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.

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.

Characterization and distribution of novel alleles of the vernalization gene Vrn-A1 in Chinese wheat(Triticum aestivum L.) cultivars

The ability of wheat to adapt to a wide range of environmental conditions is determined mostly by allelic diversity among genes regulating vernalization requirement.Vrn-1 is a major regulator of this requirement.In this study,two novel alleles of Vrn-A1 were discovered in Chinese cultivars:vrn-A1n was identified in two landraces,Jiunong 2 and Ganchun 16,and Vrn-A1o was detected in Duanhongmangmai.Both novel alleles showed a linked duplication in the promoter region.The common copy of these two alleles was identical to the recessive allele vrn-A1.Compared with the recessive allele vrn-A1,the other copy of vrn-A1n contained a 54-bp deletion in the promoter region and the distinct copy of Vrn-A1o contained an11-bp deletion in the promoter region.In segregating populations in the greenhouse under nonvernalizing(20–25°C)and long-day(16 h light)conditions,plants with the novel vrn-A1n allele did not head earlier than those with the recessive vrn-A1 allele.However,plants that were either homozygous or heterozygous for the novel Vrn-A1o allele headed earlier than those with the recessive vrn-A1 allele.To identify the novel allele with the small-sized product and facilitate screening,a DNA marker for the novel dominant allele Vrn-A1o was designed.Analysis of the novel-allele distribution showed that two cultivars carrying the vrn-A1n allele were dispersed in the northwestern spring wheat zone,and 12 cultivars carrying the dominant Vrn-A1o allele were widely distributed in the northwestern spring wheat zone,Xinjiang winter and spring wheat zone,Yellow and Huai River valley winter wheat zone,and QinghaiTibetan Plateau spring and winter wheat zone.Our study identifies useful germplasm and a DNA marker for wheat breeding.

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.

A network pharmacology approach to explore the mechanism of action of Yiqi Fumai lyophilized injection in the treatment of novel coronavirus disease

Background:Shengmai decoction,which has been included in the diagnosis and treatment of coronavirus disease 2019(COVID-19),is effective in the early treatment of patients with severe COVID-19.Yiqi Fumai lyophilized injection(YQFM)is a modern Chinese medicine preparation of the Shengmai decoction.The mechanism of its intervention at the molecular level in the severe stage of COVID-19 remains unclear.Therefore,it is necessary to investigate the mechanism of YQFM in the treatment of patients with severe COVID-19.Methods:The corresponding target genes of the main active ingredients in YQFM and COVID-19 were obtained by using multiple databases and literature retrieval.A protein-protein interaction network was constructed,and enrichment analysis of the target was performed using Cytoscape 3.8.1.Lastly,the docking of all the identified compounds with angiotensin-converting enzyme II was confirmed by applying molecular docking technology.Results:YQFM has anti-inflammatory effects on RAW267.4 macrophages.The main active compounds of YQFM are all effective anti-inflammatory agents,and these active compounds also show beneficial physiological functions,such as anti-oxidation,anti-bacterial,and anticancer activities.Gene Ontology analysis showed enrichment in the following pathways:lipopolysaccharides,interleukins,NF-kappa B,interleukin-2 and others,revealing that YQFM may play a role in the treatment of patients with severe COVID-19 through these pathways.Conclusion:YQFM has multicomponent and multitarget characteristics,and it could reduce lung injury by inhibiting inflammatory reactions,promoting antiviral activities,and regulating immunity,among other functions,to treat patients with severe COVID-19.

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.

Impact of Novel Coronavirus Vaccination on the Clinical Characteristics and Parental Care Needs of Infected Children During a High-Intensity Epidemic Period

Objective:This study aimed to investigate the impact of COVID-19 vaccination on the clinical characteristics and care needs of infected children during a high-intensity pandemic and to measure the potential effects of vaccination on children's health status and healthcare utilization.Methods:A sample of 903 children who had recently been infected with the novel coronavirus and came to our hospital's emergency department from January 11 to January 30,2023,was used as the research object in this retrospective study.The questionnaire on unknown coronavirus infection was filled out anonymously,and SPSS20.0 software was used for statistical data analysis.Results:The baseline conditions of 903 subjects were studied,including 505 males,accounting for 55.92%,and 398 females,accounting for 44.08%.The age of infection was mainly concentrated in preschool children(26.02%)and school-age children(38.76%).Regarding vaccination,561 cases were vaccinated,accounting for 62.13%.Among them,37 children received one dose of vaccine,accounting for 4.1%,463 children received two doses,accounting for 51.27%,and 61 children received three doses,accounting for 6.76%.For previous allergic diseases,180 children had a history of allergic diseases,accounting for 19.93%.Regarding sources of infection,the most common source was someone at home,accounting for 82.61%.Vaccination can effectively reduce the fever of children infected with the new coronavirus,the number of outpatient and emergency doctor visits,and the risk of hospitalization.In addition,regarding treatment,children in the vaccinated group were more likely to be treated at home,and the types of drugs used also differed from those in the non-vaccinated group.However,the vaccination group has a relatively high incidence of symptoms such as sore throat,cough,abnormal sense of smell and taste,muscle soreness,and headache.However,these are mild clinical symptoms and do not affect children's physical health and development.Parental care needs for children infected with COVID-19 are disparate,and parents of vaccinated children have lower proportions of needs for child care.Conclusion:Vaccination positively impacts the clinical outcomes of children infected with COVID-19 and their parents'well-being.

Primary animal experiment to test the feasibility of a novel Y-Z magnetic hepatic portal blocking band

BACKGROUND Hepatic portal blood flow occlusion is a common technique for reducing hepatic hemorrhage during hepatectomy.We designed a novel Y-Z magnetic hepatic portal blocking band(Y-Z MHPBB)based on the principle of magnetic compression technique.AIM To introduce the Y-Z MHPBB device and verify the feasibility of this device for hepatic portal blood flow occlusion in dogs.METHODS Ten beagles were randomly divided into the experimental group and control group.The operation time,intraoperative blood loss,the number of portal blood flow occlusions,the total time spent on adjusting the blocking band,and the average time spent on adjusting the blocking band were recorded.The surgeons evaluated the feasibility and flexibility of the two portal occlusion devices.RESULTS Laparoscopic hepatectomy was successfully performed in both the experimental group and control group.There was no statistical difference between the two groups in the operation time,intraoperative blood loss,and the number of hepatic portal blood flow occlusions.With respect to the total time spent on adjusting the blocking band and the average time spent on adjusting the blocking band,the experimental group showed significantly better outcomes than the control group,with a statistical difference(P<0.05).The operators found that the Y-Z MHPBB was superior to the modified T-tube in terms of operational flexibility.CONCLUSION The Y-Z MHPBB seems to be an ingenious design,accurate blood flow occlusion effect,and good flexibility;and it can be used for hepatic portal blood flow occlusion during laparoscopic hepatectomy.

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.

A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus(2019-nCoV) infected pneumonia(standard version)

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development;we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control(including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

The Sunspot Cycle Leads to Origin and Epidemic Mechanism of Novel Coronavirus COVID-19

Listed examples of virus transmission epidemics that can be strongly transmitted through the air caused by sunspot change cycle, analyzed the mechanism that promotes the generation of new viruses. From the schematic diagram of the changes in the combined force of the hydrodynamic effect of the sun sweeping the earth and the sweeping force, we obtain the places that are prone to light vortices are 30 degrees north latitude and 30 degrees south latitude on the east coast of the mainland creatively. The curved continental lines are perfect, the range of the light vortex generated is more obviously, and the effect is stronger. And the curved continental lines are perfect, the range of the light vortex generated is more obviously, and the effect is stronger. It is inferred that the light vortex produces the special amplified energy so that can make the virus mutate to produce a new highly infectious novel coronavirus. The earliest known place and time of the novel coronavirus origin are consistent with the reasoning of the new theory. Because the radius and frequency of the light vortex are different, the resulting virus strains are also different. Moreover, the fatality rate in the light vortex area is much higher than that in the non-light vortex area, indicating that the virus’s toxicity and lethality are higher in the light vortex area, so it can explain why Russia, India, and countries in the African equatorial region mortality are much lower than the United States, Italy, Spain and Brazil. Finally, preventive and recommended measures are proposed.

High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes

Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening （HTS） data for 3 762 distinct global gene knockout （KO） mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type （WT） cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging, ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass： 23 previously reported genes （Calcr, Cebpb, Crtap, Dcstamp, Dkkl, Duoxa2, Enppl, Fgf23, Kissl/Kisslr, Kl （Klotho）, Lrp5, Mstn, Neol, Npr2, Ostml, Postn, Sfrp4, S1c30a5, Sic39a13, Sost, Sumf1, Src, Wnt10b）, five novel genes extensively characterized （Cldn18, Fam20c, Lrrkl, Sgpll, Wnt16）, five novel genes with preliminary characterization （Agpat2, RassfS, Slc10a7, Stc26a7, Slc30a10） and three novel undisclosed genes coding for potential osteoporosis drug targets.

SYNTHESIS AND CHARACTERIZATION OF NOVEL MULTIFUNCTIONAL HOST COMPOUNDS.1.β-CYCLODEXTRIN DERIVATIVE BEARING DIETHANOLAMINE MOIETY

A novel β-cyclodextrin(β-CD)derivative bearing diethanolamine moiety was synthesized by a convenient method with 63% yield,and the new host compound was characterized by (13)~C-NMR,FT-IR spectra etc,

Application of the Modality of Multiple Disciplinary Team for a Perioperative Patient with Suspected Novel Coronavirus Pneumonia and Cervical Spine Fracture in Nursing

With the explosive spread of novel coronavirus pneumonia, a major public major public health emergency has been declared around the world. Our country has come to a crucial stage of “external defense input, internal defense rebound” and strict quarantine measures are taken in all ports of entry throughout the country. Operations on patients with cervical spine during the quarantine, which not only increases the risk of surgical treatment, but also increases the difficulty of perioperative nursing. The objective is to explore the result of application of the modality of multiple disciplinary team for a perioperative patient with suspected novel coronavirus pneumonia and cervical spine fracture in nursing. The patient’s condition and nursing measures are studied and discussed from various specialist angle through the multidisciplinary team established by the isolation ward, orthopedics department, emergency department, anesthesiology department, operating room, rehabilitation department, psychology department and so on, and the overall and personalized surgical and nursing planning is formed through interdisciplinary advice. The nursing experience is summarized in this paper.

A Novel Method of Fabricating Flexible Transparent Conductive Large Area Graphene Film

We fabricate flexible conductive and transparent graphene films on position-emission-tomography substrates and prepare large area graphene films by graphite oxide sheets with the new technical process. The multi-layer graphene oxide sheets can be chemically reduced by HNO3 and HI to form a highly conductive graphene film on a substrate at lower temperature. The reduced graphene oxide sheets show a high conductivity sheet with resistance of 476Ω/sq and transmittance of 76% at 550nm （6 layers）. The technique used to produce the transparent conductive graphene thin film is facile, inexpensive, and can be tunable for a large area production applied for electronics or touch screens.

A novel mode of retinal regeneration:the merit of a new Xenopus model

Retinal regeneration： The retina is a part of the central nervous system （CNS） and has long attracted neurobiologists as an excellent model organ for the study of CNS regeneration. In classical studies using urodele amphibians like the salamander newt, it has been shown that the retina regenerates after the removal of the whole tissue even in the adulthood. This type of regeneration is considered as an example of ＂transdifferentiation＇, since the source of the regenerating retina is the retinal pigmented epithelial cells （RPE cells） （Okada, 1991;

Astrocytic Kir4.1 potassium channels as a novel therapeutic target for epilepsy and mood disorders

Astrocytic Kir4.1 channels and spatial potassium buffering：Astrocytes play a crucial role in maintaining the structural and functional integrity of the brain,which includes formation of the blood-brain barrier,maintenance of water and ion homeostasis,metabolism of neurotransmitters and secretion of various neuroactive molecules.

BRAF inhibitor:a novel therapy for ameloblastoma in mandible

Ameloblastoma is a benign but locally aggressive odontogenic neoplasm that accounts for 10% of all tumors arising in the mandible and maxilla (1). Eighty percent of ameloblastomas arise in the mandible, and they are usually found in young adults. It frequently recurs if not adequately

ISOLATION AND STRUCTURE ELUCIDATION OF A NOVEL STEROL FROM THE SOUTH CHINA SEA SPONGE DYSIDEA SP.

A novel and unusual sterol with unsaturation in the△^(5(14)) position,5α-cholesta-8(14),24(25)-diene-3β,6α-diol 1,was isolated from the South China Ses sponge Dysidea sp.The structure and relative stereochemistry of 1 was established by spectral analysis and comparison to the spectral data of known sterols.