Macrolide resistance of Mycoplasma pneumoniae in several regions of China from 2013 to 2019.

This paper retrospectively analysed the prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) in some parts of China. Between January 2013 and December 2019, we collected 4,145 respiratory samples, including pharyngeal swabs and alveolar lavage fluid. The highest PCR-positive rate of M. pneumoniae was 74.5% in Beijing, the highest resistance rate was 100% in Shanghai, and Gansu was the lowest with 20%. The highest PCR-positive rate of M. pneumoniae was 74.5% in 2013, and the highest MRMP was 97.4% in 2019; the PCR-positive rate of M. pneumoniae for adults in Beijing was 17.9% and the MRMP was 10.48%. Among the children diagnosed with community-acquired pneumonia (CAP), the PCR-positive and macrolide-resistant rates of M. pneumoniae were both higher in the severe ones. A2063G in domain V of 23S rRNA was the major macrolide-resistant mutation, accounting for more than 90%. The MIC values of all MRMP to erythromycin and azithromycin were ≥ 64 µg/ml, and the MICs of tetracycline and levofloxacin were ≤ 0.5 µg/ml and ≤ 1 µg/ml, respectively. The macrolide resistance varied in different regions and years. Among inpatients, the macrolide-resistant rate was higher in severe pneumonia. A2063G was the common mutation, and we found no resistance to tetracycline and levofloxacin.

The Value of Sports and Functional Exercise on Preventing Falls in Elderly Patients with Cognitive Impairment: A Systematic Review and Meta-Analysis.

Objective: To explore the value of sports and functional exercises in preventing falls in elderly patients with cognitive impairment. Methods: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, VIP, Wanfang Database, and China Biomedical Literature Database (CBM), from inception to January 2023, were used to search the randomized controlled trials (RCTs) of sports and functional exercises in elderly patients with cognitive impairment. Two independent researchers extracted the data and evaluated the quality of the included literature. RevMan5.4 software was adopted for data analysis. Results: The results indicated that exercise combined with functional exercise could noticeably enhance the fall effect score and shorten the Timed Up and Go Test (TUGT) time of elderly patients with cognitive impairment compared to simple drug treatment (P < .05). Our results showed that the exercise combined with functional exercise can noticeably prolong the standing time of elderly patients with cognitive impairment upon monocular eye closure. Our results also showed that exercise combined with functional exercise can noticeably improve the fear of falls in elderly patients with cognitive impairment. Conclusion: Sports and functional exercise intervention can promote the balance ability and fall self-efficacy of elderly patients with cognitive impairment and have a positive effect on enhancing patients' fear of falls. The findings need to be further verified and methodological quality needs to be improved. In addition, longer intervention times are required to verify the findings.

Responses of applied voltages on the archaea microbial distribution in sludge digestion.

As the development of urban population led to the increase of domestic water consumption, consequently the generation of surplus sludge (SS) produced increasingly during sewage treatment processes. In order to enhance the SS resource utilization efficiency, an electricity-assisted anaerobic digestion (EAAD) system was employed to examine the alterations in the digestion broth and the characteristics of gas production. Additionally, the response of applied voltages on the distribution of archaeal community near various electrodes within the sludge was explored. The results revealed that the application of high voltages exceeding 3.0 V hindered the CH4 production but stimulated the CO2 generation. Subsequently, both CH4 and CO2 production were impeded by the applied voltages. Furthermore, the increased voltages significantly decreased the abundance of Methanomicrobia, Methanosaeta, and Methanosarcina, which were crucial determinants of CH4 content in biogas. Notably, the excessively high voltages intensities caused the AD process to halt and even inactivate the microbial flora. Interestingly, the distribution characteristics of archaeal community were influenced not only by the voltages intensity but also exhibited variations between the anode and cathode regions. Moreover, as the applied voltage intensified, the discrepancy of responses between the cathode and anode regions became more pronounced, offering novel theoretical and technical foundations for the advancement of electricity-assisted with AD technology.

Investigation on characterization of novel anti-bacterial chitosan/gelatin composite membranes loaded with quercetin via electrophoretic deposition.

Peri-implantitis is characterized by inflammation resulting from bacterial infections in peri-implant connective tissue. The purpose of this study was to prepare and characterize chitosan/gelatin (CSG)-based membranes with antibacterial agents to functionalize the surface of titanium (Ti) implants. CSG membranes were prepared on Ti substrates via electrophoretic deposition (EPD). Quercetin, an active flavonoid responsible for fulfilling various plant functions, was introduced as an antibacterial agent to be loaded into the membrane during preparation. The fabrication of quercetin-loaded CSG membranes via EPD was also investigated. Fluorescent microscope, Attenuated Total Reflection Fourier transform infrared spectroscopy, and X-ray diffraction results verified the entrapment of quercetin. The membranes swelled by 150% of mass after rehydration. The antibacterial effects of quercetin on Gram-positive bacteria, such as Staphylococcus aureus and methicillin-resistant Staphylococcus aureus, were verified by spread-plate, scanning electron microscopy, and live/dead staining. Cytological experiments showed that the biocompatibility of rat bone marrow mesenchymal stromal cells was promoted by quercetin-loaded membranes, exclusively in the group with the highest content of quercetin. The quercetin-loaded groups also enhanced the antineoplastic activity of MG-63 cells. These results suggested that quercetin-loaded CSG membranes were successfully fabricated via EPD. Thus, biocompatible and antibacterial membranes could be a potential strategy to functionalize Ti implants.

Polyoxovanadate-Based Cyclomatrix Polyphosphazene Microspheres as Efficient Heterogeneous Catalysts for the Selective Oxidation and Desulfurization of Sulfides.

The [V6O13]2- cluster is successfully immobilized to the polymeric framework of cyclomatrix polyphosphazene via the facile precipitation polymerization between the phenol group symmetrically modified [V6O13]2- and hexachlorocyclotriphosphazene. The structure of the as-prepared polyoxometalate-containing polyphosphazene (HCCP-V) was characterized by FT-IR, XPS, TGA, BET, as well as SEM and zeta potential. The presence of a rigid polyoxometalate cluster not only supports the porous structure of the polymeric framework but also provides an improved catalytic oxidation property. By using H2O2 as an oxidant, the as-prepared HCCP-V exhibited improved catalytic oxidation activity toward MPS, DBT, and CEES, which can achieve as high as 99% conversion. More importantly, the immobilization of POMs in the network of cyclomatrix polyphosphazene also provides better recyclability and stability of the heterogeneous catalyst.

Least-Square-Method-Based Optimal Laser Spots Acquisition and Position in Cooperative Target Measurement.

The relative positioning precisions of coordinate points is an important indicator that affects the final accuracy in the visual measurement system of space cooperative targets. Many factors, such as measurement methods, environmental conditions, data processing principles and equipment parameters, are supposed to influence the cooperative target's acquisition and determine the precision of the cooperative target's position in a ground simulation experiment with laser projected spots on parallel screens. To overcome the precision insufficiencies of cooperative target measurement, the factors of the laser diode supply current and charge couple device (CCD) camera exposure time are studied in this article. On the hypothesis of the optimal experimental conditions, the state equations under the image coordinates' system that describe the laser spot position's variation are established. The novel optimizing method is proposed by taking laser spot position as state variables, diode supply current and exposure time as controllable variables, calculating the optimal controllable variables through intersecting the focal spot centroid line and the 3-D surface, and avoiding the inconvenience of solving nonlinear equations. The experiment based on the new algorithm shows that the optimal solution can guarantee the focal spot's variation range in 5-10 pixels under image coordinates' system equivalent to the space with a 3 m distance and 0.6-1.2 mm positioning accuracy.

Core-shell Ag@C spheres derived from Ag-MOFs with tunable ligand exchanging phase inversion for electromagnetic wave absorption.

It has become greatly significant to achieve structurally tunable electromagnetic wave absorption materials (EMAs) derived from metal-organic frameworks (MOFs) via controllably continuous phase inversion. Herein, a series of core-shell Ag@C EMAs were successfully fabricated from Ag-MOFs via adjustable phase inversion. Replacing terephthalic acid (H2BDC) with 2-methylimidazole (Hmim) continuously led to the gradual transformation of Ag-MOF-5 structure into ZIF-L, which determined the crystal and morphological structure of Ag@C EMAs. In addition, due to the optimization of relaxation loss, the minimum reflection loss (RLmin) of S2 reached -50.14 dB with a thickness of 3.0 mm. The EMA derived from the original Ag-MOF had the widest absorption bandwidth (fE) of 5.44 GHz and RLmin of -47.36 dB at only 2.2 mm, respectively. This work can shed new light on the core-shell EMAs derived from phase inversion MOFs, and provide guidance to design novel high-performance EMAs.

Research on the electrochemistry synergied cellulase enzymes strengthens the anaerobic fermentation of cow dung.

Lignocellulose degradation (LCD) was the key factor limiting the development of anaerobic fermentation (AF) by the cow dung (CD). In the research, the effects of cellulase pretreatment (CP) and microvoltage (MV) alone and combination on the gas production and LCD during the AF were investigated. The results showed that both CP and MV had an significant effect on the AF, though the synergistic reaction was more pronounced. The total biogas yield (TBY) could reach 11521 mL, and the highest methane production rate was 73% in the synergistic reactions, which was increased by 18.7% and 10.0% compared to CP and MV alone respectively. Meanwhile, the degradation rates of cellulose and lignin could be increased by 33.44% and 22.23%, respectively. The results of SEM, FT-IR and excitation emission matrix demonstrated that CP and MV played an important role in improving the fermentation efficiency. The microbial biomass change results indicated that the synergistic effect of CP and 0.8 V MV on the LCD was achieved by promoting the growth of lignocellulose-degrading bacteria. Moreover, the electricity could not only accelerate the movement of microorganisms and enzymes, but also promoted and enhanced the activity of enzymes, which provided an important reference for further development of the AF technology and the biogas industry.

Efficacy of DC-CIK-based immunotherapy combined with chemotherapy in the treatment of intermediate to advanced non-small cell lung cancer.

OBJECTIVE: To evaluate the efficacy of dendritic cell-cytokine-induced killer cell (DC-CIK)-based immunotherapy combined with chemotherapy in the treatment of intermediate to advanced non-small cell lung cancer (NSCLC) and its effect on the levels of serum carbohydrate antigen 199 (CA199), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). METHODS: Sixty patients with intermediate to advanced NSCLC who were treated in the Department of Oncology of Jiangxi Cancer Hospital from January to June 2016 were grouped according to a randomized double-blind method, including the control group (CG, n=30) receiving a routine chemotherapy regimen and the experimental group (EG, n=30) receiving DC-CIK immunotherapy plus a routine chemotherapy regimen. The treatment efficacy, major adverse reactions, immune function, level of cytokines in peripheral blood, serum tumor markers and CA-199, MMP-9, TIMP-1 and vascular endothelial growth factor (VEGF) levels were compared between the two groups. RESULTS: The overall cancer control rate of treatment in the EG (70.00%) was slightly higher than that in the CG (56.67%) (P > 0.05). The peripheral blood CD4+ and natural killer (NK) cell levels in the EG after treatment were higher than those in the CG, while interleukin-4 (IL-4), interferon-γ (IFN-γ), transforming growth factor-ß (TGF-ß), tumor necrosis factor-α (TNF-α), CA199, carbohydrate antigen 125 (CA125), CYFRA211, carcinoembryonic antigen (CEA), MMP-9, TIMP-1, and VEGF levels in the EG were lower than those in the CG (P < 0.05). CONCLUSION: DC-CIK immunotherapy combined with routine chemotherapy in the treatment of intermediate to advanced NSCLC had significant efficacy in enhancing patients' cellular immune function, reducing the inflammatory response, regulating tumor marker levels, and inhibiting tumor invasion and metastasis, without increasing adverse reactions.

Tau-tubulin kinase 1 phosphorylates TDP-43 at disease-relevant sites and exacerbates TDP-43 pathology.

TDP-43 pathology is a hallmark of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal lobar degeneration (FTLD). Namely, both diseases feature aggregated and phosphorylated TDP-43 containing inclusions in the cytoplasm and a loss of nuclear TDP-43 in affected neurons. It has been reported that tau tubulin kinase (TTBK)1/2 phosphorylate TDP-43 and TTBK1/2 overexpression induced neuronal loss and behavioral deficits in a C. elegans model of ALS. Here we aimed to elucidate the molecular mechanisms of TTBK1 in TDP-43 pathology. TTBK1 levels were observed to be elevated in ALS patients' post-mortem motor cortex. Also, TTBK1 was found to phosphorylate TDP-43 at disease-relevant sites in vitro directly, and this phosphorylation accelerated TDP-43 formation of high molecular species. Overexpression of TTBK1 in mammalian cells induced TDP-43 phosphorylation and the construction of high molecular species, concurrent with TDP-43 mis-localization and cytoplasmic inclusions. In addition, when TTBK1 was knocked down or pharmacologically inhibited, TDP-43 phosphorylation and aggregation were significantly alleviated. Functionally, TTBK1 knockdown could rescue TDP-43 overexpression-induced neurite and neuronal loss in iPSC-derived GABAergic neurons. These findings suggest that phosphorylation plays a critical role in the pathogenesis of TDP-43 pathology and that TTBK1 inhibition may have therapeutic potential for the treatment of ALS and FTLD.

The efficacy and safety of domestic and imported rapamycin drug-eluting stents and paclitaxel drug-coated balloons in the treatment of coronary bifurcation lesions.

OBJECTIVE: The study was designed to analyze the efficacy and safety of domestic and imported rapamycin drug-eluting stents (DES) and paclitaxel drug-coated balloons (DCB) in the treatment of coronary bifurcation lesions. METHODS: A total of 98 patients with coronary bifurcation lesions treated in our hospital from January 2019 to December 2019 were recruited as the study cohort and divided into four groups according to the different treatment method each patient underwent, including group A (n=25, treated with domestic rapamycin DES), group B (n=21, treated with imported rapamycin DES), group C (n=29, treated with domestic paclitaxel DCB), and group D (n=23, treated with imported paclitaxel DCB). The minimum lumen diameters (MLD), the diameter stenosis rates, the late lumen losses (LLLs), and the incidence of adverse events in each group were compared. RESULTS: The MLD in the four groups were increased immediately after the surgeries and at nine months after the surgeries (P<0.05), and the diameter stenosis rates were decreased (P<0.05). However, there were no significant differences in the MLD or the diameter stenosis rates among the four groups before the surgeries, immediately after the surgeries, or at nine months after the surgeries (P>0.05). The LLLs of groups A and B were significantly higher than the LLLs of groups C and D (P<0.05). Compared with the incidences of major adverse cardiovascular events (16.00% vs. 14.29% vs. 13.79% vs. 17.39%) and the incidences of restenosis (8.00% vs. 4.76% vs. 6.90% vs. 4.35%) in groups A, B, C, and D, there were no significant differences (P>0.05). CONCLUSION: Domestic and imported rapamycin DES and paclitaxel DCB can effectively improve MLD, reduce the diameter stenosis rate, and have fewer adverse events in the treatment of coronary bifurcation lesions, and domestic and imported paclitaxel DCB have lower LLLs.

Research on the efficient water-absorbing ceramsite generated by dredged sediments in Dian Lake-China and coal fly ash.

In order to transform the dredged sediment (DS) into an efficient water-absorbing ceramsite (EWAC), the coal fly ash (CFA) and expansion agent were used to blend, expand, and sinter with the DS in the Dian Lake-China. A new type of high EWAC was prepared with the absorption ratio of 66.71%, which was much higher than similar products. The heavy metals leaching (HML) of EWAC showed that the concentration of As was 0.90 mg/L and the Hg, Pb, Cd, and Cr were too low to be detected. The characterization analysis showed that the EWAC cross section contained a lot of hydroxyl, ether, and P-Cl hydrophilic group by Fourier transform infrared (FT-IR), scanning electron microscope (SEM), and Brunauer-Emmett-Teller (BET) specific surface area (SSA) test method. The above groups and structures could greatly improve the water absorption (WA) performance of the EWAC. What's more, the SSA of the EWAC could reach 4.468 m2 /g. The results of Comsol Multiphysics indicated that the SSA and average pore size (APS) of the EWACs were 10 and 6 times higher than the commercial ceramsites, respectively. The research provided the utilization of the DS with technical and theoretical basis for the construction of sponge city. PRACTITIONER POINTS: The article was focus on the utilization of dredged sediment (DS) and coal fly ash (CFA) for the basic material preparation technology and its toxicity test as the sponge city. First, the raw materials were the DS in Dian Lake (Kunming, Yunnan, China) and CFA (thermal power plants), which were all belonged to the hazardous solid waste and was made to the efficient water-absorbing ceramsite (EWAC). Second, the water absorption (WA) performance of the EWAC was improved greatly whose absorption ratio was much higher than similar products reached 66.71%. The specific surface area (SSA) and average pore size (APS) of the EWACs were 10 and 6 times higher than the commercial ceramsites (CCs), respectively. Finally, the heavy metals leaching (HML) of As was 0.90 mg/L, and the HML of Hg, Pb, Cd, and Cr was all lower than 0.05 mg/L, which could not only not cause secondary pollution but provide the new ideas for the resource utilization of large amount of DS. So, we thought this article was suitable for the journal.

Research on dynamics and mechanism of treatment on phenol simulated wastewater by the ultrasound cooperated electro-assisted micro-electrolysis.

In the research, the ultrasound was introduced to the electric-assisted micro-electrolysis system to improve the treatment efficiency of phenol simulated wastewater. The results showed that the phenol removal efficiency was significantly enhanced by the electric-assisted micro-electrolysis method in the presence of ultrasound, which could reach 88.61% under the initial value of pH 4, an iron dosage of 50 g/L, a mass ratio of iron/carbon of 1:1, and the initial phenol concentration of 100 mg/L. The degradation kinetics of phenol was in accordance with a second-order kinetic model. The synergistic effect of the ultrasonic and electric-assisted micro-electrolysis method was obvious with a synergistic factor at 98.02%. The degradation mechanism of phenol was that the treatment could effectively destroy the benzene ring structure of phenol in the liquid phase with ring-opening reaction and small molecules substances generated. PRACTITIONER POINTS: The article was the pretreatment of coking wastewater. First, the synergistic effects between ultrasound and electrochemical method through the removal ratio of phenol were found. Second, it was showed that the initial pH and applied intensity of voltage had the effects on removal ratio of phenol by the UEME method. Third, the synergy factor (Syn ) between ultrasonic and electrochemical method was 98.02%. Finally, the mechanism of the UEME degradation of phenol was researched. The technology could effectively improve the biodegradability of coking wastewater and provide conditions for subsequent biochemical treatment. So, we thought this article was suitable for the journal.

Knockdown of DDX46 suppresses the proliferation and invasion of gastric cancer through inactivating Akt/GSK-3ß/ß-catenin pathway.

DEAD-box RNA helicase 46 (DDX46) has recently been identified as a candidate oncogene in several types of human malignancies. To date, the role of DDX46 in gastric cancer has not been determined. The purpose of the current study was to explore the role of DDX46 in gastric cancer and the potential mechanism. DDX46-silecing or overexpressing gastric cancer cell lines were established to validate the role of DDX46. Our results showed that the expression of DDX46 was significantly increased in gastric cancer tissues and cell lines. Knockdown of DDX46 suppressed the proliferation and invasion of gastric cancer cells. Whereas, DDX46 overexpression enhanced the cell proliferation and invasion of gastric cancer cells. Furthermore, knockdown of DDX46 markedly suppressed the tumor growth of xenografts. Research into the mechanism revealed that DDX46 depletion inhibited the Akt/GSK-3ß/ß-catenin signaling pathway in gastric cancer cells. Notably, activation of Akt or ß-catenin overexpression reversed the DDX46 depletion-mediated anti-cancer effect. In conclusion, these findings indicated that DDX46 exerted an oncogenic role in gastric cancer via regulating the Akt/GSK-3ß/ß-catenin signaling pathway. Thus, DDX46 might be utilized as a therapeutic anti-cancer target.

Adsorption of arsenic from aqueous solution using a zero-valent iron material modified by the ionic liquid [Hmim]SbF6.

The environmental and health impacts caused by arsenic (As) in wastewater make it necessary to carefully manage As wastes. In the present work, a composite of the ionic liquid [Hmim]SbF6 and nano-iron (H/Fe) was used as an adsorbent to remove As(v) from aqueous solution. To better understand the removal effect of H/Fe on As(v) in aqueous solution, the reaction parameters of pH, reaction temperature, time and H/Fe dosage were systematically analyzed in detail. The results show that H/Fe has significant removal efficiency toward As(v), and that the adsorption of As(v) by 0.5 g H/Fe reaches its maximum adsorption capacity within 2 h. The adsorption of As(v) on H/Fe is a non-linear, time-varying process. The initial adsorption reaction is fast; however, unlike at the beginning, the later reaction involves sustained slow absorption, resulting in a distinct two-phase adsorption characteristic. Redox reaction may be one of the mechanisms responsible for the slow adsorption of As(v) on H/Fe. At the same time, the As(v) removal effect of H/Fe is greatly restricted by the pH. Electrostatic adsorption, adsorption co-precipitation and redox reactions act together on H/Fe in the As(v) removal process. This study provides a basis for further clarifying the adsorption, adsorption rules and mechanism of As(v) on H/Fe and a feasible method for the improvement of As(v) removal efficiency of zero-valent iron materials.

The epidemiology of paediatric Mycoplasma pneumoniae pneumonia in North China: 2006 to 2016.

Paediatric Mycoplasma pneumoniae pneumonia (MPP) is a major cause of community-acquired pneumonia in China. Data on epidemiology of paediatric MPP from China are little known. This study retrospectively collected data from June 2006 to June 2016 in Beijing Children's Hospital, Capital Medical University of North China and aims to explore the epidemiological features of paediatric MPP and severe MPP (SMPP) in North China during the past 10 years. A total of 27 498 paediatric patients with pneumonia were enrolled. Among them, 37.5% of paediatric patients had MPP. In this area, an epidemic took place every 2-3 years at the peak, and the positive rate of MPP increased during these peak years over time. The peak age of MPP was between the ages of 6 and 10 years, accounting for 75.2%, significantly more compared with other age groups (χ2 = 1384.1, P < 0.0001). The epidemics peaked in September, October and November (χ2 = 904.9, P < 0.0001). Additionally, 13.0% of MPP paediatric patients were SMPP, but over time, the rate of SMPP increased, reaching 42.6% in 2016. The mean age of paediatric patients with SMPP (6.7 ± 3.0 years old) was younger than that of patients with non-SMPP (7.4 ± 3.2 years old) (t = 3.60, P = 0.0001). The prevalence of MPP and SMPP is common in China, especially in children from 6 to 10 years old. Paediatric patients with SMPP tend to be younger than those with non-SMPP. MPP outbreaks occur every 2-3 years in North China. September, October and November are the peak months, unlike in South China. Understanding the epidemiological characteristics of paediatric MPP can contribute to timely treatment and diagnosis, and may improve the prognosis of children with SMPP.

A New Way for Beta Cell Neogenesis: Transdifferentiation from Alpha Cells Induced by Glucagon-Like Peptide 1.

Recent studies showed that alpha cells, especially immature cells and proalpha cells, might be the precursors of beta cells. Exposure to glucagon-like peptide 1 (GLP1) can ameliorate hyperglycemia in diabetic mice and restore the beta cell mass. In the present study, we adopted single high-dose (60 mg/kg, i.p.) streptozotocin (STZ) to model diabetes mellitus (DM) and randomly assigned short-tail (SD) rats to a normal group, a diabetic group, GLP1 groups (50 µg/kg, 100 µg/kg, and 200 µg/kg), a GLP1 (200 µg/kg) with exendin (9-39) group, and a GLP1 with LY294002 group. We found that the pancreatic insulin-glucagon-positive cell populations increased according to the increase in GLP1 exposure. By contrast, no insulin-amylase-positive cell populations or insulin/pan-cytokeratin cells were observed in the pancreatic sections. The GLP1 receptor antagonist exendin (9-39) and the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) family inhibitor LY294002 not only suppressed protein kinase B (Akt), pancreatic and duodenal homeobox 1 (Pdx1), forkhead box O 1 (FoxO1), and mast cell function-associated antigen A (MafA) mRNA expression but also increased MAFB expression. We concluded that treatment with GLP1 might result in beta cell neogenesis by promoting the transdifferentiation of alpha cells but not by pancreatic acinar cells, ductal cells, or the self-replication of beta cells. The regulation on the GLP1 receptor and its downstream transcription factor PI3K/AKT/FOXO1 pathway, which causes increased pancreatic and duodenal homeobox 1 (Pdx1) and MafA mRNA expression but causes decreased MAFB expression, may be the mechanism involved in this process.

The Specific Inhibition of SOD1 Selectively Promotes Apoptosis of Cancer Cells via Regulation of the ROS Signaling Network.

Multiple signaling pathways including ERK, PI3K-Akt, and NF-κB, which are essential for onset and development of cancer, can be activated by intracellularly sustained high levels of H2O2 provided by elevated activity and expression of copper/zinc superoxide dismutase (SOD1) that catalyzes the dismutation of O2 •- into H2O2. Here, tests performed by the utilization of our designed specific SOD1 inhibitor LD100 on cancer and normal cells reveal that the signaling pathways and their crosstalk to support cancer cell growth are repressed, but the signaling pathways to promote cancer cell cycle arrest and apoptosis are stimulated by specific SOD1 inhibition-mediated ROS changes. These regulated pathways constitute an ROS signaling network that determines the fate of cancer cells. This ROS signaling network is also regulated in SOD1 knockdown cells. These findings might facilitate disclosure of action mechanisms by copper-chelating anticancer agents and design of SOD1-targeting and ROS signaling pathway-interfering anticancer small molecules.

Islet Function Changes Among the Elderly Population.

BACKGROUND: China is stepping into the aging society. The prevalence of type 2 diabetes among elderly population is increasing in China in the last few decades. However, there is a lack of epidemiological investigations regarding to the aging-related changes of islet function in the elderly population. OBJECTIVE: To investigate the islet function and glycemic conditions in the elderly population of western China. METHODS: Using a complex, multistage, probability sampling design, we conducted a cross-sectional survey in a provincial representative sample of 3001 western Chinese elderly adults. A 2 h oral glucose tolerance test (OGTT) was conducted among all study participants, and islet function measurements including HOMA-ß, HOMA-IR, HOMA-IS, ΔI30/ΔG30, Ip/I0 were calculated. RESULTS: HOMA-ß, HOMA-IR and ΔI30/ΔG30 decreased gradually along with increasing age from age of 55 to age of 80 (p <0.05). HOMA-IR, HOMA-ß and ΔI30/ΔG30 were significantly higher while HOMA-IS lower among urban residents than rural residents or suburb residents (p <0.01). FPG, 2 h plasma glucose (P2hPG) and HbA1C increased with increasing age (p <0.05), while fasting insulin level (FINS) and 2 h insulin level (P2hINS) decreased with increasing age (p <0.05). FPG, P2hPG and glycated hemoglobin (HbA1C) among suburb residents were lower than among urban residents and among rural residents (p <0.05). CONCLUSION: Islet function decreased gradually along with increasing age with no gender difference among the elderly population in western China. Glycemic outcomes became worse with increasing age. These results indicated that strategies aimed at the prevention of diabetes in the elderly population were needed.

Bupleurum marginatum Wall.ex DC in Liver Fibrosis: Pharmacological Evaluation, Differential Proteomics, and Network Pharmacology.

Liver fibrosis is a common pathological feature of many chronic liver diseases. Bupleurum marginatum Wall.ex DC (ZYCH) is a promising therapeutic for liver fibrosis. In this study, 25 compounds were isolated from ZYCH, and the effects of ZYCH on DMN-induced liver fibrosis in rats were evaluated. The optimal effect group (H-ZYCH group) was selected for further proteomic analysis, and 282 proteins were altered in comparison to the DMN model group (FC > 1.2 or < 0.83, p < 0.05). Based on GO annotation analysis, clusters of drug metabolism, oxidative stress, biomolecular synthesis and metabolism, positive regulation of cell growth, extracellular matrix deposition, and focal adhesion were significantly regulated. Then networks of the altered proteins and compounds was generated by Cytoscape. Importantly, triterpenoid saponins and lignans had possessed high libdock scores, numerous targets, important network positions, and strong inhibitory activity. These findings may suggest that triterpenoid saponins and lignans are important active compounds of ZYCH in liver fibrosis and targeted by proteins involved in liver fibrosis. The combination of network pharmacology with proteomic analysis may provide a forceful tool for exploring the effect mechanism of TCM and identifying bioactive ingredients and their targets.