High-Pressure Induced Continuous Structural Evolution of Kagome Antiferromagnet MgMn3(OH)6Cl2: A Structural Analogue to Quantum Spin Liquid Herbertsmithite.

MgMn3(OH)6Cl2 serves readily as the classical Heisenberg kagome antiferromagnet lattice spin frustration material, due to its similarity to herbertsmithite in composition and crystal structure. In this work, nanosheets of MgMn3(OH)6Cl2 are synthesized through a solid-phase reaction. Low-temperature magnetic measurements revealed two antiferromagnetic transitions, occurring at ∼8 and 55 K, respectively. Utilizing high-pressure synchrotron radiation X-ray diffraction techniques, the topological structural evolution of MgMn3(OH)6Cl2 under pressures up to 24.8 GPa was investigated. The sample undergoes a second-order structural phase transition from the rhombohedral phase to the monoclinic phase at pressures exceeding 7.8 GPa. Accompanying the disappearance of the Fano-like line shape in the high-pressure Raman spectra were the emergence of new Raman active modes and discontinuities in the variations of Raman shifts in the high-frequency region. The phase transition to a structure with lower symmetry was attributed to the pressure-induced enhancement of cooperative Jahn-Teller distortion, which is caused by the mutual substitution of Mn2+ ions from the kagome layer and Mg2+ ions from the triangular interlayer. High-pressure ultraviolet-visible absorption measurements support the structural evolution. This research provides a robust experimental approach and physical insights for further exploration of classical geometrical frustration materials with kagome lattice.

Efficacy and safety of immunosuppressive therapy combined with eltrombopag for severe aplastic anemia: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the main factor limiting its efficacy is too few residual hematopoietic stem/progenitor cells (HSPC). Eltrombopag (EPAG), as a small molecule thrombopoietin receptor agonist, can stimulate the proliferation of residual HSPC and restore the bone marrow hematopoietic function of patients. In recent years, many studies have observed the efficacy and safety of IST combined with EPAG in the treatment of SAA, but the results are still controversial. The aim of this study is to systematically evaluate the efficacy and safety of IST combined with or without EPGA in the treatment of SAA. METHODS: We conducted a systematic review of all relevant literature published up to January 19, 2024. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant by Review Manager 5.4.1. The p values for the interactions between each subgroup were calculated by Stata 15.1. The Newcastle-Ottawa Scale and the Cochrane bias risk assessment tools were respectively used to evaluate the quality of the literature with cohort studies and randomized controlled trials. The Review Manager 5.4.1 and Stata 15.1 were used to assess bias risk and perform the meta-analysis. RESULTS: A total of 16 studies involving 2148 patients were included. The IST combined with the EPAG group had higher overall response rate (ORR) than the IST group at 3 months (pooled OR = 2.10, 95% CI 1.58-2.79, p < 0.00001) and 6 months (pooled OR = 2.13, 95% CI 1.60-2.83, p < 0.00001), but the difference between the two groups became statistically insignificant at 12 months (pooled OR = 1.13, 95% CI 0.75-1.72, p = 0.55). The results of complete response rate (CRR) (pooled OR at 3 months = 2.73, 95% CI 1.83-4.09, p < 0.00001, 6 months = 2.76, 95% CI 2.08-3.67, p < 0.00001 and 12 months = 1.38, 95% CI 0.85-2.23, p = 0.19) were similar to ORR. Compared with the IST group, the IST combined with the EPAG group had better overall survival rate (OSR) (pooled OR = 1.70, 95% CI 1.15-2.51, p = 0.008), but there were no statistically significant differences in event-free survival rate (EFSR) (pooled OR = 1.40, 95% CI 0.93-2.13, p = 0.11), clonal evolution rate (pooled OR = 0.68, 95% CI 0.46-1.00, p = 0.05) and other adverse events between the two groups. The results of subgroup analysis showed that different ages were a source of heterogeneity, but different study types and different follow-up times were not. Moreover, all p-values for the interactions were greater than 0.05, suggesting that the treatment effect was not influenced by subgroup characteristics. CONCLUSION: EPAG added to IST enables patients to achieve earlier and faster hematologic responses with a higher rate of complete response. Although it had no effect on overall EFSR, it improved OSR and did not increase the incidence of clonal evolution and other adverse events.

Citric Acid Promotes Immune Function by Modulating the Intestinal Barrier.

Amidst increasing concern about antibiotic resistance resulting from the overuse of antibiotics, there is a growing interest in exploring alternative agents. One such agent is citric acid, an organic compound commonly used for various applications. Our research findings indicate that the inclusion of citric acid can have several beneficial effects on the tight junctions found in the mouse intestine. Firstly, the study suggests that citric acid may contribute to weight gain by stimulating the growth of intestinal epithelial cells (IE-6). Citric acid enhances the small intestinal villus-crypt ratio in mice, thereby promoting intestinal structural morphology. Additionally, citric acid has been found to increase the population of beneficial intestinal microorganisms, including Bifidobacterium and Lactobacillus. It also promotes the expression of important protein genes such as occludin, ZO-1, and claudin-1, which play crucial roles in maintaining the integrity of the tight junction barrier in the intestines. Furthermore, in infected IEC-6 cells with H9N2 avian influenza virus, citric acid augmented the expression of genes closely associated with the influenza virus infection. Moreover, it reduces the inflammatory response caused by the viral infection and thwarted influenza virus replication. These findings suggest that citric acid fortifies the intestinal tight junction barrier, inhibits the replication of influenza viruses targeting the intestinal tract, and boosts intestinal immune function.

Polydopamine-Modified 2D Iron (II) Immobilized MnPS3 Nanosheets for Multimodal Imaging-Guided Cancer Synergistic Photothermal-Chemodynamic Therapy.

Manganese phosphosulphide (MnPS3 ), a newly emerged and promising member of the 2D metal phosphorus trichalcogenides (MPX3 ) family, has aroused abundant interest due to its unique physicochemical properties and applications in energy storage and conversion. However, its potential in the field of biomedicine, particularly as a nanotherapeutic platform for cancer therapy, has remained largely unexplored. Herein, a 2D "all-in-one" theranostic nanoplatform based on MnPS3 is designed and applied for imaging-guided synergistic photothermal-chemodynamic therapy. (Iron) Fe (II) ions are immobilized on the surface of MnPS3 nanosheets to facilitate effective chemodynamic therapy (CDT). Upon surface modification with polydopamine (PDA) and polyethylene glycol (PEG), the obtained Fe-MnPS3 /PDA-PEG nanosheets exhibit exceptional photothermal conversion efficiency (η = 40.7%) and proficient pH/NIR-responsive Fenton catalytic activity, enabling efficient photothermal therapy (PTT) and CDT. Importantly, such nanoplatform can also serve as an efficient theranostic agent for multimodal imaging, facilitating real-time monitoring and guidance of the therapeutic process. After fulfilling the therapeutic functions, the Fe-MnPS3 /PDA-PEG nanosheets can be efficiently excreted from the body, alleviating the concerns of long-term retention and potential toxicity. This work presents an effective, precise, and safe 2D "all-in-one" theranostic nanoplatform based on MnPS3 for high-efficiency tumor-specific theranostics.

Time-Course Transcriptome Analysis of Aquilegia vulgaris Root Reveals the Cell Wall's Roles in Salinity Tolerance.

Salt stress has a considerable impact on the development and growth of plants. The soil is currently affected by salinisation, a problem that is becoming worse every year. This means that a significant amount of salt-tolerant plant material needs to be added. Aquilegia vulgaris has aesthetically pleasing leaves, unique flowers, and a remarkable tolerance to salt. In this study, RNA-seq technology was used to sequence and analyse the transcriptome of the root of Aquilegia vulgaris seedlings subjected to 200 mM NaCl treatment for 12, 24, and 48 h. In total, 12 Aquilegia vulgaris seedling root transcriptome libraries were constructed. At the three time points of salt treatment compared with the control, 3888, 1907, and 1479 differentially expressed genes (DEGs) were identified, respectively. Various families of transcription factors (TFs), mainly AP2, MYB, and bHLH, were identified and might be linked to salt tolerance. Gene Ontology (GO) analysis of DEGs revealed that the structure and composition of the cell wall and cytoskeleton may be crucial in the response to salt stress. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the DEGs showed a significant enrichment of the pentose and glucuronate interconversion pathway, which is associated with cell wall metabolism after 24 and 48 h of salt treatment. Based on GO and KEGG analyses of DEGs, the pentose and glucuronate interconversion pathway was selected for further investigation. AP2, MYB, and bHLH were found to be correlated with the functional genes in this pathway based on a correlation network. This study provides the groundwork for understanding the key pathways and gene networks in response to salt stress, thereby providing a theoretical basis for improving salt tolerance in Aquilegia vulgaris.

Selenium inhibits ferroptosis in hyperglycemic cerebral ischemia/reperfusion injury by stimulating the Hippo pathway.

Hyperglycemia can exacerbate cerebral ischemia/reperfusion (I/R) injury, and the mechanism involves oxidative stress, apoptosis, autophagy and mitochondrial function. Our previous research showed that selenium (Se) could alleviate this injury. The aim of this study was to examine how selenium alleviates hyperglycemia-mediated exacerbation of cerebral I/R injury by regulating ferroptosis. Middle cerebral artery occlusion (MCAO) and reperfusion models were established in rats under hyperglycemic conditions. An in vitro model of hyperglycemic cerebral I/R injury was created with oxygen-glucose deprivation and reoxygenation (OGD/R) and high glucose was employed. The results showed that hyperglycemia exacerbated cerebral I/R injury, and sodium selenite pretreatment decreased infarct volume, edema and neuronal damage in the cortical penumbra. Moreover, sodium selenite pretreatment increased the survival rate of HT22 cells under OGD/R and high glucose conditions. Pretreatment with sodium selenite reduced the hyperglycemia mediated enhancement of ferroptosis. Furthermore, we observed that pretreatment with sodium selenite increased YAP and TAZ levels in the cytoplasm while decreasing YAP and TAZ levels in the nucleus. The Hippo pathway inhibitor XMU-MP-1 eliminated the inhibitory effect of sodium selenite on ferroptosis. The findings suggest that pretreatment with sodium selenite can regulate ferroptosis by activating the Hippo pathway, and minimize hyperglycemia-mediated exacerbation of cerebral I/R injury.

Structural phase transformation of quantum spin liquid herbertsmithite via pressure induced enhancement of the cooperative Jahn-Teller effect and antisite disorder.

Herbertsmithite, Cu3Zn(OH)6Cl2, serves as one of the most promising candidates for quantum spin liquids with a perfect quantum kagome Heisenberg antiferromagnetic system. It can comprise an ideal model system for studying the compression response of the unique structure as well as exotic properties of kagome quantum spin liquid materials, which is of fundamental importance from both scientific and technological viewpoints. In this work, the structural evolution of herbertsmithite was investigated via in situ X-ray diffraction and Raman scattering techniques up to 30 GPa. The trigonal herbertsmithite structure transformed into a monoclinic clinoatacamite-like structure at 12.6 GPa. High pressure seems to act in a reverse way as Zn-doping for herbertsmithite, with the distortion degree of the system changing continuously. The occurrence of the displacive and reversible phase transition between the polymorphs is a consequence of the interplay between the external pressure and cooperative Jahn-Teller (JT) effect, aided by the presence of antisite mutual substitution of magnetic Cu2+ ions and nonmagnetic Zn2+ ions between the kagome layer and interlayer sites.

Metformin alleviates cerebral ischemia/reperfusion injury aggravated by hyperglycemia via regulating AMPK/ULK1/PINK1/Parkin pathway-mediated mitophagy and apoptosis.

Stroke remains the main leading cause of death and disabilities worldwide, with diabetes mellitus being a significant independent risk factor for it. Metformin, as an efficient hypoglycemic drug in treating type 2 diabetes, has been reported to alleviate the risk of diabetes-related stroke. However, its underlying mechanisms remain unclear. This study aimed to investigate the role of mitophagy and its regulatory pathway in the neuroprotective mechanism of metformin against cerebral ischemia/reperfusion (I/R) injury aggravated by hyperglycemia. A hyperglycemic cerebral I/R animal model and a high glucose cultured oxygen-glucose deprivation/reperfusion (OGD/R) cell model were used in the experiment. The indexes of brain injury, cell activity, mitochondrial morphology and function, mitophagy, mitochondrial pathway apoptosis and the AMPK pathway were observed. In diabetic rats, metformin treatment decreased cerebral infarction volume and neuronal apoptosis, and improved neurological symptoms following I/R injury. Additionally, metformin induced activation of the AMPK/ULK1/PINK1/Parkin mitophagy pathway to have neuroprotective effects. In vitro, high glucose culture and OGD/R treatment impaired mitochondrial morphology and function, mitochondrial membrane potential, and induced apoptosis. However, metformin activated AMPK/ULK1/PINK1/Parkin mitophagy pathway, normalized mitochondrial injury. This protection was reversed by autophagy inhibitor 3-methyladenine (3MA) and AMPK inhibitor compound C. In conclusion, our present study validates the potential mechanism of metformin in alleviating hyperglycemia aggravated cerebral I/R injury by the activation of AMPK/ULK1/PINK1/Parkin mitophagy pathway.

Current understanding of CTLA-4: from mechanism to autoimmune diseases.

Autoimmune diseases (ADs) are characterized by the production of autoreactive lymphocytes, immune responses to self-antigens, and inflammation in related tissues and organs. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is majorly expressed in activated T cells and works as a critical regulator in the inflammatory response. In this review, we first describe the structure, expression, and how the signaling pathways of CTLA-4 participate in reducing effector T-cell activity and enhancing the immunomodulatory ability of regulatory T (Treg) cells to reduce immune response, maintain immune homeostasis, and maintain autoimmune silence. We then focused on the correlation between CTLA-4 and different ADs and how this molecule regulates the immune activity of the diseases and inhibits the onset, progression, and pathology of various ADs. Finally, we summarized the current progress of CTLA-4 as a therapeutic target for various ADs.

PI3K-AKT-mTOR signaling pathway regulates autophagy of hippocampal neurons in diabetic rats with chronic unpredictable mild stress.

It is reported that the co-morbidities of diabetes and depression will be a new challenge for humanity. However, the underlying mechanism is not clear. The present study investigated the histopathology, autophagy of hippocampal neurons, and the PI3K-AKT- mTOR signaling pathway in type 2 diabetes with depression（T2DD） rats. The results showed that, the chronic unpredictable mild stress (CUMS), Type 2 diabetes mellitus (T2DM) and T2DD in rats were induced successfully. Compared with the CUMS and T2DM groups, the T2DD group performed significantly fewer autonomic activities in the open-field test, and longer immobile in the force swimming test, and increasing of Corticosterone (CORT) in blood. The number of pyknotic neurons at cornu ammonis 1 (CA1) and dentate gyrus (DG) of the hippocampus in T2DD was significantly increased compared with CUMS and T2DM groups. Moreover, compared with the CUMS and T2DM groups, the mitochondrial autophagosomes were most abundant in the T2DD group. As shown in western blot and immunofluorescence, compared with the control group, in the CUMS, T2DM and T2DD groups, significantly increased expression of Beclin-1 and LC3B and decreased P62 were detected. In the PC12 cells, the relative amount of parkin and LC3B in the CORT+HG group was significantly higher than that in the CORT and HG groups. Compared with the control group, p-AKT/AKT and p-mTOR/mTOR in CUMS, T2DM and T2DD groups were significantly decreased. Compared with the CUMS group, p-AKT/AKT, p-PI3K/PI3K and p-mTOR/mTOR in the T2DD group exhibited further decrease. Similar results were obtained in PC12 cells in vitro. It is suggests that memory and cognitive impairment in rats with co-morbidities of diabetes and depression might be related with hippocampal neuronal damage and autophagy increase, which was involved in the PI3K-AKT-mTOR signaling pathway.

The Immunosuppressive Roles of PD-L1 during Influenza A Virus Infection.

The clinical benefits of targeting programmed death-ligand 1 (PD-L1) in various cancers represent a strategy for the treatment of immunosuppressive diseases. Here, it was demonstrated that the expression levels of PD-L1 in cells were greatly upregulated in response to H1N1 influenza A virus (IAV) infection. Overexpression of PD-L1 promoted viral replication and downregulated type-I and type-III interferons and interferon-stimulated genes. Moreover, the association between PD-L1 and Src homology region-2, containing protein tyrosine phosphatase (SHP2), during IAV/H1N1 infection was analyzed by employing the SHP2 inhibitor (SHP099), siSHP2, and pNL-SHP2. The results showed that the expressions of PD-L1 mRNA and protein were decreased under SHP099 or siSHP2 treatment, whereas the cells overexpressing SHP2 exhibited the opposite effects. Additionally, the effects of PD-L1 on the expression of p-ERK and p-SHP2 were investigated in PD-L1-overexpressed cells following WSN or PR8 infection, determining that the PD-L1 overexpression led to the decreased expression of p-SHP2 and p-ERK induced by WSN or PR8 infection. Taken together, these data reveal that PD-L1 could play an important role in immunosuppression during IAV/H1N1 infection; thus, it may serve as a promising therapeutic target for development of novel anti-IAV drugs.

Hybrid lignin particles via ion-crosslinked for selective removal of anionic dyes from water.

Hybrid lignin (HL) particles were synthesized by compounding lignosulfonate and carboxylated chitosan through a simple ionic cross-linking method, and modifying by polyvinylpolyamine. Due to the synergistic effect of recombination and modification, the material exhibits excellent adsorption performance for anionic dyes in water. The structural characteristics and adsorptive behavior were systematically investigated. The pseudo-second-order kinetic model and the Langmuir model were revealed to well describe the sorption procedure of HL for anionic dyes. The results exhibited that the sorption capacities of HL on sodium indigo disulfonate and tartrazine were 1099.01 mg/g and 436.68 mg/g, respectively. Simultaneously, the adsorbent behaved no significant adsorption capacity loss after five adsorption-desorption cycles, indicating its superb stability and recyclability. Additionally, the HL exhibited excellent selective adsorption of anionic dyes form binary dye adsorption systems. The interaction forces between adsorbent and dye molecules, such as hydrogen bonding, π-π stacking, electrostatic attraction and cation bonding bridge, are discussed in detail. The facile preparation process and superior dyes removal performance of HL were considered a potential adsorbent to remove anionic dyes from wastewater.

Tumor-Targeting Nanoassembly for Enhanced Colorectal Cancer Therapy by Eliminating Intratumoral Fusobacterium nucleatum.

Fusobacterium nucleatum (Fn) has long been found to be related to colorectal cancer (CRC), which could promote colorectal tumor progression and cause cancer resistance to chemotherapy. Great efforts have been made to understand the relationship between Fn and CRC, but how to efficiently eliminate intratumoral Fn and overcome chemoresistance remains a critical challenge. Here, an active tumor-targeting acidity-responsive nanomaterial toward eliminating intratumoral Fn is developed for enhancing the treatment of cancer. Lauric acid and phenylboric acid are conjugated to oligomethyleneimine to form OLP followed by interacting with oxaliplatin prodrug-modified polyglycidyl ether (PP) to obtain the OLP/PP nanoassembly. The nanoassembly shows good structural stability under the simulated physiological conditions and has a pH-responsive drug release in an acidic tumor microenvironment. More attractively, the nanoassembly can specifically target the tumor cell, guide cellular uptake, and efficiently eliminate tumor-resident extracellular and intracellular Fn. Through the on-site drug delivery, the nanoassembly can overcome chemoresistance and significantly inhibit tumor growth. Both in vitro and vivo studies show that the prepared nanoassembly presents good biocompatibility. Therefore, this biocompatible nanoassembly possessing efficient antibacterial and antitumor activities provides new promise for the therapy of bacterial infected tumors.

Adenosine Receptor A2B Antagonist Inhibits the Metastasis of Gastric Cancer Cells and Enhances the Efficacy of Cisplatin.

Adenosine receptors play a key role in cancer progression. This study investigated the effect of the adenosine A2B receptor (ADORA2B) on epithelial-mesenchymal transition (EMT) markers and cell metastasis of gastric cancer (GC) cells. Public databases were used to investigate the specificity of ADORA2B expression in GC tissue. We used immunohistochemistry and immunofluorescence to detect ADORA2B expression in GC tissue, paracancerous tissue, and metastatic greater omental tissue. AGS and HGC-27 GC cells were selected. The effect of ADORA2B on the invasion and migration of GC cells was examined using cell scratch and transwell assays. The effect of ADORA2B on the expression of EMT marker proteins (ß-catenin, N-cadherin, and vimentin) in GC cells was measured by cellular immunohistochemistry, immunofluorescence, and Western blot. The effects of an ADORA2B inhibitor combined with cisplatin on EMT markers in GC cells were further explored. The expression levels of ADORA2B in GC tissue, metastatic greater omental tissue, and lymphatic metastasis tissue were significantly higher than those in paracancerous tissue, and ADORA2B was associated with lymph node metastasis and invasion. ADORA2B significantly regulated the invasion and migration ability of GC cells and the expression levels of EMT marker proteins. The combination of an ADORA2B antagonist (PSB-603) and cisplatin had a more significant effect on reversing the expression of EMT marker proteins. ADORA2B was overexpressed in GC tissue, metastatic greater omental tissue, and metastatic lymph node tissue. ADORA2B regulated the expression of EMT marker proteins in GC cells and affected GC cell metastasis. Antagonizing ADORA2B expression increased the efficacy of cisplatin treatment.

Increased Metallothionein-1 Associated with Gout Activity and Tophi.

BACKGROUND AND AIMS: Gout is a chronic self-limiting inflammatory arthritis. An increase in metallothionein-1 (MT-1) has been reported in rheumatoid arthritis and osteoarthritis, and it attenuates inflammation and the pathology of diseases. This study aims to detect MT-1 levels in patients with gout and to explore its correlation with disease activity, clinical indexes, and inflammatory cytokines. METHODS: The expression of MT-1 messenger RNAs (mRNAs) and protein levels in patients with gout were measured using real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Correlations between MT-1 and clinical indexes or inflammatory mediators were analyzed using Spearman's correlation test. RESULTS: Compared with healthy controls (HCs, n = 43), patients with active gout (n = 27) showed higher levels of MT-1 mRNA in peripheral blood mononuclear cells and protein in serum, particularly those with tophi. No significant difference in serum MT-1 levels was observed among patients with inactive gout, HCs, and patients with hyperuricemia without gout. Furthermore, no significant difference was observed between patients with gout with kidney damage and HCs. In addition, serum interleukin (IL)-1ß, IL-6, and IL-8 levels were significantly increased in patients with active gout, particularly in those with tophi. The serum MT-1 level was positively correlated with C-reactive protein, as well as with IL-1ß, IL-6, and IL-18. CONCLUSION: The higher levels of MT-1 were found in patients with gout, which were correlated with disease activity and gout related pro-inflammatory cytokines. Indicating MT-1 may serve as a new marker for predicting disease activity.Abbreviations: IL-1ß: Interleukin 1ß; MT-1: Metallothionein-1; CRP: C-Reactive Protein; ROS: Reactive Oxygen Species; IL-10: Interleukin 10; TGF-ß: Transforming Growth Factor Beta.

Glutamine potentiates gentamicin to kill lab-evolved gentamicin-resistant and clinically isolated multidrug-resistant Escherichia coli.

Introduction: Gentamicin is a conventional antibiotic in clinic. However, with the wide use of antibiotics, gentamicin-resistant Escherichia coli (E. coli) is an ever-increasing problem that causes infection in both humans and animals. Thus, it is especially important to restore gentamicin-mediated killing efficacy. Method: E. coli K12 BW25113 cells were passaged in medium with and without gentamicin and obtain gentamicin-resistant (K12-R GEN ) and control (K12-S) strains, respectively. Then, the metabonomics of the two strains were analyzed by GC-MS approach. Results: K12-R GEN metabolome was characterized as more decreased metabolites than increased metabolites. Meantime, in the most enriched metabolic pathways, almost all of the metabolites were depressed. Alanine, aspartate and glutamate metabolism and glutamine within the metabolic pathway were identified as the most key metabolic pathways and the most crucial biomarkers, respectively. Exogenous glutamine potentiated gentamicin-mediated killing efficacy in glutamine and gentamicin dose-and time-dependent manners in K12-R GEN . Further experiments showed that glutamine-enabled killing by gentamicin was effective to clinically isolated multidrug-resistant E. coli. Discussion: These results suggest that glutamine provides an ideal metabolic environment to restore gentamicin-mediated killing, which not only indicates that glutamine is a broad-spectrum antibiotic synergist, but also expands the range of metabolites that contribute to the bactericidal efficiency of aminoglycosides.

Metallothionein-1 is Positively Correlated with Inflammation and Ankylosing Spondylitis Activity.

Introduction: Ankylosing spondylitis (AS) is a common form of chronic inflammatory rheumatic disease. Metallothionein-1 (MT-1) has been known to play an immunosuppressive role in various noninfectious inflammatory diseases, especially osteoarthritis and rheumatoid arthritis, thus inhibiting inflammation and pathogenesis in various diseases. However, whether MT-1 is related to AS is unclear. Here, we examined the levels of MT-1 in patients with AS and its correlation with the disease activity, complication, clinical indexes, and inflammatory cytokines and attempted to explain the effect of MT-1 on inflammation in AS. Methods: The messenger RNA (mRNA) and protein expression of MT-1 in patients with AS were detected through real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The associations between serum MT-1 protein level and clinical indexes or proinflammatory cytokines in AS were analyzed using the Spearman correlation test. Results: The mRNAs and serum protein levels of MT-1 were significantly higher in patients with AS, especially in patients with active AS and patients with osteoporosis (OP) than in healthy controls (HCs), and no difference was observed between patients with inactive AS and HCs. Serum MT-1 levels positively correlated with disease activity, proinflammatory cytokines, and clinical indexes Ankylosing Spondylitis Disease Activity Score with C-Reactive Protein, C-reactive protein level, and erythrocyte sedimentation rate in patients with AS. Conclusion: MT-1 expression was upregulated in patients with active AS but not in those with inactive AS and positively correlated with clinical indexes, especially in OP, as well as with proinflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-1ß, and IL-6 in patients with AS.

Dapagliflozin Inhibits Ventricular Remodeling in Heart Failure Rats by Activating Autophagy through AMPK/mTOR Pathway.

Objective: Heart failure (HF) is the end stage of heart disease caused by various factors which mainly involves ventricular remodeling (VR). In HF patients with reduced ejection fraction, dapagliflozin (DAPA) reduced the risk of worsening HF or cardiovascular death. Thus, we attempted to clarify the specific role of DAPA underlying HF progression. Methods: The HF rat model was established to mimic characteristics of HF in vivo. HE staining assessed histopathological changes in left ventricular myocardial tissue of rats in each group. ELISA measured plasma ANP and BNP levels of rats in each group. M-mode echocardiography detected cardiac function of rats in each group. TUNEL staining detected apoptosis of infarct margin cells in myocardial tissue of rats in each group. Western blot detected levels of apoptosis-related proteins, autophagy-related proteins, and AMPK/mTOR-related proteins in myocardial tissue of rats in each group. Immunohistochemical staining detected caspase-3 or LC3B level in myocardial tissue of rats in each group. The HF cellular model was established to mimic characteristics of HF in vitro. Flow cytometry detected H9C2 cell apoptosis under different conditions. Western blot detected levels of apoptosis-related proteins, autophagy-related proteins, and AMPK/mTOR-related proteins in H9C2 cells under different conditions. Immunofluorescence detected caspase-3 or LC3B level in H9C2 cells under different conditions. Results: DAPA attenuated left VR and improved cardiac function in HF rats. DAPA attenuated cardiomyocyte apoptosis in HF rats. DAPA facilitated cardiomyocyte autophagy in HF rats via the AMPK/mTOR pathway. DAPA repressed hypoxia-induced H9C2 cell apoptosis by facilitating autophagy. DAPA repressed hypoxia-induced H9C2 cell apoptosis via the AMPK/mTOR pathway. Conclusion: DAPA suppresses ventricular remodeling in HF through activating autophagy via AMPK/mTOR pathway, which provides a potential novel insight for seeking therapeutic plans of HF.

Robotic Intracellular Electrochemical Sensing for Adherent Cells.

Nanopipette-based observation of intracellular biochemical processes is an important approach to revealing the intrinsic characteristics and heterogeneity of cells for better investigation of disease progression or early disease diagnosis. However, the manual operation needs a skilled operator and faces problems such as low throughput and poor reproducibility. This paper proposes an automated nanopipette-based microoperation system for cell detection, three-dimensional nonovershoot positioning of the nanopipette tip in proximity to the cell of interest, cell approaching and proximity detection between nanopipette tip and cell surface, and cell penetration and detection of the intracellular reactive oxygen species (ROS). A robust focus algorithm based on the number of cell contours was proposed for adherent cells, which have sharp peaks while retaining unimodality. The automated detection of adherent cells was evaluated on human umbilical cord vein endothelial cells (HUVEC) and NIH/3T3 cells, which provided an average of 95.65% true-positive rate (TPR) and 7.59% false-positive rate (FPR) for in-plane cell detection. The three-dimensional nonovershoot tip positioning of the nanopipette was achieved by template matching and evaluated under the interference of cells. Ion current feedback was employed for the proximity detection between the nanopipette tip and cell surface. Finally, cell penetration and electrochemical detection of ROS were demonstrated on human breast cancer cells and zebrafish embryo cells. This work provides a systematic approach for automated intracellular sensing for adherent cells, laying a solid foundation for high-throughput detection, diagnosis, and classification of different forms of biochemical reactions within single cells.

The effect of extended continuous nursing strategy applied to patients with mild brain injury on their quality of life and self-efficacy.

Postoperative rehabilitation of craniocerebral injury requires a long process and has many complications. In addition, patients with severe craniocerebral injury are usually accompanied by impaired nervous system function, which will affect the patients' normal life and work in a period of time after surgery. Reasonable rehabilitation nursing plays an active role in restructuring central nervous system function and coordinating muscle and joint activities. Since the rehabilitation of cerebral trauma is a long process, how to ensure the patients to carry out limb and brain function as well as self-care ability and self-care skills according to the rehabilitation exercise plan and intervention measures formulated before discharge has aroused hot debate. This study analyzed the impact of out-of-hospital continuous nursing strategy applied to patients with mild cerebral trauma on their quality of life and self-efficacy level.