Spatiotemporal patterns and drivers of the urban air pollution island effect for 2273 cities in China.

Air pollution levels tend to be higher in urban areas than in surrounding rural areas, and this air pollution has a negative effect on human health. However, the spatiotemporal patterns of urban-rural air pollution differences and the determinants of these differences remain unclear. Here, we calculate the Urban Air Pollution Island (UAPI) intensity for PM2.5 and PM10 on a monthly, seasonal, and annual scale for 2273 cities in China from 2000 to 2020. Subsequently, we analyze the influence of urban characteristics using a combined approach of a two-way fixed effects model and a spatial Durbin model. Results show a strong downward trend in the UAPI intensity since 2013, with reductions ranging from 42 % to 61 % until 2020, for both pollutants and in summer as well as winter. Consistently, the proportion of the cities experiencing the UAPI phenomenon decreased from 94.5 % to 77.3 % for both PM2.5 and PM10. We find a significant influence of urban morphology on UAPI. Specifically, urban sprawl, polycentric development, and an increase in urban green spaces are associated with a reduction in UAPI, while dense urban areas intensify it. Our study also reveals a robust inverted U-shaped relationship between stages of economic development and UAPI. Moreover, economic development and air pollution itself show spillover effects that oppose their direct impacts. These results suggest that urban and regional planning and more ambitious climate change mitigation policies could be more effective strategies for mitigating air pollution in cities than end-of-pipe control.

Combined treatment with valsartan and fluvastatin to delay disease progression in nonpermanent atrial fibrillation with hypertension: A clinical trial.

BACKGROUND: Atrial fibrillation (AF) is a complex cardiac arrhythmia in clinical practice with increasing incidence. However, the effects of statins on patients with AF are not quite clear. HYPOTHESIS: To investigate the protective effect of calcium channel blocker (CCB) and valsartan combined fluvastatin on hypertension (HTN) patients with nonpermanent AF. METHODS: In three and a half years, 189 cases of patients diagnosed as HTN combining nonpermanent AF by eight medical centers, were recruited and randomly assigned to four groups with varied treatments: CCB group; CCB + statin group; valsartan group; and valsartan + statin group. The four groups were followed up for 24 months. The 7-day Holter ultrasound echocardiography (UCG) and biochemical indexes were completed at preset time nodes respectively. RESULTS: After 24 months of follow-up, 178 patients completed the study. Compared with CCB group, the blood lipid level, inflammatory index, ultrasonic index and electrocardiographic measurement results of CCB + statin group, valsartan group and valsartan + statin group were improved in different degrees and had statistical significance (P < .05 or P < .01). Furthermore, the improvement trend of CCB + statin group and valsartan + statin group was more obvious. CONCLUSIONS: The results indicated that valsartan can reduce AF load and recurrence rate, and delay the progression of nonpermanent AF to permanent AF in multiple ways, and the effect of combination of valsartan and fluvastatin is more significant. These results provide a new direction for the integrated upstream control strategy of AF.

Resonance assignments of bacteriophage SPO1 Gp49 protein.

Recent applications of phage therapy in localized wound and drug-resistant bacterial infection have brought bacteriophage back to the spotlight. While these works demonstrated the safety and effectiveness of engineered bacteriophages in human patients, the exact molecular machinery behind the bacteria killing remains largely uncharacterized. This is particularly noticable outside Escherichia coli phages, as most studies are based on bacteriophages of this Gram-negative model bacterium. In the attempt to extent our understanding to the bacteriophage of Gram-positive bacteria, we chose the host hijacking module of Bacillus subtilis phage SPO1 for systemic functional and structural studies. Gp49, an acidic protein located within operon 4 of this module, is believed to have a role during the host takeover event. Here we describe the complete resonance assignment of Gp49, which shares no sequence homology with any known protein, as the basis for the structure determination and further mechanism study.

Indoleamine 2,3-Dioxygenase Activation by Interferon Gamma in Vascular Endothelial Rat Cells Requires Noncanonical NF-κB Signaling.

Indoleamine 2,3-dioxygenase (IDO) is an important enzyme in immune response regulation; cells that express IDO can suppress T-cell responses. Endothelial cells (ECs) play an important role in graft rejection. Therefore, we investigated the role of IDO expression by vascular ECs in immunoregulation. We demonstrated that interferon gamma can upregulate IDO expression in cultured ECs. Moreover, IDO induction by interferon gamma required IKKα activation, a part of the noncanonical NF-κB signaling pathway. In addition, IκB kinase α (IKKα) silencing resulted in significantly reduced IPO expression, demonstrating an essential role of NF-κB signaling pathway in IDO activation in vitro. These results may have an implication for regulating the immune response to alloantigens. The results obtained are important not only in understanding the role of ECs in the regulation of the transplantation immune response, but also in determining a potential therapeutic target for inhibiting allograft rejection.

Upstream therapeutic strategies of valsartan and fluvastatin on hypertensive patients with non-permanent atrial fibrillation.

AIM: To investigate the upstream therapeutic effects of fluvastatin and valsartan on hypertensive patients with non-permanent atrial fibrillation (AF). METHODS: A total of 189 patients who were admitted to outpatient and inpatient department from eight medical centers in China, diagnosed as hypertension with non-permanent AF, were divided into four groups randomly: the CCBs group (group A, n = 45); CCB + fluvastatin group (group B, n = 48); valsartan group (group C, n = 46); valsartan + fluvastatin group (group D, n = 50). The four groups were followed up for 24 months. The blood routine, biochemical examination, echocardiography, high sensitive C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), the maintenance rate of sinus rhythm, and the recurrence of paroxysmal AF or persistent AF incidence were observed in these groups before and after 24 months' treatment. RESULTS: After 24 months of follow-up, there were 178 cases of patients who have completed the study. (a) There was no significant difference in blood routine, liver, and renal function in each group (P > 0.05). (b) The blood lipids level in groups B and D was significantly reduced after treatment (P < 0.01). There was no significant difference of hs-CRP level in group A (P > 0.05). The left ventricular remodeling was significantly alleviated in group C and group D (P < 0.05). The NT-ProBNP level was significantly decreased in group D (P < 0.05). (c) The sinus rhythm maintenance rate of group B, group C, and group D was higher than group A (77.78%, 70.45%, 79.17% vs 43.90%), the occurrence of persistent AF was significantly lower than group A (11.11%, 14.29%, 8.33% vs 31.71%; P < 0.05). CONCLUSIONS: CCB plus fluvastatin and valsartan can reduce the recurrence rate of non-permanent AF and to delay the progression from non-permanent AF to permanent AF in patients with hypertension. The combined application of valsartan and fluvastatin is more effective than valsartan or CCB alone in the upstream therapies of AF.

DKK3 regulates cell proliferation, apoptosis and collagen synthesis in keloid fibroblasts via TGF-ß1/Smad signaling pathway.

It has been reported that Dickkopf-3 (DKK3) down-regulation was examined in keloid fibroblasts, but the biological functions of DKK3 have not yet been investigated. In this study, we examined the expression of DKK3 in human keloid tissues, further evaluated the biological function of DKK3 and explored its potential molecular mechanism in transforming growth factor-ß1 (TGF-ß1)-induced keloid fibroblasts. Our results showed that DKK3 mRNA expression in human keloid tissues is down-regulated. DKK3 overexpression inhibited cell proliferation in TGF-ß1-induced keloid fibroblasts transfected with pcDNA3.1-DKK3. Furthermore, DKK3 overexpression remarkably upregulated the protein expression levels of Bax and caspase-3, but decreased the protein expression of Bcl-2. In addition, DKK3 overexpression dramatically inhibited the protein and mRNA levels of collagen I (Col-I), collagen III (Col-III) and α-smooth muscle actin (α-SMA). Moreover, the protein expression of TGF-ß receptor I (TGF-ß RI), TGF-ß receptor II (TGF-ß RII), the phosphorylation of Smad2 (p-Smad2) and Smad3 (p-Smad3) was dramatically inhibited by pcDNA3.1-DKK3. LY2109761, a TGF-ß receptor inhibitor, also suppressed cell proliferation, apoptosis and collagen synthesis in TGF-ß1-induced keloid fibroblasts. Taken together, DKK3 overexpression could inhibit cell proliferation, induced cell apoptosis, and suppressed collagen synthesis through TGF-ß1/Smad signaling in TGF-ß1-induced keloid fibroblasts. Our findings suggest that DKK3 is a novel and promising molecular target for keloid treatment.

COMP-Ang1 promotes long-term survival of allogeneic islet grafts in a bioinert perforated chamber by inhibiting inflammation via inhibition of the TLR4 signaling pathway.

OBJECTIVES: To evaluate the effects of cartilage oligomeric matrix protein (COMP)- angiopoietin-1 (Ang1) on allogeneic islet graft survival in a bioinert perforated chamber. RESULTS: COMP-Ang1 treatment significantly decreased lipopolysaccharide-induced cell apoptosis and islet-related lymph node cell proliferation (both P < 0.01). Tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 levels in the chamber exudate were significantly lower in the COMP-Ang1 + chamber group than in the chamber group (all P < 0.05), as were the protein expression levels. COMP-Ang1 significantly inhibited the expression of Toll-like receptor 4 (TLR4) in cultured islets. Finally, full COMP-Ang1 treatment resulted in the longest survival time among the treatment groups. CONCLUSION: Combined use of the bioinert perforated chamber with COMP-Ang1 is an effective strategy for improving islet allograft survival.

Cloning, expression, and antiviral activity of interferon ß from the Chinese microbat, Myotis davidii.

Bats are natural reservoir hosts for many viruses that produce no clinical symptoms in bats. Therefore, bats may have evolved effective mechanisms to control viral replication. However, little information is available on bat immune responses to viral infection. Type I interferon (IFN) plays a key role in controlling viral infections. In this study, we report the cloning, expression, and biological activity of interferon ß (IFNß) from the Chinese microbat species, Myotis davidii. We demonstrated the upregulation of IFNB and IFN-stimulated genes in a kidney cell line derived from M. davidii after treatment with polyI:C or infection with Sendai virus. Furthermore, the recombinant IFNß inhibited vesicular stomatitis virus and bat adenovirus replication in cell lines from two bat species, M. davidii and Rhinolophus sinicus. We provide the first in vitro evidence of IFNß antiviral activity in microbats, which has important implications for virus interactions with these hosts.

Upstream therapeutic strategies of Valsartan and Fluvastatin on Hypertensive patients with non-permanent Atrial Fibrillation (VF-HT-AF): study protocol for a randomized controlled trial.

BACKGROUND: Previous studies regarding rhythm control in patients with atrial fibrillation (AF) could not sufficiently demonstrate the efficacy of available anti-arrhythmic drugs. 'Upstream therapy' has emerged as a potential strategy for the prevention and treatment of AF. The use of angiotensin II receptor blockers and statins has been suggested to decrease new-onset AF, but which remains inadequately explored. This study was designed to examine whether valsartan or fluvastatin can reduce the risk of non-permanent AF in patients with hypertension. METHODS/DESIGN: The VF-HT-AF study is a multicenter, randomized, open-label, four-arm parallel group study with comparative evaluation of valsartan and fluvastatin as upstream therapies for the treatment of non-permanent AF complicated by hypertension. The primary outcome measure is change in the development of paroxysmal AF into persistent or permanent AF, the development of persistent AF to permanent AF, and change in incidence of overall and persistent AF recurrence, as evaluated by 7-days ambulatory electrocardiograph monitoring (Holter) and patients' diaries during 2 years' follow-up. Secondary outcome measures of this study include the occurrence of: (1) fatal and nonfatal myocardial infarction; (2) heart failure (New York Heart Association stage III or IV); (3) cardiogenic shock; (4) serious bleeding necessitating hospitalization; (5) malignant ventricular arrhythmia; (6) revascularization therapy; (7) radiofrequency catheter ablation of AF; (8) changes of left atrial dimension, as measured by ultrasound echocardiography; (9) stroke; (10) cardiovascular mortality; and (11) all-cause mortality. A total of 1879 patients will be investigated from 15 medical centers throughout China to obtain the relevant information. DISCUSSION: This is the first study in hypertensive patients complicated non-permanent AF in the Chinese population. Results of this study will inform the use of upstream therapies of AF. TRIAL REGISTRATION: chictr.org, ChiCTR-TRC-12002642.