Stress granules (SGs) are nonmembranous organelles that are dynamically assembled and disassembled in response to various stressors. Under stressed conditions, polyadenylated mRNAs and translation ...factors are sequestrated in SGs to promote global repression of protein synthesis. It has been previously demonstrated that SG formation enhances cell survival and stress resistance. However, the physiological role of SGs in organismal aging and longevity regulation remains unclear. In this study, we used TIAR‐1::GFP and GTBP‐1::GFP as markers to monitor the formation of SGs in Caenorhabditis elegans. We found that, in addition to acute heat stress, SG formation could also be triggered by dietary changes, such as starvation and dietary restriction (DR). We found that HSF‐1 is required for the SG formation in response to acute heat shock and starvation but not DR, whereas the AMPK‐eEF2K signaling is required for starvation and DR‐induced SG formation but not heat shock. Moreover, our data suggest that this AMPK‐eEF2K pathway‐mediated SG formation is required for lifespan extension by DR, but dispensable for the longevity by reduced insulin/IGF‐1 signaling. Collectively, our findings unveil a novel role of SG formation in DR‐induced longevity.
In addition to heat stress, starvation and dietary restriction (DR) can activate stress granule (SG) formation in Caenorhabditis elegans. HSF‐1 and AMPK are two key regulators for the SG formations. HSF‐1 is required for the SG formation in response to acute heat shock and starvation but not DR, whereas the AMPK‐eEF2K pathway is required for starvation and DR‐induced SG formation but not heat shock. Furthermore, AMPK‐mediated SG formation contributes to DR‐induced longevity.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
A new perovskite‐like coordination polymer (CH3)2NH2Cd(N3)3 is reported which undergoes a reversible ferroelastic phase transition. This transition is due to varied modes of motion of the (CH3)2NH2+ ...guest accompanied by a synergistic deformation of the Cd(N3)3− framework. The unusual two‐staged switchable dielectric relaxation reveals the molecular dynamics of the polar cation guest, which are well controlled by the variable confined space of the host framework. As the material switches from the ferroelastic phase to the paraelastic phase, a remarkable increase of the rotational energy barrier is detected. As a result, upon heating at low temperature, this compound shows a notable change from a low to a high dielectric state in the ferroelastic phase. This thermoresponsive host–guest system may serve as a model compound for the development of sensitive thermoresponsive dielectric materials and may be key to understanding and modulating molecular/ionic dynamics of guest molecules in confined space.
Flexible frameworks: A perovskite‐like coordination polymer (CH3)2NH2Cd(N3)3 undergoes a ferroelastic‐to‐paraelastic phase transition as a result of the motion of the guest cation within the host framework (see picture), which itself undergoes a simultaneous deformation. This material acts as a thermoresponsive dielectric system owing to the well‐controlled guest molecular dynamics in the confined space.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Aim
The policy enforcing visiting restriction during the COVID‐19 pandemic may cause feelings of social isolation among residents in long‐term care facilities. This study aimed to explore family ...members' concerns for their relatives during the lockdown period, assess their level of acceptance of the visiting restriction policy and determine the associated factors.
Methods
From the 156 family members interviewed, demographic data, satisfaction with overall care quality, worry and concerns for their relatives, acceptance of the visiting restriction and arrangement for the residents if cluster infections occur in the facility were recorded.
Results
Among the members interviewed, 83 (53.2%) were men; mean age of members was 56.3 ± 9.8; most were offspring of residents in the facility (n = 121, 77.6%), most visited the residents at least once a week (n = 113, 72.4%) before the lockdown. The most common concerns of the family members for their relatives were psychological stress (38.5%), followed by nursing care (26.9%) and daily activity (21.1%). Nearly 84.6% of those interviewed accepted the visiting restriction policy, and a higher satisfaction rating independently associated with acceptance of the visiting restriction policy (odds ratio 2.15).
Conclusions
During the lockdown period, staff members should provide more psychological information about residents to their family members. Higher satisfaction rating was found to be independent of the acceptance of the visiting restriction policy. Therefore, good quality of care of the facility wins the trust of family members, and this might mitigate the tension between the family members and staff during a major crisis. Geriatr Gerontol Int ••; ••: ••–•• Geriatr Gerontol Int 2020; 20: 938–942.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Herein, a new Zn-MOF material, Zn(
)(
),
, was built successfully through a one-pot solvothermal method. The 3D MOF structure was determined by Single X-ray diffraction analysis, IR, and elemental ...analysis. A series of PXRD tests of
after being immersed in different solvents and pH solutions demonstrated the good stability of
. Interestingly, this material displayed high catalytic activity for the visible-light-driven hydrogen generation under the illumination of white LED in pure water or a mixture of DMF and H
O without additional photosensitizers and cocatalysts. Besides, the studies also showed that the catalytic activity changed constantly as well as the solvent ratio adjustment of DMF and H
O from 4:6 to 2:8. Additionally, the catalytic activity reached the best value (743 μmol g
h
) when the solvent ratio was 4:6. The heterogeneous nature and recyclability of the MOF catalyst, as well as several factors that affect the catalytic activity, were investigated and described in detail. Moreover, the photocatalytic mechanism for the hydrogen generation of
was also proposed based on the fluorescence spectra and UV-vis absorption.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A novel fluorescent probe was developed by integrating chlorinated coumarin and benzothiazolylacetonitrile and exploited for simultaneous detection of cysteine (Cys), homocysteine (Hcy), and ...glutathione (GSH). Featuring four binding sites and different reaction mechanisms for different biothiols, this probe exhibited rapid fluorescence turn‐on for distinguishing Cys, Hcy, and GSH with 108‐, 128‐, 30‐fold fluorescence increases at 457, 559, 529 nm, respectively, across different excitation wavelengths. Furthermore, the probe was successfully applied to the fluorescence imaging of endogenous Cys and GSH and exogenous Cys, Hcy, and GSH in living cells.
All together now: A novel fluorescent probe was developed for simultaneous sensing of cysteine (Cys), homocysteine (Hcy), and glutathione (GSH). Featuring four binding sites and different reaction mechanisms for different biothiols, this probe exhibited rapid fluorescence turn‐on for distinguishing Cys, Hcy, and GSH. The probe was successfully applied to the fluorescence imaging of endogenous Cys and GSH and exogenous Cys, Hcy, and GSH in living cells.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
ADH1B rs1229984 and ALDH2 rs671 are the specifically prevalent functional variants in the East Asians. These variants, which result in a dramatic change in enzyme activity, are highly ...associated with alcohol‐related disorders and cancer. Previous studies focusing on the additive and synergic effects of the variants are few and inconsistent. The aim of the research was to evaluate the associations of ADH1B rs1229984 and ALDH2 rs671 with the risks of alcohol‐related disorder and cancer.
Methods
This cohort study enrolled 42,665 participants from the Taiwan Precision Medicine Initiative database, including 19,522 and 20,534, ADH1B and ALDH2 carriers, respectively. The associations between the two variants and cancer risk were analyzed by univariable and multivariable logistic regression.
Results
Compared with the noncarriers, the ADH1B rs1229984 variant had a stronger effect on alcohol‐related disorders and was related to an increased risk of alcohol‐related cancers. The CC genotype of ADH1B rs1229984 was significantly associated with cancer of the larynx, pharynx, and nasal cavities odds ratio (OR) = 1.56, p = 0.0009, cancer of the pancreas (OR = 1.66, p = 0.018), and cancer of the esophagus (OR = 4.10, p < 0.001). Participants who carried the rs1229984 TC/CC and rs671 GG genotypes were at higher risk of esophageal cancer (OR = 3.02, p < 0.001). The risk of esophageal cancer was increased by 381% (OR = 4.81, p < 0.001) in those carrying the rs1229984 TC/CC and rs671 GA/AA genotypes.
Conclusion
rs1229984 and rs671 are common and functionally important genetic variants in the Taiwanese population. Our findings provide strong evidence of additive and synergic risks of ADH1B and ALDH2 variants for alcohol‐related disorders and cancer. The results suggested that are reduction in alcohol consumption should be advised as a preventive measure for high‐risk patients carrying ADH1B rs1229984 C or the ALDH2 rs671 A allele.
Figure. The Flow char for selection of the study population (A), and the PheWAS Manhattan and QQ plots for ADH1B rs1229984 (B) and ALDH2 rs671 (C), respectively Brief Summary Our findings provide evidence of additive and synergic risks of the ADH1B and ALDH2 variants for alcohol‐related disorder and cancer. These results suggested that reduction of alcohol consumption should be advised as a preventive measure for high‐risk patients carrying the ADH1B rs1229984 C or the ALDH2 rs671 A allele.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Lenvatinib and atezolizumab plus bevacizumab(A + B) have been used for unresectable hepatocellular carcinoma (HCC) as first‐line therapy. Real‐world studies comparison of efficacy and ...safety in these two regimens are limited, we therefore conduct this study to investigate these issues.
Methods
We retrospectively reviewed patients received lenvatinib (n = 46) and A + B (n = 46) as first‐line systemic therapy for unresectable HCC in a tertiary medical center. Objective response rate (ORR), progression free survival (PFS), and overall survival (OS) were evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Inverse probability weighting (IPW) was performed for baseline clinical features balance.
Results
A total of 92 patients with median age of 63.8 year‐old, 78.3% male, 85.9% viral hepatitis infected, 67.4% BCLC stage C were enrolled. The median treatment and follow‐up duration were 4.7 months and 9.4 months, respectively. There was no significant difference in ORR (26.1% vs. 41.3%, p = 0.1226), PFS (5.9 vs. 5.3 months, p = 0.4066), and OS (not reached vs. not reached, p = 0.7128) between the lenvatinib and A + B groups. After IPW, the results of survival and response rate were also compared. Subgroup analysis suggested that using lenvatinib was not inferior to A + B in regards of PFS, including those with elder, Child‐Pugh class B, beyond up‐to‐seven, or portal vein invasion VP4 patients. Among the lenvatinib treated patients, multivariate analysis showed patients elder than 65‐year‐old was an independent predictor associated with shorter PFS (adjust HR: 2.0850.914–4.753, p = 0.0213). The incidence rates of adverse events were similar between two groups (76 vs. 63%, p = 0.1740). Both of two regimens had similarly few impact on liver function by comparison of baseline, third month, and sixth month albumin‐bilirubin index and Child‐Pugh score.
Conclusions
The efficacy and safety of lenvatinib are similar to A + B as a first‐line systemic therapy for unresectable HCC.
This study provides real‐world experience of lenvatinib and A + B as firstline treatment for unresectable HCC. The data showed that compared survival, response rate, and adverse events between two regimens.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Photocatalysis is a promising and sustainable technology in the fields of energy conversion/storage and environment purification; however, the utilization of individual component as photocatalyst is ...generally restricted due to the low catalytic activity deriving from the rapid recombination of photogenerated electrons/holes. Covalent organic framework (COF)‐semiconductor‐based composite photocatalysts with synergistic effects provide a feasible route to achieve high‐performance photocatalytic reactions with more active sites, strong light utilization ability, and high stability. In recent years, significant progress has been made in the rational design and preparation of the COF‐semiconductors‐based heterostructures for photocatalytic water splitting, carbon dioxide (CO2) reduction, and dye/pollutant degradation. In this Review, the synthetic strategies of COF‐semiconductor‐based heterostructures are first introduced, which includes the rational design of the morphology, connection modes, and type of heterojunctions. The performance of COF‐semiconductor‐based heterostructures in different photocatalytic reactions are comprehensively reviewed. The structure‐activity relationship and the synergistic effects within the heterostructures are discussed, and the photocatalytic mechanism and the role of COFs during the photocatalytic process are also presented. Finally, an outlook and challenges of realizing COF‐semiconductor‐based heterostructures with simple synthesis methods, diverse functions, high performance, and well‐defined reaction mechanisms are provided.
In this Review, we comprehensively reviewed the synthesis strategies of covalent organic framework (COF)‐semiconductor‐based heterostructures, and their photocatalytic performance in various reactions such as water splitting, CO2 reduction, and dye/pollutant degradation. Some viewpoints on the structure‐activity relationship, synergistic effects, and the photocatalytic mechanisms were also provided.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
We have collected 10,025 foreground–background quasar pairs with projected distances
d
p
< 500 kpc from the large quasar catalog of the Sloan Digital Sky Survey DR16Q. We investigate the ...properties of the Mg
ii
absorption lines with
W
r
> 0.15 Å around foreground quasars, including both the line of sight (LOS; of foreground quasars) and transverse (TRA; perpendicular to the LOS) absorptions. Both the equivalent width (the correlation coefficient
ρ
= −0.915 and the probability
P
< 10
−4
of no correlation) and incident rate (
ρ
= −0.964 and
P
< 10
−6
) of TRA Mg
ii
absorption lines are obviously anticorrelated with projected distance. The incident rate of TRA Mg
ii
absorption lines is obviously (>4
σ
) greater than that of LOS Mg
ii
absorption lines at projected distances
d
p
< 200 kpc, while the TRA and LOS Mg
ii
both have similar (<3
σ
) incident rates at scales
d
p
> 200 kpc. The anisotropic radiation from quasars would be the most possible interpretation for the anisotropic absorption around quasars. This could also indicate that the quasar radiation is not obviously impacting the gas halos of quasars at scales
d
p
> 200 kpc.
Abstract
Pulmonary fibrosis (PF) is a major public health problem with limited therapeutic options. There is a clear need to identify novel mediators of PF to develop effective therapeutics. Here we ...show that an ER protein disulfide isomerase, thioredoxin domain containing 5 (TXNDC5), is highly upregulated in the lung tissues from both patients with idiopathic pulmonary fibrosis and a mouse model of bleomycin (BLM)-induced PF. Global deletion of
Txndc5
markedly reduces the extent of PF and preserves lung function in mice following BLM treatment. Mechanistic investigations demonstrate that TXNDC5 promotes fibrogenesis by enhancing TGFβ1 signaling through direct binding with and stabilization of TGFBR1 in lung fibroblasts. Moreover, TGFβ1 stimulation is shown to upregulate TXNDC5 via ER stress/ATF6-dependent transcriptional control in lung fibroblasts. Inducing fibroblast-specific deletion of
Txndc5
mitigates the progression of BLM-induced PF and lung function deterioration. Targeting TXNDC5, therefore, could be a novel therapeutic approach against PF.
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