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The angiotensin II type 2 receptor (AT2R) is a well-established component of the renin-angiotensin system and is known to counteract classical activation of this system and protect against organ damage. Pharmacological activation of the AT2R has significant therapeutic benefits, including vasodilation, natriuresis, anti-inflammatory activity, and improved insulin sensitivity. However, the precise biological functions of the AT2R in maintaining homeostasis in liver tissue remain largely unexplored. In this study, we found that the AT2R facilitates liver repair and regeneration following acute injury by deactivating Hippo signaling and that interleukin-6 transcriptionally upregulates expression of the AT2R in hepatocytes through STAT3 acting as a transcription activator binding to promoter regions of the AT2R. Subsequently, elevated AT2R levels activate downstream signaling via heterotrimeric G protein Gα12/13-coupled signals to induce Yap activity, thereby contributing to repair and regeneration processes in the liver. Conversely, a deficiency in the AT2R attenuates regeneration of the liver while increasing susceptibility to acetaminophen-induced liver injury. Administration of an AT2R agonist significantly enhances the repair and regeneration capacity of injured liver tissue. Our findings suggest that the AT2R acts as an upstream regulator in the Hippo pathway and is a potential target in the treatment of liver damage.

Given the prominence of 3-D sensors in recent years, 3-D point clouds are worthy to be further investigated for environment perception and scene understanding. Learning accurate local and global contexts in point clouds is pivotal for semantic segmentation, and neighbor aggregation (NA) and transformers have achieved notable success in local and global perception in point cloud analysis, respectively. Nevertheless, studying each independently is far from the optimal solution for comprehensive feature learning. To address this, we take a novel step toward investigating and integrating the structures of NA and transformers. In this article, we introduce Point Neighbor Aggregation with Transformer (PointNAT), a conceptually straightforward and effective approach aiming to enhance the performance of 3-D point cloud semantic segmentation. PointNAT consists of an NA block (NAB) for local perception, a point transformer block (PTB) for global modeling, and a hybrid block to connect NABs and PTBs. NABs effectively learn complex local features at varying scales through an improved NA operation and a multihead mechanism. PTBs efficiently perform global attention using a small set of learnable key points. Hybrid blocks serve as high-and-low frequency signal hybridizers, merging the strengths of these two blocks by adaptively assigning hybrid weights to local and global contexts. We have evaluated the performance of PointNAT with state-of-the-art networks on several benchmarks, including Stanford Large-Scale 3-D Indoor Spaces (S3DIS), Toronto3D, and SensatUrban. PointNAT achieves mean intersection over union (mIoU) scores of 77.8%, 84.7%, and 65.2% in these three datasets. Furthermore, it outperforms the baseline approach PointNeXt by 3.0%, 1.3%, and 4.2% while utilizing only 59.9% of the parameters and 15.2% of the floating-point operations (FLOPs). The results demonstrate PointNAT’s superior ability in accurately segmenting large-scale 3-D point cloud scenes, emphasizing its potential to advance environment perception and scene understanding. Our code is available at https://github.com/zeng-ziyin/PointNAT.

To evaluate the role of non-metallic element (Si and C) on the microstructural evolution and mechanical properties of Fe2.5CoNiCu high-entropy alloys (HEAs), two series of Fe2.5CoNiCuSix(x=0.1−0.3, molar fraction) and Fe2.5CoNiCuCx(x=0.15−0.4, molar fraction) HEAs were prepared by vacuum induction melting. The results show that the amounts of C and Si additions significantly stimulate the transformation of BCC/FCC dual phases into a single FCC structure, and the microstructural evolution appears to be more strongly influenced by the C addition. The Fe2.5CoNiCuSi0.2HEA presents high hardness (HV 439.5) and tensile strength (868 MPa), which is attributed to the solution strengthening and grain refinement effect. Both the hardness and strength of Fe2.5CoNiCuCxHEAs increase with the addition of C, due to the formation of carbides and solution strengthening. This demonstrates that adding non-metallic element (C or Si) is a viable approach for enhancing the strength and hardness of HEAs.

This paper analyses the impact of the poverty alleviation relocation (PAR) program on rural household income and evaluates the heterogeneous income effects of various relocation modes, based on a panel dataset of relocated households from 16 counties in eight Chinese provinces. The results show that participation in the PAR increases the income of both rural and urban resettlers. More specifically, it has a significant positive effect on agricultural and wage income for rural and urban resettlers, respectively. Further analyses show that the income increase for rural resettlers was mainly due to agricultural technology training and that the income increase for town resettlers was attributed to medical security. For the village resettlers, policies should focus on strengthening the development of local industries and training of agricultural technologies. For the urban resettlers, non-agricultural employment and public services in the urban resettlement areas should be promoted.

Open-circuit fault ride-through (FRT) is indispensable for the reliable operation of modular multilevel converters (MMCs). In this paper, finite-control-set model predictive control (FCS-MPC)-based fault detection and isolation (FDI) and fault-tolerant (FT) schemes are proposed for cascaded open-circuit FRT of MMCs. Taking advantage of the known switching state in FCS-MPC, the errors between the applied and estimated inserted submodule (SM) numbers are utilized for FDI directly. These fault diagnostic signals are independent of the voltage and current ratings and not sensitive to parameter variations. Moreover, it can locate the fault very fast within a fundamental period. By introducing the healthy state set of the SMs, an FCS-MPC strategy with cascaded open-circuit FRT is developed. Switching combinations, which will insert the faulty SMs, are inherently avoided by imposing an additional constraint in the cost function. This integrates the FRT into the control scheme, thereby, resulting in seamless FT operations. The reliability improvement by the proposed FRT scheme is numerically analyzed to present the effectiveness of the proposed method. Experimental results show that open-circuit faults can be detected and isolated within several milliseconds and the cascaded open-circuit faults of MMCs can be seamlessly ridden through by the proposed scheme.

Several brain tumors is closely related to the disorder of chromatin histone modification, whereas the epigenetic mechanisms of the incidence of highly malignant adult glioma is not yet deeply studied. Deletion or mutation of the MEN1gene, which encodes the epigenetic regulator menin, specifically induces poorly differentiated neuroendocrine tumors; however, the biological and clinical importance of MEN1in the nervous system remains poorly understood. Menin expression was robustly activated in 44.4% of adult gliomas. Abnormally high expression of menin was closely related to a shorter median survival time of 20 months, a larger tumor volume and a higher percentage of Ki67 staining. Interestingly, menin expression was also activated in the cytoplasm of tumor cells (38.8%) and was also closely related to the poor prognosis of patients with glioma. Importantly, in a screening of 96 types of small-molecule targeted histone modification regulators, menin inhibitors were found to significantly block the proliferation of adult glioma cells. Our findings confirm that menin is a potential biomarker of poor prognosis in adult gliomas, independent of the WHO grade. Targeting menin may effectively inhibit certain gliomas, and this information provides novel insight into therapeutic strategies for glioma.

Three types of in-situ TiC (5 vol%, 10 vol% and 15 vol%) reinforced high entropy alloy CoCrFeNi matrix composites were produced by vacuum induction smelting. The effect of two extreme cooling conditions (i.e., slow cooling in furnace and rapid cooling in copper crucible) upon the microstructure and mechanical properties was examined. In the case of slow cooling in the furnace, TiC was found to form mostly along the grain boundaries for the 5 vol% samples. With the increase of TiC reinforcements, fibrous TiC appeared and extended into the matrix, leading to an increase in hardness. The ultimate tensile strength of the composites shows a marked variation with increasing TiC content; that is, 425.6 MPa (matrix), 372.8 MPa (5 vol%), 550.4 MPa (10 vol%) and 334.3 MPa (15 vol%), while the elongation-to-failure (i.e., ductility) decreases. The fracture pattern was found to transit from the ductile to cleavage fracture, as the TiC content increased. When the samples cooled rapidly in copper crucible, the TiC particles formed both along the grain boundaries and within the grains. With the increase of TiC volume fraction, both the hardness and ultimate tensile strength of the resulting composites improved steadily while the elongation-to-failure declined. Therefore, the fast cooling can be used to drastically improve the strength of in-situ TiC reinforced CoCrFeNi. For example, for the 15 vol% TiC/CoCrFeNi composite cooled in the copper crucible, the hardness and ultimate tensile strength can reach as high as 595 HV and 941.7 MPa, respectively. [ABSTRACT FROM AUTHOR]

Due to the size effects of rockfill materials, the settlement difference between numerical simulation and in situ monitoring of rockfill dams is a topic of general concern. The constitutive model parameters obtained from laboratory triaxial tests often underestimate the deformation of high rockfill dams. Therefore, constitutive model parameters obtained by back analysis were used to calculate and predict the long-term deformation of rockfill dams. Instead of using artificial neural networks (ANNs), the response surface method (RSM) was employed to replace the finite element simulation used in the optimization iteration. Only 27 training samples were required for RSM, improving computational efficiency compared with ANN, which required 300 training samples. RSM can be used to describe the relationship between the constitutive model parameters and dam settlements. The inversion results of the Shuibuya concrete face rockfill dam (CFRD) show that the calculated settlements agree with the measured data, indicating the accuracy and efficiency of RSM.

Poly(1,3-dioxolane) (PDO) is widely used as a pH- and temperature-sensitive water-soluble polymer applied in functional hydrogels and nanoparticles. In this contribution, we report a series of highly efficient rare-earth triflate catalysts for a Brønsted-acid-free ring-opening polymerization of DO. The repeat unit of PDO comprises perfectly alternating hydrophilic ethylene glycol and hydrophobic methyl aldehyde units leading to hydrogen-bonding-controlled self-assembly in aqueous solution. Spherical aggregates are observed in transmission electron microscopy images whose sizes can be tuned by concentration and temperature, further confirming that the hydrate is derived from “blocked” water molecules through hydrogen bonding. The size and morphology of the aggregates can be modulated not only by the annealing process owing to the realignment of semicrystalline regions but also by metal salts generating rodlike, wormlike, or spherical structures. In this case, PDO is able to act as both a surfactant and as a reductant on account of the acidolysis of acetal moieties, which form a core–shell Cu-decorated hybrid material in situ in one step, thus providing a promising future template for the generation of metal nanoparticles.

Using a household survey data collected from four leading maize producing provinces in China, this paper studies the decisions of maize farmers on seed choices and variety portfolios when asymmetrical information exists in the market. Our findings indicate, while farmers generally tend to adopt new varieties with the expectation of potential higher yield, the primary driver to do so for those who have less information on seed varieties is to reduce production risk. Improving seed market management and providing more seed information to farmers would be beneficial in choosing seed varieties and maize production.

In order to uncover truths to serve justice, case-related data collected from a digital investigation requires substantial resources to analyze, especially in time-critical situations. At present, however, digital forensics has not evolved to meet this ever-increasing demand. Digital forensic triage is a promising solution, as it is designed to maximize the use of resources according to a system of priorities, and hence the efficiency and effectiveness of forensic examinations can be increased. Nevertheless, the lack of concrete methods limits efforts to implement triage. This paper presents a practical approach that is designed to build a prioritizing solution. In this work a newprocess model is derived based on the presented approach, and it is particularly suited to scenarios where forensic examiners do not have enough time and resources to conduct a full examination and analysis. An example is described to demonstrate how this approach can be used to meet the requirements of network forensic investigations.

This paper presents a technique for monocular Structure from Motion (SFM) that reconstructs 3D world shape. The technique proposed uses optical flow for 2D pixel pair matching and Angular Bundle Ajustment (ABA) for 3D structure refinement. The proposed strategy has two main advantages. Firstly, optical flow fields provide sufficient dense correspondence of image point pairs and secondly, ABA outperforms classic BA variants, especially for the points relatively far from camera. The reconstruction results obtained in realistic scenario demonstrate the effectiveness and accuracy of the proposed algorithm.

In photovoltaic MPPT control ,Compared with the traditional methods ,the conventional fuzzy algorithm had overcome the shortcomings of low accuracy, tracking slow and low efficiency from the external environment changes, And have no need to have excessive demands on the precision of the sensor and no "false positives" , Volatile situation still exist around the track points for it is asynchronous control, so there is a steady state error .A new method was proposed which combines the principle of fuzzy control and the PID control theory in this paper , The simulation results show the fuzzy PID can not only quickly respond to changes in the external environment, which can effectively eliminate the work of the maximum power point of the oscillation in fuzzy control and also make up shortcomings of a longer transition time. the simulation results proved the superiority of this algorithm.

The surface centralized control system of belt transmission of coal mine is the main channel coal transmission in coal mine, whether or not to normally operate directly affect the safety of coal production and economic benefits. With the expansion of coal production, the original capacity and safety of the belt transport cannot meet the development needs of the current. In response to the problems above, this system will the surface belt transmission of coal mine factory. Focus on control, to realize centralized control of the system. And perfect testing and protecting of the most vital part of the system.

The factors resulted in the cracking of Xiao-wan arch dam are extremely complicated. A numerical analysis based on elastic-viscoplastic mechanics theory has been developed to study the cracks in the middle diversion pier of Xiaowan Arch Dam. This analysis aims to investigate the cause of cracks and the reliability and accuracy of the analysis model have been examined. By using this analysis and the obtained results, the following conclusions are drawn: 1) cracks were not induced by a single cause, but a multitude of various effect such as stresses induced by thermal movements, the bond between the anchor cables and the surrounding concrete and the pressure due to the impounded water, amongst which the thermal stress is the most significant reason; and 2) with the presence of water in cracks, if the drainage hole continues to run overflowing water, the stress intensity factor of a crack tip will exceed the fracture toughness of the concrete. With the hydraulic fracture effect, the crack will grow continuously. The findings derived from this study will provide useful information for future projects of the similar nature.

The behaviour of pile-groups subjected to lateral soil pressure is a key consideration in establishing the design parameters of pile-groups. In this paper, one representative section of the Chongqing Jiangdong slope is taken as an example. The existence of an arching zone around pile groups for granular and fine-grained soils is first examined using the finite element computer code CORE-3D. Pile load-displacement curves and the arching effect are considered together to explain how the stresses are transferred from the soil to the piles. The key parameters controlling the soil arching effect are centre-to-centre pile spacing (S), thickness of stable soil mass (H), depth (L) of pile embedment, pile diameter (D) and these were studied extensively. An empirical equation summarising the results is presented and the results have been adopted by the designer in practice.

With the implementation of Western Development, West-to-East Electricity Transmission Project and South-to-North Water Diversion Project, a large number of hydro-power stations have been built in the west middleland regions of China. Because of the complexity of terrain, geological and physical-mechanical conditions, the stability of large underground structures becomes one of the most important problems during the engineering design, construction and operation. This paper will take Tianchi hydro-power station as an example, according to the measured stresses at several points, the in-situ stress field is feedback analyzed by using the combination of the genetic algorithm and 3D finite element method. Then, the rheological model of bolted joint rock and nonlinear finite element method are adopted to calculate the displacement field, stress field and D-P point safety factor of the underground structure. The stability of the underground structure is discussed, the excavating and supporting scheme are also presented, and the supporting effect is evaluated. The achievements in this paper can not only be taken as the reference to the design, but also provide some design experiences for other underground structures.

A new type of poly (sulfosalicylic acid)/graphene modified electrode (PSA/GH/GCE) was fabricated by dispensing graphene (GH) on glassy carbon electrode (GCE) and then electro-polymerized sulfosalicylic acid onto GH/GCE with cyclic voltammtry method. It can be used with composite properties of biochemical materials for highly selective and sensitive detection of dopamine (DA) even in the presence of mass ascorbic acid (AA). The linear response range for DA was 70 nM to 700 μM, and the detection limit was 20 nM (S/N = 3).

The Catanchor Coefficient Method is widely adopted because of its simplicity and convenience. However, how to determine the value of catanchor coefficient is still a problem. In this paper, four typical large prestressed piers were analyzed via Finite Element Method (FEM) and the relationship between the catanchor coefficient and the tensile stress occurring inside the controlling part was studied. The results we obtained indicate that the tensile stress decreases nonlinearly when the catanchor coefficient increases. Moreover, it changes quickly when the catanchor coefficient is within the range from 1.10 to 2.00 but slowly when that is from 2.00 to 3.00 in contrast. Based on our conclusions, the range from 1.50 to 2.00 of catanchor coefficient is advised with the data of related prestressed piers.

The individually variable and unpredictable expression of CYP3A4compromises therapies with 50 of contemporary drugs. Gene variants explain only a fraction of this variability.

For currently unknown reasons, the evolution of CYP3A4 underwent acceleration in the human lineage after the split from chimpanzee. We investigated the significance of this event by comparing Escherichia coli-expressed CYP3A4 from humans, chimpanzee, and their most recent common ancestor. The expression level of chimpanzee CYP3A4 was ∼50% of the human CYP3A4, whereas ancestral CYP3A4 did not express in E. coli. Steady-state kinetic analysis with 7-benzyloxyquinoline, 7-benzyloxy-4-(trifluoromethyl)coumarin (7-BFC), and testosterone showed no significant differences between human and chimpanzee CYP3A4. Upon addition of α-naphthoflavone (25 µM), human CYP3A4 showed a slightly decreased substrate concentration at which 50% of the maximal rate Vmaxis reached for 7-BFC, whereas chimpanzee CYP3A4 showed a >2-fold increase. No significant differences in inhibition/activation were found for a panel of 43 drugs and endogenous compounds, suggesting that the wide substrate spectrum of human CYP3A4 precedes the human-chimpanzee split. A striking exception was the hepatotoxic secondary bile acid lithocholic acid, which at saturation caused a 5-fold increase in 7-BFC debenzylation by human CYP3A4 but not by chimpanzee CYP3A4. Mutagenesis of human CYP3A4 revealed that at least four of the six amino acids positively selected in the human lineage contribute to the activating effect of lithocholic acid. In summary, the wide functional conservation between chimpanzee and human CYP3A4 raises the prospect that phylogenetically more distant primate species such as rhesus and squirrel monkey represent suitable models of the human counterpart. Positive selection on the human CYP3A4 may have been triggered by an increased load of dietary steroids, which led to a novel defense mechanism against cholestasis.

CYP3A metabolizes 50 of currently prescribed drugs and is frequently involved in clinically relevant drug interactions. The understanding of roles and regulations of the individual CYP3Agenes in pharmacology and physiology is incomplete.

Sterol responsive element binding protein (SREBP) cleavage-activating protein (SCAP) is the key regulator of activation of SREBPs, which stimulate most enzymes in cholesterol and lipid synthesis. In order to investigate the molecular basis of lipid metabolism in the pig, a unique model for fat deposition, we isolated and characterized the porcine SCAP. The 4,096-bp full-length porcine SCAPcDNA contains an open reading frame of 3,840 bp. The predicted SCAP protein consists of 1,280 amino acids of 55–92% identity with its vertebrate counterparts. The porcine SCAPgene consists of at least 19 exons and 18 introns, which span over 13 kb of the genome. The porcine SCAPgene was mapped to chromosome 13q21–22 using a porcine-rodent somatic cell hybrid panel. Comparison of SCAPgenomic structures from various species revealed intron losses in porcine, Tetraodon and fugu SCAP, and intron gains in cow and chicken SCAP. Moreover, we isolated two novel splicing SCAPvariants with 193-bp (variant 2) in-frame deletion from testis and a variant with 291-bp (variant 3) in-frame deletion from liver and muscle, which may affect the function of the porcine SCAP. In conclusion, the intron gains and losses appear to have contributed to the shape of the modern SCAPfamily. The splice variants detected, first to be reported in any species, may be involved in the particulars of the fat metabolism in the pig. Our data lay foundation for further study of SCAPfunction in this species.Sterol responsive element binding protein (SREBP) cleavage-activating protein (SCAP) is the key regulator of activation of SREBPs, which stimulate most enzymes in cholesterol and lipid synthesis. In order to investigate the molecular basis of lipid metabolism in the pig, a unique model for fat deposition, we isolated and characterized the porcine SCAP. The 4,096-bp full-length porcine SCAPcDNA contains an open reading frame of 3,840 bp. The predicted SCAP protein consists of 1,280 amino acids of 55–92% identity with its vertebrate counterparts. The porcine SCAPgene consists of at least 19 exons and 18 introns, which span over 13 kb of the genome. The porcine SCAPgene was mapped to chromosome 13q21–22 using a porcine-rodent somatic cell hybrid panel. Comparison of SCAPgenomic structures from various species revealed intron losses in porcine, Tetraodon and fugu SCAP, and intron gains in cow and chicken SCAP. Moreover, we isolated two novel splicing SCAPvariants with 193-bp (variant 2) in-frame deletion from testis and a variant with 291-bp (variant 3) in-frame deletion from liver and muscle, which may affect the function of the porcine SCAP. In conclusion, the intron gains and losses appear to have contributed to the shape of the modern SCAPfamily. The splice variants detected, first to be reported in any species, may be involved in the particulars of the fat metabolism in the pig. Our data lay foundation for further study of SCAPfunction in this species.

There are currently no known acute myeloid leukemia (AML) specific antigens. Genetic ablation of CD33 using CRISPR/Cas9 engineering of the hematopoietic stem cell (HSC) transplant (VOR33) represents a synthetic biology approach to generating a leukemia-specific antigen in the transplant recipient. VOR33 enables anti-CD33 CAR-T cell killing of AML cells while sparing normal myeloid lineage development and function, thereby potentially avoiding myelosuppression and increasing the therapeutic index of anti-CD33 CAR-T therapy. Mobilized leukapheresis product represents an attractive starting material for the generation of both a CD33 null HSC transplant and a complementary CD33CAR T-cell product. In this study, we sought to determine the impact of dual mobilization with Granulocyte-Colony Stimulating Factor (G-CSF) and plerixafor (mozobil) on immune cell composition, T cell phenotype, and the functionality of these T cells to control AML tumor growth upon chimeric antigen receptor (CAR) transduction.

Canesin: Vor Biopharma: Current Employment, Current equity holder in publicly-traded company. Hoyt: Vor Biopharma: Current Employment, Current equity holder in publicly-traded company. Williams: Vor Biopharma: Current Employment, Current equity holder in publicly-traded company. Silva: Vor Biopharma: Current Employment, Current equity holder in publicly-traded company. Chng: Vor Biopharma: Current Employment, Current equity holder in publicly-traded company. Cummins: Vor Biopharma: Current Employment, Current equity holder in publicly-traded company. Ung: Vor Biopharma: Current Employment, Current equity holder in publicly-traded company. Qiu: Vor Biopharma: Current Employment, Current equity holder in publicly-traded company. Shin: Vor Biopharma: Current Employment, Current equity holder in publicly-traded company. Hu: Vor Biopharma: Current Employment, Current equity holder in publicly-traded company. Ge: Vor Biopharma: Current Employment, Current equity holder in publicly-traded company. Scherer: Vor Biopharma: Current Employment, Current equity holder in publicly-traded company. Chakraborty: Vor Biopharma: Current Employment, Current equity holder in publicly-traded company. Kassim: Vor Biopharma: Current Employment, Current equity holder in publicly-traded company.

Resistance to neoadjuvant chemotherapy in triple-negative breast cancer can be mediated by a reversible chemotherapy-tolerant state.