Populations of Hindbrain Glucagon-Like Peptide 1 (GLP1) Neurons That Innervate the Hypothalamic PVH, Thalamic PVT, or Limbic Forebrain BST Have Axon Collaterals That Reach All Central Regions Innervated by GLP1 Neurons.

Neurons in the caudal nucleus of the solitary tract (cNTS) and intermediate reticular nucleus (IRt) that express the glucagon gene (Gcg) give rise to glucagon-like peptide 1 (GLP1)-immunopositive axons in the spinal cord and many subcortical brain regions. Central GLP1 receptor signaling contributes to motivated behavior and stress responses in rats and mice, in which hindbrain GLP1 neurons are activated to express c-Fos in a metabolic state-dependent manner. The present study examined whether GLP1 inputs to distinct brain regions arise from distinct subsets of Gcg-expressing neurons, and mapped the distribution of axon collaterals arising from projection-defined GLP1 neural populations. Using our Gcg-Cre knock-in rat model, Cre-dependent adeno-associated virus (AAV) tracing was conducted in adult male and female rats to compare axonal projections of IRt versus cNTS GLP1 neurons. Overlapping projections were observed in all brain regions that receive GLP1 input, with the caveat that cNTS injections produced Cre-dependent labeling of some IRt neurons, and vice versa. In additional experiments, specific diencephalic or limbic forebrain nuclei were microinjected with Cre-dependent retrograde AAVs (AAVrg) that expressed reporters to fully label the axon collaterals of transduced GLP1 neurons. AAVrg injected into each forebrain site labeled Gcg-expressing neurons in both the cNTS and IRt. The collective axon collaterals of labeled neurons entered the spinal cord and every brain region previously reported to contain GLP1-positive axons. These results indicate that the axons of GLP1 neural populations that innervate the thalamic paraventricular nucleus, paraventricular nucleus of the hypothalamus, and/or bed nucleus of the stria terminalis collectively innervate all central regions that receive GLP1 axonal input.

Pharmacological modulation of adaptive thermogenesis: new clues for obesity management?

BACKGROUND: Adaptive thermogenesis represents the main mechanism through which the body generates heat in response to external stimuli, a phenomenon that includes shivering and non-shivering thermogenesis. The non-shivering thermogenesis is mainly exploited by adipose tissue characterized by a brown aspect, which specializes in energy dissipation. A decreased amount of brown adipose tissue has been observed in ageing and chronic illnesses such as obesity, a worldwide health problem characterized by dysfunctional adipose tissue expansion and associated cardiometabolic complications. In the last decades, the discovery of a trans-differentiation mechanism ("browning") within white adipose tissue depots, leading to the generation of brown-like cells, allowed to explore new natural and synthetic compounds able to favour this process and thus enhance thermogenesis with the aim of counteracting obesity. Based on recent findings, brown adipose tissue-activating agents could represent another option in addition to appetite inhibitors and inhibitors of nutrient absorption for obesity treatment. PURPOSE: This review investigates the main molecules involved in the physiological (e.g. incretin hormones) and pharmacological (e.g. ß3-adrenergic receptors agonists, thyroid receptor agonists, farnesoid X receptor agonists, glucagon-like peptide-1, and glucagon receptor agonists) modulation of adaptive thermogenesis and the signalling mechanisms involved.

Spatial and transcriptional heterogeneity of pancreatic beta cell neogenesis revealed by a time-resolved reporter system.

AIMS/HYPOTHESIS: While pancreatic beta cells have been shown to originate from endocrine progenitors in ductal regions, it remains unclear precisely where beta cells emerge from and which transcripts define newborn beta cells. We therefore investigated characteristics of newborn beta cells extracted by a time-resolved reporter system. METHODS: We established a mouse model, 'Ins1-GFP; Timer', which provides spatial information during beta cell neogenesis with high temporal resolution. Single-cell RNA-sequencing (scRNA-seq) was performed on mouse beta cells sorted by fluorescent reporter to uncover transcriptomic profiles of newborn beta cells. scRNA-seq of human embryonic stem cell (hESC)-derived beta-like cells was also performed to compare newborn beta cell features between mouse and human. RESULTS: Fluorescence imaging of Ins1-GFP; Timer mouse pancreas successfully dissected newly generated beta cells as green fluorescence-dominant cells. This reporter system revealed that, as expected, some newborn beta cells arise close to the ducts (ßduct); unexpectedly, the others arise away from the ducts and adjacent to blood vessels (ßvessel). Single-cell transcriptomic analyses demonstrated five distinct populations among newborn beta cells, confirming spatial heterogeneity of beta cell neogenesis such as high probability of glucagon-positive ßduct, musculoaponeurotic fibrosarcoma oncogene family B (MafB)-positive ßduct and musculoaponeurotic fibrosarcoma oncogene family A (MafA)-positive ßvessel cells. Comparative analysis with scRNA-seq data of mouse newborn beta cells and hESC-derived beta-like cells uncovered transcriptional similarity between mouse and human beta cell neogenesis including microsomal glutathione S-transferase 1 (MGST1)- and synaptotagmin 13 (SYT13)-highly-expressing state. CONCLUSIONS/INTERPRETATION: The combination of time-resolved histological imaging with single-cell transcriptional mapping demonstrated novel features of spatial and transcriptional heterogeneity in beta cell neogenesis, which will lead to a better understanding of beta cell differentiation for future cell therapy. DATA AVAILABILITY: Raw and processed single-cell RNA-sequencing data for this study has been deposited in the Gene Expression Omnibus under accession number GSE155742.

Receptor guanylyl cyclase-G is a novel thermosensory protein activated by cool temperatures.

Transmembrane guanylyl cyclases (GCs), with activity regulated by peptide ligands and/or calcium-binding proteins, are essential for various physiological and sensory processes. The mode of activation of the GC subtype GC-G, which is expressed in neurons of the Grueneberg ganglion that respond to cool temperatures, has been elusive. In searching for appropriate stimuli to activate GC-G, we found that its enzymatic activity is directly stimulated by cool temperatures. In this context, it was observed that dimerization/oligomerization of GC-G, a process generally considered as critical for enzymatic activity of GCs, is strongly enhanced by coolness. Moreover, heterologous expression of GC-G in cultured cells rendered these cells responsive to coolness; thus, the protein might be a sensor for cool temperatures. This concept is supported by the observation of substantially reduced coolness-induced response of Grueneberg ganglion neurons and coolness-evoked ultrasonic vocalization in GC-G-deficient mouse pups. GC-G may be a novel thermosensory protein with functional implications for the Grueneberg ganglion, a sensory organ responding to cool temperatures.

A novel epigenetic mechanism of FXR inhibiting GLP-1 secretion via miR-33 and its downstream targets.

Type II diabetes is a complex, chronic, and progressive disease. Previously, we demonstrate that FXR inhibits GLP-1 secretion via interacting with CREB to inhibit the transcriptional activity of CREB, thus promoting the development of type II diabetes. Epigenetic modifications, such as DNA methylation, histone acetylation, and post-transcriptional RNA regulation, are essential mediators contributing to diabetes-associated morbidity and mortality. Thus, we attempted to investigate the epigenetic mechanisms of FXR modulating GLP-1 secretion. Firstly, the involvement of histone acetylation, DNA methylation, and post-transcriptional regulation in FXR inhibiting GLP-1 secretion was verified. As FXR overexpression significantly inhibited the activity of GCG 3'-UTR, we hypothesize that miRNA might participate in the mechanism. Two online tools and real-time PCR revealed that FXR promoted miR-33 expression. Moreover, miR-33 inhibited the expression of GCG and CREB1 through direct targeting in STC-1 cells. FXR overexpression in STC-1 cells significantly reduced the mRNA expression and protein levels of both GCG and CREB1, as well as the secretion of GLP-1; miR-33 inhibition exerted opposing effects. More importantly, the effects of FXR overexpression were significantly reversed by miR-33 inhibition, indicating that FXR inhibited GLP-1 secretion through promoting miR-33 expression, therefore inhibiting the expression of miR-33 targets, GCG and CREB1. In conclusion, we provide a novel epigenetic mechanism by which FXR inhibits the secretion of GLP-1 through miR-33 and its two downstream targets, GCG and CREB1. These findings might provide innovative strategies for improving type II diabetes, which needs further in vivo and clinical investigation.

Cardiac monitoring of dogs via smartphone mechanocardiography: a feasibility study.

BACKGROUND: In the context of monitoring dogs, usually, accelerometers have been used to measure the dog's movement activity. Here, we study another application of the accelerometers (and gyroscopes)-seismocardiography (SCG) and gyrocardiography (GCG)-to monitor the dog's heart. Together, 3-axis SCG and 3-axis GCG constitute of 6-axis mechanocardiography (MCG), which is inbuilt to most modern smartphones. Thus, the objective of this study is to assess the feasibility of using a smartphone-only solution to studying dog's heart. METHODS: A clinical trial (CT) was conducted at the University Small Animal Hospital, University of Helsinki, Finland. 14 dogs (3 breeds) including 18 measurements (about one half of all) where the dog's status was such that it was still and not panting were further selected for the heart rate (HR) analysis (each signal with a duration of 1 min). The measurement device in the CT was a custom Holter monitor including synchronized 6-axis MCG and ECG. In addition, 16 dogs (9 breeds, one mixed-breed) were measured at home settings by the dog owners themselves using Sony Xperia Android smartphone sensor to further validate the applicability of the method. RESULTS: The developed algorithm was able to select 10 good-quality signals from the 18 CT measurements, and for 7 of these, the automated algorithm was able to detect HR with deviation below or equal to 5 bpm (compared to ECG). Further visual analysis verified that, for approximately half of the dogs, the signal quality at home environment was sufficient for HR extraction at least in some signal locations, while the motion artifacts due to dog's movements are the main challenges of the method. CONCLUSION: With improved data analysis techniques for managing noisy measurements, the proposed approach could be useful in home use. The advantage of the method is that it can operate as a stand-alone application without requiring any extra equipment (such as smart collar or ECG patch).

Dietary supplementation of a high-temperature-processed green tea extract attenuates cognitive impairment in PS2 and Tg2576 mice.

Green tea intake is generally recognized as an effective supplement that promotes mental clarity and cognitive function. These health benefits of green tea have been attributed mainly to its effective component, epigallocatechin gallate (EGCG). Because various catechin derivatives potently enhance these health benefits, we manipulated the extraction process with a high-temperature intervention. High-temperature-processed green tea extract (HTP-GTE) showed an elevated proportion of gallocatechin gallate (GCG) content. To investigate the preventive effects of HTP-GTE on cognitive decline, we found its neuroprotective effects against amyloid ß (Aß)-induced neurotoxicity in neurons and clarified that GCG significantly inhibited Aß aggregation in vitro. Moreover, we showed that HTP-GTE intake attenuated several cognitive-decline phenotypes in a model mouse of Alzheimer's disease. These beneficial effects of HTP-GTE against cognitive decline were due to the distinctive composition of the extract and suggest the possibility that HTP-GTE supplementation could attenuate cognitive decline of Alzheimer's disease.

Stability and stabilization of (-)-gallocatechin gallate under various experimental conditions and analyses of its epimerization, auto-oxidation, and degradation by LC-MS.

BACKGROUND: (-)-Gallocatechin gallate (GCG) shows multi-bioactivities. Its stability, however, has not been investigated systematically yet. Therefore, the objective of this study was to characterize the stability of GCG and to find ways to stabilize it in biological assays. Furthermore, the epimerization of the compound, its auto-oxidation and degradation were also analyzed by liquid chromatography mass spectrometry (LC-MS). RESULTS: The stability of GCG was concentration-dependent and was sensitive to pH, temperature, bivalent cations, and dissolved oxygen level. The results also showed that GCG was not stable in common buffers (50 mmol L-1 , pH 7.4, 37 °C) or in cell culture medium DMEM/F12 under physiological conditions (pH 7.4, 37 °C). Our experiments indicated that nitrogen-saturation and the addition of ascorbic acid (VC) could stabilize GCG in biological assays. In addition, LC-MS determination indicated that GCG was able to be epimerized to its epimer (-)-epigallocatechin gallate (EGCG). Meanwhile it was also able to be auto-oxidized to theasinensin and compound P2 and degraded to gallocatechin and gallic acid in pure water at 100 °C. CONCLUSION: The stability of GCG should be seriously considered in research on the bioactivity of it to avoid possible artifacts. Nitrogen-saturation and use of VC are good ways to make GCG stable in biological assays. © 2019 Society of Chemical Industry.

ChaC2, an Enzyme for Slow Turnover of Cytosolic Glutathione.

Glutathione degradation plays an important role in glutathione and redox homeostasis, and thus it is imperative to understand the enzymes and the mechanisms involved in glutathione degradation in detail. We describe here ChaC2, a member of the ChaC family of γ-glutamylcyclotransferases, as an enzyme that degrades glutathione in the cytosol of mammalian cells. ChaC2 is distinct from the previously described ChaC1, to which ChaC2 shows ∼50% sequence identity. Human and mouse ChaC2 proteins purified in vitro show 10-20-fold lower catalytic efficiency than ChaC1, although they showed comparable Km values (Km of 3.7 ± 0.4 mm and kcat of 15.9 ± 1.0 min-1 toward glutathione for human ChaC2; Km of 2.2 ± 0.4 mm and kcat of 225.2 ± 15 min-1 toward glutathione for human ChaC1). The ChaC1 and ChaC2 proteins also shared the same specificity for reduced glutathione, with no activity against either γ-glutamyl amino acids or oxidized glutathione. The ChaC2 proteins were found to be expressed constitutively in cells, unlike the tightly regulated ChaC1. Moreover, lower eukaryotes have a single member of the ChaC family that appears to be orthologous to ChaC2. In addition, we determined the crystal structure of yeast ChaC2 homologue, GCG1, at 1.34 Å resolution, which represents the first structure of the ChaC family of proteins. The catalytic site is defined by a fortuitous benzoic acid molecule bound to the crystal structure. The mechanism for binding and catalytic activity of this new enzyme of glutathione degradation, which is involved in continuous but basal turnover of cytosolic glutathione, is proposed.

A novel GLP-1/GIP/Gcg triagonist reduces cognitive deficits and pathology in the 3xTg mouse model of Alzheimer's disease.

Type 2 diabetes mellitus (T2DM) is an important risk factor for Alzheimer's disease (AD). Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have been identified to be effective in T2DM treatment and neuroprotection. In this study, we further explored the effects of a novel unimolecular GLP-1/GIP/Gcg triagonist on the cognitive behavior and cerebral pathology in the 7-month-old triple transgenic mouse model of AD (3xTg-AD), and investigated its possible electrophysiological and molecular mechanisms. After chronic administration of the GLP-1/GIP/Gcg triagonist (10 nmol/kg bodyweight, once daily, i.p.) for 30 days, open field, Y maze and Morris water maze tests were performed, followed by in vivo electrophysiological recording, immunofluorescence and Western blotting experiments. We found that the chronic treatment with the triagonist could improve long-term spatial memory of 3xTg-AD mice in Morris water maze, as well as the working memory in Y maze task. The triagonist also alleviated the suppression of long-term potentiation (LTP) in the CA1 region of hippocampus. In addition, the triagonist significantly reduced hippocampal pathological damages, including amyloid-ß (Aß) and phosphorylated tau aggregates, and upregulated the expression levels of S133 p-CREB, T286 p-CAMKII and S9 p-GSK3ß in the hippocampus of the 3xTg-AD mice. These results demonstrate for the first time that the novel GLP-1/GIP/Gcg triagonist is efficacious in ameliorating cognitive deficits and pathological damages of 3xTg-AD mice, suggesting that the triagonist might be potentially beneficial in the treatment of AD.

Suppressive effect of nobiletin and epicatechin gallate on fructose uptake in human intestinal epithelial Caco-2 cells.

Inhibition of excessive fructose intake in the small intestine could alleviate fructose-induced diseases such as hypertension and non-alcoholic fatty liver disease. We examined the effect of phytochemicals on fructose uptake using human intestinal epithelial-like Caco-2 cells which express the fructose transporter, GLUT5. Among 35 phytochemicals tested, five, including nobiletin and epicatechin gallate (ECg), markedly inhibited fructose uptake. Nobiletin and ECg also inhibited the uptake of glucose but not of L-leucine or Gly-Sar, suggesting an inhibitory effect specific to monosaccharide transporters. Kinetic analysis further suggested that this reduction in fructose uptake was associated with a decrease in the apparent number of cell-surface GLUT5 molecules, and not with a change in the affinity of GLUT5 for fructose. Lastly, nobiletin and ECg suppressed the permeation of fructose across Caco-2 cell monolayers. These findings suggest that nobiletin and ECg are good candidates for preventing diseases caused by excessive fructose intake.

Antimicrobial mechanism of epigallocatechin gallate and gallocatechin gallate: They target 1-deoxy-d-xylulose 5-phosphate reductoisomerase, the key enzyme of the MEP terpenoid biosynthetic pathway.

The catechins EGCG and GCG show a variety of pharmacological activities, especially an antibacterial capacity, but their modes of antimicrobial action have not been fully elucidated. 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), the first key enzyme in the MEP pathway for terpenoid biosynthesis, is a recently validated antimicrobial target. In order to disclose the antibacterial mechanism of EGCG and GCG, the DXR inhibitory activity of them was investigated in this study. The data show that EGCG and GCG both could specifically suppress the activity of DXR, with EGCG exhibiting relatively low effect against DXR (IC50 about 210 µM) and GCG displaying strong activity (IC50 27.5 µM). In addition, studies on inhibition kinetics of the catechins against DXR demonstrate that they are competitive inhibitors of DXR against DXP and uncompetitive inhibitors with respect to NADPH. Meanwhile, the possible interactions between DXR and the catechine, esyth onlols were simulated via docking experiments.

Potential role of green tea catechins in the management of oxidative stress-associated infertility.

Reactive oxygen species (ROS) are present in low concentrations in the genital tracts of males and females. Excessive ROS lead to oxidative stress, which damages DNA, lipids and proteins. Such molecular changes result in compromised vitality, increased morphological defects and decreased sperm motility in the male. In the female, oxidative stress interferes with oocyte maturation, and may inhibit in-vitro maturation of the oocyte. Recently, green tea supplementation has been reported to possess properties that may improve the quality of male and female gametes largely due to the ability of catechin polyphenols to quench ROS. Epigallocatechin-3-gallate (EGCG) is considered the most promising bioactive compound in green tea due to its strong antioxidant activity. The unique property of green tea catechins may potentially improve reproductive health and pose an important research area. We present a comprehensive overview on the effects and potential roles of green tea catechins on oxidative stress in male and female reproduction and fertility. In this review, possible mechanisms of action are highlighted to better understand the potential use of green tea catechins in the reduction of oxidative stress and its associated beneficial effects in the clinical setting.

Arabidopsis AtbHLH112 regulates the expression of genes involved in abiotic stress tolerance by binding to their E-box and GCG-box motifs.

Plant basic helix-loop-helix (bHLH) transcription factors play essential roles in abiotic stress tolerance. However, most bHLHs have not been functionally characterized. Here, we characterized the functional role of a bHLH transcription factor from Arabidopsis, AtbHLH112, in response to abiotic stress. AtbHLH112 is a nuclear-localized protein, and its nuclear localization is induced by salt, drought and abscisic acid (ABA). In addition, AtbHLH112 serves as a transcriptional activator, with the activation domain located at its N-terminus. In addition to binding to the E-box motifs of stress-responsive genes, AtbHLH112 binds to a novel motif with the sequence 'GG[GT]CC[GT][GA][TA]C' (GCG-box). Gain- and loss-of-function analyses showed that the transcript level of AtbHLH112 is positively correlated with salt and drought tolerance. AtbHLH112 mediates stress tolerance by increasing the expression of P5CS genes and reducing the expression of P5CDH and ProDH genes to increase proline levels. AtbHLH112 also increases the expression of POD and SOD genes to improve reactive oxygen species (ROS) scavenging ability. We present a model suggesting that AtbHLH112 is a transcriptional activator that regulates the expression of genes via binding to their GCG- or E-boxes to mediate physiological responses, including proline biosynthesis and ROS scavenging pathways, to enhance stress tolerance.

Deletion of retinoic acid receptor ß (RARß) impairs pancreatic endocrine differentiation.

All-trans retinoic acid (RA) signals via binding to retinoic acid receptors (RARs α, ß, and γ). RA directly influences expression of Pdx1, a transcription factor essential for pancreatic development and beta-cell (ß-cell) maturation. In this study we follow the differentiation of cultured wild-type (WT) vs. RARß knockout (KO) embryonic stem (ES) cells into pancreatic islet cells. We found that RARß KO ES cells show greatly reduced expression of some important endocrine markers of differentiated islet cells, such as glucagon, islet amyloid polypeptide (Iapp), and insulin 1 (Ins1) relative to WT. We conclude that RARß activity is essential for proper differentiation of ES cells to pancreatic endocrine cells.

(-)-Gallocatechin Gallate Mitigates Metabolic Syndrome-Associated Diabetic Nephropathy in db/db Mice.

Metabolic syndrome (MetS) significantly predisposes individuals to diabetes and is a prognostic factor for the progression of diabetic nephropathy (DN). This study aimed to evaluate the efficacy of (-)-gallocatechin gallate (GCG) in alleviating signs of MetS-associated DN in db/db mice. We administered GCG and monitored its effects on several metabolic parameters, including food and water intake, urinary output, blood glucose levels, glucose and insulin homeostasis, lipid profiles, blood pressure, and renal function biomarkers. The main findings indicated that GCG intervention led to marked improvements in these metabolic indicators and renal function, signifying its potential in managing MetS and DN. Furthermore, transcriptome analysis revealed substantial modifications in gene expression, notably the downregulation of pro-inflammatory genes such as S100a8, S100a9, Cd44, Socs3, Mmp3, Mmp9, Nlrp3, IL-1ß, Osm, Ptgs2, and Lcn2 and the upregulation of the anti-oxidative gene Gstm3. These genetic alterations suggest significant effects on pathways related to inflammation and oxidative stress. In conclusion, GCG demonstrates therapeutic efficacy for MetS-associated DN, mitigating metabolic disturbances and enhancing renal health by modulating inflammatory and oxidative responses.

Development of UHPLC-Q-Exactive Orbitrap/MS Technique for Determination of Proanthocyanidins (PAs) Monomer Composition Content in Persimmon.

The main units of persimmon proanthocyanidins (PAs) are composed of flavan-3-ols including epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG). Precise quantification of GCG is challenging due to its trace amounts in persimmon. In this study, to establish the optimal UHPLC-Q-Exactive Orbitrap/MS technique for the determination of PAs monomer composition in persimmon fruit flesh of different astringency types, mass spectrometry and chromatographic conditions were optimized. The results showed that when operating in negative ion mode, using a T3 chromatographic column (a type of C18 column with high-strength silica), acetonitrile as the organic phase, a 0.1% mobile phase acid content, and a mobile phase flow rate of 0.2 mL/min, the chromatographic peak shape and resolution of the PAs monomer composition improved. Additionally, there was no tailing phenomenon observed in the chromatographic peaks. At the same time, the intra-day and inter-day precision, stability, and recovery of the procedure were good. The relative standard deviation (RSD) of stability was less than 5%. The intra-day precision was in the range of 1.14% to 2.36%, and the inter-day precision ranged from 1.03% to 2.92%, both of which were less than 5%. The recovery rate ranged from 94.43% to 98.59% with an RSD less than 5%. The results showed that the UHPLC-Q-Exactive Orbitrap/MS technique established in this study can not only be used for the quantification of EGCG and GCG in persimmon fruit flesh but also be suitable for analyzing other PAs monomer compositions, providing robust support for the related research on persimmon PAs.

Green finance and high-pollution corporate compensation - Empirical evidence from green credit guidelines.

With the increasing focus on Environmental, Social, and Governance (ESG) and Corporate Social Responsibility (CSR) on a global scale, stakeholders expect businesses to transform and enhance social responsibility. Over time, ESG and CSR have developed into vital performance metrics for businesses. Businesses are actively putting improvement measures into place in response to this new paradigm in order to stay competitive in this changing environment. China's dual commitment to CSR and sustainable development is in line with wider objectives, such as resolving issues of pay inequality. In 2012, the China Banking Regulatory Commission (CBRC) unveiled the "Green Credit Guidelines" (GCG), which take corporate governance's environmental considerations into account. These regulations set standards and specifically target high-pollution corporations. Companies may need to restructure their corporate structures and create efficient governance mechanisms in order to comply with these regulations and reduce carbon emissions. This will have an impact on the compensation packages of executives and regular employees. The most important question is how the "GCG" will affect the wage disparity in highly polluting companies. This study examines the 2012 "GCG" and its potential to reduce internal wage disparities, viewing it as a critical element of green financial policy. The paper uses data from Chinese A-share listed companies from 2007 to 2020. Besides, it uses the Difference-in-Differences method to assess the impact of China's GCG, treating its implementation as a quasi-natural experiment and controlling for concurrent policy effects to precisely identify its net impact on corporate carbon emissions and internal wage disparities. The findings show that "GCG" considerably closed internal wage disparities. Furthermore, the "GCG" has a path of guidance, incentives, and punishments that reduce internal wage disparities and promote a more equitable wage distribution within businesses. According to heterogeneity analysis, policies have a greater impact on the wage gap in businesses that are highly dependent on outside funding and have political connection. In order to achieve a compensation balance and meet the objectives of social responsibility and corporate sustainable development, the government should strengthen the complementary effects of green financial policies. The compensation balance in highly polluting companies has important theoretical and practical ramifications. On the one hand, it represents the convergence of income equality, corporate governance, and environmental responsibility. It helps to expand knowledge of sustainable development, fair compensation, and environmental policies. On the other hand, the widening pay disparity between executives and average employees reflects the exacerbation of income inequality in China, which could potentially impact companies' long-term development. Conversely, a well-balanced pay plan can improve worker productivity and motivation while empowering stakeholders to make wise investment choices.

An Approach to Intersectionally Target Mature Enteroendocrine Cells in the Small Intestine of Mice.

Enteroendocrine cells (EECs) constitute only a small proportion of Villin-1 (Vil1)-expressing intestinal epithelial cells (IECs) of the gastrointestinal tract; yet, in sum, they build the largest endocrine organ of the body, with each of them storing and releasing a distinct set of peptides for the control of feeding behavior, glucose metabolism, and gastrointestinal motility. Like all IEC types, EECs are continuously renewed from intestinal stem cells in the crypt base and terminally differentiate into mature subtypes while moving up the crypt-villus axis. Interestingly, EECs adjust their hormonal secretion according to their migration state as EECs receive altering differentiation signals along the crypt-villus axis and thus undergo functional readaptation. Cell-specific targeting of mature EEC subtypes by specific promoters is challenging because the expression of EEC-derived peptides and their precursors is not limited to EECs but are also found in other organs, such as the brain (e.g., Cck and Sst) as well as in the pancreas (e.g., Sst and Gcg). Here, we describe an intersectional genetic approach that enables cell type-specific targeting of functionally distinct EEC subtypes by combining a newly generated Dre-recombinase expressing mouse line (Vil1-2A-DD-Dre) with multiple existing Cre-recombinase mice and mouse strains with rox and loxP sites flanked stop cassettes for transgene expression. We found that transgene expression in triple-transgenic mice is highly specific in I but not D and L cells in the terminal villi of the small intestine. The targeting of EECs only in terminal villi is due to the integration of a defective 2A separating peptide that, combined with low EEC intrinsic Vil1 expression, restricts our Vil1-2A-DD-Dre mouse line and the intersectional genetic approach described here only applicable for the investigation of mature EEC subpopulations.

Detection of heart rate using smartphone gyroscope data: a scoping review.

Heart rate (HR) is closely related to heart rhythm patterns, and its irregularity can imply serious health problems. Therefore, HR is used in the diagnosis of many health conditions. Traditionally, HR has been measured through an electrocardiograph (ECG), which is subject to several practical limitations when applied in everyday settings. In recent years, the emergence of smartphones and microelectromechanical systems has allowed innovative solutions for conveniently measuring HR, such as smartphone ECG, smartphone photoplethysmography (PPG), and seismocardiography (SCG). However, these measurements generally rely on external sensor hardware or are highly susceptible to inaccuracies due to the presence of significant levels of motion artifact. Data from gyrocardiography (GCG), however, while largely overlooked for this application, has the potential to overcome the limitations of other forms of measurements. For this scoping review, we performed a literature search on HR measurement using smartphone gyroscope data. In this review, from among the 114 articles that we identified, we include seven relevant articles from the last decade (December 2012 to January 2023) for further analysis of their respective methods for data collection, signal pre-processing, and HR estimation. The seven selected articles' sample sizes varied from 11 to 435 participants. Two articles used a sample size of less than 40, and three articles used a sample size of 300 or more. We provide elaborations about the algorithms used in the studies and discuss the advantages and disadvantages of these methods. Across the articles, we noticed an inconsistency in the algorithms used and a lack of established standardization for performance evaluation for HR estimation using smartphone GCG data. Among the seven articles included, five did not perform any performance evaluation, while the other two used different reference signals (HR and PPG respectively) and metrics for accuracy evaluation. We conclude the review with a discussion of challenges and future directions for the application of GCG technology.