Single Exposure to Low-Intensity Focused Ultrasound Causes Biphasic Opening of the Blood-Brain Barrier Through Secondary Mechanisms.

The blood-brain barrier (BBB) is selectively permeable, but it also poses significant challenges for treating CNS diseases. Low-intensity focused ultrasound (LiFUS), paired with microbubbles is a promising, non-invasive technique for transiently opening the BBB, allowing enhanced drug delivery to the central nervous system (CNS). However, the downstream physiological effects following BBB opening, particularly secondary responses, are not well understood.

-Lyophilized Fruit Extract Attenuated Acute Redox-Homeostatic Imbalance via Mutagenic and Oxidative Stress Modulation in Mice Model on Gentamicin-Induced Nephrotoxicity.

Gentamicin (GM) administration is associated with decreased metabolism, increased oxidative stress, and induction of nephrotoxicity. L., containing flavonoids, anthocyanins, and phytosterols, possesses antioxidant and anti-inflammatory potential.

The Effect of Peri-Implant Therapy on the Expression of Th17-Related Cytokines in Patients with Peri-Implant Mucositis and Peri-Implantitis: A Prospective Longitudinal Study.

: Cytokines related to the Th17 response have been associated with peri-implant diseases; however, the effect of peri-implant therapy on their modulation remains underexplored. To evaluate the effect of peri-implant therapy on the expression of cytokines related to the Th17 response in the peri-implant crevicular fluid (PICF) (GM-CSF, IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-12 (p70), IL-17A, IL-21, IL-23, and TNF-α) of partially edentulous patients with peri-implant disease (PID). : Thirty-seven systemically healthy individuals presenting with peri-implant mucositis (PIM) (n = 20) or peri-implantitis (PI) (n = 17) were treated and evaluated at baseline (T0) and three months after therapy (T1).

Evidence of Inflammatory Network Disruption in Chronic Venous Disease: An Analysis of Circulating Cytokines and Chemokines.

Chronic venous disease (CVD) comprises a set of vascular disorders that affect the venous system with important local and systemic repercussions. A growing body of evidence displays the relationship between suffering from CVD and a marked deregulation of the immune inflammatory system. In this sense, the previous literature has reported some significant changes in the level of various circulating inflammatory parameters in these patients.

Breather, lump and other wave profiles for the nonlinear Rosenau equation arising in physical systems.

This work explores the mathematical technique known as the Hirota bilinear transformation to investigate different wave behaviors of the nonlinear Rosenau equation, which is fundamental in the study of wave occurrences in a variety of physical systems such as fluid dynamics, plasma physics, and materials science, where nonlinear dynamics and dispersion offer significant functions. This equation was suggested to describe the dynamic behaviour of dense discrete systems. We use Mathematica to investigate these wave patterns and obtained variety of wave behaviors, such as M-shaped waves, mixed waves, multiple wave forms, periodic lumps, periodic cross kinks, bright and dark breathers, and kinks and anti-kinks.

Resolvin D2 restores monocyte anisocytosis and mediates a shift toward classical monocytes ex vivo in blood samples from patients after major burns.

Circulating monocytes contribute to the defense against pathogens and play a crucial role in maintaining immune homeostasis. While there is substantial evidence regarding the triggers of monocyte activation, our understanding of how monocyte function is restored toward homeostasis after activation remains limited. Here, we assessed the changes in monocyte anisocytosis upon activation in blood, measured by monocyte distribution width (MDW), a biomarker for sepsis.

Ketogenic Diet-Associated Worsening of Osteoarthritis Histologic Secerity, Increased Pain Sensitivity and Gut Microbiome Dysbiosis in Mice.

Objectives: Dietary interventions are a potentially powerful treatment option for knee osteoarthritis (OA). The objective of this study was to evaluate a well-formulated ketogenic diet (KD) in the context of knee OA histology and pain using the destabilization of the medial meniscus (DMM) mouse model and correlate with gut microbiome and systemic cytokine levels.

Methods: Adult male mice underwent unilateral DMM or sham surgery and were then fed eight weeks of KD or chow.

Role of Ciliary Neurotrophic Factor in Angiotensin II-Induced Hypertension.

Background: Ciliary neurotrophic factor (CNTF), mainly known for its neuroprotective properties, belongs to the IL-6 (interleukin-6) cytokine family. In contrast to IL-6, the effects of CNTF on the vasculature have not been explored. Here, we examined the role of CNTF in AngII (angiotensin II)-induced hypertension.

Multiplexed single-cell imaging reveals diverging subpopulations with distinct senescence phenotypes during long-term senescence induction.

Cellular senescence is a phenotypic state that contributes to the progression of age-related disease through secretion of pro-inflammatory factors known as the senescence-associated secretory phenotype (SASP). Understanding the process by which healthy cells become senescent and develop SASP factors is critical for improving the identification of senescent cells and, ultimately, understanding tissue dysfunction. Here, we reveal how the duration of cellular stress modulates the SASP in distinct subpopulations of senescent cells.

Symmetry facilitated the evolution of heterospecificity and high-order stoichiometry in vertebrate hemoglobin.

Many proteins form paralogous multimers-molecular complexes in which evolutionarily related proteins are arranged into specific quaternary structures. Little is known about the mechanisms by which they acquired their stoichiometry (the number of total subunits in the complex) and heterospecificity (the preference of subunits for their paralogs rather than other copies of the same protein). Here, we use ancestral protein reconstruction and biochemical experiments to study historical increases in stoichiometry and specificity during the evolution of vertebrate hemoglobin (Hb), an αβ heterotetramer that evolved from a homodimeric ancestor after a gene duplication.

Gabexate mesylate thermo-sensitive in-situ gel is effective for treating grade-III pancreatic trauma in beagle dogs guided by contrast-enhanced ultrasound.

Background: This study evaluates the efficacy of gabexate mesylate thermosensitive in-situ gel (GMTI) in the treatment of beagle grade III pancreatic trauma (PT) with the assistance of contrast-enhanced ultrasound (CEUS) and investigates its mechanism of action.

Methods: A grade III PT model consisting of 15 beagle dogs with severed main pancreatic ducts was created and treated with cephalic vein injection of gabexate mesylate (GM) (1.54 mL/10 kg, TID) and peripancreatic injection of GMTI (4.

RNA folding kinetics control riboswitch sensitivity in vivo.

Riboswitches are ligand-responsive gene-regulatory RNA elements that perform key roles in maintaining cellular homeostasis. Understanding how riboswitch sensitivity to ligand (EC) is controlled is critical to explain how highly conserved aptamer domains are deployed in a variety of contexts with different sensitivity demands. Here we uncover roles by which RNA folding dynamics control riboswitch sensitivity in cells.

Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients.

Total proctocolectomy with ileal pouch anal anastomosis is the standard of care for patients with severe ulcerative colitis. We generated a cell-type-resolved transcriptional and epigenetic atlas of ileal pouches using scRNA-seq and scATAC-seq data from paired biopsy samples of the ileal pouch and the ileal segment above the pouch (pre-pouch) from patients (male=4, female=2), and paired biopsies of the terminal ileum and ascending colon from healthy individuals (male=3, female=3) serving as reference. Our study finds an additional population of absorptive and secretory epithelial cells within the pouch but not the pre-pouch.

LPCAT1 reduces inflammatory response, apoptosis and barrier damage of nasal mucosal epithelial cells caused by allergic rhinitis through endoplasmic reticulum stress.

Allergic rhinitis (AR), common in children and adolescents, involves Lysophosphatidylcholine acyltransferase 1 (LPCAT1) catalyzing surfactant lipid biosynthesis and suppressing endoplasmic reticulum expression. However, the precise mechanism underlying the impact of LPCAT1 on epithelial cell damage in AR remains elusive. Hence, the present investigation elucidated the potential effect of LPCAT1 on epithelial cell damage in AR by inhibiting endoplasmic reticulum stress.

Peripheral blood age-sensitive immune markers in multiple sclerosis: relation to sex, cytomegalovirus status, and treatment.

Background: Immunosenescence is accelerated by chronic infectious and autoimmune diseases and could contribute to the pathobiology of multiple sclerosis (MS). How MS and disease-modifying therapies (DMTs) impact age-sensitive immune biomarkers is only partially understood.

Methods: We analyzed 771 serum samples from 147 healthy controls and 289 people with MS (PwMS) by multiplex immunoassays.

Accelerated enzyme engineering by machine-learning guided cell-free expression.

Enzyme engineering is limited by the challenge of rapidly generating and using large datasets of sequence-function relationships for predictive design. To address this challenge, we develop a machine learning (ML)-guided platform that integrates cell-free DNA assembly, cell-free gene expression, and functional assays to rapidly map fitness landscapes across protein sequence space and optimize enzymes for multiple, distinct chemical reactions. We apply this platform to engineer amide synthetases by evaluating substrate preference for 1217 enzyme variants in 10,953 unique reactions.

Traditional pediatric massage enhanced the skeletal muscle mass in OVA-exposed adolescent rats via regulating SCFAs-FFAR2-IGF-1/AKT pathway.

Objective: This study aimed to investigate the potential relation between the retarded growth of skeletal muscle (SM) and dysbiosis of gut microbiota (GM) in children with asthma, and to explore the potential action mechanisms of traditional pediatric massage (TPM) from the perspective of regulating GM and short-chain fatty acids (SCFAs) production by using an adolescent rat model of asthma.

Methods: Male Sprague-Dawley rats aged 3weeks were divided randomly into the 5 groups (n=6~7) of control, ovalbumin (OVA), OVA + TPM, OVA + methylprednisolone sodium succinate (MP) and OVA + SCFAs. Pulmonary function (PF) was detected by whole body plethysmograph, including enhanced pause and minute ventilation.

GM-CSF and IL-21-armed oncolytic vaccinia virus significantly enhances anti-tumor activity and synergizes with anti-PD1 immunotherapy in pancreatic cancer.

Pancreatic cancer is one of the most aggressive cancers and poses significant challenges to current therapies because of its complex immunosuppressive tumor microenvironment (TME). Oncolytic viruses armed with immunoregulatory molecules are promising strategies to overcome limited efficacy and target inaccessible and metastatic tumors. In this study, we constructed a tumor-selective vaccinia virus (VV) with deletions of the TK and A49 genes (VVLΔTKΔA49, VVL-DD) using CRISPR-Cas9-based homologous recombination.

Flow-induced bending of flagella controls bacterial surface behavior.

Bacteria engage in surface-specific behaviors that are assumed to be driven by biological signaling. However, surface behaviors could be controlled by mechanical reorientation of bacterial appendages. Here, we use microfluidics and flagellar labeling to discover how shear force bends flagella to control surface behavior of the human pathogen .

Risk of Severe Hypoglycemia After Initiation of Noninsulin Glucose-Lowering Therapies in Adults With Type 2 Diabetes at Moderate Cardiovascular Disease Risk.

In this emulated comparative effectiveness target trial of glucagon-like peptide 1 (GLP-1) receptor agonist, sodium-glucose cotransporter 2 (SGLT2) inhibitor, dipeptidyl peptidase 4 (DPP-4) inhibitor, and sulfonylurea therapy among adults with type 2 diabetes at moderate cardiovascular disease risk, sulfonylurea use was associated with a significantly higher risk of hypoglycemia requiring emergency department or hospital care than treatment with DPP-4 inhibitors, GLP-1 receptor agonists, or SGLT2 inhibitors. This consideration can guide the choice of glucose-lowering therapy in this highly prevalent patient population, in whom avoidance of hypoglycemia is important, yet among whom the risk of severe hypoglycemia has not been examined previously.

Incomplete human reference genomes can drive false sex biases and expose patient-identifying information in metagenomic data.

As next-generation sequencing technologies produce deeper genome coverages at lower costs, there is a critical need for reliable computational host DNA removal in metagenomic data. We find that insufficient host filtration using prior human genome references can introduce false sex biases and inadvertently permit flow-through of host-specific DNA during bioinformatic analyses, which could be exploited for individual identification. To address these issues, we introduce and benchmark three host filtration methods of varying throughput, with concomitant applications across low biomass samples such as skin and high microbial biomass datasets including fecal samples.

Structural studies of the IFNλ4 receptor complex using cryoEM enabled by protein engineering.

IFNλ4 has posed a conundrum in human immunology since its discovery in 2013, with its expression linked to complications with viral clearance. While genetic and cellular studies revealed the detrimental effects of IFNλ4 expression, extensive structural and functional characterization has been limited by the inability to express and purify the protein, complicating explanations of its paradoxical behavior. In this work, we report a method for robust production of IFNλ4.

Effectiveness and cytokine profile of combined anti-vascular endothelial growth factor and corticosteroid therapy for chronic retinal vein occlusion.

Purpose: To investigate whether sub-Tenon injection of triamcinolone acetonide (STTA) combined with anti-vascular endothelial growth factor (VEGF) prolongs the recurrence intervals of macular edema (ME) for chronic retinal vein occlusion (RVO) and to investigate the differences in intraocular inflammatory cytokines between good responders (GRs) and non-responders (NRs).

Methods: This retrospective, observational study involved 42 eyes of 42 patients with ME due to chronic RVO who had received only anti-VEGF for ≥ 1 year and were transitioned to combination therapy. GRs were defined as patients whose recurrence intervals were prolonged by ≥ 2 weeks compared with patients receiving anti-VEGF alone.

Enhanced sampling of protein conformational changes via true reaction coordinates from energy relaxation.

The bottleneck in enhanced sampling lies in finding collective variables that effectively accelerate protein conformational changes; true reaction coordinates that accurately predict the committor are the well-recognized optimal choice. However, identifying them requires unbiased natural reactive trajectories, which, paradoxically, require effective enhanced sampling. Using the generalized work functional method, we uncover that true reaction coordinates control both conformational changes and energy relaxation, enabling us to compute them from energy relaxation simulations.