Analysis of public opinion on employment issues using a combined approach: a case study in China.

To analyze the public opinion related to the employment situation, a combined approach is proposed to study the valuable ideas from social media. Firstly, the popularity of public opinion was analyzed according to the time series from a statistical point of view. Secondly, the feature extraction was carried out on the public opinion information, and the thematic analysis of the employment environment was carried out based on the Latent Dirichlet Allocation model. Thirdly, the Bert model was used to analyze the sentiment classification and trend of the employment-related public opinion data. Finally, the employment public opinion texts in different regions were studied based on the spatial sequence popularity analysis, keyword difference analysis. A case study in China is conducted to verify the effectiveness of proposed combined approach. Results shown that the popularity of employment public opinion reached the highest level in March 2022. Public opinions towards employment situation are negative. There is a specific relationship between the popularity of employment public opinion in different provinces.

Triterpenoids from Kochiae Fructus: Glucose Uptake in 3T3-L1 Adipocytes and α-Glucosidase Inhibition, In Silico Molecular Docking.

In this study, three new triterpenes (1-3) and fourteen known triterpenoids (4-17) were isolated from the ethanol extract of Kochiae Fructus, and their structures were elucidated by analyzing UV, IR, HR-ESI-MS, 1D, and 2D NMR spectroscopic data. Among them, compounds 6, 8, and 11-17 were isolated for the first time from this plant. The screening results of the glucose uptake experiment indicated that compound 13 had a potent effect on glucose uptake in 3T3-L1 adipocytes at 20 µM. Meanwhile, compounds 3, 9 and 13 exhibited significant inhibitory activities against α-glucosidase, with IC50 values of 23.50 ± 3.37, 4.29 ± 0.52, and 16.99 ± 2.70 µM, respectively, and their α-glucosidase inhibitory activities were reported for the first time. According to the enzyme kinetics using Lineweaver-Burk and Dixon plots, we found that compounds 3, 9 and 13 were α-glucosidase mixed-type inhibitors with Ki values of 56.86 ± 1.23, 48.88 ± 0.07 and 13.63 ± 0.42 µM, respectively. In silico molecular docking analysis showed that compounds 3 and 13 possessed superior binding capacities with α-glucosidase (3A4A AutoDock score: -4.99 and -4.63 kcal/mol). Whereas compound 9 showed +2.74 kcal/mol, which indicated compound 9 exerted the effect of inhibiting α-glucosidase activity by preferentially binding to the enzyme-substrate complex. As a result, compounds 3, 9 and 13 could have therapeutic potentials for type 2 diabetes mellitus, due to their potent hypoglycemic activities.

Kochiae Fructus: Evaluation on the antioxidant properties and oral safety of its water decoction.

Kochiae Fructus (KF) was listed as 'top grade' medicinal material by the 'Shennong's Herbal Classic of Materia Medica' and has been used in traditional Chinese medicine to delay aging and treat inflammation, such as rubella, eczema, cutaneous pruritus, etc. Our research focused on the antioxidant capability of water decoction and fractions from KF based on 2,2-iphenyl-1-picrylhydrazyl (DPPH) free radical and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) cation radical scavenging assay, the ferric reducing antioxidant power assay, and inhibitory effects on DNA and protein oxidative damage. The results of total phenolics and flavonoids contents showed that ethyl acetate fraction (EAF) possessed the highest phenolics and flavonoids with values of 112.90 ± 9.58 mg gallic acid equivalents/g and 329.60 ± 20.93 mg rutin equivalents/g, respectively. At the same time, the results of antioxidant capacities showed that EAF possessed best antioxidant abilities. In addition, in this work, we evaluated the oral safety of the water decoction of KF (KFWD) via the 14-day acute and 28-day subacute toxicity tests. The results of in vivo toxicity assessment showed that KFWD did not cause significant changes in the general clinical symptoms, hematology and biochemical parameters, organ weights, or histopathological appearances in mice or rats. In summary, the reason why KF has the traditional effect on delaying aging may be related to the fact that its rich in flavonoids and phenolics. Simultaneously, no toxicity was detected after acute or subacute treatment of KFWD, providing valuable evidence for the traditional safe use of KF.

Antidiabetic potential of Catechu via assays for α-glucosidase, α-amylase, and glucose uptake in adipocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Catechu is the dry water extract of barked branches or stems from Senegalia catechu(L. F.)P. J. H. Hurter & Mabb, which is used as a hypoglycemic regulator in recent researches. Potential anti-hyperglycemic components and the putative mechanisms were evaluated in this investigation. AIM OF THE STUDY: Evaluated the hypoglycemic activity of Catechu via α-glucosidase, α-amylase inhibition assays, and glucose uptake in 3T3-L1 adipocytes. MATERIALS AND METHODS: The effects of Catechu on α-glucosidase, α-amylase inhibition assays and glucose uptake experiment were tested after the ethanol extract of Catechu (EE) was sequentially partitioned with petroleum ether (PEE), ethyl acetate (EAE), and n-butanol fractions (NBE). Next, HPLC-MS and traditional Chinese medicine (TCM) database were used to detect and analyze the primary active ingredients presented in hypoglycemic fraction. In addition, in silico molecular docking study was used to evaluate the candidates' inhibitory activity against α-glucosidase and α-amylase. RESULTS: The results of α-glucosidase and α-amylase inhibition assays indicated that all fractions, with the exception of PEE, presented significant inhibitory effects on α-glucosidase and α-amylase. The inhibitory effect of NBE on α-glucosidase was similar to the positive control (NBE IC50 = 0.3353 ± 0.1215 µg/mL; Acarbose IC50 = 0.1123 ± 0.0023 µg/mL). Furthermore, the inhibitory kinetics of α-glucosidase revealed that all fractions except for PEE belong to uncompetitive type. In silico molecular docking analysis showed that the main compositions of NBE ((-)-epicatechin, cyanidin, and delphinidin) possessed superior binding capacities with α-glucosidase (3WY1 AutoDock score: 4.82 kcal/mol; -5.59 kcal/mol; -5.63 kcal/mol) and α-amylase (4GQR AutoDock score: 4.80 kcal/mol; -5.89 kcal/mol; -4.26 kcal/mol), respectively. The results of glucose uptake experiment indicated that EE, PEE, EAE, and NBE without significant promotion effect on glucose uptake rate of 3T3-L1 adipocytes (P > 0.05). CONCLUSION: This study revealed that the hypoglycemic effect of Catechu might be related to the inhibitory effects of phenols on digestive enzymes (α-glucosidase and α-amylase), and the possible active phenols were (-)-epicatechin, cyanidin, delphinidin and their derivatives, which provided scientific evidences for Catechu's traditional use to treat T2DM.

The essential roles of Mps1 in spermatogenesis and fertility in mice.

Monopolar spindle 1 (MPS1), which plays a critical role in somatic mitosis, has also been revealed to be essential for meiosis I in oocytes. Spermatogenesis is an important process involving successive mitosis and meiosis, but the function of MPS1 in spermatogenesis remains unclear. Here, we generated Mps1 conditional knockout mice and found that Ddx4-cre-driven loss of Mps1 in male mice resulted in depletion of undifferentiated spermatogonial cells and subsequently of differentiated spermatogonia and spermatocytes. In addition, Stra8-cre-driven ablation of Mps1 in male mice led to germ cell loss and fertility reduction. Spermatocytes lacking Mps1 have blocked at the zygotene-to-pachytene transition in the prophase of meiosis I, which may be due to decreased H2B ubiquitination level mediated by MDM2. And the expression of many meiotic genes was decreased, while that of apoptotic genes was increased. Moreover, we also detected increased apoptosis in spermatocytes with Mps1 knockout, which may have been the reason why germ cells were lost. Taken together, our findings indicate that MPS1 is required for mitosis of gonocytes and spermatogonia, differentiation of undifferentiated spermatogonia, and progression of meiosis I in spermatocytes.

Histone acetyltransferase CBP-related H3K23 acetylation contributes to courtship learning in Drosophila.

BACKGROUND: Histone modifications are critical in regulating neuronal processes. However, the impacts of individual histone modifications on learning and memory are elusive. Here, we investigated the contributions of histone H3 lysine modifications to learning and memory in Drosophila by using histone lysine-to-alanine mutants. RESULTS: Behavioural analysis indicated that compared to the H3WT group, mutants overexpressing H3K23A displayed impaired courtship learning. Chromatin immunoprecipitation analysis of H3K23A mutants showed that H3K23 acetylation (H3K23ac) levels were decreased on learning-related genes. Knockdown of CREB-binding protein (CBP) decreased H3K23ac levels, attenuated the expression of learning-related genes, led to a courtship learning defect and altered development of the mushroom bodies. A decline in courtship learning ability was observed in both larvae and adult treatments with ICG-001. Furthermore, treatment of Drosophila overexpressing mutated H3K23A with a CBP inhibitor did not aggravate the learning defect. CONCLUSIONS: H3K23ac, catalysed by the acetyltransferases dCBP, contributes to Drosophila learning, likely by controlling the expression of specific genes. This is a novel epigenetic regulatory mechanism underlying neuronal behaviours.

Sensorineural Hearing Loss after Combined Intensity Modulated Radiation Therapy and Cisplatin-Based Chemotherapy for Nasopharyngeal Carcinoma.

PURPOSE: The incidence of sensorineural hearing loss (SNHL) after treatment with combination of intensity-modulated radiation therapy (IMRT) and cisplatin-based chemotherapy in nasopharyngeal carcinoma (NPC) patients was evaluated, and relationships of SNHL with host factors, treatment-related factors, and radiation dosimetric parameters were investigated. METHODS: Fifty-one NPC patients treated with IMRT from 2004 to 2009 were analyzed. All patients received neoadjuvant, concurrent, or adjuvant use of cisplatin. Pure tone audiometry was performed during the follow-up period with a median time of 60months, ranging from 28 to 84months. Correlation of SNHL at low frequencies (pure tone average, 0.5-2kHz) with a series of factors was analyzed. RESULTS: Among 102 ears, 12.7% had low-frequency SNHL and 42.2% had high-frequency (4kHz) SNHL. The incidence of low-frequency SNHL was greater in patients with age>40, with T-stage 4, or who received cumulative cisplatin dose (CCD)>200mg/m(2) (P=.034, .011, and .003, respectively) and in ears with secretory otitis media (SOM) (P=.002). Several dosimetric parameters were found to be correlated with SNHL. Univariate analysis showed that the minimum radiation dose to 0.1ml highest dose volume (D0.1ml) of the cochlea was the best radiation-related predictive parameter. Multivariate analysis indicated that CCD, SOM, and D0.1ml of cochlea (P=.035, .012, and .022, respectively) were the factors associated with SNHL. CONCLUSION: For NPC patients treated with IMRT and chemotherapy, the incidence of treatment-related SNHL was associated with CCD, D0.1ml of cochlea, and SOM.

Effects of pentoxifylline on Wnt/ß-catenin signaling in mice chronically exposed to cigarette smoke.

BACKGROUND: Previous discovery that long-term administration of pentoxifylline (PTX) to mice chronically exposed to smoke led to the development of pulmonary fibrosis rather than emphysema initiated our curiosity on whether the Wnt/ß-catenin pathway, a set of signaling proteins essential to organ development and lung morphogenesis in particular were activated in the pathogenesis of pulmonary fibrosis. METHODS: Male BALB/c mice were randomized into four study groups: Group Sm, smoke exposure and taken regular forage; Group PTX, no smoke but taken PTX-rich forage; Group Sm + PTX, smoke exposure and taken PTX-rich forage; Group control: shamed smoke exposure and taken regular forage. Animals were sacrificed at day 120. Morphometry of the lung sections and the expressions of TGF-ß(1), hydroxyproline, ß-catenin, cyclin D1, T cell factor 1 (Tcf-1) and lymphoid enhancer factor 1 (Lef-1) mRNA, etc, in the lung homogenate or in situ were qualitatively or quantitatively analyzed. RESULTS: As expected, smoke exposure along with PTX administration for 120 days, lungs of the mice progressed to be a fibrosis-like phenotype, with elevated fibrosis score (3.9 ± 1.1 vs. 1.7 ± 0.6 in Group Sm, P < 0.05). TGF-ß(1) (pg/g) (1452.4 ± 465.7 vs. 818.9 ± 202.8 in Group Sm, P < 0.05) and hydroxyproline (mg/g) (5.6 ± 0.6, vs. 2.4 ± 0.1 in Group Sm, P < 0.05) were also consistently increased. The upregulation of ß-catenin measured either by counting the cell with positive staining in microscopic field (17.4 ± 7.9 vs. 9.9 ± 2.9 in Group Sm, P < 0.05) or by estimation of the proportion of blue-stained area by Masson's trichrome (11.8 ± 5.6 vs. 4.7 ± 2.4 in Group Sm) in Group SM + PTX was much more noticeable as than those in Group Sm. The expression of ß-catenin measured by positive cell counts was correlated to TGF-ß(1) concentration in lung tissue (r = 0.758, P < 0.001). PTX per se caused neither fibrosis nor emphysema though expression of ß-catenin and downstream gene cyclin D(1) may also be altered by this medication. CONCLUSIONS: PTX mediated transformation of pulmonary emphysema into pulmonary fibrosis under chronic cigarette smoke exposure is associated with upregulation of ß-catenin and elevation of TGF-ß(1), implying that activation of Wnt/ß-catenin signaling may be involved in the pathogenesis of pulmonary fibrosis.

Congenital long QT syndrome caused by the F275S KCNQ1 mutation: mechanism of impaired channel function.

Congenital long QT syndrome is characterized by a prolongation of ventricular repolarization and recurrent episodes of life-threatening ventricular tachyarrhythmias, often leading to sudden death. We previously identified a missense mutation F275S located within the S5 transmembrane domain of the KCNQ1 ion channel in a Chinese family with long QT syndrome. We used oocyte expression of the KCNQ1 polypeptide to study the effects of the F275S mutation on channel properties. Expression of the F275 mutant, or co-expression with the wild-type S275 polypeptide, significantly decreased channel current amplitudes. Moreover, the F275S substitution decreased the rates of channel activation and deactivation. In transfected HEK293 cells fluorescence microscopy revealed that the F275S mutation perturbed the subcelluar localization of the ion channel. These results indicate that the F275S KCNQ1 mutation leads to impaired polypeptide trafficking that in turn leads to reduction of channel ion currents and altered gating kinetics.