Explore the vast range of titles available.

Fluid‐rock dissolution occurs ubiquitously in geological systems. Surface‐volume scaling is central to predicting overall dissolution rate R involved in modeling dissolution processes. Previous works focused on single‐phase environments but overlooked the multiphase‐flow effect. Here, through limestone‐based microfluidics experiments, we establish a fundamental link between dissolution regimes and scaling laws. In regime I (uniform), the scaling is consistent with classic law, and a satisfactory prediction of R can be obtained. However, the scaling for regime II (localized) deviates significantly from classic law. The underlying mechanism is that the reaction‐induced gas phase forms a layer, acting as a barrier that hinders contact between the acid and rock. Consequently, the error between measurement and prediction continuously amplifies as dissolution proceeds; the predictability is poor. We propose a theoretical model that describes the regime transition, exhibiting excellent agreement with experimental results. This work offers guidance on the usage of scaling law in multiphase flow environments. Plain Language Summary Fluid‐rock dissolution is ubiquitous in natural and engineered systems, including karst formation, geological carbon sequestration, and acid stimulation. Recent developed method for CO2 sequestration relies on mineralization, which transforms CO2 into carbonate minerals through geochemical reactions involving dissolution. The precise modeling of dissolution processes at the continuum‐scale is dependent on the estimation of the overall dissolution rate using surface‐volume scaling laws. This important scaling law is always established in a single‐phase system. Here, through limestone‐based microfluidics experiments, we find that the scaling is significantly affected by the dissolution regime in a multiphase flow environment. When the injection rate is lower, and the geometry is more homogeneous, the dissolution regime adheres to classic law. On the other hand, when the flow is stronger and the heterogeneity exhibits, the dissolution scaling significantly diverges. Our discovery indicates that a layer of CO2 gas attaches to the uneven surface, causing a shielding effect on the dissolution and resulting in a notable deviation. Through establishing a theoretical model for the regime transition, this work offers guidance on the usage of scaling law across various dissolution scenarios. The newly developed scaling can enhance dissolution modeling precision in multiphase flow‐dissolution systems such as geologic carbon sequestration. Key Points We observe two regimes, and the scaling in regime II deviates significantly from classic law, with a poor predictability of dissolution rate We identify a barrier effect in real rock samples that inhibits the contact of acid and rock for the deviation of scaling in regime II We propose a theoretical model for regime transition that offers guidance on the usage of scaling law in multiphase environments

Salt precipitation is a crucial process occurring during CO2 injection into saline aquifers. It significantly alters the porous space, leading to reduced permeability and impaired injectivity. While the dynamics of precipitation have been studied within porous media, our understanding of precipitation patterns and permeability evolution within rough fractures remains inadequate. Here, we conduct flow‐visualization experiments on salt precipitation, wherein dry air invades brine‐filled rough fractures under various flow rate conditions. Our observations reveal that the precipitation pattern shifts from ex situ precipitation to homogeneous form as the flow rate (capillary number Ca) increases. Through real‐time imaging of the salt precipitation process, we determine that ex situ precipitation is due to capillary‐driven backflow. This backflow phenomenon occurs when previously precipitated salt, acting as a hydrophilic porous medium, attracts the brine flow backward. As a result, precipitation occurs at a location different from the original site. We further show that the impact of capillary‐driven backflow is significant at low flow rates and is gradually suppressed as the flow rate increases. We provide a theoretical estimation for the critical Ca for the occurrence of capillary‐driven backflow. As Ca is smaller than this critical value, backflow‐precipitation positive feedback causes fracture voids to become completely clogged, thereby leading to a more substantial permeability reduction. In contrast, a homogeneous precipitation pattern tends to only partially clog the fracture voids, causing a relatively smaller permeability reduction. This study enhances our understanding of the role of capillary‐driven backflow in controlling salt precipitation and permeability reduction in fractures. Plain Language Summary Injecting CO2 into underground water layers (saline aquifers) is one way to tackle climate change by storing it away from the air. However, this process can lead to salt formation within the rock fractures, especially near the injection well, which can block the flow pathways and make it more challenging to inject additional CO2. Our research focuses on how salt forms within the rock fractures when we introduce dry air into areas filled with salty water, at different flow rates. We discover that at slower flow rate, the salt forms in patches due to a process where the salt already formed pulls more water toward it, leading to blockages. At higher flow rates, this doesn’t happen, and the salt is distributed more uniformly, causing less blockage. We identify a specific flow rate at which the transition between these two types of salt formation occurs. Understanding this can help us better manage CO2 injection strategies and make it more effective by minimizing the risk of blockages. This work is important for enhancing how we store CO2 underground, an important strategy in reducing its levels in the atmosphere and fighting global warming. Key Points We show that precipitation pattern shifts from ex situ to homogeneous form and ex situ precipitation is due to capillary‐driven backflow We verify that capillary‐driven backflow occurs when previously precipitated salt, as a hydrophilic porous medium, draws brine flow back We quantify that capillary‐driven backflow causes voids to be completely clogged, leading to a more substantial permeability reductions

(-)-Epigallocatechin-3-O-gallate(EGCG), the highest catechins from green tea, has promisingly been found to sensitize the efficacy of several chemotherapy agents like doxorubicin (DOX) in hepatocellular carcinoma (HCC) treatment. However, the detailed mechanisms by which EGCG augments the chemotherapeutic efficacy remain unclear. Herein, this study was designed to determine the synergistic impacts of EGCG and DOX on hepatoma cells and particularly to reveal whether the autophagic flux is involved in this combination strategy for the HCC. Electron microscopy and fluorescent microscopy confirmed that DOX significantly increased autophagic vesicles in hepatoma Hep3B cells. Western blot and trypan blue assay showed that the increasing autophagy flux by DOX impaired about 45% of DOX-induced cell death in these cells. Conversely, both qRT-PCR and western blotting showed that EGCG played dose-dependently inhibitory role in autophagy signaling, and that markedly promoted cellular growth inhibition. Amazingly, the combined treatment caused a synergistic effect with 40 to 60% increment on cell death and about 45% augmentation on apoptosis versus monotherapy pattern. The DOX-induced autophagy was abolished by this combination therapy. Rapamycin, an autophagic agonist, substantially impaired the anticancer effect of either DOX or combination with EGCG treatment. On the other hand, using small interference RNA targeting chloroquine autophagy-related gene Atg5 and beclin1 to inhibit autophagy signal, hepatoma cell death was dramatically enhanced. Furthermore, in the established subcutaneous Hep3B cells xenograft tumor model, about 25% reduction in tumor growth as well as 50% increment of apoptotic cells were found in combination therapy compared with DOX alone. In addition, immunohistochemistry analysis indicated that the suppressed tendency of autophagic hallmark microtubule-associated protein light chain 3 (LC3) expressions was consistent with thus combined usage in vitro. Taken together, the current study suggested that EGCG emerges as a chemotherapeutic augmenter and synergistically enhances DOX anticancer effects involving autophagy inhibition in HCC.

Spinal manipulative therapy (SMT) has been shown to significantly alleviate pain in patients with lumbar disc herniation (LDH), with its effects closely associated with brain function modulation. This study investigates the neural biomarkers linked to pain relief efficacy following a complete SMT treatment cycle in LDH patients. A total of 59 LDH patients were randomized into two groups: SMT treatment (Group 1, n = 28) and sham treatment (ST) (Group 2, n = 31). A matched healthy control group (Group 3, n = 28) was also included. Functional magnetic resonance imaging (fMRI) was performed on LDH patients at two time points (TPs)—before (TP1) and after (TP2) treatment—while healthy controls were scanned once. Clinical assessments were conducted using the Visual Analogue Scale (VAS) and the Japanese Orthopaedic Association (JOA) scale. Post-treatment results indicated significant improvements in both VAS and JOA scores for Group 1, while the improvement was limited to VAS scores for Group 2. Graph properties analysis revealed notable differences in brain network connectivity between LDH patients and healthy controls, particularly between the left precentral gyrus (left PreCG) and left inferior frontal gyrus, opercular part (left IFGoperc). Enhanced functional connectivity (FC) was observed in Group 1, notably between the right angular gyrus (right ANG) and the left middle orbital gyrus (left ORBmid), with right ANG showing a significant positive correlation with clinical scores. This study identifies the sensorimotor network—salience network are significantly activated in chronic pain among LDH patients. The default mode network—dorsal attention network may serve as key neural biomarkers for the efficacy of SMT treatment in alleviating pain in LDH.

The aim of this study was to investigate the expression of minichromosome maintenance complex component 7 (MCM7) in gastric mucosal lesions, further to find its potential effect as a biomarker to distinguish intraepithelial neoplasia from gastric mucosal lesions. MCM7 and Ki67 were detected in 93 cases of gastric mucosal lesions by immunohistochemistry. MCM7 and Ki67 expression in GT were lowest compared with other groups ( P <0.001), meanwhile there were significant differences compared with Group IM and other groups in MCM7 and Ki67 expression ( P <0.001). MCM7 and Ki67 expression in GSC were highest ( P <0.05). Groups of LGN, HGN and GIC had no significant differences in MCM7 expression ( P >0.05), but there was significant difference compared with Group LGN and Group GIC in Ki67 expression ( P <0.05). MCM7 expression elevated with tumor grade increasing and had positive correlation with Ki67 significantly ( r =0.940, P <0.001). Furthermore, in some cases, some tumor cells were immunoreactive to MCM7 but negative to Ki67. So we concluded that MCM7 is helpful for us to make differential diagnosis in pathological grade, MCM7 combination of Ki67 may serve as more sensitive proliferation markers for evaluation of gastric carcinoma and precancerous lesions.

Research on the brain mechanisms underlying manual therapy (MT)-induced analgesia has been conducted worldwide. However, no bibliometric analysis has been performed on functional magnetic resonance imaging (fMRI) studies of MT analgesia. To provide a theoretical foundation for the practical application of MT analgesia, this study examined the current incarnation, hotspots, and frontiers of fMRI-based MT analgesia research over the previous 20 years. All publications were obtained from the Science Citation Index-Expanded (SCI-E) of Web of Science Core Collection (WOSCC). We used CiteSpace 6.1.R3 to analyze publications, authors, cited authors, countries, institutions, cited journals, references, and keywords. We also evaluated keyword co-occurrences and timelines, and citation bursts. The search was conducted from 2002-2022 and was completed within one day on October 7, 2022. In total, 261 articles were retrieved. The total number of annual publications showed a fluctuating but overall increasing trend. Author B. Humphreys had the highest number of publications (eight articles) and J. E. Bialosky had the highest centrality (0.45). The United States of America (USA) was the country with the most publications (84 articles), accounting for 32.18% of all publications. Output institutions were mainly the University of Zurich, University of Switzerland, and the National University of Health Sciences of the USA. The Spine (118) and the Journal of Manipulative and Physiological Therapeutics (80) were most frequently cited. The four hot topics in fMRI studies on MT analgesia were \"low back pain\", \"magnetic resonance imaging\", \"spinal manipulation\", and \"manual therapy.\" The frontier topics were \"clinical impacts of pain disorders\" and \"cutting-edge technical capabilities offered by magnetic resonance imaging\". fMRI studies of MT analgesia have potential applications. fMRI studies of MT analgesia have linked several brain areas, with the default mode network (DMN) garnering the most attention. Future research should include international collaboration and RCTs on this topic.

Recombinant neorudin (EPR-hirudin, EH) was developed through the addition of an EPR (Glu-Pro-Arg) peptide to the amino terminus of hirudin, which can be recognized and cut by coagulation factors XIa (FXIa) and/or Xa (FXa). In this study, the low-bleeding antithrombotic effects of EH were evaluated utilizing experimental models of thrombosis in rabbits and rats to provide a test basis for clinical trials. The bleeding risks of EH and hirudin were first compared in mice by the tail-clipping method, and then the antithrombotic activity of EH was investigated in a rabbit model of arteriovenous bypass thrombosis and a rat model of thrombotic cerebral infarction. In mice, intravenous administration of EH at 1.5 mg/kg and 3 mg/kg did not affect the bleeding time compared with normal saline, while the administration of hirudin at 1.5 mg/kg prolonged the bleeding time by over 3 times the administration of normal saline. Furthermore, intravenous administration of EH had a significant dose-dependent inhibitory effect on the formation and development of arteriovenous bypass thrombosis and thrombotic cerebral infarction. Compared with an equimolar dose of hirudin, the antithrombotic effect of EH was similar, while the bleeding side effects were significantly attenuated. Moreover, when the antithrombotic effects were similar, EH had a shorter bleeding time and was associated with less bleeding than low molecular weight heparin (LMWH). EH had a therapeutic effect on thrombotic cerebral infarction without increasing the occurrence of cerebral hemorrhage. The findings from the preclinical animal models used in this study showed that EH could not only effectively inhibit thrombus formation but also reduce the risk of bleeding.

Introduction The clinical symptoms of Lumbar Disc Herniation (LDH) can be effectively ameliorated through Lever Positioning Manipulation (LPM), which is closely linked to the brain's pain-regulating mechanisms. Magnetic Resonance Imaging (MRI) offers an objective and visual means to study how the brain orchestrates the characteristics of analgesic effects. From the perspective of multimodal MRI, we applied functional MRI (fMRI) and Magnetic Resonance Spectrum (MRS) techniques to comprehensively evaluate the characteristics of the effects of LPM on the brain region of LDH from the aspects of brain structure, brain function and brain metabolism. This multimodal MRI technique provides a biological basis for the clinical application of LPM in LDH. Methods and analysis A total of 60 LDH patients and 30 healthy controls, matched by gender, age, and years of education, will be enrolled in this study. The LDH patients will be divided into two groups (Group 1, n  = 30; Group 2, n  = 30) using a random number table method. Group 1 will receive LPM treatment once every two days, for a total of 12 times over 4 weeks. Group 2 will receive sham LPM treatment during the same period as Group 1. All 30 healthy controls will be divided into Group 3. Multimodal MRI will be performed on Group 1 and Group 2 at three time points (TPs): before LPM (TP1), after one LPM session (TP2), and after a full course of LPM treatment. The healthy controls (Group 3) will not undergo LPM and will be subject to only a single multimodal MRI scan. Participants in both Group 1 and Group 2 will be required to complete clinical questionnaires. These assessments will focus on pain intensity and functional disorders, using the Visual Analog Scale (VAS) and the Japanese Orthopaedic Association (JOA) scoring systems, respectively. Discussion The purpose of this study is to investigate the multimodal brain response characteristics of LDH patients after treatment with LPM, with the goal of providing a biological basis for clinical applications. Trial registration number https://clinicaltrials.gov/ct2/show/NCT05613179 , identifier: NCT05613179.

The anticoagulant application is an effective treatment modality for cardiovascular diseases such as coronary heart disease, unstable angina pectoris, and myocardial infarction. In this study, the antithrombotic effect of recombinant neorudin (EPR‐hirudin, EH) was evaluated using a canine model of coronary artery thrombosis. A canine model with platelet thrombosis in the left circumferent branch of the coronary artery was designed using Folt's method, and the anti‐thrombus activity of EH was investigated. Femoral administration of EH intravenously had a significant dose‐dependent inhibitory effect on canine coronary artery thrombosis and the effective rates were 66.7% (p < .05), 83.3% (p < .05), and 100% (p < .01) after injection of 0.3, 1.0, and 3.0 mg/kg EH, respectively. Furthermore, EH demonstrated lower bleeding, with shorter bleeding time and less bleeding loss than low molecular weight heparin (LMWH). Under the similar effect intensity of EH and LMWH (85 IU/kg), the bleeding time of the EH group at 30 min was shorter, and the blood loss at 30–120 min was less than that of LMWH (p < .05 and p < .05–.001, respectively). EH had a significant dose‐dependent inhibitory effect in the dose range of 0.3–3.0 mg/kg on the coronary artery thrombosis and lower bleeding side effects than LMWH with a similar antithrombosis effect. Inhibitory of neorudin on cornary artery thrombosis.

Objective: To explore the possible mechanism of improving the imiquimod (IMQ)-induced psoriasis-like inflammation by using polyethylene glycol (PEG) ointment. Methods: We evaluated the appearance of psoriasis lesions by Psoriasis Area and Severity Index (PASI), observed the epidermal proliferation by histopathological staining and immunohistochemical staining, and explored the key molecules and signaling pathways of improving psoriasis-like inflammation treated with PEG ointment by RNA sequencing. Finally, we verified the expression of inflammatory cells and inflammatory factors by flow cytometry, immunohistochemical staining, and Q-PCR. Results: PEG ointment could improve the appearance of psoriasis lesions and the epidermis thickness of psoriasis mouse, inhibit the proliferation of keratinocytes, and down-regulate the relative mRNA levels of IL-23, IL-22, IL-6, IL-17C, IL-17F, S100A7, S100A8, S100A9, CXCL1, CXCL2, and IL-1β in the skin lesions of psoriasis mouse by down-regulating the numbers of myeloid-derived suppressor cells (MDSCs) and T helper 17 (Th17) cells. Conclusion: PEG ointment could improve the IMQ-induced psoriasis-like inflammation by down-regulating the functions of Th17 cells and MDSCs.