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Objectives: Contacts of patients with infectious tuberculosis (TB) testing positive on interferon-gamma release assay (IGRA) are followed up to exclude active disease. However, identifying factors that predispose IGRA-negative contacts to TB could improve screening and follow-up strategies in a medium TB burden country such as Singapore. Methods: We conducted a retrospective study of IGRA-negative contacts aged ≥2 years identified during contact investigation between January 2014 and December 2022. We examined the risk factors associated with developing active TB among contacts previously testing IGRA-negative, using univariate and multivariable logistic regression and odds ratios with 95% confidence intervals. Results: Of 60,377 IGRA-negative contacts, 150 developed TB disease, and half were notified within 23 months of index patient diagnosis. IGRA-negative contacts of a smear-positive index patient were more likely to develop TB. Independent risk factors for TB were age >50 years, Malay ethnicity, having diabetes or end-stage renal failure, a “family” relationship with the index patient, or exposure in a dormitory or nursing home. Conclusions: Identifying risk factors could help optimise follow-up strategies and preventive treatment in IGRA-negative individuals. The incidence rate of TB in this group was 150 per 100,000 population, substantially higher than in the community, with a median 92 weeks to develop disease. Findings suggest that follow-up should be extended to 24 months for contacts with these risk factors.

ObjectiveThis study aimed to explore the combination effects of prenatal exposure to environment tobacco smoke (ETS) and nutrients supplement during pregnancy on childhood obesity in preschoolers.MethodsA cross-sectional study was conducted with 58,814 child-mother dyads from 235 kindergartens in Longhua District of Shenzhen, China in 2021. A self-administered structured questionnaire was completed by mothers to collect socio-demographic characteristics, prenatal ETS exposure, and nutrients supplement in pregnancy, and preschoolers' heights and weights were measured at the same time. After controlling for potential confounding variables, logistic regression models and cross-analyses were used to examine the independent and combination effects of maternal prenatal ETS exposure and nutrients supplementation during pregnancy on obesity in preschool children.ResultsThe results of our study showed that prenatal ETS exposure increased the risk of childhood obesity (AOR = 1.22, 95% CI = 1.11–1.34) in preschoolers. In addition, risk of childhood obesity was significantly higher when mothers didn't take supplements of multivitamins (AOR = 1.12, 95% CI = 1.05–1.20), folic acid (AOR = 1.23, 95% CI = 1.10–1.37) and iron (AOR = 1.11, 95% CI = 1.04–1.19) during pregnancy. The cross-over analysis showed that the combination of prenatal ETS exposure with mothers taking no multivitamins (AOR = 1.40, 95% CI = 1.21–1.62), no folic acid (AOR = 1.55, 95% CI = 1.12–2.14) and no iron (AOR = 1.38, 95% CI = 1.19–1.59) during pregnancy also increased the risk of obesity among Chinese preschoolers. We also discovered additive interactive effects between prenatal ETS exposure and no maternal multivitamin, folic acid and iron supplementation in pregnancy on the risk of obesity in preschoolers.ConclusionThe combination of prenatal exposure to ETS with no supplementation of these nutrients might jointly increase the risk of childhood obesity. Public health interventions are needed to reduce prenatal exposure to ETS and to encourage mothers to take appropriate multivitamin, folic acid and iron supplements during pregnancy.

A novel goose astrovirus (GAstV) has broken out across China in recent years, causing widespread damage to the poultry industry. In goslings infected with GAstV, the leading cause of death is visceral gout. However, our understanding of the mechanism of gout formation in GAstV infection is largely inadequate. The aim of this study was to examine the pathogenicity of a GAstV strain and explore the molecular mechanisms of visceral gout caused by viral infection in goslings. The virulent GAstV strain HR2105/1 was effectively isolated from the visceral tissue of goslings in gout-affected areas. The whole genome of the HR2105/1 strain was sequenced and analyzed. Subsequently, we established a gosling gout models with experimental GAstV infection. Finally, we conducted a study on the mechanism of GAstV induced acute kidney injury. Phylogenetic analysis of the complete genome sequence showed that it was closely related to the strain circulating in China since 2016, and it was grouped within the GAstV-1 cluster. The clinical signs were reproduced by experimental infection of healthy goslings with the isolated strain and were found to be similar to those reported in clinical cases. Moreover, the virus exhibits strong renal tropism. Infection with the GAstV strain HR2105/1 was found to cause acute kidney injury, as evidenced by increased levels of uric acid and creatinine as well as severe pathological damage. Mechanistic experiments with Masson and Picrosirius Red staining revealed fibrosis in renal tissues after GAstV infection. Furthermore, TUNEL staining revealed that GAstV infection triggered renal cell apoptosis. Additionally, RT-qPCR revealed that GAstV infection caused an excessive inflammatory response by upregulating the expression of IL-1β, IL-6, IL-10, TGF-β, and iNOS in renal tissues. Overall, our findings demonstrate that GAstV infection causes renal damage by inducing renal cell apoptosis, fibrosis, and excessive inflammatory response, which subsequently leads to hyperuricemia and lethal visceral gout formation. This is the first systematic study on the etiology of lethal gout in goslings caused by GAstV infection, and we believe that the findings can guide vaccine development and therapeutic targets for GAstV-associated renal diseases.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by impairments in social interaction, communication, and repetitive behaviors. Emerging evidence suggests that the insulin-like growth factor (IGF) signaling pathway plays a critical role in ASD pathogenesis; however, the precise pathogenic mechanisms remain elusive. This study utilizes multi-omics approaches to investigate the pathogenic mechanisms of ASD susceptibility genes within the IGF pathway. Whole-exome sequencing (WES) revealed a significant enrichment of rare variants in key IGF signaling components, particularly the IGF receptor 1 (IGF1R), in a cohort of Chinese Han individuals diagnosed with ASD, as well as in ASD patients from the SFARI SPARK WES database. Subsequent single-cell RNA sequencing (scRNA-seq) of cortical tissues from children with ASD demonstrated elevated expression of IGF receptors in parvalbumin (PV) interneurons, suggesting a substantial impact on their development. Notably, IGF1R appears to mediate the effects of IGF2R on these neurons. Additionally, transcriptomic analysis of brain organoids derived from ASD patients indicated a significant association between IGF1R and ASD. Protein-protein interaction (PPI) and gene regulatory network (GRN) analyses further identified ASD susceptibility genes that interact with and regulate IGF1R expression. In conclusion, IGF1R emerges as a central node within the IGF signaling pathway, representing a potential common pathogenic mechanism and therapeutic target for ASD. These findings highlight the need for further investigation into the modulation of this pathway as a strategy for ASD intervention.

Solid backfilling scraper conveyor is a key equipment of solid backfilling mining technology, and the degree of its high efficiency and intelligence restricts the development of solid intelligent backfilling mining technology. Currently, it is difficult to break through the bottleneck of high power, super-large mining and high reliability. The operating state is significantly affected by the main controlling factors such as geological conditions and filling process. The problem of autonomous control of abnormal working conditions needs to be solved urgently. The characteristics of solid backfilling scraper conveyor is summarized, and the posture and conveyance state characterization method of solid backfilling scraper conveyor is developed. By analyzing the formation principle of abnormal working conditions, selecting the discriminant index of abnormal working conditions, and combined with the characterization method of posture and conveyance state, the discriminant criteria of abnormal working conditions of the spatial posture and traction state of the scraper conveyor and the adjustment and control path of typical abnormal working conditions are given. The mechanism of conveyance control of solid backfilling scraper conveyor under multi-working conditions is revealed, and the efficient autonomous control method for abnormal working conditions is proposed to real-time control the transportation volume of backfilling materials, the straight line and horizontal extent. The first 260-meter-long solid filling project in China shows that through the autonomous control of abnormal working conditions, for every 100 mm reduction in horizontal offset, the traction is reduced by 85 kN and the transmission power loss is reduced by 55 kW, when the maximum vertical offset is reduced by 100 mm, the conveying power loss can be reduced by 7.2 kW, and for every 100 kN/m reduction in the mass of the cargo per unit length, the traction is reduced by 31.9 kN and the transmission power loss is reduced by 38.2 kW. The proposed autonomous control method of abnormal working conditions can significantly improve the conveying efficiency of solid backfilling scraper conveyor, and can help realize intelligent solid backfilling mining.

[Objective] In order to ensure the stability of important vertical load-bearing components in the process of station construction with PBA (pile-beam-arch) method in loess area, it is necessary to study the stress and deformation mechanism of side piles and middle columns during construction, and put forward measures to control the deformation in the most unfavorable stress stage. [Method] With Hejiaying Station of Xi’an Metro Line 2 as the research background, the methods of numerical simulation and field monitoring are used to study the horizontal displacement, internal force of steel bar, horizontal earth pressure and strain of middle column of side piles during construction. [Result & Conclusion] Construction of buckle arch, excavation of station hall layer and platform layer are the three most unfavorable stages for horizontal displacement of side piles. During the critical stages of construction, steel support should be set up inside the structure and the disturbed stratum should be properly reinforced. During construction of pile beam and buckle arch, the main rebar of side pile bears axial pressure, while during construction of residual earthwork in the station, forces borne by the rebar of side pile back on the soil side gradually change from axial pressure to axial tension. With the increase of buried depth of side pile, the growth of axial tension pressure slows down. In the construction of the initial support of the buckle arch, the earth pressure reaches the maximum value of 34.5 kPa at the buried depth of 6.6 m of the side pile. As the aforementioned depth deepens, the growth rate of the pile side pressure is significant. Therefore, the excavation of the inner side of the station is the key stage to control the earth pressure of the side pile at the earth facing side. If necessary, grouting reinforcement of the soil behind the pile is helpful to improve the bearing capacity of the pile foundation. During the construction of the mid-span arch, the strain of the middle column shows a trend of decreasing first and then increasing.

Background: Renal interstitial fibrosis is the pathophysiological basis of type 2 diabetes mellitus (T2DM). Exercise appears to improve kidney interstitial fibrosis in T2DM, in which silent information regulator factor 2-related enzyme 1 (Sirt1) is a critical regulator. However, the role of Sirt1 in mediating exercise on renal tissue as well as its mechanism remains unknown. Methods: T2DM mouse models were created using a high-fat diet mixed with streptozotocin, followed by 8 weeks of treadmill exercise and niacinamide (Sirt1 inhibitor) intervention. Kits for detecting biochemical indices of renal function were used. The pathological appearance and severity of renal tissue were examined using hematoxylin and eosin, Masson and immunohistochemical staining. The mRNA and protein expression of relevant signaling pathway factors were determined to use real-time reverse transcriptase-polymerase chain reaction and western blotting. Results: T2DM can promote renal interstitial fibrosis, increase kidney index, serum creatinine, blood urea nitrogen and 24 h urinary total protein and cause pathological changes in renal tissue and affect renal function. After 8 weeks of exercise intervention, the biochemical indicators in the kidney of T2DM mice were decreased, Sirt1 expression was increased, the expression of TGF-β1, Smad3, collagen type I (COL1) and collagen type III (COL3) were decreased, and the renal interstitial fibrosis, renal tissue structural lesions and renal function were improved. However, after the nicotinamide intervention, renal interstitial fibrosis of T2DM mice was aggravated, and the improvement effect of exercise on renal interstitial fibrosis of T2DM mice was abolished. Conclusion: The upregulation of Sirt1 expression by exercise can inhibit the transforming growth factor β1/Smad3 pathway, thereby inhibiting the expression and deposition of COL1 and COL3 in renal interstitium, thereby improving renal interstitial fibrosis in T2DM.

In order to improve the anti-friction property of common mineral oil and develop a high-performance lubricant, MoS2 and SiO2 nano-additives were individually dispersed into the 350SN mineral oil at various weight percentages to prepare nanolubricants. Then, the viscosity, wettability, and tribological properties of the nanolubricants were measured and analyzed with a rotary viscometer, a contact angle measuring instrument, and a friction tester. Finally, the action mechanism of two nano-additives was explained based on the energy spectrum test results of the abrasion surface. The results show that MoS2 and SiO2 nano-additives could improve the viscosity of the base fluid and change its wettability, giving nanolubricants better anti-friction performance than the base fluid. Due to the difference in physical properties, SiO2 and MoS2 nanolubricants presented different friction reduction rules with the increase in nano-additive percentage. Under experimental conditions, SiO2 nanolubricants showed better anti-friction effects than MoS2 nanolubricants. When the SiO2 percentage was 10 wt% and 15 wt%, the maximum friction coefficient was reduced to 0.06, which was about 1/3 of that with the base fluid. In this case, the abrasion surface quality was significantly improved, and the abrasion trace size was about half that of the base fluid. The energy spectrum test results show that the action mechanism of the MoS2 nano-additive is the adsorption film effect and mending effect of nanoparticles, while the main action mechanism of the SiO2 nano-additive should be the polishing effect and rolling effect of nanoparticles.

Active front-end converters are part of high power installations for regenerative energy systems, feeding the regenerated energy into the utility. Under the island mode operation of the regenerative energy system, the load characteristics are difficult to detect, and the change of the load characteristics will cause the corresponding resonance. V/f control is usually used to ensure the harmonic quality. At high switching frequency, it has a good control effect. However, high switching frequency causes high switching loss. In order to reduce the switching loss, it will produce more harmonic distortion. Furthermore, the commonly used modulation strategies in this case face the problem of low real-time performance. Therefore, in order to avoid the harm caused by circuit resonance under the condition of reducing the switching frequency, this paper proposes a specific harmonic suppression algorithm with high real-time performance, which can be used as an optional control algorithm in the island operation state of power system. At the same time, aiming at the difficulty of adjusting the weight factors, this paper proposes a weight factor automatic tuner, which automatically adjusts the weight factors according to the harmonic component.

Noise pollution is the most serious environmental pollution, which seriously affects people’s normal life and physical and mental health, as well as normal production work. Therefore, noise control is necessary, but before noise control, the first thing to do is to identify the location of the noise source, and the noise control work is meaningless when the noise cannot be identified. Flat plate structures are a fundamental part of complex ship structures, and their vibration, noise, and their interrelationships when excited by the outside world are receiving increasing attention. The core of the research in this paper is the identification of the sound source of the vibrating plate. A method combining phase conjugation with interior boundary element method is developed for the identification of the pressure and normal velocity distribution of a vibrating plate. An interior problem is formed by enclosing the phase conjugation array plane and the plate surface. The pressures at the array elements are phase-conjugated as the specified pressure boundary condition. The impedance relationship between the surface pressure and the surface normal velocity of the plate is utilized as a specified impedance boundary condition. The interior boundary element method is applied to solve the interior problem. The identification of the surface pressure and normal velocity distribution is studied numerically. The numerical results show that with the array located in the near field the proposed method achieves subwavelength focusing to identify the surface pressure and normal velocity distribution and clearly shows the response shapes.

Middle and low frequency band sound waves have strong penetration and diffraction abilities during the propagation process, making it difficult to attenuate. The control of middle and low frequency broadband sound waves has become a challenging topic. Therefore, it is necessary to develop new materials or structures with middle and low frequency sound absorption, insulation, and noise reduction functions. The special properties of acoustic metamaterial provide new ideas for the development of sound absorption and insulation. In order to effectively control the noise in the lower frequency band, a new spatial spiral acoustic metamaterial was designed. First, the mechanism of band gap characteristics of a new spatial spiral acoustic metamaterial is analyzed. Then, a new spatial spiral acoustic metamaterial is completed through the finite element software COMSOL Multiphysics and the calculation and analysis of sound absorption and insulation performance in the 100–2500 Hz frequency band are completed. With the help of 3D printing, the preparation of metamaterial is completed, and the comparative experimental study of sound absorption and insulation performance of spiral acoustic metamaterial is carried out to verify the accuracy of the calculation method.

The extraction of weak acoustic signals under strong background noise is of great significance in the applications of target identification and localization. In this paper, the pulse signal with high randomness is set as the weak signal sound source, random noise and sine sound are used as the background noise. Under the condition of a signal-to-noise ratio of −20 dB, combined with blind source separation and neural network methods, the collected observation signals are subjected to weak sound signal separation and recognition research. The optimization method of centralization and scaling processing is used to eliminate the unfavorable influence of the uncertainty of the separated signal amplitude caused by the blind source separation method on the pattern recognition. The recognition result is verified by the combination of “weak impulse acoustic signal” and “random noise signal,” and the output vector (0.99 0.01 0.01) approaches (1 0 0), which is recognized as impulse acoustic signal. By combining blind source separation and neural network methods, the separation and identification of weak pulse signals under the condition of a signal-to-noise ratio of −20 dB can be achieved.

BackgroundLiver transplantation (LT) is one of the main curative treatments for hepatocellular carcinoma (HCC). Milan criteria has long been applied to candidate LT patients with HCC. However, the application of Milan criteria failed to precisely predict patients at risk of recurrence. As a result, we aimed to establish and validate a deep learning model comparing with Milan criteria and better guide post-LT treatment.MethodsA total of 356 HCC patients who received LT with complete follow-up data were evaluated. The entire cohort was randomly divided into training set (n = 286) and validation set (n = 70). Multi-layer-perceptron model provided by pycox library was first used to construct the recurrence prediction model. Then tabular neural network (TabNet) that combines elements of deep learning and tabular data processing techniques was utilized to compare with Milan criteria and verify the performance of the model we proposed.ResultsPatients with larger tumor size over 7 cm, poorer differentiation of tumor grade and multiple tumor numbers were first classified as high risk of recurrence. We trained a classification model with TabNet and our proposed model performed better than the Milan criteria in terms of accuracy (0.95 vs. 0.86, p < 0.05). In addition, our model showed better performance results with improved AUC, NRI and hazard ratio, proving the robustness of the model.ConclusionA prognostic model had been proposed based on the use of TabNet on various parameters from HCC patients. The model performed well in post-LT recurrence prediction and the identification of high-risk subgroups.

Abstract Cancer is one of the most life‐threatening diseases worldwide. Numerous diagnostic and therapeutic techniques, such as nanomaterials‐based cancer detection and imaging‐guided focal therapy, are successfully developed to achieve highly precise cancer theranostic strategies. However, due to unpredictive alterations occurring in cancer cell morphology, a lack of sensitivity and selectivity is a critical challenge among most biomarkers’ detection. To address this issue, instead of targeting proteins or biomarkers, the detection of cancer using whole cell‐based biosensors are ubiquitously discovered through a selective oligonucleotide, so‐called aptamer. Aptamer‐based whole‐cell detection is concurrently engaged with various nanomaterials, such as magnetic beads, gold (Au) nanoparticles, and graphene family to establish a better performance of the biosensor. In this research review, the recent strategies and prospects on whole‐cell cancer detection platform based on electrochemical aptasensors integrated with nanomaterials are thoroughly discussed and summarized. Finally, future challenges and prospects are also provided.

The severe vibration of BHA directly affect the drilling efficiency, borehole trajectory, and wellbore quality. Therefore, it is crucial for developing dynamic mechanics of drill string system by studying the mechanical behavior of BHA. In this paper, considering the continuity condition of double-span drill collar, the expression of lateral vibration of drill collars is firstly obtained by using the assumption mode method. Then, the lateral vibration equation of double-span drill collar is derived by Lagrange equation. Finally, a self-programming model is established based on dynamic mechanics of drill string system, the lateral vibration characteristics of double-span drill collar in four different types of BHA is further determined by the fourth-order Runge-Kutta algorithm. It is obviously found that the lateral vibration is enhanced with increasing the length of drill collar; the rotation speed of BHA, weight on bit (WOB), and the size of stabilizer have a significant influence on the lateral vibration of drill collar. In the practical application, the lengths of the first-span and the second-span drill collar are given as 10 and 19 m, respectively; and the stabilizer diameter approached to bit diameter is recommend in practical gas drilling engineering; under WOB of 10–40 kN, the rotation speed of the drilling string should be controlled nearby 60 r/min. The theoretical investigation is a guidance for structure design of BHA and optimization of drilling parameter.

Abstract Background Tumor immunotherapy can not only eliminate the primary lesion, but also produce long-term immune memory, effectively inhibiting tumor metastasis and recurrence. However, immunotherapy also showed plenty of limitations in clinical practice. In recent years, the combination of nanomaterials and immunotherapy has brought new light for completely eliminating tumors with its fabulous anti-tumor effects and negligible side effects. Methods The Core Collection of Web of Science (WOSCC) was used to retrieve and obtain relevant literatures on antitumor nano-immunotherapy since the establishment of the WOSCC. Bibliometrix, VOSviewer, CiteSpace, GraphPad Prism, and Excel were adopted to perform statistical analysis and visualization. The annual output, active institutions, core journals, main authors, keywords, major countries, key documents, and impact factor of the included journals were evaluated. Results A total of 443 related studies were enrolled from 2004 to 2022, and the annual growth rate of articles reached an astonishing 16.85%. The leading countries in terms of number of publications were China and the United States. Journal of Controlled Release, Biomaterials, Acta Biomaterialia, Theranostics, Advanced Materials, and ACS Nano were core journals publishing high-quality literature on the latest advances in the field. Articles focused on dendritic cells and drug delivery accounted for a large percentage in this field. Key words such as regulatory T cells, tumor microenvironment, immune checkpoint blockade, drug delivery, photodynamic therapy, photothermal therapy, tumor-associated macrophages were among the hottest themes with high maturity. Dendritic cells, vaccine, and T cells tend to become the popular and emerging research topics in the future. Conclusions The combined treatment of nanomaterials and antitumor immunotherapy, namely antitumor nano-immunotherapy has been paid increasing attention. Antitumor nano-immunotherapy is undergoing a transition from simple to complex, from phenotype to mechanism. Graphical abstract

Abstract Objective Despite amyloid deposition as a hallmark of hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy, this pathology could not completely account for nerve degeneration. ATTRv patients frequently have vasomotor symptoms, but microangiopathy hypothesis in ATTRv was not systemically clarified. Methods This study examined the vascular pathology of sural nerves in ATTRv patients with transthyretin (TTR) mutation of p.Ala117Ser (TTR‐A97S), focusing on morphometry and patterns of molecular expression in relation to nerve degeneration. We further applied human microvascular endothelial cell (HMEC‐1) culture to examine the direct effect of TTR‐A97S protein on endothelial cells. Results In ATTRv nerves, there was characteristic microangiopathy compared to controls: increased vessel wall thickness and decreased luminal area; both were correlated with the reduction of myelinated fiber density. Among the components of vascular wall, the area of collagen IV in ATTRv nerves was larger than that of controls. This finding was validated in a cell model of HMEC‐1 culture in which the expression of collagen IV was upregulated after exposure to TTR‐A97S. Apoptosis contributed to the endothelial cell degeneration of microvasculatures in ATTRv endoneurium. ATTRv showed prothrombotic status with intravascular fibrin deposition, which was correlated with (1) increased tissue factor and coagulation factor XIIIA and (2) reduced tissue plasminogen activator. This cascade led to intravascular thrombin deposition, which was colocalized with upregulated p‐selectin and thrombomodulin, accompanied by complement deposition and macrophages infiltration, indicating thromboinflammation in ATTRv. Interpretation Microangiopathy with thromboinflammation is characteristic of advanced‐stage ATTRv nerves, which provides an add‐on mechanism and therapeutic target for nerve degeneration.