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Abstract Recent years have witnessed the remarkable progress in wireless communication systems due to the escalating demand for higher data rates, improved reliability, and increased energy efficiency. In this regard, Non-Orthogonal Multiple Access (NOMA) has emerged as a promising technology, enhancing spectral efficiency and accommodating multiple users concurrently within the same time and frequency resources. Simultaneously, the energy harvesting has surfaced as a sustainable solution, converting ambient environmental energy into usable electrical power for operating communication nodes. This paper proposes a cooperative NOMA transmission scheme integrating energy harvesting and utilizing Least Squares (LS) channel estimation for precise Channel State Information (CSI) acquisition. The objective is to establish an optimal communication path from source to destination. Relay selection methods: Optimal Relay Selection (ORS) and Max-Min Relay Selection (MMRS), are compared, focusing on their impact on the system performance. The analysis considers the influence of the number of relays and power allocation factor on the system, with a specific emphasis on the outage probability expressions. Comparative analysis between the cooperative-NOMA and the traditional cooperative relaying without NOMA reveals the superior performance of the cooperative-NOMA. Additionally, the ORS scheme outperforms MMRS in terms of the outage performance.

To improve the load-bearing capacity and the rotation range about the normal of the moving platform in a spherical parallel mechanism (SPM), a type synthesis method for spherical hybrid mechanisms (SHMs) with fixed centers of rotation is proposed by coupling a serial transmission chain with the central passive limb chain of the SPM near its center area. Based on the analysis of the spherical mechanism configuration’s research status with a fixed rotation center, a method for systematically synthesizing SHMs is given, and four types of limb chains are developed. The possible limb constraint systems provided by each type of limb chain are analyzed via screw theory, and the type synthesis of each type of limb chain is carried out. Screening rules are proposed to obtain the preferred limb chains from the limb chain configuration results. By selecting and permuting preferred limb chains based on the mechanism’s center position of rotation and the constraint type, a series of SHMs that rotate unrestricted about the normal of the moving platform are produced. Selecting the RBR-2RRR SHM as an example, its workspace, singularity, dexterity, and stiffness are analyzed to verify the effectiveness of the research. This work enriches the configuration types of SHMs and provides theoretical support for the design and applications of SHMs in engineering.

Abstract Background This study aimed to identify disease‐causing variants within a Chinese family affected by Birt–Hogg–Dubé syndrome (BHDS), which arises from an autosomal dominant inheritance pattern attributed to variants in the folliculin (FLCN) gene, recognized as a tumor suppressor gene. Methods A Chinese proband diagnosed with BHDS due to renal tumors underwent next‐generation sequencing (NGS), revealing a novel variant in the FLCN gene. Sanger sequencing was subsequently performed on blood samples obtained from family members to confirm the presence of this variant. Results A novel germline frameshift variant (NM_144997.5:c.977dup) was identified in five individuals among the screened family members, marking the first report of this variant. Additionally, a somatic frameshift variant (NM_144997.5:c.1252del) was detected in the renal tumors of the proband. No variant was detected in unaffected family members. Conclusions A novel heterozygous variant was identified in exon 9 of the FLCN gene, which broadens the spectrum of FLCN variants. We recommend that molecular analysis of the FLCN gene be performed in patients with suspected BHDS and their families.

Monostatic backscatter has garnered significant interest due to its distinct benefits in low-cost passive sensing. Observing and sensing with backscatter necessitates determining the phase and amplitude of the backscatter channel to identify the state of the target of interest. In the detection of multiple targets, colliding signals can distort the backscatter channel, complicating channel state recovery. It becomes even more challenging when multiple backscattering devices (BDs) are used. This paper proposes a novel channel estimation scheme to tackle the challenge, which is applied to a monostatic backscatter communication system with multiple reader antennas (RAs) and backscatter devices. Specifically, we propose a backscatter communication model and subsequently develop a de-interfering channel estimation framework that considers the ambient interference in the channel, named model-driven unfolded channel estimation (MUCE). To validate the effectiveness and advantages of the MUCE method, it is compared with the least square (LS) algorithm and convolutional neural network (CNN). The results prove that MUCE requires lower computational costs for the same channel estimation performance and achieves an optimal balance between estimation performance and computational expense.

Acute respiratory infections are mainly caused by viruses and the incidences of the infections are high in various populations, especially in young children, the elderly, and immunocompromised patients. Acute respiratory infections has resulted in high morbidity, mortality, and heavy disease burden worldwide. Therefore, effective prevention on virus-induced respiratory infections has become one of global issues of concern. Non-pharmaceutical interventions (NPIs, including personal protection, case isolation, travel restriction and other measures) are important ways to prevent respiratory virus infection and transmission. The NPIs implemented during COVID-19 pandemic not only effectively contained global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but also exerted an impact on the spread of other respiratory infectious viruses. In this article, we discussed changes in epidemiological characteristics of common respiratory viruses before and after the implementation of NPIs and reviewed the effects of NPIs on the transmission of respiratory infectious viruses.

To improve the workspace, linear displacement stiffness, and driving torque utilization of humanoid robot shoulder joint mechanisms, an offset-designed RBR-2RRR (R represents the revolute pair, and B represents the ball cage joint) spherical hybrid bionic shoulder joint configuration (SHBSJC) is proposed and its structural parameters are optimized. Firstly, the shoulder joint’s physiological structure is biomimetically designed, a prototype mechanism of RBR-2RRR SHBSJC is proposed, and its kinematics are solved. The deformation response of RBR-2RRR and 3-RRR under the same load is compared to verify the obtained configuration can improve the linear displacement stiffness. Considering the workspace and singularity, using the GCI and GDCI as optimization functions, the recommended and adopted values of structural parameters are obtained. The distribution diagrams of the LCI and LDCI demonstrate that the configuration meets performance expectations. To further increase the prototype mechanism’s workspace and match the human shoulder joint’s motion range, an offset-designed RBR-2RRR SHBSJC is proposed, and the offset angle, installation posture angle, and spatial mapping relationship of the mechanism are determined. The results of workspace comparison and virtual model machine action simulation indicate that the final configuration meets the workspace expectations. This work enriches the shoulder joint configuration types and has engineering application value.

Actuators based on moisture-sorption-responsive materials can convert moisture energy into mechanical/electrical energy, making the development of moisture-sorption materials a promising pathway for harnessing green energy to address the ongoing global energy crisis. The deformability of these materials plays a crucial role in the overall energy conversion performance, where moisture sorption capacity determines the energy density. Efforts to boost the moisture absorption capacity and rate have led to the development of a variety of moisture-responsive materials in recent years. These materials interact with water molecules in different manners and have shown diverse application scenarios. Here, in this review, we summarize the recent progress on moisture-sorption-responsive materials and their applications. We begin by categorizing moisture-sorption materials—biomaterials, polymers, nanomaterials, and crystalline materials—according to their interaction modes with water. We then review the correlation between moisture-sorption and energy harvesting performance. Afterwards, we provide examples of the typical applications using these moisture-sorption materials. Finally, we explore future research directions aimed at developing next-generation high-performance moisture-sorption materials with higher water uptake, tunable water affinity, and faster water absorption.

Aqueous zinc ion batteries (AZIBs) have garnered significant attention in large-scale static energy storage battery systems due to their low cost, high safety and environmental friendliness. However, it has some inherent problems during operation, such as the occurrence of side reactions (hydrogen evolution reaction, HER) and anode corrosion, formation of by-products and growth of metal dendrites. To analyze the mechanism of generation from aspect of the electrolyte solvation structure and make cell efficiency further improvements based on it, so we use DFT calculations to find the most stable solvation structure in AZIBs with ZnCl2 as the electrolyte and analyze it. We define the relative concentration Cr, and calculate different groups metal cation cluster structures such as [Zn(H2O)n]2+, [ZnCl(H2O)n]+, [ZnCl2(H2O)n] and [ZnCl3(H2O)n]‐ that exist at different Cr. We discuss the effect of different clusters formed due to the Cr variations on the battery performance in terms of three aspects: the structural conformation, the cluster characteristics (including the hydrogen bonding network, bond lengths, bond angles, as well as the electrostatic potential ESP) and the cluster performance (including the adsorption energy Ea, binding energy Eb, and desolvation energy Edes). The results shows that the electrolyte metal cation Zn2+ can be coordinated with up to six H2O molecules in first shell, and this metal cation solvation structure contributes to the occurrence and formation of side reactions and by-products, which reduces the battery efficiency. Increasing the electrolyte anion Cl− concentration by appropriately increasing the Cr helps to desolvate the metal cation cluster structure, which greatly improves the battery efficiency and suppresses the side reactions and by-products. Yet the improvement effect was not obviously further improved by further increasing the Cl− concentration.

In myocardial ischemia/reperfusion injury (MIRI), moderate mitophagy is a protective or adaptive mechanism because of clearing defective mitochondria accumulates during MIRI. However, excessive mitophagy lead to an increase in defective mitochondria and ultimately exacerbate MIRI by causing overproduction or uncontrolled production of mitochondria. Phosphatase and tensin homolog (PTEN)-induced kinase 1 (Pink1), Parkin, FUN14 domain containing 1 (FUNDC1) and B-cell leukemia/lymphoma 2 (BCL-2)/adenovirus E1B19KD interaction protein 3 (BNIP3) are the main mechanistic regulators of mitophagy in MIRI. Pink1 and Parkin are mitochondrial surface proteins involved in the ubiquitin-dependent pathway, while BNIP3 and FUNDC1 are mitochondrial receptor proteins involved in the non-ubiquitin-dependent pathway, which play a crucial role in maintaining mitochondrial homeostasis and mitochondrial quality. These proteins can induce moderate mitophagy or inhibit excessive mitophagy to protect against MIRI but may also trigger excessive mitophagy or insufficient mitophagy, thereby worsening the condition. Understanding the actions of these mitophagy mechanistic proteins may provide valuable insights into the pathological mechanisms underlying MIRI development. Based on the above background, this article reviews the mechanism of mitophagy involved in MIRI through Pink1/Parkin pathway and the receptor mediated pathway led by FUNDC1 and BNIP3, as well as the related drug treatment, aim to provide effective strategies for the prevention and treatment of MIRI.

BackgroundCervical cancer is primarily caused by HPV infection. The epidemiology of HPV infection in specific areas is of great meaning of guide cervical cancer screening and formulating HPV vaccination strategies. Here, we evaluated the epidemiological characteristics of HPV infection in Xiamen population.MethodsIn total, 159,049 cervical exfoliated cell samples collected from female outpatients in Women and Children’s Hospital, School of Medicine, Xiamen between January 2013 and July 2023 were analyzed. HPV DNA detection was performed using HPV genotyping kits (Hybribio Limited Corp, China). An analysis was conducted on the prevalence of HPV infection, taking into account factors such as age, year, and multiple patterns of HPV infection. The differences in prevalence among age groups and years were compared using χ2 test.ResultsThe overall prevalence of any 21 HPV genotypes was 18.4%, of which the high-risk HPV (HR-HPV) positive rate was 14.6%. The age-specific prevalence of HPV infection showed a bimodal distribution, with two distinct peaks, one at

Abstract Due to the inherent disorder and fluidity of water, precise machining of water through laser cutting are challenging. Herein we report a strategy that realizes the laser cutting machining of water through constructing hydrophobic silica nanoparticle-encased water pancakes with sub-millimeter depth. Through theoretical analysis, numerical simulation, and experimental studies, the developed process of nanoparticle-encased water pancake laser cutting and the parameters that affect cutting accuracy are verified and elucidated. We demonstrate that laser-fabricated water patterns can form diverse self-supporting chips (SSCs) with openness, transparency, breathability, liquid morphology, and liquid flow control properties. Applications of laser-fabricated SSCs to various fields, including chemical synthesis, biochemical sensing, liquid metal manipulation, patterned hydrogel synthesis, and drug screening, are also conceptually demonstrated. This work provides a strategy for precisely machining water using laser cutting, addressing existing laser machining challenges and holding significance for widespread fields involving fluid patterning and flow control in biological, chemical, materials and biomedical research.

Abstract Background Observational studies and conventional Mendelian randomization (MR) studies showed inconclusive evidence to support the association between omega-3 fatty acids and type 2 diabetes. We aim to evaluate the causal effect of omega-3 fatty acids on type 2 diabetes mellitus (T2DM), and the distinct intermediate phenotypes linking the two. Methods Two-sample MR was performed using genetic instruments derived from a recent genome-wide association study (GWAS) of omega-3 fatty acids (N = 114,999) from UK Biobank and outcome data obtained from a large-scale T2DM GWAS (62,892 cases and 596,424 controls) in European ancestry. MR-Clust was applied to determine clustered genetic instruments of omega-3 fatty acids that influences T2DM. Two-step MR analysis was used to identify potential intermediate phenotypes (e.g. glycemic traits) that linking omega-3 fatty acids with T2DM. Results Univariate MR showed heterogenous effect of omega-3 fatty acids on T2DM. At least two pleiotropic effects between omega-3 fatty acids and T2DM were identified using MR-Clust. For cluster 1 with seven instruments, increasing omega-3 fatty acids reduced T2DM risk (OR: 0.52, 95%CI 0.45–0.59), and decreased HOMA-IR (β = − 0.13, SE = 0.05, P = 0.02). On the contrary, MR analysis using 10 instruments in cluster 2 showed that increasing omega-3 fatty acids increased T2DM risk (OR:1.10; 95%CI 1.06–1.15), and decreased HOMA-B (β = − 0.04, SE = 0.01, P = 4.52 × 10–5). Two-step MR indicated that increasing omega-3 fatty acid levels decreased T2DM risk via decreasing HOMA-IR in cluster 1, while increased T2DM risk via decreasing HOMA-B in cluster 2. Conclusions This study provides evidence to support two distinct pleiotropic effects of omega-3 fatty acids on T2DM risk influenced by different gene clusters, which could be partially explained by distinct effects of omega-3 fatty acids on insulin resistance and beta cell dysfunction. The pleiotropic feature of omega-3 fatty acids variants and its complex relationships with T2DM need to be carefully considered in future genetic and clinical studies.

Upon a variety of environmental stresses, eukaryotic cells usually recruit translational stalled mRNAs and RNA-binding proteins to form cytoplasmic condensates known as stress granules (SGs), which minimize stress-induced damage and promote stress adaptation and cell survival. SGs are hijacked by cancer cells to promote cell survival and are consequently involved in the development of anticancer drug resistance. However, the design and application of chemical compounds targeting SGs to improve anticancer drug efficacy have rarely been studied. Here, we developed two types of SG inhibitory peptides (SIPs) derived from SG core proteins Caprin1 and USP10 and fused with cell-penetrating peptides to generate TAT-SIP-C1/2 and SIP-U1-Antp, respectively. We obtained 11 SG-inducing anticancer compounds from cell-based screens and explored the potential application of SIPs in overcoming resistance to the SG-inducing anticancer drug sorafenib. We found that SIPs increased the sensitivity of HeLa cells to sorafenib via the disruption of SGs. Therefore, anticancer drugs which are competent to induce SGs could be combined with SIPs to sensitize cancer cells, which might provide a novel therapeutic strategy to alleviate anticancer drug resistance.

IntroductionMetastatic renal cell carcinoma (mRCC) with sarcomatoid features has a poor prognosis. Cytoreductive radical nephrectomy (CRN) can improve prognosis, but patient selection is unclear. This study aimed to develop a prediction model for selecting patients suitable for CRN.Materials and methodsPatients with a diagnosis of mRCC with sarcomatoid features in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 were retrospectively reviewed. CRN benefit was defined as a survival time longer than the median overall survival (OS) in patients who did not receive CRN. A prediction nomogram was established and validated using the SEER cohort (training and internal validation) and an external validation cohort.ResultsOf 900 patients with sarcomatoid mRCC, 608 (67.6%) underwent CRN. OS was longer in the CRN group than in the non-CRN group (8 vs. 6 months, hazard ratio (HR) = 0.767, p = 0.0085). In the matched CRN group, 124 (57.7%) patients survived >6 months after the surgery and were considered to benefit from CRN. Age, T-stage, systematic therapy, metastatic site, and lymph nodes were identified as independent factors influencing OS after CRN, which were included in the prediction nomogram. The monogram performed well on the training set (area under the receiver operating characteristic (AUC) curve = 0.766, 95% confidence interval (CI): 0.687–0.845), internal validation set (AUC = 0.796, 95% CI: 0.684–0.908), and external validation set (AUC = 0.911, 95% CI: 0.831–0.991).ConclusionsA nomogram was constructed and validated with good accuracy for selecting patients with sarcomatoid mRCC suitable for CRN.

Objective: Multiple human papillomavirus (HPV)-associated diseases have put a significant disease burden on the world. Therefore, we conducted a study to explore the epidemiological characteristics of HPV and the transmissibility of its genotypes. Methods: HPV testing data was collected from Hospital. A transmission dynamics model of HPV was constructed to simulate and compare the transmissibility of different HPV genotypes, which was quantitatively described by the basic reproduction number (R0). Results: The collected HPV subjects were mainly from Xiamen City, Zhangzhou City and Quanzhou City, together, they are known as the Hokkien golden triangle. There were variations in the distribution of HPV infections by age groups. Among all HPV genotypes, 13 of them had R0 > 1, with 10 of them being high-risk types. The top five were HPV56, 18, 58, 52 and 53, among which, HPV56, 18, 58 and 42 were of high risk, whereas HPV53 was not, and the R0 values for the five were 3.35 (CI: 0.00–9.99), 3.20 (CI: 0.00–6.46), 3.19 (CI: 1.27–6.94), 3.19 (CI: 1.01–8.42) and 2.99 (CI: 0.00–9.39), respectively. In addition, HPV52 had R0 > 1 for about 51 months, which had the longest duration. Conclusion: Most high-risk HPV types in the Hokkien golden triangle could transmit among the population. Therefore, there is a need of further optimization for developing HPV vaccines and better detection methods in the region.

This contribution presents a type synthesis method for parallel robots with special topologies. First, we defined the constraint-incidence matrix (CIM) to describe serial chains by utilizing the geometric properties of screw theory, revealing the motion and constraint attributes and their internal relationship of serial chains. Then, a CIM-based synthesis method is proposed to convert the type synthesis of parallel robots into the geometric derivation of the CIM, and the specific operation steps of the proposed method are given. Finally, we demonstrated the application of the proposed method to the type synthesis of metamorphic, and wheeled parallel robots. Compared with existing type synthesis methods, the CIM-based synthesis method takes advantage of the known topological features of parallel robots with special topologies and can improve the efficiency of type synthesis.

Objective: A combination of glucocorticoids with mycophenolate is recommended by current guidelines to boost response to Graves’ orbitopathy (GO) therapy. This study was designed to evaluate the therapeutic effects and safety of m ethotrexate (MTX) plus reduced (3.0 g) or full-dose (4.5 g) i.v. methylprednisolone (MP) vs full-dose i.v. MP alone. Design and methods: This was a prospective, randomized, observer-masked, singlecenter clinical trial conducted in a tertiary clinical center. Ninety-seven patients with active moderate-to-severe GO were screened and 90 patients underwent randomization between April 2018 and Oct 2019. All patients completed 12 weeks of treatment and received clinical assessment. The patients received either MP 4.5 g only, MP 4.5 g plus oral MTX, or MP 3.0 g plus oral MTX. The primary outcome was th e CAS response at week 12. Secondary outcomes were adverse events and other individual ophthalmic parameters. Results: At week 12, 53.3% of MP, 76.7% of reduced MP plus MTX, and 76.7 % of MP plus MTX achieved a CAS response, although the difference was not sig nificant (P = 0.1). The overall response rates of the MP group, the reduced MP plus MTX group, and the MP plus MTX group were 43.3%, 53.3%, and 60%, respectively ( P = 0.5). Subgroup analysis found that smoking status interacted with marginal significance with treatment effect (P = 0.048). Importantly, adverse event incidence was significantly lower in the reduced MP + MTX group (P = 0.017). Conclusions: Our study shows that reduced MP plus MTX therapy is effective and safer in treating active and moderate-to-severe GO patients than 4.5 g MP monotherapy.

Abstract Background Tumorigenic phenotype of M2 tumor-associated macrophages promote tumor progression in response to exosomes cues imposed by tumor cells. However, the effect and underlying mechanisms of clear cell renal cell carcinoma (ccRCC)-derived exosomes (ccRCC-exo) on instructing macrophages phenotype remains unclear. Methods Macrophages were cocultured with ccRCC-exo and then evaluate the polarization of macrophages and migration of ccRCC cells. The effect and mechanism of lncRNA AP000439.2 overexpressed or deleted exosomes on macrophages M2 polarization were examined. Xenograft tumor mice model was used for in vivo validation. Results The ccRCC-exo significantly activated macrophages to M2 phenotype presented by increased expression of transforming growth factor-beta (TGF-β) and interleukin 10 (IL-10) at mRNA and protein levels, and these M2 macrophages in turn facilitating the migration of ccRCC cells. LncRNA AP000439.2 was highly enriched in the ccRCC-exo. Overexpression of exosomal AP000439.2 promoted M2 macrophage polarization whereas AP000439.2-deficient exosome had the opposite effects. Nuclear-localized AP000439.2 directly interacted with signal transducer and activator of transcription 3 (STAT3) proteins and phosphorylated STAT3 in macrophages. RNA-Seq results showed overexpression of AP000439.2 activated NF-κB signaling pathway. Silencing of STAT3 suppressed overexpression of AP000439.2-induced up-regulation of TGF-β and IL-10 expression, and p65 phosphorylation. AP000439.2-deleted exosome inhibited tumor growth in vivo. Conclusion Exosomes from ccRCC deliver AP000439.2 to promote M2 macrophage polarization via STAT3, thus enhancing ccRCC progression, indicating exosomal AP000439.2 might be a novel therapeutic target in ccRCC. Video Abstract

Abstract In the present study, the over-constrained hybrid manipulator R(2RPR)R/SP+RR is considered as the research objective. In this paper, kinematics of the hybrid manipulator, including the forward and inverse position, are analyzed. Then, the workspace is checked based on the inverse position solution to evaluate whether the workspace of the hybrid manipulator meets the requirements, and the actual workspace of the hybrid robot is analyzed. After that, the force analysis of the over-constrained parallel mechanism is carried out, and an ADAMS-ANSYS rigid-flexible hybrid body model is established to verify the simulation. Based on the obtained results from the force analysis, the manipulator structure is designed. Then, the structure optimization is carried out to improve the robot stiffness. Finally, calibration and workspace verification experiments are performed on the prototype, cutting experiment of an S-shaped aluminum alloy workpiece is completed, and the experiment verifies the machining ability of the prototype. This work conducts kinematics, workspace, force analyses, structural optimization design and experiments on the over-constrained hybrid manipulator R(2RPR)R/SP+RR, providing design basis and technical support for the development of the novel hybrid manipulator in practical engineering.

Abstract There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole‐exome sequencing on normal‐tumor‐thrombus‐metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C‐index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501–0.610, 0.667 versus 0.544–0.651, and 0.719 versus 0.511–0.700 for Training, China‐Validation, and Poland‐Validation cohorts, respectively). We constructed a risk predicting model, TT‐GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT‐GPS score displayed better discriminatory ability (OS, c‐index: 0.706–0.840, AUC: 0.788–0.874; DFS, c‐index: 0.691–0.717, AUC: 0.771–0.789) than previously reported models in risk assessment. In conclusion, we identified for the first‐time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT‐GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.

PurposeThis study presents a novel approach to predict postoperative biochemical recurrence (BCR) in prostate cancer (PCa) patients which involves constructing a signature based on anoikis-related genes (ARGs).MethodsIn this study, we utilised data from TCGA-PARD and GEO databases to identify specific ARGs in prostate cancer. We established a signature of these ARGs using Cox regression analysis and evaluated their clinical predictive efficacy and immune-related status through various methods such as Kaplan-Meier survival analysis, subject work characteristics analysis, and CIBERSORT method. Our findings suggest that these ARGs may have potential as biomarkers for prostate cancer prognosis and treatment. To investigate the biological pathways of genes associated with anoikis, we utilised GSVA, GO, and KEGG. The expression of ARGs was confirmed by the HPA database. Furthermore, we conducted PPI analysis to identify the core network of ARGs in PCa.ResultsBased on analysis of the TCGA database, a set of eight ARGs were identified as prognostic signature genes for prostate cancer. The reliability and validity of this signature were well verified in both the TCGA and GEO codifications. Using this signature, patients were classified into two groups based on their risk for developing BCR. There was a significant difference in BCR-free time between the high and low risk groups (P < 0.05).This signature serves as a dependable and unbiased prognostic factor for predicting biochemical recurrence (BCR) in prostate cancer (PCa) patients. It outperforms clinicopathological characteristics in terms of accuracy and reliability. PLK1 may play a potential regulatory role as a core gene in the development of prostate cancer.ConclusionThis signature suggests the potential role of ARGs in the development and progression of PCa and can effectively predict the risk of BCR in PCa patients after surgery. It also provides a basis for further research into the mechanism of ARGs in PCa and for the clinical management of patients with PCa.

With the rapid development of the retail industry and its transition to omni-channel, a critical challenge that how to fulfill customer orders by choosing the proper channels arises for the retailers. In omni-channel retailing, customers can make a purchase online or offline, and the online customers are offered the options of home delivery or collection at a specified store, delivering immediately or during an appointed time window, and accepting split delivery or not. For the effective execution of omni-channel retailing in such a circumstance, this paper proposes an intuitive order fulfillment policy, aiming to gain lower service cost and higher customer satisfaction, as a reference for the retailers’ operation management. Via experimental analyses under various service costs and demand forecasts, their influences on channel selection and the policy performance are illustrated. Furthermore, the comparison of the performances of the omni-channel with independent channels quantitatively reveals one crucial reason for the surge of omni-channel.

Abstract Tuberculosis (TB) is a global health problem of major concern. Identification of immune biomarkers may facilitate the early diagnosis and targeted treatment of TB. We used public RNA-sequencing datasets of patients with TB and healthy controls to identify differentially expressed genes and their associated functional networks. GBP1 expression was consistently significantly upregulated in TB, and 4492 differentially expressed genes were simultaneously associated with TB and high GBP1 expression. Weighted gene correlation analysis identified 12 functional modules. Modules positively correlated with TB and high GBP1 expression were associated with the innate immune response, neutrophil activation, neutrophil-mediated immunity, and NOD receptor signaling pathway. Eleven hub genes (GBP1, HLA-B, ELF4, HLA-E, IFITM2, TNFRSF14, CD274, AIM2, CFB, RHOG, and HORMAD1) were identified. The least absolute shrinkage and selection operator model based on hub genes accurately predicted the occurrence of TB (area under the receiver operating characteristic curve = 0.97). The GBP1-module-pathway network based on the STRING database showed that GBP1 expression correlated with the expression of interferon-stimulated genes (GBP5, BATF2, EPSTI1, RSAD2, IFI44L, IFIT3, and OAS3). Our study suggests GBP1 as an optimal diagnostic biomarker for TB, further indicating an association of the AIM2 inflammasome signaling pathway in TB pathology.

Abstract Protein analysis is an important approach for disease diagnosis, in which sample pretreatment is an essential step since protein samples are often complex and many protein biomarkers are of low abundance. Here, given the good openness and light transmission of liquid plasticine (LP), which is a liquid entity formed by SiO2 nanoparticles and encapsulated aqueous solution, we developed a LP‐based field‐amplified sample stacking (FASS) system for protein enrichment. The system was composed of a LP container, a sample solution and a Tris‐HCl solution containing hydroxyethyl cellulose (HEC). The system design, mechanism investigation, optimization of experimental parameters and characterization of LP‐FASS performance for protein enrichment were well studied. Under the optimized experimental conditions of 1 % HEC, 100 mm Tris‐HCl and 100 V in the LP‐FASS system, a 40–80 times enrichment of proteins was obtained in 40 min using bovine hemoglobin (BHb) as the model protein using the constructed LP‐FASS system. The simultaneous enrichment of multiple proteins (phycocyanin, BHb and cytochrome C) was also realized using the system. The LP‐FASS system can serve as a new platform for protein enrichment which is easy to be combined with online and offline detections.

Objective: To explore the clinical, imaging, pathologic features, treatment, and prognostic outcomes in 23 cases of collecting duct carcinoma (CDC) from a single center. Methods: The clinical and imaging findings, pathological features, treatment methods, and outcomes of the 23 patients with CDC confirmed by microscopic examination between 2003 and 2020 at our institution were retrospectively reviewed. Descriptive statistics of demographic and clinical variables were applied. Kaplan–Meier method was used to analyze survival data and log-rank test statistic survival differences between groups. Cox regression analysis was employed to identify variables independently related to overall survival (OS). Results: A total of 23 patients with CDC were identified. The mean age was 50.8 years. Stage III or IV tumors were diagnosed in 82.6% of the patients at diagnosis. The average size of the tumor was 6.58 cm, and the left kidney was more involved than the right. The median OS was 12 months. The OS rates at 1 and 2 years were 43.5% and 26.1%, respectively. Twenty patients underwent nephrectomy, 3 underwent nephroureterectomy, and 9 (39.1%) patients received subsequent therapeutic interventions following surgery. Distant metastasis and no symptoms at initial diagnosis proved to be an independent factor of unfavorable survival in Cox regression analysis. Conclusions: CDC is a rare and highly aggressive malignant renal tumor, and most patients present at an advanced stage at initial diagnosis. More than half of the patients died within 1 year after surgery. Distant metastasis and no clinical symptoms at initial diagnosis were independent risk prognostic factors for patients with CDC.

BackgroundAlthough the etiology of women’s cancer has been extensively studied in the last few decades, there is still little evidence comparing the temporal pattern of these cancers among different populations.MethodsCancer incidence and mortality data from 1988 to 2015 were extracted from the Changle Cancer Register in China, and cancer incidence data for Los Angeles were extracted from Cancer Incidence in Five Continents plus database. A Joinpoint regression model was used to analyze the temporal trends of incidence and mortality for breast, cervical, corpus uteri and ovarian cancers. The standardized incidence ratios were applied to compare the cancer risk across populations.ResultsAn increasing trend of incidence rate for breast, cervical, corpus uteri and ovarian cancer was observed in Changle, although the rate leveled off for breast and cervical cancer after 2010, although not statistically significant. The mortality rate of breast and ovarian cancer was slightly increased during this period, while we found a decreased mortality of cervical cancer from 2010. The mortality of corpus uteri cancer showed a decreasing and then increasing trend. The incidence of breast, corpus uteri and ovarian cancer in Chinese American immigrants in Los Angeles was significantly higher than indigenous Changle Chinese and lower than Los Angeles whites. However, the incidence of cervical cancer in Chinese American immigrants shifted from significantly exceeding to lower than Changle Chinese.ConclusionThe incidence and mortality of women’s cancers in Changle were generally on the rise, and this study concluded that environmental changes were important factors affecting the occurrence of these cancers. Appropriate preventive measures should be taken to control the occurrence of women’s cancers by addressing different influencing factors.

Online-to-offline (O2O) food delivery service refers to an emerging modern business model that enables customers to order foods from local restaurants via an online platform, and then receive and enjoy them offline after the delivery, offered by couriers. Such service, discussed in this article, specifies that a customer can order from multiple restaurants in a single order and choose for them to be delivered together or separately, whereas the commonly discussed mode only permits placing an order in one restaurant at once. In this service, one crucial issue is how to dispatch these orders to couriers for offline delivery. For this, we propose a new three-stage order dispatch scheme, namely, pseudo-assign first, re-route second, and courier selection last, aiming to deliver the orders in time and balance the couriers’ workload. Due to the dynamism and uncertainty inherently involved in this issue, we also take responsiveness to future demands and robustness into consideration when making the dispatch. Compared with existing approaches, the new one significantly balances the couriers’ workload and, meanwhile, keeps good performance in delay rate, making the decisions more practical. Furthermore, this study analyzes the influence of customers’ preference for order splitting and number of couriers on the efficiency of the distribution system, thereby interesting managerial insights for O2O food delivery are revealed.

Depressive disorders can occur in up to 50% of people with multiple sclerosis in their lifetime. If left untreated, comorbid major depressive disorders may not spontaneously remit and is associated with an increased morbidity and mortality. Conversely, epidemiological evidence supports increased psychiatric visit as a significant prodromal event prior to diagnosis of MS. Are there common molecular pathways that contribute to the co-development of MS and psychiatric illnesses? We discuss immune cells that are dysregulated in MS and how such dysregulation can induce or protect against depressive symptoms. This is not meant to be a comprehensive review of all molecular pathways but rather a framework to guide future investigations of immune responses in depressed versus euthymic people with MS. Currently, there is weak evidence supporting the use of antidepressant medication in comorbid MS patients. It is our hope that by better understanding the neuroimmune crosstalk in the context of depression in MS, we can enhance the potential for future therapeutic options.

This study aims to determine the prognostic value of SII for non-metastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). We retrospectively collected and analyzed 328 non-metastatic ccRCC patients with VTT who underwent radical nephrectomy and thrombectomy from 3 tertiary centers in China between 2011 to 2021. Kaplan-Meier analyses and Cox proportional hazard analyses were used to determine its prognostic value for overall survival (OS) and disease free survival (DFS). The Harrell concordance index (C-index), receiver operating characteristic curve (ROC) analysis, and decision curve analysis (DCA) were used to evaluate its role in the improvement of prognostic accuracy of the existing models. Nomogram models containing the SII were then developed and evaluated by R. Patients were divided into low-SII and high-SII groups based on the SII optimal cut-off value 912 calculated by the Youden index in all patients. Higher SII was correlated with more symptoms, longer surgical time, higher WHO/ISUP grade, and longer tumor diameter. Kaplan-Meier analyses revealed significant differences in OS and DFS between two groups. Multivariate analyses revealed that SII was an independent prognostic factor for OS (HR:2.220, p=0.002) and DFS (HR:1.846, p=0.002). Compared with other indicators, SII had a superior accuracy (c-index=0.630 for OS and 0.595 for DFS). It also improved the performance of models for predicting OS and DFS (all p

Abstract Background We aimed to define refined body shapes by using multiple anthropometric traits that represent fat distribution, and evaluate their associations with risk of insulin resistance (IR) and cardiometabolic disorders in a Chinese population. Methods We performed a cross-sectional analysis in 6570 community-based participants aged ≥ 40 years. Four body circumferences (neck, waist, hip, and thigh) and their ratios were put simultaneously into an open-source Waikato Environment for Knowledge Analysis platform to select the worthiest indicators in determining IR. The ratio of the top 3 fat distribution indicators was used to define the refined body shapes. Results We defined 8 distinct body shapes based on sex-specific combinations of waist-to-hip ratio (WHR), waist-to-thigh ratio (WTR), and waist-to-neck ratio (WNR), which differed in participants’ distribution and risk of IR and related cardiometabolic disorders. In women, as compared to the low WHR-low WTR-low WNR shape, all body shapes were significantly associated with IR and related cardiometabolic disorders; while in men, the low WHR-high WTR-high WNR shape and the higher WHR related shapes were significantly associated with IR and related cardiometabolic disorders. Stratified by WHR, the results were consistent in women; however, no significant associations were detected in men. Conclusions We defined 8 distinct body shapes by taking WHR, WTR, and WNR, simultaneously into account, which differed in association with the risk of IR and related cardiometabolic disorders in women. This study suggests that body shapes defined by multiple anthropometric traits could provide a useful, convenient, and easily available method for identifying cardiometabolic risk.

Abstract Cell-free fetal DNA fraction (FF) in maternal plasma is a key parameter affecting the performance of noninvasive prenatal testing (NIPT). Accurate quantitation of FF plays a pivotal role in these tests. However, there are few methods that could determine FF with high accuracy using shallow‐depth whole‐genome sequencing data. In this study, we hypothesized that the actual FF in maternal plasma should be proportional to the discrepancy rate between the observed genotypes and inferred genotypes based on the linkage disequilibrium rule in certain polymorphism sites. Based on this hypothesis, we developed a method named Linkage Disequilibrium information-based cell-free Fetal DNA Fraction (LDFF) to accurately quantify FF in maternal plasma. This method achieves a high performance and outperforms existing methods in the fetal DNA fraction estimation. As LDFF is a gender-independent method and developed on shallow-depth samples, it can be easily incorporated into routine NIPT test and may enhance the current NIPT performance.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which is caused by pathogenic variants of G6PD that result in decreased G6PD activity, is an X-linked inherited inborn error of metabolism that occurs worldwide. Individuals with G6PD deficiency and heterozygous females with normal G6PD activity (i.e., all individuals with pathogenic G6PD variants) are at risk of developing hemolytic anemia under increased oxidative challenge. However, this risk can be minimized by timely diagnosis. Currently, two assays are used to diagnose G6PD deficiency in China: evaluation of enzymatic activity and targeted genotyping. In terms of identification of all individuals with pathogenic G6PD variants, the performance and cost of different diagnostic strategies (isolated or combined evaluation of G6PD activity and G6PD genotyping) can vary, and these factors should be comprehensively evaluated. In this study, we examined 555 infants (437 males and 118 females) who were positive for the newborn screening of G6PD deficiency. We first evaluated the diagnostic performances of enzymatic testing and targeted genotyping. Both assays attained 100% specificities and positive predictive values for both male and female infants. In contrast, the sensitivities and negative predictive values (NPVs) of the diagnostic tests were different for male and female infants. For male infants, the sensitivities were 99.8 and 98.3%, and the NPVs were 94.1% and 69.6%, for enzymatic testing and targeted genotyping, respectively. For female infants, the sensitivities were 62.5% and 97.9%, and the NPVs were 37.9% and 91.7%, for enzymatic testing and targeted genotyping, respectively. We also evaluated the cost of the five different diagnostic strategies. The combination of G6PD activity testing of all infants, followed by genotyping of female infants with normal G6PD activity, attained high diagnostic sensitivity (99.8%) at a low cost (8.60 USD per diagnosed case). In the future, simultaneous examination of G6PD activity and whole-exon or whole-gene G6PD sequencing could become a standard clinical practice. Our data provide references for clinical practice on the standardization of current and future interventions for G6PD deficiency in China.

Dynamic performance is an important performance of robots used for machine processing. This paper studies the dynamic modeling and evaluation method of a 5-DOF (Degree of Freedom) hybrid robot used in aerospace composite material processing. With the consideration of the dynamics of the serial part, the complete dynamic model of the hybrid robot is established based on the virtual work principle. In addition to the widely considered acceleration term, a dynamic performance evaluation index that comprehensively considers the acceleration term, velocity term and gravity term in the dynamic model is proposed. Using the dynamic performance index, the effect of the placement direction of the robot and the arrangement of the double symmetric limbs on robot dynamics are investigated. The results indicate that the vertical placement is beneficial to the dynamics of the hybrid robot, and the arrangement of double symmetric limbs has different effects on different limbs.

Abstract Monocytes are important mediators of immune system and are reported to be altered in autoimmune disorders. Little is known about the pathological role of monocytes in Graves’ disease (GD). Thus, we investigated monocytes in periphery and thyroid tissue in GD. Untreated GD patients were enrolled and followed up until remission. Monocytes were significantly increased and positively correlated with anti-thyrotropin receptor antibody (TRAb) in untreated GD (r counts = 0.269, P

Polysaccharides from Grifola frondosa (G. frondosa) have anti-obesity and anti-inflammatory activities. In this study, the major type, molecular weight, homogeneity and structure of a polysaccharide purified from G. frondosa (denoted GFPA) were determined. In high-fat diet (HFD)-treated mice, 8 weeks of GFPA administration efficiently decreased body weight and blood glucose concentration and counteracted hyperlipidemia. GFPA efficiently decreased adipocyte size and ameliorated inflammatory infiltration in the three types of white adipose tissue and alleviated steatosis, fat accumulation and inflammatory infiltration in the livers of HFD-fed mice. GFPA also decreased the concentrations of aspartate aminotransferase, alanine aminotransferase and pro-inflammatory factors in the sera and livers of HFD-treated mice. Furthermore, GFPA was found to regulate lipid metabolism via the inhibition of ceramide levels in HFD-treated mice. GFPA exhibited strong anti-obesity effects via the modulation of chronic inflammation through Toll-like receptor 4/nuclear factor kappa-B signaling, which supports the use of GFPA for the treatment of obesity.

Abstract Background Noninvasive prenatal testing (NIPT) has been wildly used to screen for common aneuplodies. In recent years, the test has been expanded to detect rare autosomal aneuploidies (RATs) and copy number variations (CNVs). This study was performed to investigate the performance of expanded noninvasive prenatal testing (expanded NIPT) in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RATs), and copy number variations (CNVs) and parental willingness for invasive prenatal diagnosis in a Chinese prenatal diagnosis center. Methods A total of 24,702 pregnant women were retrospectively analyzed at the Women and Children’s Hospital from January 2013 to April 2019, among which expanded NIPT had been successfully conducted in 24,702 pregnant women. The high-risk expanded NIPT results were validated by karyotype analysis and chromosomal microarray analysis. All the tested pregnant women were followed up for pregnancy outcomes. Results Of the 24,702 cases, successful follow-up was conducted in 98.77% (401/446) of cases with common trisomies and SCAs, 91.95% (80/87) of RAT and CNV cases, and 76.25% (18,429/24,169) of cases with low-risk screening results. The sensitivity of expanded NIPT was 100% (95% confidence interval[CI], 97.38–100%), 96.67%(95%CI, 82.78–99.92%), and 100%(95%CI, 66.37–100.00%), and the specificity was 99.92%(95%CI, 99.87–99.96%), 99.96%(95%CI, 99.91–99.98%), and 99.88% (95%CI, 99.82–99.93%) for the detection of trisomies 21, 18, and 13, respectively. Expanded NIPT detected 45,X, 47,XXX, 47,XXY, XYY syndrome, RATs, and CNVs with positive predictive values of 25.49%, 75%, 94.12%, 76.19%, 6.45%, and 50%, respectively. The women carrying fetuses with Trisomy 21/Trisomy 18/Trisomy 13 underwent invasive prenatal diagnosis and terminated their pregnancies at higher rates than those at high risk for SCAs, RATs, and CNVs. Conclusions Our study demonstrates that the expanded NIPT detects fetal trisomies 21, 18, and 13 with high sensitivity and specificity. The accuracy of detecting SCAs, RATs, and CNVs is still relatively poor and needs to be improved. With a high-risk expanded NIPT result, the women at high risk for common trisomies are more likely to undergo invasive prenatal diagnosis procedures and terminate their pregnancies than those with unusual chromosome abnormalities.

Abstract Background KBG syndrome is a rare autosomal dominant genetic disease mainly caused by pathogenic variants of ankyrin repeat domain-containing protein 11 (ANKRD11) or deletions involving ANKRD11. Herein, we report a novel de novo heterozygous frameshift ANKRD11 variant via whole exome sequencing in a Chinese girl with KBG syndrome. Case presentation A 2-year-2-month-old girl presented with a short stature and developmental delay. Comprehensive physical examinations, endocrine laboratory tests and imaging examination were performed. Whole‐exome sequencing and Sanger sequencing were used to detect and confirm the variant associated with KBG in this patient, respectively. The pathogenicity of the variant was further predicted by several in silico prediction tools. The patient was diagnosed as KBG syndrome with a short stature and developmental delay, as well as characteristic craniofacial abnormalities, including a triangular face, long philtrum, wide eyebrows, a broad nasal bridge, prominent and protruding ears, macrodontia of the upper central incisors, dental crowding, and binocular refractive error. Her skeletal anomalies included brachydactyly, fifth finger clinodactyly, and left-skewed caudal vertebrae. Electroencephalographic results generally showed normal background activity with sporadic spikes and slow wave complexes, as well as multiple spikes and slow wave complexes in the bilateral parietal, occipital, and posterior temporal regions during non-rapid-eye-movement sleep. Brain MRI showed a distended change in the bilateral ventricles and third ventricle, as well as malformation of the sixth ventricle. Whole exome sequencing revealed a novel heterozygous frameshift variant in the patient, ANKRD11 c.1366_1367dup, which was predicted to be pathogenic through in silico analysis. The patient had received physical therapy since 4 months of age, and improvement of gross motor dysfunction was evident. Conclusions The results of this study expand the spectrum of ANKRD11 variants in KBG patients and provide clinical phenotypic data for KBG syndrome at an early age. Our study also demonstrates that whole exome sequencing is an effective method for the diagnosis of rare genetic disorders.

Graves’ disease (GD) is a common autoimmune disease that affects the thyroid gland. As a new class of modulators of gene expression, long noncoding RN As (lncRNAs) have been reported to play a vital role in immune functions and in the development of autoimmunity and autoimmune disease. The aim of this study is to identify ln cRNAs in CD4+ T cells as potential biomarkers of GD. lncRNA and mRNA microarrays were performed to identify differentially expressed lncRNAs and mRNAs in GD CD4+ T cells compared with healthy control CD4+ T cells. Quantitative PCR (qPCR) was used to validate the results, and correlation analysis was used to analyze the relationship b etween these aberrantly expressed lncRNAs and clinical parameters. The microarray ident ified 164 lncRNAs and 93 mRNAs in GD CD4+ T cells differentially expressed compared to healthy control CD4+ T cells (fold change >2.0 and a P < 0.05). Further analysis consistently showed that the expression of HMlincRNA1474 (P < 0.01) and TCONS_00012608 (P < 0.01) was suppressed, while the expression of AK021954 (P < 0.01) and AB075506 (P < 0.01) was upregulated from initial GD patients. In addition, their expression levels were recovered in euthyroid GD patients and GD patients in remission. Moreover, these four aberrantly expressed lncRNAs were correlated with GD clinical parameters. Moreover, the areas under the ROC curve were 0.8046, 0.7579, 0.8115 for AK021954, AB075506, HMlincRNA1474, respectively. The present work revealed that differentially expressed lncRNAs were associated with GD, which might serve as novel biomarkers of GD and potential targe ts for GD treatment.

The hedgehog (HH) signaling pathway is one of the key pathways that is indispensable for many developmental processes and postnatal tissue homeostasis. Dysregulated HH signaling could lead to developmental disorders and tumorigenesis in a variety of tissues via inherited or sporadic mutation, gene overexpression, and crosstalk with other signaling pathways. Recently, accumulating evidence has shown that HH signaling is targeted by viruses to facilitate viral transcription, immune evasion, and uncontrolled growth, leading to effective viral replication and pathogenesis. In this study, we will summarize recent advances in functional interaction between HH signaling and different types of viruses, particularly focusing on the pathological role of HH signaling in viral infections and related diseases.

Abstract Background Particulate Matter (PM) is known to cause inflammatory responses in human. Although prior studies verified the immunogenicity of PM in cell lines and animal models, the effectors of PM exposure in the respiratory system and the regulators of the immunogenicity of PM is not fully elucidated. Methods To identify the potential effector of PM exposure in human respiratory system and to better understand the biology of the immunogenicity of PM, We performed gene-expression profiling of peripheral blood mononuclear cells from 171 heathy subjects in northern China to identify co-expressed gene modules associated with PM exposure. We inferred transcription factors regulating the co-expression and validated the association to T-cell differentiation in both primary T-cells and mice treated with PM. Results We report two transcription factors, IRF4 and STAT3, as regulators of the gene expression in response to PM exposure in human. We confirmed that the activation of IRF4 and STAT3 by PM is strongly associated with imbalanced differentiation of T-cells in the respiratory tracts in a time-sensitive manner in mouse. We also verified the consequential inflammatory responses of the PM exposure. Moreover, we show that the protein levels of phosphorylated IRF4 and STAT3 increase with PM exposure. Conclusions Our study suggests the regulatory activities of IRF4 and STAT3 are associated with the Th17-mediated inflammatory responses to PM exposure in the respiratory tracts, which informs the biological background of the immunogenicity of particulate matters.

Abstract Geostationary BeiDou satellites monitor the total electron content (TEC) in the ionosphere over certain locations 24 hr per day without interruption and act as ionosphere‐based seismometers. The system detected perturbations in TEC before both the M6.1 Dali and M7.3 Qinghai earthquakes that occurred during the night of 21–22 May 2021. The TEC perturbations reside mainly over an area within a distance of ∼700 km from the epicenters of the earthquakes. The standing waves revealed the persistence of a subsurface wave source before the occurrences of the earthquakes, which differs from the co‐seismic ionospheric distributions propagating away from the epicenters. The resident waves in TEC and ground vibrations share a frequency of ∼0.004 Hz, which can be attributed to the resonant coupling between the lithosphere and ionosphere.

Background: The prenatal BACs-on-Beads™ (PNBoBs™) assay has been applied worldwide for prenatal diagnosis. However, there are neither guidelines nor consensus on choosing patients, sample types, or clinical pathways for using this technique. Moreover, different perspectives have emerged regarding its clinical value. This study aimed to evaluate its clinical utility in the context of clinical practice located in a prenatal diagnostic center in Xiamen, a city in southeast China.Methods: We tested 2,368 prenatal samples with multiple referral indications using both conventional karyotyping and PNBoBs™. Positive results from PNBoBs™ were verified using current gold-standard approaches.Results: The overall rates for the detection of pathogenic copy number variation (pCNV) by karyotyping and PNBoBs™ were 1.9% (46/2,368) and 2.0% (48/2,368), respectively. The overall detection rate of karyotyping combined with PNBoBs™ for pCNV was 2.3% (54/2,368). A total of 13 cases of copy number variation (CNV)with a normal karyotype were detected by PNBoBs™. Another case with a normal karyotype that was detected as a CNV of sex chromosomes by PNBoBs™ was validated to be maternal cell contamination by short tandem repeat analysis.Conclusion: Karyotyping combined with PNBoBs™ can improve both the yield and efficiency of prenatal diagnosis and is appropriate in the second trimester in all patients without fetal ultrasound anomalies who undergo invasive prenatal diagnosis.

As the working tool of the robot, the importance of the gripper becomes more prominent with the extensive use of the robot. This paper proposes a new type of underactuated universal gripper that can be applied to handle lightweight parts of any shape. It integrates a crank train and a four-bar mechanism to grasp objects. The kinematics and statics analysis of the proposed gripper were carried out; and in this paper, we briefly introduce the concept and control system design. Then, the motion characteristics and grasping ability of the underactuated gripper are presented. A prototype of the gripper was designed and manufactured based on the simulation analysis, and relevant grasping experiments were carried out. The experimental results verify that the proposed universal gripper has the advantages of safe design, easy manufacturing, effective gripping, and stable holding of objects.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzymatic defect. The purpose of this study was to evaluate the profile of G6PD deficiency and investigate the factors associated with the accuracy of newborn screening (NBS) in Xiamen, China.Methods: A total of 99,546 newborns were screened by modified fluorescent spot test at the Women and Children’s Hospital, Xiamen University. High-risk neonates were recalled for diagnosis by either a measurement of G6PD activity or genetic testing for the presence of pathogenic G6PD variants using a quantitative G6PD enzymatic assay or the MeltPro® G6PD assay, respectively.Results: In the first-tier screening, 1,256 newborns were categorized as high risk. Of these, 1,051 were diagnosed with G6PD deficiency, indicating a prevalence of 1.39% in Xiamen, China. Among the 1,013 neonates who underwent genotyping, 851 carried hemizygous, heterozygous, homozygous, or compound heterozygous variants, for a positive predictive value (PPV) of 84.01%. In total, 12 variants and 32 genotypes were identified, and the six most common variants were c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, c.871G>A, and c.392G>T, which accounted for approximately 94% of the identified alleles. Different variants showed characteristic enzymatic activities, although high phenotypic heterogeneity was observed for each variant. The use of cold-chain transportation significantly improved the PPV of NBS.Conclusions: We determined the profile of G6PD deficiency in Xiamen, including the prevalence, variant spectrum, and genotype-phenotype correlations and confirmed that maintaining a low temperature during sample transport is essential to ensure the high screening accuracy of NBS. Our data provides epidemiological, genotypic, phenotypic, and clinical practice references to standardize future interventions for G6PD deficiency.

ObjectiveTo investigate the exact age‐adjusted incidence (AAI), clinical characteristics, and survival data of collecting duct carcinoma of the kidney (CDCK) recorded in the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute.MethodsPatients with CDCK confirmed by microscopic examination from 2004 to 2018 were selected from the SEER database. AAI rates were calculated using SEER*Stat software (version 8.3.9). The Kaplan‐Meier method was used to evaluate cancer-specific survival (CSS) rates according to tumor size, tumor stage, and treatment methods, and differences among these variables were assessed by the log‐rank test. Cox regression analysis was employed to identify variables independently related to CSS.ResultsA total of 286 patients with CDCK were identified from the database. The majority of the patients were white (69.2%), male (67.5%), and married (60.5%), and the median age was 59 years. Most patients with CDCK (74.4%) presented with stages III or IV disease. The diameter of most (59.4%) tumors was less than 7 cm, and the tumors were more commonly found on the left than on the right (55.2% vs. 44.8%). The incidence of CDCK decreased over time. The median CSS time was 17 months. In terms of the treatment modalities used, 83.9% of the patients underwent surgery; 32.9% underwent chemotherapy, and 13.6% underwent radiotherapy. The CSS rates at 1, 2, and 5 years were 57.3%, 43.2%, and 30.7%, respectively. In patients with stage IV CDCK treated with surgery alone, chemotherapy alone, and surgery plus chemotherapy, the median survival time was 5 months, 9 months, and 14 months, respectively (P =0.024). Multivariate Cox regression analysis showed surgery, chemotherapy, stage, regional lymph node metastasis, and distant metastasis were independent prognostic factors for patients with CDCK.ConclusionsCDCK is an uncommon malignant renal carcinoma, and its incidence is decreasing based on the analysis of current data. CDCK is a high stage, regional lymph-nodes positive, and metastatic disease. Compared with surgery alone or chemotherapy alone, patients with stage IV could gain survival benefit from surgery combined with chemotherapy.

Background: The bioassay of thyroid-stimulating immunoglobulin was reported to have a similar performance to the commonly used thyroid-stimulating hormone binding inhibition assay, also known as thyroid receptor antibody assay. The normal reference range of thyroid receptor antibody levels indicates the withdrawal of anti-thyroid drugs in the recent clinical guidelines. Methods: A prospective, longitudinal observational study was conducted to evaluate the prognostic value of thyroid-stimulating immunoglobulin in patients with Graves’ disease. Results: A total of 77 patients with Graves’ disease treated with anti-thyroid drugs were in a continuous follow-up until 1 year after anti-thyroid drugs discontinuation. Commercial kits of thyroid-stimulating immunoglobulin and M22-thyroid-stimulating hormone binding inhibition assay were used and compared. Thyroid-stimulating immunoglobulin was all negative in healthy controls, Hashimoto thyroiditis, and subacute thyroiditis. Thyroid-stimulating immunoglobulin value was highest in untreated patients with Graves’ disease ( p

BackgroundLiver cancer is one of the most malignant human cancers, with few treatments and a poor prognosis. Erianin (ERN) is a natural compound with multiple pharmacological activities that has been reported to have numerous excellent effects against liver cancer in experimental systems. However, its application in vivo has been limited due to its poor aqueous solubility and numerous off-target effects. This study aimed to improve the therapeutic efficacy of ERN by developing novel ERN-loaded tumor-targeting nanoparticles.ResultsIn this study, ERN was loaded into liposomes by ethanol injection (LP-ERN), and the resulting LP-ERN nanoparticles were treated with transferrin to form Tf-LP-ERN to improve the solubility and enhance the tumor-targeting of ERN. LP-ERN and Tf-LP-ERN nanoparticles had smooth surfaces and a uniform particle size, with particle diameters of 62.60 nm and 88.63 nm, respectively. In HepG2 and SMMC-7721 cells, Tf-LP-ERN induced apoptosis, decreased mitochondrial membrane potentials and increased ERN uptake more effectively than free ERN and LP-ERN. In xenotransplanted mice, Tf-LP-ERN inhibited tumor growth, but had a minimal effect on body weight and organ morphology. In addition, Tf-LP-ERN nanoparticles targeted tumors more effectively than free ERN and LP-ERN nanoparticles, and in tumor tissues Tf-LP-ERN nanoparticles promoted the cleavage PARP-1, caspase-3 and caspase-9, increased the expression levels of Bax, Bad, PUMA, and reduced the expression level of Bcl-2. Moreover, in the spleen of heterotopic tumor model BALB/c mice, ERN, LP-ERN and Tf-LP-ERN nanoparticles increased the expression levels of Nrf2, HO-1, SOD-1 and SOD-2, but reduced the expression levels of P-IKKα+β and P-NF-κB, with Tf-LP-ERN nanoparticles being most effective in this regard. Tf-LP-ERN nanoparticles also regulated the expression levels of TNF-α, IL-10 and CCL11 in serum.ConclusionTf-LP-ERN nanoparticles exhibited excellent anti-liver cancer activity in vivo and in vitro by inducing cellular apoptosis, exhibiting immunoregulatory actions, and targeting tumor tissues, and did so more effectively than free ERN and LP-ERN nanoparticles. These results suggest that the clinical utility of a Tf-conjugated LP ERN-delivery system for the treatment of liver cancer warrants exploration.

ObjectiveGlobal developmental delay has markedly high phenotypic and genetic heterogeneity, and is a great challenge for clinical diagnosis. Hypotonia, ataxia, and delayed development syndrome (HADDS), first reported in 2017, is one type of global development delay. The aim of the present study was to investigate the genetic etiology of a Chinese boy with global developmental delay.MethodsWe combined clinical and imaging phenotyping with trio whole-exome sequencing and Sanger sequencing to the patient and his clinically unaffected parents. A luciferase reporter and immunofluorescence were performed to detect the effect of mutation on transcriptional activity and subcellular localization.ResultsThe patient presented with several previously unreported symptoms in the patients with HADDS, including hemangiomas, mild hearing abnormalities and tracheomalacia. A novel EBF3 c.589A > G missense mutation (p.Asn197Asp, p.N197D) was identified in the patient but not in his parents. By constructing the plasmid and transfecting HEK293T cells, EBF3-N197D mutant showed impaired activation of luciferase reporter expression of the p21 promoter, and the mutant affected its entry into the nucleus.ConclusionTo the best of our knowledge, this is the first report of EBF3 pathogenic mutation which associated with HADDS in the Chinese population. Our results expand the phenotypes and pathogenic mutation spectrum of HADDS, thus potentially facilitating the clinical diagnosis and genetic counseling of HADDS patients.

Abstract Background Congenital hearing loss affects approximately 1–2 infants out of every 1000, with 50% of the cases resulting from genetic factors. Targeted gene panels have been widely used for genetic diagnosis of hearing loss. This study aims to reveal new diagnoses via reanalyzing historical data of a multigene panel, and exam the reasons for new diagnoses. Methods A total of 210 samples were enlisted, including clinical reports and sequencing data of patients with congenital/prelingual hearing loss who were referred to clinical genetic testing from October 2014 to June 2017. All variants listed on the original clinical reports were reinterpreted according to the standards and guidelines recommended by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP). Expanded analysis of raw data were performed in undiagnosed cases. Results Re-analysis resulted in nine new diagnoses, improving the overall diagnostic rate from 39 to 43%. New diagnoses were attributed to newly published clinical evidence in the literature, adoption of new interpretation guidelines and expanded analysis range. Conclusion This work demonstrates benefits of reanalysis of targeted gene panel data, indicating that periodical reanalysis should be performed in clinical practice.

This study aimed to evaluate the analgesic efficacy of astilbin and its underlying mechanisms. Astilbin suppressed the symptoms of acetic acid–induced writhing, lengthened the latency period on the hot plate, and reduced the licking and biting response of formalin-injected mice, suggesting its analgesic efficacy on the central nervous system. Astilbin suppressed neuronal nitric oxide synthase and enhanced serotonin and norepinephrine in serum and brains of mice after 30 s of thermal stimulation, but it failed to influence their levels before thermal stimulation. Among six chosen antagonists, only nimodipine, a calcium channel blocker, strongly enhanced the abirritation of astilbin, as indicated by the lengthened latency period of mice treated with nimodipine plus astilbin in the hot plate test. The expression levels of c-Fos and phosphorylated calmodulin-dependent protein kinase II and c-Jun N-terminal kinase in the brains were reduced in the astilbin-treated mice. Astilbin-mediated analgesia is partially related to Ca2+ channels.