The relationships between dietary protein intake and risk of all-cause, cardiovascular disease (CVD), and cancer mortality are still unclear. We conducted a systematic review with meta-analysis of ...cohort studies to summarize the evidence.
We searched PubMed and Web of Science for relevant studies through February 2020. The associations of total, animal, and plant proteins with all-cause, CVD, and cancer mortality were evaluated. Study-specific relative risks (RR) were pooled using the fixed effect model when no significant heterogeneity was detected; otherwise the random effect model was employed. Twelve cohort studies were eligible for the study. Increased total protein showed no clear association with risk of all-cause, CVD, and cancer mortality. In the stratified analysis by protein sources, higher plant protein intake was associated with a reduced risk of all-cause mortality (highest vs lowest intake: RR = 0.92; 95% CI: 0.88, 0.96; each 3% increment of intake: RR = 0.97; 95% CI: 0.94, 0.99), and may be associated with a reduced risk of CVD mortality (highest vs lowest intake: RR = 0.90; 95% CI: 0.80, 1.01; each 3% increment of intake: RR = 0.95; 95% CI: 0.91, 0.99). Moreover, higher intake of animal protein may be associated with an increased risk of CVD mortality (highest vs lowest intake: RR = 1.11; 95% CI: 1.01, 1.22; each 3% increment of intake: RR = 1.02; 95% CI: 0.98, 1.06).
This study demonstrates that higher plant protein intake is associated with a reduced risk of all-cause and CVD-related mortality. Persons should be encouraged to increase their plant protein intake to potentially decrease their risk of death.
•Different protein sources rather than total protein relate to a person's death risk.•Plant protein intake was associated with a reduced risk of all-cause and CVD mortality.•Animal protein intake may be associated with an increased risk of CVD mortality.•Persons may be encouraged to increase plant protein intake to lower their death risk.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Metastatic non-small cell lung cancer (NSCLC) remains largely incurable and the prognosis is extremely poor once it spreads to the brain. In particular, in patients with brain metastases, the blood ...brain barrier (BBB) remains a significant obstacle for the biodistribution of antitumor drugs and immune cells. Here we report that chimeric antigen receptor (CAR) T cells targeting B7-H3 (B7-H3.CAR) exhibit antitumor activity in vitro against tumor cell lines and lung cancer organoids, and in vivo in xenotransplant models of orthotopic and metastatic NSCLC. The co-expression of the CCL2 receptor CCR2b in B7-H3.CAR-T cells, significantly improves their capability of passing the BBB, providing enhanced antitumor activity against brain tumor lesions. These findings indicate that leveraging T-cell chemotaxis through CCR2b co-expression represents a strategy to improve the efficacy of adoptive T-cell therapies in patients with solid tumors presenting with brain metastases.
Abstract
Chiral aldehyde catalysis is a burgeoning strategy for the catalytic asymmetric α-functionalization of aminomethyl compounds. However, the reaction types are limited and to date include no ...examples of stereodivergent catalysis. In this work, we disclose two chiral aldehyde-catalysed diastereodivergent reactions: a 1,6-conjugate addition of amino acids to
para
-quinone methides and a bio-inspired Mannich reaction of pyridinylmethanamines and imines. Both the
syn
- and
anti
-products of these two reactions can be obtained in moderate to high yields, diastereo- and enantioselectivities. Four potential reaction models produced by DFT calculations are proposed to explain the observed stereoselective control. Our work shows that chiral aldehyde catalysis based on a reversible imine formation principle is applicable for the α-functionalization of both amino acids and aryl methylamines, and holds potential to promote a range of asymmetric transformations diastereoselectively.
Self‐powered photodetectors are considered as a new type of photodetectors enabling self‐powered photodetection without external power. The excellent photoresponsivity, fast photoresponse rate, low ...dark current, and large light on/off ratio of these photodetectors have attracted wide interest among scholars. 2D materials are widely used in self‐powered photodetectors due to their excellent optical and electrical properties, unique 2D structures, and their capabilities to exhibit excellent photodetection performance. According to the self‐driving mechanism of 2D material‐based self‐powered photodetectors, they are divided into three categories: p–n junction photodetectors, Schottky junction photodetectors, and photoelectrochemical photodetectors. From these three perspectives, the research progress of 2D material‐based self‐powered photodetectors is summarized in detail here. Research reports indicate that 2D material‐based self‐powered photodetectors have excellent self‐powered photoresponse behavior, good light on/off characteristics, and wideband spectral response ranges. The excellent photoresponse performance of 2D material‐based self‐powered photodetectors facilitates their potential applications in the field of optoelectronic devices. In particular, self‐powered photodetectors have great potential as novel emerging self‐driven optoelectronic devices. Finally, directions for the further development of 2D material‐based self‐powered photodetectors are anticipated.
According to the self‐driving mechanism of 2D material‐based self‐powered photodetectors, they are divided into three categories: p–n junction photodetectors, Schottky junction photodetectors, and photoelectrochemical‐type photodetectors. Here, the research progress of 2D material‐based self‐powered photodetectors is reviewed from these three aspects.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Macrophage infiltration plays an important role in the progression of diabetic nephropathy (DN). Previously, we demonstrated that highglucose‐stimulated macrophage‐derived exosomes (HG‐exo) induces ...proliferation and extracellular matrix accumulation in glomerular mesangial cells, but its effect on tubular cells is unclear. This study aimed to explore the role of HG‐exo on renal tubular injury in DN. The results show that HG‐exo could induce dysfunction, autophagy inhibition, and inflammation in mouse tubular epithelial cell (mTEC) and C57 mouse kidney. Moreover, miR‐7002‐5p was differentially expressed in HG‐exo based on miRNAs sequencing and bioinformatics analysis. A dual‐luciferase reporter assay confirmed that Atg9b was the direct target gene of miR‐7002‐5p. Further experimentation showed that miR‐7002‐5p inhibition in vivo and vitro reserves HG‐exo effects. These results demonstrated that HG‐exo carries excessive miR‐7002‐5p and inhibits autophagy through targeting Atg9b; this process then induces renal tubular dysfunction and inflammation. In conclusion, our study clarifies the important role of macrophage‐derived exosomes in DN and is expected to provide new insight on DN prevention and treatment.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Large‐size 2D black phosphorus (BP) nanosheets have been successfully synthesized by a facile liquid exfoliation method. The as‐prepared BP nanosheets are used to fabricate electrodes for a ...self‐powered photodetector and exhibit preferable photoresponse activity as well as environmental robustness. Photoelectrochemical (PEC) tests demonstrate that the current density of BP nanosheets can reach up to 265 nA cm−2 under light irradiation, while the dark current densities fluctuate near 1 nA cm−2 in 0.1 M KOH. UV–vis and Raman spectra are carried out and confirm the inherent optical and physical properties of BP nanosheets. In addition, the cycle stability measurement exhibits no detectable distinction after processing 50 and 100 cycles, while an excellent on/off behavior is still preserved even after one month. Furthermore, the PEC performance of BP nanosheets‐based photodetector is evaluated in various KOH concentrations, which demonstrates that the as‐prepared BP nanosheets may have a great potential application in self‐powered photodetector. It is anticipated that the present work can provide fundamental acknowledgement of the performance of a PEC‐type BP nanosheets‐based photodetector, offering extendable availabilities for 2D BP‐based heterostructures to construct high‐performance PEC devices.
2D black phosphorus (BP) nanosheets are fabricated as self‐powered photodetector in KOH electrolyte. The photoelectrochemical tests demonstrate that BP nanosheets achieve preferable photoresponse activity as well as environmental robustness. Besides this, the photoresponse performance of BP nanosheets can be further optimized by adjusting KOH concentrations. This work presents a fundamental acknowledgement of the photoresponsivity of BP nanosheets for self‐powered photodetecting.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Anecdote clinical observations hint that non‐small cell lung cancer (NSCLC) with exon‐20 insertions might respond poorly to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), ...contrasting to those with classic mutations. Lack of patient‐derived experimental models has been a major hurdle for the discovery of new treatment for the diseases. We established two NSCLC‐PDXs harboring two different exon‐20 insertions, LU0387‐adenocarcinoma (ADC) with a nine‐base insertion at 2319 (H773‐V774insNPH) and LU3075‐squamous cell carcinoma (SCC) with a nine‐base insertion at 2316 (P772‐H773insDNP). Both insertions immediately follow the regulatory C‐helix of the kinase domain. Contrary to the generally good responses to EGFR inhibitors observed in PDXs with classic mutations, both exon‐20 insertions are largely resistant to cetuximab and TKIs in vivo, suggesting fundamental difference from the classic EGFR mutations, consistent with the poor response rate to TKI seen in anecdotal clinic reports. It is worth noting that although responses are generally poor, they differ between the two exon‐20 mutants depending on the type of TKI. In vitro drug sensitivity assays using established primary cell lines from our two PDXs largely confirmed the in vivo data. Our data from patient‐derived experimental models confirmed that exon‐20 insertions in domain immediately following the C‐helix confer poor response to all known EGFR inhibitors, and suggested that these models can be utilized to facilitate the discovery of new therapies targeting NSCLC harboring exon‐20 insertions.
What's new?
Anecdotal clinical observations suggest that, in contrast to classic mutations, non‐small cell lung cancers (NSCLCs) with exon‐20 insertions respond poorly to EGFR tyrosine kinase inhibitors. The lack of patient‐derived experimental models, however, has been a major hurdle for the discovery of new treatments. Here, the authors report establishing for the first time two NSCLC‐patient derived xenografts with two different exon‐20 insertions, both of them following the C‐helix domain. The data confirm that such exon‐20 insertions confer poor response to all known EGFR inhibitors. The models may be used to facilitate the discovery of new therapies targeting NSCLCs harboring exon‐20 insertions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Tumor microenvironment (TME) is a complex dynamic system with many tumor-interacting components including tumor-infiltrating leukocytes (TILs), cancer associated fibroblasts, blood vessels, and other ...stromal constituents. It intrinsically affects tumor development and pharmacology of oncology therapeutics, particularly immune-oncology (IO) treatments. Accurate measurement of TME is therefore of great importance for understanding the tumor immunity, identifying IO treatment mechanisms, developing predictive biomarkers, and ultimately, improving the treatment of cancer. Here, we introduce a mouse-IO NGS-based (NGSmIO) assay for accurately detecting and quantifying the mRNA expression of 1080 TME related genes in mouse tumor models. The NGSmIO panel was shown to be superior to the commonly used microarray approach by hosting 300 more relevant genes to better characterize various lineage of immune cells, exhibits improved mRNA and protein expression correlation to flow cytometry, shows stronger correlation with mRNA expression than RNAseq with 10x higher sequencing depth, and demonstrates higher sensitivity in measuring low-expressed genes. We describe two studies; firstly, detecting the pharmacodynamic change of interferon-γ expression levels upon anti-PD-1: anti-CD4 combination treatment in MC38 and Hepa 1-6 tumors; and secondly, benchmarking baseline TILs in 14 syngeneic tumors using transcript level expression of lineage specific genes, which demonstrate effective and robust applications of the NGSmIO panel.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
► Antimicrobial peptides (AMPs) produced by several species including insects, other animals, micro organisms and synthesis, are a critical component of the natural defense system. ► With the growing ...problem of pathogenic organisms resistant to conventional antibiotics, especially with the emergence of NDM-1, there is increased interest in the pharmacological application of AMPs. ► They can protect against a broad array of infectious agents, such as bacteria, fungi, parasite, virus and cancer cells. ► AMPs have a good future in the application in pharmaceuticals industry and food additive.
Antimicrobial peptides (AMPs), which are produced by several species including insects, other animals, micro-organisms and synthesis, are a critical component of the natural defense system. With the growing problem of pathogenic organisms resistant to conventional antibiotics, especially with the emergence of NDM-1, there is increased interest in the pharmacological application of AMPs. They can protect against a broad array of infectious agents, such as bacteria, fungi, parasite, virus and cancer cells. AMPs have a very good future in the application in pharmaceuticals industry and food additive. This review focuses on the AMPs from different origins in these recent years, and discusses their various functions and relative mechanisms of action. It will provide some detailed files for clinical research of pharmaceuticals industry and food additive in application.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A highly efficient atom‐economic method for the preparation of chiral 3,3′‐bis(indolyl)methanes (3,3′‐BIMs) was developed. A chiral phosphoric acid (1 mol %) was found to promote the formation of ...structurally divers BIMs with quaternary stereogenic carbon centers in excellent yields with excellent enantioselectivities. Control experiments indicated that the simultaneous formation of two hydrogen bonds between the catalyst and the substrate was the key factor to obtain a good stereoselective outcome.
Dol‐ing out: The chiral Brønsted acid catalyzed Friedel–Crafts reaction of 3‐vinylindole with substituted indoles is an efficient method to build chiral 3,3′‐bis(indolyl)methanes (BIMs). Structurally divers BIMs with quaternary stereogenic carbon centers are produced in excellent yields with excellent enantioselectivities.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
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