Tendon Anomaly Identification in Prestressed Concrete Beams Based on an Advanced Monitoring MEMS and Data-Driven Detection of Structural Damage.

The growing importance of state assessments in civil engineering has led to intensive research into the development of damage identification methods based on vibrations. Natural frequencies and modal shapes have garnered great interest because modal parameters are invariant of structure. Moreover, thanks to the global nature of modal parameters, their variations are not limited to the location of the damage.

Germline Variant Spectrum in Southern Italian High-Risk Hereditary Breast Cancer Patients: Insights from Multi-Gene Panel Testing.

Hereditary breast cancer accounts for 5-10% of all cases, with pathogenic variants in and other susceptibility genes playing a crucial role. This study elucidates the prevalence and spectrum of germline variants in 13 cancer predisposition genes among high-risk hereditary breast cancer patients from Southern Italy. We employed next-generation sequencing (NGS) to analyze 254 individuals selected through genetic counseling.

Th17 Cell-Derived Amphiregulin Promotes Colitis-Associated Intestinal Fibrosis Through Activation of mTOR and MEK in Intestinal Myofibroblasts.

Background & Aims: Intestinal fibrosis is a significant complication of Crohn's disease (CD). Gut microbiota reactive Th17 cells are crucial in the pathogenesis of CD; however, how Th17 cells induce intestinal fibrosis is still not completely understood.

Methods: In this study, T-cell transfer model with wild-type (WT) and Areg Th17 cells and dextran sulfate sodium (DSS)-induced chronic colitis model in WT and Areg mice were used.

Glucose promotes regulatory T cell differentiation to maintain intestinal homeostasis.

Glucose, the critical energy source in the human body, is considered a potential risk factor in various autoimmune diseases when consumed in high amounts. However, the roles of glucose at moderate doses in the regulation of autoimmune inflammatory diseases and CD4 T cell responses are controversial. Here, we show that while glucose at a high concentration (20% w/v) promotes intestinal inflammation, it suppresses colitis at a moderate dose (6% w/v), which increases the proportion of intestinal regulatory T (Treg) cells but does not affect effector CD4 T cells.

Genetic Variation among Pharmacogenes in the Sardinian Population.

Pharmacogenetics (PGx) aims to identify the genetic factors that determine inter-individual differences in response to drug treatment maximizing efficacy while decreasing the risk of adverse events. Estimating the prevalence of PGx variants involved in drug response, is a critical preparatory step for large-scale implementation of a personalized medicine program in a target population. Here, we profiled pharmacogenetic variation in fourteen clinically relevant genes in a representative sample set of 1577 unrelated sequenced Sardinians, an ancient island population that accounts for genetic variation in Europe as a whole, and, at the same time is enriched in genetic variants that are very rare elsewhere.

Ureteral reconstruction for complex strictures: a review of the current literature.

Purpose: Frequently employed procedures for ureteral reconstruction include balloon dilation, pyeloplasty and ureteral re-implants. However, these procedures do not work for complex ureteral disease. The goal of this literature review is to report on techniques and success rates for the following techniques: buccal graft ureteroplasty, appendiceal interposition, transureteroureterostomy, ileal ureter and autotransplantation.

MicroRNA-10a Negatively Regulates CD4 T Cell IL-10 Production through Suppression of Blimp1.

An uncontrolled CD4 T cell response is a critical hallmark of autoimmune diseases. IL-10, which can be produced by both effector and regulatory CD4 T cells, plays an essential role in the inhibition of autoimmunity. MicroRNAs are key molecules involved in regulating immune responses.

L-lactate promotes intestinal epithelial cell migration to inhibit colitis.

Lactate, one of the most common primary metabolites of bacteria and human cells, has been shown to play essential roles in the regulation of inflammatory diseases, including inflammatory bowel diseases. However, whether and how host-derived lactate affects intestinal epithelial homeostasis is still not completely understood. Here, we investigated how L-lactate, mainly produced by host cells, regulates intestinal epithelial cell (IEC) migration to promote intestinal wound healing.

Dissecting Outcomes: Should Cytoreductive Nephrectomy Be Performed for Patients With Metastatic Renal Cell Carcinoma With Sarcomatoid Dedifferentiation?

Background: It is highly contested whether cytoreductive nephrectomy for treating advanced renal cell carcinoma (RCC) with sarcomatoid features (sRCC) benefits overall survival. Patients with sRCC are known to have a poor prognosis, and these tumors have a more aggressive biology than those without sarcomatoid features.

Methods: Patients with clear cell RCC or non-clear cell RCC underwent cytoreductive nephrectomy in efforts to improve overall survival (OS).

Propionate Enhances Cell Speed and Persistence to Promote Intestinal Epithelial Turnover and Repair.

Background And Aims: Gut bacteria-derived short-chain fatty acids (SCFAs) play crucial roles in the maintenance of intestinal homeostasis. However, how SCFAs regulate epithelial turnover and tissue repair remain incompletely understood. In this study, we investigated how the SCFA propionate regulates cell migration to promote epithelial renewal and repair.

STING controls intestinal homeostasis through promoting antimicrobial peptide expression in epithelial cells.

Stimulator of interferon genes (STING) has been shown to play a critical role in orchestrating immune responses to various pathogens through sensing cyclic dinucleotides. However, how STING regulates intestinal homeostasis is still not completely understood. In this study, we found that STING mice were more susceptible to enteric infection with Citrobacter rodentium compared to wild-type (WT) mice evidenced by more severe intestinal inflammation and impaired bacterial clearance.

Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity.

Innate lymphoid cells (ILCs) and CD4 T cells produce IL-22, which is critical for intestinal immunity. The microbiota is central to IL-22 production in the intestines; however, the factors that regulate IL-22 production by CD4 T cells and ILCs are not clear. Here, we show that microbiota-derived short-chain fatty acids (SCFAs) promote IL-22 production by CD4 T cells and ILCs through G-protein receptor 41 (GPR41) and inhibiting histone deacetylase (HDAC).

IL-21 Promotes Intestinal Memory IgA Responses.

The role of IL-21, produced mainly by Th17 cells and T follicular helper cells, has been intensively investigated in B cell differentiation and Ab class switch. However, how IL-21 regulates memory IgA B cell development and memory IgA responses in the intestines is still not completely understood. In this study, we found the total IgA B cells as well as CD38CD138IgA memory B cells were significantly increased in intestinal lamina propria (LP) of TCRβxδ mice after transfer of microbiota Ag-specific Th17 cells but not Th1 cells.

Effects of Defects on Bond Behavior of Fiber Reinforced Cementitious Matrix Materials.

High-strength fibers embedded in inorganic matrix i.e., Fiber Reinforced Cementitious Mortar materials (FRCM) are commonly used as strengthening technique for existing masonry structures, due to the low sensitivity to debonding phenomena between substrate and matrix.

Gut microbiota metabolite regulation of host defenses at mucosal surfaces: implication in precision medicine.

The gut microbiota has a well-established role in the regulation of host homeostasis. Multiple factors control the composition and function of the microbiota. The westernization of diet, a shift away from nutrient-dense foods toward diets high in saturated fats, has been implicated in the rise of chronic inflammatory diseases such as inflammatory bowel disease (IBD).

Microbiota Metabolite Short-Chain Fatty Acids Facilitate Mucosal Adjuvant Activity of Cholera Toxin through GPR43.

The gut microbiota has been shown critical for mucosal adjuvant activity of cholera toxin (CT), a potent mucosal adjuvant. However, the mechanisms involved remain largely unknown. In this study, we report that depletion of gut bacteria significantly decreased mucosal and systemic Ab responses in mice orally immunized with OVA and CT.

Serine Threonine Kinase 17A Maintains the Epithelial State in Colorectal Cancer Cells.

Serine threonine kinase 17A (STK17A) is a ubiquitously expressed kinase originally identified as a regulator of apoptosis; however, whether it functionally contributes to colorectal cancer has not been established. Here, we have analyzed STK17A in colorectal cancer and demonstrated decreased expression of STK17A in primary tumors, which is further reduced in metastatic lesions, indicating a potential role in regulating the metastatic cascade. Interestingly, changes in STK17A expression did not modify proliferation, apoptosis, or sensitivity of colorectal cancer cell lines to treatment with the chemotherapeutic 5-fluorouracil.

Neutrophils Promote Amphiregulin Production in Intestinal Epithelial Cells through TGF-β and Contribute to Intestinal Homeostasis.

Neutrophils are the first responders to sites of inflammation when the intestinal epithelial barrier is breached and the gut microbiota invade. Despite current efforts in understanding the role of neutrophils in intestinal homeostasis, the complex interactions between neutrophils and intestinal epithelial cells (IECs) is still not well characterized. In this study, we demonstrated that neutrophils enhanced production of amphiregulin (AREG), a member of the EGFR ligand family, by IECs, which promoted IEC barrier function and tissue repair.

Design, Synthesis, Biological Activity, and Structural Analysis of Lactam-Constrained PTPRJ Agonist Peptides.

PTPRJ is a receptor-like protein tyrosine phosphatase mainly known for its antiproliferative and tumor-suppressive functions. PTPRJ dephosphorylates several growth factors and their receptors, negatively regulating cell proliferation and migration. We recently identified a disulfide-bridged nonapeptide, named PTPRJ-19 (H-[Cys-His-His-Asn-Leu-Thr-His-Ala-Cys]-OH), which activates PTPRJ, thereby causing cell growth inhibition and apoptosis of both cancer and endothelial cells.

The receptor protein tyrosine phosphatase PTPRJ negatively modulates the CD98hc oncoprotein in lung cancer cells.

PTPRJ, a receptor protein tyrosine phosphatase strongly downregulated in human cancer, displays tumor suppressor activity by negatively modulating several proteins involved in proliferating signals. Here, through a proteomic-based approach, we identified a list of potential PTPRJ-interacting proteins and among them we focused on CD98hc, a type II glycosylated integral membrane protein encoded by , corresponding to the heavy chain of a heterodimeric transmembrane amino-acid transporter, including LAT1. CD98hc is widely overexpressed in several types of cancers and contributes to the process of tumorigenesis by interfering with cell proliferation, adhesion, and migration.

GPR43 mediates microbiota metabolite SCFA regulation of antimicrobial peptide expression in intestinal epithelial cells via activation of mTOR and STAT3.

The antimicrobial peptides (AMP) produced by intestinal epithelial cells (IEC) play crucial roles in the regulation of intestinal homeostasis by controlling microbiota. Gut microbiota has been shown to promote IEC expression of RegIIIγ and certain defensins. However, the mechanisms involved are still not completely understood.

A novel splice variant of the protein tyrosine phosphatase PTPRJ that encodes for a soluble protein involved in angiogenesis.

PTPRJ is a receptor protein tyrosine phosphatase with tumor suppressor activity. Very little is known about the role of PTPRJ ectodomain, although recently both physiological and synthetic PTPRJ ligands have been identified. A putative shorter spliced variant, coding for a 539 aa protein corresponding to the extracellular N-terminus of PTPRJ, is reported in several databases but, currently, no further information is available.

Myeloid translocation genes differentially regulate colorectal cancer programs.

Myeloid translocation genes (MTGs), originally identified as chromosomal translocations in acute myelogenous leukemia, are transcriptional corepressors that regulate hematopoietic stem cell programs. Analysis of The Cancer Genome Atlas (TCGA) database revealed that MTGs were mutated in epithelial malignancy and suggested that loss of function might promote tumorigenesis. Genetic deletion of MTGR1 and MTG16 in the mouse has revealed unexpected and unique roles within the intestinal epithelium.