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Granitic veins (GVs) have a significant influence on the mechanical responses of tunnels excavated in granitic strata. Distinguishing the mechanical properties of host granites (HGs), GVs and vein-granite interfaces (VGIs) is critical. For this, this paper analyzed the mechanical behaviors and rupture processes of typical HG, GV, and VGI samples under uniaxial compression condition. For the rocks studied, although the linear axial stress‒strain relation can be identified and the deformation modulus can be determined, the transverse deformation developed nonlinearly with axial stress. As a result, the instantaneous Poisson's ratio increases continuously and may even exceed 0.5, making it extremely difficult to accurately determine the Poisson's ratio. In addition, the studied GV samples were found to be significantly brittle, indicating that large-scale GVs cannot be ignored when assessing rockburst hazards in granitic strata with brittle GVs. In terms of the rupture process, the HG and GV samples were gradually damaged by the formation of small-scale cracks and then ruptured by large cracks formed from small-scale cracks, whereas the VGI samples ruptured along large cracks with significant energy release. By examining the characteristic stress thresholds of these three granites, it is noted that the crack closure stress σcc exceeds both the crack initiation stress σci and the crack damage stress σcd for the HG and VGI samples. The transverse damage to a tested sample appears to be significantly greater than the axial damage, which is essentially related to the rock grain size and grain size distribution.

High-performance grinding wheels are critical tools for precision surface generation. In precision grinding processes, the coolant supply at the wheel-workpiece interface is critical for reducing grinding temperature and detrimental friction. For better lubrication and chip removal performance, the cavities or pores need to be generated throughout the grinding wheel. The ideal morphology of pores in grinding wheels should be inter-connected and capable of providing sufficient coolant. Conventional grinding wheel design and fabrication methods can only passively generate closed circular pores by using pore-forming agents. Increasing the percentage of pores in this way generally leads to an uncontrollable reduction in mechanical strength, while the closed pores are insufficient in cooling performance. In this paper, the grinding wheels with triply periodic minimal surface lattice structure are designed and fabricated, which achieves the regulable and inter-connected internal structure of grinding wheels. Meanwhile, to balance the relationship between the structural properties and performance indicators of porous grinding wheels, an optimal design method for the porous structure of grinding wheels is proposed. Finally, the grinding performance of the novel grinding wheels in comparison to electroplated diamond grinding wheels is investigated in terms of grinding force, specific grinding energy and ground surface roughness.

RNA plays an extensive role in a multi-dimensional regulatory system, and its biomedical relationships are scattered across numerous biological studies. However, text mining works dedicated to the extraction of RNA biomedical relations remain limited. In this study, we established a comprehensive and reliable corpus of RNA biomedical relations, recruiting over 30,000 sentences manually curated from more than 15,000 biomedical literature. We also updated RIscoper 2.0, a BERT-based deep learning tool to extract RNA biomedical relation sentences from literature. Benefiting from approximately 100,000 annotated named entities, we integrated the text classification and named entity recognition tasks in this tool. Additionally, RIscoper 2.0 outperformed the original tool in both tasks and can discover new RNA biomedical relations. Additionally, we provided a user-friendly online search tool that enables rapid scanning of RNA biomedical relationships using local and online resources. Both the online tools and data resources of RIscoper 2.0 are available at http://www.rnainter.org/riscoper.

TRIB3, a pseudokinase, was previously studied within only some specific cancer types, leaving its comprehensive functions in pan-cancer contexts largely unexplored. Here, we performed an integrated analysis of TRIB3 expression, prognosis, genetic alterations, functional enrichment and tumor immune-related characteristics in 33 cancer types. Our results showed that TRIB3 exhibits high expression levels across 24 different cancer types and correlates closely with unfavorable prognoses. Meanwhile, TRIB3 shows mutations in a wide spectrum of 22 distinct cancer types, with the predominant mutation types being missense mutations and gene amplifications, and significant changes in DNA methylation levels in 14 types of cancer. We further discovered that TRIB3 expression is significantly associated with cancer immune-related genome mutations, such as tumor mutational burden (TMB), microsatellite instability (MSI) and DNA mismatch repair (MMR), and infiltration of immunosuppressive cells, such as CD4+ Th2 cells and myeloid-derived suppressor cells (MDSCs), into the tumor microenvironment. These results indicated that the expression of TRIB3 might reshape the tumor immune microenvironment (TIME) and lead to immunosuppressive ''cold'' tumors. In addition, our results confirmed that the loss of function of TRIB3 inhibits cell proliferation, promotes apoptosis, and leads to significant enrichment of ''hot'' tumor-related immune pathways, at least in breast cancer cells, which further supports the important role of TRIB3 in cancer prognosis and TIME regulation. Together, this pan-cancer investigation provided a comprehensive understanding of the critical role of TRIB3 in human cancers, and suggested that TRIB3 might be a promising prognostic biomarker and a potential target for cancer immunotherapy.

For projects near the tectonic belt, mylonite of varying metamorphic degrees may be present. The matrix proportion of rock reflects its internal microscopic characteristics, thus it is beneficial for engineering geology to study the effect of the matrix proportion on the mechanical properties and rupture behaviors of rock. Samples of mylonitic granite and granitic protomylonite with varying matrix proportions were obtained from a ductile shear zone for a series of uniaxial compression and acoustic emission (AE) tests. The results showed that with the increase in matrix proportion, the average strength and elastic modulus of the samples increased, and the rock sample with the largest matrix proportion exhibited the maximum peak stress of 244.42 MPa, which was 45.86% greater than the average peak stress of the rock samples with the smallest matrix proportions. For the rock samples with larger matrix proportion, their mechanical parameters exhibited greater dispersion and the large-scale appearance of AE events occurred earlier, showing a relatively gradual failure process. These samples had larger accumulated AE parameter values and greater degree of failure. In contrast, for samples with smaller matrix proportions, the large-scale appearance of AE events occurred close to the peak stress, indicating that the occurrence of damage and fractures was centralized and instantaneous. These samples had lower accumulated AE parameter values and fewer cracks after failure. Additionally, for the rock samples with more matrix proportion, the average variance of the b-value was 1.1, which was lower than that of rock samples with the smallest matrix proportion (the average variance of the b-value was 3.7). Furthermore, it can be predicted that under certain stress, the failure depth around a tunnel is generally smaller when the strength of rock samples with larger matrix proportion is greater.

Novel plate-like (Ti, Zr)B2 toughened (Zr, Ti, W, Ta)C medium-entropy ceramics were designed based on the atomic scale, nanoscale, and microscale, and prepared via the in-situ reaction hot-pressing adopting (Ti, W, Ta)C and ZrB2 powders. The multiphase ceramics were primarily composed of the (Zr, Ti, W, Ta)C matrix and plate-like (Ti, Zr)B2. When the addition of ZrB2 exceeds 50 mol%, the residual ZrB2 causes the secondary primary phase to change from (Ti, Zr)B2 to (Zr, Ti)B2. The improvement of fracture toughness is primarily influenced by the plate-like (Ti, Zr)B2 on crack propagation mechanisms such as bridging effect and crack deflection. (Ti, W, Ta)C- 50 mol% ZrB2 (raw powder composition) exhibits outstanding mechanical properties, boasting a Vickers hardness of 24.9 GPa, fracture toughness of 5.5 MPa·m1/2, and flexural strength of 552 MPa, which present a novel avenue for achieving a synergistic enhancement in Vickers hardness and fracture toughness within medium-entropy carbide ceramics.

Remote sensing-based surface energy balance algorithms have been used to estimate water use of various crops. However, citrus evapotranspiration (ET) estimation is challenging mainly due to evergreen leaves and a clumped canopy structure. In this study, we evaluated the performance of two methods for calculating ET: the ensemble of OpenET models, which are mostly satellite thermal-based models, and the BAITSSS water and energy balance model. Calculated ET was compared with (i.) eddy covariance (EC) ET measurements and (ii.) water received (irrigation plus precipitation) data for two citrus orchards in San Joaquin Valley, California. Polaris-based soil hydraulic properties and measured volumetric water content were used for BAITSSS parameterization and initialization, respectively. Sentinel-2 based NDVI was used for BAITSSS simulation. Results showed that annual ET based on the OpenET ensemble model (1169 mm) was on average 30 % larger (r2 ∼ 0.71, RMSE ∼ 1.16 mm) than both EC ET (908 mm) and water received (886 mm). The disparity mostly occurred in spring. BAITSSS, on the other hand, showed mixed results compared to observations (r2 ∼ 0.77, RMSE ∼ 0.94 mm). Both measured from EC and modeled ET from BAITSSS and ensemble OpenET values were below grass reference ET (ETo) for the majority of the simulation period. Soil moisture and water received data indicated the orchards may have been deficit irrigated. Overall, this study highlights the challenges of ET modeling in citrus orchards and the need for improved estimation of ET for this specialty crop.

Summary: The onset of atherosclerosis (AS) is insidious, and early stage patients have atypical clinical symptoms. After being diagnosed in late stage, it is often prone to sudden and fatal cardiovascular events. Therefore, it is highly desirable to develop precise and efficient diagnosis and therapy strategies of AS. Benefiting from high signal-to-noise ratio, low detection limit, high specificity and sensitivity, a series of activatable fluorescent probes based on atherosclerotic microenvironment have emerged for identification and treatment of AS. In this review, we focus on the atherosclerotic microenvironment and briefly summarize the correlation between the structural transformation and fluorescence signal changes of mono-/double-activatable fluorescent probes upon biomarkers stimulation. Moreover, their cutting-edge progress for AS theranostics is described. Finally, the outlook for activatable theranostic probes based on atherosclerotic microenvironment is discussed to aim at promoting innovative research in imaging-guided precise AS therapy.

Background and objective: The intrinsic link between the compositional and structural attributes and the biomechanical functionality is evident in intervertebral discs. However, it remains unclear from a biomechanical perspective whether cartilage endplate (CEP) degeneration exacerbates intervertebral disc degeneration. Methods: This study developed and quantitatively validated four biphasic swelling-based finite element models. We then applied four quasi-static tests and simulated daily loading scenarios to examine the effects of CEP degradation. Results: Under free-swelling conditions, short-term responses were prevalent, with CEP performance changes not significantly impacting response proportionality. The creep test results showed the more than 50 % of the strain was attributed to long-term responses. Stress-relaxation testing indicated that all responses increased with disc degeneration, yet CEP degeneration's impact was minimal. Daily load analyses revealed that disc degeneration significantly reduces nucleus pulposus pressure and disc height, whereas CEP degeneration marginally increases nucleus pressure and slightly decreases disc height. Conclusions: Glycosaminoglycan content and CEP permeability are critical to the fluid-dependent viscoelastic response of intervertebral discs. Our findings suggest that CEP contributes to disc degeneration under daily loading conditions.

Summary: Optical imaging technology has become increasingly recognized for its utility in diagnosing atherosclerosis thanks to advantages such as high spatial resolution, rapid data acquisition, lack of radiation exposure, cost-effectiveness, minimal invasiveness, and limited side effects. However, traditional luminogens employed in optical diagnostics are often troubled by aggregation-caused quenching (ACQ) effect, causing diagnostic errors in vivo. Since Professor Tang discovered the aggregation-induced emission (AIE) phenomenon, AIE luminogens (AIEgens) have been rapidly developing and are considered as the next-generation fluorescent contrast agents for angiography and atherosclerotic diagnosis. This mini review will outline the use of AIEgens in angiography and the diagnosis of atherosclerosis, exploring different imaging models, including second near-infrared, two/multi-photon, and photoacoustic imaging, and will provide a forward-looking perspective on their potential in atherosclerotic diagnosis.

Permafrost in Mongolia is located in the transition zone between high-latitude and high-altitude permafrost regions of the Northern Hemisphere, with large temperature differences and complex subsurface characteristics. In this study, the reliability of the skin temperature data from the ERA5-Land product covering Mongolia is assessed via site observations. The ERA5-Land skin temperature dataset shows a cold bias, which is more pronounced in the cold season. Following calibration based on elevation differences, significant improvements are observed at both the annual scale (92 % improvement in RMSE (root mean square error) and 98 % improvement in MBE (mean bias error)) and the seasonal scale (78 % improvement in RMSE and 82 % improvement in MBE). Additionally, the spatial variations in the surface freezing index (SFI) and surface thawing index (STI) are most pronounced in the central and northeastern Mongolia. The SFI exhibits a significant decreasing trend of 7.16 °C·d/year, while the STI shows a significant increasing trend of 4.49 °C·d/year. Furthermore, the permafrost extent in Mongolia is simulated from 1950 to 2022 using the frost number (Fn) model and the temperature on top of permafrost (TTOP) model. The validated results indicate that the accuracy of the Fn model is relatively high, with an overall accuracy of 0.9 and a Kappa coefficient of 0.47. The permafrost extent in Mongolia has declined from 734.7 × 103 km2 in the 1950 s to 480.1 × 103 km2 in the 2010 s, with a prominent decrease of 3.2 × 103 km2/decade after 1994. According to the variations in permafrost extent during past 72 years, the Hovsgol and Khentii Mountain ranges have experienced significant permafrost degradation.

This study explores the thermal behavior of graphite-enhanced expanded polystyrene (GEPS) both with and without a rendering cover during cone calorimeter testing. We designed a sample holder with inserted thermocouples to capture temperature variations at different levels. Without a cover, the sample remained unignited under radiant intensity of 25 kW m−2, experiencing a brief temperature rise followed by stabilization. At 50 kW m−2, ignition occurred after a period of steady temperature. However, at 75 kW m−2, the temperature soared rapidly without a stable phase, leading to swift ignition. With a cover, the temperatures for all tested scenarios ultimately stabilized without ignition, even though the recorded values exceeded the ignition point under high heat fluxes. This indicates that the protective mechanism of render lies mainly in isolating mass transfer. Increasing the render's thickness from 3 mm to 5 mm delayed and slowed the initial temperature rise but had little impact on the final steady temperatures. Based on the energy conservation principles, a steady temperature prediction model for liquified GEPS and rendering cover was established. Notably, the calculated outcomes closely align with the measured temperatures. These findings provide valuable insights into the fire safety characteristics of GEPS and the protective effects of rendering covers.

Predation on livestock by large carnivores, such as snow leopard (Panthera uncia), is a global issue that leads to human-wildlife conflicts (HWC). In the Sanjiangyuan National Park (SNP) located in western China, traditional grazing practices have resulted in extensive utilization of snow leopard habitats as pasturelands. The presence of domestic animals in snow leopard habitats increases the likelihood of predation by snow leopards, thereby exacerbating human-snow leopard conflict. In this study, questionnaire surveys were utilized to investigate the attitudes of local herders in Bagan, a township at the southeastern periphery of SNP, towards snow leopard attacks on livestock. Additionally, infrared camera trapping was employed to explore the spatial and temporal overlap between snow leopards, bharals (Pseudois nayaur) and free-ranging livestock. The resulting overlap coefficients were utilized to quantify the competition in the space use and the overlap of daily activity rhythms respectively between these species based on infrared camera records. The questionnaire surveys revealed that snow leopards primarily targeted livestock during nocturnal hours, leading to negative attitudes among herders. Spatial overlap results indicated that bharal and livestock exhibited the highest degree of spatial utilization overlap (OI = 0.78), followed by snow leopard and bharal (OI = 0.75), as well as snow leopard and livestock (OI = 0.75). Furthermore, the temporal overlap results for daily activity rhythms demonstrated a high level of consistency between bharal and livestock (Δ = 0.95). Our findings indicated a high spatial overlap between free-ranging livestock and snow leopards, thereby increasing the likelihood of encounters between these two groups and subsequently heightening the potential for predation on livestock by snow leopards. This heightened predation risk was considered one of the primary drivers behind HWC. To mitigate retaliatory killing on snow leopards by herders and to safeguard herders’ interests, we have proposed a multipronged conservation program encompassing regular removal of animal traps, regulation of grazing areas, and reinforcement of supervision to minimize livestock susceptibility to predation.

Imaging the wave velocity field surrounding a borehole while drilling is a promising and urgently needed approach for extending the exploration range of the borehole point. This paper develops a drilling process detection (DPD) system consisting of a multifunctional sensor and a pilot geophone installed at the top of the drilling rod, geophones at the tunnel face, a laser rangefinder, and an onsite computer. A weighted adjoint-state first arrival travel time tomography method is used to invert the P-wave velocity field of rock mass while borehole drilling. A field experiment in the ongoing construction of a deep buried tunnel in southwestern China demonstrated the DPD system and the tomography method. Time-frequency analysis of typical borehole drilling detection data shows that the impact drilling source is a pulse-like seismic exploration wavelet. A velocity field of the rock mass in a triangular area defined by the borehole trajectory and geophone receiving line can be obtained. Both the borehole core and optical image validate the inverted P-wave velocity field. A numerical simulation of a checkerboard benchmark model is used to test the tomography method. The rapid convergence of the misfits and consistent agreement between the inverted and observed travel times validate the P-wave velocity imaging.

The fully dense Ti3SiC2-(Ti, Zr)B2 toughened (Ti, Zr)C-based composites were fabricated at 1400–1600 °C for the first time by dual in situ reactions hot-pressing with TiC, ZrB2, and Si as the initial powders. The influence of ZrB2, Si content and sintering temperature on the microstructure and mechanical properties of the composite was reported. When 10 mol% ZrB2 was added, Si combined with residual TiC to form Ti3SiC2 and SiC. However, with the addition of ZrB2 increase to 20 mol% and 30 mol%, Si participated in the formation of ZrSi and was not enough to react with TiC to form Ti3SiC2. The low-temperature in situ reactions, multiphase coupling effects, and the pinning effect of nano-SiC refine the microstructure of the composites. There are specific crystal orientation relationships between (Zr, Ti)C and (Ti, Zr)B2, as well as between (Ti, Zr)C and SiC. The layered Ti3SiC2 and plate-like (Ti, Zr)B2 by dual in situ reactions effectively improve the fracture toughness of the composites. The 10 ZB-15 possesses a highest fracture toughness of 6.1 MPa⋅m1/2. The 30 ZB-16 has the good comprehensive mechanical properties. The fracture toughness, flexural strength, and hardness of 30 ZB-16 is 5.6 MPa⋅m1/2, 679 MPa, and 26.4 GPa, respectively. The Ti3SiC2 and TiB2 formed during dual in situ reactions enables the composite to exhibit excellent oxidation resistance and wear resistance.

The integration of vegetable oil-based minimum quantity lubrication (VMQL) and cutting process has received widespread attention due to its great sustainability. Taking the great potential of biomimetics into consideration, constructing biomimetic structure on tool surface is expected to cause effective improvement of VMQL assisted cutting process. Inspired by five different kinds of biological structures, assembled multi-biomimetic structure (AMBS) was designed on Al2O3/TiC micro-nano-composite ceramic tool. Moreover, this work explored the effects of AMBS on VMQL assisted interrupted turning. Durable lubricant-transport behavior was examined experimentally and theoretically for the proposed AMBS. In addition, a theoretical index PAS integrating fracture resistance and cutting load was established to evaluate the mechanical performance of AMBS. Furthermore, tool wear was employed to analyze the experimental performance and validate the effectiveness of AMBS. The present work focused on the influences caused by the side length Lb of the biomimetic hexagonal structure, the laser angle Al and the shape of the superlipophilic region. It was found that impact, scratch and high temperature had limited effects on the wetting behavior of AMBS, resulting in the durable lubricant-transport behavior of AMBS. Index PAS can be utilized as a useful tool for pre-evaluating the mechanical performance of AMBS. The construction of AMBS led to decrease of both fracture resistance and cutting load. The tool performance was effectively enhanced since the decrease of cutting load had a greater impact. The optimum AMBS appeared when Lb was 250 μm, Al was 90° and the superlipophilic region had a convex shape.

The 2D limit equilibrium method is widely used for slope stability analysis. However, with the advancement of dump engineering, composite slopes often exhibit significant 3D mechanical effects. Consequently, it is of significant importance to develop an effective 3D stability calculation method for composite slopes to enhance the design and stability control of open-pit slope engineering. Using the composite slope formed by the mining stope and inner dump in Baiyinhua No. 1 and No. 2 open-pit coal mine as a case study, this research investigates the failure mode of composite slopes and establishes spatial shape equations for the sliding mass. By integrating the shear resistance and sliding force of each row of microstrip columns onto the bottom surface of the strip corresponding to the main sliding surface, a novel 2D equivalent physical and mechanical parameters analysis method for the strips on the main sliding surface of 3D sliding masses is proposed. Subsequently, a comprehensive 3D stability calculation method for composite slopes is developed, and the quantitative relationship between the coordinated development distance and its 3D stability coefficients is examined. The analysis reveals that the failure mode of the composite slope is characterized by cutting-bedding sliding, with the arc serving as the side interface and the weak layer as the bottom interface, while the destabilization mechanism primarily involves shear failure. The spatial form equation of the sliding mass comprises an ellipsoid and weak plane equation. The analysis revealed that when the coordinated development distance is 1500 m, the error rate between the 3D stability calculation result and the 2D stability calculation result of the composite slope is less than 8%, thereby verifying the proposed analytical method of equivalent physical and mechanical parameters and the 3D stability calculation method for composite slopes. Furthermore, the 3D stability coefficient of the composite slope exhibits an exponential correlation with the coordinated development distance, with the coefficient gradually decreasing as the coordinated development distance increases. These findings provide a theoretical guideline for designing similar slope shape parameters and conducting stability analysis.

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by the breakdown of joint cartilage and underlying bone. Macrophages are a type of white blood cell that plays a critical role in the immune system and can be found in various tissues, including joints. Research on the relationship between OA and macrophages is essential to understand the mechanisms underlying the development and progression of OA. Objective: This study was performed to analyze the functions of the IRF1-GCN5-SETD2-SMARCC1 axis in osteoarthritis (OA) development. Methods: A single-cell RNA sequencing (scRNA-seq) dataset, was subjected to a comprehensive analysis aiming to identify potential regulators implicated in the progression of osteoarthritis (OA). In order to investigate the role of IRF1 and SMARCC1, knockdown experiments were conducted in both OA-induced rats and interleukin (IL)-1β-stimulated chondrocytes, followed by the assessment of OA-like symptoms, secretion of inflammatory cytokines, and polarization of macrophages. Furthermore, the study delved into the identification of aberrant epigenetic modifications and functional enzymes responsible for the regulation of SMARCC1 by IRF1. To evaluate the clinical significance of the factors under scrutiny, a cohort comprising 13 patients diagnosed with OA and 7 fracture patients without OA was included in the analysis. Results: IRF1 was found to exert regulatory control over the expression of SMARCC1, thus playing a significant role in the development of osteoarthritis (OA). The knockdown of either IRF1 or SMARCC1 disrupted the pro-inflammatory effects induced by IL-1β in chondrocytes, leading to a mitigation of OA-like symptoms, including inflammatory infiltration, cartilage degradation, and tissue injury, in rat models. Additionally, this intervention resulted in a reduction in the predominance of M1 macrophages both in vitro and in vivo. Significant epigenetic modifications, such as abundant H3K27ac and H3K4me3 marks, were observed near the SMARCC1 promoter and 10 kb upstream region. These modifications were attributed to the recruitment of GCN5 and SETD2, which are functional enzymes responsible for these modifications. Remarkably, the overexpression of either GCN5 or SETD2 restored SMARCC1 expression in rat cartilages or chondrocytes, consequently exacerbating the OA-like symptoms. Conclusion: This research postulates that the transcriptional activity of SMARCC1 can be influenced by IRF1 through the recruitment of GCN5 and SETD2, consequently regulating the H3K27ac and H3K4me3 modifications in close proximity to the SMARCC1 promoter and 10 kb upstream region. These modifications, in turn, facilitate the M1 skewing of macrophages and contribute to the progression of osteoarthritis (OA). The Translational Potential of this Article: The study demonstrated that the regulation of SMARCC1 by IRF1 plays a crucial role in the development of OA. Knocking down either IRF1 or SMARCC1 disrupted the pro-inflammatory effects induced by IL-1β in chondrocytes, leading to a mitigation of OA-like symptoms in rat models. These symptoms included inflammatory infiltration, cartilage degradation, and tissue injury. These findings suggest that targeting the IRF1-SMARCC1 regulatory axis, as well as the associated epigenetic modifications, could potentially be a novel approach in the development of OA therapies, offering new opportunities for disease management and improved patient outcomes.

Background: Intravenous immune checkpoint inhibitors (ICIs) have shown efficacy in treating locally advanced rectal cancer (LARC), but concerns about systemic toxicity persist. This study developed a unique approach termed chemo-immuno-embolization with transcatheter rectal arterial intervention (CIETAI), aiming to enhance the anti-tumor response while minimizing systemic toxicity. Method: This is a prospective, single-arm, phase II clinical trial conducted in Daping hospital. Patients with previously untreated stage II/III LARC underwent preoperative CIETAI combined with PD-1 inhibitor tislelizumab plus oxaliplatin, followed by standard concomitant chemoradiotherapy (capecitabine and 50.4 Gy radiation). Intravenous tislelizumab was administered for an additional two cycles. Results: Between January 2023 and December 2023, a total of 38 patients were enrolled. As the primary endpoint, 17 (44.74 %) patients achieved pathological complete response (TRG0), with a major pathologic response (MPR) rate of 65.79 %. The anal preservation rate was 84.21 % (32/38), and importantly, 15 of 21 patients with low rectal cancer achieved organ preservation with functional maintenance. Eight patients experienced grade 3–4 adverse events (AEs). All immune-related AEs were grade 1–2, with the most common being endocrine toxicity (5/6, 83.33 %). No grade 5 AEs occurred. Conclusion: This study provides preliminary evidence supporting the safety and efficacy of intraarterial tislelizumab delivery in the neoadjuvant setting for LARC. These promising results encourage further exploration in larger cohorts to validate the clinical impact of this novel CIETAI strategy. Trial registration: ClinicalTrials.gov Identifier: NCT05957016.

Sea urchins produced by aquaculture could enhance declining wild populations and provide a sufficient roe product to satisfy increasing market demand. This study reports a method for large-scale rearing of the edible tropical sea urchin Salmacis sphaeroides, from induction of larval metamorphosis and settlement, to juvenile rearing and grow-out. Larvae were reared in 500-L hatchery tanks, on a diet of the microalga Chaetoceros muelleri at concentrations ranging from 2500 to 24,000 cells mL−1, with daily water renewal of one-third to two-thirds of the volume depending on their developmental stage. The larvae breeding protocol proved suitable for this species, and competent larvae occurred at 12 days post-fertilization. To induce metamorphosis, we tested exposure to potassium chloride (KCl) at different concentrations (0, 25, 50, 100, 200, and 400 mmol L−1) and for different durations (5, 10, and 20 min). Exposure to 200 mmol L−1 KCl for 5 min resulted in the highest proportion of metamorphosed individuals (41.67 ± 2.89 %). Using this method, the densities of juveniles attaching to settlement plates (232.50 ± 41.23 ind. per plate; settlement percentage ca. 3.88 ± 0.69 %) were approximately twice as high as those of the controls (105.75 ± 15.52 ind. per plate; settlement percentage ca. 1.76 ± 0.26 %). Next, two batches of juveniles were grown out in sea cages. In the first batch (deployed for ca. 4 months), the absolute growth rate of the test diameter (AGRD) was 12.79 ± 0.98 mm month−1 from May to September; in the second batch (deployed for 6 months), the AGRD was 5.68 ± 0.90 mm month−1 from October to May of the following year. Survival of the juvenile S. sphaeroides in the sea cages was high (86.56 %–100 %). Finally, the S. sphaeroides cultivated in the second batch were harvested (at a mean test diameter of 71.24 ± 1.45 mm, and wet weight of 101.24 ± 1.91 g) on May 28 of the second year; all animals had matured and could be successfully utilized as broodstock. The fatty acid composition of the gonads was then compared between cultivated and wild-collected adult S. sphaeroides. The proportion of polyunsaturated fatty acids in the cultivated sea urchins (16.59 ± 0.67 %) exceeded that in wild-collected individuals (13.13 ± 0.42 %). From these experiments we conclude that S. sphaeroides is a sea urchin species with excellent potential for aquaculture; the present methods and data will provide helpful information for their mass production in South China.

Plastic waste has caused a global environmental crisis. Biocatalytic depolymerization mediated by enzymes has emerged as an efficient and sustainable alternative for plastic treatment and recycling. However, it is challenging and time-consuming to discover novel plastic-degrading enzymes using conventional cultivation-based or omics methods. There is a growing interest in developing effective computational methods to identify new enzymes with desirable plastic degradation functionalities by exploring the ever-increasing databases of protein sequences. In this study, we designed an innovative machine learning-based framework, named PEZy-Miner, to mine for enzymes with high potential in degrading plastics of interest. Two datasets integrating information from experimentally verified enzymes and homologs with unknown plastic-degrading activity were created respectively, covering eleven types of plastic substrates. Protein language models and binary classification models were developed to predict enzymatic degradation of plastics along with confidence and uncertainty estimation. PEZy-Miner exhibited high prediction accuracy and stability when validated on experimentally verified enzymes. Furthermore, by masking the experimentally verified enzymes and blending them into homolog dataset, PEZy-Miner effectively concentrated the experimentally verified entries by 14∼30 times while shortlisting promising plastic-degrading enzyme candidates. We applied PEZy-Miner to 0.1 million putative sequences, out of which 27 new sequences were identified with high confidence. This study provided a new computational tool for mining and recommending promising new plastic-degrading enzymes.

The uncertainty principle is deemed as one of cornerstones in quantum mechanics, and exploring its lower limit of uncertainty will be helpful to understand the principle's nature. In this study, we propose a generalized entropic uncertainty relation for arbitrary multiple-observable in multipartite system, and further derive a tighter lower bound by considering Holevo quality and mutual information. Importantly, we detailedly discuss the proposed uncertainty relations and quantum coherence in the context of Schwarzschild space-time. It is interesting to find that Hawking radiation will damage the coherence of the physically accessible region and increase the uncertainty. Furthermore, we argue that the properties of the uncertainty in Schwarzschild space-time can be explained from the systems' purity and the information redistribution of the different regions. Therefore, it is believed that our findings provide the generalized entropic uncertainty relations in multipartite systems, which may facilitate us deeper understanding of quantumness and information paradox of the black holes.

Study region: The Huai River Basin, China. Study focus: This study chooses the daily flow data of Huai River and its tributaries, Shi River and Hong River during 1959–2016. The co-occurrence of floods in different tributaries of the catchment is assessed by analyzing the flood peak and flood timing at three different gauging stations located in the river network. What’s more, the parameters(estimated from the 30-year scale time windows) of the marginal and joint distributions are assumed stationary and nonstationary respectively to explore how the trend of coincidence probability(CP) is effected by them. New hydrological insights for the region: The results show that, over the period analyzed, the most probable time of flood co-occurrence over the gauge stations in the study area tends to move backwards from 10 July to about 20 July. The probability of flood co-occurrence at the Bantai and Jiangjiaji gauging stations, which singularly experience an increase in flood peak, increases from 9.25×10−9(the 1st window) to 1.17×10−5(the 25th window) when the return period of flood is 20 year, while in the same condition, the CP of Bantai and Wangjiaba decreased from 6.16×10−6 to 2.48×10−7.

Ongoing inflammation in the heart is positively correlated with adverse remodeling, characterized by elevated levels of cytokines that stimulate activation of cardiac fibroblasts. It was found that CaMKIIδ response to Ang II or TAC triggers the accumulation of ROS in cardiomyocytes, which subsequently stimulates NF-κB/NLRP3 and leads to an increase in IL-6, IL-1β, and IL-18. This is an important causative factor in the occurrence of adverse remodeling in heart failure. Sweroside is a biologically active natural iridoids extracted from Lonicerae Japonicae Flos. It shows potent anti-inflammatory and antioxidant activity in various cardiovascular diseases. In this study, we found that sweroside inhibited ROS-mediated NF-κB/NLRP3 in Ang II-treated cardiomyocytes by directly binding to CaMKIIδ. Knockdown of CaMKⅡδ abrogated the effect of sweroside regulation on NF-κB/NLRP3 in cardiomyocytes. AAV-CaMKⅡδ induced high expression of CaMKⅡδ in the myocardium of TAC/Ang II-mice, and the inhibitory effect of sweroside on TAC/Ang Ⅱ-induced elevation of NF-κB/NLRP3 was impeded. Sweroside showed significant inhibitory effects on CaMKIIδ/NF-κB/NLRP3 in cardiomyocytes from TAC/Ang Ⅱ-induced mice. This would be able to mitigate the adverse events of myocardial remodeling and contractile dysfunction at 8 weeks after the onset of the inflammatory response. Taken together, our findings have revealed the direct protein targets and molecular mechanisms by which sweroside improves heart failure, thereby supporting the further development of sweroside as a therapeutic agent for heart failure.

The study aimed to test the hypothesis that biochar's unique properties, such as its microporous structure, can enhance concrete's resilience to high temperatures. Despite expectations of reduced crack formation and enhanced fire resistance, the experimental results revealed a limited impact on concrete's fire behaviour. The investigation involved the use of two biochar types, fine and coarse biochar as replacements for cement and aggregates, respectively. Fine biochar exhibited higher water absorption and Young's modulus than coarse biochar, but both resisted ignition at 35 kW/m2 radiative heat flux and had peak heat release rates below 40 kW/m2. Incorporating these biochars at varying weight percentages (10, 15, and 20 wt.%) into concrete led to a gradual decline in compressive and tensile strength due to reduced binding ability with increased biochar content. Exposure to 1000 °C compromised mechanical properties across all the samples. However, the biochar concrete maintained compressive strength (compared to the control) with up to 20 wt.% biochar as a fine aggregate substitute after exposure to 600 °C, and as a cement replacement after exposure to 200 °C. This substitution also yielded a significant reduction in CO2 emissions (50 % reduction as the biochar loading amount doubled) from concrete manufacturing, showcasing biochar's potential for sustainable construction practices. Despite not fully supporting the initial hypothesis, the study demonstrated biochar's viability in reducing carbon footprint while maintaining concrete strength under certain fire conditions.

Background: The purpose of this study was to examine the relationship between sleep duration and risk of sarcopenia in in general U.S. population. Methods: Utilizing publicly available data from the National Health and Nutrition Examination Survey spanning from 2011 to 2014, we explored the association between sleep duration and prevalence of sarcopenia. To investigate their relationship, we conducted weighted multivariate logistic regression analysis, restricted cubic splines (RCS) curve, and subgroup analysis. Results: The study included 8,200 individuals, among whom 99 (0.9 %) had sarcopenia. The RCS curve revealed a U-shaped association of sarcopenia with sleep duration (P for nonlinearity = 0.020), showing that the risk of sarcopenia decreases with increasing sleep duration, reaching the lowest risk around 6.67 h. After controlling for underlying cofounders, compared to individuals with sleep duration 9 h group. The U-shaped association between sleep time and prevalence of sarcopenia also was observed in the subjects who aged

Plant-derived extracellular vesicles (PDEV) constitute nanoscale entities comprising lipids, proteins, nucleic acids and various components enveloped by the lipid bilayers of plant cells. These vesicles play a crucial role in facilitating substance and information transfer not only between plant cells but also across different species. Owing to its safety, stability, and the abundance of raw materials, this substance has found extensive utilization in recent years within research endeavors aimed at treating various diseases. This article provides an overview of the pathways and biological characteristics of PDEV, along with the prevalent methods employed for its isolation, purification, and storage. Furthermore, we comprehensively outline the therapeutic implications of diverse sources of PDEV in musculoskeletal system disorders. Additionally, we explore the utilization of PDEV as platforms for engineering drug carriers, aiming to delve deeper into the significance and potential contributions of PDEV in the realm of the musculoskeletal system.

The global prevalence of nonalcoholic fatty liver disease (NAFLD) has reached 30 %, with an annual increase. The incidence of NAFLD-induced cirrhosis is rapidly rising and has become the leading indicator for liver transplantation in the US. However, there are currently no US Food and Drug Administration-approved drugs for NAFLD. Increasing evidence underscores the close association between NAFLD and bile acid metabolism disorder, highlighting the feasibility of targeting the bile acid signaling pathway for NAFLD treatment. The farnesoid X receptor (FXR) is an endogenous receptor for bile acids that exhibits favorable effects in ameliorating the metabolic imbalance of bile acids, lipid disorders, and disruption of intestinal homeostasis, all of which are key characteristics of NAFLD, making FXR a promising therapeutic target for NAFLD. The present review provides a comprehensive overview of the diverse mechanisms through which FXR improves NAFLD, with particular emphasis on its involvement in regulating bile acid homeostasis and the recent advancements in drug development targeting FXR for NAFLD treatment.

The degeneration of intervertebral discs is strongly associated with the occurrence of pyroptosis in nucleus pulposus (NP) cells. This pyroptosis is characterized by abnormal metabolism of fatty acids in the degenerative pathological state, which is further exacerbated by the inflammatory microenvironment and degradation of the extracellular matrix. In order to address this issue, we have developed a fibrin hydrogel complex (FG@PEV). This intricate formulation amalgamates the beneficial attributes of platelet extravasation vesicles, contributing to tissue repair and regeneration. Furthermore, this complex showcases exceptional stability, gradual-release capabilities, and a high degree of biocompatibility. In order to substantiate the biological significance of FG@PEV in intervertebral disc degeneration (IVDD), we conducted a comprehensive investigation into its potential mechanism of action through the integration of RNA-seq sequencing and metabolomics analysis. Furthermore, these findings were subsequently validated through experimentation in both in vivo and in vitro models. The experimental results revealed that the FG@PEV intervention possesses the capability to reshape the inflammatory microenvironment within the disc. It also addresses the irregularities in fatty acid metabolism of nucleus pulposus cells, consequently hindering cellular pyroptosis and slowing down disc degeneration through the regulation of extracellular matrix synthesis and degradation. As a result, this injectable gel system represents a promising and innovative therapeutic approach for mitigating disc degeneration.

Objective: To report a patient of pseudoaneurysm of carotid artery caused by brucellosis infection and improve the recognition, diagnosis and treatment of this disease. Methods: The etiology, clinical data and treatment of false aneurysm were reviewed A 75-year-old man with a high probability of pseudoaneurysm of the left common carotid artery was found by enhanced CT. Open surgery was performed. Bacterial culture return was Brucella. After regular oral drug treatment, the patient recovered well. Results: The patient recovered well after surgery and took oral medication regularly for 3 months without recurrence. Conclusion: Pseudoaneurysms of the carotid artery caused by brucella infection are very rare, and correct diagnosis and open surgery combined with drug therapy are the best choices.

Background: Mutations in Slc26a2 cause a spectrum of autosomal-recessive chondrodysplasia with a significant and negligible influence on the quality of life. It has been reported that Slc26a2 deficiency triggers the ATF6 branch of the UPR, which may, in turn, activate the negative regulator of the FGFR3 signaling pathway. However, the correlation between the deletion of Slc26a2 and the augmentation of downstream phosphorylation of FGFR3 has not been investigated in vivo. Methods: First, we constructed Slc26a2 and Fgfr3 double knockout mouse lines and observed gross views of the born mice and histological staining of the tibial growth plates. The second approach was to construct tamoxifen-inducible Cre-ERT2 mouse models to replicate SLC26A2-related non-lethal dysplastic conditions. Pharmacological intervention was performed by administering the FGFR3 inhibitor NVP-BGJ398. The effect of NVP-BGJ398 on chondrocytes was assessed by Alcian blue staining, proliferation, apoptosis, and chondrocyte-specific markers and then verified by western blotting for variations in the downstream markers of FGFR3. The growth process was detected using X-rays, micro-CT examination, histomorphometry staining of growth plates, and immunofluorescence. Results: Genetic ablation of Fgfr3 in embryonic Slc26a2-deficient chondrocytes slightly attenuated chondrodysplasia. Subsequently, in the constructed mild dysplasia model, we found that postnatal intervention with Fgfr3 gene in Slc26a2-deficient chondrocytes partially alleviated chondrodysplasia. In chondrocyte assays, NVP-BGJ398 suppressed the defective phenotype of Slc26a2-deficient chondrocytes and restored the phosphorylation downstream of FGFR3 in a concentration-dependent manner. In addition, in vivo experiments showed significant alleviation of impaired chondrocyte differentiation, and micro-CT analysis showed a clear improvement in trabecular bone microarchitectural parameters. Conclusion: Our results suggested that inhibition of FGFR3 signaling pathway overactivation and NVP-BGJ398 has promising therapeutic implications for the development of SLC26A2-related skeletal diseases in humans. The translational potential of this article: Our data provide genetic and pharmacological evidence that targeting FGFR3 signaling via NVP-BGJ398 could be a route for the treatment of SLC26A2-associated skeletal disorders, which promisingly advances translational applications and therapeutic development.

The rapid solidification speed and significant temperature gradient observed in the wire and arc additive manufacturing (WAAM) process result in a deviation of the solid-liquid interface from the equilibrium state assumed by the conventional directional solidification phase field (PF) model. This, in turn, limits the ability of the traditional directional solidification PF model to accurately depict the microstructure evolution in additive manufacturing, where non-equilibrium effects dominate. In this work, we employed a 3D finite element (FE) model to simulate the temperature distribution during the wire and arc additive manufacturing (WAAM) process. Additionally, a modified PF model that applies to additive manufacturing is also used to simulate the dendrite morphology and solute segregation behavior in the WAAM process at different scanning speeds. Experimental validation of the simulation results was also conducted. We observed a significant reduction in dendrite growth velocity and solute segregation with increasing scanning speed, attributable to the combined effects of the temperature gradient G(t) and solidification speed Vp. Furthermore, higher scanning speeds were found to increase the primary dendrite arm spacing (PDAS) and average dendrite width. Importantly, our results demonstrated a quantitative agreement between the simulation results using the modified directional solidification PF model and the experimental observations. This approach provides a foundation for selecting and predicting processing parameters and microstructural characteristics under additive manufacturing conditions, facilitating a comprehensive analysis of dendrite growth and solute segregation at different scanning speeds in the WAAM process.

Plastic film mulch in agricultural production becomes essential to maintaining crop yields in arid and semiarid areas. However, the presence of residual film in farmland soil has also drawn much attention. In this study, three experiments were conducted. The first two experimental designs included 0, 450, 1 350, and 2 700 kg ha−1 of residual film pieces of approximately 5 cm side length added to field soil (0–20 cm soil depth) for seven years and added to pots for four years. In the third experiment, 1 350 kg ha−1 of the residual film with different side lengths (2–5, 5–10, 10–15, and 15–20 cm) was added to field soil for six years to explore the effect of residual film fragment size on soil nutrients, soil microorganisms, crop growth and yields. The residual film had little effect on the soil moisture at a field depth of 0–2 (or 0–1.8) m. There were no significant effects on organic carbon, total nitrogen, inorganic nitrogen, total phosphorus or available phosphorus in the 0–20 cm soil layer. The presence of residual film decreased the richness and diversity of the bacterial community of the surface soil of the residual film, but it had no significant effect on the microbial community of the non-surface soil. The emergence rates of wheat and lentils occasionally decreased significantly with different amounts of residue fragments added to the field. At 450–2 700 kg ha−1, the residual film reduced the plant height and stem diameter of maize and significantly reduced the shoot biomass of harvested maize by 11–19%. The average yields of maize and potato over the seven years decreased, but there were almost no significant statistical differences among the treatments. These results provide important data for a comprehensive scientific understanding of the effects of residual film on soil and crops in dryland farming systems.

The paper reviews studies of rural transformation in three dimensions - definition, measurement, and indicators - and summarises the findings of rural transformation research. The scope of rural transformation includes four elements - productivity, rurality, inclusiveness, and sustainability. Current concepts of the dimensions of rural transformation and their associated indicators are insufficient for policy decision-making, as they lack objectivity, feasibility, accountability, comprehensiveness, and comparability. Future research to develop new measures to assess rural transformation in developing countries is valuable. Furthermore, there is potential to explore the topic in some directions: urbanisation strategy, public intervention (i.e., institution, policy, and investment), gender inclusiveness, market creation, and international trade.

While soil nitrogen (N) losses under drip irrigation water and fertilizer management have become a key issue in global environmental N pollution, no current systematic review of this issue exists in the literature. Drawn from the Web of Science Core Collection database, 290 related articles were identified as research subjects (1991–2022). To reveal the basic characteristics, research power, hotspots and future perspectives of this research field, an in-depth bibliometrics analysis and graphical knowledge display were undertaken by using CiteSpace software. By analyzing the evolution process of keywords, greenhouse gases, water use efficiency and crop yield have been research hotspots of this field in recent years. Irrigation systems, soil moisture, fertigation and N losses have always been the core research topics. The focus on N losses pathways has gradually shifted from nitrate (NO3-) leaching alone to comprehensive consideration of multiple losses pathways including NO3- leaching, and emissions of N2O, NH3 and NO. The corresponding water and fertilizer management strategies have gradually shifted from concentrating on water and fertilizer application amounts to diversified management methods involving combinations of amounts, methods and types. Moreover, the development and widespread application of new water and fertilizer management technologies and exogenous additives have further enriched the research direction of soil N losses under drip irrigation water and fertilizer management. Future research still needs to explore how to balance high crop yields and minimize environmental impacts, which will provide effective strategies for controlling agricultural non-point source pollution and mitigating global warming.

Background: Hepatocellular carcinoma (HCC) continues to endanger human health worldwide. Regulatory networks of competing endogenous RNAs (ceRNAs) play important roles in HCC. TP53 is the second most often altered gene in HCC and has a significant role in regulating target genes such as miRNAs and lncRNAs. Methods: Data from patients with TP53 mutation were collected through the cBioPortal database and differential analysis was performed to screen RNAs related to TP53 mutation. The lncRNA-miRNA–mRNA relationship was predicted by the miRcode, miRDB, and TargetScan databases. The ceRNA networks were screened and visualized by Cytoscape. Core ceRNA networks were generated by differential analysis, coexpression analysis, prognostic analysis and subcellular localization. Finally, methylation, mutation, PPI, GSEA, immunity and drug sensitivity analyses of MEX3A were performed to determine the role of MEX3A in HCC. Results: We identified 1508 DEmRNAs, 85 DEmiRNAs and 931 DElncRNAs and obtained a ceRNA network including 28 lncRNAs, 4 miRNAs and 31 mRNAs. Twenty hub DERNAs in the TP53-altered-related ceRNA network were screened out by Cytoscape and the core ceRNA network (LINC00491/TCL6-hsa-miR-139-5p-MEX3A) was obtained by multiple analyses. In addition, we discovered that the methylation level of MEX3A was decreased and the mutation frequency was raised in HCC. Furthermore, elevated MEX3A expression was associated with alterations in the HCC immunological microenvironment. Conclusion: We successfully constructed a reciprocal ceRNA network, which could provide new ideas for exploring HCC mechanisms and therapeutic approaches.

Battery recycling is viewed in China as an important means of achieving primary sustainability goals and greater economic and environmental development. With the notice of high battery recycling intentions through relevant investigations, this study examine the influencing factors of these recycling behaviors of e-bikes citizens by incorporating the place identity and environmental concern into the Extended Normative Activation Model (NAM), which fill the research gap on how place identity and environmental concern affect the batteries recycling behavior. This study proposes that the consequence awareness, personal norms, and attitudes have mediating effect on place identity to the recycling behavior, and the environmental concern has moderating effect on consequence awareness, personal norms, and attitudes to the recycling behavior, respectively. Based on 1068 valid surveys, hypotheses were examined using partial least square structural equation modeling (PLS-SEM). The results show that personal norms and awareness of consequences positively impact e-bike users' intentions to recycle waste batteries, and environmental concerns have no moderating effect on attitude, recycling intention, personal norms, and recycling intention. Theoretical and practical implications are discussed at last.

ABSTRACT: The objective of this study was to investigate the protective effects and mechanisms of dietary administration of sodium humate (HNa) and its zinc and selenium chelate (Zn/Se-HNa) in mitigating Salmonella Typhimurium (S. Typhi) induced intestinal injury in broiler chickens. Following the gavage of 109 CFU S. Typhi to 240 broilers from 21-d to 23-d aged, various growth performance parameters such as body weight (BW), average daily gain (ADG), average daily feed intake (ADFI), and feed ratio (FCR) were measured before and after infection. Intestinal morphology was assessed to determine the villus height, crypt depth, and chorionic cryptologic ratio. To evaluate intestinal barrier integrity, levels of serum diamine oxidase (DAO), D-lactic acid, tight junction proteins, and the related genes were measured in each group of broilers. An analysis was conducted on inflammatory-related cytokines, oxidase activity, and Nuclear Factor Kappa B (NF-κB) and Nuclear factor erythroid2-related factor 2 (Nrf2) pathway-related proteins and mRNA expression. The results revealed a significant decrease in BW, ADG, and FCR in S. typhi-infected broilers. HNa tended to increase FCR (P = 0.056) while the supplementation of Zn/Se-HNa significantly restored BW and ADG (P < 0.05). HNa and Zn/Se-HNa exhibit favorable and comparable effects in enhancing the levels of serum DAO, D-lactate, and mRNA and protein expression of jejunum and ileal tight junction. In comparison to HNa, Zn/Se-HNa demonstrates a greater reduction in S. Typhi shedding in feces, as well as superior efficacy in enhancing the intestinal morphology, increasing serum catalase (CAT) activity, inhibiting pro-inflammatory cytokines, and suppressing the activation of the NF-κB pathway. Collectively, Zn/Se-HNa was a more effective treatment than HNa to alleviate adverse impact of S. Typhi infection in broiler chickens.

Background: Oesophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths worldwide because existing treatments are often insufficient. Therefore, new, reliable biomarkers must be identified. CTSL overexpression is closely associated with tumour progression and poor prognosis. However, the role and mechanism of CTSL as an oncogene in ESCC remain unclear. Methods: Genome-wide association study (GWAS) data were used for Mendelian randomization analysis to investigate the possible relationships between CTSL and ESCC. The correlation between CTSL expression and prognosis was analysed using GEO, TCGA, and GEPIA data. We compared CTSL expression among the cell types using single-cell sequencing. Correlations between CTSL and the tumour microenvironment, immune cell infiltration, tumour mutational load, immunological checkpoints, and treatment sensitivity in patients with ESCC were investigated. Finally, using mouse models and cellular investigations, we assessed the effects of CTSL on the growth, apoptosis, and metastasis of ESCC tumour cells. Results: CTSL was overexpressed in ESCC and correlated with prognosis. We also discovered its close association with cell immunity, especially with tumour-associated macrophages and immune checkpoints in the tumour microenvironment. CTSL may play a key role in ESCC development by affecting M2 macrophage polarisation. CTSL and the M2 macrophage marker genes showed significant positive correlations. Mendelian randomization analysis confirmed a relationship between CTSL and ESCC. Finally, our in vitro and in vivo experiments demonstrated that CTSL promoted the proliferation and migration of ESCC cells, validating our bioinformatic analysis. Conclusion: CTSL emerged as a crucial gene in ESCC that influences patient prognosis and immunity, particularly in association with M2 macrophages. Therefore, targeting or modulating CTSL levels may provide new therapeutic strategies for patients with ESCC.

Alfalfa is one of the major perennial forage crops in California, vital for the livestock industry, and provides environmental benefits to the ecosystem in the state. Information on subsurface drip irrigation (SDI) practices on alfalfa is limited particularly in areas related to drip tape spacings and installation depths and their impacts on topsoil profile wetting patterns and alfalfa productivity. The objective of this study was to compare three different depths of drip lines: 15, 30, and 45 cm on topsoil profile wetting patterns and identify the optimum depth for achieving sustainable management practices for alfalfa production under SDI. Crop water requirements were determined using Tule Technologies system. Volumetric soil water contents from twelve cuts were simulated using HYDRUS-2D. Initial volumetric soil water contents from Watermark sensors were used in the model and measured volumetric soil water distributions were used for hydraulic conductivity calibration. Simulated results showed that there was no significant difference between root water uptake (RWU) among the various drip depths. RWU was 171.6, 170.0, and 168.2 cm at drip line depths of 15, 30, and 45 cm, respectively. Applied irrigation water during the study period was 195.1 cm while rainfall was 4.1 cm. A 10% reduction in topsoil volumetric soil water content was observed for drip lines at 30 cm depth as compared with 15 cm depth, while a 20% reduction in topsoil volumetric soil water content was observed for drip lines at 45 cm depth as compared with 15 cm depth. Drip lines at 30 cm depth are likely the optimal for RWU and free drainage; however, drip lines at 45 cm depth may allow growers to provide additional irrigation events (without increasing the topsoil volumetric soil water content) closer to the harvest date, potentially resulting in higher yield and water use efficiency.

Summary: Long non-coding RNAs (lncRNAs) work together with diverse RNA-binding proteins (RBPs) to fulfill key regulations in important cellular functions. Here, we present a protocol to detect lncRNA-RBP interactions in vitro using a tRNA scaffold containing a streptavidin aptamer pull-down assay. We describe steps for preparing both protein and lncRNA transcripts, lncRNA-protein interaction detection with an in vitro binding assay, and western blot analysis. This protocol is applicable to screen for RNA-interacting proteins using cell lysates followed by mass spectrometry analysis.For complete details on the use and execution of this protocol, please refer to Yang et al. (2023).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Background: Anemia is common in the preoperative setting and associated with increased postoperative complications and mortality. However, it is unclear if preoperative anemia optimization reduces postoperative complications. We aimed to assess the association between preoperative anemia optimization and a composite endpoint of major cardiovascular, renal, and pulmonary complications and all-cause mortality within 30 days after noncardiac surgery in adult patients. Methods: In this retrospective analysis preoperative anemia was defined as hemoglobin concentration below 12.0 g.dl−1 in women and 13.0 g.dl−1 in men within 6 months before surgery. A propensity score-based generalized estimating equation analysis was used to determine the association between preoperative anemia optimization and the primary outcome. Moreover, mediation analysis was conducted to investigate whether intraoperative red blood cell transfusion or duration of intraoperative hypotension were mediators of the relation between anemia optimization and the primary outcome. Results: Fifty-seven hundred anemia optimized, and 8721 non-optimized patients met study criteria. The proportion of patients having any component of the composite of major complications and all-cause mortality was 21.5% in the anemia-optimized versus 18.0% in the non-optimized, with confounder-adjusted odds ratio estimate of 0.99 (95% CI 0.86‒1.15) for anemia optimization versus non-optimization, p = 0.90. Intraoperative red blood cell transfusion had a minor mediation effect on the relationship between preoperative anemia optimization and the primary outcome, whereas duration of intraoperative hypotension was not found to be a mediator. Conclusion: Preoperative anemia optimization did not appear to be associated with a composite outcome of major in-hospital postoperative cardiovascular, renal, and pulmonary complications and all-cause in-hospital mortality.

Paclitaxel is a potent anti-cancer drug that is mainly produced through semi-synthesis, which still requires plant materials as precursors. The content of paclitaxel and 10-deacetyl baccatin III (10-DAB) in Taxus yunnanensis has been found to differ from that of other Taxus species, but there is little research on the mechanism underlying the variation in paclitaxel content in T. yunnanensis of different provenances. In this experiment, the contents of taxoids and precursors in twigs between a high paclitaxel-yielding individual (TG) and a low paclitaxel-yielding individual (TD) of T. yunnanensis were compared, and comparative analyses of transcriptomes as well as chloroplast genomes were performed. High-performance liquid chromatography (HPLC) detection showed that 10-DAB and baccatin III contents in TG were 18 and 47 times those in TD, respectively. Transcriptomic analysis results indicated that genes encoding key enzymes in the paclitaxel biosynthesis pathway, such as taxane 10-β-hydroxylase (T10βH), 10-deacetylbaccatin III 10-O-acetyltransferase (DBAT), and debenzoyl paclitaxel N-benzoyl transferase (DBTNBT), exhibited higher expression levels in TG. Additionally, qRT-PCR showed that the relative expression level of T10βH and DBAT in TG were 29 and 13 times those in TD, respectively. In addition, six putative transcription factors were identified that may be involved in paclitaxel biosynthesis from transcriptome data. Comparative analysis of plastid genomes showed that the TD chloroplast contained a duplicate of rps12, leading to a longer plastid genome length in TD relative to TG. Fifteen mutation hotspot regions were identified between the two plastid genomes that can serve as candidate DNA barcodes for identifying high-paclitaxel-yield individuals. This experiment provides insight into the difference in paclitaxel accumulation among different provenances of T. yunnanensis individuals.

Enniatin B1 (ENN B1) is a mycotoxin that can be found in various foods. However, whether ENN B1 is hazardous to the reproductive system is still elusive. Leydig cells are testosterone-generating cells that reside in the interstitial compartment between seminiferous tubules. Dysfunction of Leydig cells could result in male infertility. This study aimed to examine the toxicological effects of ENN B1 against TM3 Leydig cells. ENN B1 significantly inhibited cell viability in a dose-dependent manner. ENN B1 treatment also decreased the expression of functional genes in Leydig cells. Moreover, ENN B1 induced Leydig cells apoptosis and oxidative stress. Mechanistically, ENN B1 leads to the upregulation of Bax and downregulation of Bcl-2 in Leydig cells. In addition, ENN B1 inhibited the Nrf2/HO-1 pathway, which is critical for the induction of oxidative stress. Additionally, ENN B1 treatment repressed the JAK/STAT3 signaling pathway in Leydig cells. Rescue experiments showed that activation of STAT3 resulted in alleviation of ENN B1-induced damage in Leydig cells. Collectively, our study demonstrated that ENN B1 induced Leydig cell dysfunction via multiple mechanisms.

The present study used the techniques of gene expression programming (GEP) and multi-expression programming (MEP) to assess the compressive strength (CS) and flexural strength (FS) and develop predictive models of sustainable mortar modified with waste eggshell powder (WEP) and waste glass powder (WGP) as a replacement of cement. In order to get more insights into the impact and relation of raw components on the CS and FS of a developed sustainable mortar, a comprehensive study using the SHapley Additive exPlanations (SHAP) methodology was performed. When comparing the efficiency of both employed models, it was seen that the MEP model exhibited superior performance with an R2 value of 0.871 and 0.894 for CS and FS, as compared to the GEP model, which had an R2 value of 0.842 and 0.845 for CS and FS respectively.

Summary: Studying fetal hematopoiesis is challenging as hematopoiesis transitions from the liver to bone marrow. Obtaining human samples is not possible, and small animal models may not provide sufficient biological material. Here, we present a protocol for isolating hematopoietic cells from the nonhuman primate fetal liver and bone. We describe steps for using cells from the same fetus for fluorescence lifetime imaging microscopy to measure metabolism, assessing cellular function, and flow cytometry for immunophenotyping at the single-cell level.For complete details on the use and execution of this protocol, please refer to Nash et al. (2023).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Summary: Analyses of long non-coding RNA (lncRNA)-protein interactions provide key clues for understanding the molecular basis of lncRNA-modulated biological processes. Here, we detail a yeast three-hybrid assay to identify the lncRNA-interacting protein. We describe steps for lncRNA bait preparation, screening an RNA-binding proteins (RBPs) cDNA library, and validation of the lncRNA-RBP interaction. The assay can also be further applied to delineate the region of RBP that mediates the RNA-protein interaction.For complete details on the use and execution of this protocol, please refer to Zhang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.