduction of MtDNA. Suppression of EGFR activation or mitochondrial translocation significantly improved mitochondrial morphology and increased mitochondrial DNA, ultimately preventing hepatic steatosis. In conclusion, these results suggest that EGFR binding to Mfn1 plays an important role in NAFLD zebrafish model and that inhibition of their binding could be a potential therapeutic target.

Attapulgite Nanorod-Incorporated Polyimide Membrane for Enhanced Gas Separation Performance.

Polyimide (PI) membrane is an ideal gas separation material due to its advantages of high designability, good mechanical properties and easy processing; however, it has equilibrium limitations in gas selectivity and permeability. Introducing nanoparticles into polymers is an effective method to improve the gas separation performance. In this work, nano-attapulgite (ATP) functionalized with KH-550 silane coupling agent was used to prepare polyimide/ATP composite membranes by in-situ polymerization. A series of characterization and performance tests were carried out on the membranes. The obtained results suggested a significant increase in gas permeability upon increasing the ATP content. When the content of ATP was 50%, the gas permeability of H2, He, N2, O2, CH4, and CO2 reached 11.82, 12.44, 0.13, 0.84, 0.10, and 4.64 barrer, which were 126.87%, 119.40%, 160.00%, 140.00%, 150.00% and 152.17% higher than that of pure polyimide, respectively. No significant change in gas selectivity was observed. The gas permeabilities of membranes at different pressures were also investigated. The inefficient polymer chain stacking and the additional void volume at the interface between the polymer and TiO2 clusters leaded to the increase of the free volume, thus improving the permeability of the polyimide membrane. As a promising separation material, the PI/ATP composite membrane can be widely used in gas separation industry.

Mitochondria-targeted cyclometalated iridium (III) complex for H2S-responsive intracellular redox regulation as potent photo-oxidation anticancer agent.

Owing to the safety and low toxicity, photodynamic therapy (PDT) for cancer treatment has received extensive attention. However, the excess H2S in cancer cells reduces the PDT efficiency, because H2S indirectly depletes the reactive oxygen species (ROS). To improve anticancer efficiency, a mitochondria-targeted iridium(III) complex Ir-MMB has been developed as H2S consumer and photo-oxidation anticancer agent. On the one hand, complex Ir-MMB can consume H2S with sensitive phosphorescence turn-on, which has been successfully applied to exogenous and endogenous H2S response imaging in living cells. On the other hand, Ir-MMB can enhance its anticancer activity and cause photo-oxidation damage via catalyzing the oxidation of reduced form of nicotinamide-adenine dinucleotide (NADH) to NAD+ and producing H2O2 under light, and ultimately results in cell apoptosis through mitochondrial depolarization and ROS production.

Metagenomics Approach to the Intestinal Microbiome Structure and Abundance in High-Fat-Diet-Induced Hyperlipidemic Rat Fed with (-)-Epigallocatechin-3-Gallate Nanoparticles.

The effects of nanoparticles (NPs) on microbiota homeostasis and their physiological relevance are still unclear. Herein, we compared the modulation and consequent pharmacological effects of oral administration of (-)-epigallocatechin-3-gallate (EGCG)-loaded ß-cyclodextrin (ß-CD) NPs (EGCG@ß-CD NPs) and EGCG on gut microbiota. EGCG@ß-CD NPs were prepared using self-assembly and their influence on the intestinal microbiome structure was analyzed using a metagenomics approach. The "Encapsulation efficiency (EE), particle size, polydispersity index (PDI), zeta potential" of EGCG@ß-CD NPs were recorded as 98.27 ± 0.36%, 124.6 nm, 0.313 and -24.3 mV, respectively. Surface morphology of EGCG@ß-CD NPs was observed as spherical. Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and molecular docking studies confirmed that EGCG could be well encapsulated in ß-CD and formed as EGCG@ß-CD NPs. After being continuously administered EGCG@ß-CD NPs for 8 weeks, the serum cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and liver malondialdehyde (MDA) levels in the rats were significantly decreased, while the levels of catalase (CAT) and apolipoprotein-A1 (apo-A1) in the liver increased significantly in the hyperlipidemia model of rats, when compared to the high-fat-diet group. Furthermore, metagenomic analysis revealed that the ratio of Verrucomicrobia/Bacteroidetes was altered and Bacteroidetes decreased in the high-fat diet +200 mg/kg·bw EGCG@ß-CD NPs group, while the abundance of Verrucomicrobia was significantly increased, especially Akkermansia muciniphila in rat feces. EGCG@ß-CD NPs could be a promising EGCG delivery strategy to modulate the gut microbiota, enhancing its employment in the prevention of hyperlipidemia.

The risk factors for urinary incontinence in female adults with chronic cough.

BACKGROUND: Female patients with chronic cough are more likely to suffer from urinary incontinence (UI). However, there are few data in regard of risks related with UI in female adults with chronic cough. METHOD: We recruited female adult patients with chronic cough from the cough specialist clinic. Demographic information and clinical characteristics including age, BMI, duration of cough, severity of cough, nature and timing of cough, cough triggers, concomitant symptoms, comorbidities and UI condition were collected. The demographics and clinical features of patients with UI and those without UI were compared. RESULT: A total of 700 female patients with the main symptom of chronic cough were included, of whom 351 (50.1%) presented with UI. As compared with patients without UI, patients with UI showed a longer mean age (years) (49.5 vs. 42.4, p < 0.001), a more severe cough symptom (median of cough Visual Analogue Scale: 65 vs. 50, p < 0.001), a higher prevalence of chronic sinusitis (17.6% vs. 8.6%, p = 0.002), and combined with a higher incidence of abdominal muscle pain due to cough (39.6% vs. 18.7%, p < 0.001).In addition, patients in UI group whose cough were more easily triggered by exercise (28.2% vs. 17.2%, p = 0.048). Multivariate logistic regression analysis indicated the above five variables were risk factors for UI in female adult patients with chronic cough. CONCLUSION: Urinary incontinence is a common complication in female patients with chronic cough. Older age, severe cough, combing with a higher proportion of chronic sinusitis and abdominal muscle pain, a cough easily triggered by exercise are identified as risk factors for urinary incontinence. We should pay more attention to female chronic coughers with these risk factors in clinics.

Brominated cyclometalated iridium(III) complexes for mitochondrial immobilization as potential anticancer agents.

Mitochondria-targeted iridium complexes for anticancer studies have received increasing attention in recent years. Herein, three cyclometalated iridium(III) complexes Ir1-Ir3 [Ir(N^C)2(N^N)](PF6) (N^N = 2,2'-bipyridine (bpy)) or 2-(5-bromopyridin-2-yl)benzo[d]thiazole (bpybt); [N^C = 2-phenylpyridine (ppy) or 2-phenylquinoline (pq) or 2-(4-bromophenyl)benzo[d]thiazole (bpbt)] had been explored as potential mitochondria-targeted anticancer agents. All of the complexes mainly localized in the mitochondria and could be fixed on the mitochondria through a nucleophilic reaction with reactive mitochondrial proteins. Further studies revealed that these complexes showed high anticancer activity, induced mitochondrial depolarization, elevated intracellular reactive oxygen species (ROS) levels, restrained thioredoxin reductase (TrxR) activity, and inhibited the formation of tumor cell colonies and angiogenesis. Further mechanistic studies showed that complex Ir2 could markedly stimulate the activation of caspase-3, regulate the expression of Bax and KI67, and trigger apoptosis.

Quantifying the impact of environment factors on the risk of medical responders' stress-related absenteeism.

Medical emergency response staff are exposed to incidents which may involve high-acuity patients or some intractable or traumatic situations. Previous studies on emergency response staff stress-related absence have focused on perceived factors and their impacts on absence leave. To date, analytical models on absenteeism risk prediction use past absenteeism to predict risk of future absenteeism. We show that these approaches ignore environment data, such as stress factors. The increased use of digital systems in emergency services allows us to gather data that were not available in the past and to apply a data-driven approach to quantify the effect of environment variables on the risk of stress-related absenteeism. We propose a two-stage data-driven framework to identify the variables of importance and to quantify their impact on medical staff stress-related risk of absenteeism. First, machine learning techniques are applied to identify the importance of different stressors on staff stress-related risk of absenteeism. Second, the Cox proportional-hazards model is applied to estimate the relative risk of each stressor. Four significant stressors are identified, these are the average night shift, past stress leave, the squared term of death confirmed by the Emergency Services and completion of the safeguarding form. We discuss counterintuitive results and implications to policy.