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OBJECTIVE This study aimed to explore the long-term course of posterior circulation changes and predictors in patients with moyamoya disease (MMD). METHODS The authors retrospectively enrolled patients who were diagnosed with MMD and underwent encephaloduroarteriosynangiosis (EDAS) surgery at the authors’ department from December 2002 to September 2011. A comparative study between short-term (6–12 months) and long-term (≥ 9 years) follow-up angiography was conducted. The progression of lesions was defined from lower to higher stages of the posterior cerebral artery (PCA). RESULTS Eighty-eight patients who received indirect EDAS were enrolled in the study. The mean age at first surgery was 28.1 ± 15.0 years. Among these 88 patients with MMD, 39 (44.3%) exhibited transient ischemic attack and 27 (30.7%) exhibited infarction, comprising 5 with occipital lobe infarction, 14 (15.9%) with hemorrhagic symptoms, and 8 (9.1%) with atypical symptoms as the initial symptoms. Heterozygous mutations occurred significantly more frequently in the cases that presented with PCA involvement. During follow-up, stage progression of PCA was observed in 21 patients (28 hemispheres). At short-term follow-up, 21/176 (11.9%) hemispheres had progression of steno-occlusive lesions in the PCA. At long-term follow-up, 7 (4.0%) hemispheres had progression of steno-occlusive lesions in the PCA. At short-term follow-up, the progression of steno-occlusive lesions in the PCA was associated with progression of the internal carotid artery. Stage progression of PCA occurred significantly more frequently in the cases with PCA involvement on preoperative angiography. Nine strokes (10.2%) occurred in 88 patients during long-term follow-up. Four patients (4.5%) presented with ischemic stroke, including 2 with occipital lobe infarctions. CONCLUSIONS Progression of PCA stenosis is common in patients with MMD, even if the PCA is normal initially. Mutations of RNF213 p.R4810K may predict PCA involvement or progression. Follow-up of the PCA in MMD patients should be conducted, and timely surgical revascularization is needed.

We compared the immunologic characteristics of mycoplasma pneumoniae-triggered Kawasaki disease (MP-KD) with Kawasaki disease (KD) not associated with mycoplasma pneumoniae (MP), with mycoplasma pneumoniae-triggered Henoch-Schönlein purpura (MP-HSP), and with healthy controls.Complement levels, cellular and humoral immunity were assessed in KD, in MP-KD, in MP-HSP, and in healthy children.Of 622 children with KD, 74 had MP-KD. Complement C3 and CD4/CD8 ratio were significantly increased in MP-KD compared to KD. C3, C4, and the ratio of CD4/CD8 in the MP-KD group were higher than those in the MP-HSP group. IgA and CD56 were lower in the MP-KD group than the MP-HSP group.Both C3 and polyclonal CD4

Shen-Shi-Jiang-Zhuo formula (SSJZF) exhibits a definite curative effect in the clinical treatment of non-alcoholic fatty liver disease (NAFLD).To explore the therapeutic effect and mechanism of SSJZF on NAFLD.Sprague Dawley rats were randomly divided into control, NAFLD, positive drug (12 mg/kg/day), SSJZF high-dose (200 mg/kg/day), SSJZF middle-dose (100 mg/kg/day), and SSJZF low-dose (50 mg/kg/day) groups. After daily intragastric administration of NAFLD rats for 8 weeks, lipid metabolism and hepatic fibrosis were evaluated by biochemical indices and histopathology. Then we uncovered the main active compounds and mechanism of SSJZF against NAFLD by integrating RNA-sequencing and network pharmacology, and PI3K/AKT pathway activity was verified by western blot.High dose SSJZF had the best inhibitory effect on hepatic lipid accumulation and fibrosis in rats with NAFLD, which significantly down-regulatedWe found for first time that SSJZF improved NAFLD in rats by activating the PI3K/Akt pathway. These findings provide scientific support for SSJZF in the clinical treatment of NAFLD and contribute to the development of new NAFLD drugs.

The ribose and phosphorus contents in Haemophilus influenzae type b (Hib) capsular polysaccharide (CPS) are two important chemical indexes for the development and quality control of Hib conjugate vaccine. A quantitative

Bacterial surface glycans perform a diverse and important set of biological roles, and have been widely used in the treatment of bacterial infectious diseases. The majority of bacterial surface glycans are decorated with diverse rare functional groups, including amido, acetamidino, carboxamido and pyruvate groups. These functional groups are thought to be important constituents for the biological activities of glycans. Chemical synthesis of glycans bearing these functional groups or their variants is essential for the investigation of structure-activity relationships by a medicinal chemistry approach. To date, a broad choice of synthetic methods is available for targeting the different rare functional groups in bacterial surface glycans. This article reviews the structures of naturally occurring rare functional groups in bacterial surface glycans, and the chemical methods used for installation of these groups.

A field study was conducted to evaluate control efficacy of ground ultra-low-volume (ULV applications (Aquareslin® against a natural population of Culex pipiens pallens in three different vegetation areas (dense, open (grassland, and sparsely vegetated in Changping county, Beijing City, China. Over 80% population decline rates (PDRs were achieved from the different vegetation levels. Significantly higher PDR was achieved in the sparsely vegetated habitat compared to the dense and open habitats. Significant higher reduction (% of parity in female mosquitoes was found in the open grassland and sparse vegetation level, compared with the dense vegetation level. Control efficacy of ground ULV spray against a natural population of Cx. pipiens pallens was impacted by the different vegetation levels.

BackgroundThe relationship between inflammatory bowel disease (IBD) and the risk of Parkinson’s Disease (PD) has been investigated in several epidemiological studies. However, the results of these studies were inconclusive and inconsistent. We evaluated the potential relationship between IBD and PD risk by a meta-analysis.MethodsSearch the electronic databases PubMed, Embase and Cochrane databases from inception to November 30, 2022, to identify relevant studies that assess the risk of PD in patients with IBD. The cohort, cross-sectional, mendelian randomization and case-control studies that reported risk estimates of PD and IBD were included in our analysis. The random-effect model and fixed-effects model were used to calculate the summary relative risks (RRs) with 95% confidence intervals (CIs).ResultsIn total, 14 studies (nine cohort studies, two cross-sectional studies, two mendelian randomization studies and one case-control study) involving more than 13.4 million individuals were analyzed in our analysis. Our results suggested that the risk of PD in IBD patients is moderately increased, with the pooled RR was 1.17 (95% CI: 1.03–1.33, P = 0.019). Omit of any single study from this analysis had little effect on the combined risk estimate. No evidence of publication bias was found. In the subgroup analysis, the combined RR was 1.04 (95% CI: 0.96, 1.12, P = 0.311) for Crohn’s disease (CD), and 1.18 (95% CI: 1.06, 1.31, P = 0.002) for ulcerative colitis (UC). In addition, a significant association was identified in patients with IBD aged ≥ 60 years (RR = 1.22; 95% CI: 1.06–1.41, P = 0.007), but not in age < 60 years (RR = 1.19; 95% CI: 0.58–2.41, P = 0.639). Meanwhile, the meta-analysis results suggested a protective role for IBD medication use against PD development, with the RR was 0.88 (95% CI: 0.74, 1.04, P = 0.126).ConclusionOur results indicated that patients with IBD had a moderately higher risk of PD compared to non-IBD individuals. Patients with IBD should be aware of the potential risks for PD, especially who were ≥ 60 years old.

Multiple genetic changes in the enteric pathogen Yersinia pseudotuberculosis have driven the emergence of Yesinia pestis, the arthropod-borne, etiological agent of plague. These include developing the capacity for biofilm-dependent blockage of the flea foregut to enable transmission by flea bite. Previously, we showed that pseudogenization of rcsA, encoding a component of the Rcs signalling pathway, is an important evolutionary step facilitating Y. pestis flea-borne transmission. Additionally, rcsD, another important gene in the Rcs system, harbours a frameshift mutation. Here, we demonstrated that this rcsD mutation resulted in production of a small protein composing the C-terminal RcsD histidine-phosphotransferase domain (designated RcsD-Hpt) and full-length RcsD. Genetic analysis revealed that the rcsD frameshift mutation followed the emergence of rcsA pseudogenization. It further altered the canonical Rcs phosphorylation signal cascade, fine-tuning biofilm production to be conducive with retention of the pgm locus in modern lineages of Y. pestis. Taken together, our findings suggest that a frameshift mutation in rcsD is an important evolutionary step that fine-tuned biofilm production to ensure perpetuation of flea-mammal plague transmission cycles.

Deep eutectic solvents (DES) pretreatment is a promising approach to decrease “biomass recalcitrance” and boost the cellulose bioconversion as well as lignin valorization. In this study, a short-time DES pretreatment strategy was performed to enhance the production of high-yield fermentable sugars and tailored lignin nanoparticles (LNPs) from abaca. The glucose yield reached 92.4% under the optimal pretreatment condition (110 °C, 30 min), which was dramatically increased in comparison with that (9.5%) of control abaca. Simultaneously, nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC) techniques indicated that the removed and regenerated DES lignin fractions displayed depolymerized structures and have relatively low molecular weight with relatively homogeneous morphology and narrow size distribution. Transmission electron microscope (TEM) analysis indicated that these lignin fractions are LNPs and the size of the optimal LNPs fraction is ranged from 30 nm to 50 nm. Moreover, all the DES lignin exhibited excellent antioxidant activities as compared to the commercial antioxidant butylated hydroxytoluene (BHT), which can be used as a promising natural antioxidant in industry. In short, this study demonstrated that the short-time DES pretreatment will improve the enzymatic digestibility and facilitate the controllable production and valorization of LNPs from abaca biomass, which will further promote the economic and overall benefits of biorefinery.

Chronic atrophic gastritis (CAG) is a pathological stage in the Correa's cascade, whereby Helicobacter pylori (H. pylori) infection is the primary cause. Cellular senescence is an inducing factor for cancer occurrence and cellular senescence is an obvious phenomenon in gastric mucosal tissues of H. pylori-positive CAG patients.In this review, we collated the information on cellular senescence and H. pylori-positive CAG.At present, only a few studies have observed the effect of cellular senescence on precancerous lesions. In combination with the latest research, this review has collated the information on cellular senescence and H. pylori-positive CAG from four aspects- telomere shortening, DNA methylation, increased reacive oxygen species (ROS) production, and failure of autophagy.This is expected to be helpful for exploring the relevant mechanisms underlying inflammatory cancerous transformation and formulating appropriate treatment strategies.

In this paper, a CMOS relaxation oscillator with trimming and temperature compensation is presented for the on-chip multi-sensor systems which need MHz level frequency source. The proposed scheme uses a single current branch to charge the capacitor to generate the oscillation with voltage average feedback (VAF) circuit. Binary-weight current trimming array is adopted to reduce the frequency variation caused by the process variation under different process corners. A compensation calibration resistor array with Kelvin connection is utilized to improve the frequency variation with temperature. With the help of VAF, the frequency spread caused by the comparator delay is suppressed. This relaxation oscillator with a typical frequency of 13.4[Formula: see text]MHz is implemented in a standard 180[Formula: see text]nm CMOS process. Simulation results show that it achieves a frequency temperature coefficient of 28.3[Formula: see text]ppm/∘C from [Formula: see text]C to 125∘C and a 0.074%/0.1[Formula: see text]V frequency variation when supply voltage changes from 2.9 to 3.7[Formula: see text]V.

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM. Improving the Ability of Diagnosis and Treatment of Difficult Diseases

Chronic visceral pain (CVP) is one of the common symptoms of many diseases triggered by underlying diseases of the internal organs of the human body. Its causes include vascular mechanisms, mechanical factors, persistent inflammation, and unexplained functional mechanisms. Although the pathogenesis is unclear, more and more research has begun to shift from the neuronal aspect to the glial cells in recent years. Some data highlight that the spinal glial cells, particularly the microglia and astrocytes, play an essential role in CVP. Based on this, we highlight the mechanisms of microglia and astrocytes in CVP concerning the release of cytokines, chemokines, and neuroactive substances and alterations in intracellular signaling pathways during the process. Finally, because CVP is widespread in various diseases, we present future perspectives targeting microglia and astrocytes for treatment.

Privacy preserving methods supporting for data aggregating have attracted the attention of researchers in multidisciplinary fields. Among the advanced methods, differential privacy (DP) has become an influential privacy mechanism owing to its rigorous privacy guarantee and high data utility. But DP has no limitation on the bound of noise, leading to a low-level utility. Recently, researchers investigate how to preserving rigorous privacy guarantee while limiting the relative error to a fixed bound. However, these schemes destroy the statistical properties, including the mean, variance and MSE, which are the foundational elements for data aggregating and analyzing. In this paper, we explore the optimal privacy preserving solution, including novel definitions and implementing mechanisms, to maintain the statistical properties while satisfying DP with a fixed relative error bound. Experimental evaluation demonstrates that our mechanism outperforms current schemes in terms of security and utility for large quantities of queries.

Resection of high-grade glioma with sodium fluorescein can improve the resection rate of the glioma and improve survival. However, it is unclear whether the yellow fluorescence boundary of the high-grade glioma is consistent with the actual boundary of the tumor. This study explores the yellow fluorescence boundary and the actual tumor boundary in high-grade glioma surgery.This is a retrospective analysis of 10 patients with high-grade gliomas who underwent tumor visualization with sodium fluorescein. After staining of the tumor, random selections of both developed and non-developed yellow fluorescent border tissue at the fluorescence chromogenic boundary were made, followed by pathological examination. Claudin-5, an important component of the tight connections between vascular endothelial cells, was assessed by immunohistochemistry and qRT-PCR in the tumor and surrounding tissues in order to determine the tumor cell content of the tissue, blood-brain barrier damage, and vascular proliferation. The yellow fluorescence boundary was compared with the actual tumor boundary and the results analyzed.Tumor cells were still detected outside the yellow fluorescence boundary during high-grade glioma surgery (There is a difference between the yellow fluorescence boundary and the actual boundary of the tumor in high-grade glioma, and there are glioma cell infiltrations in the brain tissue of the undeveloped yellow fluorescent border. To ensure patient recovery and function, it is recommended that tumor resection be expanded based on yellow fluorescence visualization. Claudin-5 is overall up-regulated in high-grade gliomas, but some Claudin-5 expression is disconnected. This Claudin-5 expression pattern may be related to the development of yellow fluorescence.

To investigate the therapeutic effect of rabeprazole and rebamipide on patient age over 60 with dual antiplatelet therapy (DAPT)–related upper gastrointestinal hemorrhage following percutaneous coronary intervention (PCI). A total of 360 patients age over 60 undergoing PCI were recruited for antiplatelet therapy involving a combined treatment of aspirin (100 mg/d) and clopidogrel (75 mg/d). The enrolled patients were divided into 4 groups: the control group, the rabeprazole group, the rebamipide group, and the rabeprazole + rebamipide group. The incidence and severity of any upper gastrointestinal hemorrhage and the incidence of major adverse cardiac events (MACEs) were observed 6 months after the operation. The incidence of upper gastrointestinal hemorrhage in the 4 groups was 11.1%, 3.3%, 8.9%, and 1.1%, respectively, and the differences were statistically significant ( P 0.05). For patients age over 60 receiving DAPT following PCI in our study population, treatment with rabeprazole or a combination of rabeprazole and rebamipide could reduce the risk of upper gastrointestinal hemorrhage, as well as reduce its severity.

Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and poor prognoses around the world. Within-cell polarity is crucial to cell development and function maintenance, and some studies have found that it is closely related to cancer initiation, metastasis, and prognosis. The aim of our research was to find polarity-related biomarkers which improve the treatment and prognosis of HCC. For the knowledge-driven analysis, 189 polarity-related genes (PRGs) were retrieved and curated manually from the molecular signatures database and reviews. Meanwhile, in the data-driven part, genomic datasets and clinical records of HCC was obtained from the cancer genome atlas database. The potential candidates were considered in the respect to differential expression, mutation rate, and prognostic value. Sixty-one PRGs that passed the knowledge and data-driven screening were applied for function analysis and mechanism deduction. Elastic net model combing least absolute shrinkage and selection operator and ridge regression analysis refined the input into a 12-PRG risk model, and its pharmaceutical potency was evaluated. These findings demonstrated that the integration of multi-omics of PRGs can help us in untangling the liver cancer pathogenesis as well as illustrate the underlying mechanisms and therapeutic targets.

Phagocyte oxidase plays an essential role in the first line of host defense against pathogens. It oxidizes intracellular NADPH to reduce extracellular oxygen to produce superoxide anions that participate in pathogen killing. The resting phagocyte oxidase is a heterodimeric complex formed by two transmembrane proteins NOX2 and p22. Despite the physiological importance of this complex, its structure remains elusive. Here, we reported the cryo-EM structure of the functional human NOX2-p22 complex in nanodisc in the resting state. NOX2 shows a canonical 6-TM architecture of NOX and p22 has four transmembrane helices. M3, M4, and M5 of NOX2, and M1 and M4 helices of p22 are involved in the heterodimer formation. Dehydrogenase (DH) domain of NOX2 in the resting state is not optimally docked onto the transmembrane domain, leading to inefficient electron transfer and NADPH binding. Structural analysis suggests that the cytosolic factors might activate the NOX2-p22 complex by stabilizing the DH in a productive docked conformation.

Oral antiseizure medications are the preferred option for the clinical treatment of epilepsy. Therapeutic drug monitoring has become an important means of achieving individualized treatment of epilepsy. A sensitive, accurate and rapid LC-ESI-MS/MS method was developed and validated for the simultaneous determination of 15 antiseizure medications in human plasma (carbamazepine, gabapentin, pregabalin, phenytoin, zonisamide, oxcarbazepine, tiagabine, lamotrigine, topiramate, phenobarbital, lacosamide, primidone, 10,11-Dihydro-10-hydroxy carbamazepine, ethosuximide, and levetiracetam). The sample preparation procedure was an one-step protein precipitation with methanol. Mass detection was performed in ionization polarity switching mode (positive-negative-positive) using multiple reaction monitoring mode. A "boot-shaped" gradient elution program was applied to separate and concentrate those target analytes, resulting in symmetrical peak shapes within 10 min, without endogenous interference. The method showed great linearity over the concentration ranges with acceptable correlation coefficients (0.9966-0.9996). The precision and accuracy values for intra- and inter-assays were within ±15%. Consequently, the method was successfully implemented on pediatric patients undergoing mono- or polytherapy for epilepsy and provided timely concentration results to ordering clinicians.

Investigating the efficacy and safety of noninvasive cerebellar stimulation in improving the balance and walking function of patients with stroke.We searched 7 databases for randomized controlled trials (RCTs) related to noninvasive cerebellar stimulation in the treatment of stroke. The Berg Balance Scale (BBS), 6-minute walk test (6MWT), and Barthel Index (BI) were used as the outcome indexes to evaluate balance, walking and activities of daily living (ADL). The quality of the research was evaluated using the Cochrane Risk of Bias Tool. A meta-analysis was performed to evaluate the difference between the noninvasive cerebellar stimulation and control groups. Heterogeneity tests were performed to assess differences in treatment effects across noninvasive cerebellar stimulation modalities. A sensitivity analysis was performed to evaluate the robustness of the results.Seven studies were included, and 5 articles (71.43%) were rated as having a low risk of bias. Among the primary outcome indicators, 4 of the 7 articles were combined into the fixed effect model (I2 = 38%, P = .18). Compared with the control group, noninvasive cerebellar stimulation improved the BBS score, and the difference was statistically significant (mean difference [MD]: 3.00, 95% confidence interval [CI]: 1.10-5.40, P = .03); the sensitivity analysis showed that the statistical model was still stable after sequentially eliminating each article. Compared with the control group, noninvasive cerebellar stimulation improved the 6MWT results of patients with stroke (MD: 25.29, 95% CI: 4.86-45.73, P = .02). However, noninvasive cerebellar stimulation did not improve the BI (MD: 15.61, 95% CI: -7.91 to 39.13, P = .19). No safety problems or adverse reactions to noninvasive cerebellar stimulation were observed.Noninvasive cerebellar stimulation improves balance and walking function of patients with stroke, but its effect on ADL is uncertain. Due to the methodological weaknesses in the included trials, more RCTs are needed to confirm our conclusions.

Ring-opening transformations of donor-acceptor (D-A) cyclopropanes enable the rapid assembly of complex molecules. However, the enantioselective formation of chiral quaternary stereocenters using substrates bearing two different acceptors remains a challenge. Herein, we describe the first palladium-catalyzed highly diastereo- and enantioselective (3+2) cycloaddition of vinyl cyclopropanes bearing two different electron-withdrawing groups, a subset of D-A cyclopropanes. The key to the success of this reaction is the remote stereoinduction through hydrogen bond from chiral ligands, which thereby addressed the aforementioned challenge. A variety of chiral five-membered heterocycles were produced in good yields and with high stereoselectivity (up to 99 % yields, 99 : 1 er and19 : 1 dr). In-depth mechanistic investigations, including control experiments and theoretical calculations, revealed the origin of the stereoselectivity and the importance of H-bonding in stereocontrol.

Microneedles (MNs) have been developed for various applications such as drug delivery, cosmetics, diagnosis, and biosensing. To meet the requirements of MNs used in these areas, numerous materials have been used for the fabrication of MNs. However, MNs will be exposed to skin tissues after piercing the stratum corneum barrier. Thus, it is necessary to ensure that the matrix materials of MNs have the characteristics of low toxicity, good biocompatibility, biodegradability, and sufficient mechanical properties for clinical application. In this review, the matrix materials currently used for preparing MNs are summarized and reviewed in terms of these factors. In addition, MN products used on the market and their applications are summarized in the end. This work may provide some basic information to researchers in the selection of MN matrix materials and in developing new materials.

Polystyrene nanoplastics (PS-NPs) are typical accumulated nanoplastics in the marine environment and organisms, and have strong potential risks to marine ecological environment and human health. MiRNAs could respond to and participate in the response process of environmental stressors. However, the response of miRNAs to nanoplastics has not been fully explored. In this study, miRNA responses of digestive glands in mussels Mytilus galloprovincialis treated by 200 nm PS-NPs (20, 200, 2000 μg/L) for 7 days were characterized by BGISEQ-500 deep sequencing and bioinformatics analysis, along with histopathological quantification with planimetric parameters on hematoxylin and eosin (HE) staining. Results showed that one novel miRNA (novel_mir63) and seven known miRNAs (miR-34_2, miR-34_5, miR-281_8, let-7-5p_6, miR-10, miR-124, miR-29b-3p) were significantly (adjusted P-value0.05) differentially expressed after PS-NPs treatments, and most of them were down-regulated expect for novel_mir63 and miR-34_2. Function analysis of target genes corresponding to these differentially expressed miRNAs indicated that PS-NPs disturbed the process related to metabolism, aging, cardiac function, neural excitation, and repairment. Among them, acetyl-CoA C-acetyltransferase and purine metabolism pathway played vital connection roles. Meanwhile, significantly morphology changes of digestive tubes obtained from HE stained sections also implied severely disrupted metabolic capability in digestive glands, reflected by significantly increased mean diverticular radius (MDR) and mean luminal radius (MLR) values and the ratio of MLR to mean epithelial thickness (MET), and significantly decreased MET value and MET/MDR. Overall, these findings have revealed new characterization of miRNAs and their target genes in mussel M. galloprovincialis under PS-NPs stress, and provide important clues to further elucidate the toxicity mechanisms of PS-NPs.

Tuberculosis, caused by mycobacteria, continues to pose a substantial public health threat. Mycobacteria typically use cholesterol from the membranes of host macrophages as a carbon and energy source. Most genes that control cholesterol degradation are regulated by KstR, which is highly conserved in Mycobacterium tuberculosis and Mycobacterium smegmatis. Through bioinformatic analysis, we found a typical global nitrogen regulator (GlnR)-binding motif (CCGAC-AACAGT-GACAC) in the promoter region of kstR of M. smegmatis, and we determined its binding activity in vitro using electrophoretic mobility shift assays. Using RT-qPCR, we found that nine genes involved in side-chain or sterol-ring oxidation were upregulated in a ΔglnR M. smegmatis strain compared to the WT strain and glnR-complemented strains under nitrogen limitation. ATP assays in macrophages revealed that coordinated GlnR-KstR regulation significantly reduced the viability of M. smegmatis in macrophages. Thus, we found that various genes involved in cholesterol catabolism are regualted by GlnR via KstR in response to environmental nitrogen, and that they further affect the invasive ability of M. smegmatis. These findings revealed a novel regulatory mechanism of cholesterol catabolism, which may be useful in the development of new strategies for controlling tuberculosis. This article is protected by copyright. All rights reserved.

Under the Paris Agreement, India has pledged that 40 percent of its electricity generating capacity will come from non-fossil-fuel sources by the year 2030; however, this pledge does not limit total coal-fired generating capacity. As of 2019, planned increases in coal-fired capacity totaled 95 gigawatts--46 percent of installed coal-fired capacity in 2018. In this paper, we estimate the carbon dioxide benefits and health co-benefits of not building these plants. We also estimate the mortality impacts of the 2018 stock of coal-fired power plants and use it to calculate the tax on electricity generation from coal that would internalize these damages.

Background Gastrointestinal cytomegalovirus (CMV) disease occurs commonly in immunocompromised/immunodeficient patients with advanced human immunodeficiency virus infection, neoplasm, solid organ transplantation, hematopoietic stem cell transplantation, or treatment with immunosuppressants, but is rarely reported in association with measles infection. Case summary We describe a case of extensive gastrointestinal CMV disease secondary to measles infection in a 9-mo-old boy who presented with persistent fever and bloody diarrhea. His condition was improved after ganciclovir treatment. Serological analysis of CMV showed negative immunoglobulin (Ig) M and positive IgG. Blood CMV-DNA was 9.26 × 103 copies/mL. The diagnosis of gastrointestinal CMV disease was confirmed by histopathological findings of intranuclear and intracytoplasmic inclusions and Owl's eye inclusion. This case highlights the differential diagnosis and histopathological characteristics of gastrointestinal CMV infection and laboratory tests. Conclusion Extensive gastrointestinal CMV lesions can be induced by the immune suppression secondary to measles infection. Rational, fast, and effective laboratory examinations are essential for suspected patients.

Mitochondrial uncoupling protein 2 (UCP2) deficiency exacerbates brain damage following cerebral ischemia/reperfusion (I/R). The Nod-like receptor protein-3 (NLRP3) inflammasome also plays a vital role in cerebral I/R damage. However, the effect of UCP2 on NLRP3 inflammasome-mediated hyperglycemia and I/R damage is not clear. In the present study, UCP2-knockout (UCP2−/−) and wild-type (WT) mice were used to establish a model of middle cerebral artery occlusion (MCAO) and reperfusion under normo- and hyperglycemic conditions. HT22 cells were established as a model of oxygen–glucose deprivation and reoxygenation (OGD/R) with high glucose to mimic hyperglycemia and I/R in vitro. HT22 cells were treated with/without different concentrations of the UCP2-specific inhibitor genipin for different periods of time. The results showed that UCP2 deficiency significantly increased histopathological changes and apoptosis after cerebral I/R damage in hyperglycemic mice. Moreover, UCP2 deficiency enhanced NLRP3 inflammasome activation in neurons when cerebral I/R damage was exacerbated by hyperglycemia. Furthermore, UCP2 deficiency enhanced NLRP3 inflammasome activation and reactive oxygen species (ROS) production in HT22 cells under OGD/R and high-glucose conditions. UCP2 deficiency aggravated hyperglycemia-induced exacerbation of cerebral I/R damage. UCP2 deficiency also enhanced NLRP3 inflammasome activation and ROS production in neurons in vitro and in vivo. These findings suggest that UCP2 deficiency enhances NLRP3 inflammasome activation following hyperglycemia-induced exacerbation of cerebral I/R damage in vitro and in vivo. UCP2 may be a potential therapeutic target for hyperglycemia-induced exacerbation of cerebral I/R damage.

BACKGROUND Most small intestinal lipomas are treated surgically, and some require repeated surgeries for multiple lipomas. However, application of endoscopic submucosal dissection (ESD) technology in the deep small intestine is rarely reported owing to the special anatomical structure of the small intestine, medical equipment limitations, and the lack of relevant experience among endoscopists. CASE SUMMARY Two patients with small intestinal lipomas treated at the Air Force Medical Center from November 2015 to September 2019 were selected to undergo balloon-assisted ESD to treat the lipomas and explore the technical feasibility and safety of ESD for treating small intestinal lipomas. The two patients successfully underwent balloon-assisted ESD to treat four small intestinal lipomas, with a complete resection rate of 100% (4/4), without intraoperative or postoperative bleeding, perforation, or other complications. After 3-6 mo of postoperative follow-up, the clinical symptoms caused by the lipomas were significantly relieved or disappeared after treatment. CONCLUSION Balloon-assisted ESD is a safe and reliable new method for treating deep intestinal lipomas and shows good clinical feasibility.

Primary Epstein–Barr virus (EBV)-associated poorly differentiated nasopharyngeal adenocarcinoma (NAC) is an extremely rare tumor. In this study, we report a case of EBV-associated poorly differentiated NAC in a 35-year-old man who presented with a clogging sensation in the right ear for 1 month. The first biopsy of the nasopharynx was suggestive of nonkeratinizing carcinoma with weak positivity for CK5/6 and p63. Based on magnetic resonance imaging of the nasopharynx and neck, chest computed tomography, abdominal ultrasound, and whole-body bone scan, the patient was diagnosed with T3N2M0 disease. After the patient received neoadjuvant chemotherapy, concurrent chemoradiotherapy, and adjuvant chemotherapy, partial remission was observed. However, reassessment after 7 months of treatment revealed tumor enlargement. Transnasal endoscopic resection was performed to remove the nasopharyngeal tumor. The postoperative immunostaining results were as follows: CK5/6 (−), p63 (−), MOC31 (+), and Ber-EP4 (+). Meanwhile, EBV-encoded RNA in situ hybridization was positive. A final diagnosis of EBV-associated poorly differentiated NAC was made. Then, the patient received chemotherapy and irradiation but died several months later because of disease progression. Our patient presented with highly malignant EBV-associated poorly differentiated NAC insensitive to chemoradiotherapy with a short survival time of 27 months.

Local ischemia in the cerebra leads to vascular injury and necrosis. Ferroptosis is involved in the pathophysiological process of many diseases and widely exists when ischemia-reperfusion injury occurs in many organs. The aim of this study was to evaluate the effect of Butylphthalide (NBP) on middle cerebral artery occlusion (MCAO) rats model-caused neuron injury. Sprague Dawley Rats were randomly allocated to receive sham and MCAO operation. NBP low-dose (40 mg/kg b.w), and high-dose (80 mg/kg b.w) were administrated in MACO rats. Results showed NBP improves infarct volume, attenuates neuronal apoptosis in the brain tissue of MCAO rats. The tumor necrosis factor (TNF-α), IL-6, and malondialdehyde (MDA) levels decreased after NBP administration, while the activity of superoxide dismutase (SOD) and the ratio of GSH/GSSG in MACO rats increased. MACO caused non-heme iron accumulation in the brain tissue and Perl’s staining confirmed NBP attenuates ferroptosis in MACO rats. The protein expressions of SCL7A11 and glutathione peroxidase 4 (GPX4) decreased following MCAO, and NBP treatment subsequently increased the expression of SCL7A11 and GPX4. In vitro analysis in cortical neuron cells indicated that the GPX4 inhibitor reverses the inhibition of ferroptosis by NBP, which suggested that the SCL7A11/GPX4 pathway majorly contributed to the NBP ferroptosis protection effect.

Background: Repeated administration has resulted in serious drug resistance in gastric cancer (GC). Previous studies showed that miR-129-5p had a low expression in GC, and homeobox gene C10 (HOXC10...

Breast cancer is the most common type of cancer amongst women worldwide, and numerous microRNAs (miRNAs/miRs) are involved in the initiation and progression of breast cancer. The aim of the present study was to identify hub miRNAs and determine the underlying mechanisms regulated by these miRNAs in breast cancer. Breast invasive carcinoma transcriptome data (including mRNAs and miRNAs), and clinical data were acquired from The Cancer Genome Atlas database. Differential gene expression analysis, co‑expression network analysis, gene set enrichment analysis (GSEA) and prognosis analysis were used to screen the hub miRNAs and explore their functions. Functional experiments were used to determine the underlying mechanisms of the hub miRNAs in breast cancer cells. The results revealed that low miR150 expression predicted a more advanced disease stage, and was associated with a less favorable prognosis. Through the combined use of five miRNA‑target gene prediction tools, 31 potential miR150 target genes were identified. GSEA revealed that low miR150 expression was associated with the upregulation of several cancer‑associated signaling pathways, and the downregulation of several tumor suppressor genes. Furthermore, miR150 independently affected overall survival in patients, and interacted with its target genes to indirectly affect overall and disease‑free survival. Functional experiments demonstrated that miR150 positively regulated B and T lymphocyte attenuator (BTLA), and the downregulation of miR150 and BTLA combined promoted cell migration. In conclusion, the present study revealed that low miR150 expression was associated with less favorable clinical features, upregulation of several carcinogenic signaling pathways, and poor patient survival. Additionally, a miR150‑BTLA axis was suggested to regulate cell viability and migration.

Objectives: This study aims to present the characteristics of the undergraduate dental curriculum system using network modelling and visualisation analysis based on complex network theory, thus providing a theoretical foundation for the course development and curriculum reform. Methods: The correlation coefficient was used to quantify the intensity of the correlation between courses, and a visualisation complex network of the dental curriculum was built to explore the curriculum pattern from a dynamic perspective. Further, the statistical measurements of curriculum network were adopted to express the most relevant topological features. Subsequently, the minimum spanning tree and parallel coordinates plot were drawn to explore the curriculum community structure, quantify the key courses, and present different courses in time and space relationships. Results: The correlation analysis results show that the courses are closely related to each other. The main courses focus on pathology, pathophysiology, oral anatomy and physiology, closely connecting almost all medicine-related courses. The whole course network has an average degree value of 41.53, and a clustering coefficient of 0.78, indicating an obvious small-world characteristic. From the perspective of curriculum attributes, the number of public and theoretical courses was more than that of skills and practical courses. Moreover, the academic performance of skills and practical courses was lower than that of public and theoretical courses. Conclusion: The undergraduate dental courses have a progressive structure from basic professional knowledge to professional skills, which is reasonable for the dental education in China. However, some efforts towards curriculum reform based on this study are needed.

Recent advances in Landsat archive data processing and characterization enhanced our capacity to map land cover and land use globally with higher precision, temporal frequency, and thematic detail. Here, we present the first results from a project aimed at annual multidecadal land monitoring providing critical information for tracking global progress towards sustainable development. The global 30-m spatial resolution dataset quantifies changes in forest extent and height, cropland, built-up lands, surface water, and perennial snow and ice extent from the year 2000 to 2020. Landsat Analysis Ready Data served as an input for land cover and use mapping. Each thematic product was independently derived using locally and regionally calibrated machine learning tools. Thematic maps validation using a statistical sample of reference data confirmed their high accuracy (user’s and producer’s accuracies above 85% for all land cover and land use themes, except for built-up lands). Our results revealed dramatic changes in global land cover and land use over the past 20 years. The bitemporal dataset is publicly available and serves as a first input for the global land monitoring system.

IKZF1/IKAROS is a key transcription factor of lymphocyte development expressed throughout hematopoiesis. Heterozygous germline IKZF1 haploinsufficient ( IKZF1 HI ) and dominant-negative ( IKZF1 DN ) variants in humans cause B cell immune deficiency and combined immunodeficiency. Here, we identified previously unidentified heterozygous IKZF1 variants (R183C/H) located in the DNA binding domain in eight individuals with inflammatory, autoimmune, allergic symptoms, and abnormal plasma cell (PC) proliferation. Leukocytes of patients exhibited specific defects including impaired IL-2 production by T cells, T helper (T H ) skewing toward T H 2, low numbers of regulatory T cells (T reg ), eosinophilia, and abnormal PC proliferation. In contrast to IKZF1 HI and IKZF1 DN , IKZF1 R183H/C proteins showed increased DNA binding associated with increased gene expression of T H 2 and PC differentiation, thus demonstrating that IKZF1 R183H/C behave as gain-of-function (GOF) alleles. In vitro treatment with lenalidomide, known to degrade IKZF1, corrected T H 2 and PC abnormalities caused by IKZF1 R183H/C . These data extend the spectrum of pathological mechanisms associated with IKZF1 deficiencies and highlight the role of IKZF1 in late lymphoid differentiation stages.

Background Endoscopic papillectomy (EP) is rapidly replacing traditional surgical resection and is a less invasive procedure for the treatment of duodenal papillary tumors in selected patients. With the expansion of indications, concerns regarding EP include not only technical difficulties, but also the risk of complications, especially delayed duodenal perforation. Delayed perforation after EP is a rare but fatal complication. Exposure of the artificial ulcer to bile and pancreatic juice is considered to be one of the causes of delayed perforation after EP. Draining bile and pancreatic juice away from the wound may help to prevent delayed perforation. Aim To evaluate the feasibility and safety of placing overlength biliary and pancreatic stents after EP. Methods This is a single-center, retrospective study. Five patients with exposure or injury of the muscularis propria after EP were included. A 7-Fr overlength biliary stent and a 7-Fr overlength pancreatic stent, modified by an endoscopic nasobiliary drainage tube, were placed in the common bile duct and pancreatic duct, respectively, and the bile and pancreatic juice were drained to the proximal jejunum. Results EP and overlength stents placement were technically feasible in all five patients (63 ± 12 years), with an average operative time of 63.0 ± 5.6 min. Of the five lesions (median size 20 mm, range 15-35 mm), four achieved en bloc excision and curative resection. The final histopathological diagnoses of the endoscopic specimen were one tubular adenoma with high-grade dysplasia (HGD), one tubulovillous adenoma with low-grade dysplasia, one hamartomatous polyp with HGD, one poorly differentiated adenocarcinoma and one atypical juvenile polyposis with tubulovillous adenoma, HGD and field cancerization invading the muscularis mucosae and submucosa. There were no stent-related complications, but one papillectomy-related complication (mild acute pancreatitis) occurred without any episodes of bleeding, perforation, cholangitis or late-onset duct stenosis. Conclusion For patients with exposure or injury of the muscularis propria after EP, the placement of overlength biliary and pancreatic stents is a feasible and useful technique to prevent delayed perforation.

20–40% of lung cancer patients develop bone metastasis (BM) with significantly decreased overall survival. Currently, BM is mainly diagnosed by computerized tomography (CT) scan or magnetic resonance imaging (MRI) when symptom develops. Novel biomarkers with higher prediction value of BM are needed. Plasma-derived exosomal microRNAs had been isolated and sequenced of total 30 non-small cell lung cancer (NSCLC) patients including 16 with bone metastasis and 14 without bone metastasis. Hierarchical clustering based on the total miRNA profile can clearly separate cancer patients and healthy individuals (H), but not patients with (BM +) or without (BM−) BM. Weight Co-expression network of miRNAs (WGCNA) analyses identified three consensus clusters (A, B, C) of highly correlated miRNAs, among which cluster B (144 miRNAs) showed significantly differential expression in lung cancer patients, especially in BM + group. Pathway analysis of cluster B miRNAs revealed enrichment in metabolic pathways that may involve in preconditioning of the metastatic niche. Three differentially expressed miRNAs between BM + and BM− patients within cluster B were identified as miR-574-5p, a suppressor of Wnt/β-catenin pathway, was down-regulated, while miR-328-3p and miR-423-3p, two activators of the same pathway, were up-regulated in BM + patients. Cluster A miRNAs (n = 49) also showed trend of upregulation in BM + patients. Interestingly, pathway analysis indicated that 43 of them are associated with chromosome14, which has been suggested to promote epithelial-mesenchymal transition (EMT) and bone metastasis. Electronic supplementary material The online version of this article (10.1007/s10585-020-10062-y) contains supplementary material, which is available to authorized users.

To evaluate if valproic acid (VPA) therapy is associated with vitamin D deficiency among infants and toddlers with epilepsy, a cross-sectional clinical study was conducted in 25 children with epilepsy taking VPA. Blood levels of calcium, phosphorus, alkaline phosphatase, and 25-hydroxy vitamin D [25(OH)D] and plasma VPA level were measured at 1- to 3-month intervals. At the initial and final measurements, vitamin D deficiency or insufficiency was recognized in 8 (32%) and 12 (42%), respectively. In girls, a decreasing trend in serum 25(OH)D levels (P

Pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection emerged in Wuhan City, Hubei Province, China in December 2019. By Feb. 11, 2020, the World Health Organization (WHO) officially named the disease resulting from infection with SARS-CoV-2 as coronavirus disease 2019 (COVID-19). COVID-19 represents a spectrum of clinical manifestations that typically include fever, dry cough, and fatigue, often with pulmonary involvement. SARS-CoV-2 is highly contagious and most individuals within the population at large are susceptible to infection. Wild animal hosts and infected patients are currently the main sources of disease which is transmitted via respiratory droplets and direct contact. Since the outbreak, the Chinese government and scientific community have acted rapidly to identify the causative agent and promptly shared the viral gene sequence, and have carried out measures to contain the epidemic. Meanwhile, recent research has revealed critical aspects of SARS-CoV-2 biology and disease pathogenesis; other studies have focused on epidemiology, clinical features, diagnosis, management, as well as drug and vaccine development. This review aims to summarize the latest research findings and to provide expert consensus. We will also share ongoing efforts and experience in China, which may provide insight on how to contain the epidemic and improve our understanding of this emerging infectious disease, together with updated guidance for prevention, control, and critical management of this pandemic.

The pneumonia caused by the coronavirus disease-2019 (COVID-19) outbreak in Wuhan, China constitutes a public health emergency of international concern. The gastrointestinal symptoms of vomiting, diarrhea and abdominal pain and the detection of COVID-19 nucleic acid from fecal specimens in a small number of patients suggest the possibility of transmission via the gastrointestinal tract. People of all ages are vulnerable to this virus, including children. Digestive endoscopy is an invasive procedure during which children cannot wear masks; therefore, they have higher risks of exposure to COVID-19, and the digestive endoscopy center is a relatively high-risk area for COVID-19 infection. Based on these factors and in combination with related policies and regulations, a prevention and control program for the COVID-19 pneumonia in a children's digestive endoscopy center was established to prevent the COVID-19 nosocomial infection.

The basic helix-loop-helix (bHLH) transcription factor 4 (TCF4) had been identified as a susceptibility gene associated with schizophrenia (SCZ) by GWAS, but inconsistent results have been found in other studies. To validate these findings and to reveal the effects of different inheritance models, rs2958182, rs1261085, rs8766, and rs12966547 of the TCF4 gene were genotyped in the Northwest Han Chinese population (448 cases and 628 controls) via a multiplex polymerase chain reaction SNPscan assay. Single SNP, genotype, and association analyses with three different models were performed. We observed genotype and allele distributions of four SNPs that showed nonsignificant associations in the Northwest Han Chinese population. However, published datasets (51,892 cases and 68,498 controls) were collected and combined with our experimental results to ascertain the association of the TCF4 gene SNPs and SCZ, which demonstrated that rs2958182 (P=0.003) was a significant signal based on a systematic meta-analysis. To clarify the biological role of rs2958182, it is important to improve the understanding of the pathophysiology of SCZ.