Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with antiviral and anti-inflammatory effects. Here, an integrative pharmacological strategy was applied to identify the antiviral and anti-inflammatory bioactive compounds from Q-14. Overall, a total of 343 chemical compounds were initially characterized, and 60 prototype compounds in Q-14 were subsequently traced in plasma using ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Among the 60 compounds, six compounds (magnolol, glycyrrhisoflavone, licoisoflavone A, emodin, echinatin, and quercetin) were identified showing a dose-dependent inhibition effect on the SARS-CoV-2 infection, including two inhibitors (echinatin and quercetin) of the main protease (Mpro), as well as two inhibitors (glycyrrhisoflavone and licoisoflavone A) of the RNA-dependent RNA polymerase (RdRp). Meanwhile, three anti-inflammatory components, including licochalcone B, echinatin, and glycyrrhisoflavone, were identified in a SARS-CoV-2-infected inflammatory cell model. In addition, glycyrrhisoflavone and licoisoflavone A also displayed strong inhibitory activities against cAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4). Crystal structures of PDE4 in complex with glycyrrhisoflavone or licoisoflavone A were determined at resolutions of 1.54 Å and 1.65 Å, respectively, and both compounds bind in the active site of PDE4 with similar interactions. These findings will greatly stimulate the study of TCMT-NDRD against COVID-19.

Coupling capillary electrophoresis with mass spectrometry for the analysis of oxidized phospholipids in human high-density lipoproteins.

The oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (ox-PAPC) products in human high-density lipoproteins (HDLs) were investigated by low-flow capillary electrophoresis-mass spectrometry (low-flow CE-MS). To accelerate the optimization, native PAPC (n-PAPC) standard was first analyzed by a commercial CE instrument with a photodiode array detector. The optimal separation buffer contained 60% (v/v) acetonitrile, 40% (v/v) methanol, 20 mM ammonium acetate, 0.5% (v/v) formic acid, and 0.1% (v/v) water. The selected separation voltage and capillary temperature were 20 kV and 23°C. The optimal CE separation buffer was then used for the low-flow CE-MS analysis. The selected MS conditions contained heated capillary temperature (250°C), capillary voltage (10 V), and injection time (1 s). No sheath gas was used for MS. The linear range for n-PAPC was 2.5-100.0 µg/mL. The coefficient of determination (R2 ) was 0.9918. The concentration limit of detection was 1.52 µg/mL, and the concentration limit of quantitation was 4.60 µg/mL. The optimal low-flow CE-MS method showed good repeatability and sensitivity. The ox-PAPC products in human HDLs were determined based on the in vitro ox-PAPC products of n-PAPC standard. Twenty-one ox-PAPC products have been analyzed in human HDLs. Uremic patients showed significantly higher levels of 15 ox-PAPC products than healthy subjects.

Function and prognostic value of N6-methyladenosine-modified RNAs in lung adenocarcinoma.

BACKGROUND: Aberrant regulation of N6-methyladenosine (m6A) modification is reportedly vital for cancer progression, including lung adenocarcinoma (LUAD). However, current studies mainly focus on the function and mechanism of m6A-modified regulators, such as m6A writers (METTL3 and METTL14), erasers (ALKBH5 and FTO), and readers (YTHDF1 and YTHDF2). The landscape, function, and prognostic value of RNAs by m6A-modified have not been fully clarified until now. METHODS: The present study identified 57 RNAs with significantly different m6A-methylation levels in LUAD tissues using epitranscriptomic microarray analysis. RESULTS: Among the 57 RNAs, 28 and 29 were hypermethylated and hypomethylated, respectively. The m6A-methylation level increased in mRNA and long non-coding RNA (lncRNA) but decreased in small non-coding RNA. After pathway enrichment analyses, RNA metabolism-associated pathways such as nucleotide metabolism were enriched in total and m6A-hypermethylated mRNAs. Furthermore, lncRNA networks were built using miRNet tools, revealing that the immune system was closed to m6A-modified lncRNAs. To evaluate the prognostic value of mRNAs with hypermethylated or hypomethylated, we calculated the risk scores, and constructed signatures to predict the survival time of patients with LUAD using multicox regression analysis. In addition, hypermethylated-mRNA and hypomethylated-mRNA signatures were established. The survival plotter showed that these two signatures effectively predicted the survival time of patients with LUAD. CONCLUSIONS: The results of the present study support the evidence for understanding the expression, function, and potential prognostic values of m6A-modified RNAs, possibly promoting effective therapies for patients with LUAD.

Noteworthy perspectives on microglia in neuropsychiatric disorders.

Microglia are so versatile that they not only provide immune surveillance for central nervous system, but participate in neural circuitry development, brain blood vessels formation, blood-brain barrier architecture, and intriguingly, the regulation of emotions and behaviors. Microglia have a profound impact on neuronal survival, brain wiring and synaptic plasticity. As professional phagocytic cells in the brain, they remove dead cell debris and neurotoxic agents via an elaborate mechanism. The functional profile of microglia varies considerately depending on age, gender, disease context and other internal or external environmental factors. Numerous studies have demonstrated a pivotal involvement of microglia in neuropsychiatric disorders, including negative affection, social deficit, compulsive behavior, fear memory, pain and other symptoms associated with major depression disorder, anxiety disorder, autism spectrum disorder and schizophrenia. In this review, we summarized the latest discoveries regarding microglial ontogeny, cell subtypes or state spectrum, biological functions and mechanistic underpinnings of emotional and behavioral disorders. Furthermore, we highlight the potential of microglia-targeted therapies of neuropsychiatric disorders, and propose outstanding questions to be addressed in future research of human microglia.

A reusable fiber-embedded microfluidic chip for rapid and sensitive on-site detection of kanamycin residues in water environments.

The overuse and abuse of antibiotics have led to increased pollution in water environments. Thus, it is crucial to develop a rapid, high-frequency, and cost-effective method for on-site detection of antibiotics. In this regard, a reusable fiber-embedded microfluidic chip was constructed by combining a microfluidic chip with a functionalized fiber bioprobe that served as both a biorecognition element and an optical transducer. The fiber-embedded microfluidic chip enabled the quantitative detection of kanamycin (KANA) by integrating a portable all-fiber evanescent wave fluorescence detection device. Under optimized conditions, quantitative KANA detection was achieved with a detection limit of 0.03 µg L-1 and a linear detection range of 0.21-10.3 µg L-1. The accurate detection of KANA in various water samples can be completed within 25 min without pretreatment. The functionalized fiber-embedded microfluidic chip could be reused more than 200 times without significant performance loss. To demonstrate its suitability for practical applications, the fiber-embedded microfluidic chip was used to investigate KANA residues in surface waters obtained from the Qinghe River in Beijing, China. The results were compared with those of a traditional enzyme-linked immunosorbent assay, which showed a high correlation. Compared to conventional optical microfluidic chips, the proposed fiber-embedded microfluidic chip has several advantages, including its ease of use, miniaturization, cost-effectiveness, reusability, and high flexibility. It is an ideal alternative for rapid, sensitive on-site detection of antibiotics and other trace substances in environmental, food, and medical fields.

Metalloborospherenes with a Stabilized Classical Fullerene-like Borospherene B40 Act as Nonlinear Optical Switches, Electron Reservoirs, Molecular Capacitors, and Molecular Reactors.

Using a new method of η5-Li and η6-Mg atoms capping the faces of the classical fullerene-like borospherene Td B40, we theoretically predict an exohedral metalloborospherene Td Mg10Li12&B40 molecule. Remarkably, a newfangled endoexo cage isomerism is proposed. Further, embedding Mg atoms in the Td B40 cage forms endohedral derivatives. Due to the intramolecular pull-push electron transfer relay, these obtained molecules possess unequal multilayered and alternant spherical charge distribution. The outer is an excess electron layer, bringing a molecular nonlinear switch character and an electron reservoir behavior with strong electron-donating and -accepting abilities. The middle (Mg2+)10(Li+)12 and the outer layers together constitute an electric double layer, presenting the behavior of a molecular capacitor where the electronic charge-discharge process occurs in the outer excess electron layer. The inner part is an empty cage B4026- with a strong negative electric field. The valence electrons of the embedded Mg atoms are transformed into new excess electrons and added in the outer excess electron layer, also exhibiting the charging behavior of the molecular capacitor. Considering the chemical reaction in the inner cage, the embedded Mg atom is ionized, forming an Mg2+ cation and 2e under the strong negative electric field; meanwhile, 2e is powerfully pushed into the outer excess electron layer. This chemical process shows a generalized Coulomb explosion, and thus the exohedral metalloborospherene molecules with cage B4026- may act as molecular reactors. The new species mark the genesis of classical fullerene-like borospherene chemistry and stimulate their applications in molecular nonlinear optical and nanoelectronics.

Discovery of novel cGAS inhibitors based on natural flavonoids.

Cyclic GMP-AMP synthase (cGAS) plays an important role in the inflammatory response. It has been reported that aberrant activation of cGAS is associated with a variety of immune-mediated inflammatory disorders. The development of small molecule inhibitors of cGAS has been considered as a promising therapeutic strategy for the diseases. Flavonoids, a typical class of natural products, are known for their anti-inflammatory activities. Although cGAS is closely associated with inflammation, the potential effects of natural flavonoid compounds on cGAS have been rarely studied. Therefore, we screened an in-house natural flavonoid library by pyrophosphatase (PPiase) coupling assay and identified novel cGAS inhibitors baicalein and baicalin. Subsequently, crystal structures of the two natural flavonoids in complex with human cGAS were determined, which provide mechanistic insight into the anti-inflammatory activities of baicalein and baicalin at the molecular level. After that, a virtual screening based on the crystal structures of baicalein and baicalin in complex with human cGAS was performed. As a result, compound C20 was identified to inhibit both human and mouse cGAS with IC50 values of 2.28 and 1.44 µM, respectively, and its detailed interactions with human cGAS were further revealed by the X-ray crystal structure determination. These results demonstrate the potential of natural products used as hits in drug discovery and provide valuable hints for further development of cGAS inhibitors.

Exploring the training of chinese medical staff oriented to the need for clinical drug information services: from the perspective of drug information patients obtained and need.

BACKGROUND: There are some gaps between the training of drug information service competencies for medical staff and drug information patients need in China. OBJECTIVE: To investigate drug information patients obtained and need for further providing directions for the training of drug information service competencies among medical staff in China from patients' perspectives. METHODS: A face-to-face nationwide survey was conducted using a stratified sampling method. Data were analyzed descriptively using frequencies, percentages and mean. Several subgroup analyses using Chi-square tests were conducted to identify patients' need for drug information in China. RESULTS: A total of 1994 questionnaires from medical institutions in China were returned. Most of the drug information obtained by patients came from physicians, and different types of drug information were important to patients. Additionally, patients had different needs for drug information due to age, gender, diagnosis and treatment status, and education level. CONCLUSIONS: The training of medical staff needs to increase the presence of nurses and pharmacists in drug information services, enhance the awareness of "patient-centered" services, and improve the ability to provide information services specific to the characteristics of patients.

Structural Insights into the Binding of Red Fluorescent Protein mCherry-Specific Nanobodies.

Red fluorescent proteins (RFPs) have broad applications in life science research, and the manipulation of RFPs using nanobodies can expand their potential uses. However, the structural information available for nanobodies that bind with RFPs is still insufficient. In this study, we cloned, expressed, purified, and crystallized complexes formed by mCherry with LaM1, LaM3, and LaM8. Then, we analyzed the biochemical properties of the complexes using mass spectrometry (MS), fluorescence-detected size exclusion chromatography (FSEC), isothermal titration calorimetry (ITC), and bio-layer interferometry (BLI) technology. We determined the crystal structure of mCherry-LaM1, mCherry-LaM3, and mCherry-LaM8, with resolutions of 2.05 Å, 3.29 Å, and 1.31 Å, respectively. In this study, we systematically compared various parameters of several LaM series nanobodies, including LaM1, LaM3, and LaM8, with previously reported data on LaM2, LaM4, and LaM6, specifically examining their structural information. After designing multivalent tandem LaM1-LaM8 and LaM8-LaM4 nanobodies based on structural information, we characterized their properties, revealing their higher affinity and specificity to mCherry. Our research provides novel structural insights that could aid in understanding nanobodies targeting a specific target protein. This could provide a starting point for developing enhanced mCherry manipulation tools.

Continental-scale niche differentiation of dominant topsoil archaea in drylands.

Archaea represent a diverse group of microorganisms often associated with extreme environments. However, an integrated understanding of biogeographical patterns of the specialist Haloarchaea and the potential generalist ammonia-oxidizing archaea (AOA) across large-scale environmental gradients remains limited. We hypothesize that niche differentiation determines their distinct distributions along environmental gradients. To test the hypothesis, we use a continental-scale research network including 173 dryland sites across northern China. Our results demonstrate that Haloarchaea and AOA dominate topsoil archaeal communities. As hypothesized, Haloarchaea and AOA show strong niche differentiation associated with two ecosystem types mainly found in China's drylands (i.e. deserts vs. grasslands), and they differ in the degree of habitat specialization. The relative abundance and richness of Haloarchaea are higher in deserts due to specialization to relatively high soil salinity and extreme climates, while those of AOA are greater in grassland soils. Our results further indicate a divergence in ecological processes underlying the segregated distributions of Haloarchaea and AOA. Haloarchaea are governed primarily by environmental-based processes while the more generalist AOA are assembled mostly via spatial-based processes. Our findings add to existing knowledge of large-scale biogeography of topsoil archaea, advancing our predictive understanding on changes in topsoil archaeal communities in a drier world.

Allometric releases of nitrogen and phosphorus from sediments mediated by bacteria determines water eutrophication in coastal river basins of Bohai Bay.

Although the Chinese government has conducted much work in recent years to reduce land-based pollutant discharge, eutrophication continues to occur frequently in many rivers, estuaries, and coastal waters. This may indicate that sediment is a major source rather than a sink for nitrogen (N) and phosphorus (P). To clarify the endogenous mechanisms of eutrophication in coastal river basins, the eutrophication status, physicochemical properties, and bacterial parameters of overlying waters and sediments in the catchment (CA), estuarine (EA), and offshore (OA) areas in the Duliujian River Basin of Bohai Bay were investigated. The results showed that the eutrophication index (EI) of CA, EA, and OA were 62.71, 57.86, and 36.51, respectively. The EI was more sensitive to increases in P (slope = 3.887) than to increases in N (slope = 0.734) of the overlying water, indicating that P is the main factor driving eutrophication in the coastal river basin. However, a nonlinear relationship was found between P in sediments and overlying waters, suggesting that bacterial mediation may occur during P release. As speculated in this study, P in the overlying water increased more quickly than N with increasing bacterial diversity and metabolic abundance, indicating that the allometric release of N and P mediated by bacteria increases the risk of eutrophication. Redundancy analysis showed that organic matter and total N in sediment have positive effects on bacterial communities, which explains 21.8% and 23.7% variation in bacterial diversity, and explains 31.3% and 7.1% variation in bacterial metabolism. This also suggests that the accumulation of N in the sediment promotes the release of P and further aggravates the eutrophication of water. Therefore, simultaneous control of N and P is necessary to control water eutrophication in coastal river basins.

EZH2-CCF-cGAS Axis Promotes Breast Cancer Metastasis.

Cytoplasmic chromatin fragments (CCF) are recognized by the cytoplasmic DNA sensor cyclic GMP-AMP synthase (cGAS), which activates the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) pathway and promotes the production of inflammatory factors and breast cancer metastasis. However, the mechanisms by which CCF are formed in tumor cells and CCF activation cGAS promotes breast cancer metastasis remain unclear. Here, we report that the enhancer of zeste homolog 2 (EZH2) can promote the formation of CCF and activate the cGAS-STING pathway to promote breast cancer metastasis. Further research found that the EZH2-mediated CCF formation depended on high mobility group A1 (HMGA1), while the stability of EZH2 required ubiquitin-specific peptidase 7 (USP7), indicating that the EZH2-HMGA1-USP7 complex regulated CCF formation. Moreover, EZH2 can activate cGAS through CCF, requiring USP7 to deubiquitinate cGAS and stabilize cGAS. In vivo experimental results showed that EZH2 could promote breast cancer metastasis through CCF. Our findings highlight a new target for breast cancer metastasis. Targeting the EZH2-CCF-cGAS axis may be a potential therapeutic strategy for inhibiting breast cancer metastasis.

Tailored design of a novel composite foam of sodium alginate used for fluoride ion removal.

Fluoride is an essential micronutrient for humans. Nonetheless, when the amount of fluoride ion is greater than required, it will cause skeletal fluorosis and dental fluorosis to threaten human health. In this paper, a series of sodium alginate (SA)-based foam materials are prepared by freeze-drying technique and anchored with the nano-activated alumina (nAl2O3) in the SA to obtain a novel adsorbent of SA-nAl2O3 foam used for fluoride ions removal. The SA-nAl2O3 foam morphology was further explored and confirmed that nAl2O3 existed stably in the SA. The adsorption results showed that the maximal fluoride ion adsorption capacity was 5.09 mg/g with 20 mg/L fluorine solutions at a pH of 3. The adsorption isotherm fitted adequately to the Langmuir isotherm model, which demonstrated that the adsorption process is closer to monolayer adsorption. The adsorption kinetics behavior of SA-nAl2O3 foam was described by a pseudo-second-order model, and the adsorption process occurred by chemisorption. Adsorption thermodynamics analysis emphasized that the adsorption process was spontaneous and endothermic. The main mechanism of the foam is ion exchange. The SA-nAl2O3 foam exhibited excellent regeneration performance and stability after three cycles.

Fluorescence enhancement of CdSe/ZnS quantum dots induced by mercury ions and its applications to the on-site sensitive detection of mercury ions.

The significant fluorescence enhancement of CdSe/ZnS quantum dots (QDs) induced by Hg2+ was observed for the first time based on a CdSe/ZnS QD-modified fiber nanoprobe. The fluorescence enhancement mechanism contributed to the Zn-to-Hg cation exchange in the ZnS shell, which allowed to form a HgxZn1-xS/CdSe heterojunction and increase the separation of electrons and holes and reduce the recombination rate. High concentrations of Hg2+ accelerated the generation of the fluorescence signal and lead to higher fluorescence intensity. The maximum fluorescence intensity increased more than eight times when Hg2+ concentration was 1 µM. The characteristic time (θc), i.e., the rising time to achieve the maximum fluorescence intensity, was linearly dependent on  initial concentration of Hg2+ solution in accordance with our proposed theory. When the evanescent wave optofluidic fluorescence platform was used, the linear detection range and detection limit of Hg2+ were 5.0-1000 nM and 0.80 nM, respectively. The fiber nanoprobe can be applied to the rapid, sensitive, and accurate on-site detection of Hg2+ in real water samples without significant matrix effect. Our work paves a novel way to develop a simple and reliable nanoprobe for mercuric pollution control, and achieve the high quantum efficiency of QDs by limiting the diffusion of Hg2+ in the ZnS shell.

The efficacy of internet-based cognitive behavioural therapy for social anxiety disorder: A systematic review and meta-analysis.

Social anxiety disorder (SAD) is one of the most common lifelong anxiety disorders. Although cognitive behavioural therapy (CBT) has proven to be effective in treating people with SAD, it may not be available for a considerable proportion of patients. Internet-based CBT (ICBT) is more accessible than face-to-face treatment. This meta-analysis evaluated the efficacy of ICBT in patients with SAD. We searched five databases, PubMed, Cochrane Central Register of Controlled Trials, Health Management Information Consortium, Ovid MEDLINE and EMBASE, and identified 20 eligible randomized controlled trials published from inception to 25 July 2020, with the outcome data from 1,743 participants. The results indicated that ICBT had a significant positive effect on patients with SAD compared with the control groups (g = -0.55). A subgroup analysis revealed that ICBT and CBT had an equal effect on treating patients with SAD (g = -0.18). There was also no difference between ICBT and ICBT plus other therapies in the treatment of patients with SAD (g = -0.07). The effect size of ICBT on patients with SAD was maintained at the 6-month follow-up (g = -0.08) and at the 12-month follow-up (g = -0.17). The findings of this review demonstrated that ICBT can significantly reduce SAD symptoms and that ICBT and face-to-face CBT produce equivalent effects. The results of this meta-analysis contributed to the literature on ICBT for the treatment of patients with SAD, although numerous aspects of ICBT were identified for future investigations.

A novel circulating miRNA-based signature for the early diagnosis and prognosis prediction of non-small-cell lung cancer.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is a significant public health issue worldwide. The aim of our study was to develop a serum miRNA-based molecular signature for the early detection and prognosis prediction of NSCLC. METHODS: The significantly altered circulating miRNAs were profiled in GSE24709. The top ten upregulated miRNAs were miR-432, miR-942, miR-29c-5p, miR-601, miR-613, miR-520d-3p, miR-1261, miR-132-5p, miR-302b, and miR-154-5p, while the top ten downregulated miRNAs were miR-562, miR-18b, miR-9-3p, miR-154-3p, miR-20b, miR-18a, miR-487a, miR-20a, miR-103, and miR-144. Then, the top four upregulated serum miRNAs (miR-432, miR-942, miR-29c-5p, and miR-601) were validated by real-time quantitative PCR. The clinical significance of two candidate serum miRNAs, miR-942 and miR-601, was further explored. RESULTS: Our results showed that the expression levels of serum miR-942 and serum miR-601 were significantly upregulated in NSCLC. In addition, serum miR-942 and serum miR-601 showed better performance than CEA, CYFRA21-1, and SCCA for early diagnosis of NSCLC. Combining serum miR-942 and serum miR-601 enhanced the efficacy of detecting early-stage NSCLC. Moreover, high serum miR-942 and serum miR-601 were both associated with adverse clinical variables and poor survival. The NSCLC patients with simultaneously high serum miR-942 and serum miR-601 suffered worst clinical outcome, while those with simultaneously low serum miR-942 and serum miR-601 had most favorable outcome. The multivariate analysis showed that serum miR-942 and serum miR-601 were independent prognostic factors for NSCLC. CONCLUSIONS: Taken together, serum miR-942 and serum miR-601 might serve as a promising molecular signature for the early detection and prognosis prediction of NSCLC.

A composite of graphene oxide and iron oxide nanoparticles for targeted drug delivery of temozolomide.

A magnetic targeting nanoparticle based on graphene oxide-ferroferric oxide (GO-Fe3O4) was investigated as a potential drug delivery vehicle. The formation of GO/Fe3O4 hybrid material was confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy and transmission electron microscopy. The GO/Fe3O4 hybrid still shows a higher saturation magnetization of 58.42 emu/g after coating with graphene oxide. Drug loading and releasing experiments demonstrate the GO-Fe3O4 hybrid has a good loading capacity of (6.47±0.08) mg/mg for temozolomide and a satisfactory release under slightly acidic condition. The MTT assays of glioma C6 cells exhibits the GO-Fe3O4 hybrid does not display toxicity with the concentration ranged from 40 to 120 µg/mL in vitro, while the complex of temozolomide loaded on GO/Fe3O4 has a better inhibitory effect on the proliferation of rat glioma C6 cells. All results suggest the prepared GO/Fe3O4 has potential applications in targeted anticancer drug delivery.

Cause of PM2.5 pollution during the 2016-2017 heating season in Beijing, Tianjin, and Langfang, China.

To investigate the cause of fine particulate matter (particles with an aerodynamic diameter less than 2.5 µm, PM2.5) pollution in the heating season in the North China Plain (specifically Beijing, Tianjin, and Langfang), water-soluble ions and carbonaceous components in PM2.5 were simultaneously measured by online instruments with 1-hr resolution, from November 15, 2016 to March 15, 2017. The results showed extreme severity of PM2.5 pollution on a regional scale. Secondary inorganic ions (SNA, i.e., NO3-+SO42+ NH4+) dominated the water-soluble ions, accounting for 30%-40% of PM2.5, while the total carbon (TC, i.e., OC + EC) contributed to 26.5%-30.1% of PM2.5 in the three cities. SNA were mainly responsible for the increasing PM2.5 pollution compared with organic matter (OM). NO3- was the most abundant species among water-soluble ions, but SO42- played a much more important role in driving the elevated PM2.5 concentrations. The relative humidity (RH) and its precursor SO2 were the key factors affecting the formation of sulfate. Homogeneous reactions dominated the formation of nitrate which was mainly limited by HNO3 in ammonia-rich conditions. Secondary formation and regional transport from the heavily polluted region promoted the growth of PM2.5 concentrations in the formation stage of PM2.5 pollution in Beijing and Langfang. Regional transport or local emissions, along with secondary formation, made great contributions to the PM2.5 pollution in the evolution stage of PM2.5 pollution in Beijing and Langfang. The favourable meteorological conditions and regional transport from a relatively clean region both favored the diffusion of pollutants in all three cities.

Noble gas insertion compounds of hydrogenated and lithiated hyperhalogens.

Based on density functional theory (DFT) calculations, hydrogenated hyperhalogen HM(BO2)2, lithiated hyperhalogen LiM(BO2)2 (M = Cu, Ag, Au), and their compounds with xenon were studied. Different insertion sites of Xe resulted in various isomers. According to the natural population analysis, the Xe atom donated 0.12-0.77 electrons to HM(BO2)2 and 0.14-0.41 electrons to LiM(BO2)2 when they combined, leading to metastable charge-transfer compounds in most cases. The nature of bonding between xenon and HM(BO2)2/LiM(BO2)2 was found to be related to its location. Covalent bonds were formed when Xe bound with hydrogen atoms, as indicated by the large Wiberg bond indices of the Xe-H bonds. The same was true for most Xe-M bondings. When an Xe-O connection was formed, it was either an ionic or van der Waals force in nature depending on the specific structural feature of the isomer. A parallel study on hyperhalogen-supported Ar and Kr compounds indicated that they were not very stable and were less likely to exist at room temperature, which was in accordance with the high inertness of both Ar and Kr atoms.

Risk factors for survival in patients with von Hippel-Lindau disease.

BACKGROUND: Historically, von Hippel-Lindau (VHL) disease is characterised by a poor survival. Although genotype-phenotype correlation has been described in many studies, the risk factors for VHL survival remain unclear. This study aims to evaluate the median survival of Chinese patients with VHL disease and explore whether VHL survival is influenced by genetic and clinical factors. METHODS: In this retrospective study, we recruited 340 patients from 127 VHL families. Kaplan-Meier plot and Cox regression model were used to evaluate the median survival and assess how survival was influenced by birth year, birth order, sex, family history, mutation type, onset age and first presenting symptom. RESULTS: The estimated median life expectancy for Chinese patients with VHL disease was 62 years. Patients with early-onset age, positive family history and truncating mutation types had poorer overall and VHL-related survival. Patients with haemangioblastoma as their first presenting symptom were related to a higher risk of death from central nervous system haemangioblastoma than those with abdominal lesions (HR 8.84, 95% CI 2.04 to 38.37, P=0.004). CONCLUSIONS: This largest VHL survival analysis indicates that onset age, family history, mutation type and first presenting symptom have an effect on the survival of patients with VHL disease, which is helpful to genetic counselling and clinical decision-making.