Multi-faceted dysregulated immune response for COVID-19 infection explaining clinical heterogeneity.

Clinical heterogeneity and varied prognosis are well noted for SARS-CoV-2 infection. Altered immune response is a major feature for the adverse prognosis however focus on altered immune response has been primarily limited to hyper-inflammatory responses like Cytokine storm. A deeper understanding of viral pathobiology and the interplay of innate and adaptive immune cells against SARS-CoV-2 infection is essential to optimize intervention strategy and future preparedness for SARS-CoV-2 or its related viral diseases. To uncover the immunological signatures driving the progression of SARS-CoV-2 infection, we performed an extensive immunophenotype on blood samples from 79 hospitalized patients with mild/moderate to severe infections as well as from healthy controls and recovered donors to understand the interplay between innate and adaptive responses impacting severity and prognosis. We observed multifarious immune dysregulation, varied across patients of the clinical spectrum. We observed 4 major dysregulations of immune phenotypes 1) depletion of M1φ (impaired antiviral response as APC), 2) immune suppression/exhaustion via activation of repressor like CD4+/CD8+PD1, TIM3, LAG3 3) inappropriate differentiation of lymphocyte (extreme elevated proportion of CD4 naive, memory B and T cells along with reduction of inflammatory activator like TLR2/4/TIGIT) and 4) cytokine storm. Our results show the identification of biomarkers to differentiate the different trajectories for SARS-CoV-2 infection.

TANK Binding Kinase 1 Promotes BACH1 Degradation through Both Phosphorylation-Dependent and -Independent Mechanisms without Relying on Heme and FBXO22.

BTB and CNC homology 1 (BACH1) represses the expression of genes involved in the metabolism of iron, heme and reactive oxygen species. While BACH1 is rapidly degraded when it is bound to heme, it remains unclear how BACH1 degradation is regulated under other conditions. We found that FBXO22, a ubiquitin ligase previously reported to promote BACH1 degradation, polyubiquitinated BACH1 only in the presence of heme in a highly purified reconstitution assay. In parallel to this regulatory mechanism, TANK binding kinase 1 (TBK1), a protein kinase that activates innate immune response and regulates iron metabolism via ferritinophagy, was found to promote BACH1 degradation when overexpressed in 293T cells. While TBK1 phosphorylated BACH1 at multiple serine and threonine residues, BACH1 degradation was observed with not only the wild-type TBK1 but also catalytically impaired TBK1. The BACH1 degradation in response to catalytically impaired TBK1 was not dependent on FBXO22 but involved both autophagy-lysosome and ubiquitin-proteasome pathways judging from its suppression by using inhibitors of lysosome and proteasome. Chemical inhibition of TBK1 in hepatoma Hepa1 cells showed that TBK1 was not required for the heme-induced BACH1 degradation. Its inhibition in Namalwa B lymphoma cells increased endogenous BACH1 protein. These results suggest that TBK1 promotes BACH1 degradation in parallel to the FBXO22- and heme-dependent pathway, placing BACH1 as a downstream effector of TBK1 in iron metabolism or innate immune response.

mTORC1-independent translation control in mammalian cells by methionine adenosyltransferase 2A and S-adenosylmethionine.

Methionine adenosyltransferase (MAT) catalyzes the synthesis of S-adenosylmethionine (SAM). As the sole methyl-donor for methylation of DNA, RNA, and proteins, SAM levels affect gene expression by changing methylation patterns. Expression of MAT2A, the catalytic subunit of isozyme MAT2, is positively correlated with proliferation of cancer cells; however, how MAT2A promotes cell proliferation is largely unknown. Given that the protein synthesis is induced in proliferating cells and that RNA and protein components of translation machinery are methylated, we tested here whether MAT2 and SAM are coupled with protein synthesis. By measuring ongoing protein translation via puromycin labeling, we revealed that MAT2A depletion or chemical inhibition reduced protein synthesis in HeLa and Hepa1 cells. Furthermore, overexpression of MAT2A enhanced protein synthesis, indicating that SAM is limiting under normal culture conditions. In addition, MAT2 inhibition did not accompany reduction in mechanistic target of rapamycin complex 1 activity but nevertheless reduced polysome formation. Polysome-bound RNA sequencing revealed that MAT2 inhibition decreased translation efficiency of some fraction of mRNAs. MAT2A was also found to interact with the proteins involved in rRNA processing and ribosome biogenesis; depletion or inhibition of MAT2 reduced 18S rRNA processing. Finally, quantitative mass spectrometry revealed that some translation factors were dynamically methylated in response to the activity of MAT2A. These observations suggest that cells possess an mTOR-independent regulatory mechanism that tunes translation in response to the levels of SAM. Such a system may acclimate cells for survival when SAM synthesis is reduced, whereas it may support proliferation when SAM is sufficient.

Colony-stimulating factor 1 receptor signaling in the central nervous system and the potential of its pharmacological inhibitors to halt the progression of neurological disorders.

Colony Stimulating Factor-1 (CSF-1)/Colony Stimulating Factor-1 Receptor (CSF-1R) signaling axis plays an essential role in the development, maintenance, and proliferation of macrophage lineage cells. Within the central nervous system, CSF-1R signaling primarily maintains microglial homeostasis. Microglia, being the resident macrophage and first responder to any neurological insults, plays critical importance in overall health of the human brain. Aberrant and sustained activation of microglia along with continued proliferation and release of neurotoxic proinflammatory cytokines have been reported in various neurological and neurodegenerative diseases. Therefore, halting the neuroinflammatory pathway via targeting microglial proliferation, which depends on CSF-1R signaling, has emerged as a potential therapeutic target for neurological disorders. However, apart from regulating the microglial function, recently it has been discovered that CSF-1R has much broader role in central nervous system. These findings limit the therapeutic utility of CSF-1R inhibitors but also highlight the need for a complete understanding of CSF-1R function within the central nervous system. Moreover, it has been found that selective inhibitors of CSF-1R may be more efficient in avoiding non-specific targeting and associated side effects. Short-term depletion of microglial population in diseased conditions have also been found to be beneficial; however, the dose and therapeutic window for optimum effects may need to be standardized further.This review summarizes the present understanding of CSF-1R function within the central nervous system. We discuss the CSF-1R signaling in the context of microglia function, crosstalk between microglia and astroglia, and regulation of neuronal cell function. We also discuss a few of the neurological disorders with a focus on the utility of CSF-1R inhibitors as potential therapeutic strategy for halting the progression of neurological diseases.

Effects of genotype, parity, season and their interactions on milk yield in crossbred dairy cattle.

The crossbred dairy cattle (CDC) have been gaining popularity in the tropical countries for their increased milk yield within a short period of time because of heterogenic additive gene action. Hence, we aimed to investigate whether genotype, parity, season and their interactions had any effect on average daily milk yield (ADMY) of the CDC in a dairy farm at Chattogram district, Bangladesh, for a period of 3 years from January 2016 to December 2019. Total 16,425 retrospective lactation records of 150 multiparous Sahiwal × Friesian1 (Sahiwal = 50%, HF = 50%), Local × Friesian1 (Local = 50%, HF = 50%) and Local × Friesian2 (Local = 25%, HF = 75%) CDC from the first to the third parities (50 for each parity) were collected from the farm records. The generalized linear model and principal component analysis identified substantial impacts of genotype, parity, season and their interactions on ADMY of the CDC. The herd level least squared ADMY was 11.22 ± 0.04 kg/days on a 305-days typical lactation period. The Sahiwal × Friesian1 CDC produced 7.2% and 5.5% more milk than the Local × Friesian1 and Local × Friesian2 respectively. The CDC produced maximum milk in the second parity, which was 7.8% and 0.34% more than the first and third parities. Similarly, the highest ADMY was recorded in the spring, which was 10.8%, 7.3% and 6.6% more than the fall, summer and winter respectively. It was concluded that the Sahiwal × Friesian1 crossbred produced maximum milk in the spring season at the second parity while other determinants remained constant. The changing patterns of milk yield in different genotype, parity and seasons provided scientific evidence for improving feeding strategy to optimize herd level milk yield of CDC in the commercial dairy farms under tropical perspective.

Retrieval action of zinc and folic acid for the restoration of normal reproductive function in bisphenol-A exposed male albino mice.

Bisphenol-A (BPA) has become a great concern due to its toxic effects. The present study investigated the retrieval action of zinc (Zn) and folic acid (FA) supplementation against BPA-induced reproductive toxicities in male albino mice. A total of seventy-five 25-28 day-old mice were divided into five equal groups (group A-E, 15 mice in each group). The mice were given normal rations (control, group A) or administered with daily doses of BPA at 50 mg/kg body weight (b.w.) (group B-E). The mice from groups C, D and E were supplemented with Zn (10 mg/kg b.w.), FA (3 mg/kg b.w.) and both in the feed, respectively, daily for 12 weeks. Blood samples were collected, and the sera were separated for biochemical and hormonal analyses. The standard method was followed to test the sperm motility and sperm count. The testis samples were processed for a routine histopathological study using haematoxylin and eosin staining. The sperm counts, motility, and serum testosterone significantly declined in the BPA-exposed animals, but dramatically increased after the Zn and FA supplementation. There was significant degeneration of the seminiferous tubules in the testes of the BPA-exposed mice, which was recovered moderately by the Zn and FA supplementation. The study shows the retrieval action of zinc and folic acid in the restoration of normal reproductive function in bisphenol-A exposed male mice.

Microglial mTOR is Neuronal Protective and Antiepileptogenic in the Pilocarpine Model of Temporal Lobe Epilepsy.

Excessive activation of mammalian target of rapamycin (mTOR) signaling is epileptogenic in genetic epilepsy. However, the exact role of microglial mTOR in acquired epilepsy remains to be clarified. In the present study, we found that mTOR is strongly activated in microglia following excitatory injury elicited by status epilepticus. To determine the role of microglial mTOR signaling in excitatory injury and epileptogenesis, we generated mice with restrictive deletion of mTOR in microglia. Both male and female mice were used in the present study. We found that mTOR-deficient microglia lost their typical proliferative and inflammatory responses to excitatory injury, whereas the proliferation of astrocytes was preserved. In addition, mTOR-deficient microglia did not effectively engulf injured/dying neurons. More importantly, microglial mTOR-deficient mice displayed increased neuronal loss and developed more severe spontaneous seizures. These findings suggest that microglial mTOR plays a protective role in mitigating neuronal loss and attenuating epileptogenesis in the excitatory injury model of epilepsy.SIGNIFICANCE STATEMENT The mammalian target of rapamycin (mTOR) pathway is strongly implicated in epilepsy. However, the effect of mTOR inhibitors in preclinical models of acquired epilepsy is inconsistent. The broad presence of mTOR signaling in various brain cells could prevent mTOR inhibitors from achieving a net therapeutic effect. This conundrum has spurred further investigation of the cell type-specific effects of mTOR signaling in the CNS. We found that activation of microglial mTOR is antiepileptogenic. Thus, microglial mTOR activation represents a novel antiepileptogenic route that appears to parallel the proepileptogenic route of neuronal mTOR activation. This may explain why the net effect of mTOR inhibitors is paradoxical in the acquired models of epilepsy. Our findings could better guide the use of mTOR inhibitors in preventing acquired epilepsy.

Microwave and ultrasound-assisted extraction of bioactive compounds from Papaya: A sustainable green process.

The demand for sustainable and eco-friendly extraction methods for bioactive compounds from natural sources has increased significantly in recent years. In this study, we investigated the effectiveness of the microwave pretreated ultrasound-assisted extraction (MPUAE) process for the extraction of antioxidants (TPC, DPPH, and FRAP) from papaya pulp and peel. The optimized variables for the MPUAE process were determined using the Box-Behnken design tool of response surface methodology. Our results showed that the optimized variables for pulp and peel were 675.76 and 669.70 W microwave power, 150 s of irradiation time, 30 °C ultrasound temperature, and 19.70 and 16.46 min of ultrasonic extraction time, respectively. Moreover, the MPUAE process was found to be more energy-efficient and environmentally friendly compared to the conventional ultrasound-associated extraction (UAE) technique. The MPUAE process emitted less CO2 to the environment and had a shorter extraction time, resulting in a more sustainable and cost-effective extraction process. Our study suggests that the MPUAE process has the potential to be a promising and eco-friendly alternative for the industrial extraction of bioactive compounds from papaya and other natural sources.

Coral fossil: A potential adsorbent of natural source for cadmium removal in broilers.

Cadmium (Cd) is a pollutant that poses a health risk for humans and animals. Coral fossil (CF) acts as an adsorbent, yet limited knowledge is available on impacts of CF on Cd toxicities. The work was performed to figure out the effects of CF on hematobiochemical details and specific organs in Cd exposed broilers. The experiment was carried out with 45 broilers and were divided into three groups (15 in each). Group A was served as control. The birds in group B received Cd (75 mg /kg b. w.) orally. Whereas group C was orally supplemented with Cd (75 mg /kg b. w.) and CF (1 gm/kg b. w.). The trial was lasted for 30 days. For hematobiochemical analysis, blood samples were drawn, and sera were separated. Liver, kidney and muscle were collected to assess accumulation concentration. Brain, liver and kidney samples were also collected for histopathological study. The results showed that hematological parameters (TEC, Hb, PCV, MCV, MCH, MCHC and DLC) were altered by Cd but restored with CF supplementation. Liver (AST, ALT and ALP) and kidney (total protein and creatinine) biomarkers were increased significantly in Cd treated broilers while decreased significantly after CF supplementation. CF reduced accumulation concentration of Cd in liver, kidney and muscle. Cd intoxicated broilers showed degenerative changes in brain, hyperplastic bile duct and proliferation of renal tubular epithelium with focal degeneration and necrosis; and these were improved after CF supplementation. Therefore, it can be concluded that CF is a potential adsorbent against Cd toxicities.

Antiviral foods in the battle against viral infections: Understanding the molecular mechanism.

Viruses produce a variety of illnesses, which may also cause acute respiratory syndrome. All viral infections, including COVID-19, are associated with the strength of the immune system. Till now, traditional medicine or vaccines for most viral diseases have not been effective. Antiviral and immune-boosting diets may provide defense against viral diseases by lowering the risk of infection and assisting rapid recovery. The purpose of this review was to gather, analyze, and present data based on scientific evidence in order to provide an overview of the mechanistic insights of antiviral bioactive metabolites. We have covered a wide range of food with antiviral properties in this review, along with their potential mechanism of action against viral infections. Additionally, the opportunities and challenges of using antiviral food have been critically reviewed. Bioactive plant compounds, not only help in maintaining the body's normal physiological mechanism and good health but are also essential for improving the body's immunity and therefore can be effective against viral diseases. These agents fight viral diseases either by incorporating the body's defense mechanism or by enhancing the cell's immune system. Regular intake of antiviral foods may prevent future pandemic and consumption of these antiviral agents with traditional medicine may reduce the severity of viral diseases. Therefore, the synergistic effect of antiviral foods and medication needs to be investigated.

Effects of varying doses of conjugated estrogen on body weight, hormonal and histological alterations of reproductive organs in adult swiss albino female mice.

Estrogens are a group of hormones that have diverse effects on both reproductive and non-reproductive organs. Conjugated estrogens are medicine that contains a mixture of estrogen hormones. The study was conducted to observe the effects of varying doses of conjugated estrogen on body weight, hormonal and histological alterations of reproductive organs in adult swiss albino female mice. In this study, 60 female swiss albino mice (Mus musculus) aged 28-30 days with an average body weight of 28.2 ± 1 g were used. At first, the mice were randomly divided into 4 groups each containing 15 mice. Group A was served as vehicle control and fed on standard mice pellet and fresh drinking water. While, groups B, C and D were administered with conjugated estrogen orally at the daily dose rate of 125 µg, 250 µg and 500 µg/kg body weight respectively with 1 mL sesame oil as a vehicle by mixing with feed. The experiment was carried out for 90 days. After humanly euthanized, blood was collected and serum was prepared and organs were collected for histopathology. The results revealed that higher doses of conjugated estrogen resulted in weight loss in premenopausal female mice compared to lower doses. Serum estrogen and thyroxine concentration was increased significantly following the doses of conjugated estrogen. Ovarian histotexture showed congested blood vessels and cystic space with degeneration of follicles and corpus luteum. Uterine lesions included massive macrophage infiltration in endometrium and hyperplasia of glandular epithelium at a lower dose; hyperplasia and hypertrophy of glandular epithelium (pleomorphism) with normal macrophage infiltration in endometrium at a higher dose. Therefore, it can be concluded that oral conjugated estrogen therapy at high dose has more detrimental impacts on body weight and reproductive function compared to lower dose in female adult mice.

Knowledge, attitudes, and practices regarding immunity boosting dietary behavior of mass population amid COVID-19.

During the increasing spread of COVID-19 occurrences in Chattogram Metropolitan Area (CMA) of Bangladesh, a series of measures were taken to control the transmission. These measures greatly influenced the knowledge, attitudes, and practices (KAP) of the population on their dietary behavior. However, there are no current studies demonstrating the KAP of the CMA citizens regarding their dietary habit that can boost the immunity. In this study, we appraised KAP in regard to immunity boosting dietary behavior from April 26, 2021 to November 17, 2021 during implementation of lockdown measures by the government of Bangladesh. Apart from the basic knowledge and attitudes toward immunity boosting dietary behavior, we have also aimed to assess the practices of the population by whether the nutrients, especially vitamin A, B6, B9, B12, C, D, E, and trace minerals such as zinc, selenium, and iron were included in their diet and in what frequency. This study is a cross-sectional study, and the participants were recruited using both online platforms during the lockdown and through in-person interviews after the withdrawal of lockdown. After obtaining the proper consent from the participants, their sociodemographic variables, and KAP towards immunity boosting dietary behavior were assessed. Total 400 participants were included in this study and a non-probability sampling technique named purposive sampling has been followed for participants recruitment. Among the 400 participants, the majority of them (64.3%) were male, most of them (62.7%) were students, unmarried (69.5%), aged between 18-35 years (82.5%), had a bachelor's degree (50.0%), and had a monthly family income between 10000-30000 BDT (35.5%). This study indicated that 82.8% of the populations had the correct knowledge, 71.3% had favorable attitudes, and 44% had good practices regarding immunity boosting diet during COVID-19. The majority (79.3%) of the participants had an idea about nutrition, most of them (78.5%) knew the nutrients needed to strengthen their immune system, almost all (98.5%) washed fruits and vegetables purchased from the market before eating them, 78% did not often purchase food online, and 53% often ate junk food. In a binary logistic regression, correct knowledge was significantly associated with the females, having HSC or bachelor's degree, being in the occupation of business, laborer or others, and having a monthly family income between 50000-100000 or >100000. The favorable attitudes were significantly associated with having a master's degree or above, and for government job holders. However, the good practices did not show any significant association with the sociodemographic factors in binary logistic regression. Moreover, the study found the presence of bad or unhealthy practices among the populations despite having correct knowledge and favorable attitudes. Thus, this study could identify the variables, such as gender differences, education, monthly family income, and occupation on which emphasis should be given during public health campaigns or training programs to improve the KAP regarding immunity boosting diet.

Influence of Maternal Breast Milk and Vaginal Microbiome on Neonatal Gut Microbiome: a Longitudinal Study during the First Year.

It is believed that establishment of the gut microbiome starts very early in life and is crucial for growth, immunity, and long-term metabolic health. In this longitudinal study, we recruited 25 mothers in their third trimester, of whom 15 had vaginal delivery while 10 had an unplanned cesarean section (C-section). The mother-neonate pairs were followed for 1 year, and we generated 16S metagenomic data to study the neonatal gut microbiome along with mother's breast milk and vaginal microbiomes through 12 months after delivery, at 1, 3, 6, and 12 months. We inferred (i) mode of delivery is an important factor influencing both composition and entropy of the neonatal gut microbiome, and the genus Streptococcus plays an important role in the temporal differentiation. (ii) Microbial diversity monotonically increases with age, irrespective of the mode of delivery, and it is significantly altered once exclusive breastfeeding is stopped. (iii) We found little evidence in favor of the microflora of mother's breast milk and a vaginal swab being directly reflected in the offspring's gut microbiome; however, some distinction could be made in the gut microbiome of neonates whose mothers were classified as community state type III (CSTIII) and CSTIV, based on their vaginal microbiomes. (iv) A lot of the mature gut microbiome is possibly acquired from the environment, as the genera Prevotella and Faecalibacterium, two of the most abundant flora in the neonatal gut microbiome, are introduced after initiation of solidified food. The distinction between the gut microbiome of babies born by vaginal delivery and babies born by C-section becomes blurred after introduction of solid food, although the diversity in the gut microbiota drastically increases in both cases. IMPORTANCE Gut microbiome architecture seems to have a potential impact on host metabolism, health, and nutrition. Early life gut microbiome development is considered a crucial phenomenon for neonatal health as well as adulthood metabolic complications. In this longitudinal study, we examined the association of neonatal gut microbiome entropy and its temporal variation. The study revealed that adult-like gut microbiome architecture starts taking shape after initiation of solidified food. Further, we also observed that the difference of microbial diversity was reduced between vaginally delivered and C-section babies compared to exclusive breastfeeding tenure. We found evidence in favor of the inheritance of the microflora of mother's posterior vaginal wall to the offspring's gut microbiome.

Rise of the human-mouse chimeric brain models.

Human-mouse chimeras offer advantages for studying the pathophysiology of human cells in vivo. Chimeric mouse brains have been created by engrafting human fetal tissue- or pluripotent stem cell-derived progenitor cells into the neonatal mouse brain. This provides new opportunities to understand human brain development and neurological disorders.

Rag2-/- accelerates lipofuscin accumulation in the brain: Implications for human stem cell brain transplantation studies.

Immunodeficient mice are widely used in human stem cell transplantation research. Recombination activating gene 1 (Rag1) deletion results in immunodeficiency and leads to accelerated aging in zebrafish with increased cytosolic accumulation of lipofuscin (LF). Unlike zebrafish, mammals have two homologs, Rag1 and Rag2, that regulate adaptive immunity. Currently, little is known if and how Rag1-/- and Rag2-/- may impact aging and LF accumulation in immunodeficient mouse brains and how this may confound results in human neural cell transplantation studies. Here, we demonstrate that in Rag2-/- mouse brains, LF appears early, spreads broadly, emits strong autofluorescence, and accumulates with age. LF is found in various types of glial cells, including xenografted human microglia. Surprisingly, in Rag1-/- mouse brains, LF autofluorescence is seen at much older ages compared with Rag2-/- brains. This study provides direct evidence that Rag2-/- expedites LF occurrence and sets a context for studies using aged immunodeficient mice.

Antimicrobial activity of peels and physicochemical properties of juice prepared from indigenous citrus fruits of Sylhet region, Bangladesh.

Scientists are indeed fascinated by the pharmacologically important chemicals found in medicinal plants. Citrus fruits possess several curing agents for the prevention of diseases. Therefore, experiments were carried out to test the antibacterial activity of methanolic extracts of peels from various locally available citrus fruits such as citron (Citrus medica), satkora (Citrus macroptera) and adajamir (Citrus assamensis) against Bacillus spp. and E. coli using the disc diffusion method. Different physicochemical characteristics of fruit juice were also determined. Methanolic extract of satkora peel had the highest antibacterial activity of 2.2 and 2.6 cm while adajamir had the lowest antibacterial activity of 1.7 and 2.1 cm as ZOI against Bacillus spp. and E. coli, respectively. In the case of pH and total soluble solids (TSS), the three citrus varieties showed a small variation where satkora showed the highest total phenolic content (TPC), vitamin C content, and antioxidant activity than the others. Citrus fruits can be exploited as antibacterial and antioxidant ingredients in food and nutraceuticals, according to the findings of this study.

Application of nanotechnology in food: processing, preservation, packaging and safety assessment.

Even though nanotechnology is extensively applied in agriculture, biochemistry, medicine and many other sectors, it is a developing field that conforms to new and more complex applications in food systems as compared to other technologies. It offers a viable strategy for integrating cutting-edge technology into a wide range of operations related to the production, development, fabrication, packaging, storage and distribution of food. The most fundamentally sophisticated technology in nano-based food science, nanoparticles deal with a wide range of nanostructured materials and nano methods, including nanofood, nanotubes, nanocomposites, nano packaging, nanocapsules, nanosensors, liposomes, nanoemulsions, polymeric nanoparticles and nanoencapsulation. This method is developed to increase food solubility and shelf life, availability of bioactive chemical, the protection of food constituents, nutritional supplementation, fortification and food or constituent delivery. Additionally, it serves as an antibacterial agent by generating reactive oxygen species (ROS) which cause bacterial DNA damage, protein denaturation and cell damage. Although the use of nanotechnology in food applications is advancing, there are certain negative or dangerous effects on health related to the toxicity and dangers of ingesting nanoparticles in food. The use of nanotechnology in the food industry, notably in processing, preservation and packaging, with its promising future, was addressed in this study. The toxicity of nanoparticles in food as well as its development in food safety assessments with certain areas of concern were also reviewed.

Temporal dynamics of oropharyngeal microbiome among SARS-CoV-2 patients reveals continued dysbiosis even after Viral Clearance.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has posed multiple challenges to global public health. Clinical features and sequela of SARS-CoV-2 infection include long-term and short-term complications often clinically indistinguishable from bacterial sepsis and acute lung infection. Post-hoc studies of previous SARS outbreaks postulate secondary bacterial infections with microbial dysbiosis. Oral microbial dysbiosis, particularly the altered proportion of Firmicutes and Proteobacteria, observed in other respiratory virus infection, like influenza, has shown to be associated with increased morbidity and mortality. Oropharynx and lung share similar kinds of bacterial species. We hypothesized that alteration in the Human Oropharyngeal Microbiome in SARS-CoV-2 patients can be a clinical indicator of bacterial infection related complications. We made a longitudinal comparison of oropharyngeal microbiome of 20 SARS-CoV-2 patients over a period of 30 days; at three time points, with a 15 days interval; contrasting them with a matched group of 10 healthy controls. Present observation indicates that posterior segment of the oropharyngeal microbiome is a key reservoir for bacteria causing pneumonia and chronic lung infection on SARS-CoV-2 infection. Oropharyngeal microbiome is indeed altered and its α-diversity decreases, indicating reduced stability, in all SARS-CoV-2 positive individuals right at Day-1; i.e. within ~24 h of post clinical diagnosis. The dysbiosis persists long-term (30 days) irrespective of viral clearance and/or administration of antibiotics. There is a severe depletion of commensal bacteria phyla like Firmicutes among the patients and that depletion is compensated by higher proportion of bacteria associated with sepsis and severe lung infection from phyla Proteobacteria. We also found elevated proportions of certain genus that have previously been shown to be causal for lung pneumonia in studies of model organisms and human autopsies' including Stenotrophomonas, Acenetobactor, Enterobactor, Klebsiella and Chryseobacterium that were to be elevated among the cases. We also show that responses to the antibiotics (Azithromycin and Doxycycline) are not uniform for all individuals.

Type-I-interferon signaling drives microglial dysfunction and senescence in human iPSC models of Down syndrome and Alzheimer's disease.

Microglia are critical in brain development and Alzheimer's disease (AD) etiology. Down syndrome (DS) is the most common genetic developmental disorder and risk factor for AD. Surprisingly, little information is available on the impact of trisomy of human chromosome 21 (Hsa21) on microglial functions during DS brain development and in AD in DS. Using induced pluripotent stem cell (iPSC)-based organoid and chimeric mouse models, we report that DS microglia exhibit an enhanced synaptic pruning function, which alters neuronal synaptic functions. In response to human brain tissue-derived pathological tau, DS microglia undergo cellular senescence and exhibit elevated type-I-interferon signaling. Mechanistically, knockdown of Hsa21-encoded type I interferon receptors, IFNARs, rescues the DS microglial phenotypes both during brain development and in response to pathological tau. Our findings provide in vivo evidence that human microglia respond to pathological tau by exhibiting dystrophic phenotypes. Targeting IFNARs may improve DS microglial functions and prevent senescence.

Impacts of stocking density rates on welfare, growth, and hemato-biochemical profile in broiler chickens.

OBJECTIVE: The study investigated the effect of different stocking density (SD) rates on the welfare, growth, and hemato-biochemical parameters in broiler chickens. MATERIALS AND METHODS: 106 broiler chicks of 10 days old were used and assigned into four groups: A, B, C, and D. The chicks of group A were reared in floor space containing one bird per square foot area (SD1.0). The chicks of groups B, C, and D were reared at 1.5, 2.0, and 2.5 birds per square foot area (SD1.5, SD2.0, and SD2.5). Welfare, body weight, and hemato-biochemical parameters were assessed and monitored by physical observation and laboratory methods. RESULTS: The birds reared at SD2.0, and SD2.5 rates showed increased panting breathing. Wet feces adhered below the vent. There were a significant number of birds showing dirtiness of body and feathers. Birds reared in SD2.5 were familiar with moist litters and high ammonia smell. Foot-pad dermatitis, scratches, and blister formation were detected in the leg. The study revealed that the higher SD negatively correlated to the welfare behavior indicators. Live body weight was significantly (p < 0.05) decreased in birds reared at higher SD rates. Birds housed in SD1.0 and SD1.5 are optimum for body weight and improved feed conversion ratio. The hemato-biochemical parameters of birds reared at various SD rates did not differ. The total leucocyte count increased significantly, while total serum proteins decreased gradually as SD rates increased. CONCLUSION: This work explores that higher SD negatively affects welfare and growth performance in broiler chickens.