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The room-and-pillar mined-out area has the characteristics of small recovery rate and large coal pillar, and its overburden movement law and surface deformation law are quite different from those of long-wall mined-out area. In the case of coal pillar failure, the surface will produce large deformation, threatening the safety of surface structures. In order to study the deformation and development mechanism of overlying rock and unconsolidated formation in shallow and gently tilted room-and-pillar mined-out area, based on PIV image processing technology and modular assembly idea, a physical model was established in the laboratory to carry out physical simulation experiments, inversion of the deformation and development process of overlying rock and unconsolidated formation in room-and-pillar mined-out area, and analysis of the deformation mechanism of overlying rock and unconsolidated formation under the condition of room-and-pillar mining and coal pillar instability. The research results show that: ① the overburden deformation of shallow buried and gently mined goaf can be divided into three areas: “banded” deformation area, “trapezoidal” deformation area and “inverted funnel” deformation area. The deformation in the unconsolidated formation is “trapezoidal”. ② Under the instability condition of coal pillar, the overburden deformation law remains unchanged, and the deformation characteristics of unconsolidated formation develop from “trapezoidal” to “funnel”. With the increase of unstable coal pillar, the deformation of unconsolidated formation increases, and the “funnel” deformation area gradually expands from the center to both ends. ③ After the end of room-and-pillar mining, the stress of the goaf roof can be simplified to simply supported beams bearing uniform load. In the case of continuous instability of coal pillar, the static load of overlying rock and unconsolidated formation will lead to the goaf roof reaching the ultimate equilibrium state. The failure mode of the roof is tensile breaking, and cracks are generated under the action of tensile stress, but the roof is not completely broken. The goaf roof forms a cantilever beam structure with cracks. The instability of coal pillar in shallow and gently tilting room-and-pillar mined-out area has a strong influence on the surface deformation, and the deformation of unconsolidated formation and overlying rock are in the same order of magnitude.

BackgroundMetatarsal stress fracture is common in people engaged in repetitive weight-bearing activities, especially athletes and recruits. Identifying risk factors in these contexts is crucial for effective prevention.MethodsA systematic search on Web of Science, PubMed, EBSCO, SPORTDiscus, MEDLINE, and Cochrane Library was conducted and the date range for the retrieval was set from January 1984 to April 2024.Results32 eligible studies were selected from 1,728 related research. Anatomical and biomechanical factors, such as higher foot arch, abnormal inversion/eversion of foot, and longer metatarsal length or larger angles, relatively influence stress fracture risk. However, given that there is no standardized measurement, the results remain to be examined. Soccer is associated with fifth metatarsal fractures, while long-distance running and recruit training often lead to fractures of the second or third metatarsals. High exercise intensity, non-adaptive training, and inadequate equipment heighten fracture risk.ConclusionThis review highlights the complex interplay of anatomical, biomechanical, and sports-related factors in the risk of metatarsal stress fractures. Relatively, high arches, specific metatarsal morphologies, and foot inversion/eversion patterns are significant risk factors, particularly among athletes. Sports type also correlates with metatarsal stress fracture locations. Despite extensive research, study heterogeneity and inherent biases necessitate cautious interpretation. Comprehensive, multifactorial approaches and personalized injury prevention strategies are essential for reducing the incidence of these injuries and improving the health and performance of athletes.

Abstract The advancement of autonomous driving heavily relies on the ability to accurate lane lines detection. As deep learning and computer vision technologies evolve, a variety of deep learning-based methods for lane line detection have been proposed by researchers in the field. However, owing to the simple appearance of lane lines and the lack of distinctive features, it is easy for other objects with similar local appearances to interfere with the process of detecting lane lines. The precision of lane line detection is limited by the unpredictable quantity and diversity of lane lines. To address the aforementioned challenges, we propose a novel deep learning approach for lane line detection. This method leverages the Swin Transformer in conjunction with LaneNet (called ST-LaneNet). The experience results showed that the true positive detection rate can reach 97.53% for easy lanes and 96.83% for difficult lanes (such as scenes with severe occlusion and extreme lighting conditions), which can better accomplish the objective of detecting lane lines. In 1000 detection samples, the average detection accuracy can reach 97.83%, the average inference time per image can reach 17.8 ms, and the average number of frames per second can reach 64.8 Hz. The programming scripts and associated models for this project can be accessed openly at the following GitHub repository: https://github.com/Duane711/Lane-line-detection-ST-LaneNet .

Background: /Aim: Chronic hepatitis B patients often develop concomitant fatty liver disease, which is associated with increased risk of liver cirrhosis and hepatocarcinoma. Our previous studies have shown that apolipoprotein H (APOH) levels are gradually decreased in patients with chronic HBV infection at different stages of disease progression, and APOH deficiency disrupted hepatic lipid metabolism and caused fatty liver. We focus on the relationship between APOH and hepatocellular carcinoma (HCC) in the context of chronic HBV infection. Methods and results: APOH was downregulated at the transcriptional level in HBV-related HCC patients from open-source human liver transcriptome databases, and relatively high expression of APOH might be a favourable prognostic marker in HCC. APOH downregulation was positively associated with tumour grade and HCC subtypes. The analysis result of CHCC-HBV database showed that APOH-associated differential expression genes (DEGs) enriched in lipid metabolic pathways and downregulated APOH correlated with macrophage, neutrophil and CD8 T cell infiltration levels. Next, in vitro experiments were performed and APOH gene was silenced in HepG2.2.15 cells, an HBV producing human HCC cells. Further transcriptomic assay and analysis revealed the DEGs were enriched in cholesterol metabolism. The subsequent RT-qPCR experiments identified that CYP7A1 expression was higher upregulated in APOH silencing HepG2.2.15 cells than vehicle control cells (p

Abstract Under the condition of small roof deformation before the occurrence of fractures and collapse in room and pillar mined-out areas caused by coal pillar instability, the surface deformation may be large, which threatens the safety of ground structures. Interferometric synthetic aperture radar, geophysical exploration, geotechnical exploration and physical simulation tests were conducted to analyse the deformation and development mechanism of the overlying strata in the mined-out area in this case. The results show that in terms of surface deformation, the surface deformation caused by coal pillar instability in the room and pillar mined-out area exhibits the slow deformation stage, uniform deformation stage and accelerated deformation stage. In terms of deformation of overlying strata, after the completion of room and pillar mining, a strip-shaped deformation area and trapezoidal deformation area are developed in the overlying rock. With the occurrence of coal pillar instability, a trapezoidal deformation area and inverted funnel-shaped deformation area are developed in the overlying rock. The deformation characteristics of unconsolidated formations transition from trapezoidal deformation after room and pillar mining to funnel-shaped deformation due to coal pillar instability. Moreover, the maximum surface deformation point is located at the centre of the funnel. In terms of spatial morphology of mined-out area deformation, the maximum surface deformation point corresponds to the position of the initial coal pillar instability and the crack in the mined-out area roof along the vertical direction. The mined-out area treatment method can be optimized based on the deformation characteristics of the overlying strata in the room and pillar mined-out area under the condition of coal pillar instability.

Rheumatoid arthritis is a chronic, systemic autoimmune disease predominantly based on joint lesions with an extremely high disability and deformity rate. Several drugs have been used for the treatment of rheumatoid arthritis, but their use is limited by suboptimal bioavailability, serious adverse effects, and nonnegligible first-pass effects. In contrast, transdermal drug delivery systems (TDDSs) can avoid these drawbacks and improve patient compliance, making them a promising option for the treatment of rheumatoid arthritis (RA). Of course, TDDSs also face unique challenges, as the physiological barrier of the skin makes drug delivery somewhat limited. To overcome this barrier and maximize drug delivery efficiency, TDDSs have evolved in terms of the principle of transdermal facilitation and transdermal facilitation technology, and different generations of TDDSs have been derived, which have significantly improved transdermal efficiency and even achieved individualized controlled drug delivery. In this review, we summarize the different generations of transdermal drug delivery systems, the corresponding transdermal strategies, and their applications in the treatment of RA.

The pathogenesis of inflammatory bowel disease (IBD) is still unknown. Mesenteric lymphatics (MLs), which are closely related to the intestine in both anatomy and physiology, have been suggested to be involved in IBD. In the present study, we aim to investigate the effects of ML immune cells on IBD and explore the potential associated mechanisms. Acute colitis was induced in rats using dextran sulfate sodium salt (DSS). Mesenteric lymphangiogenesis, ML stenosis, and dilation were observed, with an increased proportion of MLB cells in DSS-induced colitis rats. The adoptive transfer of B cells isolated from ML (MLB) was employed to investigate their effects on colitis. MLB cells derived from DSS-induced colitis rats exhibited a higher propensity to migrate to the intestine. The proportion of colonic T cells was altered, along with the aggravated colitis induced by the adoptive transfer of MLB cells derived from DSS-induced colitis rats. RNA sequencing revealed increased Cxcr5 expression in MLB cells from colitis rats, while real-time PCR indicated an upregulation of its ligand Cxcl13 in the colon of colitis rats. These findings suggest that MLB cells may migrate to the intestine and aggravate colitis. In summary, colonic T cells respond to MLB cells from colitis rats, and MLB cells aggravate DSS-induced colitis via the CXCR5–CXCL13 axis.

Apolipoprotein H (APOH) downregulation can cause hepatic steatosis and gut microbiota dysbiosis. However, the mechanism by which APOH-regulated lipid metabolism contributes to metabolic dysfunction–associated steatotic liver disease (MASLD) remains undetermined. Herein, we aim to explore the regulatory effect of APOH, mediated through various pathways, on metabolic homeostasis and MASLD pathogenesis. We analyzed serum marker levels, liver histopathology, and cholesterol metabolism–related gene expression in global ApoH−/− C57BL/6 male mice. We used RNA sequencing and metabolomic techniques to investigate the association between liver metabolism and bacterial composition. Fifty-two differentially expressed genes were identified between ApoH−/− and WT mice. The mRNA levels of de novo lipogenesis genes were highly upregulated in ApoH−/− mice than in WT mice. Fatty acid, glycerophospholipid, sterol lipid, and triglyceride levels were elevated, while hyodeoxycholic acid levels were significantly reduced in the liver tissues of ApoH−/− mice than in those of WT mice. Microbial beta diversity was lower in ApoH−/− mice than in WT mice, and gut microbiota metabolic functions were activated in ApoH−/− mice. Moreover, ApoH transcripts were downregulated in patients with MASLD, and APOH-related differential genes were enriched in lipid metabolism. Open-source transcript-level data from human metabolic dysfunction–associated steatohepatitis livers reinforced a significant association between metabolic dysfunction–associated steatohepatitis and APOH downregulation. In conclusion, our studies demonstrated that APOH downregulation aggravates fatty liver and induces gut microbiota dysbiosis by dysregulating bile acids. Our findings offer a novel perspective on APOH-mediated lipid metabolic dysbiosis and provide a valuable framework for deciphering the role of APOH in fatty liver disease.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to deformities and disabilities in patients. Conventional treatment focuses on delaying progression; therefore, new treatments are necessary. The present study reported a novel ionic liquid transdermal platform for efficient RA treatment, and the underlying mechanism was elucidated using FTIR, 1H-NMR, Raman, XPS, and molecular simulations. The results showed that the reversibility of the semi-ionic hydrogen bonding facilitated high drug loading and enhanced drug permeability. Actarit’s drug loading had an approximately 11.34-times increase. The in vitro permeability of actarit and ketoprofen was improved by 5.46 and 2.39 times, respectively. And they had the same significant effect in vivo. Furthermore, through the integration of network pharmacology, Western blotting (WB), and radiology analyses, the significant osteoprotective effects of SIHDD-PSA (semi-ionic H-bond double-drug pressure-sensitive adhesive transdermal patch) were revealed through the modulation of the JAK-STAT pathway. The SIHDD-PSA significantly reduced paw swelling and inflammation in the rat model, and stimulatory properties evaluation confirmed the safety of SIHDD-PSA. In conclusion, these findings provide a novel approach for the effective treatment of RA, and the semi-ionic hydrogen bonding strategy contributes a new theoretical basis for developing TDDS.

The number of people with eye diseases has increased with the use of electronics. However, the bioavailability of eye drops remains low owing to the presence of the ocular barrier and other reasons. Although many drug delivery systems have been developed to overcome these problems, they have certain limitations. In recent years, the development of contact lenses that can deliver drugs for long periods with high bioavailability and without affecting vision has increased the interest in using contact lenses for drug delivery. Hence, a review of the current state of research on drug delivery contact lenses has become crucial. This article reviews the key physical and chemical properties of drug-laden contact lenses, development and classification of contact lenses, and features of the commonly used materials. A review of the methods commonly used in current research to create contact lenses has also been presented. An overview on how drug-laden contact lenses can overcome the problems of high burst and short release duration has been discussed. Overall, the review focuses on drug delivery methods using smart contact lenses, and predicts the future direction of research on contact lenses.

Abstract Lane detection is one of the key techniques to realize advanced driving assistance and automatic driving. However, lane detection networks based on deep learning have significant shortcomings. The detection results are often unsatisfactory when there are shadows, degraded lane markings, and vehicle occlusion lanes. Therefore, a continuous multi-frame image sequence lane detection network is proposed. Specifically, the continuous six-frame image sequence is input into the network, in which the scene information of each frame image is extracted by an encoder composed of Swin Transformer blocks and input into the PredRNN. Continuous multi-frame of the driving scene is modeled as time-series by ST-LSTM blocks, and then, the shape changes and motion trajectory in the spatiotemporal sequence are effectively modeled. Finally, through the decoder composed of Swin Transformer blocks, the features are obtained and reconstructed to complete the detection task. Extensive experiments on two large-scale datasets demonstrate that the proposed method outperforms the competing methods in lane detection, especially in handling difficult situations. Experiments are carried out based on the TuSimple dataset. The results show: for easy scenes, the validation accuracy is 97.46%, the test accuracy is 97.37%, and the precision is 0.865. For complex scenes, the validation accuracy is 97.38%, the test accuracy is 97.29%, and the precision is 0.859. The running time is 4.4 ms. Experiments are carried out based on the CULane dataset. The results show that, for easy scenes, the validation accuracy is 97.03%, the test accuracy is 96.84%, and the precision is 0.837. For complex scenes, the validation accuracy is 96.18%, the test accuracy is 95.92%, and the precision is 0.829. The running time is 6.5 ms.

Abstract Background Alcohol-related liver disease (ALD) is a major chronic liver ailment caused by alcohol overconsumption and abuse. Apolipoprotein H (APOH) participates in lipid metabolism and might have a potential regulatory role in ALD. Therefore, this study aimed to explore the effects of ApoH on alcohol-induced liver injury and gut microbiota dysbiosis. Methods ApoH −/− mice were generated and the synergic alcoholic steatohepatitis mouse model was constructed, which were used to assess liver function and pathological changes. Results ApoH −/− mice clearly exhibited spontaneous steatohepatitis. Severe hepatic steatosis was observed in alcohol-fed WT and ApoH −/− mice, in which ApoH expression was reduced post alcohol consumption. Moreover, RNA-seq and KEGG pathway analyses indicated that differential expression genes enriched in lipid metabolism and oxidation–reduction process between in alcohol-fed ApoH −/− mice and pair-fed control mice. Finally, gut microbiota diversity and composition were assessed by 16S rRNA Illumina next-generation sequencing. Alpha diversity of enterobacteria was lower in ApoH −/− mice with ethanol feeding than in ethanol-fed WT mice and all control-fed mice (P

Abstract Background At present, surgery is the primary clinical treatment for SCIWORA patients, but conservative treatment still plays an important role in patients with incomplete spinal cord injury. As an important index of cervical spine degeneration, cervical curvature has an impact on the prognosis of spinal cord injury patients. This paper studied the prognosis of conservatively treated patients with SCIWORA and the correlation between cervical curvature and neurological prognosis. Methods A retrospective study was conducted in all the patients with SCI admitted to the Third Affiliated Hospital of Hebei Medical University between January 2017 and June 2020. Data were recorded in 106 eligible patients, including sex, age, injury factors, Cobb angle, CCI, CSA, and ASIA motor and sensory scores. The Wilcoxon sign rank sum test was used to analyze the data postinjury and at the 1-year follow-up. Pearson correlation analysis was performed for the Cobb angle, CCI and CSA. Simple linear regression analysis and multiple linear regression analysis were performed for each group of variables. Results The Wilcoxon signed rank sum test confirmed that the Cobb angle, the CCI and the CSA of the patients were not significantly different at the 1-year follow-up when compared with the postinjury values, and the ASIA motor and sensory scores were significantly improved. The Pearson correlation analysis showed correlations among the Cobb angle, the CCI and the CSA. Simple linear regression analysis and multiple linear regression analysis showed that the nerve recovery rate was negatively correlated with age and was positively correlated with the Cobb angle. Conclusion Conservative treatment of incomplete SCIWORA can achieve a good prognosis. There is a clear correlation between the Cobb angle, CCI and CSA, and the Cobb angle, as an important influencing factor, needs to be considered. For SCIWORA patients undergoing nonsurgical treatment, improving cervical curvature is beneficial to the prognosis of patients. Age negatively affects the neurological prognosis.

Summary: Apolipoprotein H (APOH) is involved in lipid metabolism and functions as an acute-phase protein during hepatitis B virus (HBV) infection. Herein, we explored whether APOH acts on the development of fatty liver upon chronic HBV infection. Serum APOH level was significantly lower in cirrhosis patients than in healthy controls or patients with chronic infection. It showed sex bias, with elevated levels in female patients with chronic infection. Also, serum APOH levels were negatively correlated with HBV surface antigen (HBsAg) but positively correlated with albumin and triglyceride levels. In In vitro HBV infection model, HBV upregulated APOH expression in a non-temporal manner, and HBsAg levels were elevated by silencing APOH. RNA sequencing (RNA-seq) demonstrated bidirectional expression of APOH, which impacted the immunoregulation upon infection or the metabolic regulation in HepG2.2.15 cells. Then, ApoH−/− mice with persistent HBV replication displayed steatohepatitis and gut microbiota dysbiosis with synergistic sex differences. Our study deciphers the roles of APOH in chronic liver diseases.

BackgroundCholangiocarcinoma (CCA) is primary liver cancer originating from the biliary tract. The epidemiology of CCA is diverse across the globe. There are no reliably effective options for systemic therapy and CCA outcomes are poor. Herein, we examined the association between overall survival and clinical characteristics of CCA patients in our region.MethodsWe included 62 CCA cases diagnosed between 2015 and 2019. Demographics, clinical history, therapeutic procedures, and concomitant diseases were abstracted. Patient survival was obtained from a household registration system.ResultsThe cohort was 69% male and 31% female, with 26 (42%) iCCA, 27 (44%) pCCA, and 9 (15%) dCCA. No age differences were observed between the three subtypes. Bile duct and metabolic disorders were the major concomitant diseases and showed varying associations with CCA subgroups. Serum triglycerides (TG) were higher in pCCA and dCCA than iCCA patients (p

Crowded living conditions and increasingly severe noise problems necessitate the development of a low-thickness sound absorption material with remarkable sound absorption performance. Here, simple materials such as sodium alginate aerogel (SA) and polyurethane (PU) foam are used to combine with special 3D spacer fabric to design an innovative highly-efficient acoustic absorber composite (B&M−L composite). It integrates a “backing cavity-like” (BC-L) structure and “filled-microperforated plate-like” (MPP-L) structure. Thereby, it realizes porous and resonant sound absorption at a small thickness. The superior structure design combining strong resonance with porous structure endows the new type of composite with a remarkable absorption performance. Specifically, the peak absorption coefficient is 0.98, the average absorption coefficient at a thickness of 10 mm is 0.71, and the noise reduction coefficient per unit thickness of B&M−L composites exceeds those of most of the reported sound absorption materials. Based on its remarkable acoustic performance, good mechanical properties, heat insulation performance, and thermal stability, the B&M−L composite provides a convenient and inexpensive method to improve the overall performance of porous sound absorption materials, and displays significant potential for use in the fields of construction, transportation, and large mechanical equipment.

Fluorescent materials are used broadly for anti‐counterfeiting, including currency, passports, identity cards, and other secure documents. However, a universal procedure to print fluorescent materials is still missing due to the wide variety of properties found in fluorescent materials. Here, flash nanoprecipitation (FNP) is reported as a universal procedure for fast‐fabricating large‐scale fluorescent nanoparticles to construct cutting‐edge‐level encryption in anti‐counterfeiting, such as full‐color and dual‐mode “codes‐in‐code” large‐format fluorescent patterns. The large‐format fluorescent patterns are printed with a commercial inkjet printer. They exhibitd high concealment and environmental durability for daily use. The security labels of the 2021 Chinese Racing Pigeon Association (CRPA) certificate are then industrially fabricated based on this universal procedure. The monochrome fluorescent pattern is also upgraded into a full‐color fluorescent pattern for evolutionary encryption and anti‐counterfeiting. Finally, a “codes‐in‐code” dual‐mode encryption is realized in the UV bands. The results lead to cutting‐edge and high‐security anti‐counterfeiting technology, which will broaden the use of fluorescent materials in anti‐counterfeiting due to its universality.

Abstract Shikonin is the main component of the traditional Chinese medicine comfrey, which can inhibit the activity of PKM2 by regulating glycolysis and ATP production. Rheumatoid arthritis synovial cells (RA-FLSs) have been reported to increase glycolytic activity and have other similar hallmarks of metabolic activity. In this study, we investigated the effects of shikonin on glycolysis, mitochondrial function, and cell death in RA-FLSs. The results showed that shikonin induced apoptosis and autophagy in RA-FLSs by activating the production of reactive oxygen species (ROS) and inhibiting intracellular ATP levels, glycolysis-related proteins, and the PI3K-AKT-mTOR signaling pathway. Shikonin can significantly reduce the expression of apoptosis-related proteins, paw swelling in rat arthritic tissues, and the levels of inflammatory factors in peripheral blood, such as TNF-α, IL-6, IL-8, IL-10, IL-17A, and IL-1β while showing less toxicity to the liver and kidney.

Conjugated polymers (CPs) are an active research area and have been commonly used in optoelectronic devices, anticounterfeiting, bioimaging, and drug delivery due to their outstanding properties, such as a high quantum yield, photothermal stability, tunable spectra, and good biocompatibility. However, there have only been a few reports regarding flexible lighting due to the insoluble conjugated structure of CPs. Herein, a facile microemulsion method is used to solve the insolubility issue and fabricate CP nanoparticles for flexible lighting and microdeformation monitoring via high‐resolution inkjet printing. These CP nanoparticles are tuned to emit white light (color coordinates are (0.35, 0.35), and the correlated color temperature is 4810 K) by adjusting the CP ratios and polystyrene content. A CP‐based white light‐emitting diode (WLED) with a high color‐rendering index (up to 95) can be fabricated by coating these nanoparticles onto an ultraviolet light‐emitting diode (UVLED). At a driving current of 30 mA, the luminous efficacy of this WLED is 64 lm W−1 for at least 100 h. The resolution of the printing array is ≈40 μm (635 dots in−1), which can be used to detect 2 μm irreversible microdeformation. This approach may broaden the applications of CPs for flexible lighting and microdeformation monitoring.

In order to study the application of nanofluids for enhancing heat transfer in the field of liquid-cooled data centers, a mathematical and physical model of liquid-cooled servers was established in this paper. FC–40 was used as the server cooling liquid base, and simulation studies were conducted on the flow and heat transfer of five types of nanofluid: Cu–FC40, CuO–FC40, Al–FC40, Al2O3–FC40, and TiO2–FC40. The results showed that using Al–FC40 nanofluids as the cooling medium had the best heat transfer effect. Under the same operating conditions, the average Nusselt number Nu and friction resistance coefficient f of five types of nanofluid were analyzed, and the heat transfer state of Al–FC40 nanofluid had the smallest f. Further analysis was conducted on the influence of ‘nanoparticle volume fraction’ α and ‘server inlet flow rate’ u on fluid flow and heat transfer. Our research found that an increase in α and the acceleration of u can effectively reduce the surface temperature of server components. As u increases, Nu gradually increases and f generally decreases, but the amplitude of the increase and decrease becomes smoother.

Abscisic acid (ABA) is an important plant endogenous hormone that participates in the regulation of various physiological processes in plants, including the occurrence and development of somatic embryos, seeddevelopment and dormancy. ABA is called “plant stress resistance factor”, while with the limitation of the rapid metabolic inactivation and photoisomerization inactivation of ABA for its large-scale use. Understanding the function and role of ABA in plants is of great significance to promote its application. For decades, scientists have conducted in-depth research on its mechanism of action and signaling pathways, a series of progress were achieved, and hundreds of ABA analogues (similar in structure or function) have been synthesized to develop highly active plant growth regulators and tools to elucidate ABA perception. In this review, we summarize a variety of ABA analogues, especially the ABA receptor analogues, and explore the mechanisms of ABA action and catabolism, which will facilitate the development of novel ABA analogues with high biological activities.

Abstract Tenofovir and entecavir are currently designated as the preferred oral antiviral drugs for chronic hepatitis B. However, only less than 40% of patients can achieve HBeAg seroconversion. We aim at investigating the role of intestinal microbiome in HBeAg seroconversion induced by oral antiviral therapy and describe multi-omics characteristics of HBeAg seroconversion associated intestinal flora. In this study, we prospectively collected fecal samples at baseline from the patients with HBeAg positive chronic hepatitis B who would have oral antiviral therapy. 16S rDNA sequencing and metabolomics were performed. We identified HBeAg seroconversion-related microbial signature and constructed prediction model for HBeAg seroconversion. Thirty-seven of these subjects achieved HBeAg seroconversion within 156 weeks after the initiation of oral antiviral therapy, while 41 subjects remained HBeAg positive even after over 156 weeks of therapy. A computational statistical and machine learning approach allowed us to identify a microbial signature for HBeAg seroconversion. Using random forest method, we further constructed a classifier based on the microbial signature, with area under curve being 0.749 for the test set. Patients who achieved HBeAg seroconversion tended to have lower abundance of certain fecal metabolites such as essential amino acids, and several dipeptides. By analyzing the fecal microbiota from the patients with and without HBeAg seroconversion, we showed intestinal microbiome play a critical role in HBeAg seroconversion induced by oral antiviral therapy. We also identified intestinal microbial signature that is associated with HBeAg seroconversion after oral antiviral therapy.

Micromotors have gained increasing attention in last two decades, due to their controllable self-propulsion maneuverability at micro scales. However, the effect of particle size on micromotors is still vague and interwoven due to the micromotors’ size, polydisperse distribution, and structural variations. Microfluidic technology is used to clarify the phenomenon, due to its precise micro scale fabrication. Herein, we fabricated a H2O2-driven self-electrophoretic Janus micromotor and systematically explored the effects of particle size on their dynamics, the sputtering distribution, and the rectifying voltages. Their speeds were found to be inversely proportional to their sizes. When the particle size was fixed, their speeds increased as coating thickness increased until its hemisphere was fully coated, and this critical coating thickness was also proportional to the sizes of the micromotors. As further investigation goes on, we noticed that electrical voltage to rectify micromotor was proportional to its size too. To summarize, our results showed that larger micromotors moved more slowly, required a thicker metal coating to reach full speeds, and needed higher voltages to be rectified. Through all of these investigations, we believed that microfluidic technology is a valuable tool, which can systematically probe micromotors dynamics and clarify our understanding of micromotors behaviors.

Flexible electronics can be seamlessly attached to human skin and used for various purposes, such as pulse monitoring, pressure measurement, tensile sensing, and motion detection. Despite their broad applications, most flexible electronics do not possess both high sensitivity and wide detection range simultaneously; their sensitivity drops rapidly when they are subjected to even just medium pressure. In this study, ultrabroad-range, high-sensitivity flexible electronics are fabricated through additive manufacturing to address this issue. The key to possess high sensitivity and a wide detection range simultaneously is to fabricate flexible electronics with large depth-width ratio circuit channels using the additive manufacturing inner-rinsing template method. These electronics exhibit an unprecedented high sensitivity of 320 kPa−1 over the whole detection range, which ranges from 0.3 to 30,000 Pa (five orders of magnitude). Their minimum detectable weight is 0.02 g (the weight of a fly), which is comparable with human skin. They can stretch to over 500% strain without breaking and show no tensile fatigue after 1000 repetitions of stretching to 100% strain. A highly sensitive and flexible electronic epidermal pulse monitor is fabricated to detect multiple physiological signals, such as pulse signal, breathing rhythm, and real-time beat-to-beat cuffless blood pressure. All of these signals can be obtained simultaneously for detailed health detection and monitoring. The fabrication method does not involve complex expensive equipment or complicated operational processes, so it is especially suitable for the fabrication of large-area, complex flexible electronics. We believe this approach will pave the way for the application of flexible electronics in biomedical detection and health monitoring.

Cholangiocarcinoma (CCA) is a malignant hepatic tumor with a poor prognosis, which needs early diagnosis urgently. The gut microbiota has been shown to play a crucial role in the progression of liver cancer. Here, we explored a gut microbiota model covering genera Burkholderia-Caballeronia-Paraburkholderia, Faecalibacterium, and Ruminococcus_1 (B-F-R) for CCA early diagnosis. A case-control study was conducted to enroll 53 CCA patients, 47 cholelithiasis patients, and 40 healthy controls. The feces samples and clinical information of participants were collected in the same period. The gut microbiota and its diversity of individuals were accessed with 16S rDNA sequencing, and the gut microbiota profile was evaluated according to microbiota diversity. Finally, four enriched genera in the CCA group (genera Bacteroides, Muribaculaceae_unclassified, Muribaculum, and Alistipes) and eight enriched genera in the cholelithiasis group (genera Bifidobacterium, Streptococcus, Agathobacter, Ruminococcus_gnavus_group, Faecalibacterium, Subdoligranulum, Collinsella, Escherichia-Shigella) constitute an overall different microbial community composition (P = 0.001). The B-F-R genera model with better diagnostic value than carbohydrate antigen 19-9 (CA19-9) was identified by random forest and Statistical Analysis of Metagenomic Profiles (STAMP) to distinguish CCA patients from healthy controls [area under the curve (AUC) = 0.973, 95% CI = 0.932–1.0]. Moreover, the correlative analysis found that genera Burkholderia-Caballeronia-Paraburkholderia were positively correlated with body mass index (BMI). The significantly different microbiomes between cholelithiasis and CCA were found via principal coordinates analysis (PCoA) and linear discriminant analysis effect size (LEfSe), and Venn diagram and LEfSe were utilized to identify four genera by comparing microbial compositions among patients with malignant obstructive jaundice (MOJ-Y) or not (MOJ-N). In brief, our findings suggest that gut microbiota vary from benign and malignant hepatobiliary diseases to healthy people and provide evidence supporting gut microbiota to be a non-invasive biomarker for the early diagnosis of CCA.

The aim of the present paper is to determine the sex of the individual using three-dimensional geometric and inertial analyses of metatarsal bones. Metatarsals of 60 adult Chinese subjects of both sexes were scanned using Aquilion One 320 Slice CT Scanner. The three-dimensional models of the metatarsals were reconstructed, and thereafter, a novel software using the center of mass set as the origin and the three principal axes of inertia was employed for model alignment. Eight geometric and inertial variables were assessed: the bone length, bone width, bone height, surface-area-to-volume ratio, bone density, and principal moments of inertia around the x, y, and z axes. Furthermore, the discriminant functions were established using stepwise discriminant function analysis. A cross-validation procedure was performed to evaluate the discriminant accuracy of functions. The results indicated that inertial variables exhibit significant sexual dimorphism, especially principal moments of inertia around the z axis. The highest dimorphic values were found in the surface-area-to-volume ratio, principal moments of inertia around the z axis, and bone height. The accuracy rate of the discriminant functions for sex determination ranged from 88.3% to 98.3% (88.3%–98.3% cross-validated). The highest accuracy of function was established based on the third metatarsal bone. This study showed for the first time that the principal moment of inertia of the human bone may be successfully implemented for sex estimation. In conclusion, the sex of the individual can be accurately estimated using a combination of geometric and inertial variables of the metatarsal bones. The accuracy should be further confirmed in a larger sample size and be tested or independently developed for distinct population/age groups before the functions are widely applied in unidentified skeletons in forensic and bioarcheological contexts.

Many diseases are closely related to abnormal concentrations of ascorbic acid (AA), dopamine (DA), and uric acid (UA). Therefore, the detection of these small molecules is significant for monitoring life metabolism and healthy states. Electrochemical detection has been widely used to detect small molecules due to its good selectivity, high sensitivity, and good economics. Fabrication and application are two sides of the coin, and we cannot give up one for the other. Graphene (GN) is a very suitable material for electrochemical sensing due to its excellent catalytic performance and large specific surface area. It possesses many excellent properties but cannot hold itself alone due to its nanoscale thickness. Herein, we have fabricated three-dimensional (3D) GN nanosheets (GNSs) on flexible carbon cloth (CC) by thermal chemical vapor deposition (CVD). The GNSs/CC can successfully detect AA, DA, and UA simultaneously. We find that these GNSs/CC sensors show good performance with 7 h CVD modification. The linear ranges of AA, DA, and UA are 0.02–0.1, 0.0005–0.02, and 0.0005–0.02 mM, respectively. The detection sensitivity rates of AA, DA, and UA are 5,470, 60,500, and 64,000 μA mM−1 cm−2, respectively. Our GNSs/CC flexible sensors can be successfully applied in the human serum for UA detection. The result matches with commercial sensors very well.

The emergence of secondary resistance is the main failure cause of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) as a targeted therapy for non-small cell lung cancer (NSCLC). EGFR mutations of NSCLC cells can markedly increase glutamine transporter (SLC1A5) expression, thereby increasing glutamine metabolism. Glutamine metabolites can activate EGFR downstream signals, including mTOR, ERK1/2, STAT3, etc., which is an important cause for the decreased sensitivity of NSCLC to EGFR-TKIs. CCK8 and Annexin V/PI assays were conducted to detect the effects of Almonertinib and/or V9302 on the proliferation and apoptosis of NSCLC cells. Proteomics was used to determine the effect of Almonertinib on energy metabolism-related proteins in NSCLC. siRNA transfection was performed to study the effect of SLC1A5 down-regulation on cell proliferation. In addition, the effects of drugs on colony formation capacity were determined by colony formation assay. Immunofluorescence and Western blot were utilized to detect the apoptosis- and autophagy-related proteins expression. DAPI staining was utilized to detect the effect of drugs on the nucleus. Transmission electron microscope was used to observe the changes of submicroscopic structure such as autophagosomes and nucleus of cells. mCherry-GFP-LC3B tandem fluorescent protein was to used to detect the level of autophagy flux. Tumor-bearing nude mouse model was utilized to detect the effect of V9302 on the anti-tumor effect of Almonertinib in vivo. As a result, Almonertinib suppressed H1975 and A549 cell proliferation depended on its dosage and treatment duration, and it also induced apoptosis. A549 cells with wild-type EGFR had lower sensitivity to Almonertinib. The expression of SLC1A5 was up-regulated by stimulating with low concentration of Almonertinib in NSCLC cells. SLC1A5 was highly expressed in A549 cells with wild-type EGFR. Glutamine deletion or SLC1A5 inhibition/silencing inhibited the proliferation of NSCLC cells, and decreased cellular glutamine uptake. The combination of SLC1A5 inhibitor V9302 and Almonertinib had a synergistic inhibitory effect on the proliferation of NSCLC. V9302 enhanced the effect of Almonertinib in apoptosis-inducing in NSCLC cells. The combination of V9302 and Almonertinib might induce apoptosis by inhibiting autophagy.

Hallux valgus (HV), the bunion of the first metatarsophalangeal joint (MTPJ), bothers many adults. No consensus has been reached about the causes of HV, be it a hereditary, or acquired, or multifactorial disease. Nor has agreement been reached using MTPJ angle to assess HV based on X-ray because in most cases the assessment of MTPJ is not reliable as it depends on the posture during scanning. In this study, we assume that HV is predominately acquired and that shoe wearing per se is an important player in HV pathogenesis. To verify our hypothesis, a CT-based finite element (FE) model of the first MTPJ of fossil remains of bear-footed Homo naledi was created and compared to that of five contemporary shoe-wearing wrestlers (10 models from two scans at an interval of about 18 months) because Homo naledi's first MTPJ is an ideal model for non-shoe wearing with parallel sesamoid grooves. We developed the first MTPJ structure transformation method and created MTPJ joint capsule model for both Homo naledi and wrestlers. Constraint on the medial side of the first MTPJ capsule was set to simulate shoe-wearing conditions compared to the lack of medial constraint for barefooted conditions. Analysis of eight FE models of different angles for the first MTPJ of Homo naledi was performed by the first MTPJ transformation method and results showed that stress concentrated on the medial capsule of the first MTPJ in simulated shoe-wearing conditions, even at MTPJ angle of 0°. Increase in the first MTPJ angle further increased stress concentration on the medial side, and stress-growth relationship might reveal the causes of HV. We further developed a method to position the first MTPJ in wrestlers and created CT-based models at two time points. It was evident that the first MTPJ angle increased in all but one athlete, with a maximal increase of 4.03 degrees. This verifies our hypothesis that HV might be developed by wearing shoes. Further longitudinal studies with larger sample sizes are needed to additionally validate our results and determine the magnitude of the effects of shoe wearing on development and progression of HV.

Abstract Background Carcinoembryonic antigen (CEA) is a glycoprotein associated with colorectal cancer (CRC). While the functions of its gene and protein have been fully characterized, its post-translational modifications in the context of CRC development remain undefined. Methods To show the correlation between the different stages of CRC development and changes in the glycosylation patterns of CEA, we analyzed CEA in tumor tissues (CEA-T) and paired tumor-adjacent normal tissues (CEA-A) from 53 colorectal cancer patients using a high-density lectin microarray containing 56 plant lectins. Results We detected higher expression levels of fucose, mannose and Thomsen–Friedenreich antigen, and lower expression levels of N-acetylgalactosamine, N-acetylglucosamine, galactose, branched and bisecting N-glycans on CEA in the tumor tissues relative to the tumor-adjacent normal tissues. Furthermore, a combinatorial assessment of 9 lectins is sufficient to distinguish CRC tumor tissues from tumor-adjacent normal tissues with 83% sensitivity and ~ 90% specificity. Moreover, the levels of N-acetylgalactosamine, mannose, galactose, N-acetylglucosamine on CEA showed a downward trend after first experiencing an increase at Stage II with the stages of CRC. Conclusions Our insights into the changing CEA glycosylation patterns and their role in the development of CRC highlight the importance of glycan variants on CEA for early clinical detection and staging of CRC.

Based on the latest seismic, logging and reservoir reserve data, through hydrocarbon accumulation elements analysis, the play of Putomayo-Oriente-Maranon (POM) basin, South America is divided. The POM basin was divided into 9 plays, and the undiscovered petroleum resources of these plays are estimated as 11.0×108t by using subjective probability method and scale sequential method; and the total undiscovered petroleum resources of the Hollin sandstone play, Napo T member sandstone play, Napo U member sandstone play and Napo M1 member sandstone play are 10.4×108t (accounting for 94% of the whole basin). Based on hydrocarbon accumulation factors analysis, including source rock, reservoir, trap, migration, seal and preservation, the plays have been evaluated and ranked by using double factors method of resources-geological risks, including four class I plays, two class II and three class III plays. Favorable exploration areas have been optimized by using “play area overlaying” method: the central part of the basin is the class I favorable area. Key words: South America, Putomayo-Oriente-Maranon basin, play, resources evaluation, favorable exploration area

Introduction: There is much controversy about the optimal application of tranexamic acid (TXA) in total knee arthroplasty (TKA). The purpose of this meta-analysis was to compare the efficacy of the intra-articular and intravenous regimens of TXA in TKA. Material and methods : A literature search of the PubMed, Embase and Cochrane Library databases was performed. Randomized controlled trials comparing the result of intra-articular and intravenous application of TXA during TKA were included. The focus was on the outcomes of blood loss, transfusion requirement and thromboembolic complications. Results: Six studies were eligible for data extraction and meta-analysis. We found no statistically significant difference between intra-articular and intravenous administration of tranexamic acid in terms of total blood loss (WMD, 6.01; 95% CI: –96.78 to 108.79; p = 0.91), drain output (WMD = –20.26; 95% CI: –51.34 to 10.82; p = 0.20), hemoglobin drop (WMD = 0.33; 95% CI: –0.31 to 0.98; p = 0.31), or the incidences of transfusion (RR = 0.98; 95% CI: 0.56–1.70; p = 0.93) as well as deep vein thrombosis (RR = 0.49; 95% CI: 0.09–2.73; p = 0.42). Conclusions : In comparison with intravenous application of TXA, intra-articular application had a comparable effect on reducing blood loss and the transfusion rate without increasing the complication rate.

An optical fiber Fabry-Pérot interferometer (FPI) based on an air cavity with a microchannel is proposed and demonstrated for gas pressure measurement. The inner air cavity is fabricated by fusion splicing a single-mode fiber (SMF) with a microhole at the end facet to another section of SMF, then creating a microchannel to vertically cross the air cavity to allow gas to flow in. As the air cavity is cascaded to a short section of SMF, a three-beam interference pattern is produced, which shifts with the gas pressure variation in the inner air cavity due to the refractive index change of the gas. In order to compensate the temperature effect, the multiple-dip tracing technique and the Fourier band pass filtering (FBPF) method are used simultaneously for gas pressure and temperature measurement. It is also found that by using the FBPF method, the gas pressure sensitivity does not depend on the resonant peaks/dips selected in the filtered spectrum of the device. The proposed device has a robust tip structure, miniature size, and high sensitivity (~4.028 nm/MPa) and is easy to fabricate, which makes it attractive for highly sensitive and precise gas pressure measurement.

The aim of the present study was to develop a new method to reconstruct damaged metatarsophalangeal joint (MTPJ) of Homo naledi's fossil and to deepen the understanding of the first metatarsal head (FMH) morphological adaptation in different gait patterns. To this purpose three methods were introduced. The first served to compare the anthropometric linear and volumetric measurements of Homo naledi's MTPJ to that of 10 various athletes. The second was employed to measure curvature diameter in FMH's medial and lateral grooves for sesamoid bones. The third was used to determine the parallelism between medial and lateral FMH grooves. The anthropometric measurements of middle-distance runner to the greatest extent mimicked that of Homo naledi. Thus, it was used to successfully reconstruct the damaged Homo naledi's MTPJ. The highest curvature diameter of medial FMH groove was found in Homo naledi, while in lateral FMH groove it was the highest in volleyball player, suggesting their increased bear loading. The parallelism of medial and lateral FMH grooves was observed only in Homo naledi, while in investigated athletes it was dis-parallel. Athletes' dis-paralleled structures make first MTPJ simple flexion movement a complicated one: not rotating about one axis, but about many, which may result in bringing a negative effect on running. In conclusion, the presented method for the reconstruction of the damaged foot bone paves the way for morphological and structural analysis of modern population and fossil hominins' gait pattern.

The finite element method is playing an increasingly important role in osteoporosis screening. An accurate bone geometric model, a prerequisite for the finite element analysis, is affected by voxels. Isotropic voxel has advantages in three-dimensional reconstruction, but field of view setting usually results in anisotropic voxels. The main goal of this study was to investigate the influence of anisotropic voxel on the accuracy of three-dimensional reconstruction of bone geometric models. Sixty metatarsal bones were scanned twice with an interval of 18 months with different fields of view. We reconstructed these metatarsals and compared them. The results showed that there was no significant difference in volume, surface, length, width and height and two principal moments of inertia, indicating that anisotropic voxel caused by field of view setting has a neglectable effect on the three-dimensional reconstruction of bone geometric models, and that using finite element method based on bone geometric model reconstructed by anisotropic voxel to predict bone strength is reliable.

Abstract: Aimed at the small size, large quantity of traps and high environmental requirements of resource countries on slope belt of South America foreland basins, a new evaluation method is proposed for trap exploration on slope by taking the area controlled by a cluster platform as one evaluation unit. The evaluation process is: (1) trap geological risk analysis: including key oil & gas accumulation element analysis such as source, reservoir, seal, trap, migration and preservation; (2) trap resources calculation: including trap resources calculated with volumetric method, trap accumulation probability evaluation by geological risk analysis, and finally the risk trap resources by multiplying the above two values; (3) platform and drilling target selection: count the total risk trap resources and average risk trap resource of different platform and rank the drilling platforms according to the calculated resources; and rank the trap drilling sequence according to the risk trap resources. The method was used in ranking undrilled traps in the M1 layer of Block X, Oriente Basin, and the platform construction and trap drilling order was recommended accordingly which shows good results in practice. Key words: foreland basin, slope, trap evaluation, Oriente Basin, cluster platform, evaluation method

Based on special exploitation mode of heavy oil-oil sand, this paper established a recoverable reserves calculation method for heavy oil-oil sand. First, calculate recoverable reserves of single exploitation mode according to oil layer selection criterion including four parameters of buried depth, single layer thickness, porosity and oil saturation for different exploitation models. Second, calculate recoverable reserves for different exploitation model combination and the max recoverable reserves of the block; Last, set up heavy oil-oil sand recoverable reserves database. The method has great correlation with PRMS reserves evaluation system. The method has been used in the heavy oil classification evaluation for larger M of the J block in Venezuela heavy oil belt, the recoverable reserves are 4.06×108 t, 15.23×108 t and 7.40×108 t respectively by cold production, steam drive and steam-assisted gravity drainage, and the max recoverable reserves are 15.97×108 t, which provides reserves basement for block development. Key words: heavy oil, oil sand, reserves classification, exploitation mode, recoverable reserves

Based on the CT scanned images, a realistic geometric model from nasal cavity to upper six-generation bronchia is rebuilt. In order to effectively simulate the particle movement and deposition, LES model is used and the particles are tracked in the frame of Lagrange. Seven kinds of typical particles, including micron particles (1, 5, and 10 μm) and nanoparticles (1, 5, 20, and 100 nm), and three representative respiratory intensities are adopted as computational case, respectively. Deposition efficiency ( D E ), deposition concentration ( D C ), and capture efficiency ( C E ) are introduced. Furthermore, the locations of particle deposition are visualized. The results indicate that the injecting particles from different nasal inlet present “transposition effect.”The D E values of micron particles are much higher than nanoparticles. The particle diameter plays a weaker role in nanoparticle depositions than micron particles. The highest values of D E and D C both occur in nasal cavity, while the highest C E up to 99.5% occurs in bronchus region.

Direct numerical simulation method is used to investigate the small scale ( d p < η/10) turbulence modulation for a spatially evolving free round jet. Because the turbulence modulation phenomena can not be accurately measured by experimental method, the turbulence modulations are poorly understood. The particle diameter in our simulation is smaller than the Kolmogorov length scale η ( d p < η/10), and the point force method can be accurately used for the research of small scale turbulence modulation based strictly on the theory of point force method. The simulation uses an explicit coupling scheme between particles and the fluid, which considers two-way coupling between the particle and the fluid. The DNS results are compared with experimental data with equal Reynolds number (Re = 1700). The particles modulation on the fluid turbulence properties and coherent vortex structures are quantitatively given in our paper, and some new findings on the particles modulation are explicitly explained in this paper, which will further refine our understanding of intricate mechanism of small scale ( d p < η/10) turbulence modulation for a spatially evolving free round jet.