The Formation and Stabilization of a Novel G-Quadruplex in the 5′-Flanking Region of the Relaxin Gene

It has been reported that binding of STAT3 protein to the 5′-flanking region of the relaxin gene may result in downregulation of the relaxin expression. There is a Guanine(G)-rich segment located in about 3.8 Kb upstream of the relaxin gene and very close to the STAT3's binding site. In our study, NMR spectroscopy revealed the formation of G-quadruplex by this G-rich strand, and the result was confirmed by ESI mass spectrometry and CD spectroscopy. The theoretical structure of RLX G-quadruplex was constructed and refined by molecular modeling. When this relaxin G-quadruplex was stabilized by berberine(ΔTm = 10°C), a natural alkaloid from a Chinese herb, the gene expression could be up-regulated in a dose-dependent manner which was proved by luciferase assay. This result is different from the general G-quadruplex function that inhibiting the telomere replication or down-regulating many oncogenes expression. Therefore, our study reported a novel G-quadruplex in the relaxin gene and complemented the regulation mechanism about gene expression by G-quadruplexes

Prokineticin 2 Regulates the Electrical Activity of Rat Suprachiasmatic Nuclei Neurons

Neuropeptide signaling plays roles in coordinating cellular activities and maintaining robust oscillations within the mammalian suprachiasmatic nucleus (SCN). Prokineticin2 (PK2) is a signaling molecule from the SCN and involves in the generation of circadian locomotor activity. Prokineticin receptor 2 (PKR2), a receptor for PK2, has been shown to be expressed in the SCN. However, very little is known about the cellular action of PK2 within the SCN. In the present study, we investigated the effect of PK2 on spontaneous firing and miniature inhibitory postsynaptic currents (mIPSCs) using whole cell patch-clamp recording in the SCN slices. PK2 dose-dependently increased spontaneous firing rates in most neurons from the dorsal SCN. PK2 acted postsynaptically to reduce γ-aminobutyric acid (GABA)-ergic function within the SCN, and PK2 reduced the amplitude but not frequency of mIPSCs. Furthermore, PK2 also suppressed exogenous GABA-induced currents. And the inhibitory effect of PK2 required PKC activation in the postsynaptic cells. Our data suggest that PK2 could alter cellular activities within the SCN and may influence behavioral and physiological rhythms

Can Fulfillment of Social Responsibility Enable Enterprises to Innovate? The Role of Corporate Financialization and Agency Costs

This study constructs a panel model to conduct an empirical analysis on the influence of fulfillment of social responsibility on corporate innovation and its mechanism based on the annual data of A-share listed companies in China from 2010 to 2020. Research results show that (1) fulfillment of social responsibility has a positive effect on corporate innovation. Compared with enterprises with high economic policy uncertainty and low equity balance and non-state-owned enterprises, the implementation of social responsibility has a larger impact on the innovation of enterprises with low economic policy uncertainty and high equity balance and state-owned enterprises. (2) Corporate financialization and agency costs play a mediating role in the relationship between fulfillment of social responsibility and corporate innovation. Fulfillment of social responsibility can promote enterprise innovation by alleviating the capital-crowding effect caused by enterprise financialization and reducing agency costs. (3) Commercial credit has a positive moderating effect on the relationship between fulfillment of social responsibility and enterprise innovation. (4) Institutional investors have a negative moderating effect on the relationship between the fulfillment of social responsibility and enterprise innovation. The results can provide important theoretical guidance and serve as a decision-making reference for standardizing corporate social responsibility behavior and realizing the high-quality development of the Chinese economy

Nurse managers' experience during the COVID‐19 pandemic in China: A qualitative study

Abstract Aims The aim of the study was to explore the experiences of female new nurse managers during the COVID‐19 pandemic. Design This was a phenomenological study, and qualitative descriptive analysis was used. Methods New nurse managers were defined as new nurse managers with less than 3 years of management experience in this study. During November and December of 2021, 18 female new nurse managers were interviewed face‐to‐face with a semi‐structured interview guide in three municipal hospitals. The study followed the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines for evaluating qualitative research reports. Data analysis was performed using Colaizzi's seven‐step method. Results Four main themes and 10 sub‐themes were extracted from the collected data. The four major themes were as follows: (1) a shift in stress; (2) work‐related physical and psychological discomfort; (3) reflection on the cause; (4) coping and struggles. Conclusions New nurse managers were experiencing great stress and exhaustion in their roles. It is important that they are helped to handle situations. Providing them with readily accessible support, addressing their psychosocial needs and addressing exhaustion is necessary. Considering their short management time, the hospital should provide adequate support in human, financial and material areas and provide training to help new nurse managers better adapt to their new roles. In addition, nurse directors should create a culture of mutual respect, identify workplace bullying and create a harmonious and cooperation‐oriented work environment for new nurse managers. Patient or Public Contribution No patient or public contribution

Growth and feeding habits of invasive Pseudorasbora parva in the Chabalang Wetland (Lhasa, China) and its trophic impacts on native fish

In recent years, fish invasion has become one of the main reasons for the decline of native fish stocks. Pseudorasbora parva is considered one of the major invasive species worldwide. The present study investigated the fish resources of the Chabalang Wetland (Lhasa, Tibet) during different seasons in 2009 and 2013. Four hundred and twelve individuals were subsampled to estimate age, growth, and feeding habit of P. parva. Furthermore, food relationships between P. parva and the native Schizothoracinae fish were also examined. The results revealed a significant shift in species composition and community structure characterized by the disappearance of native fish and outbreak of non-native fish. The percentage of nonnative P. parva in the fish collections significantly increased from 33.64% in 2009 to 64.08% in 2013. The standard length (SL) ranged from 22.00 to 78.71 mm, and their age was 1-5 yr. The von Bertalanffy function was used to model the observed length-at-age data as L-t =112.19(1-e(-0.1495 ( t +0.8012)) ) for females and as L-t =123.12 (1-e(-0.1500 ( t +0.7132))) for males. The results indicated that P. parva in Tibet has lower growth and mortality rates compared with that from the native ranges. Ninety-seven prey taxa belonging to 9 prey categories were identified in the gut of 38 P. parva. P. parva can be considered a generalized and opportunistic predator, competing with the native fish, especially Schizothorax o'connori, Schizopygopsis younghusbandi younghusbandi, and Ptychobarbus dipogon, for Bacillariophyta and Chironomid larvae. This is an important reason for the decline in native fish population

Dynamics of Cyanobacteria and Related Environmental Drivers in Freshwater Bodies Affected by Mitten Crab Culturing: A Study of Lake Guchenghu, China

Mitten crab aquaculture is prevalent in China, however, knowledge about the threat of cyanobacteria in mitten crab aquaculture-impacted water bodies is limited. Here, seasonal variations of cyanobacteria and their relationships with environmental factors were investigated for Lake Guchenghu area. Results suggested the changes of cyanobacteria community in crab ponds distinguished from the adjacent lake. In the lake, cyanobacterial biomass (3.86 mg/L, 34.6% of the total phytoplankton) was the highest in autumn with the dominance of Oscillatoria, Aphanocapsa and Pesudanabaena. By contrast, in crab ponds, cyanobacteria (46.80 mg/L, 97.2% of the total phytoplankton biomass) were the most abundant in summer when Pesudanabaena and Raphidiopsis were the dominant species. Of particular note was that obviously higher abundance of filamentous and potentially harmful species (e.g., Raphidiopsis raciborskii and Dolichospermum circinale) were observed in ponds compared to the lake. Specifically, water depth (WD), permanganate index (CODMn), total phosphorus (TP), N:P ratio, and NO 2 −-N were the key environmental variables affected cyanobacteria composition. For crab ponds, N:P ratio, water temperature (WT) and TP were the potential environmental drivers of cyanobacteria development. This study highlighted the fact that mitten crab culture had non-negligible influences on the cyanobacteria community and additional attention should be paid to the cyanobacteria dynamics in mitten crab culture-impacted water bodies, especially for those potentially harmful species

Time-dependent inhibition and induction of human cytochrome P450A4/5 by an oral IAP antagonist, LCL161, in vitro and in vivo in healthy subjects

Tumor cells can evade programmed cell death via up-regulation of inhibitor of apoptosis proteins (IAPs). LCL161 is a small molecule oral IAP antagonist in development for use in combination with cytotoxic agents. The effect of LCL161 on CYP3A4/5 (CYP3A) activity was investigated in vitro and in a clinical study. Results in human liver microsomes indicated LCL161 inhibited CYP3A in a concentration- and time-dependent manner (KI of 0.797 uM and kinact of 0.0803 min-1). LCL161 activated human PXR in a reporter gene assay and induced CYP3A4 mRNA up to ~5-fold in human hepatocytes. In healthy subjects, the dual inhibitor and inductive effects of a single dose of LCL161 were characterized using single midazolam doses, given before and at three time points after the LCL161 dose. Midazolam Cmax increased 3.22-fold and AUC(0-inf) increased 9.32-fold when administered four hours after LCL161. Three days later, midazolam Cmax decreased by 27% and AUC(0-inf) decreased by 30%. No drug interaction remained one week later. The strong CYP3A inhibition by LCL161 was accurately predicted using dynamic physiologically-based pharmacokinetic (PBPK) modeling approaches in Simcyp. However, the observed induction effect after the LCL161 dose could not be modeled; suggesting direct enzyme induction by LCL161 was not the underlying mechanism