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Abstract Acute cartilage injuries, such as intra-articular fractures and blunt impacts, frequently result in chondrocyte death and extracellular matrix (ECM) degradation, significantly elevating the risk of post-traumatic osteoarthritis (PTOA). Despite advances in treatment, no effective therapies currently exist to fully cure PTOA or halt its progression. This study explores the protective effects of the dietary fatty acid eicosapentaenoic acid (EPA) on human primary chondrocytes (HPCs) and cartilage explants exposed to mechanical overload and blunt trauma. HPCs were isolated and subjected to mechanical stretching using BioFlex six-well culture plates, while cartilage explants were subjected to impact loading via a customized drop tower. EPA was incorporated into the culture medium, followed by assays to evaluate cell viability, calcium (Ca²⁺) influx, apoptosis, reactive oxygen species (ROS) levels, and collagen type II alpha (Col-2a) expression. EPA treatment markedly decreased chondrocyte mechanical sensitivity, as demonstrated by enhanced cell viability and reduced lactate dehydrogenase (LDH) release. Furthermore, EPA inhibited Piezo1 activation, leading to lower intracellular Ca²⁺ concentrations, decreased apoptosis, and diminished ROS levels. In cartilage explants, EPA improved chondrocyte viability, minimized structural damage, and sustained higher Col-2a expression compared to the blunt trauma group. These results indicate that EPA effectively shields chondrocytes and cartilage explants from mechanical overload-induced damage by inhibiting Piezo1 activation and mitigating Ca²⁺ influx, apoptosis, and oxidative stress. The findings suggest that EPA supplementation could offer a promising strategy for preventing PTOA progression following acute cartilage injuries. Further research is warranted to assess the clinical applications of EPA and confirm its efficacy in larger animal models and human trials.

Abstract Purpose The risk factors for excessive blood loss and transfusion during total knee arthroplasty (TKA) remain unclear. The present study aimed to determine the risk factors for excessive blood loss and establish a predictive model for postoperative blood transfusion. Methods This retrospective study included 329 patients received TKA, who were randomly assigned to a training set (n = 229) or a test set (n = 100). Univariate and multivariate linear regression analyses were used to determine risk factors for excessive blood loss. Univariate and multivariate logistic regression analyses were used to determine risk factors for blood transfusion. R software was used to establish the prediction model. The accuracy and stability of the models were evaluated using calibration curves, consistency indices, and receiver operating characteristic (ROC) curve analysis. Results Risk factors for excessive blood loss included timing of using a tourniquet, the use of drainage, preoperative ESR, fibrinogen, HCT, ALB, and free fatty acid levels. Predictors in the nomogram included timing of using a tourniquet, the use of drainage, the use of TXA, preoperative ESR, HCT, and albumin levels. The area under the ROC curve was 0.855 (95% CI, 0.800 to 0.910) for the training set and 0.824 (95% CI, 0.740 to 0.909) for the test set. The consistency index values for the training and test sets were 0.855 and 0.824, respectively. Conclusions Risk factors for excessive blood loss during and after TKA were determined, and a satisfactory and reliable nomogram model was designed to predict the risk for postoperative blood transfusion.

Abstract The destruction of the microvascular structure and function can seriously affect the survival and prognosis of patients with acute myocardial infarction (AMI). Nuciferine has a potentially beneficial effect in the treatment of cardiovascular disease, albeit its role in microvascular structure and function during AMI remains unclear. This study aimed to investigate the protective effect and the related mechanisms of nuciferine in microvascular injury during AMI. Cardiac functions and pathological examination were conducted in vivo to investigate the effect of nuciferine on AMI. The effect of nuciferine on permeability and adherens junctions in endothelial cells was evaluated in vitro, and the phosphorylation level of the PI3K/AKT pathway (in the presence or absence of PI3K inhibitors) was also analyzed. In vivo results indicated that nuciferine inhibited ischemia-induced cardiomyocyte damage and vascular leakage and improved cardiac function. In addition, the in vitro results revealed that nuciferine could effectively inhibit oxygen–glucose deprivation (OGD) stimulated breakdown of the structure and function of human coronary microvascular endothelial cells (HCMECs). Moreover, nuciferine could significantly increase the phosphorylation level of the PI3K/AKT pathway. Finally, the inhibitor wortmannin could reverse the protective effect of nuciferine on HCMECs. Nuciferine inhibited AMI-induced microvascular injury by regulating the PI3K/AKT pathway and protecting the endothelial barrier function in mice.

Abstract Background To investigate the accuracy and safety of a newly constructed robotic arm which can cover the whole process of THA, we performed a series of robot-assisted total hip replacement on the cadaver. Methods Fifteen frozen cadaveric specimens (30 hips) were used for this study. In this investigation, united hip system and Longwell robotic-assisted system were used. The entire lower limb was CT scanned prior to surgery. The 3D model was produced based on CT data; the site of the prosthesis, including acetabular anteversion, inclination angle, and the position of femoral prosthesis, was planned. With the assistance of a robotic arm, the surgeon changed the parameters based on the preoperative plan and the actual condition during surgery, and completed the whole procedure. Following surgery, we measured the acetabular anteversion angle, acetabular inclination angle, femur anteversion angle, combined anteversion angle, stem angulation, and canal fill ratio. Results The parameters proved that the acetabular anteversion angle was 16.85 ± 3.00°, the acetabular inclination angle was 40.38 ± 5.37°, femur anteversion angle was 15.90 ± 9.01°, combined anteversion angle was 32.75 ± 9.03°, stem angulation was 1.84 ± 0.99°, and leg length discrepancy was 2.47 ± 1.43 mm. The canal fill ratio (CFR) of femoral prosthesis of osteotomy line in sagittal section is 99.72 ± 1.54% and in coronal section is 62.94 ± 8.91%; below osteotomy line 2.5 cm in sagittal section is 100.00% and in coronal section is 81.48 ± 12.94%; below osteotomy line 7.5 cm in sagittal section is 59.51 ± 12.94% and in coronal section is 89.79 ± 11.13%; femoral shaft isthmus in sagittal section is 56.41 ± 13.80% and in coronal section is 84.95 ± 15.17%. Conclusion The accuracy and safety of this novel robotic arm are suitable for preparing both the acetabular and femoral sides, providing evidence for clinical trial.

A high-precision low-cost mid-infrared photoacoustic sensor for greenhouse composite gases based on aspherical beam shaping is proposed and demonstrated. The assembled optical source module and luminous characteristics of infrared source are innovatively investigated and analyzed with aspherical beam shaping. The proposed aspherical-beam-shaping-technique could effectively reduce optical loss and enhance system sensitivity, achieving an effective power utilization ratio of a radiation source of 91% and sidewall noise ratio of 8.9%. Experiments verify the 1.7 times improvement in responsivity and 50% enhancement in minimum detection limit (MDL) on average. In terms of comprehensive greenhouse gas composites and with short integration time of 1 s, MDLs of CO2, CH4, N2O, NF3, SF6, PFC-14, and HFC-134a are 73 ppb, 267 ppb, 72 ppb, 81 ppb, 14 ppb, 9 ppb and 115 ppb, respectively. Furthermore, a 48 h continuous monitoring of H2O, CO2 and CH4 in the atmosphere is conducted and verifies the performance of the gas sensor. The developed sensor allows for the rapid route of low-cost and high-precision detection of multiple greenhouse gases.

Deployable hind wings of beetles led to a bio-inspired idea to design deployable micro aerial vehicles (MAVs) to meet the requirement of miniaturization. In this paper, a bionic deployable wing (BD-W) model is designed based on the folding mechanism and elliptical wing vein structure of the Protaetia brevitarsis hindwing, and its structural static and aerodynamic characteristics are analyzed by using ANSYS Workbench. Finally, the 3D-printed bionic deployable wing was tested in a wind tunnel and compared with simulation experiments to explore the effects of different incoming velocity, flapping frequency, and angle of attack on its aerodynamic characteristics, which resulted in the optimal combination of the tested parameters, among which, the incoming velocity is 3 m/s, the flapping frequency is 10 Hz, the angle of attack is 15°, and the lift-to-drag ratio of this parameter combination is 4.91. The results provide a theoretical basis and technical reference for the further development of bionic flapping wing for MAV applications.

Total hip revision with osseous defects can be very difficult. Artificial intelligence offers preoperative planning, real-time measurement, and intraoperative judgment, which can guide prothesis placement more accurately. Three-dimensional printed metel augment modules which are made according to the individualized osseous anatomy, can fit the osseous defects well and provide mechanical support. In this case, we used AI to plan the size and position of the acetabular cup and 3D-printed augmented modules in a complicated hip revision with an acetabular bone defects, which achieved stable fixation and relieved hip pain postoperatively.

ABSTRACT Orofacial granulomatosis (OFG) is a chronic inflammatory disease characterized by nontender swelling of the orofacial tissues, the underlying cause of which remains unknown. Our previous study demonstrated that tooth apical periodontitis (AP) is involved in the development of OFG. To characterize the AP bacterial signatures of OFG patients and identify possible pathogenic bacteria that cause OFG, the compositions of the AP microbiotas in OFG patients and controls were compared using 16S rRNA gene sequencing. Pure cultures of putative bacterial pathogens were established by growing bacteria as colonies followed by purification, identification, and enrichment and then were injected into animal models to determine the causative bacteria contributing to OFG. A specific AP microbiota signature in the OFG patients was shown, characterized by the predominance of phyla Firmicutes and Proteobacteria, notably members of the genera Streptococcus, Lactobacillus, and Neisseria, were found. Streptococcus spp., Lactobacillus casei, Neisseria subflava, Veillonella parvula, and Actinomyces spp. from OFG patients were isolated and successfully cultured in vitro and then injected into mice. Ultimately, footpad injection with N. subflava elicited granulomatous inflammation. IMPORTANCE Infectious agents have long been considered to play a role in the initiation of OFG; however, a direct causal relationship between microbes and OFG has not yet been established. In this study, a unique AP microbiota signature was identified in OFG patients. Moreover, we successfully isolated candidate bacteria from AP lesions of OFG patients and assessed their pathogenicity in laboratory mice. Findings from this study may help provide in-depth insights into the role of microbes in OFG development, providing the basis for targeted therapeutic approaches for OFG.

Renal inflammation and fibrosis are the important pathological phenomena associated with obstructive nephropathy. However, the underlying mechanism associated with this disease has yet to be fully elucidated. The present study, therefore, aimed to investigate the effects mediated by C1q/tumor necrosis factor-related protein 13 (CTRP13) on renal inflammation and fibrosis in addition to elucidating the underlying mechanism. To meet this aim, a mouse unilateral ureteral obstruction (UUO)-mediated renal dysfunction model was established. In addition, hematoxylin–eosin staining (H&E) staining and immunofluorescence experiments as well as Western blotting and reverse transcription quantitative (RT q) PCR analyses were performed. Recombinant CTRP13 was used to investigate the role of CTRP13 in chronic renal inflammation and fibrosis. A decreased expression level of CTRP13 was identified in the plasma of patients with renal fibrosis and in UUO-model mice. The renal histopathological and functional analyses revealed that CTRP13 could both reverse UUO mediated renal dysfunction and ameliorate the conditions of tubulointerstitial fibrosis and tubular injury. Additionally, CTRP13 was found to inhibit the expression levels of extracellular matrix proteins and proinflammatory mediators. In terms of the underlying mechanism, the protective effects on inflammation and fibrosis of the kidneys of CTRP13-treated mice undergoing UUO were found to be associated with the inactivation of the TGF β/Smad and NF κB p65 signaling pathways. Taken together, these findings have suggested that CTRP13 fulfills a vital role in the progression of obstructive nephropathy, thereby uncovering brand new insights into possible leads for the therapeutic treatment of chronic kidney disease (CKD).

Abstract Background This study aimed to compare the mid-term clinical and radiographic outcomes between medial-pivotal (MP) insert and double-high (DH) insert used under the cruciate-retaining condition in ADVANCE® total knee arthroplasty (TKA). Methods The follow-up was conducted for 158 consecutive patients who underwent unilateral ADVANCE® TKA from January 2011 to April 2014. Eighty-four MP inserts and 74 DH inserts were used under cruciate-retaining conditions. A 1:1 propensity score matching (PSM) analysis was performed between MP inserts and DH inserts to compare the clinical and radiographic outcomes. Results After a 1:1 PSM, 120 patients (60 pairs) were matched between the MP and DH inserts groups. The baseline demographic parameters and clinical scores were comparable between the two groups. The postoperative clinical outcomes at an averaged 8-year follow-up of both groups were significantly improved. The range of motion (ROM) of the DH group was better than that of the MP group, and equivalent Knee Society Function Score (KSFS) between the two groups was found. However, the Knee Society Score (KSS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and Forgotten Joint Score (FJS) of the MP group were found to be significantly superior to those of the DH group. Comparable complication and revision rates were observed between the two groups. The radiographic results were also equally good between MP and DH groups. Conclusions Although the mid-term clinical and radiographic outcomes of the DH inserts are fairly good, the clinical scores of the DH group were worse than those of the MP group.

Objectives: To image knee osteochondral specimens using magnetic resonance (MR) ultrashort echo time imaging with pointwise encoding time reduction with radial acquisition combined fat suppression (PETRA-FS) sequence to determine whether it can reveal non-calcified cartilage, including the deep radial layer, and to assess its effectiveness in cartilage damage diagnosis. Materials and methods: PETRA-FS imaging was performed on 58 osteochondral specimens of the lower femur and upper tibia to observe depth of cartilage damage, combined with histological results to observe signal intensity composition. Sensitivity, specificity, and reliability of PETRA-FS sequence for diagnosing cartilage damage were evaluated using histological results as the gold standard. Diagnostic efficacy was assessed using receiver operating characteristic (ROC) curve. Results: MR ultrashort echo time imaging PETRA-FS sequence showed non-calcified cartilage, including tangential, transitional, and radial layers, which showed a high signal. PETRA-FS sequence showed 37 cases of cartilage damage and 21 cases of no damage among 58 specimens, kappa value of 0.75. Histological analysis of the 58 osteochondral specimens revealed 38 cases of cartilage injury and 20 cases of undamaged cartilage. Using histological results as the gold standard, PETRA-FS sequence had a sensitivity of 87.00%, specificity of 80.00%, kappa value of 0.81, and an area under the ROC curve (AUC) of 0.83 for cartilage injury diagnosis. Conclusion: MR ultrashort echo time imaging PETRA-FS sequence can show non-calcified cartilage, including the deep radial layer (which cannot be shown by conventional MR), by exhibiting a high signal in knee osteo-chondral specimens. Thus, PETRA-FS sequences may have important diagnostic value for cartilage injury diagnosis.

The research mainly starts from the development trend of 5G+ satellite integration, and conducts research and analysis on typical domestic and foreign satellite Internet of things/internet solutions, and then leads to application scenarios and services requirement for the development of 5G+ satellite integration, including research and discussion on the technical requirements of 5G satellite space-ground integrated dual-mode terminals, finally, the challenges faced by 5G satellite dual-mode communication terminals are given.With a view to providing industry with guidance on the challenging aspects of standardization and pre-development of 5G+ satellite dual-mode terminals, and to provide useful suggestions and references for overcoming these challenges.

Aiming at the trend of industrial enterprises facing the evolution from the traditional business management information architecture to the cloud-native platform management, an evolutionary architecture of the transitional industrial internet business management platform was proposed, including platform base, management business domain, industrial business domain.Overall, the platform base, the management business domain, and the industrial business domain are vertically penetrated through the network to allow different levels of management business applications and industrial business applications to directly use related data.The platform realizes the sharing of integrated digital capabilities, intensification and integrated management and control, and facilitates the rapid replication and promotion of applications of industrial group enterprises and that similar subsidiaries at all levels.

Abstract Glioblastoma (GBM) is a lethal brain cancer known for its potent immunosuppressive effects. Loss of Methylthioadenosine Phosphorylase (MTAP) expression, via gene deletion or epigenetic silencing, is one of the most common alterations in GBM. Here we show that MTAP loss in GBM cells is correlated with differential expression of immune regulatory genes. In silico analysis of gene expression profiles in GBM samples revealed that low MTAP expression is correlated with an increased proportion of M2 macrophages. Using in vitro macrophage models, we found that methylthioadenosine (MTA), the metabolite that accumulates as a result of MTAP loss in GBM cells, promotes the immunosuppressive alternative activation (M2) of macrophages. We show that this effect of MTA on macrophages is independent of IL4/IL3 signaling, is mediated by the adenosine A2B receptor, and can be pharmacologically reversed. This study suggests that MTAP loss in GBM cells may contribute to the immunosuppressive tumor microenvironment, and that MTAP status should be considered for characterizing GBM immune states and devising immunotherapy-based approaches for treating MTAP-null GBM.

Hydrogen permeation reduces a material’s properties and increases the risk of brittle fracture, which causes a potential safety hazard. A workpiece’s hydrogen permeation resistance could be improved by improving its surface integrity through surface processing. This paper studies low-alloy steel’s surface integrity and its hydrogen permeation resistance in a hydrogen production reactor, using the electrochemical cathodic hydrogen-charging method to carry out electrochemical hydrogen-charging experiments. After the specimens were pretreated using different surface-grinding methods and shot peening pressure strengthening, they were hydrogen-charged on a self-designed and built electrolytic hydrogen charging platform. Before and after hydrogen charging, the specimens’ section hardness and tensile strength were tested, and the fracture morphology of the specimens was observed. The influence laws of surface roughness and surface residual compressive stress on the distribution of material hardness along the depth, the variation in material hardness, the fracture morphology, and the decline in the tensile properties of the low-alloy steel specimens after 5 h of hydrogen charging were analyzed. The reasons for the influence of surface integrity indexes on the hydrogen permeation resistance of the specimens were also analyzed. Based on the experimental results, a series of mechanical processing parameters were proposed to improve the material’s permeation resistance, which provides a theoretical and practical basis for the processing of materials with high surface integrity and hydrogen permeation resistance. Through the experiments, it was found that the hydrogen permeation resistance of the Ra 0.17 μm surface roughness specimen was the best of all specimens with different surface roughness values, and its hydrogen embrittlement sensitivity index was 20.96%. The specimen had the best hydrogen permeation resistance under 336 MPa surface residual compress stress, and its hydrogen embrittlement sensitivity index was 16.45%.

Background Benzodiazepine receptor agonists (BZRAs) are commonly used clinically and data on their hazardous use from large populations of psychiatric patients is limited. Aims To assess the current status of hazardous BZRA use and related factors in Chinese out-patient psychiatric settings. Method The study included out-patients with at least one BZRA prescription from five psychiatric settings in east, central and west China in 2018. Demographic and prescription information were extracted from the electronic prescription database. We defined the co-occurrence of overdose and long-term use as hazardous use, and patients whose recorded diagnoses did not meet any indications approved by the Chinese Food and Drug Administration as over-indication users. Additionally, 200 hazardous users were randomly selected for follow-up interview to confirm the actual situation. Results Among 720 054 out-patients, 164 450 (22.8%) had at least one BZRA prescription; 55.9% of patients were prescribed over-indication and 3% were defined as hazardous users. Multilevel multivariate regression analysis with hospital as a random effect showed that factors associated with hazardous use were older age (18–64 years: β = 0.018; 95% CI 0.013–0.023; >65 years: β = 0.015; 95% CI 0.010–0.021), male (β = 0.005, 95% CI 0.003–0.007), over-indication (β = 0.013, 95% CI 0.012–0.015), more out-patient visits (β = 0.006, 95% CI 0.006–0.006) and more visits to different doctors (β = 0.007, 95% CI 0.007–0.008); 98.5% of hazardous users (197/200) could not be contacted. Conclusions BZRAs are commonly used and there is a relatively large proportion of over-indication users among Chinese psychiatric out-patients. However, only a small proportion of hazardous users were detected. The study highlights how to use prescription data to support improvements in clinical practice.

Corrosion can hurt the quality and service life of a workpiece, which could create potential safety hazards. However, improving the workpiece’s surface integrity through surface treatment could improve the effect of corrosion resistance. To study the effect of surface integrity on the corrosion resistance of low-alloy steel for hydrogen reactors, electrolytic corrosion experiments were carried out on specimens that were processed using different grit sandpapers or using different shot peening pressures using a self-built electrolytic platform. The influence regulation of initial surface roughness and surface residual stress on the corrosion rate of the low-alloy steel for a hydrogen reactor under different lengths of corrosion time, surface roughness after corrosion, and the tensile property degradation of the specimens after 4 h of corrosion were analyzed, respectively. In this paper, based on experimental research, we obtain the influence regulation of the processing parameters on the corrosion resistance of low-alloy steel for hydrogen reactors and provide processing parameters that could improve the corrosion resistance of low-alloy steel, which guides the corrosion resistance processing of hydrogen production reactors. It was found through experiments that with an increase in the initial surface roughness of the specimens, the corrosion rate of the specimen tends to decrease with the increase in corrosion duration; the surface roughness of the specimen after corrosion first increases and then decreases with the increase in corrosion time; and the tensile strength of specimen with the initial surface roughness of Ra 0.168 μm is relative good after 4 h of corrosion. With the increase in residual compressive stress on the surface of the specimen, the corrosion rate of the specimen decreases with the increase in corrosion time; the surface roughness of the specimen after corrosion first increases and then decreases with the increase in corrosion time; and the tensile strength of specimen with the surface residual stress of −335.64 MPa is relative good after 4 h of corrosion.

Abstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory deficits and cognitive decline. Current drugs can only relieve symptoms, but cannot really cure AD. Cerebralcare Granule® (CG) is a Traditional Chinese medicine (TCM) containing a variety of biologically active compounds. In our previous studies, CG has shown a beneficial effect against memory impairment in mice caused by d-galactose. However, whether CG can be used as a complementary medicine for the treatment of AD remains unexplored. Here, we use a combination of CG and memantine hydrochloride (Mm) to treat Alzheimer-like pathology and investigate the effects and mechanisms in vivo. Methods The histology of brain was examined with Hematoxylin–eosin (HE) staining, Golgi staining and Thioflavin S staining. ELISA was applied to assess the expression levels or activities of CAT, SOD, GSH-Px, MDA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL) in serum, as well as the levels of IL-6, IL-1β, and TNF-α in the mice brain. Western blotting was used to assess the expression of β-secretase (BACE1), amyloid precursor protein (APP), APPβ, APPα, synaptophysin (SYN), growth-associated protein 43 (GAP43), and postsynaptic density 95 (PSD95). Results In the present study, the combination group (CG + Mm) significantly attenuated Alzheimer-like behavior without adverse effects in APP/PS1 mice, indicating its high degree of safety and efficacy after long-term treatment. CG + Mm reduced AD pathological biomarker Aβ plaque accumulation by inhibiting BACE1 and APP expression (P

Cardiac fibrosis is a pathogenic factor of many cardiovascular diseases (CVD), which seriously affects people's life and health, causing huge economic losses.Therefore, it is very significant to find an effective treatment for myocardial fibrosis. Adipokines are mainly derived from adipose tissue and have an prominent regulatory effect on glucose and lipid metabolism, inflammation, immune response and cardiovascular function. Adipose tissue is composed of a variety of cell types, including adipocytes, endothelial cells, macrophages and smooth muscle cells. Adipokines mainly include adiponectin, leptin, resistin, visfatin and omentin, which are synthesized and secreted by adipocytes. More and more evidence shows that adipokines can regulate the progress of cardiac fibrosis. This scientific review provides new ideas for targeting adipokines in the treatment of myocardial fibrosis and provides strategies for the development of new, safe, and effective pharmacological antagonists against myocardial fibrosis based on adipokines activity.

Abstract Background The incidence rates of cervical cancer in developing countries have been steeply increasing while the medical resources for prevention, detection, and treatment are still quite limited. Computer-based deep learning methods can achieve high-accuracy fast cancer screening. Such methods can lead to early diagnosis, effective treatment, and hopefully successful prevention of cervical cancer. In this work, we seek to construct a robust deep convolutional neural network (DCNN) model that can assist pathologists in screening cervical cancer. Methods ThinPrep cytologic test (TCT) images diagnosed by pathologists from many collaborating hospitals in different regions were collected. The images were divided into a training dataset (13,775 images), validation dataset (2301 images), and test dataset (408,030 images from 290 scanned copies) for training and effect evaluation of a faster region convolutional neural network (Faster R-CNN) system. Results The sensitivity and specificity of the proposed cervical cancer screening system was 99.4 and 34.8%, respectively, with an area under the curve (AUC) of 0.67. The model could also distinguish between negative and positive cells. The sensitivity values of the atypical squamous cells of undetermined significance (ASCUS), the low-grade squamous intraepithelial lesion (LSIL), and the high-grade squamous intraepithelial lesions (HSIL) were 89.3, 71.5, and 73.9%, respectively. This system could quickly classify the images and generate a test report in about 3 minutes. Hence, the system can reduce the burden on the pathologists and saves them valuable time to analyze more complex cases. Conclusions In our study, a CNN-based TCT cervical-cancer screening model was established through a retrospective study of multicenter TCT images. This model shows improved speed and accuracy for cervical cancer screening, and helps overcome the shortage of medical resources required for cervical cancer screening.

Ferroptosis is a type of lipid peroxidation-induced cell death that can be regulated in various ways, from changing the activity of antioxidant enzymes to the levels of transcription factors. The p53 tumor suppressor gene is the ''guardian of the genome'' and is involved in controlling cell survival and division under various pressures. In addition to its effects on apoptosis, autophagy, and cell cycle, p53, through the way of transcription dependent or independent two-way, also regulates the biological processes of tumor cell sensitivity to ferroptosis, including the metabolism of amino acids, nicotinamide adenine dinucleotide phosphate, and lipid peroxidation, as well as the biosynthesis of glutathione, phospholipids, NADPH and coenzyme Q10. As reviewed here, we summarized the metabolic network of p53 and its signaling pathway in regulating ferroptosis and elucidated possible factors and potential clinical application of p53 regulating ferroptosis. This review will provide a basis for further understanding the role of p53 in tumor ferroptosis and new strategies for cancer therapeutic avenues.

ABSTRACT Pyroptosis, a programmed cell death, functions as an innate immune effector mechanism and plays a crucial role against microbial invasion. Gasdermin D (GSDMD), as the main pyroptosis effector, mediates pyroptosis and promotes releasing proinflammatory molecules into the extracellular environment through pore-forming activity, modifying inflammation and immune responses. While the substantial importance of GSDMD in microbial infection and cancer has been widely investigated, the role of GSDMD in virus infection, including coronaviruses, remains unclear. Enteric coronavirus transmissible gastroenteritis virus (TGEV) and porcine deltacoronavirus (PDCoV) are the major agents for lethal watery diarrhea in neonatal pigs and pose the potential for spillover from pigs to humans. In this study, we found that alphacoronavirus TGEV upregulated and activated GSDMD, resulting in pyroptosis after infection. Furthermore, the fragment of swine GSDMD from amino acids 242 to 279 (242-279 fragment) was required to induce pyroptosis. Notably, GSDMD strongly inhibited both TGEV and PDCoV infection. Mechanistically, the antiviral activity of GSDMD was mediated through promoting the nonclassical release of antiviral beta interferon (IFN-β) and then enhancing the interferon-stimulated gene (ISG) responses. These findings showed that GSDMD dampens coronavirus infection by an uncovered GSDMD-mediated IFN secretion, which may present a novel target of coronavirus antiviral therapeutics. IMPORTANCE Coronaviruses, primarily targeting respiratory and gastrointestinal epithelia in vivo, have a serious impact on humans and animals. GSDMD, a main executioner of pyroptosis, is highly expressed in epithelial cells and involves viral infection pathogenesis. While the functions and importance of GSDMD as a critical regulator of inflammasome activities in response to intracellular bacterial infection have been extensively investigated, the roles of GSDMD during coronavirus infection remain unclear. We here show that alphacoronavirus TGEV triggered pyroptosis and upregulated GSDMD expression, while GSDMD broadly suppressed the infection of enteric coronavirus TGEV and PDCoV by its pore-forming activity via promoting unconventional release of IFN-β. Our study highlights the importance of GSDMD as a regulator of innate immunity and may open new avenues for treating coronavirus infection.

Yiqi Fumai lyophilized injection (YQFM) is the recombination of Sheng mai san (SMS).YQFM has been applied clinically to efficaciously and safely treat chronic heart failure (CHF). However, the mechanism of YQFM is still not fully elucidated. The purpose of our study was to investigate the protective mechanism of YQFM against abdominal aortic coarctation (AAC) in rats by proteomic methods. After YQFM treatment, the cardiac function were obviously meliorated. One hundred and fifty-seven important differentially expressed proteins (DEPs) were identified, including 109 in model rat compared with that in control rat (M:C) and 48 in YQFM-treated rat compared with that in model rat (T:M) by iTRAQ technology to analyze the proteomic characteristics of heart tissue. Bioinformatics analysis showed that DEPs was mainly involved in the body’s energy metabolism and was closely related to oxidative phosphorylation. YQFM had also displayed efficient mitochondrial dysfunction alleviation properties in hydrogen peroxide (H2O2)-induced cardiomyocyte damage by Transmission Electron Microscope (TEM), Metabolic assay, and Mitotracker staining. What’s more, the levels of total cardiomyocyte apoptosis were markedly reduced following YQFM treatment. Furthermore, Western blot analysis showed that the expressions of peroxisome proliferator activated receptor co-activator-1α(PGC-1α) (p < 0.01 or p < 0.001), perixisome proliferation-activated receptor alpha (PPAR-α) (p < 0.001)and retinoid X receptor alpha (RXR-α) were upregulated (p < 0.001), PGC-1α as well as its downstream effectors were also found to be upregulated in cardiomyocytes after YQFM treatment(p < 0.001).These results provided evidence that YQFM could enhance mitochondrial function of cardiomyocytes to play a role in the treatment of CHF by regulating mitochondrial biogenesis-related proteins.

Background: Cardiac fibrosis occurs in ischemic and non-ischemic heart failure, hereditary cardiomyopathy, diabetes and aging. Energy metabolism, which serves a crucial function in the course and treatment of cardiovascular diseases, might have therapeutic benefits for myocardial fibrosis. Ginsenoside Rb3 (G-Rb3) is one of the main components of Ginseng and exhibits poor oral bioavailability but still exerts regulate energy metabolism effects in some diseases. Therefore, the study investigated the effect of chitosan (CS) @ sodium tripolyphosphate (TPP) nanoparticles conjugation with ginsenoside Rb3 (NpRb3) on myocardial fibrosis and studied its possible mechanisms. The results showed that NpRb3 directly participates in the remodeling of myocardial energy metabolism and the regulation of perixisome proliferation-activated receptor alpha (PPARα), thereby improving the degree of myocardial fibrosis. The study also verifies the protective effect of NpRb3 on energy metabolism and mitochondrial function by targeting the PPARα pathway. Therefore, the prepared nanodrug carrier may be a potential solution for the delivery of G-Rb3, which is a promising platform for oral treatment of myocardial fibrosis.

Accurate and automatic segmentation of pulmonary nodules in 3D thoracic Computed Tomography (CT) images is of great significance for Computer-Aided medical Diagnosis (CAD) of lung cancer. Currently, this important task remains challenging for lack of the voxel-level annotation and training strategies that balance target/background voxels in thoracic CT images. In this paper, a new region-based network, called Nodule-plus Region-based CNN, is proposed to detect pulmonary nodules in 3D thoracic CT images effectively while synchronously generating an instance segmentation mask for every detected instance. Our new network is constructed with a stack of convolutional blocks in which lateral connections are used to alleviate the difficulty of vanishing gradients. In addition, in order to reduce annotation workload and make best use of unannotated samples, we proposed a new Deep Self-paced Active Learning (DSAL) strategy by combining Active Learning (AL) and Self-Paced Learning (SPL) strategies. For the purpose of evaluating the performance of our proposed Nodule-plus R-CNN, we conduct a series of experiments on the public LIDC-IDRI dataset, and our model achieves 0.66 Dice and 0.96 TP Dice, which are state-of-the-art best results of pulmonary nodule segmentation. When the amount of available annotated samples is limited, our model trained with the DSAL strategy performs much better than that trained with the standard strategy.

In order to solve the problems of high millet agglomerates rate, high damage rate, and high undelivered net loss rate in the process of mechanized harvesting of millet, a longitudinal axial flow-staggered flexible threshing device for millet was designed on the basis of the existing threshing device. The “staggered teeth” threshing drum and the micro rotating circular tube concave screen work together to realize the flexible and low damage threshing of millet. The pre experiment was carried out first, and the factors that have a great impact on the millet agglomerates rate, the undelivered net loss rate, and the damage rate were found to be the feeding amount, the rotating speed of the drum, and the threshing clearance. In order to further explore the influence of the interaction between the factors on the millet agglomerates rate, the undelivered net loss rate, and the damage rate, the regression orthogonal rotation combination test was carried out, and after the test, the optimal parameter combination of feeding amount, drum speed, and threshing clearance was determined. The results showed that when the feeding amount was 1.3 kg/s, the rotating speed of the drum was 762 r/min−1 and the concave clearance was 15 mm, the millet agglomerates rate was 2.92%, the high undelivered net loss rate was 1.58%, and the damage rate was 0.37%.

With the increasing daily workload of physicians, computer-aided diagnosis (CAD) systems based on deep learning play an increasingly important role in pattern recognition of diagnostic medical images. In this paper, we propose a framework based on hierarchical convolutional neural networks (CNNs) for automatic detection and classification of focal liver lesions (FLLs) in multi-phasic computed tomography (CT). A total of 616 nodules, composed of three types of malignant lesions (hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and metastasis) and benign lesions (hemangioma, focal nodular hyperplasia, and cyst), were randomly divided into training and test sets at an approximate ratio of 3:1. To evaluate the performance of our model, other commonly adopted CNN models and two physicians were included for comparison. Our model achieved the best results to detect FLLs, with an average test precision of 82.8%, recall of 93.4%, and F1-score of 87.8%. Our model initially classified FLLs into malignant and benign and then classified them into more detailed classes. For the binary and six-class classification, our model achieved average accuracy results of 82.5 and73.4%, respectively, which were better than the other three classification neural networks. Interestingly, the classification performance of the model was placed between a junior physician and a senior physician. Overall, this preliminary study demonstrates that our proposed multi-modality and multi-scale CNN structure can locate and classify FLLs accurately in a limited dataset, and would help inexperienced physicians to reach a diagnosis in clinical practice.

Neoantigens play important roles in cancer immunotherapy. Current methods used for neoantigen prediction focus on the binding between human leukocyte antigens (HLAs) and peptides, which is insufficient for high-confidence neoantigen prediction. In this study, we apply deep learning techniques to predict neoantigens considering both the possibility of HLA-peptide binding (binding model) and the potential immunogenicity (immunogenicity model) of the peptide-HLA complex (pHLA). The binding model achieves comparable performance with other well-acknowledged tools on the latest Immune Epitope Database (IEDB) benchmark datasets and an independent mass spectrometry (MS) dataset. The immunogenicity model could significantly improve the prediction precision of neoantigens. The further application of our method to the mutations with pre-existing T-cell responses indicating its feasibility in clinical application. DeepHLApan is freely available at https://github.com/jiujiezz/deephlapan and http://biopharm.zju.edu.cn/deephlapan.

Currently, there is no available biomarker for lung cancer diagnosis. Here we recruited 844 lung cancer patients and 620 healthy participants from six hospitals. A total of four serum proteins was identified and subsequently assessed in the training and validation cohorts. The concentrations of four serum proteins were found to be significantly higher in lung cancer patients compared with healthy participants. The area under the curve (AUC) for the 4-biomarker were 0.86 in the training cohort, and 0.87 in the validation cohort. The classification improved to a corrected AUC of 0.90 and 0.89 respectively following addition of sex, age and smoking status. Similar results were observed for early-stage lung cancer. Remarkably, in a blinded test with a suspicious pulmonary nodule, the adjusted prediction model correctly discriminated the patients with 86.96% sensitivity and 98.25% specificity. These results demonstrated the 4-biomarker panel improved lung cancer prediction beyond that of known risk factors. Moreover, the biomarkers were valuable in differentiating benign nodules which will remain indolent from those that are likely to progress and therefore might serve as an adjuvant diagnosis tool for LDCT scanning.

Lung cancer is the leading cause of cancer-related deaths for both men and women. Early diagnosis of lung cancer has a 5-year survival rate of 48.8%, however, nearly 35% of stage I patients relapses after surgical resection, thus portending a poor prognosis. Therefore, detecting lung cancer in early stage and further identifying the high-risk patients would allow the opportunity to provide adjuvant therapy and possibly increase survival. There is considerable evidence that the immune system produces an autoantibody response to neoplastic cells. The detection of such autoantibodies has been shown to have diagnostic and prognostic value. Here we took advantage of the high-throughput Luminex technique to multiplex a total of 14 tumor-associated autoantigens to detect the autoantibody from the patients sera. The 14 antigens were expressed by in vitro transcription/translation system with HaloTag at N-terminus. The fusion proteins were then covalently immobilized onto the Luminex microspheres conjugated by the halo-link ligand, thus eliminating the protein purification procedure. Sera samples from cancer patients and healthy controls were interacted with the microsphere-antigen complex to measure the autoantibodies. We have developed a quick multiplex detection system for measuring autoantibody signature from patient sera with minimal cross-reaction. A panel of seven autoantibody biomarkers has generated an AUC>80% in distinguishing the lung cancers from healthy controls. This study is the first report by combining Luminex platform and HaloTag technology to detect humoral immune response in cancer patients. Due to the flexibility of the Luminex technology, this approach can be applied to others conditions such as infectious, neurological, and metabolic diseases. One can envision that this multiplex Luminex system as well as the panel of seven biomarkers could be used to screen the high-risk population with subsequent CT test based on the blood test result.