Geochronology, geochemistry and Hf isotopes of andesites in the Sandaowanzi gold deposit(Great Xing’an Range, NE China): implications for petrogenesis, tectonic setting,and mineralization

The Sandaowanzi gold deposit is an extremely Au-rich deposit in the Northern Great Hinggan Range in recent years.Zircon U-Pb geochronology,Hf isotope analysis,and the geochemistry of andesites of the Longjiang Formation from the Sandaowanzi gold deposit were used to investigate the origin,magmatic evolution as well as mineralization and tectonic setting of the Early Cretaceous epithermal gold deposits in the northern Great Hinggan Range area.Zircon U-Pb dating reveals an emplacement age of 123.4±0.3 Ma,indicating that the andesites of the Sandaowanzi gold deposit was formed during the Early Cretaceous.The andesites are enriched in light rare earth elements relative to heavy rare earth elements and have weak negative Eu anomalies(δEu=0.76-0.90).The rocks are also enriched in large-ion lithophile elements,such as Rb,Ba,Th,U,and K,and depleted in the high-field-strength elements,such as Nb,Ta,and P.These characteristics are typical of volcanic rocks related to subduction.Igneous zircons from the andesite samples have relatively homogeneous Hf isotope ratios,176Hf/177Hf values of 0.282343-0.282502,εHf(t)values of-12.58 to-6.95,and two-stage model ages(TDM2)of 1743-1431 Ma.The characteristics of the andesites of the Longjiang Formation are consistent with derivation from partial melting of enriched mantle wedge metasomatized by subducted-slab-derived fluids.These rocks formed in an extensional environment associated with the closure of the Mongol-Okhotsk Ocean and subduction of the Paleo-Pacific Plate.Mineralization occurred towards the end of volcanism,and the magmatic activity and mineralization are products of the same geodynamic setting.

Research on the Cultivation of Innovative Talents in Software Engineering Based on the OBE Concept

Under the background of New Engineering,focusing on talent cultivation,this article explores the teaching reform and innovation of software engineering majors.Starting from the goal of cultivating software engineering talents in the context of New Engineering,the concept of outcome-based education is introduced to study and explore the construction of innovative talent training models for software engineering majors in universities.Through recent years’application practice,initial results have been achieved,which can provide feasible methods and ideas for the cultivation of innovative talents in other majors.

Ce-and La-doped polymetallic layered double hydroxides for enhanced oxygen evolution reaction performance at high current density

Polymetallic layered double hydroxides are promising cost-effective catalysts for the oxygen evolution reaction(OER) due to their versatile anionic and cationic tunability. Nevertheless, several challenges persist, notably, issues related to low electrical conductivity, poor catalytic activity, and stability, especially at high current density. Herein, we report the design of Ce-and Ladoped Co Ni Fe-layered double hydroxide(Ce La Co Ni Fe-LDH) nanosheets through a facile and scalable in situ self-assembly strategy that displays enhanced OER activity. Experimental and theoretical investigations provide insights into the impact of Ceand La-doping by comparing Ce Co Ni Fe-LDH, La Co Ni Fe-LDH, and pristine Co Ni Fe-LDH, all synthesized using the same methodology. These results reveal that doping Ce^(3+)and La^(3+)into Co Ni Fe-LDH substantially improves its electronic structure,resulting in enhanced conductivity, more oxygen vacancies(Vo), electron interaction, and active site formation. Consequently,significantly reduced overpotentials of 175, 314, and 424 m V at 10, 100, and 500 m A cm^(-2), respectively, and a highly stable current density of 120 h in 1 M KOH were achieved. Notably, these performance metrics surpass those of unmodified LDHs and are competitive with many lanthanide-doped transition metal-based LDH electrocatalysts, as well as noble metal catalysts like ruthenium catalysts. This work represents a pioneering effort in doping Ce^(3+)and La^(3+)ions into a functional Co Ni Fe-based electrocatalyst, offering inspiring OER performance and scalability potential.

3D打印个体化模具在宫颈癌近距离治疗中的应用

目的:通过3D打印个体化模具辅助插植,降低宫颈癌近距离治疗难度。方法:前瞻性研究2019年6月至2020年7月30例于重庆大学附属肿瘤医院行根治性放化疗宫颈鳞状细胞癌患者,随机分为15例3D打印组(试验组)和15例通用施源器组(对照组)。评估两组治疗情况、靶区适形指数(coformity index,CI)、高危临床靶区(high-risk clinical target area,HR-CTV)90%体积的最低吸收剂量(D90)、危及器官(organs-at-risk,OARs)受量及临床治疗结果。结果:试验组无子宫穿孔,对照组子宫穿孔率为8.97%(7/78)。试验组的CI为0.81±0.01,与对照组的0.61±0.01相比,差异具有统计学意义(P<0.05);试验组HR-CTV D90及膀胱的分次/总外照射等效剂量(equivalent dose in 2 Gy per fraction,EQD2)分别为6.65±0.06/91.84±1.35及3.75±0.07/71.02±1.39,与对照组的6.17±0.06/88.59±0.11及4.09±0.07/74.81±1.50相比,差异均具有统计学意义(均P<0.05)。试验组直肠及乙状结肠的受量降低,差异无统计学意义(P>0.05),试验组治疗结束后3个月完全缓解(complete response,CR)率为93.33%(14/15),与对照组的86.67%(13/15)相比,差异具有统计学意义(P<0.05)。结论:3D打印个体化模具在辅助宫颈癌近距离插植治疗中有明显的优势,操作简单、安全性高、有利于组织间插植技术推广。

Molecular simulation of diffusion of rigidity-tuned nanoparticles in biological hydrogels

The penetration capability of the drug nano-carriers (NCs) in biological hydrogels, such as mucus and tumor interstitial matrix, would typically influence the efficiency of drug delivery. Understanding the effect of the physicochemical property of the drug carriers on their diffusion capability in biological hydrogel becomes important for designing and optimizing the nano-carriers. Here, using a coarse-grained molecular dynamics model, we studied how the rigidity of NCs affected their diffusivity in biological hydrogel. The results showed that semi-elastic NCs have higher diffusivity than the hard and the soft NCs. Furthermore, the affinity between the NCs and biological hydrogels and the size ratio between the hydrogel meshes and NCs have also affected the diffusivity of the NCs. Further analysis revealed the mechanism that the deformation of the NCs dominates their diffusivity. These findings demonstrated that the rigidity of NCs is a key parameter in designing efficient NCs for deep penetration into the biological hydrogels.

IC Testing by Phase Classification Based on Behavioral Description of RTL

The growing complexity of integrated circuits (ICs) is driving the trend of IC testing towards testing based on behavioral descriptions of register-transfer level (RTL). A behavioral description contains an algorithmic specification of functionality of design. It may contain little or even no information about the design’s cycle-by-cycle behavior or structural implementation. However, it usually has an interior variable to lead the process of its functional phases. This interior variable is named phase variable. The functional behavior of a digital circuit changes according to different values of a phase variable. By analyzing some ITC99 benchmark circuits, this paper presents a way to generate tests for a circuit by tracing the value change of a phase variable in the circuit.

An Efficient Method for Behavioral RTL ATPG

The paper proposes an ATPG method for the Synchronous Sequential circuits described in synthesizable VHDL behavioral RTL. The method extracts a controlling tree for each process in the behavioral description and forms a graph to represent the static data-flow for the target circuit. A fault-model is defined at RT-Level. The ATPG method is then presented. Experimental results show that the ATPG method is time effective and can generate tests with fairly good quality, the fault coverage of some circuits is to be enhanced though.

NO_(3)^(-)缓解小麦根部NH_(4)^(+)毒性机理

该研究探讨了小麦(Triticum aestivum)根系NH_(4)^(+)毒性以及NO_(3)^(-)缓解其毒性机理。与7.5 mmol·L^(-1)NO_(3)^(-)处理(CK)相比,7.5 mmol·L^(-1)NH_(4)^(+)处理(SA)抑制小麦根系生长,添加1 mmol·L^(-1)NO_(3)^(-)(AN)后缓解了对根系生长的抑制。转录组分析表明,与CK相比,SA处理下,编码糖酵解途径酶、发酵关键酶、呼吸爆发性氧化酶同源物(Rbohs)、交替氧化酶(AOX)和双加氧酶相关基因显著上调表达;编码TCA循环酶、ATP合酶和水通道蛋白(AQPs)相关基因显著下调表达。与SA相比,AN处理下,糖酵解、发酵途径、Rbohs、AOX和双加氧酶相关基因的表达下调,编码TCA循环酶、ATP合酶和AQPs的基因表达上调。蛋白质组分析表明,SA处理下,糖酵解与发酵相关酶以及AOX相关基因表达上调,而AQPs相关基因表达下调。AN处理下,糖酵解与发酵相关酶以及AOX相关基因表达下调,AQPs相关基因表达上调。综上所述,单独NH_(4)^(+)处理促进糖酵解和发酵途径,抑制TCA循环,能量生成减少,最终抑制小麦根系生长,这可能与NH_(4)^(+)处理引起根系缺O_(2)胁迫有关。添加NO_(3)^(-)后抑制了糖酵解和发酵途径,促进TCA循环和能量产生,显著缓解了根系缺O_(2)胁迫以及NH_(4)^(+)对根系生长的抑制。

Novel heterozygous USH1C mutation impacts hair cell mechanotransduction and causes progressive hearing loss

Hearing loss is one of the most common sensory disorders worldwide,affecting approximately 466 million people,including 34 million children[1].Genetic mutations accounts for approximately 60%of inherited hearing loss cases[2,3].These genetic changes result in a wide variety of clinical manifestations,ranging from nonsyndromic hearing loss(NSHL)to over 400 syndromes involving hearing loss and from mild adult-onset hearing loss to profound congenital deafness,covering the entire spectrum of Mendelian inheritance.

Regeneration of hair cells in the mammalian vestibular system

Hair cells regenerate throughout the lifetime of non-mammalian vertebrates, allowing these animals to recover from hearing and balance deficits. Such regeneration does not occur efficiently in humans and other mammals. Thus, balance deficits become permanent and is a common sensory disorder all over the world. Since Forge and Warchol discovered the limited spontaneous regeneration of vestibular hair cells after gentamicin- induced damage in mature mammals, significant efforts have been exerted to trace the origin of the limited vestibular regeneration in mammals after hair cell loss. Moreover, recently many strategies have been developed to promote the hair cell regeneration and subsequent functional recovery of the vestibular system, including manipulating the Wnt, Notch and Atohl. This article provides an overview of the recent advances in hair cell regeneration in mammalian vestibular epithelia. Furthermore, this review highlights the current limitations of hair cell regeneration and provides the possible solutions to regenerate functional hair cells and to partially restore vestibular function.

Spatiotemporal expression of Ezh2 in the developing mouse cochlear sensory epithelium

The enhancer of zeste 2 polycomb repressive complex 2 subunit （Ezh2） is a histone-lysine N- methyltransferase enzyme that participates in DNA methylation. Ezh2 has also been reported to play crucial roles in stem cell proliferation and differentiation. However, the detailed expression profile of Ezh2 during mouse cochlear development has not been investigated. Here, we examined the spatiotemporal expression of Ezh2 in the cochlea during embryonic and postnatal development. Ezh2 expression began to be observed in the whole otocyst nuclei at embryonic day 9.5 （E9.5）. At E12.5, Ezh2 was expressed in the nuclei of the cochlear prosensory epithelium. At E13.5 and E15.5, Ezh2 was expressed from the apical to the basal turns in the nuclei of the differentiating cochlear epithelium. At postnatal day （P） 0 and 7, the Ezh2 expression was located in the nuclei of the cochlear epithelium in all three turns and could be clearly seen in outer and inner hair cells, supporting cells, the stria vascularis, and spiral ganglion cells. Ezh2 continued to be expressed in the cochlear epithelium of adult mice. Our results provide the basic Ezh2 expression pattern and might be useful for further investigating the detailed role of Ezh2 during cochlear development.

A novel mutation in the MITF may be digenic with GJB2 mutations in a large Chinese family of Waardenburg syndrome type Ⅱ

Waardenburg syndrome typeⅡ（WS2） is associated with syndromic deafness.A subset of WS2,WS2A,accounting for approximately 15%of patients,is attributed to mutations in the microphthalmia-associated transcription factor（MITF） gene.We examined the genetic basis of WS2 in a large Chinese family.All 9 exons of the MITF gene,the single coding exon（exon 2） of the most common hereditary deafness gene GJB2 and the mitochondrial DNA（mtDNA） 12S rRNA were sequenced.A novel heterozygous mutation c.[742_743delAAinsT;746_747delCA]in exon 8 of the MITF gene co-segregates with WS2 in the family.The MITF mutation results in a premature termination codon and a truncated MITF protein with only 247 of the 419 wild type amino acids.The deaf proband had this MITF gene heterozygous mutation as well as a c.[109G〉A]＋ [235delC]compound heterozygous pathogenic mutation in the GJB2 gene.No pathogenic mutation was found in mtDNA 12S rRNA in this family.Thus,a novel compound heterozygous mutation,c.[742_743delAAinsT;746_747delCA]in MITF exon 8 was the key genetic reason for WS2 in this family,and a digenic effect of MITF and GJB2 genes may contribute to deafness of the proband.

HTDet:A Clustering Method Using Information Entropy for Hardware Trojan Detection

Hardware Trojans(HTs)have drawn increasing attention in both academia and industry because of their significant potential threat.In this paper,we propose HTDet,a novel HT detection method using information entropybased clustering.To maintain high concealment,HTs are usually inserted in the regions with low controllability and low observability,which will result in that Trojan logics have extremely low transitions during the simulation.This implies that the regions with the low transitions will provide much more abundant and more important information for HT detection.The HTDet applies information theory technology and a density-based clustering algorithm called Density-Based Spatial Clustering of Applications with Noise(DBSCAN)to detect all suspicious Trojan logics in the circuit under detection.The DBSCAN is an unsupervised learning algorithm,that can improve the applicability of HTDet.In addition,we develop a heuristic test pattern generation method using mutual information to increase the transitions of suspicious Trojan logics.Experiments on circuit benchmarks demonstrate the effectiveness of HTDet.

Inhibiting DNA methylation alleviates cisplatininduced hearing loss by decreasing oxidative stress-induced mitochondria-dependent apoptosis via the LRP1-PI3K/AKT pathway

Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss.This study aimed to assess the potential effect of the DNA methyltransferase(DNMT)inhibitor RG108 on cisplatin-induced ototoxicity.Immunohistochemistry,apoptosis assay,and auditory brainstem response(ABR)were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells(HCs)and spiral ganglion neurons(SGNs).Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential(MMP)assessment.Reactive oxygen species(ROS)amounts were evaluated by Cellrox green and Mitosox-red probes.Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates(OCRs).The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs,and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation.Furthermore,RG108 upregulated BCL-2 and downregulated APAF1,BAX,and BAD in HEI-OC1 cells,and triggered the PI3K/AKT pathway.Decreased expression of low-density lipoprotein receptor-related protein 1(LRP1)and high methylation of the LRP1 promoter were observed after cisplatin treatment.RG108 treatment can increase LRP1expression and decrease LRP1 promoter methylation.In conclusion,RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.

Phase structure of sputtered Ta coating and its ablation behavior by laser pulse heating(LPH)

Phase structure of sputtered Ta coating in the negative glow space and LPH effect were explored.The whole coating/substrate system is substrate→physically gas-absorbed Fe surface→oxygen-enriched TaOx layer→amorphous Ta→αandβdual phase→singleαphase.After LPH course,micro structure of Ta coating shows intact,only a few cracks emerge after 100 laser pulses,exhibiting thin HAZ but thick Fe/Ta ICZ,without martensitic transformation.For the electrodeposited Cr coating,continuous thermal stresses produce many extra micro-crack,substrate oxidation and martensitic transformation,leading to crack propagations and final bulk delamination,without any ICZ.

Effect of defects on the electronic structure of a PbI2/MoS2 van der Waals heterostructure: A first-principles study

PbI2/MoS2,as a typical van der Waals(vdW)heterostructure,has attracted intensive attention owing to its remarkable electronic and optoelectronic properties.In this work,the effect of defects on the electronic structures of a PbI2/MoS2 heterointerface has been systematically investigated.The manner in which the defects modulate the band structure of PbI2/MoS2,including the band gap,band edge,band alignment,and defect energy-level density within the band gap is discussed herein.It is shown that sulfur defects tune the band gaps,iodine defects shift the positions of the band edge and Fermi level,and lead defects realize the conversions between the straddling-gap band alignment and valence-band-aligned gap,thus enhancing the light-absorption ability of the material.

Astaxanthine attenuates cisplatin ototoxicity in vitro and protects against cisplatin-induced hearing loss in vivo

Astaxanthine(AST) has important biological activities including antioxidant and antiinflammatory effects that could alleviate neurological and heart diseases, but its role in the prevention of cisplatin-induced hearing loss(CIHL) is not yet well understood. In our study, a steady interaction between AST and the E3 ligase adapter Kelch-like ECH-associated protein 1, a predominant repressor of nuclear factor erythroid 2-related factor 2(NRF2), was performed and tested via computer molecular docking and dynamics. AST protected against cisplatin-induced ototoxicity via NRF2 mediated pathwayusing quantitative PCR and Western blotting. The levels of reactive oxygen species(ROS) and mitochondrial membrane potential revealed that AST reduced ROS overexpression and mitochondrial dysfunction.Moreover, AST exerted anti-apoptosis effects in mouse cochlear explants using immunofluorescence staining and HEI-OC1 cell lines using quantitative PCR and Western blotting. Finally, AST combined with poloxamer was injected into the middle ear through the tympanum, and the protection against CIHL was evaluated using the acoustic brain stem test and immunofluorescent staining in adult mice. Our results suggest that AST reduced ROS overexpression, mitochondrial dysfunction, and apoptosis via NRF2-mediated pathway in cisplatin-exposed HEI-OC1 cell lines and mouse cochlear explants, finally promoting cell survival. Our study demonstrates that AST is a candidate therapeutic agent for CIHL.

Preventing autosomal-dominant hearing loss in Bth mice with CRISPR/CasRx-based RNA editing

CRISPR/RfxCas13d(CasRx)editing system can specifically and precisely cleave single-strand RNAs,which is a promising treatment for various disorders by downregulation of related gene expression.Here,we tested this RNA-editing approach on Beethoven(Bth)mice,an animal model for human DFNA36 due to a point mutation in Tmc1.We first screened 30 sgRNAs in cell cultures and found that CasRx with sgRNA3 reduced the Tmc1^(Bth)transcript by 90.8%,and the Tmc1 wild type transcript(Tmc1^(+))by 44.3%.We then injected a newly developed AAV vector(AAV-PHP.eB)based CasRx into the inner ears of neonatal Bth mice,and we found that Tmc1^(Bth)was reduced by 70.2%in 2 weeks with few off-target effects in the whole transcriptome.Consistently,we found improved hair cell survival,rescued hair bundle degeneration,and reduced mechanoelectrical transduction current.Importantly,the hearing performance,measured in both ABR and DPOAE thresholds,was improved significantly in all ages over 8 weeks.We,therefore,have validated the CRISPR/CasRx-based RNA editing strategy in treating autosomal-dominant hearing loss,paving way for its further application in many other hereditary diseases in hearing and beyond.

The p.(Pro170Leu) variant in NOG impairs noggin secretion and causes autosomal dominant congenital conductive hearing loss due to stapes ankylosis

Conductive hearing loss is the impairment in the mechanical transduction of sound wave through the external ear and the middle ear.Although most cases are sporadic due to acquired causes such as infections(otitis media and otitis externa),cerumen obstruction,and injuries,congenital structural defects are uncommon for significant etiologies to recognize.Stapes ankylosis is characterized by conductive hearing loss.It may be difficult to differentiate from otosclerosis,the most common cause of progressive conductive hearing loss,by audiologic evaluation,when the diagnosis is delayed.Skeletal anomalies may be subtle,such that the syndrome may not be recognized(Brown et al.,2002).

Atypical manifestations of acute coronary syndrome—throat discomfort:a multi-center observational study

To present the clinical characteristics and the misdiagnosis rate of acute coronary syndrome manifested primarily as throat discomfort,we conducted a multicentric and retrospective study in the cardiology and otorhinolaryngology departments.Records of patients with primary complaint of throat discomfort,absence of chest pain at onset,and an ultimate diagnosis of acute coronary syndrome,as well as patients with pharyngitis(as controls)were collected from May 2015 to April 2016.The patients’main manifestations were compared.Logistic regression results showed that chest tightness,dyspnea,perspiring,and exertional throat symptoms were significantly associated with acute coronary syndrome,with odds ratios of 8.3(95%CI 2.2–31.5),10.9(95%CI 1.8–66.9),25.4(95%CI 3.6–179.9),and 81.2(95%CI 13.0–506.7).A total of 25(56.82%)out of 44 acute coronary syndrome patients,who were first admitted to the otorhinolaryngology department,were misdiagnosed,with a 12%(3/25)mortality rate.Throat discomfort can be the principal manifestation of acute coronary syndrome.Such patients exhibit high misdiagnosis and mortality rates.Exertional throat symptoms,chest tightness,perspiring,and dyspnea were important indicators of acute coronary syndrome in patients whose main complaint was throat discomfort.The awareness of this condition will result in prompt diagnosis and reduce morbidity and mortality.