Balancing selection shapes population differentiation of major histocompatibility complex genes in wild golden snub-nosed monkeys

Small and isolated populations face several intrinsic risks,such as genetic drift,inbreeding depression,and reduced gene fow.Thus,patterns of genetic diversity and differentiation have become an important focus of conservation genetics research.The golden snub-nosed monkey Rhinopithecus roxellana,an endangered species endemic to China,has experienced rapid reduction in population size and severe population fragmentation over the past few decades.We measured the patterns of genetic diversity and population differentiation using both neutral microsatellites and adaptive major histocompatibility complex(MHC)genes in 2 R.roxellana populations(DPY and GNG)distributed on the northern and southern slopes of the Qinling Mountains,respectively.Eight MHC-linked haplotypes formed by 5 DQA1 alleles,5 DQB1 alleles,5 DRB1 alleles,and 4 DRB2 alleles were detected in the 2 populations.The larger GNG population showed higher genetic variation for both MHC and microsatellites than the smaller DPY population,suggesting an effect of genetic drift on genetic variation.Genetic differentiation index(FST)outlier analyses,principal coordinate analysis(PCoA),and inferred population genetic structure showed lower genetic differentiation in the MHC variations than microsatellites,suggesting that pathogen-mediated balancing selection,rather than local adaptation,homogenized the MHC genes of both populations.This study indicates that both balancing selection and genetic drift may shape genetic variation and differentiation in small and fragmented populations.

Recognition System for Diagnosing Pneumonia and Bronchitis Using Children’s Breathing Sounds Based on Transfer Learning

Respiratory infections in children increase the risk of fatal lung disease,making effective identification and analysis of breath sounds essential.However,most studies have focused on adults ignoring pediatric patients whose lungs are more vulnerable due to an imperfect immune system,and the scarcity of medical data has limited the development of deep learning methods toward reliability and high classification accuracy.In this work,we collected three types of breath sounds from children with normal(120 recordings),bronchitis(120 recordings),and pneumonia(120 recordings)at the posterior chest position using an off-the-shelf 3M electronic stethoscope.Three features were extracted from the wavelet denoised signal:spectrogram,mel-frequency cepstral coefficients(MFCCs),and Delta MFCCs.The recog-nition model is based on transfer learning techniques and combines fine-tuned MobileNetV2 and modified ResNet50 to classify breath sounds,along with software for displaying analysis results.Extensive experiments on a real dataset demonstrate the effectiveness and superior performance of the proposed model,with average accuracy,precision,recall,specificity and F1 scores of 97.96%,97.83%,97.89%,98.89%and 0.98,respectively,achieving superior performance with a small dataset.The proposed detection system,with a high-performance model and software,can help parents perform lung screening at home and also has the potential for a vast screening of children for lung disease.

Protective mechanism of quercetin in alleviating sepsis-related acute respiratory distress syndrome based on network pharmacology and in vitro experiments

BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.

Microstructure and martensitic transformation in quaternary NiTiHfV alloy

The effect of age hardening on the microstructure,martensitic transformation behavior,and shape memory properties of the(Ni_(50)Ti_(30)Hf_(20))_(95)V_(5)alloy was investigated by scanning electron microscopy,transmission electron microscopy,X-ray diffraction,differential scanning calorimetry,microhardness,and bending tests.The results demonstrate a significant influence of V addition on the microstructure of the alloy.V addition leads to the formation of a(Ni,V)_(2)(Ti,Hf)-type Laves phase,which coexists with B19'martensite at room temperature.Aging at 550℃results in precipitation hardening due to the formation of nano-scale orthorhombic H-phase,with the peak hardness observed after 3 h of aging.The alloy at peak hardness state exhibits higher transformation strain and lower unrecovered strain compared to the solution-treated sample.The aged sample achieves a maximum transformation strain of 1.56%under 500 MPa.

A blockchain-empowered authentication scheme for worm detection in wireless sensor network

Wireless Sensor Network(WSN)is a distributed sensor network composed a large number of nodes with low cost,low performance and self-management.The special structure of WSN brings both convenience and vulnerability.For example,a malicious participant can launch attacks by capturing a physical device.Therefore,node authentication that can resist malicious attacks is very important to network security.Recently,blockchain technology has shown the potential to enhance the security of the Internet of Things(IoT).In this paper,we propose a Blockchain-empowered Authentication Scheme(BAS)for WSN.In our scheme,all nodes are managed by utilizing the identity information stored on the blockchain.Besides,the simulation experiment about worm detection is executed on BAS,and the security is evaluated from detection and infection rate.The experiment results indicate that the proposed scheme can effectively inhibit the spread and infection of worms in the network.

Effects of age, sex and manual task on hand preference in wild Rhinopithecus roxellana

Golden snub-nosed monkeys(Rhinopithecus roxellana),as typical arboreal group-living Old World monkeys,provide an appropriate animal model to research manual laterality and explore the factors affecting hand preference in non-human primates(NHP).This study investigated hand preference based on63 subjects and four spontaneous manual tasks(including unimanual and bimanual feeding and grooming), and assessed the effects of age, gender and type of task on handedness in R. roxellana.A population-level left-handedness was found not only in the bimanual coordinated tasks(bimanual feeding and grooming), but also in one unimanual reaching task(unimanual feeding). There were no significant differences between the sexes in either direction or strength of hand preference among any task. However, a significant difference between adults and juveniles was found in the unimanual feeding task. This is the first report on handedness in unimanual and bimanual feeding tasks that require bipedal posture in wild R. roxellana. Furthermore,this study demonstrated spontaneous feeding tasks reported previously only in the quadrupedal posture in this species, supporting the importance of factors such as posture and task complexity in the evolution of primate manual lateralization.

Integration of“Learning to Strengthen the Country”and“Offline Teaching”Concepts in the“Curriculum Ideology and Politics”Education among Graduate Students

Since the socialism with Chinese characteristics has entered this new era,the“curriculum ideology and politics”concept has become one of the innovative achievements in the reformation of ideological and political education courses in colleges as well as universities.Based on the emphasis of“curriculum ideology and politics”among graduate students and the influence of the“learning to strengthen the country”concept,this article analyzes universities in regard to the curriculum settings,faculties,and their graduate students.It also explores the“curriculum ideology and politics”concept in consideration of the ontology of teaching,school education,social influence,etc.,and propose practical and extendable countermeasures.

Ballistic Transport through a Strained Region on Monolayer Phosphorene

We investigate quanturn transport of carriers through a strained region on monolayer phosphorene theoretically. The electron tunneling is forbidden when the incident angle exceeds a critical value. The critical angles for electrons tunneling through a strain region for different strengths and directions of the strains are different. Owing to the anisotropic effective masses, the conductance shows a strong anisotropic behavior. By tuning the Fermi energy and strain, the channels can be transited from opaque to transparent, which provides us with an efiqcient way to control the transport of monolayer phosphorene-based microstruetures.

Dispersal behaviors stimulated by habitat alterations in golden snub-nosed monkeys(Rhinopithecus roxellana)in the Qinling Mountains, China

DEAR EDITOR,Combining location data, species distribution modeling(Max Ent), and major conservation events, we analyzed historical distribution changes in golden snub-nosed monkeys(Rhinopithecus roxellana) in the Qinling Mountains of China.

An Improved Pair Method to Probe the Dust Extinction Law

Dust extinction law is crucial to recover the intrinsic energy distribution of celestial objects and infer the characteristics of interstellar dust.Based on the traditional pair method,an improved pair method is proposed to model the dust extinguished spectral energy distribution(SED)of an individual star.Instead of the mathematically parameterizing extinction curves,the extinction curves in this work are directly from the silicate-graphite dust model,so that the dust extinction law can be obtained and the dust properties can be analyzed simultaneously.The ATLAS9 stellar model atmosphere is adopted for the intrinsic SEDs in this work,while the silicate-graphite dust model with a dust size distribution of dn da~a^(-a)exp(-a a_(c)),0.005<a<5μmfor each component is adopted for the model extinction curves.One typical extinction tracer in the dense region(V410 Anon9)and one in the diffuse region(Cyg OB2#12)of the Milky Way are chosen to test the reliability and the practicability of the improved pair method in different stellar environments.The results are consistent with their interstellar environments and are in agreement with the previous observations and studies,which prove that the improved pair method is effective and applicable in different stellar environments.In addition to the reliable extinction results,the derived parameters in the dust model can be used to analyze the dust properties,which cannot be achieved by other methods with the mathematical extinction models.With the improved pair method,the stellar parameters can also be inferred and the extinction law beyond the wavelengths of observed data can be predicted based on the dust model as well.

1g/L花青素护眼贴治疗轻中度干眼疗效

目的:探讨1g/L花青素护眼贴应用于轻中度干眼的临床疗效。方法:本研究为前瞻性、多中心设计。收集2016-10/2017-04长沙、重庆、武汉等8家爱尔眼科医院轻、中度干眼患者共320例640眼,以随机数字表法分为护眼贴组(160例)和人工泪液组(160例)。护眼贴组夜间睡眠时使用1g/L花青素护眼贴6h以上;人工泪液组滴用聚乙烯醇滴眼液4次/d。于治疗前1d及治疗后14d对症状及体征进行评价,症状评价采用眼表疾病指数(ocular surface disease index,OSDI)评分,体征观察包括泪液分泌试验(Schirmer I test,SⅠt)以及采用Oculus眼表综合分析仪测量非侵入式首次泪膜破裂时间(first noninvasive tear break-up time,NITBUTf)和非侵入式平均泪膜破裂时间(average noninvasive tear break-up time,NITBUTav)。结果:两组患者治疗后的OSDI评分、NITBUTf、NITBUTav较治疗前有明显改善,差异有统计学意义(P<0.05),SⅠt治疗前后差异无统计学意义(P>0.05)。两组间治疗后OSDI评分、NITBUTf、NITBUTav、SⅠt比较差异无统计学意义(P>0.05)。结论:对于轻、中度干眼,1g/L花青素护眼贴与人工泪液具有类似的疗效,能有效改善干眼症状、提高泪膜稳定性。

结晶高分子薄膜的内部和表面结构及光学性能

高分子薄膜的雾度贡献可分为表面雾度和内部雾度两部分。文中介绍了如何分离结晶高分子薄膜光学雾度的表面贡献和内部贡献,如何用白光干涉仪(轮廓仪)研究高分子薄膜表面的三维形态及表面粗糙度。相比于原子力显微镜而言,白光干涉轮廓仪可快速获得面积大很多倍的表面三维形态及统计性更好的表面粗糙度。并在此基础上进一步介绍了如何定量地研究高分子薄膜的表面粗糙度与表面雾度之间的关系。研究表明,尽管所研究的薄膜材料不同,制造工艺也不同,薄膜的厚度也有不相同,但由白光干涉仪得到的薄膜的表面粗糙度与表面雾度之间呈较好的线性正相关。而且,相对于内部雾度,薄膜的表面雾度对总雾度的贡献更大。此外还介绍了用激光散射研究高分子薄膜中较小球晶结构的方法,实验结果表明,用偏光显微镜研究这类尺寸较小的球晶是很困难的。对于结晶度相同的薄膜样品,其内部雾度可以差别很大。在结晶度相近的情况下,有无球晶形成,球晶形态的完善程度及大小是调节内部雾度的主要因素。球晶尺寸越大结构越完善,内部雾度也越大。

Function of microglia and macrophages in secondary damage after spinal cord injury

Spinal cord injury （SCI） is a devastating type of neurological trauma with limited therapeutic op- portunities. The pathophysiology of SCI involves primary and secondary mechanisms of injury. Among all the secondary injury mechanisms, the inflammatory response is the major contrib- utor and results in expansion of the lesion and further loss of neurologic function. Meanwhile, the inflammation directly and indirectly dominates the outcomes of SCI, including not only pain and motor dysfunction, but also preventingneuronal regeneration. Microglia and macrophages play very important roles in secondary injury. Microglia reside in spinal parenchyma and survey the microenvironment through the signals of injury or infection. Macrophages are derived from monocytes recruited to injured sites from the peripheral circulation. Activated resident microglia and monocyte-derived macrophages induce and magnify immune and inflammatory responses not only by means of their secretory moleculesand phagocytosis, but also through their influence on astrocytes, oligodendrocytes and demyelination. In this review, we focus on the roles of mi- croglia and macrophages in secondary injury and how they contribute to the sequelae of SCI.

Risk factors for progression to acute-on-chronic liver failure during severe acute exacerbation of chronic hepatitis B virus infection

BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus(HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation(HD) and acute-on-chronic liver failure(ACLF) in patients with severe acute exacerbation(SAE) of chronic HBV infection remain unknown.AIM To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection.METHODS The baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation(AE model) and the model for end-stage liver disease(MELD) score in predicting the development of ACLF were evaluated.RESULTS Among 164 patients with SAE, 83(50.6%) had compensated liver cirrhosis(LC),43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase(AST) levels, and low prothrombin activity(PTA). The area under the receiver operating characteristic of the AE model [0.844, 95%confidence interval(CI): 0.779-0.896] was significantly higher than that of MELD score(0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF.CONCLUSION In patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score.

Involvement of ayu NOD2 in NF-κB and MAPK signaling pathways: Insights into functional conservation of NOD2 in antibacterial innate immunity

Nucleotide oligomerization domain 2(NOD2) is a major cytoplasmic sensor for pathogens and is critical for the clearance of cytosolic bacteria in mammals.However, studies regarding NOD2, especially the initiated signaling pathways, are scarce in teleost species. In this study, we identified a NOD2 molecule(PaNOD2) from ayu(Plecoglossus altivelis).Bioinformatics analysis showed the structure of NOD2 to be highly conserved during vertebrate evolution. Dual-luciferase reporter assays examined the activation of NF-κB signaling and Western blotting analysis detected the phosphorylation of three MAP kinases(p-38, Erk1/2, and JNK1/2).Functional study revealed that, like its mammalian counterparts, PaNOD2 was the receptor of the bacterial cell wall component muramyl dipeptide(MDP), and the leucine-rich repeat motif was responsible for the recognition and binding of Pa NOD2 with the ligand. Overexpression of PaNOD2 activated the NF-κB signaling pathway, leading to the upregulation of inflammatory cytokines, including TNF-α and IL-1β in HEK293 T cells and ayu head kidney-derived monocytes/macrophages(MO/MΦ).Particularly, we found that PaNOD2 activated the MAPK signaling pathways, as indicated by the increased phosphorylation of p-38, Erk1/2, and JNK1/2, which have not been characterized in any teleost species previously. Our findings proved that the NOD2 molecule and initiated pathways are conserved between mammals and ayu. Therefore, ayu could be used as an animal model to investigate NOD2-based diseases and therapeutic applications.

Overexpression of the Watermelon Ethylene Response Factor ClERF069 in Transgenic Tomato Resulted in Delayed Fruit Ripening

Watermelon fruit undergoes distinct development stages with dramatic changes during fruit ripening.To date,the molecular mechanics of watermelon ripening remain unclear.Genetic and transcriptome evidences suggested that the ethylene response factor(ERF)gene ClERF069 may be an important candidate factor affecting watermelon fruit ripening.To dissect the roles of ClERF069 in fruit ripening,structure and phylogenetic analysis were performed using the amplified full-length sequence.Normal-ripening watermelon 97103,non-ripening watermelon PI296341-FR and the RIL population were used to analyze ClERF069 expression dynamics and the correlation with fruit ripening indexs.The results indicated that ClERF069 belongs to ERF family group VI and show high homology(83%identity)to melon ERF069-like protein.ClERF069 expression in watermelon flesh was negatively correlated with fruit lycopene content and sugar content during fruit ripening progress.Further transgenic evidences indicated that overexpression of 35S:ClERF069 in tomato noticeably delayed the ripening process up to 5.2 days.Lycopene,β-carotenoid accumulation patterns were altered and ethylene production patterns in transgenic fruits was significantly delayed during fruit ripening.Taken together,watermelon ethylene response factor ClERF069 was concluded to be a negative regulator of fruit ripening.

Liquorice-induced severe hypokalemic rhabdomyolysis with Gitelman syndrome and diabetes: A case report

BACKGROUND Licorice-induced severe hypokalemic rhabdomyolysis is clinically rare. Gitelman syndrome(GS) is the most common inherited renal tubular disease, while diabetes is one of the most prevalent diseases in the world. Recently, some studies have found that GS patients had higher diabetic morbidity. However, the coexistence of these three diseases has yet to be reported.CASE SUMMARY We report the case of a 62-year-old Chinese man who was admitted with weakness in the extremities, muscle pain, and dark-colored urine. He had consumed liquorice water daily for seven days prior to admission. The laboratory tests revealed a serum potassium level of 1.84 mmol/L, magnesium 0.68 mmol/L, creatinine phosphokinase(CK) 10117 IU/L, and marked hemoglobinuria. Fractional chloride excretion and fractional magnesium excretion were increased. Plasma renin activity and aldosterone concentration were within the normal ranges. Sequence analysis of the SLC12 A3 gene revealed that he had compound heterozygous mutations. The diagnosis of liquoriceinduced severe hypokalemic rhabdomyolysis with GS and diabetes was thus genetically confirmed. Serum potassium and CK quickly improved with potassium replacement therapy, hydration, and discontinuation of liquorice ingestion. Upon follow-up at 3 mo, the levels of CK, myoglobin, and potassium remained normal, and magnesium was above 0.6 mmol/L.CONCLUSION This case emphasizes that liquorice consumption and GS should be considered causes of hypokalemia and that the diabetic status of GS patients should be noted in the clinic.

多次碰撞条件下金阳离子诱导的甲烷碳-碳偶联

金属正离子与甲烷的反应活性有着广泛的研究,但已报道的离子分子反应通常在单次碰撞或低碰撞能条件下发生。本文介绍最近搭建的一个由迁移管与离子漏斗组成的离子分子反应装置,在多次碰撞与可变碰撞能条件下研究离子分子反应。离子源产生的Au+在迁移管内与甲烷反应,经漏斗与离子阱收集后由质谱检测。该反应装置的反应气压可达100Pa,且离子与分子的碰撞能可通过迁移管与离子漏斗间的电势差调节。利用该装置,我们研究了闭壳层Au+离子与甲烷的反应,并观测到碳―碳偶联产物Au C2H4+生成。密度泛函理论计算表明经由Au―CH2与Au―CH3物种的两条反应通道均可发生碳―碳偶联反应(Au++2CH4→Au C2H4++2H2)。离子轨迹模拟表明迁移管与漏斗间的电场可提供足够的碰撞能促进碳―碳偶联反应发生。

工艺参数对玻纤增强硅树脂复合材料模压成型制品热稳定性与力学性能的影响

随着核电的发展,其极端的环境对绝缘部件提出了更高的要求。玻璃纤维增强硅树脂由于优异的物理化学性能,被广泛应用于高温高电压的工况下。为了提高硅树脂的固化度并确保制品性能与材料特性相匹配,以压水堆(PWR)核电机组中控制棒驱动机构(CRDM)的磁轭线圈骨架作为玻纤增强硅树脂的模压成型制品,通过热重分析法和差示扫描量热法研究了硅树脂模塑料的固化热行为,优化了制品的模压工艺参数,采用热重分析和拉伸测试表征了制品的热稳定性和力学性能,研究了后固化参数对制品性能的影响。结果表明,与常温相比,175℃后固化24 h的制品拉伸强度增幅最大,提高了122%,热失重质量分数最小,减少了82.25%。硅树脂的失重固化和热氧化降解是影响制品性能的原因。磁轭线圈骨架模压成型工艺参数为模具温度130℃、成型压力50 MPa、保压时间10 min、固化温度175℃、烘烤时间24 h。成型制品通过了核电机组的热老化性能测试验证。

Angiopoietin and vascular endothelial growth factor expression in colorectal disease models

AIM:To investigate angiopoietin(Ang) and vascular endothelial growth factor(VEGF) expression in rats with ulcerative colitis(UC) and colorectal cancer(CRC).METHODS:Dysplasia and cancer were investigatedin rats that received three cycles of 3.5% dextran sulfate sodium(DSS) in drinking water for 7 d followed by distilled water for 14 d after intraperitoneal pretreatment with 20 mg/kg 1,2-dimethylhydrazine(DMH)(CRC group).Colitis was investigated in rats that received three cycles of 3.5% DSS in drinking water for 7 d followed by distilled water for 14 d after intraperitoneal pretreatment with saline(UC group).Rats without DSS or DMH treatment served as controls.Expression of the tyrosine kinase with immunoglobulinlike and EGF-like domains(Tie)-2 and its ligands,Ang-1 and Ang-2,as well as VEGF were evaluated in the colorectum by Western blotting.RESULTS:Compared with rats in the control group,rats in the CRC and UC groups developed the symptoms of acute colitis with diarrhea,rectal bleeding,wasting,and loss of body weight(P < 0.05).In addition,the mean length of colorectum of CRC and UC rats was significantly shorter than that of control rats(8.29 ± 0.21 and 8.31 ± 0.86,respectively,vs 12.34 ± 0.12 cm; P < 0.05).Furthermore,rats in the CRC group,but not in the UC or control groups,developed multiple tumors in the colorectal region.Western blot analysis revealed that rats in the CRC and UC groups had markedly increased protein levels of Ang-1,Ang-2,Tie-2,and VEGF in the colorectum compared to rats in the control group.CONCLUSION:Increased expression of Ang-1,Ang-2,Tie-2,and VEGF in ulcerative colitis-derived colorectal cancer might lead to chronic colitis and pathologic angiogenesis in rats.