miR-140-5p attenuates hepatic fibrosis by directly targeting TGFßR1.

OBJECTIVE: To explore the protective effect and related mechanism of miR-140-5p on liver fibrosis by interfering with TGF-ß/Smad signaling pathway. METHODS: Liver fibrosis mice models were established by intraperitoneal injection of CCL4. Hematoxylin and eosin (HE) staining was used to detect the structural and morphological changes of the liver. Masson staining was used to detect collagen deposition. Human hepatic stellate cells (HSCs, LX-2) were transfected with miR-140-5p mimic or inhibitor then treated with TGF-ß1. The qRT-PCR and Western blotting was used to detect the expression of related molecules. The luciferase reporter assay was used to identify the target of miR-140-5p. RESULTS: Our results indicated that miR-140-5p expression was downregulated in fibrotic liver tissues of model mice and LX-2 cells treated with TGF-ß1. The overexpression of miR-140-5p decreased the expression of collagen1(COL1) and α-smooth muscle actin(α-SMA), inhibited the phosphorylation of Smad-2/3 (pSmad-2/3) in LX-2 cells. Conversely, the knockdown of miR-140-5p upregulated COL1 and α-SMA expression, increased Smad-2/3 phosphorylation. A dual-luciferase reporter assay showed that TGFßR1 was a target gene of miR-140-5p. The overexpression of miR-140-5p suppressed TGFßR1 expression in LX-2 cells. Additionally, knockdown of TGFßR1 decreased the expression of COL1 and α-SMA. Conversely, the overexpression of TGFßR1 reversed the inhibitory effect of miR-140-5p upregulation on expression of COL1 and α-SMA. CONCLUSION: miR-140-5p bound to TGFßR1 mRNA 3'-untranslated region(3'UTR) and inhibited the expression of TGFßR1, pSmad-2/3, COL1 and α-SMA, thereby exerting a potential therapeutic effect on hepatic fibrosis.

[Effect of diosgenin on mTOR/FASN/HIF-1α/VEGFA expression in rats with non-alcoholic fatty liver disease].

The present study aimed to investigate the effect of diosgenin on mammalian target of rapamycin(mTOR), fatty acid synthase(FASN), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor A(VEGFA) expression in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin on lipogenesis and inflammation in NAFLD. Forty male SD rats were divided into a normal group(n=8) fed on the normal diet and an experimental group(n=32) fed on the high-fat diet(HFD) for the induction of the NAFLD model. After modeling, the rats in the experimental group were randomly divided into an HFD group, a low-dose diosgenin group(150 mg·kg~(-1)·d~(-1)), a high-dose diosgenin group(300 mg·kg~(-1)·d~(-1)), and a simvastatin group(4 mg·kg~(-1)·d~(-1)), with eight rats in each group. The drugs were continuously given by gavage for eight weeks. The levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were detected by the biochemical method. The content of TG and TC in the liver was detected by the enzyme method. Enzyme-linked immunosorbent assay(ELISA) was used to measure interleukin 1ß(IL-1ß) and tumor necrosis factor α(TNF-α) in the serum. Lipid accumulation in the liver was detected by oil red O staining. Pathological changes of liver tissues were detected by hematoxylin-eosin(HE) staining. The mRNA and protein expression levels of mTOR, FASN, HIF-1α, and VEGFA in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction(PCR) and Western blot, respectively. Compared with the normal group, the HFD group showed elevated body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1ß, and TNF-α(P<0.01), increased lipid accumulation in the liver(P<0.01), obvious liver steatosis, up-regulated mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.01), and increased protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). Compared with the HFD group, the groups with drug treatment showed lowered body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1ß, and TNF-α(P<0.05, P<0.01), reduced lipid accumulation in the liver(P<0.01), improved liver steatosis, decreased mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.05, P<0.01), and declining protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). The therapeutic effect of the high-dose diosgenin group was superior to that of the low-dose diosgenin group and the simvastatin group. Diosgenin may reduce liver lipid synthesis and inflammation and potentiate by down-regulating the mTOR, FASN, HIF-1α, and VEGFA expression, playing an active role in preventing and treating NAFLD.

A Fast North-Finding Algorithm on the Moving Pedestal Based on the Technology of Extended State Observer (ESO).

We propose a kind of fast and high-precision alignment algorithm based on the ESO technology. Firstly, in order to solve the problems of rapid, high-accuracy, and anti-interference alignment on the moving pedestal in the north-seeker, the ESO technology in control theory is introduced to improve the traditional Kalman fine-alignment model. This method includes two stages: the coarse alignment in the inertial frame and fine alignment based on the ESO technology. By utilizing the ESO technology, the convergence speed of the heading angle can be greatly accelerated. The advantages of this method are high-accuracy, fast-convergence, strong ability of anti-interference, and short time-cost (no need of KF recursive calculation). Then, the algorithm model, calculation process, and the setting initial-values of the filter are shown. Finally, taking the shipborne north-finder based on the FOG (fiber-optic gyroscope) as the investigated subject, the test on the moving ship is carried out. The results of first off-line simulation show that the misalignment angle of the heading angle of the proposed (traditional) method is ≤2.1' (1.8') after 5.5 (10) minutes of alignment. The results of second off-line simulation indicate that the misalignment angle of the heading angle of the proposed (traditional) method is ≤4.8' (14.2') after 5.5 (10) minutes of alignment. The simulations are based on the ship-running experimental data. The measurement precisions of Doppler velocity log (DVL) are different in these two experiments.

Research progress on classical traditional Chinese medicine formula Baihe Zhimu (Lilium lancifolium bulb and Anemarrhena asphodeloides rhizome) decoction in the treatment of depression.

Depression is considered to be an "emotional disease" in ancient books of traditional Chinese medicine. Its clinical features are similar to those of "Lily disease" in the ancient Chinese medicine book Synopsis of the Golden Chamber written by Zhang Zhongjing in the Han Dynasty. Baihe Zhimu (Lilium lancifolium bulb and Anemarrhena asphodeloides rhizome) decoction (LBRAD) is the first prescription of "Lily Disease" in this book. It is also a special remedy for "Lily disease" after sweating. The classic recipe LBRAD consists of two herbs, fresh lily bulbs and dried Rhizoma Anemarrhena slice. It has the effect of supplementing nutrition and clearing heat, nourishing Yin and moistening. After more than two thousand years of clinical practice, it has been currently widely used in clinical treatment of depression. In this paper, the relationship between LBRAD and depression was systematically reviewed from both clinical and experimental studies, as well as the preparation, the clinical application, the pharmacological mechanism and the effective material basis for the treating depression of LBRAD. The core targets and biological processes of the depression treatment were explored through network pharmacological analysis, so as to speculate its potential mechanism. Finally, the association between LBRAD and post-COVID-19 depression was discussed. We concluded with a summary and future prospects. This review may provide a theoretical basis for the expansion of the clinical application of LBRAD and the development of new drugs for the treatment of depression, as well as new ideas for the secondary development of classical prescriptions.

Shuangyu Tiaozhi decoction alleviates non-alcoholic fatty liver disease by improving lipid deposition, insulin resistance, and inflammation in vitro and in vivo.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Our previous studies have found that Shuangyu Tiaozhi Decoction (SYTZD) could produce an improvement in NAFLD-related indicators, but the underlying mechanism associated with this improvement remains unclear. The study aimed to investigate the potential mechanism of SYTZD against NAFLD through network pharmacology and experimental verification. The components of SYTZD and SYTZD drug containing serum were analyzed using ultra-performance liquid chromatography to quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). Active components and targets of SYTZD were screened by the traditional Chinese medical systems pharmacology (TCMSP) and encyclopedia of traditional Chinese medicine (ETCM) databases. NAFLD-related targets were collected from the GeneCards and DisGeNET databases. The component-disease targets were mapped to identify the common targets of SYTZD against NAFLD. Protein-protein interaction (PPI) network of the common targets was constructed for selecting the core targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the core targets was performed using the database for annotation, visualization, and integrated discovery (DAVID) database. Furthermore, animal and cell models were constructed for validating the predictions of network pharmacology. Lipid accumulation, liver histopathology, insulin resistance, and core gene expression were measured by oil red O staining, hematoxylin and eosin staining, insulin tolerance test, real-time quantitative polymerase chain reaction, and Western blotting, respectively. Two components and 22 targets of SYTZD against NAFLD were identified by UPLC-Q/TOF-MS and relevant databases. PPI analysis found that ESR1, FASN, mTOR, HIF-1α, VEGFA, and GSK-3ß might be the core targets of SYTZD against NAFLD, which were mainly enriched in the thyroid hormone pathway, insulin resistance pathway, HIF-1 pathway, mTOR pathway, and AMPK pathway. Experimental results revealed that SYTZD might exert multiple anti-NAFLD mechanisms, including improvements in lipid deposition, inflammation, and insulin resistance. SYTZD treatment led to decreases in the lipid profiles, hepatic enzyme levels, inflammatory cytokines, and homeostatic model assessment for insulin resistance (HOMA-IR). SYTZD treatment affected relative mRNA and protein levels associated with various pathways. Our findings reveal that SYTZD could alleviate NAFLD through a multi-component, multi-target, and multi-pathway mechanism of action.

Study on the effect of the ballistocardiography-based "Internet + Smart Bed" health management system on the quality of life of elderly users with chronic diseases.

Background: To study the effect of the "Internet + Smart Bed" health management system (IPBS) established with ballistocardiography (BCG) technology on the quality of life of elderly patients with chronic diseases. Methods: A total of 150 users with chronic diseases who had been staying in a nursing home during the period from January 2020 to March 2021 were enrolled and divided into 2 groups for experiments. The t-test and Bayesian methods were used to establish a generalized linear regression model to evaluate the effect of the IPBS on the quality of life of the subjects in the experiment. The control group (n=71) received routine examination and daily health risk management in pension facilities. Health service workers provided daily door-to-door care, and the users received regular diet, exercise, and medication supervision and guidance. The intervention group (n=79) was composed of users with chronic diseases, who accepted the IPBS. The health service workers, in addition to implementing routine examination and health risk management, conducted continuous monitoring and intervention management of the users' vital signs by means of the IPBS. Results: The results obtained with the Bayesian generalized linear regression model tended to agree with those of the t-test analysis. After 15 months of follow-up in the intervention group, the rates of body function, emotion, behavior compliance (BC), and health knowledge (HK) awareness were 1.47 times, 1.75 times, 1.53 times, and 1.69 times higher than those in the control group, respectively. In the intervention group, after using the IPBS, all scores of quality of life were better than those before use, and the differences were statistically significant P=0 or P=0.1 (P<0.05). In the control group, there were no statistically significant differences before and after observation (P>0.05). Conclusions: Routine management in elderly users with chronic diseases by means of the IPBS, which could change the users' bad living habits and eating habits, raise the patients' HK awareness, and comprehensively improve the quality of life of patients with chronic diseases, is a self-health management model worthy of application and promotion.

[Monitoring models of the plant nitrogen content based on cotton canopy hyperspectral reflectance].

Cotton production for accurate non-destructive, rapid monitoring of plant nitrogen content there is an urgent demand. Canopy spectral characteristics of the cotton plant and its quantitative relationship between nitrogen content, can achieve non-destructive monitoring of cotton nitrogen. Two consecutive years by different nitrogen test, cotton canopy hyperspectral data collection and simultaneous determination of canopy nitrogen content, analysis of different fertilizer treatments of cotton canopy spectral characteristics and the relationship between nitrogen content of cotton, the results show that: nitrogen content of cotton plant in different periods and spectral reflectance in the visible band (400-700 nm) was negatively related to the near-infrared 700-1300 nm band was a significant positive correlation, and in the short-wave infrared 1300-1800 nm band correlation is more complicated. Canopy scale, the whole growth stage of cotton, the visible band are sensitive to nitrogen content in cotton band, and near-infrared only is the cotton boll nitrogen content of the sensitive band; short-wave infrared band only in the budding period Cotton nitrogen sensitive band. Using nitrogen-sensitive bands in different periods can be constructed Cotton Cotton Nitrogen monitoring indicators.

[Study on hyperspectral estimation of pigment contents in leaves of cotton under disease stress].

The spectrum reflectance and pigment contents of cotton leaves infected with Verticillium wilt were measured in cotton disease nursery and field in different growth phases, and severity level of Verticillium wilt was investigated. The correlation between pigment contents of cotton leaves with Verticillium wilt and spectra reflectance, the first derivative of reflectance and spectral characteristic parameters were analyzed respectively. The estimation models about leaves pigment contents of disease cotton were established and tested. The results indicated that the correlations were best significant between chlorophyll a, b and a+b contents of leaves and spectral reflectance in visible wave bands, the first derivative spectrum at the wavelength regions of blue edge, yellow edge and red edge, and all spectral characteristic parameters (excluding red edge swing Dr). The models of transformed chlorophyll absorption in reflectance index (TCAR) and the new model of normalized difference vegetation index (NDVI [702,758]) had best estimated precision, and the relative errors were in average within 1.3%. Given that the model of NDVI [702,758] is very simple and practical, it was commended as a best model to estimate chlorophyll a, b and a+b contents of disease cotton. This study shows that leaves hyperspectra data can be used to estimate the pigment contents of cotton leaves quantitatively. This conclusion has also great practice and application value for monitoring the growth state and disease influence evaluation on cotton by using hyperspectral remote sensing.

Antidepressant mechanism of classical herbal formula lily bulb and Rehmannia decoction: insights from gene expression profile of medial prefrontal cortex of mice with stress-induced depression-like behavior.

According to traditional Chinese medicine, lily bulb and Rehmannia decoction (LBRD) is a specialized formula for the treatment of "lily disease", the symptoms of which resemble the clinical manifestations of major depression. However, the molecular basis of the antidepressant mechanism of LBRD and the quality marker ingredients of LBRD remain unclear. This study aimed to investigate the quality marker ingredients of LBRD and to show the molecular mechanism of its antidepressant activities. In this study, we adopted the chronic unpredicted mild stress paradigm to construct a depression model. High-performance liquid chromatography (HPLC) was used to determine the levels of the main markers in LBRD. The underlying mechanism of LBRD was explored by measuring neurotransmitter and cytokine levels using enzyme-linked immunosorbent assay, and by quantifying differentially expressed gene (DEG) of transcriptome in the medial prefrontal cortex (mPFC) tissue through RNA sequencing. HPLC results showed that the average levels of quality marker ingredients of LBRD (ferulic acid, dioscin, verbascoside and catalpol) were 0.00079%, 0.00039%, 0.7% and 1.6% (w/w), respectively. LBRD intervention significantly attenuated the depressive phenotype compared with that in the depressed group. LBRD treatment altered the enriched DEGs in the signaling pathways of γ-aminobutyric acid (GABA) and glutamate neurotransmitter, synaptic plasticity and axon guidance, circadian rhythm and neural-immunity. GABAergic and glutamatergic synapses as well as brain-derived neurotrophic factor (BDNF)/TrkB-dependent phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin-1 (mTOR1), might be the main signaling pathways underlying the multi-target therapeutic effects of LBRD against depression.