Density Of Granules Research Articles

Adrenal Gland of Poultry: Anatomy, Microscopy, Morphometry, and Histochemistry

The adrenal gland plays a crucial role in poultry’s body. Its hormones affect growth, tissue differentiation, and metabolism regulation, as well as the bird body’s resistance to infections, intoxication, stress, and low temperature. For poultry farming, veterinary medicine, and ornithology, it is of scientific interest to study the morphological features of the adrenal gland of birds. This review aimed to assess poultry adrenal anatomy, microscopy, morphometry, and histochemistry by summarizing research data from various published articles. The structure of the adrenal gland has been morphologically investigated in clinically healthy chickens, ducks, geese, and quails. Data from the anatomical level of the adrenal gland have indicated that the shape of this organ in poultry of different species is not the same. In most cases, the shape of the adrenal gland of poultry is close to an oval, triangle, or pyramid. The color of the adrenal gland of poultry varies from gray to brown, which depends on the tissue saturation of this organ with carotenoids. The mass of the adrenal glands of poultry correlates with their age. The left adrenal gland has higher mass, volume, and length indicators than the right gland. The microscopic structure of the adrenal gland corresponds to the general laws of the structure and function of endocrine organs. However, the adrenal glands of poultry are characterized by class features of its histoarchitectonics. The adrenal capsule contains ganglia of the autonomic nervous system, the cell strands of cortical and medullary tissues are intertwined, and the configuration of these cell strands determines the formation of two or three zones of the adrenal gland. Studies of the adrenal glands of poultry at the cellular level have indicated that cortical tissue is represented by acidophilic cells and medullary tissue by basophilic cells. Depending on the shape and electron density of secretory granules, medullary tissue cells are divided into epinephrine and norepinephrine. Data on morphometric parameters (capsule thickness, area of cortical and medullary tissues, cortical-medullary ratio) of the adrenal gland are not the same and depend on the type, age, gender, and sexual activity of poultry. In conclusion, morphologists have paid great attention to studying the features of the anatomy, microscopy, morphometry, and histochemistry of the adrenal gland in clinically healthy poultry. Therefore, the presented data can be used to assess deviations in the morphofunctional state of the adrenal gland in poultry under the influence of various factors and pathology. Keywords: Adrenal gland, Anatomy, Morphological features, Histological and cellular levels, Poultry

Indirect Induction Sintering of Metal Parts Produced through Material Extrusion Additive Manufacturing.

Avoiding loose powders and resins, material extrusion additive manufacturing is a powerful technique to produce near-net shape parts, being a cheap and safe alternative for developing complex industrial-grade products. Filaments embedded with a high packing density of metallic or ceramic granules are being increasingly used, resulting in almost fully dense parts, whereby geometries are shaped, debinded and sintered sequentially until the completion of the part. Traditionally, "brown" debinded geometries are transported to conventional furnaces to densify the powder compacts, requiring careful tailoring of the heating profiles and sintering environment. This approach is decoupled and often involves time-consuming post-processing, whereby after the completion of the shaping and debinding steps, the parts need to be transported to a sintering furnace. Here, it is shown that sintering via indirect induction heating of a highly filled commercially available filament embedded with stainless steel 316L powder can be an effective route to densify Fused Filament Fabricated (FFF) parts. The results show that densities of 99.8% can be reached with very short soaking times, representing a significant improvement compared to prior methods. A hybrid machine is proposed, whereby a custom-built machine is integrated with an induction heater to combine FFF with local indirect induction sintering. Sintering in situ, without the need for part transportation, simplifies the processing of metal parts produced through material extrusion additive manufacturing.

MORPHOLOGICAL CHARACTERISTICS OF THE ENDOCRINE FUNCTION OF THE HEART IN COMORBID PATHOLOGY.

Aim: To study the ultrastructural remodeling of atrial myoendocrine cells (AMC) of the atrial myocardium in streptozotocin-induced diabetes (SID) under chronic immobilization stress (CIS). Materials and methods: 40 sexually mature white male rats (body weight 150-180 g) were included in the study. Four groups were formed: group 1 - animals with comorbid pathology (SID and CIS), group 2 - animals with SID, group 3 - animals with CIS, group 4 - intact animals. Results: On the 14th day of the development of SID and CIS, an increase in the functional activity of AMC is noted, which is confirmed by hyperplasia and hypertrophy of the protein-synthesizing apparatus, an increase in the volume density of secretory granules (SG), especially diffusing ones, and indicates enhanced release of atrial natriuretic peptide (ANP) from cells during the experiment. On the 56th day of the experiment, in groups 1 and 2 of , destructive changes in AMC were noted, such as vacuolar and balloon dystrophy, colliquative and partial necrosis. At the same time, the functional activity of AMC of different regions of the myocardium significantly. In animals with CIS, the volume density of young and diffusing SG in AMC is decreased. Conclusions: Therefore, in the early stages of the development of SID and CIS, an increase in the morpho-functional activity of AMC is noted. The long course of SID and its combination with CIS lead to destructive changes in AMC and to decrease in their secretory activity.

A DEFICIENCY OR DEVELOPMENTAL DEFECT IN PANETH CELLS MAY LEAD TO ACUTE APPENDICITIS IN CHILDREN

Objective The aim of this study was to investigate whether there were differences in the Paneth cells between children with acute appendicitis (AA) and those with normal appendix (NA), and to reveal the distribution of and morphological changes in Paneth cells in appendix inflammation. Materials and Methods The data of 63 patients who underwent appendectomy diagnosed with acute appendicitis between January 2021 and December 2022, including age, gender, operative diagnosis, and postoperative histopathological examination results, were analyzed retrospectively. To evaluate the distribution and changes of Paneth cells throughout AA and NA groups, samples with hematoxylin and eosin (H & E)-stained sections were obtained from the Department of Histopathology's archives. Selected blocks were stained with Masson-Trichrome. The number of Paneth cells and the degree of granular density in the appendicitis tissues were statistically evaluated and compared with the results of the control group. Results A total of 63 appendectomies were performed, including 31 incidental appendectomies and 32 performed for preoperative diagnosis of acute appendicitis. There were no statistically significant differences between the groups that underwent surgery for AA and the NA in terms of gender and age (p>0.05). It was observed that the number of Paneth cells and granule density decreased significantly in acute appendicitis (AA) group (p<0.05). Conclusion Reduction or developmental deficiency in Paneth cells, which results in the loss of protective secretion, may increase the appendix's susceptibility to bacterial infection by allowing organisms to adhere and move across the mucosa. Such enhancement of infection may contribute to the pathogenesis of appendicitis.

Experimental and Mathematical Investigation of Anaerobic Granulate Density via Settling Velocity

The objective of this study was to determine the density of anaerobic granules on different heights of a full-scale Upflow Anaerobic Sludge Bed reactor. The density was defined through the settling velocities of anaerobic granules, measured in a full-scale Upflow Anaerobic Sludge Bed reactor. In this study, granular density was calculated with the measured settling velocities and developed mathematical model. The developed mathematical model is based on the Stokes model. In the experiment, granules were taken from different heights of an Upflow Anaerobic Sludge Bed reactor, from 0.6 to 7.6 m. The granules’ diameters varied between 1 and 5 mm. The granules were taken from six different heights through the reactor. The settling velocity of the active granules (with gas in the granule pore and on the surface of the granule) was measured first. After the active granules’ settling velocity measurement, the granules were placed in a vortex to obtain degassed granules (granules without any gas in the pores or on the surface), for which the settling velocities were also measured later. It is shown that granules’ densities at different heights are independent of the reactor height.

Synaptic inputs to displaced intrinsically-photosensitive ganglion cells in macaque retina

Ganglion cells are the projection neurons of the retina. Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and also receive input from rods and cones via bipolar cells and amacrine cells. In primates, multiple types of ipRGCs have been identified. The ipRGCs with somas in the ganglion cell layer have been studied extensively, but less is known about those with somas in the inner nuclear layer, the “displaced” cells. To investigate their synaptic inputs, three sets of horizontal, ultrathin sections through central macaque retina were collected using serial block-face scanning electron microscopy. One displaced ipRGC received nearly all of its excitatory inputs from ON bipolar cells and would therefore be expected to have ON responses to light. In each of the three volumes, there was also at least one cell that had a large soma in the inner nuclear layer, varicose axons and dendrites with a large diameter that formed large, extremely sparse arbor in the outermost stratum of the inner plexiform layer. They were identified as the displaced M1 type of ipRGCs based on this morphology and on the high density of granules in their somas. They received extensive input from amacrine cells, including the dopaminergic type. The vast majority of their excitatory inputs were from OFF bipolar cells, including two subtypes with extensive input from the primary rod pathway. They would be expected to have OFF responses to light stimuli below the threshold for melanopsin or soon after the offset of a light stimulus.

Study of Orally Disintegrating Tablets Using Erythritol as an Excipient Produced by Moisture-Activated Dry Granulation (MADG).

Moisture-activated dry granulation (MADG) is an eco-friendly granulation method that uses a small amount of water and insoluble excipients to absorb moisture. MADG is expected to improve productivity and reduce costs. Erythritol, an excipient used for preparing orally disintegrating tablets (ODTs), has poor tabletability and is difficult to form into tablets by conventional methods, such as high-shear granulation (HSG) and direct compression. In this study, we optimized the manufacturing conditions for ODTs to improve the tabletability of erythritol using MADG. The disintegration time of tablets made using the MADG method was approximately one-tenth that of those made using the HSG method, and the hardness was approximately 1.4 times higher. Moreover, MADG could delay disintegration and improve tabletability. We further attempted to optimize the manufacturing conditions using MADG, particularly in terms of the amount of water used. The disintegration time increased as the amount of added water increased. Moreover, water absorption tests revealed that capillary wetting decreased as the amount of water added increased, but the initial wetting did not change. These results suggested that the disintegration time was prolonged because of the increase in granule density and decrease in capillary wetting with the increase in the amount of added water. The hardness of the tablets increased because of the easy deformation of the granules after the addition of up to 3% water; however, when more than 3% water was added, the hardness decreased because of the aggregation of the granules with the excess water. Finally, two-dimensional maps of the effect of the amount of added water and water activity indicated that tablets with a hardness of ≥80 N and a disintegration time of ≤15 s could be produced by adjusting the amount of added water to within the range of 2.2–3.3% and water activity to 0.3–0.53. These results indicate that MADG can improve the tabletability of erythritol and be used for the granulation of ODTs. Tablets with appropriate hardness and disintegration properties can be produced by adjusting the water content to approximately 2.7% and the water activity to approximately 0.4 when producing ODTs with MADG.

Corpora amylacea are associated with tau burden and cognitive status in Alzheimer’s disease

Corpora amylacea (CA) and their murine analogs, periodic acid Schiff (PAS) granules, are age-related, carbohydrate-rich structures that serve as waste repositories for aggregated proteins, damaged cellular organelles, and other cellular debris. The structure, morphology, and suspected functions of CA in the brain imply disease relevance. Despite this, the link between CA and age-related neurodegenerative diseases, particularly Alzheimer’s disease (AD), remains poorly defined. We performed a neuropathological analysis of mouse PAS granules and human CA and correlated these findings with AD progression. Increased PAS granule density was observed in symptomatic tau transgenic mice and APOE knock-in mice. Using a cohort of postmortem AD brain samples, we examined CA in cognitively normal and dementia patients across Braak stages with varying APOE status. We identified a Braak-stage dependent bimodal distribution of CA in the dentate gyrus, with CA accumulating and peaking by Braak stages II–III, then steadily declining with increasing tau burden. Refined analysis revealed an association of CA levels with both cognition and APOE status. Finally, tau was detected in whole CA present in human patient cerebrospinal fluid, highlighting CA-tau as a plausible prodromal AD biomarker. Our study connects hallmarks of the aging brain with the emergence of AD pathology and suggests that CA may act as a compensatory factor that becomes depleted with advancing tau burden.

How weak static magnetic field contributes to rapid granulation and better performance of microalgal-bacterial granular sludge?

Microalgal-bacterial granular sludge (MBGS) has received considerable attention as an emerging sustainable process for wastewater treatment, whereas achieving rapid granulation is still challenging. Herein, we applied a static magnetic field (5 mT) to accelerate MBGS granulation in photo-sequencing batch reactors (PSBRs). Results showed that complete granulation of MBGS in the reactor with magnetic field (RM) was achieved 20 days before that in the control reactor (RC). The magnetic field significantly promoted microbial growth, sludge settleability and granule density. The treatment performance for COD (84.1 %–96.7 %), ammonium (91.7 %–100 %) and phosphorus (71.5 %–83.3 %) was efficient and similar in both reactors. However, the volumetric removal rate for total nitrogen (TN) was greatly improved by magnetic field due to increased nitrogen assimilation and denitrification. Moreover, mature MBGS in RM showed higher specific oxygen production rate (SOPR) and specific oxygen uptake rate (SOUR), approximately 90 % and 16 % greater than those in RC. The accumulation of metal ions (iron and calcium), the enhanced production of extracellular polymeric substances (EPS, especially proteins (PN)), and the enrichment of functional bacteria (EPS producers and potential denitrifiers) and phototrophs (Tetradesmus, Monoraphidium and Desmodesmus) contributed to rapid granulation and better performance of MBGS. This study provides an economic, effective and environmental-friendly method for rapid cultivation of MBGS, which would be helpful for large scale applications of MBGS.

320-OR: Maternal Overnutrition Confers Increased Spare Respiratory Capacity and Glucose-Stimulated Insulin Secretion in Nonhuman Primate Offspring Islets

The Developmental Origins of Health and Disease hypothesis states that the intrauterine environment influences postnatal health and adult disease susceptibility. In the United States, over 30% of women of childbearing age are obese, in part due to Western Style Diet (WSD) consumption. Previous data from our group using a Japanese macaque model, revealed that maternal overnutrition increases the β:α cell ratio in the islets of offspring. WSD-exposed offspring islets also exhibit inappropriate hypersecretion of insulin in response to glucose at 1 and 3 years of age. We hypothesize that fetal exposure to WSD induces a compensatory increase in β-cell fuel metabolism resulting in an inappropriate increase in insulin secretion by offspring islets. When we assessed the effect of maternal diet on mitochondrial respiration in offspring islets, we found that spare respiratory capacity is increased in islets of one year old WSD-exposed male offspring, suggesting an increased capacity to adapt to increased metabolic demand. This could be due to increased mitochondrial abundance; however, maternal overnutrition does not appear to increase β cell mitochondrial density when analyzed via transmission electron microscopy (TEM) . Insulin granule density is increased in male offspring islets in TEM micrographs, implying that insulin production is increased in response to intrauterine WSD exposure. Transcripts for CACNA1C (voltage gated calcium channel subunit) , ABCC8 (ATP-sensitive potassium channel subunit) , and VAMP2 (vesicle fusion) are increased in response to maternal WSD exposure in offspring islets. Thus, our data suggest that increases in insulin secretion in offspring exposed to maternal overnutrition result from changes in metabolic and secretion pathways. Importantly, these mechanisms could potentiate hyperinsulinism which may predispose offspring to insulin resistance and beta cell failure in adulthood. Disclosure D.T. Carroll: None. V.F. Ricciardi: None. J.C. Dunn: None. S.R. Lindsley: None. T. Dean: None. M. Kirigiti: None. S.R. Wesolowski: None. C.E. McCurdy: None. P. Kievit: Research Support; Novo Nordisk A/S. J.E. Friedman: None. M. Gannon: None. Funding NIH-NIDDK (5T32 DK7563-30, R24DK090964-06, 1R01DK128187)

Comparison of ANP and BNP Granular Density in Atria of Rats After Physiological and Pathological Hypertrophy.

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones located in atria granules. Both peptides respond to cardiac pressure and volume dynamics and accordingly serve as translation biomarkers for the clinical treatment of heart failure. Serum ANP and BNP play central secretary roles in blood pressure and cardiac output regulation and have proven utility as differential biomarkers of cardiovascular proficiency and drug-induced maladaptation, yet both peptides are impervious to exercise-induced hypertrophy. We employed immunoelectron microscopy to examine the effects of 28 days of chronic swim exercise or administration of a PPARγ agonist on atrial granules and their stored natriuretic peptides in Sprague Dawley rats. Chronic swimming and drug treatment both resulted in a 15% increase in heart weight compared with controls, with no treatment effects on perinuclear granule area in the left atria (LAs). Drug treatment resulted in larger size granules with greater BNP density in the right atria. Comparing swimming and PPARγ agonist treatment effects on ANP:BNP granule density ratios between atrial chambers revealed a shift toward a greater proportion of ANP than BNP in LAs of swim-trained rats. These data suggest a distinction in the population of ANP and BNP after chronic swim or PPARγ that makes it a novel metric for the differentiation of pathological and physiological hypertrophy.

The role of ABCC4 in pigment granule migration in RPE of mice

ABCC4 is an ATP‐binding cassette protein that exports many substrates, including cyclic adenosine monophosphate (cAMP). In mammals, cyclic AMP accumulates in retinal photoreceptors in dark conditions. We conjecture that cyclic AMP is exported from the photoreceptors into the sub‐retinal space, where it becomes available for uptake by the retinal pigment epithelium (RPE), activating the process of pigment granule aggregation. We hypothesize that ABCC4 in photoreceptors mediates cAMP‐export and therefore is essential to the process of pigment granule migration in the RPE of mice. To investigate the involvement of ABCC4 in pigment granule movement, pigment granule density was measured along the basal part of the RPE for both wildtype and Abcc4 knockout mice that were light‐ or dark‐adapted (N = 3 for each treatment). Dark‐adapted wildtype mice showed significantly higher pigment granule density compared to light‐adapted wildtype mice, and no significant difference was seen between light‐adapted and dark‐adapted Abcc4knockout mice. A polyclonal antibody to ABCC4 used on zebrafish retinal sections showed the presence of ABCC4 in the outer retina by immunohistochemistry. These results are consistent with the hypothesis that ABCC4 plays a role in the regulating pigment granule position in RPE of mice.

A wet granulation method to prepare graphite particles with a high tap density for high volumetric energy density lithium-ion storage

Graphite is the most widely used anode material for lithium ion batteries (LIBs). Increasing the sphericity and tap density of the graphite particles is important for improving their volumetric energy density. We report a simple approach to prepare high tap-density graphite granules by high-shear wet granulation. Graphitic onion-like carbon (GOC) and artificial graphite (AG) were densified into granules by wet-granulation to obtain WG-GOC and WG-AG, respectively. Results indicate that, compared with the original graphite before granulation, the tap densities of WG-GOC and WG-AG increased by 34% and 44%, respectively. The respective volumetric energy densities of WG-GOC and WG-AG increased by 35% and 55% at a current density of 50 mA g−1. The rate performance of WG-GOC was also significantly improved. The volumetric capacity of WG-GOC at a current density of 2000 mA g−1 was 169.1% of the original GOC. The significant improvement of electrochemical performance is ascribed to the increased tap density of the graphite granules.

Acupoint catgut embedment may reduce airway inflammation reaction by down-regulating ICAM-1 and EOS by suppressing p38MAPK signaling in lung tissue of asthmatic rats

To observe the effect of acupoint catgut embedment(ACE) on expression of p38 mitogen activated protein kinase (p38MAPK), intercellular adhesion molecule-1(ICAM-1), interleukin-4 (IL-4) and eosinophils (EOS) in lung tissue of asthmatic rats, so as to explore its mechanism underlying improvement of asthma. Forty male Wistar rats were randomly divided into control, model, ACE and dexamethasone (DEX) groups, with 10 rats in each group. The asthmatic model was established by intraperitoneal injection of mixture suspension (1 mL) of ovalbumin (OVA,10%) and 10% Al (OH)3+ normal saline, followed by inhalation of atomized 1% OVA solution for 30 min, once daily for 2 weeks to trigger occurrence of asthmatic symptoms. The ACE was applied once to "Feishu" (BL13), "Dingchuan" (EX-B1) and "Danzhong" (CV17). Rats of the DEX group were given intraperitoneal injection of DEX once a day for 2 weeks. H.E. staining was used to evaluate histopathological changes of the lung tissue. The relative number of EOS in the bronchoalveolar lavage fluid (BALF) was detected by Wright Giemsa staining. The apoptosis level of EOS in the lung tissue was detected by TUNEL staining. The ultrastructural changes of EOS in the lung tissues were observed by transmission electron microscope (TEM). The expression of p38MAPK, ICAM-1 and IL-4 mRNAs in the lung tissue was detected by quantitative real-time PCR. Findings of optical microscope and TEM showed obvious bronchial deformation and inflammatory cell infiltration, rupture of EOS cell membrane, uneven cytoplasm with swelling and uneven density of eosinophilic granules in EOS of the model group, which was relatively milder in the ACE and DEX groups. Compared with the control group, the EOS number in BALF and the expressions of p38MAPK, ICAM-1 and IL-4 mRNAs in the lung tissue were significantly increased (P<0.01), and the apoptosis index of EOS in the lung tissue was significantly decreased (P<0.01) in the model group. After intervention, the EOS number in BALF and expression levels of p38MAPK, ICAM-1 and IL-4 mRNAs in the lung tissue of ACE and DEX groups were significantly decreased (P<0.01, P<0.05), as well as the apoptosis index of EOS in the lung tissue was significantly increased in both ACE and DEX groups (P<0.01) in comparison with the model group. The EOS number in BALF and expression of ICAM-1 mRNA were significantly lower in the DEX group than those in the ACE group (P<0.05). Catgut embedding at acupoints may alleviate the airway inflammatory response in asthma rats, which may be related with its effects in down-regulating p38MAPK signaling, ICAM-1 and IL-4 mRNA expression, reducing the aggregation of EOS, and promoting the apoptosis of EOS.

Switching from batch to continuous granulation: A case study of metoprolol succinate ER tablets

Continuous manufacturing (CM) has been used to produce several immediate release drug products. No extended-release (ER) product manufactured employing CM technology has been approved yet. This study investigated the critical aspects of switching from the batch mode of high shear granulation to the continuous operation of twin-screw granulation for extended-release tablets. Metoprolol succinate ER tablets was used as a model ER formulation for this purpose. A central composite design (CCD) was employed to determine the effects of high shear granulator (HSG) parameters, namely impeller speed, granulation time, and binder liquid feeding rate, on the critical granulation characteristics important for product performance. These critical granulation characteristics served as a guide for switching from the batch processing to the continuous operation for achieving the same breaking strength and dissolution for this ER metoprolol tablets.The granulation time was the most critical factor affecting the bulk properties of granules which contributed to tablet dissolution. The higher density and lower compressibility of granules were attained at the longest granulation time of 5.4 min with the fastest liquid feeding rate of 75 g/min. The granules’ density was the primary factor negatively affecting the dissolution of metoprolol tablets. However, the breaking strength of tablets confounded the effect of granules density on metoprolol dissolution. Switching the processing parameters of high shear granulation to twin-screw granulation achieved similar dissolution profiles (F2 greater than 50). The screw speed was not found to affect bulk properties of granules. The root cause of granulation failures in twin-screw granulation, such as premature consolidation, excessive swelling, poor cohesion, inconsistent shearing effects, and formation of deformed agglomerates, were identified. In conclusion, the use of critical granulation characteristics through a performance-based approach of ER tablets facilitated the switching of manufacturing of an ER formulation form batch to continuous operation.

Density measurements of aerobic granular sludge

ABSTRACT Granular sludge processes are frequently used in domestic and industrial wastewater treatment. The granule buoyant density and biomass density are important parameters for the design and operation of granular sludge reactors. Different methods to measure the granule density include the pycnometer method, the Percoll density gradient method, the dextran blue method, and the settling velocity method. In this study, a comparison was made between these four methods to measure granule density for granules from a full-scale granular sludge plant treating domestic sewage. The effect of salinity on granule density was assessed as well. Three out of the four evaluated methods yielded comparable results, with granule buoyant densities between 1025.7 and 1028.1 kg/m3 and granule biomass densities between 71.1 and 71.5 g/L (based on volatile suspended solids (VSS)). The settling velocity method clearly underestimated the granule density, due to the complex relation between granule properties and settling velocity. The pycnometer method was the most precise method, but it was also quite susceptible to bias. The granule buoyant density increased proportionally with salinity, to 1049.2 kg/m3 at 36 g/L salinity. However, the granule biomass density, based on VSS, remained constant. This showed that the granule volume was not affected by salinity and that the buoyant density increase was the result of diffusion of salts into the granule pores. Overall, the granule density can be measured reliably with most methods, as long as the effect of salinity is considered. The results are discussed in light of operational aspects for full-scale granular sludge plants.

Effect of filter granules properties on flow behavior in a moving granular filter

The moving granular filter technology based on size segregation is a hot gas purification technology which is expected to be applied in large-scale industrial applications. We studied the effect of granule size ratio (γ), surface friction coefficient (μs), and equivalent granule density (ρe) on the degree of size segregation of two-component granules based on the discrete element method (DEM). We also experimentally investigated the difference in flow behavior between single-component and two-component granules before and after dust attachment. Results showed that the degree of size segregation increased rapidly when γ < 2, and decreased slowly when γ > 2. μs and ρe had little effect on the degree of size segregation. When the dust concentration C = 0–24.0 g/m3, the adhesion of dust can increase the granule falling velocity, the maximum was about 1.66 times that without dust. High dust deposition rate weakened the lifting effect.

Long-term effects of mineral precipitation on process performance, granules' morphology and microbial community in anammox granular sludge

When treating wastewaters prone to inert precipitation with granular sludge systems, mineral formation needs to be properly controlled to ensure system’s long-term stability. In this work, an extensive study on mineral precipitation on the surface of anammox granular sludge is presented. A 7-L reactor was inoculated with one-year stored biomass and volumetric load up to 0.48 gN-NO2-/l/d were achieved, with nitrite removal above 95% and total nitrogen removal rate of almost 1 gN/l/d. Severe mineral precipitation was observed on the granules’ surface after three months of hard-water feeding and resulted in a dramatic deterioration of reactor performance and biomass activity. Substrate diffusion limitation in the inner layers, insufficient mixing due to higher granule density and biofilm erosion due to shear stress increase were deemed the main mechanisms that lead to progressive process disruption. Gravimetric selection was applied to discard granules affected by precipitation and allowed for process restoration. Microbial community analyses revealed that mineral composition possibly affected competition between “Ca. Brocadia” and “Ca. Kuenenia”. The knowledge gathered in the present study details the dramatic consequences on process performance lead by severe mineral precipitation and it is presented as a warning for full-scale applications treating wastewaters prone to precipitation.

EVIDENCE OF APOPTOSIS IN PARVOCELLULAR NUCLEI OF HYPOTHALAMUS IN DIABETES MELLITUS

Diabetes mellitus (DM) causes great socio-economic damage, which is determined by medical expenses and expenditure on social security to patients due to invalidity and loss of labour capacity. Researchers are studying the role of hypothalamic neuropeptides and their involvement in the regulation of pancreatic islet function. In view of the above, the aim of our study was to establish the features of morphofunctional changes in the arcuate nucleus (AN) and ventromedial nucleus (VN) of the hypothalamus in streptozotocin-induced diabetes mellitus (SIDM).&#x0D; Histological, immunohistochemical, electron-microscopic, biochemical and statistical research methods were used.&#x0D; Polymorphic changes were noted in AN and VN at early stages of development of SIDM (on the 14th day). In AN, the area of neurons and their nuclei became larger, the numerical density of dark functionally more active neurons increased, and dinuclear light neuroendocrine cells (NC) appeared. In light and dark NCs of AN, there was a significant increase in the bulk density of neurosecretory granules – by 2-4 times compared with the control, in VN – by 1.2-2 times.&#x0D; Such morphofunctional changes in parvocellular nuclei of the hypothalamus and the increase in the bulk density of neurosecretory granules in their NCs indicate boosted synthesis of neurohormones which directly affect the adenohypophysis and improving functional activity of NCs in AN and VN.&#x0D; On the 70th day of SIDM in AN and VN of the hypothalamus, there was a decrease in the numerical density of neurons due to light NC and increase in the numerical density of vacuolated, dark pycnomorphic and apoptotic neurons. The apoptotic index in the studied nuclei of the hypothalamus increased by 2-4 times compared with the control. The area of the profile field of NC increased and the area of nuclei decreased, which led to the reduced nuclear-cytoplasmic index and indicated a decrease in their functional activity and was confirmed by a decrease in the bulk density of neurosecretory granules in NC by 1.9-2.1 times in AN and by 2.7-4.7 times in VN. At the ultrastructural level, pronounced destructive processes such as vacuolar dystrophy, development of satelliteosis and neuronophagia were observed in light NCs.&#x0D; Thus, prolonged hyperglycemia in SIDM in parvocellular nuclei of the hypothalamus causes neuronal death to a lesser extent due to apoptosis, and to a greater extentdue due to hydropic dystrophy and colliquative necrosis, especially in the long term of the experiment (on the 70th day), and leads to the development of diabetic neuroendocrinopathy.

High shear wet granulation: Improved understanding of the effects of process variables on granule and tablet properties of a high-dose, high-hydrophobicity API based on quality by design and multivariate analysis approaches

High shear wet granulation (HSWG), as a widely used granulation technology, has been studied extensively. However, for the HSWG of formulations containing hydrophobic components, the influence of process variables on the properties of granules and tablets has not been reported. In the present study, based on a combination of quality by design and multivariate analysis (MVA) approaches, quercetin with high-dose and high-hydrophobicity was used to study the relationship between process variables, granule properties, and tablet properties in HSWG systematically. Control and response variables were determined using risk assessment. The optimal fitting empirical models established by Box-Behnken design showed that the liquid to solid ratio and impeller speed were the most important factors, which affected all product properties except Carr’s index and yield pressure. Instead, the influence of wet massing time was relatively small (only the effects on yield, granule size, granule hardness, and compression ratio were significant). Then, the process design space was obtained by limiting the related critical quality attributes, which was verified effectively. Scanning electron microscope images showed that smooth granules were produced using higher process parameters, whereas rough and porous granules resulted at lower process parameters. Furthermore, the MVA results demonstrated that increasing the granule hardness led to an increase in the compression ratio and a decrease in tensile strength of the tablets. Tablet fragility and disintegration time were mainly affected by granule density and bulk density, respectively, and both were negatively correlated. The established research paradigm is not only conducive to the successful development of quercetin products, but also provides valuable guidance for improving HSWG–based product development with such formulation characteristics.