Population impact of fine particulate matter on tuberculosis risk in China: a causal inference.

BACKGROUND: Previous studies have suggested the potential association between air pollution and tuberculosis incidence, but this association remains inconclusive and evidence to assess causality is particularly lacking. We aimed to draw causal inference between fine particulate matter less than 2.5 µm in diameter (PM2.5) and tuberculosis in China. METHODS: Granger causality (GC) inference was performed within vector autoregressive models at levels and/or first-differences using annual national aggregated data during 1982-2019, annual provincial aggregated data during 1982-2019 and monthly provincial aggregated data during 2004-2018. Convergent cross-mapping (CCM) approach was used to determine the backbone nonlinear causal association based on the monthly provincial aggregated data during 2004-2018. Moreover, distributed lag nonlinear model (DLNM) was applied to quantify the causal effects. RESULTS: GC tests identified PM2.5 driving tuberculosis dynamics at national and provincial levels in Granger sense. Empirical dynamic modeling provided the CCM causal intensity of PM2.5 effect on tuberculosis at provincial level and demonstrated that PM2.5 had a positive effect on tuberculosis incidence. Then, DLNM estimation demonstrated that the PM2.5 exposure driven tuberculosis risk was concentration- and time-dependent in a nonlinear manner. This result still held in the multi-pollutant model. CONCLUSIONS: Causal inference showed that PM2.5 exposure driving tuberculosis, which showing a concentration gradient change. Air pollutant control may have potential public health benefit of decreasing tuberculosis burden.

Acute liver failure: A systematic review and network meta-analysis of optimal type of stem cells in animal models.

BACKGROUND: The therapeutic effects of various stem cells in acute liver failure (ALF) have been demonstrated in preclinical studies. However, the specific type of stem cells with the highest therapeutic potential has not been determined. AIM: To validate the efficacy of stem cells in ALF model and to identify the most promising stem cells. METHODS: A search was conducted on the PubMed, Web of Science, Embase, Scopus, and Cochrane databases from inception to May 3, 2022, and updated on November 16, 2022 to identify relevant studies. Two independent reviewers performed the literature search, identification, screening, quality assessment, and data extraction. RESULTS: A total of 89 animal studies were included in the analysis. The results of traditional meta-analysis showed that stem cell therapy could significantly reduce the serum levels of alanine aminotransferase [weighted mean difference (WMD) = -181.05 (-191.71, -170.39)], aspartate aminotransferase [WMD = -309.04 (-328.45, -289.63)], tumor necrosis factor-alpha [WMD = -8.75 (-9.93, -7.56)], and interleukin-6 [WMD = -10.43 (-12.11, -8.76)] in animal models of ALF. Further subgroup analysis and network meta-analysis showed that although mesenchymal stem cells are the current research hotspot, the effect of liver stem cells (LSCs) on improving liver function is significantly better than that of the other five types of stem cells. In addition, the ranking results showed that the possibility of LSCs improving liver function ranked first. This fully proves the great therapeutic potential of LSCs, which needs to be paid more attention in the future. CONCLUSION: LSCs may have a higher therapeutic potential. Further high-quality animal experiments are needed to explore the most effective stem cells for ALF.

Downregulation of MDM2 by small interference RNA induces apoptosis and sensitizes MCF-7 breast cells to resveratrol.

Recent studies have demonstrated the mouse double minute gene (MDM2), a main oncogene, as a novel and interesting therapeutic target for cancer therapy. The aim of this study was to investigate the involvement of MDM2 in antiproliferative and antimetastatic effects of resveratrol in breast cancer cells. MCF-7 cells were transfected with siRNA against MDM2 and resveratrol. Proliferation and apoptosis were evaluated by MTT assay and cell death ELISA assay, respectively. MDM2, p53, Bax, Bcl-2, caspase-3, MMP-2, and MMP9 expressions were determined by qRT-PCR and Western blotting. Transfection with si-MDM2 significantly suppressed the expression of MDM2 expression, resulting in MCF-7 cell growth inhibition and spontaneous apoptosis. Pretreatment with Si-MDM2 synergically increased antiproliferation and antimetatstatic effects of resveratrol. No significant anticancer effects were detected with negative control siRNA treatment. Our findings suggest that silencing of MDM2 by specific siRNA effectively induce apoptosis and also enhanced anticancer effects of resveratrol. Therefore, siMDM2 may be a potent combination in breast therapy.

The role of P62 in the development of human thyroid cancer and its possible mechanism.

BACKGROUND: Thyroid cancer is the most common malignancy in human endocrine system. Increasing evidence has indicated that p62 plays a key role in tumorigenesis. The roles and underlying molecular mechanisms of P62 in thyroid cancer, however, remain to be elucidated. METHODS: The expression levels of P62 in thyroid tumor tissues and thyroid cancer cells were detected by western blotting and qRT-PCR. Then, the effects of up-regulation or down-regulation of P62 on thyroid cancer cell proliferation, migration, invasion, cell cycle and apoptosis were measured by CCK-8 assay, transwell assay, flow cytometry and transwell assay, respectively. In terms of the mechanism, P62 could stimulate thyroid cancer progression by the activation of nuclear factor-kappa B (NF-κB) signaling pathway. RESULTS: P62 was highly expressed in thyroid tumor tissues. Furthermore, high expression of p62 was observed in PTC cell lines, and especially in the K1 and TPC-1 cells. In vitro, the up-regulation of p62 promoted cell proliferation, migration, and invasion of thyroid cancer cells, whereas the knockdown of p62 resulted in the opposite effect. Knock-down of P62 increased the number of cells in the G0/G1 phase but reduced it in the S and G2/M phase. Moreover, we confirmed that overexpression of p62 inactivated NF-κB pathway with sequencing analysis and bioinformatics analysis. CONCLUSION: This research work suggested that p62 could promote PTC cell proliferation, migration, and invasion via NF-κB signaling pathway. Furthermore, p62 is a potential biomarker which might be closely related to the tumorigenesis in PTC. Its potential role as a therapeutic target for PTC is worthy of further study.

Using activated attapulgite as sorbent for solid-phase extraction of melamine in milk formula samples.

In this study, a simple solid-phase extraction (SPE) approach by using activated attapulgite as sorbent was successfully developed for the determination of melamine in milk formula samples. Crucial factors impacting the extraction efficiency, including sample solvent, elution solvent, and sample loading volume, were investigated. Under the optimal extraction conditions, the sample loading volume was up to 200 mL and the adsorption capacity of the melamine gave rise to 1154 µg g(-1). Excellent linear calibration curves (r (2) > 0.999) were achieved, and then the limit of detection (S/N = 3) and the limit of quantification (S/N = 10) were found to be 0.15 and 0.5 ng mL(-1), respectively. The recoveries of the melamine spiked in four milk formula samples at three concentration levels ranged from 83.5 to 111.0 % with relative standard deviations (RSDs) less than 10.2 %. Furthermore, RSDs of batch to batch (n = 4) of the acidified attapulgite used in this developed method were in the range of 2.3∼7.3 %. In comparison to the commercial Oasis MCX, the acidified attapulgite sorbent even outperformed (at least in terms of reproducibility) for melamine analysis in real food samples. Because of its simplicity, the newly developed SPE method based on acidified attapulgite nanoparticles should provide a promising tool for daily monitoring of doped melamine in milk formula or other complex matrices.

Epigallocatechin-3-gallate (EGCG) inhibits 3-hydroxy-3-methylglutaryl-CoA reductase in the presence of glycerol.

The inhibition of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) is considered able to decrease serum cholesterol levels and dramatically reduce the risk for cardiovascular and cerebrovascular diseases. The statins, competitive inhibitors of HMGCR, have been employed to control hypercholesterolemia. But their side effects, especially their safety of long-term administration have attracted great attention. Therefore, there is still an urgent requirement for the development of safer inhibitors of HMGCR with less serious side effects. In this study, we cloned and purified the catalytic domain of human HMGCR (△HMGCR), and applied the method of Ultra Performance Liquid Chromatography (UPLC) to assay △HMGCR activity and screen its inhibitors from natural products. The results indicated that EGCG can inhibit △HMGCR in the presence of some glycerol in vitro and can decrease cellular total cholesterol in HepG2 cells. As a consequence, it is promising to put EGCG into the development of hypolipidemic health product.

Caenorhabditis elegans eyes absent ortholog EYA-1 is required for stress resistance.

Eyes absent (Eya) is a highly conserved transcription cofactor and protein phosphatase that regulates multiple developmental processes throughout the metazoans. It is a dual function protein, working as a transcription factor in the nucleus and as a tyrosine phosphatase in the cytoplasm. In this study, we isolated EYA-1 of Caenorhabditis elegans, the only homolog of Eyes absent, and set up an effective feeding-based RNAi (RNA interference) against the gene. We found that knockdown of EYA-1 decreased heat and oxidative stress tolerance and accelerated the onset of paralysis mediated by Aß1-42 proteotoxicity and polyQ. Under heat stress (35°C), EYA-1 knockdown shortened the mean lifespan by 16.8%, which could be attributed to decrease in heat shock protein-16.2 (hsp-16.2) expression. Under oxidative stress, EYA-1 knockdown could shorten the mean lifespan by 18.7%, which could be attributed to intracellular ROS accumulation and the decrease of superoxide dismutase-3 (sod-3) protein expression. Moreover, EYA-1 knockdown animals also showed increased lipofuscin accumulation under oxidative stress. Further studies demonstrated that EYA-1 knockdown could not inhibit daf-16 nuclear accumulation in wild-type worms in response to stress. On the other hand, EYA-1 deficiency did not further reduce stress resistance of daf-16 mutants, which are stress sensitive. Quantitative real-time PCR results also showed that the expression of two daf-16 target genes, hsp-12.3 and sod-3, was downregulated in EYA-1 RNAi-treated worms under stress. All this evidence indicates EYA-1 is required for stress resistance of worms, and it might act downstream of daf-16 to regulate expression of stress resistance-associated genes.

A novel ionic liquid-modified organic-polymer monolith as the sorbent for in-tube solid-phase microextraction of acidic food additives.

A novel ionic liquid-modified organic-polymer monolithic capillary column was prepared and used for in-tube solid-phase microextraction (SPME) of acidic food additives. The primary amino group of 1-aminopropyl-3-methylimidazolium chloride was reacted with the epoxide group of glycidyl methacrylate. The as-prepared new monomer was then copolymerized in situ with acrylamide and N,N'-methylenebisacrylamide in the presence of polyethylene glycol (PEG)-8000 and PEG-10,000 as porogens. The extraction performance of the developed monolithic sorbent was evaluated for benzoic acid, 3-hydroxybenzoic acid, cinnamic acid, 2,4-dichlorophenoxyacetic acid, and 3-(trifluoromethyl)-cinnamic acid. Such a sorbent, bearing hydrophobic and anion-exchange groups, had high extraction efficiency towards the test compounds. The adsorption capacities for the analytes dissolved in water ranged from 0.18 to 1.74 µg cm(-1). Good linear calibration curves (R(2) > 0.99) were obtained, and the limits of detection (S/N = 3) for the analytes were found to be in the range 1.2-13.5 ng mL(-1). The recoveries of five acidic food additives spiked in Coca-Cola beverage samples ranged from 85.4 % to 98.3 %, with RSD less than 6.9 %. The excellent applicability of the ionic liquid (IL)-modified monolithic column was further tested by the determination of benzoic acid content in Sprite samples, further illustrating its good potential for analyzing food additives in complex samples.

Brachialis insertion measurement: an anatomic cadaver study for plate fixation of the coronoid process fracture.

Detailed assessment of the proximity of the brachialis insertion to the anterior bundle of the medial collateral ligament and its potential influence on plate application for the treatment of the coronoid process fracture has not been reported previously. The purpose of this study was to describe the anatomic interval used for coronoid plate and the measurement of the brachialis insertion to confirm partial release of the insertion site may be required during plate fixation of the coronoid process fracture. After eight fresh-frozen cadaveric elbows were dissected, the interval between the brachialis insertion and the attachment of the anterior bundle of medial collateral ligament was identified, and the gross morphological characteristics of the brachialis insertion were also recorded. The average width of the interval was 4.14 mm, and the brachialis was found to be consisted of a superficial head and a deep head, and insertion of the deep head was composed of three units: a medial aponeurosis, a lateral aponeurosis, and muscle fibers inserted directly into the ulna. The interval between the brachialis insertion and the attachment of the anterior bundle of medial collateral ligament can be used for placement of the coronoid plate regardless of the plate type. Partial release of the brachialis insertion is necessary during the operation, while the width of the plate is larger than that of the interval. This study may provide some useful information on plate application for the treatment of the coronoid process fracture.