Dysfunction of degradation machineries causes cancers, including hepatocellular carcinoma (HCC). Overexpression of cyclin D1 in HCC has been reported. We previously reported that autophagy ...preferentially recruits and degrades the oncogenic microRNA (miR)‐224 to prevent HCC. Therefore, in the present study, we attempted to clarify whether cyclin D1 is another oncogenic factor selectively regulated by autophagy in HCC tumorigenesis. Initially, we found an inverse correlation between low autophagic activity and high cyclin D1 expression in tumors of 147 HCC patients and three murine models, and these results taken together revealed a correlation with poor overall survival of HCC patients, indicating the importance of these two events in HCC development. We found that increased autophagic activity leads to cyclin D1 ubiquitination and selective recruitment to the autophagosome (AP) mediated by a specific receptor, sequestosome 1 (SQSTM1), followed by fusion with lysosome and degradation. Autophagy‐selective degradation of ubiquitinated cyclin D1 through SQSTM1 was confirmed using cyclin D1/ubiquitin binding site (K33‐238R) and phosphorylation site (T286A) mutants, lentivirus‐mediated silencing autophagy‐related 5 (ATG5), autophagy‐related 7 (ATG7), and Sqstm1 knockout cells. Functional studies revealed that autophagy‐selective degradation of cyclin D1 plays suppressive roles in cell proliferation, colony, and liver tumor formation. Notably, an increase of autophagic activity by pharmacological inducers (amiodarone and rapamycin) significantly suppressed tumor growth in both the orthotopic liver tumor and subcutaneous tumor xenograft models. Our findings provide evidence of the underlying mechanism involved in the regulation of cyclin D1 by selective autophagy to prevent tumor formation. Conclusion: Taken together, our data demonstrate that autophagic degradation machinery and the cell‐cycle regulator, cyclin D1, are linked to HCC tumorigenesis. We believe these findings may be of value in the development of alternative therapeutics for HCC patients. (Hepatology 2018;68:141‐154).
Pandemics have become more frequent and more complex during the twenty-first century. Posttraumatic stress disorder (PTSD) following pandemics is a significant public health concern. We sought to ...provide a reliable estimate of the worldwide prevalence of PTSD after large-scale pandemics as well as associated risk factors, by a systematic review and meta-analysis. We systematically searched the MedLine, Embase, PsycINFO, Web of Science, CNKI, WanFang, medRxiv, and bioRxiv databases to identify studies that were published from the inception up to August 23, 2020, and reported the prevalence of PTSD after pandemics including sudden acute respiratory syndrome (SARS), H1N1, Poliomyelitis, Ebola, Zika, Nipah, Middle Eastern respiratory syndrome coronavirus (MERS-CoV), H5N1, and coronavirus disease 2019 (COVID-19). A total of 88 studies were included in the analysis, with 77 having prevalence information and 70 having risk factors information. The overall pooled prevalence of post-pandemic PTSD across all populations was 22.6% (95% confidence interval (CI): 19.9-25.4%, I
: 99.7%). Healthcare workers had the highest prevalence of PTSD (26.9%; 95% CI: 20.3-33.6%), followed by infected cases (23.8%: 16.6-31.0%), and the general public (19.3%: 15.3-23.2%). However, the heterogeneity of study findings indicates that results should be interpreted cautiously. Risk factors including individual, family, and societal factors, pandemic-related factors, and specific factors in healthcare workers and patients for post-pandemic PTSD were summarized and discussed in this systematic review. Long-term monitoring and early interventions should be implemented to improve post-pandemic mental health and long-term recovery.
Abstract
Backgroud
The current diagnostic criteria for refractory
Mycoplasma pneumoniae
pneumonia (RMPP) among
Mycoplasma pneumoniae
Pneumonia (MPP) are insufficient for early identification, and ...potentially delayed appropriate treatment. This study aimed to develop an effective individualized diagnostic prediction nomogram for pediatric RMPP.
Methods
A total of 517 hospitalized children with MPP, including 131 with RMPP and 386 without RMPP (non-RMPP), treated at Lianyungang Maternal and Child Health Care Hospital from January 2018 to December 2021 were retrospectively enrolled as a development (modeling) cohort to construct an RMPP prediction nomogram. Additionally, 322 pediatric patients with MPP (64 with RMPP and 258 with non-RMPP, who were treated at the Affiliated Hospital of Xuzhou Medical University from June 2020 to May 2022 were retrospectively enrolled as a validation cohort to assess the prediction accuracy of model. Univariable and multivariable logistic regression analyses were used to identify RMPP risk factors among patients with MPP. Nomogram were generated based on these risk factors using the rms package of R, and the predictive performance was evaluated based on receiver operating characteristic (ROC) curves and using decision curve analysis (DCA).
Results
Multivariate analysis revealed five significant independent predictors of RMPP among patients with MPP: age (hazard ratio
HR
1.16, 95% confidence interval
CI
1.08–1.33,
P
= 0.038), fever duration (
HR
1.34, 95%
CI
1.20–1.50,
P
< 0.001), lymphocyte count (
HR
0.45, 95%
CI
0.23–0.89,
P
= 0.021), serum D-dimer (D-d) level (
HR
1.70, 95%
CI
1.16–2.49,
P
= 0.006), and pulmonary imaging score (
HR
5.16, 95%
CI
2.38–11.21,
P
< 0.001). The area under the ROC curve was 90.7% for the development cohort and 96.36% for the validation cohort. The internal and external verification calibration curves were almost linear with slopes of 1, and the DCA curve revealed a net benefit with the final predictive nomogram.
Conclusion
This study proposes a predictive nomogram only based on five variables. The nomogram can be used for early identification of RMPP among pediatric patients with MPP, thereby facilitating more timely and effective intervention.
In eukaryotes, MEDIATOR is a conserved multi‐subunit complex that links transcription factors and RNA polymerase II and that thereby facilitates transcriptional initiation. Although the composition ...of MEDIATOR has been well studied in yeast and mammals, relatively little is known about the composition of MEDIATOR in plants. By affinity purification followed by mass spectrometry, we identified 28 conserved MEDIATOR subunits in Arabidopsis thaliana, including putative MEDIATOR subunits that were not previously validated. Our results indicated that MED34, MED35, MED36, and MED37 are not Arabidopsis MEDIATOR subunits, as previously proposed. Our results also revealed that two homologous CBP/p300 histone acetyltransferases, HAC1 and HAC5 (HAC1/5) are in fact plant‐specific MEDIATOR subunits. The MEDIATOR subunits MED8 and MED25 (MED8/25) are partially responsible for the association of MEDIATOR with HAC1/5, MED8/25 and HAC1/5 co‐regulate gene expression and thereby affect flowering time and floral development. Our in vitro observations indicated that MED8 and HAC1 form liquid‐like droplets by phase separation, and our in vivo observations indicated that these droplets co‐localize in the nuclear bodies at a subset of nuclei. The formation of liquid‐like droplets is required for MED8 to interact with RNA polymerase II. In summary, we have identified all of the components of Arabidopsis MEDIATOR and revealed the mechanism underlying the link of histone acetylation and transcriptional regulation.
The Arabidopsis CBP/p300 histone acetyltransferases function as MEDIATOR subunits and thereby link histone acetylation and transcriptional regulation.
ABSTRACT
Innovations in genomics have enabled the development of low‐cost, high‐resolution, single nucleotide polymorphism (SNP) genotyping arrays that accelerate breeding progress and support basic ...research in crop science. Here, we developed and validated the SoySNP618K array (618,888 SNPs) for the important crop soybean. The SNPs were selected from whole‐genome resequencing data containing 2,214 diverse soybean accessions; 29.34% of the SNPs mapped to genic regions representing 86.85% of the 56,044 annotated high‐confidence genes. Identity‐by‐state analyses of 318 soybeans revealed 17 redundant accessions, highlighting the potential of the SoySNP618K array in supporting gene bank management. The patterns of population stratification and genomic regions enriched through domestication were highly consistent with previous findings based on resequencing data, suggesting that the ascertainment bias in the SoySNP618K array was largely compensated for. Genome‐wide association mapping in combination with reported quantitative trait loci enabled fine‐mapping of genes known to influence flowering time, E2 and GmPRR3b, and of a new candidate gene, GmVIP5. Moreover, genomic prediction of flowering and maturity time in 502 recombinant inbred lines was highly accurate (>0.65). Thus, the SoySNP618K array is a valuable genomic tool that can be used to address many questions in applied breeding, germplasm management, and basic crop research.
To accelerate breeding progress and support basic research in soybean, the customized SoySNP618K array contains 618,888 SNPs selected from > 2,000 diverse, re‐sequenced soybean genomes. SoySNP618K is a valuable genomic tool to address questions in applied breeding, germplasm management, and basic research.
WRKY transcription factors in plants are known to be able to mediate either transcriptional activation or repression, but the mechanism regulating their transcriptional activity is largely unclear. ...We found that group IId WRKY transcription factors interact with OBERON (OBE) proteins, forming redundant WRKY-OBE complexes in Arabidopsis thaliana. The coiled-coil domain of WRKY transcription factors binds to OBE proteins and is responsible for target gene selection and transcriptional repression. The PHD finger of OBE proteins binds to both histones and WRKY transcription factors. WRKY-OBE complexes repress the transcription of numerous stress-responsive genes and are required for maintaining normal plant growth. Several WRKY and OBE mutants show reduced plant size and increased drought tolerance, accompanied by increased expression of stress-responsive genes. Moreover, expression levels of most of these WRKY and OBE genes are reduced in response to drought stress, revealing a previously uncharacterized regulatory mechanism of the drought stress response. These results suggest that WRKY-OBE complexes repress transcription of stress-responsive genes, and thereby balance plant growth and stress tolerance.
Infectious diseases, including COVID-19, are crucial public health issues and may lead to considerable fear among the general public and stigmatization of, and discrimination against, specific ...populations. This meta-analysis aimed to estimate the pooled prevalence of stigma in infectious disease epidemics. We systematically searched PubMed, PsycINFO, Embase, MEDLINE, Web of Science, and Cochrane databases since inception to June 08, 2021, and reported the prevalence of stigma towards people with infectious diseases including SARS, H1N1, MERS, Zika, Ebola, and COVID-19. A total of 50 eligible articles were included that contributed 51 estimates of prevalence in 92722 participants. The overall pooled prevalence of stigma across all populations was 34% 95% CI: 28-40%, including enacted stigma (36% 95% CI: 28-44%) and perceived stigma (31% 95% CI: 22-40%). The prevalence of stigma in patients, community population, and health care workers, was 38% 95% CI: 12- 65%, 36% 95% CI: 28-45%, and 30% 95% CI: 20-40%, respectively. The prevalence of stigma in participants from low- and middle-income countries was 37% 95% CI: 29-45%, which is higher than that from high-income countries (27% 95% CI: 18-36%) though this difference was not statistically significant. A similar trend of prevalence of stigma was also observed in individuals with lower education (47% 95% CI: 23-71%) compared to higher education level (33% 95% CI: 23-4%). These findings indicate that stigma is a significant public health concern, and effective and comprehensive interventions are needed to counteract the damaging effects of the infodemics during infectious disease epidemics, including COVID-19, and reduce infectious disease-related stigma.
The elaborate selection of capping ligands is of great importance in the synthesis of atomically precise metal nanoclusters. Organic thiolates, alkynyls, phosphines, and/or their combinations are the ...ligands most widely utilized to protect metal nanoclusters, while inorganic oxo anions have been almost neglected in this field. Herein, the first CrO4 2–/ t BuCC– co-capped Ag48 nanocluster (SD/Ag48, SD = SunDi) was synthesized and structurally characterized by single-crystal X-ray diffraction. The pseudo-5-fold symmetric metal skeleton of SD/Ag48 shows a core–shell structure composed of a Ag23 cylinder encircled by an outer Ag25 shell. Unprecedentedly, coexistence of inorganic (CrO4 2–) and organic ( t BuCC–) ligands was observed on the surface of SD/Ag48. The inorganic CrO4 2– anion plays three important roles in the construction of silver nanoclusters: (i) passivating the Ag23 kernel; (ii) connecting the core and shell; and (iii) protecting the Ag25 shell. This nanocluster belongs to a 14e superatom system and exhibits successive molecule-like absorption bands from the visible to the ultraviolet region. This work not only establishes a fresh inorganic ligand strategy in the synthesis of silver nanoclusters but also provides a new insight into the important surface coordination chemistry of CrO4 2– in the shape control of silver nanoclusters.
Abstract
A precise transit ephemeris serves as the premise for follow-up exoplanet observations. We compare TESS Object of Interest (TOI) transit timings of 262 hot Jupiters with the archival ...ephemeris and find 31 of them having TOI timing offsets, among which WASP-161b shows the most significant offset of −203.7 ± 4.1 minutes. The median value of these offsets is 17.8 minutes, equivalent to 3.6
σ
. We generate TESS timings in each sector for these 31 hot Jupiters, using a self-generated pipeline. The pipeline performs photometric measurements to TESS images and produces transit timings by fitting the light curves. We refine and update the previous ephemeris, based on these TESS timings (uncertainty ∼1 minute) and a long timing baseline (∼10 yr). Our refined ephemeris gives the transit timing at a median precision of 0.82 minutes until 2025 and 1.21 minutes until 2030. We regard the timing offsets to mainly originate from the underestimated ephemeris uncertainty. All the targets with timing offset larger than 10
σ
present earlier timings than the prediction, which cannot be due to underestimated ephemeris uncertainty, apsidal precision, or Rømer effect as those effects should be unsigned. For some particular targets, timing offsets are likely due to tidal dissipation. Our sample leads to the detection of period-decaying candidates of WASP-161b and XO-3b reported previously.
The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also called 2019-nCoV) causes different morbidity risks to individuals in different age groups. This study attempts ...to quantify the age-specific transmissibility using a mathematical model.
An epidemiological model with five compartments (susceptible-exposed-symptomatic-asymptomatic-recovered/removed SEIAR) was developed based on observed transmission features. Coronavirus disease 2019 (COVID-19) cases were divided into four age groups: group 1, those ≤ 14 years old; group 2, those 15 to 44 years old; group 3, those 45 to 64 years old; and group 4, those ≥ 65 years old. The model was initially based on cases (including imported cases and secondary cases) collected in Hunan Province from January 5 to February 19, 2020. Another dataset, from Jilin Province, was used to test the model.
The age-specific SEIAR model fitted the data well in each age group (P < 0.001). In Hunan Province, the highest transmissibility was from age group 4 to 3 (median: β
= 7.71 × 10
; SAR
= 3.86 × 10
), followed by group 3 to 4 (median: β
= 3.07 × 10
; SAR
= 1.53 × 10
), group 2 to 2 (median: β
= 1.24 × 10
; SAR
= 6.21 × 10
), and group 3 to 1 (median: β
= 4.10 × 10
; SAR
= 2.08 × 10
). The lowest transmissibility was from age group 3 to 3 (median: β
= 1.64 × 10
; SAR
= 8.19 × 10
), followed by group 4 to 4 (median: β
= 3.66 × 10
; SAR
= 1.83 × 10
), group 3 to 2 (median: β
= 1.21 × 10
; SAR
= 6.06 × 10
), and group 1 to 4 (median: β
= 7.20 × 10
; SAR
= 3.60 × 10
). In Jilin Province, the highest transmissibility occurred from age group 4 to 4 (median: β
= 4.27 × 10
; SAR
= 2.13 × 10
), followed by group 3 to 4 (median: β
= 1.81 × 10
; SAR
= 9.03 × 10
).
SARS-CoV-2 exhibits high transmissibility between middle-aged (45 to 64 years old) and elderly (≥ 65 years old) people. Children (≤ 14 years old) have very low susceptibility to COVID-19. This study will improve our understanding of the transmission feature of SARS-CoV-2 in different age groups and suggest the most prevention measures should be applied to middle-aged and elderly people.
PDF
![[Ag48(CC t Bu)20(CrO4)7]: ...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0002-7863/small "[Ag48(CC t Bu)20(CrO4)7]: An Atomically Precise Silver Nanocluster Co-protected by Inorganic and Organic Ligands")
