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Abstract Water structures at electrolyte/electrode interfaces play a crucial role in determining the selectivity and kinetics of electrochemical reactions. Despite extensive experimental and theoretical efforts, atomic-level details of ion-specific water structures on metal surfaces remain unclear. Here we show, using scanning tunneling microscopy and noncontact atomic force microscopy, that we can visualize water layers containing alkali metal cations on a charged Au(111) surface with atomic resolution. Our results reveal that Li+ cations are elevated from the surface, facilitating the formation of an ice-like water layer between the Li+ cations and the surface. In contrast, K+ and Cs+ cations are in direct contact with the surface. We observe that the water network structure transitions from a hexagonal arrangement with Li+ to a distorted hydrogen-bonding configuration with Cs+. These observations are consistent with surface-enhanced infrared absorption spectroscopy data and suggest that alkali metal cations significantly impact hydrogen evolution reaction kinetics and efficiency. Our findings provide insights into ion-specific water structures on metal surfaces and underscore the critical role of spectator ions in electrochemical processes.

Abstract Multiple myeloma (MM) remains an incurable hematological malignancy disease characterized by the progressive dysfunction of the patient’s immune system. In this context, immunotherapy for MM has emerged as a prominent area of research in recent years. Various targeted immunotherapy strategies, such as monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, chimeric antigen receptor T cells/natural killer (NK) cells, and checkpoint inhibitors have been developed for MM. This review aims to discuss promising experimental and clinical evidence as well as the mechanisms of action underlying these immunotherapies. Specifically, we will explore the design of exosome-based bispecific monoclonal antibodies that offer cell-free immunotherapy options. The treatment landscape for myeloma continues to evolve with the development of numerous emerging immunotherapies. Given their significant advantages in modulating the MM immune environment through immune-targeted therapy, these approaches provide novel perspectives in selecting cutting-edge treatments for MM.

Abstract The plastic deformation of crystalline materials can be understood by considering their structural defects such as disclinations and dislocations. Although also glasses are solids, their structure resembles closely the one of a liquid and hence the concept of structural defects becomes ill-defined. As a consequence it is very challenging to rationalize on a microscopic level the mechanical properties of glasses close to the yielding point and to relate plastic events to structural properties. Here we investigate the topological characteristics of the eigenvector field of the vibrational excitations of a two-dimensional glass model, notably the geometric arrangement of the topological defects as a function of vibrational frequency. We find that if the system is subjected to a quasistatic shear, the location of the resulting plastic events correlate strongly with the topological defects that have a negative charge. Our results provide thus a direct link between the structure of glasses prior their deformation and the plastic events during deformation.

Abstract Background Lung cancer is the most lethal malignancy, with non-small cell lung cancer (NSCLC) being the most common type (~ 85%). Abnormal activation of epidermal growth factor receptor (EGFR) promotes the development of NSCLC. Chemoresistance to tyrosine kinase inhibitors, which is elicited by EGFR mutations, is a key challenge for NSCLC treatment. Therefore, more thorough understanding of EGFR expression and dynamics are needed. Methods Human non-small cell lung cancer cells and HEK293FT cells were used to investigate the molecular mechanism of gasdermin E (GSDME) regulating EGFR stability by Western blot analysis, immunoprecipitation and immunofluorescence. GSDME and EGFR siRNAs or overexpression plasmids were used to characterize the functional role of GSDME and EGFR in vitro. EdU incorporation, CCK-8 and colony formation assays were used to determine the proliferation ability of non-small cell lung cancer cells. Results GSDME depletion reduced the proliferation of non-small cell lung cancer cells in vitro. Importantly, both GSDME-full length (GSDME-FL) and GSDME-N fragment physically interacted with EGFR. GSDME interacted with cytoplasmic fragment of EGFR. GSDME knockdown inhibited EGFR dimerization and phosphorylation at tyrosine 1173 (EGFRY1173), which activated ERK1/2. GSDME knockdown also promoted phosphorylation of EGFR at tyrosine 1045 (EGFRY1045) and its degradation. Conclusion These results indicate that GSDME-FL increases the stability of EGFR, while the GSDME N-terminal fragment induces EGFR degradation. The GSDME-EGFR interaction plays an important role in non-small cell lung cancer development, reveal a previously unrecognized link between GSDME and EGFR stability and offer new insight into cancer pathogenesis. Video abstract

Glucose transporters GLUT1 belong to the major facilitator superfamily and are essential to human glucose uptake. The overexpression of GLUT1 in tumor cells designates it as a pivotal target for glycoconjugate anticancer drugs. However, the interaction mechanism of glycoconjugate drugs with GLUT1 remains largely unknown. Here, we employed all-atom molecular dynamics simulations, coupled to steered and umbrella sampling techniques, to examine the thermodynamics governing the transport of glucose and two glycoconjugate drugs (i.e., 6-D-glucose-conjugated methane sulfonate and 6-D-glucose chlorambucil) by GLUT1. We characterized the specific interactions between GLUT1 and substrates at different transport stages, including substrate recognition, transport, and releasing, and identified the key residues involved in these procedures. Importantly, our results described, for the first time, the free energy profiles of GLUT1-transporting glycoconjugate drugs, and demonstrated that H160 and W388 served as important gates to regulate their transport via GLUT1. These findings provide novel atomic-scale insights for understanding the transport mechanism of GLUT1, facilitating the discovery and rational design of GLUT1-targeted anticancer drugs.

Exosomes have emerged as a promising cell-free therapeutic approach. However, challenges in large-scale production, quality control, and heterogeneity must be overcome before they can be used clinically. Biomimetic exosomes containing key components of natural exosomes have been assembled through extrusion, artificial synthesis, and liposome fusion to address these limitations. These exosome-mimetics (EMs) possess similar morphology and function but provide higher yields, faster large-scale production, and similar size compared to conventional exosomes. This article provides an overview of the chemical and biological properties of various synthetic exosome systems, including nanovesicles (NVs), EMs, and hybrid exosomes. We highlight recent advances in the production and applications of nanobiotechnology and discuss the advantages, limitations, and potential clinical applications of programming assembly of exosome mimetics.

In order to improve the oxidation resistance of traditional yak ghee, extend the shelf life, the yak ghee was embedded in gum Arabic and gelatin by complex coacervation method to prepare yak ghee microcapsules. The optimal preparation technology was obtained via single factor and orthogonal experiment with embedding rate as an index, and the physical and chemical properties, morphology structure, stability and properties in simulate gastrointestinal digestion were also investigated. The results showed that the best parameters of yak ghee microcapsules were as follows: Core-to-wall ratio was 1:1.5, mass fraction of wall material was 1.5%, complex coacervation pH was 4.2, the complex coacervation temperature was 40 ℃, and encapsulation efficiency of microcapsules was 81.39%. The average particle size, moisture content, solubility and angle of repose were 19.728 μm, 3.62%, 96.48% and 37.7°, respectively. Scanning electron microscope and fourier transform infrared spectroscopy showed that the surface of yak ghee microcapsules was smooth, the morphology was irregular, and yak ghee was successfully embedded in wall materials. Differential scanning calorimeter and thermogravimetric analysis proved that yak ghee microcapsules possessed good thermal stability. In addition, the release of yak ghee microcapsules could be controlled in simulated gastric and intestinal fluid, and the release rate in simulated intestinal fluid was 99.74%. Storage experiments exhibited that microencapsulation could slow down the oxidation rate of yak ghee and prolong the shelf life. This study will help provide theoretical basis for improving the bioavailability of yak ghee.

Abstract The recombinase RAD51 catalyzes the DNA strand exchange reaction in homologous recombination (HR) during both mitosis and meiosis. However, the physiological role of RAD51 during spermatogenesis remains unclear since RAD51 null mutation is embryonic lethal in mice. In this study, we generated a conditional knockout mouse model to study the role of RAD51 in spermatogenesis. Conditional disruption of RAD51 in germ cells by Vasa-Cre led to spermatogonial loss and Sertoli cell-only syndrome. Furthermore, tamoxifen-inducible RAD51 knockout by UBC-CreERT2 confirmed that RAD51 deletion led to early spermatogenic cells loss and apoptosis. Notably, inducible knockout of RAD51 in adult mice caused defects in meiosis, with accumulated meiotic double-strand breaks (DSBs), reduced numbers of pachytene spermatocytes and less crossover formation. Our study revealed an essential role for Rad51 in the maintenance of spermatogonia as well as meiotic progression in mice.

Abstract Introduction De novo balanced reciprocal translocations mosaicism in fetus conceived using preimplantation genetic testing from a different balanced translocation carrier parent has been rarely reported. Methods Chromosomal microarray analysis, karyotype analysis and fluorescent in situ hybridization were performed to verify the type and heredity of the rearrangement. STR analysis was conducted to identify potential contamination and verify kinship. In addition, a local BLAST engine was performed to locate potentially homologous segments which might contribute to the translocation in breakpoints of chromosome. Results A rare de novo balanced reciprocal translocations mosaicism mos 46,XY,t(1;3)(q42;q25)[40]/46,XY[39] was diagnosed in a fetus conceived using preimplantation genetic testing due to a 46,XY,t(12;14)(q22;q13) balanced translocation carrier father through multiplatform genetic techniques. Two of the largest continuous high homology segments were identified in chromosomal band 1q42.12 and 3q25.2. At the 21-months follow up, infant has achieved all psychomotor development milestones as well as growth within the normal reference range. Conclusion We present a prenatal diagnosis of a rare de novo balanced reciprocal translocations mosaicism in a fetus who conceived by preimplantation genetic testing. The most reasonable driving mechanism was that a de novo mitotic error caused by nonallelic homologous recombination between 1q42.12 and 3q25.2 in a zygote within the first or early cell divisions, which results in a mosaic embryo with the variant present in a half proportion of cells.

SPOP functions as a tumour suppressor in prostate cancer but how the protein is regulated is unclear. Here, the authors identify G3BP1 as a competitive inhibitor of SPOP and show that G3BP1-SPOP axis activates androgen signalling to drive tumorigenesis.

Abstract Articular cartilage repair is a critical issue in osteoarthritis (OA) treatment. The insulin-like growth factor (IGF) signaling pathway has been implicated in articular cartilage repair. IGF-1 is a member of a family of growth factors that are structurally closely related to pro-insulin and can promote chondrocyte proliferation, enhance matrix production, and inhibit chondrocyte apoptosis. Here, we reviewed the role of IGF-1 in cartilage anabolism and catabolism. Moreover, we discussed the potential role of IGF-1 in OA treatment. Of note, we summarized the recent progress on IGF delivery systems. Optimization of IGF delivery systems will facilitate treatment application in cartilage repair and improve OA treatment efficacy.

Visual object detection is an essential task for the intelligent navigation of an Unmanned Surface Vehicle (USV), which can sense the obstacles while navigating. However, the harsh illumination conditions and large scale variation of the objects significantly harm the performance of object detection methods. To address the above problems, we propose a robust water surface object detection method named multi-scale feature fusion network with intrinsic decomposition generative adversarial network data augmentation (MFFDet-IDGAN). We introduce intrinsic decomposition as data augmentation for the object detection to achieve illumination adapting. And an intrinsic decomposition generative adversarial network (IDGAN) is proposed to achieve unsupervised intrinsic decomposition. Moreover, the multi-scale feature fusion network (MFFDet) adopts an improved bidirectional feature pyramid network (BiFPN) and spatial pyramid pooling (SPP) blocks to fuse features of different resolution for better multi-scale detection. And an improved weighted stochastic weight averaging (SWA) is proposed and applied in the training process to improve the generalization performance. We conduct extensive experiments on the Water Surface Object Detection Dataset (WSODD), and the results show that the proposed method can achieve 44% improvement over the baseline. And we further test our method on a real USV in the sailing process, the results show that our method can exceeding the baseline by 4.5%.

Abstract Despite the central role of hemocytes in crustacean immunity, the process of hemocyte differentiation and maturation remains unclear. In some decapods, it has been proposed that the two main types of hemocytes, granular cells (GCs) and semigranular cells (SGCs), differentiate along separate lineages. However, our current findings challenge this model. By tracking newly produced hemocytes and transplanted cells, we demonstrate that almost all the circulating hemocytes of crayfish belong to the GC lineage. SGCs and GCs may represent hemocytes of different developmental stages rather than two types of fully differentiated cells. Hemocyte precursors produced by progenitor cells differentiate in the hematopoietic tissue (HPT) for 3 ~ 4 days. Immature hemocytes are released from HPT in the form of SGCs and take 1 ~ 3 months to mature in the circulation. GCs represent the terminal stage of development. They can survive for as long as 2 months. The changes in the expression pattern of marker genes during GC differentiation support our conclusions. Further analysis of hemocyte phagocytosis indicates the existence of functionally different subpopulations. These findings may reshape our understanding of crustacean hematopoiesis and may lead to reconsideration of the roles and relationship of circulating hemocytes.

Abstract Background In the new therapeutic era, comparisons between regimens containing lenalidomide and bortezomib are needed. Methods In this single‐center, prospective study, patients received four to six cycles of lenalidomide+liposomal doxorubicin+dexamethasone (RAD) or bortezomib+liposomal doxorubicin+dexamethasone (PAD) every 4 weeks, with subsequent autologous stem cell transplantation (ASCT) and maintenance therapy. We compared the efficacy, safety, patients’ quality of life, and doctors’ occupational stress between RAD and PAD induction in newly diagnosed MM patients. Results The complete response (CR) rate was comparable between the RAD and PAD groups after induction (30.8% vs. 32.0%, p = 0.92). Common adverse events, including infections, peripheral neuropathy, and gastrointestinal disturbances, were more frequent in the PAD group, while leukopenia and rashes were more common in the RAD group. Compared with PAD, RAD improved patients’ quality of life more quickly and caused less occupational stress for doctors. However, only 31.6% of patients collected adequate CD34+ cells (≥2 × 106/kg) in the RAD group, which was significantly lower than that in the PAD group (95.5%, p

Network topology construction plays an important role in the application of large-scale unmanned aerial vehicle (UAV) swarm. Current researches usually perform the topology construction in terms of criteria of nodes energy consumption, transmission delay and network throughput, etc. However, another important criterion, the stability of swarm network topology, which is much critical for dynamic scenarios, has not been fully considered. In this paper, a novel topology construction method for UAV swarm network based on the criterion of topology duration is proposed. Specially, the topology construction of swarm network is formulated as an optimization problem of maximizing the topology duration while satisfying the constraints of certain network throughput, end-to-end delay, and nodes energy consumption. Then, a novel Group Trend Similarity based double-head Clustering method(GTSC) is employed to solve this problem, in which group similarity of movement, intra- and inter-cluster distance, node forwarding delay, and energy strategy are comprehensively taken into account. The proposed method is effective when used to perform the network topology construction for UAV swarm, which is verified by the simulation results. Furthermore, in comparison with representative algorithms, the proposed GTSC method exhibits better performance on topology duration, network throughput, end-to-end delay and energy consumption balance especially in a large-scale swarm scenarios.

Decapod iridescent virus 1 (DIV1) is one of the major pathogens of farmed shrimp. In this study, the structural proteins of DIV1 were analyzed by mass spectrometry. DIV1 virions were purified from the hemolymph of artificially infected Cherax quadricarinatus. The viral proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and a total of 28 protein bands were obtained. These protein bands were in-gel digested with trypsin and the resulting tryptic peptide mixtures were subjected to liquid chromatography with tandem mass spectrometry analysis. Thirty virus-encoded proteins were identified. Among them, 6 proteins were predicted to contain transmembrane domains, 3 proteins were predicted to contain an Arg-Gly-Asp motif. Nine proteins showed significant homology with functionally characterized proteins. Antibodies were produced for these candidate proteins and 23 of them were confirmed to be the components of DIV1 virions by Western blotting. This study provides the first proteomic analysis of DIV1, which establishes a foundation for further investigation of viral infection and replication.

Abstract Background Disparities in multiple myeloma (MM) prognosis based on sociodemographic factors may exist. We investigated whether education level at diagnosis influenced Chinese MM patient outcomes. Methods We performed a multicenter retrospective analysis of data from 773 MM patients across 9 centers in China from 2006 to 2019. Sociodemographic and clinical factors at diagnosis and treatment regimens were recorded, and univariate and multivariate analyses were performed. Results Overall, 69.2% of patients had low education levels. Patients with low education levels differed from those with high education levels in that they were more likely to be older, and a higher proportion lived in rural areas, were unemployed, had lower annual incomes and lacked insurance. Additionally, compared to patients with high education levels, patients with low education levels had a higher proportion of international staging system (ISS) stage III classification and elevated lactate dehydrogenase (LDH) levels and underwent transplantation less often. Patients with high education levels had a median progression-free survival (PFS) of 67.50 (95% confidence interval (CI): 51.66–83.39) months, which was better than that of patients with low education levels (30.60 months, 95% CI: 27.38–33.82, p

We point out that the largest private shareholders can use their information advantage of the industry to influence banks' industry lending behavior. Using a sample of Chinese city commercial banks, we find that increasing of ownership stake of the largest private shareholders leads banks to lend more to their industries. Interestingly, the largest state-owned shareholders do not have this effect. More importantly, we confirmed the channel of the information advantage by analyzing the bank's industry NPL ratio and the listed company's maximum loan amount in the bank. Of course, the effect of the largest private shareholders is achieved by intervening in board decisions. In addition, the ownership structure can influence this effect.

This study was conducted to identify whether the TLR4/MyD88/NF-κB signalling pathway plays a vital role in osteoarthritis (OA) treatment with Duhuo Jisheng Decoction (DHJSD) on the basis of a network pharmacology approach (NPA)-integrated experiment. Two experiments were conducted as follow: NPA for DHJSD using six OA-related gene series and the key pathway was screened out using NPA. NPA identified a vital role for the TLR4/MyD88/NF-κB signalling pathway in OA treatment with DHJSD, the conventional western blot analysis and qPCR confirmed it. Furthermore, changes of miR-146a-5p and miR-34a-5p in the cellular models were recovered by DHJSD administration, which synergistically contributed to OA therapy. The toll-like receptor signalling pathway and the NF-κB signalling pathway were meaningfully enriched by the miRNA-regulated gene pathways. This study identified and confirmed the TLR4/MyD88/NF-κB signalling pathway is an essential inflammatory signalling pathway in the DHJSD underlying OA treatment. The results provide a basis for further evaluation of the regulatory mechanism of the drug’s efficacy in treating OA.

In crustaceans, the number of circulating hemocytes changes rapidly in response to pathogen infection and injury, but the underlying mechanism remains unclear. In this study, we investigated the regulation of hemocytes homeostasis in crayfish after hemolymph withdrawal. We showed that the circulating hemocytes increased by over 2 folds within 1 h post hemolymph withdrawal and returned to normal level within 8 h. New hemocytes produced by hematopoiesis accounted for

Proteolytic targeting chimeras (PROTACs) is a rapid and reversible chemical knockout method. Compared with traditional gene-editing tools, it can avoid potential genetic compensation, misunderstandings caused by spontaneous mutations, or gene knockouts that lead to embryonic death. To study the role of estrogen receptor alpha (ERα) in the occurrence and progression of menopausal arthritis, we report a chemical knockout strategy in which stable peptide-based (PROTACs) against ERα to inhibit their function. This chemical knockdown strategy can effectively and quickly inhibit ERα protein in vivo and in vitro. In the rat menopausal arthritis model, this study showed that inhibiting estrogen function by degrading ERα can significantly interfere with cartilage matrix metabolism and cause menopausal arthritis by up-regulating matrix metalloproteinase (MMP-13). The results of this study indicate that ERα is a crucial estrogen receptor for maintaining cartilage metabolism. Inhibition of ERα function by PROTACs can promote the progression of osteoarthritis.

Interfacial water is closely related to many core scientific and technological issues, covering a broad range of fields, such as material science, geochemistry, electrochemistry and biology. The understanding of the structure and dynamics of interfacial water is the basis of dealing with a series of issues in science and technology. In recent years, atomic force microscopy (AFM) with ultrahigh resolution has become a very powerful option for the understanding of the complex structural and dynamic properties of interfacial water on solid surfaces. In this perspective, we provide an overview of the application of AFM in the study of two dimensional (2D) or three dimensional (3D) interfacial water, and present the prospect and challenges of the AFM-related techniques in experiments and simulations, in order to gain a better understanding of the physicochemical properties of interfacial water.

Glasses show peculiar relaxation dynamics below glass transition temperature, yet a deeper understanding of this phenomenon is still lacking. Wu et al. show the coexistence of stretched and compressed relaxation in a metallic glass system and attribute their origins to different local cluster structures.

The emerging clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated system (Cas) gene-editing system represents a promising tool for genome manipulation. However, its low intracellular delivery efficiency severely compromises its use and potency for clinical applications. Nanocarriers, such as liposomes, polymers, and inorganic nanoparticles, have shown great potential for gene delivery. The remarkable development of nanoparticles as non-viral carriers for the delivery of the CRISPR/Cas9 system has shown great promise for therapeutic applications. In this review, we briefly summarize the delivery components of the CRISPR/Cas9 system and report on the progress of nano-system development for CRISPR/Cas9 delivery. We also compare the advantages of various nano-delivery systems and their applications to deliver CRISPR/Cas9 for disease treatment. Nano-delivery systems can be modified to fulfill the tasks of targeting cells or tissues. We primarily emphasize the novel exosome-based CRISPR/Cas9 delivery system. Overall, we review the challenges, development trends, and application prospects of nanoparticle-based technology for CRISPR/Cas9 delivery.

This paper presents an accurate solution of finite-time Cartesian trajectory tracking control problem of a quadrotor system by designing and implementing a novel robust flight-control algorithm. The quadrotor is subject to nonlinearities, unmodeled dynamics, parameters’ uncertainties, and external time-varying disturbances. To reject the disturbances and enhance the control system’s robustness, a terminal sliding mode-based active antidisturbance control (TSMBAADC) approach is proposed for rotational and translational subsystems. To improve the tracking performance, a nonlinear continuous terminal sliding manifold and a fast reaching law are proposed in this work to quickly drive the systems’ states to the equilibrium point even in the presence of lumped disturbances. The convergence time of the states can be pretuned based on the parameters of the sliding manifold and the reaching law. Lyapunov theorem is used to provide a rigorous stability proof for the feedback control system. Numerical simulations and processor-in-the-loop (PIL) experiments are conducted to validate and implement the designed flight control algorithm on real autopilot hardware. The novelty of the proposed research lies in hardware implementation of a sophisticated version of modern control technique that exhibits a multitude of distinguishing features including but not limited to (i) finite-time tracking stability featuring fast convergence is ensured, (ii) chattering and singularity problems in sliding mode control (SMC) are avoided, and (iii) null steady-state error is achieved along with enhanced robustness. Finally, the proposed control law is compared with two recently reported research works. Results of performance comparison in term of the integral of square error (ISE) and the absolute value of the derivative of the input ut (IADU) dictate that the proposed technique overperforms by precision and chattering alleviation.

The Vibrio genus inhabit estuarine and marine ecosystem throughout the world and can cause severe infections in humans and animals. Previous studies have demonstrated the dynamics of Vibrio at both community and population levels and assessed the close relationship between environmental factors and Vibrio diversity and abundance, such as temperature, salinity, and dissolved oxygen. It is also generally believed that aquaculture is the fastest-growing food sector, which is also applying great environmental impacts on microbial communities in aquatic ecosystems. However, our understanding of the spatiotemporal quantification of Vibrio throughout the four seasons in the aquaculture zone and response to environmental factors remains poor. To explore the spatiotemporal distribution and abundance of the Vibrio community with their related environmental factors and detect the relationships among them, we collected 10 seawater sites spanning four seasons across the whole year in Dongshan Bay for investigating the Vibrio community dynamics. Marked differences in diversity and abundance of the Vibrio community were observed between seasons, which were mainly driven by temperature, dissolved oxygen, nitrate, and nitrite. qPCR analysis showed that Vibrio abundance was most abundant in the summer (5.37 × 106 copies/L), compared with the autumn (4.58 × 106 copies/L), spring (1.18 × 106 copies/L), and winter (1.55 × 104 copies/L). A total of 22 Vibrio operational taxonomic units (OTUs) and 28 species were identified by universal bacteria 16S rRNA gene and cultivation methods, with Vibrio fortis the dominant in these aquaculture areas. To summarize, our present study is one of the few studies to research the occurrence of Vibrio in marine aquaculture of South China, and the results indicate that Vibrio are widely distributed in aquaculture environment and that a further risk assessment is needed to be conducted.

Ovarian cancer is the most lethal gynecological malignancy. Abnormal homologous recombination repair, high level of reactive oxygen species (ROS) and upregulation of antioxidant genes are characteristic features of ovarian cancer. However, the molecular mechanisms governing the redox homeostasis in ovarian cancer cells remain to be fully elucidated. We here demonstrated a critical role of RAD51, a protein essential for homologous recombination, in the maintenance of redox homeostasis. We found that RAD51 is overexpressed in high grade serous ovarian cancer and is associated with poor prognosis. Depletion or inhibition of RAD51 results in G2/M arrest, increased production of reactive oxygen species and accumulation of oxidative DNA damage. Importantly, antioxidant N-acetylcysteine (NAC) significantly attenuated the induction of DNA damage and the perturbation of proliferation caused by RAD51 depletion. We further demonstrated that RAD51 inhibition or depletion led to elevated production of mitochondrial superoxide and increased accumulation of mitochondria. Moreover, CHK1 activation is required for the G2/M arrest and the generation of mitochondrial stress in response to RAD51 depletion. Together, our results indicate that nuclear DNA damage caused by RAD51 depletion may trigger mitochondria-originated redox dysregulation. Our findings suggest that a vicious cycle of nuclear DNA damage, mitochondrial accumulation and oxidative stress may contribute to the tumor-suppressive effects of RAD51 depletion or inhibition.

Abstract Background Difference between combined inspiratory and expiratory muscle training in same respiratory cycle or different cycles remained unclarified. We explored the difference between both patterns of combined trainings in patients with COPD. Methods In this randomized, open-label, controlled trial, stable COPD subjects trained for 48 minutes daily, for 8 weeks, using a monitoring device for quality control. Ninety-two subjects were randomly and equally assigned for sham training, inspiratory muscle training(IMT), combined inspiratory and expiratory muscle training in same cycle(CTSC) or combined inspiratory and expiratory muscle training in different cycles(CTDC). Respiratory muscle strength, as the primary endpoint, was measured before and after training. Registry: ClinicalTrials.gov (identifier: NCT02326181). Results Respiratory muscle training improved maximal inspiratory pressure(PImax), while no significant difference was found in PImax among IMT, CTSC and CTDC. Maximal expiratory pressure(PEmax) in CTSC and CTDC was greater than IMT(P = 0.026, and P=0.04, respectively) and sham training (P = 0.001). IMT, CTSC, and CTDC shortened inhalation and prolonged exhalation(P < 0.01). Subjects with respiratory muscle weakness in IMT and CTDC exhibited greater increase in PImax than those without. IMT, CTSC and CTDC showed no difference in symptoms and quality of life scales among themselves(P > 0.05). Conclusion Both patterns of CTSC and CTDC improved inspiratory and expiratory muscle strength, while IMT alone only raised PImax. Respiratory muscle training might change the respiratory cycles, and be more beneficial for COPD patients with inspiratory muscle weakness.

Scanning probe microscopy has been extensively applied to probe interfacial water but the probes tend to disturb the structure of water easily. Here, the authors report submolecular-resolution imaging of water clusters within the nearly non-invasive region by qPlus noncontact atomic force microscopy.

Abstract White spot syndrome virus (WSSV) is a major pathogen of penaeid shrimp. Here we identified a new WSSV strain, WSSV-CN04, from naturally infected Marsupenaeus japonicus. Whole genomic sequencing results indicate that the WSSV-CN04 genome was 281 054 bp in length, and encoded 157 hypothetic proteins. The genome sequence of WSSV-CN04 was most closely related to the low-virulent strain WSSV-CN03, sharing 97.5% sequence identity. Notably, in WSSV-CN04, the major envelop protein VP24 was not only truncated but also absent in the virions. Since VP24 was previously reported to be essential for WSSV per os infection by mediating WSSV-chitin interaction, we further analyzed the peroral infection of WSSV-CN03 and -CN04 in Litopenaeus vannamei, and show that the infectivity of WSSV-CN04 was significantly lower than that of WSSV-CN03. When compared with WSSV-CN03-infected shrimp, fewer virions were detected in the digestive tract tissues of WSSV-CN04-infected shrimp at 4 hours post-infection (hpi), and the viral titers in the animals at 24 hpi were much lower. Moreover, a peptide corresponding to VP24 chitin-binding domain reduced the amount of WSSV-CN03 in the midgut to a level similar to that of WSSV-CN04 at 4 hpi. These findings indicate that the truncation of VP24 may attenuate the peroral infectivity of WSSV-CN04, and therefore verify the important role of VP24 in WSSV per os infection.

The structure and dynamics of interfacial water, determined by the water-interface interactions, are important for a wide range of applied fields and natural processes, such as water diffusion (Kim et al., 2013), electrochemistry (Markovic, 2013), heterogeneous catalysis (Over et al., 2000), and lubrication (Zilibotti et al., 2013). The precise understanding of water-interface interactions largely relies on the development of atomic-scale experimental techniques (Guo et al., 2014) and computational methods (Hapala et al., 2014b). Scanning probe microscopy has been extensively applied to probe interfacial water in many interdisciplinary fields (Ichii et al., 2012; Shiotari and Sugimoto, 2017; Peng et al., 2018a). In this perspective, we review the recent progress in the noncontact atomic force microscopy (nc-AFM) imaging and AFM simulation techniques and discuss how the newly developed techniques are applied to study the properties of interfacial water. The nc-AFM with the quadrupole-like CO-terminated tip can achieve ultrahigh-resolution imaging of the interfacial water on different surfaces, trace the reconstruction of H-bonding network and determine the intrinsic structures of the weakly bonded water clusters and even their metastable states. In the end, we present an outlook on the directions of future AFM studies of interfacial water as well as the challenges faced by this field.

This paper proposes a unified system framework based on linear frequency modulation (LFM) and orthogonal frequency-division multiplexing (OFDM) as a solution for resource sharing, especially sharing space and hardware. The proposed OFDM-LFM framework can not only transmit data flow by OFDM but also make it possible to extract features from the signal by LFM. Further, the signal features are used to construct a pseudospectrum related to the target speed and distance, thereby estimating the speed and distance of the target. Unified means using signal features to estimate target speed and distance while ensuring data transmission including communication and remote control data information. Besides the traditional data transmission mode, the ability of estimating target speed and distance is an additional benefit. The proposed unified framework makes control of transmission easier and saves more hardware resources. The simulation results show that the proposed LFM-OFDM framework can not only transmit data information including communication and remote control data information, but also estimate the speed and distance of the target by its signal features.