Uncovering the diverse hosts of tigecycline resistance gene tet(X4) in anaerobic digestion systems treating swine manure by epicPCR.

The tet(X4) gene is a clinically important tigecycline resistance gene and has shown high persistence in livestock-related environments. However, the bacterial hosts of tet(X4) remain unknown due to the lack of appropriate approaches. Herein, a culture-independent and high-throughput epicPCR (emulsion, paired isolation, and concatenation polymerase chain reaction) method was developed, optimized, and demonstrated for the identification of bacterial hosts carrying tet(X4) from environmental samples. Considering the high sequence similarity between tet(X4) and other tet(X)-variant genes, specific primers and amplification conditions were screened and optimized to identify tet(X4) accurately and link tet(X4) with the 16S rRNA gene, which were further validated using artificially constructed bacterial communities. The epicPCR targeting tet(X4) was applied for the identification of bacterial hosts carrying this resistance gene in anaerobic digestion systems treating swine manure. A total of 19 genera were identified as tet(X4) hosts, which were distributed in the phyla Proteobacteria, Bacteroidota, Firmicutes, and Caldatribacteriota. Sixteen genera and two phyla that were identified have not been previously reported as tet(X4) bacterial hosts. The results indicated that a far more diverse range of bacteria was involved in harboring tet(X4) than previously realized. Compared with the tet(X4) hosts determined by correlation-based network analysis and metagenomic binning, epicPCR revealed a high diversity of tet(X4) hosts even at the phylum level. The epicPCR method developed in this study could be effectively employed to reveal the presence of tet(X4) bacterial hosts from a holistic viewpoint.

Identifying research progress, focuses, and prospects of local climate zone (LCZ) using bibliometrics and critical reviews.

The local climate zone (LCZ) has been an important land surface classification used to differentiate urban climate between localities. The general knowledge maps of LCZ studies are needed when LCZ-related research has attracted great attention. This study integrated bibliometrics and critical review to understand the status quo and suggest future research directions. Bibliometrics provided a statistical technique to explore large volumes of article data from the Web of Science, ScienceDirect, and Scopus databases, based on the Co-Occurrence 13.4 (COOC) software. The bibliometric results indicated a rapid increase in LCZ publications and identified the high-frequency keywords which can be clustered into two groups, including a human thermal comfort-related group and the other urban climatology-related one. From 2011 to 2020, the effects of land use and urban morphology on urban climate and heat island effects predominated the LCZ-related research. Since 2021, the research focuses had shifted to the fields of thermal environment and heatwave, due to the growing demand for human thermal comfort and heat risk reduction. Moreover, this study identified 'Land Surface Temperature' and 'Heatwave' as two focuses of LCZ-related research during the last decade. Their critical reviews demonstrated the need for additional in-depth LCZ-heatwave studies that consider the risk of human exposure. This study also recommended incorporating hydrological concerns and social issues into the LCZ plan for a more integrated LCZ research outlook. Overall, this study provides not only a comprehensive understanding of LCZ knowledge networks, but also critical details on research focuses and potential research prospects.

Intraperitoneal injection of iron dextran induces peripheral iron overload and mild neurodegeneration in the nigrostriatal system in C57BL/6 mice.

AIMS: Elevated iron levels in the affected areas of brain are linked to several neurodegenerative diseases including Parkinson's disease (PD). This study investigated the influence of peripheral iron overload in peripheral tissues, as well as its entry into the brain regions on lysosomal functions. The survival of dopaminergic neurons in the nigrostriatal system and motor coordination were also investigated. MAIN METHODS: An intraperitoneal injection of iron dextran (FeDx) mouse model was established. Western blot was used to detect iron deposition and lysosomal functions in the liver, spleen, hippocampal (HC), striatum (STR), substantia nigra (SN) and olfactory bulb (OB). Iron in serum and cerebrospinal fluid (CSF) was determined by an iron assay kit. Immunofluorescence and immunohistochemical staining were applied to detect dopaminergic neurons and fibers. Motor behavior was evaluated by gait analysis. KEY FINDINGS: Iron was deposited consistently in the liver and spleen, and serum iron was elevated. While iron deposition occurred late in the HC, STR and SN, without apparently affecting CSF iron levels. Although cathepsin B (CTSB), cathepsin D (CTSD), glucocerebrosidase (GCase) and lysosome integrated membrane protein 2 (LIMP-2) protein levels were dramatically up-regulated in the liver and spleen, they were almost unchanged in the brain regions. However, CTSB was up-regulated in acute iron-overloaded OB and primary cultured astrocytes. The number of dopaminergic neurons in the SN remained unchanged, and mice did not exhibit significant motor incoordination. SIGNIFICANCE: Intraperitoneal injection of FeDx in mice induces largely peripheral iron overload while not necessarily sufficient to cause severe disruption of the nigrostriatal system.

Interrater agreement between children's self-reported and their mothers' proxy-reported dental anxiety: a Chinese cross-sectional study.

BACKGROUND: Children's dental anxiety is common in dental clinics. This study aimed to determine the interrater agreement between children's self-reported and their mothers' proxy-reported dental anxiety and its affecting factors. METHODS: In this cross-sectional study performed in a dental clinic, primary school students and their mothers were assessed for enrollment eligibility. The Modified Dental Anxiety Scale plus Facial Image Scale (MDAS-FIS) was employed to test both the children's self-reported and their mothers' proxy-reported dental anxiety independently. The interrater agreement was analyzed using percentage agreement and the linear weighted kappa (k) coefficient. Factors affecting children's dental anxiety were analyzed using univariate and multivariate logistic regression models. RESULTS: One hundred children and their mothers were enrolled. The median ages of the children and mothers were 8.5 and 40.0 years old, respectively, and 38.0% (38/100) of the children were female. The scores of children's self-reported dental anxiety were significantly higher than their mothers' proxy-reported dental anxiety (MDAS-Questions 1-5, all p < 0.05); moreover, there was no agreement between the two groups in terms of all anxiety hierarchies (kappa coefficient = 0.028, p = 0.593). In the univariate model, a total of seven factors (age, gender, maternal anxiety, number of dental visits, mother's presence or absence, oral health status, and having siblings or not) were involved for analysis, and age [every 1-year increase, odds ratio (OR) = 0.661, 95% confidence interval (CI) = 0.514-0.850, p = 0.001], several dental visits (every 1 visit increase, OR = 0.409, 95% CI = 0.190-0.880, p = 0.022), and mother presence (OR = 0.286, 95% CI = 0.114-0.714, p = 0.007) were affecting factors. In the multivariate model, only age (every 1 year increase) and maternal presence were associated with 0.697-fold (95% CI = 0.535-0.908, p = 0.007) and 0.362-fold (95% CI = 0.135-0.967, p = 0.043) decreases in the risk of children's dental anxiety during dental visits and treatment, respectively. CONCLUSION: There was no significant agreement between elementary school students' self-reported dental anxiety and mothers' proxy ratings of children's dental anxiety, which suggests that self-reported dental anxiety by children should be encouraged and adopted, and the mother's presence during dental visits is strongly recommended.

Clinical Outcomes of Cardiac Shockwave Therapy in Severe Coronary Artery Disease Patients after Coronary Artery Bypass Grafting.

Cardiac shockwave therapy (CSWT) is a noninvasive treatment for patients with refractory angina or myocardial ischemia. This study aims to evaluate the potential beneficial effect and safety of CSWT in patients with severe coronary artery disease (CAD) who have undergone coronary artery bypass grafting (CABG).This was a single-arm prospective cohort study. A total of 30 patients with severe CAD who were not suitable for coronary revascularization and who had undergone CABG were enrolled. All patients received CSWT for nine sessions. Evaluation was performed before and after CSWT, including the Canadian Cardiovascular Society (CCS) classification, New York Heart Association (NYHA) classification, 6-minute walk test (6MWT), Seattle Angina Questionnaire (SAQ) score, nitroglycerin dosage, echocardiography, myocardial perfusion imaging (MPI), and safety parameters. All patients were followed up at both 1 month and 9 months after CSWT.After treatment, CSWT significantly improved CCS classification (P < 0.05), NYHA classification (P < 0.05), nitroglycerin dosage (P < 0.001), and 6MWT (P < 0.05) at 1 month and 9 months after CSWT. SAQ score (P < 0.05) and left ventricular ejection fraction (LVEF; P = 0.037) by echocardiography significantly improved at 1 month after CSWT. Significant decreases in summed stress score (SSS), summed difference score (SDS), ischemic area stress, and ischemic area difference by MPI were observed at 1 month and 9 months after CSWT (P < 0.01). There were no changes in safety parameters before and after CSWT.CSWT may have a beneficial effect on improving myocardial perfusion, clinical symptoms, exertional capacity, and quality of life and is a safe alternative treatment for patients with severe CAD who have undergone CABG.

Accessibility and Utilization of Telehealth Services During the COVID-19 Pandemic Among Medicare Beneficiaries by Diabetes Status.

Due to the influence types of telehealth services (i.e., phone and/or video) can have on patient care and outcomes, we sought to examine factors associated with the types of telehealth services offered and used among Medicare beneficiaries. We analyzed the Medicare Current Beneficiary Survey COVID-19 Public Use File (N = 1,403 and N = 2,218 for individuals with and without diabetes, respectively) and performed multinomial logit models to examine factors (e.g., sociodemographics, comorbidities, digital access/knowledge) associated with types of telehealth services offered and used among beneficiaries aged ≥65 years by diabetes status. Medicare beneficiaries seemed to prefer using telehealth via phone than video. Regardless of diabetes status, having not previously participated in video or voice calls or conferencing can be a barrier to telehealth being offered and used via video for beneficiaries. For older adults with diabetes, disparities in accessibility of telehealth via video by income and languages spoken other than English were observed. [Research in Gerontological Nursing, xx(x), xx-xx.].

Effects of Mineral on Taxonomic and Functional Structures of Microbial Community in Tengchong Hot Springs via in-situ cultivation.

Diverse mineralogical compositions occur in hot spring sediments, but the impact of minerals on the diversity and structure of microbial communities remains poorly elucidated. In this study, different mineral particles with various chemistries (i.e., hematite, biotite, K-feldspar, quartz, muscovite, aragonite, serpentine, olivine, barite, apatite, and pyrite) were incubated for ten days in two Tengchong hot springs, one alkaline (pH ~ 8.34) with a high temperature (~ 82.8 °C) (Gumingquan, short as GMQ) and one acidic (pH ~ 3.63) with a relatively low temperature (~ 43.3 °C) (Wenguangting, short as WGT), to determine the impacts of minerals on the microbial communities taxonomic and functional diversities. Results showed that the mineral-associated bacterial taxa differed from those of the bulk sediment samples in the two hot springs. The relative abundance of Proteobacteria, Euryarchaeota, and Acidobacteria increased in all minerals, indicating that these microorganisms are apt to colonize on solid surfaces. The α-diversity indices of the microbial communities on the mineral surfaces in the WGT were higher than those from the bulk sediment samples (p < 0.05), which may be caused by the stochastically adhering process on the mineral surface during 10-day incubation, different from the microbial community in sediment which has experienced long-term environmental and ecological screening. Chemoheterotrophy increased with minerals incubation, which was high in most cultured minerals (the relative contents were 5.8 - 21.4%). Most notably, the sulfate respiration bacteria (mainly related to Desulfobulbaceae and Syntrophaceae) associated with aragonite in the acidic hot spring significantly differed from other minerals, possibly due to the pH buffering effect of aragonite providing more favorable conditions for their survival and proliferation. By comparison, aragonite cultured in the alkaline hot spring highly enriched denitrifying bacteria and may have promoted the nitrogen cycle within the system. Collectively, we speculated that diverse microbes stochastically adhered on the surface of minerals in the water flows, and the physicochemical properties of minerals drove the enrichment of certain microbial communities and functional groups during the short-term incubation. Taken together, these findings thereby provide novel insights into mechanisms of community assembly and element cycling in the terrestrial hydrothermal system associated with hot springs.

Hybrid aortic arch procedure in acute type A aortic dissection with right carotid artery occlusion.

Acute type A aortic dissection(ATAAD) complicated by carotid artery is associated with a high risk of perioperative stroke. We reported a case of application of hybrid aortic arch debranching procedure in ATAAD complicated by right carotid artery occlusion, which resulted in no neurological complications after operation and patent carotid artery after discharging.

Unsaturated bond recognition leads to biased signal in a fatty acid receptor.

Individual free fatty acids (FAs) play important roles in metabolic homeostasis, many via engagement with more than 40 GPCRs. Searching for receptors to sense beneficial ω-3 FAs of fish oil enabled the identification of GPR120, involving with a spectrum of metabolic diseases. Here, we report six cryo-EM structures of GPR120 in complex with FA hormones or TUG891 and Gi or Giq trimers. Aromatic residues inside the GPR120 ligand pocket were responsible for recognizing different double-bond positions of these FAs and connect ligand recognition to distinct effector coupling. We also investigated synthetic ligand selectivity and the structural basis of missense single nucleotide polymorphisms. We reveal how GPR120 differentiates rigid double bonds and flexible single bonds and may facilitate rational drug design targeting to GPR120.

Near-Infrared Fluorescent Probe for Imaging Upregulated Hydrogen Sulfide Levels in Rice under Salt and Drought Stress.

Hydrogen sulfide (H2S) is a hazardous gas found in living organisms and is directly tied to our daily lives. Recent studies show that it plays a significant role in plant growth, development, and response to environmental stresses. However, few of the reported near-infrared (NIR) fluorescent probes have been applied to rice and deeply investigated the influence of the external environment on the biological molecules in its internal environment. Therefore, our team created BSZ-H2S, which has the advantage of an emission wavelength of up to 720 nm with fast response, successfully applying it to cell and zebrafish imaging. More importantly, the probe detected H2S in rice roots by in situ imaging in a facile manner and verified the existence of an upregulation process of H2S in response to salt and drought stress. This work provides a concept for the intervention of external stresses in rice culture.

The long-range interaction between two GNAS imprinting control regions delineates pseudohypoparathyroidism type 1B pathogenesis.

Genetic defects of GNAS, the imprinted gene encoding the stimulatory G protein α-subunit, are responsible for multiple diseases. Abnormal GNAS imprinting causes pseudohypoparathyroidism type 1B (PHP1B), a prototype of mammalian end-organ hormone resistance. Hypomethylation at the maternally methylated GNAS A/B region is the only shared defect in PHP1B patients. In autosomal dominant (AD) PHP1B kindreds, A/B hypomethylation is associated with maternal microdeletions at either the GNAS NESP55 differentially methylated region or the STX16 gene located ~170 kb upstream. Functional evidence is meager regarding the causality of these microdeletions. Moreover, the mechanisms linking A/B methylation and these putative imprinting control regions (ICRs), NESP-ICR and STX16-ICR, remain unknown. Here, we generated a human embryonic stem cell model of AD-PHP1B by introducing ICR deletions using CRISPR/Cas9. Using this model, we showed that NESP-ICR is required for methylation and transcriptional silencing of A/B on the maternal allele. We also found that SXT16-ICR is a long-range enhancer of NESP55 transcription, which originates from maternal NESP-ICR. Furthermore, we demonstrated that STX16-ICR is an embryonic stage-specific enhancer enabled by the direct binding of pluripotency factors. Our findings uncover an essential GNAS imprinting control mechanism and advance the molecular understanding of the PHP1B pathogenesis.

TRIM21 inhibits irradiation-induced mitochondrial DNA release and impairs antitumour immunity in nasopharyngeal carcinoma tumour models.

Although radiotherapy can promote antitumour immunity, the mechanisms underlying this phenomenon remain unclear. Here, we demonstrate that the expression of the E3 ubiquitin ligase, tumour cell-intrinsic tripartite motif-containing 21 (TRIM21) in tumours, is inversely associated with the response to radiation and CD8+ T cell-mediated antitumour immunity in nasopharyngeal carcinoma (NPC). Knockout of TRIM21 modulates the cGAS/STING cytosolic DNA sensing pathway, potentiates the antigen-presenting capacity of NPC cells, and activates cytotoxic T cell-mediated antitumour immunity in response to radiation. Mechanistically, TRIM21 promotes the degradation of the mitochondrial voltage-dependent anion-selective channel protein 2 (VDAC2) via K48-linked ubiquitination, which inhibits pore formation by VDAC2 oligomers for mitochondrial DNA (mtDNA) release, thereby inhibiting type-I interferon responses following radiation exposure. In patients with NPC, high TRIM21 expression was associated with poor prognosis and early tumour relapse after radiotherapy. Our findings reveal a critical role of TRIM21 in radiation-induced antitumour immunity, providing potential targets for improving the efficacy of radiotherapy in patients with NPC.

Hydroxylation with Unusual Stereoinversion Catalyzed by an FeII /2-OG Dependent Oxidase and 3,6-Diene-2,5-diketopiperazine Formation in the Biosynthesis of Brevianamide†K.

Natural products with the 3,6-diene-2,5-diketopiperazine core are widely distributed in nature; however, the biosynthetic mechanism of 3,6-diene-2,5-diketopiperazine in fungi remains to be further elucidated. Through heterologous expression and biochemical investigation of an FeII /2-oxoglutarate-dependent oxidase (AspE) and a heme-dependent P450 enzyme (AspF), we report that AspE, AspF and subsequent dehydration account for the formation of the 3,6-diene-2,5-diketopiperazine substructure of brevianamide K from Aspergillus sp. SK-28, a symbiotic fungus of mangrove plant Kandelia candel. More interestingly, in-depth investigation of the enzymatic mechanism showed that AspE promotes hydroxylation of brevianamide Q with unprecedented stereoinversion through hydrogen atom abstraction and water nucleophilic attack from the opposite face of the resultant iminium cation intermediate.

EFHD1, a novel mitochondrial regulator of tumor metastasis in clear cell renal cell carcinoma.

The biological function of many mitochondrial proteins in mechanistic detail has not been well investigated in clear cell renal cell carcinoma (ccRCC). A seven-mitochondrial-gene signature was generated by Lasso regression analysis to improve the prediction of prognosis of patients with ccRCC, using The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium cohort. Among those seven genes, EFHD1 is less studied and its role in the progression of ccRCC remains unknown. The decreased expression of EFHD1 was validated in clinical samples and was correlated with unfavorable outcome. Overexpression of EFHD1 in ccRCC cells resulted in the reduction of mitochondrial Ca2+ , and the inhibition of cell migration and invasion in vitro and tumor metastasis in vivo. Mechanistically, EFHD1 physically bound to the core mitochondrial calcium transporter (mitochondrial calcium uniporter, MCU) through its N-terminal domain. The interaction between EFHD1 and MCU suppressed the uptake of Ca2+ into mitochondria, and deactivated the Hippo/YAP signaling pathway. Further data revealed that the ectopic expression of EFHD1 upregulated STARD13 to enhance the phosphorylation of YAP protein at Ser-127. The knockdown of STARD13 or the overexpression of MCU partly abrogated the EFHD1-mediated induction of phosphorylation of YAP at Ser-127 and suppression of cell migration. Taken together, the newly identified EFHD1-MCU-STARD13 axis participates in the modulation of the Hippo/YAP pathway and serves as a novel regulator in the progression of ccRCC.

Bioequivalence study of ipratropium bromide inhalation aerosol using PBPK modelling.

Aims: Systemic pharmacokinetic (PK) studies can reflect the overall exposure of orally inhaled drug Products (OIDPs) in the blood after inhalation into the lung and can be used to evaluate the bioequivalence of test and reference products. The aim of this article is: (1) to study the PK characteristics and bioequivalence of ipratropium bromide (IB) inhalation aerosol, reference and test products in healthy Chinese subjects; (2) to establish a physiologically based pharmacokinetic (PBPK) model and verify the accuracy of the model in predicting bioequivalence; (3) attempt to use the model to predict the regional distribution of particles in the lung after inhalation, and discuss the effect of gastrointestinal drug absorption of IB on systemic exposure. Methods: The study involved two clinical studies. Clinical study-1 (registration number: CTR20201284) was used with non-clinical data to construct and validate a PBPK model in the B2O simulator, a web-based virtual drug development platform. This model assessed different test and reference products' bioequivalence. Results were compared to a second clinical study (Clinical study-2: registration number CTR20202291). The particles' regional distribution in the lung and the gastrointestinal absorption effect on systemic exposure were discussed based on the simulation results. Results: The established PBPK model successfully simulated the in vivo PK characteristics of IB inhalation aerosol, with r 2 close to 1. Gastrointestinal absorption had a negligible effect on systemic exposure. Particles accumulated in the alveolar area were cleared within an hour, followed by particles in the bronchioles and bronchi. Conclusion: This model provided a reliable method for exploring the correlation between in vitro and in vivo PK studies of IB inhalation aerosols. According to the simulation results, the test and reference products were bioequivalent.

Analysis of salivary steroid hormones in boys with autism spectrum disorder.

BACKGROUND: Autism spectrum disorders (ASD) is a neurodevelopmental disorder with high incidence rate and difficult diagnosis. The purpose of this study was to explore whether salivary cortisol, dehydroepiandrosterone (DHEA) and pregnenolone can be used as biomarkers of ASD children. METHODS: The saliva samples of 55 boys with ASD were collected as the experimental group, and the saliva samples of 24 neurotypical boys were collected as the control group. The Child Behavior Checklist (CBCL), Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), Repetitive Behavior Scale (RBS) were used to assess the severity of symptoms in boys with ASD. Cortisol, DHEA and pregnenolone concentrations in saliva were measured using an ABSSCIEX QTRAP® 6500 + LC/MS/MS system. SPSS 23.0 was used for statistical analysis. Comparisons between the two groups which conform to normal distribution were performed by T-test, and those which don't conform to normal distribution were performed by Mann-Whitney U test. Correlation analysis between two variables was performed using Spearman's correlation analysis. Receiver operating characteristic curve (ROC) analysis was performed to evaluate the discriminatory sensitivity of each hormone between ASD and normal control groups. Logistic regression models were used to analyze whether DHEA and salivary pregnenolone can be used as a biomarker of ASD. RESULTS: There were no significant differences in age, and weight between the ASD group and the normal control group. The ABC, SRS, RBS and CBCL scale scores in the ASD group were significantly higher than those in the normal control group. The salivary DHEA and pregnenolone concentrations in the ASD group were significantly higher than those in the normal control group, but there was no significant difference in cortisol. Spearman's correlation analysis showed that only pregnenolone associated with ABC. Logistic regression model analysis suggested that pregnenolone in saliva was an independent predictor of ASD. ROC analysis found that pregnenolone had good discrimination sensitivity between ASD and normal controls. CONCLUSION: Gave salivary preoperative a space for utilization as biomarker as number of cases are limited to this high expectation.

Multi-MEMS-microphone schemes in a miniature photoacoustic cell for acetylene trace gas measurement.

Dissolved gas analysis is a strong tool for online health monitoring of electrical power equipment. The industry's large-scale deployment of photoacoustic (PA) sensors is still constrained by cost and sensitivity, despite the great accuracy achieved with a mid-infrared light source or optical sensors. We provide a low-cost PA sensor for ppb-level trace gas sensing based on a near-infrared distributed feedback laser source, miniature gas cell, and multiple microelectromechanical system (MEMS) microphones. Five multi-MEMS-microphones schemes are modeled. The simulation indicates that the sensor, including two MEMS microphones in the center of the resonator, is the most cost-efficient option. The experiments that present this scheme can be realized easily by modifying a traditional single microphone PA cell and with ppb-level sensitivity.

Patient attitudes, experiences, and satisfaction with healthcare and office visit utilization among Medicare beneficiaries with type 2 diabetes.

OBJECTIVES: To examine patient attitudes, experiences, and satisfaction with healthcare associated with office visit utilization among Medicare beneficiaries with type 2 diabetes. METHODS: We analyzed the 2019 Medicare Current Beneficiary Survey Public Use File of beneficiaries aged ≥65 years with type 2 diabetes (n = 1092). The ordinal dependent variable was defined as 0, 1 to 5, and ≥6 office visits. An ordinal partial proportional odds model was conducted to examine associations of beneficiaries' attitudes, experiences, and satisfaction with healthcare and office visit utilization. RESULTS: Among the beneficiaries, approximately 17.7%, 22.8%, and 59.5% reported having 0, 1 to 5, and ≥6 office visits, respectively. Being male (OR = 0.67, p = 0.004), Hispanic (OR = 0.53, p = 0.006), divorced/separated (OR = 0.62, p = 0.038) and living in a non-metro area (OR = 0.53, p < 0.001) were associated with a lower likelihood of attending more office visits. Trying to keep sickness to themselves (OR = 0.66, p = 0.002) and dissatisfaction with the ease and convenience of getting to providers from home (OR = 0.45, p = 0.010) were associated with a lower likelihood of having more office visits. DISCUSSION: The proportion of beneficiaries foregoing office visits is concerning. Attitudes concerning healthcare and transportation challenges can be barriers to office visits. Efforts to ensure timely and appropriate access to care should be prioritized for Medicare beneficiaries with diabetes.

Artificial Intelligence in microbiomes analysis: A review of applications in dermatology.

Microorganisms are closely related to skin diseases, and microbiological imbalances or invasions of exogenous pathogens can be a source of various skin diseases. The development and prognosis of such skin diseases are also closely related to the type and composition ratio of microorganisms present. Therefore, through detection of the characteristics and changes in microorganisms, the possibility for diagnosis and prediction of skin diseases can be markedly improved. The abundance of microorganisms and an understanding of the vast amount of biological information associated with these microorganisms has been a formidable task. However, with advances in large-scale sequencing, artificial intelligence (AI)-related machine learning can serve as a means to analyze large-scales of data related to microorganisms along with determinations regarding the type and status of diseases. In this review, we describe some uses of this exciting, new emerging field. In specific, we described the recognition of fungi with convolutional neural networks (CNN), the combined application of microbial genome sequencing and machine learning and applications of AI in the diagnosis of skin diseases as related to the gut-skin axis.

[Mechanism of Buyang Huanwu Decoction glycosides against atherosclerotic inflammation through NF-κB signaling pathway].

This study aims to explore the effect of Buyang Huanwu Decoction glycosides on the inflammatory response of apolipoprotein E~(-/-)(ApoE~(-/-)) mice and RAW264.7 cells through nuclear factor kappa-B(NF-κB) signaling pathway. In the in vivo experiment, ApoE~(-/-) mice were fed with high-fat diets for 12 weeks to induce the animal model of atherosclerosis, and 75 µg·mL~(-1) oxidized low-density lipoprotein(Ox-LDL) incubated RAW264.7 cells for 24 h to establish the atherosclerosis cell model. Automatic biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay(ELISA), Western blot, and droplet digital polymerase chain reaction(PCR) were used to determine the blood lipid levels, aortic intimal thickness, inflammatory factor content, NF-κB pathway-related proteins, and mRNA expression levels, and evaluate arterial atherosclerotic lesions and anti-atherosclerotic mechanisms of the drug. The model of atherosclerosis was successfully established in ApoE~(-/-) mice after 12 weeks of feeding with high-fat diets. In the model group, the plasma levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-C) were increased(P<0.01), the intima of the blood vessels was thickened, the levels of inflammatory factors tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were increased, and the protein and mRNA expressions of NF-κB and inhibitor of NF-κB(IκBα) were significantly increased as compared with the control group. Compared with the model group, the high-dose Buyang Huanwu Decoction glycoside group decreased the plasma levels of TC, TG, and LDL-C, reduced the plaque area and thickness and the content of inflammatory factor TNF-α, and inhibited the protein and mRNA expressions of NF-κB and IκBα, with the effect same as Buyang Huanwu Decoction. In the in vivo experiment, 75 µg·mL~(-1) Ox-LDL stimulated RAW264.7 cells for 24 h to successfully establish a foam cell model. As compared with the control group, the nuclear amount of NF-κB and the protein and mRNA expressions of IκBα in the model group increased. Compared with the model group, the middle-dose and high-dose Buyang Huanwu Decoction glycoside groups decreased the nuclear amount of NF-κB and the protein and mRNA expressions of IκBα. The above results show that the glycosides are the main effective substances of Buyang Huanwu Decoction against atherosclerosis, which inhibit the NF-κB pathway and reduce the inflammatory response, thus playing the role against atherosclerotic inflammation same as Buyang Huanwu Decoction.