Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion.

BACKGROUND: The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear. AIM: To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model. METHODS: DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence. RESULTS: After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity. CONCLUSION: GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.

In situ imaging of intracellular miRNAs in tumour cells by branched hybridisation chain reaction.

The ability to visualise microRNA in situ is crucial for studying microRNAs, their microRNA-associated biological functions and disease diagnosis. Traditional fluorescence in situ hybridisation methods based on paraformaldehyde fixation of microRNAs suffer from release of microRNAs from cells, which limits the sensitivity of in situ hybridisation, making them unsuitable for the detection of small, low-abundance microRNAs. To reduce the loss, microRNAs were covalently cross-linked to proteins within cells by combining EDC and paraformaldehyde, and the target microRNA was used as the initiator chain for a branched hybridisation chain reaction to detect microRNA expression levels in situ. A simplified branched hybridisation chain reaction can be realised by coupling two hybridisation chain reaction circuits with a hairpin linker. Upon forming the primary hybridisation chain reaction product with extended sequence, this sequence reacts with the linker hairpin H3 to release the initiator sequence, resulting in the formation of numerous dendritic branched hybridisation chain reaction products. Imaging results show that this technique can detect microRNAs with high sensitivity and selectivity at both the single-cell and single-molecule levels. Compared with the traditional fluorescence in situ hybridisation technique, this method greatly improves the sensitivity and image resolution of in situ imaging detection. Therefore, we believe that the target-initiated branched hybridisation chain reaction based in situ detection method provides a reliable assay platform for analysing disease-related microRNA expression.

ß-cyclodextrin/spiropyran-functionalized optical-driven hydrogel film for bisphenol A detection in food packaging.

Bisphenol A (BPA), an endocrine disruptor, is widely used in food packaging materials, including drink containers. Sensitive detection of BPA is crucial to food safety. Herein, we have developed a novel optical-driven hydrogel film sensor for sensitive BPA detection based on the displacement of spiropyran (SP) from ß-cyclodextrin (ß-CD) cavity by BPA followed by the photochromism of the released SP. The released SP converts to the ring-opened merocyanine form which shows an enhanced red fluorescence in the dark. The sensor demonstrates a linear detection range from 0.1 to 20 µg mL-1 with a limit of detection at 0.027 µg mL-1 and a limit of quantification at 0.089 µg mL-1. Notably, the proposed ß-CD/SP hydrogel can be reused due to the reversible isomerization of SP and the reversible host-guest interaction. This sensor also shows good performance for BPA determination in real samples, indicating its great potential for food safety monitoring.

Catalytic Hairpin Assembly-Based Self-Ratiometric Gel Electrophoresis Detection Platform for Reliable Nucleic Acid Analysis.

The development of gel electrophoresis-based biodetection assays for point-of-care analysis are highly demanding. In this work, we proposed a ratiometric gel electrophoresis-based biosensing platform by employing catalytic hairpin assembly (CHA) process functions as both the signal output and the signal amplification module. Two types of nucleic acids, DNA and miRNA, are chosen for demonstration. The proposed strategy indeed provides a new paradigm for the design of a portable detection platform and may hold great potential for sensitive diagnoses.

Hsa_circ_0080608 Attenuates Lung Cancer Progression by Functioning as a Competitive Endogenous RNA to Regulate the miR-661/ADRA1A Pathway.

Circular RNAs (circRNAs) participate in the progression of human cancers and have been broadly elucidated. Here, we aimed to elucidate the roles and functional mechanisms of hsa_circ_0080608 (circ_0080608) in lung cancer. Quantitative real-time PCR (qPCR) was performed to assess the mRNA expression levels of circ_0080608, miR-661, and adrenoceptor alpha 1A (ADRA1A). Western blotting was performed to measure ADRA1A protein levels. CCK-8, colony formation, and Transwell assays were performed to determine the effect of circ_0080608 on cell proliferation and migration. Animal models were used to assess how circ_0080608 influences tumor progression in vivo. The binding relationships of miR-661's with circ_0080608 and ADRA1A was confirmed using dual-luciferase reporter and RIP assays. Circ_0080608 exhibited relatively low expression in lung cancer samples and cells. Lung cancer cells overexpressing circ_0080608 exhibited reduced migratory and proliferative abilities. Additionally, circ_0080608 binds to miR-661 and operates as a competing endogenous RNA (ceRNA) and shares a miR-661 binding site with the 3' UTR of ADRA1A. Furthermore, circ_0080608 inversely regulates miR-661 expression, consequently restraining the aggressive behavior of lung cancer cells. Lung cancer cells overexpressing ADRA1A also exhibit repressed migratory and proliferative abilities. However, reintroduction of miR-661 led to a decline in ADRA1A expression, thereby attenuating the functional effects of ADRA1A. Circ_0080608 impedes lung cancer progression by regulating the miR-661/ADRA1A pathway. Our findings provide new insights into the progression of lung cancer.

A new lithophilous species of Gesneriaceae, Petrocodonrubrostriatus, from the karst area of South Yunnan, China.

A new lithophytic species of Gesneriaceae, Petrocodonrubrostriatus K.Tan, X.Q.Song & M.X.Ren, sp. nov. from Lvchun County, South Yunnan, China, is described and illustrated here. It closest resembles P.mollifolius (W.T.Wang) A.Weber & Mich.Möller, but the new species is differentiated from it by red to brownish-red stripes in the yellow corolla throat and 4.5 mm long bract lobes, a ca. 10 mm long style, and staminodes inserted at 2.5-3 mm from the corolla base. The species is preliminarily assessed as 'Critically Endangered' (CR) according to IUCN criteria, since currently only one single locality is known with a few subpopulations on a fragmented limestone cliff, with fewer than 300 individuals.

Liang-Ge Decoction Ameliorates Coagulation Dysfunction in Cecal Ligation and Puncture-Induced Sepsis Model Rats through Inhibiting PAD4-Dependent Neutrophil Extracellular Trap Formation.

Liang-Ge (LG) decoction could ameliorate coagulation dysfunction in septic model rats. However, the mechanism of LG in treating sepsis still needs to be clarified. Our current study established a septic rat model to evaluate the effect of LG on coagulation dysfunction in septic rats first. Second, we investigated the effect of LG on NET formation in septic rats. Finally, NETs and PAD4 inhibitors were further used to clarify if LG could improve the mechanism of sepsis coagulation dysfunction by inhibiting NET formation. Our findings indicated that treatment with LG improved the survival rate, reduced inflammatory factor levels, enhanced hepatic and renal function, and reduced pathological changes in rats with sepsis. LG could also alleviate coagulation dysfunction in septic model rats. Besides, LG treatment reduced NETs formation and decreased PAD4 expression in neutrophiles. In addition, LG treatment showed a similar result in comparison to the treatment with either NET inhibitors or PAD4 inhibitors alone. In conclusion, this study confirmed that LG has therapeutic effects on septic rats. Furthermore, the improvement of coagulation dysfunction in septic rats by LG was achieved through inhibiting PAD4-mediated NET formation.

Gastrodiabawanglingensis (Orchidaceae, Epidendroideae), a new species from Hainan Island, China.

Gastrodiabawanglingensis, a new species of Orchidaceae from Hainan Island, China, is described and illustrated. It is morphologically similar to G.theana, G.albidoides and G.albida with dwarf habits, scarcely opening flowers, elongated fruit stems, curved and fleshy perianth tubes and similar columns and lips, but can be easily distinguished from them by having a pair of lateral wings bent outwards at the apex of the column and lateral wings with acuminate tips lower than the anther. According to the IUCN Red List Categories and Criteria, the new species is assessed as Endangered (EN). The plastome of G.bawanglingensis is greatly reduced and reconfigured with approximately 30876 bp in size and 25.36% in GC content. Morphological characteristics and molecular phylogenetic results based on chloroplast gene sequences support the recognition of G.bawanglingensis as a new species within Gastrodia.

Genetic spectrum of CAKUT and risk factors for kidney failure: a pediatric multicenter cohort study.

BACKGROUND: Congenital anomalies of the kidney and urinary tracts (CAKUT) are the leading cause of kidney failure in children with phenotypic and genotypic heterogeneity. Our objective was to describe the genetic spectrum and identify the risk factors for kidney failure in children with CAKUT. METHODS: Clinical and genetic data were derived from a multicenter network (Chinese Children Genetic Kidney Disease Database, CCGKDD) and the Chigene database. A total of 925 children with CAKUT who underwent genetic testing from 2014 to 2020 across China were studied. Data for a total of 584 children wereobtained from the CCGKDD, including longitudinal data regarding kidney function. The risk factors for kidney failure were determined by the Kaplan-Meier method and Cox proportional hazards models. RESULTS: A genetic diagnosis was established in 96 out of 925 (10.3%) children, including 72 (8%) with monogenic variants, 20 (2%) with copy number variants (CNVs), and 4 (0.4%)with major chromosomal anomalies. Patients with skeletal abnormalities were more likely to have large CNVs or abnormal karyotypes than monogenic variants. Eighty-two patients from the CCGKDD progressed to kidney failure at a median age of 13.0 (95% confidence interval, 12.4-13.6) years, and twenty-four were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48, XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors. CONCLUSIONS: The genetic spectrum of CAKUT varies among different subphenotypes. The identified factors indicate areas that require special attention.

Forsythiaside B ameliorates coagulopathies in a rat model of sepsis through inhibition of the formation of PAD4-dependent neutrophil extracellular traps.

Forsythiaside B (FTB) is one of the main components of Forsythia suspensa (Thunb.) Vahl and exerts anti-inflammatory and anti-oxidative effects. However, its mechanism of action as a treatment for sepsis remains unclear. In this study, we developed a rat model of sepsis using cecal ligation and puncture (CLP) to investigate the effects of FTB on sepsis-associated coagulopathies. Using rats with sepsis, we investigated the effects of FTB on neutrophil extracellular trap (NETs) formation and peptidylarginine deiminase 4 (PAD4) expression in neutrophils. NET (DNase1) and PAD4 (Cl-amidine) inhibitors were used to further investigate whether FTB mitigates sepsis-associated coagulopathies by inhibiting PAD4-dependent NETs production. Our results showed that treatment with FTB increased the survival rate, ameliorated the CLP-induced inflammatory response and multiple organ dysfunction, and reduced CLP-induced pathological changes. FTB also alleviated the associated coagulopathies. Additionally, we demonstrated that treatment with FTB inhibited NETs formation and downregulated PAD4 expression in peripheral neutrophils. The effects of FTB on coagulopathies were similar to those of monotherapy with NET or PAD4 inhibitors. In conclusion, our study confirmed that FTB can alleviate coagulopathies in rats with sepsis. The underlying mechanism of FTB's effect consists in inhibition of PAD4-dependent NETs formation.

Liang-Ge decoction ameliorates acute lung injury in septic model rats through reducing inflammatory response, oxidative stress, apoptosis, and modulating host metabolism.

Liang-Ge decoction (LG) has been used in the treatment of early stage of spesis and can ameliorate sepsis-associated lung injury. However, the mechanism of LG on sepsis-associated lung injury remains unknown. In this study, we established a rat model of sepsis-associated lung injury using the cecal ligation and puncture (CLP) method, and investigated the therapeutic effects of LG on lung injury in rats with sepsis. In addition, the anti-inflammatory, anti-oxidative and anti-apoptotic effects of LG on sepsis-associated lung injury model rats were evaluated. Besides, untargeted metabolomics was used to investigate the regulation of metabolites in rats with sepsis-associated lung injury after LG treatment. Our results showed that LG could decrease the wet/dry (W/D) ratio in lung and the total cell count and total protein concentration in bronchoalveolar lavage fluid (BALF) in septic model rats. Hematoxylin and eosin (HE) staining showed that LG reduced the infiltration of pro-inflammatory cells in lung. In addition, LG treatmment down-regulated the gene and protein expression of pro-inflammatory cytokins in lung tissue and BALF. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were increased and the level of methane dicarboxylic aldehyde (MDA) was decreased in lung tissue homogenate in septic model rats after LG treament. Moreover, the numbers of apoptotic cells in lung were reduced and the activity of lactic dehydrogenase (LDH) in BALF was decreased in septic model rats after LG treament. Untargeted metabolomics analysis showed that LG treatment affected the levels of 23 metabolites in lung in septic model rats such as citric acid, methionine, threonine, alpha-ketoglutaric acid, and inositol, these metabolites were associated with the glycine, serine and threonine metabolism, cysteine and methionine metabolism, inositol phosphate metabolism and citrate cycle (TCA cycle) pathways. In conclusion, our study demonstrated the therapeutic effetcts of LG on sepsis-associated lung injury model rats. Moreover, LG could inhibit the inflammatory response, oxidative stress, apoptosis and regulate metabolites related to glycine, serine and threonine metabolism, cysteine and methionine metabolism, inositol phosphate metabolism and TCA cycle in lung in sepsis-associated lung injury model rats.

Identification of Senescence-Related Subtypes, the Development of a Prognosis Model, and Characterization of Immune Infiltration and Gut Microbiota in Colorectal Cancer.

Cellular senescence is associated with tumorigenesis, and the subtype and prognostic signatures of senescence-related genes (SRGs) in the tumor microenvironment (TME) and gut microbiota have not been fully determined. Analysis of 91 SRGs obtained from the GSEA and MSigDB, and mRNA sequencing of genes in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases enabled the identification of two distinct molecular types of colorectal cancer (CRC). Patient samples were clustered into two subtypes, with Kaplan-Meier survival analyses showing significant differences in patient survival between the two subtypes. Cluster C2 was associated with patient clinicopathological features, high immune score, high abundance of immune infiltrating cells and somewhat high abundance of bacteria. A risk model based on eight SRGs showed that a low risk score was characterized by inhibition of immune activity and was indicative of better prognosis in patients with CRC. In combination with clinical characteristics, risk score was found to be an independent prognostic predictor of survival in patients with CRC. In conclusion, the present study showed that senescence-related subtypes and a signature consisting of eight SRGs were associated with CRC patient prognosis, as well as with immune cell infiltration and gut microbiota. These findings may enable better prediction of CRC patient prognosis and facilitate individualized treatments.

Finite-Time Synchronization of Complex Dynamical Networks via a Novel Hybrid Controller.

The issue of finite-time synchronization (FTS) of complex dynamical networks (CDNs) is investigated in this article. A new control strategy coupling weak finite-time control and finite times of impulsive control is proposed to realize the FTS of CDNs, where the impulses are synchronizing and restricted by maximal impulsive interval (MII), differing from the existing results. In this framework, several global and local FTS criteria are established by using the concept of impulsive degree. The times of impulsive control in the controllers and the settling time, which are all dependent on initial values, are derived optimally. A technical lemma is developed, reflecting the core idea of this article. A simulation example is given to demonstrate the main results finally.

Whole genome sequencing identifies a deletion mutation in the unknown-functional KCNG2 from familial sick sinus syndrome.

Sick sinus syndrome (SSS) is a term used for a variety of disorders defined by abnormal cardiac impulse formation and by abnormal propagation from the heart's sinoatrial node. In this study, we present a case from a Chinese family in which two closely related individuals had the symptoms and electrocardiographic evidence of SSS. We hypothesized that multiple individuals affected by the disease in the family was an indication of its genetic predisposition, and thus performed high-throughput sequencing for the participants from the family to detect potential disease-associated variants. One of the potential variants that was identified was a KCNG2 gene variant (NC_000018.9: g.77624068_77624079del). Further bioinformatic analysis showed that the observed variant may be a pathogenic mutation. The results of protein-protein docking and whole cell patch-clamp measurements implied that the deletion variant in KCNG2 could affect its binding the KV2.1 protein, and finally affect the function of Kv channel, which is an important determinant in regulation of heartbeat. Therefore, we inferred that the variable KCNG2 gene may affect the function of Kv channel by changing the binding conformation of KCNG2 and KV2.1 proteins and then adversely affect propagation from the sinoatrial node and cardiac impulse formation by changing the action potential repolarization of heart cells. In summary, our findings suggested that the dominant KCNG2 deletion variant in the examined Chinese family with SSS may be a potential disease-associated variant.

Economic Policy Uncertainty, Social Development, Political Regimes and Environmental Quality.

This paper aims to examine the influence of Economic Policy Uncertainty (EPU) on environmental performance, as well as the moderating effect of social development and the political regimes in EPU's influence on environmental performance. To investigate such essential issues, we conducted Generalized Method of Moments (GMM) estimations by utilizing cross-country data covering 137 countries during the period of 2001-2018, according to the Stochastic Impacts by Regression on Population, Affluence and Technology (STIRPAT) model. Our empirical estimations support that EPU negatively affects environmental performance; this idea was still supported when we conducted an empirical analysis by changing the measurements, employing alternative estimations and constructing new samples. Furthermore, not only would the absolute level of EPU bring worse environmental performance, but so would an increase in EPU. Moreover, higher economic performance, globalization and a high quality of governance can help countries to alleviate the adverse environmental effect of EPU. Additionally, EPU's negative effect on environmental performance is stronger in right-wing countries, autocracies and non-OECD countries, compared to their counterparts. Our study provides substantial policy implications for governments participating in the international treaties of environmental protection, to mitigate environmental degradation.

ITGA7, CD133, ALDH1 are inter-correlated, and linked with poor differentiation, lymph node metastasis as well as worse survival in surgical cervical cancer.

AIM: Integrin alpha 7 (ITGA7) regulates cancer stemness and metastasis in several malignancies, while its role in cervical cancer is obscure. Therefore, the current study aimed to investigate the correlation among ITGA7, cluster of differentiation 133 (CD133), and aldehyde dehydrogenase isoform 1 (ALDH1), as well as their relation to tumor features and survival in cervical cancer patients. METHODS: A total of 133 surgical cervical cancer patients were enrolled. Tumor ITGA7, CD133, and ALDH1 expressions were determined by immunohistochemistry (IHC). Furthermore, the clinicopathological features, disease-free survival (DFS), and overall survival (OS) were collected. RESULTS: ITGA7 expression positively related to CD133 expression (p = 0.040) and ALDH1 expression (p < 0.001). Besides, ITGA7 (p = 0.001), CD133 (p = 0.016), and ALDH1 (p = 0.009) high expressions linked with poor tumor differentiation; meanwhile, ITGA7 (p = 0.010) and ALDH1 (p = 0.004) high expressions correlated with more prevalence of lymph node metastasis. However, ITGA7, CD133, or ALDH1 expression was not associated with other clinicopathological features. Inspiringly, it was worth noting that ITGA7 (p = 0.009), CD133 (p = 0.041), and ALDH1 (p = 0.035) high expressions predicted unfavorable DFS; meanwhile, both ITGA7 (p = 0.021) and ALDH1 (p = 0.023) high expressions but not CD133 expression (p = 0.169) forecasted exasperated OS. CONCLUSION: ITGA7, CD133, ALDH1 are inter-correlated, and linked with poor differentiation, lymph node metastasis as well as worse survival in surgical cervical cancer.

The Impact of Globalization on Forest Growth: Evidence from Multinational Panel Data.

Even though some existing literature has studied the impact of globalization on forest growth, this research remains inconclusive; moreover, little clarification has emerged as to whether the influence of globalization on forest growth is consistent among different countries. To fill this research gap, we investigated the impact of globalization on forest growth and considered what factors could change the influence of the former upon the latter. To empirically investigate these essential issues, we utilized cross-country data covering 108 countries during the period 1991-2018 to conduct a system generalized method of moment (GMM) estimation. The baseline results confirm the positive impact of globalization on forest growth, which is also supported by several robustness tests, such as changing the measurements and setting new samples. Furthermore, an increase in globalization would bring about higher forest growth. Aside from this, two specific dimensions of globalization, namely economics and trade, can also protect forest growth. Additionally, a higher FDI strengthens the positive impact of globalization on forest growth, while aging, industrial share, and CO2 emissions weaken it. Finally, the impact of globalization on forests is weaker in democracies, emerging markets, and countries with higher fiscal freedoms, while it is stronger in countries with higher political stability. Our study provides substantial policy implications for governments participating in international treaties related to forest growth. The structure of this paper is organized as follows.

[Therapeutic effect of electric-balance stimulation with scalp acupuncture for motor aphasia after cerebral infarction].

OBJECTIVE: To compare the clinical efficacy between scalp acupuncture electrical stimulation and routine scalp acupuncture for motor aphasia in subacute stage of cerebral infarction. METHODS: A total of 54 patients with motor aphasia in subacute stage of cerebral infarction were randomly divided into an observation group (27 cases, 1 case dropped off) and a control group (27 cases, 2 cases dropped off ). Both groups were treated with routine medication and language training. In the observation group, scalp acupuncture was given at bilateral lower 2/5 of the parietal and temporal anterior oblique line and temporal frontline; after the arrival of qi, the electrical stimulation with disperse-dense wave was given at the affected side and continuous wave was given at healthy side. The control group was treated with routine scalp acupuncture at lower 2/5 of the parietal and temporal anterior oblique line and temporal frontline of the affected side, once a day, five times as a course, totaling two courses of treatment. The aphasia battery of Chinese (ABC) score and Boston diagnostic aphasia examination (BDAE) grade were observed before and after treatment. The levels of oxygenated hemoglobin (HbO2), deoxyhemoglobin (D-Hb) and total hemoglobin (T-Hb) in local cerebral cortex of the two groups were measured in real time using functional near-infrared spectroscopy (fNIRS) before and after treatment. The clinical efficacy of the two groups was compared. RESULTS: After treatment, the scores of listening comprehension, retelling, naming, spontaneous conversation and BDAE grade in the two groups were improved compared with those before treatment (P<0.01, P<0.05), and those in the observation group were better than the control group (P<0.05). Compared before treatment, the levels of HbO2 and T-Hb were increased (P<0.01), and the levels of D-Hb were decreased (P<0.01) after treatment in the two groups. The levels of HbO2 and T-Hb in the observation group were higher than those in the control group (P<0.05), and the level of D-Hb was lower than that in the control group (P<0.05). The total effective rate was 92.3% (24/26) in the observation group, which was higher than 84.0% (21/25) in the control group (P<0.05). CONCLUSION: The scalp acupuncture electrical stimulation could improve cerebral circulation, activate specific functional areas of cerebral cortex, and promote the reconstruction and recovery of brain language function. Its curative effect is better than conventional scalp acupuncture.