Analysis on the factors associated with COVID-19 infection among Chinese residents after the implementation of the 10 new rules to optimize COVID-19 response: a cross-sectional study

IntroductionThis study aimed to investigate the status of COVID-19 infection and the associated factors among Chinese residents after the implementation of the 10 New Rules to optimize COVID response.MethodsParticipants were recruited using convenience sampling. The study used self-filled questionnaires to examine COVID-19 infection and associated factors among Chinese residents, from December 29, 2022, to January 2, 2023. For the statistical analysis, descriptive and quantitative analyses were used. The potential risk factors for COVID-19 infection were identified by multivariable logistic regression analysis.ResultsAfter the adjustments in control strategies against COVID-19, the infection rate of COVID-19 was high among respondents, and 98.4% of individuals who tested positive showed symptoms including cough, fever, fatigue, headache, sore throat, nasal congestion, sputum production, muscle and joint pain, and runny nose. The main problems respondents reported were the shortage of drugs and medical supplies, the increased burden on families, and the unreliable information source of COVID-19 infection. Logistic regression showed that isolating patients with COVID-19 at home was associated with a lower risk of COVID-19 infection (OR = 0.58, 95%CI: 0.42–0.81).ConclusionCOVID-19 infection among residents is closely related to age, gender, and epidemic prevention measures. The government needs to strengthen education for individuals and centrally manage and properly address difficulties that may arise during COVID-19

Notch Inhibition Allows Oncogene-Independent Generation of iPS Cells

The reprogramming of somatic cells to pluripotency using defined transcription factors holds great promise for biomedicine. However, human reprogramming remains inefficient and relies either on the use of the potentially dangerous oncogenes ​KLF4 and ​CMYC or the genetic inhibition of the tumor suppressor gene ​p53. We hypothesized that inhibition of signal transduction pathways that promote differentiation of the target somatic cells during development might relieve the requirement for non-core pluripotency factors during induced pluripotent stem cell (iPSC) reprogramming. Here, we show that inhibition of Notch greatly improves the efficiency of iPSC generation from mouse and human keratinocytes by suppressing ​p21 in a ​p53-independent manner and thereby enriching for undifferentiated cells capable of long-term self-renewal. Pharmacological inhibition of Notch enabled routine production of human iPSCs without ​KLF4 and ​CMYC while leaving ​p53 activity intact. Thus, restricting the development of somatic cells by altering intercellular communication enables the production of safer human iPSCs.Molecular and Cellular BiologyStem Cell and Regenerative Biolog

CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases

Acoustic emission study on tensile damage and failure behavior of fibre-reinforced aluminum alloy laminates with hole

Real-time monitoring of the axial tensile damage process of GLARE laminates with hole was carried out by combining acoustic emission（AE）technology and digital image correlation（DIC）technology. The effect of hole size on the mechanical behavior and failure mechanism was further analyzed. The peak frequency（PF）range of different damage modes was determined based on the k-means method, and the characteristics of AE parameters such as amplitude（PA）, energy（E）, and cumulative impact number were used to clarify the tensile failure mechanism of GLARE laminates with hole. The results show that there were mainly four damage modes during the entire tensile process of GLARE laminates, namely metal layer damage, matrix cracking, fiber debonding and interface delamination, and fiber fracture. The occurrence of the four damage modes is sequential in time. The size of the hole had a significant impact on the bearing capacity of GLARE, and as the aperture increased, the specimen changed from sudden fracture to ductile fracture at the end of the failure stage

Tailoring Amine-Functionalized Ti-MOFs via a Mixed Ligands Strategy for High-Efficiency CO2 Capture

Amine-functionalized metal-organic frameworks (MOFs) are a promising strategy for the high-efficiency capture and separation of CO2. In this work, by tuning the ratio of 1,3,5-benzenetricarboxylic acid (H3BTC) to 5-aminoisophthalic acid (5-NH2-H2IPA), we designed and synthesized a series of amine-functionalized highly stable Ti-based MOFs (named MIP-207-NH2-n, in which n represents 15%, 25%, 50%, 60%, and 100%). The structural analysis shows that the original framework of MIP-207 in the MIP-207-NH2-n (n = 15%, 25%, and 50%) MOFs remains intact when the mole ratio of ligand H3BTC to 5-NH2-H2IPA is less than 1 to 1 in the resulting MOFs. By the introduction of amino groups, MIP-207-NH2-25% demonstrates outstanding CO2 capture performance up to 3.96 and 2.91 mmol g−1, 20.7% and 43.3% higher than those of unmodified MIP-207 at 0 and 25 °C, respectively. Furthermore, the breakthrough experiment indicates that the dynamic CO2 adsorption capacity and CO2/N2 separation factors of MIP-207-NH2-25% are increased by about 25% and 15%, respectively. This work provides an additional strategy to construct amine-functionalized MOFs with the maintenance of the original MOF structure and high performance of CO2 capture and separation

Mechanosensor Piezo1 mediates bimodal patterns of intracellular calcium and FAK signaling

Piezo1 belongs to mechano-activatable cation channels serving as biological force sensors. However, the molecular events downstream of Piezo1 activation remain unclear. In this study, we used biosensors based on fluorescence resonance energy transfer (FRET) to investigate the dynamic modes of Piezo1-mediated signaling and revealed a bimodal pattern of Piezo1-induced intracellular calcium signaling. Laser-induced shockwaves (LIS) and its associated shear stress can mechanically activate Piezo1 to induce transient intracellular calcium (Ca[i] ) elevation, accompanied by an increase in FAK activity. Interestingly, multiple pulses of shockwave stimulation caused a more sustained calcium increase and a decrease in FAK activity. Similarly, tuning the degree of Piezo1 activation by titrating either the dosage of Piezo1 ligand Yoda1 or the expression level of Piezo1 produced a similar bimodal pattern of FAK responses. Further investigations revealed that SHP2 serves as an intermediate regulator mediating this bimodal pattern in Piezo1 sensing and signaling. These results suggest that the degrees of Piezo1 activation induced by both mechanical LIS and chemical ligand stimulation may determine downstream signaling characteristics

The C9ORF72 repeat expansion alters neurodevelopment

Summary: Genetic mutations that cause adult-onset neurodegenerative diseases are often expressed during embryonic stages, but it is unclear whether they alter neurodevelopment and how this might influence disease onset. Here, we show that the most common cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), a repeat expansion in C9ORF72, restricts neural stem cell proliferation and reduces cortical and thalamic size in utero. Surprisingly, a repeat expansion-derived dipeptide repeat protein (DPR) not known to reduce neuronal viability plays a key role in impairing neurodevelopment. Pharmacologically mimicking the effects of the repeat expansion on neurodevelopment increases susceptibility of C9ORF72 mice to motor defects. Thus, the C9ORF72 repeat expansion stunts development of the brain regions prominently affected in C9ORF72 FTD/ALS patients