Differential associations of fine and coarse particulate air pollution with cause-specific pneumonia mortality: A nationwide, individual-level, case-crossover study.

BACKGROUND: The connections between fine particulate matter (PM2.5) and coarse particulate matter (PM2.5-10) and daily mortality of viral pneumonia and bacterial pneumonia were unclear. OBJECTIVES: To distinguish the connections between PM2.5 and PM2.5-10 and daily mortality due to viral pneumonia and bacterial pneumonia. METHODS: Using a comprehensive national death registry encompassing all areas of mainland China, we conducted a case-crossover investigation from 2013 to 2019 at an individual level. Residential daily particle concentrations were evaluated using satellite-based models with a spatial resolution of 1 km. To analyze the data, we employed the conditional logistic regression model in conjunction with polynomial distributed lag models. RESULTS: We included 221,507 pneumonia deaths in China. Every interquartile range (IQR) elevation in concentrations of PM2.5 (lag 0-2 d, 37.6 µg/m3) was associated with higher magnitude of mortality for viral pneumonia (3.03%) than bacterial pneumonia (2.14%), whereas the difference was not significant (p-value for difference = 0.38). An IQR increase in concentrations of PM2.5-10 (lag 0-2 d, 28.4 µg/m3) was also linked to higher magnitude of mortality from viral pneumonia (3.06%) compared to bacterial pneumonia (2.31%), whereas the difference was not significant (p-value for difference = 0.52). After controlling for gaseous pollutants, their effects were all stable; however, with mutual adjustment, the associations of PM2.5 remained, and those of PM2.5-10 were no longer statistically significant. Greater magnitude of associations was noted in individuals aged 75 years and above, as well as during the cold season. CONCLUSION: This nationwide study presents compelling evidence that both PM2.5 and PM2.5-10 exposures could increase pneumonia mortality of viral and bacterial causes, highlighting the more robust effects of PM2.5 and somewhat higher sensitivity of viral pneumonia.

Unsupervised blind image quality assessment via joint spatial and transform features.

A novel unsupervised blind image quality assessment (BIQA) method, which requires no mean opinion scores for model training is presented in this paper. The method employs joint spatial and transform features as quality degradation metrics, specifically, phase congruency, gradient magnitude (GM), and GM and Laplacian of Gaussian response and local normalized coefficient are extracted as spatial features, and Karhunen-Loéve transform coefficient and discrete cosine transform coefficient are modeled as transform features. Both spatial and transform features are well analyzed to remove the redundancy, and then fitted to the multivariate Gaussian model for no-reference image quality assessment. Extensive experiments conducted on seven IQA databases demonstrate the superiority of the proposed method over the state-of-the-art both supervised and unsupervised BIQA methods.

Differentiating the impacts of ambient temperature on pneumonia mortality of various infectious causes: a nationwide, individual-level, case-crossover study.

BACKGROUND: It remains unknown how ambient temperature impact pneumonia of various infectious causes. METHODS: Based on the national death registry covering all counties in Chinese mainland, we conducted an individual-level case-crossover study in China from 2013 to 2019. Exposures were assigned at residential addresses for each decedent. Conditional logistic regression model combined with distributed lag non-linear models were used to estimate the exposure-response associations. The attributable fractions due to non-optimum temperature were calculated after accounting for spatial and temporal patterns for the excess risks. FINDINGS: The exposure-response curves were inversely J-shaped with both low and high temperature increasing the risks, and the effect of low temperature was stronger. Extremely low temperature was associated with higher magnitude of influenza-related pneumonia [relative risk (RR): 2.46, 95% confidence interval (CI): 1.62-3.74], than viral pneumonia (RR: 1.89, 95% CI: 1.55-2.30) and bacterial pneumonia (RR: 1.81, 95% CI: 1.56-2.09). The magnitudes of RRs associated with extremely high temperature were similar among the three categories of pneumonia. The mortality attributable fraction for influenza-related pneumonia (29.78%) was the highest. The effects were stronger in people of low education level or residence in the north. INTERPRETATION: This nationwide study presents findings on the varied risk and burden of pneumonia mortality of various infectious causes, and highlights the susceptibility of influenza-related pneumonia to ambient low temperature. FUNDING: This study is supported by the National Key Research and Development Program (2022YFC3702701), the Shanghai Municipal Science and Technology Commission (21TQ015) and Shanghai International Science and Technology Partnership Project (21230780200).

Differential associations of particle size ranges and constituents with stroke emergency-room visits in Shanghai, China.

BACKGROUND AND PURPOSE: Fine particulate matter (PM2.5) has been associated with increased risks of stroke, but it remains unclear which specific size ranges and chemical constituents dominate the effects of PM2.5 on stroke. We aimed to evaluate the associations of size-segregated particles and various constituents of PM2.5 with daily emergency-room visits for stroke. METHODS: We conducted a time-series study to investigate the associations of 5 particle size ranges from 0.01 to 2.5 µm and 35 constituents of PM2.5 with the daily emergency-room visits for stroke in Shanghai, from 2014 to 2019. Over-dispersed generalized additive models were used to estimate the associations. The robustness of these associations was evaluated by additionally controlling for PM2.5 mass. RESULTS: For size ranges from 0.01 to 0.3 µm, there were significant positive associations between particle number concentrations and daily emergency-room visits for stroke with the strongest associations occurring for the size range 0.05-0.1 µm. The size-dependent pattern was not changed by adjusting for PM2.5 and gaseous pollutants. The associations of daily emergency-room visits for stroke also varied considerably by various PM2.5 constituents. After controlling for the simultaneous exposure to PM2.5 and gaseous pollutants in two-pollutant models, we identified 11 out of 35 constituents that had robust associations, these being organic carbon, elemental carbon, chlorine, magnesium, ammonium, nitrate, sulfate, copper, manganese, lead and zinc. CONCLUSION: Ultra-fine particles and some PM2.5 constituents (i.e., carbonaceous fractions, inorganic ions and some elements) may be mainly responsible for the excess risk of stroke induced by PM2.5.

Exogenous H2S Ameliorates High Salt-Induced Hypertension by Alleviating Oxidative Stress and Inflammation in the Paraventricular Nucleus in Dahl S Rats.

Hydrogen sulfide (H2S) is an important gaseous signaling molecule that regulates cardiovascular activity in animals. The hypothalamic paraventricular nucleus (PVN) is a major integrative region involved in blood pressure (BP) regulation. We explored whether exogenous H2S application by intraperitoneal injection of sodium hydrosulfide (NaHS) alleviates BP increase induced by a high salt diet (HSD) and the role of PVN in Dahl salt-sensitive (Dahl S) rats. Dahl S rats were divided into four groups according to diet regime (normal salt diet [NSD] and HSD) and treatment method (daily intraperitoneal NaHS or saline injection). We monitored BP, food and water intake, and body weight for 8 weeks. Plasma, kidney, and brain tissues were collected at the end of the experiment. We found that exogenous H2S not only delayed BP elevation but also attenuated the increase in the levels of norepinephrine, cystatin C, and blood urea nitrogen in the plasma of Dahl S rats with an HSD. Furthermore, H2S enhanced the total antioxidant capacity, superoxide dismutase, and glutathione peroxidase in the PVN. Exogenous H2S attenuated the protein expression of the nuclear factor-κB pathway and proinflammatory cytokines, which were significantly higher in the PVN in rats with an HSD than in rats with an NSD. Additionally, exogenous H2S relieved PVN neuronal apoptosis induced by an HSD. These findings suggest that exogenous H2S attenuates hypertension caused by an HSD by ameliorating oxidative stress, inflammation, and apoptosis in the PVN. This study provides evidence of the benefits of peripheral H2S therapy for hypertension.

The Potential of Hydrogen Sulfide Donors in Treating Cardiovascular Diseases.

Hydrogen sulfide (H2S) has long been considered as a toxic gas, but as research progressed, the idea has been updated and it has now been shown to have potent protective effects at reasonable concentrations. H2S is an endogenous gas signaling molecule in mammals and is produced by specific enzymes in different cell types. An increasing number of studies indicate that H2S plays an important role in cardiovascular homeostasis, and in most cases, H2S has been reported to be downregulated in cardiovascular diseases (CVDs). Similarly, in preclinical studies, H2S has been shown to prevent CVDs and improve heart function after heart failure. Recently, many H2S donors have been synthesized and tested in cellular and animal models. Moreover, numerous molecular mechanisms have been proposed to demonstrate the effects of these donors. In this review, we will provide an update on the role of H2S in cardiovascular activities and its involvement in pathological states, with a special focus on the roles of exogenous H2S in cardiac protection.

The relationship between cardiac muscularis propria and clinical outcomes of peroral endoscopic myotomy in achalasia.

BACKGROUND AND AIM: Achalasia patients usually present lower esophageal sphincter thickening, which can impact the expansibility of cardia. We aimed to investigate the effect of cardiac muscularis propria (MP) on perioperative adverse events (AEs) and treatment outcomes of patients treated with peroral endoscopic myotomy (POEM). METHODS: We retrospectively reviewed 114 patients with achalasia undergoing pre-POEM endoscopic ultrasonography (EUS) between May 2013 and November 2019. Cardiac MP thickness was measured using EUS. POEM failure was defined as Eckardt score >3. Risk factors for perioperative AEs and POEM failure were identified. RESULTS: Patients were divided into the thin (n = 52) and the thick group (n = 62) based on the median of cardiac MP thickness (3.0 mm). Perioperative AEs rate of the thin group seemed to be slightly higher than that of the thick group (11.5% vs. 4.8%, P = 0.30). During a median follow-up of 30 months (range 1-77), 100 patients completed follow-up, 16 (16%) of which occurred clinical failure. The clinical outcomes of patients in the thin group were significantly poorer than those patients in the thick group (P = 0.006). Cardiac MP thickness was an independent risk factor for POEM failure (hazard ratio 3.9, P = 0.02; Cox regression), but not the risk factor for perioperative AEs (odds ratio 2.6, P = 0.2; logistic regression). CONCLUSION: Cardiac MP thickness could be a novel predictive factor for POEM failure in patients with achalasia.

Relationship between a 7-mRNA signature of the pancreatic adenocarcinoma microenvironment and patient prognosis (a STROBE-compliant article).

The potential association between the prognosis of the pancreatic adenocarcinoma (PAAD) and its microenvironment is unclear. This study aims to construct a prognostic index (PI) model of the PAAD microenvironment to predict PAAD patient survival outcomes.The mRNA sequencing and the clinical parameters data were obtained from The Cancer Genome Atlas. Immune and stromal scores were computed using the expression data algorithm to capture infiltration of immune and stromal cells in the PAAD tissue, where patients were categorized as high and low score groups according to these scores. Differentially expressed genes were identified using the R package LIMMA. Univariate and multivariate Cox regression analysis were conducted to select candidate survival-correlated gene signatures from the tumor microenvironment for constructing a model. The Kaplan-Meier method was used to access overall survival of the primary and validation cohorts. The immunological features of the PI model was explored using the Tumor Immune Estimation Resource (TIMER) database. Bioinformatic analyses were conducted based on the DAVID database.A total of 1266 overlapping differentially expressed genes and 49 prognosis-associated genes were identified. A 7-mRNA signature (GBP5, BICC1, SLC7A14, CYSLTR1, P2RY6, VENTX, and RAB39B) was screened for the construction of a PI model (area under the curve = 0.791). In both the primary and validation cohorts, Kaplan Meier analysis revealed that the overall survival of the high-risk group was significantly worse compared to the low-risk group (P < .0001, P = .0028 respectively). The TIMER database described that the 7 signature genes were correlated with immune infiltrating cells and tumor purity. Bioinformatic analyses revealed that these prognosis-associated genes were significantly enriched during inflammation, the defense response, would response, calcium ion transport, and plasma membrane part.A list of the prognosis-correlated genes was generated based on the PAAD microenvironment. A 7-mRNA PI model may be used for predicting the prognosis of PAAD patients.

The presence of zinc reduced cadmium uptake and translocation in Cosmos bipinnatus seedlings under cadmium/zinc combined stress.

Cadmium (Cd) and zinc (Zn) coexist in the environment but interact differently in plants. Cosmos bipinnatus has been potentially considered as a Cd-accumulator. Thus, this study investigated the detoxification mechanism in C. bipinnatus seedlings under Cd, Zn and Cd + Zn stresses. In the present study, the presence of Zn inhibited Cd uptake and translocation, whereas Cd merely hindered Zn uptake. The concentration of Cd in soluble fraction significantly decreased and Cd was bounded to the cell wall in root under Cd + Zn stress. Meanwhile, Zn and Cd mutually decreased their concentrations in the ethanol extractable form (FE) and water extractable form (FW) in roots and shoots. Furthermore, Cd + Zn stress enhanced the activities of superoxide dismutase (SOD, EC 1.15.1.1), peroxidase (POD, EC 1.11.1.7) and catalase (CAT, EC 1.11.1.6) compared to Cd stress alone. These results suggested that Zn effectively decreased Cd uptake and translocation, changed their subcellular distributions, regulated their chemical forms composition and increased antioxidative enzyme activities, thereby enhancing the tolerance to Cd in C. bipinnatus. This study physiologically revealed the interactive effect of Cd and Zn on the detoxification mechanism of Cd in C. bipinnatus and provided new information on phytoremediation of the heavy metal contaminated soils.

Prognostic value and prospective molecular mechanism of miR-100-5p in hepatocellular carcinoma: A comprehensive study based on 1,258 samples.

The prognostic value and molecular mechanism of microRNA-100-5p (miR-100-5p) in hepatocellular carcinoma (HCC) are still unclear. To explore the prognostic value and the mechanism of miR-100-5p in HCC, the present study analyzed the results of 18 previous studies and bioinformatic datasets. The clinical significance of miR-100-5p and its targets in HCC were investigated using The Cancer Genome Atlas and the Gene Expression Omnibus, as well as relevant literature. In total, 12 online tools were used to predict the target genes of miR-100-5p. Bioinformatics analysis and Spearman correlation analysis were performed, and genomic alterations of the hub genes were evaluated. A meta-analysis with 1,258 samples revealed that miR-100-5p was significantly downregulated in HCC [standard mean difference (SMD), -0.94; 95% confidence interval (CI), -1.14 to -0.74; I2, 35.2%]. Lower miR-100-5p expression was associated with poorer clinical characteristics and a poorer prognosis for patients with HCC. Additionally, bioinformatics analysis revealed that the 'regulation of transcription', 'chromatin remodeling complex', 'transcription regulator activity', 'pathways in cancer' and 'heparan sulfate biosynthesis' were the most enriched terms. Furthermore, expression of histone deacetylase (HDAC)2, HDAC3, SHC-transforming protein 1 (SHC1), Ras-related protein Rac1 (RAC1) and E3 ubiquitin-protein ligase CBL (CBL) was negatively correlated with miR-100-5p expression. Among these, upregulated HDAC2 [hazard ratio (HR), 1.910; 95% CI, 1.309-2.787; P=0.0007], HDAC3 (HR, 1.474; 95% CI, 1.012-2.146; P=0.0435), SHC1 (HR, 1.52; 95% CI, 1.043-2.215; P=0.0281) and RAC1 (HR, 1.817; 95% CI, 1.248-2.645; P=0.0022) were associated with shorter survival. Alterations in HDAC2, SHC1, RAC1 and IGF1R were linked with a poorer outcome for HCC, and alternative splicing of SHC and RAC1 were significantly decreased and increased in HCC, respectively. In summary, the downregulation of miR-100-5p may be involved in the progression and prognosis of HCC. The upregulation of HDAC2, HDAC3, SHC1 and RAC1 may indicate a poorer survival rate for patients with HCC. Thus, miR-100-5p and these 4 potential target genes may provide novel therapeutic targets and prognostic predictors for patients with HCC.

Unidirectional Magneto-Resistance in Modulation-Doped Magnetic Topological Insulators.

Nonlinear unidirectional spin Hall magnetoresistance (USMR) has been reported in heavy metal/ferromagnet bilayers, which could be employed as an effective method in detecting the magnetization orientation in spintronic devices with two-terminal geometry. Recently, another unidirectional magnetoresistance (UMR) was reported in magnetic topological insulator (TI)-based heterostructures at cryogenic temperature, whose amplitude is orders of magnitude larger than the USMR measured in heavy metal-based magnetic heterostructures at room temperature. Here, we report the UMR effect in the modulation-doped magnetic TI structures. This UMR arises due to the interplay between the magnetic dopant's magnetization and the current-induced surface spin polarization, when they are parallel or antiparallel to each other in the TI material. By varying the dopant's position in the structure, we reveal that the UMR is mainly originating from the interaction between the magnetization and the surface spin-polarized carriers (not bulk carriers). Furthermore, from the magnetic field-, the angular rotation-, and the temperature-dependence, we highlight the correlation between the UMR effect and the magnetism in the structures. The large UMR versus current ratio in TI-based magnetic bilayers promises the easy readout in TI-based spintronic devices with two-terminal geometry.

MicroRNA-152 inhibits ovarian cancer cell proliferation and migration and may infer improved outcomes in ovarian cancer through targeting FOXP1.

microRNA (miR) are a class of endogenous small non-coding RNA that are aberrantly expressed and are critical in tumorigenesis. Amongst them, miR-152 was reported to be dysregulated in epithelial ovarian cancer (EOC). However, the function and mechanism of miR-152 is not well understood. In the present study, total RNA was extracted from 58 ovarian epithelial carcinoma tissue samples and adjacent non-tumor tissues and measured by reverse transcription-quantitative polymerase chain reaction. The observations of the present study revealed that the expression of miR-152 was significantly downregulated in EOC specimens, as well as three ovarian cancer (OC) cell lines. The higher expression of miR-152 indicated a better overall survival rate in patients with EOC. Following miR-152 mimic transfection into SKOV3 or OVCAR3 cells, MTT assay revealed that cell proliferation was significantly inhibited (P<0.05). Although miR-152 had no effect on SKOV3 cell migration, miR-152 inhibited OVCAR3 cell migration. Bioinformatics analyses and luciferase reporter assays demonstrated that miR-152 targeted the 3'-untranslated region (3'-UTR) of the forkhead box protein 1 (FOXP1). Furthermore, introducing FOXP1 without the 3'-UTR abrogated the effect of miR-152-induced proliferation and migration alteration, respectively. In addition, the expression level of FOXP1 was higher in the EOC tumor tissues and cell lines. Additionally, the level of miR-152 and FOXP1 was inversely correlated in grade 3 and 4 ovarian tumor tissues. Altogether, these observations indicated that miR-152 may be involved in the inhibition of OC through repression of FOXP1. In the future, miR-152 and FOXP1 may act as novel biomarkers for early detection of EOC or therapeutic targets.

Fermentative Production of Phenolic Glucosides by Escherichia coli with an Engineered Glucosyltransferase from Rhodiola sachalinensis.

Three rosmarinic acid analogs produced by recombinant Escherichia coli, two xanthones from fungi and honokiol from plants, were explored as the substrates of E. coli harboring a glucosyltransferase mutant UGT73B6FS to generate phenolic glucosides. Six new and two known compounds were isolated from the fermentation broth of the recombinant strain of the feeding experiments, and the compounds were identified by spectroscopy. The biotransformation of rosmarinic acid analogs and xanthones into corresponding glucosides was presented for the first time. This study not only demonstrated the substrate flexibility of the glucosyltransferase mutant UGT73B6FS toward aromatic alcohols but also provided an effective and economical method to produce phenolic glucosides by fermentation circumventing the use of expensive precursor UDP-glucose.

Nanoengineering of an Si/MnGe quantum dot superlattice for high Curie-temperature ferromagnetism.

The realization and application of spintronic devices would be dramatically advanced if room-temperature ferromagnetism could be integrated into semiconductor nanostructures, especially when compatible with mature silicon technology. Herein, we report the observation of such a system - an Si/MnGe superlattice with quantum dots well aligned in the vertical direction successfully grown by molecular beam epitaxy. Such a unique system could take full advantage of the type-II energy band structure of the Si/Ge heterostructure, which could trap the holes inside MnGe QDs, significantly enhancing the hole-mediated ferromagnetism. Magnetic measurements indeed found that the superlattice structure exhibited a Curie temperature of above 400 K. Furthermore, zero-field cooling and field cooling curves could confirm the absence of ferromagnetic compounds, such as Ge8Mn11 (Tc ∼ 270 K) and Ge3Mn5 (Tc ∼ 296 K) in our system. Magnetotransport measurement revealed a clear magnetoresistance transition from negative to positive and a pronounced anomalous Hall effect. Such a unique Si/MnGe superlattice sets a new stage for strengthening ferromagnetism due to the enhanced hole-mediation by quantum confinement, which can be exploited for realizing the room-temperature Ge-based spin field-effect transistors in the future.

Production of Cinnamyl Alcohol Glucoside from Glucose in Escherichia coli.

Rosin, a cinnamyl alcohol glucoside, is one of the important ingredients in Rhodiola rosea, which is a valuable medicinal herb used for centuries. Rosin displayed multiple biological activities. The traditional method for producing rosin and derivatives is direct extraction from R. rosea, which suffers from limited availability of natural resources and complicated purification procedure. This work achieved de novo biosynthesis of rosin in Escherichia coli. First, a biosynthetic pathway of aglycon cinnamyl alcohol from phenylalanine was constructed. Subsequently, the UGT genes from Rhodiola sachalinensis (UGT73B6) or Arabidopsis thaliana (UGT73C5) were introduced into the above recombinant E. coli strain to produce rosin. Then the phenylalanine metabolic pathway of E. coli was optimized by genetic manipulation, and the production of rosin by the engineered E. coli reached 258.5 ± 8.8 mg/L. This study lays a significant foundation for microbial production of rosin and its derivatives using glucose as the renewable carbon source.

Enhancing electric-field control of ferromagnetism through nanoscale engineering of high-Tc MnxGe1-x nanomesh.

Voltage control of magnetism in ferromagnetic semiconductor has emerged as an appealing solution to significantly reduce the power dissipation and variability beyond current CMOS technology. However, it has been proven to be very challenging to achieve a candidate with high Curie temperature (Tc), controllable ferromagnetism and easy integration with current Si technology. Here we report the effective electric-field control of both ferromagnetism and magnetoresistance in unique MnxGe1-x nanomeshes fabricated by nanosphere lithography, in which a Tc above 400 K is demonstrated as a result of size/quantum confinement. Furthermore, by adjusting Mn doping concentration, extremely giant magnetoresistance is realized from ∼8,000% at 30 K to 75% at 300 K at 4 T, which arises from a geometrically enhanced magnetoresistance effect of the unique mesh structure. Our results may provide a paradigm for fundamentally understanding the high Tc in ferromagnetic semiconductor nanostructure and realizing electric-field control of magnetoresistance for future spintronic applications.

Silencing of Transient Receptor Potential Channel 4 Alleviates oxLDL-induced Angiogenesis in Human Coronary Artery Endothelial Cells by Inhibition of VEGF and NF-κB.

BACKGROUND: Transient receptor potential channel 4 (TRPC4) plays central roles in endothelial cell function. The aim of this study was to investigate the silencing effects of TRPC4 on oxidized low-density lipoprotein (oxLDL)-induced angiogenesis in human coronary artery endothelial cells (HCAECs), as well as the underlying molecular mechanism involved in this process. MATERIAL/METHODS: HCAECs were transfected with small interfering RNA (siRNA) targeting TRPC4 (TRPC4-siRNA) or with a negative control (NC)-siRNA. The expression of TRPC4 was confirmed by real-time polymerase chain reaction (RT-PCR) and Western blotting. After the siRNA transfection, oxLDL was added to the medium. Cell proliferation, migration, and in vitro angiogenesis were determined by bromodeoxyuridine (BrdU) enzyme-linked immunosorbent assay (ELISA), Transwell assay and scratch-wound assay, respectively, and tube formation on Matrigel. Expression of vascular endothelial growth factor (VEGF) and nuclear factor (NF)-κB p65 were assessed by Western blotting. RESULTS: Both the mRNA and protein levels of TRPC4 were significantly reduced by transfection with TRPC4-siRNA compared to the control group or NC-siRNA group (P<0.05). Silencing of TRPC4 significantly decreased the cell proliferation, migration, and tube formation (all P<0.05). Furthermore, the expression levels of VEGF and NF-κB p65 were markedly lowered by silencing of TRPC4 in HCAECs. CONCLUSIONS: These results suggest that silencing of TRPC4 alleviates angiogenesis induced by oxLDL in HCAECs through inactivation of VEGF and NF-κB. Suppression of TRPC4 might be an alternative therapeutic strategy for atherosclerotic neovascularization.