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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.

Oncolytic viruses (OVs), a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact, are emerging as promising living anticancer agents. Unlike traditional drugs composed of non-replicating compounds or biomolecules, the replicative nature of viruses confer unique pharmacokinetic properties that require further studies. Despite some pharmacokinetics studies of OVs, mechanistic insights into the connection between OV pharmacokinetics and antitumor efficacy remain vague. Here, we characterized the pharmacokinetic profile of oncolytic virus M1 (OVM) in immunocompetent mouse tumor models and identified the JAK‒STAT pathway as a key modulator of OVM pharmacokinetics. By suppressing the JAK‒STAT pathway, early OVM pharmacokinetics are ameliorated, leading to enhanced tumor-specific viral accumulation, increased AUC and Cmax, and improved antitumor efficacy. Rather than compromising antitumor immunity after JAK‒STAT inhibition, the improved pharmacokinetics of OVM promotes T cell recruitment and activation in the tumor microenvironment, providing an optimal opportunity for the therapeutic outcome of immune checkpoint blockade, such as anti-PD-L1. Taken together, this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in OV therapy.

Abstract Objective Solanum nigrum L. (SNL) is a natural drugwith diverse bioactive components and multi‐targeted anti‐tumor effects, gaining increasing attention in clinical application. Method and Results This paper reviews the studies on SNL by searching academic databases (Google Scholar, PubMed, Science Direct,and Web of Science, among others), analyzing its chemical compositions (alkaloids, saponins, polysaccharides, and polyphenols, among others), andbriefly describes the anti‐tumor mechanisms of the main components. Discussion This paper discusses the shortcomings of the current research on SNL and proposes corresponding solutions, providing theoretical support for further research on its biological functions and clinical efficacy.

Abstract Van der Waals (vdW) assembly of low-dimensional materials has proven the capability of creating structures with on-demand properties. It is predicted that the vdW encapsulation can induce a local high-pressure of a few GPa, which will strongly modify the structure and property of trapped materials. Here, we report on the structural collapse of carbon nanotubes (CNTs) induced by the vdW encapsulation. By simply covering CNTs with a hexagonal boron nitride flake, most of the CNTs (≈77%) convert from a tubular structure to a collapsed flat structure. Regardless of their original diameters, all the collapsed CNTs exhibit a uniform height of ≈0.7 nm, which is roughly the thickness of bilayer graphene. Such structural collapse is further confirmed by Raman spectroscopy, which shows a prominent broadening and blue shift in the Raman G-peak. The vdW encapsulation-induced collapse of CNTs is fully captured by molecular dynamics simulations of the local vdW pressure. Further near-field optical characterization reveals a metal-semiconductor transition in accompany with the CNT structural collapse. Our study provides not only a convenient approach to generate local high-pressure for fundamental research, but also a collapsed-CNT semiconductor for nanoelectronic applications.

This paper studied the response of rice yield and soil nitrogen (N) cycling microorganisms to the combined application of animal slurry and mineral fertiliser. A pot experiment was conducted on typical yellow-brown paddy soil. There were five treatments: (1) CK - no N fertilisation; (2) S0 - mineral fertilisation; (3) S30 - 30% slurry with 70% mineral fertilisation; (4) S60 - 60% slurry with 40% mineral fertilisation; and (5) S100 - slurry application. Rice yield, yield components, and soil properties were investigated at harvest. The abundance of soil N cycle functional genes abundance was quantified via quantitative real-time PCR. The rice yield reached a high level when the proportion of slurry used to replace mineral fertiliser was 30-50%. The yield in response to mineral fertiliser (S0) was equivalent to that in response to no N fertilisation since the formation of effective panicles was inhibited. With the slurry replacement ratio increase, the available phosphorus and potassium contents in the soil improved, but the nitrate content decreased. Considering the entire soil N cycle, nitrogen-fixing microbes (nifH), ammonia-oxidising archaea (AOA amoA) and nitrite-reducing microbes (nirS and nirK) had greater abundances, reaching 108 copies. Compared with those in the S0 treatment, the abundances of most N cycle functional genes in the S30 treatment, except for napA, significantly increased from 31.2% to 100.9%, and the increase in the abundance of nirS and nosZ in the S100 treatment reached 4 times, which was obviously greater than that of the other genes. Correlation analysis revealed that high soil pH promoted N fixation and nitrification, while NH4+-N had the opposite effect on N fixation and nitrification, and available phosphorus and potassium actively influenced denitrification. These results showed that a 30-50% slurry application ratio was recommended for rice, which was beneficial for maintaining high yields and high abundances of soil N cycle functional genes.

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are characterized by excessive triglyceride accumulation in the liver. However, due to an incomplete understanding of its pathogenesis, more efforts are needed to identify specific and effective treatments. N4-acetylcytidine (ac4C) is a newly discovered RNA modification to regulate mRNA. N-acetyltransferase 10 (NAT10) has not been fully explored in MASLD and MASH. Methods: The clinical relevance of NAT10 was evaluated based on its expression in various mouse and human models of MASLD and MASH. Acetylated RNA immunoprecipitation sequencing and mRNA stability assays were used to explore the role of NAT10 in regulating ac4C modification and expression of target genes. Genetically engineered mice were employed to investigate the role of NAT10 in MASLD and MASH progression. Results: Hepatic NAT10 expression was significantly increased in multiple mice and humans of MASLD and MASH. Genetic knockout of NAT10 protected mice from diet-induced hepatic steatosis and steatohepatitis, whereas overexpression of NAT10 exacerbated high-fat-diet-induced liver steatosis. Mechanistically, NAT10 binds to Srebp-1c mRNA, promoting its stability and expression, thereby upregulating lipogenic enzymes. Treatment with Remodelin, a NAT10-specific inhibitor, effectively ameliorates liver steatosis and dyslipidemia in a preclinical mouse model. Conclusions: Our findings indicate that NAT10 could regulate lipid metabolism in MASLD and MASH by stabilizing Srebp-1c mRNA and upregulating lipogenic enzymes. This study highlights the role of NAT10 and RNA acetylation in the pathogenesis of MASLD and MASH. Thus, our findings suggest a promising new therapeutic approach, such as the use of NAT10 inhibitor, for treating metabolic liver disease.

ObjectiveThe purpose of this study is to investigate the drug safety of three Transthyretin (TTR) inhibitors in the real world using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.MethodsThis study extracted reports received by the FAERS database from the first quarter of 2018 to the third quarter of 2023 for descriptive analysis and disproportionality analysis. Safety signal mining was conducted at the Preferred Term (PT) level and the System Organ Class (SOC) level using reporting odds ratio (ROR). The characteristics of the time-to-onset curves were analyzed using the Weibull Shape Parameter (WSP). The cumulative incidence of TTR inhibitors was evaluated using the Kaplan-Meier method. Subgroup analyses were conducted based on whether the reporter was a medical professional.ResultsA total of 3,459 reports of adverse events (AEs) caused by TTR inhibitors as the primary suspect (PS) drug were extracted. The top three reported AEs for patisiran were fatigue, asthenia, and fall, with the most unexpectedly strong association being nonspecific reaction. The top three reported AEs for vutrisiran were fall, pain in extremity and malaise, with the most unexpectedly strong association being subdural haematoma. The top three reported AEs for inotersen were platelet count decreased, blood creatinine increased, and fatigue, with the most unexpectedly strong association being blood albumin decreased. Vitamin A decreased, arthralgia, and dyspnea were the same AEs mentioned in the drug labels of all three drugs, while malaise and asthenia were the same unexpected significant signals. This study offers evidence of the variability in the onset time characteristics of AEs associated with TTR inhibitors, as well as evidence of differences in adverse event reporting between medical professionals and non-medical professionals.ConclusionIn summary, we compared the similarities and differences in drug safety of three TTR inhibitors in the real world using the FAERS database. The results indicate that not only do these three drugs share common AEs, but they also exhibit differences in drug safety profiles. This study contributes to enhancing the understanding of medical professionals regarding the safety of TTR inhibitors.

Background: The impact of capsular closure vs non-closure in hip arthroscopy for femoracetabular impingement (FAI) was assessed by a meta-analysis. Methods: With the most recent search update occurring in August 2022, relevant studies were found by searching the Pubmed and EMBASE databases. A collection of studies was made that conducted hip arthroscopy for FAI. Review Manager 5.3 was used to carry out the meta-analysis. The dichotomous and continuous factors were compared using the odds ratios (OR) and mean differences (MD). A fixed-effect or random-effect model was chosen, depending on the degree of heterogeneity (I2). Forest plots were used to assess the results. A significance level of P

Ground-based arc-scanning synthetic aperture radar (GB-ArcSAR) can perform 360° scanning and has a large field of view. Based on the differential interferometry technique, GB-ArcSAR can be utilized to measure the surface deformation. However, affected by the rotating motion, rescanning angle error and rotation center offset during repeated scanning could occur. Through theoretical analysis, this article proves that the rescanning angle error has nearly no effect on the interferometric phase and can be negligible. The phase error caused by the rotation center offset can be built as a linear multiparameter model based on the multivariate Taylor expansion. Simulations are made to analyze the effect of the rotation center offset. A compensation method based on permanent scatterer technology is proposed, by using the least squares method, which jointly compensates the rotation center offset error and the atmospheric phase disturbance error. The compensation performance of the proposed method is validated in different scenarios, which can effectively improve the accuracy of deformation measurement.

Weather radar holds the capability to monitor the extensive migration of bird and insect species. In particular, polarimetric weather radar can enhance aerial ecological monitoring by quantifying target shape through the measurement of polarization moments. This article introduces an intelligent algorithm to classify bird and insect migration using polarimetric weather radar data. A radar image dataset was formed by intentionally curating typical migratory data of birds and insects captured by the polarimetric weather radar. Next, point features and spatial texture features were extracted from the radar images in the dataset for training a classifier using a supervised learning approach, resulting in a classification accuracy of 93.56%. Furthermore, the importance of the features was analyzed, uncovering that the most influential attribute was the reflectivity factor at 33.83%, surpassing the cumulative influence of other dual-polarization moments. In addition, spatial textures also played an essential role for the classifier, collectively weighing 35.65%. Lastly, the proposed method was validated with bird radar data, attaining an accuracy level of 95.36%.

Ground clutter poses a significant challenge to the accuracy of weather radar products, especially for aeroecology monitoring. Operational weather radar commonly employs a fixed coherent pulse integration (CPI) for clutter suppression. However, the phenomenon of strong clutter spanning multiple CPIs can result in severe spectral leakage. The independent implementation of clutter suppression within each CPI fails to fully utilize clutter data, significantly compromising clutter suppression effectiveness. Therefore, we propose an adaptive coherent pulse integration (ACPI) method based on the amplitude-phase characteristics of echoes in azimuth. Clutter and nonclutter regions are determined firstly based on the stability of the echo phase in azimuth. Then, the clutter region is further subdivided using phase discontinuities and amplitude notches between different clutter areas. Finally, an appropriate CPI can be assigned to each strong clutter instance. The effectiveness and the practicality of the ACPI are verified through the simulations and measured data from Chinese operational weather radar.

Geosynchronous synthetic aperture radar (GEO SAR) has the advantages of a short revisit time and a large beam footprint. Enhancing spatial resolution has become a hotspot in spaceborne SAR research areas. The existing designs of GEO SAR suffer from the problem of poor resolution (greater than 10 m) and cause low-precision observation in urban areas. First time, this article points out that GEO SAR has the ability to improve the two-dimensional (2-D) resolution of SAR images by spatial spectrum synthesis based on 2-D baselines, and proposes models and a signal processing method involved in GEO SAR spectrum synthesis. The 2-D spatial baselines of GEO SAR are analyzed and evaluated first based on satellite software and real ephemeris from Beidou Inclined Geosynchronous Orbit (IGSO) navigation satellites to demonstrate the potential of 2-D resolution improvement. Then the analytical models of the spectral shape and relative spectral shift between GEO SAR images are derived. Furthermore, a 2-D spectrum synthesis algorithm suitable for GEO SAR is also proposed, where we use deramping operation instead of the traditional spectrum shifting process. Nonideal factors are considered in the processing of synthesized. In addition, performances of the proposed algorithm, including the resolution improvement factor, the amplitude fluctuation, and the critical baseline, are constructed. Finally, computer simulations and equivalent experiments based on Beidou IGSO navigation satellites verify the proposed algorithm.

Due to the specific arc-scanning way of ground-based arc-scanning synthetic aperture radar (GB-ArcSAR) to synthesize aperture, when a target's height is large enough and deviates much from the reference imaging plane, the image defocus would occur since that the target's range migration trajectory cannot be completely compensated. This article makes a theoretical analysis of the reasons for GB-ArcSAR imaging defocus, when it is utilized to observe those targets with large height differences, i.e., large elevation angles, from the imaging plane. A quantitative relationship between the imaging defocus level and the elevation angle is deduced with the simulation of an ideal target. Aiming at solving the problem of imaging defocus, an optimized imaging method of GB-ArcSAR based on the reference plane construction is proposed. A series of reference planes with different inclination angles or starting ranges are constructed and utilized for radar imaging separately. The minimum entropy criterion is then taken to search for the optimal plane. The qualitative and quantitative comparisons of the simulated and experimental datasets with other methods both prove the effectiveness of the proposed method.

ABSTRACT Aims Nearly 85% of maternally inherited diabetes and deafness (MIDD) are caused by the m.3243A>G mutation in the mitochondrial DNA. However, the clinical phenotypes of MIDD may also be influenced by the nuclear genome, this study aimed to investigate nuclear genome variants that influence clinical phenotypes associated with m.3243A>G mutation in MIDD based on whole‐genome sequencing of the patients belonging to pedigrees. Materials and Methods We analyzed a whole‐genome sequencing (WGS) dataset from blood samples of 38 MIDD patients with the m.3243A > G mutation belonging to 10 pedigrees, by developing a Kinship‐graph convolutional network approach, called Ki‐GCN, integrated with the conventional genome‐wide association study (GWAS) methods. Results We identified eight protective alleles in the nuclear genome that have protective effects against the onset of MIDD, related deafness, and also type 2 diabetes. Based on these eight protective alleles, we constructed an effective logistic regression model to predict the early or late onset of MIDD patients. Conclusions There are protective alleles in the nuclear genome that are associated with the onset‐age of MIDD patients and might also provide protective effects on the deafness derived from MIDD patients.

Differential synthetic aperture radar tomography (D-TomoSAR) uses multiple SAR acquisitions at different times to form an elevation-time 2-D synthetic aperture, enabling recovery of the target's 3-D structure and deformation velocity. However, the imaging performance of D-TomoSAR is influenced by the spatial-temporal baseline distribution, which is one of the crucial factors. Due to the difference in orbit altitude, the effects of various perturbation forces on geosynchronous SAR (GEO SAR) are significantly different from those on low Earth orbit SAR (LEO SAR), leading to different geometries in the spatial-temporal baseline distributions of GEO SAR and LEO SAR in the repeat-pass acquisitions. The spatial-temporal baseline distribution of LEO SAR is random, while that of GEO SAR is coupled. Although GEO SAR obtains a large number of acquisitions due to the short repeat-pass time, using data under all spatial-temporal baselines for D-TomoSAR does not necessarily provide the best imaging results. Therefore, how to select spatial-temporal baselines that can improve the estimation accuracy is important. In this article, the Cramér–Rao lower bound of GEO D-TomoSAR estimation accuracy is determined by considering multiple factors, including baseline decorrelation and spatial-temporal coupling. The optimal spatial-temporal baseline selection is modeled as a multiobjective problem and solved by the Nondominated Sorting Genetic Algorithm II (NSGA-II). Given the absence of in-orbit GEO SAR and the orbital similarity between GEO SAR and BeiDou Inclined Geosynchronous Orbit (IGSO) satellite, the real ephemeris of BeiDou IGSO satellite is used to simulate the baseline distribution of GEO SAR and verify the baseline optimization method.

This is an essay in the field of ceramics and composites. With the rapid development of the new energy vehicle industry, the production of power lithium-ion batteries has increased dramatically. However, due to the short service life of power Li-ion batteries and their imminent mass retirement, it is necessary to effectively manage power Li-ion batteries in a resourceful manner. This paper first introduces the main components of power lithium-ion batteries and clarifies the stepwise utilization and pre-treatment process before their cathode materials are recycled. It focuses on an overview of the thermal, wet and biological recycling technologies for used power lithium-ion battery cathode materials, and presents the opportunities and challenges faced by biological recycling in the resourceful disposal of used power lithium-ion battery cathode materials. Our results can provide a certain reference for the green resource-based recycling of power lithium-ion batteries and promote the healthy development of the new energy vehicle industry.

This study aimed to explore the optimal conditions for the preparation of β-glucan/nanosized selenium (Se NPs) complexes (DNT-Se) and determining the safety of DNT-Se. The concentration of polysaccharides (DNTs), the ratio of vitamin C (VC) to Na2SeO3, the concentration of Na2SeO3, the reaction time, and the reaction temperature were used as experimental factors. The dual-wavelength colorimetric method and the Malvern particle-size assay method were used to characterize changes in the particle size of Se NPs in DNT-Se, and the single-factors and orthogonal experimental design were used to investigate the preparation process of DNT-Se, and the toxicity of DNT-Se to 293T human embryonic kidney cells and normal liver cells of AML-12 mice was evaluated by using CCK-8. The results showed that the optimal conditions for DNT-Se preparation were list as follows: 1.0 mg/mL of DNTs, and 1.0 mg/mL of Na2SeO3 with the ratio of vitamin C to Na2SeO3 6:1. Moreover, the reaction time was 12 h, and the reaction temperature was 25 ℃. The mean diameter of DNT-Se prepared under such conditions was around 34.50 nm. Cell proliferation experiment results showed that DNT-Se was non-toxic to 293T human embryonic kidney cells and normal liver cells of AML-12 mice, but it could inhibit the proliferation of HepG2 cells, and the IC50 value of DNT-Se for HepG2 cells at 72 h was 42.54 μg/mL. The synthesis process of DNT-Se was fixed in this work, and the obtained nanoparticles were with smaller size and uniform distribution. Moreover, the DNT-Se could significantly inhibit the proliferation of HepG2 hepatoma cells without toxicity to normal cells, which was of good biosafety.

Little is known about the effect of the long-term application of organic and inorganic fertilizers on P-use efficiency, P budget, and the residual effect of P fertilizer. To clarify the effect of different fertilization on soil P balance in a rice (Oryza sativa L.)–wheat (Triticum aestivum L.) rotation system is helpful to promote the sustainable development of agriculture. Thus, a thirty-five-year fertilizer experiment was conducted with eight treatments, including an unfertilized control (CK); chemical nitrogen (N), phosphorus (P), and potassium (K) fertilizers; and organic manure (M) either alone or in combination treatments (N, NP, NPK, M, MN, MNP, and MNPK). The results indicated that crop yields and P uptake were higher in the combined application of manure and chemical fertilizer treatments than in the manure or chemical fertilizer alone treatments. Soil P budget indicated a 23.4–55.4 kg P ha−1 yr−1 surplus in the organic combined with or without mineral fertilizer treatments, but the soil P budget indicated a 20.0 and 21.9 kg P ha−1 yr−1 deficit in the control and N treatments. The proportion of residual fertilizer P converted to soil available P in NP, NPK, M, MN, MNP, and MNPK treatments was 4.5%, 4.8%, 19.1%, 19.0%, 11.5%, and 13.3%, respectively, over a 35-year period. Furthermore, according to the higher P content and crop uptake in organic manure treatment compared with chemical P fertilizer alone, an organic addition could effectively reduce the use of chemical fertilizer and become an effective way of sustainable development in practice. Therefore, the combined application of organic and inorganic fertilizer will be a practical method to increase crop yields and soil P status in a rice–wheat planting system.

Understanding the rivalry in infringement-litigation dynamics is critical for firms in the telecommunication industry. While the number of cross-border patent disputes in these years has surged owing to the globalized economy, the existing literature primarily focuses on patent disputes among telecommunication companies in the national jurisdiction. Hence, to capture the rivalry in the telecommunication industry more comprehensively, we utilize the evolutionary social network to explore the patent dispute data in the International Trade Commission (ITC), which is a crucial legal battleground for enterprises with international business. Through developing a dynamic litigation network and discussing the possible role of the positions in compliance with their interacting relationship, we illustrated that companies involved in ITC investigations can be segmented into key players, frequent respondents, strategic applicants, as well as peripheral enterprises, and the litigation strategies implicated behind four groups of firms stress the strategic nature of ITC investigations. According to the findings, this study contributes to the literature on patent litigation in the telecommunication field and social network relationships. In addition, this paper suggests that telecommunication companies should develop litigation strategies based on their positions and roles in the competition network, and policymakers need to have a deeper understanding of the competition practices in the global legal context.

IntroductionPhysical exercise is considered a useful non-pharmacological adjunctive treatment for promoting recovery from substance use disorders (SUD). However, adherence to physical exercise treatments is low, and little is known about what factors are associated with the initiation and maintenance of physical exercise behaviors. The aim of this study was to explore the psychosocial factors underlying these behaviors in individuals with SUD using an integrated theoretical model based on the health action process approach (HAPA) and the theory of planned behavior (TPB).MethodsA total of 1,197 individuals with SUDs (aged 37.20 ± 8.62 years) were recruited from 10 compulsory isolation drug rehabilitation centers in Zhejiang Province via convenience sampling according to a set of inclusion criteria. Self-reported data were collected to assess task self-efficacy (TSE), maintenance self-efficacy (MSE), recovery self-efficacy (RSE), outcome expectations (OE), action planning (AP), coping planning (CP), social support (SS), subjective norms (SN), attitude behavior (AB), behavioral intention (BI), perceived behavioral control (PBC), risk perception (RP), exercise stage, and exercise behavior in this integrated model. ANOVA and structural equation modeling (SEM) were used to evaluate this model.ResultsOne-way ANOVA revealed that the majority of the moderating variables were significantly different in the exercise phase. Further SEM showed that the model fit the data and revealed several important relationships. TSE, RP, SS, AB, and SN were indirectly associated with physical exercise behavior in individuals with SUD through the BI in the SUD initiation stage. In addition, PBC was directly related to physical exercise behavior in individuals with SUD. In the maintenance stage, MSE, AP, CP and exercise behavior were significantly related. Moreover, AP and CP were mediators of BI and MSE.ConclusionThis study is the first attempt to integrate patterns of physical exercise behavior in individuals with SUD. The HAPA-TPB integration model provides a useful framework for identifying determinants of physical exercise behavioral intentions and behaviors in individuals with SUD and for explaining and predicting the initiation and maintenance of physical exercise behaviors in these individuals. Moreover, the model provides scientific guidance for the enhancement of physical exercise adherence in individuals with SUD.

Endocannabinoids (eCBs) exert considerable influence over energy metabolism, lipid metabolism, and glucose metabolism within the human body. Among the most biologically active cannabinoids identified thus far are 2-arachidonoylglycerol (2-AG), arachidonoyl ethanolamide (AEA), 1-stearoylglycerol (1-SRG), and stearoyl ethanolamide (SEA), which are derived from arachidonic acid (AA) and stearic acid (SA). However, despite the unique in bioactivities exhibited by eCBs, their determination in plasma has been hindered by the lack of sensitive analytical methods. The aim of this study was to develop and validate a highly sensitive and rapid method using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for accurate measurement of AEA, SEA, 2-AG, 1-SRG, AA, and SA levels in human plasma samples. Sample preparation involved a protein precipitation method and a methyl tert-butyl ether liquid-liquid extraction method. Chromatographic separation was accomplished by utilizing an ACQUITY UPLC BEH C8 column with a mobile phase of acetonitrile containing 0.1% formic acid and water containing 0.1% formic acid, flowing at a rate of 0.35 mL/min. AA-d8, 2-AG-d5, and AEA-d8 were selected as deuterated internal standards. The analytes were determined with MRM in both positive and negative ion mode. The lower limit of quantification ranged from 0.1 to 400 ng/mL, and the correlation coefficient (R2) was >0.99. Inter-day and intra-day precision exhibited values of 0.55–13.29% and 0.62%–13.90%, respectively. Recovery and matrix effect were within the range of 77.7%–109.7%, and 90.0%–113.5%, respectively. Stability tests confirmed the acceptability of all analytes. To demonstrate the effectiveness of the approach, it was implemented to assess and compare plasma samples from healthy volunteers (n = 49) and individuals with non-alcoholic fatty liver disease (NAFLD) (n = 62). The study revealed significant differences in AEA, SEA, AA, and SA levels between the two groups.

Summary: Iron overload is closely associated with metabolic dysfunction. However, the role of iron in the hypothalamus remains unclear. Here, we find that hypothalamic iron levels are increased, particularly in agouti-related peptide (AgRP)-expressing neurons in high-fat-diet-fed mice. Using pharmacological or genetic approaches, we reduce iron overload in AgRP neurons by central deferoxamine administration or transferrin receptor 1 (Tfrc) deletion, ameliorating diet-induced obesity and related metabolic dysfunction. Conversely, Tfrc-mediated iron overload in AgRP neurons leads to overeating and adiposity. Mechanistically, the reduction of iron overload in AgRP neurons inhibits AgRP neuron activity; improves insulin and leptin sensitivity; and inhibits iron-induced oxidative stress, endoplasmic reticulum stress, nuclear factor κB signaling, and suppression of cytokine signaling 3 expression. These results highlight the critical role of hypothalamic iron in obesity development and suggest targets for treating obesity and related metabolic disorders.

This study aimed to assess the influences of short-term straw return combined with nitrogen (N) fertilizer on crop yield, soil properties, the bacterial community, and soil nitrogen cycling gene abundance in a rice–rapeseed planting system. A two-year field experiment was conducted in a paddy field from 2019 to 2021. There were four treatments in the experiment: −N−S, no N applied with no straw return; −N+S, no N applied with straw return; +N−S, N applied with no straw return; and +N+S, N applied with straw return. The results showed that short-term straw return combined with N fertilizer could increase crop yield and N use efficiency. N fertilizer application had a positive effect on Gemmatimonadota and Desulfobacterota abundance. Straw returning had a positive effect on Desulfobacterota and Proteobacteria abundance. N fertilization significantly increased the abundance of amoA-AOA, amoA-AOB, and nxrB in agricultural soils. Straw return and N fertilization were not conducive to denitrification. We conclude that short-term straw return combined with N fertilizer in rice-growing areas not only increase crop yield and improve crop N uptake but also increase SOM, total N, and NH4+ and improve the soil microbial activity and N use efficiency.

Magnetic soft microrobots have a wide range of applications in targeted drug therapy, cell manipulation, and other aspects. Currently, the research on magnetic soft microrobots is still in the exploratory stage, and most of the research focuses on a single helical structure, which has limited space to perform drug-carrying tasks efficiently and cannot satisfy specific medical goals in terms of propulsion speed. Therefore, balancing the motion speed and drug-carrying performance is a current challenge to overcome. In this paper, a magnetically controlled cone-helix soft microrobot structure with a drug-carrying function is proposed, its helical propulsion mechanism is deduced, a dynamical model is constructed, and the microrobot structure is prepared using femtosecond laser two-photon polymerization three-dimensional printing technology for magnetic drive control experiments. The results show that under the premise of ensuring sufficient drug-carrying space, the microrobot structure proposed in this paper can realize helical propulsion quickly and stably, and the speed of motion increases with increases in the frequency of the rotating magnetic field. The microrobot with a larger cavity diameter and a larger helical pitch exhibits faster rotary advancement speed, while the microrobot with a smaller helical height and a smaller helical cone angle outperforms other structures with the same feature sizes. The microrobot with a cone angle of 0.2 rad, a helical pitch of 100 µm, a helical height of 220 µm, and a cavity diameter of 80 µm achieves a maximum longitudinal motion speed of 390 µm/s.

Objective It is very important to study the upscaling transformation of hydraulic conductivity in fracture media for accurately characterizing the seepage field characteristics. Methods Based on the fracture medium statistics of crystalline rock in an underground water-sealed cavern, a 2-dimensional discrete fracture network (DFN) model is generated using the Monte-Carlo stochastic simulation technique. The hydraulic conductivity parameters of the variable size simulation domain and the equivalent hydraulic conductivity of each grid element after meshing in different sizes are calculated. The hydraulic conductivity representative elementary volume (REV) of the study area was analysed by the variation in hydraulic conductivity parameters with the size of the simulation area, and the equivalent hydraulic conductivity of grid cells smaller than REV was calculated by upscaling. Results The results show that the simulation domain can be regarded as an equivalent continuum when the size of the REV reaches 22 m×22 m. After meshing treatment, the equivalent hydraulic conductivity of the mesh cells which is smaller than REV calculated by the upscaling operation is significantly smaller than that of the corresponding composite mesh cells calculated by the crack network model. Conclusion Therefore, when the size of the seepage calculation unit reaches the REV size, its hydraulic conductivity parameters can effectively represent the hydraulic conductivity characteristics of a larger area in the study area. However, when the size of the seepage calculation unit is smaller than the REV size, its hydraulic conductivity parameters cannot effectively represent the hydraulic conductivity characteristics of the larger area in the study area. As a consequence, parameter upscaling calculation on the hydraulic conductivity parameters often has underestimated errors and is not of practical significance. For fractured media study areas with insufficient data, it is often difficult to determine the hydraulic conductivity REV of the study area. In this case, it can be considered that there is usually an underestimation error when the hydraulic conductivity of the small-scale area obtained from the hydrogeological test is upscaled. This conclusion provides a theoretical basis for the numerical simulation of the seepage field in fracture media in various related engineering projects.

Objective The morphological structure of the fractures in the rock mass is complex, and the fissures rough characteristics of the rock have a great influence on the permeability of the fractures. The current traditional numerical simulation software is mainly based on the macroscopic evaluation of equivalent continuous media, which cannot simulate the mesoscopic fluid flow characteristics within the tiny structure of the fracture. Although there exist models for assessing the permeability of rough fractures considering fracture roughness characteristics, it lacks physical meaning and has limitations in taking standard deviation of the profile height of rough fractures as the quantitative representation of rough characteristics. Methods Firstly, the W-M (Weierstrass-Mandelbrot) function was applied to construct a numerical model of a two-dimensional rough single fracture with different fractal dimensions. Secondly, the simulation of fluid flow at the mesoscopic scale was realized by programming based on the lattice Boltzmann method theory and analysed by combining the cubic law formulation with the value of standard deviation of the fracture profile height as a quantitative characterization of roughness. Results The results show that the cubic law formula using standard deviation value of the fracture profile height as a quantitative characterization of the roughness feature is inadequate. It is feasible to use the fractal dimension as a local modified cubic law formulation for the quantization of rough features. Conclusion The study of rock fracture fluid flow has important engineering practical significance for groundwater pollution control and groundwater resource assessment.

Magnesium (Mg) alloy is a focus biomaterial at present, while the rapid degradation rate in body fluid will hinder the practical clinical application. Therefore, surface modification of Mg alloy is essential. In the study, Mg–2Zn–Mn (ZM21) alloys and micro-arc oxidation (MAO) are used as the substrate and surface modification method. Then, the influence of potassium fluotitanate (K2TiF6) concentration in silicate basic electrolyte on the corrosion resistance and degradation of MAO coatings are studied. The results show that (1) TiF62− has obviously thickening effect, and adding 0.25 and 0.50 g/L K2TiF6 make the better corrosion resistance. (2) TiF62− concentration affects the coating quality, which is mainly attributed to F− generated by the reaction of TiF62− + 4OH− = TiO2 + 6F− + 2H2O. (3) Anatase TiO2 formed by ionization of TiF62− plays a role in sealing the micro-pores of MAO coating. (4) The hydrophilicity is improved, weight loss rate and pH value of MAO samples after immersion are obviously reduced, and available biological safety are improved, of which it is worth noting that the surface of K-0.75 sample has generated particles with a Ca/P ratio similar to hydroxyapatite (Ca10(PO4)6(OH)2, HA). (5) Cell adhesion test proves the available cytocompatibility.

Abstract Background EGFR‐mutant (EGFR‐M) and ALK‐positive (ALK‐P)are common in malignant pleural effusion (MPE) with metastatic non‐small‐cell lung cancer (NSCLC) (MPE‐NSCLC). The impact of thoracic tumor radiotherapy on survival in such patients remains unclear. We aimed to investigate whether thoracic tumor radiotherapy could improve overall survival (OS) in such patients. Methods According to whether or not patients accepted thoracic tumor radiotherapy, 148 patients with EGFR‐M or ALK‐P MPE‐NSCLC treated with targeted therapy were classified into two groups: DT group without thoracic tumor radiotherapy and DRT group with thoracic tumor radiotherapy. Propensity score matching (PSM) was performed to balance clinical baseline characteristics. Overall survival was analyzed by Kaplan–Meier, compared by log‐rank test, and evaluated using Cox proportional hazards model. Results Median survival time (MST) was 25 months versus 17 months in the DRT group and DT group. The OS rates at 1, 2, 3, 5 years in the DRT group and DT group were 75.0%, 52.8%, 26.8%, 11.1% and 64.5%, 28.4%, 9.2%, 1.8%, respectively (χ2 = 12.028, p = 0.001). Compared with DT group, the DRT group still had better survival after PSM (p = 0.007). Before and after PSM, factors associated with better OS through multivariable analysis were that thoracic tumor radiotherapy, radiotherapy, N0‐2, and ALK‐TKIs. Grades 4–5 radiation toxicities were not observed in patients; 8 (11.6%) and 7 (10.1%) out of the DRT group suffered from Grade 3 radiation esophagitis and radiation pneumonitis, respectively. Conclusion Our results for EGFR‐M or ALK‐P MPE‐NSCLC showed that thoracic tumor radiotherapy may be crucial factor in improving OS with acceptable toxicities. Potential biases should not be neglected: Further randomized controlled trials are necessary to confirm this result.

Abstract Aim To explore the genetic effects of CYP2C8, CYP2C9, CYP2J2, and EPHX2, the key genes involved in epoxyeicosatrienoic acid processing and degradation pathways in gestational diabetes mellitus (GDM) and metabolic traits in Chinese pregnant women. Methods A total of 2548 unrelated pregnant women were included, of which 938 had GDM and 1610 were considered as controls. Common variants were genotyped using the Infinium Asian Screening Array. Association studies of single nucleotide polymorphisms (SNPs) with GDM and related traits were performed using logistic regression and multivariable linear regression analyses. A genetic risk score (GRS) model based on 12 independent target SNPs associated with GDM was constructed. Logistic regression was used to estimate odds ratios and 95% confidence intervals, adjusting for potential confounders including age, pre-pregnancy body mass index, history of polycystic ovarian syndrome, history of GDM, and family history of diabetes, with GRS entered both as a continuous variable and categorized groups. The relationship between GRS and quantitative traits was also evaluated. Results The 12 SNPs in CYP2C8, CYP2C9, CYP2J2, and EPHX2 were significantly associated with GDM after adjusting for covariates (all P

Abstract Oncolytic viruses (OVs) represent a type of encouraging multi-mechanistic drug for the treatment of cancer. However, attenuation of virulence, which is generally required for the development of OVs based on pathogenic viral backbones, is frequently accompanied by a compromised killing effect on tumor cells. By exploiting the property of viruses to evolve and adapt in cancer cells, we perform directed natural evolution on refractory colorectal cancer cell HCT-116 and generate a next-generation oncolytic virus M1 (NGOVM) with an increase in the oncolytic effect of up to 9690-fold. The NGOVM has a broader antitumor spectrum and a more robust oncolytic effect in a range of solid tumors. Mechanistically, two critical mutations are identified in the E2 and nsP3 genes, which accelerate the entry of M1 virus by increasing its binding to the Mxra8 receptor and antagonize antiviral responses by inhibiting the activation of PKR and STAT1 in tumor cells, respectively. Importantly, the NGOVM is well tolerated in both rodents and nonhuman primates. This study implies that directed natural evolution is a generalizable approach for developing next-generation OVs with an expanded scope of application and high safety.

Abstract Background This study explored the feasibility of using EEG gamma-band (30–49 Hz) power as an index of cue-elicited craving in METH-dependent individuals. Methods Twenty-nine participants dependent on methamphetamine (METH) and 30 healthy participants were instructed to experience a METH-related virtual reality (VR) social environment. Results Individuals with METH dependence showed significantly stronger self-reported craving and higher gamma power in a VR environment than healthy individuals. In the METH group, the VR environment elicited a significant increase in gamma power compared with the resting state. The METH group then received a VR counterconditioning procedure (VRCP), which was deemed useful in suppressing cue-induced reactivity. After VRCP, participants showed significantly lower self-reported craving scores and gamma power when exposed to drug-related cues than the first time. Conclusions These findings suggest that the EEG gamma-band power may be a marker of cue-induced reactivity in patients with METH dependence.

Energy footprint(EnF) quantifies the impact of human energy activities and the concept is evolving due to its broad coverage of environmental, social, economic and technical implications. This study performs the first comprehensive retrospective study on the general EnF concept with the aim to clarify its definition, mark recent practical developments and key modeling considerations. Given the existing variability in the definition of EnF, we propose a comprehensive and adaptive definition framework to address and better integrate this concept. The EnF has a wide range of practical uses for the country, industry, company, product and process. Typically, it can be considered as a sub-dimension of environmental footprint, serving to raise public awareness, guide energy policy, and inform technical improvements. Furthermore, we contend that EnF, as a practical indicator, can encompass not only environmental burden but also other facets such as economic well-beings, social costs and benefits. Thus, future studies should be carried out in a holistic perspective, considering the complex nexus between the energy-environment and the socioeconomic system. Priorities should be placed on detailed environmental and social life cycle assessment in renewable products and technology, with particular attention directed towards addressing uncertainty issues.

Insects exhibit remarkable abilities in navigating complex natural environments, whether it be evading predators, capturing prey, or seeking out con-specifics, all of which rely on their compact yet reliable neural systems. We explore the field of bio-inspired robotic vision systems, focusing on the locust inspired Lobula Giant Movement Detector (LGMD) models. The existing LGMD models are thoroughly evaluated, identifying their common meta-properties that are essential for their functionality. This article reveals a common framework, characterized by layered structures and computational strategies, which is crucial for enhancing the capability of bio-inspired models for diverse applications. The result of this analysis is the Strategic Prototype, which embodies the identified meta-properties. It represents a modular and more flexible method for developing more responsive and adaptable robotic visual systems. The perspective highlights the potential of the Strategic Prototype: LGMD-Universally Prototype (LGMD-UP), the key to re-framing LGMD models and advancing our understanding and implementation of bio-inspired visual systems in robotics. It might open up more flexible and adaptable avenues for research and practical applications.

Objective: G-protein-signaling modulator 1 (GPSM1) has been proved the potential role in brain tissues, however, whether GPSM1 in hypothalamic nuclei, especially in POMC neurons is essential for the proper regulation of whole-body energy balance remains unknown. The aim of our current study was to explore the role of GPSM1 in POMC neurons in metabolic homeostasis. Methods: We generated POMC neuron specific GPSM1 deficiency mice and subjected them to a High Fat Diet to monitor metabolic phenotypes in vivo. By using various molecular, biochemical, immunofluorescent, immunohistochemical analyses, and cell culture studies to reveal the pathophysiological role of GPSM1 in POMC neurons and elucidate the underlying mechanisms of GPSM1 regulating POMC neurons activity. Results: We demonstrated that mice lacking GPSM1 in POMC neurons were protected against diet-induced obesity, glucose dysregulation, insulin resistance, and hepatic steatosis. Mechanistically, GPSM1 deficiency in POMC neurons induced enhanced autophagy and improved leptin sensitivity through PI3K/AKT/mTOR signaling, thereby increasing POMC expression and α-MSH production, and concurrently enhancing sympathetic innervation and activity, thus resulting in decreased food intake and increased brown adipose tissue thermogenesis. Conclusions: Our findings identify a novel function of GPSM1 expressed in POMC neurons in the regulation of whole-body energy balance and metabolic homeostasis by regulating autophagy and leptin sensitivity, which suggests that GPSM1 in the POMC neurons could be a promising therapeutic target to combat obesity and obesity-related metabolic disorders.

Autoclaved aerated concrete (AAC), a lightweight porous material, has been widely used in the building field because of its energy savings. A solid waste called carbide slag with a high Ca(OH)2 content is a potential substitution for CaO to prepare AAC. In this study, carbide slag was used to replace quicklime to prepare carbide slag-based autoclaved aerated concrete (CS-AAC). The temperature, foaming rate, and rheological properties of the slurry during the foaming stage, the strength of the rough body, and the physical and mechanical properties of the autoclaved products were investigated. Hydration products, microstructure, and pore structure were further analyzed to investigate the mechanisms of carbide slag on the properties of AAC, and the use of sodium carbonate (SC) to improve the performance of CS-AAC was explored. The results show that the addition of carbide slag causes a degradation of the properties, including foaming rate and physic-mechanical properties. The “water locking” effect due to the irregular surface of the carbide slag results in an increase in slurry consistency. The increase in slurry consistency, as well as the decrease in slurry temperature is the main reason for the decrease in slurry foaming rate and roundness of bubbles, which are unfavorable for the strength development of AAC. Due to the alkali excitation characteristics of sodium carbonate. The addition of SC can react with Ca(OH)2 in the slurry to produce OH-, to promote cement hydration, which can accelerate the development of rough body strength, and save pre-curing time. The carbide slag-based AAC with 0.25% SC has a significant improvement in foaming properties and facilitates the generation of more C-S-H gels to form tobermorite under hydrothermal conditions, which improves the AAC properties. However, too much SC can consume a large amount of Ca(OH)2 and affects the production of tobermorite, which is not beneficial to the mechanical properties.

IntroductionObesity has been historically associated with nonalcoholic fatty liver disease (NAFLD), but it can also occur in lean individuals. However, limited data is available on this special group. To investigate the clinical and proteomic characteristics of lean subjects with NAFLD, and to identify potential clinical variables and plasma proteins for diagnosing NAFLD in lean individuals, we collected clinical data from a large cohort of 2,236 subjects.MethodsDiagnosis of NAFLD relied on detecting pronounced hepatic steatosis through abdominal ultrasonography. Participants were categorized into four groups based on body mass index: overweight NAFLD, overweight control, lean NAFLD, and lean control. Plasma proteomic profiling was performed on samples from 20 subjects in each group. The lean NAFLD group was compared to both lean healthy and obese NAFLD groups across all data.Results and discussionThe results indicated that the lean NAFLD group exhibited intermediate metabolic profiles, falling between those of the lean healthy and overweight NAFLD groups. Proteomic profiling of plasma in lean subjects with or without NAFLD revealed 45 statistically significant changes in proteins, of which 37 showed high diagnostic value (AUC > 0.7) for lean NAFLD. These potential biomarkers primarily involved lipid metabolism, the immune and complement systems, and platelet degranulation. Furthermore, AFM, GSN, CFH, HGFAC, MMP2, and MMP9 have been previously associated with NAFLD or NAFLD-related factors such as liver damage, insulin resistance, metabolic syndromes, and extracellular homeostasis. Overall, lean individuals with NAFLD exhibit distinct clinical profiles compared to overweight individuals with NAFLD. Despite having worse metabolic profiles than their healthy counterparts, lean NAFLD patients generally experience milder systemic metabolic disturbances compared to obese NAFLD patients. Additionally, the plasma proteomic profile is significantly altered in lean NAFLD, highlighting the potential of differentially expressed proteins as valuable biomarkers or therapeutic targets for diagnosing and treating NAFLD in this population.

Migratory pests are sudden outbreaks and widespread, putting national food security at risk. Entomological radar is most effective segment in monitoring insect migration, providing critical information for early warning and pest control. Traditional entomological radar can measure biological parameters such as mass and orientation using a low-resolution waveform and rotating linear polarization antenna. The new entomological radar uses a stepped chirp high-resolution waveform and instantaneous fully polarimetric system, which can considerably improve the accuracy of measuring insect biological data. However, in addition to the traditional polarization measurement errors, the stepped chirp waveform introduces new multiplicative error components to different polarization channels, resulting in a more complex imbalance between polarization channels, which requires high-precision polarization calibration. In response to the above issues, the fully polarimetric measurement model is optimized according to the characteristics of the high-resolution system, and a high-resolution system polarization error estimation method based on a sphere and a wire is proposed in this study, which can complete polarization calibration under the loose constraint of the calibrator attitude and compensate for the influence of channel inconsistency on polarization information measurement; additionally, an insect orientation estimation method based on a biological symmetry model is proposed, and the mechanism of cross-talk between polarization channels on orientation estimation is analyzed analytically. Finally, multifrequency high-resolution fully polarimetric radar (X, Ku, Ka) is used for polarimetric calibration and insect orientation measurement experiments, and the measurement error of orientation is less than 3°, which verified the feasibility and effectiveness of the proposed method.

Abstract Each year, billions of birds migrate across the globe, and interpretation of weather radar signals is increasingly being used to document the spatial and temporal migration patterns in Europe and America. Such approaches are yet to be applied in the East Asian‐Australasian Flyway (EAAF), one of the most species‐rich and threatened flyways in the world. Logistical challenges limit direct on‐ground monitoring of migratory birds in many parts of the EAAF, resulting in knowledge gaps on population status and site use that limit evidence‐based conservation planning. Weather radar data have great potential for achieving comprehensive migratory bird monitoring along the EAAF. In this study, we discuss the feasibility and challenges of using weather radar to complement on‐ground bird migration surveys in the flyway. We summarize the location, capacity and data availability of weather radars across EAAF countries, as well as the spatial coverage of the radars with respect to migrants' geographic distribution and migration hotspots along the flyway, with an exemplar analysis of biological movement patterns extracted from Chinese weather radars. There are more than 430 weather radars in EAAF countries, covering on average half of bird species' passage and non‐breeding distributions, as well as 70% of internationally important sites for migratory shorebirds. We conclude that the weather radar network could be a powerful resource for monitoring bird movements over the full annual cycle throughout much of the EAAF, providing estimates of migration traffic rates, site use, and long‐term population trends, especially in remote and less‐surveyed regions. Analyses of weather radar data would complement existing ornithological surveys and help understand the past and present status of the avian community in a highly threatened flyway.

Abstract Background The biomechanics generated by the clear aligner (CA) material changes continuously during orthodontic tooth movement, but this factor remains unknown during the computer-aid design process and the predictability of molars movement is not as expected. Therefore, the purpose of this study was to propose an iterative finite element method to simulate the long-term biomechanical effects of mandibular molar mesialization (MM) in CA therapy under dual-mechanical systems. Methods Three groups including CA alone, CA with a button, and CA with a modified lever arm (MLA) were created. Material properties of CA were obtained by in vitro mechanical experiments. MM was conducted by the rebound force exerted by CA material and the mesial elastic force (2N, 30° to the occlusal plane) applied to the auxiliary devices. Stress intensity and distribution on periodontal ligament (PDL), attachment, button and MLA, and displacement of the second molar (M2) during the iterations were recorded. Results There was a significant difference between the initial and cumulative long-term displacement. Specifically, compared to the beginning, the maximum stress of PDL decreased by 90% on average in the intermediate and final steps. The aligner was the main mechanical system at first, and then, the additional system exerted by the button and MLA dominated gradually. The stress of attachments and auxiliary devices is mainly concentrated on their interfaces with the tooth. Additionally, MLA provided a distal tipping and extrusive moment, which was the only group that manifested a total mesial displacement of the root. Conclusions The innovatively designed MLA was more effective in reducing undesigned mesial tipping and rotation of M2 than the traditional button and CA alone, which provided a therapeutic method for MM. The proposed iterative method simulated tooth movement by considering the mechanical characteristic of CA and its long-term mechanical force changes, which will facilitate better movement prediction and minimize the failure rate.

Early lipid accumulation is thought to contribute to liver regeneration through unclear functional mechanisms. Here the authors identify an epigenetic regulator, MIER1, that bridges the acute lipid accumulation and cell cycle gene transcription during liver regeneration after surgical resection in male mice.

Abstract Background Age‐associated sarcopenia is characterized of progressed loss of skeletal muscle power, mass, and function, which affects human physical activity and life quality. Besides, accompanied with sarcopenia, aged population also faces a series of metabolic dysfunctions. Irisin, the cleaved form of fibronectin type III domain‐containing protein 5 (FNDC5), is a myokine induced by exercise and has been shown to exert multiple beneficial effects on health. The goal of the study is to investigate the alterations of Fndc5/irisin in skeletal muscles during ageing and whether irisin administration could ameliorate age‐associated sarcopenia and metabolic dysfunction. Methods The mRNA and protein levels of FNDC5/irisin in skeletal muscle and serum from 2‐ and 24‐month‐old mice or human subjects were analysed using qRT‐PCR and western blot. FNDC5/irisin knockout mice were generated to investigate the consequences of FNDC5/irisin deletion on skeletal muscle mass, as well as morphological and molecular changes in muscle during ageing via histological and molecular analysis. To identify the therapeutic effects of chronic irisin treatment in mice during ageing, in vivo intraperitoneal administration of 2 mg/kg recombinant irisin was performed three times per week in ageing mice (14‐month‐old) for 4 months or in aged mice (22‐month‐old) for 1 month to systematically investigate irisin's effects on age‐associated sarcopenia and metabolic performances, including grip strength, body weights, body composition, insulin sensitivity, energy expenditure, serum parameters and phenotypical and molecular changes in fat and liver. Results We showed that the expression levels of irisin, as well as its precursor Fndc5, were reduced at mRNA and protein expression levels in muscle during ageing. In addition, via phenotypic analysis of FNDC5/irisin knockout mice, we found that FNDC5/irisin deficiency in aged mice exhibited aggravated muscle atrophy including smaller grip strength (−3.23%, P

The study of the mechanisms affecting the preparation parameters of carbonated steel slag is of great significance for the development of carbon sequestration materials. In order to elucidate the mechanism of the influence of moisture on CO2 diffusion and particle cementation in steel slag, the effects of different water–solid ratios and water contents on the mechanical properties, carbonation products, and pore structure of steel slag after carbonation were investigated. The results show that increasing the water–solid ratio of steel slag can control the larger initial porosity and improve the carbon sequestration capacity of steel slag, but it will reduce the mechanical properties. The carbonation process relies on pores for CO2 diffusion and also requires a certain level of moisture for Ca2+ dissolution and diffusion. Increasing the water content enhances particle cementation and carbonation capacity in steel slag specimens; however, excessive water hinders CO2 diffusion. Reducing the water content can increase the carbonation depth but may compromise gelling and carbon sequestration ability. Therefore, achieving a balance is crucial in controlling the water content. The compressive strength of the steel slag with suitable moisture and initial porosity can reach 118.7 MPa, and 217.2 kg CO2 eq./t steel slag can be sequestered.

In this paper, the fixed-time and preassigned-time synchronization issues of fully quaternion-valued fuzzy memristive neural networks are studied based on the dynamic event-triggered control mechanism. Initially, the fuzzy rules are defined within the quaternion domain and the relevant properties are established through rigorous analysis. Subsequently, to conserve resources and enhance the efficiency of the controller, a kind of dynamic event-triggered control mechanism is introduced for the fuzzy memristive neural networks. Based on the non-separation analysis, fixed-time and preassigned-time synchronization criteria are presented and the Zeno phenomenon under the event-triggered mechanism is excluded successfully. Finally, the effectiveness of the theoretical results is verified through numerical simulations.

The asymptotic synchronization of quaternion-valued delayed neural networks with impulses and inertia is studied in this article. Firstly, a convergence result on piecewise differentiable functions is developed, which is a generalization of the Barbalat lemma and provides a powerful tool for the convergence analysis of discontinuous systems. To achieve synchronization, a constant gain-based control scheme and an adaptive gain-based control strategy are directly proposed for response quaternion-valued models. In the convergence analysis, a direct analysis method is developed to discuss the synchronization without using the separation technique or reduced-order transformation. In particular, some Lyapunov functionals, composed of the state variables and their derivatives, are directly constructed and some synchronization criteria represented by matrix inequalities are obtained based on quaternion theory. Some numerical results are shown to further confirm the theoretical analysis.

Migration flocks have different forms, including single individuals, formations, and irregular clusters. The shape of a flock can change swiftly over time. The real-time clustering of multiple groups with different characteristics is crucial for the monitoring of dynamically changing migratory flocks. Traditional clustering algorithms need to set various prior parameters, including the number of groups, the number of nearest neighbors, or the minimum number of individuals. However, flocks may display complex group behaviors (splitting, combination, etc.), which complicate the choice and adjustment of the parameters. This paper uses a real-time clustering-based method that utilizes concepts from the algebraic graph theory. The connected graph is used to describe the spatial relationship between the targets. The similarity matrix is calculated, and the problem of group clustering is equivalent to the extraction of the partitioned matrices within. This method needs only one prior parameter (the similarity distance) and is adaptive to the group’s splitting and combination. Two modifications are proposed to reduce the computation burden. First, the similarity distance can be broadened to reduce the exponent of the similarity matrix. Second, the omni-directional measurements are divided into multiple sectors to reduce the dimension of the similarity matrix. Finally, the effectiveness of the proposed method is verified using the experimental results using real radar data.

Transient receptor potential vanilloid 4 (TRPV4) is a widely expressed cation channel that plays an important role in many physiological and pathological processes. However, most TRPV4 drugs carry a risk of side effects. Moreover, existing screening methods are not suitable for the high-throughput screening (HTS) of drugs. In this study, a cell model and HTS method for targeting TRPV4 channel drugs were established based on a calcium-activated chloride channel protein 1 Anoctamin 1 (ANO1) and a double mutant (YFP-H148Q/I152L) of the yellow fluorescent protein (YFP). Patch-clamp experiments and fluorescence quenching kinetic experiments were used to verify that the model could sensitively detect changes in intracellular Ca2+ concentration. The functionality of the TRPV4 cell model was examined through temperature variations and different concentrations of TRPV4 modulators, and the performance of the model in HTS was also evaluated. The model was able to sensitively detect changes in the intracellular Ca2+ concentration and also excelled at screening TRPV4 drugs, and the model was more suitable for HTS. We successfully constructed a drug cell screening model targeting the TRPV4 channel, which provides a tool to study the pathophysiological functions of TRPV4 in vitro.

In this article, a robust index named first-order network coherence (FONC) for the multi-agent systems (MASs) with layered lattice-like structure is studied via the angle of the graph spectra theory. The union operation of graphs is utilized to construct two pairs of non-isomorphic layered lattice-like structures, and the expression of the index is acquired by the approach of Laplacian spectra, then the corresponding asymptotic results are obtained. It is found that when the cardinality of the node sets of coronary substructures with better connectedness tends to infinity, the FONC of the whole network will have the same asymptotic behavior with the central lattice-like structure in the considered classic graph frameworks. The indices of the networks were simulated to illustrate the the asymptotic results, as described in the last section.

Conductive hydrogels, characterized by their excellent conductivity and flexibility, have attracted widespread attention and research in the field of flexible wearable sensors. This paper reviews the application progress, related challenges, and future prospects of conductive hydrogels in flexible wearable sensors. Initially, the basic properties and classifications of conductive hydrogels are introduced. Subsequently, this paper discusses in detail the specific applications of conductive hydrogels in different sensor applications, such as motion detection, medical diagnostics, electronic skin, and human–computer interactions. Finally, the application prospects and challenges are summarized. Overall, the exceptional performance and multifunctionality of conductive hydrogels make them one of the most important materials for future wearable technologies. However, further research and innovation are needed to overcome the challenges faced and to realize the wider application of conductive hydrogels in flexible sensors.

FOXO3a is a protein of the forkhead box family that inhibits tumour cell growth. One of the regulatory modes affecting the role of FOXO3a is microRNA targeting and degradation of its mRNA expression, and conversely, aberrant expression of FOXO3a as a transcription factor also influences microRNA levels. We summarized the results of the regulatory interactions of twenty-five microRNAs with FOXO3a in five types of malignant tumours and found that dual microRNAs synergize with FOXO3a to inhibit breast cancer cell growth including two groups; Three individual microRNAs collaborated with FOXO3a to restrain hepatocellular carcinoma progression; Twelve individual microRNAs antagonized FOXO3a to promote the development of a single tumour cell, respectively; and five microRNAs antagonized FOXO3a to contribute to the progression of more than two types of tumours. The above findings demonstrated the tumour suppressor effect of FOXO3a, but another result revealed that miR-485-5p and miR-498 inhibited the growth of hepatocellular carcinoma cells by antagonizing FOXO3a when acting in combination with other long-stranded non-coding RNAs, respectively, suggesting that FOXO3a at this moment plays the function of promoting the tumour progression. The PI3K/AKT, Snail, VEGF-NRP1, and Wnt/β-catenin signalling pathways perform crucial roles in the above process. It is anticipated that the above studies will assist in understanding the effects of FOXO3a-MicroRNA interactions in cancer genesis and development, and provide new perspectives in the treatment of malignant tumours.