Human infection with the novel avian-origin influenza A (H7N9) virus has aroused global concern. In this report, the clinical characteristics of 111 laboratory-confirmed cases in China are presented.
...On March 30, 2013, three patients with fatal cases of rapid, progressive pneumonia were confirmed to be infected with a novel avian-origin influenza A (H7N9) virus that had not been detected in humans and animals previously.
1
,
2
The new human H7N9 viruses are the product of reassortment of viruses that are of avian origin.
Global attention was soon focused on the situation because of the increasing number of new cases and the high rate of death associated with these infections.
3
As of May 9, the World Health Organization (WHO) had reported 131 laboratory-confirmed cases, including 32 deaths.
4
However, data on . . .
Administration of exosomes derived from mesenchymal stromal cells (MSCs) could improve some neurologic conditions by transferring functional biomolecules to recipient cells. Furthermore, exosomes ...from hypoxic progenitor cells exerted better therapeutic effects in organ injury through specific cargoes. However, there are no related reports about whether exosomes derived from MSCs or hypoxia‐preconditioned MSCs (PC‐MSCs) could prevent memory deficits in Alzheimer disease (AD). In this study, the exosomes derived from MSCs or PC‐MSCs were systemically administered to transgenic APP/PS1 mice. The expression of miR‐21 in MSCs was significantly increased after hypoxic treatment. Injection of exosomes from normoxic MSCs could rescue cognition and memory impairment according to results of the Morris water maze test, reduced plaque deposition, and Aβ levels in the brain; could decrease the activation of astrocytes and microglia; could down‐regulate proinflammatory cytokines (TNF‐α and IL‐1β); and could up‐regulate anti‐inflammatory cytokines (IL‐4 and ‐10) in AD mice, as well as reduce the activation of signal transducer and activator of transcription 3 (STAT3) and NF‐κB. Compared to the group administered exosomes from normoxic MSCs, in the group administered exosomes from PC‐MSCs, learning and memory capabilities were significantly improved; the plaque deposition and Aβ levels were lower, and expression of growth‐associated protein 43, synapsin 1, and IL‐10 was increased; and the levels of glial fibrillary acidic protein, ionized calcium‐binding adaptor molecule 1, TNF‐α, IL‐1β, and activation of STAT3 and NF‐κB were sharply decreased. More importantly, exosomes from PC‐MSCs effectively increased the level of miR‐21 in the brain of AD mice. Additionally, replenishment of miR‐21 restored the cognitive deficits in APP/PS1 mice and prevented pathologic features. Taken together, these findings suggest that exosomes from PC‐MSCs could improve the learning and memory capabilities of APP/PS1 mice, and that the underlying mechanism may lie in the restoration of synaptic dysfunction and regulation of inflammatory responses through regulation of miR‐21.—Cui, G.‐H., Wu, J., Mou, F.‐F., Xie, W.‐H., Wang, F.‐B., Wang, Q.‐L., Fang, J., Xu, Y.‐W., Dong, Y.‐R., Liu, J.‐R., Guo, H.‐D. Exosomes derived from hypoxia‐preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP/PS1 mice. FASEB J. 32, 654–668 (2018). www.fasebj.org
Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell ...therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM).
This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m
. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 10
cells/kg range, 0.07 to 2.1 × 10
) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group.
At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval CI, 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached.
LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM.
ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.
The human ABC transporter ABCC3 (also known as MRP3) transports a wide spectrum of substrates, including endogenous metabolites and exogenous drugs. Accordingly, it participates in multiple ...physiological processes and is involved in diverse human diseases such as intrahepatic cholestasis of pregnancy, which is caused by the intracellular accumulation of bile acids and estrogens. Here, we report three cryogenic electron microscopy structures of ABCC3: in the apo‐form and in complexed forms bound to either the conjugated sex hormones β‐estradiol 17‐(β‐D‐glucuronide) and dehydroepiandrosterone sulfate. For both hormones, the steroid nuclei that superimpose against each other occupy the hydrophobic center of the transport cavity, whereas the two conjugation groups are separated and fixed by the hydrophilic patches in two transmembrane domains. Structural analysis combined with site‐directed mutagenesis and ATPase activity assays revealed that ABCC3 possesses an amphiphilic substrate‐binding pocket able to hold either conjugated hormone in an asymmetric pattern. These data build on consensus features of the substrate‐binding pocket of MRPs and provide a structural platform for the rational design of inhibitors.
Synopsis
The human ABC transporter ABCC3/MRP3 transports diverse metabolites and drugs in multiple physiological processes. Here, both structural analysis and biochemical assays of ABCC3 are used to refine the common features of substrate‐binding pockets in multidrug resistance proteins.
Three cryo‐EM structures of human ABCC3 are reported: the apo‐, E217βG‐ and DHEAS‐bound forms.
The two substrate‐bound ABCC3 complexes display a similar V‐shaped binding pocket, the hydrophobic center of which accommodates the steroid nuclei, whereas the hydrophilic patches stabilize the two conjugation groups of the substrate.
The conjugation groups confer substrate specificity, and are coordinated by the conserved positively charged residues.
A common substrate‐binding feature is proposed for all MRPs.
This cryo‐EM study uses the location of two substrates to reveal a common steroid‐binding pocket within the human ABCC3 protein.
Uranium is a key resource for the development of the nuclear industry, and extracting uranium from the natural seawater is one of the most promising ways to address the shortage of uranium resources. ...Herein, a semiconducting covalent organic framework (named NDA‐TN‐AO) with excellent photocatalytic and photoelectric activities was synthesized. The excellent photocatalytic effect endowed NDA‐TN‐AO with a high anti‐biofouling activity by generating biotoxic reactive oxygen species and promoting photoelectrons to reduce the adsorbed UVI to insoluble UIV, thereby increasing the uranium extraction capacity. Owing to the photoinduced effect, the adsorption capacity of NDA‐TN‐AO to uranium in seawater reaches 6.07 mg g−1, which is 1.33 times of that in dark. The NDA‐TN‐AO with enhanced adsorption capacity is a promising material for extracting uranium from the natural seawater.
Photoelectric and photocatalytic effects endow the covalent organic framework NDA‐TN‐AO with good anti‐biofouling activity. This occurs by generating biotoxic reactive oxygen species and promoting photoelectrons to reduce the adsorbed UVI to insoluble UIV, thereby improving the uranium adsorption capacity.
Background and Aims
The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3–5‐cm HCC over time.
Approach and Results
From ...2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008–2019 (n = 335 in each group) and 2014–2019 (n = 257 in each group) cohorts, respectively. For cohort 2008–2019, during a median follow‐up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65–1.19, p = 0.420), and MWA was inferior to LLR regarding disease‐free survival (DFS) (HR 1.36, 95% CI 1.05–1.75, p = 0.017). For cohort 2014–2019, there was comparable OS (HR 0.85, 95% CI 0.56–1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98–1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1–4.0‐cm HCCs (HR 0.88, 95% CI 0.53–1.47, p = 0.630) and 4.1–5.0‐cm HCCs (HR 0.77, 95% CI 0.37–1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001).
Conclusions
MWA might be a first‐line alternative to LLR for solitary 3–5‐cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.
Bio and nanomaterials based on Fe3O4 Xu, Jia-Kun; Zhang, Fang-Fang; Sun, Jing-Jing ...
Molecules,
12/2014, Volume:
19, Issue:
12
Journal Article, Book Review
Peer reviewed
Open access
During the past few years, nanoparticles have been used for various applications including, but not limited to, protein immobilization, bioseparation, environmental treatment, biomedical and ...bioengineering usage, and food analysis. Among all types of nanoparticles, superparamagnetic iron oxide nanoparticles, especially Fe3O4, have attracted a great deal of attention due to their unique magnetic properties and the ability of being easily chemical modified for improved biocompatibility, dispersibility. This review covers recent advances in the fabrication of functional materials based on Fe3O4 nanoparticles together with their possibilities and limitations for application in different fields.
This study aimed to determine the levels of health-related behaviours (physical activity, screen exposure and sleep status) among Chinese students from primary, secondary and high schools during the ...pandemic of COVID-19, as well as their changes compared with their status before the pandemic. A cross-sectional online survey of 10,933 students was conducted among 10 schools in Guangzhou, China, between 8th and 15th March, 2020. After getting the informed consent from student's caregivers, an online questionnaire was designed and used to obtain time spending on health-related behaviours during the pandemic of COVID-19, as well as the changes compared with 3 months before the pandemic, which was completed by students themselves or their caregivers. Students were stratified by regions (urban, suburban, exurban), gender (boys and girls), and grades (lower grades of primary school, higher grades of primary schools, secondary schools and high schools). Data were expressed as number and percentages and Chi-square test was used to analyse difference between groups. Overall, the response rate of questionnaire was 95.3% (10,416/10,933). The median age of included students was 13.0 (10.0, 16.0) years and 50.1% (n = 5,219) were boys. 41.4%, 53.6% and 53.7% of total students reported less than 15 min per day in light, moderate and vigorous activities and 58.7% (n = 6,113) reported decreased participation in physical activity compared with the time before pandemic. Over 5 h of screen time spending on online study was reported by 44.6% (n = 4,649) of respondents, particular among high school students (81.0%). 76.9% of students reported increased screen time compared with the time before pandemic. Inadequate sleep was identified among 38.5% of students and the proportion was highest in high school students (56.9%). Our study indicated that, during the COVID-19 pandemic, the school closure exerted tremendous negative effects on school-aged children's health habits, including less physical activity, longer screen exposure and irregular sleeping pattern.
To examine the association between blood urea nitrogen (BUN) and risk of type 2 diabetes (T2DM) among Chinese adults, we performed an ongoing cohort study of 38578 Chinese adults (56.3% males; ...average age, 41.6 y) who underwent repeated health check-up examinations between 2009 and 2016 and without T2DM at baseline. During follow-up, incident T2DM cases were identified based on self-report, medication use, measurements of fasting plasma glucose, 2 h post oral glucose, or haemoglobinA1c. 2009 (5.2%) cases confirmed with incident T2DM were identified during median follow-up of 3.1 years. With increasing quartiles of BUN levels, the incidences of T2DM gradually increased with 0.69%, 1.11%, 1.53%, and 1.87% for quartile 1 to quartile 4 (p trend <0.001). Compared with quartile 1, the multivariate-adjusted hazard ratios (HRs) and its 95% confidence intervals (95% CIs) for T2DM risk were 1.16 (0.97–1.38) for quartile 2, 1.28 (1.07–1.51) for quartile 3, and 1.28 (1.08–1.52) for quartile 4 (p trend = 0.005). HR for per each standard deviation increase in BUN level was 1.10 (1.04–1.16) (p trend <0.001). This association tended to be more pronounced in those with a lower body mass index at baseline (p-interaction <0.001). Our results suggested that BUN levels were positively associated with incident T2DM risk among Chinese adults. Future prospective investigations in other populations are necessary to confirm our findings.
PDF
