MicroRNA-200c-targeted contactin 1 facilitates the replication of influenza A virus by accelerating the degradation of MAVS.

Influenza A viruses (IAVs) continuously challenge the poultry industry and human health. Elucidation of the host factors that modulate the IAV lifecycle is vital for developing antiviral drugs and vaccines. In this study, we infected A549 cells with IAVs and found that host protein contactin-1 (CNTN1), a member of the immunoglobulin superfamily, enhanced viral replication. Bioinformatic prediction and experimental validation indicated that the expression of CNTN1 was reduced by microRNA-200c (miR-200c) through directly targeting. We further showed that CNTN1-modulated viral replication in A549 cells is dependent on type I interferon signaling. Co-immunoprecipitation experiments revealed that CNTN1 specifically interacts with MAVS and promotes its proteasomal degradation by removing its K63-linked ubiquitination. Moreover, we discovered that the deubiquitinase USP25 is recruited by CNTN1 to catalyze the deubiquitination of K63-linked MAVS. Consequently, the CNTN1-induced degradation cascade of MAVS blocked RIG-I-MAVS-mediated interferon signaling, leading to enhanced viral replication. Taken together, our data reveal novel roles of CNTN1 in the type I interferon pathway and regulatory mechanism of IAV replication.

The Lnc-RNA APPAT Suppresses Human Aortic Smooth Muscle Cell Proliferation and Migration by Interacting With MiR-647 and FGF5 in Atherosclerosis.

PURPOSE: LncRNA-Atherosclerotic plaque pathogenesis-associated transcript (APPAT) could be detected in circulating blood and has been demonstrated to correlate with the development of atherosclerosis in our previous work. It could be a potential noninvasive biomarker for earlier diagnoses of clinical cardiovascular disease. Moreover, the expression of miR-647 increased in ox-LDL-treated vascular smooth muscle cells and peripheral blood of patients with coronary heart disease. A negative correlation between APPAT and miR-647 was confirmed, and FGF5 was screened as molecular target of miR-647. However, it is largely unclear how APPAT, miR-647, and FGF5 interact and function in disease development. Here, we aim to explore the underlying molecular mechanism in this progression. MATERIALS AND METHODS: APPAT, miR-647, and FGF5 expression levels were detected by quantitative reverse transcription polymerase chain reaction; cell proliferation was detected by EdU incorporation assay; cell migration was detected by wound-healing assay; the molecular interaction of APPAT/FGF5 with miR-647 was verified by dual-luciferase reporter assay; the western blot was performed to determine the gene expression at protein levels; subcellular localizations of APPAT and miR-647 were observed by fluorescence in situ hybridization; cytosolic and nucleus fractionation assay was performed to further detect the distribution of miR-647. RESULTS: APPAT and miR-647 have inverse effects on human aortic smooth muscle cells' (HASMCs) proliferation and migration. APPAT negatively regulated the cell activity, whereas miR-647 did it in a positive way (p<0.05). Three pairs of molecular interplay were found: mutual negative regulation between APPAT and miR-647, APPAT downregulated FGF5, miR-647 regulation on FGF5 (p<0.05). Subcellular location assay confirmed the molecular interaction of APPAT and miR-647. CONCLUSIONS: APPAT could suppress the migration and proliferation of ox-LDL-treated HASMCs via interacting with miR-647 and FGF5. We revealed a nontypical competing endogenous RNA mechanism of long noncoding RNA in the progression of atherosclerosis.

Characterizing Operating Condition-Based Formaldehyde Emissions of Light-Duty Diesel Trucks in China Using a PEMS-HCHO System.

Formaldehyde (HCHO) plays a critical role in atmospheric photochemistry and public health. While existing studies have suggested that vehicular exhaust is an important source of HCHO, the operating condition-based diesel truck HCHO emission measurements remain severely limited due to the limited temporal resolution and accuracy of measurement techniques. In this study, we characterized the second-by-second HCHO emissions from 29 light-duty diesel trucks (LDDTs) in China over dynamometer and real-world driving tests using a portable online HCHO emission measurement system (PEMS-HCHO), considering various operating conditions. Our results suggested that the HCHO emissions from LDDTs might be underestimated by the widely used offline DNPH-HPLC method. The HCHO emissions at a 200 s cold start from China V LDDT can be up to 50 mg/start. Different driving conditions over dynamometer and real-world driving tests led to a 2-4 times difference in the HCHO emission factors (EFs). Under real-world hot-running conditions, the HCHO EFs of China III, IV, V, and VI LDDTs were 43.5 ± 35.7, 10.6 ± 14.2, 8.8 ± 5.1, and 3.2 ± 1.2 mg/km, respectively, which significantly exceeded the latest California low emission vehicle III HCHO emission standard (2.5 mg/km). These findings highlighted the significant impact of vehicle operating conditions on HCHO emissions and the urgency of regulating HCHO emissions from LDDTs in China.

Characteristics of wintertime carbonaceous aerosols in two typical cities in Beijing-Tianjin-Hebei region, China: Insights from multiyear measurements.

In order to investigate the impact of "Blue Sky War" implemented during 2018-2020 on carbonaceous aerosols in Beijing-Tianjin-Hebei (BTH) region, China, fine particulate matter (PM2.5) samples were collected simultaneously in Tianjin and Handan in three consecutive winters from 2018 to 2020. Organic carbon (OC) and elemental carbon (EC) in PM2.5 were measured with the same thermal-optical methods and analysis protocols. Significant reductions in primary organic carbon (POC) and EC concentrations were observed both in Tianjin and Handan, with decreasing rates of 0.65 and 2.95 µg m-3 yr-1 for POC and 0.13 and 0.64 µg m-3 yr-1 for EC, respectively. The measured absorption coefficients of EC (babs, EC) also decreased year by year, with a decreasing rate of 1.82 and 6.16 Mm-1 yr-1 in Tianjin and Handan, respectively. The estimated secondary organic carbon (SOC) concentrations decreased first and then increased in both Tianjin and Handan, accounting for more than half of the total OC in winter of 2020-2021 and with increasing contributions especially in highly polluted days. SOC was recognized as one of key factors influencing EC light absorption. EC in the two cities was relatively more related to coal combustion and industrial sources. The reductions of primary carbonaceous components may be attributed to the air quality regulations targeting coal combustion and industrial sources emissions in BTH area. Potential source contribution function (PSCF) analysis results indicated that the major source areas of OC and EC in Tianjin were the southwest region of the sampling site, while the southeast areas for Handan. These findings demonstrated the effectiveness of air quality regulation in primary emissions in typical polluted cities in BTH region and highlighted the needs for further control and in-depth investigation of SOC formation along with implementation of air pollution control act in the future.

Analgesic Electrical Stimulation Combined with Wrist-Ankle Acupuncture Reduces the Cortical Response to Pain in Patients with Myofasciitis: A Randomized Clinical Trial.

OBJECTIVE: Transcutaneous electrical nerve stimulation (TENS) based on wrist-ankle acupuncture has been shown to relieve pain levels in patients with myofascial pain syndrome (MPS). However, its efficacy is highly subjective. The purpose of this study was to evaluate the feasibility and effectiveness of TENS based on wrist-ankle acupuncture for pain management in patients with MPS from the perspective of cerebral cortex hemodynamics. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: We designed a double-blind, randomized, controlled clinical trial. Thirty-one male patients with MPS were randomly assigned to two parallel groups. The experimental group (n = 16) received TENS based on wrist-ankle acupuncture for analgesic treatment, while the control group (n = 15) did not. The pain was induced by mechanically pressurized at acupoint Jianjing. The multichannel functional near-infrared spectroscopy (fNIRS) equipment was utilized for measuring oxyhemoglobin (HbO) levels in the cerebral cortex during the tasks. RESULTS: After the intervention, visual analog scale (VAS), the activation degree and activation area of pain perception cortices were significantly reduced in the experimental group compared to the baseline values (P < .05). Particularly, Frontopolar Area (FPA), and Dorsolateral Prefrontal Cortex (DLPFC) are highly involved in the pain process and pain modulation. CONCLUSION: Compared to no intervention, TENS based on wrist-ankle acupuncture can be effective in relieving pain in patients with MPS in terms of cerebral cortical hemodynamics. However, further studies are necessary to quantify the analgesic effect in terms of cerebral hemodynamics and brain activation.

METTL3-mediated m6A modification of pri-miR-148a-3p affects prostate cancer progression by regulating TXNIP.

OBJECTIVE: Prostate cancer (PCa) severely affects men's health worldwide. The mechanism of methyltransferase-like 3 (METTL3) in affecting PCa development by regulating miR-148a-3p expression via N6-methyladenosine (m6A) modification was investigated. METHODS: METTL3, miR-148a-3p, and thioredoxin interacting protein (TXNIP) levels were determined using RT-qPCR and Western blotting. The m6A modification level of miR-148a-3p was observed by Me-RIP assay. Bioinformatics website predicted miR-148a-3p and TXNIP levels in PCa and their correlation, and the binding site between them was verified by dual-luciferase assay. The proliferation, migration, invasion, and apoptosis of PCa cells were examined by CCK-8 assay, Transwell assay, and flow cytometry. A transplanted tumor model was established in nude mice to observe the tumor growth ability, followed by determination of TXNIP levels in tumor tissues by immunohistochemistry. RESULTS: METTL3 interference restrained the proliferation, migration, and invasion and promoted apoptosis of PCa cells. METTL3 up-regulated miR-148a-3p by promoting the m6A modification of pri-miR-148a-3p in PCa cells. miR-148a-3p overexpression nullified the inhibitory actions of silencing METTL3 on PCa cell growth. miR-148a-3p facilitated PCa cell growth by silencing TXNIP. METTL3 interference inhibited tumor growth by down-regulating miR-148a-3p and up-regulating TXNIP. CONCLUSION: METTL3 promoted miR-148a-3p by mediating the m6A modification of pri-miR-148a-3p, thereby targeting TXNIP, interfering with METTL3 to inhibit the proliferation, migration and invasion of PCa cells, promote apoptosis, and inhibit tumor growth in nude mice.

Optimization of ultrasound-assisted aqueous two-phase extraction of polysaccharides from seabuckthorn fruits using response methodology, physicochemical characterization and bioactivities.

BACKGROUND: Seabuckthorn fruits contains many active subtances, among them, the seabuckthorn polysaccharide is one of the main active ingredients, and exhibits diverse bioactivities. The extraction of polysaccharides from seabuckthorn fruits is the most important step for their wide applications. Ultrasound-assisted aqueous two-phase extraction (UA-ATPE) is a promising green method for extracting polysaccharides. Additionally, physicochemical characterization and antioxidant activities can evaluate the potential functions and applications in the food and medicine industries. RESULTS: Based on the single-factor experiments, 20.70% (w/w) ammonium sulfate ((NH4 )2 SO4 ) and 27.56% (w/w) ethanol were determined as the suitable composition for aqueous two-phase. The optimum conditions of UA-ATPE obtained by response surface methodology were as follows: ultrasonic power (390 W), extraction time (41 min), liquid-to-material ratio (72: 1 mL/g), and the total yield of the polysaccharides reached 34.14 ± 0.10%, The molecular weights of the purified upper-phase seabuckthorn polysaccharide (PUSP) and the purified lower-phase seabuckthorn polysaccharide (PLSP) were 65 525 and 26 776 Da, respectively. PUSP and PLSP contained the same six monosaccharides (galacturonic acid, rhamnose, xylose, mannose, glucose and galactose), but with different molar ratios. Furthermore, PUSP and PLSP displayed certain viscoelastic property, had no triple helical structure, possessed different thermal stability, surface morphology and conformation in aqueous solution. PUSP and PLSP displayed strong antioxidant properties by the assays of scavenging ability of ABTS+ ·, the protection of DNA damage and erythrocyte hemolysis. CONCLUSION: UA-ATPE significantly increased the yield of seabuckthorn polysaccharides. PUSP and PLSP were different in many aspects, such as molar ratio, surface shape and antioxidant activities. Seabuckthornpolysaccharides possess great potential in medicine and functional foods. © 2022 Society of Chemical Industry.

HDAC5, negatively regulated by miR-148a-3p, promotes colon cancer cell migration.

Histone deacetylases (HDACs) are involved in many processes including tumor cell growth and proliferation and regulation of gene expression. To clarify the role of class IIa HDACs in the metastasis of colon adenocarcinoma, we used the class IIa HDAC inhibitor TMP269 and found that it effectively inhibited the migration ability of colon adenocarcinoma cells. Next, we silenced the member of class IIa HDACs and confirmed that the migratory ability of colon adenocarcinoma cells was significantly inhibited by silencing HDAC5 or HDAC7. HDAC5 plays a variety of roles in human cancers. Here, we examined the role of HDAC5 in colon adenocarcinoma. The results indicated that HDAC5 was highly expressed in tumor tissues and negatively correlated with the expression of miR-148a-3p. Moreover, the expression of HDAC5 was correlated with tumor progression. HDAC5 markedly increased the invasion and migration of cancer cells in vitro, an effect that could be inhibited by overexpression of miR-148a-3p. Following an intraperitoneal injection of colon adenocarcinoma cells in athymic nude mice, HDAC5 promoted tumor implant. Together, these findings showed that HDAC5 overexpression in colon adenocarcinoma is consistent with tumor progression and tumor cell migration and the impact of HDAC5 overexpression is reduced by miR-148a-3p.

Interaction between m6A and ncRNAs and Its Association with Diseases.

Noncoding RNAs (ncRNA) are a kind of endogenous RNA that regulate many vital bioprocesses with limited ability to encode polypeptides. Most of them are involved in transcriptional and posttranscriptional regulations, thus showing some biological effects. N6-methyladenosine (m6A) RNA modification is a reversible modification that adjusts RNA's functions and stability. The enzymes that regulate m6A can be divided into "writers," "readers," and "erasers." Mechanically, m6A modification of microRNA is mainly identified by DGVR8, participating in the processing of primary micro-RNAs, while m6A modification on long noncoding RNA (lnc-RNA) can change its spatial structure and stability to regulate its RNA- or protein-binding ability. The m6A-modified lnc-RNA and circular RNA can act as competing endogenous RNAs, sponge downstream miRNA. Moreover, ncRNA can also regulate m6A level of downstream molecules. Here, we elaborate on recent advances about pathways and underlying molecular mechanisms of how the interaction between m6A and ncRNA is involved in the occurrence and development of various diseases, especially cancer.

Characterizing the particle number emissions of light-duty gasoline vehicles under different engine technologies and driving conditions.

Vehicle particle number (PN) emissions have attracted increasing public attention due to their severe influence on human health. In this study, we selected 35 light-duty gasoline vehicles (LDGVs) with gasoline direct injection (GDI) and multi-port fuel injection (MPFI) engines to elucidate the main factors influencing PN emissions. Via real driving emission (RDE) and chassis dynamometer tests, we quantified the impact of engine technology, emission standards, engine-start conditions and engine load on vehicle PN emissions. The RDE test results indicated that GDI vehicles generated higher PN emissions than those of MPFI vehicles under hot-running conditions. MPFI vehicle PN emissions were greatly affected by rapidly changing driving conditions, especially vehicles equipped with automatic start-stop systems. In regard to China 6 GDI vehicles equipped with a gasoline particle filter (GPF), their PN emissions were usually low, and peak PN emissions could mainly be attributed to GPF regeneration. Engine manufacturers should optimize GPF regeneration conditions to further reduce particulate emissions. Furthermore, the analysis results of PN emissions for different road types indicated that PN emissions were related to vehicle driving conditions. The vehicle specific power (VSP) could be used as an important explanatory variable to characterize the PN emission rate when distinguishing different engine technologies and emission standards. A real-world LDGV VSP-based PN emission rate was suggested based on the RDE test dataset. The VSP-based emission rate could be considered to more accurately quantify vehicle PN emissions and support the formulation of urban vehicle particle emission control policies.

Chemical composition and sources of amines in PM2.5 in an urban site of PRD, China.

Atmospheric amines have attracted increasing attention due to their significant impact on new particle formation, particle hygroscopicity and particle optical properties. In this study, four low-molecule-weight amines were detected from PM2.5 filter samples collected at an urban site of Pearl River Delta (PRD) region of China in 2018 autumn. During the campaign, the mass concentrations of ambient particulate methylamine (MA, CH3NH2), dimethylamine (DMA, (CH3)2NH), trimethylamine (TMA, (CH3)3N), and diethylamine (DEA, (C2H5)2NH) were quantified at daily or 12-h resolution using an optimized Ion Chromatograph (IC) method. The total measured amine concentration was 297 ± 209 ng/m3, which can account for 0.76 ± 0.33% of PM2.5 mass concentrations. The particulate amines in PRD urban area were dominated by MA (243 ± 179 ng/m3), accounting for over 80% of total amines, then followed by DMA (49 ± 30 ng/m3, 16.5%), TMA (4 ± 2 ng/m3) and DEA (1 ± 1 ng/m3). Based on the correlation analysis, MA and DMA mainly presented as nitrate and sulfate salts. We speculate the amines tend to react with gas-phase HNO3 or particle-phase nitrate to form particulate amine salts via local process in Guangzhou. As the relative humidity (RH) increased, enhanced partitioning of amine towards the particle phase was observed. Using approach of multiple linear regression, 71% of the particulate amines in PRD urban site could be explained by acid-base process and the rest by primary emissions from combustion sources (29%).

Pain modulation induced by electronic wrist-ankle acupuncture: A functional near-infrared spectroscopy study.

BACKGROUND: As a new technology, electronic wrist-ankle acupuncture (E-WAA) combines the advantages of wrist-ankle acupuncture and transcutaneous electrical nerve stimulation, but the analgesic effect and mechanism need to be clarified. The purpose of this study was to identify the pain modulation caused by E-WAA by evaluating the response of the prefrontal cortex (PFC) from the perspective of neurophysiology. METHODS: Fifty male volunteers (age 25.00 ± 1.05 years) with trapezius myofascial pain syndrome were randomly allocated into intervention group (E-WAA treatment) or sham control group at a 1:1 ratio. An outcome evaluation system was used to induce tenderness on the Jianjing point and record the pain value. A multichannel functional near-infrared spectroscope was used to detect the PFC activation during tenderness before and after treatment to demonstrate the neuromodulation mechanism. A general linear model and t-test (p < 0.05) were used to analyze the difference in the oxyhemoglobin (HbO) concentration and pain value. RESULTS: In the intervention group, the pain value of volunteers decreased significantly (p = 0.017) after E-WAA treatment, whereas there was no statistical difference (p = 0.082) in the sham group. Before treatment, the frontopolar (FP) and dorsolateral prefrontal cortex (DLPFC) were the activation areas of the PFC. The E-WAA treatment then suppressed the activation of the two areas. The HbO concentration of the FP and DLPFC changed from a sharp rise during tenderness to not changing with tenderness stimulation. CONCLUSION: The results demonstrated that the E-WAA have a great analgesic effect. The FP and DLPFC were relative to the analgesia neuromodulation induced by the E-WAA.

High Gaseous Nitrous Acid (HONO) Emissions from Light-Duty Diesel Vehicles.

Nitrous acid (HONO) plays an important role in the budget of hydroxyl radical (•OH) in the atmosphere. Vehicular emissions are a crucial primary source of atmospheric HONO, yet remain poorly investigated, especially for diesel trucks. In this study, we developed a novel portable online vehicular HONO exhaust measurement system featuring an innovative dilution technique. Using this system coupled with a chassis dynamometer, we for the first time investigated the HONO emission characteristics of 17 light-duty diesel trucks (LDDTs) and 16 light-duty gasoline vehicles in China. Emissions of HONO from LDDTs were found to be significantly higher than previous studies and gasoline vehicles tested in this study. The HONO emission factors of LDDTs decrease significantly with stringent control standards: 1.85 ± 1.17, 0.59 ± 0.25, and 0.15 ± 0.14 g/kg for China III, China IV, and China V, respectively. In addition, we found poor correlations between HONO and NOx emissions, which indicate that using the ratio of HONO to NOx emissions to infer HONO emissions might lead to high uncertainty of HONO source budget in previous studies. Lastly, the HONO emissions are found to be influenced by driving conditions, highlighting the importance of conducting on-road measurements of HONO emissions under real-world driving conditions. More direct measurements of the HONO emissions are needed to improve the understanding of the HONO emissions from mobile and other primary sources.

Prediction of lymph node metastasis in oral tongue squamous cell carcinoma using the neutrophil-to-lymphocyte ratio and platelet-to-neutrophil ratio.

BACKGROUND: Lymph node metastasis in a variety of tumors is associated with systemic inflammatory markers. However, this association has not been reported in oral tongue squamous cell carcinoma (OTSCC). This study aimed to investigate how the preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-neutrophil ratio (PNR) in OTSCC patients correlated with the occurrence of OTSCC and lymph node metastasis. METHODS: The data of 73 patients with primary OTSCC who underwent surgical resection were retrospectively analyzed. Patients with other malignant tumors, patients who had received radiotherapy or chemotherapy before surgery, and patients with active inflammation were excluded. The enrolled patients were divided into groups N0 (no early-stage lymph node metastasis) and N1 (early-stage lymph node metastasis). Venous blood samples were collected before surgery and at the third week after surgery and subjected to complete blood counting in a blood analyzer. Eighty-seven healthy people were included as a control group. In addition, the NLR and PNR in OTSCC patients were compared with those in the controls, and the postoperative NLR and PNR of group N0 were compared with those of group N1 . RESULTS: The NLR was significantly higher in the OTSCC patients than the controls (p < 0.05). The area under the receiver operating characteristic curve was 0.595. Further comparison of the NLR and PLR between group N0 and group N1 showed that when NLR was ≤1.622, and the probability of early-stage lymph node metastasis in OTSCC patients was 73.3%, and when PNR was >60.889, the probability was 86.7%. In re-examination 3 weeks postoperatively, the NLR and PNR were not significantly different between groups. CONCLUSION: The NLR has certain reference value for the diagnosis of OTSCC. The preoperative NLR and PNR can be used to predict early-stage lymph node metastasis in patients with histopathologically confirmed OTSCC.

Radical-Mediated Strategies for the Functionalization of Alkenes with Diazo Compounds.

One of the most common reactions of diazo compounds with alkenes is cyclopropanation, which occurs through metal carbene or free carbene intermediates. Alternative functionalization of alkenes with diazo compounds is limited, and a methodology for the addition of the elements of Z-CHR2 (with Z = H or heteroatom, and CHR2 originates from N2═CR2) across a carbon-carbon double bond has not been reported. Here we report a novel reaction of diazo compounds utilizing a radical-mediated addition strategy to achieve difunctionalization of diverse alkenes. Diazo compounds are transformed to carbon radicals with a photocatalyst or an iron catalyst through PCET processes. The carbon radical selectively adds to diverse alkenes, delivering new carbon radical species, and then forms products through hydroalkylation by thiol-assisted hydrogen atom transfer (HAT), or forms azidoalkylation products through an iron catalytic cycle. These two processes are highly complementary, proceed under mild reaction conditions, and show high functional group tolerance. Furthermore, both transformations are successfully performed on a gram-scale, and diverse γ-amino esters, γ-amino alcohols, and complex spirolactams are easily prepared with commercially available reagents. Mechanistic studies reveal the plausible pathways that link the two processes and explain the unique advantages of each.

Genetic mutational analysis of pediatric acute lymphoblastic leukemia from a single center in China using exon sequencing.

BACKGROUND: Acute lymphoblastic leukemia (ALL), the most common childhood malignancy, is characterized by recurring structural chromosomal alterations and genetic alterations, whose detection is critical in diagnosis, risk stratification and prognostication. However, the genetic mechanisms that give rise to ALL remain poorly understood. METHODS: Using next-generation sequencing (NGS) in matched germline and tumor samples from 140 pediatric Chinese patients with ALL, we landscaped the gene mutations and estimated the mutation frequencies in this disease. RESULTS: Our results showed that the top driver oncogenes having a mutation prevalence over 5% in childhood ALL included KRAS (8.76%), NRAS (6.4%), FLT3 (5.7%) and KMT2D (5.0%). While the most frequently mutated genes were KRAS, NRAS and FLT3 in B cell ALL (B-ALL), the most common mutations were enriched in NOTCH1 (23.1%), FBXW7 (23.1%) and PHF6 (11.5%) in T cell ALL (T-ALL). These mutant genes are involved in key molecular processes, including the Ras pathway, the Notch pathway, epigenetic modification, and cell-cycle regulation. Strikingly, more than 50% of mutations occurred in the high-hyperdiploid (HeH) ALL existed in Ras pathway, especially FLT3 (20%). We also found that the epigenetic regulator gene KMT2D, which is frequently mutated in ALL, may be involved in driving leukemia transformation, as evidenced by an in vitro functional assay. CONCLUSION: Overall, this study provides further insights into the genetic basis of ALL and shows that Ras mutations are predominant in childhood ALL, especially in the high-hyperdiploid subtype in our research.

Insight into the Variability of the Nitrogen Isotope Composition of Vehicular NOx in China.

Nitrogen isotope (δ15N) monitoring is a potentially powerful tool in tracing atmospheric nitrogen oxides (NOx); however, the isotopic fingerprint of vehicle exhaust remains poorly interpreted. This deficiency limits our understanding of the origin of atmospheric haze pollution, especially in China. In this study, we systemically explored the δ15N-NOx fingerprints of various vehicle exhausts (n = 137) in China. The δ15N-NOx values of vehicle exhausts ranged from -18.8‰ to +6.4‰, presenting a significant correlation with NOx concentrations (p < 0.01). The highest δ15N-NOx values were observed for liquefied petroleum gas vehicles (-0.1 ± 1.8‰), followed by gasoline vehicles (-7.0 ± 4.8‰) and diesel vehicles (-12.7 ± 3.4‰), all of which displayed a rising trend as emissions standards were continuously updated. The δ15N-NOx values under working conditions followed the trend warm start (-5.9 ± 5.0‰) > driving (-7.3 ± 5.9‰) > cold start (-9.2 ± 2.7‰). By establishing a suitable model for assessing representative δ15N-NOx values, the δ15N-NOx values of various vehicles, including different fuel types with different emission standards, were evaluated. A model of δ15N-NOx associated with motor vehicle data was developed, which estimated the national δ15N-NOx value of vehicle emissions to be -12.6 ± 2.2‰, but there was considerable variation among different target areas in China.

A rhodium-catalysed three-component reaction to access C1-substituted tetrahydroisoquinolines.

A rhodium-catalyzed three-component reaction of diazo compounds, anilines and C,N-cyclic azomethine imines via trapping of transient ammonium ylides was developed. This reaction provided a simple and convenient approach for the synthesis of pharmaceutically intriguing tetrahydroisoquinoline derivatives in moderate to good yields (36-85%) with good diastereoselectivities (up to 95 : 5 dr) under mild reaction conditions.

Characteristics of size distributions and sources of water-soluble ions in Lhasa during monsoon and non-monsoon seasons.

To understand the physical and chemical characteristics, particle size distribution and sources of size-separated aerosols in Lhasa, which is located on the Tibetan Plateau (TP), six sizes of aerosol samples were collected in Lhasa in 2014. Ca2+, NH4+, NO3-, SO42- and Cl- were the dominant ions. The ratio of cation equivalents (CE) to anion equivalents (AE) for each particle size segment indicated that the atmospheric aerosols in Lhasa were alkaline. SO42- and NO3- could be neutralized by Ca2+, but could not be neutralized by NH4+, according to the [NH4+]/[NO3- + SO42-] and [Ca2+]/[NO3- + SO42-] ratios. Mobile sources were dominant in PM0.95-1.5, PM1.5-3 and PM3-7.2, while stationary sources were dominant in the other three size fractions according to the [NO3-]/[SO42-] ratios. The particle size distribution of all water-soluble ions during monsoon and non-monsoon periods was characterized by a bimodal distribution due to the different sources and formation mechanisms, and it was revealed that different ions had different sources in different seasons and different particle size segments by combining particle size distribution with correlation analysis. Source analysis of aerosols in Lhasa was performed using the Principal component analysis (PCA) for the first time, which revealed that combustion sources, motor vehicle exhaust, photochemical reaction sources and various types of dust were the main sources of Lhasa aerosols. Furthermore, Lhasa's air quality was also affected by long-distance transmission, expressed as pollutants from South Asia and West Asia, which were transmitted to Lhasa according to backward trajectory analysis.

[Application of quality by design in granulation process for ginkgo leaf tablet (⠣)： influence and control of raw materials' quality variation].

Raw materials' quality variation could affect the quality consistency of product and the clinical efficacy. In this paper, the high shear wet granulation (HSWG) process of the ginkgo leaf tablet was taken as the research object. Ginkgo biloba extracts and excipients microcrystalline cellulose collected from various sources and batches were used to simulate raw materials' quality variation. Real-time torque was recorded to analyze the viscosity of the wetting mass, and then by combining with physical fingerprint, the impact of physical quality variation of powders on granule properties could be investigated. Based on regime map thesis, whether the granules' nucleation mode was in mechanical dispersion regime was determined by calculating dimensionless parameters, which would lead to the unstable output in considerations of granule yield ratio and particle size distribution (PSD) curve. The orthogonal partial least square (OPLS) model was adopted to build the relationship between the micromeritic properties and the mediangranule size (D50) of Ginkgo biloba granules and then the critical material attributes (CMAs) were screened by variable importance in the projection (VIP) indexes. The results demonstrated that the properties of powders including hygroscopicity, angle of repose, Hausner ratio, Carr index, D10 and loss on drying affected the granule size. Besides, Ginkgo biloba granules were compressed into tablets. In view of tensile strength analysis, the raw materials' quality variation did not result in decrease of tensile strength of the ginkgo leaf tablets. The design space of critical quality attributes (CQAs) and the process design space which could cope with raw materials' quality variation were proved to be robust..