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BackgroundsGastric cancer (GC) remains a global health threat due to frequent treatment failures caused by primary or acquired resistance. Although cancer-associated fibroblasts (CAFs) have been implicated in this process, it is still unclear which specific subtype(s) of CAFs hinder T-cell infiltration and promote resistance to immunotherapy.MethodsWe analyzed the GC fibroblast atlas in detail by combining 63,955 single cells from 14 scRNA-seq datasets. We also performed RNA-seq data in a local GC cohort and examined 13 bulk RNA-seq datasets to understand the biological and clinical roles of different CAF subsets. Additionally, we conducted in vitro experiments to study the role of specific proteins in GC development.ResultsWe identified a total of 17 fibroblast subsets in gastric cancer, nine of which did not fit into the existing CAFs classification. These subsets exhibited significant heterogeneity in distribution and biological characteristics (metabolism, cell-cell interactions, differentiation state), as well as clinical functions such as prognosis and response to immunotherapy. In particular, cluster 6 stood out for its high expression of MFAP5, CFD, and PI16; it was found to be negatively associated with both overall survival and response to immunotherapy in GC. This association was linked to an immunosuppressive microenvironment characterized by an increase in M2 macrophages but higher levels of T cell dysfunction and exclusion—a feature shared by tumors expressing MFAP5. Furthermore, the addition of human recombinant MFAP5 promoted proliferation and migration of HGC-27 cells by inducing the MFAP5/NOTCH1/HEY1 signaling pathway.ConclusionWe introduce a high-resolution GC fibroblast atlas. The 17 identified fibroblast clusters provide valuable opportunities for gaining deeper biological insights into the relationship between fibroblasts and GC development. Particularly, cluster 6 and its specific marker MFAP5 could serve as prognostic factors in GC and form a foundation for personalized therapeutic combinations to address primary resistance to ICIs.

Background: Artificial intelligence (AI) is a continuously expanding field with the potential to transform a variety of industries—including health care—by providing automation, efficiency, precision, accuracy, and decision-making support for simple and complex tasks. Basic knowledge of the key features as well as limitations of AI is paramount to understand current developments in this field and to successfully apply them to shoulder surgery. The purpose of the present review is to provide an overview of AI within orthopedics and shoulder surgery exploring current and forthcoming AI applications. Methods: PubMed and Scopus databases were searched to provide a narrative review of the most relevant literature on AI applications in shoulder surgery. Results: Despite the enormous clinical and research potential of AI, orthopedic surgery has been a relatively late adopter of AI technologies. Image evaluation, surgical planning, aiding decision-making, and facilitating patient evaluations over time are some of the current areas of development with enormous opportunities to improve surgical practice, research, and education. Furthermore, the advancement of AI-driven strategies has the potential to create a more efficient medical system that may reduce the overall cost of delivering and implementing quality health care for patients with shoulder pathology. Conclusion: AI is an expanding field with the potential for broad clinical and research applications in orthopedic surgery. Many challenges still need to be addressed to fully leverage the potential of AI to clinical practice and research such as privacy issues, data ownership, and external validation of the proposed models.

Among various carbon dioxide capture technologies, the organic amine absorption is the most widely used and reliable choice today. The combination of liquefied natural gas cold energy with carbon dioxide compression and liquefaction process can not only solve the problem of liquefied natural gas cold energy utilization but also obtain the low temperature required for liquefied carbon dioxide directly, which can reduce energy consumption. A new process of carbon dioxide compression and liquefaction by applying liquefied natural gas cold energy to chemical absorption capture is proposed, using organic amine to absorb the high concentration carbon dioxide feed gas captured, and using Aspen Hysys software to simulate the process flow with Peng-Robison equation of state. Firstly, the system performance of the conventional compression process and the pumping compression process were investigated. It was found that the system unit energy consumption could be reduced from 931.65 kJ/kg gas source to 892.61 kJ/kg gas source under the pumping process, the system exergy efficiency increased from 63.28% to 63.67%, and the water consumption decreased from 3.84 kg gas source to 3.01 kg gas source. On this basis, the pumping process was optimized and five optimized processes were proposed according to the different ways of heat exchange series connection. Under the optimal optimized process, the system unit energy consumption was 892.61 kJ/kg gas source, the system exergy efficiency increased from 63.67% to 64.10%, and the water consumption decreased from 3.01 kg gas source to 2.44 kg gas source. Finally, the system sensitivity analysis of interstage cooling temperature and heat transfer medium flow rate was conducted for the optimal optimized process. The results showed that the lower the interstage cooling temperature, the lower the system energy consumption and the greater the exergy efficiency. The lowest unit energy consumption was 879.5 kJ/kg gas source at 10 ℃, and the maximum system exergy efficiency was 65.5%. The effect of heat transfer mass flow rate on the system energy consumption was not obvious, but the system exergy efficiency increased with the increase of heat transfer mass flow rate. The effect of liquefied natural gas mass flow rate on the system exergy efficiency was greater, and the system exergy efficiency was 68.91% when the water mass flow rate was 8000 kg/h and the liquefied natural gas mass flow rate was 1000 kg/h.

This study investigated a new method for controlling the emission of fine particles through heterogeneous condensation. Specifically, the research focuses on the application of single-tower double-cycle desulfurization technology in the wet flue gas desulfurization process. The establishment of a supersaturation environment necessary for heterogeneous condensation was achieved by reducing the temperature of desulfurization slurry in the oxidation zone. Numerical simulations were used to study the distribution of the supersaturation degree and fluid dynamics characteristics in the desulfurization tower after the cooling of desulfurization slurry. Furthermore, the impact of single-tower double-cycle technology on the removal efficiency of fine particles was examined. The results of the numerical simulations indicate that cooling the desulfurization slurry in the absorption zone could establish a supersaturated vapor environment, with the supersaturation degree and region increasing as the slurry temperature decreases. Under typical operating conditions, a temperature drop of approximately 8~10 °C was found to be most suitable for the desulfurization slurry. Moreover, lowering the temperature of the desulfurization slurry in the absorption zone increases the supersaturation degree from 0.93 to 1.85. Additionally, the use of single-tower double-cycle desulfurization technology is shown to significantly enhance the removal efficiency of fine particles, particularly those within the particle size range of 0.1~1 μm. Ultimately, this method could increase the removal efficiency of fine particles from 39.9% to 57.9%.

Lycorine, an isoquinoline alkaloid can exhibit significant anti-cancer effects. The present study was conducted to illustrate the underlying mechanisms of action of lycorine on breast carcinoma under in vitro and in vivo settings Tandem Mass Tag assay and Kyoto Encyclopedia of Genes and Genomes analysis revealed that 20 signaling pathways were closely related to tumorigenesis, especially Wnt signaling pathway and tight junctions. The results demonstrated that lycorine evidently inhibited the proliferation of MDA-MB-231 and MCF-7 cells with IC50 values of 1.84 ± 0.21 μM and 7.76 ± 1.16 μM, respectively. It also blocked cell cycle in G2/M phase, caused a decrease in mitochondrial membrane potential, and induced apoptosis pathways through regulating caspase-3, caspase-8, caspase-9, and PARP expression. Moreover, lycorine effectively repressed the β-catenin signaling and reversed epithelial-mesenchymal transition (EMT) process. Furthermore, 4T1/Luc homograft tumor model was used to further demonstrate that lycorine significantly inhibited the growth and metastasis of breast tumor. These findings highlight the significance of lycorine as potential anti-neoplastic agent to combat breast cancer.

Abstract Developing smart hydrogels with integrated and suitable properties to treat intervertebral disc degeneration (IVDD) by minimally invasive injection is of high desire in clinical application and still an ongoing challenge. In this work, an extraordinary injectable hydrogel PBNPs@OBG (Prussian blue nanoparticles@oxidized hyaluronic acid/borax/gelatin) with promising antibacterial, antioxidation, rapid gelation, and self-healing characteristics was designed via dual-dynamic-bond cross-linking among the oxidized hyaluronic acid (OHA), borax, and gelatin. The mechanical performance of the hydrogel was studied by dynamic mechanical analysis. Meanwhile, the swelling ratio and degradation level of the hydrogel was explored. Benefiting from its remarkable mechanical properties, sufficient tissue adhesiveness, and ideal shape-adaptability, the injectable PBNPs containing hydrogel was explored for IVDD therapy. Astoundingly, the as-fabricated hydrogel was able to alleviate H2O2-induced excessive ROS against oxidative stress trauma of nucleus pulposus, which was further revealed by theoretical calculations. Rat IVDD model was next established to estimate therapeutic effect of this PBNPs@OBG hydrogel for IVDD treatment in vivo. On the whole, combination of the smart multifunctional hydrogel and nanotechnology-mediated antioxidant therapy can serve as a fire-new general type of therapeutic strategy for IVDD and other oxidative stress-related diseases.

A potential role of berberine, a benzyl isoquinoline alkaloid, in cancer therapy is apparent. Its underlying mechanisms of berberine against breast carcinoma under hypoxia have not been elucidated. We focused on the doubt how berberine restrains breast carcinoma under hypoxia in vitro and in vivo. A molecular analysis of the microbiome via 16 S rDNA gene sequencing of DNA from mouse faeces confirmed that the abundances and diversity of gut microbiota were significantly altered in 4T1/Luc mice with higher survival rate following berberine treatment. A metabolome analysis liquid chromatography-mass spectrometer/mass spectrometer (LC-MS/MS) revealed that berberine regulated various endogenous metabolites, especially L-palmitoylcarnitine. Furthermore, the cytotoxicity of berberine was investigated in MDA-MB-231, MCF-7, and 4T1 cells. In vitro to simulate under hypoxic environment, MTT assay showed that berberine inhibited the proliferation of MDA-MB-231, MCF-7, and 4T1 cells with IC50 values of 4.14 ± 0.35 μM, 26.53 ± 3.12 μM and 11.62 ± 1.44 μM, respectively. Wound healing and trans-well invasion studies revealed that berberine inhibited the invasion and migration of breast cancer cells. RT-qPCR analysis shed light that berberine reduced the expression of hypoxia-inducible factor-1α (HIF-1α) gene. Immunofluorescence and western blot demonstrated that berberine decreased the expression of E-cadherin and HIF-1α protein. Taken together, these results provide evidence that berberine efficiently suppresses breast carcinoma growth and metastasis in a hypoxic microenvironment, highlighting the potential of berberine as a promising anti-neoplastic agent to combat breast carcinoma.

The low-low-temperature electrostatic precipitator (LLT-ESP) is considered one of the mainstream technological approaches for achieving ultra-low ash emissions and has already been applied in many coal-fired power plants. Particulate matter and SO3 can both be removed by LLT-ESP. However, the removal performance of SO3 is relatively lower than that of particulate matter, which is caused by the condensation characteristics of SO3. In this paper, the condensation characteristics of SO3 were investigated on a simulated experimental system, and several measurement and characteristic methods were used to investigate mechanisms. After reducing the flue gas temperature with a heat exchanger, the size distribution of particulate matter, the mass concentration of SO3 on different sizes of particulate matter, as well as the microscopic morphology and elemental composition of particulate matter, were all experimentally studied. The results indicate that gaseous SO3 transformed into a liquid phase by heterogeneous or homogeneous condensation and then adhered to the surface of particulate matter through nucleation–condensation, collision–coalescence, and adsorption reactions. Furthermore, the removal efficiency of SO3 in LLT-ESP was also investigated under various conditions, such as ash concentration and flue gas temperature drop, suggesting that a higher ash concentration and a more significant temperature drop were beneficial for improving SO3 removal efficiency. Nevertheless, it is worth noting that the impact was limited by a further increase in ash concentration and a drop in flue gas temperature.

Inflammatory responses of nucleus pulposus (NP) can induce imbalanced anabolism and catabolism of extracellular matrix, and the cytosolic dsDNA accumulation and STING–NF–κB pathway activation found in NP inflammation are considered as fairly important cause of intervertebral disc (IVD) degeneration. Herein, we constructed a siSTING delivery hydrogel of aldehyde hyaluronic acid (HA-CHO) and poly(amidoamine) PAMAM/siRNA complex to intervene the abnormal STING signal for IVD degeneration treatment, where the formation of dynamic Schiff base bonds in the system (siSTING@HPgel) was able to overcome the shortcomings such as low cellular uptake, short half-life, and rapid degradation of siRNA-based strategy. PAMAM not only formed complexes with siRNA to promote siRNA transfection, but also served as dynamic crosslinker to construct hydrogel, and the injectable and self-healing hydrogel efficiently and steadily silenced STING expression in NP cells. Finally, the siSTING@HPgel significantly eased IVD inflammation and slowed IVD degeneration by prolonging STING knockdown in puncture-induced IVD degeneration rat model, revealing that STING pathway was a therapeutic target for IVD degeneration and such novel hydrogel had great potential for being applied to many other diseases for gene delivery.

Abstract Background The purpose of this study was to explore the regulatory mechanism of the long non-coding RNA (lncRNA) LINC00461 underlying the breast cancer invasion and migration via the miR-144-3p/KPNA2 axis. Methods Bioinformatics methods were applied to screen differentially expressed mRNAs, miRNAs and lncRNAs for construction of a competing endogenous RNA (ceRNA) network. LINC00461, KPNA2 and miR-144-3p were identified, and KPNA2 was predicted to be a target of miR-144-3p and significantly correlated with breast cancer prognosis. To make the findings more convincible, we used qRT-PCR to detect the expression levels of LINC00461 and miR-144-3p in breast cancer cells, and conducted western blot to determine KPNA2 protein level. Then, RIP was performed to assess the combination between miR-144-3p and LINC00461 or KPNA2, and dual-luciferase reporter assay was used to validate the targeted relationship between miR-144-3p and KPNA2. Furthermore, Transwell was employed for the examination of cell invasion and migration in breast cancer. Results LINC00461 was predicted to regulate KPNA2 through sponging miR-144-3p as revealed by the ceRNA network. Besides, LINC00461 and KPNA2 were found to be remarkably highly-expressed in breast cancer cells, while miR-144-3p was poorly-expressed. Silencing LINC00461 could promote miR-144-3p expression, thus inhibiting cell invasion and migration. In addition, KPNA2 was confirmed to be a direct target of miR-144-3p. Silencing miR-144-3p or overexpressing KPNA2 could reverse the inhibitory effect of LINC00461 silencing on cell invasion and migration in breast cancer. Conclusion LINC00461 promoted the expression of KPNA2 by competitively binding to miR-144-3p, thereby promoting the invasion and migration of breast cancer cells.

Magnesium (Mg) alloys have a wide range of biomaterial applications, but their lack of biocompatibility and osteoinduction property impedes osteointegration. In order to enhance the bioactivity of Mg alloy, a composite coating of fluorinated hydroxyapatite (FHA) and tantalum (Ta) was first developed on the surface of the alloy through thermal synthesis and magnetron sputtering technologies in this study. The samples were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), energy dispersive spectroscopy (EDS) mapping, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and water contact angle measurement (WCA), which characterized the surface alternation and confirmed the deposition of the target FHA/Ta coating. The results of cell morphology showed that the MC3T3-E1 cells on the surface of Mg/FHA/Ta samples had the largest spreading area and lamellipodia. Moreover, the FHA coating endowed the surface with superior cell viability and osteogenic properties, while Ta coating played a more important role in osteogenic differentiation. Therefore, the combination of FHA and Ta coatings could synergistically promote biological functions, thus providing a novel strategy for implant design.

Abstract Background Breast cancer is the most prevalent cancer among women worldwide. WZ35, an analog of curcumin, has been demonstrated to remarkably improve the pharmacokinetic profiles in vivo compared with curcumin. WZ35 exhibits promising antitumor activity in gastric cancer, HCC, colon cancer. However, antitumor effects of WZ35 in breast cancer and its underlying molecular mechanisms remain unclear. Methods CCK8, Flow cytometry and transwell assays were used to measure cell proliferation, cell cycle arrest, apoptosis, cell migration and invasion. We constructed xenograft mouse model and lung metastasis model to assess the antitumor activities of WZ35 in vivo. To explore the underlying molecular mechanisms of WZ35, we performed a series of overexpression and knockdown experiments. The cellular oxygen consumption rates (OCRs) was measured to assess mitochondrial dysfunction. Results We found that treatment of breast cancer cells with WZ35 exerts stronger anti-tumor activities than curcumin both in vitro and in vivo. Mechanistically, our research showed that WZ35 induced reactive oxygen species (ROS) generation and subsequent YAP mediated JNK activation in breast cancer cells. Abrogation of ROS production markedly attenuated WZ35 induced anti-tumor activities as well as YAP and JNK activation. In addition, ROS mediated YAP and JNK activation induced mitochondrial dysfunction in breast cancer cells. Conclusion Our study showed that novel anti-cancer mechanisms of WZ35 in breast cancer cells and ROS-YAP-JNK pathway might be a potential therapeutic target for the treatment of breast cancer patients.

Based on the fundamentals of heterogeneous nucleation, a method to eliminate sulfuric acid aerosol associated with water recycling in the process of limestone-gypsum desulfurization was investigated. The supersaturated environment was achieved in a heat exchanger. Numerical calculation shows that high temperature drop and relative humidity are conducive to the formation of supersaturated vapor environment, and vapor heterogeneous condensation can improve the removal efficiency of sulfuric acid aerosol. Experimental results indicate that the critical supersaturation degree of the sulfuric acid aerosol is found in inverse proportion to their sizes and the removal efficiency of sulfuric acid aerosol could be increased by about 20%. The theoretical and the actual condensable water mass values have been also studied in detail. The mass of condensed water produced by the experiment system is 0.0440 kg/(Nm3·h) as the temperature drop is 5°С, and the most suitable temperature drop is about 1∼2°С for water scarce area. High temperature and humidity reveal a huge potential to recycling water.

Novel class 1 integrons In1085 and In1086, containing the class D β-lactamase -encoding gene blaOXA, were identified in clinical enterobacterial strains. In this study, we aimed to characterize the genetic contexts of In1085 and In1086, with the goal of identifying putative mechanisms of integron mobilization. Four plasmids, approximately 5.3, 5.3, 5.7, and 6.6 kb, from 71 clinical Enterobacteriaceae strains were found to contain class 1 integrons (In37, In62, In1085, and In1086, respectively). Two of these plasmids, pEco336 and pNsa292, containing In1085 and In1086, respectively, were further characterized by antibiotic susceptibility testing, conjugation experiments, PCR, sequencing, and gene mapping. The OXA-type carbapenemase activities of the parental strains were also assessed. The results revealed that the novel integrons had different genetic environments, and therefore demonstrated diverse biochemical characteristics. Using evolutionary inferences based on the recombination of gene cassettes, we also identified a role for attCaadA16 structural features during attI1 × attC insertion reactions. Our analysis showed that gene cassette insertions in the bottom strand of attCaadA16 in the correct orientation lead to the expression the encoded genes from the Pc promoter. Our study suggests that the genetic features harbored within the integrons are inserted in a discernable pattern, involving the stepwise and parallel evolution of class 1 integron variations under antibiotic selection pressures in a clinical setting.

Sixteen different variants (KPC-2 to KPC-17) in the KPC family have been reported, and most current studies are focusing on KPC-2 and KPC-3. The KPC-15 variant, which isolated from Klebsiella pneumoniae in a Chinese hospital, was a recently discovered KPC enzyme. To compare the characteristics of KPC-15 and KPC-2, the variants were determined by susceptibility testing, PCR amplification and sequencing, and study of kinetic parameters. The strain harboring the KPC-15 showed resistance to 18 conventional antimicrobial agents, especially to cabapenem antibiotics, and the strain involving the KPC-2 also indicated resistance to cabapenem antibiotics, but both strains were susceptible to polymyxin B and colistin. The conjugation experiments showed that the changes of MIC values to the antibiotics were due to the transferred plasmids. The differences of amino acids were characterised at sites of 119 leucine and 146 lysine with KPC-15 and KPC-2. The minimum evolution tree indicated the KPC alleles evolution, and showed that the KPC-15 appeared to be homogenous with KPC-4 closely. Steady-state kinetic parameters showed the catalytic efficiency of KPC-15 was higher than that of KPC-2 for all tested antibiotics in this study. The catalytic efficiency of KPC-15 caused resistance to β-lactam antibiotics was higher than that of KPC-2. Meanwhile, an evolutionary transformation changed KPC from an efficient carbapenemase to its variants (KPC-15) with better ceftazidimase catalytic efficiency, and the old antibiotics polymyxin B and colistin might play a role in the therapy for multi-resistant strains.