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Abstract This article proposes an in-situ steam-assisted thermal decomposition method for oil shale using long-distance horizontal wells.Firstly, this article establishes a coupled thermal–hydraulic hydrothermal mechanical model considering the anisotropy of oil shale to study the in-situ pyrolysis process of oil shale by steam injection in horizontal wells. Then Optimization analysis was conducted on the effects of fracture spacing, fracture length, and horizontal well length on extraction efficiency. Finally, An economic analysis was conducted on the new extraction method. The research results indicate that: (1) Compared with the traditional vertical well mining mode (1injection and 8 production well, with a well spacing of 50 m), the newly proposed long-distance horizontal well configuration (1 injection and 2 production well) has higher heating efficiency. (2) When the fracture spacing is less than 25 m, the heating efficiency is no longer significantly improved. Increasing the length of fractures has a significant effect on improving heating efficiency. (3) When the length of the horizontal well exceeds 450 m, the extraction cost no longer significantly decreases. Increasing the length of fracturing fractures can significantly reduce extraction costs. When the fracture spacing is less than 30 m, the extraction cost no longer significantly decreases. This study provides theoretical reference and data support for the efficient in-situ thermal decomposition of oil shale.

Abstract Background At present, the clinical methods for preventing and treating contrast-induced nephropathy (CIN) are limited, and statins can play a better role during this process. So, we aimed to assess the atorvastatin on renal function in nephropathy patients after percutaneous coronary intervention (PCI). Methods In this work, 100 elderly patients with coronary heart disease (CHD) were selected into an experimental group (Exp group, 50 cases, 40 mg/d po atorvastatin) and a control group (Ctrl group, 50 cases, 10 mg/d po atorvastatin). The renal function indicators, blood routine indicators, and the incidence of adverse reactions (ARs) were compared between patients in Exp and Ctrl groups. Results After surgery, the levels of serum creatinine (SCr), blood urea nitrogen (BUN), cystatin C (CysC), high-sensitivity C-reactive protein (hs-CRP), and interleukin (IL6) in patients in the Exp group were much lower, and the levels of estimated glomerular filtration rate (eGFR) and superoxide dismutase (SOD) were higher (all P 0.05). Compared with conventional doses of atorvastatin, high-dose atorvastatin can effectively prevent renal function damage in patients with CIN, decrease the inflammation and oxidative stress in patients, and will not increase the risk of ARs during hospitalization. Conclusion Taken together, high-dose atorvastatin can be applied in treating patients with CHD after PCI due to its excellent efficacy and high safety.

Grass carp, a common aquatic species in China, suffer significant annual losses due to infection by the parasitic ciliate Ichthyophthirius multifiliis (Ich), thus necessitating effective prevention and control measures. In the present study, the Ich β-tubulin gene was cloned and inserted into the eukaryotic expression vector pVAX1 plasmid to construct the Ich β-tubulin DNA vaccine (pVAX1-Bt). After two doses of the pVAX1-Bt vaccine, the relative percentage survival (RPS) reached 70.0 %, whereas the RPS after 2 doses of pVAX1 reached 10.0 %. The β-tubulin antibody, specific antibody IgM, and immune enzymes (MDA, SOD, CAT, ACP, AKP, and cortisol) were tested over13 weeks. The findings revealed a significant enhancement in the vaccinated fish compared to their unvaccinated counterparts, indicating that the vaccine can activate the humoral immune pathway and non-specific immunity in fish, thereby promoting the production of specific antibodies and memory B cells. Collectively, these results indicate that the Ich β-tubulin DNA vaccine has potential in treatment of Ich infection (ichthyophthiriasis).

BackgroundSubstantial studies reveal that tertiary lymphoid structure (TLS) correlate with prognosis and immunotherapy response in various types of cancers. However, the predictive value of TLS, the specific immune cell subtype within TLS and their anti-tumor mechanisms remain unclear.MethodsBased on 23 TLS-related genes (TLSRGs), we utilized bioinformatics methods to construct a scoring system, named TLSscore. By integrating RNA and single-cell sequencing data, we assessed the utility of TLSscore in head and neck squamous cell carcinoma (HNSCC). Flow cytometric sorting was used to isolate specific T cells subtypes, in vivo and in vitro experiments were conducted to demonstrate its anti-tumor effects.ResultsThe TLSscore model was constructed and specific TLSscore-genes were found to consistently align with the spatial location of TLS. TLSscore has proven to be a robust predictive model for predicting survival prognosis, immune cell infiltration, somatic mutation and immunotherapy response. Notably, a specific PD1+CXCL13+CD8+T cell subtype was identified within TLS. Both in vivo and in vitro experiments demonstrated that PD1+CXCL13+CD8+T cell might represent a functional cell subtype exerting anti-tumor effects during the process of immune surveillance.ConclusionsOur study presents a predictive model for TLS, which can evaluate its presence and predicts survival prognosis and immunotherapy response in HNSSC patients. Additionally, we identify a specific subtype of T cells that might elucidate the mechanism of TLS function in anti-tumor activities. This T cell subtype holds the potential to be a prognostic marker and a target for adoptive cell therapy (ACT) in the future.

Oncolytic viruses (OVs) have emerged as a potential strategy for tumor treatment due to their ability to selectively replicate in tumor cells, induce apoptosis, and stimulate immune responses. However, the therapeutic efficacy of single OVs is limited by the complexity and immunosuppressive nature of the tumor microenvironment (TME). To overcome these challenges, engineering OVs has become an important research direction. This review focuses on engineering methods and multi-modal combination therapies for OVs aimed at addressing delivery barriers, viral phagocytosis, and antiviral immunity in tumor therapy. The engineering approaches discussed include enhancing in vivo immune response, improving replication efficiency within the tumor cells, enhancing safety profiles, and improving targeting capabilities. In addition, this review describes the potential mechanisms of OVs combined with radiotherapy, chemotherapy, cell therapy and immune checkpoint inhibitors (ICIs), and summarizes the data of ongoing clinical trials. By continuously optimizing engineering strategies and combination therapy programs, we can achieve improved treatment outcomes and quality of life for cancer patients.

The arid and semi-arid region of Northwest China plays a significant role in potato production, yet yields are often hampered by drought due to limited precipitation and irrigation water. The ridge–furrow rainwater-harvesting technology is an efficient and widely used technique to relieve drought impact and improve crop yield by changing the micro-topography to harvest rainwater to meet the water demand of crops. An analysis of precipitation, water demand, and runoff data spanning 30 years guided the selection of suitable rainwater-harvesting methods tailored to meteorological conditions. The results showed that potato water demand exceeded precipitation in the region. The mulching approach performed best in the western arid region with the most significant increase in yield and water use efficiency (WUE) and was suitable for the western semi-arid region and the agro-pastoral ecotone. In the potato dryland farming areas, the water deficit increased from southeast to northwest. Specifically, northern Gansu, northern Ningxia, and midwestern Inner Mongolia experienced a water deficit of over 200 mm, and rainwater harvesting combined with irrigation was recommended. Conversely, regarding deficits below 200 mm in southern Gansu, Ningxia, and central Inner Mongolia, a 1:1 or 2:1 pattern of ridges could be applied, and mulching was needed only in the necessary areas. For the southern Qinghai, Shaanxi, and eastern Inner Mongolia regions, ridge–furrow rainwater harvesting could be replaced by flat potato cropping. In summary, rainwater harvesting addresses water deficits, aiding climate adaptation in Northwest China’s arid and semi-arid regions. The implementation of mulching and ridge–furrow technology must be location-specific.

To investigate the effects of environmental enrichment on the growth and welfare level of the Chinese hooksnout carp (Opsariichthys bidens), an experiment was carried out for 56 d with four types of enrichment environments: low-density physical enrichment, high-density physical enrichment, low-density social enrichment, and high-density social enrichment. The experimental results revealed that both physical and social enrichment treatments positively affected the growth and gonadal development of O. bidens. The physical enrichment treatment was found to increase the antioxidants’ content, such as CAT, SOD, and GSH, in the liver of O. bidens. Moreover, this treatment was able to lead to a reduction in MDA content and enhancement of the fish’s antioxidant capabilities. Behavioral observations, cortisol level analysis, and pcna gene expression analysis indicated that the physical enrichment treatment redused the clustering, aggression, and stress behaviors of O. bidens, maintaining them in a low-stress state. In most respects, the high-density physical enrichment has more positive effects than the low-density one. In contrast, the social enrichment treatments resulted in higher stress levels for O. bidens.

Abstract Background Immune cell heterogenicity is known to determine the therapeutic response to cancer progression. Neoadjuvant chemoimmunotherapy (NACI) has shown clinical benefits in some patients with advanced head and neck squamous cell carcinoma (HNSCC), but the underlying mechanism behind this clinical response is unknown. The efficacy of NACI needs to be potentiated by identifying accurate biomarkers to predict clinical responses. Here, we attempted to identify molecules predicting NACI response in advanced HNSCC. Methods We performed combined single‐cell RNA sequencing (scRNA‐seq) and multiplex immunofluorescence (mIHC) staining with tumor samples derived from NACI‐treated HNSCC patients to identify a new tumor‐infiltrating cell (TIL) subtype, CD103+CD8+ TILs, associated with clinical response, while both in vitro and in vivo assays were carried out to determine its antitumor efficiency. The regulatory mechanism of the CD103+CD8+ TILs population was examined by performing cell‐cell interaction analysis of the scRNA‐seq data and spatial analysis of the mIHC images. Results We established intratumoral CD103+CD8+ TILs density as a determinant of NACI efficacy in cancers. Our scRNA‐seq results indicated that the population of CD103+CD8+ TILs was dramatically increased in the responders of NACI‐treated HNSCC patients, while mIHC analysis confirmed the correlation between intratumoral CD103+CD8+ TILs density and NACI efficacy in HNSCC patients. Further receiver operating characteristic curve analysis defined this TIL subset as a potent marker to predict patient response to NACI. Functional assays showed that CD103+CD8+ TILs were tumor‐reactive T cells, while programmed cell death protein‐1 (PD‐1) blockade enhanced CD103+CD8+ TILs cytotoxicity against tumor growth in vivo. Mechanistically, targeting the triggering receptor expressed on myeloid cells 2‐positive (TREM2+) macrophages might enhance the population of CD103+CD8+ TILs and facilitate antitumor immunity during NACI treatment. Conclusions Our study highlights the impact of intratumoral CD103+CD8+ TILs density on NACI efficacy in different cancers, while the efforts to elevate its population warrant further clinical investigation.

Opsariichthys bidens (O. bidens) is a fish species native to China. It has become a popular ornamental fish because of its interesting colour dimorphism. Its colour pattern is unique; however, with the exception of model species, such as zebrafish, the molecular mechanisms of most fish colour patterns remain unclear. In the present study, we compared and analysed the transcriptomic data of the skin and anal fins of male and female O. bidens. A total of 9028 differentially expressed genes (DEGs) were identified, of which 5259 were upregulated and 3769 were downregulated in males. Compared with known pigmentation genes, Mitf, Tyr, Tyrp1, Dct, Pnp4a, Alx4a, Gch1, and Csf1r were identified as potential genes related to colour dimorphism. Second, we tracked the process of colour development in male O. bidens and found that there were three stages in the formation of body colour. We explored the distribution, migration, and expression patterns of genes related to pigment cells at each stage using microscopic imaging, transmission electron microscopy, enzyme-linked immunosorbent assay, and high-performance liquid chromatography. Melanophores, xanthophores, and iridophores were found to be distributed on the skin or anal fins of O. bidens. It was inferred that this unique body colour pattern is caused by the differentiation and migration of pigment cells at specific stages. This discovery provides a basis for studying the molecular mechanisms of pigmentation in ornamental fish and will contribute to the genetic selection and breeding of O. bidens in ornamental fish cultures in the future.

During in situ thermal injection in oil shale mining, the shear properties of oil shale at real-time high temperatures considerably affect the stability of injection and production wellbore as well as oil and gas production. The results of this study show that the shear strength and modulus of oil shale decrease with an increase in the shear angle at real-time high temperatures. With increasing temperature, the shear strength and modulus first decrease and then increase, reaching their lowest values at 400 °C. Thereafter, at temperatures above 400 °C, the energy accumulated in the elasticity and crack propagation stages is released and a large amount of energy is liberated during the instability failure. Finally, with rising temperature, the failure stage of oil shale changes from brittle to ductile, secondary fractures gradually increase and the failure characteristics step-by-step turn from through to nonthrough cracking characteristics.

The stability of the casing is a crucial prerequisite for implementing the in situ high-temperature steam injection method in oil shale reservoirs. In order to address the issues of substantial expansion, concentrated thermal stresses, and susceptibility to damage observed in traditional straight casings under high temperatures, this paper proposes the utilization of a corrugated casing structure. In this regard, to investigate the impact of the shape and structure of the wellbore casing on its mechanical properties, identical corrugated and straight casings were selected and studied. Uniaxial compression and tensile tests were conducted on the casings, along with coordination deformation experiments between the casing and cement sheath under varying temperatures. Numerical simulations were employed to obtain the deformation characteristics of the corrugated and straight casings under axial compression and tension loads, as well as the stress distribution on the outer casing wall. The results showed that when subjected to the same amount of deformation under axial loading, the corrugated casing experienced lower compressive and tensile loads compared to the straight casing. Moreover, under the sole constraint of cement sheath, increasing the temperature led to lower vertical strains (perpendicular to the ground) at all measuring points of the corrugated casing as compared to the corresponding strains in the straight casing. Numerical simulations revealed that, under the same temperatures, the deformation at the interface between the corrugated casing and the cement sheath was smaller, while the vertical stress at the interface of the corrugated casing was also lower than the straight casing. Overall, the corrugated casing, with its corrugated structure that enabled micro-deformation, effectively mitigated the axial deformation of the casing caused by thermal expansion. Consequently, the corrugated casing reduced the extrusion of wellbore casing on the cement sheath, thereby preserving the integrity and stability of the wellbore cementing structure.

Saikosaponins (SSs) are the main active components extracted from Bupleuri Radix (BR) which has been used as an important herbal drug in Asian countries for thousands of years. It has been reported that the intestinal bacteria plays an important role in the in vivo disposal of oral SSs. Although the deglycosylated derivatives (saikogenins, SGs) of SSs metabolized by the intestinal bacteria are speculated to be the main components absorbed into the blood after oral administration of SSs, no studies have been reported on the characteristics of SGs for their intestinal absorption, and those for SSs are also limited. Therefore, a rapid UHPLC-MS/MS method was developed to investigate and compare the apparent permeability of three common SSs (SSa, SSd, SSb2) and their corresponding SGs (SGF, SGG, SGD) through a bidirectional transport experiment on Caco-2 cell monolayer model. The method was validated according to the latest FDA guidelines and applied to quantify the six analytes in transport medium samples extracted via liquid-liquid extraction (LLE). The apparent permeability coefficient (Papp) determined in this study indicated that the permeability of SGs improved to the moderate class compared to the corresponding parent compounds, predicting a higher in vivo absorption. Moreover, the efflux ratio (ER) value demonstrated an active uptake of SSd and the three SGs, while a passive diffusion of SSa and SSb2.

Abstract Medulloblastoma (MB) is the most common type of brain malignancy in children. Molecular profiling has become an important component to select patients for therapeutic approaches, allowing for personalized therapy. In this study, we successfully identified detectable levels of tumor-derived cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) samples of patients with MB. Furthermore, cfDNA from CSF can interrogate for tumor-associated molecular clues. MB-associated alterations from CSF, tumor, and post-chemotherapy plasma were compared by deep sequencing on next-generation sequencing platform. Shared alterations exist between CSF and matched tumor tissues. More alternations were detected in circulating tumor DNA from CSF than those in genomic DNA from primary tumor. It was feasible to detect MB-associated mutations in plasma of patients treated with chemotherapy. Collectively, CSF supernatant can be used to monitor genomic alterations, as a superior technique as long as tumor-derived cfDNA can be isolated from CSF successfully.

ObjectiveTo investigate whether TCF7+ T cells constitute an important factor to improve the existing postoperative prediction model for patients with oral squamous cell carcinoma.MethodTCF7+ T cells were detected in the tissues of 167 OSCC patients by multiplex immunofluorescence. The percentage of TCF7+ T cells was transformed into a dichotomous variable, combined with the clinicopathological data for the OSCC patients, and then subjected to univariate and multivariate analyses. The derived independent predictors were then incorporated into risk models to analyze their relationship with the prognosis of patients.ResultsThe high TCF7+ group had a better prognosis than the low TCF7+ group (OS: p

BackgroundChimeric antigen receptor (CAR)-based immunotherapy has shown great potential for the treatment of both hematopoietic malignancies and solid tumors. Nevertheless, multiple obstacles still block the development of CAR-based immunotherapy in the clinical setting. In this study, we aimed to summarize the research landscape and highlight the front lines and trends of this field.MethodsLiterature published from 2001 to 2021 was searched in the Web of Science Core Collection database. Full records and cited references of all the documents were extracted and screened. Bibliometric analysis and visualization were conducted using CiteSpace, Microsoft Excel 2019, VOSviewer and R software.ResultsA total of 5981 articles and reviews were included. The publication and citation results exhibited increasing trends in the last 20 years. Frontiers in Immunology and Blood were the most productive and most co-cited journals, respectively. The United States was the country with the most productive organizations and publications in the comprehensive worldwide cooperation network, followed by China and Germany. June, C.H. published the most papers with the most citations, while Maude, S.L. ranked first among the co-cited authors. The hotspots in CAR-based therapy research were multiple myeloma, safety and toxicity, solid tumors, CAR-engineered immune cells beyond T cells, and gene editing.ConclusionCAR-based immunotherapy is a promising treatment for cancer patients, and there is an emerging movement toward using advanced gene modification technologies to overcome therapeutic challenges, especially in solid tumors, and to generate safer and more effective universal CAR-engineered cell products.

Abstract Background Two-dimensional speckle-tracking echocardiography (2D-STE) enables objective assessment of left atrial (LA) deformation through the analysis of myocardial strain, which can be measured by different speckle-tracking software. The aim of this study was to compare the consistency of 3 different commercially available software, which include vendor-specific software for measuring left ventricle (VSSLV), vendor-independent software packages for measuring LV strain (VISLV) and vendor-independent software packages for measuring LA strain (VISLA). Methods Sixty-four subjects (mean age: 44 ± 16 years, 50% males) underwent conventional echocardiograms using a GE Vivid 9 (GE Ultrasound, Horten, Norway) cardiac ultrasound system. Standard apical 4 and 2 chamber views of the left atrium were obtained in each subject with a frame-rate range of 40–71 frames/s. LA strain during the contraction phase (Sct), conduit phase (Scd), reservoir phase (Sr = Sct + Scd) were analyzed by 2 independent observers and 3 different software. Results Sct, Scd, Sr were, respectively, − 11.26 ± 2.45%, − 16.77 ± 7.06%, and 28.03 ± 7.58% with VSSLV, − 14.77 ± 3.59%, − 23.17 ± 10.33%, and 38.23 ± 10.99% with VISLV, and − 14.80 ± 3.88%, − 23.94 ± 10.48%, and 38.73 ± 11.56% when VISLA was used. A comparison of strain measurements between VSSLV and VIS (VISLV and VISLA) showed VIS had significantly smaller mean differences and narrower limits of agreement. Similar results were observed in the coefficient of variation (CV) for measurements between VSSLV and VIS (VISLV and VISLA). Comparison of the intra-class correlation coefficients (ICCs) indicated that measurement reliability was weaker with VSSLV (ICC 0.9). For intra-observer ICCs, VISLA > VSSLV = VISLV. For inter-observer ICCs, VSSLV > VISLA > VISLV. Conclusions Software measurement results of LA strain vary considerably. We recommended not measuring LA strain across vendor platforms.

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Left atrial appendage (LAA) dysfunction identified by transesophageal echocardiography (TEE) is a powerful predictor of stroke in patients with atrial fibrillation (AF). The aim of our study is to assess if there is a correlation between the left atrial (LA) functional parameter and LAA dysfunction in the AF patients. This cross-sectional study included a total of 249 Chinese AF patients who did not have cardiac valvular diseases and were undergoing cardiac ablation. TEE was performed in all the patients who were categorized into two groups according to their left atrial appendage (LAA) function. A total of 120 of the 249 AF patients had LAA dysfunction. Univariate and multivariate logistic regression was conducted to assess the independent factors that correlated with the LAA dysfunction. Different predictive models for the LAA dysfunction were compared with the receiver operating characteristic (ROC) curve. The final ROC curve on the development and validation datasets was drawn based on the calculation of each area under the curves (AUC). Univariate and multivariate analysis showed that the peak left atrial strain (PLAS) was the most significant factor that correlated with the LAA dysfunction. PLAS did not show inferiority amongst all the models and revealed strong discrimination ability on both the development and validation datasets with AUC 0.818 and 0.817. Our study showed that a decrease in PLAS is independently associated with LAA dysfunction in the AF patients.

The development of miniaturized devices for studying zebrafish embryos has been limited due to complicated fabrication and operation processes. Here, we reported on a microfluidic device that enabled the capture and culture of zebrafish embryos and real-time monitoring of dynamic embryonic development. The device was simply fabricated by bonding two layers of polydimethylsiloxane (PDMS) structures replicated from three-dimensional (3D) printed reusable molds onto a flat glass substrate. Embryos were easily loaded into the device with a pipette, docked in traps by gravity, and then retained in traps with hydrodynamic forces for long-term culturing. A degassing chamber bonded on top was used to remove air bubbles from the embryo-culturing channel and traps so that any embryo movement caused by air bubbles was eliminated during live imaging. Computational fluid dynamics simulations suggested this embryo-trapping and -retention regime to exert low shear stress on the immobilized embryos. Monitoring of the zebrafish embryogenesis over 20 h during the early stages successfully verified the performance of the microfluidic device for culturing the immobilized zebrafish embryos. Therefore, this rapid-prototyping, low-cost and easy-to-operate microfluidic device offers a promising platform for the long-term culturing of immobilized zebrafish embryos under continuous medium perfusion and the high-quality screening of the developmental dynamics.