Granulation

PURPOSE: To undertake the first ultrastructural characterization of human retinal pigment epithelial (RPE) differentiation from fetal development to adolescence. METHODS: Ten fetal eyes and three eyes aged six, nine, and 17 years were examined in the temporal retina adjacent to the optic nerve head by transmission electron microscopy. The area, number, and distribution of RPE organelles were quantified and interpreted within the context of adjacent photoreceptors, Bruch's membrane, and choriocapillaris maturation...

Granzymes are a family of serine proteases, composed of five human members: GA, B, H, M and K. They were first discovered in the 1980s within cytotoxic granules released during NK cell- and T cell-mediated killing. Through their various proteolytic activities, granzymes can trigger different pathways within cells, all of which ultimately lead to the same result, cell death. Over the years, the initial consideration of granzymes as mere cytotoxic mediators has changed due to surprising findings demonstrating their expression in cells other than immune effectors as well as new intracellular and extracellular activities...

Traditional pharmaceutical manufacturing processes for solid oral dosage forms can be inefficient and have been known to produce a large amount of undesired product. With the progressing trend of achieving carbon neutrality, there is an impetus to increase the energy efficiency of these manufacturing processes while maintaining the critical quality attributes of the product. One of the important steps in downstream pharmaceutical manufacturing is wet granulation, and within that, twin screw granulation (TSG) is a popular continuous manufacturing technique...

Cyclops lesions are characterized as fibroid nodules with granulation tissue that looks similar to a cyclops eye during arthroscopy. These are rare postoperative complications following anterior cruciate ligament reconstruction (ACLR), presenting typically within six months of their reconstruction. This case report presents a 21-year-old male, three years following hamstring autograft ACLR, with a symptomatic cyclops lesion. Contrary to the reported literature, this delayed presentation showed a painful flexion contracture of the knee and intraoperative findings consistent with a cyclops lesion...

UNLABELLED: Parvalbumin-positive (PV+) GABAergic interneurons in the dentate gyrus provide powerful perisomatic inhibition of dentate granule cells (DGCs) to prevent overexcitation and maintain the stability of dentate gyrus circuits. Most dentate PV+ interneurons survive status epilepticus, but surviving PV+ interneuron mediated inhibition is compromised in the dentate gyrus shortly after status epilepticus, contributing to epileptogenesis in temporal lobe epilepsy. It is uncertain whether the impaired activity of dentate PV+ interneurons recovers at later times or if it continues for months following status epilepticus...

INTRODUCTION: Hyperexcitability in Alzheimer's disease (AD) emerge early and contribute to disease progression. The dentate gyrus (DG) is implicated in hyperexcitability in AD. We hypothesized that mossy cells (MCs), regulators of DG excitability, contribute to early hyperexcitability in AD. Indeed, MCs generate hyperexcitability in epilepsy. METHODS: Using the Tg2576 model and WT mice (∼1month-old), we compared MCs electrophysiologically, assessed c-Fos activity marker, Aβ expression and mice performance in a hippocampal-dependent memory task...

BACKGROUND: The safety and efficacy of sofosbuvir-velpatasvir in children aged 3-17 years with chronic hepatitis C virus (HCV) infection of any genotype were evaluated. METHODS: In this Phase 2, multicenter, open-label study, patients received once daily for 12 weeks either sofosbuvir-velpatasvir 400/100 mg tablet (12-17 years), 200/50 mg low dose tablet or oral granules (3-11 years and ≥17 kg), or 150/37.5 mg oral granules (3-5 years and <17 kg)...

BACKGROUND: Photoacoustic microscopy is expected to have clinical applications as a noninvasive and three-dimensional (3D) method of observing intradermal structures. OBJECTIVE: Investigate the applicability of a photoacoustic microscope equipped with two types of pulsed lasers that can simultaneously recognize hemoglobin and melanin. METHODS: 16 skin lesions including erythema, pigmented lesions, vitiligo and purpura, were analyzed to visualize 3D structure of melanin granule distribution and dermal blood vessels...

Pharmaceutical twin-screw wet granulation is a multifaceted and intricate process pivotal to drug product development. Accurate modeling of this process is indispensable for optimizing manufacturing parameters and ensuring product quality. The fluid bed dryer, an integral component of this granulation process, significantly influences the granular critical quality attributes. This study builds upon prior research by integrating experimental findings on granule segregation during fluid bed drying into an existing compartmental model, enhancing its predictive capabilities...

Porcine epidemic diarrhea virus (PEDV) envelope protein (E) has been characterized as an important structural protein that plays critical roles in the interplay with its host to affect the virus life cycle. Stress granules (SGs) are host translationally silent ribonucleoproteins, which are mainly induced by the phosphorylation of eIF2α in the PERK/eIF2α signaling pathway. Our previous study found that PEDV E protein caused endoplasmic reticulum stress response (ERS)-mediated suppression of antiviral proteins' translation...

The basal and glucose-induced insulin secretion from pancreatic beta cells is a tightly regulated process that is triggered in a Ca2+ -dependent fashion and further positively modulated by substances that raise intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) or by certain antidiabetic drugs. In a previous study, we have temporally resolved the subplasmalemmal [Ca2+ ]i dynamics in beta cells that are characterized by trains of sharply delimited spikes, reaching peak values up to 5 µM...

BACKGROUND: Qing-Yi Recipe, a classic traditional Chinese medicine (TCM), is widely used for treating acute diseases of the abdomen, especially pancreatitis, the efficacy of which has been demonstrated in more than thirty clinical trials. However, the in-vivo pharmacodynamic material basis for this formula remains unclear. METHODS: A sensitive and accurate method for quantifying twenty-two potential bioactive constituents of Qing-Yi Recipe in biological samples was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and this method was fully validated...

Postpartum depression (PPD) has a significant impact on the physical and mental health of mothers, potentially leading to symptoms such as low mood, fatigue, and decreased appetite. It may also affect the healthy growth of the infant. The onset of PPD is closely related to abnormalities in inflammation and the immune system. PPD patients exhibit abnormalities in the proportion of peripheral blood immune cells, along with an increase in pro-inflammatory cytokines. Excessive pro-inflammatory cytokines in peripheral blood can disrupt the blood-brain barrier (BBB) by activating astrocytes and reducing transendothelial electrical resistance (TEER), allowing peripheral immune cells or cytokines to enter the brain and trigger inflammation, ultimately leading to the onset of depression...

In order to alleviate environmental problems and reduce CO2 emissions, geopolymers had drew attention as a kind of alkali-activated materials. Geopolymers are easier access to raw materials, green and environment friendly than traditional cement industry. Its special reaction mechanism and gel structure show excellent characteristics such as quick hardening, high strength, acid and alkali resistance. In this paper, geopolymer pastes were made with metakaolin (MK) and ground granulated blast furnace slag (GGBFS) as precursors...

Bronchoscopic lung volume reduction treatment with Zephyr one-way valves is an effective guideline-based treatment option for patients with severe emphysema and hyperinflation. However, in some cases the treatment response is less than anticipated or there might be a loss of initial treatment effect. Reasons for the lack of response can include incorrect assessment of collateral ventilation, improper valve placement, or patient related factors. Loss of initial benefit can be due to granulation tissue formation and subsequent valve dysfunction, or there may be side effects such as excessive coughing or infectious problems...

Recurrent seizures lead to accumulation of the activity-dependent transcription factor ∆FosB in hippocampal dentate granule cells in both mouse models of epilepsy and mouse models of Alzheimer's disease (AD), which is also associated with increased incidence of seizures. In patients with AD and related mouse models, the degree of ∆FosB accumulation corresponds with increasing severity of cognitive deficits. We previously found that ∆FosB impairs spatial memory in mice by epigenetically regulating expression of target genes such as calbindin that are involved in synaptic plasticity...

The adversities of cadmium (Cd) contamination are quite distinguished among other heavy metals (HMs), and so is the efficacy of zinc (Zn) nutrition in mitigating Cd toxicity. Rice (Oryza sativa) crop, known for its ability to absorb HMs, inadvertently facilitates the bioaccumulation of Cd, posing a significant risk to both the plant itself and to humans consuming its edible parts, and damaging the environment as well. The use of nanoparticles, such as nano-zinc oxide (nZnO), to improve the nutritional quality of crops and their counteractive implications against HMs, have gained substantial attention among scientists and farmers...

In a recent article in Cell, Zhou et al. investigate the origins, composition, and biological consequences of UV-induced stress granules. They find that UV-induced stress granules are triggered by the formation of RNA-protein crosslinks, uniquely contain DHX9 as a marker, form during mitosis independently of translation repression, and are enriched in intron-containing RNAs and splicing factors. Moreover, UV-induced granules contain double-stranded RNA (dsRNA) and trigger a dsRNA response. This work identifies a mechanism for resolving UV-damaged RNA and broadens the types of cytosolic "stress granules" that form...

BACKGROUD: Chronic fatigue syndrome (CFS) severely impact patients' quality of life and lacks well-acknowledged drug therapy. Sijunzi decoction (SJZD), a classical Chinese herbal formula, has been widely used for spleen deficiency syndrome like fatigue in China. However, there is a lack of evidence on the efficacy of SJZD in treating CFS. PURPOSE: To evaluate the efficacy and safety of SJZD for CFS. STUDY DESIGN: A multi-center, double-blinded, randomized controlled trial...

Neutrophil extracellular traps (NETs) are cell-extruded DNA strands coated with neutrophils' nuclear proteins and enzymes from cytotoxic granules, produced by NETosis, a cell death pathway. They perform an important defensive role in innate immunity, but their increased production and/or inefficient degradation expose new antigens, such as DNA or citrullinated histone peptides, triggering autoimmunity. This study aimed to access possible associations between serum NETs levels with epidemiological, clinical, and serological data from a well-characterized SLE Brazilian patients' cohort...