The epigenetic regulatory mechanism of PIWI/piRNAs in human cancers.

PIWI proteins have a strong correlation with PIWI-interacting RNAs (piRNAs), which are significant in development and reproduction of organisms. Recently, emerging evidences have indicated that apart from the reproductive function, PIWI/piRNAs with abnormal expression, also involve greatly in varieties of human cancers. Moreover, human PIWI proteins are usually expressed only in germ cells and hardly in somatic cells, so the abnormal expression of PIWI proteins in different types of cancer offer a promising opportunity for precision medicine. In this review, we discussed current researches about the biogenesis of piRNA, its epigenetic regulatory mechanisms in human cancers, such as N6-methyladenosine (m6A) methylation, histone modifications, DNA methylation and RNA interference, providing novel insights into the markers for clinical diagnosis, treatment and prognosis in human cancers.

Predictive value of ACEF II score for adverse prognosis in patients with coronary heart disease after percutaneous coronary intervention.

OBJECTIVE: To investigate the predictive value of age, creatinine and ejection fraction (ACEF) II score for the incidence of major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). METHODS: A total of 445 patients with CHD who underwent PCI were consecutively enrolled. The receiver operating characteristic (ROC) curve was used to analyse the power of the ACEF II score in predicting MACCE. Kaplan-Meier survival curves and log-rank tests were chosen for survival analysis of adverse prognosis between groups. Finally, multivariate Cox proportional risk regression analysis was used to investigate independent risk factors for MACCEs in patients with CHD after PCI. RESULTS: There was a significantly higher incidence of MACCEs in patients with high ACEF II scores. The area under the ROC curve of ACEF II score was 0.718, suggesting it had ideal predictive value for MACCE risks. The ACEF II score had a best cut-off value of 1.461 (sensitivity 79.4%, specificity 53.7%). Survival analysis indicated that patients in the high-score group had a significantly lower cumulative MACCE-free survival rate. Multivariate Cox regression analysis showed that ACEF II scores ≥1.461, Gensini scores ≥61.5, age, cardiac troponin I and previous PCI were independent risk factors of MACCE in patients with CHD after PCI, while the utilisation of statins was an independent protective factor. CONCLUSIONS: The ACEF II score has an ideal capacity for risk stratification in patients with CHD undergoing PCI and offers good predictive value for MACCE in the long term.

[Determination of calcium and magnesium in tobacco by near-infrared spectroscopy and least squares-support vector machine].

The purpose of the present paper is to determine calcium and magnesium in tobacco using NIR combined with least squares-support vector machine (LS-SVM). Five hundred ground and dried tobacco samples from Qujing city, Yunnan province, China, were surveyed by a MATRIX-I spectrometer (Bruker Optics, Bremen, Germany). At the beginning of data processing, outliers of samples were eliminated for stability of the model. The rest 487 samples were divided into several calibration sets and validation sets according to a hybrid modeling strategy. Monte-Carlo cross validation was used to choose the best spectral preprocess method from multiplicative scatter correction (MSC), standard normal variate transformation (SNV), S-G smoothing, 1st derivative, etc., and their combinations. To optimize parameters of LS-SVM model, the multilayer grid search and 10-fold cross validation were applied. The final LS-SVM models with the optimizing parameters were trained by the calibration set and accessed by 287 validation samples picked by Kennard-Stone method. For the quantitative model of calcium in tobacco, Savitzky-Golay FIR smoothing with frame size 21 showed the best performance. The regularization parameter λ of LS-SVM was e16.11, while the bandwidth of the RBF kernel σ2 was e8.42. The determination coefficient for prediction (Rc(2)) was 0.9755 and the determination coefficient for prediction (Rp(2)) was 0.9422, better than the performance of PLS model (Rc(2)=0.9593, Rp(2)=0.9344). For the quantitative analysis of magnesium, SNV made the regression model more precise than other preprocess. The optimized λ was e15.25 and σ2 was e6.32. Rc(2) and Rp(2) were 0.9961 and 0.9301, respectively, better than PLS model (Rc(2)=0.9716, Rp(2)=0.8924). After modeling, the whole progress of NIR scan and data analysis for one sample was within tens of seconds. The overall results show that NIR spectroscopy combined with LS-SVM can be efficiently utilized for rapid and accurate analysis of calcium and magnesium in tobacco.

Association between periodontitis and inflammatory comorbidities: The common role of innate immune cells, underlying mechanisms and therapeutic targets.

Periodontitis, which is related to various systemic diseases, is a chronic inflammatory disease caused by periodontal dysbiosis of the microbiota. Multiple factors can influence the interaction of periodontitis and associated inflammatory disorders, among which host immunity is an important contributor to this interaction. Innate immunity can be activated aberrantly because of the systemic inflammation induced by periodontitis. This aberrant activation not only exacerbates periodontal tissue damage but also impairs systemic health, triggering or aggravating inflammatory comorbidities. Therefore, innate immunity is a potential therapeutic target for periodontitis and associated inflammatory comorbidities. This review delineates analogous aberrations of innate immune cells in periodontitis and comorbid conditions such as atherosclerosis, diabetes, obesity, and rheumatoid arthritis. The mechanisms behind these changes in innate immune cells are discussed, including trained immunity and clonal hematopoiesis of indeterminate potential (CHIP), which can mediate the abnormal activation and myeloid-biased differentiation of hematopoietic stem and progenitor cells. Besides, the expansion of myeloid-derived suppressor cells (MDSCs), which have immunosuppressive and osteolytic effects on peripheral tissues, also contributes to the interaction between periodontitis and its inflammatory comorbidities. The potential treatment targets for relieving the risk of both periodontitis and systemic conditions are also elucidated, such as the modulation of innate immunity cells and mediators, the regulation of trained immunity and CHIP, as well as the inhibition of MDSCs' expansion.

Drivers of 2013-2020 ozone trends in the Sichuan Basin, China: Impacts of meteorology and precursor emission changes.

The Sichuan Basin (SCB) of China is known for excessive ozone (O3) pollution owing to high anthropogenic emissions combined with terrain-induced poor ventilation and weak wind fields against the surrounding mountains. While O3 pollution has emerged as a prominent concern in southwestern China yet variations in O3 levels during 2013-2020 are still unclear and the dominant factor in explaining the long-term O3 trend throughout the SCB remains elusive due to uncertainties in emission inventory and variability associated with meteorological conditions. Here, we use extensive basin-wide ambient measurements to examine the spatial pattern and trend of O3 and leverage OMI and TROPOMI satellites in conjunction with MEIC emission inventory to track emission changes. Sensitivity simulations are conducted by using WRF-CMAQ model to investigate the impacts of meteorological variability and emission changes on O3 changes over 2013-2020. O3 concentrations exhibit obvious interannual increases during 2013-2019 and a slight decrease in 2020. Both decreases in the MEIC emission inventory (-2.9% yr-1) and OMI NO2 column density (-3.1% yr-1) reflects the declining trend in NOx emissions over 2013-2020, while anthropogenic VOCs were not adequately regulated during 2013-2017, which explained the majority of deteriorated O3 pollution from 2013 to 2017. Furthermore, attribution analysis based on CMAQ simulations indicate that the unexpected aggravated O3 levels in 2019 is not only modulated by disproportional reductions in VOCs and NOx emissions, but also associated with unfavorable meteorological conditions featured by profound heatwaves and frequent stagnant conditions. In 2020, the abnormal meteorological conditions in May leads to substantial increase of O3 by 26.8 µg m-3 as compared to May 2019, while the considerable enhancement was fully offset by low O3 levels over the whole period which attributes to substantial emission reductions. This study reveals the long-term trend of O3 levels and precursor emissions and highlights the effects of meteorological variability and emission changes on O3 pollution over the SCB, with strong implications for designing effective O3 control measures.

Pyroptosis and Its Regulation in Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DbCM) is a prevalent disease, characterized by contractile dysfunction and left ventricular hypertrophy. Patients with DbCM have high morbidity and mortality worldwide. Recent studies have identified that pyroptosis, a kind of cell death, could be induced by hyperglycemia involved in the formation of DbCM. This review summarizes the regulatory mechanisms of pyroptosis in DbCM, including NOD-like receptor3, AIM2 inflammasome, long non-coding RNAs, microRNAs, circular RNA, autophagy, and some drugs.

HNRNPH1 Is a Novel Regulator Of Cellular Proliferation and Disease Progression in Chronic Myeloid Leukemia.

RNA binding proteins act as essential modulators in cancers by regulating biological cellular processes. Heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1), as a key member of the heterogeneous nuclear ribonucleoproteins family, is frequently upregulated in multiple cancer cells and involved in tumorigenesis. However, the function of HNRNPH1 in chronic myeloid leukemia (CML) remains unclear. In the present study, we revealed that HNRNPH1 expression level was upregulated in CML patients and cell lines. Moreover, the higher level of HNRNPH1 was correlated with disease progression of CML. In vivo and in vitro experiments showed that knockdown of HNRNPH1 inhibited cell proliferation and promoted cell apoptosis in CML cells. Importantly, knockdown of HNRNPH1 in CML cells enhanced sensitivity to imatinib. Mechanically, HNRNPH1 could bind to the mRNA of PTPN6 and negatively regulated its expression. PTPN6 mediated the regulation between HNRNPH1 and PI3K/AKT activation. Furthermore, the HNRNPH1-PTPN6-PI3K/AKT axis played a critical role in CML tumorigenesis and development. The present study first investigated the deregulated HNRNPH1-PTPN6-PI3K/AKT axis moderated cell growth and apoptosis in CML cells, whereby targeting this pathway may be a therapeutic CML treatment.

Origin of regional springtime ozone episodes in the Sichuan Basin, China: Role of synoptic forcing and regional transport.

The Sichuan Basin (SCB) located in southwestern China has long been considered the most polluted city cluster with exposure to unhealthy levels of ozone (O3) at times. However, the features of O3 regional transport and source contributions in SCB are poorly understood. In this study, ambient measurements, ERA5 reanalysis dataset, IASI O3 column, and the Weather Research and Forecasting-Community Multiscale Air Quality (WRF-CMAQ) modeling system coupled with the Integrated Source Apportionment Method (ISAM) module were used to investigate the formation mechanism and sources of a severe O3 episode in spring 2020 over the SCB. In the first stage of the O3 episode, a high-pressure system persisted over the western SCB and caused northeasterly wind fields, leading to enhanced regional transport from the northern boundary with the O3 contribution from the boundary exceeding 50% across the SCB. As the synoptic pattern evolved, southeasterly winds dominated the SCB and the stagnant zone over the Chengdu Plain confined O3 originating from the southern SCB and Chongqing city, leading to the accumulation of precursors and elevated O3 levels. During the O3 episode, transportation and industrial sources were major contributors to O3 formation especially for the Chengdu Plain and Chongqing city. In addition, the O3-rich air mass in the nocturnal residual layer that formed over Chongqing city was transported to the Chengdu Plain through southeastern corridor at 400-1600m above ground-level under the prevailing southeasterly winds. With sunrise and the development of the atmospheric boundary layer, the O3-rich air mass in the residual layer (RL) was entrained to the ground-level via vertical mixing, which further enhanced O3 pollution across the Chengdu Plain. Our results revealed the mechanism of regional transport via northeastern and southeastern corridors during an O3 episode and demonstrated the need for joint emission regulation across the SCB to mitigate O3 pollution.

Biological characteristics of exosomes and genetically engineered exosomes for the targeted delivery of therapeutic agents.

A primary focus of pharmacology is the accurate transport of drugs from the peripheral veins and their delivery to specific tissues and organs. Exosomes are nanoscale extracellular vesicles with comparatively enhanced circulation stability, biocompatibility, physicochemical stability and bio-barrier permeation ability, as well as reduced toxicity. Therefore, they are considered a superior drug delivery platform. Core ligands and homing peptides fuse with transmembrane proteins on the exosome surface. Genetically engineered exosomes target specific tissues or organs and agents such as siRNA, miRNA and chemotherapeutics can be loaded into exosomes to improve the regulation of target tissues and organs. Here, we review exosome biogenesis, release, uptake and isolation. We also summarise the current applications of genetically engineered exosomes for tumours, and neurological, cardiovascular and liver diseases.

miR-140-5p induces cell apoptosis and decreases Warburg effect in chronic myeloid leukemia by targeting SIX1.

microRNAs (miRNA), as tumor suppressors or oncogenes, are involved in modulating cancer cell behavior, including cell proliferation and apoptosis. The miR-140-5p acts as a tumor suppressor in several tumors, but the role of miR-140-5p in chronic myeloid leukemia (CML) remains unclear. Here, we investigated the suppression of miR-140-5p in CML patients and CML cell lines using quantitative PCR (qPCR) and fluorescence in situ hybridization (FISH). Overexpression miR-140-5p in CML cells significantly inhibited cell proliferation as revealed by the CCK-8 assay and promoted cell apoptosis as revealed by flow cytometry. Moreover, the sine oculis homeobox 1 (SIX1) gene had been confirmed as a direct target of miR-140-5p using bioinformatics analysis and luciferase reporter assays. Overexpression of miR-140-5p decreased the SIX1 protein level in CML cells. SIX1 mRNA and protein levels were significantly up-regulated in CML patients and CML cell lines. Knockdown of SIX1 expression significantly inhibited CML cell proliferation and promoted cell apoptosis. Furthermore, SIX1 as a transcriptional factor positively regulated pyruvate kinase isozyme type M2 (PKM2) expression and played an important role in the Warburg effect. In addition, these findings indicated that miR-140-5p functions as a tumor suppressor and plays a critical role in CML cell apoptosis and metabolism by targeting SIX1. Moreover, the miR-140-5p/SIX1 axis may be a potential therapeutic target in CML.

Particulate air pollution in Lanzhou China.

Concentrations of total suspended particles (TSP) and PM(10) in Lanzhou China have been kept high for the past two decades. Data collected during the intensive observational period from October 1999 to April 2001 show high TSP and PM(10) concentrations. Starting from November, the PM(10) pollution intensifies, and reaches mid to high alert level of air pollution, continues until April next year, and is at low alert level in the summer. In the winter and spring, the TSP concentration is 2-10 times higher than the third-level criterion of air quality (severe pollution). Effects of intrinsic factors (sources of pollution) and remote preconditions (propagation of dust storms) for severe PM(10) and TSP pollution in Lanzhou are analyzed.

Activin A increases arterial pressure in the hypothalamic paraventricular nucleus in rats by angiotension II.

Activin A, a member of the transforming growth factor ß superfamily, plays an important role in the central nervous system as a neurotrophic and neuroprotective factor. The hypothalamic paraventricular nucleus (PVN) in the central nervous system is characterized as an important integrative site to regulate arterial pressure (AP). However, whether activin A in the PVN is involved in the regulation of AP is not well characterized. This study aimed to determine the effect of activin A on AP in the PVN in rats. The results showed that activin ßA, activin type IIA and IIB receptors (ActRIIA and ActRIIB), and Smad2 and Smad3 mRNA expressions were detectable in the PVN of WKY rats by reverse-transcription PCR, and the expression of ActRIIA protein in the PVN was further confirmed by immunohistochemical staining. A microinjection of angiotensin II (AngII) (0.1 nmol/100 nl) or activin A (2 ng/100 nl) into the PVN increased AP significantly in WKY rats (P<0.05). Moreover, activin A (5 ng/ml) promoted AngII release from the primary cultured PVN neurons that can increase AP and upregulated the expressions of ActRIIA and Smad3 mRNA in the primary cultured PVN neurons (P<0.05). These data suggest that activin A can regulate AP in the PVN in an autocrine or a paracrine manner, which is related to AngII release and the ActRIIA-Smad3 signal pathway.