Rosace: a robust deep mutational scanning analysis framework employing position and mean-variance shrinkage.

Deep mutational scanning (DMS) measures the effects of thousands of genetic variants in a protein simultaneously. The small sample size renders classical statistical methods ineffective. For example, p-values cannot be correctly calibrated when treating variants independently. We propose Rosace, a Bayesian framework for analyzing growth-based DMS data. Rosace leverages amino acid position information to increase power and control the false discovery rate by sharing information across parameters via shrinkage. We also developed Rosette for simulating the distributional properties of DMS. We show that Rosace is robust to the violation of model assumptions and is more powerful than existing tools.

Cucurbituril-based supramolecular host-guest complexes: single-crystal structures and dual-state fluorescence enhancement.

Two supramolecular complexes were prepared using cucurbiturils [CBs] as mediators and a four-armed p-xylene derivative (M1) as a guest molecule. The single crystals of these two complexes were obtained and successfully analyzed by single-crystal X-ray diffraction (SCXRD). An unexpected and intriguing 1 : 2 self-assembly arrangement between M1 and CB[8] was notably uncovered, marking its first observation. These host-guest complexes exhibit distinctive photophysical properties, especially emission behaviors. Invaluable insights can be derived from these single-crystal structures. The precious single-crystal structures provide both precise structural information regarding the supramolecular complexes and a deeper understanding of the intricate mechanisms governing their photophysical properties.

Single-crystal polymers (SCPs): from 1D to 3D architectures.

Single-crystal polymers (SCPs) with unambiguous chemical structures at atomic-level resolutions have attracted great attention. Obtaining precise structural information of these materials is critical as it enables a deeper understanding of the potential driving forces for specific packing and long-range order, secondary interactions, and kinetic and thermodynamic factors. Such information can ultimately lead to success in controlling the synthesis or engineering of their crystal structures for targeted applications, which could have far-reaching impact. Successful synthesis of SCPs with atomic level control of the structures, especially for those with 2D and 3D architectures, is rare. In this review, we summarize the recent progress in the synthesis of SCPs, including 1D, 2D, and 3D architectures. Solution synthesis, topochemical synthesis, and extreme condition synthesis are summarized and compared. Around 70 examples of SCPs with unambiguous structure information are presented, and their synthesis methods and structural analysis are discussed. This review offers critical insights into the structure-property relationships, providing guidance for the future rational design and bottom-up synthesis of a variety of highly ordered polymers with unprecedented functions and properties.

Quercetin prevents the ferroptosis of OPCs by inhibiting the Id2/transferrin pathway.

Spinal cord injury (SCI) is a destructive neurological disorder that causes impaired mobility, sensory, and autonomic dysfunctions. The loss of oligodendrocyte progenitor cells (OPCs), which can differentiate into mature oligodendrocytes and re-myelinate damaged axons, is related to poorer recovery for SCI patients. However, inhibiting OPCs loss has always been a difficult problem to overcome. In this study, we demonstrated the anti-ferroptosis effects of quercetin as a mechanism in erastin-induced OPC ferroptosis. Quercetin ameliorated erastin-induced ferroptosis in OPCs, as indicated by decreased iron concentration, reactive oxygen species (ROS) production, and increased content of glutathione (GSH) as well as more normal mitochondria morphology. Compared with erastin-induced OPCs, the myelin basic protein (MBP)-positive myelin and NF200-positive axonal was remarkably increased in quercetin-treated OPCs. Furthermore, quercetin ameliorated the erastin-induced ferroptosis as well as the myelin and axon loss of OPCs by downregulating transferrin. Transfected OPCs with transferrin overexpression plasmids significantly abrogated the protective role of quercetin in OPC ferroptosis. Using ChIP-qPCR, a direct interaction of transferrin with its upstream gene Id2 was found. The overexpression of Id2 reversed the effect of quercetin on OPC ferroptosis. In vivo study found that quercetin greatly decreased the area of injury, and enhanced the BBB score after SCI. Furthermore, in the SCI model, quercetin significantly downregulated Id2 and transferrin expression, while significantly up-regulated GPX4 and PTGS2 expression. In conclusion, quercetin prevents the ferroptosis of OPCs by inhibiting the Id2/transferrin pathway. These findings highlight quercetin as an anti-ferroptosis agent for the treatment or prevention of spinal cord injury.

Post-synthetic Fully π-Conjugated Three-Dimensional Covalent Organic Frameworks for High-Performance Lithium Storage.

A fully π-conjugated nitrogen-rich three-dimensional covalent organic framework (PYTRI-COF-2) containing both pyrazine and triazine units was prepared through a post-synthetic strategy. The imine linkages in the pre-prepared PYTRI-COF-1 were converted into heterocyclic quinoline by the Povarov reaction. The obtained PYTRI-COF-2 displayed high Li-ion storage capacity and excellent cycling stability when it was used as the lithium (Li)-ion battery electrode.

Corporate social responsibility and frontline employees' service improvisation: The mediating role of self-efficacy.

The uncertainty of the COVID-19 pandemic has brought unprecedented challenges to frontline employees in tourism enterprises. In the context of the COVID-19 pandemic, the fulfillment of corporate social responsibility is of great significance. Based on the social cognitive theory, a conceptual framework was established to investigate the relationship between corporate social responsibility and tourism service improvisation, along with the mediating role of self-efficiency. A total of 405 self-administered questionnaires were collected through three times. The results revealed that frontline employees' perception of corporate social responsibility had a significant positive impact on self-efficacy and service improvisation, as well as self-efficacy had a significant positive impact on service improvisation. Meanwhile, self-efficacy played a partial mediating role in the relationship between corporate social responsibility and service improvisation. Theoretical and practical implications, along with limitations and future research directions, were discussed.

MACC1 Promotes the Progression and Is a Novel Biomarker for Predicting Immunotherapy Response in Colorectal Cancer.

Aims: As one of the most prevalent malignant diseases in the world, the mechanisms of metastasis in colon cancer are poorly understood. The aim of this study was to investigate the role of the HGF/c-MET axis in the proliferation and metastasis in colon cancer. Methods: The effect of MACC1 on cell proliferation and metastasis was analyzed through a series of in vitro experiments. The role of MACC1 in cancer cells was demonstrated by overexpression and silencing of MACC1 in gain or loss function experiments. To investigate the relationship between MACC1 and c-MET/HGF, we detected c-MET protein expression by disrupting with or overexpressing MACC1. The bioinformatics analysis was used to investigate the correlation between MACC1 and c-MET, and the c-MET expression after the interference of HGF with MACC1 was determined. Subsequently, the function of c-MET was verified in colon cancer cells by a series of experiments. The mouse tumor transplantation model experiment is most suitable in vivo. Results: The results indicated that the overexpression of MACC1 could accelerate proliferation and facilitate metastasis in colon cancer cell lines. Furthermore, c-MET was determined to be the downstream regulator of MACC1. The addition of HGF could stimulate the expression of MACC1. With further exploration, we proved that c-MET is downstream of MACC1 in colon cancer and that overexpression of c-MET in colon cancer enhances cell proliferation and migration capability. At last, MACC1 expression level negatively correlates with the infiltration levels and several immune checkpoint biomarkers. High MACC1 expression has a lower response rate with ICIs in COAD. Conclusions: We found that, under the regulation of the MACC1/HGF/c-MET axis, the proliferation and metastasis of colorectal cancer are increased by MACC1, which can be a novel biomarker for predicting ICIs response in colorectal cancer. Our findings provide a new idea for the targeted treatment of colorectal cancer.

Dominant change pattern of extreme precipitation and its potential causes in Shandong Province, China.

Due to global warming, global and regional extreme precipitation events occur frequently, causing severe drought and flood disasters. This has a significant impact on productivity and human life. Therefore, it is of great significance to study the characteristics of extreme precipitation and its spatiotemporal variation. In this study, we investigate the dominant variation patterns of extreme precipitation (EP), which is characterized by indices, and also analyze its potential causes in the Shandong province of China during 1961-2015 using the daily precipitation data from 123 metrological stations. The results show that there has been a dry trend in the Shandong Province in the past 55 years, that is, with the decrease in precipitation, most of the extreme precipitation index has basically showed a downward trend to varying degrees. In particular, the increase in the number of consecutive dry days (CDD) and the decrease in the number of consecutive wet days (CWD) can better explain the drought in this region. After the 1980s, the extreme precipitation index basically showed an upward trend to varying degrees, indicating that extreme precipitation events have shown an increasing trend in recent years. The spatial distribution of each extreme precipitation index generally increased from north to south. The mutation of each extreme precipitation index occurred in the 1970s and 1990s, and there was a main period of 0.9-2.2 years. In terms of influencing factors, the NINO3 area can be used as the critical sea area for the response of extreme precipitation to SSTAs in the Shandong Province. The research results are helpful to understand the temporal and spatial variations of extreme precipitation and have very important reference value for the prediction of and response to climate change and extreme events in the future.

Quercetin promotes locomotor function recovery and axonal regeneration through induction of autophagy after spinal cord injury.

Quercetin (Que), one of the flavonoids, exerts numerous actions on the central nervous system. However, the roles and underlying mechanism of Que in locomotor function recovery and axonal regeneration following spinal cord injury (SCI) have not been fully elucidated. A rat model of spinal cord injury (SCI) was established at T10 using the modified Allen's method. The results in our study indicated that Basso, Beattie and Bresnahan (BBB) locomotor scores were significantly higher after Que treatment. Additionally, Que administration cut down the latency of somatosensory evoked potentials (SEP) and motor evoked potentials (MEP), increased the amplitude of MEP and SEP following SCI. Hematoxylin-eosin (HE) staining demonstrated that Que administration reduced lesion size and cavity formation. Biotinylated dextran amine (BDA) anterograde tracing revealed that BDA positive fibres were increased by Que following SCI. Immunofluorescence staining revealed that Que elevated 5-hydroxytryptamine (5-HT) positive nerve fibres and neurofilament-200 (NF-200) positive neurons, reduced glial fibrillary acidic protein (GFAP) positive astrocytes. In addition, Que inhibited GFAP expression, increased both NeuN and NF-200 expression and facilitated the spinal cord energy metabolism. Moreover, Que increased 18 F-FDG uptake in a time-dependent manner. Furthermore, Que increased Beclin 1 and LC3 II expression, blocked the phosphorylation of Akt, mTOR and p70S6K. 3-methyladenine (3-MA) partly abolished the neuro-protective roles of Que following SCI. Taken together, our study suggested that Que might promote locomotor function recovery, axonal regeneration and energy metabolism through induction of autophagy via Akt/mTOR/p70S6K pathway.

Early Out-of-Bed Functional Exercise Benefits Elderly Patients Following Hip Fracture: A Retrospective Cohort Study.

Hip fracture is a worldwide medical problem with devastating consequences. Older adults are at higher risk for complications and have more mobility limitation. The aim of this study was to assess the impact of delay in out-of-bed functional exercise on one-year mortality and functional outcomes for elderly patients with hip fracture in China. 1,022 cases of patients with hip fracture who were older than 75 were involved in this retrospective cohort study between 2007 and 2017. One-year mortality, follow up Activities of Daily Living (ADL) score, and Harris hip score were collected. Patients with hip fracture experienced an average of 2.9 days of in-bed functional exercise, 41.4% (n = 423) taken out-of-bed functional exercise within 2 days. A Cox proportional regression model showed that after adjustment for age, sex, cardiovascular disease, and urinary disease, delayed out-of-bed functional exercise (> 2 days) associated with higher one-year mortality (OR = 1.38, 95% confidence interval [CI]: 1.09 to 1.69). Ordinary least squares regression showed that delayed out-of-bed functional exercise associated with worsen ADL scores at 1-month (difference of -3.9 points, 95% CI: -6.4 to -1.7), although the long term ADL scores did not have increased. In addition, there were no associations between out-of-bed functional exercise timing and the Harris hip score at 12 months. In conclusion, in elderly patients with hip fracture in China, delayed out-of-bed functional exercise was not associated with improved Harris hip score, but it was associated with worsen ADL capacities at 1-month postoperatively and higher one-year mortality. The present study emphasizes the benefit of early out-of-bed exercise on the majority of elderly patients with hip fracture.

Quercetin reduces neural tissue damage and promotes astrocyte activation after spinal cord injury in rats.

Spinal cord injury (SCI) is lead to locomotor impairment because of neurological damage after following trauma. Quercetin (Que) has been confirmed to have a neuro-protective effect during nerve damage processes. The purpose of this study was to determine the roles of Que in functional recovery, cavity formation, astrocyte activation, and nerve regeneration following SCI. Sprague-Dawley rats were randomly divided into three groups: Sham group, SCI group, and Que + SCI group. A rat model of SCI was made at T10 using the modified Allen's method. In the Que + SCI group, animals underwent laminectomy and were then intraperitoneally injected with 20 mg/kg Que for 7 days. Locomotor function was determined with the Basso, Beattie, Bresnahan (BBB) scores at 1, 3, 5, and 7 days post-injury. At 7 days post-injury, somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) were recorded. Hematoxylin-Eosin (HE) staining was used to investigate cavity formation. Astrocyte activation was assayed by immunohistochemistry staining with an antibody specific for glial fibrillary acidic protein (GFAP), as well as the expression of GFAP and S100ß. Axons were stained using an antibody specific for neurofilament 200 (NF200) and 5-hydroxytryptamine (5-HT). In addition, the protein level of BDNF, p-JNK2, and p-STAT3 was detected using Western blot. Que promoted locomotor function and electrophysiological recovery, reduced cavity formation, contributed to astrocyte activation and axonal regeneration after acute SCI. Moreover, Que up-regulated the expression of BDNF, but reduced p-JNK2 and p-STAT3 expression after acute SCI. Taken together, Que promoted locomotor and electrophysiological functional recovery, astrocyte activation and axonal regeneration after acute SCI, possibly through BDNF and JAK2/STAT3 signaling pathways.