Flooding Performance and Optimization of Injection Parameters of Nanosized Oil Displacement Agents in Extra-Low-Permeability Reservoirs.

There have been few studies on the role of nanofluids in oil displacement and injection parameters, despite their significant impact on the oil displacement effect. To enhance oil recovery in an ultralow-permeability reservoir, the nanosized oil-displacement agent with nano-SiO2 modified by a silane coupling agent as a main component was selected for the first time in the Changqing oilfield. To assess the performance of the nanofluid, various factors such as particle size, contact angle, interfacial tension, and emulsion stability were taken into consideration. The oil displacement effect of nanofluids was evaluated by a microscopic model and ultralow-permeability core displacement experiment, and its optimal injection parameters were determined. The average particle size of the nano-oil displacement agent is 22-30 nm. It can change the wetting condition of the rock from oil-wet to water-wet and reduce the oil-water interfacial tension. Even at 80 °C, the emulsion formed by the agent remained stable. The oil displacement experiment shows that the nano-oil displacement agent whose injection pressure increases can displace the residual oil trapped in small pores that cannot be affected by conventional water flooding. The injection mode of "nanoflooding agent drive + water drive + nanoflooding agent drive", injection rate of 0.1 mL/min, injection concentration of 0.5%, and injection volume of 0.5 PV (0.25 PV per segment), which can effectively guide the injection of the oil displacement agent, achieve the best oil displacement effect.

Levothyroxine treatment in pregnant women with thyroid stimulating hormone levels ranging between 2.5 and 10 mIU/L: A propensity score matched analysis.

OBJECTIVE: To clarify the association between levothyroxine (LT-4) treatment and various adverse pregnancy outcomes in pregnant women with thyroid stimulating hormone (TSH) levels ranging between 2.5 to 10.0 mIU/L in the first trimester, stratified according to thyroid peroxidase antibody (TPOAb) positivity and TSH level. METHODS: This retrospective analysis of retrospectively and prospectively collected cohort data included Chinese pregnant women with TSH levels of 2.5-10 mIU/L and normal free thyroxine levels (11.8-18.4 pmol/L) in the first trimester. All participants were followed up until the completion of pregnancy, and information on LT-4 treatment, pregnancy complications, and pregnancy outcomes was recorded. A 1:1 nearest-neighbor propensity score matching (PSM) between the LT-4-treated and -untreated groups with a caliper distance of 0.02 was performed using a multivariable logistic regression model. Multivariable-adjusted modified Poisson regression was used to estimate the relative risk (RR) and 95% confidence interval (CI) of LT-4 treatment for adverse pregnancy outcomes. Subgroup analyses were also performed in four subgroups simultaneously stratified by TPOAb status (negative or positive) and TSH levels (2.5-4.0 mIU/L as high-normal group and 4.0-10.0 mIU/L as SCH group). The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100047394). RESULTS: Among the 4,370 pregnant women in the study, 1,342 received LT-4 treatment, and 3,028 did not. The 1:1 PSM yielded 668 pairs of individuals and revealed that LT-4 treatment was significantly associated with a decreased risk of pregnancy loss (RR=0.528, 95% CI: 0.344-0.812) and an increased risk of small-for-gestational-age infants (RR=1.595, 95% CI: 1.023-2.485). Subgroup analyses suggested that the above effects of LT-4 treatment were mainly from TPOAb-negative participants. LT-4 treatment was associated with an increased risk of preterm birth (RR=2.214, 95% CI: 1.016-4.825) in TPOAb-positive pregnant women with high-normal TSH levels. CONCLUSION: LT-4 treatment was significantly associated with a lower risk of pregnancy loss and a higher risk of small-for-gestational-age infants in pregnant women with TSH levels of 2.5-10 mIU/L. An increased risk of preterm birth was observed in the LT-4-treated group among TPOAb-positive participants with TSH levels of 2.5-4.0 mIU/L.

[Research Progress on Influence of Centrifugal Blood Pump on Blood Injury].

Centrifugal blood pumps drive blood flow by regulating blood flow rate, and have been widely used in clinical applications, including extracorporeal membrane oxygenation (ECMO), cardiopulmonary bypass (CPB), and extracorporeal circulation carbon dioxide removal (ECCO2R). However, because different structures and different forms of centrifugal pumps have different requirements for blood extracorporeal circulation in clinical application scenarios, blood pumps face different application conditions in clinical use. In this study, the effects of different structures of centrifugal pumps and different working conditions on blood damage are summarized for reference by relevant institutions and R&D personnel.

Mitochondrial (mt)DNA-cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling promotes pyroptosis of macrophages via interferon regulatory factor (IRF)7/IRF3 activation to aggravate lung injury during severe acute pancreatitis.

BACKGROUND: Macrophage proinflammatory activation contributes to the pathology of severe acute pancreatitis (SAP) and, simultaneously, macrophage functional changes, and increased pyroptosis/necrosis can further exacerbate the cellular immune suppression during the process of SAP, where cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) plays an important role. However, the function and mechanism of cGAS-STING in SAP-induced lung injury (LI) remains unknown. METHODS: Lipopolysaccharide (LPS) was combined with caerulein-induced SAP in wild type, cGAS -/- and sting -/- mice. Primary macrophages were extracted via bronchoalveolar lavage and peritoneal lavage. Ana-1 cells were pretreated with LPS and stimulated with nigericin sodium salt to induce pyroptosis in vitro. RESULTS: SAP triggered NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation-mediated pyroptosis of alveolar and peritoneal macrophages in mouse model. Knockout of cGAS/STING could ameliorate NLRP3 activation and macrophage pyroptosis. In addition, mitochondrial (mt)DNA released from damaged mitochondria further induced macrophage STING activation in a cGAS- and dose-dependent manner. Upregulated STING signal can promote NLRP3 inflammasome-mediated macrophage pyroptosis and increase serum interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α levels and, thus, exacerbate SAP-associated LI (SAP-ALI). Downstream molecules of STING, IRF7, and IRF3 connect the mtDNA-cGAS-STING axis and the NLRP3-pyroptosis axis. CONCLUSIONS: Negative regulation of any molecule in the mtDNA-cGAS-STING-IRF7/IRF3 pathway can affect the activation of NLRP3 inflammasomes, thereby reducing macrophage pyroptosis and improving SAP-ALI in mouse model.

GATA4 regulates the transcription of MMP9 to suppress the invasion and migration of breast cancer cells via HDAC1-mediated p65 deacetylation.

GATA-binding protein 4 (GATA4) is recognized for its significant roles in embryogenesis and various cancers. Through bioinformatics and clinical data, it appears that GATA4 plays a role in breast cancer development. Yet, the specific roles and mechanisms of GATA4 in breast cancer progression remain elusive. In this study, we identify GATA4 as a tumor suppressor in the invasion and migration of breast cancer. Functionally, GATA4 significantly reduces the transcription of MMP9. On a mechanistic level, GATA4 diminishes MMP9 transcription by interacting with p65 at the NF-κB binding site on the MMP9 promoter. Additionally, GATA4 promotes the recruitment of HDAC1, amplifying the bond between p65 and HDAC1. This leads to decreased acetylation of p65, thus inhibiting p65's transcriptional activity on the MMP9 promoter. Moreover, GATA4 hampers the metastasis of breast cancer in vivo mouse model. In summary, our research unveils a novel mechanism wherein GATA4 curtails breast cancer cell metastasis by downregulating MMP9 expression, suggesting a potential therapeutic avenue for breast cancer metastasis.

ICLAMP: a novel technique to explore adenosine deamination via inosine chemical labeling and affinity molecular purification.

Recent developments in sequencing and bioinformatics have advanced our understanding of adenosine-to-inosine (A-to-I) RNA editing. Surprisingly, recent analyses have revealed the capability of adenosine deaminase acting on RNA (ADAR) to edit DNA:RNA hybrid strands. However, edited inosines in DNA remain largely unexplored. A precise biochemical method could help uncover these potentially rare DNA editing sites. We explore maleimide as a scaffold for inosine labeling. With fluorophore-conjugated maleimide, we were able to label inosine in RNA or DNA. Moreover, with biotin-conjugated maleimide, we purified RNA and DNA containing inosine. Our novel technique of inosine chemical labeling and affinity molecular purification offers substantial advantages and provides a versatile platform for further discovery of A-to-I editing sites in RNA and DNA.

Baicalein improves the symptoms of polycystic ovary syndrome by mitigating oxidative stress and ferroptosis in the ovary and gravid placenta.

BACKGROUND: Polycystic ovary syndrome is a metabolic and hormonal disorder that is closely linked to oxidative stress. Within individuals diagnosed with PCOS, changes occur in the ovaries, resulting in an excessive buildup of iron and peroxidation of lipids, both of which may be associated with the occurrence of ferroptosis. Baicalein, a flavonoid found in the roots of Scutellaria baicalensis and widely known as Chinese skullcap, is known for its anti-inflammatory and anti-ferroptotic properties, which protect against various diseases. Nevertheless, there has been no investigation into the impact of baicalein on polycystic ovary syndrome. PURPOSE: This study aimed to correlate ferroptosis with polycystic ovary syndrome and to assess the effects of baicalein on ovarian dysfunction and placental development in pregnant patients. STUDY DESIGN AND METHODS: Polycystic ovary syndrome was induced in a rat model through the administration of dehydroepiandrosterone, and these rats were treated with baicalein. Oxidative stress and inflammation levels were assessed in serum and ovaries, and tissue samples were collected for histological and protein analyses. Furthermore, different groups of female rats were mated with male rats to observe pregnancy outcomes and tissue samples were obtained for histological, protein, and RNA sequencing. Then, RNA sequencing of the placenta was performed to determine the key genes involved in ferroptosis negative regulation (FNR) signatures. RESULTS: Baicalein was shown to reduce ovarian oxidative stress and pathology. Baicalein also ameliorated polycystic ovary syndrome by decreasing lipid peroxidation and chronic inflammation and modulating mitochondrial functions and ferroptosis in the ovaries. Specifically, glutathione peroxidase and ferritin heavy chain 1 were considerably downregulated in polycystic ovary syndrome gravid rats compared to their expression in the control group, and most of these differences were reversed after baicalein intervention. CONCLUSIONS: Our findings, initially, indicated that baicalein could potentially enhance the prognosis of individuals suffering from polycystic ovary syndrome by reducing oxidative stress and ferroptosis, thus potentially influencing the formulation of a therapeutic approach to address this condition.

Casein-based hydrogels: Advances and prospects.

Casein-based hydrogels (Casein Gels) possess advantageous properties, including mechanical strength, stability, biocompatibility, and even adhesion, conductivity, sensing capabilities, as well as controlled-releasing behavior of drugs. These features are attributed to their gelation methods and functionalization with various polymers. Casein Gels is an important protein-based material in the food industry, in terms of dairy and functional foods, biological and medicine, in terms of carrier for bioactive and sensitive drugs, wound healing, and flexible sensors and wearable devices. Herein, this review aims to highlight the importance of the features mentioned above via a comprehensive investigation of Casein Gels through multiple directions and dimensional applications. Firstly, the composition, structure, and properties of casein, along with the gelation methods employed to create Casein Gels are elaborated, which serves as a foundation for further exploration. Then, the application progresses of Casein Gels in dairy products, functional foods, medicine, flexible sensors and wearable devices, are thoroughly discussed to provide insights into the diverse fields where Casein Gels have shown promise and utility. Lastly, the existing challenges and future research trends are highlighted from an interdisciplinary perspective. We present the latest research advances of Casein Gels and provide references for the development of multifunctional biomass-based hydrogels.

Determination of marker residues of quinoxaline-1,4-di-N-oxides and its prototype identification by liquid chromatography tandem mass spectrometry.

Quinoxaline-1,4-di-N-oxides (QdNOs), such as carbadox, olaquindox, mequindox, quinocetone, etc. are a class of antibacterial drugs. Prototype drugs residues can not be detected due to their rapid metabolism in animals. Quinoxaline-2-carboxylic acid (QCA) and 3-methyl-QCA (MQCA) are their common marker residues, so it has been always a challenge to trace the specific QdNOs drug used in food animal production. Herein, a liquid chromatography tandem mass spectrometry method was developed to determine QCA and MQCA, and meanwhile, the prototype drugs were identified by analyzing bis-desoxy QdNOs metabolites in single ion-pair monitoring mode. The method indicated that the average recoveries for QCA and MQCA were from 90 % to 105 % with relative standard deviations below 10 %, and the limits of quantification were 1.0 µg/kg. The limits of detection of five bis-desoxy QdNOs (qualitative markers) reached 0.5 µg/kg. This new analytical strategy can effectively solve the identification problem of QdNOs drugs in animal-derived food.

Preventive effect of human umbilical cord mesenchymal stem cells on skin aging in rats.

The irreversibility of aging makes anti-aging become an important research direction in the field of medical research. As the most direct manifestation of human aging, skin aging has been paid more and more attention. Stem cells have been used as a basis for anti-aging studies in skin, of which adipose-derived mesenchymal stem cells are more commonly used. In this study, human umbilical cord mesenchymal stem cells were used, and human umbilical cord mesenchymal stem cells were intervened while making a skin aging model, which was planned to reduce the process of preventing skin aging in the study method. At the end of the experiment, rat skin and serum were taken for relevant data detection. The results showed that the contents of EGF and VEGF in serum and skin tissue of rats increased and the content of MDA decreased after the application of human umbilical cord mesenchymal stem cells. At the same time, hUCMSC intervention increased skin thickness, increased dermal vessels, increased type I collagen type III collagen mRNA expression, and decreased MMP-1 content in rats. The results showed that hUCMSC could prevent skin aging in rats.

On-demand electrically controlled melatonin release from PEDOT/SNP composite improves quality of chronic neural recording.

Long-time and high-quality signal acquisition performance from implantable electrodes is the key to establish stable and efficient brain-computer interface (BCI) connections. The chronic performance of implantable electrodes is hindered by the inflammatory response of brain tissue. In order to solve the material limitation of biological interface electrodes, we designed sulfonated silica nanoparticles (SNPs) as the dopant of Poly (3,4-ethylenedioxythiophene) (PEDOT) to modify the implantable electrodes. In this work, melatonin (MT) loaded SNPs were incorporated in PEDOT via electrochemical deposition on nickel-chromium (Ni-Cr) alloy electrode and carbon nanotube (CNT) fiber electrodes, without affecting the acute neural signal recording capacity. After coating with PEDOT/SNP-MT, the charge storage capacity of both electrodes was significantly increased, and the electrochemical impedance at 1 kHz of the Ni-Cr alloy electrodes was significantly reduced, while that of the CNT electrodes was significantly increased. In addition, this study inspected the effect of electrically triggered MT release every other day on the quality and longevity of neural recording from implanted neural electrodes in rat hippocampus for 1 month. Both MT modified Ni-Cr alloy electrodes and CNT electrodes showed significantly higher spike amplitude after 26-day recording. Significantly, the histological studies showed that the number of astrocytes around the implanted Ni-Cr alloy electrodes was significantly reduced after MT release. These results demonstrate the potent outcome of PEDOT/SNP-MT treatment in improving the chronic neural recording quality possibly through its anti-inflammatory property.

Large scale uniform Ni-P plated carbon fiber for boosting urea electro-oxidation and electro-detection.

Seeking an excellent electrocatalyst is the trickiest issue for the application of urea electro-oxidation and electro-detection. Phosphorus-doped nickel plating on carbon fibers (Ni-P/CF) is synthesized by simple electroless plating. SEM results exhibit that the Ni-P densely and uniformly grows onto the surface of carbon fibers (CF), forming carbon fibers-like nanoarchitectures. Benefiting from the carbon fibers-like nano architectures with abundant exposed active sites on the surface of CF, electron transfer can be synchronously facilitated, and Ni-P/CF displays superior urea electrooxidation (UOR) performance with potentials of 1.40 V to reach 100 mA cm-2. Impressively, it can maintain at 20 mA cm-2 for 48 h without evident activity attenuation, demonstrating robust durability. Cycle stability shows that the voltage has only increased by 10 mV at 300 mA cm-2 from the 10th to 20000th cycles. Most importantly, Ni-P/CF at a length of 100 cm with good reproducibility was successfully synthesized, denoting great potential for large-scale industrial production. Therefore, this work not only affords cost-effective tactics for urea-rich wastewater degradation but also can achieve practical medical applications.

Effects of N-butanol extract of Amygdalus mongolica on rats with bleomycin-induced pulmonary fibrosis based on metabolomics.

Pulmonary fibrosis (PF) is a major public health issue with limited treatment options. As the active ingredient of the n-butanol extract of Amygdalus mongolica (BUT), amygdalin inhibits PF. However, its mechanisms of action are unclear and need further verification. Therefore, the purpose of the present studies was to investigate the anti-fibrotic effects of BUT on PF by serum metabolomics and the transforming growth factor ß (TGF-ß) pathway. Sixty male Sprague-Dawley rats were randomly divided into control, untreated PF, prednisone-treated (5 mg/kg), and BUT-treated (1.75, 1.25, 0.75 g/kg) groups, and the respective drugs were administered intragastrically for 21 days. The serum metabolomics profiles were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) and metabolism network analysis. The expression of TGF-ß1, Smad-3, Smad-7, and α-smooth muscle actin (α-SMA) was measured using a real-time polymerase chain reaction in the lung tissue. BUT significantly alleviated fibrosis by reducing the mRNA expressions of TGF-ß1 (from 1.73 to 1.13), Smad-3 (from 2.01 to 1.19), and α-SMA (from 2.14 to 1.19) and increasing that of Smad7 (from 0.17 to 0.62). Twenty-eight potential biomarkers associated with PF were identified. In addition, four key biomarkers were restored to baseline levels following BUT treatment, with the lowest dose showing optimal effect. Furthermore, A. mongolica BUT was found to improve PF by the pentose phosphate pathway and by taurine, hypotaurine, and arachidonic acid metabolism. These findings revealed the mechanism of A. mongolica BUT antifibrotic effects and metabolic activity in PF rats and provided the experimental basis for its clinical application.

The Role and Potential Regulatory Mechanism of STING Modulated Macrophage Apoptosis and Differentiation in Severe Acute Pancreatitis-Associated Lung Injury.

This study aims to investigate the role of STING in promoting macrophage apoptosis and regulating macrophage polarization in severe acute pancreatitis (SAP)-associated lung injury in vitro and in vivo. A murine model was established by intraperitoneal injection of caerulein and lipopolysaccharide (LPS). Meanwhile, ANA-1 cells were stimulated with LPS to induce apoptosis in vitro. More primary alveolar macrophages underwent apoptosis and M1 macrophage polarization in the SAP group compared with the control group, which was reversed by inhibiting STING. When ANA-1 cells were induced into M2-type macrophages, the reduction of M1 macrophage markers was accompanied by a decrease of LPS-induced apoptosis. Finally, the inhibitory effect of C-176 on STING ameliorates lung injury and inflammation by adjusting macrophage polarization and rescuing apoptosis. Therefore, inhibiting STING could be a new therapeutic strategy for treating acute pancreatitis-associated lung injury.

α-Catenin acetylation is essential for its stability and blocks its tumor suppressor effects in breast cancer through Yap1.

α-Catenin plays a critical role in tissue integrity, repair, and embryonic development. However, the post-translational modifications of α-catenin and the correlative roles in regulating cancer progression remain unclear. Here, we report that α-catenin is acetylated by p300, and identify three acetylation sites, K45, K866, and K881. Conversely, α-catenin acetylation can be reversed by deacetylase HDAC6. Mechanistically, α-catenin acetylation releases the transcriptional coactivator Yes-associated protein 1 (Yap1) by blocking the interaction between α-catenin and Yap1, and promotes the accumulation of Yap1 in the nucleus. Through this mechanism, acetylation weakens the capacity of α-catenin to inhibit breast cancer cell proliferation and tumor growth in mice. Meanwhile, we show that CDDP induces acetylation of α-catenin, and acetylated α-catenin resists the apoptosis under CDDP conditions. Additionally, acetylation inhibits the proteasome-dependent degradation of α-catenin, thus enhancing the stability of α-catenin for storage. Taken together, our results demonstrate that α-catenin can be acetylated, an event that is key for the subcellular distribution of Yap1 and subsequent facilitation of breast tumorigenesis.

KLF12 promotes the proliferation of breast cancer cells by reducing the transcription of p21 in a p53-dependent and p53-independent manner.

Breast cancer is the most common cancer affecting women worldwide. Many genes are involved in the development of breast cancer, including the Kruppel Like Factor 12 (KLF12) gene, which has been implicated in the development and progression of several cancers. However, the comprehensive regulatory network of KLF12 in breast cancer has not yet been fully elucidated. This study examined the role of KLF12 in breast cancer and its associated molecular mechanisms. KLF12 was found to promote the proliferation of breast cancer and inhibit apoptosis in response to genotoxic stress. Subsequent mechanistic studies showed that KLF12 inhibits the activity of the p53/p21 axis, specifically by interacting with p53 and affecting its protein stability via influencing the acetylation and ubiquitination of lysine370/372/373 at the C-terminus of p53. Furthermore, KLF12 disrupted the interaction between p53 and p300, thereby reducing the acetylation of p53 and stability. Meanwhile, KLF12 also inhibited the transcription of p21 independently of p53. These results suggest that KLF12 might have an important role in breast cancer and serve as a potential prognostic marker and therapeutic target.

Role of stem cell derivatives in inflammatory diseases.

Mesenchymal stem cells (MSCs) are pluripotent stem cells of mesodermal origin with the ability of self-renewal and multidirectional differentiation, which have all the common characteristics of stem cells and the ability to differentiate into adipocytes, osteoblasts, neuron-like cells and other cells. Stem cell derivatives are extracellular vesicles(EVs) released from mesenchymal stem cells that are involved in the process of body's immune response, antigen presentation, cell differentiation, and anti-inflammatory. EVs are further divided into ectosomes and exosomes are widely used in degenerative diseases, cancer, and inflammatory diseases due to their parental cell characteristics. However, most diseases are closely related to inflammation, and exosomes can mitigate the damage caused by inflammation in terms of suppressing the inflammatory response, anti-apoptosis and promoting tissue repair. Stem cell-derived exosomes have become an emerging modality for cell-free therapy because of their high safety and ease of preservation and transportation through intercellular communication. In this review, we highlight the characteristics and functions of MSCs-derived exosomes and discuss the regulatory mechanisms of MSCs-derived exosomes in inflammatory diseases and their potential applications in clinical diagnosis and therapy.

Exosome and virus infection.

Exosomes are messengers of intercellular communication in monolayer vesicles derived from cells. It affects the pathophysiological process of the body in various diseases, such as tumors, inflammation, and infection. It has been confirmed that exosomes are similar to viruses in biogenesis, and exosome cargo is widely involved in many viruses' replication, transmission, and infection. Simultaneously, virus-associated exosomes can promote immune escape and activate the antiviral immune response of the body, which bidirectionally modulates the immune response. This review focuses on the role of exosomes in HIV, HBV, HCV, and SARS-CoV-2 infection and explores the prospects of exosome development. These insights may be translated into therapeutic measures for viral infections and reduce the disease burden.