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The occurrence of geological hazards and the instability of geotechnical engineering structures are closely related to the time-dependent behavior of rock. However, the idealization boundary condition for constant stress in creep or constant strain in relaxation is not usually attained in natural geological systems. Therefore, generalized relaxation tests that explore the simultaneous changes of stress and strain with time under different stress levels with constant pore-water pressure are conducted in this study. The results show that in area I, area II, and area III, the stress and strain both change synchronously with time and show similar evolutionary laws as the strain-time curve for creep or the stress-time curve for relaxation. When the applied stress level surpasses the σci or σcd threshold, the variations in stress and strain and their respective rates of change exhibit a significant increase. The radial deformation and its rate of change exhibit greater sensitivity in response to stress levels. The apparent strain deforms homogeneously at the primary stage, and subsequently, gradually localizes due to the microcrack development at the secondary stage. Ultimately, interconnection of the microcracks causes the formation of a shear-localization zone at the tertiary stage. The strain-time responses inside and outside the localization zone are characterized by local strain accumulation and inelastic unloading during the secondary and tertiary stages, respectively. The width of the shear-localization zone is found to range from 4.43 mm to 7.08 mm and increased with a longer time-to-failure. Scanning electron microscopy (SEM) reveals a dominant coalescence of intergranular cracks on the fracture surface, and the degree of physiochemical deterioration caused by water-rock interaction is more severe under a longer lifetime. The brittle sandstone's time-dependent deformation is essentially controlled by microcrack development during generalized relaxation, and its expectancy-life is determined by its initial microstructural state and the rheological path.

T cell lymphoma (TCL) is a highly heterogeneous group of diseases with a poor prognosis and low 5-year overall survival rate. The current therapeutic regimens have relatively low efficacy rates. Clinical studies of single-target chimeric antigen receptor T cell (CAR-T cell) therapy in T lymphocytes require large and multiple infusions, increasing the risks and cost of treatment; therefore, optimizing targeted therapy is a way to improve overall prognosis. Despite significant advances in bispecific CAR-T cell therapy to avoid antigen escape in treatment of B cell lymphoma, applying this strategy to TCL requires further investigation. Here, we constructed an alpaca nanobody (Nb) phage library and generated high-affinity and -specificity Nbs targeting CD30 and CD5, respectively. Based on multiple rounds of screening, bispecific NbCD30-CD5-CAR T cells were constructed, and their superior anti-tumor effect against TCL was validated in vitro and in vivo. Our findings demonstrated that Nb-derived bispecific CAR-T cells significantly improved anti-tumor efficacy in TCL treatment compared with single-target CAR-T cells and bispecific single chain variable fragment (scFv)-derived CAR-T cells. Because Nbs are smaller and less immunogenic, the synergistic effect of Nb-based bispecific CAR-T cells may improve their safety and efficacy in future clinical applications.

Background: In nursing care organizations, nurses’ social networks affect their behavior and play an important role in nursing practice. This study aimed to explore the relationships among social network degree centrality, job satisfaction, work engagement and organizational citizenship behavior (OCB) among nurses. Methods: A cross-sectional survey design (one-on-one investigation) was used. The study was conducted among 254 nurses working in 10 nursing units in two hospitals in China from November 2019–February 2020. The participants completed a paper questionnaire that measured social network degree centrality, job satisfaction, work engagement and organizational citizenship behavior. A structural equation model (SEM) was used to analyze the mediating effects of job satisfaction and work engagement. SPSS 22.0 and Amos 21.0 software were used, and the significance level was set at 5% for all analyses. Results: Social network degree centrality was positively associated with job satisfaction, work engagement and organizational citizenship behavior, and job satisfaction and work engagement had significant positive relationships with organizational citizenship behavior. In addition, social network degree centrality influenced organizational citizenship behavior through the multiple mediating effects of job satisfaction and work engagement. Conclusions: Improving job satisfaction and work engagement can boost the positive effect of social network degree centrality on OCB.

Summary: Background: Since late 2019, SARS-CoV-2 infection has resulted in COVID-19 accompanied by diverse clinical manifestations. However, the underlying mechanism of how SARS-CoV-2 interacts with host and develops multiple symptoms is largely unexplored. Methods: Bioinformatics analysis determined the sequence similarity between SARS-CoV-2 and human genomes. Diverse fragments of SARS-CoV-2 genome containing Human Identical Sequences (HIS) were cloned into the lentiviral vector. HEK293T, MRC5 and HUVEC were infected with laboratory-packaged lentivirus or transfected with plasmids or antagomirs for HIS. Quantitative RT-PCR and chromatin immunoprecipitation assay detected gene expression and H3K27ac enrichment, respectively. UV-Vis spectroscopy assessed the interaction between HIS and their target locus. Enzyme-linked immunosorbent assay evaluated the hyaluronan (HA) levels of culture supernatant and plasma of COVID-19 patients. Findings: Five short sequences (24–27 nt length) sharing identity between SARS-CoV-2 and human genome were identified. These RNA elements were highly conserved in primates. The genomic fragments containing HIS were predicted to form hairpin structures in silico similar to miRNA precursors. HIS may function through direct genomic interaction leading to activation of host enhancers, and upregulation of adjacent and distant genes, including cytokine genes and hyaluronan synthase 2 (HAS2). HIS antagomirs and Cas13d-mediated HIS degradation reduced HAS2 expression. Severe COVID-19 patients displayed decreased lymphocytes and elevated D-dimer, and C-reactive proteins, as well as increased plasma hyaluronan. Hymecromone inhibited hyaluronan production in vitro, and thus could be further investigated as a therapeutic option for preventing severe outcome in COVID-19 patients. Interpretation: HIS of SARS-CoV-2 could promote COVID-19 progression by upregulating hyaluronan, providing novel targets for treatment. Funding: The National Key R&D Program of China (2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101), and the National Natural Science Foundation of China (31872814, 32000505).

A modified D-shaped photonic crystal fiber (PCF) based on Sagnac interferometer is proposed for methane concentration sensing. Two ultra-large air holes with methane-sensitive film are distributed horizontally in the PCF to shorten response time. Besides, a defect hole is introduced into the fiber core and theoretical analysis is carried out to enhance the sensing sensitivity. The dependence of gas sensitivity on the operable wavelength λ is obtained by analyzing the phase birefringence B(λ,C) and group birefringence Bg(λ,C). The average gas sensitivity is as high as 36.64 nm% in the sensing range of 0–3.5%. The modified D-Shaped and highly sensitive PCF sensor exhibits immunity to cross-sensitivity, and provides a new design idea for methane gas monitoring. Keywords: Photonic crystal fiber sensors, Methane sensing, Sagnac interferometer

Circular RNAs (circRNAs) are a novel group of noncoding RNAs characterized by a covalently closed loop. An increasing evidence suggests that deregulated circRNAs exert their essential regulatory roles in oncogenesis. However, little is explored on the biological role of novel circRNAs in cervical cancer (CC) progression. In the present study, we analyzed two GSE microarrays to screen for CC-specific circRNAs and found two circRNAs both expressed in CC cells and tissues. Among them, circ_0005576 was significantly overexpressed in both CC tissues and cell lines. Furthermore, upregulated circ_0005576 was positively associated with advanced FIGO stage, lymph node metastasis, but was negatively related with overall survival of CC patients. Additionally, circ_0005576 knockdown induced a suppressed cell growth, colony formation and metastasis of HeLa and SiHa cells. Mechanistically, circ 0005576 was mainly located in the cytoplasm and served as a sponge of miR-153-3p to increase kinesin family member 20A (KIF20A) expression. Rescue assays further validated the effects of circ_0005576/miR-153-3p/KIF20A axis on CC proliferation, migration and invasion. In conclusion, our research reveals a novel circ_0005576/miR-153-3p/KIF20A axis promoting CC progression, which may suggest a new insight into the pathogenesis of CC.