Selective Adsorption of Sr(II) from Aqueous Solution by Na3FePO4CO3: Experimental and DFT Studies.

The efficient segregation of radioactive nuclides from low-level radioactive liquid waste (LLRW) is paramount for nuclear emergency protocols and waste minimization. Here, we synthesized Na3FePO4CO3 (NFPC) via a one-pot hydrothermal method and applied it for the first time to the selective separation of Sr2+ from simulated LLRW. Static adsorption experimental results indicated that the distribution coefficient Kd remained above 5000 mL·g-1, even when the concentration of interfering ions was more than 40 times that of Sr2+. Furthermore, the removal efficiency of Sr2+ showed no significant change within the pH range of 4 to 9. The adsorption of Sr2+ fitted the pseudo-second-order kinetic model and the Langmuir isotherm model, with an equilibrium time of 36 min and a maximum adsorption capacity of 99.6 mg·g-1. Notably, the adsorption capacity was observed to increment marginally with an elevation in temperature. Characterization analyses and density functional theory (DFT) calculations elucidated the adsorption mechanism, demonstrating that Sr2+ initially engaged in an ion exchange reaction with Na+. Subsequently, Sr2+ coordinated with four oxygen atoms on the NFPC (100) facet, establishing a robust Sr-O bond via orbital hybridization.

Multi-Omics Analyses Unravel Metabolic and Transcriptional Differences in Tender Shoots from Two Sechium edule Varieties.

Chaylte vine, the tender shoot of Sechium edule, is popular among vegetable consumers because of its high nutritional content, crisp texture, and unique flavor. Existing studies on the nutrient composition of chaylte vines are mostly simple chemical determinations, which have limited the breeding of specialized cultivars and the development of related industries. Using metabolomics combined with transcriptomics, this study analyzed the metabolic characteristics and related molecular mechanisms of two common varieties of chaylte vines: green-skinned (SG) and white-skinned (SW). Between the two varieties, a total of 277 differentially accumulated metabolites (DAMs) and 739 differentially expressed genes (DEGs) were identified. Furthermore, chemical assays demonstrated that the SW exhibited a higher total flavonoid content and antioxidant capacity. In conclusion, it was found that the SG samples exhibited a higher diversity of flavonoid subclasses compared to the SW samples, despite having a lower total flavonoid content. This inconsistent finding was likely due to the differential expression of the phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS) genes in the two varieties. These results laid the foundation for investigating the mechanisms involved in flavonoid regulation and the breeding of specialized S. edule cultivars for chaylte vine production.

Aromatic Terpenes and Their Biosynthesis in Dendrobium, and Conjecture on the Botanical Perfumer Mechanism.

This review presents a systematic analysis of the studies on volatiles in Dendrobium. Among the various components, aromatic terpenes are a crucial component in the development of the aromatic characteristics of Dendrobium and other plants. Recent advancements in detection and sequencing technology have resulted in a considerable rise in research on the biosynthetic processes of aromatic terpenes in Dendrobium and other flowering plants. Nevertheless, the inquiry into the precise means by which plants regulate the proportion of diverse aromatic terpenes in their floral scent, thereby preserving their olfactory traits, requires further investigation. A conjecture on the botanical perfumer mechanism, which condensed the findings of earlier studies, was put forward to address this area of interest. Specific transcription factors likely govern the coordinated expression of multiple key terpene synthase (TPS) genes during the flowering stage of plants, thereby regulating the proportional biosynthesis of diverse aromatic terpenes and sustaining the distinctive aromatic properties of individual plants. This review serves as a significant theoretical reference for further investigations into aromatic volatile compounds in Dendrobium.

Presence of diabetes mellitus affects vertigo outcome in vestibular migraine.

OBJECTIVE: To investigate the association of diabetes mellitus (DM) with vertigo outcome in patients with vestibular migraine (VM). METHODS: Two hundred and thirty-four patients with VM were consecutively enrolled between October 2018 and January 2020 in a tertiary teaching medical center. Multivariable linear regression model and stratified analyses were used to explore the relationship between diabetes and vertigo outcome, which was measured by the visual analogue scale (VAS). RESULTS: Patients with diabetes were more likely to have poorer sleep quality and more severe vertigo symptoms measured by VAS at the follow-up than those without diabetes. After adjusting for potential confounders, presence of diabetes was significantly linked with poorer final vertigo VAS score (ß, 95 % confidence interval [CI]: 1.0 [0.1, 2.0]). This association was only significant for female patients with VM (ß, 95%CI: 1.2 [0.2, 2.3], p = 0.0244). CONCLUSIONS: Presence of diabetes was independently and inversely corrected with the vertigo outcome in women with VM. Our findings suggest that diabetes is likely a negative prognosticator of vertigo outcome in VM.

Treatment of lactational breast abscesses with cavity diameter larger than 5 cm via combined ultrasonography-guided percutaneous catheter placement and hydrostatic pressure irrigation.

This study reports on our experience of treating lactational breast abscesses larger than 5 cm via ultrasonography (US)-guided percutaneous catheter placement and hydrostatic pressure irrigation. Twelve cases of puerperal single breast abscesses larger than 5 cm were collected. These patients were treated with US-guided percutaneous catheter placement and hydrostatic pressure irrigation combined with oral antibiotics. All 12 patients using US-guided treatment were completely successful without conversion to open surgical drainage. The range of recovery time was 5-16 days, and no major complications occurred. The patients were satisfied with the appearance of the scar, and there were no reports of recurrence during the follow-up period.Overall, US-guided percutaneous catheter placement and hydrostatic pressure irrigation are successful strategies for the treatment of lactational breast abscesses larger than 5 cm. These methods not only reduce the treatment time and improve the patients' clinical course but also provide cosmetic effects.IMPACT STATEMENTWhat is already known on this subject? The current consensus on breast abscess treatment is that lesions <3 cm can be effectively treated by aspiration alone, lesions >3 cm require catheter drainage, lesions <5 cm have proven to be safe and effectively treated by US-guided ultrasound therapy, and lesions >5 cm, whether multi-loculated or longstanding, require surgical incision and drainage.What do the results of this study add? We tried to use this method to increase the cure rate of US-guided minimally invasive treatment for large abscesses. The results showed that all patients were cured successfully, requiring no further surgical intervention. Moreover, no complications occurred, and no patients developed sequelae. During the three-month follow-up period, there was no evidence of recurrence in any case.What are the implications of these findings for clinical practice and/or further research? Questions remain regarding the treatment's generalisability, potentially lengthy hospitalisation, and technical limitations of the existing instrumentation. Long-term follow up and larger sample size Randomised clinical trials studies are still needed to rigorously and scientifically ensure the method's benefits over conventional open surgery in the future.

Distinct effects of asthma and COPD comorbidity on disease expression and outcome in patients with COVID-19.

BACKGROUND: The impacts of chronic airway diseases on coronavirus disease 2019 (COVID-19) are far from understood. OBJECTIVE: To explore the influence of asthma and chronic obstructive pulmonary disease (COPD) comorbidity on disease expression and outcomes, and the potential underlying mechanisms in COVID-19 patients. METHODS: A total of 961 hospitalized COVID-19 patients with a definite clinical outcome (death or discharge) were retrospectively enrolled. Demographic and clinical information were extracted from the medical records. Lung tissue sections from patients suffering from lung cancer were used for immunohistochemistry study of angiotensin-converting enzyme II (ACE2) expression. BEAS-2B cell line was stimulated with various cytokines. RESULTS: In this cohort, 21 subjects (2.2%) had COPD and 22 (2.3%) had asthma. After adjusting for confounding factors, COPD patients had higher risk of developing severe illness (OR: 23.433; 95% CI 1.525-360.135; P < .01) and acute respiratory distress syndrome (OR: 19.762; 95% CI 1.461-267.369; P = .025) than asthmatics. COPD patients, particularly those with severe COVID-19, had lower counts of CD4+ T and CD8+ T cells and B cells and higher levels of TNF-α, IL-2 receptor, IL-10, IL-8, and IL-6 than asthmatics. COPD patients had increased, whereas asthmatics had decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. IL-4 and IL-13 downregulated, but TNF-α, IL-12, and IL-17A upregulated ACE2 expression in BEAS-2B cells. CONCLUSION: Patients with asthma and COPD likely have different risk of severe COVID-19, which may be associated with different ACE2 expression.

Comparative analysis on lung transcriptome of Mycoplasma ovipneumoniae (Mo) - infected Bashbay sheep and argali hybrid sheep.

BACKGROUND: Bashbay sheep (Bbs) has a certain degree of resistance to Mycoplasma ovipneumoniae (Mo), however, Argali hybrid sheep (Ahs) is susceptible to Mo. To understand the molecular mechanisms underlying the difference of the susceptibility for Mo infection, RNA-sequencing technology was used to compare the transcriptomic response of the lung tissue of Mo-infected Bbs and Ahs. RESULTS: Six Bbs and six Ahs were divided into experimental group and control group respectively, all of them were experimentally infected with Mo by intratracheal injection. For collecting lung tissue samples, three Bbs and three Ahs were sacrificed on day 4 post-infection, and the others were sacrificed on day 14 post-infection. Total RNA extracted from lung tissue were used for transcriptome analyses based on high-throughput sequencing technique and bioinformatics. The results showed that 212 (146 up-regulated, 66 down-regulated) DEGs were found when comparing transcriptomic data of Bbs and Ahs at 4th dpi, besides, 311 (158 up-regulated, 153 down-regulated) DEGs were found at 14th dpi. After GO analysis, three main GO items protein glycosylation, immune response and positive regulation of gene expression were found related to Mo infection. In addition, there were 20 DEGs enriched in these above items, such as SPLUC1 (BPIFA1), P2X7R, DQA, HO-1 and SP-A (SFTPA-1). CONCLUSIONS: These selected 20 DEGs associated with Mo infection laid the foundation for further study on the underlying molecular mechanism involved in high level of resistance to Mo expressed by Bbs, meanwhile, provided deeper understandings about the development of pathogenicity and host-pathogen interactions.

Recent Advances in the Reactions of Cyclic Carbynes.

The acyclic organic alkynes and carbyne bonds exhibit linear shapes. Metallabenzynes and metallapentalynes are six- or five-membered metallacycles containing carbynes, whose carbine-carbon bond angles are less than 180°. Such distortion results in considerable ring strain, resulting in the unprecedented reactivity compared with acyclic carbynes. Meanwhile, the aromaticity of these metallacycles would stabilize the ring system. The fascinating combination of ring strain and aromaticity would lead to interesting reactivities. This mini review summarized recent findings on the reactivity of the metal-carbon triple bonds and the aromatic ring system. In the case of metallabenzynes, aromaticity would prevail over ring strain. The reactions are similar to those of organic aromatics, especially in electrophilic reactions. Meanwhile, fragmentation of metallacarbynes might be observed via migratory insertion if the aromaticity of metallacarbynes is strongly affected. In the case of metallapentalynes, the extremely small bond angle would result in high reactivity of the carbyne moiety, which would undergo typical reactions for organic alkynes, including interaction with coinage metal complexes, electrophilic reactions, nucleophilic reactions and cycloaddition reactions, whereas the strong aromaticity ensured the integrity of the bicyclic framework of metallapentalynes throughout all reported reaction conditions.

Value of High-frequency Ultrasound in the Diagnosis of Peripheral Nerve Compression in Rheumatoid Arthritis Patients.

Objective To evaluate the value of high-frequency ultrasound (HFUS) in diagnosing peripheral nerve compression in patients with rheumatoid arthritis (RA). Methods The upper limb nerves were evaluated by HFUS in 80 RA patients (RA group) and 60 non-RA patients (control group),then the incidence of peripheral nerve compression was recorded respectively. RA patients with/without neurological symptoms were compared in terms of age,disease course,Health Assessment Questionnaire Disability Index (HAQ-DI) score,and clinical disease activity index (CDAI). Results The incidence of upper limb nerve compression in RA group was significantly higher than that in control group(15.0% vs. 3.3%,P=0.046).The patients with nerve compression was older [(60.2±11.4)y vs.(49.2±7.9)y;t=2.343,P=0.039] and had longer disease course [(9.50±5.99) y vs. (5.88±3.87)y;t=2.639,P=0.023] and higher HAQ-DI score (1.58±0.75 vs.0.85±0.67;t=2.490,P=0.030). These two groups had no statistical differences in CDAI (14.50±11.68 vs.16.62±9.24;t=1.141,P=0.278).Conclusions Peripheral neuropathies are common extra-articular manifestations in RA patients. HFUS can be valuable in patients suspected of RA.

Formation control of fixed-wing UAVs with communication delay.

Fixed-wing unmanned aerial vehicles (UAVs) possess high speed and non-hovering capabilities, rendering them uniquely advantages for reconnaissance and detection. The focus of this paper is to addressing the problem of formation control for fixed-wing UAVs in the presence of communication delay. To tackle this problem, for the non-holonomic kinematic model, we propose an intuitive and practical control law based on the leader-follower method to ensure that UAVs maintain a predetermined geometric formation. The stability analysis of the system with communication delay is conducted by constructing a strict Lyapunov-Krasovskii function. Furthermore, we consider the impact of communication delay on formation accuracy and present a prediction algorithm capable of forecasting the actual position of each UAV. To validate our theoretical findings, both digital simulation and hardware-in-loop experiment are conducted.

Multi-omics analyses and botanical perfumer hypothesis provide insights into the formation and maintenance of aromatic characteristics of Dendrobium loddigesii flowers.

Dendrobium loddigesii, a member of the Orchidaceae family, is a valuable horticultural crop known for its aromatic qualities. However, the mechanisms responsible for the development of its aromatic characteristics remain poorly understood. To elucidate these underlying mechanisms, we assembled the first chromosome-level reference genome of D. loddigesii using PacBio HiFi-reads, Illumina short-reads, and Hi-C data. The assembly comprises 19 pseudochromosomes with N50 contig and N50 scaffold sizes of 55.15 and 89.94 Mb, respectively, estimating the genome size to be 1.68 Gb, larger than that of other sequenced Dendrobium species. During the flowering stages, we conducted a comprehensive analysis combining volatilomics and transcriptomics to understand the characteristics and biosynthetic mechanisms pathways of the floral scent. Our findings emphasize the significant contribution of aromatic terpenoids, especially monoterpenoids, in defining the floral aroma. Furthermore, we identified two crucial terpene synthase (TPS) genes that play a key role in maintaining the aroma during flowering. Through the integration volatilomics data with catalytic assays of DlTPSbs proteins, we identified specific compounds responsible for the aromatic characteristics of D. loddigesii. This integrated analysis of the genome, transcriptome, and volatilome, offers valuable insights into the development and preservation of D. loddigesii's aromatic characteristics, setting the stage for further exploration of the botanical perfumer hypothesis.

Integrative Analysis of Transcriptome and Metabolome Sheds Light on Flavonoid Biosynthesis in the Fruiting Body of Stropharia rugosoannulata.

Flavonoids are a diverse family of natural compounds that are widely distributed in plants and play a critical role in plant growth, development, and stress adaptation. In recent years, the biosynthesis of flavonoids in plants has been well-researched, with the successive discovery of key genes driving this process. However, the regulation of flavonoid biosynthesis in fungi remains unclear. Stropharia rugosoannulata is an edible mushroom known for its high nutritional and pharmacological value, with flavonoids being one of its main active components. To investigate the flavonoid content of S. rugosoannulata, a study was conducted to extract and determine the total flavonoids at four stages: young mushroom (Ym), gill (Gi), maturation (Ma), and parachute-opening (Po). The findings revealed a gradual increase in total flavonoid concentration as the fruiting body developed, with significant variations observed between the Ym, Gi, and Ma stages. Subsequently, we used UPLC-MS/MS and transcriptome sequencing (RNA-seq) to quantify the flavonoids and identify regulatory genes of Ym, Gi, and Ma. In total, 53 flavonoid-related metabolites and 6726 differentially expressed genes (DEGs) were identified. Through KEGG pathway enrichment analysis, we identified 59 structural genes encoding flavonoid biosynthesis-related enzymes, most of which were up-regulated during the development of the fruiting body, consistent with the accumulation of flavonoids. This research led to the establishment of a comprehensive transcriptional metabolic regulatory network encompassing flavonoids, flavonoid synthases, and transcription factors (TFs). This represents the first systematic exploration of the molecular mechanism of flavonoids in the fruiting of fungi, offering a foundation for further research on flavonoid mechanisms and the breeding of high-quality S. rugosoannulata.

Combinatorial Optimization Strategies for 3-Fucosyllactose Hyperproduction in Escherichia coli.

3-Fucosyllactose (3-FL), an important fucosylated human milk oligosaccharide in breast milk, offers numerous health benefits to infants. Previously, we metabolically engineered Escherichia coli BL21(DE3) for the in vivo biosynthesis of 3-FL. In this study, we initially optimized culture conditions to double 3-FL production. Competing pathway genes involved in in vivo guanosine 5'-diphosphate-fucose biosynthesis were subsequently inactivated to redirect fluxes toward 3-FL biosynthesis. Next, three promising transporters were evaluated using plasmid-based or chromosomally integrated expression to maximize extracellular 3-FL production. Additionally, through analysis of α1,3-fucosyltransferase (FutM2) structure, we identified Q126 residues as a highly mutable residue in the active site. After site-saturation mutation, the best-performing mutant, FutM2-Q126A, was obtained. Structural analysis and molecular dynamics simulations revealed that small residue replacement positively influenced helical structure generation. Finally, the best strain BD3-A produced 6.91 and 52.1 g/L of 3-FL in a shake-flask and fed-batch cultivations, respectively, highlighting its potential for large-scale industrial applications.

De Novo Biosynthesis of Difucosyllactose by Artificial Pathway Construction and α1,3/4-Fucosyltransferase Rational Design in Escherichia coli.

Difucosyllactose (DFL) is a significant and plentiful oligosaccharide found in human breast milk. In this study, an artificial metabolic pathway of DFL was designed, focusing on the de novo biosynthesis of GDP-fucose from only glycerol. This was achieved by engineering Escherichia coli to endogenously overexpress genes manB, manC, gmd, and wcaG and heterologously overexpress a pair of fucosyltransferases to produce DFL from lactose. The introduction of α-1,2-fucosyltransferase from Helicobacter pylori (FucT2) along with α-1,3/4-fucosyltransferase (HP3/4FT) addressed rate-limiting challenges in enzymatic catalysis and allowed for highly efficient conversion of lactose into DFL. Based on these results, molecular modification of HP3/4FT was performed based on computer-assisted screening and structure-based rational design. The best-performing mutant, MH5, containing a combination of five mutated sites (F49K/Y131D/Y197N/E338D/R369A) of HP3/4FT was obtained. The best strain BLC09-58 harboring MH5 yielded 45.81 g/L of extracellular DFL in 5-L fed-batch cultures, which was the highest titer reported to date.

Relationships between the Pittsburgh Sleep Quality Index (PSQI) and vertigo outcome.

OBJECTIVE: This retrospective cohort study aimed to investigate the association of sleep characteristics measured by the Pittsburgh Sleep Quality Index (PSQI) with the vertigo outcome in vertiginous patients with comorbid cardiometabolic diseases. METHODS: Four hundred and thirteen patients with comorbid cardiometabolic diseases who consecutively visiting vertigo and dizziness clinic were enrolled between October 2018 and January 2020 in a tertiary teaching medical center. Regression analyses and stratified analyses were used to explore the relationship between PSQI and vertigo outcome, which was measured by the visual analogue scale (VAS) score. RESULTS: In the study sample, 73.8% (305/413) were defined as 'poor sleep' (PSQI>5). Participants with better recovery tended to have better baseline PSQI global score, PSQI sleep quality, PSQI sleep onset latency, PSQI daytime dysfunction, less severe baseline vertigo symptoms indicated by VAS, Vertigo Symptom Scale (VSS) and Dizziness Handicap Inventory (DHI) scores. Moreover, baseline PSQI global score and PSQI daytime dysfunction score were independently associated with the vertigo VAS scores at the last follow-up. CONCLUSION: The present results clearly indicated that poor sleep is common and inversely associated with vertigo outcome in vertiginous patients with co-morbid cardiometabolic diseases. Therefore, sleep deserves greater attention in the total medical care in specific subgroup of vertiginous patients.

Emergy synthesis of decoupling and recoupling crop-livestock systems under unified system boundary and modified indices.

Sustainability assessment of integrated crop-livestock system was crucial for regulating and improving the complex agricultural system. Emergy synthesis (ES) is a suitable tool to assess the sustainability of integrated crop-livestock systems. However, the inconsistent system boundaries and limited assessment indicators caused to subjective and misleading results when comparing the recoupling and decoupling croplivestock models. Therefore, this study defined the rational system boundary of emergy accounting for the comparison of recoupling and decoupling crop-livestock complex systems. Meanwhile, the study designed an emergy-based indices system based on "3R" principles of circular economy. An integrated crop-livestock system including sweet maize cultivation and cow dairy farm in South China was selected as the case to compare sustainability of recoupling and decoupling models under the unified system boundary and modified indices. Results showed that the new ES framework could provide more rational assessment results when comparing the recoupling and decoupling crop-livestock systems. In addition, this study illustrated, through scenario simulation, that the recoupling maize-cow model could be further optimized by regulating the material flow between subsystems and adjusting the system structure. This study would promote the application of ES method in the field of agricultural circular economy.

Molecular and metabolic insights into floral scent biosynthesis during flowering in Dendrobium chrysotoxum.

Dendrobium chrysotoxum is considered as an important ornamental dendrobium because of its strong and long-lasting floral scent. Nevertheless, few information is known about the dynamic changes and related formation mechanism of dendrobium floral scent at different flowering stages. In this study, the characteristics and biosynthetic mechanism of floral scent in D. chrysotoxum during flowering was revealed by using widely-targeted volatilomics (WTV) combined with transcriptome analysis. Over 500 kinds of volatile organic compounds (VOCs) were detected in the floral scents of D. chrysotoxum, which improved the knowledge about floral scent components of dendrobium. A total of 153 differential VOCs and 4,487 differentially expressed genes (DEGs) were identified between flowers of different flowering stages, respectively. The results for both volatilomics and transcriptomics data indicated that terpenes and related genes played an important role in the formation of floral characteristics of D. chrysotoxum. But in general, the expression of genes showed an opposite trend to the accumulation of metabolites during flowering, suggesting that the regulation of floral scent biosynthesis might have started at the budding stage in D. chrysotoxum. Additionally, a transcriptional metabolic regulatory network consisting of terpenes, terpene synthases and candidate transcription factors was established. This research is the first systematic and comprehensive exploration of floral characteristics and related mechanisms during flowering in D. chrysotoxum. It provides basis for exploration of mechanisms on the floral scents and the breeding of aromatic dendrobium.

CircSOX9 acts as a molecular sponge of miR-485-3p to promote the progression of nasopharyngeal carcinoma.

Circular RNA (circRNA) plays a vital role in the occurrence and development of nasopharyngeal carcinoma (NPC). However, the role of certain specific circRNAs in NPC are still unknown. In this study, collect tumor samples and adjacent normal tissues from clinical NPC patients and detect the expression of circSOX9 by qRT-PCR. Use nucleoplasmic separation analysis, RNase R digestion assay and FISH to detect the characteristics of circSOX9. After knocking down circSOX9, clone formation experiment and transwell assay were used to detect the proliferation and invasion ability of nasopharyngeal carcinoma cells HONE1 and CNE2, and western blot was used to further detect the level of epithelial-mesenchymal transition (EMT). Use the database to screen for possible downstream target genes and verify them with dual-luciferase experiments. Bioinformatics analysis showed that circSOX9 was significantly up-regulated in NPC, and its expression level was positively correlated with the malignant progression of cancer. Data from function gain or loss studies showed that decrease of circSOX9 inhibited the invasion and proliferation of HONE1 and CNE2 cell lines. Further analysis proved that miR-485-3p was the downstream target of circSOX9. The luciferase test showed that by acting as a molecular sponge of miR-485-3p, circSOX9 promotes the proliferation and invasion of NPC cells, while miR-485-3p can target the expression of SOX9. In conclusion, circSOX9 acts as an oncogene in the progression of NPC through miR-485-3p/SOX9, indicating that circSOX9 can be used as a potential therapeutic target and predictive marker for nasopharyngeal carcinoma.

New Target of Oxidative Stress Regulation in Cochleae: Alternative Splicing of the p62/Sqstm1 Gene.

We investigated oxidative stress and antioxidant response in the p62/Sqstm1-Keap1-Nrf2 pathway in C57BL/6 mice cochleae during age-related hearing loss (ARHL) and noise-induced hearing loss (NIHL), and the function of full-length and variant p62 in the regulation of Nrf2 activation. Groups of young (2 months), old (13-14 months), control, and acoustic trauma (AT) mice were examined cochlear damage and oxidative stress as follows: auditory brainstem response and hair cell counts; malondialdehyde (MDA) levels measured by assay kit and 7,8-dihydro-8-oxoguanine (8-oxoG) detected by immunohistochemistry. Full-length and variant p62 were examined for expression in cochleae, hippocampus (HIP), and auditory cortex (AC) using immunoblotting. Keap1-Nrf2 pathway activation was based on immunoblotting of nuclear Nrf2 and quantitative real-time PCR of Nrf2 target genes HO-1/NQO-1. The oxidative function of full-length and variant p62 was examined in HEI-OC-1 cells by flow cytometry. The results showed hearing loss, and cochlear hair cell loss was associated with MDA accumulation and 8-oxoG expression during ARHL and NIHL. Nrf2 showed no obvious changes in nuclear protein. Expression levels mRNA for HO-1 and NQO1 were lower in old mice and mildly greater in AT Mice. The expression of p62 splicing variant lacking the Keap1-interacting region was greater than full-length p62 in cochleae. However, the expression of p62 splicing variant was lesser than full-length p62 in HIP and AC. For HEI-OC-1 cells, overexpression of full-length p62 decreased ROS levels induced by H2O2. Oxidative stress is closely related to ARHL and NIHL. Changing the ratio of full-length to variant p62 protein expression may be a new target to reduce the level of oxidative stress in cochleae.

Diversified Shifts in the Cross Talk between Members of the Gut Microbiota and Development of Coronary Artery Diseases.

Coronary artery disease (CAD) is one of leading causes of mortality worldwide. Studies on roles that the gut microbiota plays in development of atherosclerosis or acute myocardial infarction (AMI) have been widely reported. However, the gut microbiota is affected by many factors, including age, body mass index (BMI), and hypertension, that lead to high CAD risk. However, the associations between gut microbiota and CAD development or other CAD risk factors remain unexplored. Here, we performed a 16S RNA gene sequencing analysis of 306 fecal samples collected from patients with mild coronary stenosis (MCS; n = 36), stable angina (SA; n = 91), unstable angina (UA; n = 48), and acute myocardial infarction (AMI; n = 66) and 65 non-CAD controls. Using a noise-corrected method based on principal-component analysis (PCA) and the random forest algorithm, we identified the interference with gut microbial profiling of multiple factors (including age, gender, BMI, and hypertension) that potentially contributed significantly to the development of CAD. After correction of noise interference from certain interfering factors, we found consistent indicator microbiota organisms (such as Vampirovibrio, Ruminococcus, and Eisenbergiella) associated with the presence of MCS, SA, and AMI. Establishment of a diagnostic model revealed better performance in early CAD than clinical indexes with indicator microbes. Furthermore, indicator microbes can improve the accuracy of clinical indexes for the diagnosis of AMI. Additionally, we found that the microbial indicators of AMI Sporobacter and Eisenbergiella showed consistent positive and negative correlations to the clinical indexes creatine kinase (CK) and hemoglobin (Hb), respectively. As a control indicator of AMI, Dorea was negatively correlated with CK but positively correlated with Hb. IMPORTANCE Our study discovered the effect of confounding factors on gut microbial variations and identified gut microbial indicators possibly associated with the CAD development after noise correction. Our discovered indicator microbes may have potential for diagnosis or therapy of cardiovascular disorders.