A Systematic Review and Meta-Analysis of Efficacy and Safety of Cilostazol Prescription in Patients With Femoropopliteal Peripheral Artery Disease After Endovascular Therapy.

PURPOSE: The purpose of this study is to assess the efficacy and safety of cilostazol prescription in patients with femoropopliteal peripheral artery disease (PAD) after endovascular therapy (EVT). MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of all studies reporting the outcomes of cilostazol after femoropopliteal EVT of PAD up to September 2022. Clinical outcomes of interest included primary patency, in-stent restenosis (ISR), vessel re-occlusion, freedom from target lesion revascularization (TLR), repeat revascularization, all-cause mortality, amputation, major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs), and bleeding complication. RESULTS: A total of 4 randomized controlled trials (RCTs) and 8 observational studies containing a total of 4898 patients met the inclusion criteria and were included in this systematic review and meta-analysis. We found that the use of cilostazol was associated with higher primary patency after femoropopliteal artery EVT (odds ratio [OR]=1.67, 95% confidence interval [CI]=1.50-1.87, p<0.001, I2=33.2%), a lower risk of ISR (OR=0.43, 95% CI=0.29-0.63, p<0.001, I2=37.6%), repeat revascularization (OR=0.43, 95% CI=0.24-0.76, p<0.005, I2=27.4%), and vessel re-occlusion (OR=0.59, 95% CI=0.38-0.93, p<0.05, I2=0%). There was an increase in freedom from TLR rate (OR=2.19, 95% CI=1.58-3.05, p<0.001, I2=0%), as well as a reduction in the occurrence of MALEs (OR=0.50, 95% CI=0.29-0.85, p<0.05, I2=0%). However, there was no significant difference in amputation, MACEs, all-cause mortality, and major bleeding complications. Subgroup analysis showed that cilostazol treatment in patients with femoropopliteal drug-eluting stents (DES) implantation remained associated with higher primary patency and a lower risk of ISR. CONCLUSIONS: After EVT of femoropopliteal artery lesions, additional oral cilostazol enhances primary patency, reduces the occurrences of ISR and vessel re-occlusion, diminishes the risks associated with MALEs, lowers the need for repeat revascularization, and increases freedom from TLR rates. However, it does not impact amputation, MACEs, all-cause mortality, or major bleeding complications. These findings suggest cilostazol as a potentially safe and effective adjunct therapy in patients with femoropopliteal PAD after EVT. CLINICAL IMPACT: After undergoing endovascular therapy (EVT) for femoropopliteal artery lesions, the addition of cilostazol to antiplatelet therapy can significantly improve primary patency, reducing the incidence of in-stent restenosis, repeat revascularization, vessel re-occlusion, and major adverse limb events while increasing freedom from target lesion revascularization rate. The simultaneous use of drug-eluting stents in the femoropopliteal artery lesions, combined with cilostazol, potentially results in a synergistic anti-stenotic effect. This therapeutic approach does not appear to be associated with an increased risk of major bleeding events or all-cause mortality. These findings provide additional evidence supporting the treatment of anti-stenosis in patients with femoropopliteal artery lesions after EVT.

A greater negative impact of future climate change on vegetation in Central Asia: Evidence from trajectory/pattern analysis.

In the context of global warming, vegetation changes exhibit various patterns, yet previous studies have focused primarily on monotonic changes, often overlooking the complexity and diversity of multiple change processes. Therefore, it is crucial to further explore vegetation dynamics and diverse change trajectories in this region under future climate scenarios to obtain a more comprehensive understanding of local ecosystem evolution. In this study, we established an integrated machine learning prediction framework and a vegetation change trajectory recognition framework to predict the dynamics of vegetation in Central Asia under future climate change scenarios and identify its change trajectories, thus revealing the potential impacts of future climate change on vegetation in the region. The findings suggest that various future climate scenarios will negatively affect most vegetation in Central Asia, with vegetation change intensity increasing with increasing emission trajectories. Analyses of different time scales and trend variations consistently revealed more pronounced downward trends. Vegetation change trajectory analysis revealed that most vegetation has undergone nonlinear and dramatic changes, with negative changes outnumbering positive changes and curve changes outnumbering abrupt changes. Under the highest emission scenario (SSP5-8.5), the abrupt vegetation changes and curve changes are 1.7 times and 1.3 times greater, respectively, than those under the SSP1-2.6 scenario. When transitioning from lower emission pathways (SSP1-2.6, SSP2-4.5) to higher emission pathways (SSP3-7.0, SSP5-8.5), the vegetation change trajectories shift from neutral and negative curve changes to abrupt negative changes. Across climate scenarios, the key climate factors influencing vegetation changes are mostly evapotranspiration and soil moisture, with temperature and relative humidity exerting relatively minor effects. Our study reveals the negative response of vegetation in Central Asia to climate change from the perspective of vegetation dynamics and change trajectories, providing a scientific basis for the development of effective ecological protection and climate adaptation strategies.

The impact of compound drought and heatwave events from 1982 to 2022 on the phenology of Central Asian grasslands.

In the context of global warming, the occurrence and severity of extreme events like atmospheric drought (AD) and warm spell duration index (WSDI) have increased, causing significant impacts on terrestrial ecosystems in Central Asia's arid regions. Previous research has focused on single extreme events such as AD and WSDI, but the effect of compound hot and dry events (CHWE) on grassland phenology in the arid regions of Central Asia remains unclear. This study utilized structural equation modeling (SEM) and the Pettitt breakpoint test to quantify the direct and indirect responses of grassland phenology (start of season - SOS, length of season - LOS, and end of season - EOS) to AD, WSDI, and CHWE. Furthermore, this research investigated the threshold of grassland phenology response to compound hot and dry events. The research findings indicate a significant increasing trend in AD, WSDI, and CHWE in the arid regions of Central Asia from 1982 to 2022 (0.51 day/year, P < 0.01; 0.25 day/year, P < 0.01; 0.26 day/year, P < 0.01). SOS in the arid regions of Central Asia showed a significant advancement trend, while EOS exhibited a significant advance. LOS demonstrated an increasing trend (-0.23 day/year, P < 0.01; -0.12 day/year, P < 0.01; 0.56 day/year). The temperature primarily governs the variation in SOS. While higher temperatures promote an earlier SOS, they also offset the delaying effect of CHWE on SOS. AD, temperature, and CHWE have negative impacts on EOS, whereas WSDI has a positive effect on EOS. AD exhibits the strongest negative effect on EOS, with an increase in AD leading to an earlier EOS. Temperature and WSDI are positively correlated with LOS, indicating that higher temperatures and increased WSDI contribute to a longer LOS. The threshold values for the response of SOS, EOS, and LOS to CHWE are 16.14, 18.49, and 16.61 days, respectively. When CHWE exceeds these critical thresholds, there are significant changes in the response of SOS, EOS, and LOS to CHWE. These findings deepen our understanding of the mechanisms by which extreme climate events influence grassland phenology dynamics in Central Asia. They can contribute to better protection and management of grassland ecosystems and help in addressing the impacts of global warming and climate change in practice.

Silencing METTL3 Stabilizes Atherosclerotic Plaques by Regulating the Phenotypic Transformation of Vascular Smooth Muscle Cells via the miR-375-3p/PDK1 Axis.

PURPOSE: Atherosclerosis (AS) is a primary cause of cardiovascular diseases. This study investigated the mechanism of methyltransferase-like 3 (METTL3) in AS plaques via modulating the phenotypic transformation of vascular smooth muscle cells (VSMCs). METHODS: AS mouse models and MOVAS cell models were established through high-fat diet and the treatment of ox-LDL, respectively. METTL3 expression in AS models was detected via RT-qPCR and Western blot. The AS plaques, lipid deposition, and collagen fibers were examined via histological staining. The levels of Ly-6c, α-SMA, and OPN were examined via Western blot. The blood lipid indexes in mouse aortic tissues were determined using kits. The proliferation and migration of MOVAS cells were detected via CCK-8 and Transwell assays. The m6A modification level of mRNA was quantified. The binding relationship between pri-miR-375 and DGCR8, and the enrichment of m6A on pri-miR-375 were detected via RIP. The binding relationship between miR-375-3p and 3-phosphoinositide-dependent protein kinase-1 (PDK1) was verified via dual-luciferase assay. Joint experiments were designed to investigate the role of miR-375-3P/PDK1 in the phenotypic transformation of VSMCs. RESULTS: METTL3 was highly expressed in AS. Silencing METTL3 alleviated AS progression and stabilized AS plaques in mice, and limited the phenotypic transformation of VSMCs induced by ox-LDL. Silencing METTL3 inhibited m6A level and decreased the binding of DGCR8 to pri-miR-375 and further limited miR-375-3p expression. miR-375-3p targeted PDK1 transcription. miR-375-3p upregulation or PDK1 downregulation facilitated the phenotypic transformation of VSMCs. CONCLUSION: METTL3-mediated m6A modification promoted VSMC phenotype transformation and made AS plaques more vulnerable via the miR-375-3p/PDK1 axis.

Cumulative effects of drought have an impact on net primary productivity stability in Central Asian grasslands.

Global warming has exacerbated the threat of drought in Central Asia, amplifying its ecological implications within the region's grassland ecosystems. This has become an increasingly prominent issue that requires attention and action. The temporal link between grassland development and drought is asymmetric. However, a quantitative assessment of the temporal effects of multiscale drought on Central Asian grasslands has yet to be explored. Based on correlation analysis and the coefficient of variation method, this study analysed the cumulative and lag effects of multitimescale drought on grassland NPP (net primary productivity) under different climatic zones, altitudes and water availabilities in Central Asia from 1982 to 2018, and discussed the impact of temporal effects on grassland NPP stability. Our results on the cumulative effects of drought on grasslands indicate the 6.72 months preceding NPP measurement was the duration for which, on average, drought was most strongly correlated with NPP. Additionally, we found a mean lagged effect of 5.36 months, meaning that the monthly drought 5.36 months prior to NPP measurement was, on average, most strongly correlated with NPP. The degree to which grassland NPP was affected by cumulative drought at a given level of water availability was inversely proportional to the number of cumulative drought months. Under different water availabilities, the lagged effect of grassland NPP was stronger in dry areas than in wet areas, and the number of lag months tended to decrease and then increase as the water availability increased. The percentage of areas where grassland NPP was dominated by the cumulative and lagging effects of drought was 30.02% and 69.98%, respectively. The stability of grassland NPP was adversely affected by the drought accumulation effect. The findings of this study contribute to a deeper understanding of the long-term effects of drought on grassland ecosystems. Additionally, it will aid in the development of strategies for mitigating and adapting to drought events, thereby minimizing their negative impacts on agriculture, livestock, and ecosystems.

Effects of drought and climate factors on vegetation dynamics in Central Asia from 1982 to 2020.

Ecological security and ecosystem stability in Central Asia depend heavily on the local vegetation. Vegetation dynamics and the response and hysteresis relationships to climate factors and drought on multiple scales over long time series in the region still need to be further explored. Using the net primary productivity (NPP) values as the vegetation change index of interest, in this study, we analyzed vegetation dynamics in Central Asia from 1982 to 2020 and assessed the responses and time lags of vegetation to climate factors and drought. The results showed that NPP gradually decreased from north to south and from east to west. Vegetation was distributed along both sides of the mountains. The temperatures rose from northeast to southwest, while precipitation gradually increased from southwest to northeast. The proportion of dry and wet years was as follows: normal (56.41%) > slightly dry (28.2%) > slightly humid (15.39%). Precipitation and drought conditions were positively correlated with NPP during the growing season, while temperature was negatively correlated with NPP. Increased spring temperature, precipitation, and drought conditions positively affected vegetation, while sustained summer temperature resulted in suppressed vegetation growth. Autumn vegetation was positively affected by temperature and drought, and precipitation was negatively correlated with autumn vegetation. Increasing winter temperatures promoted vegetation growth. The time lag between NPP and temperature gradually increased from northeast to southwest, and the time lag between NPP and precipitation gradually increased from south to north. Spring temperatures had the greatest beneficial impact on forestlands; summer climatic factors and drought had little effect on shrublands; the autumn climate exhibited small differences in its influence of each plant type; and winter temperatures had the greatest positive effect on grasslands. No time lag effect was found between any of the four vegetation types and precipitation. A one-month lag was found between cultivated lands and temperature; a two-month lag was found between forestlands and temperature; and a one-month lag was found between forestlands and drought and between shrublands and drought. The results can provide a scientific foundation for the sustainable development and management of ecosystems.

A life cycle assessment of an enterprise's low-carbon emissions model: The Xinjiang Shihezi pig farm faecal treatment biogas project as a case study.

The requirement of carbon emission reduction promotes the continuous implementation and development of low carbon emission mode in typical high-carbon industry aquaculture, especially in the resourceful treatment of terminal waste. However, the previous studies usually focus on a single process or chain, the difference between the long-chain (LC) and automated integration (AI) in the overall environmental impact needs to be quantified and standardised. This paper intends to make a comparative study on two waste treatment biogas projects of aquaculture, a typical industry with high resource consumption and pollution emission in industry and agriculture, and a typical production mode case of aquaculture. The life cycle assessment method is adopted to analyse the environmental impact intensity, identify key link materials, and put forward targeted improvement and optimization schemes. The study found the LC system's comprehensive environmental impact (CEI) is smaller, which is 59.73% less than the AI system. Biogas slurry returning to the field can effectively avoid inorganic fertilizer input. The pretreatment and storage of feces are the key stages. The key substances are NH3 and nitrogen oxides. Suggestions were put forward to optimize the manure management process. In practical pig farms, the process of dry-cleaning manure pre-treatment, automatic fermentation gas production and final biogas slurry filtration drip irrigation should be promoted.

Circular RNA-DPP4 serves an oncogenic role in prostate cancer progression through regulating miR-195/cyclin D1 axis.

BACKGROUND: Recently, more and more studies have highlighted the critical regulatory roles of circular RNAs (circRNAs), a class of non-coding RNAs, in the progression of many human cancers, including prostate cancer (PCa). circRNA microarray analysis was performed to identify circRNAs that are differentially expressed in PCa tissues. METHODS: 104 pairs of PCa tissues and matched adjacent normal prostate tissues (at least 2 cm distal to the tumor margin) were obtained. circRNA microarray analysis was performed on four pairs of PCa tissues and matched adjacent normal prostate tissues to investigate the potential involvement of circRNAs in PCa. Flow cytometric analysis was performed to investigate whether the effect of circDPP4 on PCa cell proliferation was associated with the alteration in cell cycle progression. The role of circDPP4 in PCa tumor growth was further explored in vivo. RESULTS: We found that circDPP4 was overexpressed in PCa tissues and cell lines, and its expression was closely associated with Gleason score and clinical stage of PCa patients. In vitro loss- and gain-of-function experiments demonstrated that circDPP4 knockdown inhibited, whereas circDPP4 overexpression promoted the proliferation, migration, invasion and cell cycle progression of PCa cells. Knockdown of circDPP4 also suppressed PCa tumor growth in vivo. We further found that circDPP4 functioned as a competing endogenous RNA (ceRNA) for miR-195 in PCa cells, and miR-195 negatively regulated the expression of oncogenic cyclin D1. Rescue experiments suggested that restoration of miR-195 blocked the oncogenic role of circDPP4 in PCa cells. CONCLUSIONS: Taken together, our findings revealed a novel regulatory mechanism between circDPP4 and miR-195/cyclin D1 axis, and offered novel strategies for the treatment of PCa.

Identification of novel biomarkers for hepatocellular carcinoma using transcriptome analysis.

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer in the world. To comprehensively investigate the utility of microRNAs (miRNAs) and protein-encoding transcripts (messenger RNAs [mRNAs]) in HCC as potential biomarkers for early detection and diagnosis, we exhaustively mined genomic data from three available omics datasets (GEO, Oncomine, and TCGA), analyzed the overlaps among gene expression studies from 920 hepatocellular carcinoma samples and 508 healthy (or adjacent normal) liver tissue samples available from six laboratories, and identified 178 differentially expressed genes (DEGs) associated with HCC. Paired with miRNA and lncRNA data, we identified 23 core genes that were targeted by nine differentially expressed miRNAs and 21 HCC-specific lncRNAs. We further demonstrated that alterations in these 23 genes were quite frequent, with five genes altered in over 5% of the population. Patients with high levels of YWHAZ, ENAH, and HMGN4 tended to have high-grade tumors and shorter overall survival, suggesting that these genes could be promising candidate biomarkers for disease and poor prognosis in patients with HCC. Our comprehensive mRNA, miRNA, and lncRNA omics analyses from multiple independent datasets identified robust molecules that may be used as biomarkers for early HCC detection and diagnosis.

Circular RNA Expression Profiling Identifies Prostate Cancer- Specific circRNAs in Prostate Cancer.

BACKGROUND/AIMS: Prostate cancer (PCa) is one of the main cancers that damage males' health severely with high morbidity and mortality, but there is still no ideal molecular marker for the diagnosis and prognosis of prostate cancer. METHODS: To determine whether the differentially expressed circRNAs in prostate cancer can serve as novel biomarkers for prostate cancer diagnosis, we screened differentially expressed circRNAs using SBC-ceRNA array in 4 pairs of prostate tumor and paracancerous tissues. A circRNA-miRNA-mRNA regulatory network for the differential circRNAs and their host genes was constructed by Cytoscape3.5.1 software. Quantitative real-time polymerase chain reaction analysis (qRT-PCR) was performed to confirm the microarray data. RESULTS: We found 1021 differentially expressed circRNAs in PCa tumor using SBC-ceRNA array and confirmed the expression of circ_0057558, circ_0062019 and SLC19A1 in PCa cell lines and tumor tissues through qRT-PCR analysis. We demonstrated that combination of PSA level and two differentially expressed circRNAs showed significantly increased AUC, sensitivity and specificity (0.938, 84.5% and 90.9%, respectively) than PSA alone (AUC of serum PSA was 0.854). Moreover, circ_0057558 was correlated positively with total cholesterol. The functional network of circRNA-miRNA-mRNA analysis showed that circ_0057558 and circ_0034467 regulated miR-6884, and circ_0062019 and circ_0060325 regulated miR-5008. CONCLUSION: Our results demonstrated that differentially expressed circRNAs (circ_0062019 and circ_0057558) and host gene SLC19A1 of circ_0062019 could be used as potential novel biomarkers for prostate cancer.