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Inorganic ion-exchange materials show potential application for toxic radioactive ions due to their remarkable high efficiency and selectivity features. Here, two type of carbon-supported titanate (C@TNFs and C@TNFs(H)) nanofibers have been synthesized by a cost-effective in suit growth method. The resulting C@TNFs and C@TNFs(H) microspheres present uniform flower-like morphology and large surface area. The interlayer Na+ in the titanate shell provides docking sites for ion-exchange of radioactive ions (U(VI), Ba(II), and Sr(II)). Interestingly, the exceeding theoretical cation-exchange capacities (CECs) are achieved on C@TNFs for U(VI) ∼4.76 meq g−1 and Ba(II) ∼2.65 meq g−1 and C@TNFs(H) for Ba(II) ∼2.53 meq g−1 and Sr(II) ∼2.24 meq g−1, respectively. The impressive adsorption performance is mainly attributed to the synergistic effects of ion-exchange and surface complexation. More significantly, C@TNFs and C@TNFs(H) maintain high distribution coefficients (K d U) of >104 mL g−1 over a wider pH range (pH = 3.5–9.0) and high adsorption rate with short equilibrium time within 50 min. Competitive ion-exchange investigation shows a selectivity order of U(VI) > Ba(II) > Sr(II) at individual 10 ppm concentration, pH = 6.0 and T = 298 K. The related spectroscopic studies reveal the intercalative mechanism of radionuclides in the deformed titanate structure, as a result of target ions firmly trapped in the interlayer of C@TNFs and C@TNFs(H). These advantageous features allow the C@TNFs and C@TNFs(H) to be promising candidates for the remediation of toxic radioactive ions polluted water.

This paper proposes a magnetic rheological (MR) semi-active control method based on Bidirectional Long Short-Term Memory (BiLSTM) neural network, linear quadratic regulator (LQR) control algorithm and genetic algorithm (GA). The LQR algorithm with GA optimizing the weight coefficients generates the expected damping force. Due to the nonlinear hysteresis characteristics of the MR damper (MRD) and the fact that its input and output have certain time dependence, an inverse model of MRD is established by BiLSTM. The control current is predicted by BiLSTM and then the current is input to the MR damper to obtain the damping force that is infinitely close to the expected damping force. The damping force is then applied to the suspension system to form a complete closed-loop feedback control, which realizes the damping effect and generates a real-time control. The simulation results show that the MRD inverse model can accurately predict the required control current, and the GA-optimized LQR control algorithm has a good suppression effect on the vertical vehicle acceleration (VVA), dynamic tire load (DTL) and suspension dynamic stroke (SDS).

Magnetorheological damper (MRD) is widely used in civil engineering, heavy-duty vehicles to speed up safely and so on. In this paper, a MR controller for adjusting the stiffness and damping of a semi-active air suspension is designed to improve the vibration resistance of the Electric Multiple Units (EMU) suspension system. The 3D magnetic field simulations of the MR controller are carried out. The influences of factors such as shaft material, damping channel width, cylinder wall thickness on the magnetic induction intensity at the damping channel are studied. An orthogonal experiment is carried out and the optimal combination of the structural parameters is determined. Then, the four working conditions of the MR controller are simulated and analyzed respectively, and its structure is improved to ensure its stability. Finally, using fluid simulation software analysis, it can be seen that due to the fluidity of magnetorheological fluids (MRFs), the heat generated by the coil has little effect on MRFs.

Herein, we report an efficient kinetic resolution of alkyl allylic alcohols enabled by an iridium-catalyzed enantioselective alkynylation of alkyl allylic alcohols with potassium alkynyltrifluoroborates. A wide range of chiral 1,4-enynes bearing various functional groups and unreacted enantioenriched allylic alcohols were obtained with excellent enantioselectivities and high kinetic resolution performance (

Long noncoding RNAs (lncRNA) are dysregulated in various human cancers and control tumor development and progression. However, the upstream mechanisms underlying their dysregulation remain unclear. Here, we demonstrate that the expression of hepatocyte nuclear factor 1 homeobox A antisense RNA 1 (HNF1A-AS1) is significantly upregulated in gastric cancer tissues. Overexpression of HNF1A-AS1 enhanced cell proliferation and promoted cell-cycle progression, whereas knockdown of HNF1A-AS1 elicited the opposite effects. Early growth response protein 1 (EGR1) directly bound the HNF1A-AS1 promoter region and activated its transcription. Overexpression of EGR1 enhanced cell proliferation and promoted cell-cycle promotion, similar to the function of HNF1A-AS1. HNF1A-AS1 functioned as competing endogenous RNA (ceRNA) by binding to miR-661, upregulating the expression of cell division cycle 34 (CDC34), which is a direct target of miR-661. EGR1 and HNF1A-AS1 enhanced the expression of cyclin-dependent kinase 2 (CDK2), CDK4, and cyclin E1 but inhibited the expression of p21 by promoting CDC34-mediated ubiquitination and degradation of p21. Taken together, these findings suggest that EGR1-activated HNF1A-AS1 regulates various pro- and antigrowth factors to promote the development of gastric cancer, implicating it as a possible target for therapeutic intervention in this disease.Significance: This study provides novel insights into mechanisms by which the noncoding RNA HNF1A-AS1 contributes to gastric cancer progression through modulation of the cell cycle. Cancer Res; 78(20); 5877–90. ©2018 AACR.

Figure S1 showed that the overexpression and knockdown efficiency of HNF1A-AS1 in both GC cells and the proliferation of GC cells transfected with SI-HNF1A-AS1-2 were inhibited. Figure S2 indicated that the migration, invasion and cell cycle progression of GC cells transfected with SI-HNF1A-AS1-2 were inhibited. Table S1 showed sequences of primers.

BACKGROUND Diabetic foot ulcers (DFUs) are a devastating complication of diabetes and a leading cause of non-traumatic foot amputations. Traditional methods of monitoring and managing patients with diabetes, such as periodic in-person clinic visits, may not be sufficient for preventing DFUs and amputations. Continuous Remote Temperature Monitoring has the potential to capture the critical period before the foot ulcers develop and to improve outcomes by providing real-time data and early interventions. For the first time, the effectiveness of such a strategy to prevent DFUs and amputations among high-risk patients in a real-world commercial setting is reported. OBJECTIVE The aim of this study is to evaluate the effectiveness of a real-world continuous remote temperature monitoring program in preventing DFUs and amputations in patients with diabetes. METHODS In this retrospective analysis of a real-world continuous remote temperature monitoring program, 109 high risk patients identified by clinical providers from 15 geographically diverse private podiatry offices were analyzed. Patients received continuous remote monitoring socks as part of the program. The enrollment was based on medical necessity as decided by their managing physician. We evaluated data from up to 2 years before enrollment and up to 3 years during the program. Primary outcome was the rate of wound development. Secondary outcomes included amputation rate, severity of the foot ulcers, and the number of visits to an outpatient podiatry clinic after enrolling in the program. RESULTS We observed significantly lower rates of foot ulceration (relative risk reduction (RRR) 0.69; number needed to treat (NNT) 5.0; 95% CI 0.80, 0.53; p CONCLUSIONS Our findings suggested that a real-world continuous remote temperature monitoring program was an effective strategy to prevent DFU development and non-traumatic foot amputation among high-risk patients. CLINICALTRIAL WCG-IRB (1284366)

Macrophages are highly plastic cells critical for the development of rheumatoid arthritis (RA). Macrophages exhibit a high degree of pro-inflammatory plasticity in RA, accompanied by a metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis. 2-deoxyglucose (2-DG), a glycolysis inhibitor, has previously been shown to exhibit anti-inflammatory and anti-arthritic properties. However, the specific mechanisms of inflammatory modulation by 2-DG remain unclear. This study used 2-DG to treat rats with adjuvant arthritis (AA) and investigated its specific anti-arthritic mechanisms in the murine-derived macrophage cell line RAW264.7 in vitro. 2-DG reduced the arthritis index as well as alleviated cellular infiltration, synovial hyperplasia, and bone erosion in AA rats. Moreover, 2-DG treatment modulated peritoneal macrophage polarization, increasing levels of the arginase1 (Arg1) and decreasing expression of the inducible nitric oxide synthase (iNOS). 2-DG activated AMP-activated protein kinase (AMPK) via phosphorylation and reduced activation of the nuclear factor κB (NF-κB) in peritoneal macrophages of AA rats. In vitro, we verified that 2-DG promoted macrophage transition from M1 to M2-type by upregulating the expression of p-AMPKα and suppressing NF-κB activation in LPS-stimulated RAW264.7 cells. LPS-induced macrophages exhibited a metabolic shift from glycolysis to OXPHOS following 2-DG treatment, as observed by reduced extracellular acidification rate (ECAR), lactate export, glucose consumption, as well as an elevated oxygen consumption rate (OCR) and intracellular ATP concentration. Importantly, changes in polarization and metabolism in response to 2-DG were dampened after AMPKα knockdown. These findings indicate that the anti-arthritic 2-DG effect is mediated by a modulation of macrophage polarization in an AMPK-dependent manner.

Elizabeth Brooks,1 Megan Burns,1 Ran Ma,2 Henk Jan Scholten,2 Shawn Becker3 1TTi Health Research and Economics, Westminster, MD, USA; 2Siren Care, Inc, San Francisco, CA, USA; 3Silvercat Advisors, LLC, Burlingame, CA, USACorrespondence: Megan BurnsTTi Health Research and Economics, 1231 Tech Ct Suite 201, Westminster, MD, 21157, USAEmail meganalexburns@gmail.comBackground: Foot temperature monitoring for the prevention and early detection of diabetic foot ulcers (DFU) is evidence-based and recommended in clinical practice. However, easy-to-use remote monitoring tools have been lacking, thereby preventing widespread adoption.Objective: To evaluate the cost-effectiveness of remote foot temperature monitoring (RFTM) (Siren’s Neurofabric™ Diabetic socks) in addition to standard of care (SoC) versus SoC alone for early detection of DFU with diabetic neuropathy and a moderate to high risk of DFU.Methods: A payer perspective decision-tree analysis was conducted to compare expected DFU occurrence and subsequent amputation rates and costs between treatment strategies over one year. Inputs in the model were sourced from publicly available literature and relevant health technology assessments. One-way sensitivity analyses were performed for each model variable.Results: In the base-case scenario, RFTM plus SoC was a dominant strategy compared to SoC alone. RFTM plus SoC was associated with cost savings of $38,593 per additional ulcer avoided versus SoC alone, and $8027 per patient per year on average compared to SoC alone. These results were highly robust to one-way sensitivity analysis; all scenarios remained dominant if compliance was ≥ 13%.Conclusion: RFTM is a cost-effective addition to SoC in patients with diabetic neuropathy at a moderate-to-high risk of DFU and subsequent amputation. Further, reduction in DFU and associated complications may result in improvements in the patient’s quality of life and mental health. Future studies are needed to evaluate the compliance and reduction of DFU occurrence in patients on RFTM.Keywords: diabetes mellitus, diabetic foot, technology assessment, biomedical, cost-benefit analysis, cost savings, decision trees

Breast cancer (BC) is a complex disease comprising multiple distinct subtypes with different genetic features and pathological characteristics. Although a large number of antineoplastic compounds have been approved for clinical use, patient-to-patient variability in drug response is frequently observed, highlighting the need for efficient treatment prediction for individualized therapy. Several patient-derived models have been established lately for the prediction of drug response. However, each of these models has its limitations that impede their clinical application. Here, we report that the whole-tumor cell culture (WTC) ex vivo model could be stably established from all breast tumors with a high success rate (98 out of 116), and it could reassemble the parental tumors with the endogenous microenvironment. We observed strong clinical associations and predictive values from the investigation of a broad range of BC therapies with WTCs derived from a patient cohort. The accuracy was further supported by the correlation between WTC-based test results and patients’ clinical responses in a separate validation study, where the neoadjuvant treatment regimens of 15 BC patients were mimicked. Collectively, the WTC model allows us to accomplish personalized drug testing within 10 d, even for small-sized tumors, highlighting its potential for individualized BC therapy. Furthermore, coupled with genomic and transcriptomic analyses, WTC-based testing can also help to stratify specific patient groups for assignment into appropriate clinical trials, as well as validate potential biomarkers during drug development.

A novel gold-catalyzed [4 + 1] heterocyclization of nonactivated alkyne and hydroxamic acid is developed for the regiospecific synthesis of 5-methyl-1,4,2-dioxazole, which is an important structural motif in various bioactive molecules. The current methodology is characterized by high efficiency, simple operation, mild reaction conditions, and good functional group compatibility. Moreover, gram-scale synthesis and synthetic application toward bioactive molecular skeletons have been realized.

Expanding the enzymatic toolbox for the green synthesis of valuable molecules is still of high interest in synthetic chemistry and the pharmaceutical industry. Chiral thiiranes are valuable sulfur-containing heterocyclic compounds, but relevant methods for their enantioselective synthesis are limited. Herein, we report a biocatalytic thionation strategy for the enantioselective synthesis of thiiranes, which was developed based on the halohydrin dehalogenase (HHDH)-catalyzed enantioselective ring-opening reaction of epoxides with thiocyanate and a subsequent nonenzymatic rearrangement process. A novel HHDH was identified and engineered for enantioselective biocatalytic thionation of various aryl- and alkyl-substituted epoxides on a preparative scale, affording the corresponding thiiranes in up to 43 % isolated yield and 98 % ee. Large-scale synthesis and useful transformations of chiral thiiranes were also performed to demonstrate the utility and scalability of the biocatalytic thionation strategy.

Breast cancer (BC) is the most common malignant tumor in women worldwide. Metastasis is the main cause of BC-related death. The specific mechanism underlying BC metastasis remains obscure. Recently, PRSS22 was discovered to be involved in tumor development, however, its detailed biological function and regulatory mechanism in BC are unclear. Here, we characterized that PRSS22 expression is upregulated in BC tissues compared with non-tumorous breast tissues. Dual luciferase assays, bioinformatics analyses and chromatin immunoprecipitation (ChIP) assays indicated that transcription factor E2F1 directly binds to the PRSS22 promoter region and activates its transcription. Functionally, upregulation of PRSS22 promoted invasion and metastasis of BC cells in vitro and in vivo, whereas knockdown of PRSS22 inhibited its function. Mechanistically, the combination of PRSS22 and ANXA1 protein in BC cells was first screened by protein mass spectrometry analysis, and then confirmed by co-immunoprecipitation (Co-IP) and western blot assays. Co-overexpression of PRSS22 and ANXA1 could promote BC cell migration and invasion. We further demonstrated that PRSS22 promotes the cleavage of ANXA1 and in turn generates an N-terminal peptide, which initiates the FPR2/ERK signaling axis to increase BC aggressiveness.

To explore the differences between oral and intestinal microorganisms of 860 children aged 1-6 years in Nanjing city.Eight hundred and sixty children aged 1-6 years who met the inclusion criteria were enrolled. 860 saliva samples and equivalent stool samples were collected. Microbial DNA was extracted and amplified using PCR. High-throughput sequencing was performed using Miseq sequencer, and bioinformatics analysis was performed to compare the differences of oral and intestinal microflora. SPSS 20.0 software package was used to perform the statistical analysis.At phylum level, Bacteroidetes (39.98%), Proteobacteria (25.32%) and Firmicutes (21.78%) were the most common microbes in oral cavity, while Firmicutes (45.21%) and Bacteroidetes (37.21%) were the most abundant microbes in the gut. At genus level, the top three microbes in the oral cavity included Prevotella(26.11%), Neisseria (12.39%), Porphyromonas(10.13%), while the top three microbes in the gut included Bacteroidetes(20.11%), Prevotella (9.13%), and Faecalibacterium (5.13%). There were significant alpha and beta differences in oral and intestinal microbial diversity.Bacteroidetes and Proteobacteria are the dominant species in the oral cavity, while Firmicutes and Bacteroidetes are the dominant species in the gut. There are significant differences in species composition and abundance between oral and intestinal microorganisms.

To investigate the related factors of black tooth stain in primary teeth of 3~5 years old children and caries status of primary dentition in these children.From December 2019 to August 2020, 182 3~5 years old children with black tooth stain and 200 children without pigmentation were investigated by oral examination and questionnaire survey to their guardians, while caries status , distribution range of the pigment, factors associated with black tooth stain were evaluated. SPSS 20.0 software package was used for data analysis.Children with black tooth stain had fewer dental caries. The lingual surfaces of the mandibular anterior teeth were the most affected sites. Factors associated with black tooth stain were foods with soy sauce and brushing teeth with parents' help.There is a negative correlation between the occurrence of primary dentition caries and blacktooth stain, but there is no significant correlation between formation of black tooth stain and most environmental factors.

In this interview, the Okinawa-born filmmaker/artist Chikako Yamashiro looks back at the artistic trajectories and creative processes of her representative moving-image works since the 2000s, which...

Background: Pulmonary arterial hypertension (PAH) is a severe and fatal clinical syndrome characterized by high blood pressure and vascular remodeling in the pulmonary arterioles, which is also a rapidly progressing disease of the lung vasculature with a poor prognosis. Although PAH medication made great advances in recent years, the efficacy and safety of the medication are unsatisfactory. Therefore, we aimed to update and expand previous studies to explore the efficacy and safety of PAH-targeted medications. Methods: Relevant articles were searched and selected from published or publicly available data in PubMed, Cochrane Library, CNKI, PsycInfo, and MEDLINE (from inception until October 1st, 2020). To assess the efficacy and safety of PAH therapies, five efficacy outcomes [6-minute walking distance (6MWD), mean pulmonary arterial pressure (mPAP), WHO functional class (WHO FC) improvement, clinical worsening, death] and two safety outcomes [adverse events (AEs), serious adverse events (SAEs)] were selected. And 6MWD was regarded as the primary efficacy outcome. Results: 50 trials included with 10 996participants were selected. In terms of efficacy, all targeted drugs were more effective than placebo. For 6MWD, Bosentan + Sildenafil, Sildenafil, Bosentan + Iloprost were better than others. Bosentan + Iloprost and Bosentan + Sildenafil were better for mPAP. Bosentan + Iloprost and Ambrisentan + Tadalafil were more effective in improving WHO FC. Bosentan + Tadalafil and Bosentan + Iloprost had the Ambrisentan probability to reduce the incidence of clinical worsening. It is demonstrated that Ambrisentan had clear benefits in reducing all-cause mortality. In terms of safety, no therapies had been shown to reduce the incidence of SAEs significantly, and Ambrisentan + Tadalafil significantly increased the incidence of AEs. Conclusions: Phosphodiesterase 5 inhibitor (PDE5i) + Endothelin Receptor Antagonists (ERA) seems to be better therapy for PAH. Prostacyclin analogs (ProsA) + ERA appear promising, though additional data is warranted. Registration PROSPERO CRD42020218818.

Fuke Qianjin Capsule (FKQJ) is a common TCM compound formula in the treatment of gynecological inflammation-related diseases. This study intends to explore and establish a bioassay method to further improve its quality control. The bioassay method for the determination of anti-inflammatory biopotency was established based on its inhibitory activity on recombinant human cyclooxygenase-2 (COX-2), an active target of FKQJ in the treatment of female pelvic inflammatory disease. We firstly established chemical fingerprint of 20 batches of FKQJ by ultra-high-performance liquid chromatography to identify the components and analyze the chemical similarities. The similarity within different batches of FKQJ was relatively high. The values of similarity of the 19 batches were between 0.973 and 0.995, while one batch’s similarity value was 0.813. Celecoxib, a selective inhibitor of COX-2, was chosen as the positive control drug in COX-2 activity assay to establish an anti-inflammatory biopotency detection method based on parallel line test of qualitative response. The methodological investigation showed that the method possessed good repeatability and precision. Secondly, the anti-inflammatory biopotency of 20 batches of FKQJ for inhibiting COX-2 was determined. The results showed that the biopotency of different batches of FKQJ ranged from 676 U/μg to 1310 U/μg, with average value of 918 U/μg and RSD of 16.7%. Based on multiple linear regression analysis, we found that three contents were highly correlated with the anti-inflammatory biopotency, while chlorogenic acid was validated of the strongest anti-inflammatory activity in vitro. Compared with chemical detection, bioassay can better reflect the quality fluctuation of different batches of products and correlate the known pharmacodynamic targets. The supplement of the bioassay method based on chemical evaluation is helpful to improve the quality control ability of Chinese patent medicine and ensure its clinical efficacy is stable and controllable.

Culex tritaeniorhynchus Gile is a major vector of Japanese encephalitis in China. The population genetics study is crucial as it helps understanding the epidemiological aspects of mosquito-brone di...

We investigated the responses of leaf and individual traits, growth, and fluorescence characteristics of seedlings of two dominant species of broad-leaved Korean pine forest in Changbai Mountain,本研究选择长白山阔叶红松林优势树种红松和蒙古栎幼苗为对象,研究其植株形态、生长和光合荧光特性对5种光谱处理的响应。结果表明: 红松与蒙古栎的形态结构与生长主要受蓝光与紫外B区(UV-B)辐射调控。滤除蓝光后两种幼苗的植株叶面积比和相对生长速率均显著降低,而滤除UV-B辐射显著增加了红松的叶面积比和相对生长速率,分别上升了41.8%和47.7%,降低了蒙古栎的株高、总叶面积和生物量积累。滤除UV-B辐射显著降低了2种幼苗的光合荧光调节能力,红松的下降幅度较低,其非调节性耗散的量子产量(

Whether lung ultrasound (LUS) can be used for pathogenic diagnosis remains controversial. This study was conducted to clarify whether ultrasound has diagnostic value for etiology.A total of 135 neonatal pneumonia patients with an identified pathogen were enrolled from the newborn intensive care units of 10 tertiary hospitals in China. The study ran from November 2020 to December 2021. The infants were divided into various groups according to pathogens, time of infection, gestational age, and disease severity. The distribution of pleural line abnormalities, B-line signs, and pulmonary consolidation, as well as the incidence of air bronchogram and pleural effusion based on LUS, were compared between these groups.There were significant differences in pulmonary consolidation. The sensitivity and specificity of the diagnosis of severe pneumonia based on the extent of pulmonary consolidation were 83.3% and 85.2%, respectively. The area under the receiver operating characteristic curve for the identification of mild or severe pneumonia based on the distribution of pulmonary consolidation was 0.776.LUS has good performance in diagnosing and differentiating the severity of neonatal pneumonia but cannot be used for pathogenic identification in the early stages of pneumonia.