Creation of memory-memory entanglement in a metropolitan quantum network.

Towards realizing the future quantum internet1,2, a pivotal milestone entails the transition from two-node proof-of-principle experiments conducted in laboratories to comprehensive multi-node set-ups on large scales. Here we report the creation of memory-memory entanglement in a multi-node quantum network over a metropolitan area. We use three independent memory nodes, each of which is equipped with an atomic ensemble quantum memory3 that has telecom conversion, together with a photonic server where detection of a single photon heralds the success of entanglement generation. The memory nodes are maximally separated apart for 12.5 kilometres. We actively stabilize the phase variance owing to fibre links and control lasers. We demonstrate concurrent entanglement generation between any two memory nodes. The memory lifetime is longer than the round-trip communication time. Our work provides a metropolitan-scale testbed for the evaluation and exploration of multi-node quantum network protocols and starts a stage of quantum internet research.

Build Borophite from Borophenes: A Boron Analogue Graphite.

Unlike graphene derived from graphite, borophenes represent a distinct class of synthetic two-dimensional materials devoid of analogous bulk-layered allotropes, leading to covalent bonding within borophenes instead of van der Waals (vdW) stacking. Our investigation focuses on 665 vdW-stacking boron bilayers to uncover potential bulk-layered boron allotropes through vdW stacking. Systematic high-throughput screening and stability analysis reveal a prevailing inclination toward covalently bonded layers in the majority of boron bilayers. However, an intriguing outlier emerges in δ5 borophene, demonstrating potential as a vdW-stacking candidate. We delve into electronic and topological structural similarities between δ5 borophene and graphene, shedding light on the structural integrity and stability of vdW-stacked boron structures across bilayers, multilayers, and bulk-layered allotropes. The δ5 borophene analogues exhibit metallic properties and characteristics of phonon-mediated superconductors, boasting a critical temperature near 22 K. This study paves the way for the concept of "borophite", a long-awaited boron analogue of graphite.

The Effect of Different Optic Nerve Sheath Diameter Measurements Using Ultrasound to Assess Intracranial Pressure in Patients With Acute Brain Injury.

BACKGROUND: Optic nerve sheath diameter (ONSD) is a promising, noninvasive invasive intracranial pressure (ICP) measurement method. This study aims to analyze the differences in ONSD between the left and right eyeballs and the differences in ultrasonic measurement between the transverse and sagittal planes. METHODS: Data from a total of 50 eligible patients with various types of brain injury who were admitted to our hospital from May 2019 to June 2021 were analyzed. An ONSD assessment was then performed using Philips B-mode ultrasound, measuring ONSD 3 mm posterior to the eyeballs. The left and right ONSDs in the transverse and sagittal planes were measured. Intraparenchymal fiber optic sensors and catheters were inserted into the ventricles and connected to an external pressure transducer to measure ICP. RESULTS: A total of 164 sonographic measurements of ONSD were performed in 50 patients with brain injury in a prospective observational study. Statistically significant differences were found in ONSD between the transverse and sagittal planes. The difference in the left ONSD between the transverse and sagittal planes was 0.007 ± 0.030 cm (P = 0.003). The Spearman rank correlation test showed that the correlation coefficient between ICP and left/right ONSD in the transverse/sagittal planes was 0.495 vs 0.546 and 0.559 vs 0.605, respectively. The results showed that the areas under the curve of ONSD in the transverse and sagittal planes were 0.843 and 0.805, respectively. Medcalc software was used to compare the areas under the receiver operator characteristic curve, and the results showed that ONSD in the sagittal plane is generally better than in the transverse plane (P = 0.0145). CONCLUSIONS: This study found that ONSD in the sagittal plane is superior to the transverse plane regarding the comprehensive efficacy of ICP, and unilateral measurement is sufficient.

Can optic nerve sheath diameter assessment be used as a non-invasive tool to dynamically monitor intracranial pressure?

This study aims to detect whether the optic nerve sheath diameter (ONSD) can be used to dynamically monitor intracranial pressure (ICP). Adult patients undergoing invasive ICP monitoring on the day of admission are included in this study. For each patient, the ONSD is first measured in the supine position and then in the 30° head-up position. Subsequently, a dynamic test is conducted on 16 patients. The ONSD is measured in the supine position once a day for three consecutive days starting on the day of admission. There is a strong correlation between the ONSD and ICP values in the supine position on admission (r = 0.799), and when patients are changed from the supine to the 30° head-up position, the ICP and ONSD values decrease correspondingly. However, the change in ICP is not strongly correlated with the change in ONSD (r = 0.358). In the dynamic test, a good agreement between the ICP and ONSD only exists in three patients (18.8%), and three patients have completely different profiles for ICP and ONSD. These results suggest that the changes in the ONSD and ICP values are not closely correlated after dynamic observation. Therefore, measurement of the ONSD may not be a suitable tool to dynamically monitor ICP.

Andrographolide inhibits secretagogue-induced pseudo-allergic reaction.

Many kinds of drugs induce pseudo-allergic reactions due to activation of mast cells. We investigated the anti-pseudo-allergic effect of andrographolide (Andro). The effects of Andro on pseudo-allergic reactions were investigated in vivo and in vitro. Andro suppressed compound 48/80 (C48/80) induced pseudo-allergic reactions in mice in a dose-dependent manner. Andro also inhibited C48/80-induced local inflammatory reactions in mice. In vitro studies revealed that Andro reduced C48/80-induced mast cells degranulation. Human phospho-kinase array kit and western blotting showed that Andro could inhibit pseudo-allergic responses via the calcium signaling pathway.

NLRP3 inflammasome induced liver graft injury through activation of telomere-independent RAP1/KC axis.

Acute-phase inflammation plays a critical role in liver graft injury. Inflammasomes, multi-molecular complexes in the cytoplasm, are responsible for initiating inflammation. Here, we aimed to explore the role of inflammasomes in liver graft injury and further to investigate the regulatory mechanism. In a clinical liver transplant cohort, we found that intragraft expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes was significantly up-regulated post-transplantation. Importantly, overexpression of NLRP3 was strongly associated with poor liver function characterized by high levels of ALT, AST, and urea, as well as neutrophil infiltration after transplantation. The significant correlation between NLRP3 and IL-1ß mRNA levels led us to focus on one of the associated upstream regulators, telomere-independent repressor activator protein 1 (RAP1), which was further proved to be co-localized with NLRP3 in neutrophils. In the liver of a mouse model (hepatic ischaemia/reperfusion and hepatectomy model) and isolated neutrophils from RAP1-/- mice, the expression levels of NLRP3 and keratinocyte chemoattractant (KC) were significantly down-regulated in contrast to those in wild types. The levels of ALT and AST, as well as the neutrophil infiltration, were also decreased by RAP1 deficiency. In our clinical validation, intragraft KC expression was associated with NLRP3 and co-localized with RAP1 in neutrophils. Furthermore, NLRP3 inflammasomes were up-regulated by recombinant KC in the isolated neutrophils and liver of the mouse model. Our data demonstrated that NLRP3 inflammasomes, activated by the RAP1/KC axis, played a critical role in initiating inflammation during the early stage of liver graft injury. Targeting RAP1/KC/NLRP3 inflammasomes may offer a new therapeutic strategy against liver graft injury. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Zinc Absorption from Representative Diet in a Chinese Elderly Population Using Stable Isotope Technique.

OBJECTIVE: To determine the dietary zinc absorption in a Chinese elderly population and provide the basic data for the setting of zinc (Zn) recommended nutrient intakes (RNI) for Chinese elderly people. METHODS: A total of 24 elderly people were recruited for this study and were administered oral doses of 3 mg 67Zn and 1.2 mg dysprosium on the fourth day. The primary macronutrients, energy, and phytic acid in the representative diet were examined based on the Chinese National Standard Methods. Fecal samples were collected during the experimental period and analyzed for zinc content, 67Zn isotope ratio, and dysprosium content. RESULTS: The mean (± SD) zinc intake from the representative Chinese diet was 10.6 ± 1.5 mg/d. The phytic acid-to-zinc molar ratio in the diet was 6.4. The absorption rate of 67Zn was 27.9% ± 9.2%. The RNI of zinc, which were calculated by the absorption rate in elderly men and women, were 10.4 and 9.2 mg/d, respectively. CONCLUSION: This study got the dietary Zn absorption in a Chinese elderly population. We found that Zn absorption was higher in elderly men than in elderly women. The current RNI in elderly female is lower than our finding, which indicates that more attention is needed regarding elderly females' zinc status and health.

CXCL10/CXCR3 signaling mobilized-regulatory T cells promote liver tumor recurrence after transplantation.

BACKGROUND & AIMS: Liver graft injury and tumor recurrence are the major challenges of liver transplantation for the patients with hepatocellular carcinoma (HCC). Here, we aimed to explore the role and mechanism of liver graft injury mobilizing regulatory T cells (Tregs), which lead to late phase tumor recurrence after liver transplantation. METHODS: The correlation among tumor recurrence, liver graft injury and Tregs mobilization were studied in 257 liver transplant recipients with HCC and orthotopic rat liver transplantation models. The direct roles of CXCL10/CXCR3 signaling on Tregs mobilization and tumor recurrence were investigated in CXCL10-/- and CXCR3-/- mice models with hepatic IR injury. RESULTS: Clinically, patients received the graft with graft weight ratio (GWR) <60% had higher HCC recurrence after liver transplantation than the recipients with GWR ⩾60% graft. More circulating Tregs and higher intragraft TLR4/CXCL10/CXCR3 levels were detected in recipients with GWR <60% graft. These results were further validated in rat transplantation model. Foxp3+ cells and expressions of TLR4, CXCL10, TGFß, CTLA-4 and CD274 were increased in rat liver tumor tissues from small-for-size graft group. In mouse model, the mobilization and recruitment of Tregs were decreased in TLR4-/-, CXCL10-/- and CXCR3-/- mice compared to wild-type mice. Moreover, less CXCR3+ Tregs were recruited into liver in CXCL10-/- mice after hepatic IR injury. The knockout of CXCL10 and depletion of Tregs inhibited tumor recurrence after hepatic IR injury. CONCLUSION: CXCL10/CXCR3 signaling upregulated at liver graft injury directly induced the mobilization and intragraft recruitment of Tregs, which further promoted HCC recurrence after transplantation. LAY SUMMARY: There were positive correlation among tumor recurrence, circulating Tregs and liver graft injury after human transplantation for HCC patients. The knockout of CXCL10 decreased hepatic recruitment of CXCR3+ Tregs and late phase tumor recurrence after hepatic IR injury.

Post-transplant endothelial progenitor cell mobilization via CXCL10/CXCR3 signaling promotes liver tumor growth.

BACKGROUND & AIMS: Patients with hepatocellular carcinoma (HCC) receiving living donor liver transplantation appear to possess significantly higher tumor recurrence than the recipients receiving deceased donor liver transplantation. The underlying mechanism for HCC recurrence after transplantation remains unclear. Here, we aim to investigate the impact of small-for-size liver graft injury on HCC recurrence after transplantation. METHODS: The correlation between tumor recurrence, liver graft injury, CXCL10 expression and endothelial progenitor cell (EPC) mobilization was studied in 115 liver transplant recipients and rat orthotopic liver transplantation (OLT) models. The direct role of CXCL10/CXCR3 signaling on EPC mobilization was investigated in CXCL10(-/-) mice and CXCR3(-/-) mice. The role of EPCs on tumor growth and angiogenesis was further investigated in an orthotopic liver tumor model. RESULTS: Clinically, patients with small-for-size liver grafts (<60% of standard liver weight, SLW) had significantly higher HCC recurrence (p=0.04), accompanied by more circulating EPCs and higher early-phase intragraft and plasma CXCL10 levels, than the recipients with large grafts (≥60% of SLW), which were further validated in rat OLT models. Circulatory EPC mobilization was reduced after liver injury both in CXCL10(-/-) mice and CXCR3(-/-) mice in comparison to wild-type controls. CXCL10 recruited EPCs in dose-dependent and CXCR3-dependent manners in vitro. Early-phase EPC/CXCL10 injection enhanced orthotopic liver tumor growth, angiogenesis and metastasis in nude mice. CONCLUSIONS: Post-transplant enhanced CXCL10/CXCR3 signaling in small-for-size liver grafts directly induced EPC mobilization, differentiation and neovessel formation, which further promotes tumor growth. Targeting CXCL10/CXCR3 signaling may attenuate early-phase liver graft injury and prevent late-phase tumor recurrence/metastasis after transplantation.

The inhibition of aldose reductase attenuates hepatic ischemia-reperfusion injury through reducing inflammatory response.

OBJECTIVE: We aim to investigate the role of aldose reductase (AR) in hepatic ischemia-reperfusion injury (IRI) of normal and fatty livers and to explore the underlying mechanisms. BACKGROUND: Hepatic IRI is a typical inflammatory response during liver surgery. It contributes to liver graft failure or nonfunction after transplantation. Increasing evidence implicates that AR plays a key role in a number of inflammatory diseases. However, the role of AR in hepatic IRI is still unknown. METHODS: Intragraft AR expression profile and the association with liver graft injury were investigated in both human and rat liver transplantation using normal or fatty graft. The direct role of AR in hepatic IRI was studied in the AR knockout mice IRI model with or without fatty liver. They were further validated by the simulated IRI in vitro model using fatty LO2 cells with or without AR inhibitor zopolrestat and primary peritoneal macrophages isolated from AR knockout and wild-type mice. Gene expression of inflammatory cytokines/chemokines, the infiltration of macrophages/neutrophils, and NF-κB pathway activation were compared among different groups. RESULTS: AR was overexpressed in liver graft after human and rat liver transplantation and correlated with consequent liver injuries. The knockout of AR significantly attenuated hepatic sinusoidal damage and apoptosis in both normal and fatty livers after IRI. The expression of proinflammatory cytokines/chemokines and neutrophil chemoattractants, infiltration of macrophage and neutrophil, and activation of inflammation-associated NF-κB and JNK pathway were downregulated in AR knockout mice. Furthermore, the inhibition of AR effectively suppressed macrophage migration and decreased lipopolysaccharide (LPS)-induced production of proinflammatory cytokines/chemokines in isolated macrophages. CONCLUSIONS: The deficiency of AR attenuated hepatic IRI in both normal and fatty livers by reducing liver inflammatory responses.

The roles of lipocalin-2 in small-for-size fatty liver graft injury.

OBJECTIVE: To investigate the roles and underlying mechanism of an inflammatory mediator-lipocalin-2 (Lcn2) in small-for-size fatty graft liver injury. BACKGROUND: Understanding of the distinct mechanism regulating small-for-size fatty liver graft injury will be crucial to prevent marginal graft failure during living donor liver transplantation (LDLT). METHODS: The roles of Lcn2 in small fatty graft injury were investigated in orthotopic liver transplantation model rats, human LDLT samples, an in vitro simulated ischemia-reperfusion (IR) model, and a hepatic ischemic reperfusion plus major hepatectomy (IR + H) model in mice. RESULTS: Our result showed that Lcn2 was significantly upregulated together with elevation of chemokine (C-X-C motif) ligand 10 (CXCL10) and activation/infiltration of intragraft macrophages after liver transplantation using small-for-size fatty liver graft compared with that of using small-for-size normal liver graft. Intragraft and plasma levels of Lcn2 were intensified in patients who underwent transplantation with small-for-size fatty graft after LDLT. Lcn2 and CXCL10 were expressed higher in fatty hepatocytes after the simulated IR injury compared with normal hepatocytes. Overexpression of Lcn2 significantly deteriorated IR + H-induced hepatic injury in correlation with upregulation of CXCL10 and augmentation of infiltrated macrophages. On the contrary, hepatic injury of small fatty liver remnant after IR + H operation was attenuated in the Lcn-2 mice because of suppression of CXCL10 expression and diminishment of macrophage infiltration. CONCLUSIONS: Lcn2 is an important regulator in small-for-size fatty liver graft injury and targeting Lcn2 may be feasible for preventing marginal graft failure in LDLT.

A novel oxygen carrier "YQ23" suppresses the liver tumor metastasis by decreasing circulating endothelial progenitor cells and regulatory T cells.

BACKGROUND: Surgical therapies are the first-line treatments for hepatocellular carcinoma (HCC) patients. However, the high incidence of tumor metastasis after liver surgery remains a severe problem. We aim to investigate the roles and the underlying mechanism of YQ23, stabilized non-polymeric diaspirin cross-linked tetrameric hemoglobin, in liver tumor metastasis after major hepatectomy and partial hepatic ischemia reperfusion (I/R) injury. METHODS: An orthotopic liver tumor model in Buffalo rat was established using the hepatocellular carcinoma cell line McA-RH7777. Major hepatectomy for tumor-bearing lobe and partial hepatic I/R injury were performed at two weeks after orthotopic liver tumor implantation. YQ23 (0.2 g/kg) was administered at 1 hour before ischemia and immediately after reperfusion. Blood samples were collected at day 0, 1, 7, 14, 21 and 28 for detection of circulating endothelial progenitor cells (EPCs) and regulatory T cells (Tregs). RESULTS: Our results showed that YQ23 treatment effectively inhibited intrahepatic and lung metastases together with less tumor angiogenesis at 4 weeks after major hepatectomy and partial hepatic I/R injury. The levels of circulating EPCs and Tregs were significantly decreased in YQ23 treatment group. Furthermore, YQ23 treatment also increased liver tissue oxygenation during hepatic I/R injury. Up-regulation of HO1 and down-regulation of CXCR3, TNF-α and IL6 were detected after YQ23 treatment. CONCLUSIONS: YQ23 treatment suppressed liver tumor metastasis after major hepatectomy and partial hepatic I/R injury in a rat liver tumor model through increasing liver oxygen and reducing the populations of circulating EPCs and Tregs.

Decreased expression and prognostic role of cytoplasmic BRSK1 in human breast carcinoma: correlation with Jab1 stability and PI3K/Akt pathway.

OBJECTIVE: Jun activation domain-binding protein 1 (Jab1) was overexpressed in breast cancer, which was involved in degradation of the cyclin-dependent kinase inhibitor p27(Kip1). The objective of this study was to examine the effect of brain specific kinase 1 (BRSK1) expression on Jab1 over-expression and related signaling pathway in breast cancer. METHODS: Immunohistochemical analysis was performed in 95 human breast carcinoma samples and the data were correlated with clinicopathologic features. Furthermore, Western blot analysis was performed for BRSK1 and Jab1 in breast carcinoma samples and cell lines to evaluate their protein levels and molecular interaction. RESULTS: We found that the cytoplasmic BRSK1 expression was inversely associated with Jab1 expression (P<0.01) and correlated significantly with histologic grade (P=0.006), however nuclear BRSK1 expression couldn't obtain similar results. Kaplan-Meier analysis revealed that survival curves of low versus high expressers of cytoplasmic BRSK1 and Jab1 showed a highly significant separation in breast cancer (P<0.01). While in vitro, following release of breast cancer cell lines from serum starvation, the expression of Jab1, phosphor-Akt (p-Akt) was up-regulated, whereas BRSK1 and p27(Kip1) were decreased. Treatment of phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 could diminish Jab1 expression but increase BRSK1 expression. In addition, we employed siRNA technique to knock down Jab1 and/or BRSK1 expression and observed their effects on MDA-MB-231 cell growth. CONCLUSIONS: BRSK1 is a novel tumor suppressor in breast cancer which inversely correlated with Jab1 expression, may involve in the restoring Jab1-induced suppression of p27(Kip1) and may regulate cell cycle through the PI3K/Akt pathway.

Chronic Toxicity of Genetically Modified Maize with Cry1Ab-ma Gene and Its Effect on Serum Metabolites in Rats.

Genetic engineering has inserted the crystallin (Cry) gene of Bacillus thuringiensis into the genes of maize to cultivate a variety of transgenic insect-resistant maizes. At present, genetically modified maize with Cry1Ab-ma gene (maize CM8101) was in the stage of safety verification. In this study, a 1-year chronic toxicity test was carried out to evaluate the safety of maize CM8101. Wistar rats were selected for the experiment. Rats were randomly divided into three groups and fed the corresponding diets: genetically modified maize group (CM8101 group), parental maize group (Zheng58 group), and AIN group. Rat serum and urine were collected at the third, sixth, and twelfth months of the experiment, and viscera were collected at the end of the experiment for detection. Metabolomics was used to analyze the metabolites in the serum of rats at the 12th month. While the CM8101 group rats' diets were supplemented with 60% maize CM8101, no obvious poisoning symptoms were found in rats, and no poisoning death occurred. There were no negative effects on body weight, food intake, blood and urine indices, or organ histopathological examination results. Furthermore, metabolomics results revealed that, when compared to group differences, the gender of rats had a more obvious effect on metabolites. The CM8101 group primarily changed linoleic acid metabolism in female rats, while glyceropholipid metabolism was altered in male rats. In rats, consumption of maize CM8101 did not result in significant metabolic dysfunction.

[Determination of catecholamines in urine by disperse solid-phase extraction-liquid chromatography based on Ti3C2Tx/polyimide composites].

Neurotransmitters (NTs) are basic signaling chemicals used for communication between cells. The most well-known catecholamines (CAs) are epinephrine, norepinephrine, and dopamine. CAs are an important class of monoamine NTs that contain catechins and amine groups. The accurate determination of CAs in biological samples can provide essential information on potential pathogenic mechanisms. However, biological samples generally contain only trace levels of CAs. Therefore, sample pretreatment is necessary to separate and enrich CAs before instrument analysis. Dispersive solid-phase extraction (DSPE) technology combines the principles of liquid-liquid extraction and solid-phase extraction and is a useful method for purifying and enriching the target analytes in complex matrices. This method has the advantages of low solvent consumption, environmental safety, and high sensitivity and efficiency. In addition, the adsorbents used in DSPE do not need to be packed into a column and can simply be completely dispersed in the sample solution; this excellent feature greatly improves the extraction efficiency and simplifies the extraction process. Therefore, the development of new DSPE materials with high efficiency and adsorption capacity using simple preparation procedures has received wide attention from the research community. Carbon nitrides (MXenes) are a class of two-dimensional layered materials that possess good hydrophilicity, a large number of functional groups (-O, -OH, and -F), large layer spacing, different elemental compositions, excellent biocompatibility, and environmental friendliness. However, these materials have a small specific surface area and poor adsorption selectivity, which limits their applications in SPE. The separation selectivity of MXenes can be significantly improved by functional modification. Polyimide (PI) is a crosslinking product that is mainly formed by the condensation polymerization of binary anhydride and diamine. It has a unique crosslinked network structure, as well as a large number of carboxyl groups, and shows excellent characteristics. Therefore, the synthesis of new PI-functionalized Ti3C2Tx (Ti3C2Tx/PI) composites by growing a PI layer on the surface of two-dimensional MXene nanosheets in situ may not only overcome the adsorptive limitations of MXenes but also effectively improve their specific surface area and porous structure, thereby enhancing their mass transfer capacity, adsorption capacity, and selectivity. In this study, a Ti3C2Tx/PI nanocomposite was fabricated and successfully applied as a DSPE sorbent to enrich and concentrate trace CAs in urine samples. The prepared nanocomposite was examined using various characterization methods, including scanning electron microscopy, Fourier transform-infrared spectroscopy, X-ray diffraction, and zeta potential analysis. The effects of the extraction parameters on the extraction efficiency of Ti3C2Tx/PI were also investigated in detail. The adsorption performance of Ti3C2Tx/PI can be described by pseudo-second-order kinetics and the Freundlich isotherm model. The adsorption process appeared to occur on the outer surface, as well as surface voids, of the nanocomposite. The adsorption mechanism of Ti3C2Tx/PI indicated a chemical adsorption process based on multiple electrostatic, π-π, and hydrogen-bonding interactions. The optimal adsorption conditions included an adsorbent dosage of 20 mg, sample pH of 8, adsorption and elution times of 10 and 15 min, respectively, and eluent composed of acetic acid-acetonitrile-water (5∶47.5∶47.5, v/v/v). A sensitive method for detecting CAs in urine was subsequently developed by coupling Ti3C2Tx/PI as a DSPE sorbent with HPLC-FLD analysis. The CAs were separated on an Agilent ZORBAX ODS analytical column (250 mm×4.6 mm, 5 µm). Methanol and an aqueous solution of 20 mmol/L acetic acid were used as the mobile phases for isocratic elution. Under optimal conditions, the proposed DSPE-HPLC-FLD method exhibited good linearity in the range of 1-250 ng/mL with correlation coefficients >0.99. The limits of detection (LODs) and limits of quantification (LOQs) were calculated based on signal-to-noise ratios of 3 and 10 and found to be in the range of 0.20-0.32 and 0.7-1.0 ng/mL, respectively. The recoveries of the method were in the range of 82.50%-96.85% with RSDs≤9.96%. Finally, the proposed method was successfully applied to the quantification of CAs in urine samples from smokers and nonsmokers, thereby indicating its applicability for determining trace CAs.

[Preparation of sulfonic acid functionalized covalent organic framework solid phase microextraction fibers and their application in the analysis of neurotransmitters in the mouse brain].

Neurotransmitters (NTs) are essential for intercellular communication and primarily include monoamine, amino acid, and cholinergic NTs. These molecules play important roles in the body's stress response, motor coordination, neuronal communication, and homeostatic functions. Previous studies have shown that abnormal changes in NT levels are associated with various neurological disorders. Therefore, the development of accurate analytical methods for NT detection will enhance the current understanding on complex neuropathophysiology by providing functional knowledge and techniques for early diagnosis, thereby facilitating the development of new therapeutic options for the related diseases. The solid phase microextraction (SPME) technique combines sample preparation, separation, and enrichment in a single step and is minimally invasive, low cost, solvent free, and high throughput. SPME has been successfully applied to the in vivo analysis of target analytes in animal, human, and plant tissues. The coating material plays a significant role in the development of in vivo SPME methods and must meet various analytical requirements, including a suitable geometry for the SPME device, high extraction capacity, excellent selectivity, and wide extraction coverage for the target analytes. Covalent organic frameworks (COFs) are porous crystalline polymers constructed from organic framework units through strong covalent bonds; these materials are characterized with a low density, large specific surface area, permanent porosity, excellent chemical/thermal stability, and easy functionalization.In this study, a sulfonic acid-functionalized COF material (COF-SO3H) with good crystallinity, excellent chemical/thermal stability, strong hydrophobicity, a uniform mesoporous structure, and narrow pore size distribution was prepared using 2,4,6-triformylphloroglucinol and 1,4-diamino-2-nitrobenzene as monomers. Then, the COF-SO3H was coated onto the surface of stainless-steel fibers and used for in vivo enrichment of NTs. The structural properties of COF-SO3H were characterized using various techniques, such as scanning electron microscopy (SEM), Fourier transform-infrared spectroscopy (FT-IR), and X-ray diffraction (XRD), all of which showed that COF-SO3H had a good crystalline structure and uniform mesopore distribution with a specific surface area of 46.17 m2/g. Compared with the SPME fibers of HLB, C18, MCX, amino, and PXC columns, the prepared COF-SO3H fibers showed better extraction efficiency for the target NTs. Next, the factors affecting SPME efficiency were optimized. The optimal desorption solvent was formic acid-methanol-water (0.5∶49.5∶50, v/v/v), and the optimal extraction and desorption times were 15 min. A method for the in vivo analysis of NTs in the brains of mice was established by combining the COF-SO3H fibers with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) under optimal conditions. The NTs were separated on an Acquity UPLC BEH-C18 analytical column (100 mm×2.1 mm, 1.7 µm) with 0.1% formic acid aqueous solution (A) and acetonitrile (B) as the mobile phases. The flow rate was set to 0.2 mL/min, and the gradient elution procedure was as follows: 0-4 min, 5%B-6%B; 4-7 min, 6%B-5%B; 7-11 min, 5%B. Under optimal conditions, the method showed good linearity (r2>0.99). The limits of quantification (S/N≥5) were in the range of 0.003-0.005 µg/mL and 3-5 µg/mL for monoamine and amino acid NTs, respectively, with RSDs of less than 20%. The method showed good precision (0.80%-9.70%) and accuracy (2.08%-17.72%), with absolute matrix effects in the range of 82.22%-117.92%. These values reflect the good purification and enrichment abilities of the proposed fibers for the target analytes. Finally, the established SPME method was combined with UPLC-MS/MS and successfully applied to quantify target NTs in the brains of mice. The proposed strategy provides a practical method for the in vivo detection and quantitative analysis of NTs and expands the applications of functionalized COF materials for the analysis of various targets.

Arachidonic acid activates NLRP3 inflammasome in MDSCs via FATP2 to promote post-transplant tumour recurrence in steatotic liver grafts.

Background & Aims: The steatotic grafts have been applied in liver transplantation frequently owing to the high incidence of non-alcoholic fatty liver disease. However, fatty livers are vulnerable to graft injury. Myeloid-derived suppressor cell (MDSC) recruitment during liver graft injury promotes tumour recurrence. Lipid metabolism exerts the immunological influence on MDSCs in tumour progression. Here, we aimed to explore the role and mechanism of inflammasome activation in MDSCs induced by lipid metabolism during fatty liver graft injury and the subsequent effects on tumour recurrence. Methods: MDSC populations and nucleotide-binding oligomerisation domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome levels were investigated in a clinical cohort and a rat liver transplantation model. The mechanism of NLRP3 activation by specific fatty acids was explored in mouse hepatic ischaemia/reperfusion injury (IRI) with tumour recurrence model and in vitro studies. Results: MDSC populations and NLRP3 levels were increased with higher tumour recurrent rate in patients using steatotic grafts. NLRP3 was upregulated in MDSCs with lipid accumulation post mouse fatty liver IRI. Mechanistically, arachidonic acid was discovered to activate NLRP3 inflammasome in MDSCs through fatty acid transport protein 2 (FATP2), which was identified by screening lipid uptake receptors. The mitochondrial dysfunction with enhanced reactive oxygen species bridged arachidonic acid uptake and NLRP3 activation in MDSCs, which subsequently stimulated CD4+ T cells producing more IL-17 in fatty liver IRI. Blockade of FATP2 inhibited NLRP3 activation in MDSCs, IL-17 production in CD4+ T cells, and the tumour recurrence post fatty liver IRI. Conclusions: During fatty liver graft injury, arachidonic acid activated NLRP3 inflammasome in MDSCs through FATP2, which subsequently stimulated CD4+ T cells producing IL-17 to promote tumour recurrence post transplantation. Impact and implications: The high incidence of non-alcoholic fatty liver disease resulted in the frequent application of steatotic donors in liver transplantation. Our data showed that the patients who underwent liver transplantation using fatty grafts experienced higher tumour recurrence. We found that arachidonic acid activated NLRP3 inflammasome in MDSCs through FATP2 during fatty liver graft injury, which led to more IL-17 secretion of CD4+ T cells and promoted tumour recurrence post transplantation. The inflammasome activation by aberrant fatty acid metabolism in MDSCs bridged the acute-phase fatty liver graft injury and liver tumour recurrence.

A novel enemy of cancer: recent investigations into protozoan anti-tumor properties.

Cancer remains a significant global health issue, despite advances in screening and treatment. While existing tumor treatment protocols such as surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy have proven effective in enhancing the prognosis for some patients, these treatments do not benefit all patients. Consequently, certain types of cancer continue to exhibit a relatively low 5-year survival rate. Therefore, the pursuit of novel tumor intervention strategies may help improve the current effectiveness of tumor treatment. Over the past few decades, numerous species of protozoa and their components have exhibited anti-tumor potential via immune and non-immune mechanisms. This discovery introduces a new research direction for the development of new and effective cancer treatments. Through in vitro experiments and studies involving tumor-bearing mice, the anti-tumor ability of Toxoplasma gondii, Plasmodium, Trypanosoma cruzi, and other protozoa have unveiled diverse mechanisms by which protozoa combat cancer, demonstrating encouraging prospects for their application. In this review, we summarize the anti-tumor ability and anti-tumor mechanisms of various protozoa and explore the potential for their clinical development and application.

Novel and highly efficient transformation of carbon dioxide into 2-oxazolidinones over Al-MCM-41 mesoporous-supported ionic liquids.

A type of Al-MCM-41 supported dual imidazolium ionic liquids were constructed and efficiently used as catalysts for the synthesis of 2-oxazolidinones from epoxides, amines, and CO2. The influence of the different catalysts and reaction parameters on the catalytic behaviours was investigated. Al-MCM-41@ILTiCl5 was identified as the most excellent catalyst because it could efficiently promote the three-component cycloaddition of CO2, epoxide, and amines to form the corresponding 2-oxazolidinones in high to excellent yields (84∼96%) with excellent selectivities (98∼99.7%). In addition, the recovery and reuse performances of Al-MCM-41@ILTiCl5 were examined. The catalyst could be recovered by simple filtration and reused six times without a change in the catalytic activity. Green reaction conditions, operational simplicity, feasibility, and sustainability of the functionalized catalyst are the main highlights of the present protocol.