Enantioselective Silicon-Directed Nazarov Cyclization.

The Nazarov electrocyclization reaction is a convenient, widely used method for construction of cyclopentenones. In the past few decades, catalytic asymmetric versions of the reaction have been extensively studied, but the strategies used to control the position of the double bond limit the substituent pattern of the products and thus the synthetic applications of the reaction. Herein, we report highly enantioselective silicon-directed Nazarov reactions which were cooperatively catalyzed by a Lewis acid and a chiral Brønsted acid. The chiral cyclopentenones we synthesized using this method generally cannot be obtained by means of other catalytic enantioselective reactions, including previously reported methods for enantioselective Nazarov cyclization. The silicon group in the dienone substrate stabilized the ß-carbocation of the intermediate, thereby determining the position of the double bond in the product. Mechanistic studies suggested that the combination of Lewis and Brønsted acids synergistically activated the dienone substrate and that the enantioselectivity of the reaction originated from a chiral Brønsted acid promoted proton transfer reaction of the enol intermediate.

Progress on genome-wide CRISPR/Cas9 screening for functional genes and regulatory elements.

The CRISPR/Cas9 system is a powerful tool which has been extensively used for genome editing in the past few years. Nuclease-dead Cas9 (CRISPR/dCas9), a Cas9 protein mutant without splicing ability, along with loss-of- function (LOF), gain-of-function (GOF), or non-coding genes scanning approaches can reveal genome-scale functional determinants. CRISPR/Cas9 has been widely adopted to decipher disease mechanisms and pinpoint drug targets in the life science field, and also provide novel insights into animal genetics and breeding. In this review, we summarize the research progress in high-throughput CRISPR/Cas9 screening for revealing the functional genes and regulatory elements in the whole genome. We also highlight the applications of CRISPR/Cas9 system in the animal cells, providing a reference for gene editing and other related research in related fields.

Water-soluble host-guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres.

A sugar-functionalized water-soluble tribenzotriquinacene derivative bearing six glucose residues, TBTQ-(OG) 6 , was synthesized and its interaction with C60 and C70-fullerene in co-organic solvents and aqueous solution was investigated by fluorescence spectroscopy and ultraviolet-visible spectroscopy. The association stoichiometry of the complexes TBTQ-(OG) 6 with C60 and TBTQ-(OG) 6 with C70 was found to be 1:1 with binding constants of K a = (1.50 ± 0.10) × 105 M-1 and K a = (2.20 ± 0.16) × 105 M-1, respectively. The binding affinity between TBTQ-(OG) 6 and C60 was further verified by Raman spectroscopy. The geometry of the complex of TBTQ-(OG) 6 with C60 deduced from DFT calculations indicates that the driving force of the complexation is mainly due to the hydrophobic effect and to host-guest π-π interactions. Hydrophobic surface simulations showed that TBTQ-(OG) 6 and C60 forms an amphiphilic supramolecular host-guest complex, which further assembles to microspheres with diameters of 0.3-3.5 µm, as determined by scanning electron microscopy.

Network embedding for link prediction: The pitfall and improvement.

Link prediction plays a significant role in various applications of complex networks. The existing link prediction methods can be divided into two categories: structural similarity algorithms in network domain and network embedding algorithms in the field of machine learning. However, few researchers focus on comparing these two categories of algorithms and exploring the intrinsic relationship between them. In this study, we systematically compare the two categories of algorithms and study the shortcomings of network embedding algorithms. The results indicate that network embedding algorithms have poor performance in short-path networks. Then, we explain the reasons for this phenomenon by computing the Euclidean distance distribution of node pairs after a given network has been embedded into a vector space. In the vector space of a short-path network, the distance distribution of existent and nonexistent links are often less distinguishable, which can sharply reduce the algorithmic performance. In contrast, structural similarity algorithms, which are not restricted by the distance function, can represent node similarity accurately in short-path networks. To address the above pitfall of network embedding, we propose a novel method for link prediction aiming to supplement network embedding algorithms with local structural information. The experimental results suggest that our proposed algorithm has significant performance improvement in many empirical networks, especially in short-path networks. AUC and Precision can be improved by 36.7%-94.4% and 53.2%-207.2%, respectively.

Thymine DNA Glycosylase Gene Knockdown Can Affect the Differentiation of Pig Preadipocytes.

AIMS: To study the effect of thymine DNA glycosylase (TDG) gene knockdown on the differentiation of pig preadipocytes. METHODS: Preadipocytes were obtained from subcutaneous adipose tissue from the neck of 1- to 7-day-old pigs. The TDG gene was knocked down using siRNA, and cell differentiation was induced. The mRNA expression level was measured using fluorescence quantitative PCR, and the protein expression level was determined using Western blot analysis. The DNA methylation levels in promoter regions of differentiation-related genes were also evaluated. RESULTS: TDG gene knockdown decreased the mRNA expression levels of the peroxisome proliferator-activated receptorγ (PPARγ) and Fatty acid binding proteins 4(FABP4 Also known as aP2) genes (P<0.01), while the mRNA expression level of the CCAAT/enhancer binding protein alpha(C/EBPα) gene did not change significantly (P>0.05). In addition, after induced differentiation, the lipid droplet production significantly decreased, and the percentages of methylation in the promoter regions of C/EBPα, PPARγ, and aP2 genes were 0.9%, 80%, and 76%, respectively. In contrast, the percentages of methylation in the negative control groups were 0.5%, 67.5%, and 58%, respectively. CONCLUSION: TDG gene knockdown could inhibit the differentiation of pig preadipocytes and affect the DNA methylation levels of some transcription factors.

MiR-378 Plays an Important Role in the Differentiation of Bovine Preadipocytes.

BACKGROUND: Adipocyte, the main cellular component of white adipose tissue, plays a vital role in energy balance in higher eukaryotes. In recent years, adipocytes have also been identified as a major endocrine organ involved in immunological responses, vascular diseases, and appetite regulation. In farm animals, fat content and categories are closely correlated with meat quality. MicroRNAs (miRNAs), a class of endogenous single-stranded non-coding RNA molecules, participate in the regulation of adipocyte differentiation and adipogenesis through regulating the transcription or translation of target mRNAs. MiR-378 plays an important role in a number of biological processes, including cell growth, cell differentiation, tumor cell survival and angiogenesis. METHODS: In the present study, bioinformatics analysis and dual-luciferase reporter assay were used to identify and validate the target genes of miR-378. In vitro cell transfection, quantitative reverse transcription polymerase chain reaction (RT-qPCR), western blot analysis, Oil Red O staining, and triglyceride content measurement were conducted to analyze the effects of miR-378 on bovine preadipocyte differentiation. RESULTS: MiR-378 was induced during adipocyte differentiation. In the differentiated adipocytes overexpressing miR- 378, the volume of lipid droplets was enlarged, and the triglyceride content was increased. Moreover, the mRNA expression levels of the adipocyte differentiation marker genes, peroxisome proliferator-activated receptor gamma (PPARγ) and sterol regulatory element-binding protein (SREBP), were significantly elevated in the differentiated, mature adipocytes. In contrast, the mRNA expression level of preadipocyte factor 1 (Pref-1) was markedly reduced. E2F transcription factor 2 (E2F2) and Ras-related nuclear (RAN)-binding protein 10 (RANBP10) were the two target genes of miR-378. The mRNA expression levels of E2F2 and RANBP10 did not significantly change in bovine preadipocytes overexpressing miR-378. However, the protein expression levels of E2F2 and RANBP10 were markedly reduced. CONCLUSION: MiR-378 promoted the differentiation of bovine preadipocytes. E2F2 and RANBP10 were the two target genes of miR-378, and might involve in the effects of miR-378 on the bovine preadipocyte differentiation.

The MBD4 gene plays an important role in porcine adipocyte differentiation.

BACKGROUND: MBD4 (methyl-CpG binding domain protein 4) is an important G: T glycosylase that can identify T-G mismatches. It plays a role in active demethylation through base excision repair. Overexpression of MBD4 gene can cause the demethylation of numerous genes, and the remethylation of MBD4-associated genes can occur when the MBD4 gene is knocked out. To date, the functions and regulatory mechanisms of the MBD4 gene in the differentiation of porcine preadipocytes have not been clearly established. METHODS: Subcutaneous fat cells from 1- to 7-day-old Junmu-1 piglets were cultured in vitro, induced to differentiate, and then identified. A real-time fluorescence-based quantitative polymerase chain reaction (PCR) analysis was conducted to detect MBD4 messenger RNA (mRNA) expression. Cells were treated with MBD4-siRNA (small interfering RNA) and induced to differentiate. Changes in the lipid droplets were observed by oil red O staining. Changes in the mRNA and protein expression levels of MBD4 and the adipose differentiation-associated genes C/EBPα (CCAAT-enhancer-binding protein alpha), PPARγ (peroxisome proliferator-activated receptor gamma), and aP2 (adipocyte protein 2) were detected. In addition, the bisulfite sequencing method was used to detect changes in methylation in the promoters of certain genes associated with adipose differentiation. RESULTS: Levels of MBD4 mRNA and protein expression varied with time over the course of the porcine adipocyte differentiation, with the highest levels of this expression observed on day two of the differentiation process. After silencing MBD4 and inducing differentiation, the production of lipid droplets decreased, the mRNA expression levels of C/EBPα, PPARγ, and aP2 were significantly reduced, and DNA methylation modification levels were significantly elevated in the examined promoter regions. CONCLUSION: The silencing of the MBD4 gene can influence the DNA methylation levels of preadipocyte differentiation-related genes and subsequently inhibit the differentiation of porcine preadipocytes.

The recent advance and prospect of natural source compounds for the treatment of heart failure.

Heart failure is a continuously developing syndrome of cardiac insufficiency caused by diseases, which becomes a major disease endangering human health as well as one of the main causes of death in patients with cardiovascular diseases. The occurrence of heart failure is related to hemodynamic abnormalities, neuroendocrine hormones, myocardial damage, myocardial remodeling etc, lead to the clinical manifestations including dyspnea, fatigue and fluid retention with complex pathophysiological mechanisms. Currently available drugs such as cardiac glycoside, diuretic, angiotensin-converting enzyme inhibitor, vasodilator and ß receptor blocker etc are widely used for the treatment of heart failure. In particular, natural products and related active ingredients have the characteristics of mild efficacy, low toxicity, multi-target comprehensive efficacy, and have obvious advantages in restoring cardiac function, reducing energy disorder and improving quality of life. In this review, we mainly focus on the recent advance including mechanisms and active ingredients of natural products for the treatment of heart failure, which will provide the inspiration for the development of more potent clinical drugs against heart failure.

Identification and Functional Analyses of Host Proteins Interacting with the P3a Protein of Brassica Yellows Virus.

Viruses are obligate parasites that only undergo genomic replication in their host organisms. ORF3a, a newly identified non-AUG-initiated ORF encoded by members of the genus Polerovirus, is required for long-distance movement in plants. However, its interactions with host proteins still remain unclear. Here, we used Brassica yellows virus (BrYV)-P3a as bait to screen a plant split-ubiquitin-based membrane yeast two-hybrid (MYTH) cDNA library to explain the functional role of P3a in viral infections. In total, 138 genes with annotations were obtained. Bioinformatics analyses revealed that the genes from carbon fixation in photosynthetic, photosynthesis pathways, and MAPK signaling were affected. Furthermore, Arabidopsis thaliana purine permease 14 (AtPUP14), glucosinolate transporter 1 (AtGTR1), and nitrate transporter 1.7 (AtNRT1.7) were verified to interact with P3a in vivo. P3a and these three interacting proteins mainly co-localized in the cytoplasm. Expression levels of AtPUP14, AtGTR1, and AtNRT1.7 were significantly reduced in response to BrYV during the late stages of viral infection. In addition, we characterized the roles of AtPUP14, AtGTR1, and AtNRT1.7 in BrYV infection in A. thaliana using T-DNA insertion mutants, and the pup14, gtr1, and nrt1.7 mutants influenced BrYV infection to different degrees.

Cross-cultural adaptation and construct validity of the Chinese Version of Visual Vertigo Analogue Scale by using structural equation modeling.

BACKGROUND: Visual vertigo (VV) is a disease characterized by various visual signal-induced discomforts, including dizziness, unsteady balance, activity avoiding, and so forth. Distinguishing it from other kinds of dizziness is important because it needs the combination of visual training and vestibular rehabilitation together. However, there is no appropriate tool to diagnose VV in China, thus we would like to introduce an effective tool to China. OBJECTIVE: The aim of this study was to establish the reliability and validity of the Chinese version of visual vertigo analogue scale (VVAS-CH) and to achieve its crosscultural adaptation in order to promote its further usage in China. METHODS: A total of 1681 patients complaining of vertigo or dizziness were enrolled and they were asked to complete the VVAS-CH. The cross-cultural adaptation, reliability and construct validity of the VVAS-CH were determined. RESULTS: Split-half reliability was 0.939, showing a good reliability. Factor analysis identified only one common factor for the nine items that explained 64.83% of the total variance. Most fit indices reached acceptable levels, proving the good fit of the VVAS-CH model. CONCLUSIONS: The VVAS-CH validated in this study can be used as an effective tool for diagnosing and evaluating VV in patients whose native language is Chinese.

Matricellular Protein SMOC2 Potentiates BMP9-Induced Osteogenic Differentiation in Mesenchymal Stem Cells through the Enhancement of FAK/PI3K/AKT Signaling.

Mesenchymal stem cells (MSCs) can self-renew and differentiate into multiple lineages, making MSC transplantation a promising option for bone regeneration. Both matricellular proteins and growth factors play an important role in regulating stem cell fate. In this study, we investigated the effects of matricellular protein SMOC2 (secreted modular calcium-binding protein 2) on bone morphogenetic protein 9 (BMP9) in mouse embryonic fibroblasts (MEFs) and revealed a possible molecular mechanism underlying this process. We found that SMOC2 was detectable in MEFs and that exogenous SMOC2 expression potentiated BMP9-induced osteogenic markers, matrix mineralization, and ectopic bone formation, whereas SMOC2 knockdown inhibited these effects. BMP9 increased the levels of p-FAK and p-AKT, which were either enhanced or reduced by SMOC2 and FAK silencing, respectively. BMP9-induced osteogenic markers were increased by SMOC2, and this increase was partially abolished by silencing FAK or LY290042. Furthermore, we found that general transcription factor 2I (GTF2I) was enriched at the promoter region of SMOC2 and that integrin ß1 interacted with SMOC2 in BMP9-treated MEFs. Our findings demonstrate that SMOC2 can promote BMP9-induced osteogenic differentiation by enhancing the FAK/PI3K/AKT pathway, which may be triggered by facilitating the interaction between SMOC2 and integrin ß1.

Interleukin 6 promotes BMP9-induced osteoblastic differentiation through Stat3/mTORC1 in mouse embryonic fibroblasts.

Interleukin 6 (IL-6) plays a dual role in regulating bone metabolism, although the concrete mechanism is unclear. Bone morphogenetic protein 9 (BMP9) is one of the most potent osteogenic inducers, and a promising alternative for bone tissue engineering. The relationship between IL-6 and BMP9 in osteogenic differentiation remains to be elucidated, and the osteoblastic potential of BMP9 needs to be enhanced to overcome certain shortcomings of BMP9. In this study, we used real-time PCR, western blot, immunofluorescent stain, fetal limb culture and cranial defects repair model to explore the IL-6 role in BMP9-induced osteogenic differentiation in mouse embryonic fibroblasts (MEFs). We found that the rat serum level of IL-6 was increased in the dexamethasone-induced osteoporosis model, and IL-6 expression was detectable in several progenitor cells and MEFs. BMP9 upregulated IL-6 in MEFs, and the BMP9-induced osteoblastic markers were elevated by IL-6, but reduced by IL-6 knockdown. BMP9 and/or IL-6 both activated mTOR, and the IL-6 effect on BMP9-induced osteoblastic markers and bone formation were reduced greatly by mTOR inhibition. Raptor was up-regulated by IL-6 and/or BMP9 specifically, and the osteoblastic markers induced by IL-6 and/or BMP9 were reduced by Raptor knockdown. Meanwhile, Stat-3 was activated by IL-6 and/or BMP9, and the increase of Raptor or osteoblastic markers by IL-6 and/or BMP9 were reduced by Stat-3 inhibition. The Raptor promoter activity was regulated by p-Stat-3. Our finding suggested that IL-6 can promote the BMP9 osteoblastic potential, which may be mediated through activating Stat-3/mTORC1 pathway.

LCN2 Inhibits the BMP9-induced Osteogenic Differentiation through Reducing Wnt/ß-catenin Signaling via Interacting with LRP6 in Mouse Embryonic Fibroblasts.

BACKGROUND: Due to its effective osteogenic ability, BMP9 is a promising candidate for bone regeneration medicine. Whereas, BMP9 can also induce adipogenesis simultaneously. LCN2 is a cytokine associated with osteogenesis and adipogenesis. Reducing the adipogenic potential may be a feasible measure to enhance the osteogenic capability of BMP9. OBJECTIVE: The objective of the study was to explore the role of LCN2 in regulating the BMP9-initialized osteogenic and adipogenic differentiation in mouse embryonic fibroblasts (MEFs), and clarify the possible underlying mechanism. METHODS: Histochemical stain, western blot, real-time PCR, laser confocal, immunoprecipitation, cranial defect repair, and fetal limb culture assays were used to evaluate the effects of LCN2 on BMP9-induced osteogenic and adipogenic differentiation, as well as Wnt/ß-catenin signaling. RESULTS: LCN2 was down-regulated by BMP9. The BMP9-induced osteogenic markers were inhibited by LCN2 overexpression, but the adipogenic markers were increased; LCN2 knockdown exhibited opposite effects. Similar results were found in bone defect repair and fetal limb culture tests. The level of ß-catenin nucleus translocation was found to be reduced by LCN2 overexpression, but increased by LCN2 knockdown. The inhibitory effect of LCN2 overexpression on the osteogenic capability of BMP9 was reversed by ß-catenin overexpression; whereas, the effect of LCN2 knockdown on promoting BMP9 osteogenic potential was almost eliminated by ß-catenin knockdown. LCN2 could bind with LRP6 specifically, and the inhibitory effect of LCN2 on the osteogenic potential of BMP9 could not be enhanced by LRP6 knockdown. CONCLUSION: LCN2 inhibits the BMP9-induced osteogenic differentiation but promotes its adipogenic potential in MEFs, which may be partially mediated by reducing Wnt/ß-catenin signaling via binding with LRP6.

Temporal trends in the prevalence of autoimmune diseases from 1990 to 2019.

AIM: To describe current situation and analyze temporal trends of prevalence for four autoimmune diseases including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS) and psoriasis, at the global, continental, and national levels. METHODS: The estimates and 95% uncertainty interval (UI) for age-standardized prevalence rate (ASPR) of RA, IBD, MS and psoriasis were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. ASPR of RA, IBD, MS and psoriasis in 2019 was illustrated at the global, continental, and national levels. Joinpoint regression analysis was adopted to analyze the 1990-2019 temporal trends by calculating the annual percentage change (APC) and average APC (AAPC), as well as their 95% confidence interval (CI). RESULTS: In 2019, the global ASPR of RA, IBD, MS and psoriasis was 224.25 (95% UI: 204.94 to 245.99), 59.25 (95% UI: 52.78 to 66.47), 21.25 (95% UI: 18.52 to 23.91) and 503.62 (95% UI: 486.92 to 519.22), respectively, with ASPRs generally higher in Europe and America than in Africa and Asia. From 1990 to 2019, the global ASPR increased significantly for RA (AAPC = 0.27%, 95% CI: 0.24 to 0.30; P < 0.001) and decreased significantly for IBD (AAPC = -0.73%, 95% CI: -0.76 to -0.70; P < 0.001), MS (AAPC = -0.22%, 95% CI: -0.25 to -0.18; P < 0.001) and psoriasis (AAPC = -0.93%, 95% CI: -0.95 to -0.91; P < 0.001), with the most substantial changes occurring at different continents and periods. The trends of ASPR of these four autoimmune diseases varied significantly across 204 countries and territories. CONCLUSIONS: There is a strong heterogeneity in prevalence (2019), as well as their temporal trends (1990-2019) of autoimmune diseases across the world, highlighting the strong distributive inequities of autoimmune diseases worldwide, which may be instructive for better understanding the epidemiology of these diseases, appropriately allocating the medical resources, as well as making relevant health policies.

The expression profile of Gasdermin C-related genes predicts the prognosis and immunotherapy response of pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) has a poor prognosis and is relatively unresponsive to immunotherapy. Gasdermin C (GSDMC) induces pyroptosis in cancer cells and inflammation in the tumor microenvironment. However, whether GSDMC expression in PAAD is associated with survival or response to immunotherapy remains unknown. GSDMC expression and the relationship between GSDMC and patient survival or immune infiltration in PAAD were examined using data in the The Cancer Genome Atlas (TCGA), Gene Expression Ominbus (GEO), Genotype-Tissue Expression (GTEx) and Cancer Cell Line Encyclopedia (CCLE) databases. The TCGA PAAD cohort could be divided into two distinct risk groups based on the expression of GSDMC-related genes (GRGs). The TIDE algorithm predicted that the low-risk group was more responsive to immune checkpoint blockade therapy than the high-risk group. A novel 15-gene signature was constructed and could predict the prognosis of PAAD. In addition, the 15-gene signature model predicted the infiltration of immune cells and Immune checkpoint blockade (ICB) treatment response. Immunohistochemical staining assessment of patient-derived human tissue microarray (TMA) from 139 cases of local PAAD patients revealed a positive correlation between GSDMC expression and PD-L1 expression but a negative correlation between GSDMC expression and infiltration of low CD8+ T cells. Moreover, the overexpression of GSDMC was related to poor overall survival (OS). This study suggests that GSDMC is a valuable biomarker for predicting PAAD prognosis and predicts the immunotherapy response of PAAD.

Effects of the Lipid Metabolites and the Gut Microbiota in ApoE-/- Mice on Atherosclerosis Co-Depression From the Microbiota-Gut-Brain Axis.

Background: The diagnosis, treatment, and prevention of atherosclerosis co-depression are poor, so it is urgent to explore new targets. Based on the "microbiota-gut-brain axis," this study aimed to investigate the changes of lipid metabolites in the prefrontal cortex and hippocampus regions and the characteristics of the gut microbiota in ApoE-/- mice with atherosclerosis co-depression. Methods: ApoE-/- mice (hyperlipid feeding combined with binding, HFB group, n = 14, male) fed a high-fat diet for 16 weeks with binding stimulation were used as an animal model for atherosclerosis co-depression. The depression degree of mice was evaluated by body weight, sucrose preference test, open field test, and tail suspension test. Oil-red O staining, HE staining, and biochemical parameters were used to evaluate the damage degree of atherosclerosis in mice. LC-MS/MS technique for non-targeted lipidomics analysis was used to analyze the differential lipid metabolites in the prefrontal cortex and hippocampus regions of mice. 16S rDNA amplification sequencing was used to screen the differential gut microbial, and association analysis was performed with the differential lipid metabolites. Results: Compared with the normal control group (NC group), the HFB group showed depression-like behaviors and atherosclerosis-related pathological indicators. The differential lipid metabolites in the prefrontal cortex and hippocampus regions were mainly LPC, LPE, LPS, PC, PE, PS, PI, and GD1a, and were mainly enriched in the glycerophospholipid metabolism pathway and the retrograde endocannabinoid signaling pathway. At the same time, there were significant differences in the structure of the gut microbial community between the two groups. The abundance of Deferribacteres and Proteobacteria in the HFB group increased, while the abundance of Verrucomicrobia and Actinobacteria decreased at the phylum level; the abundance of Desulfovibrio, Clostridium_IV, Helicobacter and Pseudoflavonifractor increased, while the abundance of Akkermansia decreased at the genus level. Conclusion: Atherosclerosis co-depression of ApoE-/- mice of the prefrontal cortex and hippocampus lipid metabolism pathways of disorder and the changes of to the gut microbiota, which leads to abnormal white matter and synaptic dysfunction, increased gut inflammation, and decreased gut permeability, leading to the release of inflammatory cytokines, there is a strong correlation between both, it further confirmed the existence of the "microbiota-gut-brain axis."

The Correlation Between Detection Value of Distortion-Product Otoacoustic Emissions and the Early Prognosis of Sudden Sensorineural Hearing Loss.

BACKGROUND: To explore the correlation between the detection value of distortion-product otoacoustic emissions and the early prognosis of sudden sensorineural hearing loss. METHODS: Seventy-eight patients with first-onset sudden sensorineural hearing loss (all frequencies) from April 2018 to July 2019 were included in this study. Distortion-product otoacoustic emissions and pure-tone audiometry tests were performed at days 0, 3, and 6 of admission. Repeated measures analysis of variance was performed to evaluate the changes in the signal-to-noise ratio for different distortion-product otoacoustic emissions frequencies over time and the interaction of grouping factors and time factors. RESULTS: The distortion-product otoacoustic emissions evocation rate in the 4 groups was significantly different starting at day 3 of treatment. It was higher in the cured (35.3%) and obviously effective (20.0%) groups than in the other 2 groups (0%, 0%). At the 6 f2 frequencies of 1105 Hz, 1560 Hz, 2211 Hz, 3125 Hz, 4416 Hz, and 8837 Hz, the signal-to-noise ratio was different among the groups (P < .05) and was notably higher in the cured group. The analysis of the signal-to-noise ratio change before and after treatment at the intermediate f2 frequencies of 1105 Hz, 1560 Hz, and 2211 Hz in all patients indicated a linear correlation between the signal-to-noise ratio change and the pure-tone hearing threshold change, with a correlation coefficient of 0.481. CONCLUSION: Distortion-product otoacoustic emissions evocation in the early stage (within 3 days of treatment) or the signal-to-noise ratio trend over time at intermediate frequencies may predict the prognosis of sudden sensorineural hearing loss.

Pd-Catalyzed ß-C-H Arylation of Aldehydes and Ketones Based on a Transient Directing Group.

The direct Pd-catalyzed ß-C-H arylation of aldehydes and ketones was developed by using 2-amino-N,N'-diisopropylsuccinamide as a novel transient directing group (TDG). The TDG showed good versatility in functionalizing unactivated ß-C-H bonds of aldehydes and ketones. It was effective not only for aliphatic aldehydes and ketones but also for aromatic aldehydes and ketones. Besides, it was applicable to o-methylbenzaldehydes.

Improvement of electroacupuncture on APP/PS1 transgenic mice in behavioral probably due to reducing deposition of Aß in hippocampus.

Alzheimer's disease (AD) is a fatal neurodegenerative disease for which currently no cure is available. Electroacupuncture (EA) has been widely used in China as an alternative therapeutic approach for neurological diseases. The cognitive decline in patients with AD has been reported to be closely related to the deposition of amyloid-ß (Aß) in the hippocampus of the brain, and the Morris water maze (MWM) test is a widely used method for assessing the behavior of animal models. In this study, the MWM test was performed to evaluate the effects of EA treatment on cognitive function and memory, and the micro-positron emission tomography scan was used to assess the hippocampal Aß deposition. The results showed that the cognitive function of APP/PS1 mice was significantly improved and the rate of [18F]AV-45 uptake was reduced in the EA group, compared with the AD group. Our study suggested that EA can exert a therapeutic effect in AD by improving spatial learning and memory and inhibiting the hippocampal Aß deposition.

Global distribution and environmental drivers of methylmercury production in sediments.

Neurotoxic methylmercury (MeHg) in environments poses substantial risks to human health. Saturated sediments are basic sources of MeHg in food chains; however, distribution patterns and environmental drivers of MeHg at a global scale remain largely unexplored. Here, we characterized global patterns of MeHg distribution and environmental drivers of MeHg production based on 495 sediment samples across five typical ecosystems from the literature (1995-2018) and our own field survey. Our results showed the MeHg concentration ranged from 0.009 to 55.7 µg kg-1 across the different ecosystems, and the highest MeHg concentration and Hg methylation potential were from the sediments of paddy and marine environments, respectively. Further, using combined analysis of random forest and structural equation modeling, we identified temperature and precipitation as important regulators of MeHg production after accounting for the well-known drivers including Hg availability and sediment geochemistry. More importantly, we found increased MeHg production in sediments with elevated mean annual Hg precipitation, and warmer temperature could also accelerate MeHg production by facilitating activities of microbial methylators. Together, this work advances our understanding of global MeHg distribution in sediments and environmental drivers, which are fundamental to the prediction and management of MeHg production and its potential health risk globally.