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Abstract Depression is a prevalent mental disorder with a complex biological mechanism. Following the rapid development of systems biology technology, a growing number of studies have applied proteomics and metabolomics to explore the molecular profiles of depression. However, a standardized resource facilitating the identification and annotation of the available knowledge from these scattered studies associated with depression is currently lacking. This study presents ProMENDA, an upgraded resource that provides a platform for manual annotation of candidate proteins and metabolites linked to depression. Following the establishment of the protein dataset and the update of the metabolite dataset, the ProMENDA database was developed as a major extension of its initial release. A multi-faceted annotation scheme was employed to provide comprehensive knowledge of the molecules and studies. A new web interface was also developed to improve the user experience. The ProMENDA database now contains 43,366 molecular entries, comprising 20,847 protein entries and 22,519 metabolite entries, which were manually curated from 1370 human, rat, mouse, and non-human primate studies. This represents a significant increase (more than 7-fold) in molecular entries compared to the initial release. To demonstrate the usage of ProMENDA, a case study identifying consistently reported proteins and metabolites in the brains of animal models of depression was presented. Overall, ProMENDA is a comprehensive resource that offers a panoramic view of proteomic and metabolomic knowledge in depression. ProMENDA is freely available at https://menda.cqmu.edu.cn .

Proposes To investigate the toxicological mechanism of hexavalent chromium, the effects of hexavalent chromium on the heart, gastrocnemius muscle and action potential of sciatic nerve trunk in bullfrog were studied from the perspective of electrophysiology. Methods The bullfrog hearts were treated with different concentrations of potassium dichromate solution by intraperitoneal injection and isolated heart perfusion, and the effects of hexavalent chromium on heart rate and contractility in vivo and in vitro were determined. The gastrocnemius muscle was wrapped with a gauze soaked in potassium dichromate solution, and the contractility of gastrocnemius muscle was measured. The effect of hexavalent chromium on conduction velocity of sciatic nerve trunk was measured by extracellular electrode guidance. Findings The results show that potassium dichromate has an inhibitory effect on heart rate and contractility, and the mechanism may be related to the inhibition of Ttype and L-type calcium channels activity by hexavalent chromium; However, 1 mg/L chromium increases the heart rate of in vivo frog heart after 15 to 30 min, which may be due to the “hormetic effect”; 0.001 to 10 mg/L hexavalent chromium has a concentration-dependent enhancement effect on gastrocnemius contractility, showing a positive inotropic effect, which may be the result of “hormetic effect”; Hexavalent chromium at 100 mg/L inhibits the gastrocnemius contractility, showing a negative inotropic effect, the mechanism is related to the inhibitory effect of hexavalent chromium on ryanodine receptor (RyR); Hexavalent chromium reduces the conduction velocity of sciatic nerve trunk action potential in a concentration and time-dependent manner, and the mechanism was related to the inactivation of voltage-gated Na+ channels by hexavalent chromium. Conclusions Hexavalent chromium has toxicity on heart, skeletal muscle, and nerve, which could provide some electrophysiological experimental basis for the toxicity study of hexavalent chromium.

Purposes Osteoarthritis (OA) is a degenerative joint disease that commonly occurs in middle-aged and elderly people. Mechanical microenvironment is one of the most significant factors in the development of OA. However, when the mechanical microenvironment changes, the inflammatory response of chondrocyte is elusive. Methods By adopting polydimethylsiloxane (PDMS) substrates with varying stiffness which can mimic the physiological stiffness of chondrocyte pericellular matrix (PCM), influences of co-regulated substrate stiffness and inflammatory factors interleukin-1β (IL-1β) on chondrocyte morphology, inflammatory mediators, and PCM remodeling protein expression are quantitatively analyzed. First, prostaglandin E2 (PGE2) and nitric oxide (NO) released in different stiffness substrates and IL-1β stimulated substrates with chondrocytes are detected. Second, the changes in different stiffness substrates and IL-1β stimulated substrates through immunofluorescence technique are observed and recorded. Third, the protein expressions of type Ⅱ collagen (COLII) and matrix metalloproteinase-13 (MMP13) are measured by Western blot assay. Findings The experimental results identify that substrate stiffness regulates the response of chondrocyte to inflammatory signals. Soft substrate dramatically enhances the release of PGE2 and NO (P

Due to the limited self-healing ability of cartilage, cartilage defect repair remains a challenge in clinical treatment. Therefore, there is a need to provide patients with a promising cartilage defect repair strategy. In this study, we have reported an icariin-loaded PVA based biocompatible hydrogel scaffold for cartilage defect repair. The PTGH+Icariin hydrogel was prepared by a simple physical cross-linking method and consisted of polyvinyl alcohol (PVA), tannic acid (TA), gelatin (Gel), hyaluronic acid (HA) and icariin. Inspired by the natural cartilage matrix compositions, the Gel and HA were used to improve the bioactivity and biocompatibility of hydrogel. Furthermore, icariin was introduced to further enhance the hydrogel’s ability for cartilage regeneration. The results showed that PTGH+icariin hydrogel exhibited porous microstructures and tough mechanical properties. In vitro cell experiments confirmed PTGH+Icariin hydrogels could promote chondrocytes proliferation, chondrocytes spreading and chondrocytes migration. Meanwhile, the PTGH+Icariin hydrogel demonstrated the ability to promote the cartilage regeneration in a rat cartilage defect model. In particular, the implantation of PTGH+Icariin hydrogel could facilitate the restoration of motor function in rats. This study will provide a potential approach for the treatment of cartilage defects.

Contact stress is the important cause of wear and failure of knee joint prostheses implanted in the human body during movement. The calculation of contact stress on joint prostheses is often inaccurate due to the deviation of joint position during activity. This paper proposes a correction method for contact stress based on finite element results. Firstly, the contact stress and contact radius between femoral and tibial prostheses of knee joint were calculated and analyzed by Hertz contact theory. Then, individualized finite element models based on the individualized geometry of the joint prosthesis and individualized loading were constructed, and the finite element contact stress was analyzed. The finite element results were calibrated utilizing the Hertz contact theory. Additionally, this study investigated the impact of three gait patterns (normal gait, medial thrust gait, and bouncing gait) on the contact stress experienced by the tibial insert. The research methods and results can provide ideas for theoretical analysis and finite element simulation of prosthetic joint contact, as well as offer theoretical support and analysis methods for evaluating the lifespan of prosthetic joints.

Abstract Lateral wedge insole (LWI) is a frequently recommended treatment option for early and midterm stages of medial knee osteoarthritis. However, studies of its effects on the lower limb joints are incomplete and imperfect. The main purpose of this study was to quantitatively analyze the response of intervention of LWI on lower-limb joint kinematics, ground reaction forces (GRFs), and centre of pressure (COP). Gait analysis of 16 healthy subjects was conducted. Three-dimensional motion data and force plate measurements were collected in the control (barefoot) and experimental conditions (wearing a pair of assigned shoes with 0, 7, and 10 mm LWIs). Results showed that the peak knee flexion angle was increased by 3.43°, 3.09°, and 3.27° with 0, 7, and 10 mm LWIs, respectively (p

Background: Major depressive disorder (MDD) was involved in widely transcriptional changes in central and peripheral tissues. While, previous studies focused on single tissues, making it difficult to represent systemic molecular changes throughout the body. Thus, there is an urgent need to explore the central and peripheral biomarkers with intrinsic correlation. Methods: We systematically retrieved gene expression profiles of blood and anterior cingulate cortex (ACC). 3 blood datatsets (84 MDD and 88 controls) and 6 ACC datasets (100 MDD and 100 controls) were obtained. Differential expression analysis, RobustRankAggreg (RRA) analysis, functional enrichment analysis, immune associated analysis and protein-protein interaction networks (PPI) were integrated. Furthermore, the key genes were validated in an independent ACC dataset (12 MDD and 15 controls) and a cohort with 120 MDD and 117 controls. Results: Differential expression analysis identified 2211 and 2021 differential expressed genes (DEGs) in blood and ACC, respectively. RRA identified 45 and 25 robust DEGs in blood and ACC based on DEGs, and all of them were closely associated with immune cells. Functional enrichment results showed both the robust DEGs in blood and ACC were enriched in humoral immune response. Furthermore, PPI identified 8 hub DEGs (CD79A, CD79B, CD19, MS4A1, PLP1, CLDN11, MOG, MAG) in blood and ACC. Independent ACC dataset showed the area under the curve (AUC) based on these hub DEGs was 0.77. Meanwhile, these hub DEGs were validated in the serum of MDD patients, and also showed a promising diagnostic power. Conclusions: The biomarker panel based on hub DEGs yield a promising diagnostic efficacy, and all of these hub DEGs were strongly correlated with immunity. Humoral immune response may be the key link between the brain and blood in MDD, and our results may provide further understanding for MDD.

IntroductionSchizophrenia is a complex psychiatric disorder, of which molecular pathogenesis remains largely unknown. Accumulating evidence suggest that gut microbiota may affect brain function via the complex gut-brain axis, which may be a potential contributor to schizophrenia. However, the alteration of gut microbiota showed high heterogeneity across different studies. Therefore, this study aims to identify the consistently altered gut microbial taxa associated with schizophrenia.MethodsWe conducted a systematic search and synthesis of the up-to-date human gut microbiome studies on schizophrenia, and performed vote counting analyses to identify consistently changed microbiota. Further, we investigated the effects of potential confounders on the alteration of gut microbiota.ResultsWe obtained 30 available clinical studies, and found that there was no strong evidence to support significant differences in α-diversity and β-diversity between schizophrenic patients and healthy controls. Among 428 differential gut microbial taxa collected from original studies, we found that 8 gut microbial taxa were consistently up-regulated in schizophrenic patients, including Proteobacteria, Gammaproteobacteria, Lactobacillaceae, Enterobacteriaceae, Lactobacillus, Succinivibrio, Prevotella and Acidaminococcus. While 5 taxa were consistently down-regulated in schizophrenia, including Fusicatenibacter, Faecalibacterium, Roseburia, Coprococcus and Anaerostipes.DiscussionThese findings suggested that gut microbial changes in patients with schizophrenia were characterized by the depletion of anti-inflammatory butyrate-producing genera, and the enrichment of certain opportunistic bacteria genera and probiotics. This study contributes to further understanding the role of gut microbiota in schizophrenia, and developing microbiota-based diagnosis and therapy for schizophrenia.

Abstract Background During endotracheal intubation, extubation, tracheotomy, and tracheotomy tube replacement, the splashed airway secretions of patients will increase the risk of transmission of SARS-CoV‐2 and many other potential viral and bacterial diseases, such as influenza virus, adenovirus, respiratory syncytial virus, rhinovirus, Middle East respiratory coronavirus syndrome (MERS-CoV), Streptococcus pneumoniae, and Mycobacterium tuberculosis. Therefore, it is necessary to establish a barrier between patients and medical workers to reduce the risk of operators’ infection with potentially pathogenic microorganisms. Methods We designed a “safety cap” that can be connected to the opening of an endotracheal tube or tracheotomy tube to reduce the diffusion area of respiratory secretions during the process of endotracheal intubation, extubation and tracheotomy tube replace, so as to reduce the infection risk of medical workers. Results Through a series of hydrodynamic simulation analysis and experiments, we demonstrated that the use of “safety cap” can substantially limit the spatter of airway secretions, so as to improve the hospital sanitation. Conclusion The “safety cap” can effectively limit the dissemination of patients’ respiratory secretions, thus reducing the risk of potential diseases transmission and may have certain application prospects.

The extraction of typical features of underwater target signals and excellent recognition algorithms are the keys to achieving underwater acoustic target recognition of divers. This paper proposes a feature extraction method for diver signals: frequency−domain multi−sub−band energy (FMSE), aiming to achieve accurate recognition of diver underwater acoustic targets by passive sonar. The impact of the presence or absence of targets, different numbers of targets, different signal−to−noise ratios, and different detection distances on this method was studied based on experimental data under different conditions, such as water pools and lakes. It was found that the FMSE method has the best robustness and performance compared with two other signal feature extraction methods: mel frequency cepstral coefficient filtering and gammatone frequency cepstral coefficient filtering. Combined with the commonly used recognition algorithm of support vector machines, the FMSE method can achieve a comprehensive recognition accuracy of over 94% for frogman underwater acoustic targets. This indicates that the FMSE method is suitable for underwater acoustic recognition of diver targets.

Background & Aims: The immune tolerance induced by hepatitis B virus (HBV) is a major challenge for achieving effective viral clearance, and the mechanisms involved are not well-understood. One potential factor involved in modulating immune responses is mesencephalic astrocyte-derived neurotrophic factor (MANF), which has been reported to be increased in patients with chronic hepatitis B. In this study, our objective is to examine the role of MANF in regulating immune responses to HBV. Methods: We utilized a commonly used HBV-harboring mouse model, where mice were hydrodynamically injected with the pAAV/HBV1.2 plasmid. We assessed the HBV load by measuring the levels of various markers including hepatitis B surface antigen, hepatitis B envelope antigen, hepatitis B core antigen, HBV DNA, and HBV RNA. Results: Our study revealed that following HBV infection, both myeloid cells and hepatocytes exhibited increased expression of MANF. Moreover, we observed that mice with myeloid-specific MANF knockout (ManfMye-/-) displayed reduced HBV load and improved HBV-specific T cell responses. The decreased HBV-induced tolerance in ManfMye-/- mice was associated with reduced accumulation of myeloid-derived suppressor cells (MDSCs) in the liver. Restoring MDSC levels in ManfMye-/- mice through MDSC adoptive transfer reinstated HBV-induced tolerance. Mechanistically, we found that MANF promoted MDSC expansion by activating the IL-6/STAT3 pathway. Importantly, our study demonstrated the effectiveness of a combination therapy involving an hepatitis B surface antigen vaccine and nanoparticle-encapsulated MANF siRNA in effectively clearing HBV in HBV-carrier mice. Conclusion: The current study reveals that MANF plays a previously unrecognized regulatory role in liver tolerance by expanding MDSCs in the liver through IL-6/STAT3 signaling, leading to MDSC-mediated CD8+ T cell exhaustion.

This paper investigates the threat assessment method and target assignment algorithm in multi-UAV cooperative air combat decision-making. To address the uncertainty and dynamic changes in multiple threat attributes and attribute information of UAV targets, we propose a UAV target dynamic threat assessment method based on intuitionistic fuzzy multiattribute decision-making. Firstly, we propose a mixed situation information representation method to represent interval-valued fuzzy data appropriately. Secondly, we employ the normal distribution weight assignment method to fuse the multi-time situation information. Then, by incorporating the analytic hierarchy process and entropy method, we determine the normalized threat value of the target considering both objective situation data characteristics and decision-maker preferences. Finally, a simulation example is provided to validate the rationality of our proposed algorithm. For solving the multi-weapon multi-target assignment problem, a target assignment method based on the VNS-IBPSO algorithm is introduced. This method improves upon the limitations of the BPSO algorithm, such as limited local search capability and premature convergence, by combining variable neighborhood search and an improved binary particle swarm optimization algorithm. Simulation results show that the proposed threat assessment method can obtain reasonable threat assessment results under complex dynamic environments. The proposed VNS-IBPSO algorithm can solve the target assignment model quickly and efficiently based on the assessment results, therefore ensuring that the UAV mission planning system makes the correct combat plan.

A novel standard trajectory design and tracking guidance used in the multiple active leap maneuver mode for hypersonic glide vehicles (HGVs) is proposed in this paper. First, the dynamic equation and multiconstraint model are first established in the flight path coordinate system. Second, the reference drag acceleration-normalized energy (D-e) profile of the multiple active leap maneuver mode is quickly determined by the Newton iterative algorithm with a single design parameter. The range to go error is corrected by the drag acceleration profile update algorithm, and the drag acceleration error of the gliding terminal is corrected by the aerodynamic parameter estimation algorithm. Then, the reference drag acceleration tracking guidance law is designed based on the prescribed performance control method. Finally, the CAV-L vehicle model is used for numerical simulation. The results show that the proposed method can satisfy the design requirements of drag acceleration under multiple active leap maneuver modes, and the reference drag acceleration can be tracked precisely. The adaptability and robustness of the proposed method are verified by the Monte Carlo simulations under various combined deviation conditions.

The prevention, control and treatment of cerebral aneurysm (CA) has become a common concern of human society, and by simulating the biomechanical environment of CA using finite element analysis (FEA), the risk of aneurysm rupture can be predicted and evaluated. The target models of the current study are mainly idealized single-layer linear elastic cerebral aneurysm models, which do not take into account the effects of the vessel wall structure, material constitution, and structure of the real CA model on the mechanical parameters. This study proposes a reconstruction method for patient-specific trilaminar CA structural modeling. Using two-way fluid-structure interaction (FSI), we comparatively analyzed the effects of the differences between linear and hyperelastic materials and three-layer and single-layer membrane structures on various hemodynamic parameters of the CA model. It was found that the numerical effects of the different CA membrane structures and material constitution on the stresses and wall deformations were obvious, but does not affect the change in its distribution pattern and had little effect on the blood flow patterns. For the same material constitution, the stress of the three-layer membrane structure were more than 10.1% larger than that of the single-layer membrane structure. For the same membrane structure, the stress of the hyperelastic material were more than 5.4% larger than that of the linear elastic material, and the displacement of the hyperelastic material is smaller than that of the linear elastic material by about 20%. And the maximum value of stress occurred in the media, and the maximum displacement occurred in the intima. In addition, the upper region of the tumor is the maximum rupture risk region for CA, and the neck of the tumor and the bifurcation of the artery are also the sub-rupture risk regions to focus on. This study can provide data support for the selection of model materials for CA simulation and analysis, as well as a theoretical basis for clinical studies and subsequent research methods.

A template matching method based on the contour fitting heading angle is proposed for the problem of identifying key parts of maritime ships. First, unmanned boats are used as hypothetical enemy targets to extract outer contours, build a matching template library, and establish relevant kinematic models. Based on the requirements of timeliness and relativism, the judgment conditions for fitting angles and heading angles are given. A traversal fitting framework is established based on the structural similarity index algorithm, and the target matching template is matched based on precise matching results. A motion space that combines position correlation, electro-optical detection distance, and target pitch decoupling is designed to obtain real heading angles. Finally, based on the relative position information of the template’s key parts, the key parts of the target are matched, and the normalized output matching image is obtained. The experiment shows that this method can achieve recognition instructions in real seaways where key parts of the target cannot be extracted due to the large amount of water mist, and it has advantages in timeliness, accuracy, and applicability compared with other algorithms. This method has strong robustness and provides a reference for the identification of key parts of various types of ship targets.

Infrared–visible image fusion is valuable across various applications due to the complementary information that it provides. However, the current fusion methods face challenges in achieving high-quality fused images. This paper identifies a limitation in the existing fusion framework that affects the fusion quality: modal differences between infrared and visible images are often overlooked, resulting in the poor fusion of the two modalities. This limitation implies that features from different sources may not be consistently fused, which can impact the quality of the fusion results. Therefore, we propose a framework that utilizes feature-based decomposition and domain normalization. This decomposition method separates infrared and visible images into common and unique regions. To reduce modal differences while retaining unique information from the source images, we apply domain normalization to the common regions within the unified feature space. This space can transform infrared features into a pseudo-visible domain, ensuring that all features are fused within the same domain and minimizing the impact of modal differences during the fusion process. Noise in the source images adversely affects the fused images, compromising the overall fusion performance. Thus, we propose the non-local Gaussian filter. This filter can learn the shape and parameters of its filtering kernel based on the image features, effectively removing noise while preserving details. Additionally, we propose a novel dense attention in the feature extraction module, enabling the network to understand and leverage inter-layer information. Our experiments demonstrate a marked improvement in fusion quality with our proposed method.

Hydroxylation of aryl sulfonium salts could be realized by utilizing acetohydroxamic acid and oxime as hydroxylative agents in the presence of cesium carbonate as a base, leading to a variety of structurally diverse hydroxylated arenes in 47–95% yields. In addition, the reaction exhibited broad functionality tolerance, and a range of important functional groups (e.g., cyano, nitro, sulfonyl, formyl, keto, and ester) could be well amenable to the mild reaction conditions.

Effectively strategizing the trajectories of multiple Unmanned Aerial Vehicles (UAVs) within a dynamic environment to optimize the search for and tracking of mobile targets presents a formidable challenge. In this study, a cooperative coevolution motion-encoded particle swarm optimization algorithm called the CC-MPSO search algorithm is designed to tackle the moving target search issue effectively. Firstly, a Markov process-based target motion model considering the uncertainty of target motion is investigated. Secondly, Bayesian theory is used to formulate the moving target search as an optimization problem where the objective function is defined as maximizing the cumulative probability of detection of the target in finite time. Finally, the problem is solved based on the CC-MPSO algorithm to obtain the optimal search path nodes. The motion encoding mechanism converts the search path nodes into a set of motion paths, which enables more flexible handling of UAV trajectories and improves the efficiency of dynamic path planning. Meanwhile, the cooperative coevolution optimization framework enables collaboration between different UAVs to improve global search performance through multiple swarm information sharing, which helps avoid falling into local optimal solutions. The simulation results show that the CC-MPSO algorithm demonstrates efficacy, reliability, and superior overall performance when compared to the five commonly used swarm intelligence algorithms.

Abstract Renal fibrosis is a common characteristic of various chronic kidney diseases (CKDs) driving the loss of renal function. During this pathological process, persistent injury to renal tubular epithelial cells and activation of fibroblasts chiefly determine the extent of renal fibrosis. In this study, the role of tumor protein 53 regulating kinase (TP53RK) in the pathogenesis of renal fibrosis and its underlying mechanisms is investigated. TP53RK is upregulated in fibrotic human and animal kidneys with a positive correlation to kidney dysfunction and fibrotic markers. Interestingly, specific deletion of TP53RK either in renal tubule or in fibroblasts in mice can mitigate renal fibrosis in CKD models. Mechanistic investigations reveal that TP53RK phosphorylates baculoviral IAP repeat containing 5 (Birc5) and facilitates its nuclear translocation; enhanced Birc5 displays a profibrotic effect possibly via activating PI3K/Akt and MAPK pathways. Moreover, pharmacologically inhibiting TP53RK and Birc5 using fusidic acid (an FDA‐approved antibiotic) and YM‐155(currently in clinical phase 2 trials) respectively both ameliorate kidney fibrosis. These findings demonstrate that activated TP53RK/Birc5 signaling in renal tubular cells and fibroblasts alters cellular phenotypes and drives CKD progression. A genetic or pharmacological blockade of this axis serves as a potential strategy for treating CKDs.

Doxorubicin is a broad-spectrum chemotherapy drug commonly used in clinical practice. Improving the delivery efficiency of doxorubicin can help improve the therapeutic effect of tumor and reduce the corresponding side effects. The delivery of doxorubicin based on nano-drug loading technology can provide important help for targeted killing of tumor cells. Tumor development is usually accompanied by the changes in the stiffness of extracellular matrix. The effect of substrate stiffness on the endocytic behavior of doxorubicin based on drug-loading nanoparticle technology was explored by the cellular activity regulated by doxorubicin endocytosis and the changes in the expression of important proteins associated with endocytosis. The substrate stiffness can be regulated by adjusting the ratio of PDMS binder and curing agent. The results of the experiment showed that the cell activity on the substrate with appropriate stiffness (Young's modulus of 0.578, 0.815 and 1.986 MPa) was inhibited, indicating that the transport of doxorubicin was more efficient in this range of substrate stiffness. To explore the underlying mechanism of substrate stiffness regulation of doxorubicin endocytosis, we explored the expression of αVβ5 and NUMB, which are closely related to the endocytosis process. From the results of immunofluorescence protein and Western blot experiments, the fluorescence intensity of the αVβ5 protein responsible for anchoring clathrin on the substrate with a Young's modulus of 1.986 MPa was the highest; Within the appropriate stiffness range, the fluorescence intensity of NUMB protein was significantly increased, indicating that increased expression of NUMB and αVβ5 regulated by substrate stiffness mediates doxorubicin transport, thereby affecting cell viability. This work provides a reference for further improving the efficacy of chemotherapy drugs in the treatment of tumors.

Introduction: Carboplatin (CBP) is a DNA damaging drug used to treat various cancers, including advanced melanoma. Yet we still face low response rates and short survival due to resistance. Triptolide (TPL) is considered to have multifunctional antitumor effects and has been confirmed to enhance the cytotoxic effects of chemotherapeutic drugs. Herein, we aimed to investigate the knowledge about the effects and mechanisms for the combined application of TPL and CBP against melanoma.Methods: Melanoma cell lines and xenograft mouse model were used to uncover the antitumor effects and the underlying molecular mechanisms of the alone or combined treatment of TPL and CBP in melanoma. Cell viability, migration, invasion, apoptosis, and DNA damage were detected by conventional methods. The rate-limiting proteins of the NER pathway were quantitated using PCR and Western blot. Fluorescent reporter plasmids were used to test the NER repair capacity.Results: Our results showed that the presence of TPL in CBP treatment could selectively inhibit NER pathway activity, and TPL exerts a synergistic effect with CBP to inhibit viability, migration, invasion, and induce apoptosis of A375 and B16 cells. Moreover, combined treatment with TPL and CBP significantly inhibited tumor progression in nude mice by suppressing cell proliferation and inducing apoptosis.Discussion: This study reveals the NER inhibitor TPL which has great potential in treating melanoma, either alone or in combination with CBP.

To determine the high dynamic change characteristics of the relative space position between a ballistic missile and an early warning satellite during detection, a centric motion model of the ballistic missile and the early warning satellite are established first. Then, the space geometric relationship is presented. Based on the gray body radiation characteristics, the calculation model of the infrared radiation characteristics of the ballistic missile in the boost phase is established. Then, a method of early warning satellite detection and discrimination considering geometric visibility and infrared visibility is proposed. Finally, the simulation and key factor comparison analysis are carried out with a typical early warning satellite, infrared detector, and ballistic missile data. Validation results show that this method can quickly and accurately calculate the discovery time and flight height of ballistic missiles detected by early warning satellites. The validation results reveal that the missile trajectory and detection bands have a significant effect on the discovery time, and the discovery time in the 2.7 µm band is earlier than that in the 4.3 µm band for the same missile trajectory. It is also found that the change in SNRth between 4.24 and 7.58 has limited influence (less than 2 s) on the discovery time. The research conclusions have important significance for improving the detection strategy of ballistic missile defense. It can also provide support for optimizing missile trajectories.

For a defender protecting a target from an incoming high-maneuvering homing missile, an Optimal Predictive Guidance Law (OPGL) is proposed based on a guidance law identification algorithm. First, a guidance law identification algorithm based on the Interactive Multiple Guidance law Model (IMGM) is designed. IMGM uses multiple sub-filters for parallel processing, and there is interaction between the inputs and outputs of the sub-filters. Second, the VSIMGM algorithm is further designed based on the IMGM algorithm. In this algorithm, a new guidance law model subset is constructed based on the original guidance law model set. By reducing the number of models, the model error is reduced, and the identification probability of the guidance law model is improved. Then, based on the identification result of the identification algorithm, the OPGL is given by using the variational method through the steps of linearizing the kinematic model and reducing the order of state equation. The OPGL reduces the overload requirement of the defender and improves interception accuracy without assuming the maneuver mode of a homing missile. Finally, the effectiveness of the proposed OPGL and guidance law identification algorithm based on VSIMGM is demonstrated using numerical simulation. Compared with the guidance law identification algorithm based on MMAE and IMGM, the guidance law identification algorithm based on VSIMGM can quickly, stably, and accurately identify the guidance law. In addition, based on the guidance law identification results of the homing missile, compared with proportional navigation, augmented proportional navigation, differential game guidance (DGG), and sliding mode guidance (SMG), OPGL can reduce the required overload of the missile and achieve accurate interception.

For maneuvering target tracking, the interactive multiple model (IMM) algorithm and its variants have shown good performance, among which the variable structure IMM (VSIMM) algorithm is the most widely studied one. The approximation degree of the algorithm and the matching degree of the model subset will affect the performance of the VSIMM. In addition, considering that smoothing can provide better estimation of the target state, a new adaptive VSIMM filtering and smoothing (AVSIMMFS) algorithm is proposed in this paper. First, an accurate model of the VSIMM algorithm is established, in which the IMM is run in parallel with and independently from the different model subsets, and the state estimation of the model subset with the highest probability is selected as the final estimation result. Then, an adaptive VSIMM (AVSIMM) algorithm was designed based on the VSIMM algorithm. The adaptation is reflected in the construction of a new model subset from the original model subsets, which improves the matching degree between the model subset and the actual maneuvering model of the target. Finally, by smoothing the filtering data of the AVSIMM algorithm, the AVSIMMFS algorithm is obtained. Because of the combination of forward filtering and backward smoothing, the target tracking accuracy is further improved. Simulation results show that the tracking performance of the AVSIMMFS algorithm is better than that of other methods.

Genes of the cytochrome P450 (CYP450) superfamily are known to be involved in the evolution of insecticide resistance. In this study, the transcriptomes of two Megalurothrips usitatus Bagnall (Thysanoptera: Thripidae) strains (resistant and susceptible) were screened for detoxification genes. MusiDN2722 encodes a protein composed of 504 amino acid residues with a relative molecular mass of 57.3 kDa. Multiple sequence alignment and phylogenetic analysis showed that MusiDN2722 is a member of the CYP450 family and has characteristics of the conserved CYP6 domain shared by typical CYP450 family members. RT-qPCR (real-time quantitative polymerase chain reaction) analysis showed that MusiDN2722 was upregulated in the acetamiprid-resistant strain compared with the susceptible strain (p < 0.05), and the relative expression level was significantly higher at 48 h after exposure than at 24 h after exposure. The interference efficiency of the injection method was higher than that of the membrane-feeding method. Silencing of MusiDN2722 through RNA interference significantly increased the sensitivity of M. usitatus to acetamiprid. Overall, this study revealed that MusiDN2722 plays a crucial role in the resistance of M. usitatus to acetamiprid. The findings will not only advance our understanding of the role of P450s in insecticide resistance but also provide a potential target for the sustainable control of destructive pests such as thrips.

The morphological quantification of the proximal tibia of the knee joint is important in knee replacement. Accurate knowledge of these parameters provides the basis for design of the tibial prosthesis and its fixation. Ideally, a prosthesis that is suitable for the morphological characteristics of Chinese knees is needed. In this paper, a deep learning automatic network framework is designed to achieve automatic segmentation and automatic quantitative analysis of magnetic resonance images of the tibia. An enhanced feature fusion network structure is designed, including high and low-level feature fusion path modules to create accurate segmentation of the tibia. A new method of extracting feature points and lines from outline contours of the proximal tibia is designed to automatically calculate six clinical morphological linear parameters of the tibia in real-time. The final result is an automatic visualisation of the tibial contour and automated extraction of tibial morphometric parameters. Validation of the results from our system against a gold standard obtained by manual processing by expert clinicians showed the Dice coefficient to be 0.97, the accuracy to be 0.98, and the correlation coefficients for all six morphological parameters of the automatic quantification of the tibia are above 0.96. The gender-specific study found that the values of the proximal tibial linear parameters of internal and external tibial diameter, anterior and posterior diameter, lateral plateau length, lateral plateau width, medial plateau length, and medial plateau width in male patients are significantly greater than in female patients (all P values ​

BackgroundThe number of people suffering from overweight or obesity has been steadily increasing in recent years. As a new form of diet, the efficacy of time-restricted eating (TRE) remains debatable.ObjectiveThis meta-analysis quantified the effect of TRE on weight change and other physical parameters in obese and overweight adults.MethodsWe did a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the TRE interventions on weight loss and other metabolic parameters by searching PubMed, Embase, and Cochrane Central Register of Controlled Trials to identify eligible trials published from database inception up until 23 August 2022. The risk of bias was assessed using the Revised Cochrane risk-of-bias tool (ROB-2.0). Meta-analysis was performed using Review Manager 5.4.1 software.ResultsNine RCTs with 665 individuals (345 in the TRE group while 320 in the control group) were included. Results indicated that TRE had a greater decrease in body weight (−1.28 kg; 95% CI [−2.05, −0.52], p = 0.001), fat mass (−0.72 kg; 95% CI [−1.40, −0.03], p = 0.04), body mass index (−0.34 kg/m2; 95% CI [−0.64, −0.04], p = 0.03) and diastolic blood pressure (−2.26 mmHg 95% CI [−4.02, −0.50], p = 0.01). However, the meta-analysis demonstrated that there was no significant difference between TRE and the control group in lean mass, systolic blood pressure, waist circumference, fasting glucose, fasting insulin, homeostasis model assessment-insulin resistance (HOMA-IR), total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides. Besides, the duration of the study and daily eating window also had an impact on weight change.ConclusionTRE was associated with reductions in weight and fat mass and can be a dietary intervention option for adults with obesity. But high-quality trials and longer follow-ups are needed to draw definitive conclusions.

Abstract Numerous studies have investigated metabolite alterations resulting from pharmacological treatment in depression models although few quantitative studies explored metabolites exhibiting constant alterations. This study aimed to identify consistently dysregulated metabolites across such studies using a knowledgebase-driven approach. This study was based on 157 studies that identified an assembly of 2757 differential metabolites in the brain, blood, urine, liver, and feces samples of depression models with pharmacological medication. The use of a vote-counting approach to identify consistently upregulated and downregulated metabolites showed that serotonin, dopamine, norepinephrine, gamma-aminobutyric acid, anandamide, tryptophan, hypoxanthine, and 3-methoxytyramine were upregulated in the brain, while quinolinic acid, glutamic acid, 5-hydroxyindoleacetic acid, myo-inositol, lactic acid, and the kynurenine/tryptophan ratio were downregulated. Circulating levels of trimethylamine N-oxide, isoleucine, leucine, tryptophan, creatine, serotonin, valine, betaine, and low-density lipoprotein were elevated. In contrast, levels of alpha-d-glucose, lactic acid, N-acetyl glycoprotein, glutamine, beta-d-glucose, corticosterone, alanine, phenylacetylglycine, glycine, high-density lipoprotein, arachidonic acid, myo-inositol, allantoin, and taurine were decreased. Moreover, 12 metabolites in urine and nine metabolites in the liver were dysregulated after treatment. Pharmacological treatment also increased fecal levels of butyric acid, acetic acid, propionic acid, and isovaleric acid. Collectively, metabolite disturbances induced by depression were reversed by pharmacological treatment. Pharmacological medication reversed the reduction of brain neurotransmitters caused by depression, modulated disturbance of the tryptophan-kynurenine pathway and inflammatory activation, and alleviated abnormalities of amino acid metabolism, energy metabolism, lipid metabolism, and gut microbiota-derived metabolites.

Aging is a systemic physiological degenerative process, with alterations in gut microbiota and host metabolism. However, due to the interference of multiple confounding factors, aging-associated molecular characteristics have not been elucidated completely. Therefore, based on 16S ribosomal RNA (rRNA) gene sequencing and non-targeted metabolomic detection, our study systematically analyzed the composition and function of the gut microbiome, serum, and fecal metabolome of 36 male rhesus monkeys spanning from 3 to 26 years old, which completely covers juvenile, adult, and old stages. We observed significant correlations between 41 gut genera and age. Moreover, 86 fecal and 49 serum metabolites exhibited significant age-related correlations, primarily categorized into lipids and lipid-like molecules, organic oxygen compounds, organic acids and derivatives, and organoheterocyclic compounds. Further results suggested that aging is associated with significant downregulation of various amino acids constituting proteins, elevation of lipids, particularly saturated fatty acids, and steroids. Additionally, age-dependent changes were observed in multiple immune-regulatory molecules, antioxidant stress metabolites, and neurotransmitters. Notably, multiple age-dependent genera showed strong correlations in these changes. Together, our results provided new evidence for changing characteristics of gut microbes and host metabolism during aging. However, more research is needed in the future to verify our findings.

Background: Moderate renal artery stenosis (50–70%) may lead to uncontrolled hypertension and eventually cause irreversible damage to renal function. However, the clinical criteria for interventional treatment are still ambiguous in this condition. This study investigated the impact of the position and degree of renal artery stenosis on hemodynamics near the renal artery to assess the short-term and long-term risks associated with this disease. Methods: Calculation models with different degrees of stenosis (50%, 60%, and 70%) located at different positions in the right renal artery were established based on the computed tomography angiography (CTA) of a personalized case. And computational fluid dynamics (CFD) was used to analyze hemodynamic surroundings near the renal artery. Results: As the degree of stenosis increases and the stenosis position is far away from the aorta, there is a decrease in renal perfusion. An analysis of the wall shear stress (WSS)-related parameters indicated areas near the renal artery (downstream of the stenosis and the entrance of the right renal artery) with potential long-term risks of thrombosis and inflammation. Conclusion: The position and degree of stenosis play a significant role in judging short-term risks associated with renal perfusion. Moreover, clinicians should consider not only short-term risks but also independent long-term risk factors, such as certain regions of 50% stenosis with adequate renal perfusion may necessitate prompt intervention.

In order to study the CTFs in three-dimensional state, a Parylene-C microplate was fabricated on glass substrate by vapor deposition of Parylene-C film, and subsequent patterning by photolithography and etching using the micro-electromechanical systems (MEMS) technology. For Parylene-C etching process, its low etching rate accuracy and poor etching uniformity make it difficult to precisely etch 2.9 μm-deep and 100 nm-thick grooves on 3 μm thick Parylene-C patterns. In this paper, through design optimization and process improvement, the process of one deposition step and two etching steps was changed to the process of two deposition steps and two etching steps, and the corresponding thickness groove was formed by the second direct deposition of 100 nm-thick Parylene-C film and etching the area outside the groove. The Parylene-C thin film was patterned accurately and efficiently. Finally, a pair of Parylene-C square patterns with thickness of 3 μm, side length of 50 μm, and spacing of 5 μm were obtained. The Parylene-C link with a thickness of 100 nm was formed between the square patterns. After the fabrication of the microplate, the surface of the glass substrate was treated by acyloxyethyl phosphocholine polymer coating. Fibroblast was seeded on Parylene-C microplate. The results show that Parylene-C microplate had good biocompatibility, and single fibroblast grew well on the microplate. The connection between square patterns had good flexibility and deformability, and the microplate was folded easily by touching the microplate gently with a micro-needle. The microplate can provide a new means for measuring the stretch force of cells in three-dimensional state.

Hepatocellular carcinoma (HCC), a common malignant tumor of the liver, remains high incidence and poor prognosis. Although pyroptosis as well as lncRNA have been believed to play important roles in the tumorigenesis, diagnosis and prognosis, the role of pyroptosis-related lncRNAs (PRlncRs) in HCC remains obscure. Here, we identified 73 significantly differentially expressed and overall survival (OS) related pyroptosis-related lncRNAs (PRlncRs) in noncancerous and HCC samples. Based on LASSO regression and Cox regression analyses, we set up a novel prognostic model including six PRlncRs (MKLN1-AS, AC139491.2, AC145207.5, AC099850.3, AL590705.3 and AL049840.5), which showed good correlation with the OS of HCC patients. Considering that the risk score was negatively related to clinicopathologic features including T stage (T1-2 and T3-4), clinical stage (stage I-II and stage III-IV) and histological grade (G1, G2, G3 and G4), we further constructed a predictive nomogram containing the risk score and other clinicopathological features to predict the OS rates for HCC patients. In addition, the proposed signature was closely related to immune infiltration and offered improved clinical utility for immune checkpoint inhibitors (ICIs) strategies and chemotherapeutic drug selection in HCC. In conclusion, we established a considerable accurate risk signature consisting of 6 PRlncRs in HCC, which could predict the prognosis and efficacy of immunotherapy for HCC patients.

As a novel minimally invasive technique, percutaneous endoscopic transforaminal lumbar interbody fusion (PE-TLIF) has been widely used in the treatment of lumbar degenerative diseases. The purpose of this study was to analyze these two operation types’ biomechanical performances of PE-TLIF and traditional minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) using the finite element (FE) method. The intact FE models of L4-L5 were established and validated based on the CT images. On this basis, the FE models of MIS-TLIF and PE-TLIF were established and analyzed. It is demonstrated that for lumbar interbody fusion with the oblique asymmetrically implanted cage under bilateral pedicle screws and rods fixation, such as MIS-TLIF and PE-TLIF, different degrees of articular process resection have no significant effect on the cage subsidence, and the surgical segment can achieve similar stability. In addition, the maximum stress of the L4 inferior endplate of MIS-TLIF and PE-TLIF is greater than that of the L5 superior endplate, which indicates that MIS-TLIF and PE-TLIF can cause cage subsidence in the L4 inferior endplate.

Background The oral microbiota plays vital roles in both oral and systemic health, but limited studies have explored the transition of the female oral microbiota from preconception to pregnancy along with pronounced hormonal fluctuations.Aim To characterize the oral microbiota among women in preconception and pregnancy through a prospective study and to explore the associations between the oral microbiota and oral hygiene practices.Methods A total of 202 unstimulated saliva samples were collected from 101 women in both preconception and late pregnancy. The oral microbiota was analyzed using 16S rRNA gene sequencing.Results The Ace and phylogenetic diversity (PD) index were significantly lower in the third trimester than preconception. The pathogenic taxa Prevotella and Atopobium parvulum were significantly higher during late pregnancy than preconception. Women with overall better oral hygiene practice showed lower richness and diversity in preconception compared to women with poorer oral hygiene practice. The abundance of pathogens such as Dialister during both preconception and pregnancy decreased among women with better oral hygiene practice.Conclusions The composition of the oral microbiota changed slightly from preconception to late pregnancy, with more pathogens in saliva samples during pregnancy. Improving oral hygiene practices has the potential to maintain oral micro-ecological balance.

Spinal orthoses were designed to correct poor posture; however, they may restrict trunk movements at all times, making daily activities difficult. Detecting trunk movements can provide instructions for adjusting the stiffness of the spinal orthosis. This study evaluated the feasibility of identifying movements based on surface electromyography (sEMG) signals. Ten participants were tested for different movements with two different modalities: motion without the spinal orthosis (Normal) and with the spinal orthosis (Spinal orthosis). The sEMG signals were collected from eight muscles using surface electrodes during four movements [flexion-extension, lateral bending, axial rotation, and stand to sit to stand]. Four time domain features were extracted, with a total of 32 feature vectors. The principal component analysis (PCA) method was adopted to feature selection, and it was found that eight feature dimensions can make cumulative explained variance exceed 95%. The results showed that machine learning algorithms could not only identify Normal and Spinal orthosis movement modalities, but also distinguish four daily movements. Moreover, the classification performance of Random Forest (RF), k-Nearest Neighbor (k-NN), and Support Vector Machine (SVM) algorithms were also compared. The results showed that all three machine algorithms have high classification accuracy. The machine learning methods can accurately identify movement patterns by considering sEMG signals, which may provide instructions for adjusting the stiffness of the spinal orthosis. In the future, the spinal orthosis with adjustable stiffness controlled by sEMG signals could help correct poor posture, and permit the wearer to achieve free movement when needed.

Dopamine acts on neurons in the arcuate nucleus (ARC) of the hypothalamus, which controls homeostatic feeding responses. Here we demonstrate a differential enrichment of dopamine receptor 1 (Drd1) expression in food intake–promoting agouti related peptide (AgRP)/neuropeptide Y (NPY) neurons and a large proportion of Drd2-expressing anorexigenic proopiomelanocortin (POMC) neurons. Owing to the nature of these receptors, this translates into a predominant activation of AgRP/NPY neurons upon dopamine stimulation and a larger proportion of dopamine-inhibited POMC neurons. Employing intersectional targeting of Drd2-expressing POMC neurons, we reveal that dopamine-mediated POMC neuron inhibition is Drd2 dependent and that POMCDrd2+ neurons exhibit differential expression of neuropeptide signaling mediators compared with the global POMC neuron population, which manifests in enhanced somatostatin responsiveness of POMCDrd2+ neurons. Selective chemogenetic activation of POMCDrd2+ neurons uncovered their ability to acutely suppress feeding and to preserve body temperature in fasted mice. Collectively, the present study provides the molecular and functional characterization of POMCDrd2+ neurons and aids our understanding of dopamine-dependent control of homeostatic energy-regulatory neurocircuits.

A multi-resonance Cymbal hydrophone for detection of the open-circuit self-contained underwater breathing apparatus (scuba) diver was designed and fabricated in this work, which has the advantages of multi-resonant frequency, high sensitivity, and narrow bandwidth. By using standard hydrophones, the underwater acoustic signal of the open-circuit scuba diver in the pool was collected and the characteristics of the signal were analyzed: the signal was mainly distributed in high frequency and low frequency. According to this characteristic, a Cymbal hydrophone with multi-resonance frequencies was designed in the finite element method, and the resonant frequency, receiving sensitivity, and bandwidth of the hydrophone were calculated. The accuracy of the calculation was verified with the performance test of the prototypes fabricated in this work. Finally, the underwater acoustic signal of an open-circuit scuba diver in the pool was tested by the prototype to demonstrate that the multi-resonance Cymbal hydrophone developed in this paper can be used for open-circuit scuba diver detection.

Abstract Background Because of osteoporosis, traffic accidents, falling from high places, and other reasons, the vertebral body can be compressed and even collapse. Vertebral implants can be used for clinical treatment. Because of the advantages of honeycomb sandwich structures, such as low cost, less material, light weight, high strength, and good cushioning performance. In this paper, the honeycomb sandwich structure was used as the basic structure of vertebral implants. Methods The orthogonal experiment method is applied to analyse the size effect of honeycomb sandwich structures by the finite element method. Based on the minimum requirements of three indexes of peak stress, axial deformation, and anterior–posterior deformation, the optimal structure size was determined. Furthermore, through local optimization of the overall structure of the implant, a better honeycomb sandwich structure vertebral implant was designed. Results The optimal structure size combination was determined as a panel thickness of 1 mm, wall thickness if 0.49 mm, cell side length of 1 mm, and height of 6 mm. Through local optimization, the peak stress was further reduced, the overall stress distribution was uniform, and the deformation was reduced. The optimized peak stress decreased to 1.041 MPa, the axial deformation was 0.1110%, and the anterior–posterior deformation was 0.0145%. A vertebral implant with good mechanical performance was designed. Conclusions This paper is the first to investigate vertebral implants with honeycomb sandwich structures. The design and analysis of the vertebral implant with a honeycomb sandwich structure were processed by the finite element method. This research can provide a feasible way to analyse and design clinical implants based on biomechanical principles.

Abstract Background We estimated the predictive effects of ART-related perceptions on the actual ART uptake behavior among ART naïve PLWH stratified by different time of HIV diagnosis under the new strategy. Methods A prospective cohort study was conducted among ART naïve PLWH in Guangzhou, China from June 2016 to June 2017. Cox regression model was used to evaluate the predictive effects of ART-related perceptions on ART initiation among PLWH stratified by different timepoint of HIV diagnosis (i.e., before or after the update of the new treatment policy). Results Among 411 participants, 150 and 261 were diagnosed before (pre-scaleup group) and after (post-scaleup group) the implementation of the new strategy, respectively. The ART initiation rate in the post-scaleup group (88.9%) was higher than that in the pre-scaleup group (73.3%) (p 0.05). Conclusions The ART initiation rate was high particularly among participants who diagnosed after the new treatment strategy. The important role of the time of HIV diagnosis on ART initiation identified in this study suggested that future implementation interventions may consider to modify the ART-related perceptions for HIV patients who diagnosed before the implementation of the new ART strategy, while expand the accessibility of ART service for those who diagnosed after the implementation of the new strategy.

The evidence linking sleep duration and metabolic body size phenotypes is limited, especially in young adulthood. In this study, we aimed to examine the association between sleep duration and metabolic body size phenotypes among Chinese young workers and investigate whether discrepancies exist among shift and non-shift workers. A cross-sectional study was performed between 2018 and 2019 in Wuhan, China and 7,376 young adults aged 20–35 years were included. Self-reported sleep duration was coded into four groups:

The olfactory system is an important component of insect behavior and is vital for survival and reproduction. However, the genomic characterization and molecular basis of the olfactory response of Megalurothrips usitatus remain relatively unknown. RNA sequencing-built developmental transcriptomes of nymphs, pupae, and adult M. usitatus were examined in order to establish the sequence-based background of M. usitatus olfactory responses. A total of 56,669 unigenes were annotated using GO, NR, Pfam, eggNOG, SwissProt, and KEGG. The number of differentially expressed genes between pupae and nymphs, males and nymphs, and females and nymphs were 10,498, 9,235, and 10,964, respectively. One odorant-binding protein (MusiOBP1) and one chemosensory protein (MusiCSP1) were selected from the transcriptome, and their full-length sequences were obtained using RACE PCR. The relative expression of MusiOBP1 was the highest in primordial females, whereas the relative expression of MusiCSP1 was the highest in primordial pupae. The strongest binding ability to the odor-binding protein MusiOBP1 was observed for β-citronellol. 3-Hydroxy-2-methyl-4-pyrone showed the strongest binding affinity to MusiCSP1. Our analysis suggests that MusiOBP1 and MusiCSP1 may play significant roles in mediating M. usitatus host recognition. This research will improve our knowledge of odorant-binding proteins and chemosensory proteins, which will in turn improve our understanding of insect olfactory systems.

Adhesion behavior, existed on the damaged interface, was responsible for the safety and stability of the post-operative cornea refer to the refractive surgeries. In this study, we inferred that the force loss generated by the post-operative cornea must do not surpass the interfacial adhesion force of the cornea. In case of that, the corneal flap (or cap) would trend to separate from the residual stromal bed, and then became a threat to the visual health of the corrected myopic patient. According to this inference, we derived the theoretical maximum ablated ratio, which was well matched with the empirically clinical safety standard employing the commonly programmed optical zone.

BackgroundThe NF-κB signaling pathway plays an important role in associating inflammation with tumor development and progression. However, few studies have reported that roles of genetic variants of the NF-κB signaling pathway genes in survival of patients with HBV-related hepatocellular carcinoma (HBV-HCC), especially with regards to potentially functional SNPs.MethodsWe used multivariate Cox proportional hazards regression to evaluate associations between 2,060 single nucleotide polymorphisms (SNPs) in 20 NF-κB signaling pathway genes and survival of 866 HBV-HCC patients, which were randomly split (1:1) into discovery and validation datasets. Expression quantitative trait loci (eQTL) analysis was conducted to identify associations between survival-associated SNPs and mRNA expression of corresponding genes. Furthermore, online database was used to assess mRNA expression of corresponding genes and survival. Finally, receiver operating characteristic (ROC) curves were used to assess the prediction accuracy of models integrating both clinical and genetic variables on HCC survival.ResultsA total of 6 SNPs in MAP3K14 remained significantly associated with OS of HBV-HCC patients (PA) A allele was associated with higher mRNA expression levels of MAP3K14 (P=0.044) in normal liver tissue, which was associated with worse survival of HBV-HCC patients. In the additive model, after adjusting for age, sex, smoking status, drinking status, AFP level, cirrhosis, embolus and BCLC stage, the combined dataset showed that HBV-HCC patients carrying the rs2074292 AA and GA genotypes (HR=1.71, 95%CI= 1.29-2.27, P=0.000) (HR=1.40, 95%CI=1.10-1.77, P=0.005) have worse OS than GG genotype, respectively. The addition of risk genotypes to the prediction models increased the AUC significantly from 71.15% to 73.11% (P=0.012) and from 72.55% to 74.21% (P=0.010) for 1-year and 3-year OS, respectively.ConclusionOur study indicated that MAP3K14 rs2074292 A allele may be a potential predictor of HBV-HCC survival, likely regulating MAP3K14 mRNA expression.

The main motivation of this work was to demonstrate a hollow telescopic rod structure that could be used for minimally invasive surgery. The telescopic rods were fabricated using 3D printing technology to make mold flips. During fabrication, differences in biocompatibility, light transmission, and ultimate displacement were compared between telescopic rods fabricated via different processes, so as to select the appropriate process. To achieve these goals, flexible telescopic rod structures were designed and 3D-printed molds were fabricated using Fused Deposition Modeling (FDM) and Stereolithography (SLA) techniques. The results showed that the three molding processes had no impact on the doping of the PDMS specimens. However, the FDM molding process had lower surface flatness accuracy compared to SLA. The SLA mold flip fabrication exhibited superior surface accuracy and light transmission compared to the other methods. The sacrificial template method and the use of HTL direct demolding technique had no significant impact on cellular activity and biocompatibility, but the mechanical properties of the PDMS specimens were weakened after swelling recovery. The height and radius of the hollow rod were found to have a significant impact on the mechanical properties of the flexible hollow rod. The hyperelastic model was fitted appropriately with the mechanical test results, and the ultimate elongation increased with an increase in hollow–solid ratios under the uniform force.

Oxidative stress and inflammatory factors are closely related to keratoconus. As an important gene expression regulator, MiRNAs participate in the physiological and pathological process of keratoconus. In this study, in order to investigate whether MiRNAs can regulate the expression of matrix remodeling-related genes in keratoconus fibroblasts by targeting IL-1β, potential MiRNAs(miR-21-5p, miR-24-3p, miR-26b-3p, miR-27b-5p, miR-181d-5p, miR-383-3p, MiR-548d-3p, miR-4700-3p) that may be related to IL-1β targeting were predicated by using bioinformatics methods. Hydrogen peroxide was added to human keratoconic corneal fibroblasts in vitro. quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of MiRNAs and IL-1β mRNA at 0, 6, 12, and 24 h. IL-1β was found to be a target of MiR-548d-3p by using a dual luciferase reporter assay. After transfection of MiR-548d-3p mimics into human keratoconus fibroblasts, it was found that under oxidative stress, MiR-548d-3p mimics significantly down-regulated the gene expression of IL-1β, decreased the expression of MMP-1 and MMP-3, and increased the expression of collagenI-α2. These results indicate that MiR-548d-3p may promote corneal matrix synthesis and attenuate matrix degradation by down-regulating the expression of IL-1β, which retards keratoconus progression under oxidative stress. This might provide a new potential target for keratoconus treatment.