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Adventitia-induced vascular remodeling plays an important role in vascular aging. However, the mechanism remains unclear. In this study, we found that sirtuin 6 (SIRT6) expression was downregulated in the aortae of aged rats compared with those of young rats. Adventitial fibroblasts (AFs) were isolated and cultured from rat aortae to clarify the relationship between SIRT6 expression and vascular aging. Lentivirus-mediated SIRT6 knockdown promoted the aging phenotype in AFs, affecting proliferation, collagen secretion, migration, and α-smooth muscle actin expression. Moreover, angiotensin II (Ang II) decreased SIRT6 expression, activated the NF-κB pathway, and led to vascular aging. The NF-κB pathway inhibitor BAY 11-7082 reduced Ang II-induced nuclear translocation of the NF-κB p65 subunit and other effects of Ang II, such as AF proliferation, collagen secretion, and migration. Mechanistically, SIRT6 suppression increased acetyl-NF-κB p65 (Lys310) expression and NF-κB transcriptional activity in SIRT6-knockdown AFs. SIRT6 could directly bind to the p65 subunit and attenuate Ang II-induced NF-κB activation and vascular aging. In summary, this study was the first to correlate SIRT6 expression and adventitia-induced vascular senescence. SIRT6 maybe a biomarker of vascular aging, and activating SIRT6 maybe a therapeutic strategy for delaying vascular aging.

Background and Aim Remnant cholesterol (RC) is substantially related to negative outcomes in cardiac patients. Patients with coexisting hypertension and heart failure (HF) often develop left ventricular hypertrophy (LVH) and have poor prognoses. This study investigated baseline RC levels and LV remodelling and patients’ prognoses. Methods and results Six hundred thirty consecutive individuals with hypertension and HF participated in this prospective trial from October 2018 to August 2020. Based on left ventricular mass index (LVMI), 560 those eligible were separated into LVH and non-LVH groups. Multiple linear regression and receiver operating characteristic (ROC) curves examined the RC and LV relationship. A Cox regression analysis was conducted to examine the predictive value of RC for clinical outcomes. The LVH group presented significantly elevated values of RC, triglyceride, and cholesterol and decreased high-density lipoprotein cholesterol (HDLC). The optimal cutoff value for RC to predict LV remodelling was 0.49. The subjects were observed for a median of 58 months, and 104 participants met the primary endpoint. The risk models involving the two Cox models were adjusted to incorporate confounding factors, which revealed that those with elevated baseline levels of RC were more susceptible to cardiovascular mortality, as shown by an increased hazard ratio. (HR: 1.91, 95% CI: 1.62–2.26 vs. HR: 1.75, 95% CI: 1.43–2.16, P  < 0.001). Conclusions RC is linked to LV remodelling in patients with hypertensive HF, with LVH having greater RC values. Moreover, patients with hypertensive HF who had a higher RC suffered from an increased risk of cardiovascular mortality. Trial registration NCT 03727828, 21 Oct 2018.

Background Cotton phenol is a yellowish-brown polyphenol hydroxybinaphthyl aldehyde compound mainly found in the roots, stems, leaves and seeds of cotton; a plant of the mallow family that has been widely used in the study of antifertility and antitumor drugs. However, there has been no report of serious renal injuries caused by cotton phenol. We report a case of granulomatous acute interstitial nephritis caused by exposure to large amounts of cotton phenol. Case description The patient was a 56-year-old male with nausea and a blood creatinine level of 4.95 mg/dL 2 month prior to admission. He was admitted to the hospital with worsening nausea, blood creatinine level of 7.21 mg/dL, and a renal puncture biopsy suggesting granulomatous acute interstitial nephritis. The patient had no specific past medical history. Laboratory tests (double-stranded DNA, antineutrophil cytoplasmic antibody, extractable nuclear antigen, rheumatoid subunit, serum and urine protein electrophoresis, complement levels, immunoglobulin subclasses, streptococcal serology, and hepatitis B and C serology were negative, normal or undetectable. Follow-up history revealed that the patient receives large quantities of cotton phenol at work. The diagnosis was granulomatous acute interstitial nephritis induced by exposure to cotton phenol. Treatment was volume management, maintenance of a stable internal environment, and glucocorticoid activation. Blood creatinine level gradually decreased to 1.86 mg/dL after 3 month and his condition improved. Conclusions Physicians encountering patients with acute interstitial nephritis of uncertain etiology are obligated to conduct a prompt and comprehensive history review. Special attention should be given to cotton phenol and its derivatives as they may potentially act as nephrotoxic agents. The application of glucocorticoids in the treatment of acute interstitial nephritis remains a subject of debate. However, in this particular case, the patient exhibited a rapid restoration of renal function following the administration of glucocorticoids.

Numerous studies have demonstrated that free Ig light chain (FLC), a novel inflammation mediator, participates in many inflammatory diseases by activating mast cells and extending the survival of neutrophils. However, it remains unclear whether FLC is involved in colitis and colitis-associated colon carcinogenesis (CAC). In this study, we found a significant increase in FLC in murine models of DSS (Dextran Sulfate Sodium Salt)-induced colitis and CAC compared to controls. Peptide F991, a functional blocker of FLC, significantly attenuated colitis progression, which included abrogating the development of diarrhea and tumor burden, elevating survival rate, greatly reducing the infiltration of inflammatory cells (such as ROS + active neutrophils), especially reducing tumorigenesis in CAC. Furthermore, we demonstrated that F991 inhibited the activation of the inflammasome by reducing the expression of cleaved caspase-1 and the maturation of IL-1β and IL-18. Altogether, our findings demonstrate that FLC can promote the pathogenesis of colitis and CAC and may be used as novel biomarker for the diagnosis of inflammatory bowel disease. Additionally, F991 may become a potential therapeutic option for colitis or colorectal cancer.

SCP1 as a nuclear transcriptional regulator acts globally to silence neuronal genes and to affect the dephosphorylation of RNA Pol ll. However, we report the first finding and description of SCP1 as a plasma membrane-localized protein in various cancer cells using EGFP- or other epitope-fused SCP1. Membrane-located SCP1 dephosphorylates AKT at serine 473, leading to the abolishment of serine 473 phosphorylation that results in suppressed angiogenesis and a decreased risk of tumorigenesis. Consistently, we observed increased AKT phosphorylation and angiogenesis followed by enhanced tumorigenesis in Ctdsp1 (which encodes SCP1) gene - knockout mice. Importantly, we discovered that the membrane localization of SCP1 is crucial for impeding angiogenesis and tumor growth, and this localization depends on palmitoylation of a conserved cysteine motif within its NH2 terminus. Thus, our study discovers a novel mechanism underlying SCP1 shuttling between the plasma membrane and nucleus, which constitutes a unique pathway in transducing AKT signaling that is closely linked to angiogenesis and tumorigenesis. Cancerous tumors are the leading cause of death worldwide. Tumors cannot grow beyond a couple of millimeters in diameter unless they are supplied with nutrients and oxygen. To receive these, tumors connect to the body’s blood supply by stimulating the growth of new blood vessels. Drugs that reduce the ability of new blood vessels to form have therefore been investigated as possible anti-cancer treatments. New blood vessels emerge from pre-existing ones in a process called angiogenesis. The first stage of angiogenesis involves the endothelial cells that line the inner wall of the blood vessels moving outwards to form new ‘sprouts’. Within the endothelial cells, a signaling protein called AKT drives angiogenesis by moving to the cell membrane, where it is activated and triggers further signaling events. The activation of AKT occurs via a phosphate group being attached to a particular site on the protein. Enzymes called phosphatases remove phosphate groups from proteins and so can inactivate AKT, hence preventing angiogenesis. Although some phosphatases are known to inactivate AKT, they cannot easily be counted or analyzed. This means that they cannot be used to develop new cancer treatments. In addition, for the phosphatase to best prevent tumor growth, it should inactivate AKT at the cell membrane. Liao, Wang, Li, Wang, Jin et al. now show that a phosphatase called SCP1 can localize to the cell membrane and inactivate AKT there. SCP1 was not previously known to anchor to the cell membrane. Liao et al. found that this anchoring occurs via a modification that attaches a fatty acid molecule to SCP1. Further experiments showed that mice that lacked SCP1 had increased levels of AKT phosphorylation in their endothelial cells, more new blood vessel growth and, consequently, had tumors that grew faster. Further research is now needed to investigate exactly how SCP1 moves to the cell membrane from elsewhere in the cell. Ultimately, this knowledge could play an important role in identifying potential drugs that prevent or reduce the growth of tumors.

With a rapid growth in the available resource description framework (RDF) data from disparate domains, the SPARQL query processing with graph structures has become increasingly important. In this pursuit, we designed a two-phase SPARQL query optimization method to process the SPARQL query. The structural characteristics of RDF data graphs, predicate path sequence indices (PPS-indices), were used to efficiently prune the search space, which captured the inherent features of the RDF data graphs, while the database is updated. Our storage model was based on a relational database. Compared to a baseline solution, the proposed method effectively reduced the cardinalities of the intermediate results during the query processing, and at least an order of magnitude improvement is achieved in filtering performance, thereby improving the efficiency of the query execution.

ABSTRACT Rhizoctonia solani AG1 IA is a harmful necrotrophic fungus responsible for various crop diseases, including maize and rice sheath blight, which can lead to significant production losses. However, the pathogenic mechanisms and the roles of effectors in this pathogen remain poorly understood. In this study, we identified a glycoside hydrolase 16 family gene, RsEG146, from R. solani that was upregulated during its infection of Zea mays leaves. When transiently expressed through agroinfiltration, RsEG146 induced cell death in the leaves of tobacco (Nicotiana tabacum ‘Samsun’). The predicted signal peptide of RsEG146 was essential for its cell death‐inducing activity, while the conserved enzymic active site was not required. The chitin‐binding domain was critical for the cell death‐inducing activity of RsEG146, with Gly47 identified as the key residue. Substitution of Gly47 with aspartate, glutamate, or proline significantly impaired the cell death‐inducing activity of RsEG146. Additionally, transient and heterogeneous expression of RsEG146 enhanced the pathogenicity of Botrytis cinerea on tobacco, and silencing this gene through spray‐induced gene silencing (SIGS) reduced the severity of the disease in maize, indicating that RsEG146 functions as an effector. Furthermore, RsEG146 triggered a plant immune response in tobacco. This study demonstrates that RsEG146 is a potential effector and plays a crucial role in the interactions between R. solani AG1 IA and its host. We identified a glycoside hydrolase 16 family member RsEG146 from Rhizoctonia solani AG1 IA that acts as an effector by inducing Nicotiana tabacum cell death via its chitin‐binding domain.

Remnant cholesterol (RC) is substantially related to negative outcomes in cardiac patients. Patients with coexisting hypertension and heart failure (HF) often develop left ventricular hypertrophy (LVH) and have poor prognoses. This study investigated baseline RC levels and LV remodelling and patients' prognoses. Six hundred thirty consecutive individuals with hypertension and HF participated in this prospective trial from October 2018 to August 2020. Based on left ventricular mass index (LVMI), 560 those eligible were separated into LVH and non-LVH groups. Multiple linear regression and receiver operating characteristic (ROC) curves examined the RC and LV relationship. A Cox regression analysis was conducted to examine the predictive value of RC for clinical outcomes. The LVH group presented significantly elevated values of RC, triglyceride, and cholesterol and decreased high-density lipoprotein cholesterol (HDLC). The optimal cutoff value for RC to predict LV remodelling was 0.49. The subjects were observed for a median of 58 months, and 104 participants met the primary endpoint. The risk models involving the two Cox models were adjusted to incorporate confounding factors, which revealed that those with elevated baseline levels of RC were more susceptible to cardiovascular mortality, as shown by an increased hazard ratio. (HR: 1.91, 95% CI: 1.62-2.26 vs. HR: 1.75, 95% CI: 1.43-2.16, P < 0.001). RC is linked to LV remodelling in patients with hypertensive HF, with LVH having greater RC values. Moreover, patients with hypertensive HF who had a higher RC suffered from an increased risk of cardiovascular mortality.

Antibacterial and pH-responsive composite films for active food packaging were fabricated based on polyvinyl alcohol (PVA), cassava starch, ethyl lauroyl arginate (LAE), and mulberry anthocyanin. With the incorporation of LAE and mulberry anthocyanin, the PVA/starch blend films exhibited a less compact and more heterogeneous surface structure. The tensile strength and elongation at break of the active films were not significantly affected when the mulberry anthocyanin content was less than 20%. Moreover, the incorporation of mulberry anthocyanin effectively improved the UV barrier property of the blend films. Notably, while mulberry anthocyanin showed obvious color changes in buffer solutions with different pH values, the changes were indistinguishable for the PVA/starch/mulberry anthocyanin films. By contrast, the color changes of the PVA/starch/LAE/mulberry anthocyanin films were more noticeable, indicating the addition of LAE increased the pH sensitivity of the blend films. Furthermore, the PVA/starch/LAE/mulberry anthocyanin films efficiently inhibited the growth of both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) due to the strong antibacterial activity of LAE. According to the spoilage test, the active films containing 5% mulberry anthocyanin and 5% LAE effectively indicated and slowed down the spoilage process of dairy milk. Our results demonstrate that PVA/starch/LAE/mulberry anthocyanin films have high potential as bioactive packaging materials applied in the food industry.