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IntroductionGenitourinary syndrome of menopause (GSM) describes the symptoms and signs resulting from the effect of estrogen deficiency on the female genitourinary tract, including genital, urinary, and sexual symptoms. However, besides estrogen deficiency, little is known about the etiology of GSM. The objective of this study was to investigate the effects of vaginal microbiota dysbiosis on the occurrence and development of GSM in perimenopausal and postmenopausal women.MethodsIn total, 96 women were enrolled in this cross-sectional study and clinical data were collected. GSM symptoms were divided into three types: genital, urological, and sexual symptoms. Full-length 16S rRNA gene sequencing using the third-generation PacBio sequencing technology was performed to analyze the vaginal microbiome using vaginal swabs of non-GSM and GSM women with different types of GSM symptoms. Live Lactobacillus Capsule for Vaginal Use (LLCVU) treatment was used to verify the effects of Lactobacillus on GSM symptoms.ResultsWe found that 83.58% (56/67) of women experienced GSM symptoms in the perimenopausal and postmenopausal stages. Among these women with GSM, 23.21% (13/56), 23.21% (13/56), and 53.57% (30/56) had one type, two types, and three types of GSM symptoms, respectively. The richness and diversity of vaginal microbiota gradually increased from reproductive to postmenopausal women. There were significant differences in vaginal microbial community among non-GSM women and GSM women with different types of symptoms. Lactobacillus was found to be negatively associated with the onset, severity, and type of GSM while some bacteria, such as Escherichia-shigella, Anaerococcus, Finegoldia, Enterococcus, Peptoniphilus_harei, and Streptococcus, were found to be positively associated with these aspects of GSM, and these bacteria were especially associated with the types of genital and sexual symptoms in GSM women. LLCVU significantly relieved genital symptoms and improved the sexual life of GSM women in shortterm observation.ConclusionsThe onset, severity, and type of GSM symptoms may be associated with changes in vaginal microbiota in perimenopausal and postmenopausal women. Vaginal microbiota dysbiosis probably contributes to the occurrence and development of GSMsymptoms, especially vaginal and sexual symptoms. Lactobacillus used in the vagina may be a possible option for non-hormonal treatment of GSM women with genital and sexual symptoms.Clinical Trial Registrationhttps://www.chictr.org.cn/indexEN.html, identifier ChiCTR2100044237.

Abstract There are a series of challenges in microgrid transactions, and blockchain technology holds the promise of addressing these challenges. However, with the increasing number of users in microgrid transactions, existing blockchain systems may struggle to meet the growing demands for transactions. Therefore, this paper proposes an efficient and secure blockchain consensus algorithm designed to meet the demands of large-scale microgrid electricity transactions. The algorithm begins by utilizing a Spectral clustering algorithm to partition the blockchain network into different lower-level consensus set based on the transaction characteristics of nodes. Subsequently, a dual-layer consensus process is employed to enhance the efficiency of consensus. Additionally, we have designed a secure consensus set leader election strategy to promptly identify leaders with excellent performance. Finally, we have introduced an authentication method that combines zero-knowledge proofs and key sharing to further mitigate the risk of malicious nodes participating in the consensus. Theoretical analysis indicates that our proposed consensus algorithm, incorporating multiple layers of security measures, effectively withstands blockchain attacks such as denial of service. Simulation experiment results demonstrate that our algorithm outperforms similar blockchain algorithms significantly in terms of communication overhead, consensus latency, and throughput.

Cardiovascular diseases have been identified as vital factors in global morbidity and mortality in recent years. The available evidence suggests that various cytokines and pathological proteins participate in these complicated and changeable diseases. The thrombospondin (TSP) family is a series of conserved, multidomain calcium-binding glycoproteins that cause cell-matrix and cell-cell effects via interactions with other extracellular matrix components and cell surface receptors. The TSP family has five members that can be divided into two groups (Group A and Group B) based on their different structures. TSP-1, TSP-2, and TSP-4 are the most studied proteins. Among recent studies and findings, we investigated the functions of several family members, especially TSP-5. We review the basic concepts of TSPs and summarize the relevant molecular mechanisms and cell interactions in the cardiovascular system. Targeting TSPs in CVD and other diseases has a remarkable therapeutic benefit.

Network data plane performs packet processing and forwarding, which is one of the core factors determining the network performance.High bandwidth, low latency and rapid evolution of the network infrastructure require building an efficient and programmable network data plane.The packet processing and forwarding model was firstly introduced, and on this basis, the challenges of the network data plane in the performance and programmability were outlined.Then the basic ideas and core technology progress were elaborated to deal with the above challenges by analyzing the theory of packet processing algorithms and hardware-software codesign implementations.Finally, the trend and technical route of constructing an efficient programmable data plane were discussed.

Microorganisms play very important roles in carcinogenesis, tumor progression, and resistance upon treatment. Due to the challenge of accurately acquiring samples and quantifying low-biomass tissue microorganisms, most studies have focused on the effect of gut microorganisms on cancer treatments, especially the efficacy of immunotherapy. Although recent publications reveal the potential interactions between intratumor microorganisms and the immune microenvironment, whether and to what extent the intratumor microorganism could affect progression and treatment outcome remain controversial. This study is aiming to evaluate the associations among intratumor microorganisms, DNA methylation cancer driver genes, immune response, and clinical outcomes from a pan-cancer perspective, using 6,876 TCGA samples across 21 cancer types. We revealed that tumor microorganism dysbiosis is closely associated with the abnormal tumor methylome and/or tumor microenvironment, which might serve to enhance the proliferation ability and fitness for the therapy of tumors. These findings shed the light on a better understanding of the interactions between tumor cells and carcinogens during and after tumor formation, as well as microorganism-associated methylation alterations that could further serve as biomarkers for clinical outcome assessment.

Abstract Background Chemotherapy can induce premature ovarian insufficiency (POI). POI causes multiple sequelae and is currently incurable. As shown in our previous studies, systemically transplanted human amnion-derived mesenchymal stem cells (hAD-MSCs) home to ovaries with chemotherapy-induced POI and subsequently reduce ovarian injury and improve ovarian function in rats with POI. However, the cellular mechanisms that direct the migration and homing of hAD-MSCs to ovaries with chemotherapy-induced POI are incompletely understood. This study investigated the role of the SDF-1/CXCR4 axis in the migration and homing of systemically transplanted hAD-MSCs to ovaries with chemotherapy-induced POI and its relevant downstream signalling pathways. Methods CXCR4 expression in hAD-MSCs was assessed using Western blotting and immunofluorescence staining. hAD-MSC migration was tested using Transwell migration assays. SDF-1 levels were detected using ELISA. Seventy-two female SD rats were randomly divided into the control, POI, hAD-MSCs and hAD-MSCs + AMD3100 groups. Cyclophosphamide was used to establish rat POI models. For inhibitor treatment, hAD-MSCs were pretreated with AMD3100 before transplantation. PKH26-labeled hAD-MSCs were injected into the tail vein of POI rats 24 h after chemotherapy. After hAD-MSC transplantation, the homing of hAD-MSCs to ovaries and ovarian function and pathological changes were examined. We further investigated the molecular mechanisms by detecting the PI3K/Akt and ERK1/2 signalling pathways. Results hAD-MSCs expressed CXCR4. SDF-1 induced hAD-MSC migration in vitro. SDF-1 levels in ovaries and serum were significantly increased in rats with chemotherapy-induced POI, and ovaries with POI induced the homing of hAD-MSCs expressing CXCR4. Blocking the SDF-1/CXCR4 axis with AMD3100 significantly reduced the number of hAD-MSCs homing to ovaries with POI and further reduced their efficacy in POI treatment. The binding of SDF-1 to CXCR4 activated the PI3K/Akt signalling pathway, and LY294002 significantly inhibited hAD-MSC migration induced by SDF-1 in vitro. Moreover, inhibition of the PI3K/Akt signalling pathway significantly reduced the number of systemically transplanted hAD-MSCs homing to chemotherapy-induced ovaries in rats with POI. Conclusions SDF-1/CXCR4 axis partially mediates the migration and homing of systemically transplanted hAD-MSCs to the ovaries of rats with chemotherapy-induced POI, and the PI3K/Akt signalling pathway might be involved in the migration and homing of hAD-MSCs mediated by the SDF-1/CXCR4 axis.

Bone morphogenetic proteins (BMPs) are secretory proteins belonging to the transforming growth factor-β (TGF-β) superfamily. These proteins play important roles in embryogenesis, bone morphogenesis, blood vessel remodeling and the development of various organs. In recent years, as research has progressed, BMPs have been found to be closely related to cardiovascular diseases, especially atherosclerosis, vascular calcification, cardiac remodeling, pulmonary arterial hypertension (PAH) and hereditary hemorrhagic telangiectasia (HHT). In this review, we summarized the potential roles and related mechanisms of the BMP family in the cardiovascular system and focused on atherosclerosis and PAH.

Abstract This letter proposes a direction of arrival (DOA) and time of delay (TOA) joint estimation algorithm with deep transfer learning. Recently deep learning technique has been applied to solve the joint estimation problem by using the pretrained network and perform well. But in real applications, different scenarios require to cost much time to obtain different pretrained network. In order to overcome these problems, a transfer scheme for DOA and TOA joint estimation is proposed based on a multi‐task network, which uses a shared‐private structure to enhance the transferability of the pretrained network in different signal‐to‐noise ratio (SNR) scenarios. Thus, for different target scenarios, the proposed transferring scheme just uses a few of data from new scenario to fine‐tune pretrained network, which can effectively reduce the computation complexity with satisfied estimation accuracy. Simulation results show that the proposed algorithm is superior to other traditional methods in estimation accuracy and efficiency under different SNR testing scenarios.

Targeting lineage-defined transcriptional dependencies has emerged as an effective therapeutic strategy in cancer treatment. Through screening for molecular vulnerabilities of mantle cell lymphoma (MCL), we identified a set of transcription factors (TFs) including FOXO1, EBF1, PAX5, and IRF4 that are essential for MCL propagation. Integrated chromatin immunoprecipitation and sequencing (ChIP-Seq) with transcriptional network reconstruction analysis revealed FOXO1 as a master regulator that acts upstream in the regulatory TF hierarchy. FOXO1 is both necessary and sufficient to drive MCL lineage commitment through supporting the lineage-specific transcription programs. We further show that FOXO1, but not its close paralog FOXO3, can reprogram myeloid leukemia cells and induce B-lineage gene expression. Finally, we demonstrate that cpd10, a small molecule identified from an enriched FOXO1 inhibitor library, induces a robust cytotoxic response in MCL cells in vitro and suppresses MCL progression in vivo. Our findings establish FOXO1 inhibition as a therapeutic strategy targeting lineage-driven transcriptional addiction in MCL.

Chronic lymphocytic leukemia has been studied using multiple levels of omics data. Here, the authors use exome sequencing, SNP, protein and gene expression data to identify distinct biologic tumor subtypes with heterogeneous prognostic impact after chemo- or immunochemotherapy.

BackgroundCardiac dysfunction is one of the most common complications of sepsis and is associated with the adverse outcomes and high mortality of sepsis patients. IL-12p40, the common subunit of IL-12 and IL-23, has been shown to be involved in a variety of inflammation-related diseases, such as psoriasis and inflammatory bowel disease. However, the role of IL-12p40 in lipopolysaccharide (LPS)-induced cardiac dysfunction remains obscure. This study aimed to explore the role of IL-12p40 in LPS-induced cardiac dysfunction and its potential mechanisms.MethodsIn this study, mice were treated with LPS and the cardiac expression of IL-12p40 was determined. Then, IL-12p40–/– mice were used to detect the role and mechanisms of IL-12p40 in LPS-induced cardiac injury. In addition, monocytes were adoptively transferred to IL-12p40–/– mice to explore their effects on LPS-induced cardiac dysfunction.ResultsThe results showed that cardiac IL-12p40 expression was significantly increased after treated with LPS. In addition, IL-12p40 deletion significantly aggravated LPS-induced cardiac dysfunction, evidenced by the increased serum levels of cardiomyocyte injury markers and heart injury scores, as well as by the deteriorated cardiac function. Moreover, IL-12p40 deletion increased LPS-induced monocyte accumulation and cardiac expression of inflammatory cytokines, as well as enhanced the activation of the NF-κB and MAPK pathways. Furthermore, adoptive transfer WT mouse monocytes to IL-12p40−/− mice alleviated LPS-induced cardiac dysfunction and decreased the phosphorylation of p65.ConclusionIL-12p40 deletion significantly aggravated LPS-induced cardiac injury and cardiac dysfunction in mice by regulating the NF-κB and MAPK signaling pathways, and this process was related to monocytes. Therefore, IL-12p40 show a protective role in SIC, and IL-12p40 deficiency or anti-IL-12p40 monoclonal antibodies may be detrimental to patients with SIC.

Cardiovascular disease is one of the main causes of human mortality. Cytokines play crucial roles in the development of cardiovascular disease. Interleukin (IL)-6 family members are a series of cytokines, including IL-6, IL-11, IL-30, IL-31, OSM, LIF, CNTF, CT-1, CT-2, and CLC, that regulate multiple biological effects. Experimental and clinical evidence shows that IL-6 family members are closely related to cardiovascular diseases such as atherosclerosis, hypertension, aortic dissection, cardiac fibrosis, and cardiomyopathy. This review mainly discusses the role of IL-6 family members in cardiovascular disease for the sake of identifying possible intervention targets for cardiovascular disease prevention and treatment.

A series of Sm3+ ions doped Sr3Al2O6 phosphors was successfully synthesized via hydrothermal method. The crystal structure, morphology and luminescent properties of samples were analyzed by X-ray diffraction, scanning electron microscopy and photoluminescence spectra. All the samples took on cubic structure with Pa-3 space group. The Sr3Al2O6:Sm3+ phosphors could be excited by 405 nm and emit orange-red light peaked at 565, 609 and 660 nm. The effect of hydrothermal reaction time on the morphology and luminescent properties of phosphor was investigated. The influence of molar fraction of Sm3+ ions on the emission intensity of samples was studied and it has been found that the optimal dosage is 0.01. The calculated results by the first principle indicated that the Sm3+ ions will easily occupy the symmetric center site (Sr1). The results indicated that the luminescent intensity of Sr3Al2O6:Sm3+ phosphors could be modulated by reaction conditions of hydrothermal method.

Benign prostatic hyperplasia (BPH) is one of the most common diseases affecting aging men with limited therapeutic options. In this study, the authors describe the molecular characterization of BPH performing genomic, transcriptomic and epigenetic analysis of 18 BPH cases.

The Internet of Things (IoT) and cloud technologies have significantly facilitated healthcare. In such a context, medical data are collected by the terminals from the patients, manipulated, and stored on the cloud by hospitals (doctors). This brings asymmetry problems in medical data access control, processing, and storage between doctors and patients, which results in medical data sharing face many challenges such as privacy leakage and malicious feedback from cloud servers on queries. To solve these asymmetry problems, this paper proposes a medical data sharing scheme with cloud-chain cooperation and policy fusion in the IoT. Regarding asymmetrical access control rights, a conflict resolution and fusion algorithm that enables co-authorization of medical data by the doctor and the patient is introduced. To balance the symmetry of medical data storage and processing, a cloud-chain cooperation ciphertext retrieval method is proposed by means of two-stage joint searching from cloud servers and the blockchain, which can not only detect malicious medical data feedback from cloud servers, but also improve the data search efficiency. The security analysis showed that this scheme satisfies the confidentiality and verifiability of the retrieved information, and the feasibility of the proposed scheme was demonstrated through experiments.

The Internet of Things technology has been used in many fields with its powerful functions, diverse forms, and advanced technologies. The Internet of Things technology can be connected with various technologies and models through the cognitive recognition layer, network construction layer, management service layer, and integrated application layer, to get better functionality. In order to make medical technology more advanced, the IoT technology is applied to the 3D medical image model to improve the treatment effect. First, 30 volunteers were selected to perform X-ray scanning on the human body through the sensor module to obtain the data. Then, the data were transmitted to the Geomagic Studio module through the Zig-Bee module, and the orthopedic rehabilitation device was adjusted to complete the establishment of the 3D model. Finally, the CAE finite-element analysis module is used to analyze the performance of the model, and the optimal structure is calculated to print the best 3D model. Then, the volunteers are tracked to integrate the data from the size and weight. The 3D printed models were investigated in eight aspects: adjustment, safety, durability, ease of use, comfort, and effectiveness. Finally, it is concluded that the application of the Internet of Things technology to the 3D medical image model can improve the convenience, safety, durability, and effectiveness of the 3D medical image model, thereby improving the overall medical level.

A family G of connected graphs is a family with unbounded metric dimension if dim(G) is not constant and depends on the order of graph. In this paper, we compute the metric dimension of the splitting graphs S(Pn) and S(Cn) of a path and cycle. We prove that the metric dimension of these graphs varies and depends on the number of vertices of the graph.

Fabrication of dense aluminum (Al-1100) parts (>99.3% of relative density) by our recently developed laser-foil-printing (LFP) additive manufacturing method was investigated as described in this paper. This was achieved by using a laser energy density of 7.0 MW/cm2 to stabilize the melt pool formation and create sufficient penetration depth with 300 μm thickness foil. The highest yield strength (YS) and ultimate tensile strength (UTS) in the LFP-fabricated samples reached 111 ± 8 MPa and 128 ± 3 MPa, respectively, along the laser scanning direction. These samples exhibited greater tensile strength but less ductility compared to annealed Al-1100 samples. Fractographic analysis showed elongated gas pores in the tensile test samples. Strong crystallographic texturing along the solidification direction and dense subgrain boundaries in the LFP-fabricated samples were observed by using the electron backscattered diffraction (EBSD) technique.

Stretchable electronics represent a new generation of electronics that utilize soft, deformable elastomers as the substrate or matrix instead of the traditional rigid printed circuit boards. As the most essential component of stretchable electronics, the conductors should meet the requirements for both high conductivity and the capability to maintain conductive under large deformations such as bending, twisting, stretching, and compressing. This review summarizes recent progresses in various aspects of this fascinating and challenging area, including materials for supporting elastomers and electrical conductors, unique designs and stretching mechanics, and the subtractive and additive patterning techniques. The applications are discussed along with functional devices based on these conductors. Finally, the review is concluded with the current limitations, challenges, and future directions of stretchable conductors.

The Laser Direct Synthesis and Patterning (LDSP) technology has advantages in terms of processing time and cost compared to nanomaterials-based laser additive microfabrication processes. In LDSP, a scanning laser on the substrate surface induces chemical reactions in the reactive liquid solution and selectively deposits target material in a preselected pattern on the substrate. In this study, we experimentally investigated the effect of the processing parameters and type and concentration of the additive solvent on the properties and growth rate of the resulting metal film fabricated by this LDSP technology. It was shown that reactive metal ion solutions with substantial viscosity yield metal films with superior physical properties. A numerical analysis was also carried out the first time to investigate the coupled opto-thermo-fluidic transport phenomena and the effects on the metal film growth rate. To complete the simulation, the optical properties of the LDSP deposited metal film with a variety of thicknesses were measured. The characteristics of the temperature field and the thermally induced flow associated with the moving heat source are discussed. It was shown that the processing temperature range of the LDSP is from 330 to 390 K. A semi-empirical model for estimating the metal film growth rate using this process was developed based on these results. From the experimental and numerical results, it is seen that, owing to the increased reflectivity of the silver film as its thickness increases, the growth rate decreases gradually from about 40 nm at initial to 10 nm per laser scan after ten scans. This self-controlling effect of LDSP process controls the thickness and improves the uniformity of the fabricated metal film. The growth rate and resulting thickness of the metal film can also be regulated by adjustment of the processing parameters, and thus can be utilized for controllable additive nano/microfabrication.