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Abstract Background In this study, the potential anticancer activity and mechanism of action of SBD-2, a chalcone isolated from Shuteria involucrata, was investigated in colorectal cancer (CRC) cells. Results SBD-2 inhibited the proliferation of Caco-2 cells in a dose-dependent manner. It elicited the cells arrested in the G2/M phase and induced apoptosis. Mechanistically, SBD-2 inhibited Akt phosphorylation, which suppressed the ani-apoptotic protein Bcl-2 and cell cycle regulator Cyclin B1, leading to apoptosis ad cycle arrest, respectively. Conclusions The presented chalcone compound SBD-2 from Shuteria involucrata induced apoptosis and cell cycle arrest through inhibiting Akt pathway, highlighting the possibility to develop as a new agent for CRC treatment.

Abstract Background As disseminated extrapulmonary tuberculosis infection can involve multiple systems and result in atypical clinical manifestations that mimic other diseases, the diagnosis may be difficult, especially in elderly patients. Delaying treatment can adversely affect the prognosis. And to achieve better prognosis, early detection and diagnosis are necessary, as well as early initiation of comprehensive treatment. Case presentation We present the case of a 78-year-old man with disseminated tuberculosis who developed the uncommon complication of urinary retention due to a psoas abscess, meningoencephalitis, and the rare secondary hemophagocytic lymphohistiocytosis syndrome. The patient achieved a favorable outcome following targeted therapy with antitubercular medications. Conclusions This case highlights that disseminated extrapulmonary tuberculosis infection can present with a variety of manifestations, and may exhibit many rare and complex clinical presentations. Prompt and accurate diagnosis and treatment play a crucial role in improving prognosis for the patients with persistent fever.

Abstract Background To date, although most thyroid carcinoma (THCA) achieves an excellent prognosis, some patients experience a rapid progression episode, even with differentiated THCA. Nodal metastasis is an unfavorable predictor. Exploring the underlying mechanism may bring a deep insight into THCA. Methods A total of 108 THCA from Chinese patients with next-generation sequencing (NGS) were recruited. It was used to explore the gene alteration spectrum of THCA and identify gene alterations related to nodal metastasis in papillary thyroid carcinoma (PTC). The Cancer Genome Atlas THCA cohort was further studied to elucidate the relationship between specific gene alterations and tumor microenvironment. A pathway enrichment analysis was used to explore the underlying mechanism. Results Gene alteration was frequent in THCA. BRAF, RET, POLE, ATM, and BRCA1 were the five most common altered genes. RET variation was positively related to nodal metastasis in PTC. RET variation is associated with immune cell infiltration levels, including CD8 naïve, CD4 T and CD8 T cells, etc. Moreover, Step 3 and Step 4 of the cancer immunity cycle (CIC) were activated, whereas Step 6 was suppressed in PTC with RET variation. A pathway enrichment analysis showed that RET variation was associated with several immune-related pathways. Conclusion RET variation is positively related to nodal metastasis in Chinese PTC, and anti-tumor immune response may play a role in nodal metastasis triggered by RET variation.

Objective: This study was conducted to investigate the purification process aimed at obtaining a shiitake glycoprotein with lead eliminating effect, and to explore its preventive and therapeutic efficacy against lead acetate-induced lead toxicity in a rat model. Methods: The crude polysaccharide was extracted from shiitake mushrooms using a hot water extraction method, followed by further purification involving protein removal and chromatography techniques to obtain the bioactive glycoprotein. The molecular characteristics of the glycoprotein were determined through various analytical methods, including infrared spectroscopy analysis, monosaccharide composition analysis, N-terminal amino acid sequencing, and internal amino acid sequence analysis. To evaluate the bioactive potential of shiitake polysaccharide-peptide in addressing lead poisoning in rats, 63 male Sprague-Dawley rats were randomly distributed into nine groups, including a control group, a model group, a positive control group, and shiitake glycoprotein treatment groups at doses of 4, 8 and 160 mg/kg, as well as shiitake fruiting body treatment groups at doses of 4, 12 and 36 g/kg. Lead poisoning was induced in the rats via intraperitoneal injection of lead acetate. The rats were administered polysaccharide-peptide and shiitake fruiting body treatments for a duration of 30 days, with observations made regarding their physical condition. Parameters assessed included body weight, lead content in blood and various organs, as well as biochemical markers in serum. Results: The monosaccharide composition analysis showed that the purified shiitake glycoprotein (LEPP) was composed of glucose, mannose, galactose, glucuronic acid, xylose, fucose, ribose, galacturonic acid, arabinose and rhamnose. The amino acid sequence analysis showed that the N-terminal sequence was MPEQVVVADA, indicating that the shiitake glycoprotein had polysaccharide and protein components. The findings indicated that shiitake glycoprotein effectively promoted weight gain in rats afflicted with lead poisoning. It significantly reduced lead concentrations in both blood and liver, mitigated lead deposition within the liver, enhanced the activities of superoxide dismutase (SOD) and catalase (CAT) in the serum, lowered the levels of malondialdehyde (MDA) （P

Abstract Glioma, with its heterogeneous microenvironments and genetic subtypes, presents substantial challenges for treatment prediction and development. We integrated 3D bioprinting and multi-algorithm machine learning as a novel approach to enhance the assessment and understanding of glioma treatment responses and microenvironment characteristics. The bioprinted patient-derived glioma tissues successfully recapitulated molecular properties and drug responses of native tumors. We then developed GlioML, a machine learning workflow incorporating nine distinct algorithms and a weighted ensemble model that generated robust gene expression-based predictors, each reflecting the diverse action mechanisms of various compounds and drugs. The ensemble model superseded the performance of all individual algorithms across diverse in vitro systems, including sphere cultures, complex 3D bioprinted multicellular models, and 3D patient-derived tissues. By integrating bioprinting, the evaluative scope of the treatment expanded to T cell-related therapy and anti-angiogenesis targeted therapy. We identified promising compounds and drugs for glioma treatment and revealed distinct immunosuppressive or angiogenic myeloid-infiltrated tumor microenvironments. These insights pave the way for enhanced therapeutic development for glioma and potentially for other cancers, highlighting the broad application potential of this integrative and translational approach.

BackgroundIgG4-related disease (IgG4-RD) was characterized by single or multiple masses in organs, which may mimic various inflammatory and malignant diseases. Here, we summarize 4 patients with aggressive manifestations of IgG4-RD that mimic nasopharynx cancer to provide some new sights for the diagnosis of IgG4-RD.Case summaryFour patients were included in our series. The age ranged from 53 to 64 years old, and the duration of the disease ranged from 4 to 6 months. The chief complaints included headache, rhinorrhea, or diplopia. All patients had more than 10 IgG4+ plasma cells/HPF in immunohistochemistry with plasma lgG4 levels ranging from 218 mg/dL to 765 mg/dL. All of them met the diagnostic criteria of lgG4-RD.ConclusionThe described case is highly similar to the clinical manifestations of nasopharyngeal carcinoma. Although pathology is the gold standard, there are still limitations. Serological IgG4 can help confirm the diagnosis. Timely diagnosis of IgG4-RD is of great significance in preventing secondary organ damage in patients with active diseases.

For mutual coupling evaluation between antennas on the platform, present an enhanced algorithm that combines the spherical wave expansion (SWE), the uniform theory of diffraction (UTD), and the reaction theorem to accurately calculate the mutual coupling between two antennas mounted on a platform. The algorithm begins by employing SWE to compute the direct electromagnetic field radiated by the antennas. Subsequently, UTD is introduced to capture the field scattered by the platform. Finally, the mutual coupling is evaluated through the reaction integral. Numerical examples highlight the algorithm's promising speed and accuracy, surpassing the performance of the MLFMA and MoM-UTD methods. With a computational complexity of O(LMN3), our approach offers significant improvements for mutual coupling analysis in platform-based antenna systems.

Salient object detection (SOD) aims to detect the most attractive region in an image. Fully supervised SOD based on deep learning usually needs a large amount of data with human annotation. Researchers have gradually focused on the SOD task using weakly supervised annotation such as category, scribble, and bounding-box, while these existing weakly supervised methods achieve limited performance and demonstrate a huge performance gap with fully supervised methods. In this work, we proposed one novel two-stage weakly supervised method based on bounding-box annotation and the recent large visual model Segment Anything (SAM). In the first stage, we regarded the bounding-box annotation as the box prompt of SAM to generate initial labels and proposed object completeness check and object inversion check to exclude low quality labels, then we selected reliable pseudo labels for the training initial SOD model. In the second stage, we used the initial SOD model to predict the saliency map of excluded images and adopted SAM with the everything mode to generate segmentation candidates, then we fused the saliency map and segmentation candidates to predict pseudo labels. Finally we used all reliable pseudo labels generated in the two stages to train one refined SOD model. We also designed a simple but effective SOD model, which can capture rich global context information. Performance evaluation on four public datasets showed that the proposed method significantly outperforms other weakly supervised methods and also achieves comparable performance with fully supervised methods.

Abstract Background The tumor immune microenvironment can influence the prognosis and treatment response to immunotherapy. We aimed to develop a non-invasive radiomic signature in high-grade glioma (HGG) to predict the absolute density of tumor-associated macrophages (TAMs), the preponderant immune cells in the microenvironment of HGG. We also aimed to evaluate the association between the signature, and tumor immune phenotype as well as response to immunotherapy. Methods In this retrospective setting, total of 379 patients with HGG from three independent cohorts were included to construct a radiomic model named Radiomics Immunological Biomarker (RIB) for predicting the absolute density of M2-like TAM using the mRMR feature ranking method and LASSO classifier. Among them, 145 patients from the TCGA microarray cohort were randomly allocated into a training set (N=101) and an internal validation set (N=44), while the immune-phenotype cohort (N=203) and the immunotherapy-treated cohort (N=31, patients from a prospective clinical trial treated with DC vaccine) recruited from Huashan Hospital were used as two external validation sets. The immunotherapy-treated cohort was also used to evaluate the relationship between RIB and immunotherapy response. Radiogenomic analysis was performed to find functional annotations using RNA sequencing data from TAM cells. Results An 11-feature radiomic model for M2-like TAM was developed and validated in four datasets of HGG patients (area under the curve = 0.849, 0.719, 0.674, and 0.671) using MRI images of post contrast enhanced T1-weighted (T1CE). Patients with high RIB scores had a strong inflammatory response. Four hub-genes (SLC7A7, RNASE6, HLA-DRB1 and CD300A) expressed by TAM were identified to be closely related to the RIB, providing important evidence for biological interpretation. Only individuals with a high RIB score were shown to have survival benefits from DC vaccine [DC vaccine vs. Placebo: median progression-free survival (mPFS), 10.0 mos vs. 4.5 mos, HR=0.17, P=0.0056, 95%CI=0.041-0.68; median overall survival (mOS), 15.0 mos vs. 7.0 mos, HR=0.17, P =0.0076, 95%CI=0.04-0.68]. Multivariate analyses also confirmed that treatment by DC vaccine was an independent factor for improved survival in the high RIB score group. However, in the low RIB score group, DC vaccine was not associated with improved survival. Furthermore, a radiomic nomogram based on the RIB score and clinical factors could efficiently predict the 1-, 2-, and 3-year survival rates, as confirmed by ROC curve analysis (AUC for 1-, 2- and 3-year survival: 0.705, 0.729 and 0.684, respectively). Conclusions The radiomic model could allow for non-invasive assessment of the absolute density of TAM from MRI images in HGG patients. Of note, our RIB model is the first immunological radiomic model confirmed to have the ability to predict survival benefits from DC vaccine in gliomas, thereby providing a novel tool to inform treatment decisions and monitor patient treatment course by radiomics.

Abstract To explore the research status on mechanism of the skid-resistance for asphalt pavement, the related achievements of the rubber friction, the tire–road contact, and the influence factors were reviewed. The rubber friction was reviewed from the mechanism and rubber friction model. The tire-road contact was studied from the modeling methods, the evaluation methods, and the skid-resistance mechanisms at different conditions. The influence factors of skid-resistance were summarized from different designing processes. This review showed that the appropriate contact or evaluation model should be selected according to the required parameters. Although the finite element method is widely used, the accuracy of the model, the boundary conditions, and the load cases need to be further improved. The optimized aggregates and asphalt binders, reasonable gradation, reasonable geometric design, and strict construction quality control are necessary for good initial skid-resistance. Pavement texture as an important factor affecting skid-resistance should be considered in pavement gradation design, especially for wearing layer technology.

Abstract Aberrant activation of the PI3K/AKT signaling axis along with the sustained phosphorylation of downstream BAD is associated with a poor outcome of TNBC. Herein, the phosphorylated to non-phosphorylated ratio of BAD, an effector of PI3K/AKT promoting cell survival, was observed to be correlated with worse clinicopathologic indicators of outcome, including higher grade, higher proliferative index and lymph node metastasis. The structural optimization of a previously reported inhibitor of BAD-Ser99 phosphorylation was therefore achieved to generate a small molecule inhibiting the phosphorylation of BAD at Ser99 with enhanced potency and improved oral bioavailability. The molecule 2-((4-(2,3-dichlorophenyl)piperazin-1-yl)(pyridin-3-yl)methyl) phenol (NCK) displayed no toxicity at supra-therapeutic doses and was therefore assessed for utility in TNBC. NCK promoted apoptosis and G0/G1 cell cycle arrest of TNBC cell lines in vitro, concordant with gene expression analyses, and reduced in vivo xenograft growth and metastatic burden, demonstrating efficacy as a single agent. Additionally, combinatorial oncology compound library screening demonstrated that NCK synergized with tyrosine kinase inhibitors (TKIs), specifically OSI-930 or Crizotinib in reducing cell viability and promoting apoptosis of TNBC cells. The synergistic effects of NCK and TKIs were also observed in vivo with complete regression of a percentage of TNBC cell line derived xenografts and prevention of metastatic spread. In patient-derived TNBC xenograft models, NCK prolonged survival times of host animals, and in combination with TKIs generated superior survival outcomes to single agent treatment. Hence, this study provides proof of concept to further develop rational and mechanistic based therapeutic strategies to ameliorate the outcome of TNBC.

The rapid development of deep learning has made a great progress in salient object detection task. Fully supervised methods need a large number of pixel-level annotations. To avoid laborious and consuming annotation, weakly supervised methods consider low-cost annotations such as category, bounding-box, scribble, etc. Due to simple annotation and existing large-scale classification datasets, the category annotation based methods have received more attention while still suffering from inaccurate detection. In this work, we proposed one weakly supervised method with category annotation. First, we proposed one coarse object location network (COLN) to roughly locate the object of an image with category annotation. Second, we refined the coarse object location to generate pixel-level pseudo-labels and proposed one quality check strategy to select high quality pseudo labels. To this end, we studied COLN twice followed by refinement to obtain a pseudo-labels pair and calculated the consistency of pseudo-label pairs to select high quality labels. Third, we proposed one multi-decoder neural network (MDN) for saliency detection supervised by pseudo-label pairs. The loss of each decoder and between decoders are both considered. Last but not least, we proposed one pseudo-labels update strategy to iteratively optimize pseudo-labels and saliency detection models. Performance evaluation on four public datasets shows that our method outperforms other image category annotation based work.

Abstract Perineural invasion (PNI) leads to the poor prognosis of head and neck squamous cancer (HNSCC) patients, but the mechanism of PNI remains unclear. Dickkopf‐1 (DKK1), a secretory protein in the Wnt signaling pathway, was found indeed upregulated in HNSCC cells and tissues. Higher expression of DKK1 was statistically relevant to T stage, N stage, PNI, and poor prognosis of HNSCC. DKK1 overexpression enhanced the migration abilities of cancer cells. Moreover, DKK1‐overexpressing cancer cells promoted cancer cells invasion of peripheral nerves in vitro and in vivo. Mechanistically, DKK1 could promote the PI3K–AKT signaling pathway. The migration abilities of neuroblastoma cells, which were enhanced by DKK1‐overexpressing HNSCC cell lines, could be reversed by an inhibitor of Akt (MK2206). The association of DKK1 with PNI was also confirmed in HNSCC samples. Variables, including T stage, N stage, DKK1 expression, and PNI, were used to establish a nomogram to predict the survival probability and disease‐free probability at 3 and 5 years. In summary, DKK1 can promote the PI3K–AKT signaling pathway in tumor cells and then could induce neuritogenesis and facilitate PNI. MK2206 may be a potential therapeutic target drug for HNSCC patients with PNI.

Abstract Many rubber friction theories or some method combined theories and field-experiments are employed to evaluate the pavement skid-resistance deterioration due to the evolution of surface textures. However, these methods are difficult to be implemented in the analysis of situations with multi-factor coupling and some extreme conditions. This study developed a framework to evaluate the skid-resistance deterioration of asphalt pavements. In this framework, the portable laser scanning was used to create the digital worn pavement model, and a hydroplaning finite element (FE) model for these digital worn pavements was constructed to evaluate coupling effects of the texture evolution and factors of slip ratio, slip angle, velocity and water film on braking-cornering characteristics of tire. In this study, the deterioration of skid-resistance of five typical asphalt pavements due the surface texture wear was systematically investigated by this framework. Compared with previous works, this study established the rubber friction models for each digital worn pavement considering the energy hysteresis of rubber and the power spectrum density of surface texture. And the rubber friction model was used to define the interaction behaviors between the tire and corresponding wore pavements in the FE hydroplaning model, rather than using an empirical friction model or a fixed friction coefficient.

Abstract Conventional chemotherapy targets malignant cells without evaluating counter protection from the tumor microenvironment that often causes treatment failure. Herein, we establish chemoresistant fibroblasts (rCAFs) as regulators of neoadjuvant chemotherapeutic (NACT) response in head and neck squamous cell carcinoma (HNSCC). Clinically, high expression of CAF-related gene signature correlates with worse prognosis and chemotherapeutic response in multiple cancers, while the population of CAFs in the residual tumors of chemoresistant HNSCC patients remains unchanged after NACT treatment, compared to chemosensitive patients. Using a murine cancer model or patient-derived organoid, and primary CAFs isolated from chemo-sensitive (sCAFs) or -resistant patients, we show that rCAFs, but not sCAFs, are resistant to chemotherapy-induced apoptosis while reducing HNSCC cell chemosensitivity via paracrine signals. Combined multi-omics and biochemical analyses indicate an elevated PI3K/AKT/p65 driven cell survival and cytokine production in rCAFs, while rCAF-secreted TGFα promotes cancer cell chemoresistance by activating EGFR/Src/STAT3 survival signaling axis. Treatment with anti-EGFR cetuximab restores the chemosensitivity of tumors derived from co-injection of cancer cells and rCAFs in vivo, while the serum level of TGFα determines NACT response in HNSCC patients. Overall, our findings uncover a novel insight whereby the crosstalk between tumor cell and rCAF determines chemotherapeutic response and prognosis in cancer patients.

Abstract Background Frailty is an age-related geriatric syndrome that leads to a series of clinically negative events. A better understanding of the factors associated with frailty assists in preventing its progression. The triglyceride-glucose (TyG) index, a simple alternative index of insulin resistance, has not yet been proven to be associated with frailty. The present study aimed to investigate the association between the TyG index and its trajectory with frailty from a cross-sectional, retrospective and prospective level based on an ongoing cohort. Methods This longitudinal study included 1,866 older residents from the “Fujian prospective aging cohort” (ChiCTR 2,000,032,949). The TyG index was calculated as ln [fasting triglyceride (mg/dL) ╳ fasting plasma glucose (mg/dL)/2] and group-based trajectory model (GBTM) was applied to identify the trajectory of TyG index. The association between different trajectory groups of TyG index with frailty risk were estimated using multinomial logistic regression analysis. Results In the cross-sectional analysis, the highest quartile of the TyG index was associated with an increased risk of frailty (TyG index Q4 vs. Q1, OR = 1.50, 95% CI 1.00–2.25, P = 0.048). Restricted cubic splines demonstrated an increasing trend for TyG index and frailty risk. During a follow-up of ten years, three distinct trajectories of the TyG index were identified: low-stable (n = 697, 38.3%), moderate-stable (n = 910, 50.0%) and high-stable (n = 214, 11.7%). Compared with those in the stable-low group of TyG index trajectory, the ORs (95% CI) of prefrailty and frailty risk were 1.79 (95% CI 1.11–2.88) and 2.17 (95% CI 1.01–3.88) for the high-stable group, respectively (P = 0.017 and P = 0.038). In the subgroup analysis, the association of the high-stable trajectory of TyG and frailty status were only observed in subjects with BMI ≥ 24 kg/m2. Prospectively, the highest quartile of the TyG index was associated with a 2.09-fold significantly increased risk of one-year ADL/IADL decline (P = 0.045). Conclusions The present study suggests a potential role for a high and sustainable level of TyG index in the risk of frailty. The trajectories of the TyG index can help to identify older individuals at a higher risk of frailty who deserve primitive preventive and therapeutic approaches.

Exostosis (also known as osteochondroma) is the most common benign bony lump of young people, usually arising at the distal femur. Vascular complications associated with exostoses are rare and include true aneurysm or pseudoaneurysm formation, deep vein thrombosis, arteriovenous fistula, and arterial insufficiency of the limbs. Few case reports describe pseudoaneurysms resulting from exostoses in mature adults, and no consensus has been reached regarding the optimal therapy. We report the case of a 51-year-old male patient complaining of persistent right thigh pain with a pulsatile mass and right calf swelling, without a history of trauma or hereditary multiple exostoses. The diagnosis was confirmed by computed tomography angiography, which showed a pseudoaneurysm of the popliteal artery resulting from an exostosis on the lateral aspect of the distal femur. A Doppler ultrasound examination confirmed popliteal vein thrombosis caused by the compression of the pseudoaneurysm. Surgical treatment consisted of removing the exostosis, excision of the pseudoaneurysm, and an end-to-end anastomosis. The deep vein thrombosis was treated with rivaroxaban for 3 months. The patient was discharged after 6 days and followed up for 6 months with satisfactory results.

Co-inhibitory immune checkpoints play a crucial role in tumor progression, and PD-1/PD-L1 inhibitor has been a breakthrough for treating multiple refractory tumors in last decade. Nevertheless, results of several phase III clinical trials of PD-1/PD-L1 inhibitor are unsatisfactory in high grade gliomas recently. This article reviews the promising biomarkers which can predict the efficacy of PD-1/PD-L1 blockade immunotherapy and current status of emerging strategies involving PD-1/PD-L1 inhibitors, especially the combination treatment and neoadjuvant PD-1 therapy in gliomas. In addition, B7-H4, one of the most promising immune checkpoints, is also briefly reviewed here for its clinical significance, regulatory mechanism and developing immunotherapeutic strategies in pre-clinical glioma models.

【Objective】It is complex, time-consuming and laborious for conventional chemical detection method to detect the content of total nitrogen, potassium, total sugars, reducing sugars, total alkali, chlorine and magnesium in wrapper tobacco, while near-infrared spectroscopy technology is simple to operate and rapid to detect. The aims is to establish a near infrared spectroscopy detection model to achieve rapid quantitative analysis of the content of the seven chemical components in wrapper tobacco.【Method】Taking Yunnan cigar wrapper tobacco as the material, conventional chemical method was used to detect the content of seven chemical components in wrapper tobacco, and then near infrared spectroscopy was used to analyze the content of seven chemical components and their spectruml data of wrapper tobacco by using near infrared spectroscopy combined with partial least squares method, and the model with the optimal predictive performance was determined by comparing the root mean square error and correlation coefficient of the model.【Result】The optimal prediction results of the seven chemical components were established by the preprocessing methods of original spectrum, first derivative, first derivative, original spectrum, original spectrum, first derivative + median filtering and first derivative + median filtering, and the optimal principal component numbers were 20, 7, 4, 24, 21, 9 and 7, respectively; The training set correlation coefficients (r) of the seven models were 0.9441, 0.8589, 0.7664, 0.9511, 0.9547, 0.9031 and 0.8620, respectively. The root mean square error of cross validation (RMSECV) were 0.1288, 0.2846, 0.0280, 0.0096, 0.1894, 0.2965 and 0.0795; The correlation coefficients (r) of the validation set were 0.8958, 0.7675, 0.7181, 0.7928, 0.7282, 0.8062 and 0.7980, and the root mean square error of prediction (RMSEP) were 0.1789, 0.3011, 0.0324, 0.0193, 0.3855, 0.3990 and 0.0999. Moreover, the models were externally verified, and the results indicated that the average RSD of the predicted values and chemical values of the seven chemical components were less than 32%.【Conclusion】It was feasible to use near infrared spectroscopy to rapidly and quantitatively analyze the contents of seven chemical components in wrapper tobacco. The models had good prediction effect on the contents of seven chemical components, and could provide a reference for the rapidly and quantitatively analysis of seven chemical components in wrapper tobacco.

Statins are 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors widely used in the treatment of hyperlipidemia. The inhibition of HMG-CoA reductase in the mevalonate pathway leads to the suppression of cell proliferation and induction of apoptosis. The cyclic GMP-AMP synthase (cGAS) stimulator of the interferon genes (STING) signaling pathway has been suggested to not only facilitate inflammatory responses and the production of type I interferons (IFN), but also activate other cellular processes, such as apoptosis. It has not been studied, however, whether cGAS-STING activation is involved in the apoptosis induced by statin treatment in human colorectal cancer cells. In this study, we reported that lovastatin impaired mitochondrial function, including the depolarization of mitochondrial membrane potential, reduction of oxygen consumption, mitochondrial DNA (mtDNA) integrity, and mtDNA abundance in human colorectal cancer HCT116 cells. The mitochondrial dysfunction markedly induced ROS production in mitochondria, whereas the defect in mitochondria respiration or depletion of mitochondria eliminated reactive oxygen species (ROS) production. The ROS-induced oxidative DNA damage by lovastatin treatment was attenuated by mitochondrial-targeted antioxidant mitoquinone (mitoQ). Upon DNA damage, mtDNA was released into the cytosol and bound to DNA sensor cGAS, thus activating the cGAS-STING signaling pathway to trigger a type I interferon response. This effect was not activated by nuclear DNA (nuDNA) or mitochondrial RNA, as the depletion of mitochondria compromised this effect, but not the knockdown of retinoic acid-inducible gene-1/melanoma differentiation-associated protein 5 (RIG-I/MDA5) adaptor or mitochondrial antiviral signaling protein (MAVS). Moreover, lovastatin-induced apoptosis was partly dependent on the cGAS-STING signaling pathway in HCT116 cells as the knockdown of cGAS or STING expression rescued cell viability and mitigated apoptosis. Similarly, the knockdown of cGAS or STING also attenuated the antitumor effect of lovastatin in the HCT116 xenograft model in vivo. Our findings suggest that lovastatin-induced apoptosis is at least partly mediated through the cGAS-STING signaling pathway by triggering mtDNA accumulation in the cytosol in human colorectal cancer HCT116 cells.

Film bulk acoustic-wave resonators (FBARs) are widely utilized in the field of radio frequency (RF) filters due to their excellent performance, such as high operation frequency and high quality. In this paper, we present the design, fabrication, and characterization of an FBAR filter for the 3.0 GHz–3.2 GHz S-band. Using a scandium-doped aluminum nitride (Sc0.2Al0.8N) film, the filter is designed through a combined acoustic–electromagnetic simulation method, and the FBAR and filter are fabricated using an eight-step lithographic process. The measured FBAR presents an effective electromechanical coupling coefficient (keff2) value up to 13.3%, and the measured filter demonstrates a −3 dB bandwidth of 115 MHz (from 3.013 GHz to 3.128 GHz), a low insertion loss of −2.4 dB, and good out-of-band rejection of −30 dB. The measured 1 dB compression point of the fabricated filter is 30.5 dBm, and the first series resonator burns out first as the input power increases. This work paves the way for research on high-power RF filters in mobile communication.

With the development of wireless communication, increasing signal processing presents higher requirements for radio frequency (RF) systems. Piezoelectric acoustic filters, as important elements of an RF front-end, have been widely used in 5G-generation systems. In this work, we propose a Sc0.2Al0.8N-based film bulk acoustic wave resonator (FBAR) for use in the design of radio frequency filters for the 5G mid-band spectrum with a passband from 3.4 to 3.6 GHz. With the excellent piezoelectric properties of Sc0.2Al0.8N, FBAR shows a large Keff2 of 13.1%, which can meet the requirement of passband width. Based on the resonant characteristics of Sc0.2Al0.8N FBAR devices, we demonstrate and fabricate different ladder-type FBAR filters with second, third and fourth orders. The test results show that the out-of-band rejection improves and the insertion loss decreases slightly as the filter order increases, although the frequency of the passband is lower than the predicted ones due to fabrication deviation. The passband from 3.27 to 3.47 GHz is achieved with a 200 MHz bandwidth and insertion loss lower than 2 dB. This work provides a potential approach using ScAlN-based FBAR technology to meet the band-pass filter requirements of 5G mid-band frequencies.

In this study, the electrical performance and bias stability of InSnO/a-InGaZnO (ITO/a-IGZO) heterojunction thin-film transistors (TFTs) are investigated. Compared to a-IGZO TFTs, the mobility (µFE) and bias stability of ITO/a-IGZO heterojunction TFTs are enhanced. The band alignment of the ITO/a-IGZO heterojunction is analyzed by using X-ray photoelectron spectroscopy (XPS). A conduction band offset (∆EC) of 0.5 eV is observed in the ITO/a-IGZO heterojunction, resulting in electron accumulation in the formed potential well. Meanwhile, the ∆EC of the ITO/a-IGZO heterojunction can be modulated by nitrogen doping ITO (ITON), which can affect the carrier confinement and transport properties at the ITO/a-IGZO heterojunction interface. Moreover, the carrier concentration distribution at the ITO/a-IGZO heterointerface is extracted by means of TCAD silvaco 2018 simulation, which is beneficial for enhancing the electrical performance of ITO/a-IGZO heterojunction TFTs.

A spherical hinge structure is a key swivel bridge element that must be considered when evaluating friction characteristics and lubrication properties to meet the rotation requirement. Polytetrafluoroethylene (PTFE)-based spherical hinge sliders and lubrication coating have been employed for over 20 years, but with the growing tonnage of swivel bridge construction, their capacity to accommodate the required lubrication properties can be exceeded. In this manuscript, the optimal friction coefficient of the spherical hinge is obtained through the finite element analysis method. Four lubrication coatings and four spherical hinge sliders are prepared and tested through a self-developed rotation friction coefficient test, four-ball machine test, dynamic shear rheological test, and compression and shear performance test to evaluate the lubrication and friction properties of the spherical hinge structure. The results of the finite element analysis show that the optimum rotation friction coefficient of the spherical hinge structure is 0.031–1.131. The test results illustrate that the friction coefficient, wear scar diameter, maximum non-seize load, phase transition point, and thixotropic ring area of graphene lubrication coating are 0.065, 0.79 mm, 426 N, 14.6%, and 64,878 Pa/s. The graphene lubrication coating has different degrees of improvement compared with conventional polytetrafluoroethylene lubrication coating, showing more excellent lubrication properties, bearing capacity, thixotropy, and structural strength. Compressive and shear tests demonstrate that polyether ether ketone (PEEK) has good compressive and shear mechanical properties. The maximum compressive stress of PEEK is 87.7% higher than conventional PTFE, and the shear strength of PEEK is 6.07 times higher than that of PTFE. The research results can provide significantly greater wear resistance and a lower friction coefficient of the spherical hinge structure, leading to lower traction energy consumption and ensuring smooth and precise bridge rotation.

Abstract Cancer-associated fibroblasts (CAFs) are a kind of stromal cells in the cholangiocarcinoma (CCA) microenvironment, playing crucial roles in cancer development. However, the potential mechanisms of the interaction between CCA cells and CAFs remain obscure. This work investigated the role of circ_0020256 in CAFs activation. We proved circ_0020256 was up-regulated in CCA. High circ_0020256 expression facilitated TGF-β1 secretion from CCA cells, which activated CAFs via the phosphorylation of Smad2/3. Mechanistically, circ_0020256 recruited EIF4A3 protein to stabilize KLF4 mRNA and upregulate its expression, then KLF4 bound to TGF-β1 promoter and induced its transcription in CCA cells. KLF4 overexpression abrogated the inhibition of circ_0020256 silencing in TGF-β1/Smad2/3-induced CAFs activation. Furthermore, CCA cell growth, migration, and epithelial-mesenchymal transition were favored by CAFs-secreted IL-6 via autophagy inhibition. We also found circ_0020256 accelerated CCA tumor growth in vivo. In conclusion, circ_0020256 promoted fibroblast activation to facilitate CCA progression via EIF4A3/KLF4 pathway, providing a potential intervention for CCA progression.

Abstract Background Pertussis is a highly contagious respiratory disease caused by the bacterium Bordetella pertussis, characterized by paroxysms of severe coughing, and predominantly affects children. We report the first case of multiple fractures in the ribs, lumbar spine, and sacrum associated with severe coughing caused by Bordetella pertussis infection in an adult. Case presentation A 49-year-old female presented with acute-onset chest wall pain for 3 weeks. Imaging results revealed multiple fractures in the ribs and vertebrae, as well as bilateral pleural effusion, pericardial effusion, right pneumothorax, and enlargement of the left parapharyngeal and subclavian lymph nodes. The patient’s bone density scan, autoimmune antibodies, bone marrow biopsy, and sacral bone biopsy all came back normal. Imaging test results found no evidence of solid tumors or active TB infection. The patient later recalled having violent coughing prior to the onset of chest pain and several family members having similar symptoms. Her blood sample was sent to the CDC, revealing Bordetella pertussis toxin (PT) IgG titer of 110.68 IU/mL. The patient was diagnosed with pertussis and multiple stress fractures from violent coughing. Symptomatic treatments were administered, and the patient’s symptoms improved. The patient was followed up 8 weeks later, she reported no more coughing or chest pain. Conclusions Pertussis is not just a pediatric disease, but diagnosis in adults is challenging as patients may present with a myriad of confusing symptoms, such as multiple stress fractures due to violent coughing. Medical and epidemiological histories are key to reaching the correct diagnosis, which is essential for appropriate treatments to avoid further complications. Adult immunization should be suggested both for the protection of the adult population and to prevent transmission to children.

We have injected dish-cultured oncogenic RasV12 cells into adult male flies and analyzed by single cell transcriptomics their destiny within the host after 11 days. We identified in the preinjection samples and in the 11-day postinjection samples in all 16 clusters of cells, of which 5 disappeared during the experiment in the host. The other cell clusters expanded and expressed genes involved in the regulation of cell cycle, metabolism, and development. In addition, three clusters expressed genes related to inflammation and defense. Predominant among these were genes coding for phagocytosis and/or characteristic for plasmatocytes (the fly equivalent of macrophages). A pilot experiment indicated that the injection into flies of oncogenic cells, in which two of most strongly expressed genes had been previously silenced by RNA interference, into flies resulted in a dramatic reduction of their proliferation in the host flies as compared to controls. As we have shown earlier, the proliferation of the injected oncogenic cells in the adult flies is a hallmark of the disease and induces a wave of transcriptions in the experimental flies. We hypothesize that this results from a bitter dialogue between the injected cells and the host, while the experiments presented here should contribute to deciphering this dialogue.

Abstract Background Head and neck squamous cell carcinomas (HNSCC) are the most common type of head and neck cancer with an unimproved prognosis over the past decades. Although the role of cancer‐associated‐fibroblast (CAF) has been demonstrated in HNSCC, the correlation between CAF‐derived gene expression and patient prognosis remains unknown. Methods A total of 528 patients from TCGA database and 270 patients from GSE65858 database were contained in this study. After extracting 66 CAF‐related gene expression data from TCGA database, consensus clustering was performed to identify different HNSCC subtypes. Limma package was used to distinguish the differentially expression genes (DEGs) between these subtypes, followed by Lasso regression analysis to construct a prognostic model. The model was validated by performing Kaplan‐Meier survival, ROC and risk curve, univariate and multivariate COX regression analysis. GO, KEGG, GSEA, ESTIMATE and ssGSEA analyses was performed to explort the potential mechanism leading to different prognosis. Results Based on the 66 CAF‐related gene expression pattern we stratitied HNSCC patients into two previously unreported subtypes with different clinical outcomes. A prognostic model composed of 15 DEGs was constructed and validated. In addition, bioinformatics analysis showed that the prognostic risk of HNSCC patients was also negatively correlated to immune infiltration, implying the role of tumor immune escape in HNSCC prognosis and treatment option. Conclusions The study develops a reliable prognostic prediction tool and provides a theoretical treatment guidance for HNSCC patients.

The application of robots in high-precision automated machining is constrained by their limited multi-directional repeatability. In contrast, robots demonstrate superior levels of unidirectional repeatability, implying the potential for enhancing their precision. To further improve the positioning accuracy of robots, backlash error induced by rotating direction is considered, the concept of robot joint extended space is proposed, and the robot kinematic model is used to analyze the spatial similarity of robot error in the extended joint space. The dynamic Kriging method based on the optimization of basis functions is proposed to avoid overfitting of the surrogate model, and a model for estimating the robot’s positioning error in the joint extended space is constructed. Based on the estimated positioning error, the proposed calibration method is finally experimentally validated by error feedforward compensation. The results indicate that after Kriging interpolation in the robot joint space and feedforward compensation, the maximum/average positioning error of the robot is improved from 1.5157 mm and 0.8562 mm before compensation to 0.3471 mm and 0.1856 mm after compensation, and then further improved to 0.1848 mm and 0.1197 mm after adopting joint expansion space and dynamic Kriging interpolation, which decreases by 46.7% and 33.5%, respectively. This method effectively compensates the multi-directional repeatability error introduced by the joint backlash and improves the robot’s positioning accuracy.

Enhancing the resolution of images by super-resolution reconstruction algorithm is less costly compared with the way of upgrading hardware devices. At present, the image super-resolution algorithm can recover the texture details of the image well, but the performance is relatively general on the remote sensing images with lower contrast and more complex texture, and the reconstructed images are prone to noise, missing texture and checkerboard effect. This paper proposes a super-resolution adversarial network based on inverse feature fusion for the characteristics of remote sensing images, which combines the high-level semantics of the image with the low-level semantics to make the reconstructed images perform better in overall performance, and enhance the local details of the reconstructed image by feature expansion module. Experiments are carried out on RSSCN7 Dataset and representative algorithms are used for comparison. Experimental results show that RFSRNet and RFSRGAN offer better results than other methods, and ablation study show proposed modules are effective in enhancing the perceived similarity.

Abstract Background The prevalence of carbapenem-resistant Klebsiella pneumoniae bloodstream infection (CRKP-BSI) is increasing worldwide. CRKP-BSI is associated with high rates of morbidity and mortality due to limited antibiotic choices. Here, we aim to identify the prevalence and risk factors for infection and mortality of CRKP BSI. Methods This was a retrospective study of the past data from January 1st, 2012 to December 31st, 2019 of adult patients with KP-BSI in Xiangya Hospital, China. Results Among the 706 incidences included in this study, 27.4% of them (212/753) being CR-KP strains. The occurrence of CRKP-BSI was increased from 20.69 to 37.40% from 2012 to 2019. Hematologic malignancies and ICU acquired infection were identified to be substantial risk factors of carbapenem resistance. The overall 28-day mortality rates of CRKP-BSI patients was significantly higher than that of CSKP-BSI (P

To calculate and analyze the equivalent resilient modulus of a submerged subgrade, a constitutive model considering the effect of saturation and matrix suction was introduced using ABAQUS’s user-defined material (UMAT)subroutine. The pavement response under falling weight deflectometer (FWD) load was simulated at various water levels based on the derived distribution of the resilient modulus within the subgrade. The equivalent resilient modulus of the subgrade was then calculated using the equivalent iteration and weighted average methods. Based on this, the influence of the material and structural parameters of the subgrade was analyzed. The results indicate that the effect of water level rise on the tensile strain at the bottom of the asphalt layer and the compressive strain at the top of the subgrade is obvious, and its trend is similar to an exponential change. The equivalent resilient modulus of the subgrade basically decreases linearly with the rise in the water level, and there is high consistency between the equivalent iteration and weighted average methods. The saturated permeability coefficient and subgrade height have the most significant effect on the resilient modulus of the subgrade, which should be emphasized in the design of submerged subgrades, and the suggested values of the resilient modulus of the subgrade should be proposed according to the relevant construction conditions.

Haploinsufficiency of GATA2, also known as GATA2 deficiency, leads to a wide spectrum of clinical manifestations. Here we described another 28-year-old man with a GATA2 variant who also suffered from hemophagocytic lymphohistiocytosis(HLH), who was finally diagnosed with HLH triggered by Mycobacterium avium bloodstream infection due to primary immunodeficiency. We reviewed GATA2 deficiency patients with HLH and found that GATA2 variants causing loss of zinc finger domains were associated with HLH, and erythema nodosa might be an accompanying symptom.

BackgroundWe initiated the Fujian Tulou Pedigree-based Cohort (FTPC) as the integration of extended pedigrees and prospective cohort to clarify the genetic and environmental risk factors of cardiometabolic diseases.MethodsFTPC was carried out in Nanjing County, Fujian Province, China from August 2015 to December 2017 to recruit probands with the same surnames and then enroll their first-degree and more distant relatives. The participants were asked to complete questionnaire interview, physical examination, and blood collection. According to the local genealogical booklets and family registry, we reconstructed extended pedigrees to estimate the heritability of cardiometabolic traits. The follow-up of FTPC is scheduled every 5 years in the future.ResultsThe baseline survey interviewed 2,727 individuals in two clans. A total of 1,563 adult subjects who completed all baseline examinations were used to reconstruct pedigrees and 452 extended pedigrees were finally identified, including one seven-generation pedigree, two five-generation pedigrees, 23 four-generation pedigrees, 186 three-generation pedigrees, and 240 two-generation pedigrees. The average age of the participants was 57.4 years, with 43.6% being males. The prevalence of hypertension, diabetes and dyslipidemia in FTPC were 49.2, 10.0, and 45.2%, respectively. Based on the pedigree structure, the heritability of systolic blood pressure, diastolic blood pressure, fast blood glucose, total cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein was estimated at 0.379, 0.306, 0.386, 0.452, 0.568, 0.852, and 0.387, respectively.ConclusionAs an extended pedigree cohort in China, FTPC will provide an important source to study both genetic and environmental risk factors prospectively.

Background and objectives: The associations of intrinsic capacity (IC) with dietary diversity and body mass index (BMI) remain unclear in older adults. This study aimed to examine the associations of dietary diversity and BMI on high IC. Methods: The cross-sectional study used data from the Fujian Prospective Aging Cohort, which included 1972 individuals aged 60–98 from 2020 to 2021. The dietary diversity score (DDS) was constructed with eight food varieties, and consuming ≥five varieties of food daily was considered a high DDS. BMI was grouped into underweight, normal weight, overweight, and obesity according to the Chinese guidelines. High IC was defined as ≥three unimpaired domains of cognition, locomotion, sensory, vitality, and psychology. Results: Multivariate logistic regression analysis was used to assess the separate association of high DDS and BMI groups with high IC. Compared with low DDS, high DDS had a positive association with high IC (OR = 1.42, 95 % CI = 1.16–1.74). Compared with normal weight, underweight was inversely related to high IC (OR = 0.18, 95 % CI = 0.09–0.36), overweight was positively related to high IC (OR = 1.65, 95 % CI = 1.33–2.06), while no significant association was observed between obesity and high IC. The restricted cubic spline model exhibited an inverted U-shaped nonlinear curve of BMI and high IC and identified an optimal BMI of 25.7 kg/m2 for high IC. Conclusions: High DDS is a protective factor of high IC in older adults. Overweight had the most protective association with high IC among the four BMI subgroups. Individuals with overweight and higher dietary diversity had higher IC.

Abstract High-speed rail (HSR) has recently expanded its networks globally, but its 350 km/h bridges have not yet been tested for high-level earthquakes. This study tests the typical HSR bridge on a shaking table to assess the seismic performance in high-level earthquakes such as Maximum Considered Earthquake. Based on the model similarity theory, it creates nine round-ended rectangular-shaped cross-section solid RC HSR bridge piers. It employs the orthogonal testing method to conduct experimental design considering four influential factors: aspect ratio, axial load ratio, longitudinal reinforcement rate, and volumetric stirrup ratio. Experimental research was conducted to examine the dynamic response of these piers subjected to varying seismic impacts and design parameters, and the implications of the four factors on the seismic performance of the piers were discussed. After all the earthquake circumstances, the test findings demonstrate that the concrete of the pier specimens has not cracked or spalled much. An earthquake with a peak acceleration of 0.96 g indicates that the pier body of the standard high-speed rail round-end solid pier retains its integrity and stability. The extent of the pier's earthquake damage is not immediately evident. HSR bridges' seismic design may benefit from this research, which examines the impact of dynamic characteristics, including aspect ratio, axial load ratio, and longitudinal reinforcement rate, on HSR bridge piers' seismic performance.

Abstract Background We have witnessed frailty, which characterized by a decline in physiological reserves, become a major public health issue in older adults. Understanding the influential factors associated with frailty may help prevent or if possible reverse frailty. The present study aimed to investigate factors associated with frailty status and frailty transition in a community-dwelling older population. Methods A prospective cohort study on community-dwelling subjects aged ≥ 60 years was conducted, which was registered beforehand (ChiCTR 2,000,032,949). Participants who had completed two visits during 2020–2021 were included. Frailty status was evaluated using the Fried frailty phenotype. The least absolute shrinkage and selection operator (LASSO) regression was applied for variable selection. Bayesian network analysis with the max-min hill-climbing (MMHC) algorithm was used to identify factors related to frailty status and frailty transition. Results Of 1,981 subjects at baseline, 1,040 (52.5%) and 165 (8.33%) were classified as prefrailty and frailty. After one year, improved, stable, and worsening frailty status was observed in 460 (35.6%), 526 (40.7%), and 306 (23.7%) subjects, respectively. Based on the variables screened by LASSO regression, the Bayesian network structure suggested that age, nutritional status, instrumental activities of daily living (IADL), balance capacity, and social support were directly related to frailty status. The probability of developing frailty is 14.4% in an individual aged ≥ 71 years, which increases to 20.2% and 53.2% if the individual has balance impairment alone, or combined with IADL disability and malnutrition. At a longitudinal level, ADL/IADL decline was a direct predictor of worsening in frailty state, which further increased the risk of hospitalization. Low high-density lipoprotein cholesterol (HDL-C) and diastolic blood pressure (DBP) levels were related to malnutrition, and further had impacts on ADL/IADL decline, and ultimately led to the worsening of the frailty state. Knowing the status of any one or more of these factors can be used to infer the risk of frailty based on conditional probabilities. Conclusion Older age, malnutrition, IADL disability, and balance impairment are important factors for identifying frailty. Malnutrition and ADL/IADL decline further predict worsening of the frailty state.

In the field of heat manipulation, active thermal cloaks based on thermoelectric chips (TECs) have received much less attention than passive thermal cloaks based on metamaterials. This work focuses on active thermal cloaks and explores in-depth their mechanism of heat flow regulation. For a two-dimensional circular object located in a rectangular background plate with uniform temperature gradient, the theoretical design of an active cloak was realized by analytically solving for the target temperature field. A parameter study was conducted numerically for the designed thermal cloak. The results show that the object-to-background thermal conductivity ratio (m) is the key parameter that determines the working mode of the cloak. When m < 1, the TECs work in a heating mode with less power consumption; when m > 1, the TECs work in a chilling/heat pump mode with higher power consumption. If the change of a certain parameter increases the heat flow regulation, it will also cause performance degradation and an increase of the thermal cloak’s power consumption, especially when m is greater than 1. Improvement can be achieved by increasing the number of TECs (N), but the impact of N diminishes rapidly beyond a certain value. The systematic study in this work reveals the high flexibility and wide adaptability of the TE-chip-based thermal cloak in heat flow regulation.

With the development of offshore wind power development to deep and far sea, offshore flexible low-frequency AC (LFAC) transmission technology has attracted more and more attention from academia and industry in recent years. The control and protection system is the brain of flexible LFAC transmission, which is directly related to the performance, safety and benefit of LFAC transmission. In order to improve its operation reliability and limit the impact caused by any control link fault, in this paper, the control system is divided into system level control strategy, converter station level control strategy and valve level control strategy, which is from high level to low level according to the stratification principle. For the protection system, a specific zoning protection scheme is proposed. Finally, a two-terminal flexible LFAC transmission system is built in PSCAD/EMTDC. The simulation results prove the validity and correctness of the proposed control and protection strategy.

The hybrid DC system combined with line commutated converter (LCC) and hybrid modular multilevel converter (HY-MMC), which is named LCC-HY-MMC, has technical advantages and economy. Shutdown is a key problem that any DC system needs to face. In order to ensure that the DC system and the sub-module capacitors of HY-MMC can be discharged quickly during shutdown stage, a complete shutdown control strategy is proposed in this paper. From the characteristics of shutdown, it can be basically regarded as three stages: DC energy feedback stage, controllable dissipation stage of sub-module capacitor energy and uncontrollable dissipation stage of sub-module capacitor energy. Finally, based on the 200 MW/ 200 kV digital simulation model built in the electromagnetic transient simulation software PSCAD/EMTDC, the effectiveness of the proposed method is verified.

Magnesium phosphate cement (MPC) cementitious material is a phosphate cement-based material with strength formed by a serious of acid-base neutralization reactions among magnesium oxide, phosphate retarder and water, which has a high early strength and a broad application prospect in the field of pavement rehabilitation. This review collects and organizes the latest progress in the field of research on the influencing factors of mechanical properties of magnesium phosphate cementitious materials worldwide in recent years, and discusses the possibilities of application in airport engineering.The type of phosphate has a great influence on the reaction products, and the strength of the reaction products of ammonium salt is higher. Borax is the most commonly used retarder, and the retarding effect is related to the ratio of boron to magnesium. However, borax retarders have an adverse effect on the strength of MPC. In terms of the influence of mineral admixtures on the properties of MPC, fly ash, silica fume and metakaolin, as common mineral admixtures, have a positive influence on the mechanical properties of MPC, but the mechanism and degree of the influence of the three materials on the strength of MPC are slightly different; Aggregates can also improve the volume stability and mechanical properties of MPC by forming skeleton structure and slowing down the exothermic reaction. In fiber reinforced MPC matrix, steel fiber is the most widely used and the bonding performance between special-shaped steel fiber and MPC matrix is higher than that of straight fiber; basalt fiber has also been proved to be used to improve the mechanical properties of MPC system.

Abstract Background An outbreak of Plasmodium malariae infection among forest goers in Sanya City of Hainan Island, China was reported in 2015. In response to this outbreak, an innovative three-layer strategy (TLS) targeted forest goers was adapted based on the 1-3-7 approach. Main text Key elements of TLS are: (i) The village with five malaria cases and adjacent villages were set as the first layer. All residents including forest goers were taken as the high-risk population (HRP). Active case detection (ACD) by blood smear microscopy and PCR was selected as the primary measure, and passive case detection (PCD) as complementary measure. One case was identified under TLS implementation. (ii) The township with cases (Gaofeng Town) and the nearby towns were chosen as the second layer. Only forest goers were screened by ACD, while PCD as a routine screening method. 7831 blood smears collected by ACD and PCD and tested with negative results. (iii) The city with cases (Sanya City) and others 12 counties/county-level cities were selected as the third layer. Malaria cases were monitored passively. A total of 77,555 blood slides were screened by PCD with zero positive sample. For each layer, the malaria vector mosquitoes were monitored using light traps, cattle-baited/human-bait traps. Anopheles minimus (dominant species), An. sinensis and An. dirus were captured. Vector control measures mainly include insecticide residual spraying and long-lasting insecticide nets. The capacity of clinicians, public health practitioners and laboratory technicians has been improved through training. During 2016‒2018, TLS and chemoprophylaxis were implemented in the same areas. In the first layer, all residents were monitored by ACD, and malaria chemoprophylaxis were distributed, 89.5% of forest goers were using chemoprophylaxis against malaria. The blood smears (3126 by ACD plus 1516 by PCD) were with zero positive results. Chemoprophylaxis and ACD were offered to forest goers once a year, and PCD in residents as a complementary measure in the second and third layer, 77.8% and 95.1% of forest goers received chemoprophylaxis. In each layer, vector surveillance and control of malaria and trainings for medical staff were still in place. Conclusions TLS was effective in blocking the outbreak by P. malariae among forest goers in Hainan in malaria elimination stage. However, whether it could prevent the malaria resurgence in the post-elimination phase needs to be further assessed. Graphical Abstract

During the energization of transformer with high-impedance (HT), the zero-sequence overcurrent protection (ZSOCP) often malfunction with the inrush current of primary winding (iP-inrush) shows a large unbalance. In order to clarify the cause of the misoperation and prepare for a solution, the imbalance characteristic is studied in this paper. The imbalance is visually displayed by dynamic phasor diagram. Through the method of numerical simulation, it can be obtained that the peak value of the zero-sequence current always appears near characteristic opening and switching angles (COSAs). At this time, the two phases are deep saturated and one phase is not saturated. The iP-inrushof the saturated phase is large, and that of the unsaturated phase is numerically the same as the circulating current (iD). According to the parameters characteristics of HT, the iDis small, so iPpresents a large imbalance. The research conclusions provide a theoretical basis for zero-mode inrush current suppression.

Summary: To understand the research status of asphalt pavement texture, the related achievements and progress of pavement surface texture were systematically sorted out from three aspects: the characterization of pavement surface texture, the texture measurement and evaluation, and the relationship between texture and the skid resistance. Based on the statistical geometric characteristics, the spectral characteristics, the fractal characteristics and the multifractal characteristics, the characteristics of pavement texture were discussed. The test methods of pavement texture were divided into two categories: direct measurement methods and indirect measurement methods. The advantages and disadvantages of each measurement method were summarized. The effects of macro-texture and micro-texture on asphalt pavement were discussed, respectively. The relationship between texture and skid resistance was studied. This review shows that multifractal theory should be further studied from the aspect of road engineering. High-precision non-contact integrated detection technology should be further studied to meet the needs of complex testing environments. The method of finite element numerical simulation has potential for the analysis of pavement skid resistance. In addition, methods such as big data analysis, neural network, and deep learning should be studied to achieve the intelligent perception and management of the whole state of skid resistance prediction.

(1) Background: Previous studies suggest that exposure to nitrogen dioxide (NO2) has a negative impact on health. But few studies have explored the association between NO2 and blood lipids or fasting plasma glucose (FPG), as well as gene–air pollution interactions. This study aims to fill this knowledge gap based on a pedigree cohort in southern China. (2) Methods: Employing a pedigree-based design, 1563 individuals from 452 families participated in this study. Serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), and FPG were measured. We investigated the associations between short-term NO2 exposure and lipid profiles or FPG using linear mixed regression models. The genotype–environment interaction (GenoXE) for each trait was estimated using variance component models. (3) Results: NO2 was inversely associated with HDLC but directly associated with TG and FPG. The results showed that each 1 μg/m3 increase in NO2 on day lag0 corresponded to a 1.926% (95%CI: 1.428–2.421%) decrease in HDLC and a 1.400% (95%CI: 0.341–2.470%) increase in FPG. Moreover, we observed a significant genotype–NO2 interaction with HDLC and FPG. (4) Conclusion: This study highlighted the association between NO2 exposure and blood lipid profiles or FPG. Additionally, our investigation suggested the presence of genotype–NO2 interactions in HDLC and FPG, indicating potential loci-specific interaction effects. These findings have the potential to inform and enhance the interpretation of studies that are focused on specific gene–environment interactions.

Background: Tied-arch bridges’ hangers are crucial load-bearing parts, and their excellent condition directly influences bridge safety. However, assessing in-service hangers’ continuing functional performance is irrelevant and incomplete, particularly for unique hangers covered by outer steel tubes. Objective: This research uses a case study of an under-bearing tied-arch bridge with substantial hanger damage to determine the origin of the damage and analyze the hanger’s remaining operational ability. Methodology/approach: This study presents a set of assessment methodologies and procedures for in-service hangers’ remaining functioning performance using field inspection and indoor tests. First, an appearance inspection of the full bridge hanger’s upper and lower anchor heads was carried out, and the categories of anchor head damage and distribution rules are summarized. The causes of major water damage and the lower anchor head’s water infiltration channel were explored. Then, a full interior test was performed on the disassembled sick hanger to establish its present mechanical qualities. Finally, field inspection and indoor test findings assessed the bridge hanger’s operational performance. The findings suggest that the anchor box drainage prevention system should be improved to prevent rainfall and condensation from pooling in the lower anchor box and causing anticorrosive grease failure and anchor head corrosion. Results: The hanger’s mechanical qualities have deteriorated and no longer meet usage standards. Most of the water accumulated in the anchor head of the conventional construction hanger enters from the bridge deck or rope surface, but because of the outer steel pipe, rainwater can flow into the lower anchor box through the upper anchor box along the gap between the hanger and the outer steel pipe, so the waterproof system of the upper anchor box should be checked. Conclusions: This research may be used for safety evaluation and maintenance of the same hanger in service.

For the problem of fault isolation and power flow control in DC grid, this paper proposes a DC power flow controllable multi-port DC circuit breaker. Under the normal operation, this breaker has the function of DC power flow regulation, which is used to regulate the power flow on DC lines. After the DC system fails, this breaker is equivalent to the hybrid DC breaker, which is used to cut off the fault current and isolate the fault line. In the paper, the steady-state power flow regulation mechanism and transient current interrupting mechanism of the breaker are described in detail. Finally, a meshed DC grid is built in PSCAD/ EMTDC simulation platform. The simulation results show that the proposed topology has good performance in power flow control and current interrupting.

Non-small cell lung cancer (NSCLC) has a high morbidity and mortality, and it is imperative to explore the latent pathogenesis mechanism of NSCLC progression to find potential prognostic biomarkers and therapeutic targets. The present study aimed to explore the biological function of circSHKBP1 in NSCLC. circSHKBP1 was found to be upregulated in NSCLC tissues and cell lines and was enriched in exosomes derived from NSCLC cells. Exosomal circSHKBP1 enhanced the proliferation, migration, invasion, and stemness of NSCLC cells. miRNA-1294 was identified as a target for circSHKBP1, and circSHKBP1 upregulated PKM2 expression by sponging miR-1294. Exosomal circSHKBP1 regulated glycolysis through PKM2 in a HIF-1α-dependent manner in NSCLC cells and promoted M2 polarization and macrophage recruitment. Moreover, exosomal circSHKBP1 promoted NSCLC cell growth, metastasis, and M2 infiltration in vivo. Thus, exosomal circSHKBP1 participated in the progression of NSCLC via the miR-1294/PKM2 axis. circSHKBP1 may be potential biomarker for the diagnosis and treatment of NSCLC.