AgNPs are nanomaterials with many potential biomedical applications. In this study, the two novel yeast strains HX-YS and LPP-12Y capable of producing biological silver nanoparticles were isolated. ...Sequencing of ribosomal DNA-ITS fragments, as well as partial D1/D2 regions of 26S rDNA indicated that the strains are related to species from the genus Metschnikowia. The BioAgNPs produced by HX-YS and LPP-12Y at pH 5.0-6.0 and 26 °C ranged in size from 50 to 500 nm. The antibacterial activities of yeast BioAgNPs against five pathogenic bacteria were determined. The highest antibacterial effect was observed on P. aeruginosa, with additional obvious effects on E. coli ATCC8099 and S. aureus ATCC10231. Additionally, the BioAgNPs showed antiproliferative effects on lung cancer cell lines H1975 and A579, with low toxicity in Beas 2B normal lung cells. Therefore, the AgNPs biosynthesized by HX-YS and LPP-12Y may have potential applications in the treatment of bacterial infections and cancer.
The construction of C(sp3)‐sulfonyl bonds through direct sulfonylation of C(sp3)−H bond presents a number of challenges, so an electrochemical oxidation‐induced direct sulfonylation of the xanthene ...C(sp3)−H bond was developed. Significant advantages of this method are high atom efficiency, functional group tolerance, transition metal‐ and oxidant‐free conditions. The in vitro cytotoxicity of all product is evaluated by MTT assay against human cancer cell lines. The results reveal that most of the compounds 3 da and 3 af have good inhibitory activity on tumor cell lines.
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovitis and the destruction of small joints. Emerging evidence shows that immunoglobulin D (IgD) stimulation ...induces T-cell activation, which may contribute to diseases pathogenesis in RA. In this study, we investigated the downstream signaling pathways by which IgD activated T cells as well as the possible role of IgD in the T-B interaction. Peripheral blood mononuclear cells were isolated from peripheral blood of healthy controls and RA patients. We demonstrated that IgD activated T cells through IgD receptor (IgDR)-lymphocyte-specific protein tyrosine kinase (Lck)-zeta-associated protein 70 (ZAP70)/phosphatidylinositol 3-kinase (PI3K)/nuclear factor kappa-B (NF-κB) signaling pathways; IgD-induced CD4
T cells promoted the proliferation of CD19
B cells in RA patients. A novel fusion protein IgD-Fc-Ig (composed of human IgD-Fc domain and IgG
Fc domain, which specifically blocked the IgD-IgDR binding) inhibited the coexpression of IgDR and phosphorylated Lck (p-Lck) and the expression levels of p-Lck, p-ZAP70, p-PI3K on CD4
T cells, and decreased NF-κB nuclear translocation in Jurkat cells. Meanwhile, IgD-Fc-Ig downregulated the expression levels of CD40L on CD4
T cells as well as CD40, CD86 on CD19
B cells in RA patients and healthy controls. It also decreased the expression levels of CD40L on CD4
T cells and CD40 on CD19
B cells from spleens of collagen-induced arthritis (CIA) mice and reduced IL-17A level in mouse serum. Moreover, administration of IgD-Fc-Ig (1.625-13 mg/kg, iv, twice a week for 4 weeks) in CIA mice dose-dependently decreased the protein expression levels of CD40, CD40L, and IgD in spleens. IgD-Fc-Ig restrains T-cell activation through inhibiting IgD-IgDR-Lck-ZAP70-PI3K-NF-κB signaling, thus inhibiting B-cell activation. Our data provide experimental evidences for application of IgD-Fc-Ig as a highly selective T cell-targeting treatment for RA.
While high-speed rail (HSR) has achieved success in major cities in Europe and Asia, it is a new phenomenon in the US, and few studies on HSR in the US are available, especially from the users’ ...perspective. This study aims to fill the research gap by investigating the mode choice behavior in the Los Angeles and San Francisco corridor where HSR may soon become a feasible option. The impact of COVID-19 was also examined with regard to how people view modes of domestic travel and how their view may change. The geographic locations of travelers and the possible HSR characteristics in the US were also explored. Survey data of US travelers was collected on MTurk, which was analyzed using logistics regression and Two-Way MANOVA. The results indicated that convenience in transport, travel frequency, gender, mobility issues, income, and total travel time were determinants in the choice between HSR and air service, while travel frequency and total travel time were important in the choice between HSR and car transport. Most US travelers changed their views following COVID-19 in terms of domestic travel and exhibited a higher intention to travel by train and HSR. Geographic patterns were identified, such as people in the southern US were the most knowledgeable of HSR and had the greatest intention to use HSR, while people in the northeast exhibited the lowest intention. The findings indicate potential interest in HSR among US travelers, and offer much-needed empirical evidence for the potential success of HSR in the US.
AbstractObjectiveTo assess the effects of Helicobacter pylori treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer.DesignBlinded randomized placebo ...controlled trial.SettingLinqu County, Shandong province, China.Participants3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to H pylori were randomly assigned to H pylori treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 H pylori seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design.InterventionsH pylori treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003).Main outcome measuresPrimary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease.Results151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of H pylori treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for H pylori treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of H pylori treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease.ConclusionsH pylori treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years. H pylori treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer.Trial registrationClinicalTrials.gov NCT00339768.
A pulsed muon facility (the so‐called EMuS) at the China Spallation Neutron Source (CSNS) has been studied since 2007. It aims for multidisciplinary applications but with a focus on those based on ...muon spin rotation/relaxation/resonance techniques. As a standalone facility, EMuS will take about 5% or 25 kW of the total beam power (500 kW) from the CSNS‐II accelerator complex. Two schemes have been designed: the baseline scheme is based on an inner conical target in graphite and superconducting solenoids for the capture and transport of pions and muons; the simplified scheme is based on a conventional thick target and room‐temperature magnets for transport. With the former, multiple kinds of muon beams can be provided, from surface muons, decay muons, negative muons, to low‐energy muons. Mainly surface muons are available with the simplified scheme. With a number of novel design concepts such as forward capture of pions/muons from a target station based on superconducting solenoids and triple spatial beam splitting of a muon beam, the design aspects of EMuS are presented here. The wide application potential and the R&D progress are also included.
At the Experimental Muon Source at the China Spallation Neutron Source, a novel target station design is adopted to produce high‐intensity and different muon beam types. A conical graphite target is installed inside a series of superconducting solenoids. With a tapered magnetic field and forward collection, surface muons, decay muons, and high‐momentum muons can be provided in the downstream beamline.
Background and Purpose
Pancreatic islets are modulated by cross‐talk among different cell types and paracrine signalling plays important roles in maintaining glucose homeostasis. Urocortin 3 (UCN3) ...secreted by pancreatic β cells activates the CRF2 receptor (CRF2R) and downstream pathways mediated by different G protein or arrestin subtypes in δ cells to cause somatostatin (SST) secretion, and constitutes an important feedback circuit for glucose homeostasis.
Experimental Approach
Here, we used Arrb1−/−, Arrb2−/−, Gsfl/fl and Gqfl/fl knockout mice, the G11‐shRNA‐GFPfl/fl lentivirus, as well as functional assays and pharmacological characterization to study how the coupling of Gs, G11 and β‐arrestin1 to CRF2R contributed to UCN3‐induced SST secretion in pancreatic δ cells.
Key Results
Our study showed that CRF2R coupled to a panel of G protein and arrestin subtypes in response to UCN3 engagement. While RyR3 phosphorylation by PKA at the S156, S2706 and S4697 sites may underlie the Gs‐mediated UCN3‐ CRF2R axis for SST secretion, the interaction of SYT1 with β‐arrestin1 is also essential for efficient SST secretion downstream of CRF2R. The specific expression of the transcription factor Stat6 may contribute to G11 expression in pancreatic δ cells. Furthermore, we found that different UCN3 concentrations may have distinct effects on glucose homeostasis, and these effects may depend on different CRF2R downstream effectors.
Conclusions and Implications
Collectively, our results provide a landscape view of signalling mediated by different G protein or arrestin subtypes downstream of paracrine UCN3‐ CRF2R signalling in pancreatic β‐δ‐cell circuits, which may facilitate the understanding of fine‐tuned glucose homeostasis networks.
Objectives
To evaluate the diagnostic value of computer-aided diagnosis (CAD) software on ultrasound in distinguishing benign and malignant breast masses and avoiding unnecessary biopsy.
Methods
This ...prospective, multicenter study included patients who were scheduled for pathological diagnosis of breast masses between April 2019 and November 2020. Ultrasound images, videos, CAD analysis, and BI-RADS were obtained. The AUC, accuracy, sensitivity, specificity, PPV, and NPV were calculated and compared with radiologists.
Results
Overall, 901 breast masses in 901 patients were enrolled in this study. The accuracy, sensitivity, specificity, PPV and NPV of CAD software were 89.6%, 94.2%, 87.0%, 80.4%, and 96.3, respectively, in the long-axis section; 89.0%, 91.4%, 87.7%, 80.8%, and 94.7%, respectively, in the short-axis section. With BI-RADS 4a as the cut-off value, CAD software has a higher AUC (0.906 vs 0.734 vs 0.696, all
p
< 0.001) than both experienced and less experienced radiologists. With BI-RADS 4b as the cut-off value, CAD software showed better AUC than less experienced radiologists (0.906 vs 0.874,
p
< 0.001), but not superior to experienced radiologists (0.906 vs 0.883,
p
= 0.057). After the application of CAD software, the unnecessary biopsy rate of BI-RADS categories 4 and 5 was significantly decreased (33.0% vs 11.9%, 37.8% vs 14.5%), and the malignant rate of biopsy in category 4a was significantly increased (11.6% vs 40.7%, 7.4% vs 34.9%, all
p
< 0.001).
Conclusions
CAD software on ultrasound can be used as an effective auxiliary diagnostic tool for differential diagnosis of benign and malignant breast masses and reducing unnecessary biopsy.
Clinical trial registration
ClinicalTrials.gov (NCT 03887598)
Key Points
•
Prospective multicenter study showed that computer-aided diagnosis software provides greater diagnostic confidence for differentiating benign and malignant breast masses
.
•
Computer-aided diagnosis software can help radiologists reduce unnecessary biopsy
.
•
The management of patients with breast masses becomes more appropriate
.
Soft magnetic alloy powder NdNi
5-x
Fe
x
(
x
= 0.0, 0.1, 0.3, 0.4) was prepared by vacuum arc melting, homogenization annealing and ball milling methods. The reflection loss of NdNi
5-x
Fe
x
powders ...were discussed based on the structural morphology, measured hysteresis loops and electromagnetic parameters. The lattice distortion and the saturation magnetization of NdNi
5-x
Fe
x
powders increase and the formant of the electromagnetic parameter moves toward the low frequency. The absorption peak of reflection loss also moves toward low frequency. In addition, the Nd–Ni–Fe alloy powder can achieve the best absorption bandwidth, and the minimum reflection loss value of 1.29 GHz and − 29.29 dB, respectively, with the addition of Fe content is 0.1. Add Fe content appropriately, and adjusting the thickness can effectively improve the absorbing performance of the material in c-band, so the powder has a good application prospect in c-band.
Primary familial brain calcification is a monogenic disease characterized by bilateral calcifications in the basal ganglia and other brain regions, and commonly presents motor, psychiatric, and ...cognitive symptoms. Currently, four autosomal dominant (SLC20A2, PDGFRB, PDGFB, XPR1) and one autosomal recessive (MYORG) causative genes have been identified. Compared with patients with autosomal dominant primary familial brain calcification, patients with the recessive form of the disease present with more severe clinical and imaging phenotypes, and deserve more clinical and research attention. Biallelic mutations in MYORG cannot explain all autosomal recessive primary familial brain calcification cases, indicating the existence of novel autosomal recessive genes. Using homozygosity mapping and whole genome sequencing, we detected a homozygous frameshift mutation (c.140delT, p.L48*) in the JAM2 gene in a consanguineous family with two affected siblings diagnosed with primary familial brain calcification. Further genetic screening in a cohort of 398 probands detected a homozygous start codon mutation (c.1A>G, p.M1?) and compound heterozygous mutations c.504G>C, p.W168C and c.(67+1_68-1)_(394+1_395-1), p.Y23_V131delinsL, respectively, in two unrelated families. The clinical phenotypes of the four patients included parkinsonism (3/4), dysarthria (3/4), seizures (1/4), and probable asymptomatic (1/4), with diverse onset ages. All patients presented with severe calcifications in the cortex in addition to extensive calcifications in multiple brain areas (lenticular nuclei, caudate nuclei, thalamus, cerebellar hemispheres, ± brainstem; total calcification scores: 43-77). JAM2 encodes junctional adhesion molecule 2, which is highly expressed in neurovascular unit-related cell types (endothelial cells and astrocytes) and is predominantly localized on the plasma membrane. It may be important in cell-cell adhesion and maintaining homeostasis in the CNS. In Chinese hamster ovary cells, truncated His-tagged JAM2 proteins were detected by western blot following transfection of p.Y23_V131delinsL mutant plasmid, while no protein was detected following transfection of p.L48* or p.1M? mutant plasmids. In immunofluorescence experiments, the p.W168C mutant JAM2 protein failed to translocate to the plasma membrane. We speculated that mutant JAM2 protein resulted in impaired cell-cell adhesion functions and reduced integrity of the neurovascular unit. This is similar to the mechanisms of other causative genes for primary familial brain calcification or brain calcification syndromes (e.g. PDGFRB, PDGFB, MYORG, JAM3, and OCLN), all of which are highly expressed and functionally important in the neurovascular unit. Our study identifies a novel causative gene for primary familial brain calcification, whose vital function and high expression in the neurovascular unit further supports impairment of the neurovascular unit as the root of primary familial brain calcification pathogenesis.
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