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Abstract When the solar wind interacts with the ionosphere of an unmagnetized planet, it induces currents that form an induced magnetosphere. These currents and their associated magnetic fields play a pivotal role in controlling the movement of charged particles, which is essential for understanding the escape of planetary ions. Unlike the well-documented magnetospheric current systems, the ionospheric current systems driven by solar wind and atmospheric neutral winds have not been quantitatively observed, which constrains the quantification of energy transfer from stars to these planets. Here, utilizing eight years of data from the Mars Atmosphere and Volatile EvolutioN (MAVEN) mission, we investigate the global distribution of ionospheric currents on Mars. We identify two distinct current systems in the ionosphere: one aligns with the solar wind electric field but exhibits hemispheric asymmetry perpendicular to the solar wind electric field direction; the other corresponds to the flow pattern of annually averaged neutral winds. We propose that these two current systems are driven by the solar wind and atmospheric neutral winds, respectively. Our findings reveal that Martian ionospheric dynamics are influenced by the neutral winds from below and the solar wind from above, highlighting the complex and intriguing nature of current systems on unmagnetized planets.

Abstract The accurate monitoring of vital physiological parameters, exemplified by heart rate, respiratory rate, and intracranial pressure (ICP), is of paramount importance, particularly for managing severe cranial injuries. Despite the rapid development of implantable ICP sensing systems over the past decades, they still suffer from, for example, wire connection, low sensitivity, poor resolution, and the inability to monitor multiple variables simultaneously. Here, we propose an ultrasensitive multimodal biotelemetric system that amalgamates an iontronic pressure transducer with exceptional point (EP) operation for the monitoring of ICP signals. The proposed system can exhibit extraordinary performance regarding the detection of minuscule ICP fluctuation, demonstrated by the sensitivity of 115.95 kHz/mmHg and the sensing resolution down to 0.003 mmHg. Our system excels not only in the accurate quantification of ICP levels but also in distinguishing respiration and cardiac activities from ICP signals, thereby achieving the multimodal monitoring of ICP, respiratory, and heart rates within a single system. Our work may provide a pragmatic avenue for the real-time wireless monitoring of ICP and thus hold great potential to be extended to the monitoring of other vital physiological indicators.

Abstract Osteoporosis is a major degenerative metabolic bone disease that threatens the life and health of postmenopausal women. Owing to limitations in detection methods and prevention strategy awareness, the purpose of osteoporosis treatment is more to delay further deterioration rather than to fundamentally correct bone mass. We aimed to clarify the pathogenesis of postmenopausal osteoporosis and optimize treatment plans. Our experiments were based on previous findings that oxidative stress mediates bone metabolism imbalance after oestrogen deficiency. Through energy metabolism-targeted metabolomics, we revealed that purine metabolism disorder is the main mechanism involved in inducing oxidative damage in bone tissue, which was verified via the use of machine-learning data from human databases. Xanthine and xanthine oxidase were used to treat osteoblasts to construct a purine metabolism disorder model. The activity and differentiation ability of osteoblasts decreased after X/XO treatment. Transcriptomic sequencing indicated that autophagic flux damage was involved in purine metabolism-induced oxidative stress in osteoblasts. Additionally, we performed serum metabolomics combined with network pharmacology to determine the pharmacological mechanism of metformin in the treatment of postmenopausal osteoporosis. HPRT1 was the potential target filtered from the hub genes, and FoxO1 signalling was the key pathway mediating the effect of metformin in osteoblasts. We also revealed that SIRT3-mediated deacetylation promoted the nuclear localization of FoxO1 to increase the expression of HPRT1. HPRT1 upregulation promoted purine anabolism and prevented the accumulation of ROS caused by purine catabolism to reverse oxidative damage in osteoblasts. We propose that purine metabolism disorder-induced oxidative stress is important for the pathogenesis of postmenopausal osteoporosis. The therapeutic mechanism of metformin should be confirmed through subsequent drug optimization and development studies to improve bone health in postmenopausal women.

The difficulty in grain refinement during the casting of superalloy turbine guides is the primary factor of their low percent of pass. This study innovatively employs the electromagnetic oscillation (EMO) process during pouring and solidification using self-developed device to break through this problem. The effect of various process parameters on blade microstructure is also investigated. The result shows that implementing 300 A/20 Hz optimal EMO process produces uniformly fine equiaxed grains, reducing average grain sizes by 71.83% at the blade concave and 75.80% at the inlet edge. Yield and tensile strength increased by 22.34% and 27.15%, respectively, reaching a tensile strength of 1208.09 MPa. Elongation and section shrinkage also increased by 69.67% and 19.57%, respectively. The forced oscillation of melt caused by alternating magnetic field flushes and fragments dendrites, creating numerous nucleation sites, thus promoting grain refinement. The current intensity is linearly correlated with the electromagnetic force within the melt, influencing consequent oscillation effects. The optimal electromagnetic oscillation penetration depth, calculated at 42 mm, is determined by the number of oscillations and skin effect. This depth, calculated based on the inherent properties of the alloy, is instrumental in ascertaining the optimum current frequency for this model of turbine guides, applicable across different alloy compositions. The tensile deformation behavior of castings is altered by the grain refinement induced by the EMO process, enhancing tensile properties through the promotion of more homogeneous deformation and the inhibition effect of grain boundaries and one-dimensional defects on dislocations.

In order to understand the long-term evolution of meteorological drought in Chongqing， the localized revised meteorological drought comprehensive index （RMCI） of 34 national stations in Chongqing from 1960 to 2022 was used in conjunction with local standard for regional meteorological drought process evaluation to synchronously compare with the meteorological drought comprehensive index （MCI） process data from 1981 to 2020， then analysed the data structure and spatiotemporal distribution characteristics of the historical 63 a RMCI.The conclusion was as follows： （1） The cumulative frequency of the 40a RMCI single station process in Chongqing was 4.2% higher than that of MCI， and the frequency-intensity fitting of both showed a significant exponential distribution.The difference rate in the start time between RMCI and MCI single station processes was only 8.1%.The northeast of Chongqing was a consistently high incidence district of drought at all levels for RMCI and MCI single station processes， while the frequencies were relatively low in the central urban area， southwest， and middle districts.（2） The daily data of Chongqing's 63 a RMCI showed a normal distribution overall， with small（significant） differences in the distribution of mild， moderate， and severe drought（extreme drought） daily data across whole region and various districts.The daily data of RMCI severe and extreme drought in the central urban area was consistently relatively high and low compared to other districts， respectively.The frequency-intensity of RMCI single station process and regional process data were significantly inversely correlated， with the station-averaged frequency of mild， moderate， and extreme droughts for single station processes occurring in the western district of Chongqing being the highest， and the absolute range of extreme drought in regional process data was the highest， followed by moderate drought.（3） The intensity trends of RMCI single station and regional meteorological drought processes in Chongqing during the 63 a were not significant， but both showed a significant decreasing trend from 1962 to 2013.The overall weakening of both processes intensity in Chongqing after 2013 was related to the interdecadal decrease in high-temperature days since the 21st century.It could be considered that meteorological drought process events had complex interannual and interdecadal signals.The RMCI single station process events mainly exhibited periodic oscillations of 2~6 a and quasi-20 a， with the "drying out" of single station process events occurring in parts of Chongqing northeastern and southeastern districts being particularly significant.The RMCI regional process events exhibited periodic oscillations of 2~3 a， 4~6 a， and 8~12 a， with the highest frequency and strongest intensity of regional process events starting during the hot summer drought period and July， while the frequency and intensity of autumn drought period and December was relatively lowest and weakest， respectively.

Abstract Background Since 2022, Norway has employed a vaccine-only COVID-19 strategy. Primary healthcare in Norway uses International Classification of Primary Care version 2 (ICPC-2) codes. This study aims to systematically compare medically certified sick leave and primary healthcare consultations in 2023 with the pre-pandemic 2010–2019 trends, and subsequently estimate the magnitude of these changes. Methods For the respective outcomes of (A) working person-years lost to medically certified sick leave (WYLSL) and (B) number of primary healthcare consultations, 556 and 85 ICPC-2 code combinations were extracted from the Norwegian Labour and Welfare Administration’s sick leave registry and the Norwegian Syndromic Surveillance System. For each ICPC-2 code combination, a Bayesian linear regression was performed using data between 2010 and 2019 to estimate an expected baseline for 2023, which was then used to calculate the deviation from the pre-pandemic trend. A false discovery rate of 5% was used to account for multiple testing. Results All years from 2020 to 2023 had excess WYLSL, corresponding to 14,491 (90% PI: 8,935 to 20,016) in 2020, 12,911 (90% PI: 5,916 to 19,996) in 2021, 21,263 (90% PI: 12,627 to 29,864) in 2022, and 24,466 (90% PI: 14,023 to 34,705) in 2023. This corresponded to an economic loss of approximately 1.5 billion USD in 2023. Excess WYLSL due to A* (General and unspecified) increased from 2020 to 2023, with an estimated excess of 4,136 WYLSL in 2023 (69% higher than expected). More than half of this increase was explained by A04 (Weakness/tiredness general), whose excess WYLSL in 2023 were estimated at 2,640 (80% higher than expected). The excess in A04 (Weakness/tiredness general) corresponded to an economic loss of 161 million USD and accounted for 11% of the total excess WYLSL in 2023. The excess WYLSL in R* (Respiratory) in 2023 was 3,408, which correspond to an economic loss of 207 million USD and accounted for 14% of the total excess in 2023. Conclusions Significant excesses in working person-years lost to medically certified sick leave and primary healthcare consultations in 2023. A sizable proportion of the excesses were due to diseases/symptoms associated with acute and post-acute sequelae of COVID-19.

Abstract Aims To investigate the fundus characteristics and macular optical coherence tomography angiography (OCTA) metrics in patients with myelinated retinal nerve fibers (MRNF) and to identify the associations among myopic parameters, fundus metrics, and OCTA metrics. Methods The single-center case-control study included 15 patients with monocular MRNF and 15 patients without MRNF, matched for age, affected eyes’ spherical equivalent error (SER), and axial length (AL) between May 2021 and December 2021. Fundus features, including the entire MRNF area (Area1), the denser MRNF area (Area2), and the shortest distance from the fovea to the MRNF border (Df−m), along with ocular parameters, including SER, AL, best corrected visual acuity (BCVA), and OCTA metrics at the fovea, including choroidal (ChT) and retinal (ReT) thicknesses at the fovea, the foveal avascular zone area (FAZ), foveal avascular zone perimeter (FAZP), FAZ-circularity index (FAZ-CI), and foveal vessel density in a 300-µm wide region (FD-300), were assessed. Results The SER, AL, and BCVA were significantly different, and the ChT was thinner in the affected eyes than in the contralateral eyes. Compared with matched eyes, affected eyes had reduced BCVA and thinner ReT. In the affected eyes, both Area1 and Area2 were negatively correlated with SER (r 1 = -0.84, r 2 = -0.65), △SER (r 1 = -0.86, r 2 = -0.61), ReT at the vertical superior 3 mm (VS) (r 1 = -0.78, r 2 = -0.67), and ChT_VS (r 1 = -0.64, r 2 = -0.62), and positively correlated with AL (r 1 = 0.82, r 2 = 0.52) and BCVA (r 1 = 0.54, r 2 = 0.59). Df−m was negatively correlated with BCVA (r = -0.57). Conclusion The presence of MRNF affects BCVA and ReT at the fovea. The area of the MRNF, as well as the distance from the MRNF to the fovea, are closely associated with the affected eyes’ BCVA, SER, AL, and the degree of anisometropia.

Abstract With the rapid advancement of digital games, serious games have emerged as a significant medium for engaging with cultural heritage. As a primary visual element in cultural heritage, color plays a crucial role in users’ digital learning. However, there is currently a scarcity of serious game designs that specifically focus on cultural heritage colors, indicating potential for improvement in the user experience. To further enhance users’ perception of color and create a more engaging and enriching digital cultural heritage experience, this study proposes a virtual reality serious game (VR SG) design method specifically tailored to cultural heritage colors. Additionally, it explores the potential of VR SG in enhancing the education, entertainment, and dissemination aspects of these colors within cultural heritage. Specifically, we explore how to integrate relevant knowledge of cultural heritage colors into the application process of VR SG and assess users’ learning performance, engagement, and interactive willingness within these VR SG. The study employs the colors of the Dunhuang cave frescoes as a case study for design practice. A total of 30 participants took part in a between-group comparison experiment, utilizing a mixed-methods approach that combined quantitative and qualitative assessments to compare the performance of a VR SG with a VR exhibition game. The results indicate that both the VR SG and the VR exhibition game effectively enhance users’ understanding and retention of knowledge, with VR SG users demonstrating higher levels of task engagement, emotional engagement, willingness to explore, and willingness to share. This study confirms the potential of VR SG to enhance the education, entertainment, and dissemination aspects of cultural heritage colors and discusses the implications of VR SG in supporting digital cultural heritage experiences.

The stratification phenomenon resulting from differences in the physical properties of solid‒liquid components seriously affect the final combustion and explosion characteristics of mixed fuel under the action of oscillation. The effects of oscillation on the physical stability of mixed fuel with two solid‒liquid ratios and three liquid component distribution ratios have been investigated using a self-designed experimental system at oscillation frequencies of 60–300 r/min. The explosion characteristics of mixed fuel before and after oscillation are gained from a 20 L spherical explosion container system. When the mass ratio of liquid components is controlled at 66.9%, 64.7%, 62.6% the final explosion characteristics are stable, with a maximum difference of only 0.71%. The volume of liquid fuel precipitation increases with increasing oscillation frequency when the mass ratio of liquid components reaches 71.7%, 69.6%, 67.7%. The fuel explosion overpressure after oscillation decreases with increasing liquid precipitation volume, and the repeatability is poor, with a maximum standard deviation of 82.736, which is much higher than the ratio without stratification. Properly controlling the mass ratio of liquid components of the mixed fuel can effectively combat the impact of oscillation on the physical state and maintain the stability of the final explosion characteristics.

Abstract Understanding the distribution of cutting force provides a foundation for the design and optimization of cutterhead layout. The simulation of rotary cutting with a large cutting radius remains a challenge for laboratory tests. In this study, taking the driving condition of the Mawan Tunnel located in the Guangdong-Hong Kong-Macao Greater Bay Area as a case study, a full-scale rotary cutting platform with large cutting radius was used to investigate the rock-breaking effects. Rotary cutting with cutting depths of 1–8 mm and cutting radii of 200–1400 mm were carried out on the granite testing platform using a 19-in disc cutter. The normal force, rolling force, and side force during the cutting process were systematically monitored. Moreover, the time–frequency characteristics of the rock breaking process and the effects of cutting depth, cutting radius and stress state on the average and peak loads were investigated. The results show that the average normal force and rolling force increased with increasing cutting depth, while the side force was less affected by cutting depth through the Boltzman model analysis. The average normal force and rolling force were not significantly affected by the cutting radius, but the average side force decreased as a power function with increasing cutting radius, and showed a stable side force when the installation radius exceeded 1000 mm. The dominant frequency of the cutting force was 0–1.2 Hz, exhibiting notable low-frequency characteristics. Additionally, the ratio of peak to average (RPA) with respect to triaxial cutting force demonstrated an increase with the growth of cutting depth, while RPA in terms of side force exhibited a corresponding growth with the increasing cutting radius. In particular, the cutting force characteristics of the cutterhead obtained in this study can inform the layout of disc cutters and real-life TBM operations, thereby avoiding severe overloading of internal disc cutters.

Abstract Background This study explored the significance of consolidation maintenance chemotherapy after concurrent chemoradiotherapy with different regimens in patients with esophageal squamous cell carcinoma. Method A prospective randomized controlled phase III clinical trial was designed and registered in the China Clinical Trials Registry (Registration number: ChiCTR‐TRC‐12002719). Survival data were analyzed in terms of intention‐to‐treat (ITT) and per‐protocol (PP) sets for patients undergoing cisplatin and 5‐fluorouracil (PF) (group A), or cisplatin and paclitaxel (TP) (group B). Results The incidence risk of grade III–IV leukopenia in group B was higher than in group A (49.2% vs. 25.5%, p = 0.012). The survival rates at 1, 2, 3, and 5 years were 83.8%, 62.6%, 53.1%, and 41.3%, respectively. Consolidation chemotherapy after concurrent chemoradiation therapy had no benefit on median progression‐free survival (PFS) (p = 0.95) and overall survival (OS) (p = 0.809). According to the ITT analysis, the median PFS in group A and group B was 28.6 months and 30.3 months (X2 = 0.242, p = 0.623), while the median OS was 31.0 months and 50.3 months (X2 = 1.25，p = 0.263). For the PP analysis, the median PFS in group A and group B were 28.6 months and 30.3 months (p = 0.584), while the median OS was 31.0 months and 50.3 months (p = 0.259), respectively. Patients receiving consolidation chemotherapy did not show significant OS benefits (46.9 months vs. 38.3 months; X2 = 0.059, p = 0.866). Conclusion Similar PFS and OS were found between PF and TP regimens with concurrent chemoradiotherapy. Consolidation chemotherapy did not show any significant OS benefits.

Shipwreck salvage is a risky, time-consuming, and expensive process. Although there are many sunken ships along coastlines and in the open seas, the salvage process of a sunken ship has rarely been reported. The integrated salvage of the “Yangtze River Estuary II” shipwreck used a novel method with 22 closely locked curved rectangular pipes to form a watertight base that wrapped the shipwreck inside. The basing was lifted out of the water using a powerful crane situated on an engineering ship. For the first time, the tunneling method was used in a shipwreck salvage project, significantly reducing the disturbance to the shipwreck and its stowage, thereby preserving the original state and integrity of the shipwreck to the greatest extent. In this study, the basic concepts of the salvage method and process are explained. Solutions to critical issues in the new salvage method are provided, including jacking force prediction and major considerations for the structural design of the salvage system. The design of the salvage system and salvage process of the “Yangtze River Estuary II” shipwreck are introduced. The monitored jacking force, pipe deformation, and observed water-tightness verified that the proposed method was effective and efficient. Other possible application scenarios for the proposed method are presented at the end.

Abstract Androgen receptor (AR) overexpression has been identified in gliomas and its stem cells, suggesting that AR plays an important role in tumor carcinogenesis. The prognostic significance of AR overexpression in gliomas remains unknown. AR mRNA expression in gliomas and relevant clinical data were obtained from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. AR expression levels were compared across gliomas of different histopathologic grades and molecular subtypes. Kaplan–Meier analyses in patients with different AR expression levels were investigated for the potential prognostic values of AR. Compared with normal brain tissue, gliomas show significantly higher AR mRNA expression (p

Abstract Single-particle tracking (SPT) is an immensely valuable technique for studying a variety of processes in the life sciences and physics. It can help researchers better understand the positions, paths, and interactions of single objects in systems that are highly dynamic or require imaging over an extended time. Here, we propose an all-dielectric one-dimensional photonic crystal (1D PC) that enhances spin-to-orbital angular momentum conversion for three-dimensional (3D) SPTs. This well-designed 1D PC can work as a substrate for optical microscopy. We introduce this effect into the interferometric scattering (iSCAT) technique, resulting in a double-helix point spread function (DH-PSF). DH-PSF provides more uniform Fisher information for 3D position estimation than the PSFs of conventional microscopy, such as encoding the axial position of a single particle in the angular orientation of DH-PSF lobes, thus providing a means for 3D SPT. This approach can address the challenge of iSCAT in 3D SPT because DH-PSF iSCAT will not experience multiple contrast inversions when a single particle travels along the axial direction. DH-PSF iSCAT microscopy was used to record the 3D trajectory of a single microbead attached to the flagellum, facilitating precise analysis of fluctuations in motor dynamics. Its ability to track single nanoparticles, such as 3D diffusion trajectories of 20 nm gold nanoparticles in glycerol solution, was also demonstrated. The DH-PSF iSCAT technique enabled by a 1D PC holds potential promise for future applications in physical, biological, and chemical science.

The widespread utilisation of tunnel boring machines (TBMs) in underground construction engineering requires a detailed investigation of the cutter-rock interaction. In this paper, we conduct a series of large-scale standing rotary cutting tests on granite in conjunction with high-fidelity numerical simulations based on a particle-type discrete element method (DEM) to explore the effects of key cutting parameters on the TBM cutter performance and the distribution of cutter-rock contact stresses. The assessment results of cutter performance obtained from the cutting tests and numerical simulations reveal similar dependencies on the key cutting parameters. More specifically, the normal and rolling forces exhibit a positive correlation with penetration but are slightly influenced by the cutting radius. In contrast, the side force decreases as the cutting radius increases. Additionally, the side force shows a positive relationship with the penetration for smaller cutting radii but tends to become negative as the cutting radius increases. The cutter's relative effectiveness in rock breaking is significantly impacted by the penetration but shows little dependency on the cutting radius. Consequently, an optimal penetration is identified, leading to a low boreability index and specific energy. A combined Hertz-Weibull function is developed to fit the cutter-rock contact stress distribution obtained in DEM simulations, whereby an improved CSM (Colorado School of Mines) model is proposed by replacing the original monotonic cutting force distribution with this combined Hertz-Weibull model. The proposed model outperforms the original CSM model as demonstrated by a comparison of the estimated cutting forces with those from the tests/simulations. The findings from this work that advance our understanding of TBM cutter performance have important implications for improving the efficiency and reliability of TBM tunnelling in granite.

Using over eight years of Mars Atmosphere and Volatile EvolutioN (MAVEN) data, from November 2014 to May 2023, we have investigated the Martian nightside ionospheric magnetic field distribution under the influence of upstream solar wind drivers, including the interplanetary magnetic field intensity (\begin{document}$ \left|{{\boldsymbol{B}}}_{\mathrm{I}\mathrm{M}\mathrm{F}}\right| $\end{document}), solar wind dynamic pressure (\begin{document}$ {P}_{\mathrm{S}\mathrm{W}} $\end{document}), solar extreme ultraviolet flux (EUV), and Martian seasons (\begin{document}$ {L}_{\mathrm{s}} $\end{document}). Our analysis reveals pronounced correlations between magnetic field residuals and both \begin{document}$ \left|{{\boldsymbol{B}}}_{\mathrm{I}\mathrm{M}\mathrm{F}}\right| $\end{document} and \begin{document}$ {P}_{\mathrm{S}\mathrm{W}} $\end{document}. Correlations observed with EUV flux and \begin{document}$ {L}_{\rm{s}} $\end{document} were weaker — notably, magnetic field residuals increased during periods of high EUV flux and at Mars perihelion. We find that the IMF penetrates to an altitude of 200 km under a wide range of upstream conditions, penetrating notably deeper under high \begin{document}$ \left|{{\boldsymbol{B}}}_{{\mathrm{IMF}}}\right| $\end{document} and \begin{document}$ {P}_{{\mathrm{SW}}} $\end{document} conditions. Our analysis also indicates that EUV flux and IMF cone angle have minimal impact on IMF penetration depth. Those findings provide useful constraints on the dynamic nature of Martian atmospheric escape processes and their evolution, suggesting that historical solar wind conditions may have facilitated deeper IMF penetration and higher rates of ionospheric escape than are observed now. Moreover, by establishing criteria for magnetic ‘quiet’ conditions, this study offers new insights into the planet’s magnetic environment under varying solar wind influences, knowledge that should help refine models of the Martian crustal magnetic field.

Abstract With the outbreak and continued spread of the COVID-19 pandemic, people's demand for daily disinfection products has increased rapidly, and its innovative design has received widespread attention. In this context, this study aims to propose a design methodology for home entrance disinfection devices based on AHP-FAST-FBS. Firstly, the design requirements of the home entrance disinfection device were collected and analyzed through in-depth interviews and the KJ method, and a hierarchical model of design demand indicators was constructed. Secondly, the Analytical Hierarchy Process (AHP) was employed to quantify these design demand indicators, and core design demands for home entrance disinfection devices were identified by weight calculations. On this basis, the Functional Analysis System Technique (FAST) method was combined to rationally transform the design demands into product functional indicators, constructing a functional system model for the home entrance disinfection device through systematic decomposition and categorization. Lastly, based on the Function-Behavior-Structure (FBS) theoretical model, the mapping of each function of the product to its structure was realized, the product structure modules were determined, and the comprehensive design and output of the innovative design scheme for the home entrance disinfection device were completed. The results of this study indicate that the design methodology combining AHP-FAST-FBS can effectively improve the scientific rigor and effectiveness of the home entrance disinfection device design, thereby generating an ideal product design scheme. This study provides systematic theoretical guidance and practical reference for designers of subsequent related disinfection products and also offers a new path for improving social health and safety.

Context Achyranthes bidentata Blume (ABB), a plant of Amaranthaceae family, has been one of the more commonly used phytomedicine remedies for thousands of years, and recent studies have highlighted the efficacy of its extracts in the treatment of osteoporosis. Nonetheless, a thorough analysis of its benefits is currently absent.Objective This meta-analysis assessed the effects of ABB root extract (ABBRE) on osteoporotic rats and provides a rationale for future clinical studies.Methods Searches were conducted in seven different Chinese and English databases, and the search period was from their establishment to January 2024. This study was registered in PROSPERO (CRD42023418917). Selected research regarding the ABBRE treatment of osteoporotic rats, and the corresponding research has distinctly reported outcomes, and the data on the bone mineral density (BMD), bone histomorphometrics, biomechanical parameters, and bone biochemical markers of osteoporotic rats can be extracted.Results Through screening, 11 studies met the eligibility requirements for inclusion, in which 222 animals were studied. The treatment group with ABBRE exhibited increased bone mineral density (standardized mean difference [SMD] = 1.64, 95% CI = 0.52 to 2.77). Based on subgroup analysis, the greatest increase in bone mineral density was observed when the dose of ABBRE was ≤ 400 mg/kg/day and the duration of treatment was ≤ 12 weeks.Conclusions ABBRE is a phytomedicine that can effectively promote the enhancement of bone mineral density and ease osteoporosis. It can be developed into a new alternative therapy by conducting experiments and clinical studies on larger samples.

Isoquinolinone is an important heterocyclic framework in natural products and biologically active molecules, and the efficient synthesis of this structural motif has received much attention in recent years. Herein, we report a (phenyliodonio)sulfamate (PISA)-mediated, solvent-dependent synthesis of different isoquinolinone derivatives. The method provides highly chemoselective access to 3- or 4-substituted isoquinolinone derivatives by reacting o-alkenylbenzamide derivatives with PISA in either acetonitrile or wet hexafluoro-2-isopropanol.

Abstract Background Stroke is a type of acute brain damage that can lead to a series of serious public health challenges. Demonstrating the molecular mechanism of stroke-related neural cell degeneration could help identify a more efficient treatment for stroke patients. Further elucidation of factors that regulate microglia and nuclear factor (erythroid-derived 2)-like 1 (Nrf1) may lead to a promising strategy for treating neuroinflammation after ischaemic stroke. In this study, we investigated the possible role of pterostilbene (PTS) in Nrf1 regulation in cell and animal models of ischaemia stroke. Methods We administered PTS, ITSA1 (an HDAC activator) and RGFP966 (a selective HDAC3 inhibitor) in a mouse model of middle cerebral artery occlusion–reperfusion (MCAO/R) and a model of microglial oxygen‒glucose deprivation/reperfusion (OGD/R). The brain infarct size, neuroinflammation and microglial availability were also determined. Dual-luciferase reporter, Nrf1 protein stability and co-immunoprecipitation assays were conducted to analyse histone deacetylase 3 (HDAC3)/Nrf1-regulated Nrf1 in an OGD/R-induced microglial injury model. Results We found that PTS decreased HDAC3 expression and activity, increased Nrf1 acetylation in the cell nucleus and inhibited the interaction of Nrf1 with p65 and p65 accumulation, which reduced infarct volume and neuroinflammation (iNOS/Arg1, TNF-α and IL-1β levels) after ischaemic stroke. Furthermore, the CSF1R inhibitor PLX5622 induced elimination of microglia and attenuated the therapeutic effect of PTS following MCAO/R. In the OGD/R model, PTS relieved OGD/R-induced microglial injury and TNF-α and IL-1β release, which were dependent on Nrf1 acetylation through the upregulation of HDAC3/Nrf1 signalling in microglia. However, the K105R or/and K139R mutants of Nrf1 counteracted the impact of PTS in the OGD/R-induced microglial injury model, which indicates that PTS treatment might be a promising strategy for ischaemia stroke therapy. Conclusion The HDAC3/Nrf1 pathway regulates the stability and function of Nrf1 in microglial activation and neuroinflammation, which may depend on the acetylation of the lysine 105 and 139 residues in Nrf1. This mechanism was first identified as a potential regulatory mechanism of PTS-based neuroprotection in our research, which may provide new insight into further translational applications of natural products such as PTS.

Weaving sections on roads are crucial areas with high concentrations of mandatory lane changes, which can increase the likelihood of traffic accidents. Speed is a key factor in determining traffic safety, and the development of an accurate speed prediction method is essential for improving safety in weaving sections. While current methods are effective in predicting speeds in straightforward situations, they face challenges in more complex scenarios such as weaving sections. This study presents a refined traffic speed prediction approach specifically designed for weaving sections in order to tackle the aforementioned issue. Initially, novel variables were formulated to capture the unique traffic flow attributes present in weaving sections, which distinguish them from standard road segments. Subsequently, supplementary empirical variables that are known to impact speed were incorporated. We conducted a variable importance assessment to ascertain the extent and direction of each variable’s contribution. Lastly, variables with significant positive effects were chosen as inputs for three machine learning algorithms: Random Forest (RF), Backpropagation Neural Network optimised with Genetic Algorithm (BPNN-GA) and Support Vector Regression (SVR). This method was evaluated using aerial footage from five distinct weaving sections in China, maintaining an approximately 3 km/h prediction error. In addition, the study also finds that the speed distribution in weaving sections is negatively correlated with the number of lane-changing. Vehicles experience deceleration at both on-ramp and off-ramp, with a more significant deceleration occurring at the on-ramp. Speed is significantly affected by short length, number of lanes and proportion of large vehicles. The proposed method can be embedded into intelligent traffic systems for safe speeds of autonomous vehicles in weaving sections. Reconstructing spatiotemporal patterns of traffic congestion, predicting traffic accidents and implementing active traffic management strategies in weaving sections could be investigated in the future.

Abstract The positive electrode|electrolyte interface plays an important role in all-solid-state Li batteries (ASSLBs) based on garnet-type solid-state electrolytes (SSEs) like Li6.4La3Zr1.4Ta0.6O12 (LLZTO). However, the trade-off between solid-solid contact and chemical stability leads to a poor positive electrode|electrolyte interface and cycle performance. In this study, we achieve thermodynamic compatibility and adequate physical contact between high-entropy cationic disordered rock salt positive electrodes (HE-DRXs) and LLZTO through ultrafast high-temperature sintering (UHS). This approach constructs a highly stable positive electrode|electrolyte interface, reducing the interface resistance to 31.6 Ω·cm2 at 25 °C, making a 700 times reduction compared to the LiCoO2 | LLZTO interface. Moreover, the conformal and tight HE-DRX | LLZTO solid-state interface avoids the transition metal migration issue observed with HE-DRX in liquid electrolytes. At 150 °C, HE-DRXs in ASSLBs (Li|LLZTO | HE-DRXs) exhibit an average specific capacity of 239.7 ± 2 mAh/g at 25 mA/g, with a capacity retention of 95% after 100 cycles relative to the initial cycle—a stark contrast to the 76% retention after 20 cycles at 25 °C in conventional liquid batteries. Our strategy, which considers the principles of thermodynamics and kinetics, may open avenues for tackling the positive electrode|electrolyte interface issue in ASSLBs based on garnet-type SSEs.

Abstract Dementia represents a significant global health challenge, with early screening during the preclinical stage being crucial for effective management. Traditional diagnostic biomarkers for Alzheimer’s Disease, the most common form of dementia, are limited by cost and invasiveness. Mild cognitive impairment (MCI), a precursor to dementia, is currently identified through neuropsychological tests like the Montreal Cognitive Assessment (MoCA), which are not suitable for large-scale screening. Eye-tracking technology, capturing and quantifying eye movements related to cognitive behavior, has emerged as a promising tool for cognitive assessment. Subtle changes in eye movements could serve as early indicators of MCI. However, the interpretation of eye-tracking data is challenging. This study introduced a dementia screening tool, VR Eye-tracking Cognitive Assessment (VECA), using eye-tracking technology, machine learning, and virtual reality (VR) to offer a non-invasive, efficient alternative capable of large-scale deployment. VECA was conducted with 201 participants from Shenzhen Baoan Chronic Hospital, utilizing eye-tracking data captured via VR headsets to predict MoCA scores and classify cognitive impairment across different educational backgrounds. The support vector regression model employed demonstrated a high correlation (0.9) with MoCA scores, significantly outperforming baseline models. Furthermore, it established optimal cut-off scores for identifying cognitive impairment with notable sensitivity (88.5%) and specificity (83%). This study underscores VECA’s potential as a portable, efficient tool for early dementia screening, highlighting the benefits of integrating eye-tracking technology, machine learning, and VR in cognitive health assessments.

Abstract Background Hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis constitutes a pivotal response by surgical trauma, manifesting as a critical aspect of the acute stress reaction. This hyperactivity resulted in adverse surgical outcomes and is often associated with increased postoperative anxiety. Increased evidence suggests that Nesfatin-1 plays a crucial role in stress responses and stress-related psychiatric disorders. Electroacupuncture (EA) is widely used to alleviate stress responses and anxiety, although its mechanism of action remains unclear. This study aimed to assess the mechanisms by which hypothalamic Nesfatin-1 contribute to the alleviation of HPA axis hyperactivity and anxiety by EA. Methods Partial hepatectomy (HT) was performed to simulate surgical trauma, and EA was applied at Zusanli (ST36) and Sanyinjiao (SP6). The levels of hypothalamic Nesfatin-1, c-Fos, and corticotropin-releasing hormone (CRH) were detected, and serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were regarded as indicators of HPA axis activity. Anxiety levels were assessed through open field tests (OFT), elevated plus maze (EPM), and light–dark box tests (LDBT). To investigate the role of Nesfatin-1, its expression was modulated using stereotactic viral injections or plasmid transfections. Transcriptome sequencing was employed to explore the downstream signaling pathways of Nesfatin-1. Additionally, brain cannula implantation was performed to facilitate targeted drug administration. Results Our findings demonstrated that EA reduced the hypothalamic overexpression of CRH and Nesfatin-1, as well as serum levels of ACTH and CORT. Additionally, it alleviated anxiety-like behaviors resulting from surgical trauma. We observed that overexpression of Nesfatin-1 in the hypothalamic paraventricular nucleus (PVN) triggered hyperactivity of the HPA axis and anxiety. Conversely, knocking down Nesfatin-1 in the PVN reversed these effects caused by surgical trauma. Transcriptome sequencing identified the extracellular regulated protein kinases (ERK)/cAMP-response element binding protein (CREB) pathway as a key mediator in the impacts of surgical trauma and EA on the hypothalamus. Both in vivo and in vitro studies showed that overexpression of Nesfatin-1 activated the ERK/CREB pathway. Furthermore, administering ERK or CREB inhibitors into the PVN mitigated HPA axis hyperactivity and anxiety-like behaviors induced by surgical trauma. Finally, EA was observed to decrease the phosphorylation levels of ERK and CREB in the PVN. Conclusion EA alleviates HPA axis hyperactivity and anxiety-like behaviors caused by surgical trauma through inhibition of Nesfatin-1/ERK/CREB pathway in the hypothalamus.

Abstract Transcriptional heterogeneity of tumor-associated macrophages (TAMs) has been investigated in individual cancers, but the extent to which these states transcend tumor types and represent a general feature of cancer remains unclear. We performed pan-cancer single-cell RNA sequencing analysis across nine cancer types and identified distinct monocyte/TAM composition patterns. Using spatial analysis from clinical study tissues, we assessed TAM functions in shaping the tumor microenvironment (TME) and influencing immunotherapy. Two specific TAM clusters (pro-inflammatory and pro-tumor) and four TME subtypes showed distinct immunological features, genomic profiles, immunotherapy responses, and cancer prognosis. Pro-inflammatory TAMs resided in immune-enriched niches with exhausted CD8+ T cells, while pro-tumor TAMs were restricted to niches associated with a T-cell-excluded phenotype and hypoxia. We developed a machine learning model to predict immune checkpoint blockade response by integrating TAMs and clinical data. Our study comprehensively characterizes the common features of TAMs and highlights their interaction with the TME.

Abstract Background The TetR family of transcriptional regulators (TFRs), serving as crucial regulators of diverse cellular processes, undergo conformational changes induced by small-molecule ligands, which either inhibit or activate them to modulate target gene expression. Some ligands of TFRs in actinomycetes and their regulatory effects have been identified and studied; however, regulatory mechanisms of the TetR family in the lincomycin-producing Streptomyces lincolnensis remain poorly understood. Results In this study, we found that AbrT (SLCG_1979), a TetR family regulator, plays a pivotal role in regulating lincomycin production and morphological development in S. lincolnensis. Deletion of abrT gene resulted in increased lincomycin A (Lin-A) production, but delayed mycelium formation and sporulation on solid media. AbrT directly or indirectly repressed the expression of lincomycin biosynthetic (lin) cluster genes and activated that of the morphological developmental genes amfC, whiB, and ftsZ. We demonstrated that AbrT bound to two motifs (5′-CGCGTACTCGTA-3′ and 5′-CGTACGATAGCT-3′) present in the bidirectional promoter between abrT and SLCG_1980 genes. This consequently repressed abrT itself and its adjacent gene SLCG_1980 that encodes an arabinose efflux permease. D-arabinose, not naturally occurring as L-arabinose, was identified as the effector molecule of AbrT, reducing its binding affinity to abrT-SLCG_1980 intergenic region. Furthermore, based on functional analysis of the AbrT homologue in Saccharopolyspora erythraea, we inferred that the TetR family regulator AbrT may play an important role in regulating secondary metabolism in actinomycetes. Conclusions AbrT functions as a regulator for governing lincomycin production and morphological development of S. lincolnensis. Our findings demonstrated that D-arabinose acts as a ligand of AbrT to mediate the regulation of lincomycin biosynthesis in S. lincolnensis. Our findings provide novel insights into ligand-mediated regulation in antibiotic biosynthesis.

To investigate the effects of nitrogen source nutrients on the growth and metabolism of Lactobacillus rhamnosus GG (LGG), this study used soybean protein isolates (dSPI) and soybean peptides (dPEP) from simulated gastrointestinal digestion as raw materials. The number of viable cells and the production of lactic acid and acetic acid in LGG were measured through mono-culture. LGG was co-cultured with Listeria monocytogenes to determine its utilization of soybean protein isolates and soybean peptides in the presence of pathogens. The results of mono-culture showed that both dPEP and dSPI could increase the viable number of LGG (P

Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.

Enhancing the thermal shock resistance of Y2O3 ceramic crucibles, coupled with advancements in melting and casting technologies to reduce the adverse influence of interfacial reactions, is essential for producing low-energy consumption, high-quality titanium-aluminum (TiAl) alloys. In this study, the Y2O3 ceramic crucible with good thermal shock resistance was developed through the optimization of particle size distribution and sintering holding time. The interaction mechanisms between Y2O3 ceramics and TiAl alloys under extreme conditions were investigated, and strategies for enhancing the mechanical properties of TiAl alloys through the integration of Y2O3 crucibles with centrifugal casting were discussed. The results indicated that introducing large particles of 1–3 mm under sintering conditions of 2023 K and 6 h effectively enhances the thermal shock resistance of Y2O3 crucible. The interaction between Y2O3 and TiAl alloys primarily involved physical erosion (spalling/dispersion), dissolution of separated particles, and surface modification of interface layer particles (reaction). Physical erosion played an important role in this dynamic interaction, with the extent of erosion intensifying through continuous use of the crucible, while electromagnetic forces ensured the uniform distribution of inclusions within the TiAl alloy matrix. Moreover, the application of centrifugal casting technology substantially refines the grain size and reduces the inclusion count, thereby significantly enhancing the mechanical properties of TiAl alloy.

Abstract This special issue explores the relationship between digital trade and security, emphasizing the geopolitical implications for the global economy in the digital age. The rapid growth of digital trade has introduced significant challenges and opportunities, necessitating robust data governance to balance national security interests with the free flow of goods, services, and data across borders. The papers explore the different models of data governance championed by the US, China, and the EU, highlighting the complexities of cross-border data flows and their impact on international relations. Through detailed analyses of various international agreements and frameworks, this special issue provides a comprehensive overview of the current landscape of digital trade and its security implications, with a particular focus on China's evolving approach to data governance and its global influence.

Abstract Adipose tissue, aside from adipocytes, comprises various abundant immune cells. The accumulation of low-grade chronic inflammation in adipose tissue serves as a primary cause and hallmark of insulin resistance. In this study, we investigate the physiological roles of FADD in adipose tissue inflammation, adipogenesis, and adipocyte survival. High levels of Fadd mRNA were observed in mitochondrial-rich organs, particularly brown adipose tissue. To explore its metabolic functions, we generated global Fadd knockout mice, resulting in embryonic lethality, while heterozygous knockout (Fadd+/−) mice did not show any significant changes in body weight or composition. However, Fadd+/− mice exhibited reduced respiratory exchange ratio (RER) and serum cholesterol levels, along with heightened global and adipose inflammatory responses. Furthermore, AT masses and expression levels of adipogenic and lipogenic genes were decreased in Fadd+/− mice. In cellular studies, Fadd inhibition disrupted adipogenic differentiation and suppressed the expression of adipogenic and lipogenic genes in cultured adipocytes. Additionally, Fadd overexpression caused adipocyte death in vitro with decreased RIPK1 and RIPK3 expression, while Fadd inhibition downregulated RIPK3 in iWAT in vivo. These findings collectively underscore the indispensable role of FADD in adipose inflammation, adipogenesis, and adipocyte survival.

Abstract Background Medical research in complementary and alternative medicine (CAM) has increased recently, raising ethical concerns about the moral status of CAM. Medical academic journals are responsible for conducting ethical review (ER) of manuscripts to protect the interests of human subjects and to make ethical results available before deciding to publish. However, there has been no systematic analysis of the ER in CAM journals. This study is aim to evaluate the current status of ethical requirements and compliance in CAM journals. Methods This is a cross-sectional study. We reviewed instructions for authors (IFAs) of CAM journals included in the Journal Citation Reports (2021) ( https://jcr.clarivate.com ) for general information and requirements for ER. We also browsed the manuscripts regarding randomized controlled trials published by CAM journals in Q1 and Q2 section from January to June, 2023, to check the actual situation of ethical requirement. Descriptive statistics and Fisher’s exact test were used for statistical analysis. Results 27 journals and 68 manuscripts were ultimately included. 92.6% (25/27) IFAs included keywords of ER, indicating the presence of ethical considerations. However, no specific ER was required for CAM (n = 0). We categorized journals by Geographic origin, JCR section, Year of electronic JCR, Types of studies, % of OA Gold to explore the factors that could influence CAM journals to have certain ethical review policies. The results showed there was no statistical significance in certain ethical review policy in any classification of journals (p > 0.05). All RCT manuscripts included in the study generally met the requirements of the published journals for ethical review. Conclusions All IFAs discussed ER, but the content was scattered, unfocused, and there were no specific ER requirements regarding CAM. Although the manuscripts basically met the requirements of the journal, it was not possible to get closer to the process of ER in the manuscript. To ensure full implementation of these policies in the future, CAM journals should require authors to provide more details, or to form a list of items necessary for CAM ethical review.

Abstract In recent years, immunotherapy, particularly PD-1 antibodies, have significantly enhanced the outcome of gastric cancer patients. Despite these advances, some patients do not respond well to treatment, highlighting the need to understand resistance mechanisms and develop predictive markers of treatment effectiveness. This study retrospectively analyzed data from 106 patients with stage IV gastric cancer who were treated with first-line immunotherapy in combination with chemotherapy. By comparing plasma cytokine levels between patients resistant and sensitive to PD-1 antibody therapy, the researchers identified elevated IL-4 expression in the resistant patients. Mechanical investigations revealed that IL-4 induces metabolic changes in macrophages that activate the PI3K/AKT/mTOR pathway. This alteration promotes ATP production, enhances glycolysis, increases lactic acid production, and upregulates FcγRIIB expression in macrophages. Ultimately, these changes lead to CD8+ T cell dysfunction and resistance to PD-1 antibody therapy in gastric cancer. These findings highlight the role of IL-4-induced macrophage polarization and metabolic reprogramming in immune resistance and verify IL-4 as potential targets for improving treatment outcomes in gastric cancer patients.

Abstract Background Toxoplasma gondii infection affects a significant portion of the global population, leading to severe toxoplasmosis and, in immunocompromised patients, even death. During T. gondii infection, disruption of gut microbiota further exacerbates the damage to intestinal and brain barriers. Therefore, identifying imbalanced probiotics during infection and restoring their equilibrium can regulate the balance of gut microbiota metabolites, thereby alleviating tissue damage. Methods Vimentin gene knockout (vim−/−) mice were employed as an immunocompromised model to evaluate the influence of host immune responses on gut microbiota balance during T. gondii infection. Behavioral experiments were performed to assess changes in cognitive levels and depressive tendencies between chronically infected vim−/− and wild-type (WT) mice. Fecal samples were subjected to 16S ribosomal RNA (rRNA) sequencing, and serum metabolites were analyzed to identify potential gut probiotics and their metabolites for the treatment of T. gondii infection. Results Compared to the immunocompetent WT sv129 mice, the immunocompromised mice exhibited lower levels of neuronal apoptosis and fewer neurobehavioral abnormalities during chronic infection. 16S rRNA sequencing revealed a significant decrease in the abundance of probiotics, including several species of Lactobacillus, in WT mice. Restoring this balance through the administration of Lactobacillus murinus and Lactobacillus gasseri significantly suppressed the T. gondii burden in the intestine, liver, and brain. Moreover, transplantation of these two Lactobacillus spp. significantly improved intestinal barrier damage and alleviated inflammation and neuronal apoptosis in the central nervous system. Metabolite detection studies revealed that the levels of various Lactobacillus-related metabolites, including indole-3-lactic acid (ILA) in serum, decreased significantly after T. gondii infection. We confirmed that L. gasseri secreted much more ILA than L. murinus. Notably, ILA can activate the aromatic hydrocarbon receptor signaling pathway in intestinal epithelial cells, promoting the activation of CD8+ T cells and the secretion of interferon-gamma. Conclusion Our study revealed that host immune responses against T. gondii infection severely disrupted the balance of gut microbiota, resulting in intestinal and brain damage. Lactobacillus spp. play a crucial role in immune regulation, and the metabolite ILA is a promising therapeutic compound for efficient and safe treatment of T. gondii infection. Graphical Abstract

Purpose: The poor retention and ambiguous differentiation of stem cells (SCs) within corpus cavernosum (CC) limit the cell application in erectile dysfunction (ED). Herein, the effects and mechanism of microRNA-145 (miR-145) gene modification on modulating the traits and fate of bone marrow-derived mesenchymal stem cells (BMSCs) were investigated. Materials and Methods: The effects of miR-145 on cell apoptosis, proliferation, migration, and differentiation were determined by flow cytometry, cell counting kit-8, transwell assays and myogenic induction. Then, the age-related ED rats were recruited to four groups including phosphate buffer saline, BMSC, vector-BMSC, overexpressed-miR-145-BMSC groups. After cell transplantation, the CC were harvested and prepared to demonstrate the retention and differentiation of BMSCs by immunofluorescent staining. Then, the target of miR-145 was verified by quantitative real-time polymerase chain reaction and immunohistochemical. After that, APTO-253, as an inducer of Krüppel-like factor 4 (KLF4), was introduced for rescue experiments in corpus cavernosum smooth muscle cells (CCSMCs) under the co-culture system. Results: In vitro, miR-145 inhibited the migration and apoptosis of BMSCs and promoted the differentiation of BMSCs into smooth muscle-like cells with stronger contractility. In vivo, the amount of 5-ethynyl-2'-deoxyuridine (EdU)+ cells within CC was significantly enhanced and maintained in the miR-145 gene modified BMSC group. The EdU/CD31 co-staning was detected, however, no co-staining of EdU/α-actin was observed. Furthermore, miR-145, which secreted from the gene modified BMSCs, dampened the expression of KLF4. However, the effects of miR-145 on CCSMCs could be rescued by APTO-253. Conclusions: Overall, miR-145 modification prolongs the retention of the transplanted BMSCs within the CC, and this effect might be attributed to the modulation of the miR-145/KLF4 axis. Consequently, our findings offer a promising and innovative strategy to enhance the local stem cell-based treatments.

Remote sensing systems are important means of space-based Earth observation, due to issues such as delayed measurement and control commands, data transmission, data processing, and product distribution in the ＆quot;collection-processing-distribution＆quot; process, it is difficult to effectively achieve real-time intelligent remote sensing application services that cover all day, all weather, and the world.The combination of low earth orbit communication and remote sensing satellite constellations is an effective way to solve service delay and separate control problems in existing systems.It summarized the current situation of communication and remote sensing integration over the world, and then imagined the architecture, development stages, and service modes of the integration of communication and remote sensing.Finally, key technologies under the communication and remote sensing integration architecture were proposed, and the application process of communication and remote sensing integration used typical application scenarios were explored.

Abstract Background Acute pancreatitis is one of the most common diseases requiring emergency surgery. Rapid and accurate recognition of acute pancreatitis can help improve clinical outcomes. This study aimed to develop a deep learning-powered diagnostic model for acute pancreatitis. Materials and methods In this investigation, we enrolled a cohort of 190 patients with acute pancreatitis who were admitted to Sichuan Provincial People’s Hospital between January 2020 and December 2021. Abdominal computed tomography (CT) scans were obtained from both patients with acute pancreatitis and healthy individuals. Our model was constructed using two modules: (1) the acute pancreatitis classifier module; (2) the pancreatitis lesion segmentation module. Each model’s performance was assessed based on precision, recall rate, F1-score, Area Under the Curve (AUC), loss rate, frequency-weighted accuracy (fwavacc), and Mean Intersection over Union (MIOU). Results Upon admission, significant variations were observed between patients with mild and severe acute pancreatitis in inflammatory indexes, liver, and kidney function indicators, as well as coagulation parameters. The acute pancreatitis classifier module exhibited commendable diagnostic efficacy, showing an impressive AUC of 0.993 (95%CI: 0.978–0.999) in the test set (comprising healthy examination patients vs. those with acute pancreatitis, P

Abstract Background and aim Traditional Chinese medicine (TCM) is widely used by patients with amyotrophic lateral sclerosis (ALS). However, their reasons and experience in using TCM have received insufficient attention. Therefore, we conducted a mixed method study to gain insights into this issue. Materials and methods This study was conducted on the basis of the China Amyotrophic Lateral Sclerosis Registry of Patients with Traditional Chinese Medicine (CARE-TCM). Data were collected from Dongzhimen Hospital through a mixed method approach, including a questionnaire and a semi-structured interview. Patients with ALS who were using TCM when they were initially registered with CARE-TCM and who had been followed-up for over six months were recruited. The questionnaires’ outcomes were statistically outlined, and the interview transcripts were thematically analysed to identify themes and sub-themes. Results Fifty-two and sixteen patients were included in the questionnaire and semi-structured interview groups, respectively. Patients used TCM with the hope of regulating their body holistically to improve nonmotor symptoms and quality of life (QOL). Those who recognised TCM as ineffective tended to discontinue it after a three-month trial period. Although quality was a major concern, herbal medicine (HM) was the most frequently used modality among all participants (n = 52), with the majority (n = 44, 84.6%) continuing to use it. Patients emphasised in-person consultations as a crucial part of TCM treatment. However, the disability caused by disease often made this interaction unattainable. Conclusion Nonmotor symptoms and QOL hold substantial importance for patients with ALS using TCM. HM is a more suitable modality than other TCM treatment modalities, but patients are facing challenges in seeking HM treatment. It is necessary to promote the implementation of hierarchical diagnosis and treatment, thus making TCM more accessible. Trial registration ClinicalTrials.gov identifier: NCT04885374 (registered on May 13, 2021).

Abstract Background Hepatocellular carcinoma (HCC) is a common type of malignant tumor where the prognosis is dismal. Circular RNA (CircRNA) is a novel RNA that regulates downstream gene transcription and translation to influence the progression of HCC. However, the regulatory relationship that exists between E3 ligases, which is a class of post-translational modifying proteins, and circRNA remains unclear. Methods Based on the E3 ubiquitin ligase in the competitive endogenous RNA (ceRNA) network, a circRNA-regulated E3 ubiquitin ligase signature (CRE3UL) was developed. A CRE3UL signature was created using the least absolute shrinkage and selection operator (Lasso) and Cox regression analysis and merged it with clinicopathologic characteristics to generate a nomogram for prognosis prediction. The pRRophetic algorithm was utilized and immunological checkpoints were analyzed to compare the responses of patients in the high-risk group (HRG) and low-risk group (LRG) to targeted therapy and immunotherapy. Finally, experimental research will further elucidate the relationship between E3 ubiquitin ligase signature and HCC. Results HRG patients were found to have a worse prognosis than LRG patients. Furthermore, significant variations in prognosis were observed among different subgroups based on various clinical characteristics. The CRE3UL signature was identified as being an independent prognostic indicator. The nomogram that combined clinical characteristics and the CRE3UL signature was found to accurately predict the prognosis of HCC patients and demonstrated greater clinical utility than the current TNM staging approach. According to anticancer medication sensitivity predictions, the tumors of HRG patients were more responsive to gefitinib and nilotinib. From immune-checkpoint markers analysis, immunotherapy was identified as being more probable to assist those in the HRG. Conclusions We found a significant correlation between the CRE3UL signature and the tumor microenvironment, enabling precise prognosis prediction for HCC patients. Additionally, a nomogram was developed that performs well in predicting the overall survival (OS) of HCC patients. This provides valuable guidance for clinicians in devising specific personalized treatment strategies. Graphical Abstract

Abstract Diminishing Arctic sea ice has led to enhanced evaporation from the Arctic marginal seas (AMS), which is expected to alter precipitation over land. In this work, AMS evaporation is numerically tracked to quantify its contribution to cold-season (October–March) precipitation over land in the Northern Hemisphere during 1980–2021. Results show a significant 32% increase in AMS moisture contribution to land precipitation, corresponding to a 16% increase per million square km loss of sea ice area. Especially over the high-latitude land, despite the fractional contribution of AMS to precipitation being relatively low (8%), the augmented AMS evaporation contributed disproportionately (42%) to the observed upward trend in precipitation. Notably, northern East Siberia exhibited a substantial rise in both the amount and fraction of extreme snowfall sourced from the AMS. Our findings underscore the importance of the progressively ice-free Arctic as an important contributor to the escalating levels of cold-season precipitation and snowfall over northern high-latitude land.

Background: The prevalence of different types/subtypes varies across seasons and countries for seasonal influenza viruses, indicating underlying interactions between types/subtypes. The global interaction patterns and determinants for seasonal influenza types/subtypes need to be explored. Methods: Influenza epidemiological surveillance data, as well as multidimensional data that include population-related, environment-related, and virus-related factors from 55 countries worldwide were used to explore type/subtype interactions based on Spearman correlation coefficient. The machine learning method Extreme Gradient Boosting (XGBoost) and interpretable framework SHapley Additive exPlanation (SHAP) were utilized to quantify contributing factors and their effects on interactions among influenza types/subtypes. Additionally, causal relationships between types/subtypes were also explored based on Convergent Cross-mapping (CCM). Results: A consistent globally negative correlation exists between influenza A/H3N2 and A/H1N1. Meanwhile, interactions between influenza A (A/H3N2, A/H1N1) and B show significant differences across countries, primarily influenced by population-related factors. Influenza A has a stronger driving force than influenza B, and A/H3N2 has a stronger driving force than A/H1N1. Conclusion: The research elucidated the globally complex and heterogeneous interaction patterns among influenza type/subtypes, identifying key factors shaping their interactions. This sheds light on better seasonal influenza prediction and model construction, informing targeted prevention strategies and ultimately reducing the global burden of seasonal influenza.

Aspergillus niger is an efficient cell factory for organic acids production, particularly l-malic acid, through genetic manipulation. However, the traditional method of collecting A. niger spores for inoculation is labor-intensive and resource-consuming. In our study, we used the CRISPR-Cas9 system to replace the promoter of brlA, a key gene in Aspergillus conidiation, with a xylose-inducible promoter xylP in l-malic acid-producing A. niger strain RG0095, generating strain brlAxylP. When induced with xylose in submerged liquid culture, brlAxylP exhibited significant upregulation of conidiation-related genes. This induction allowed us to easily collect an abundance of brlAxylP spores (>7.1 × 106/mL) in liquid xylose medium. Significantly, the submerged conidiation approach preserves the substantial potential of A. niger as a foundational cellular platform for the biosynthesis of organic acids, including but not limited to l-malic acid. In summary, our study offers a simplified submerged conidiation strategy to streamline the preparation stage and reduce labor and material costs for industrial organic acid production using Aspergillus species.

Background: Endoscopy is important for the diagnosis and treatment of acute upper gastrointestinal bleeding (AUGIB), especially acute variceal bleeding (AVB), in liver cirrhosis. However, the optimal timing of endoscopy remains controversial, primarily because the currently available evidence is of poor quality, and the definition of early endoscopy is also very heterogeneous among studies. Herein, a multicenter randomized controlled trial (RCT) is performed to explore the impact of the timing of endoscopy on the outcomes of cirrhotic patients with AVB. Methods: A total of 368 cirrhotic patients presenting with AUGIB who are highly suspected to be from AVB will be enrolled. They will be stratified according to the severity of liver function and clinical presentation at admission and then randomly assigned at a 1:1 ratio into early (within 12 h after admission) and delayed (within 12–24 h after admission) endoscopy groups within each stratum. The primary outcomes include the rates of 5-day failure to control bleeding after admission and 6-week rebleeding. The secondary outcomes include 6-week mortality and incidence of adverse events. Conclusion: Considering existing evidence originates from non-randomized studies, this RCT will provide high-quality evidence to uncover whether cirrhotic patients with AVB should undergo early endoscopy to control bleeding and improve survival. Trial registration: ClinicalTrials.gov identifier: NCT06031402.

Background and AimsDiabetic foot ulcers (DFUs) are a serious complication of diabetes mellitus (DM), affecting around 25% of individuals with DM. Primary treatment of a DFU involves wound off-loading, surgical debridement, dressings to provide a moist wound environment, vascular assessment, and appropriate antibiotics through a multidisciplinary approach. Three-dimensional (3D) printing technology is considered an innovative tool for the management of DFUs. The utilization of 3D printing technology in the treatment of DFU involves the modernization of traditional methods and the exploration of new techniques. This review discusses recent advancements in 3D printing technology for the application of DFU care, and the development of personalized interventions for the treatment of DFUs.MethodsWe searched the electronic database for the years 2019–2024. Studies related to the use of 3D printing technology in Diabetic foot were included.ResultsA total of 25 identified articles based on database search and citation network analysis. After removing duplicates, 18 articles remained, and three articles that did not meet the inclusion criteria were removed after reading the title/abstract. A total of 97 relevant articles were included during the reading of references. In total, 112 articles were included.Conclusion3D printing technology offers unparalleled advantages, particularly in the realm of personalized treatment. The amalgamation of traditional treatment methods with 3D printing has yielded favorable outcomes in decelerating the progression of DFUs and facilitating wound healing. However, there is a limited body of research regarding the utilization of 3D printing technology in the domain of DFUs.

AimThe objective of this study was to gain insight into the nature of cognitive fatigue and to identify future trends of objective assessment techniques in this field.MethodsOne thousand and eighty-five articles were retrieved from the Web of Science Core Collection database. R version 4.3.1, VOSviewer 1.6.20, CiteSpace 6.2.R4, and Microsoft Excel 2019 were used to perform the analysis.ResultsA total of 704 institutes from 56 countries participated in the relevant research, while the People’s Republic of China contributed 126 articles and was the leading country. The most productive institute was the University of Gothenburg. Johansson Birgitta from the University of Gothenburg has posted the most articles (n = 13). The PLOS ONE published most papers (n = 38). The Neurosciences covered the most citations (n = 1,094). A total of 3,116 keywords were extracted and those with high frequency were mental fatigue, performance, quality-of-life, etc. Keywords mapping analysis indicated that cognitive fatigue caused by continuous work and traumatic brain injury, as well as its rehabilitation, have become the current research trend. The most co-cited literature was published in Sports Medicine. The strongest citation burst was related to electroencephalogram (EEG) event-related potential and spectral power analysis.ConclusionPublication information of related literature on the objective assessment of cognitive fatigue from 2007 to 2024 was summarized, including country and institute of origin, authors, and published journal, offering the current hotspots and novel directions in this field.

BackgroundSnakehead vesiculovirus (SHVV) has led to huge economic losses in snakehead aquaculture, and its pathogenic mechanisms is still not fully understood. MicroRNAs (miRNAs), as an important class of non-coding RNAs, play a key regulatory role in the process of viral infection.MethodsWe examined the effect of SHVV infection on the expression of miR-130c-5p and the effect of overexpression of miR-130c-5p on the proliferation of SHVV. Cotransfection of viral N protein and miR-130c-5p, and the effect of miR-130c-5p on the expression of N protein was detected. Meanwhile, the effect of overexpression of miR-130c-5p on the expression of various immune factors in the case of viral infection were also tested.ResultsIn this study, SHVV infection significantly upregulated the expression of miR-130c-5p in channel catfish ovary (CCO) cells in a time- and dose-dependent manner. The further research revealed that miR-130c-5p mimic significantly inhibited, while its inhibitors promoted SHVV replication. In addition, miR-130c-5p could directly target the viral mRNA of n gene, and overexpression of miR-130c-5p could significantly decrease, and conversely, downregulation of miR-130c-5p could increase the mRNA and protein expression of the viral n gene. Meanwhile, overexpression of miR-130c-5p also upregulated the expression of immune-related genes, such as nucleotide-oligomerization domain (NOD)-like receptor subfamily C3 (NLRC3), myeloid differentiation factor 88 (MyD88), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), interleukin-22 (IL-22), and interleukin-1beta (IL-1β) in host cells.ConclusionmiR-130c-5p was upregulated in the host during SHVV infection, and the upregulated miR-130c-5p directly inhibited viral replication by targeting the n gene of SHVV and promoting viral nucleoprotein degradation. The up-regulated miR-130c-5p also activated the expression of immune-related genes such as NLRC3, MyD88, NF-κB, IL-6, IL-22, and IL-1β, which were involved in the regulation of the signaling pathways including NF-κB, MyD88, Toll-like receptor (TLR), NLR, and janus tyrosine kinase-signal converter and activator of transcription (JAK-STAT), to enhance the host's antiviral immune response, and thus indirectly inhibited the viral proliferation.

The composite structure wick has been proven to significantly enhance the heat transfer performance of vapor chambers. Aluminum vapor chambers offer advantages such as being lightweight and cost-effective, meeting the requirements for lightweight cooling in fields like aviation. This study presented two novel composite porous wick structures with regular-shaped pores, designed and controlled via selective laser melting (SLM): the vertical square pore composite wick structure and the round-vertical square pore composite wick structure. A water-cooling test platform was built to investigate the effects of parameters such as wick structure thickness, round pore diameter, and round pore depth on the heat transfer performance and thermal resistance of the vapor chambers. The results indicate that the optimal thickness for the vertical square pore composite wick structure was 1.5 mm, yielding a minimum thermal resistance of 0.04 K/W. When the thickness was below 1.5 mm, it caused a reduction in the density of the vaporized core and insufficient liquid transport capacity. Conversely, when the thickness exceeded 1.5 mm, the primary limiting factor for heat transfer shifts to vapor-liquid flow resistance. Furthermore, the round-vertical square pore composite wick structure can provide further improvements in vapor-liquid transport within the structure.