A pumpless liver-on-a-chip for drug hepatotoxicity analysis.

This study presents the development and validation of an innovative microfluidic liver-on-a-chip device utilizing gravity-driven perfusion for the evaluation of drug hepatotoxicity. This research involved the construction of a hydrogel-based coculture chip that integrates liver parenchymal and stellate cells within a tri-channel configuration. The assembly and operation of the liver-on-a-chip and its accompanying custom rocker were straightforward. The cells in the chip maintained high viability and continuously synthesized liver albumin over extended culture durations. Acetaminophen (APAP), a hepatic injury-inducing drug, was utilized as a positive control in hepatic toxicity assays on the chip. The liver chip exhibited hepatotoxic responses comparable to those observed in 2D models. Furthermore, in this study we evaluated the effects of two plant-derived natural compounds, aristolochic acid I (AA) and its analog aristolactam AII (AL), in both 2D cell models and the liver-on-a-chip system. AA, known for its hepatorenal toxicity, was observed to cause hepatotoxicity in both the 2D models and on the chip. The flow cytometry and mRNA sequencing results confirmed the propensity of these compounds to induce liver cell apoptosis. Notably, AL, previously considered nontoxic, provoked a significant decrease in the hepatic functionality marker albumin exclusively in the liver chip but not in 2D models, indicating the liver chip's enhanced sensitivity to toxic substances. In summary, this pumpless liver-on-a-chip is a simple yet powerful tool for drug hepatotoxicity studies.

Concurrent Hearing and Genetic Screening of 180,469 Neonates with Follow-up in Beijing, China.

Concurrent hearing and genetic screening of newborns is expected to play important roles not only in early detection and diagnosis of congenital deafness, which triggers intervention, but also in predicting late-onset and progressive hearing loss and identifying individuals who are at risk of drug-induced HL. Concurrent hearing and genetic screening in the whole newborn population in Beijing was launched in January 2012. This study included 180,469 infants born in Beijing between April 2013 and March 2014, with last follow-up on February 24, 2018. Hearing screening was performed using transiently evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected and nine variants in four genes, GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened using a DNA microarray platform. Of the 180,469 infants, 1,915 (1.061%) were referred bilaterally or unilaterally for hearing screening; 8,136 (4.508%) were positive for genetic screening (heterozygote, homozygote, or compound heterozygote and mtDNA homoplasmy or heteroplasmy), among whom 7,896 (4.375%) passed hearing screening. Forty (0.022%) infants carried two variants in GJB2 or SLC26A4 (homozygote or compound heterozygote) and 10 of those infants passed newborn hearing screening. In total, 409 (0.227%) infants carried the mtDNA 12S rRNA variant (m.1555A>G or m.1494C>T), and 405 of them passed newborn hearing screening. In this cohort study, 25% of infants with pathogenic combinations of GJB2 or SLC26A4 variants and 99% of infants with an m.1555A>G or m.1494C>T variant passed routine newborn hearing screening, indicating that concurrent screening provides a more comprehensive approach for management of congenital deafness and prevention of ototoxicity.

Research on the Robustness of the Chinese Input-Output Network Based on Relative Entropy Theory.

The input-output (IO) network is the quantitative description of an IO-based economy in which nodes represent industries and edges connecting nodes represent the economic connection between industries. Robustness refers to the ability of tolerating perturbations that might affect the system's functional body. There is both practical and theoretical significance to explore the robustness of the IO network for economic development. In this paper, we probe the robustness of the Chinese IO network based on the relative entropy of the probability distribution of network parameters (node degree, strongest path betweenness, downstream closeness and upstream closeness) under random node or edge failure and intentional node or edge attack. It is found that the Chinese IO network shows relatively weak robustness when it is under intentional attack, but relatively strong robustness when it is under random failure. Our experiment also verifies the applicability and effectiveness of the relative entropy model in measuring the robustness of the IO network.

Risk Transmission of Trade Price Fluctuations from a Nickel Chain Perspective: Based on Systematic Risk Entropy and Granger Causality Networks.

Nickel is a strategic mineral resource, with 65% of nickel being used in stainless steel. The situation in Ukraine starting in February 2022 has led to significant fluctuations in nickel prices, with prices of nickel products along the same chain affecting and passing through each other. Using systematic risk entropy and granger causality networks, we measure the volatility risk of trade prices of nickel products using the nickel industry chain trade data from 2000-2019 and explore the transmission patterns of different volatility risk prices from the industry chain perspective. The findings show that: (1) Nickel ore has the highest risk of import trade price volatility and a strong influence, but low risk transmission. Stainless steel has the highest trade price impact but is also subject to the strongest passive influence. (2) The Americas have a higher risk of trade price volatility but a weaker influence. The influence and sensitivity of trade prices is stronger in Asia and Europe. (3) Indonesia's stainless steel export prices have a high rate of transmission and strong influence. Germany's ferronickel export prices are highly susceptible to external influences and can continue to spread loudly. Russian nickel ore export prices are able to quickly spread their impact to other regions.

Variations in traffic-related polycyclic aromatic hydrocarbons in PM2.5 in Kanazawa, Japan, after the implementation of a new vehicle emission regulation.

A three-year sampling campaign was conducted at a roadside air pollution monitoring station in the urban area of Kanazawa, Japan. Due to a new emission regulation, PAHs levels decreased over the sampling campaign, exhibiting values of 706 ± 413 pg/m3 in 2017, 559 ± 384 pg/m3 in 2018, and 473 ± 234 pg/m3 in 2019. In each year, similar seasonal variations in PAHs levels were observed, with higher levels observed in winter and lower levels in summer. Among the PAHs isomer ratios, we observed that the ratio of benzo[b]fluoranthene (BbF) and benzo[k]fluoranthene (BkF), [BbF]/([BbF] + [BkF]), and the ratio of indeno[1,2,3-cd]pyrene (IDP) and benzo[ghi]perylene (BgPe), [IDP]/([BgPe] + [IDP]), showed stability over the sampling campaign and were less affected by the new emission regulation, seasonal variations, and regional characteristics. When using the combined ratio ranges of 0.66 - 0.80 ([BbF]/([BbF] + [BkF]) and 0.26-0.49 ([IDP]/([BgPe] + [IDP]), traffic emissions were clearly distinguished from other PAHs emission sources. Principal component analysis (PCA) and positive matrix factorization (PMF) were also performed to further analyse the characteristics of traffic-related PAHs. Overall, this study affirmed the effectiveness of the new emission regulation in the reduction of PAHs emissions and provided a combined range for identifying PAHs traffic emission sources.

A Highly Automated Mobile Laboratory for On-site Molecular Diagnostics in the COVID-19 Pandemic.

BACKGROUND: Infectious disease outbreaks such as the COVID-19 (coronavirus disease 2019) pandemic call for rapid response and complete screening of the suspected community population to identify potential carriers of pathogens. Central laboratories rely on time-consuming sample collection methods that are rarely available in resource-limited settings. METHODS: We present a highly automated and fully integrated mobile laboratory for fast deployment in response to infectious disease outbreaks. The mobile laboratory was equipped with a 6-axis robot arm for automated oropharyngeal swab specimen collection; virus in the collected specimen was inactivated rapidly using an infrared heating module. Nucleic acid extraction and nested isothermal amplification were performed by a "sample in, answer out" laboratory-on-a-chip system, and the result was automatically reported by the onboard information platform. Each module was evaluated using pseudovirus or clinical samples. RESULTS: The mobile laboratory was stand-alone and self-sustaining and capable of on-site specimen collection, inactivation, analysis, and reporting. The automated sampling robot arm achieved sampling efficiency comparable to manual collection. The collected samples were inactivated in as short as 12 min with efficiency comparable to a water bath without damage to nucleic acid integrity. The limit of detection of the integrated microfluidic nucleic acid analyzer reached 150 copies/mL within 45 min. Clinical evaluation of the onboard microfluidic nucleic acid analyzer demonstrated good consistency with reverse transcription quantitative PCR with a κ coefficient of 0.979. CONCLUSIONS: The mobile laboratory provides a promising solution for fast deployment of medical diagnostic resources at critical junctions of infectious disease outbreaks and facilitates local containment of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) transmission.

Exploratory development of PCR-fluorescent probes in rapid detection of mutations associated with extensively drug-resistant tuberculosis.

This study aims to evaluate the clinical value of PCR-fluorescent probes for detecting the mutation gene associated with extensively drug-resistant tuberculosis (XDR-TB). The molecular species identification of 900 sputum specimens was performed using polymerase chain reaction (PCR)-fluorescent probe. The mutations of the drug resistance genes rpoB, katG, inhA, embB, rpsL, rrs, and gyrA were detected. The conventional drug susceptibility testing (DST) and PCR-directed sequencing (PCR-DS) were carried out as control. DST demonstrated that there were 501 strains of rifampicin resistance, 451 strains of isoniazid resistance, 293 strains of quinolone resistance, 425 strains of streptomycin resistance, 235 strains of ethambutol resistance, and 204 strains of amikacin resistance. Furthermore, 427 (47.44%) or 146 (16.22%) strains were MDR-TB or XDR-TB, respectively. The mutations of the rpoB, katG, inhA, embB, rpsL, rrs, and gyrA genes were detected in 751 of 900 TB patients by PCR-fluorescent probe method, and the rate of drug resistance was 751/900 (83.44%). No mutant genes were detected in the other 149 patients. Compared with DST, the mutant rates of rpoB, katG/inhA, rpsL, rrs, embB, and gyrA of six drugs were higher than 88%; five of six drugs were higher than 90% except for SM (88.11%). The MDR and XDR mutant gene types were found in 398 (42.22%) and 137 (15.22%) samples. PCR-DS was also employed and confirmed the PCR-fluorescent probe method with the accordance rate of 100%. The PCR-fluorescent probe method is rapid and straightforward in detecting XDR-TB genotypes and is worthy of being applied in hospitals.

Impact of COVID-19 Outbreak on the Long-Range Transport of Common Air Pollutants in KUWAMS.

As a background sampling site in western Japan, the Kanazawa University Wajima Air Monitoring Station (KUWAMS) continuously observes the air pollutants, including PM1, PM2.5, organic carbon (OC) and element carbon (EC). Data for September 2019 to April 2020 were compared with data for September 2018 to April 2019. The mean concentrations of both PM1 and PM2.5 were 4.10 µg/m3 (47%) and 5.82 µg/m3 (33%) lower, respectively in the Coronavirus Disease 2019 (COVID-19) period (January to April) than in the same period in 2019. Notably, the average concentrations of both classes of particulate matter (PM) in the COVID-19 period were the lowest for that period in all years since 2016. OC and EC also considerably lower (by 69 and 63%, respectively) during the COVID-19 period than during the same period in 2019. All pollutants were then started to increase after the resumption of the work in 2020. The pollutant variations correspond to the measure implemented during the COVID-19 period, including the nationwide lockdown and work resumption. Furthermore, the reductions in the ratios PM1/PM2.5 and OC/EC during COVID-19 period indicate lighter pollution and fewer emission sources. This analysis of the changes in the pollutant concentrations during the epidemic and non-epidemic periods illustrates the significance of the dominant pollution emissions at KUWAMS and the impact of pollution from China that undergoes long-range transport to KUWAMS.

Responses of anaerobic digestion of food waste to coupling effects of inoculum origins, organic loads and pH control under high load: Process performance and microbial characteristics.

This study investigated responses of anaerobic digestion (AD) of food waste (FW) with different inocula to varying organic loads and to pH control under high load in terms of process performance and microbial characteristics. Without pH control, digester inoculated by thickened sludge obtained high methane yield of 547.8 ± 27.8 mL/g VS under organic load of 7.5 g VS/L but was inhibited by volatile fatty acids (VFAs) under higher loads (15 and 30 g VS/L). However, digesters inoculated by anaerobic sludge obtained high methane yields of 575.9 ± 34.2, 569.3 ± 24.8 and 531.9 ± 26.2 mL/g VS under organic loads of 7.5, 15 and 30 g VS/L and VFAs inhibition only appeared under extremely high load of 45 g VS/L. Digesters under VFA inhibition with high load were significantly enhanced by controlling single ecological factor pH at 6.5, 7.0 and 7.5, as indicated by shorter lag phases, higher peak values of methane production rate, greater methane yields and fast VFAs degradation. Maximum methane recovery was obtained with pH control at 7.5 under high load. VFA inhibition was accompanied by the degeneration of ecological functions of Syntrophomonadaceae and unidentified Bacteroidales and the dominant growth of unidentified Clostridiales. Under high load and pH control, high stability was strongly associated with obvious growth of Methanosarcina, which enriched methanogenic pathways thus improved system robustness and tolerance to VFAs. Moreover, pH control stimulated the growth of syntrophic Bacteria Syntrophomonadaceae while maintaining the high activity of hydrogenotrophic methanogens therefore sustained efficient syntrophic communities of Bacteria and methanogens and avoided over accumulation of VFAs. pH control promoted adaptive selection of methanogens, leading to obvious decline of archaeal community diversity. This study provided practical guidance on digester configurations of high-load AD of FW and expanded the understanding of responses to coupling effects of inoculum origins, organic loads and pH control under high load concerning process performance and microbial community dynamics.

Yearly variation in characteristics and health risk of polycyclic aromatic hydrocarbons and nitro-PAHs in urban shanghai from 2010-2018.

This study encompassed the regular observation of nine polycyclic aromatic hydrocarbons (PAHs) and three nitro-PAHs (NPAHs) in particulate matter (PM) in Shanghai in summer and winter from 2010 to 2018. The results showed that the mean concentrations of Æ©PAHs in summer decreased by 24.7% in 2013 and 18.1% in 2017 but increased by 10.2% in 2015 compared to the data in 2010. However, the mean concentrations of Æ©PAHs in winter decreased by 39.7% from 2010 (12.8 ± 4.55 ng/m3) to 2018 (7.72 ± 3.33 ng/m3), and the mean concentrations of 1-nitropyrene in winter decreased by 79.0% from 2010 (42.3 ± 16.1 pg/m3) to 2018 (8.90 ± 2.09 pg/m3). Correlation analysis with meteorological conditions revealed that the PAH and NPAH concentrations were both influenced by ambient temperature. The diagnostic ratios of PAHs and factor analysis showed that they were mainly affected by traffic emissions with some coal and/or biomass combustion. The ratio of 2-nitrofluoranthene to 2-nitropyrene was near 10, which indicated that the OH radical-initiated reaction was the main pathway leading to their secondary formation. Moreover, backward trajectories revealed different air mass routes in each sampling period, indicating a high possibility of source effects from the northern area in winter in addition to local and surrounding influences. Meanwhile, the mean total benzo[a]pyrene-equivalent concentrations in Shanghai in winter decreased by 50.8% from 2010 (1860 ± 645 pg/m3) to 2018 (916 ± 363 pg/m3). These results indicated the positive effects of the various policies and regulations issued by Chinese authorities.

[Bayesian network Meta-analysis of Chinese medicine injections in treatment of chronic renal insufficiency].

In this study, Honghua Injection, Danshen Injection, Shenkang Injection, Shuxuetong Injection, Lulutong Injection, Shenxiong Glucose Injection and Chuanxiong Injection were compared for their clinical efficacy on chronic renal insufficiency by using the method of network Meta-analysis, with Western medicine as the common reference. The randomized controlled trial(RCT) of Hong-hua Injection, Danshen Injection, Shenkang Injection, Shuxuetong Injection, Lulutong Injection, Shenxiong Glucose Injection and Chuanxiong Injection for the treatment of chronic renal insufficiency were obtained by computer-based retrieval. The literature quality was evaluated by using the method in Cochrane Reviewer's Handbook 5.1 after independent screening of the included literature by two reviewers. The RJAGS package and GEMTC package of RevMan 5.3, GEMTC software, R software were used for statistical analysis to compare and sort the different injections in terms of efficacy. A total of 6 197 patients with chronic renal failure were included in 79 RCTs, involving 8 treatment measures. The effective rates of conventional treatment combined with Shenxiong Injection(OR=3.55, 95%CI[1.98, 6.37], P<0.000 1), Honghua Injection(OR=3.77, 95%CI[2.45, 5.81], P<0.000 01), Shuxuetong Injection(OR=6.71, 95%CI[3.30, 13.65], P<0.000 01) and Shenkang Injection(OR=4.14, 95%CI[3.42, 5.03], P<0.000 01) were all better than that in control group, and the effective rate of Honghua Injection combined with conventional treatment(OR=3.89, 95%CI[1.73, 8.74], P=0.001) was better than that in Danshen Injection combined with conventional treatment, all with statistically significant differences. By comprehensive comparison, Shuxuetong Injection, Honghua Injection and Shenkang Injection combined with Western medicine had good clinical effect on the effective rate, serum creatinine reduction and urea nitrogen reduction in patients with chronic renal insufficiency. However, due to the relatively low quality of the included literature, the conclusion has yet to be verified clinically.

The efficacy and safety of cold atmospheric plasma as a novel therapy for diabetic wound in vitro and in vivo.

Cold atmospheric plasma (CAP) is a group of various chemical active species, such as ozone and nitric oxide, generated by working gas. CAP was demonstrated to have an effect on tissue regeneration and wound healing. We conducted this study to evaluate the efficacy and safety of CAP as a novel therapy for diabetic wounds in vitro and in vivo. The plasma consists of ionised helium gas that is produced by a high-voltage and high-frequency power supply. Eight-week-old male db/db mice and C57BL mice were treated with helium gas (control group), 90s' CAP (low-dose group), and 180s' CAP (high-dose group). Mice were treated and observed for 2 weeks. Skin samples from around the wound and blood samples were collected. Our in vitro analysis included scratch wound-healing assays by using human HaCaT immortalised human epidermal cells. After 14 days of treatment, CAP could obviously promote diabetic wound healing. Wound closure rates were significantly higher in the low-dose group and high-dose groups compared with the control group. Meanwhile, compared with the control group, the protein expression of IL-6, tumour necrosis factor-α, inducible nitric oxide synthase, and superoxide dismutase in two CAP groups significantly decreased, while the protein expression of vascular endothelial growth factor and transforming growth factor-ß in two CAP groups significantly increased (all P < .05); these data show good agreement with the change in mRNA level (all P < .05). In vitro, scratch wound-healing assays showed that plasma treatment could effectively ensure healing within 3 minutes of exposure (all P < .05). In addition, no difference was found in histological observations of normal skin and the level of serum alanine transaminase, aspartate aminotransferase, blood urea nitrogen, creatinine, and white blood cells among the CAP groups and control group. CAP treatment for 3 minutes every day improves wound healing in diabetic mice by suppressing inflammation, reducing oxidative stress, and enhancing angiogenesis, involving several proteins signalling, and it is safe for the liver and kidney.

Size distribution of particulate polycyclic aromatic hydrocarbons in fresh combustion smoke and ambient air: A review.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the atmosphere and they mostly stem from the imperfect combustion of fossil fuels and biofuels. PAHs are inherently associated with homogenous fine particles or distributed to different-sized particles during the aging of air masses. PAHs carried by fine particles undergo a long-range transport to remote areas while those adsorbed on coarse particles have a shorter lifetime in ambient air. More importantly, PAHs with higher molecular weights tend to be bound with finer particles and can deeply enter the lungs, posing severe health risks to humans. Thus, the environmental fate and health effects of particulate PAHs are strongly size-dependent. This review summarizes the size distributions of particulate PAHs freshly emitted from combustion sources as well as the distribution patterns of PAHs in ambient particles. It was found that PAHs from stationary sources are primarily bound to fine particles, which are slightly larger than particles to which PAHs from mobile sources are bound. In ambient air, particulate PAHs are distributed in larger size modes than those in the combustion fume, and the particle size decreases with PAH molecular weight increasing. The relevant mechanisms and influencing factors of particle size distribution changes are illustrated in this article, which are essentially attributed to combustion and ambient temperature as well as the physical and chemical properties of PAHs. Overall, the study on the particle size distribution of PAHs will contribute for a full understanding of the origin, atmospheric behaviors and health effects of particulate PAHs.

Isolation and Visible Detection of Tumor-Derived Exosomes from Plasma.

Exosomes are nanosized extracellular vesicles (ranging from 30 to 120 nm) released from many cells that provide promising biomarkers for the noninvasive diagnosis of cancer. However, traditional exosome-isolation methods are tedious, nonstandardized, and require bulky instrumentation, thus limiting its clinical applications. In this paper, an anion-exchange (AE)-based isolation method was first proposed to isolate exosomes directly from plasma and cell-culture medium with AE magnetic beads within 30 min. Exosomes isolated with AE magnetic beads had higher recovery efficiency (>90%) and less protein impurities than those isolated by ultracentrifugation (UC). Prostate-cancer (PCa) exosomes in plasma were detected in a visual, label-free, and quantitative manner with aptamer-capped Fe3O4 nanoparticles for the first time. The linear range of PCa exosomes was estimated from 0.4 × 108 to 6.0 × 108 particles/mL with a detection limit of 3.58 × 106 particles/mL. The present study provides an efficient and practical approach for the rapid isolation and visible detection of exosomes, which is promising for the early diagnosis of PCa.

Biological-Profiling-Based Systematic Analysis of Rhizoma Coptidis from Different Growing Regions and Its Anticholesterol Biosynthesis Activity on HepG2 Cells.

Rhizoma Coptidis is a widely cultivated traditional Chinese herb. Although the chemical profiles of Rhizoma Coptidis have been established previously, the biological profiling of Rhizoma Coptidis has not been conducted yet. In this study, we collected Rhizoma Coptidis varieties from four distinct growing regions and performed genome-wide biological response fingerprinting (BioReF) on HepG2 cells using a gene expression array. Similar biological pathways were affected by extracts of all four Rhizoma Coptidis varieties but not by their analogue, Mahoniae Caulis. Among these pathways, the terpenoid backbone biosynthesis pathway was highly enriched, and six genes in the mevalonate (MVA) pathway were all down-regulated. However, the expression, maturation, as well as the specific DNA binding capacity of their coordinate transcription factor, sterol response element binding protein 2 (SREBP2), was not affected by Rhizoma Coptidis extract (RCE) or its typical active alkaloid berberine. Cellular cholesterol content tests further verified the cholesterol-lowering function of RCE in vitro, which supplements evidence for the use of Rhizoma Coptidis in hyperlipidemia treatment. This is the first described example of evaluating the quality of Rhizoma Coptidis with BioReF and a good demonstration of using BioReF to uncover the mechanisms of herbs at a systematic level.

Reduced Graphene Oxide-Based Solid-Phase Extraction for the Enrichment and Detection of microRNA.

MicroRNAs (miRNAs) are endogenous molecules with regulatory functions. The purification and enrichment of miRNA are essential for its precise and sensitive detection. miRNA isolated using commercial kits contains abundant interfering RNAs, and the concentration of miRNA may not be adequate for detection. Herein, we prepared a reduced graphene oxide (rGO)-based magnetic solid-phase extraction material for the enrichment and ultrasensitive detection of miRNA from intricate nucleic acid solutions. In situ reverse transcription (RT) was developed as the most efficient approach to desorb miRNA from rGO among the methods that are compatible for the subsequent amplification reported thus far. Additionally, rolling circle amplification and qPCR were used to detect let-7a with a decrease of the limit of detection by 24.7- and 31.3-fold, respectively. This material was also successfully used to extract and detect miRNA from total RNA isolated from human plasma. Our results show that the material prepared in this study has the potential for cancer biopsy in clinics and the discovery of new miRNAs in scientific research.

Rapid and visual detection of Mycobacterium tuberculosis complex using recombinase polymerase amplification combined with lateral flow strips.

To definitively diagnose active pulmonary Tuberculosis (TB), Mycobacterium tuberculosis complex (MTBC) bacilli must be identified within clinical specimens from patients. In this study, we introduced a rapid and visual detection method of MTBC using recombinase polymerase amplification (RPA) combined with lateral flow (LF) strips. The LF-RPA assay, read results with naked eyes, could detect as few as 5 genome copies of M. tuberculosis H37Rv (ATCC 27294) per reaction and had no cross-reactions with other control bacteria even using excessive amount of template DNA. The system could work well at a broad range of temperature 25-45 °C and reach detectable level even within 5 min. When testing a total of 137 clinical specimens, the sensitivity and specificity of the LF-RPA assay were 100% (95% CI: 95.94%-100%) and 97.92% (95% CI: 88.93%-99.95%), respectively, compared to culture identification method. Therefore, the LF-RPA system we have demonstrated is a rapid, simple, robust method for MTBC detection which, subject to the availability of a suitable sample extraction method, has the potentiality to diagnose TB at the point-of-care testing.

Regulatory Roles of MicroRNAs in Diabetes.

MicroRNAs (miRNAs), a class of endogenous small noncoding RNAs in eukaryotes, have been recognized as significant regulators of gene expression through post-transcriptional mechanisms. To date, >2000 miRNAs have been identified in the human genome, and they orchestrate a variety of biological and pathological processes. Disruption of miRNA levels correlates with many diseases, including diabetes mellitus, a complex multifactorial metabolic disorder affecting >400 million people worldwide. miRNAs are involved in the pathogenesis of diabetes mellitus by affecting pancreatic ß-cell functions, insulin resistance, or both. In this review, we summarize the investigations of the regulatory roles of important miRNAs in diabetes, as well as the potential of circulating miRNAs as diagnostic markers for diabetes mellitus.

Numerical built-in method for the nonlinear JRC/JCS model in rock joint.

The joint surface is widely distributed in the rock, thus leading to the nonlinear characteristics of rock mass strength and limiting the effectiveness of the linear model in reflecting characteristics. The JRC/JCS model is the nonlinear failure criterion and generally believed to describe the characteristics of joints better than other models. In order to develop the numerical program for JRC/JCS model, this paper established the relationship between the parameters of the JRC/JCS and Mohr-Coulomb models. Thereafter, the numerical implement method and implementation process of the JRC/JCS model were discussed and the reliability of the numerical method was verified by the shear tests of jointed rock mass. Finally, the effect of the JRC/JCS model parameters on the shear strength of the joint was analyzed.

Coordinated development and driving factor heterogeneity of different types of urban agglomeration carbon emissions in China.

Carbon emission (CE) reduction has become the primary task of China's urban agglomerations (UAs) in achieving sustainable development goals. This paper uses a decoupling model and coupling coordination model to measure the relationship between the development levels of different types of UAs and CEs in China from 2004 to 2016. Concurrently, the geographically and temporally weighted regression model is used to explore the spatial heterogeneity of the impact of different driving factors on the CEs of UAs. The results show the following: Most UAs have the potential to further decouple CEs and economic growth. Most UAs are still in coordinated development (> 0.5). Among the service innovation UAs, the Yangtze River Delta UA has a coupling coordination of less than 0.3, while the Pearl River Delta UA has a coupling coordination of more than 0.8, showing polarization. Manufacturing and resource-based UAs are still in the grinding adaptation stage (0.5-0.8). There are apparent spatiotemporal differences in the impacts of various driving factors on the CE of UAs. The level of land urbanization and investment in fixed assets promote CEs. However, the level of population urbanization and industrial structure restrain CEs. Therefore, reducing land development and industrial transformation can be an effective means to reduce CEs in UAs. These findings will provide extensive insights for different UAs to achieve differentiated low-carbon development.