Prevention and Nursing of Adverse Reactions of Novel Coronavirus Inactivated Vaccine (Vero Cells)

Objective:To discuss and analyze the causes of adverse reactions caused by the inactivated novel coronavirus vaccine(Vero cells),and to propose methods of prevention and care.Methods:A questionnaire was used to randomly select 229 adults who were vaccinated with the inactivated novel coronavirus vaccine(Vero cells)at Xi’an People’s Hospital(Xi’an Fourth Hospital).The adverse reactions were statistically analyzed.Results:Among the 229 adults vaccinated with the inactivated novel coronavirus vaccine(Vero cells),30 experienced vaccination reactions.The main reaction was local induration at the inoculation site,and dizziness was the primary systemic symptom.Conclusion:To reduce the incidence of adverse reactions to the inactivated novel coronavirus vaccine(Vero cells),it is necessary to effectively evaluate the health status of adults before vaccination,select the correct vaccination site,and strictly implement the rules of 3-inspections,7-checks,and 1-verification.Standardizing the operation process and providing thorough health education after vaccination can effectively reduce the occurrence of adverse reactions.

Functional analysis of the novel mitochondrial tRNA^(Trp)and tRNA^(Ser(AGY))variants associated with type 2 diabetes mellitus

BACKGROUND Mutations in mitochondrial tRNA(mt-tRNA)genes that result in mitochondrial dysfunction play important roles in type 2 diabetes mellitus(T2DM).We previously reported a large Chinese pedigree with maternally inherited T2DM that harbors novel mt-tRNA^(Trp)A5514G and tRNA^(Ser(AGY))C12237T variants,however,the effects of these mt-tRNA variants on T2DM progression are largely unknown.AIM To assess the potential pathogenicity of T2DM-associated m.A5514G and m.C12237T variants at genetic,molecular,and biochemical levels.METHODS Cytoplasmic hybrid(cybrid)cells carrying both m.A5514G and m.C12237T variants,and healthy control cells without these mitochondrial DNA(mtDNA)variants were generated using trans-mitochondrial technology.Mitochondrial features,including mt-tRNA steady-state level,levels of adenosine triphosphate(ATP),mitochondrial membrane potential(MMP),reactive oxygen species(ROS),mtDNA copy number,nicotinamide adenine dinucleotide(NAD+)/NADH ratio,enzymatic activities of respiratory chain complexes(RCCs),8-hydroxy-deoxyguanine(8-OhdG),malondialdehyde(MDA),and superoxide dismutase(SOD)were examined in cell lines with and without these mt-tRNA variants.RESULTS Compared with control cells,the m.A5514G variant caused an approximately 35%reduction in the steady-state level of mt-tRNA^(Trp)(P<0.0001);however,the m.C12237T variant did not affect the mt-tRNA^(Ser(AGY))steady-state level(P=0.5849).Biochemical analysis revealed that cells with both m.A5514G and m.C12237T variants exhibited more severe mitochondrial dysfunctions and elevated oxidative stress than control cells:ATP,MMP,NAD+/NADH ratio,enzyme activities of RCCs and SOD levels were markedly decreased in mutant cells(P<0.05 for all measures).By contrast,the levels of ROS,8-OhdG and MDA were significantly increased(P<0.05 for all measures),but mtDNA copy number was not affected by m.A5514G and m.C12237T variants(P=0.5942).CONCLUSION The m.A5514G variant impaired mt-tRNA^(Trp)metabolism,which subsequently caused mitochondrial dysfunction.The m.C12237T variant did not alter the steady-state level of mt-tRNA^(Ser(AGY)),indicating that it may be a modifier of the m.A5514G variant.The m.A5514G variant may exacerbate the pathogenesis and progression of T2DM in this Chinese pedigree.

Fatty acid binding protein 5 is a novel therapeutic target for hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive subtype of liver cancer and is one of the most common cancers with high mortality worldwide.Reprogrammed lipid metabolism plays crucial roles in HCC cancer cell survival,growth,and evolution.Emerging evidence suggests the importance of fatty acid binding proteins(FABPs)in contribution to cancer progression and metastasis;however,how these FABPs are dysregulated in cancer cells,especially in HCC,and the roles of FABPs in cancer progression have not been well defined.AIM To understand the genetic alterations and expression of FABPs and their associated cancer hallmarks and oncogenes in contributing to cancer malignancies.METHODS We used The Cancer Genome Atlas datasets of pan cancer and liver hepatocellular carcinoma(LIHC)as well as patient cohorts with other cancer types in this study.We investigated genetic alterations of FABPs in various cancer types.mRNA expression was used to determine if FABPs are abnormally expressed in tumor tissues compared to non-tumor controls and to investigate whether their expression correlates with patient clinical outcome,enriched cancer hallmarks and oncogenes previously reported for patients with HCC.We determined the protein levels of FABP5 and its correlated genes in two HCC cell lines and assessed the potential of FABP5 inhibition in treating HCC cells.RESULTS We discovered that a gene cluster including five FABP family members(FABP4,FABP5,FABP8,FABP9 and FABP12)is frequently co-amplified in cancer.Amplification,in fact,is the most common genetic alteration for FABPs,leading to overexpression of FABPs.FABP5 showed the greatest differential mRNA expression comparing tumor with non-tumor tissues.High FABP5 expression correlates well with worse patient outcomes(P<0.05).FABP5 expression highly correlates with enrichment of G2M checkpoint(r=0.33,P=1.1e-10),TP53 signaling pathway(r=0.22,P=1.7e-5)and many genes in the gene sets such as CDK1(r=0.56,P=0),CDK4(r=0.49,P=0),and TP53(r=0.22,P=1.6e-5).Furthermore,FABP5 also correlates well with two co-expressed oncogenes PLK1 and BIRC5 in pan cancer especially in LIHC patients(r=0.58,P=0;r=0.58,P=0;respectively).FABP5high Huh7 cells also expressed higher protein levels of p53,BIRC5,CDK1,CDK2,and CDK4 than FABP5low HepG2 cells.FABP5 inhibition more potently inhibited the tumor cell growth in Huh7 cells than in HepG2 cells.CONCLUSION We discovered that FABP5 gene is frequently amplified in cancer,especially in HCC,leading to its significant elevated expression in HCC.Its high expression correlates well with worse patient outcome,enriched cancer hallmarks and oncogenes in HCC.FABP5 inhibition impaired the cell viability of FABP5high Huh7 cells.All these support that FABP5 is a novel therapeutic target for treating FABP5high HCC.

Molecular profiles and long-term outcomes of Thai children with hepatic glycogen storage disease in Thailand

BACKGROUND Thus far,genetic analysis of patients clinically diagnosed with glycogen storage diseases(GSDs)in Thailand has not been reported.AIM To evaluate the clinical and biochemical profiles,molecular analysis and long-term outcomes of Thai children diagnosed with hepatic GSD.METHODS Children aged<18 years diagnosed with hepatic GSD and followed up at King Chulalongkorn Memorial Hospital were recruited.Whole-exome sequencing(WES)was performed to identify the causative gene variants.Medical records were assessed.RESULTS All eight children with histopathologically confirmed diagnosis were classified by WES into subtypes Ia(n=1),III(n=3),VI(n=3),and IX(n=1).A total number of 10 variants were identified including G6PC(n=1),AGL(n=4),PYGL(n=5),and PHKA2(n=1).AGL had two novel variants.The clinical manifestations were hepatomegaly(n=8),doll-like facies(n=3),wasting(n=2),and stunting(n=5).All patients showed hypoglycemia,transaminitis,and dyslipidemia.The mainstay of treatment was cornstarch supplementation and high-protein and low-lactosefructose diet.After a median follow-up time of 9.59 years,height turned to normal for age in 3/5 patients and none had malnutrition.Liver enzymes,blood sugar,and lipid profiles improved in all.CONCLUSION Hepatomegaly,transaminitis,and hypoglycemia are the hallmarks of GSD confirmed by liver histopathology.Molecular analysis can confirm the diagnosis or classify the subtype that might benefit from personalized treatment,prognosis,and long-term care.

Analyzing the Adaptation of Rebecca from the Novel to the Film in Light of the Black-and-White

Classical Chinese aesthetics is based on Chinese philosophy.The characteristic of classical Chinese aesthetics regards“artistic conception”as one of the basic aesthetic categories.Chinese art speaks highly of the charm of the black-and-white.During the adaptation,there is the same beauty in the black-and-white photography and the“color without color”of Chinese paintings.The“artistic conception”is similar between them from the aesthetic perspective.Therefore,the unique“artistic conception”of the novel should be mastered,if the adapter aims to retain the“soul”of it.In other words,film adaptation not only considers“similarity in form”,but also draws much attention to“similarity in spirit”.The latter is the essence of film adaptation.

The Application of Newmark’s Metaphor Theory in Novel Translation--A Case Study of“the Jade King:History of a Chinese Muslim Family”

This paper examines the metaphorical part of“The Jade King:History of a Chinese Muslim Family”,Hoda’s novel,under the guidance of Newmark’s theory of metaphor.Newmark proposes six categories of metaphors,namely Dead Metaphor,ClichéMetaphor,Stock or Standard Metaphor,Adapted Metaphor,Recent Metaphor,Original Metaphor;and seven strategies of metaphor translation,including reproducing the same image in the target language,replacing the image in the source language with a standard target language image,translation of metaphor by simile,translation of metaphor(or simile)by simile plus sense,conversion of metaphor to sense,deletion and same metaphor combined with sense.They can provide a strong theoretical support for analyzing the expressions of metaphors in novels and their translation methods.By deeply analyzing the expressions of metaphor and its translation methods in novels,it not only helps to understand the metaphorical meaning and cultural connotation of the original works,but also helps to explore the cultural differences and challenges faced by English and Chinese bilingualism in the process of metaphor translation,thereby significantly improving the translation level and promoting the development of translation research.

Clinical and genetic characteristics of retinoblastoma patients in a single center with four novel RB1 variants

AIM:To assess the clinical and genetic characteristics of children diagnosed with retinoblastoma(RB)at Gazi University Faculty of Medicine’s Department of Pediatric Oncology.METHODS:All cases diagnosed with RB and received treatment and follow-up in the Ophthalmology and Pediatric Oncology Department,October 2016 to May 2021 were evaluated retrospectively.The RB1 gene was analyzed by next-generation sequencing(NGS)technique in DNAs obtained from peripheral blood samples of the patients.RESULTS:This study included 53 cases with 67 RBaffected eyes during the study period.The mean age was 24.6(median:18.5,range:3–151)mo.There were 15(22.3%)Group D eyes and 39(58.2%)Group E eyes.The RB1 gene was sequenced by the NGS method in 19 patients.Heterozygous RB1:NM_000321.3:c.54_76del(p.Glu19AlafsTer4)variant was detected in a 15-month-old female with bilateral RB.Heterozygous RB1:NM_000321.3:c.1814+3A>T variant was detected in a 5.5-month-old male with bilateral RB.The intronic RB1:NM_000321.3:c.1332+4A>G variant was detected in patient 14,a 13-month-old male with unilateral RB.The RB1:NM_000321.3:c.575_576del(p.Lys192SerfsTer10)variant was found in an 18-month-old female with an allele frequency of 37%.These variants have not been reported in the literature and mutation databases.CONCLUSION:Four novel variants are described and one of them is found in two different patients.This data is crucial for assessing prognosis.It serves as a guide for estimating the long-term risk of secondary malignancy as well as the short-term risk of developing additional malignancies in the same eye and the other eye.

The Influence of Integrated Chinese and Western Medicine Treatment on the Quality of Life and Laboratory Indicators of Patients with Novel Coronavirus Pneumonia

Objective: To investigate the influence of integrated Chinese and Western medicine treatment on the quality of life and laboratory indicators of patients with novel coronavirus pneumonia (COVID-19). Methods: A prospective, self-controlled study was conducted to analyze the changes in corresponding laboratory indicators and quality of life in 75 confirmed COVID-19 patients treated with integrated Chinese and Western medicine in our hospital during the early stage, middle stage, recovery period, and two weeks after discharge. The effectiveness and safety of the treatment regimen were evaluated in conjunction with the time for 2019-nCoV nucleic acid conversion, disease progression, and adverse reactions. Results: The PLT levels in the initial stage were significantly lower than those in the recovery period in 75 patients. The CRP levels in the initial stage were significantly lower than those after discharge for 2 weeks. The TBIL, IBTL, and DHIL levels in the initial stage were significantly lower than those in the middle stage. The K+ levels in the initial stage were significantly lower than those in the recovery period and after discharge for 2 weeks. The LYMGH levels in the initial stage were significantly lower than those in the recovery period and after discharge for 2 weeks. The TP and ALB levels in the initial stage were higher than those in the middle stage and the recovery period. The LDH levels, scores of daily activity limitation, scores of respiratory distress symptoms, scores of psychological emotions, CT imaging scores, and positive rate of nucleic acid were significantly lower than those in the recovery period and after discharge for 2 weeks. The AG, CK, CK-MB, and α-HBDH levels in the initial stage were significantly higher than those in the recovery period. However, the AMY level in the initial stage was significantly lower than that in the recovery period and after discharge for 2 weeks (p Conclusion: Integrated Chinese and Western medicine treatment has a significant impact on laboratory indicators such as PLT, LYMGH, CRP, TBIL, IBTL, DHIL, TP, ALB, K+, AG, LDH, CK, CK-MB, α-HBDH, AMY, CT imaging, and 2019-nCoV nucleic acid in COVID-19 patients. It has good clinical efficacy and safety, and can improve the quality of life of patients.

AENO:a Novel Reconstruction Method in Conjunction with ADER Schemes for Hyperbolic Equations

In this paper,we present a novel spatial reconstruction scheme,called AENO,that results from a special averaging of the ENO polynomial and its closest neighbour,while retaining the stencil direction decided by the ENO choice.A variant of the scheme,called m-AENO,results from averaging the modified ENO(m-ENO)polynomial and its closest neighbour.The concept is thoroughly assessed for the one-dimensional linear advection equation and for a one-dimensional non-linear hyperbolic system,in conjunction with the fully discrete,high-order ADER approach implemented up to fifth order of accuracy in both space and time.The results,as compared to the conventional ENO,m-ENO and WENO schemes,are very encouraging.Surprisingly,our results show that the L_(1)-errors of the novel AENO approach are the smallest for most cases considered.Crucially,for a chosen error size,AENO turns out to be the most efficient method of all five methods tested.

Novel Radiation-Adjustable Heating Terminal Based on Flat Heat Pipe Combined with Air Source Heat Pump

The electrification of building heating is an effective way to meet the global carbon target. As a clean and sustainable electrified heating technology, air-source heat pumps (ASHPs) are widely used in areas lacking central heating. However, as a major component of space heating, heating terminals might not fit well with ASHP in order to achieve both intermittency and comfort. Therefore, this study proposes a novel radiation-adjustable heating terminal combined with an ASHP to achieve electrification, intermittency, and better thermal comfort. Radiant terminals currently suffer from three major problems: limited maximum heating capacity, inability to freely adapt, and difficulty with combining them with ASHPs. These problems were solved by improving the structural design of the novel terminal (Improvement A–E). Results showed that the maximum heating capacity increased by 23.6% and radiation heat transfer ratio from 10.1% to 30.9% was provided for users with the novel terminal. Further, new flat heat pipe (FHP) design improved stability (compressor oil return), intermittency (refrigerant thermal inertia), and safety (refrigerant leakage risk) by reducing the length of exposed refrigerant pipes. Furthermore, a new phased operation strategy was proposed for the novel terminal, and the adjustability of the terminal was improved. The results can be used as reference information for decarbonizing buildings by electrifying heating terminals.

Novel endoscopic papillectomy for reducing postoperative adverse events(with videos)

BACKGROUND Pancreatic adenoma can potentially transform into adenocarcinoma, so it is recommended to be resected surgically or endoscopically. Endoscopic papillectomy is one of the main treatments for papillary adenoma, and bleeding, perforation, and pancreatitis are the most frequent and critical adverse events that restrict its wider use. There is no standard procedure for endoscopic papillectomy yet. The procedure is relevant to postoperative adverse events.AIM To reduce the postoperative adverse event rates and improve patients' postoperative condition, we developed a standard novel procedure for endoscopic papillectomy.METHODS The novel endoscopic papillectomy had two main modifications based on the conventional method: The isolation of bile from pancreatic juice with a bile duct stent and wound surface protection with metal clips and fibrin glue. We performed a single-center retrospective comparison study on the novel and conventional methods to examine the feasibility of the novel method for reducing postoperative adverse events.RESULTS A total of 76 patients, of whom 23 underwent the novel procedure and 53 underwent the conventional procedure, were retrospectively evaluated in this study. The postoperative bleeding and pancreatitis rates of the novel method were significantly lower than those of the conventional method(0 vs 20.75%, P = 0.028, and 17.4% vs 41.5%, P = 0.042, respectively). After applying the novel method, the most critical adverse event, perforation, was entirely prevented, compared to a prevalence of 5.66% with the conventional method. Several postoperative symptoms, including fever, rapid pulse, and decrease in hemoglobin level, were significantly less frequent in the novel group(P = 0.042, 0.049, and 0.014, respectively). Overall, the total adverse event rate of the novel method was lower(0 vs 24.5%, P = 0.007) than that of the conventional method.CONCLUSION Patients who underwent the novel procedure had lower postoperative adverse event rates. This study demonstrates the potential efficacy and safety of the novel endoscopic papillectomy in reducing postoperative adverse events.

Pangenome and multi-tissue gene atlas provide new insights into the domestication and highland adaptation of yaks

Background The genetic diversity of yak,a key domestic animal on the Qinghai-Tibetan Plateau(QTP),is a vital resource for domestication and breeding efforts.This study presents the first yak pangenome obtained through the de novo assembly of 16 yak genomes.Results We discovered 290 Mb of nonreference sequences and 504 new genes.Our pangenome-wide presence and absence variation(PAV)analysis revealed 5,120 PAV-related genes,highlighting a wide range of variety-specific genes and genes with varying frequencies across yak populations.Principal component analysis(PCA)based on binary gene PAV data classified yaks into three new groups:wild,domestic,and Jinchuan.Moreover,we pro-posed a‘two-haplotype genomic hybridization model'for understanding the hybridization patterns among breeds by integrating gene frequency,heterozygosity,and gene PAV data.A gene PAV-GWAS identified a novel gene(Bos-Gru3G009179)that may be associated with the multirib trait in Jinchuan yaks.Furthermore,an integrated transcrip-tome and pangenome analysis highlighted the significant differences in the expression of core genes and the muta-tional burden of differentially expressed genes between yaks from high and low altitudes.Transcriptome analysis across multiple species revealed that yaks have the most unique differentially expressed m RNAs and lnc RNAs(between high-and low-altitude regions),especially in the heart and lungs,when comparing high-and low-altitude adaptations.Conclusions The yak pangenome offers a comprehensive resource and new insights for functional genomic studies,supporting future biological research and breeding strategies.

Recent innovations in laser additive manufacturing of titanium alloys

Titanium(Ti)alloys are widely used in high-tech fields like aerospace and biomedical engineering.Laser additive manufacturing(LAM),as an innovative technology,is the key driver for the development of Ti alloys.Despite the significant advancements in LAM of Ti alloys,there remain challenges that need further research and development efforts.To recap the potential of LAM high-performance Ti alloy,this article systematically reviews LAM Ti alloys with up-to-date information on process,materials,and properties.Several feasible solutions to advance LAM Ti alloys are reviewed,including intelligent process parameters optimization,LAM process innovation with auxiliary fields and novel Ti alloys customization for LAM.The auxiliary energy fields(e.g.thermal,acoustic,mechanical deformation and magnetic fields)can affect the melt pool dynamics and solidification behaviour during LAM of Ti alloys,altering microstructures and mechanical performances.Different kinds of novel Ti alloys customized for LAM,like peritecticα-Ti,eutectoid(α+β)-Ti,hybrid(α+β)-Ti,isomorphousβ-Ti and eutecticβ-Ti alloys are reviewed in detail.Furthermore,machine learning in accelerating the LAM process optimization and new materials development is also outlooked.This review summarizes the material properties and performance envelops and benchmarks the research achievements in LAM of Ti alloys.In addition,the perspectives and further trends in LAM of Ti alloys are also highlighted.

Advances in Zika virus vaccines and therapeutics:A systematic review

Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

从Verse知识范式向Metaverse知识范式的转变——从文字媒介异化到数字媒介异化

人类知识从Verse范式向Metaverse范式的转变是由媒介变革导致的。Verse范式以时间线性模式组织个体生命体验和人类文化,是以语言为媒介的诗性范式。Metaverse范式是对诗性范式的超越,以现代数字技术为媒介,是人类生命和文化在空间中的绽开。这两种范式都强有力地表达了人的主体性。基于人类大脑可塑性,两种范式都在塑造和改变着人的神经连接,从而导致人类身体向着虚拟化方向改变。在Verse范式中,语言媒介的线性特质导致人类思维向着线性方向异化,人从其创造的Verse中已不能完整观照人自身;而在Metaverse范式中,Metaverse侵入会导致人的感官被全面过度取悦,而被全面过度取悦之后的感官会变得麻木,甚至失灵,导致人类感官进一步异化,进一步加深人类的主体性危机。

Inversion of O_(2) 1.27 μm nightglow emissions: A climatological analysis using satellite Limb-Viewed spectra and Harmonic analysis method

This study employs a linear inversion algorithm to retrieve volume emission rates(VERs)of molecular O_(2) nightglow at 1.27μm,utilizing Limb-Viewed spectra obtained from the SCanning Imaging Absorption spectroMeter for Atmospheric for CHartographY(SCIAMACHY)payload on board the Envisat satellite.The retrieved results are compared with VERs data from the SABER payload on the Thermosphere Ionosphere Mesosphere Energetics and Dynamics(TIMED)satellite,exhibiting consistency.This will help to facilitate accurate revelation of spatial distribution and periodic variation in O_(2) nightglow.VERs are extracted monthly within the altitude range of 75-110 km from 2002 to 2012,yielding a climatology of spatial and temporal distributions.The meridional structure exhibits two maxima,at the equator and at 45°N.Between August and October,the VERs exhibit a meridional bimodal structure,with the weaker one above the equator and the stronger one above 45°N.In April,the VERs reach their annual maximum.Additionally,harmonic analysis reveals significant temporal variations on different scales.The emission shows characteristics of annual and semi-annual variation,and a non-linear long-term trend associated with solar cycle activity.

A novel molybdenite depressant for efficient selective flotation separation of chalcopyrite and molybdenite

A novel small molecule depressant(M-DEP)was used to separate chalcopyrite and molybdenite via flotation.The results showed that M-DEP had an excellent selective depression on molybdenite,while had little effect on the flotation of chalcopyrite.The adsorption capacity of M-DEP on the surface of molybdenite was greater than that on chalcopyrite surface.The adsorption of M-DEP reduced the floatability of molybdenite and had less effect on the floatability of chalcopyrite,which was due to its different adsorption modes on the surface of the two minerals.Furthermore,the interaction between chalcopyrite and M-DEP was mainly chemical interaction,and almost all of the adsorbed M-DEP molecules were removed and replaced by sodium butyl xanthate(SBX).By contrast,hydrophobic interaction was the main way in which M-DEP was adsorbed on the molybdenite surface with little chemical interaction,which was less interfered by SBX addition.Therefore,M-DEP had a super selective depression on molybdenite.The study provided a novel depressant and approach for the deep separation of chalcopyrite and molybdenite via flotation.

Synthesis and Characterization of Naproxen-Salicylate Derivatives as Potential Dual-Targeted Inhibitors of Dihydrofolate Reductase

Dihydrofolate reductase (DHFR) is an enzyme that catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF). Chemotherapy drugs such as methotrexate help to slow the progression of cancer by limiting the ability of dividing cells to make nucleotides by competitively inhibiting DHFR. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been previously reported to exhibit competitive inhibition of DHFR, in addition to their primary action on cyclooxygenase enzymes. This interaction interferes with the enzymatic reduction of dihydrofolate to tetrahydrofolate, thereby impeding the folate metabolism pathway essential for nucleotide synthesis and cell proliferation. This activity stems from their structural resemblance to the p-aminobenzoyl-l-glutamate (pABG) moiety of folate, a substrate of DHFR. It has been established that NSAIDs containing a salicylate group (which has structural similarities to pABG), such as diflunisal, exhibit stronger DHFR-binding activity. In this study, we synthesized salicylate derivatives of naproxen with the aim of exploring their potential as inhibitors of DHFR. The interactions between these derivatives and human DHFR were characterized using a combination of biochemical, biophysical, and structural methods. Through polyacrylamide gel electrophoresis (PAGE) analysis, enzymatic assays, and quantitative ELISA, we investigated the binding affinity and inhibitory potency of the synthesized salicylate derivatives towards DHFR. The findings of this study suggest the potential of salicylate derivatives of naproxen as promising candidates for the inhibition of DHFR, thereby offering novel therapeutic opportunities for modulating the inflammatory process through multiple pathways. Further optimization of these derivatives could lead to the development of more efficacious dual-targeted analogs with enhanced therapeutic benefits.

The“depict”strategy for discovering new compounds in complex matrices:Lycibarbarspermidines as a case

The comprehensive detection and identification of active ingredients in complex matrices is a crucial challenge.Liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS)is the most prominent analytical platform for the exploration of novel active compounds from complex matrices.However,the LC-HRMS-based analysis workflow suffers from several bottleneck issues,such as trace content of target compounds,limited acquisition for fragment information,and uncertainty in interpreting relevant MS2 spectra.Lycibarbarspermidines are vital antioxidant active ingredients in Lycii Fructus,while the reported structures are merely focused on dicaffeoylspermidines due to their low content.To comprehensively detect the new structures of lycibarbarspermidine derivatives,a“depict”strategy was developed in this study.First,potential new lycibarbarspermidine derivatives were designed according to the biosynthetic pathway,and a comprehensive database was established,which enlarged the coverage of lycibarbarspermidine derivatives.Second,the polarity-oriented sample preparation of potential new compounds increased the concentration of the target compounds.Third,the construction of the molecular network based on the fragmentation pathway of lycibarbarspermidine derivatives broadened the comprehensiveness of identification.Finally,the weak response signals were captured by data-dependent scanning(DDA)followed by parallel reaction monitoring(PRM),and the efficiency of acquiring MS2 fragment ions of target compounds was significantly improved.Based on the integrated strategy above,210 lycibarbarspermidine derivatives were detected and identified from Lycii Fructus,and in particular,170 potential new compounds were structurally characterized.The integrated strategy improved the sensitivity of detection and the coverage of low-response components,and it is expected to be a promising pipeline for discovering new compounds.