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Abstract Break-induced replication (BIR) is mutagenic, and thus its use requires tight regulation, yet the underlying mechanisms remain elusive. Here we uncover an important role of 53BP1 in suppressing BIR after end resection at double strand breaks (DSBs), distinct from its end protection activity, providing insight into the mechanisms governing BIR regulation and DSB repair pathway selection. We demonstrate that loss of 53BP1 induces BIR-like hyperrecombination, in a manner dependent on Polα-primase-mediated end fill-in DNA synthesis on single-stranded DNA (ssDNA) overhangs at DSBs, leading to PCNA ubiquitination and PIF1 recruitment to activate BIR. On broken replication forks, where BIR is required for repairing single-ended DSBs (seDSBs), SMARCAD1 displaces 53BP1 to facilitate the localization of ubiquitinated PCNA and PIF1 to DSBs for BIR activation. Hyper BIR associated with 53BP1 deficiency manifests template switching and large deletions, underscoring another aspect of 53BP1 in suppressing genome instability. The synthetic lethal interaction between the 53BP1 and BIR pathways provides opportunities for targeted cancer treatment.

Changing the N content in the Ti3AlC2−yNy MAX phase solid solutions allows for the fine-tuning of their properties. However, systematic studies on the synthesis and properties of Ti3AlC2−yNy solid solution bulks have not been reported thus far. Here, previously reported Ti3AlC2−yNy solid solution bulks (y = 0.3, 0.5, 0.8, and 1.0) were synthesized via hot pressing of their powder counterparts under optimized conditions. The prepared Ti3AlC2−yNy bulks are dense and have a fine microstructure with grain sizes of 6–8 μm. The influence of the N content on the mechanical properties, electrical conductivities, and coefficients of thermal expansion (CTEs) of the prepared Ti3AlC2−yNy bulk materials was clarified. The flexural strength and Vickers hardness values increased with increasing N content, suggesting that solid solution strengthening effectively improved the mechanical properties of Ti3AlC2−yNy. Ti3AlCN (y = 1) had the highest Vickers hardness and flexural strength among the studied samples, reaching 5.54 GPa and 550 MPa, respectively. However, the electrical conductivity and CTEs of the Ti3AlC2−yNy solid solutions decreased with increasing N content, from 8.93×10−6 to 7.69×10−6 K−1 and from 1.33×106 to 0.95×106 S/m, respectively. This work demonstrated the tunable properties of Ti3AlC2−yNy solid solutions with varying N contents and widened the MAX phase family for fundamental studies and applications.

Objective 28–55% of chronic hepatitis B (CHB) patients belong to the grey zone (GZ). By analyzing the pathological characteristics of the liver of patients in the GZ, this study clarified whether the patients in the GZ need anti-hepatitis B virus treatment.Method We reviewed 324 cases of liver pathology that underwent liver biopsy between 2011 and 2022. According to the total score of inflammation G, 0–6 points are classified as mild, 7–12 points are classified as moderate, and 13–18 points are classified as severe. According to the total score of fibrosis F, 0–2 is mild, 3–4 is moderate, and 5–6 is severe. Significant histological diseases (SHD) are defined as the presence of inflammation G ≥ 6 and/or fibrosis F ≥ 2 in liver biopsy specimens.Result 324 GZ patients were scored using the Ishak method, with G7-18 accounting for 9%, F3-6 accounting for 19.2%, and SHD accounting for 37%. The inflammation, fibrosis, and SHD in the HBeAg (+) group were more pronounced than those in the HBeAg (-) group. Among the GZ-A ∼ GZ-D subgroups, the highest proportion of SHD in the GZ-B group was 58.35%.Conclusion More than 1/3 of the patients in GZ need anti-hepatitis B virus treatment. More than half of GZ-B patients need anti-hepatitis B virus treatment. It is very necessary to carry out rescue anti-hepatitis B virus treatment for patients in GZ as soon as possible.

Bisphenols (BPs), prevalent endocrine disruptors in daily life, have been widely studied in vitro for their potential to cause liver diseases, including liver cancer. However, there is a dearth of research exploring BP levels in clinical populations with liver issues. This study comprehensively analyzed the distribution and characteristics of ten BPs in paired serum, blood, and urine samples from 197 hepatocellular carcinoma (HCC) patients and 100 non-HCC patients. The study investigated the impact of sociodemographic factors, such as gender, BMI (Body Mass Index), age, drinking, and smoking habits, on BP distribution. Additionally, it analyzed the relationship between BPs and three liver function biomarkers: γ-glutamyl transferase (GGT), alanine aminotransferase (ALT) and alpha-fetoprotein (AFP). Notably, some BP levels were higher in non-HCC patients compared to HCC patients across all three sample types. For HCC patients, the BP concentrations followed the order of serum (29.12 ng/mL) > blood (18.36 ng/mL) > urine (14.91 ng/mL), whereas for non-HCC patients, the order was urine (30.79 ng/mL) > serum (29.51 ng/mL) > blood (24.34 ng/mL). Moreover, BP levels in all patient samples, regardless of HCC status, increased with age. Among HCC patients, females were found to have a higher exposure to BPs compared to males, while the opposite trend was observed in non-HCC patients. Furthermore, the study revealed positive correlations between BPs and liver function indicators, such as ALT and BPAF, BPAP, BPBP; GGT and BPF; and AFP and BPF. These findings suggest a potential association between BPs and liver disease. This comprehensive analysis of BP concentrations in bio-samples from liver disease patients provides valuable insights into the relationship between BPs and liver disease in clinical settings, serving as a reference for future research and clinical practice.

The TixMo1-xC precursor was rendered porous through PUF foam replication using a slurry of TiC and Mo powders. Mo was incorporated to increase the strength of pressureless sintering (PS). The precursor served as a reinforcement for bicontinuous TixMo1-xC/Fe composites through pressureless infiltration. The interaction between Fe and TixMo1-xC was studied through experimental and theoretical analyses, establishing interfacial adhesion as a key determinant of wettability. At 1550 °C, the TiC/Fe interface exhibits non-reactive wetting, with a contact angle of 9.5°. Addition of 10 wt% Mo escalates interfacial adhesion to 3.768 J/m2 and reduces the contact angle to 9.3° at 1400 °C. TixMo1-xC's precursor has a continuous structure, while composites exhibit slight continuity as predicated by convolutional neural networks (CNNs). The morphological classifications of TixMo1-xC/Fe composites were posited. Alteration from TiC to Ti0.95Mo0.05C increases Young's modulus and hardness from 449.74 GPa to 28.58 GPa–520.55 GPa and 32.32 GPa, respectively. Without heat treatment, the tensile strength of composites rises from 125 MPa to 208 MPa. Increased strain energy density increases the prominence of dimples.

Background: A. baumannii is an important and common clinical pathogen, especially in the intensive care unit (ICU). This study aimed to characterize one hypervirulent A. baumannii strain in a patient with community-acquired pneumonia and herpes simplex type 1 virus infection. Methods: Minimum inhibitory concentrations (MICs) were determined using the Kirby-Bauer (K-B) and broth microdilution methods. Galleria mellonella infection model experiment was conducted. Whole-genome sequencing (WGS) was performed using the Illumina and Nanopore platforms. The resistance and virulence determinants were identified using the ABRicate program with ResFinder and the VFDB database. The capsular polysaccharide locus (K locus) and lipooligosaccharide outer core locus (OC locus) were identified using Kleborate with Kaptive. Phylogenetic analyses were conducted using the BacWGSTdb server. Results: A. baumannii XH2146 strain belongs to ST10Pas and ST447Oxf. The strain was resistant to cefazolin, ciprofloxacin, and trimethoprim/sulfamethoxazole (TMP-SMX). Bautype and Kaptive analyses showed that XH2146 contains OCL2 and KL49. WGS analysis revealed that the strain harbored blaADC-76, blaOXA-68, ant(3′’)-IIa, tet(B), and sul2. Notably, tet(B) and sul2, both were located within a 114,700-bp plasmid (designated pXH2146–1). Virulence assay revealed A. baumannii XH2146 possessed higher virulence than A. baumannii AB5075 at 12 h. Comparative genomic analysis showed that A. baumannii ST447 strains were mainly isolated from the USA and exhibited a relatively close genetic relationship. Importantly, 11 strains were observed to carry blaOXA-58; blaOXA-23 was identified in 11 isolates and three ST447 A. baumannii strains harbored blaNDM-1. Conclusions: Early detection of community-acquired hypervirulent Acinetobacter baumannii strains is recommended to prevent their extensive spread in hospitals.

Abstract Background Hepatocellular carcinoma (HCC), which is featured with high morbidity and mortality worldwide, is a primary malignant tumor of the liver. Recently, there is a wealth of supporting evidence revealing that NK cell-related immune traits are strongly associated with the development of HCC, but the causality between them has not been proven. Methods Two-sample Mendelian randomization (MR) study was performed to probe the causal correlation between NK cell-related immune traits and HCC. Genetic variations in NK cell-related immune traits were extracted from recent genome-wide association studies (GWAS) of individuals with European blood lineage. HCC data were derived from the UK Biobank Consortium's GWAS summary count data, including a total of 372,184 female and male subjects, with 168 cases and 372,016 controls, all of whom are of European ancestry. Sensitivity analysis was mainly used for heterogeneity and pleiotropy testing. Results Our research indicated the causality between NK cell-related immune traits and HCC. Importantly, CD8+NKT cells had protective causal effects on HCC (OR = 0.9996;95%CI,0.9993–0.9999; P = 0.0489). CD16−CD56 caused similar effects on NK cells (OR = 0.9997;95%CI,0.9996–0.9999; P = 0.0117) as CD8+NKT cells. Intercepts from Egger showed no pleiotropy and confounding factors. Furthermore, insufficient evidence was found to support the existence of heterogeneity by Cochran's Q test. Conclusion MR analysis suggested that low CD8+NKT cells and CD16−CD56 expression on NK cells were linked with a higher risk of HCC.

BackgroundAccording to the latest guidelines on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), patients with CIDP with anti-neurofascin 155 (NF155) antibodies are referred to as autoimmune nodopathy (AN), an autoimmune disorder distinct from CIDP. We aimed to compare the clinical data of patients with AN with anti-NF155 antibodies with those of anti-NF155 antibodies-negative patients with CIDP, and to summarize the clinical characteristics of patients with AN with anti-NF155 antibodies.MethodsNine patients with AN with anti-NF155 antibodies and 28 serologically negative patients with CIDP were included in this study. Diagnosis was made according to the diagnostic criteria in the European Academy of Neurology (EAN)/Peripheral Nerve Society (PNS) guidelines on CIDP published in 2021. Demographics, clinical manifestations, electrophysiological examination, cerebrospinal fluid (CSF) tests, and response to treatment were retrospectively analyzed.ResultsCompared with serologically negative patients with CIDP, those patients with AN with anti-NF155 antibodies were younger (p=0.007), had a younger onset age (p=0.009), more frequent ataxia (p=0.019), higher CSF protein levels (p=0.001), and more frequent axon damage in electrophysiology (p=0.025). The main characteristics of patients with AN with anti-NF155 antibodies include younger age and onset age, limb weakness, sensory disturbance, ataxia, multiple motor−sensory peripheral neuropathies with demyelination and axonal damage on electrophysiological examination, markedly elevated CSF protein levels, and varying degrees of response to immunotherapy.ConclusionsPatients with AN with anti-NF155 antibodies differed from serologically negative patients with CIDP in terms of clinical characteristics. When AN is suspected, testing for antibodies associated with the nodes of Ranvier is essential for early diagnosis and to guide treatment.

As the high carbon emission entities in the city, laying photovoltaic (PV) panels for public buildings is an effective way to reduce building carbon emissions. Meanwhile, public buildings play an important role as charging station access for the explosive growth of electric vehicles. However, the disorderly charging behavior of single-phase charging piles exacerbates the existing three-phase unbalance inside the buildings, which in turn affects operating costs and PV consumption. Energy storage system (ESS) configuration is considered an effective solution. Thus, An ESS configuration strategy is proposed for public buildings aiming at PV local consumption and three-phase unbalance management. To quantify the correlation between multiple loads and PV output, an improved affinity-propagation clustering algorithm based on the spatial weighted matrix distance is developed to obtain operational typical power supply-demand modes. Based on the construction of the three-phase power supply system with both single-phase and three-phase ESSs, a bi-level planning model is formulated for the configuration and operation optimization of ESSs inside the public building. The upper-level problem aims to minimize the life cycle cost of ESS allocation. The lower-level model deals with the coordinated economic scheduling of single-phase ESS and three-phase ESS under the obtained typical operational modes. Numerical results show the effectiveness and rationality of the proposed clustering algorithm and ESS configuration strategy.

Abstract This paper addresses the problem of distributed finite‐time (FT) event‐triggered consensus of multi‐agent systems (MASs) under fixed and switching topologies. To conserve the limited communication resources, a new distributed event‐triggered control protocol is proposed, in which the agents exchange information via discontinuous communication among the follower agents. Then, to solve the FT consensus problem, norm‐normalized sign functions are employed, and sufficient Lyapunov conditions are provided. On this basis, the MASs proves capable of reaching consensus within finite time under fixed and switching topologies. Finally, the effectiveness of the developed algorithm is verified via numerical simulation.

Given the complex powertrain of fuel cell electric vehicles (FCEVs) and diversified vehicle platooning synergy constraints, a control strategy that simultaneously considers inter-vehicle synergy control and energy economy is one of the key technologies to improve transportation efficiency and release the energy-saving potential of platooning vehicles. In this paper, an energy-oriented hybrid cooperative adaptive cruise control (eHCACC) strategy is proposed for an FCEV platoon, aiming to enhance energy-saving potential while ensuring stable car-following performance. The eHCACC employs a hybrid cooperative control architecture, consisting of a top-level centralized controller (TCC) and bottom-level distributed controllers (BDCs). The TCC integrates an eco-driving CACC (eCACC) strategy based on the minimum principle and random forest, which generates optimal reference velocity datasets by aligning the comprehensive control objectives of the platoon and addressing the car-following performance and economic efficiency of the platoon. Concurrently, to further unleash energy-saving potential, the BDCs utilize the equivalent consumption minimization strategy (ECMS) to determine optimal powertrain control inputs by combining the reference datasets with detailed optimization information and system states of the powertrain components. A series of simulation evaluations highlight the improved car-following stability and energy efficiency of the FCEV platoon.

High Cr white irons (HCWIs) are often used as high-temperature components exposed to the temperatures exceeding 500 °C. Improving oxidation resistance of HCWI components is necessary for engineering applications. In the present study, oxidation behaviors of high Cr white iron (HCWI) and its composites reinforced with 1–2 μm nonstoichiometric TiCx resulting from the decomposition of Ti3AlC2 (in situ TiCx/HCWI), and 2–4 μm irregular-shape of TiC (TiC/HCWI) at 600 °C for 96 h in air were investigated. Results showed that the two composites exhibited better oxidation resistance than the pure HCWI material. The oxidation test revealed a weight loss for the unreinforced HCWI but a weight gain for the composites. Among these materials, the in situ TiCx/HCWI composite has the best oxidation resistance due to its dense and fine microstructure. Oxidative thermodynamics and oxidation mechanism were discussed. This work suggests that in situ formed TiCx is an effective reinforcement to improve the oxidation resistance of HCWIs.

Purpose: The specialty of Laboratory Genetics and Genomics (LGG) was created in 2017 in an effort to reflect the increasing convergence in technologies and approaches between clinical molecular genetics and clinical cytogenetics. However, there has not yet been any formal evaluation of the merging of these disciplines and the challenges faced by Program Directors (PDs) tasked with ensuring the successful training of laboratory geneticists under the new model. Methods: An electronic multi-question Qualtrics survey was created and was sent to the PD for each of the Accreditation Council for Graduate Medical Education–accredited LGG fellowship programs at the time. The data were collected, and the responses were aggregated for each question. Results: All of the responding PDs had started training at least 1 LGG fellow. PDs noted challenges with funding, staff shortages, molecular/cytogenetics content integration, limited total training time, increased remote work, increased sendout testing, and a lack of prior cytogenetics knowledge among incoming fellows. Conclusion: This survey attempted to assess the challenges that LGG PDs have been facing in offering and integrating clinical molecular genetics and clinical cytogenetics fellowship training. Common challenges between programs were noted, and a set of 6 concluding comments are provided to facilitate future discussion.

Abstract Hepatic sinusoids play a key role in maintaining high activities of liver cells in the hepatic acinus. However, the construction of hepatic sinusoids has always been a challenge for liver chips, especially for large-scale liver microsystems. Herein, we report an approach for the construction of hepatic sinusoids. In this approach, hepatic sinusoids are formed by demolding a self-developed microneedle array from a photocurable cell-loaded matrix in a large-scale liver-acinus-chip microsystem with a designed dual blood supply. Primary sinusoids formed by demolded microneedles and spontaneously self-organized secondary sinusoids can be clearly observed. Benefiting from significantly enhanced interstitial flows by formed hepatic sinusoids, cell viability is witnessed to be considerably high, liver microstructure formation occurs, and hepatocyte metabolism is enhanced. In addition, this study preliminarily demonstrates the effects of the resulting oxygen and glucose gradients on hepatocyte functions and the application of the chip in drug testing. This work paves the way for the biofabrication of fully functionalized large-scale liver bioreactors.

Two-dimensional (2D) MoB metal borides (MoB MBene) have attracted much attention due to their fascinating properties and functional applications. So far, work on the synthesis of 2D MoB nanosheets by acid or alkaline etching of MoAlB has not been very successful. It has been proposed that the 2D MoB MBene may be fabricated by chemical etching of a Mo2AlB2 precursor, but further investigations were not performed possibly due to the difficult preparation of the metastable Mo2AlB2 compound at high temperatures by solid-state reactions. Here, we report on the successful synthesis of the Mo2AlB2 compound and 2D MoB nanosheets by the deintercalation of Al from MoAlB through a ZnCl2 molten salt etching approach at relatively low temperatures. The influence of etching temperature, etching time, and starting mixtures on the formation of desirable phases have been investigated. A pure Mo2AlB2 compound was synthesized at temperatures below 600 ℃, while the 2D MoB MBene nanosheets were obtained at 700 ℃ through the molten salt etching of MoAlB. In addition, the present work further confirms that the MoB MBene can be prepared by etching the as-synthesized Mo2AlB2 precursor in LiF–HCl solution. Our work demonstrates that the molten salt etching is an effective method to prepare 2D MoB MBene.

Abstract COVID-19 has emerged as a global pandemic, challenging the world’s economic and health systems. Human oral microbiota comprises the second largest microbial community after the gut microbiota and is closely related to respiratory tract infections; however, oral microbiomes of patients who have recovered from COVID-19 have not yet been thoroughly studied. Herein, we compared the oral bacterial and fungal microbiota after clearance of SARS-CoV-2 in 23 COVID-19 recovered patients to those of 29 healthy individuals. Our results showed that both bacterial and fungal diversity were nearly normalized in recovered patients. The relative abundance of some specific bacteria and fungi, primarily opportunistic pathogens, decreased in recovered patients (RPs), while the abundance of butyrate-producing organisms increased in these patients. Moreover, these differences were still present for some organisms at 12 months after recovery, indicating the need for long-term monitoring of COVID-19 patients after virus clearance.

During the braking process of electric vehicles, both the regenerative braking system (RBS) and anti-lock braking system (ABS) modulate the hydraulic braking force, leading to control conflict that impacts the effectiveness and real-time capability of coordinated control. Aiming to enhance the coordinated control effectiveness of RBS and ABS within the electro-hydraulic composite braking system, this paper proposes a coordinated control strategy based on explicit model predictive control (eMPC-CCS). Initially, a comprehensive braking control framework is established, combining offline adaptive control law generation, online optimized control law application, and state compensation to effectively coordinate braking force through the electro-hydraulic system. During offline processing, eMPC generates a real-time-oriented state feedback control law based on real-world micro trip segments, improving the adaptiveness of the braking strategy across different driving conditions. In the online implementation, the developed three-dimensional eMPC control laws, corresponding to current driving conditions, are invoked, thereby enhancing the potential for real-time braking strategy implementation. Moreover, the state error compensator is integrated into eMPC-CCS, yielding a state gain matrix that optimizes the vehicle braking status and ensures robustness across diverse braking conditions. Lastly, simulation evaluation and hardware-in-the-loop (HIL) testing manifest that the proposed eMPC-CCS effectively coordinates the regenerative and hydraulic braking systems, outperforming other CCSs in terms of braking energy recovery and real-time capability.

With the rapid development of the intelligent driving technology, achieving accurate path planning for unmanned vehicles has become increasingly crucial. However, path planning algorithms face challenges when dealing with complex and ever-changing road conditions. In this paper, aiming at improving the accuracy and robustness of the generated path, a global programming algorithm based on optimization is proposed, while maintaining the efficiency of the traditional A* algorithm. Firstly, turning penalty function and obstacle raster coefficient are integrated into the search cost function to increase the adaptability and directionality of the search path to the map. Secondly, an efficient search strategy is proposed to solve the problem that trajectories will pass through sparse obstacles while reducing spatial complexity. Thirdly, a redundant node elimination strategy based on discrete smoothing optimization effectively reduces the total length of control points and paths, and greatly reduces the difficulty of subsequent trajectory optimization. Finally, the simulation results, based on real map rasterization, highlight the advanced performance of the path planning and the comparison among the baselines and the proposed strategy showcases that the optimized A* algorithm significantly enhances the security and rationality of the planned path. Notably, it reduces the number of traversed nodes by 84%, the total turning angle by 39%, and shortens the overall path length to a certain extent.

The aim of our study was to explore circular RNA (circRNA) expression profiles associated with human endometrial carcinoma (EC) and to analyse the molecular mechanisms involved in cancer development and their potential clinical importance. Differential expression profiles were revealed by Arraystar human circRNA microarray analysis. The results of the circRNA microarray were confirmed by quantitative real-time PCR. Interactions between circRNAs and microRNAs (miRNAs) were predicted using Arraystar’s miRNA target prediction software. The functions of the circRNA-miRNA coexpression network were identified by KEGG pathway analysis and GO analysis. Compared with para-tumorous tissues, 14 genes were significantly upregulated and 12 genes were significantly downregulated in EC tissues (P

Abstract Background Near 70% of hepatocellular carcinoma (HCC) recurrence is early recurrence within 2-year post surgery. Long non-coding RNAs (lncRNAs) are intensively involved in HCC progression and serve as biomarkers for HCC prognosis. The aim of this study is to construct a lncRNA-based signature for predicting HCC early recurrence. Methods Data of RNA expression and associated clinical information were accessed from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) database. Recurrence associated differentially expressed lncRNAs (DELncs) were determined by three DEG methods and two survival analyses methods. DELncs involved in the signature were selected by three machine learning methods and multivariate Cox analysis. Additionally, the signature was validated in a cohort of HCC patients from an external source. In order to gain insight into the biological functions of this signature, gene sets enrichment analyses, immune infiltration analyses, as well as immune and drug therapy prediction analyses were conducted. Results A 4-lncRNA signature consisting of AC108463.1, AF131217.1, CMB9-22P13.1, TMCC1-AS1 was constructed. Patients in the high-risk group showed significantly higher early recurrence rate compared to those in the low-risk group. Combination of the signature, AFP and TNM further improved the early HCC recurrence predictive performance. Several molecular pathways and gene sets associated with HCC pathogenesis are enriched in the high-risk group. Antitumor immune cells, such as activated B cell, type 1 T helper cell, natural killer cell and effective memory CD8 T cell are enriched in patients with low-risk HCCs. HCC patients in the low- and high-risk group had differential sensitivities to various antitumor drugs. Finally, predictive performance of this signature was validated in an external cohort of patients with HCC. Conclusion Combined with TNM and AFP, the 4-lncRNA signature presents excellent predictability of HCC early recurrence.

ObjectiveChromosomal 1q21.1 deletions and duplications are genomic disorders that are usually diagnosed postnatally. However, the genotype–phenotype correlations of 1q21.1 copy number variants (CNVs) during the prenatal period are still not clear. This study aimed to provide a systematic summary of prenatal phenotypes for such genomic disorders.MethodsIn total, 26 prenatal amniotic fluid samples diagnosed with 1q21.1 microdeletions/microduplications were obtained from pregnant women who opted for invasive prenatal testing. Karyotypic analysis and chromosomal microarray analysis (CMA) were performed for all cases simultaneously. The pregnancy outcomes and health conditions after birth in all cases were followed up. Meanwhile, prenatal cases with 1q21.1 microdeletions or microduplications in the literature were retrospectively collected.ResultsIn total, 11 pregnancies (11/8,252, 0.13%) with 1q21.1 microdeletions and 15 (15/8,252, 0.18%) with 1q21.1 microduplications were identified. Among these 1q21.1 CNVs, 4 cases covered the thrombocytopenia-absent radius (TAR) region, 16 cases covered the 1q21.1 recurrent microdeletion/microduplication region, and 6 cases covered all regions mentioned above. The prenatal abnormal ultrasound findings were recorded in four participants with 1q21.1 deletions and seven participants with 1q21.1 duplications. Finally, three cases with 1q21.1 deletions and five with 1q21.1 duplications terminated their pregnancies.ConclusionIn the prenatal setting, 1q21.1 microdeletions were associated with increased nuchal translucency (NT), anomalies of the urinary system, and cardiovascular abnormalities, while 1q21.1 microduplications were correlated with cardiovascular malformations, nasal bone dysplasia, and increased NT. In addition, cerebral ventriculomegaly might be correlated with 1q21.1 microduplications. Considering the variable expressivity and incomplete penetrance of 1q21.1 CNVs, long-term follow-up after birth should be carried out in these cases.

Abstract Currently X‐ray images are clinically graded by experienced clinicians using the Kellgren and Lawrence (KL) scoring method. However, individual scoring is subjective and error prone. This study proposes an approach for automated knee osteoarthritis classification based on deep neural networks. The knee X‐ray images are first pre‐processed with frequency‐domain filtering and histogram normalisation, making the trabecular bone texture more obvious and benefiting the subsequent classification task. Then, a two‐step classification strategy is proposed by extracting the joint centre based on the VGG network and classifying osteoarthritis grades based on the ResNet‐50 network. In addition, a rebalance operation is proposed to deal with the dataset unbalance problem, and a quick search technique is proposed to improve the iterative search efficiency for the joint centre. With all of these techniques, a classification accuracy of 81.41% is obtained, which is higher compared to the state‐of‐the‐art approaches.

Abstract Background Partial trisomy of the long arm of chromosome 11 is a rare cytogenetic abnormality. It has been characterized by variable sized duplications that lead to a range of phenotypes including growth retardation, developmental delay/intellectual disability, and distinctive craniofacial abnormalities. Congenital heart defects, skeletal abnormalities, urogenital anomalies, and hypotonia are found in some affected individuals. Methods We describe a 16-year-old patient presented with most of the hallmark phenotypes of trisomy 11q syndrome as well as exhibiting symptoms of hearing loss, seizures, and abnormal endocrinological and ophthalmological findings. Routine chromosome analysis and subsequent chromosomal microarray analysis (CMA) were performed to detect genetic abnormalities in this patient. Results We identified an abnormal male karyotype with a derivative chromosome 4 due to an unbalanced translocation between chromosomes 4 and chromosome 11. The CMA results revealed a 56 Mb duplication of chromosome 11q14.1-qter and a 874 Kb terminal deletion of the short arm of chromosome 4. Conclusion A genomic imbalance resulting in partial trisomy 11q was found in a patient with multiple congenital anomalies. We compared the phenotypes of all known “pure” trisomy 11q cases in the literature and find that trisomy 11q23-qter is both recurrent and the most common cytogenetic abnormality found in the reported cases. It is associated with the core features of trisomy 11q syndrome. Graphical abstract

The signaling pathways and networks regulating expression of chondroitin sulfate proteoglycan 4 (CSPG4), a cancer-related protein that serves as a receptor for Clostridiodes difficile TcdB, are poorly defined. In this study, TcdB-resistant/CSPG4-negative HeLa cells were generated by exposure to increasing concentrations of the toxin. The cells that emerged (HeLa R5) lost expression of CSPG4 mRNA and were resistant to binding by TcdB. mRNA expression profiles paired with integrated pathway analysis correlated changes in the Hippo and estrogen signaling pathways with a CSPG4 decrease in HeLa R5 cells. Both signaling pathways altered CSPG4 expression when modulated chemically or through CRISPR-mediated deletion of key transcriptional regulators in the Hippo pathway. Based on the in vitro findings, we predicted and experimentally confirmed that a Hippo pathway inactivating drug (XMU-MP-1) provides protection from C. difficile disease in a mouse model. These results provide insights into key regulators of CSPG4 expression and identify a therapeutic for C. difficile disease.

Abstract MAX phases (Ti3SiC2, Ti3AlC2, V2AlC, Ti4AlN3, etc.) are layered ternary carbides/nitrides, which are generally processed and researched as structure ceramics. Selectively removing A layer from MAX phases, MXenes (Ti3C2, V2C, Mo2C, etc.) with two-dimensional (2D) structure can be prepared. The MXenes are electrically conductive and hydrophilic, which are promising as functional materials in many areas. This article reviews the milestones and the latest progress in the research of MAX phases and MXenes, from the perspective of ceramic science. Especially, this article focuses on the conversion from MAX phases to MXenes. First, we summarize the microstructure, preparation, properties, and applications of MAX phases. Among the various properties, the crack healing properties of MAX phase are highlighted. Thereafter, the critical issues on MXene research, including the preparation process, microstructure, MXene composites, and application of MXenes, are reviewed. Among the various applications, this review focuses on two selected applications: energy storage and electromagnetic interference shielding. Moreover, new research directions and future trends on MAX phases and MXenes are also discussed.

Aims: To explore the contagiousness and new SARS-CoV-2 mutations in pediatric COVID-19.Methods: This cohort study enrolled all pediatric patients admitted to 8 hospitals in Zhejiang Province of China between 21 January and 29 February 2020, their family members and close-contact classmates. Epidemiological, demographic, clinical and laboratory data were collected. Bioinformatics was used to analyze the features of SARS-CoV-2. Individuals were divided into 3 groups by the first-generation case: Groups 1 (unclear), 2 (adult), and 3 (child). The secondary attack rate (SAR) and R0 were compared among the groups.Results: The infection rate among 211 individuals was 64% (135/211). The SAR in Groups 2 and 3 was 71% (73/103) and 3% (1/30), respectively; the median R0 in Groups 2 and 3 was 2 (range: 1-8) and 0 (range: 0-1), respectively. Compared with adult cases, the SAR and R0 of pediatric cases were significantly lower (p

Bone drilling is a common procedure in orthopedic surgery and is frequently attempted using robot-assisted techniques. However, drilling on rigid, slippery, and steep cortical surfaces, which are frequently encountered in robot-assisted operations due to limited workspace, can lead to tool path deviation. Path deviation can have significant impacts on positioning accuracy, hole quality, and surgical safety. In this paper, we consider the deformation of the tool and the robot as the main factors contributing to path deviation. To address this issue, we establish a multi-stage mechanistic model of tool–bone interaction and develop a stiffness model of the robot. Additionally, a joint stiffness identification method is proposed. To compensate for path deviation in robot-assisted bone drilling, a force-position hybrid compensation control framework is proposed based on the derived models and a compensation strategy of path prediction. Our experimental results validate the effectiveness of the proposed compensation control method. Specifically, the path deviation is significantly reduced by 56.6%, the force of the tool is reduced by 38.5%, and the hole quality is substantially improved. The proposed compensation control method based on a multi-stage mechanistic model and joint stiffness identification method can significantly improve the accuracy and safety of robot-assisted bone drilling.

The multi-level disturbance of underground and surface caused by coal mining activities intensifies the deterioration of the ecological environment in the mining area. Among them, the uneven settlement caused by coal mining is the most intuitive manifestation of surface environmental damage. The uneven settlement in the mining area has the characteristics of large settlement magnitude and severe deformation. Therefore, based on 15 Sentinel-1A image data, this paper uses three methods: SBAS InSAR, continuous D-InSAR and offset tracking technology to monitor the surface deformation of the mining area. The results show that the continuous D-InSAR technology SBAS-InSAR technology is applied to the small deformation in the edge area of the subsidence basin. The mining area with low gradient subsidence of SBAS-InSAR can obtain better performance than continuous D-InSAR technology. The offset tracking technique is used to monitor the large gradient deformation in the center of the subsidence basin. Therefore, this paper proposes to expand the quantitative analysis through the spatial coherence threshold and the accuracy and successful image elements of the interference fringe displacement. Combine the advantages of the three methods and overcome the shortcomings of each method, fuse the deformation information of the three methods, and obtain the deformation law of the whole surface subsidence. The results show that the mean absolute error (MAE1-1) of continuity D-InSAR is 0.92 m, the mean absolute error (MAE2-1) of SBAS-InSAR is 0.94 m, and the mean absolute error (MAE3-1) of Offset-tracking is 0.25 m. The results of this fusion method are in good agreement with the measured data, and the mean absolute error (MAE4-1) of vertical displacement is 7 cm. Therefore, the fusion method has advantages over individual methods and provides a new idea in monitoring the large gradient deformation of coal mining subsidence in mining areas.

ABSTRACT Infections caused by antibiotic-resistant pathogens pose high risks to human and animal health worldwide. In recent years, the environment and wildlife as major sources and reservoirs of antibiotic resistance genes (ARGs) are being increasingly investigated. There have been many reports on bacterial community in ticks, but little is known about ARGs they carry, and the correlation between bacterial and ARGs in wild ticks also remains unknown. Here, the profiles of microbial community and antibiotic resistome in wild tick species were investigated using high-throughput 16S rRNA sequencing and smart chip-based high-throughput quantitative PCR approach (HT-qPCR), respectively. We found that bacterial composition in wild tick species is variable; the sequenced reads from all samples were assigned to 37 different phyla at the phylum level. The dominant phylum was Proteobacteria, which accounted for 75.60 ± 10.34%, followed by Bacteroidetes accounting for 13.78 ± 11.68% of the total bacterial community. In total, 100 different ARGs across 12 antibiotic classes and 20 mobile genetic elements (MGEs) were identified by HT-qPCR, and among them aminoglycosides, multidrug, macrolide-clinolamide-streptogramin B, and tetracycline resistance genes were the dominant ARG types. Co-occurrence patterns revealed by network analysis showed that eight bacterial genera may serve as the potential hosts for different ARGs. For the first time, this study provides comprehensive overview of the diversity and abundance of ARGs in wild ticks and highlights the possible role of wild ticks as ARG disseminators into the environment and vertebrate hosts, with implications for human and animal health. IMPORTANCE The emergence of antibiotic-resistant bacteria poses serious threat to the public health around the world. Ticks are obligate hematophagous ectoparasites, surviving via feeding on the blood of various animal hosts. Although some previous studies have confirmed wild ticks carried various bacterial community, the role of wild ticks in the antibiotic resistance remains unknown. Here, identification of microbial community and antibiotic resistome in wild tick species revealed that wild ticks are the reservoir, postulated potential spreaders of antibiotic resistance. Our findings highlight the contribution of wild ticks to the maintenance and dissemination of ARGs, and the associated health risks.

Abstract Background Acute myeloid leukemia (AML) is a complex hematological disease characterized by genetic and clinical heterogeneity. The identification and understanding of chromosomal abnormalities are important for the diagnosis and management of AML patients. Compared with recurrent chromosomal translocations in AML, t(8;16)(p11.2;p13.3) can be found in any age group but is very rare and typically associated with poor prognosis. Methods Conventional cytogenetic studies were performed among 1,824 AML patients recorded in our oncology database over the last 20 years. Fluorescence in situ hybridization (FISH) was carried out to detect the translocation fusion. Array comparative genome hybridization (aCGH) was carried out to further characterize the duplication of chromosomes. Results We identified three AML patients with t(8;16)(p11.2;p13.3) by chromosome analysis. Two of the three patients, who harbored an additional 1q duplication, were detected by FISH and aCGH. aCGH characterized a 46.7 Mb and 49.9 Mb gain in chromosome 1 at band q32.1q44 separately in these two patients. One patient achieved complete remission (CR) but relapsed 3 months later. The other patient never experienced CR and died 2 years after diagnosis. Conclusion A 1q duplication was detected in two of three AML patients with t(8;16)(p11.2;p13.3), suggesting that 1q duplication can be a recurrent event in AML patients with t(8;16). In concert with the findings of previous studies on similar patients, our work suggests that 1q duplication may also be an unfavorable prognostic factor of the disease.

Abstract Background Severe fever and thrombocytopenia bunyavirus (SFTSV) infection causes severe fever and thrombocytopenia syndrome with high mortality. It is extremely rare that a transmitting tick can be directly captured in bite wounds, and that SFTSV can be isolated from both the captured tick and patient’s serum to establish a solid pathogen diagnosis. Case presentation We report a case infected with severe fever and thrombocytopenia bunyavirus. The 69-year-old male patient presented with fever and tenderness on two lymph nodes in the right groin. A visible tick bite mark appeared on right upper quadrant of the patient’s abdomen, and a live tick was captured in the bite wound upon physical examination. The virus was detected in both the blood of the patient and in the tick that stayed in the bite wound for 7 days. The phylogenetic analysis indicated that the SFTSV isolated from the tick and the patient’s serum sample belonged to type B, in which the L/S segment of these two isolates shared 100% homology, while the M segment had 99.9% homology. The bitten patient was given various supportive care, but eventually died of multiple organ failure. Conclusion The present case provides strong evidence of SFTSV transmission from H. longicornis to humans, and suggests that direct cross-species transmission can occur without additional intermediate hosts.

Two kinds of high Cr white iron (HCWI) composites reinforced with directly added TiC (TiC/HCWI) and in situ formed TiCx (TiCx/HCWI) have been successfully synthesized by powder metallurgy method. The directly added TiC grains are irregular in shape with a mean size of about 2−4 μm, but the in situ formed TiCx grains from the decomposition of Ti3AlC2 are spherical and about 1–2 μm in size. The microstructure, mechanical properties and wear resistance of the two composites were compared. The in situ TiCx/HXCWI composite possesses finer microstructures and superior mechanical and wear resistant properties than TiC/HCWI composite. The phase composition and microstructure were characterized with X-ray diffraction analysis, scanning electron microscopy and transmission electron microscopy.

Abstract Common fragile sites (CFSs) are large chromosomal regions that exhibit breakage on metaphase chromosomes upon replication stress. They become preferentially unstable at the early stage of cancer development and are hotspots for chromosomal rearrangements in cancers. Increasing evidence has highlighted the complexity underlying the instability of CFSs, and a combination of multiple mechanisms is believed to cause CFS fragility. We will review recent advancements in our understanding of the molecular mechanisms underlying the maintenance of CFS stability and the relevance of CFSs to cancer-associated genome instability. We will emphasize the contribution of the structure-prone AT-rich sequences to CFS instability, which is in line with the recent genome-wide study showing that structure-forming repeat sequences are principal sites of replication stress.

In robot-assisted endoscopic nasal surgery, due to the slender and complicated nasal cavity and sinus anatomical structure, the nasal endoscope of robot end-effector is prone to injure surrounding tissues during surgical approaches. In order to improve the movement safety of the endoscope in robot-assisted endoscopic nasal surgery, a path planning method for endoscopic surgical approaches based on medical image pixel map searching is proposed in this paper, and safe surgical paths from the nasal entrance point to the operating areas are obtained. Firstly, through the trajectory analysis of nasal endoscope tip during surgery, the path planning requirements of endoscope tip are analyzed and obtained. Then, considering the slender and complicated anatomy of the nasal cavity, a binarized three-dimensional grid map containing the spatial anatomy of the nasal cavity is constructed based on the patient's CT medical image sequence. The endoscopic surgical approaches are searched and optimized by introducing the A-star algorithm, and safe surgical paths from the nasal entrance point to the operating areas are obtained. Finally, a virtual nasal endoscopy system is developed and tested on a head model containing nasal tissue, and the effectiveness of the planned surgical paths is verified by automatic virtual nasal endoscopy browsing experiment.

Sprouty-related, EVH1 domain-containing protein 1 (SPRED1) has been identified as a novel tumor suppressor gene in acute myeloid leukemia (AML). Previous studies showed that SPRED1 methylation levels were significantly increased in AML patients, making it an interesting candidate for further investigations. To confirm the association of SPRED1 methylation, clinical parameters, and known molecular prognosticators and to identify the impact of methylation level on treatment outcome, we conducted this study in a larger cohort of 75 AML patients. Significantly increased methylation levels of SPRED1 were detected at four of ten CpG units by quantitative high-resolution mass spectrometry-based approach (MassARRAY) in AML patients. Whereas overall survival (OS) and relapse-free survival (RFS) showed no statistical difference between hypermethylation and hypomethylation subgroups, the relationship between methylation level and treatment response was indicated in paired samples from pre- and post-induction. To determine the possible mechanism of SPRED1 methylation in AML, we performed in vitro experiments using THP-1 cells, as the latter showed the highest methylation level (determined by utilizing bisulfite modification) among the three AML cell lines we tested. When treated with 5-AZA and lentivirus transfection, upregulated SPRED1 expression, decreased cell proliferation, increased cell differentiation and apoptosis, and inactivated phosphorylated extracellular signal-regulated kinase (p-ERK) were detected in THP-1 cells. These results show that demethylation of SPRED1 can inhibit the proliferation of AML cells and promote their differentiation and apoptosis, possibly by the ERK pathway. The hypermethylation of SPRED1 is a potential therapeutic target for AML.

A novel nitrogen-free austenitic stainless steel with a hardness of >200 HV was developed using metal injection molding (MIM), and the effects of graphite addition on the sintering behavior, mechanical properties, and corrosion resistance of heat-treated samples were investigated. The results show that a certain amount of graphite addition increases the relative density to >98%. In samples with the addition of 0–500 ppm graphite, large grain-boundary precipitates reduced corrosion resistance and ductility. In contrast, when graphite addition was increased to 750–1500 ppm, fine precipitates, which exhibited coherent lattice relationships with the matrix, were uniformly distributed within the grain and grain boundaries; this significantly improved the mechanical properties and corrosion resistance. The tensile strength and elongation intervals were 546.94–608.62 MPa and 29.68–24.63%, respectively. To prevent overburning, samples with a graphite content higher than 3000 ppm were sintered at a lower temperature, resulting in a higher porosity and lower performance.

The mechanical coupling of multiple powertrain components makes the energy management of 4-wheel-drive (4WD) plug-in fuel cell electric vehicles (PFCEVs) relatively complex. Optimizing energy management strategies (EMSs) for this complex system is essential, aiming at improving the vehicle economy and the adaptability of operating conditions. Accordingly, a novel adaptive equivalent consumption minimization strategy (A-ECMS) based on the dragonfly algorithm (DA) is proposed to achieve coordinated control of the powertrain components, front and rear motors, as well as the fuel cell system and the battery. To begin with, the equivalent consumption minimization strategy (ECMS) with extraordinary instantaneous optimization ability is used to distribute the vehicle demand power into the front and rear motor power, considering the different motor characteristics. Subsequently, under the proposed novel hierarchical energy management framework, the well-designed A-ECMS based on DA empowers PFCEVs with significant energy-saving advantages and adaptability to operating conditions, which are achieved by precise power distribution considering the operating characteristics of the fuel cell system and battery. These provide state-of-the-art energy-saving abilities for the multi-degree-of-freedom systems of PFCEVs. Lastly, a series of detailed evaluations are performed through simulations to validate the improved performance of A-ECMS. The corresponding results highlight the optimal control performance in the energy-saving performance of A-ECMS.

An energy management strategy is a key technology used to exploit the energy-saving potential of a plug-in hybrid electric vehicle. This paper proposes the environmental perceiver-based equivalent consumption minimization strategy (EP-ECMS) for parallel plug-in hybrid vehicles. In this method, the traffic characteristic information obtained from the intelligent traffic system is used to guide the adjustment of the equivalence factor, improving the environmental adaptiveness of the equivalent consumption minimization strategy (ECMS). Two main works have been completed. First, a high-accuracy environmental perceiver was developed based on a graph convolutional network (GCN) and attention mechanism to complete the traffic state recognition of all graph regions based on historical information. Moreover, it provides the grade of the corresponding region where the vehicle is located (for the ECMS). Secondly, in the offline process, the search for the optimal equivalent factor is completed by using the Harris hawk optimization algorithm based on the representative working conditions under various grades. Based on the identified traffic grades in the online process, the optimized equivalence factor tables are checked for energy management control. The simulation results show that the improved EP-ECMS can achieve 7.25% energy consumption optimization compared with the traditional ECMS.

Accurate traffic prediction is significant in intelligent cities’ safe and stable development. However, due to the complex spatiotemporal correlation of traffic flow data, establishing an accurate traffic prediction model is still challenging. Aiming to meet the challenge, this paper proposes SGGformer, an advanced traffic grade prediction model which combines a shifted window operation, a multi-channel graph convolution network, and a graph Transformer network. Firstly, the shifted window operation is used for coarsening the time series data, thus, the computational complexity can be reduced. Then, a multi-channel graph convolutional network is adopted to capture and aggregate the spatial correlations of the roads in multiple dimensions. Finally, the improved graph Transformer based on the advanced Transformer model is proposed to extract the long-term temporal correlation of traffic data effectively. The prediction performance is evaluated by using actual traffic datasets, and the test results show that the SGGformer proposed exceeds the state-of-the-art baseline.

BackgroundSubmicroscopic segmental imbalances detected by array-comparative genomic hybridization (array-CGH) were discovered to be common in chronic myeloid leukemia (CML) patients with t(9;22) as the sole chromosomal anomaly. To confirm the findings of the previous study and expand the investigation, additional CML patients with t(9;22) as the sole chromosomal anomaly were recruited and copy number variants (CNVs) were searched for.MethodsKaryotyping tests were performed on 106 CML patients during January 2010–September 2019 in our Genetics Laboratory. Eighty-four (79.2%) patients had the Philadelphia (Ph) chromosome as the sole chromosomal anomaly. Only 49(58.3%) of these 84 patients had sufficient marrow or leukemia blood materials to additionally be included in the array-CGH analysis. Fluorescence in situ hybridization (FISH) was carried out to confirm the genes covered by the deleted or duplicated regions of the CNVs.Results11(22.4%) out of the 49 patients were found to have one to three somatic segmental somatic segmental (CNVs), including fourteen deletions and three duplications. The common region associated with deletions was on 9q33.3-34.12. Identified in five (45.5%) of the 11 positive patients with segmental CNVs, the deletions ranged from 106 kb to 4.1 Mb in size. Two (18.2%) cases had a deletion in the ABL1-BCR fusion gene on der (9), while three (27.3%) cases had a deletion in the ASS1 gene. The remaining CNVs were randomly distributed on different autosomes.ConclusionSubtle genomic CNVs are relatively common in CML patients without cytogenetically visible additional chromosomal aberrations (ACAs). Long-term studies investigating the potential impact on patient prognosis and treatment outcome is underway.

Summary: The structure-specific endonuclease ERCC1/XPF plays an important role in nucleotide excision repair and interstrand cross-link repair. In this study, we identified new functions of ERCC1/XPF in DNA double-strand break (DSB) repair. We found that the conserved function of ERCC1/XPF to remove non-homologous sequences at DSBs is a rate-limiting step for homologous recombination in mammalian cells, and more importantly, we uncovered an indispensable role of ERCC1/XPF in repair of DSBs containing DNA secondary structures, including the structure-prone AT-rich DNA sequences derived from common fragile sites and G-quadruplexes (G4s). We also demonstrated a synthetic lethal interaction of XPF with DNA translocase FANCM that is involved in removing DNA secondary structures. Furthermore, inactivation of XPF sensitizes FANCM-deficient cells to G4-interacting compounds. These results suggest an important function of ERCC1/XPF in protecting DNA secondary structures and provide a rationale for targeted treatment of FANCM-deficient tumors through inhibition of XPF. : Biological Sciences; Molecular Biology; Cell Biology Subject Areas: Biological Sciences, Molecular Biology, Cell Biology

Abstract Background MYCN amplification directly correlates with the clinical course of neuroblastoma and poor patient survival, and serves as the most critical negative prognostic marker. Although fluorescence in situ hybridization (FISH) remains the gold standard for clinical diagnosis of MYCN status in neuroblastoma, its limitations warrant the identification of rapid, reliable, less technically challenging, and inexpensive alternate approaches. Methods In the present study, we examined the concordance of droplet digital PCR (ddPCR, in combination with immunohistochemistry, IHC) with FISH for MYCN detection in a panel of formalin-fixed paraffin-embedded (FFPE) human neuroblastoma samples. Results In 112 neuroblastoma cases, ddPCR analysis demonstrated a 96–100% concordance with FISH. Consistently, IHC grading revealed 92–100% concordance with FISH. Comparing ddPCR with IHC, we observed a concordance of 95–98%. Conclusions The results demonstrate that MYCN amplification status in NB cases can be assessed with ddPCR, and suggest that ddPCR could be a technically less challenging method of detecting MYCN status in FFPE specimens. More importantly, these findings illustrate the concordance between FISH and ddPCR in the detection of MYCN status. Together, the results suggest that rapid, less technically demanding, and inexpensive ddPCR in conjunction with IHC could serve as an alternate approach to detect MYCN status in NB cases, with near-identical sensitivity to that of FISH.

The pore ratio is an important parameter affecting the stability and safety of tailings reservoirs; however, the relationship between the pore ratio and physical properties of tailings sand has not been researched in-depth. In this paper, using the tailings from a tungsten mine in southern Shaanxi as a case study, the correlation between the minimum void ratio and related parameters is analyzed, based on laboratory test data, and the optimal marginal distribution function of the parameters is determined. The Gumbel-Hougard copula function that best describes the correlation between parameters is identified, and it is used to establish the joint probability distribution model of the three parameters, and the guarantee rate α is introduced to estimate and analyze the minimum void ratio. The results show that the optimal edge distribution of the fine particle content and specific gravity follows a truncated normal distribution, and the optimal edge distribution of the minimum void ratio follows a logarithmic normal distribution. According to AIC criterion, the Gumbel-Hougard copula is the best three-dimensional copula function to fit the minimum void ratio and related parameters. When the guarantee rate α is 0.485, the joint probability distribution model achieves optimal performance in terms of estimating the minimum void ratio. The maximum error of the estimation is 1.99%, which is verified through data, and the estimation meets the requirements for practical engineering. The method proposed in this paper uses the existing measured data to establish a joint probability distribution model and combines the collected fine particle content and specific gravity data with the guarantee rate to estimate the minimum void ratio, providing a novel basis for the study of the physical properties of tailings.

Minimum void ratio of tailings and its value change with fine content and are key design parameters for tailing consolidation and seepage stability. Based on the distribution of tailing grains with the sedimentary beach, we establish a minimum void ratio model for tailing grain in binary size, which requires only two parameters (ε and ω). Calibrations of the model using 168 groups of tests (22 kinds of grain size ratios with 7-9 kinds of fine contents) show two parameters that are fitting for power function, and the exponent values increase with the dominant grain size expanded. Besides, the exponent values are related to the equivalent grain size ratio, dominant grain size, and shape characteristics. The minimum void ratios with fine content are predicted under the derived model. Good agreement was obtained between the predictions and measurements, and the average discrepancies are less than 10%. And optimal void ratio and optimal fine content can be predicted, and the values are in good agreement with the experimental ones. Furthermore, based on the predicted optimal void ratio, the exponential relationship between the optimal void ratio and the equivalent grain size ratio may have no influence on the derived dominant grain size and shape characteristics. For tailings, further work is needed to verify if the derived exponential relationship between the optimal void ratio and the equivalent grain size ratio is valid.

The shear behavior of saturated loess was examined by performing a series of ring shear tests with different shearing rates. The effects of shearing rates on the shear behavior of saturated loess with different normal stress are presented and discussed. The results showed that peak shear strength and steady-state shear strength were greater when the shearing rate was low and vice versa. Compared with high and low shearing rates, the maximum strength reduction ratios of peak shear strength and steady-state shear strength were 34.2% and 37.2%, respectively. The axial displacement during shearing was measured and was found to increase with increasing shear displacement in all tests. A comparison of sample height reduction (when the shear rate was stopped) found that the low shearing rate test sample underwent a much greater reduction than the high shearing rate test sample; however, the variation reduction range was within 4 mm. Monitoring the pore-water pressure during the shearing process revealed that it increased with shear displacement, and a higher excess pore-water pressure was generated within the shear zone during the fast-shearing process. Comparing the particle size distribution of the samples after the test and the original sample showed that the particles were crushed during the shearing process. The percentage that was finer than 0.005 mm increased with shearing rates and normal stress, and the soil structure implosion became more pronounced with increasing normal stress.

Underground structures in earthquake-prone zones should be designed to withstand both static overburden pressures and earthquake shocks. This paper presents a case study on a large-span powerhouse cavern. With seismic data selected from past earthquake records, lab and in situ tests of the cavern’s geological and geomechanical conditions were performed to analyze the static and dynamic stability of the cavern through the continuum modeling approach. Performance analyses via both 2D and 3D modeling were carried out under seismic conditions and for selected design ground motions. The dynamic response of the surrounding rock mass and of the reinforcement system was detected. The results obtained will facilitate future stability analyses of large underground caverns constructed in the past on the basis of seismic design analyses and input data from post-earthquake records that were recently made available on the site.

The subchromosomal region 1q21.1 is one of the hotspots in the human genome for deletions and reciprocal duplications, owing to the existence of hundreds of segmental duplications. Recurrent deletions and duplications in this region are thought to be causative in patients with variable clinical manifestations. Based on the genomic locations, deletions and duplications at the 1q21.1 locus have been associated with distinguishable syndromes: chromosome 1q21.1 deletion syndrome, chromosome 1q21.1 duplication syndrome, and thrombocytopenia-absent radius (TAR) syndrome, which is partially due to deletions at the proximal 1q21.1 region. We report here diverse, recurrent deletions and duplications at the 1q21.1 locus in 36 patients from a cohort of 5,200 individuals. Among the 36 patients, 18 patients carry 1q21.1 deletions, nine individuals have reciprocal duplications at 1q21.1, two patients share an identical short deletion, and the remaining seven possess variable sizes of duplications at the proximal 1q21.1 region. Furthermore, we provide cytogenetic characterization and detailed clinical features for each patient. Notably, duplications at the proximal 1q21.1 region have not been associated with a defined disorder in publications. However, recurrent duplications at the proximal 1q21.1 region among the seven patients strongly suggested that the variants are likely pathogenic. The common phenotypical features of those disorders are also summarized to facilitate clinical diagnoses and genetic counseling.