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Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.

CF3SO2OCF3 was proved to be a useful “F”/“CO” reagent in the selective preparation of alkyl fluorides and carbonates from alcohols by varying the bases.

Coronavirus disease 2019 (COVID-19) remains an uncontained, worldwide pandemic. While battling the disease in China, the Chinese government has actively promoted the use of traditional Chinese medicine, and many studies have been conducted to determine the efficacy of traditional Chinese medicine for treating COVID-19. The present review discusses the effectiveness and safety of traditional Chinese medicine in curing COVID-19 and provides clinical evidence from all confirmed cases in China. Applications of traditional Chinese medicine and specific recipes for treating other viral infections, such as those caused by severe acute respiratory syndrome coronavirus and influenza A viruses (including H1N1), are also discussed. Studies have reported that traditional Chinese medicine treatment plays a significant role in improving clinical symptoms. Therefore, further investigation may be of high translational value in revealing novel targeted therapies for COVID-19.

Bootleg Innovation helps enterprises create unconventional innovation achievements, and has gradually become an important approach for radical innovation under the background of open innovation. Through the integration of the cognitive-affective processing system and conservation of resources (COR) theory, the present study takes integrative complexity as a moderator, and explores the mechanism of LMX ambivalence on employees' bootleg innovation.A total of 387 employees and 110 supervising managers participated in the two-wave dyadic survey. To test our hypotheses, we performed the hierarchical regression and conducted bootstrapping analyses to test our hypotheses.Findings indicated that LMX ambivalence not only improves employees' cognitive flexibility and promotes bootleg innovation, but also aggravates employees' job anxiety and hinders bootleg innovation. In addition, integrative complexity significantly moderates the above two mediating paths. Specifically, when integrative complexity was higher, the negative mediating effect of job anxiety was attenuated, and the positive mediating effect of cognitive flexibility was enhanced.Contrasting with previous research, this research analyzed the triggering mechanism of bootleg innovation combined with the dynamic interaction of environmental stimulus, emotion and cognition. The findings provide novel insight into how to achieve bootleg innovation.

The aim of this study was to develop and internally validate a nomogram of the probability EC patients surviving longer than 5 years. Quantitative real-time PCR (qRT-PCR) was implemented to analyze the expression of lncRNA-LA16c-313D11.11 in 60 EC tissues. The clinicopathological characteristics and follow-up data were retrospectively gathered and analyzed. To establish the prediction model, multivariate logistic regression analysis was applied, and the discrimination, calibration, and clinical practicability of the prediction model were assessed with a concordance index (C-index), calibration chart, and decision curve analysis. Bootstrap validation was performed for internal validation. The prediction factors included the age of patients, myometrial invasion, lymphovascular space invasion, histological subtype, and the expression of lncRNA-LA16C-313D11.11. The model demonstrated good calibration and modest discrimination (C-index = 0.860, 95% confidence interval: 0.724-0.946). Moreover, the interval validation achieved a high C-index value of 0.778. This study revealed the predictive value of lncRNA-LA16C-313D11.11 and successfully developed a nomogram for predicting EC patients survival longer than 5 years, which may facilitate the institution of personalized treatment algorithms, surveillance strategies, and lifestyle interventions.

Background Distant hybridization is an important breeding technique for creating new strains with superior traits by integrating two different genomes. Successful hybridization of Megalobrama amblycephala (BSB, 2n = 48) and Culter alburnus (TC, 2n = 48) was achieved to establish hybrid lineages (BT and TB), which provide valuable materials for exploring the mechanisms of distant hybridization fertility. In this study, the gonadal tissue transcriptomes of BSB, TC, BT-F1, and TB-F1 were sequenced using Illumina high-throughput sequencing technology to analyze the reproductive characteristics of BT and TB.Results Differential gene expression analysis showed that the differentially expressed genes in BT vs BSB and BT vs TC were mainly enriched in signaling pathways not directly associated with meiosis. The differentially expressed genes of TB vs BSB and TB vs TC were mainly enriched in pathways related to meiosis, and most of them were down-regulated, indicating that meiosis is suppressed in TB. UD (under-dominance) genes were enriched in pathways related to meiosis and DNA repair in TB. OD (over-dominance) genes were enriched in MAPK signaling pathway, and ELD-B (expression level dominance-BSB) genes were enriched in pathways related to steroid hormone synthesis in both BT and TB.Conclusions These results suggest that meiotic progression may not be affected in BT, whereas it is clearly inhibited in TB. Offspring of M. amblycephala maternal parent may have better genomic compatibility and fertility. Our study provides important information on the molecular mechanisms of breaking reproductive isolation in distantly hybridized fertile lineages.

BackgroundMutations in the dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene are linked to malformations of cortical development (MCD), which may be accompanied by central nervous system (CNS) manifestations. Here, we present the case of a patient with MCD harboring a variant of DYNC1H1 and review the relevant literature to explore genotype-phenotype relationships.Case presentationA girl having infantile spasms, was unsuccessfully administered multiple antiseizure medications and developed drug-resistant epilepsy. Brain magnetic resonance imaging (MRI) at 14 months-of-age revealed pachygyria. At 4 years-of-age, the patient exhibited severe developmental delay and mental retardation. A de novo heterozygous mutation (p.Arg292Trp) in the DYNC1H1 gene was identified. A search of multiple databases, including PubMed and Embase, using the search strategy DYNC1H1 AND [malformations of cortical development OR seizure OR intellectual OR clinical symptoms] up to June 2022, identified 129 patients from 43 studies (including the case presented herein). A review of these cases showed that patients with DYNC1H1-related MCD had higher risks of epilepsy (odds ratio [OR] = 33.67, 95% confidence interval [CI] = 11.59, 97.84) and intellectual disability/developmental delay (OR = 52.64, 95% CI = 16.27, 170.38). Patients with the variants in the regions encoding the protein stalk or microtubule-binding domain had the most prevalence of MCD (95%).ConclusionMCD, particularly pachygyria, is a common neurodevelopmental disorder in patients with DYNC1H1 mutations. Literature searches reveales that most (95%) patients who carried mutations in the protein stalk or microtubule binding domains exhibited DYNC1H1-related MCD, whereas almost two-thirds of patients (63%) who carried mutations in the tail domain did not display MCD. Patients with DYNC1H1 mutations may experience central nervous system (CNS) manifestations due to MCD.

Purpose To evaluate the effects of a novel technique using an isolated lens anterior capsule disc (LACD) to protect corneal endothelial cells in rabbit eyes during femtosecond laser-assisted cataract surgery. Methods Experimental study. 40 rabbits were divided into endothelium-protected (experimental) and control groups, with 20 rabbits in each group. In the experimental group, after femtosecond laser capsulotomy, the isolated capsule disc was lifted to the corneal endothelium by an ophthalmic viscosurgical device. The endothelium was damaged for 1 min with an ultrasonic probe. The control group underwent the same surgery, except that the disc was removed immediately after capsulorhexis. Corneal endothelioscopy was performed preoperatively and on postoperative days (PODs) 3 and 7 to observe endothelial cell counts (ECC) and endothelial cell loss rate. Central corneal thickness (CCT) was measured before and at PODs 1, 3 and 7. Results There were 3.59%±1.88% (p Conclusions The isolated LACD technique significantly reduced damage to the endothelium caused by ultrasonic energy and protects corneal endothelial cells during phacoemulsification.

Background The long-term excessive intake of exogenous cholesterol can lead to abnormally elevated blood lipid levels and induce cardiovascular and cerebrovascular diseases. However, the influence and relevance of exogenous cholesterol on plasma cholesterol components were still unclear, and the influence on intestinal lipid metabolism targets needs to be further explored. Methods In vivo, the C57BL/6 + NF group and ApoE−/− + NF group mice were fed a normal specific pathogen-free (SPF) diet; the ApoE−/− + HF group mice were fed a high-cholesterol SPF diet. The plasma and jejunum tissue homogenate were obtained for non-targeted lipid metabolomics. The lipid droplets in tissues were observed by transmission electron microscope and oil red O staining. Jejunum tissue morphology was observed by HE staining. The kits were used to detect lipid content in plasma, tissues, intestinal contents, and cells. Western blot, RT-PCR, immunohistochemistry (IHC), and immunofluorescence (IF) were used to observe the key target of lipid metabolism. In vitro, the final concentration of cholesterol was 100 μmol/L in Caco-cells. Oil red O staining, western blot, RT-PCR and immunofluorescence (IF) were used to observe the changes of lipid metabolism. Finally, the influence of liver X receptor alpha (LXRα) on intestinal cholesterol metabolism was clarified by applying the LXRα inhibitor GSK2033 and siRNA targeting LXRα. Results The aortic arch and intestinal villi of the two groups of ApoE−/− mice showed apparent lesions and lipid accumulation, and there were significant changes in a variety of lipids in the plasma and jejunum. Additionally, jejunum LXRα was markedly activated. High cholesterol can significantly activate LXRα in Caco-2 cells. After LXRα was inhibited, the protein level of ATP-binding cassette transporter A1/G5/G8 (ABCA1/G5/G8) decreased, and the quantity and volume of intracellular lipids soared. Conclusion In a high-cholesterol environment, the intestine promotes the excretion of cholesterol from the cell through the LXRα-ABCA1/G5/G8 pathway, reduces the intestinal intake of a variety of exogenous cholesterol, and reduces the risk of AS. Graphical Abstract

The structural and mechanical properties of low-dimensional nanostructured metals have been attracting tremendous interest in the fast-growing fields of nanosciences and nanotechnologies. However, it still remains a challenge today to develop strong yet ductile low-dimensional metals that can support the further development of nanodevices. Here, through the polymer-assisted assembly of gold nanocrystals, we successfully fabricated the freestanding, ultrathin gold nanomaterial. Unlike conventional bulk gold or other low-dimensional gold nanostructures (i.e., nanowires and nanosheets), these gold nanosheets are composed of highly distorted gold nanocrystals that are 3-5 nm in size, which are joined together through nanosized amorphous carbon interphases. As a result, the gold nanosheets exhibit superb strength (up to 1.2 GPa), excellent ductility (50%), and superior fracture toughness (100 J/m

Marine molluscs are seafood consumed worldwide and could cause food allergies, while investigation on their sensitizing components and cross-reactivity seems to be rare. Furthermore, allergy to mites may result in anaphylaxis in mollusc-allergic individuals owing to their cross-reactivity. The aim of the study was to identify cross-reactive allergens and investigate the cross-reactivity between different mollusc groups and mite-mollusc. The extracted mollusc and dust mite proteins were separated by SDS-PAGE, and IgE-binding components were recognized by immunoblotting with sera from patients sensitized to mollusc and mite. Cross-reactivity of different mollusc groups and mite-mollusc was assessed using ELISA and inhibition ELISA. The results of the immune detection, ELISA, and inhibition ELISA indicated that different mollusc groups and mite-mollusc showed varying degrees of cross-reactivity. The most frequently recognized cross-reactive protein was paramyosin from different mollusc groups and dust mite, while cross-reactive allergen paramyosin in the mite extract was identified and evaluated by MS and Allermatch, respectively. Inhibition ELISA studies also revealed that paramyosin played an important role in molluscan and mite-molluscan cross-reactivity. These findings contribute to a better understanding of the cross-reactivity involving mollusc species and mite-mollusc, which can be used to assist in the diagnosis and treatment of mite- and mollusc-allergic disorders.

Rationale and Objectives Standardized Uptake Value (SUV) is an important semiquantitative measurement used in the clinical and research domains to assess radiopharmaceutical concentration in tumors versus normal organs, but is susceptible to many factors beyond the tumor biological environment. So, the aim of this study is to identify the optimum internal reference among organs with physiological uptake in 68Ga-DOTATATE PET/CT (DOTA PET/CT) scans. Materials and Methods This HIPAA-compliant, IRB-approved study with waiver of consent included retrospective imaging review of 180 consecutive patients with neuroendocrine tumors presenting for DOTA PET/CT image acquisition: Ga-68 DOTATATE dose was reported as (0.054 mCi/Kg) scans between September 2018 and May 2019. Mean value of body weight normalized SUV (SUVbw) and lean body mass normalized SUV (SUL) of liver and spleen were measured. Information about the patients and scan characteristics were collected. The paired Grambsch test was used to compare variance among the measured SUVs. Spearman's rank correlation coefficient was used to assess correlation between SUVs and potential patient- and scan-specific confounding factors. Results Variance of SUL was significantly lower than variance of SUVbw in both liver and spleen (p-value Conclusion SUL is a more reproducible, less variable, and therefore more reliable quantitative measure in DOTA PET/CT scans, compared SUVbw. Among the available organs with physiological uptake, liver SUL is the optimum internal reference given the liver's larger size and uniform SUL values resulting in lower variability and better reproducibility.

Let $ \{X_n, n\geq 1\} $ be a sequence of independent and identically distributed random variables in a sublinear expectation $ (\Omega, \mathcal H, {\mathbb {\widehat{E}}}) $ with a capacity $ {\mathbb V} $ under $ {\mathbb {\widehat{E}}} $. In this paper, under some suitable conditions, I show that a general form of precise asymptotics for complete convergence holds under sublinear expectation. It can describe the relations among the boundary function, weighted function, convergence rate and limit value in studies of complete convergence. The results extend some precise asymptotics for complete convergence theorems from the traditional probability space to the sublinear expectation space. The results also generalize the known results obtained by Xu and Cheng [34].

The Yangtze River Economic Belt (YEB) and the Yellow River Ecological Economic Belt (YREB) surround the two biggest inland rivers and emit the greatest amount of carbon emissions in China. In order to implement China’s dual carbon goal, this research applies a Meta-frontier DN-DEA model, including the carbon reduction factor (CRF), to assess the emission efficiency of energy, CO2, and atmospheric pollutants for a total of 19 regions in YEB and YREB from 2011 to 2017. The synergistic climate risk control efficiency of atmospheric pollutants in the two economic belts are verified by tests for CO2 and three atmospheric pollutants emission elasticity coefficient and Kendall’s coordination coefficient. The results are as follows: First, the overall efficiencies of the two economic belts are both improved by over 30% when subject to CRF. YREB has great potential for carbon emission reduction, and the growth rate of its overall efficiency is higher than that of YEB. Second, YEB’s input term efficiency performs better affected by CRF, while YREB’s environmental pollution control input is insufficient. Third, CO2 and atmospheric pollutants emission efficiencies are significantly improved in YEB, while the environmental regulation of YREB is not obvious for the climate co-benefit of CO2 and atmospheric pollutants. Lastly, high level of climate co-benefit has revealed in YEB during 2011 to 2016, while in 2017 it plummets sharply. Conversely, YREB maintains a stable climate co-benefit.

Lung cancer (LC) remains the leading cause of cancer-related deaths worldwide, with extremely high morbidity and mortality rates. Non-small cell lung cancer (NSCLC) is the most critical type of LC. It seriously threatens the life and health of patients because of its early metastasis, late clinical symptoms, limited early screening methods, and poor treatment outcomes. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), participate in cell proliferation, metastasis, and chemoresistance. Several previous studies have proven that ncRNAs are vital regulators of tumorigenesis. Ubiquitination plays the most crucial role in protein post-translational modification (PTM). Deubiquitination and ubiquitination form a homeostasis. In summary, ubiquitination and deubiquitination play essential roles in mediating the degradation or overexpression of a range of crucial proteins in various cancers. A growing number of researchers have found that interactions between ncRNAs and ubiquitination (or deubiquitination) play a crucial role in NSCLC. This review presents several typical examples of the important effects of ncRNAs and ubiquitination (or deubiquitination) in NSCLC, aiming to provide more creative ideas for exploring the diagnosis and treatment of NSCLC.

The energy used by the heart is generated mainly by the metabolism of fatty acids and glucose. Trimetazidine (TMZ) inhibits fatty acid metabolism and is used for the treatment of heart diseases such as heart failure. 3-Bromopyruvate (3-BrPA) can suppress glucose metabolism, and it is considered a promising candidate agent for tumor therapy. Because TMZ and 3-BrPA can separately inhibit the 2 main cardiac energy sources, it is necessary to investigate the effects of 3-BrPA combined with TMZ on the heart. Forty male Wistar rats were randomly divided into 4 groups: a control group, a TMZ group, a 3-BrPA group, and a 3-BrPA + TMZ group. Weight was recorded every day, and echocardiography was performed 14 days later. Heart function, the levels of adenosine triphosphate, oxidative stress-related factors (ROS, glutathione, oxidized glutathione, malondialdehyde, superoxide dismutase and total antioxidant capacity), and apoptosis in heart tissues were assessed to evaluate the effects of 3-BrPA and TMZ on the heart. In our study, no obvious changes occurred in the 3-BrPA group or the TMZ group compared with the control group. The combination of 3-BrPA and TMZ worsened heart function, decreased adenosine triphosphate levels, and increased oxidative stress and myocardial apoptosis. In conclusion, 3-BrPA and TMZ are not recommended for concurrent use.

Kesterite Cu

Purpose To evaluate the effects of a novel technique using an isolated lens anterior capsule flap (LACF) to protect corneal endothelial cells in rabbit eyes during femtosecond laser-assisted cataract surgery. Methods Experimental study. 40 rabbits were divided into endothelium-protected (experimental) and control groups, with 20 rabbits in each group. In the experimental group, after femtosecond laser capsulotomy, the isolated capsule flap was lifted to the corneal endothelium by an ophthalmic viscosurgical device. The endothelium was damaged for 1 minute with an ultrasonic probe. The control group underwent the same surgery, except that the flap was removed immediately after capsulorhexis. Corneal endothelioscopy was performed preoperatively and on postoperative days (PODs) 3 and 7 to observe endothelial cell counts (ECC) and endothelial cell loss rate (ECL). Central corneal thickness (CCT) was measured before and at PODs 1, 3 and 7. Results There were 3.59%±1.88% (p

In this paper, we model the cellular network consisting of aerial base stations (ABSs) which follow homogeneous Poisson Point Process (PPP) and an independent collection of random users is considered. We assume that each user communicates with the closest ABS. In particular, we deal the interference signals with Laplace transform. As a result, we can obtain a tractable expression of the coverage probability. We have found that there is a maximum coverage probability which can be reached by an optimal ABS density and with low signal-to-noise ratio (SNR), the optimal ABS density gets larger when path loss exponent (PLE) increases. Simulations under high or low SNR condition have shown that the influence of PLE on coverage probability is quite different in spite of changing signal-to-interference-plus-noise ratio (SINR) threshold or ABS density.

Thiopurine dose optimization by thiopurine-S-methyltransferase (TPMT) or nudix hydrolase-15 (NUDT15) significantly reduced early leucopenia in Asia. However, it fails to avoid the late incidence (> 2 months). Although laboratory monitoring of 6-thioguanine nucleotides (6TGN) to optimize thiopurine dose was suggested in White patients the exact association between leucopenia and 6TGN was controversial in Asian patients. In the present study, we aimed to explore whether DNA-thioguanine nucleotides (DNA-TGs) in leukocytes, compared with 6TGN in erythrocytes, can be a better biomarker for late leucopenia. This was a prospective, observational study. Patients with inflammatory bowel disease (IBD) prescribed thiopurine from February 2019 to December 2019 were recruited. Thiopurine dose was optimized by NUDT15 C415T (rs116855232). DNA-TG and 6TGN levels were determined at the time of late leucopenia or 2 months after the stable dose was obtained. A total of 308 patients were included. Thiopurine induced late leucopenia (white blood cells

AIM: To evaluate the potential efficacy and mechanisms of nintedanib in corneal neovascularization (NV) in rabbit models. METHODS: Corneal NV was induced using 1 mol/L NaOH. Rabbits (n=21) were randomized to 3 groups: Group 1 were treated with 0.9% NaCl, Group 2 with Avastin (5 mg/mL), and Group 3 with nintedanib (1 mg/mL). All treatments started 1d after alkaline burns and were topically performed 3 times a day for 2wk. Photographs were taken on a slit lamp microscope on day 7 and 14. The NV area, the length of the vascularization and angiogenesis index (AI) were used to evaluate the corneal NV. On day 14, the immunohistochemical (IHC) studies of the cornea were examined. Western blot was performed to test the expression levels of vascular endothelial growth factor (VEGF), Akt, p-Akt, P38, p-P38, MMP-2 and MMP-9. RESULTS: The corneal NV area, vessel length and AI in Group 3 were significantly lower than Group 2, with both being lower than Group 1. IHC staining showed that VEGF was significantly overexpressed in the epithelium and stroma of cornea following alkaline burns. In contrast, the level of VEGF was significantly suppressed in both Group 2 and Group 3. Western blot results further confirmed that, compared with Group 1, Group 3 had significantly reduced expressions of VEGF, Akt, p-Akt, p-P38, MMP-2, and MMP-9 in corneal tissues. Trends of lower levels of MMP-2, AKT, and p-AKT in Group 3 than Group 2 were identified. CONCLUSION: Nintedanib and Avastin can effectively inhibit corneal NV, with P38 MAPK and AKT signaling pathways being possibly involved. Nintedanib seems more effective than Avastin and has the potential to be a novel therapy for preventing corneal NV.

In this paper, we consider the limit properties of the largest entries of sample covariance matrices and the sample correlation matrices. In order to make the statistics based on the largest entries of the sample covariance matrices and the sample correlation matrices more applicable in high-dimensional tests, the identically distributed assumption of population is removed. Under some moment’s assumption of the underlying distribution, we obtain that the almost surely limit and asymptotical distribution of the extreme statistics as both the dimension p and sample size n tend to infinity.

Neurofibromatosis type 2 is an autosomal dominant multiple neoplasia syndrome and is usually caused by mutations in the neurofibromin 2 (NF2) gene, which encodes a tumor suppressor and initiates the Hippo pathway. However, the mechanism by which NF2 functions in the Hippo pathway isn't fully understood. Here we identified a NF2 c.770-784del mutation from a neurofibromatosis type 2 family. MD simulations showed that this mutation significantly changed the structure of the F3 module of the NF2-FERM domain. Functional assays indicated that the NF2 c.770-784del variant formed LLPS in the cytoplasm with LATS to restrain LATS plasma membrane localization and inactivated the Hippo pathway. Besides, this deletion partly caused a skipping of exon 8 and reduced the protein level of NF2, collectively promoting proliferation and tumorigenesis of meningeal cells. We identified an unrecognized mechanism of LLPS and splicing skipping for the NF2-induced Hippo pathway, which provided new insight into the pathogenesis of neurofibromatosis type 2.

Viruses are strict intracellular parasites that rely on the proteins encoded in their genomes for the effective manipulation of the infected cell that ultimately enables a successful infection. Viral proteins have to be produced during the cell invasion and takeover in sufficient amounts and in a timely manner. Silencing suppressor proteins evolved by plant viruses can boost the production of viral proteins; although, additional mechanisms for the regulation of viral protein production likely exist. The strongest silencing suppressor encoded by the geminivirus tomato yellow leaf curl virus (TYLCV) is V2: V2 suppresses both post-transcriptional and transcriptional gene silencing (PTGS and TGS), activities that are associated with its localization in punctate cytoplasmic structures and in the nucleus, respectively. However, V2 has been previously described to largely localize in the endoplasmic reticulum (ER), although the biological relevance of this distribution remains mysterious. Here, we confirm the association of V2 to the ER in Nicotiana benthamiana and assess the silencing suppression activity-independent impact of V2 on protein accumulation. Our results indicate that V2 has no obvious influence on the localization of ER-synthesized receptor-like kinases (RLKs) or ER quality control (ERQC)/ER-associated degradation (ERAD), but dramatically enhances the accumulation of the viral C4 protein, which is co-translationally myristoylated, possibly in proximity to the ER. By using the previously described V2C84S/86S mutant, in which the silencing suppression activity is abolished, we uncouple RNA silencing from the observed effect. Therefore, this work uncovers a novel function of V2, independent of its capacity to suppress silencing, in the promotion of the accumulation of another crucial viral protein.

Ecosystem service value (ESV) is a crucial indicator for evaluating ecological environment health, and identifying its spatial driving factors will help to provide scientific decision support for ecological protection and restoration. This study takes the Liuxi River Basin in China as the research object and uses the value equivalent method to estimate regional ESV. In the process of using the Geodetector model (GDM), the study area is spatially stratified by using the local bivariate spatial correlation pattern to mine the potential drivers of ESV. The results show that: (1) From 2005 to 2018, the total value of ecosystem services in the Liuxi River Basin showed a fluctuating and increasing trend. ESV has high-value aggregation in the northeastern mountainous areas with high green space coverage and high river distance accessibility and low-value aggregation in the central and southwestern urban areas with frequent human activities. Its spatial heterogeneity and aggregation pattern are of statistical significance. (2) The spatial distribution characteristics of ESV are affected by various driving factors to varying degrees. The order of their degree of influence on ESV is per capita green area > slope > proportion of urban and rural human settlements > river distance accessibility > population. (3) Compared to the previous study, the stratification method employing the local bivariate spatial correlation pattern more fully considers the spatial autocorrelation and spatial heterogeneity. It effectively captures the spatial explanatory power of driving factors. This study can provide new ideas for capturing the driving mechanisms of ESV and insights into the sustainable development of the ecological environment in other regions with similar characteristics worldwide.

Plexiform neurofibroma(PNF) is a rare benign tumor of the peripheral nerve, belonging to a subtype of neurofibroma. PNF is common in the head, neck and trunk. It is uncommonly observed in the mesentery. We report a case of mesenteric PNF in a 64-year-old man history of neurofibromatosis type I(NF1), which caused abdomen pain. In addition, the computer tomography(CT) and endoscopic ultrasonography(EUS) manifestations of mesenteric PNF were analyzed. The imaging appearance of a mesenteric plexiform neurofibroma is that many low-density (CT) /mixed echo (EUS) soft tissue masses surrounding the superior mesenteric artery, but not surrounding the superior mesenteric vein. Our case adds to the limited literature regarding NF1 presenting with mesenteric PNF. The computer tomography and endoscopic ultrasonography may facilitate confirma diagnosis of mesenteric PNF.

The X-ray fluorescence (XRF) core scanning method is widely applied in studies of sedimentary paleoenvironments due to its convenient pretreatment, nondestructive characteristics, fast execution, continuous scanning, and high resolution. XRF core scanning for sediments is commonly used in the studies on the South China Sea. This study compares XRF-scanned intensities and measured inductively coupled plasma (ICP) elemental contents of core CS11 in the northeast South China Sea deep basin. The results show that the analyzed elements can be separated into three classes. Class I includes elements with high correlation coefficients, such as Ca, Sr, and Zr; Class II contains elements with average correlation coefficients, such as Fe, Mn, Ti, and Cu; and Class III comprises elements with low correlation coefficients, such as K, Ni, Zn, Rb, and Al. In the South China Sea deep basin, pore water, compaction, and grain size have weak effects on the elemental intensities and contents of short core sediments. Hence, for elements with high correlation coefficients, a linear relationship model can be established by the least-squares method, in which the converted XRF intensities are approximately equal to the measured ICP contents. Based on the established log-ratio calibration model, the resulting ln(K/Ca), ln(Ti/Ca), ln(Fe/Ca), and ln(Zr/Ca) values generally display the same variation trends as the measured curves. The elemental contents and ratios produced by the linear model via the least-squares method and the log-ratio calibration model are expected to provide high-resolution data support for future paleoenvironmental research on the South China Sea deep basin.

Background Hepatocellular carcinoma (HCC) is a multifactor-driven malignant tumor with rapid progression, which causes the difficulty to substantially improve the prognosis of HCC. Limited understanding of the mechanisms in HCC impedes the development of efficacious therapies. Despite Krüpple-Like factors (KLFs) were reported to be participated in HCC pathogenesis, the function of KLF14 in HCC remains largely unexplored. Methods We generated KLF14 overexpressed and silenced liver cancer cells, and nude mouse xenograft models for the in vitro and in vivo study. Luciferase reporter assay, ChIP-qPCR, Co-IP, immunofluorescence were performed for mechanism research. The expression of KLF14 in HCC samples was analyzed by quantitative RT-PCR, Western blotting, and immunohistochemistry (IHC) analysis. Results KLF14 was significantly downregulated in human HCC tissues, which was highly correlated with poor prognosis. Inhibition of KLF14 promoted liver cancer cells proliferation and overexpression of KLF14 suppressed cells growth. KLF14 exerts its anti-tumor function by inhibiting Iron-responsive element-binding protein 2 (IRP2), which then causes transferrin receptor-1(TfR1) downregulation and ferritin upregulation on the basis of IRP-IREs system. This then leading to cellular iron deficiency and HCC cells growth suppression in vitro and in vivo. Interestingly, KLF14 suppressed the transcription of IRP2 via recruiting SIRT1 to reduce the histone acetylation of the IRP2 promoter, resulting in iron depletion and cell growth suppression. More important, we found fluphenazine is an activator of KLF14, inhibiting HCC cells growth through inducing iron deficiency. Conclusion KLF14 acts as a tumor suppressor which inhibits the proliferation of HCC cells by modulating cellular iron metabolism via the repression of IRP2. We identified Fluphenazine, as an activator of KLF14, could be a potential compound for HCC therapy. Our findings therefore provide an innovative insight into the pathogenesis of HCC and a promising therapeutic target.

To investigate the expression of programmed death receptor-1 (PD-1) and inducible costimulator (ICOS) on the surface of CD8A total of 28 ITP patients treated in Tianjin Medical University General Hospital from September to December 2020 were selected, including 13 patients with newly diagnosed ITP, 15 patients with chronic ITP, and 22 healthy volunteers were recruited as control group. Flow cytometry was used to detect the expression levels of PD-1 and ICOS, and evaluate their correlation with clinical indicators.The percentage of CD8In ITP patients, the unbalanced expression of PD-1 and ICOS may interfere with the immune homeostasis of the body, which can be used as a therapeutic target for ITP patients.PD-1、ICOS在ITP患者中的表达及意义.检测原发免疫性血小板减少症（ITP）患者外周血CD8选取2020年9月至12月于天津医科大学总医院血液科就诊的ITP患者28例，包括 13例新诊断患者，15例慢性患者，同时选取健康志愿者22名作为对照组。采用流式细胞术检测外周血CD8慢性组ITP患者CD8在ITP患者中，PD-1和ICOS的不平衡表达可能干扰机体的免疫稳态，可以作为ITP患者的治疗靶标。.

The accumulation of macrophages and cholesterol crystals in atherosclerotic plaques is an important pathological feature of patients with the acute coronary syndrome (ACS). Decreased estrogen levels and estrogen receptors (ERs) lead to an increase in atherosclerosis in postmenopausal women. Whether estrogen prevents atherosclerosis by promoting macrophage cholesterol crystal metabolism via estrogen receptor alpha (ERα) is unknown. The ascending aorta of postmenopausal women decreased the fibrous cap around the plaque, increased the aggregation of CC and macrophages, and reduced the expression of ERα, and transcription factor EB (TFEB). Estrogen supplementation ameliorated atherosclerosis, and reduced CC and macrophages in the cardiac aorta and CC in primary peritoneal macrophages in OVX LDLR−/− mice. Silencing TFEB eliminated the effect of estrogen in enhancing lysosomal function, promoting CC internalization in lysosomes, and promoting reverse cholesterol transport (RCT) through APOA1, but did not affect triglyceride (TG) accumulation or RCT mediated by HDL in macrophages. Inhibition of hormone-sensitive lipase (HSL) decreased the effect of estrogen in increasing RCT through APOA1 and HDL and decreasing TG in macrophages. Inhibition of ERα weakened the effect of estrogen in reducing CC, TG, total cholesterol(TC), free cholesterol(FC), and cholesterol ester (CE) in macrophages. Silencing ERα eliminated the effect of estrogen in increasing lysosomal function and promoting the expression of TFEB, HSL, ABCA1/ABCG1 and inhibiting the expression of NLRP3 and IL-1β in macrophages. Our results provide evidence that estrogen promotes macrophage CC metabolism, which includes increasing the internalization of CC in lysosomes through rescuing the lysosomal biogenesis program by the ERα-TFEB pathway and promoting RCT via ERα-TFEB and HSL pathways to increase the cholesterol efflux.

This paper considers the Bayesian empirical likelihood (BEL) inference and order shrinkage for a class of sparse autoregressive models without assuming the distributions for the errors. By introducing a nonparametric likelihood, parameters’ point and interval estimators, as well as some asymptotic properties of the estimators are obtained. By introducing a spike-and-slab prior, the order and the non-zero autoregressive coefficients of the model can be easily and accurately determined together via the Markov Chain Monte Carlo (MCMC) techniques. Simulation studies are conducted to evaluate the proposed methods. Finally, a real data example of the US industrial production index data set is applied to show the good performances of the BEL methods.

One recent development to improve optoelectronic properties of perovskites is to use a larger cation for multication engineering. The chain-like ethylammonium (EA) [(C2H5)NH3]+ cation is more likely to form a one-dimensional perovskite structure; however, there is no remarkable evidence in this connection. Therefore, in this work, for the first time, the EA cation as an alternative cation was introduced into FAPbBr3 cubic crystals to explore the stabilities and optoelectronic properties of mixed FA x EA(1-x)PbBr3 perovskites. The results indicate that replacing FA with EA is a more effective way to realize band gap tuning and morphology transformation between the cubic shape and microwires. The tuned band gap of perovskite is due to the variation of Pb-Br-Pb angles induced by the insertion of the larger EA cation. We highlight that this work provides new physical insights into the correlation between the engineering of organic cations and the formation of perovskite microwires and the tunable band gap. This observation will help us to find new ways to grow perovskite microwires and subsequently study the optoelectronic performance of low-dimensional perovskites devices.