Graphitic carbon nitride (g-C3N4) has drawn great attention recently because of its visible light response, suitable energy band gap, good redox ability, and metal-free nature. g-C3N4 can absorb ...visible light directly, therefore has better photocatalytic ability under solar irradiation and is more energy-efficient than TiO2. However, pure g-C3N4 still has the drawbacks of insufficient light absorption, small surface area and fast recombination of photogenerated electron and hole pairs. This review summarizes the recent progress in the development of g-C3N4 nanocomposites to photodegrade organic contaminants in water. Element doping especially by potassium has been reported to be an efficient method to promote the degradation efficacy. In addition, compound doping improves photodegradation performance of g-C3N4, especially Ag3PO4-g-C3N4 which can completely degrade 10mgL−1 of methyl orange under visible light irradiation in 5min, with the rate constant (k) as high as 0.236min−1. Moreover, co-doping enhances the photodegradation rate of multiple contaminants while immobilization significantly improves catalyst stability. Most of g-C3N4 composites possess high reusability enabling their practical applications in wastewater treatment. Furthermore, environmental conditions such as solution pH, reaction temperature, dissolved oxygen, and dissolved organic matter all have important effects on the photocatalytic ability of g-C3N4 photocatalyst. Future work should focus on the synthesis of innovative g-C3N4 nanocomposites for the efficient removal of organic contaminants in water and wastewater.
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•g-C3N4 catalyst performs better than TiO2 in visible photocatalysis of dyes.•Photodegradation by g-C3N4 is particularly enhanced by K-doping.•Compound doping especially Ag3PO4-g-C3N4 improves photodegradation effect.•Co-doping can degrade multiple contaminants with high degradation rate constant.•Synthesized g-C3N4 nanocomposites have shown good reusability.
Background
The prevalence of drug allergies documented in electronic health records (EHRs) of large patient populations is understudied.
Objective
We aimed to describe the prevalence of common drug ...allergies and patient characteristics documented in EHRs of a large healthcare network over the last two decades.
Methods
Drug allergy data were obtained from EHRs of patients who visited two large tertiary care hospitals in Boston from 1990 to 2013. The prevalence of each drug and drug class was calculated and compared by sex and race/ethnicity. The number of allergies per patient was calculated and the frequency of patients having 1, 2, 3…, or 10+ drug allergies was reported. We also conducted a trend analysis by comparing the proportion of each allergy to the total number of drug allergies over time.
Results
Among 1 766 328 patients, 35.5% of patients had at least one reported drug allergy with an average of 1.95 drug allergies per patient. The most commonly reported drug allergies in this population were to penicillins (12.8%), sulfonamide antibiotics (7.4%), opiates (6.8%), and nonsteroidal anti‐inflammatory drugs (NSAIDs) (3.5%). The relative proportion of allergies to angiotensin‐converting enzyme (ACE) inhibitors and HMG CoA reductase inhibitors (statins) have more than doubled since early 2000s. Drug allergies were most prevalent among females and white patients except for NSAIDs, ACE inhibitors, and thiazide diuretics, which were more prevalent in black patients.
Conclusion
Females and white patients may be more likely to experience a reaction from common medications. An increase in reported allergies to ACE inhibitors and statins is noteworthy.
Antiangiogenic therapy resistance occurs frequently in patients with metastatic renal cell carcinoma (RCC). The purpose of this study was to understand the mechanism of resistance to sunitinib, an ...antiangiogenic small molecule, and to exploit this mechanism therapeutically. We hypothesized that sunitinib-induced upregulation of the prometastatic MET and AXL receptors is associated with resistance to sunitinib and with more aggressive tumor behavior. In the present study, tissue microarrays containing sunitinib-treated and untreated RCC tissues were stained with MET and AXL antibodies. The low malignant RCC cell line 786-O was chronically treated with sunitinib and assayed for AXL, MET, epithelial-mesenchymal transition (EMT) protein expression and activation. Co-culture experiments were used to examine the effect of sunitinib pretreatment on endothelial cell growth. The effects of AXL and MET were evaluated in various cell-based models by short hairpin RNA or inhibition by cabozantinib, the multi-tyrosine kinases inhibitor that targets vascular endothelial growth factor receptor, MET and AXL. Xenograft mouse models tested the ability of cabozantinib to rescue sunitinib resistance. We demonstrated that increased AXL and MET expression was associated with inferior clinical outcome in patients. Chronic sunitinib treatment of RCC cell lines activated both AXL and MET, induced EMT-associated gene expression changes, including upregulation of Snail and β-catenin, and increased cell migration and invasion. Pretreatment with sunitinib enhanced angiogenesis in 786-0/human umbilical vein endothelial cell co-culture models. The suppression of AXL or MET expression and the inhibition of AXL and MET activation using cabozantinib both impaired chronic sunitinib treatment-induced prometastatic behavior in cell culture and rescued acquired resistance to sunitinib in xenograft models. In summary, chronic sunitinib treatment induces the activation of AXL and MET signaling and promotes prometastatic behavior and angiogenesis. The inhibition of AXL and MET activity may overcome resistance induced by prolonged sunitinib therapy in metastatic RCC.
Dysbiotic oral microbiota has been associated with multiple sclerosis. However, the role and mechanism of oral microbiota in the development of multiple sclerosis are still elusive. Here, we ...demonstrated that ligature-induced periodontitis (LIP) aggravated experimental autoimmune encephalomyelitis (EAE) in mice, and this was likely dependent on the expansion of T helper 17 (Th17) cells. LIP increased the splenic richness of Enterobacter sp., which was able to induce the expansion of splenic Th17 cells and aggravate EAE in mice. LIP also led to enrichment of Erysipelotrichaceae sp. in the gut and increased Th17 cells in the large intestinal lamina propria of EAE mice. Fecal microbiota transplantation from EAE mice with LIP also promoted EAE symptoms. In conclusion, periodontitis exacerbates EAE, likely through ectopic colonization of oral pathobionts and expansion of Th17 cells.
Timely completion of eukaryotic genome duplication requires coordinated DNA replication initiation at multiple origins. Replication begins with the loading of the Mini-Chromosome Maintenance (MCM) ...complex, proceeds by the activation of the Cdc45-MCM-GINS (CMG) helicase, and ends with CMG removal after chromosomes are fully replicated. Post-translational modifications on the MCM and associated factors ensure an orderly transit of these steps. Although the mechanisms of CMG activation and removal are partially understood, regulated MCM loading is not, leaving an incomplete understanding of how DNA replication begins. Here we describe a site-specific modification of Mcm3 by the Small Ubiquitin-like MOdifier (SUMO). Mutations that prevent this modification reduce the MCM loaded at replication origins and lower CMG levels, resulting in impaired cell growth, delayed chromosomal replication, and the accumulation of gross chromosomal rearrangements (GCRs). These findings demonstrate the existence of a SUMO-dependent regulation of origin-bound MCM and show that this pathway is needed to prevent genome rearrangements.
Concentration of eight heavy metals in surface and groundwater around Dhaka Export Processing Zone (DEPZ) industrial area were investigated, and the health risk posed to local children and adult ...residents via ingestion and dermal contact was evaluated using deterministic and probabilistic approaches. Metal concentrations (except Cu, Mn, Ni, and Zn) in Bangshi River water were above the drinking water quality guidelines, while in groundwater were less than the recommended limits. Concentration of metals in surface water decreased as a function of distance. Estimations of non-carcinogenic health risk for surface water revealed that mean hazard index (HI) values of As, Cr, Cu, and Pb for combined pathways (i.e., ingestion and dermal contact) were >1.0 for both age groups. The estimated risk mainly came from the ingestion pathway. However, the HI values for all the examined metals in groundwater were <1.0, indicating no possible human health hazard. Deterministically estimated total cancer risk (TCR) via Bangshi River water exceeded the acceptable limit of 1 × 10−4 for adult and children. Although, probabilistically estimated 95th percentile values of TCR exceeded the benchmark, mean TCR values were less than 1 × 10−4. Simulated results showed that 20.13% and 5.43% values of TCR for surface water were >1 × 10−4 for adult and children, respectively. Deterministic and probabilistic estimations of cancer risk through exposure to groundwater were well below the safety limit. Overall, the population exposed to Bangshi River water remained at carcinogenic and non-carcinogenic health threat and the risk was higher for adults. Sensitivity analysis identified exposure duration (ED) and ingestion rate (IR) of water as the most relevant variables affecting the probabilistic risk estimation model outcome.
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•Deterministic and probabilistic approaches were used to determine health risk.•Water Ingestion pathway contributed the most to estimated risk.•People exposed to river water were at risk.•No health hazard was observed for groundwater drinking.•ED and IR of water were the major contributors to probabilistic risk calculation.
We report on the experimental studies of laser driven ion acceleration from a double-layer target where a near-critical density target with a few-micron thickness is coated in front of a ...nanometer-thin diamondlike carbon foil. A significant enhancement of proton maximum energies from 12 to ∼30 MeV is observed when a relativistic laser pulse impinges on the double-layer target under linear polarization. We attributed the enhanced acceleration to superponderomotive electrons that were simultaneously measured in the experiments with energies far beyond the free-electron ponderomotive limit. Our interpretation is supported by two-dimensional simulation results.
Background
Several previous researches had found artery stiffness associated skeletal muscle mass, but not considering muscle strength and physical performance, which also were compositions of ...sarcopenia. This study aims to reveal the relationship of artery stiffness and sarcopenia using the Asian Working Group for Sarcopenia criteria.
Methods
Study was performed on 1002 Chinese community dwelling participants aged ≥65 years from November 2016 to March 2017. Body composition, muscle strength, physical performance, and brachial-ankle pulse wave velocity (baPWV) considering as artery stiffness index were measured.
Results
In multiple regression analysis, baPWV was associated with handgrip (β=−0.13, P=0.04) and Relative skeletal muscle mass index (ASM/Ht
2
) (β=−0.02, P<0.01), but not with 4-meter velocity (P=0.21). Multiple logistic regression analysis showed that 1-SD (3.50m/s) increased in baPWV was still associated with a 11% (CI, 4%–20%; P<0.01) higher odds of being sarcopenia. In the gender subgroup analysis, the relationship of baPWV and sarcopenia remain significant in men (OR, 1.23; 95% CI, 1.07–1.42, P<0.01), but not in women (P=0.07).
Conclusions
High brachial-ankle pulse wave velocity is associated with sarcopenia in Chinese community-dwelling elderly, with gender differences.
Basal autophagy is tightly regulated by transcriptional and epigenetic factors to maintain cellular homeostasis. Dysregulation of cardiac autophagy is associated with heart diseases, including ...cardiac hypertrophy, but the mechanism governing cardiac autophagy is rarely identified. To analyze the in vivo function of miR-199a in cardiac autophagy and cardiac hypertrophy, we generated cardiac-specific miR-199a transgenic mice and showed that overexpression of miR-199a was sufficient to inhibit cardiomyocyte autophagy and induce cardiac hypertrophy in vivo. miR-199a impaired cardiomyocyte autophagy in a cell-autonomous manner by targeting glycogen synthase kinase 3β (GSK3β)/mammalian target of rapamycin (mTOR) complex signaling. Overexpression of autophagy related gene 5 (Atg5) attenuated the hypertrophic effects of miR-199a overexpression on cardiomyocytes, and activation of autophagy using rapamycin was sufficient to restore cardiac autophagy and decrease cardiac hypertrophy in miR-199a transgenic mice. These results reveal a novel role of miR-199a as a key regulator of cardiac autophagy, suggesting that targeting miRNAs controlling autophagy as a potential therapeutic strategy for cardiac disease.
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