Prion diseases are caused by the misfolding of prion protein (PrP). Misfolded PrP forms protease-resistant aggregates in vivo (PrP
) that are able to template the conversion of the native form of the ...protein (PrP
), a property shared by in vitro-produced PrP fibrils. Here we produced amyloid fibrils in vitro from recombinant, full-length human PrP
(residues 23-231) and determined their structure using cryo-EM, building a model for the fibril core comprising residues 170-229. The PrP fibril consists of two protofibrils intertwined in a left-handed helix. Lys194 and Glu196 from opposing subunits form salt bridges, creating a hydrophilic cavity at the interface of the two protofibrils. By comparison with the structure of PrP
, we propose that two α-helices in the C-terminal domain of PrP
are converted into β-strands stabilized by a disulfide bond in the PrP fibril. Our data suggest that different PrP mutations may play distinct roles in modulating the conformational conversion.
Colorectal cancer (CRC) is a major contributor to cancer death globally. Several studies showed some protections by certain individual dietary antioxidants against CRC development. Epidemiologic data ...on the composite dietary antioxidant index (CDAI) in relation to CRC risk are sparse. Using the Singapore Chinese Health Study, an ongoing prospective cohort consisting of 61 321 cancer‐free participants aged 45 to 74 years at baseline, a food‐based CDAI was calculated according to a previously established and validated method that included six food‐sourced antioxidants including vitamins A, C and E, manganese, selenium and zinc. Cox proportional hazard regression method was used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) for CRC associated with various levels of CDAI with adjustment for multiple potential confounders. After an average of 17.5 years of follow‐up, 2140 participants developed CRC. HRs (95% CIs) of CRC for quartiles 2, 3 and 4 of CDAI were 0.94 (0.83‐1.07), 0.86 (0.75‐1.00) and 0.80 (0.66‐0.98), respectively, compared to the lowest quartile (Ptrend = .02). This inverse association between CDAI and CRC risk was more apparent in women or those without a history of diabetes, without family history of CRC, never smokers or overweight/obese individuals. However, none of the heterogeneity tests for the CDAI‐CRC risk association reached statistical significance. Our findings suggest that food‐based antioxidants may be beneficial for reducing the risk of CRC in the general population.
What's new?
Epidemiological studies on individual dietary antioxidants such as vitamins and minerals and the risk of colorectal cancer have produced inconsistent results. In this large prospective Asian cohort study, the authors apply a recently developed composite dietary antioxidant index (CDAI) that includes vitamins A, C and E, manganese, selenium and zinc. The analysis shows that a higher CDAI is associated with a lower risk of developing CRC overall. These findings support the notion that food‐based antioxidants may offer a beneficial effect and provide a potential strategy for the primary prevention of colorectal cancer.
The outbreak of coronavirus infectious disease-2019 (COVID-19) pneumonia raises the concerns of effective deactivation of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in medical ...wastewater by disinfectants. In this study, we evaluated the presence of SARS-CoV-2 viral RNA in septic tanks of Wuchang Cabin Hospital and found a striking high level of (0.5–18.7) × 103 copies/L after disinfection with sodium hypochlorite. Embedded viruses in stool particles might be released in septic tanks, behaving as a secondary source of SARS-CoV-2 and potentially contributing to its spread through drainage pipelines. Current recommended disinfection strategy (free chlorine ≥0.5 mg/L after at least 30 min suggested by World Health Organization; free chlorine above 6.5 mg/L after 1.5-h contact by China Centers for Disease Control and Prevention) needs to be reevaluated to completely remove SARS-CoV-2 viral RNA in non-centralized disinfection system and effectively deactivate SARS-CoV-2. The effluents showed negative results for SARS-CoV-2 viral RNA when overdosed with sodium hypochlorite but had high a level of disinfection by-product residuals, possessing significant ecological risks.
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•First report on disinfection performance for SARS-CoV-2 in medical wastewater•Incomplete removal of SARS-CoV-2 RNA under WHO guideline•High level of DBPs when SARS-CoV-2 is completed removed.
An approach for the preparation of boronated γ‐lactams via palladium‐catalyzed boryldifluoroalkylation of alkenes with α‐bromodifluoroacetamides was developed. This method exhibits good functional ...group tolerance. Various boronated products were obtained in moderate to good yields for 1 h. Mechanistic studies indicated that this reaction may involve an intramolecular radical cascade cyclization process.
Background
Nonalcoholic fatty liver disease (NAFLD) is a major contributor to the rising incidence of hepatocellular carcinoma (HCC). Magnesium is a major cation in cellular activities. ...Epidemiological data on magnesium level and its relation to HCC are sparse. This study aimed to examine the associations between serum levels of magnesium and the risk of HCC among patients with NAFLD.
Methods
A total of 26,053 patients with NAFLD were identified in the University of Pittsburgh Medical Center Electronic Health Records from 2004 through 2018. After an average of 5.15 years of follow‐up, 395 patients developed HCC after the first measurement of serum magnesium. Cox proportional hazards regression model was used to calculate hazard ratios (HRs) and 95% CIs of HCC incidence associated with quartile levels of serum magnesium after adjustment for age, sex, race, body mass index, diuretics use, history of type 2 diabetes, history of hypertension, history of hyperlipidemia, and tobacco smoking.
Results
Patients with NAFLD who developed HCC had a significantly lower mean (± standard deviation) serum magnesium (0.769 ± 0.131 mmol/L) than those who remained free of HCC (0.789 ± 0.125 mmol/L; p = .003). Compared with the lowest quartile, the HRs (95% CIs) of HCC second, third, and fourth quartiles of serum magnesium were 0.87 (0.67–1.12), 0.77 (0.57–1.04), and 0.73 (0.56–0.96), respectively, after adjustment for multiple potential confounders (P
trend = .02).
Conclusion
This finding suggests higher levels of serum magnesium were significantly associated with decreased risk of HCC among patients with NAFLD.
Monitoring serum magnesium levels among those with nonalcoholic fatty liver disease may be beneficial in hepatocellular carcinoma primary prevention.
With the improvement in children's acute lymphoblastic leukemia (ALL) care, the survival rate in children ALL has improved much. Methotrexate (MTX) plays an essential role in the success of ...children's ALL treatment. Since hepatotoxicity is commonly reported in individuals treated with intravenous or oral MTX, our study further examined the hepatic effect following intrathecal MTX treatment, which is an essential treatment for leukemia patients. Specifically, we examined the pathogenesis of MTX hepatotoxicity in young rats and explored the impact of melatonin treatment in protection against MTX hepatotoxicity. Successfully, we found that melatonin was able to protect against MTX hepatotoxicity.
Summary
Distributed are common threats in many networks, where attackers attempt to make victim servers unavailable to other users by flooding them with worthless requests. These attacks cannot be ...easily stopped by firewalls, since they forge lots of connections to victims with various IP addresses. The paper aims to exploit the software‐defined networking (SDN) technique to defend against DDoS attacks. However, the controller has to handle lots of connections launched by DDoS attacks, which burdens it with a heavy load and degrades SDN's performance. Therefore, the paper proposes an efficient and low‐cost DDoS defense (ELD) mechanism for SDN. It adopts a nested reverse‐exponential data storage scheme to help the controller efficiently record the information of packets in the limited memory. Once there are many packets with high IP variability sent to a certain server and this situation lasts for a while, then a DDoS attack is likely happening. In this case, the controller asks switches to block malicious connections by installing flow rules. Experimental results verify that the ELD mechanism rapidly recognizes protocol‐based DDoS attacks and stops them in time, including TCP SYN flood, UDP flood, and ICMP flood, and also greatly reduces the overhead for the controller to defend against attacks. Moreover, ELD can distinguish DDoS flows from legitimate ones with similar features such as elephant flows and impulse flows, thereby eliminating false alarms.
We propose an efficient ELD mechanism to defend against DDoS attacks in SDN‐based networks. Simulation results show that ELD can fast identify and stop DDoS attacks while saving the controller's cost.
Microplastics, defined as particles <5 mm in diameter, are emerging environmental pollutants that pose a threat to ecosystems and human health. Biofilm degradation of microplastics may be an ...ecologically friendly approach. This review systematically summarises the factors affecting biofilm degradation of microplastics and proposes feasible methods to improve the efficiency of microplastic biofilm degradation. Environmentally insensitive microorganisms were screened, optimized, and commercially cultured to facilitate the practical application of this technology. For strain screening, technology should focus on microorganisms/strains that can modify the hydrophobicity of microplastics, degrade the crystalline zone of microplastics, and metabolise additives in microplastics. The biodegradation mechanism is also described; microorganisms secreting extracellular oxidases and hydrolases are key factors for degradation. Measuring the changes in molecular weight distribution (MWD) enables better analysis of the biodegradation behaviour of microplastics. Biofilm degradation of microplastics has relatively few applications because of its low efficiency; however, enrichment of microplastics in freshwater environments and wastewater treatment plant tailwater is currently the most effective method for treating microplastics with biofilms.
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•The rate and quality of biofilm formation on the surface of microplastics affect the degradation of microplastics.•Measuring changes in molecular weight distribution can provide a better understanding of biodegradation behavior.•The strains in biofilms that play a role in the degradation of microplastics can be screened and optimized for commercial cultivation.•Biofilms can be applied to the in situ treatment of microplastics in freshwater environments.
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•67 Brazilian coffees were analyzed for their δ13C, δ18O, δ2H and δ15N signatures.•Organic coffee presented higher δ15N values.•k-Nearest neighbors was not efficient in classifying ...coffees from different sites.•Support vector machines correctly classified coffees from São Paulo.•Linear discriminant analysis correctly classified conventional coffees.
Authentication of ground coffee has become an important issue because of fraudulent activities in the sector. In the current work, sixty-seven Brazilian coffees produced in different geographical origins using organic (ORG, n = 25) and conventional (CONV, n = 42) systems were analyzed for their stable isotope ratios (δ13C, δ18O, δ2H, and δ15N). Data were analyzed by inferential analysis to compare the factors whereas linear discriminant analysis (LDA), k-nearest neighbors (k-NN), and support vector machines (SVM) were used to classify the coffees based on their origin. ORG and CONV cultivated coffees could not be differentiated according to C stable isotope ratio (δ13C; p = 0.204), but ORG coffees presented higher values of the N stable isotope ratio (δ15N; p = 0.0006). k-NN presented the best classification results for both ORG and CONV coffees (87% and 67%, respectively). SVM correctly classified coffees produced in São Paulo (75% accuracy), while LDA correctly classified 71% of coffees produced in Minas Gerais.
Perfluorodecanoic acid (PFDA) is a highly toxic food contaminant that is extensively used in food applications as surface antifouling agent. In this present study, we aimed to assess whether green ...tea polyphenols (GTPs) and epigallocatechin-3-gallate (EGCG) exert protective effects against PFDA-induced liver damage and inflammation in mice. A mouse model to evaluate liver toxicity was established by giving mice drinking water containing different concentrations of PFDA. GTPs or EGCG (0.32%, w/v) were co-administered to mice exposed to PFDA in drinking water. Overall, GTPs and EGCG extended the survival time and inhibited weight loss among mice who received a lower dose of PFDA. Moreover, GTPs and EGCG ameliorated hepatic oxidative stress, cell apoptosis, necrosis, steatosis, edema, and degeneration, reduced hepatic inflammation and NLRP3 inflammasome activation caused by a moderate dose of PFDA. Taken together, these results show that GTPs or EGCG (or green tea intake) supplements can be beneficial for people exposed to PFDA.
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•GTPs and EGCG reduced mortality of mice exposed to PFDA•GTPs extended survival time and inhibited weight loss among mice caused by PFDA.•GTPs and EGCG ameliorated PFDA-induced liver toxicity and inflammation.•GTPs and EGCG inhibited PFDA-induced NLRP3 inflammasome activation.
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