Benzodiazepines in complex biological matrices: Recent updates on pretreatment and detection methods

Benzodiazepines(BDZs)are used in clinics for anxiolysis,anticonvulsants,sedative hypnosis,and muscle relaxation.They have high consumptions worldwide because of their easy availability and potential addiction.They are often used for suicide or criminal practices such as abduction and drug-facilitated sexual assault.The pharmacological effects of using small doses of BDZs and their detections from complex biological matrices are challenging.Efficient pretreatment methods followed by accurate and sensitive detections are necessary.Herein,pretreatment methods for the extraction,enrichment,and preconcentration of BDZs as well as the strategies for their screening,identification,and quantitation developed in the past five years have been reviewed.Moreover,recent advances in various methods are summarized.Characteristics and advantages of each method are encompassed.Future directions of the pretreatment and detection methods for BDZs are also reviewed.

DCDC2 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children

Developmental dyslexia is a complex reading and writing disorder with strong genetic components. In previous genetic studies about dyslexia, a number of candidate genes have been identified. These include DCDC2, which has repeatedly been associated with developmental dyslexia in various European and American populations. However, data regarding this relationship are varied according to population. The Uyghur people of China represent a Eurasian population with an interesting genetic profile. Thus, this group may provide useful information about the association between DCDC2 gene polymorphisms and dyslexia. In the current study, we examined genetic data from 392 Uyghur children aged 8–12 years old from the Xinjiang Uyghur Autonomous Region of China. Participants included 196 children with dyslexia and 196 grade-, age-, and gender-matched controls. DNA was isolated from oral mucosal cell samples and fourteen single nucleotide polymorphisms（rs6456593, rs1419228, rs34647318, rs9467075, rs793862, rs9295619, rs807701, rs807724, rs2274305, rs7765678, rs4599626, rs6922023, rs3765502, and rs1087266） in DCDC2 were screened via the SNPscan method. We compared SNP frequencies in five models（Codominant, Dominant, Recessive, Heterozygote advantage, and Allele） between the two groups by means of the chi-squared test. A single-locus analysis indicated that, with regard to the allele frequency of these polymorphisms, three SNPs（rs807724, rs2274305, and rs4599626） were associated with dyslexia. rs9467075 and rs2274305 displayed significant associations with developmental dyslexia under the dominant model. rs6456593 and rs6922023 were significantly associated with developmental dyslexia under the dominant model and in the heterozygous genotype. Additionally, we discovered that the T-G-C-T of the four-marker haplotype（rs9295619-rs807701-rs807724-rs2274305） and the T-A of the two-marker haplotype（rs3765502-1087266） were significantly different between cases and controls. Thus, we conclude that DCDC2 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children.

Where is the future of China's biogas? Review, forecast,and policy implications

This paper discusses the history and present status of different categories of biogas production in China,most of which are classified into rural household production,agriculture-based engineering production,and industry-based engineering production.To evaluate the future biogas production of China,five models including the Hubbert model,the Weibull model,the generalized Weng model,the H-C-Z model,and the Grey model are applied to analyze and forecast the biogas production of each province and the entire country.It is proved that those models which originated from oil research can also be applied to other energy sources.The simulation results reveal that China＇s total biogas production is unlikely to keep on a fast-growing trend in the next few years,mainly due to a recent decrease in rural household production,and this greatly differs from the previous goal set by the official department.In addition,China＇s biogas production will present a more uneven pattern among regions in the future.This paper will give preliminary explanation for the regional difference of the three biogas sectors and propose some recommendations for instituting corresponding policies and strategies to promote the development of the biogas industry in China.

Novel mutations in the BEST1 gene cause distinct retinopathies in two Chinese families

AIM:To describe the clinical heterogeneity of patients with novel mutations in BEST1.METHODS:All the members in the two Chinese families underwent detailed clinical evaluations including best-corrected visual acuity,slit-lamp examination,applanation tonometry,and dilated fundus examination.Fundus autofluorescence,fundus fluorescein angiography,spectral-domain optical coherence tomography,electrooculography,and electroretinogram were also performed.Genomic DNA was extracted from venous blood for all the participants.The targeted next-generation sequencing of inherited retinal disease-associated genes was conducted to identify the causative mutation.RESULTS:A novel BEST1 missense mutation c.41T>C(p.Leu14Ser) was identified in Family 1.It was co-segregated with the phenotype of best vitelliform macular dystrophy(BVMD) and bioinformatics analysis confirmed it was harmful.Another novel BEST1 frameshift mutation c.345_(3)46insGGCAAGGACG(p.Glu119Glyfs*116) and a novel USH2A missense mutation c.12560G>A,p.Arg4187 His were identified in family 2 with retinitis pigmentosa(RP),which might interact and lead to the phenotype of RP.CONCLUSION:Two novel mutations in the BEST1 gene in two unrelated families with distinct phenotypes and BEST1 mutation accompanied with USH2A mutation would result in RP,which could be enormously helpful in understanding the pathogenesis of the inherited retinal disease caused by a BEST1 mutation.

New-onset heart failure masking a massive retroperitoneal liposarcoma

Liposarcoma is one of the most common soft tissue sarcomas,representing 50%of all retroperitoneal sarcomas.A large retroper-itoneal sarcoma can exert mass effect on intraab-dominal organs and the thoracic cavity producing symptoms similar to those seen in acute decompe-nsated heart failure(HF),such as abdominal swell-ing,dyspnea on exertion,and orthopnea.However,the presentation with new-onset HF masking a mas-sive retroperitoneal liposarcoma is exceedingly rare.Here,we present an interesting case of an elderly patient with new-onset decompensated HF in the setting of multi-vessel coronary artery disease who responded well to intravenous diuretic therapy with-out complete symptom resolution.Further workup showed a massive retroperitoneal sarcoma as the con-tributing etiology.Given his poor cardiac function,he was not initially a surgical candidate.However,after being placed on appropriate goal-directed med-ical therapy,he experienced recovery in his ejection fraction(EF)and is now a surgical candidate.

Discrimination of Pb-Zn deposit types using sphalerite geochemistry: New insights from machine learning algorithm

Due to the combined influences such as ore-forming temperature,fluid and metal sources,sphalerite tends to incorporate diverse contents of trace elements during the formation of different types of Lead-zinc(Pb-Zn)deposits.Therefore,trace elements in sphalerite have long been utilized to distinguish Pb-Zn deposit types.However,previous discriminant diagrams usually contain two or three dimensions,which are limited to revealing the complicated interrelations between trace elements of sphalerite and the types of Pb-Zn deposits.In this study,we aim to prove that the sphalerite trace elements can be used to classify the Pb-Zn deposit types and extract key factors from sphalerite trace elements that can dis-criminate Pb-Zn deposit types using machine learning algorithms.A dataset of nearly 3600 sphalerite spot analyses from 95 Pb-Zn deposits worldwide determined by LA-ICP-MS was compiled from peer-reviewed publications,containing 12 elements(Mn,Fe,Co,Cu,Ga,Ge,Ag,Cd,In,Sn,Sb,and Pb)from 5 types,including Sedimentary Exhalative(SEDEX),Mississippi Valley Type(MVT),Volcanic Massive Sulfide(VMS),skarn,and epithermal deposits.Random Forests(RF)is applied to the data processing and the results show that trace elements of sphalerite can successfully discriminate different types of Pb-Zn deposits except for VMS deposits,most of which are falsely distinguished as skarn and epithermal types.To further discriminate VMS deposits,future studies could focus on enlarging the capacity of VMS deposits in datasets and applying other geological factors along with sphalerite trace elements when con-structing the classification model.RF’s feature importance and permutation feature importance were adopted to evaluate the element significance for classification.Besides,a visualized tool,t-distributed stochastic neighbor embedding(t-SNE),was used to verify the results of both classification and evalua-tion.The results presented here show that Mn,Co,and Ge display significant impacts on classification of Pb-Zn deposits and In,Ga,Sn,Cd,and Fe also have relatively important effects compared to the rest ele-ments,confirming that Pb-Zn deposits discrimination is mainly controlled by multi-elements in spha-lerite.Our study hence shows that machine learning algorithm can provide new insights into conventional geochemical analyses,inspiring future research on constructing classification models of mineral deposits using mineral geochemistry data.

High-density lipoprotein regulates angiogenesis by long non-coding RNA HDRACA

Normal high-density lipoprotein(nHDL)can induce angiogenesis in healthy individuals.However,HDL from patients with coronary artery disease undergoes various modifications,becomes dysfunctional(dHDL),and loses its ability to promote angiogenesis.Here,we identified a long non-coding RNA,HDRACA,that is involved in the regulation of angiogenesis by HDL.In this study,we showed that nHDL downregulates the expression of HDRACA in endothelial cells by activating WW domain-containing E3 ubiquitin protein ligase 2,which catalyzes the ubiquitination and subsequent degradation of its transcription factor,Kruppel-like factor 5,via sphingosine 1-phosphate(S1P)receptor 1.In contrast,dHDL with lower levels of S1P than nHDL were much less effective in decreasing the expression of HDRACA.HDRACA was able to bind to Ras-interacting protein 1(RAIN)to hinder the interaction between RAIN and vigilin,which led to an increase in the binding between the vigilin protein and proliferating cell nuclear antigen(PCNA)mRNA,resulting in a decrease in the expression of PCNA and inhibition of angiogenesis.The expression of human HDRACA in a hindlimb ischemia mouse model inhibited the recovery of angiogenesis.Taken together,these findings suggest that HDRACA is involved in the HDL regulation of angiogenesis,which nHDL inhibits the expression of HDRACA to induce angiogenesis,and that dHDL is much less effective in inhibiting HDRACA expression,which provides an explanation for the decreased ability of dHDL to stimulate angiogenesis.

氟效应在酮亚胺镍催化乙烯聚合与共聚中的系统研究

相比于烯烃聚合过渡金属催化剂的空间位阻与电子效应,氟效应是一种简单且有效调控烯烃聚合反应的重要方法,但研究却相对较少.在本工作中,通过把不同位置(邻、间、对)和不同数目(0、1、2、3、5)的氟原子引入到N,O配位型的单组分阳离子酮亚胺镍催化剂中,系统地考察了氟效应对乙烯聚合反应的催化活性、催化剂热稳定性、聚合物分子量以及聚合物支化度的全面影响.发现邻位氟取代基有利于聚合物分子量的显著提高,而间位与对位氟取代基导致聚合活性下降;特别是全氟取代基不仅造成催化剂热稳定性的下降,同时导致聚合活性与聚合物分子量的大幅下降.在乙烯与丙烯酸甲酯的共聚合研究中,无氟取代的镍催化剂出现失活,但邻氟取代的镍催化剂则表现出聚合活性以及赋予共单体插入率,这些行为在长链极性单体共聚中表现更加优异.本工作有助于理解氟效应在烯烃聚合中的重要作用.

The Aviation Technology Two-Sided Matching with the Expected Time Based on the Probabilistic Linguistic Preference Relations

The two-sided matching has been widely applied to the decision-making problems in the field of management.With the limited working experience,the two-sided agents usually cannot provide the preference order directly for the opposite agent,but rather to provide the preference relations in the form of linguistic information.The preference relations based on probabilistic linguistic term sets(PLTSs)not only allowagents to provide the evaluation with multiple linguistic terms,but also present the different preference degrees for linguistic terms.Considering the diversities of the agents,they may provide their preference relations in the form of the probabilistic linguistic preference relation(PLPR)or the probabilistic linguistic multiplicative preference relation(PLMPR).For two-sided matching with the expected time,we first provide the concept of the time satisfaction degree(TSD).Then,we transform the preference relations in different forms into the unified preference relations(u-PRs).The consistency index to measure the consistency of u-PRs is introduced.Besides,the acceptable consistent u-PRs are constructed,and an algorithm is proposed to modify the unacceptable consistent u-PRs.Furthermore,we present the whole two-sided matching decisionmaking process with the acceptable consistent u-PRs.Finally,a case about aviation technology suppliers and demanders matching is presented to exhibit the rationality and practicality of the proposed method.Some analyses and discussions are provided to further demonstrate the feasibility and effectiveness of the proposed method.

Benzosuberyl Substituents as a"Sandwich-like"Function in Olefin Polymerization Catalysis

For the rational design of metal catalyst in olefin polymerization catalysis,various strategies were applied to suppress the chain transfer by bulking up the axial positions of the metal center,among which the"sandwich"type turned out to be an eficient category in achieving high molecular weight polyolefin.In the a-dimine system,the"sandwich"type catalysts were built using the typical 8-aryl-naphthyI framework.In this contribution,by introducing the rotationally restrained benzosuberyl substituent into the ortho-position of N-aryl rings,a new class of "sandwich-like"a-diimine nickel catalysts was constructed and fully identified.The rotationally restrained benzosuberyl substituents played a"sandwich-like"function by capping the nickel center from two axial sites.Compared to the nickel catalyst Ni1 bearing freely rotated benzhydryl substituent,Ni2 featuring benzosubery|substituent enabled the increase(8 times)of polymer molecular weights from 8 kDa to 65 kDa in the polymerization of ethylene.By further increasing the steric bulk of another ortho-site of the N-aryl ring,the polymer molecular weight even reached an ultrahigh level of 833 kDa(Mw=1857 kDa)using the optimized Ni3.Notably,these nickel catalysts could also mediate the copolymerization of ethylene with methyl 10-undecenoate,with Ni3 giving the highest copolymer molecular weight(88 kDa)and the highest incorporation of comonmer(2.0 mol1%),along with high activity of up to 10^(5)g·mol^(-1)·h^(-1).

Influence of Backbone and Axial Substituent of Catalyst onα-Imino-ketone Nickel Mediated Ethylene(Co)Polymerization

Theα-imino-ketone nickel catalyst is an emerging versatile platform that is easy to prepare and allows for the production of branched high molecular weight functionalized polyethylenes.However,study on this catalyst system is rare thus far.In this contribution,by introducing different backbones,flexible and rigid axial substituents into theα-imino-ketone framework,a family of cationic nickel catalysts were synthesized and fully characterized.Without the addition of any activator,systematic studies on ethylene polymerization and copolymerization with polar monomers were performed to explore the influence of both backbone and axial substituent on catalytic activity,polymer molecular weight,branching density and incorporation.In particular,owing to the unique semi-opening feature of theα-imino-ketone framework,the preferred nickel catalyst exhibited high activity of 175 kg·mol^(-1)·h^(-1)to produce functionalized polyethylene with molecular weight of 13.4 kg·mol^(-1)and comonomer incorporation of 2.9 mol%.

Fabrication of a polypseudorotaxane nanoparticle with synergistic photodynamic and chemotherapy

A polypseudorotaxane（PPR） nanoparticle was fabricated by the self-assembly of m PEG-protoporphyrin IX（PpIX） conjugate and a-CDs via the host-guest interaction.The nanoparticle loaded with anticancer drug doxorubicin（DOX） exerted synergistic photodynamic and chemotherapy.The nanoparticle was spherical with the mean size of 89 nm,the low critical micelle concentration（CMC） of DOX-loaded nanoparticle was 9.3 mg/m L and the drug loading content was 9.93%.The in vitro anticancer activity test revealed that the DOX-loaded nanoparticle exhibited promising reactive oxygen species（ROS）cytotoxicity and chemotherapeutic efficacy to cancer cells.The PPR nanoparticle is potentially promising for synergistic photodynamic and chemotherapy for cancers.