Identifying patients at high risk of diabetic kidney disease (DKD) helps improve clinical outcome.
To establish a model for predicting DKD.
The derivation cohort was from a meta-analysis. The ...validation cohort was from a Chinese cohort.
Cohort studies that reported risk factors of DKD with their corresponding risk ratios (RRs) in patients with type 2 diabetes were selected. All patients had estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m
and urinary albumin-to-creatinine ratio (UACR) <30 mg/g at baseline.
Risk factors and their corresponding RRs were extracted. Only risk factors with statistical significance were included in our DKD risk prediction model.
Twenty cohorts including 41,271 patients with type 2 diabetes were included in our meta-analysis. Age, BMI, smoking, diabetic retinopathy, hemoglobin A
, systolic blood pressure, HDL cholesterol, triglycerides, UACR, and eGFR were statistically significant. All these risk factors were included in the model except eGFR because of the significant heterogeneity among studies. All risk factors were scored according to their weightings, and the highest score was 37.0. The model was validated in an external cohort with a median follow-up of 2.9 years. A cutoff value of 16 was selected with a sensitivity of 0.847 and a specificity of 0.677.
There was huge heterogeneity among studies involving eGFR. More evidence is needed to power it as a risk factor of DKD.
The DKD risk prediction model consisting of nine risk factors established in this study is a simple tool for detecting patients at high risk of DKD.
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•Bi2WO6/Fe2O3 heterojunctions were used to efficiently activate PDS under visible light.•Simultaneous rapid degradation and mineralization of tetracycline were achieved.•The ...constructed system exhibited good stability and a wide range of pH values.•Multiple tools were adopted for an in-depth dissection of the reaction mechanism.•The removal pathways and toxicity of the formed intermediates were carefully studied.
Heterogeneous iron materials show potential for activating peroxydisulfate (PDS). However, these systems may be constrained by low efficiency and secondary pollution. The visible-light-assisted activation has been demonstrated as a feasible and effective approach to enhance PDS activation by iron-based materials. In this study, a visible-light-responsive Bi2WO6/Fe2O3 heterojunction photocatalyst was synthesized to improve the ability of Fe2O3 for PDS activation through an effective Fe(III)/Fe(II) cycle. Rapid tetracycline (TC, a common antibiotic) removal (91.7% within 60 min at a concentration of 20 mg·L-1) was achieved in the constructed Bi2WO6/Fe2O3/PDS/vis system under conditions of 0.3 g·L-1 PDS and 0.3 g·L-1 catalyst. The corresponding pseudo-first-order rate constant reached 4.16 × 10-2 min-1, which was 8.42 and 16.38 times higher than those of Bi2WO6/Fe2O3/vis and Bi2WO6/Fe2O3/PDS systems, respectively. Moreover, the Bi2WO6/Fe2O3 exhibited favorable stability and reusability even after five cycles. Lastly, a catalytic mechanism for TC removal and PDS activation was proposed based on quenching experiments and electron spin resonance (ESR) tests. The SO4•- and •OH played a major role in TC removal, while •O2– and 1O2 contributed as auxiliary factors. This study presents a promising strategy for activating PDS using cost-effective and stable Fe(III)-based heterojunctions, and such an idea can be used to design catalysts for other high-value reactions.
The palladium-catalysed allylic substitution reaction is one of the most important reactions in transition-metal catalysis and has been well-studied in the past decades. Most of the reactions proceed ...through an outer-sphere mechanism, affording linear products when monosubstituted allyl reagents are used. Here, we report an efficient Palladium-catalysed protocol for reactions of β-substituted ketones with monosubstituted allyl substrates, simply by using N-heterocyclic carbene as ligand, leading to branched products with up to three contiguous stereocentres in a (syn, anti)-mode with excellent regio and diastereoselectivities. The scope of the protocol in organic synthesis has been examined preliminarily. Mechanistic studies by both experiments and density functional theory (DFT) calculations reveal that the reaction proceeds via an inner-sphere mechanism-nucleophilic attack of enolate oxygen on Palladium followed by C-C bond-forming 3,3'-reductive elimination.
Mitochondria are promising targeting organelles for anticancer strategies; however, mitochondria are difficult for antineoplastic drugs to recognize and bind. Mitochondria-penetrating peptides (MPPs) ...are unique tools to gain access to the cell interior and deliver a bioactive cargo into mitochondria. MPPs have combined or delivered a variety of antitumor cargoes and obviously inhibited the tumor growth in vivo and in vitro. MPPs create new opportunities to develop new treatments for cancer. Areas covered: We review the target sites of mitochondria and the target-penetration mechanism of MPPs, different strategies, and various additional strategies decorated MPPs for tumor cell mitochondria targeting, the decorating mattes including metabolism molecules, RNA, DNA, and protein, which exploited considered as therapeutic combined with MPPs and target in human cancer treatment. Expert opinion/commentary: Therapeutic selectivity that preferentially targets the mitochondrial abnormalities in cancer cells without toxic impact on normal cells still need to be deepen. Moreover, it needs appropriate study designs for a correct evaluation of the target delivery outcome and the degradation rate of the drug in the cell. Generally, it is optimistic that the advances in mitochondrial targeting drug delivery by MPPs plasticity outlined here will ultimately help to the discovery of new approaches for the prevention and treatment of cancers.
Background. During 2014–2015, an outbreak of Ebola virus disease (EVD) swept across parts of West Africa. No approved antiviral drugs are available for Ebola treatment currently. Methods. A ...retrospective clinical case series was performed for EVD patients in Sierra Leone–China Friendship Hospital. Patients with confirmed EVD were sequentially enrolled and treated with either World Health Organization (WHO)–recommended supportive therapy (control group) from 10 to 30 October, or treated with WHO-recommended therapy plus favipiravir (T-705) from 1 to 10 November 2014. Survival and virological characteristics were observed for 85 patients in the control group and 39 in the T-705 treatment group. Results. The overall survival rate in the T-705 treatment group was higher than that of the control group (56.4% 22/39 vs 35.3% 30/85; P = .027). Among the 35 patients who finished all designed endpoint observations, the survival rate in the T-705 treatment group (64.8% 11/17) was higher than that of the control group (27.8% 5/18). Furthermore, the average survival time of the treatment group (46.9 ± 5.6 days) was longer than that of the control group (28.9 ± 4.7 days). Most symptoms of patients in the treatment group improved significantly. Additionally, 52.9% of patients who received T-705 had a >100-fold viral load reduction, compared with only 16.7% of patients in the control group. Conclusions. Treatment of EVD with T-705 was associated with prolonged survival and markedly reduced viral load, which makes a compelling case for further randomized controlled trials of T-705 for treating EVD.
Abstract
Background
The blood clam, Scapharca (Anadara) broughtonii, is an economically and ecologically important marine bivalve of the family Arcidae. Efforts to study their population genetics, ...breeding, cultivation, and stock enrichment have been somewhat hindered by the lack of a reference genome. Herein, we report the complete genome sequence of S. broughtonii, a first reference genome of the family Arcidae.
Findings
A total of 75.79 Gb clean data were generated with the Pacific Biosciences and Oxford Nanopore platforms, which represented approximately 86× coverage of the S. broughtonii genome. De novo assembly of these long reads resulted in an 884.5-Mb genome, with a contig N50 of 1.80 Mb and scaffold N50 of 45.00 Mb. Genome Hi-C scaffolding resulted in 19 chromosomes containing 99.35% of bases in the assembled genome. Genome annotation revealed that nearly half of the genome (46.1%) is composed of repeated sequences, while 24,045 protein-coding genes were predicted and 84.7% of them were annotated.
Conclusions
We report here a chromosomal-level assembly of the S. broughtonii genome based on long-read sequencing and Hi-C scaffolding. The genomic data can serve as a reference for the family Arcidae and will provide a valuable resource for the scientific community and aquaculture sector.
Stimulator of interferon genes (STING) activation induces type I interferons and pro-inflammatory cytokines which stimulate tumor antigen cross presentation and the adaptive immune responses against ...tumor. The first-generation of STING agonists, cyclic di-nucleotide (CDN), mimicked the endogenous STING ligand cyclic guanosine monophosphate adenosine monophosphate, and displayed limited clinical efficacy. Here we report the discovery of SHR1032, a novel small molecule non-CDN STING agonist. Compared to the clinical CDN STING agonist ADU-S100, SHR1032 has much higher activity in human cells with different STING haplotypes and robustly induces interferon β (IFNβ) production. When dosed intratumorally, SHR1032 induced strong anti-tumor effects in the MC38 murine syngeneic tumor model. Pharmacodynamic studies showed induction of IFNβ, tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) in the tumors and, to a lower extent, in the plasma. More importantly, we found SHR1032 directly causes cell death in acute myeloid leukemia (AML) cells. In conclusion, our findings demonstrate that in addition to their established ability to boost anti-tumor immune responses, STING agonists can directly eradicate AML cells, and SHR1032 may present a new and promising therapeutic agent for cancer patients.
The blood-brain barrier (BBB), a dynamic and complex barrier formed by endothelial cells, can impede the
entry of unwanted substances – pathogens and therapeutic molecules alike – into the central ...nervous system (CNS) from
the blood circulation. Taking into account the fact that CNS-related diseases are the largest and fastest growing unmet
medical concern, many potential protein- and nucleic acid-based medicines have been developed for therapeutic purposes.
However, due to their poor ability to cross the BBB and the plasma membrane, the above-mentioned bio-macromolecules
have limited use in treating neurological diseases. Finding effective, safe, and convenient ways to deliver therapeutic
molecules into the CNS is thus urgently required. In recent decades, much effort has been expended in the development of
drug delivery technologies, of which cell-penetrating peptides (CPPs) have the most promising potential. The present
review covers the latest advances in CPP delivery technology, and provides an update on their use in CNS-targeted drug
delivery.
There are numerous articles published for geographical discrimination of tea. However, few research works focused on the authentication and traceability of Westlake Longjing green tea from the first‐ ...and second‐grade producing regions because the tea trees are planted in a limited growing zone with identical cultivate condition. In this work, a comprehensive analytical strategy was proposed by ultrahigh performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry‐based untargeted metabolomics coupled with chemometrics. The automatic untargeted data analysis strategy was introduced to screen metabolites that expressed significantly among different regions. Chromatographic features of metabolites can be automatically and efficiently extracted and registered. Meanwhile, those that were valuable for geographical origin discrimination were screened based on statistical analysis and contents in samples. Metabolite identification was performed based on high‐resolution mass values and tandem mass spectra of screened peaks. Twenty metabolites were identified, based on which the two‐way encoding partial least squares discrimination analysis was built for geographical origin prediction. Monte Caro simulation results indicated that prediction accuracy was up to 99%. Our strategy can be applicable for practical applications in the quality control of Westlake Longjing green tea.
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