A Highly Sensitive and Selective Fluorescent Sensor for Folic Acid Detection Based on D-penicillamine Stabilized Ag/Cu Alloy Nanoclusters.

In this work, a highly sensitive and selective method for detecting folic acid (FA) was developed using D-penicillamine (DPA) stabilized Ag/Cu alloy nanoclusters (DPA@Ag/Cu NCs). The yellow emission of DPA@Ag/Cu NCs was found to be quenched upon the addition of FA to the system. The fluorescence intensity quenching value demonstrated a linear relationship with FA concentrations ranging from 0.01 to 1200 µM, with a limit of detection (LOD) of 5.3 nM. Furthermore, the detection mechanism was investigated through various characterization analyses, including high resolution transmission electron microscopy, fluorescence spectra, ultraviolet-visible absorption spectra, and fluorescence lifetime. The results indicated that the fluorescence quenching induced by FA was a result of electron transfer from FA to the ligands of DPA@Ag/Cu NCs. The selectivity of the FA sensor was also evaluated, showing that common amino acids and inorganic ions had minimal impact on the detection of FA. Moreover, the standard addition method was successfully applied to detect FA in human serum, chewable tablets and FA tablets with promising results. The use of DPA@Ag/Cu NCs demonstrates significant potential for detecting FA in complex biological samples.

[Quality-based soil fertility quality assessment of American ginseng main production areas in Shandong province].

The soil fertility quality is one of the most critical indicators of soil productivity. It directly affects the yield, quality and agricultural efficiency of Chinese medicinal materials. In order to establish the American ginseng planting soil fertility quality evaluation method based on the effective components of American ginseng, Wendeng district, Weihai city, Shandong province, the main producing area of American ginseng, was cited as a case for the study. Twenty-two 4-years American ginseng sampling sites are located at 7 towns. The samples of soil and plant root were collected in the autumn of 2017-2019. The saponin contents of American ginseng and 11 soil chemical properties were measured. The minimum data set(MDS) for assessment of the quality of soil fertility quality was established by correlation analysis and principal component analysis. The evaluation indexes were normalized by membership function. Soil quality index(SQI) that indicates soil comprehensive fertility quality level was calculated according to the critical value of membership function and weight value of each soil index in MDS. The results showed that the total saponin(Rg_1+Re+Rb_1) content of American ginseng in samples ranged from 1.76% to 7.94%. The yield of 8 plots in 2019 ranged from 3 818.7 kg·hm~(-2) to 8 996.4 kg·hm~(-2). MDS includes organic matter, alkaline nitrogen, exchangeable calcium, exchangeable magnesium, effective iron, effective copper, and effective zinc. Based on the mean of 4.825% of total saponin, threshold value of SQI for the region was determined to be 0.15, and 86.36% of soil samples in the county were above the threshold value. The methods and parameters are applicable to selection of high quality American ginseng planting sites and guiding rational fertilization. It also provides a reference for the evaluation of soil fertility quality of other medicinal plants.

[Application research of entropy weight-based grey systematic theory in quality evaluation of Angelicae Sinensis Radix slices].

In order to discuss the "entropy weight method" for weighting various indicators in the comprehensive evaluation of Angelicae Sinensis Radix slices(ASR), the quality of ASR was comprehensively evaluated by entropy weight-based gray systematic theory and cluster analysis. In this study, the contents of ferulic acid, volatile oil, polysaccharide, alcohol extract, water extract, moisture, total ash and acid-insoluble ash in 44 batches of ASR from different sources were determined. The entropy weight method was used for objective weighting. With relative correlation(r_i) as a measure, a multi-index comprehensive evaluation model was constructed for the quality of ASR. The results showed that the relative correlation value of 44 batches of ASR ranged from 0.301 9 to 0.662 9. There were certain differences in the quality of ASR from different sources. The ASR S1-S8, traceable and standardized in processing techno-logy, showed a high relative correlation degree and high quality ranking, indicating that the implementation of systemic management of the production chain of Chinese herbal pieces was beneficial to the quality control of ASR. The quality evaluation results of 44 batches of ASR were consistent with those of traditional geo-authentic habitats for ASR and the mainstream varieties of ASR on market, and basically consistent with the results of cluster analysis. This study suggests that the gray systematic theory based on the entropy weighting method can be used for the quality evaluation of ASR. The objective weighting of the entropy weight method improves the reliability of the gray correlation method and the scientificity of ASR quality evaluation.

Armillariella Oral Solution Ameliorates Small Intestinal Damage in a Mouse Model of Chemotherapy-Induced Mucositis.

Background: Armillariella oral solution (AOS) shows therapeutic effect on gastrointestinal disorders. We aimed to investigate the potential efficacy of AOS on chemotherapy-induced intestinal mucositis in mice. Methods: Intestinal mucositis was induced in C57BL/6 mice by daily intraperitoneal injection of 5-FU (50 mg/kg) for 7 days. Effects of AOS (at 1, 5, and 10 mL/kg), or combined Bifidobacterium and Lactobacillus (CBL, 450 mg/kg) on the accompanying morphometry and histology, expression of Ki-67, caspase-3, Lgr5 and apoptosis of intestinal crypt cells were assessed. Results: Continuous administration of 5-FU to mice caused severe intestinal mucositis, which was histologically characterized by the destruction of intestinal crypts and shortening of villi, accompanied by diarrhea and body weight loss. Daily AOS administration dose-dependently reduced the severity of intestinal mucositis, diarrhea and body weight loss. Similar beneficial effects were observed with CBL. The expression of Ki-67 and Lgr5 decreased and the expression of caspase-3, and the number of apoptotic cells increased 24 h after the first 5-FU administration (P < 0.05), and these responses were significantly reduced by AOS treatment (P < 0.05, at 5 or 10 mL/kg). Conclusions: AOS can alleviate 5-FU-induced mucositis in mice via increasing Lgr5 expression and suppressing apoptotic responses in the intestinal crypt cells.

Use of echocardiography to monitor myocardial damage during anthracycline chemotherapy.

BACKGROUND: Anthracycline-related cardiotoxicity has a poor prognosis; therefore, early detection of any change in LV function is critical. OBJECTIVE: The aim of this study was to evaluate the two-dimensional speckle tracking technique for the early detection of cardiac toxicity after low-dose anthracycline chemotherapy in the Chinese population. METHODS: Forty breast cancer patients were treated by chemotherapy using anthracycline for 4-6 cycles. Patients were examined by echocardiography before chemotherapy (T0) and after the second (T2), fourth (T4), and sixth (T6) cycle. LV ejection fraction (LVEF), LV global longitudinal strain (GLS) and endocardium, mid-myocardium, and epicardium global longitudinal strain (GLS-Endo, GLS-Mid, and GLS-Epi). Additionally, global circumferential strain (GCS), RV global longitudinal strain (RVGLS), and LA global longitudinal strain (LAGLS) were evaluated. RESULTS: Left ventricular ejection fraction was significantly reduced at T4 (P < 0.05). Compared with T0, GLS, GLS-Endo, GLS-Mid, and GLS-Epi were significantly reduced at T2, T4, and T6 (P < 0.05 for all), the apical septum wall (AS) was also reduced significantly at T2 (P < 0.05), and the apical anterior wall (AA) and the basal anterior wall (BA) longitudinal strains were significantly reduced at T4 (P < 0.05). GCS, RVGLS, and LAGLS were not significantly changed after treatment (P > 0.05). CONCLUSIONS: LV stratified strains and strain of the segments supplied by the left anterior descending coronary artery are more sensitive to the cardiac toxicity of anthracycline.

The polymorphism of ARNTL2 (BMAL2) gene rs2306074 C>T is associated with susceptibility of Alzheimer disease in Chinese population.

In the present study, we investigated whether polymorphism of ARNTL2 (BMAL2) gene rs2306074 T/C was associated with susceptibility of Alzheimer disease (AD) in Chinese population. A case-control method was employed in this study. 296 unrelated AD patients and 423 control subjects were recruited in current study. The prevalence of C carriers in BMAL2 gene rs2306074 T/C in AD patients was significantly higher than that of control subjects in both the whole sample and APOE ε 4 non-carriers (in the whole sample: χ (2) = 5.938, P = 0.012; in APOE ε 4 non-carriers: χ (2) = 9.048, P < 0.0001). In addition, both in the whole sample and APOE ε 4 non-carriers, prevalence of CC genotypes in BMAL2 gene rs2306074 of AD patients was also significantly higher than that in controls (in the whole sample: χ (2) = 5.126, P = 0.018; in APOE ε 4 non-carriers: χ (2) = 7.389, P = 0.023). However, there was no significant difference of prevalence of C carriers and CC genotypes in BMAL2 gene rs2306074 T/C between AD patients and control subjects among APOE ε 4 carriers (C carriers: χ (2) = 0.020, P = 0.900; CC genotypes: χ (2) = 0.017, P = 0.946). C carriers in BMAL2 gene rs2306074 T/C are associated with a high susceptibility of AD among APOE ε 4 non-carriers but not among APOE ε 4 carriers in Chinese population.

Identification of an 8 HPV-related RNA signature as a novel prognostic biomarker for squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of the head and neck (SCCHN) is a commonly detected cancer worldwide. Human papillomavirus (HPV) is emerging as an important risk factor affecting SCCHN prognosis. Therefore, identification of HPV status is essential for effective therapies in SCCHN. The aim of this study was to investigate the prognostic value of HPV-associated RNA biomarkers for SCCHN. The clinical data, survival data, and RNA-seq data of SCCHN were downloaded from The Cancer Genome Atlas database. Before the differential expression analysis, the heterogeneity between the 2 groups (HPV+ vs HPV-) of samples was analyzed using principal component analysis. The differentially expressed genes (DEGs) between HPV+ and HPV- SCCHN samples were analyzed using the R edgeR package. The Gene Ontology functional annotations, including biological process, molecular function and cellular component (CC), and Kyoto Encyclopedia of Genes And Genomes pathways enriched by the DEGs were analyzed using DAVID. The obtained matrix was analyzed by weighed gene coexpression network analysis. A total of 350 significant DEGs were identified through differential analysis, and these DEGs were significantly enriched in functions associated with keratinization, and the pathway of neuroactive ligand-receptor interaction. Moreover, 72 hub genes were identified through weighed gene coexpression network analysis. After the hub genes and DEGs were combined, we obtained 422 union genes, including 65 survival-associated genes. After regression analysis, a HPV-related prognostic model was established, which consisted of 8 genes, including Clorf105, CGA, CHRNA2, CRIP3, CTAG2, ENPP6, NEFH, and RNF212. The obtained regression model could be expressed by an equation as follows: risk score = 0.065 × Clorf105 + 0.012 × CGA + 0.01 × CHRNA2 + 0.047 × CRIP3 + 0.043 × CTAG2-0.034 × ENPP6 - 0.003 × NEFH - 0.068 × RNF212. CGA interacted with 3 drugs, and CHRNA2 interacted with 11 drugs. We have identified an 8 HPV-RNA signature associated with the prognosis of SCCHN patients. Such prognostic model might serve as possible candidate biomarker and therapeutic target for SCCHN.

Clinical characteristics, survival analysis and influencing factors of distant metastasis in patients with acromelanomas: A retrospective study.

The prognosis of acromelanomas (AM) is worse. The objective of this study was to investigate the clinical features of distant metastasis of AM and the factors affecting the survival and prognosis of patients. In this study, a retrospective study was conducted to select 154 AM patients admitted to Nanjing Pukou People's Hospital from January 2018 to April 2021 for clinical research. The clinical characteristics of distant metastasis were statistically analyzed, and the survival curve was drawn with 5-year follow-up outcomes. The median survival time of the patients was calculated, and the clinicopathological features and peripheral blood laboratory indexes of the surviving and dead patients were analyzed. Logistic regression model was used to analyze the risk factors affecting the prognosis of AM patients. In this study, 154 patients with AM were treated, including 88 males and 76 females, aged from 27 to 79 years old, with an average age of (59.3 ±â€…11.7) years old. Among them, 90 cases had distant metastasis. The main metastatic sites were lung (47.78%) and lymph nodes (42.22%). Among them, single site metastasis accounted for 41.11% and multiple site metastasis 58.89%. 89 cases survived and 65 cases died. The survival time was 22 months to 60 months, and the median survival time was 48.0 months. The Breslow thickness, stage at diagnosis, distant metastasis, site of metastasis and ulceration were compared between the survival group and the death group (P < .05). serum lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR) and lymphocyte monocyte ratio (LMR) were compared between the survival group and the death group (P < .05). The results of Logistic regression model showed that LDH ≥ 281 U/L, NLR ≥ 2.96, LMR ≤ 3.57, newly diagnosed stage > stage II, distant metastasis, multiple site metastasis and tumor ulcer were independent risk factors for poor prognosis of AM patients (P < .05). Patients with AM had a higher proportion of distant metastasis, mainly lung and lymph node metastasis. Increased LDH, increased NLR, decreased LMR, higher initial stage, distant metastasis, multiple site metastasis, and combined tumor ulcer were closely related to the poor prognosis of patients after surgery.

Synthesis, characterization, and efficacy evaluation of a PH-responsive Fe-MOF@GO composite drug delivery system for the treating colorectal cancer.

Luteolin is a potent anti-colorectal cancer chemical. However, its effectiveness is hindered by its poor solubility in water and fat, and it is easy to degrade by gastrointestinal enzymes. In this study, a nano-composite carrier, NH2-MIL-101(Fe)@GO (MG), based on aminated MIL-101(Fe) and graphene oxide (GO) was developed and evaluated. This carrier co-delivered luteolin and matrine, while marine was used to balance the pH for the nano-preparation. The loading capacities for luteolin and matrine were approximately 9.8% and 14.1%, respectively. Luteolin's release at pH = 5 was significantly higher than at pH = 7.4, indicating it had an acidic pH response release characteristic. Compared to MOF and GO alone, MG and NH2-MIL-101(Fe)@GO@Drugs (MGD) enhanced anti-cancer activity by inhibiting tumor cell migration, increasing ROS generation, and upregulating the expression of Caspase-3 and Caspase-9. In conclusion, this study contributes new ideas and methods to the treatment strategy of multi-component anti-colorectal cancer therapy. It also advances drug delivery systems and supports the development of more effective and targeted treatment approaches for colorectal cancer.

GbWRKY1, a novel cotton (Gossypium barbadense) WRKY gene isolated from a bacteriophage full-length cDNA library, is induced by infection with Verticillium dahliae.

WRKY transcription factor proteins play important roles in diverse stress responses. In this study, we first cloned a novel WRKY from our constructed bacteriophage full-length cDNA library for cotton (Gossypium barbadense). The plants were stressed by exposure to a defoliating strain of Verticillium dahliae. The capacity of primary cDNA library was 1.28 x 10(6) PFU and the titer of the amplified cDNA library was > 10(10) PFU mL(-1). The recombination rate of the library was 94% and average insert size was about 1.1 kb. This novel gene, named GbWRKY1 was 1971 bp long and encodes a protein of 489 amino acids. It contains two characteristic WRKY domains and two zinc finger motifs. The sub-cellular assay indicated that GbWRKY1-GFP fusion protein was localized in the nucleus. Furthermore, Northern blot analysis showed that expression pattern of GbWRKY1 was similar among tissue types (roots, stems and leaves), but differed between pathogen-infiltrated and Czapek medium-infiltrated (untreated control) plants. Quantitative real-time PCR showed that GbWRKY1 could also be induced by salicylic acid (SA), methyl jasmonate (MeJA) and 1-aminocyclopropane-1-carboxylic acid (ACC). These findings clearly suggest that as a pathogen-inducible transcription factor GbWRKY1 plays an important role in plant defense responses.

SWATH-MS-based proteomics reveals functional biomarkers of Th1/Th2 responses of tropomyosin allergy in mouse models.

Type-I food allergies are hypersensitive reactions compromising the immune organs and epithelial barriers. To investigate the organ-specific proteomic alterations of the allergy responses, the spleen and intestine of mice sensitized with high (shrimp and clam) and weak (fish) allergenic tropomyosins were analyzed using sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS)-based proteomics. The results showed that Th1 and Th2 tropomyosin-induced responses in the spleen are characterized by the unique upregulation of innate (cochlin) and adaptive (Ig κ chain V-III region PC 7175) immune regulators, respectively. In the intestine, tropomyosin allergy concurred with the downregulation of 35 differentiating proteins featuring the overall impairment of metabolic pathways, absorption processes and ammonium ion responses. These data provide new functional biomarkers of tropomyosin-induced immune responses as well as candidate targets for intervention.

Determination of L-tetrahydropalmatine in human plasma by HPLC and pharmacokinetics of its disintegrating tablets in healthy Chinese.

The objective of the study was to establish an HPLC method for the determination of L: -tetrahydropalmatine in human plasma, and to investigate the pharmacokinetics after oral administration of L: -tetrahydropalmatine disintegrating tablets in healthy Chinese. L: -tetrahydropalmatine in human plasma was separated on a Phenomenex luna C(18) column (250 mm × 4.6 mm, 5 µm), eluted using methanol-water (75:25, v/v) as mobile phase, and detected by photodiode array detector at a wavelength of 281 nm. A single 60 mg of L: -tetrahydropalmatine orally disintegrating tablets were orally given to 12 healthy male volunteers after fasting overnight. Before and after administration 4 mL of blood samples was collected at the scheduled time. The plasma concentration of L: -tetrahydropalmatine was determined by the established HPLC method after disposition and its pharmacokinetic parameters were analyzed and evaluated by both compartmental and noncompartmental models using Drug and Statistic (version 2.0). The disintegrating time and the sense of mouth were observed and recorded. The lowest limit of quantification (LLOQ) for L: -tetrahydropalmatine in plasma was 0.01 µg mL(-1), and a linearity was obtained in the range of 0.01-1 µg mL(-1) (r = 0.9998). The disposal procedure of L: -tetrahydropalmatine in human was fitted using the DAS program, following a double-compartment open model system (w = 1). L: -tetrahydropalmatine was absorbed quickly with t (1/2ka) of 0.5 ± 0.054 h, distributed fast with t (1/2α) of 0.74 ± 0.088 h, and eliminated slowly with t (1/2ß) of 11.42 ± 2.43 h. L: -tetrahydropalmatine was distributed mainly in the periphery compartment with the V(1)/F of 133.30 ± 30.78 L. L: -tetrahydropalmatine orally disintegrating tablets with good taste were disintegrated in the mouth within 16 s. The established HPLC method was sensitive, rapid, and suitable for both L: -tetrahydropalmatine pharmacokinetic studies and its content assay in traditional Chinese medicine (TCM). The procedure of L: -tetrahydropalmatine in human was fit to double-compartmental model (w = 1). L: -tetrahydropalmatine orally disintegrating tablets were palatable, well-tolerated, disintegrated and absorbed quickly.

Expression and role of adiponectin receptor 1 in lipopolysaccharide-induced proliferation of cultured rat adventitial fibroblasts.

Adiponectin is an adipose-derived hormone that has anti-diabetic and anti-atherogenic effects through interaction with AdipoR1 and AdipoR2 (adiponectin receptors 1 and 2), but little is known about the expression and function of adiponectin and its receptors in adventitia and adventitial fibroblasts. In the present study, we have demonstrated that AdipoR1 is highly expressed in rat adventitia and cultured adventitial fibroblasts by quantitative real-time PCR, Western blotting and immunofluorescent staining, whereas Adipo2 is low-expressed. The expression of AdipoR1 have been observed to decrease gradually in adventitial fibroblasts in response to LPS (lipopolysaccharide) treatment. No local expression of adiponectin has been detected in adventitial tissues, indicating that serum adiponectin is the ligand for AdipoR1 in adventitial fibroblasts. In addition, treatment of recombinant adiponectin inhibited LPS-induced proliferation of adventitial fibroblasts via activation of the AMPK (adenosine monophosphate-activated protein kinase). AdipoR1 siRNA (small interfering RNA) transfection potently knocked down the receptor protein. The siRNA-AdipoR1 transfected cells and AMPK inhibitor compound C treated cells showed decreased phosphorylated level of AMPK as determined by Western blot analysis, and increased the proliferation of adventitial fibroblasts as determined by BrdU (5-bromo-29-deoxyuridine) staining. These results demonstrated that adiponectin stimulates the proliferation of adventitial fibroblasts via the AdipoR1 and AMPK signalling pathways.

Health status and risk for depression among the elderly: a meta-analysis of published literature.

OBJECTIVE: the goal of this study was to determine the relationship between health status, including self-rated health status and chronic disease, and risk for depression among the elderly. METHOD: MEDLINE, EMBASE and The Cochrane Library Database were used to identify potential studies. The studies were classified into cross-sectional and longitudinal subsets. For each study, the numbers of the total participants, cases (for cross-sectional study) or incident cases (for longitudinal study) of depression in each health status group were extracted and entered into Review Manager 4.2. The quantitative meta-analysis of cross-sectional studies and that of longitudinal studies were performed, respectively. For prevalence and incidence rates of depression, odds risk and relative risk (RR) were calculated, respectively. RESULTS: the quantitative meta-analysis showed that, compared with the elderly without chronic disease, those with chronic disease had higher risk for depression (RR: 1.53, 95% confidence intervals (CI): 1.20-1.97). Compared with the elderly with good self-rated health, those with poor self-rated health had higher risk for depression (RR: 2.40, 95% CI: 1.94-2.97). CONCLUSIONS: despite the methodological limitations of this meta-analysis, both poor self-rated health status and the presence of chronic disease are risk factors for depression among the elderly. In the elderly, poor self-reported health status appears to be more strongly associated with depression than the presence of chronic disease.

Effect of carvedilol on coronary flow reserve in patients with hypertensive left-ventricular hypertrophy.

OBJECTIVE: Patients with hypertensive left-ventricular hypertrophy (LVH) have lower coronary flow reserve (CFR). Whether carvedilol can improve CFR of patients with hypertensive LVH is unknown. We aimed to investigate the effects of carvedilol on CFR in patients with hypertensive LVH. METHODS: Sixty-three patients were randomly divided into two groups for treatment with carvedilol or metoprolol. The peak diastolic coronary flow velocity in the left anterior descending coronary artery at rest and at maximal vasodilation with dipyridamole infusion was recorded by transesophageal echocardiography (TEE), then CFR was calculated at baseline and at the end of 6 months of therapy. Left-ventricular mass index (LVMI) was calculated by 2-D echocardiography. Endothelium-dependent and -independent reactivity of the brachial artery was measured. Levels of plasma endothelin-1 (ET1), nitric oxide (NO) and other metabolites were monitored and analyzed before and after 6-month therapy. RESULTS: Both blood pressure and heart rate decreased significantly in the two treatment groups after therapy (p<0.05). With carvedilol treatment, LVMI was lower (p<0.05), endothelium function of the brachial artery was higher (p<0.05), and peak diastolic coronary flow velocity at rest and at maximal vasodilation after dipyridamole infusion was significantly higher (p<0.05) than with metoprolol treatment, which led to a significantly higher CFR (p<0.05). Changes in CFR and LVMI with carvedilol treatment were inversely correlated (R(2)=0.474, p=0.036). With carvedilol treatment, plasma level of ET-1 was lower, but that of NO was significantly higher than with metoprolol treatment (both p<0.05). CONCLUSIONS: The CFR of patients with hypertensive LVH but not coronary artery disease could increase with 6-month carvedilol therapy.

Prospective study of the efficacy of a ketogenic diet in 20 patients with Dravet syndrome.

PURPOSE: We evaluated the efficacy and tolerability of the ketogenic diet (KD) on generalised convulsions and status epilepticus (SE) in patients with Dravet syndrome (DS). METHODS: Patients with DS having ≥2 generalised convulsions/month despite drug treatment were included in this study and placed on a KD for 6 months. From 3 months before (baseline) to 6 months after KD initiation, caregivers recorded patients' seizure activity, antiepileptic drug use, and adverse events. The KD efficacy was determined by examining the frequency and duration of seizures at 3 and 6 months vs. baseline. Responders were defined as individuals whose generalised convulsions decreased in frequency by ≥50% vs. baseline. Seizures lasting ≥5 min and SE were specifically evaluated. Patients' cognition was also assessed at 3 and 6 months via questionnaire. RESULTS: Twenty patients continued the KD for at least 3 months. Of the 17 responders identified at month 3, seizures decreased by 50-89% and 90-99% in nine and two patients, respectively; six patients were seizure free. The KD was ineffective in three patients, who discontinued the diet. By month 6, seizures decreased by 50-89% and 90-99% in six and one patient(s), respectively; 10 patients were seizure free. The frequency of other seizure types also improved. During all 6 months, neither generalised convulsions lasting ≥5 min nor SE was detected in the 17 responders. The KD also improved patients' cognition. CONCLUSION: The KD is a good treatment option for medically intractable epilepsy.

[Cadherin switching induced by P120-catenin can promote the migration and invasion of oral squamous cell cancer cells].

OBJECTIVE: The main goal is to investigate the role of P120-catenin (P120ctn) in cadherin switching, as well as migration and invasion, of oral squamous cell cancer (OSCC) cells. METHODS: The plasmid pGFP-V-RS-P120ctn shRNA was used to transfect TSCCA cells and significantly reduce the expression of P120ctn in these cells. Real-time fluorescent quantitative polymerase chain reaction and Western blot were conducted to determine the mRNA and protein expression levels of P120ctn, E-cadherin (E-cad), and N-cadherin (N-cad). By contrast, the Transwell cell invasion and cell migration assay was used to determine the invasion and migration capacities before and after the transfection. RESULTS: After the plasmid pGFP-V-RS-P120ctn shRNA was transfected into the TSCCA cells, we found that as the P120ctn expression significantly decreased, E-cad mRNA and protein expression decreased significantly. Moreover, N-cad mRNA and protein expression increased significantly (P<0.05). Lastly, the cell migration and invasion capacities were augmented significantly (P<0.05). CONCLUSIONS: In OSCC cells, P120ctn may be involved in cadherin switching and promote metastasis and invasion.

PGC-1α regulates the cell cycle through ATP and ROS in CH1 cells.

Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) is a transcriptional co-activator involved in mitochondrial biogenesis, respiratory capacity, and oxidative phosphorylation (OXPHOS). PGC-1α plays an important role in cellular metabolism and is associated with tumorigenesis, suggesting an involvement in cell cycle progression. However, the underlying mechanisms mediating its involvement in these processes remain unclear. To elucidate the signaling pathways involved in PGC-1α function, we established a cell line, CH1 PGC-1α, which stably overexpresses PGC-1α. Using this cell line, we found that over-expression of PGC-1α stimulated extra adenosine triphosphate (ATP) and reduced reactive oxygen species (ROS) production. These effects were accompanied by up-regulation of the cell cycle checkpoint regulators CyclinD1 and CyclinB1. We hypothesized that ATP and ROS function as cellular signals to regulate cyclins and control cell cycle progression. Indeed, we found that reduction of ATP levels down-regulated CyclinD1 but not CyclinB1, whereas elevation of ROS levels down-regulated CyclinB1 but not CyclinD1. Furthermore, both low ATP levels and elevated ROS levels inhibited cell growth, but PGC-1α was maintained at a constant level. Together, these results demonstrate that PGC-1α regulates cell cycle progression through modulation of CyclinD1 and CyclinB1 by ATP and ROS. These findings suggest that PGC-1α potentially coordinates energy metabolism together with the cell cycle.

[Malaria endemic situation and comprehensive prevention and control measures in Caoxian County].

OBJECTIVE: To understand the malaria endemic characteristics and control measures in Caoxian County, Shandong Province, so as to summarize the experiences of malaria elimination. METHODS: The data of malaria endemic situation and control measures in Caoxian County from 1953 to 2014 were collected and descriptively analyzed, and the control effectiveness was evaluated. RESULTS: The incidence of malaria reduced from 13.25% in 1970 to 0.33% in 1983, and no malaria case was found in 1986. The goal of basic malaria elimination was achieved. The sporadic malaria infections were found from 2006 to 2010, and three imported malaria cases were found in Caoxian County from 2011 to 2014. CONCLUSIONS: The effect of comprehensive prevention and control measures taken in Caoxian County is significant, and the goal of malaria elimination has been reached. The imported malaria and secondary cases are future focuses of malaria control work.

Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome.

Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Previous studies have identified interferon-induced transmembrane proteins (IFITMs) as an interferon-stimulated gene family. However, the role of IFITMs in HTNV infection is unclear. In this study, we observed that IFITM3 single nucleotide polymorphisms (SNP) rs12252 C allele and CC genotype associated with the disease severity and HTNV load in the plasma of HFRS patients. In vitro experiments showed that the truncated protein produced by the rs12252 C allele exhibited an impaired anti-HTNV activity. We also proved that IFITM3 was able to inhibit HTNV infection in both HUVEC and A549 cells by overexpression and RNAi assays, likely via a mechanism of inhibiting virus entry demonstrated by binding and entry assay. Localization of IFITM3 in late endosomes was also observed. In addition, we demonstrated that the transcription of IFITM3 is negatively regulated by an lncRNA negative regulator of interferon response (NRIR). Taken together, we conclude that IFITM3, negatively regulated by NRIR, inhibits HTNV infection, and its SNP rs12252 correlates with the plasma HTNV load and the disease severity of patients with HFRS.