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Abstract The increasing mortality rate of pancreatic cancer globally necessitates the urgent identification for novel therapeutic targets. This study investigated the expression, functions, and mechanistic insight of G protein inhibitory subunit 3 (Gαi3) in pancreatic cancer. Bioinformatics analyses reveal that Gαi3 is overexpressed in human pancreatic cancer, correlating with poor prognosis, higher tumor grade, and advanced classification. Elevated Gαi3 levels are also confirmed in human pancreatic cancer tissues and primary/immortalized cancer cells. Gαi3 shRNA or knockout (KO) significantly reduced cell viability, proliferation, cell cycle progression, and mobility in primary/immortalized pancreatic cancer cells. Conversely, Gαi3 overexpression enhanced pancreatic cancer cell growth. RNA-sequencing and bioinformatics analyses of Gαi3-depleted cells indicated Gαi3’s role in modulating the Akt-mTOR and PKA-Hippo-YAP pathways. Akt-S6 phosphorylation was decreased in Gαi3-depleted cells, but was increased with Gαi3 overexpression. Additionally, Gαi3 depletion elevated PKA activity and activated the Hippo pathway kinase LATS1/2, leading to YAP/TAZ inactivation, while Gαi3 overexpression exerted the opposite effects. There is an increased binding between Gαi3 promoter and the transcription factor TCF7L2 in pancreatic cancer tissues and cells. Gαi3 expression was significantly decreased following TCF7L2 silencing, but increased with TCF7L2 overexpression. In vivo, intratumoral injection of Gαi3 shRNA-expressing adeno-associated virus significantly inhibited subcutaneous pancreatic cancer xenografts growth in nude mice. A significant growth reduction was also observed in xenografts from Gαi3 knockout pancreatic cancer cells. Akt-mTOR inactivation and increased PKA activity coupled with YAP/TAZ inactivation were also detected in xenograft tumors upon Gαi3 depletion. Furthermore, bioinformatic analysis and multiplex immunohistochemistry (mIHC) staining on pancreatic cancer tissue microarrays showed a reduced proportion of M1-type macrophages and an increase in PD-L1 positive cells in Gαi3-high pancreatic cancer tissues. Collectively, these findings highlight Gαi3’s critical role in promoting pancreatic cancer cell growth, potentially through the modulation of the Akt-mTOR and PKA-Hippo-YAP pathways and its influence on the immune landscape.

Kiwifruit bacterial canker, caused by Pseudomonas syringae pv. actinidiae (PSA), poses a grave threat to the global kiwifruit industry. In this study, we examined the role of microRNAs (miRNAs) in kiwifruit’s response to PSA. Kiwifruit seedlings subjected to PSA treatment showed significant changes in both miRNA and gene expression compared to the control group. We identified 364 differentially expressed miRNAs (DEMs) and 7170 differentially expressed genes (DEGs). Further analysis revealed 180 miRNAs negatively regulating 641 mRNAs. Notably, two miRNAs from the miRNA482 family, miRNA-215-3p and miRNA-29-3p, were found to increase kiwifruit’s sensitivity to PSA when overexpressed. These miRNAs were linked to the regulation of NBS-LRR target genes, shedding light on their role in kiwifruit’s defence against PSA. This study offers insights into the miRNA482-NBS-LRR network as a crucial component in enhancing kiwifruit bioresistance to PSA infestation and provides promising candidate genes for further research.

This manuscript introduces an improved Cuckoo Search (CS) algorithm, known as BASCS, designed to address the inherent limitations of CS, including insufficient search space coverage, premature convergence, low search accuracy, and slow search speed. The proposed improvements encompass four main areas: the integration of tent chaotic mapping and random migration in population initialization to reduce the impact of random errors, the guidance of Levy flight by the directional determination strategy of the Beetle Antennae Search (BAS) algorithm during the global search phase to improve search accuracy and convergence speed, the adoption of the Sine Cosine Algorithm for local exploitation in later iterations to enhance local optimization and accuracy, and the adaptive adjustment of the step-size factor and elimination probability throughout the iterative process to convergence. The performance of BASCS is validated through ablation experiments on 10 benchmark functions, comparative experiments with the original CS and its four variants, and application to a robot path planning problem. The results demonstrate that BASCS achieves higher convergence accuracy and exhibits faster convergence speed and superior practical applicability compared to other algorithms. [ABSTRACT FROM AUTHOR]

After hydraulic fracturing, unconventional reservoirs frequently encounter challenges related to limited effective proppant support distance and suboptimal proppant placement. Due to the strong heterogeneity of offshore reservoirs, which causes varying fracture roughnesses depending on different lithologies, a systematic study of the relationship between roughness and proppant transport could optimize operational parameters. This study incorporates the box dimension method for fractal dimension analysis to quantify roughness in auto-correlated Gaussian distributed surfaces created by true triaxial tests. Combined with the numerical analysis of (computational fluid dynamics) CFD-DEM (discrete element method) for bidirectional coupling, the laws of proppant deposition and transport processes within fractures with different roughnesses are obtained through comparative verification simulations. The results show that for rougher fractures of shale, the proppants are transported farther, but at JRC_52, (joint roughness coefficient), where there may be plugging in curved areas, there is a risk of near-well blockages. Compared to the smooth model, fluctuations in JRC_28 (tight sandstone) drastically increase turbulent kinetic energy within the fracture, altering particle transport dynamics. Moreover, smaller proppants (d/w ≤ 0.3) exhibit better transport capacity due to gravity, but the conductivity of the proppant is limited when the particles are too small. A d/w of 0.4 is recommended to guarantee transport capacity and proppant efficiency near the well. Additionally, proppants injected sequentially from small to large in shale fractures offer optimal propping effects, and can take advantage of the better transport capacity of smaller proppants in rough fractures. The large proppant (d/w = 0.8) is primarily deposited by gravity and forms a sloping sand bed, which subsequently ensures the aperture of the fractures. This research provides a fresh perspective on the influence of fracture roughness on proppant transport in offshore unconventional reservoirs and offers valuable considerations for the order of proppant injection. [ABSTRACT FROM AUTHOR]

Human pose estimation is an important task in computer vision, which can provide key point detection of human body and obtain bone information. At present, human pose estimation is mainly utilized for detection of large targets, and there is no solution for detection of small targets. This paper proposes a multi-channel spatial information feature based human pose (MCSF-Pose) estimation algorithm to address the issue of medium and small targets inaccurate detection of human key points in scenarios involving occlusion and multiple poses. The MCSF-Pose network is a bottom-up regression network. Firstly, an UP-Focus module is designed to expand the feature information while reducing parameter computation during the up-sampling process. Then, the channel segmentation strategy is adopted to cut the features, and the feature information of multiple dimensions is retained through different convolutional groups, which reduces the parameter lightweight network model and makes up for the loss of the feature information associated with the depth of the network. Finally, the three-layer PANet structure is designed to reduce the complexity of the model. With the aid of the structure, it also to improve the detection accuracy and anti-interference ability of human key points. The experimental results indicate that the proposed algorithm outperforms YOLO-Pose and other human pose estimation algorithms on COCO2017 and MPII human pose datasets. [ABSTRACT FROM AUTHOR]

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Water-induced mechanically adaptive rubber nanocomposites were prepared by mixing bacterial cellulose whiskers (BCWs) suspension with carboxylated acerlonitrilebutadiene rubber (XNBR) latex, followed by latex blending method. The introduction of BCWs into XNBR enhanced the tensile storage modulus (F) significantly, which originated from the formation of a rigid 3D filler network within matrix as well as the interfacial interaction between filler and matrix. The water uptake ratio of nanocomposite films increased with BCWs content, from 5.5% for neat XNBR to 54% for nanocomposite with 20 phr (parts per hundred rubber) BCWs. Upon submersed in water, the nanocomposite films showed dramatic decrease in E', especially for which filled with high BCWs loadings. For example, E of nanocomposite with 20 phr BCWs was decreased by 98.04% after equilibrium swelling compared with only 52.02% for nanocomposite with 3 phr BCWs. The remarkable watertriggered modulus changes are attributed to the disentanglement of BCWs network after swelling. The prepared XNBR-BCWs nanocomposites with mechanically adaptive properties could contribute to develop the new type of rubber-based smart materials. POLYM. ENG. SCI., 59:58-65, 2019., INTRODUCTION Functional polymer nanocomposites which associate desirable nanofiller with polymer matrix and possess a broad range of properties (e.g., mechanics, electricity, thermology, and impermeability) have been devoted into academia and [...]

The oil and gas resources in the deep Paleogene system of the South China Sea are abundant. However, due to its poor reservoir physical properties and strong heterogeneity, the deep Paleogene system needs to be commercially exploited by hydraulic fracturing technology. In view of the challenges of offshore low-permeability reservoirs, large-scale fracturing is not allowed because of the limited operation sites and complex string structure. Taking the H oilfield in the South China Sea as the target, based on the concept of the integration of geologic and engineering techniques, parameters such as the number of fracturing stages and the fracture length were optimized by a numerical simulation, and a study on the slurry rate and fracturing scale was carried out based on the type of fracturing and the pipe string structure. The results show that multistage fracturing technology is available in low-permeability offshore oil fields. It is suggested to adopt networking fracturing technology with a "slick water + high slurry rate" framework. A higher rate is recommended, and the fracturing scale of each stage should be 50 m3 of the sands and 700 m3 of the fluids. This research provides a new model for offshore low-permeability oilfield development. [ABSTRACT FROM AUTHOR]

Reservoir rocks of the Pearl River Mouth Basin's Lufeng Sag have low porosity (average porosity 12.6%) and low permeability (average permeability 16.5 mD), requiring hydraulic fracturing to obtain economic production of oil and gas. To contribute to the understanding of these reservoirs, and to promote successful production in the region, we analyzed the mechanical properties of tight sandstone. Moreover, we introduced the shear/tensile strength factor, in combination with the fracture toughness and horizontal stress difference coefficient, as an innovative approach to characterize the ease of forming a complex fracture network after reservoir fracturing. Based on this, we established a fracability evaluation model suitable for offshore low-permeability sandstone reservoirs by an analytic hierarchy process from the perspective of whether the reservoir can form an effective transformation volume and complex fracture network after fracturing. The results indicate that the primary minerals of the target reservoir are quartz and clay minerals, and the natural fractures are not developed. The mechanical properties exhibit a high Young's modulus (ranging from 30.4 to 34.4 GPa) and high compressive strength (with cohesion between 41 and 45 MPa and an angle of internal friction between 31.0 and 33.5°). The relatively low tensile strength and fracture toughness values are conducive to fracture initiation and extension during the fracturing process. Through the fracability evaluation model constructed in this paper, the depth interval at 4155.1–4172.1 m is identified as a high-quality fractured layer. The results of this study not only provide theoretical guidance for target well and formation selection in the Lufeng Sag, but also have important practical implications for increasing oil and gas production from tight sandstone reservoirs. [ABSTRACT FROM AUTHOR]

Summary: Beta‐thalassaemia is an inherited haemoglobin disorder characterised by ineffective erythropoiesis (IE). The detailed pathogenesis of IE remains unclear. In this study, we used single‐cell RNA sequencing (scRNA‐seq) to examine IE in Th3/+ β‐thalassaemic mice. The results showed that the erythroid group was remarkably expanded, and genes involved in biological processes such as iron metabolism, haeme synthesis, protein folding, and response to heat were significantly upregulated from erythroid progenitors to reticulocytes in β‐thalassaemic mice. In particular, we identified a unique cell population close to reticulocytes, named ThReticulocytes, characterised by a high level of heat shock protein 70 (Hsp70) expression and dysregulation of iron metabolism and haeme synthesis signalling. Treatment of β‐thalassaemic mice with the haeme oxygenase inhibitor tin‐mesoporphyrin effectively improved the iron disorder and IE, and the ThReticulocyte population and Hsp70 expression were significantly suppressed. This study revealed in detail the progression of IE at the single‐cell level and possibly provided clues to find therapeutic targets in thalassaemia. [ABSTRACT FROM AUTHOR]

The Frank-Starling relation is a fundamental auto-regulatory property of the heart that ensures the volume of blood ejected in each heartbeat is matched to the extent of venous filling. At the cellular level, heart muscle cells generate higher force when stretched, but despite intense efforts the underlying molecular mechanism remains unknown. We applied a fluorescence-based method, which reports structural changes separately in the thick and thin filaments of rat cardiac muscle, to elucidate that mechanism. The distinct structural changes of troponin C in the thin filaments and myosin regulatory light chain in the thick filaments allowed us to identify two aspects of the Frank-Starling relation. Our results show that the enhanced force observed when heart muscle cells are maximally activated by calcium is due to a change in thick filament structure, but the increase in calcium sensitivity at lower calcium levels is due to a change in thin filament structure.