Farnesoid X Receptor Protects Murine Lung against IL-6-promoted Ferroptosis Induced by Polyriboinosinic-Polyribocytidylic Acid.

Various infections trigger a storm of proinflammatory cytokines in which IL-6 acts as a major contributor and leads to diffuse alveolar damage in patients. However, the metabolic regulatory mechanisms of IL-6 in lung injury remain unclear. Polyriboinosinic-polyribocytidylic acid [poly(I:C)] activates pattern recognition receptors involved in viral sensing and is widely used in alternative animal models of RNA virus-infected lung injury. In this study, intratracheal instillation of poly(I:C) with or without an IL-6-neutralizing antibody model was combined with metabonomics, transcriptomics, and so forth to explore the underlying molecular mechanisms of IL-6-exacerbated lung injury. We found that poly(I:C) increased the IL-6 concentration, and the upregulated IL-6 further induced lung ferroptosis, especially in alveolar epithelial type II cells. Meanwhile, lung regeneration was impaired. Mechanistically, metabolomic analysis showed that poly(I:C) significantly decreased glycolytic metabolites and increased bile acid intermediate metabolites that inhibited the bile acid nuclear receptor farnesoid X receptor (FXR), which could be reversed by IL-6-neutralizing antibody. In the ferroptosis microenvironment, IL-6 receptor monoclonal antibody tocilizumab increased FXR expression and subsequently increased the Yes-associated protein (YAP) concentration by enhancing PKM2 in A549 cells. FXR agonist GW4064 and liquiritin, a potential natural herbal ingredient as an FXR regulator, significantly attenuated lung tissue inflammation and ferroptosis while promoting pulmonary regeneration. Together, the findings of the present study provide the evidence that IL-6 promotes ferroptosis and impairs regeneration of alveolar epithelial type II cells during poly(I:C)-induced murine lung injury by regulating the FXR-PKM2-YAP axis. Targeting FXR represents a promising therapeutic strategy for IL-6-associated inflammatory lung injury.

Association of clonal hematopoiesis and mosaic chromosomal alterations with solid malignancy incidence and mortality.

BACKGROUND: Understanding the impact of clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) on solid tumor risk and mortality can shed light on novel cancer pathways. METHODS: The authors analyzed whole genome sequencing data from the Trans-Omics for Precision Medicine Women's Health Initiative study (n = 10,866). They investigated the presence of CHIP and mCA and their association with the development and mortality of breast, lung, and colorectal cancers. RESULTS: CHIP was associated with higher risk of breast (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.03-1.64; p = .02) but not colorectal (p = .77) or lung cancer (p = .32). CHIP carriers who developed colorectal cancer also had a greater risk for advanced-stage (p = .01), but this was not seen in breast or lung cancer. CHIP was associated with increased colorectal cancer mortality both with (HR, 3.99; 95% CI, 2.41-6.62; p < .001) and without adjustment (HR, 2.50; 95% CI, 1.32-4.72; p = .004) for advanced-stage and a borderline higher breast cancer mortality (HR, 1.53; 95% CI, 0.98-2.41; p = .06). Conversely, mCA (cell fraction [CF] >3%) did not correlate with cancer risk. With higher CFs (mCA >5%), autosomal mCA was associated with increased breast cancer risk (HR, 1.39; 95% CI, 1.06-1.83; p = .01). There was no association of mCA (>3%) with breast, colorectal, or lung mortality except higher colon cancer mortality (HR, 2.19; 95% CI, 1.11-4.3; p = .02) with mCA >5%. CONCLUSIONS: CHIP and mCA (CF >5%) were associated with higher breast cancer risk and colorectal cancer mortality individually. These data could inform on novel pathways that impact cancer risk and lead to better risk stratification.

How close are we to a breakthrough? The hunt for blood biomarkers in Parkinson's disease diagnosis.

Parkinson's disease (PD), being the second largest neurodegenerative disease, poses challenges in early detection, resulting in a lack of timely treatment options to effectively manage the disease. By the time clinical diagnosis becomes possible, more than 60% of dopamine neurons in the substantia nigra (SN) of patients have already degenerated. Therefore, early diagnosis or identification of warning signs is crucial for the prompt and timely beginning of the treatment. However, conducting invasive or complex diagnostic procedures on asymptomatic patients can be challenging, making routine blood tests a more feasible approach in such cases. Numerous studies have been conducted over an extended period to search for effective diagnostic biomarkers in blood samples. However, thus far, no highly effective biomarkers have been confirmed. Besides classical proteins like α-synuclein (α-syn), phosphorylated α-syn and oligomeric α-syn, other molecules involved in disease progression should also be given equal attention. In this review, we will not only discuss proposed biomarkers that are currently under investigation but also delve into the mechanisms underlying the disease, focusing on processes such as α-syn misfolding, intercellular transmission and the crossing of the blood-brain barrier (BBB). Our aim is to provide an updated overview of molecules based on these processes that may potentially serve as blood biomarkers.

Clostridium butyricum inhibits the inflammation in children with primary nephrotic syndrome by regulating Th17/Tregs balance via gut-kidney axis.

BACKGROUND: Primary nephrotic syndrome (PNS) is a common glomerular disease in children. Clostridium butyricum (C. butyricum), a probiotic producing butyric acid, exerts effective in regulating inflammation. This study was designed to elucidate the effect of C. butyricum on PNS inflammation through the gut-kidney axis. METHOD: BALB/c mice were randomly divided into 4 groups: normal control group (CON), C. butyricum control group (CON+C. butyricum), PNS model group (PNS), and PNS with C. butyricum group (PNS+C. butyricum). The PNS model was established by a single injection of doxorubicin hydrochloride (DOX) through the tail vein. After 1 week of modeling, the mice were treated with C. butyricum for 6 weeks. At the end of the experiment, the mice were euthanized and associated indications were investigated. RESULTS: Since the successful modeling of the PNS, the 24 h urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), urine urea nitrogen (UUN), urine creatinine (UCr), lipopolysaccharides (LPS), pro-inflammatory interleukin (IL)-6, IL-17A were increased, the kidney pathological damage was aggravated, while a reduction of body weights of the mice and the anti-inflammatory IL-10 significantly reduced. However, these abnormalities could be dramatically reversed by C. butyricum treatment. The crucial Th17/Tregs axis in PNS inflammation also was proved to be effectively regulated by C. butyricum treatment. This probiotic intervention notably affected the expression levels of signal transducer and activator of transcription 3 (STAT3), Heme oxygenase-1 (HO-1) protein, and retinoic acid-related orphan receptor gamma t (RORγt). 16S rRNA sequencing showed that C. butyricum could regulate the composition of the intestinal microbial community and found Proteobacteria was more abundant in urine microorganisms in mice with PNS. Short-chain fatty acids (SCFAs) were measured and showed that C. butyricum treatment increased the contents of acetic acid, propionic acid, butyric acid in feces, acetic acid, and valeric acid in urine. Correlation analysis showed that there was a closely complicated correlation among inflammatory indicators, metabolic indicators, microbiota, and associated metabolic SCFAs in the gut-kidney axis. CONCLUSION: C. butyricum regulates Th17/Tregs balance via the gut-kidney axis to suppress the immune inflammatory response in mice with PNS, which may potentially contribute to a safe and inexpensive therapeutic agent for PNS.

PHB2 Maintains the Contractile Phenotype of VSMCs by Counteracting PKM2 Splicing.

BACKGROUND: Phenotypic transition of vascular smooth muscle cells (VSMCs) accounts for the pathogenesis of a variety of vascular diseases during the early stage. Recent studies indicate the metabolic reprogramming may be involved in VSMC phenotypic transition. However, the definite molecules that link energy metabolism to distinct VSMC phenotype remain elusive. METHODS: A carotid artery injury model was used to study postinjury neointima formation as well as VSMC phenotypic transition in vivo. RNA-seq analysis, cell migration assay, collagen gel contraction assay, wire myography assay, immunoblotting, protein interactome analysis, co-immunoprecipitation, and mammalian 2-hybrid assay were performed to clarify the phenotype and elucidate the molecular mechanisms. RESULTS: We collected cell energy-regulating genes by using Gene Ontology annotation and applied RNA-Seq analysis of transforming growth factor-ß or platelet-derived growth factor BB stimulated VSMCs. Six candidate genes were overlapped from energy metabolism-related genes and genes reciprocally upregulated by transforming growth factor-ß and downregulated by platelet-derived growth factor BB. Among them, prohibitin 2 has been reported to regulate mitochondrial oxidative phosphorylation. Indeed, prohibitin 2-deficient VSMCs lost the contractile phenotype as evidenced by reduced contractile proteins. Consistently, Phb2SMCKO mice were more susceptible to postinjury VSMC proliferation and neointima formation compared with Phb2flox/flox mice. Further protein interactome analysis, co-immunoprecipitation, and mammalian 2-hybrid assay revealed that prohibitin 2, through its C-terminus, directly interacts with hnRNPA1, a key modulator of pyruvate kinase M1/2 (PKM) mRNA splicing that promotes PKM2 expression and glycolysis. Prohibitin 2 deficiency facilitated PKM1/2 mRNA splicing and reversion from PKM1 to PKM2, and enhanced glycolysis in VSMCs. Blocking prohibitin 2-hnRNPA1 interaction resulted in increased PKM2 expression, enhanced glycolysis, repressed contractile marker genes expression in VSMCs, as well as aggravated postinjury neointima formation in vivo. CONCLUSIONS: Prohibitin 2 maintains VSMC contractile phenotype by interacting with hnRNPA1 to counteract hnRNPA1-mediated PKM alternative splicing and glucose metabolic reprogramming.

The platelet storage lesion, what are we working for?

BACKGROUND: Platelet concentrate (PC) transfusions are crucial in prevention and treatment of bleeding in infection, surgery, leukemia, and thrombocytopenia patients. Although the technology for platelet preparation and storage has evolved over the decades, there are still challenges in the demand for platelets in blood banks because the platelet shelf life is limited to 5 days due to bacterial contamination and platelet storage lesions (PSLs) at 20-24°C under constant horizontal agitation. In addition, the relations between some adverse effects of platelet transfusions and PSLs have also been considered. Therefore, understanding the mechanisms of PSLs is conducive to obtaining high quality platelets and facilitating safe and effective platelet transfusions. OBJECTIVE: This review summarizes developments in mechanistic research of PSLs and their relationship with clinical practice, providing insights for future research. METHODS: Authors conducted a search on PubMed and Web of Science using the professional terms "PSL" and "platelet transfusion." The obtained literature was then roughly categorized based on their research content. Similar studies were grouped into the same sections, and further searches were conducted based on the keywords of each section. RESULTS: Different studies have explored PSLs from various perspectives, including changes in platelet morphology, surface molecules, biological response modifiers (BMRs), metabolism, and proteins and RNA, in an attempt to monitor PSLs and identify intervention targets that could alleviate PSLs. Moreover, novel platelet storage conditions, including platelet additive solutions (PAS) and reconsidered cold storage methods, are explored. There are two approaches to obtaining high-quality platelets. One approach simulates the in vivo environment to maintain platelet activity, while the other keeps platelets at a low activity level in vitro under low temperatures. CONCLUSION: Understanding PSLs helps us identify good intervention targets and assess the therapeutic effects of different PSLs stages for different patients.

Exploring the origins of the indentation size effect at submicron scales.

The origin of the indentation size effect has been extensively researched over the last three decades, following the establishment of nanoindentation as a broadly used small-scale mechanical testing technique that enables hardness measurements at submicrometer scales. However, a mechanistic understanding of the indentation size effect based on direct experimental observations at the dislocation level remains limited due to difficulties in observing and quantifying the dislocation structures that form underneath indents using conventional microscopy techniques. Here, we employ precession electron beam diffraction microscopy to "look beneath the surface," revealing the dislocation characteristics (e.g., distribution and total length) as a function of indentation depth for a single crystal of nickel. At smaller depths, individual dislocation lines can be resolved, and the dislocation distribution is quite diffuse. The indentation size effect deviates from the Nix-Gao model and is controlled by dislocation source starvation, as the dislocations are very mobile and glide away from the indented zone, leaving behind a relatively low dislocation density in the plastically deformed volume. At larger depths, dislocations become highly entangled and self-arrange to form subgrain boundaries. In this depth range, the Nix-Gao model provides a rational description because the entanglements and subgrain boundaries effectively confine dislocation movement to a small hemispherical volume beneath the contact impression, leading to dislocation interaction hardening. The work highlights the critical role of dislocation structural development in the small-scale mechanistic transition in indentation size effect and its importance in understanding the plastic deformation of materials at the submicron scale.

Risk factors for sternal wound infection after median sternotomy: A nested case-control study and time-to-event analysis.

Although potential risk factors for sternal wound infection (SWI) have been extensively studied, the onset time of SWI and different risk factors for superficial and deep SWI were rarely reported. This nested case-control study aims to compare the onset time and contributors between superficial and deep SWI. Consecutive adult patients who underwent cardiac surgery through median sternotomy in a single center from January 2011 to January 2021 constituted the cohort. The case group was those who developed SWI as defined by CDC and controls were matched 6:1 per case. Kaplan-Meier analysis, LASSO and univariate and multivariate Cox regressions were performed. A simple nomogram was established for clinical prediction of the risk of SWI. The incidence of SWI was 1.1% (61 out of 5471) in our cohort. Totally 366 controls were matched to 61 cases. 26.2% (16 of 61) SWI cases were deep SWI. The median onset time of SWI was 35 days. DSWI had a longer latency than SSWI (median time 46 days vs. 32 days, p = 0.032). Kaplan-Meier analyses showed different time-to-SWI between patients with and without DM (p = 0.0011) or MI (p = 0.0019). Multivariate Cox regression showed that BMI (HR = 1.083, 95% CI: 1.012-1.116, p = 0.022), DM (HR = 2.041, 95% CI: 1.094-3.805, p = 0.025) and MI (HR = 2.332, 95% CI: 1.193-4.557, p = 0.013) were independent risk factors for SWI. Superficial SWI was only associated with BMI (HR = 1.089, 95% CI: 1.01-1.175, p = 0.027), while deep SWI was associated with DM (HR = 3.271, 95% CI: 1.036-10.325, p = 0.043) and surgery time (HR = 1.004, 95% CI: 1.001-1.008, p = 0.027). The nomogram for SWI prediction had an AUC of 0.67, good fitness and clinical effectiveness as shown by the calibration curve and decision curve analyses. BMI, DM and MI were independent risk factors for SWI. DSWI had a longer latency and different risk factors compared to SSWI. The nomogram showed a fair performance and good effectiveness for the clinical prediction of SWI.

The tumor characteristics, treatment strategy, and prognosis in colorectal cancer patients with synchronous liver metastasis in China and the USA.

PURPOSE: This study performed an analysis of clinicopathological characteristics, surgical treatment strategy, and survival for CRC patients with LM between China and the USA. METHODS: The CRC patients with simultaneous LM were identified from the Surveillance, Epidemiology, and End Results (SEER) registry and the Chinese National Cancer Center (CNCC) database from 2010 to 2017. We assessed 3-year cancer-specific survival (CSS) according to surgical treatment strategy and time period. RESULTS: Differences in patient age, gender, primary tumor location, tumor grade, tumor histology, and tumor stage were observed between the USA and China. Compared to the USA, a larger proportion of patients in China underwent both primary site resection (PSR) and hepatic resection (HR) (35.1% vs 15.6%, P < 0.001), and fewer patients underwent only PSR in China (29.1% vs 45.1%, P < 0.001). From 2010 to 2017, the proportion of patient who underwent both PSR and HR has increased from 13.9% to 17.4% in the USA and from 25.4% to 39.4% in China. The 3-year CSS were increasing over time in both the USA and China. The 3-year CSS of patients receiving HR and PSR were significantly higher than those receiving only PSR and patients treated with no surgery in the USA and China. There were no significant differences of 3-year CSS between the USA and China after adjustment (P = 0.237). CONCLUSIONS: Despite the distinctions of tumor characteristics and surgical strategy in patients with LM between the USA and China, increased adoption of HR has contributed to the profound improvements of survival during recent decade.

LncRNA ODRUL regulates progression of osteosarcoma by regulating IL-6 via sponging miR-6874-3p.

Accumulating evidence has shown that many long non-coding RNAs (lncRNA) participate in the tumorigenesis, including osteosarcoma (OS). Of them, lncRNA ODRUL was previously reported to act as a possible oncogene in OS doxorubicin resistance. However, the underlying molecular mechanism of ODRUL involved in the progression of OS still remains to be thoroughly investigated. In the current study, we reported another mechanism by which ODRUL regulates OS progression. QRT-PCR and WB were conducted to detect ODRUL, miR-6874-3p and IL-6 expression in OS tissues and cells. The Kaplan-Meier was used to assess the relevance between the expression level of miR-6874-3p and the overall survival of OS patients. Wound healing assays and Transwell assays were used to evaluate the invasion and migration of OS cells. Furthermore, the binding sites of ODRUL and IL-6 to miR-6874-3p were predicted by bioinformatics and verified by dual-luciferase reporter gene assays. ODRUL and IL-6 were highly expressed in OS cells and tissues, while miR-6874-3p was expressed at low levels. The overall survival of high miR-6874-3p expression of OS patients was longer than that of low miR-6874-3p expression of OS patients. MiR-6874-3p overexpression markedly inhibited the progression of OS cells. Both ODRUL and IL-6 could bind to miR-6874-3p at the predicted binding sites which were authenticated by dual-luciferase reporter gene assay. MiR-6874-3p could inhibit OS cell proliferation and metastasis and ODRUL could reverse the suppression induced by miR-6874-3p in vivo. In conclusion, ODRUL could effectively sponge miR-6874-3p to upregulate the expression of IL-6 in OS progression.

(E)-SIS3 suppressed osteosarcoma progression via promoting cell apoptosis, arresting cell cycle, and regulating the tumor immune microenvironment.

Osteosarcoma is a prevalent malignant bone tumor with a poor prognosis. Mothers against decapentaplegic homolog 3 (Smad3) present as a therapeutic target in antitumor treatment, whereas its functions in the osteosarcoma have not been well explored. In the current study, we aimed to investigate the effects of Smad3 in the progression of osteosarcoma. The tumor immune single-cell hub 2 website was used for graph-based visualization of Smad3 status in osteosarcoma single-cell database. Western Blot was applied to detect the expression of Smad3 protein in cell lines. Colony formation and cell counting kit-8 assays were used to evaluate cell proliferation. Transwell and wound healing assays were used to detect the migration and invasion abilities of cells. Cell apoptosis rates and cell cycle changes were explored by using flow cytometry analysis. The xenograft tumor growth model was applied to explore the effect in tumor growth after Smad3 blockage in vivo. Moreover, to confirm the potential mechanism of Smad3's effects on osteosarcoma, bioinformatics analysis was performed in TARGET-Osteosarcoma and GSE19276 databases. Our study found that the Smad3 protein is overexpressed in 143B and U2OS cells, suppressing the expression of Smad3 protein in osteosarcoma cells by Smad3 target inhibitor (E)-SIS3 or lentivirus can inhibit the proliferation, migration, invasion, promote cell apoptosis, arrest cell G1 cycle in osteosarcoma cells in vitro, and suppress tumor growth in vivo. Furthermore, the bioinformatics analysis demonstrated that high expression of Smad3 is closely associated with low immune status in TARGET-Osteosarcoma and GSE19276 databases. Our study suggested that Smad3 could contribute positively to osteosarcoma progression via the regulation of tumor immune microenvironment, and Smad3 may represent as an valuable potential therapeutic target in osteosarcoma therapy.

Fe-Ni/MWCNTs Nano-Composites for Hexavalent Chromium Reduction in Aqueous Environment.

A novel Cr (VI) removal material was designed and produced comprising multi-walled carbon nanotubes (MWCNTs) as a support with a high specific surface area and the loaded Fe-Ni bimetallic particles as catalytic reducing agents. Such a design permits the composite particle to perform the adsorption, reduction, and immobilisation of Cr (VI) quickly and efficiently. Due to MWCNTs' physical adsorption, Cr (VI) in solution aggregates in the vicinity of the composite, and Fe rapidly reduces Cr (VI) to Cr (III) catalysed by Ni. The results demonstrated that the Fe-Ni/MWCNTs exhibits an adsorption capacity of 207 mg/g at pH = 6.4 for Cr (VI) and 256 mg/g at pH 4.8, which is about twice those reported for other materials under similar conditions. The formed Cr (III) is solidified to the surface by MWCNTs and remains stable for several months without secondary contamination. The reusability of the composites was proven by retaining at least 90% of the adsorption capacity for five instances of reutilization. Considering the facile synthesis process, low cost of raw material, and reusability of the formed Fe-Ni/MWCNTs, this work shows great potential for industrialisation.

New Process Combining Fe-Based Chemical Looping and Biomass Pyrolysis for Cogeneration of Hydrogen, Biochar, Bio-Oil and Electricity with In-Suit CO2 Separation.

Fe-based chemical looping gasification is a clean biomass technology, which has the advantage of reducing CO2 emissions and the potential of self-sustaining operation without supplemental heating. A novel process combining Fe-based chemical looping and biomass pyrolysis was proposed and simulated using Aspen Plus. The biomass was first subjected to pyrolysis to coproduce biochar, bio-oil and pyrolysis gas; the pyrolysis gas was subjected to an Fe looping process to obtain high-purity hydrogen and carbon dioxide. The influences of the pyrolysis reactor operating temperature and fuel reactor operation temperature, and the steam reactor and air reactor on the process performance are researched. The results showed that, under the operating condition of the established process, 23.07 kg/h of bio-oil, 24.18 kg/h of biochar, 3.35 kg/h of hydrogen and a net electricity of 3 kW can be generated from 100 kg/h of rice straw, and the outlet CO2 concentration of the fuel reactor was as high as 80%. Moreover, the whole exergy efficiency and total exergy loss of the proposed process was 58.98% and 221 kW, respectively. Additionally, compared to biomass direct chemical looping hydrogen generation technology, the new process in this paper, using biomass pyrolysis gas as a reactant in the chemical looping hydrogen generation process, can enhance the efficiency of hydrogen generation.

Resveratrol Enhances Wound Healing in Type 1 Diabetes Mellitus by Promoting the Expression of Extracellular Vesicle-Carried MicroRNA-129 Derived from Mesenchymal Stem Cells.

Recent studies have shown the promotive effect of resveratrol on wound healing. This study aims to explore the underlying molecular mechanism of resveratrol in type 1 diabetes mellitus (T1DM) through microRNA (miR)-129-containing extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) based on in silico analysis. The rat model of T1DM was established by intraperitoneal injection of sodium citrate containing streptozotocin, and the wound was made around the deep fascia. Rat MSCs were isolated and treated with resveratrol (SRT501), and the corresponding EVs (SRT501-EVs) were isolated, where the expression of miR-129 was determined. By performing function experiments, the effect of SRT501-EVs and miR-129 on the biological functions of human umbilical vein endothelial cells (HUVECs) was determined. Finally, the binding relationship between miR-129 and tumor necrosis factor receptor-associated factor 6 (TRAF6) was also determined by the dual-luciferase reporter gene assay. miR-129 was shown as a candidate related to both resveratrol and wound healing in T1DM. SRT501-EVs promoted the skin wound healing of T1DM rats and also further improved the proliferative, migratory, and tube formation potentials of HUVECs. Resveratrol inhibited the expression of TRAF6 in HUVECs stimulated by MSC-conditioned medium and promoted the transfer of miR-129 via EVs, while TRAF6 was confirmed as a target gene of miR-129. Furthermore, inhibition of miR-129 attenuated the proangiogenic effect of resveratrol on HUVECs. Resveratrol exerts promotive role in wound healing in T1DM through downregulation of TRAF6 via MSC-EV-carried miR-129, suggesting a regulatory network involved in the wound healing process in T1DM.

hUCMSCs carrying exenatide prevent T1DM by improving intestinal microflora composition and islet tissue damage repair.

BACKGROUND: Exenatide is a stable analogue of glucagon-like peptide 1 that can reduce postprandial hyperglycemia and has been utilized as adjunctive therapy for type 1 diabetes mellitus (T1DM). The human umbilical cord is a rich source of MSCs, and human umbilical cord mesenchymal stem cells (hUCMSCs) also show potential to enhance insulin secretion. Here, we aimed to explore the effects of hUCMSCs carrying exenatide in T1DM and further identify the possible mechanisms involved. METHODS: hUCMSCs were isolated from human umbilical cord tissues, identified, and transduced with recombinant lentivirus carrying exenatide to obtain exenatide-carrying hUCMSCs (hUCMSCs@Ex-4). RESULTS: The results showed that hUCMSCs@Ex-4 restored the blood glucose levels and body weight of NOD mice, and repressed immune cell infiltration and islet tissue changes. Additionally, in T1DM mice, treatment with hUCMSCs@Ex-4 reduced the blood glucose levels and promoted repair of islet tissue damage. Moreover, hUCMSCs@Ex-4 attenuated renal tissue lesions in T1DM mice. Applying bioinformatic analysis, the effects of hUCMSCs@Ex-4 were suggested to correlate with decreased abundance of pro-inflammatory intestinal bacteria and increased abundance of anti-inflammatory intestinal bacteria. CONCLUSION: Overall, the study indicated that hUCMSCs carrying exenatide might improve beneficial intestinal microflora abundance and promote islet tissue damage repair, thereby alleviating T1DM.

Structural characterization and biological activities of a new polysaccharide isolated from Morchella Sextelata.

Morchella is the famous medicinal fungi in the ascomycetes. In this study, a new water-soluble polysaccharide (MSP-3-1) with an average molecular weight of 2.35 × 107 Da was extracted and purified from fruiting bodies of cultivated M. Sextelata. The structural characterization and biological activities of purified polysaccharide was further investigated. The results indicated that MSP-3-1 was mainly a α-glucan, mainly consisting of mannose (Man), glucose (Glc) and galactose (Gal) in a ratio of 5.10: 91.39: 3.51. Its surface morphology exhibited irregular lamellar structures with small voids. And the particle size analysis showed that MSP-3-1 was the homogeneous nanoparticle in water solution. Furthermore, the antioxidant activity analysis showed that MSP-3-1 possessed certain scavenging activity against hydroxyl radicals, DPPH radicals and ABTS radicals in a dose-dependent manner. Immunological tests suggested that MSP-3-1 could significantly promote the proliferation, phagocytosis and nitric oxide (NO) production of macrophage RAW264.7. Thus, our results will provide a theoretical basis for the development and utilization of Morchella Sextelata polysaccharides as an immunmodulatory component in functional foods.

NSun2 regulates aneurysm formation by promoting autotaxin expression and T cell recruitment.

Abdominal aortic aneurysm (AAA) is characterized by inflammatory cell infiltration and aggravated by hyperhomocysteinemia (HHcy). It is unknown whether the homocysteine (Hcy)-activated RNA methyltransferase NOP2/Sun domain family member 2 (NSun2) is associated with AAA. Here, we found that NSun2 deficiency significantly attenuated elastase-induced and HHcy-aggravated murine AAA with decreased T cell infiltration in the vessel walls. T cell labeling and adoptive transfer experiments confirmed that NSun2 deficiency inhibited the chemotaxis of vessels to T cells. RNA sequencing of endothelial cells showed that Hcy induced the accumulation of various metabolic enzymes of the phospholipid PC-LPC-LPA metabolic pathway, especially autotaxin (ATX). In the elastase-induced mouse model of AAA, ATX was specifically expressed in the endothelium and the plasma ATX concentration was upregulated and even higher in the HHcy group, which were decreased dramatically by NSun2 knockdown. In vitro Transwell experiments showed that ATX dose-dependently promoted T cell migration. HHcy may upregulate endothelial ATX expression and secretion and in turn recruit T cells into the vessel walls to induce vascular inflammation and consequently accelerate the pathogenesis of AAA. Mechanistically, secreted ATX interacted with T cells by binding to integrin α4, which subsequently activated downstream FAK/Src-RhoA signaling pathways and then induced T cell chemokinesis and adhesion. ATX overexpression in the vessel walls reversed the inhibited development of AAA in the NSun2-deficient mice. Therefore, NSun2 mediates the development of HHcy-aggravated AAA primarily by increasing endothelial ATX expression, secretion and T cell migration, which is a novel mechanism for HHcy-aggravated vascular inflammation and pathogenesis of AAA.

Clinical application of metagenomic next-generation sequencing technology in the diagnosis and treatment of pulmonary infection pathogens: A prospective single-center study of 138 patients.

INTRODUCTION: Rapid and accurate pathogen identification is essential for the treatment of pneumonia. Metagenomic next-generation sequencing (mNGS) is a newly developed technology to obtain microbial nucleic acid sequence information quickly, efficiently, and without bias. METHODS: We performed shotgun metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) for pathogen identification in pneumonia in a prospective study with 138 patients from a single center. We compared the results of mNGS with standard methods including culture, staining, and targeted PCR and evaluated the clinical applicability of mNGS. RESULTS: Most of the patients (128/138, 92.75%) were cured or improved. One patient (1/138, 0.72%) died because of acute gastrointestinal bleeding, and 9 patients (9/138, 6.52%) showed no improvement. mNGS identified more bacteria (53 versus 27), fewer fungi (8 versus 31), and more viruses (16 versus 1) than standard methods. In total, treatment in 34 out of 138 cases (24.64%) was adjusted and optimized because of mNGS results. Positive mNGS results contributed to a definitive diagnosis in 23 cases (16.67%), which helped guide treatment decision by either adjusting the antibiotics without de-escalation or continuing the empirical treatment. mNGS also confirmed no active infection in 11 cases (7.97%) allowed for antibiotic de-escalation. CONCLUSION: This prospective clinical study evaluated the clinical utility of mNGS for the diagnosis of pneumonia and showed that mNGS of BALF provides valuable information for effective treatment.

Utilization of Hematite Particles for Economical Removal of o-xylene in a High-Temperature Gas-Solid Reactor.

To establish a novel approach for VOCs resource utilization, coupled o-xylene oxidation and hematite reduction was investigated in this study in a high-temperature gas-solid reactor in the temperature range 300-700 °C. As the o-xylene-containing inert gas (N2) stream traveled through the hematite particle bed, its reaction behavior was determined in programmed heating and constant temperature modes. Consequently, the effect of bed temperature, flow rate and o-xylene inlet concentration on both o-xylene removal performance and degree of hematite reduction was studied. The raw hematite and solid products were analyzed by TGA, XRF, XRD and SEM-EDS. The results showed that a temperature above 300 °C was required to completely eliminate o-xylene by hematite, and both o-xylene removal capacity and degree of hematite reduction at 5% breakthrough points enhanced on increasing the temperature and decreasing the flow rate. The increment in temperature from 300 °C to 700 °C led to a gradual reduction of Fe2O3 to Fe3O4, FeO and metallic iron. Thus, this study provides a novel, economic and promising technology for treating the VOC pollutants.

Reactive Adsorption Performance and Behavior of Gaseous Cumene on MCM-41 Supported Sulfuric Acid.

Efficient removal of cumene from gaseous streams and recovery of its derivatives was accomplished using a MCM-41-supported sulfuric acid (SSA/MCM-41) adsorbent. The results indicated that the removal performance of the SSA/MCM-41 for cumene was significantly influenced by the process conditions such as bed temperature, inlet concentration, bed height, and flow rate. The dose-response model could perfectly describe the collected breakthrough adsorption data. The SSA/MCM-41 adsorbent exhibited a reactive temperature region of 120-170 °C, in which the cumene removal ratios (Xc) were greater than 97%. Rising the bed height or reducing the flow rate enhanced the theoretical adsorption performance metrics, such as theoretical breakthrough time (tB,th) and theoretical breakthrough adsorption capacity (QB,th), whereas increasing the inlet concentration resulted in tB,th shortening and QB,th rising. As demonstrated in this paper, the highest tB,th and QB,th were 69.60 min and 324.50 mg g-1, respectively. Meanwhile, the spent SSA/MCM-41 could be desorbed and regenerated for cyclic reuse. Moreover, two recoverable adsorbed products, 4-isopropylbenzenesulfonic acid and 4, 4'-sulfonyl bis(isopropyl-benzene), were successfully separated and identified using FTIR and 1H/13C NMR characterization. Accordingly, the relevance of a reactive adsorption mechanism was confirmed. This study suggests that the SSA/MCM-41 has remarkable potential for application as an adsorbent for the resource treatment of cumene pollutants.