Human iPSC-derived photoreceptor transplantation in the cone dominant 13-lined ground squirrel.

Several retinal degenerations affect the human central retina, which is primarily comprised of cones and is essential for high acuity and color vision. Transplanting cone photoreceptors is a promising strategy to replace degenerated cones in this region. Although this approach has been investigated in a handful of animal models, commonly used rodent models lack a cone-rich region and larger models can be expensive and inaccessible, impeding the translation of therapies. Here, we transplanted dissociated GFP-expressing photoreceptors from retinal organoids differentiated from human induced pluripotent stem cells into the subretinal space of damaged and undamaged cone-dominant 13-lined ground squirrel eyes. Transplanted cell survival was documented via noninvasive high-resolution imaging and immunohistochemistry to confirm the presence of human donor photoreceptors for up to 4 months posttransplantation. These results demonstrate the utility of a cone-dominant rodent model for advancing the clinical translation of cell replacement therapies.

An ERP Study of Face Processing in Schizophrenia, Bipolar Disorder, and Socially Isolated Individuals from the Community.

People with schizophrenia (SCZ) and bipolar disorder (BD) have impairments in processing social information, including faces. The neural correlates of face processing are widely studied with the N170 ERP component. However, it is unclear whether N170 deficits reflect neural abnormalities associated with these clinical conditions or differences in social environments. The goal of this study was to determine whether N170 deficits would still be present in SCZ and BD when compared with socially isolated community members. Participants included 66 people with SCZ, 37 with BD, and 125 community members (76 "Community-Isolated"; 49 "Community-Connected"). Electroencephalography was recorded during a face processing task in which participants identified the gender of a face, the emotion of a face (angry, happy, neutral), or the number of stories in a building. We examined group differences in the N170 face effect (greater amplitudes for faces vs buildings) and the N170 emotion effect (greater amplitudes for emotional vs neutral expressions). Groups significantly differed in levels of social isolation (Community-Isolated > SCZ > BD = Community-Connected). SCZ participants had significantly reduced N170 amplitudes to faces compared with both community groups, which did not differ from each other. The BD group was intermediate and did not differ from any group. There were no significant group differences in the processing of specific emotional facial expressions. The N170 is abnormal in SCZ even when compared to socially isolated community members. Hence, the N170 seems to reflect a social processing impairment in SCZ that is separate from level of social isolation.

Social cognition and social motivation in schizophrenia and bipolar disorder: are impairments linked to the disorder or to being socially isolated?

BACKGROUND: People with schizophrenia on average are more socially isolated, lonelier, have more social cognitive impairment, and are less socially motivated than healthy individuals. People with bipolar disorder also have social isolation, though typically less than that seen in schizophrenia. We aimed to disentangle whether the social cognitive and social motivation impairments observed in schizophrenia are a specific feature of the clinical condition v. social isolation generally. METHODS: We compared four groups (clinically stable patients with schizophrenia or bipolar disorder, individuals drawn from the community with self-described social isolation, and a socially connected community control group) on loneliness, social cognition, and approach and avoidance social motivation. RESULTS: Individuals with schizophrenia (n = 72) showed intermediate levels of social isolation, loneliness, and social approach motivation between the isolated (n = 96) and connected control (n = 55) groups. However, they showed significant deficits in social cognition compared to both community groups. Individuals with bipolar disorder (n = 48) were intermediate between isolated and control groups for loneliness and social approach. They did not show deficits on social cognition tasks. Both clinical groups had higher social avoidance than both community groups. CONCLUSIONS: The results suggest that social cognitive deficits in schizophrenia, and high social avoidance motivation in both schizophrenia and bipolar disorder, are distinct features of the clinical conditions and not byproducts of social isolation. In contrast, differences between clinical and control groups on levels of loneliness and social approach motivation were congruent with the groups' degree of social isolation.

Evidence of a Hardening in the Cosmic Ray Proton Spectrum at around 166 TeV Observed by the GRAPES-3 Experiment.

We present the measurement of the cosmic ray proton spectrum from 50 TeV to 1.3 PeV using 7.81×10^{6} extensive air shower events recorded by the ground-based GRAPES-3 experiment between 1 January 2014 and 26 October 2015 with a live time of 460 day. Our measurements provide an overlap with direct observations by satellite and balloon-based experiments. The electromagnetic and muon components in the shower were measured by a dense array of plastic scintillator detectors and a tracking muon telescope, respectively. The relative composition of the proton primary from the air shower data containing all primary particles was extracted using the multiplicity distribution of muons which is a sensitive observable for mass composition. The observed proton spectrum suggests a spectral hardening at ∼166 TeV and disfavors a single power law description of the spectrum up to the Knee energy (∼3 PeV).

Kisspeptin stimulates sheep ovarian follicular development in vitro through homologous receptors.

The present study was conducted to elucidate (1) the influence of kisspeptin (KP) on the in vitro development of preantral follicles (PFs) and (2) evolution of KP receptor gene (KISS1R) expression during ovarian follicular development in sheep. Kisspeptin was supplemented (0-100 µg/ml) in the culture medium of PFs for 6 days. The cumulus-oocyte complexes (COCs) from cultured PFs were subsequently matured to metaphase II (MII) for an additional 24 h. The proportions of PFs exhibiting growth, antrum formation, average increase in diameter, and maturation of oocytes to MII stage were the indicators of follicular development in vitro. The expression of the kisspeptin receptor gene at each development stages of in vivo developed (preantral, early antral, antral, large antral and COCs from Graafian follicles) and in vitro cultured PFs supplemented with KP was assessed using a real-time polymerase chain reaction. The best development in all the parameters under study was elicited with 10 µg/ml of KP. Supplementation of KP (10 µg/ml) in a medium containing other growth factors (insulin-like growth factor-I) and hormones (growth hormone, thyroxine, follicle-stimulating hormone) resulted in better PF development. The KISS1R gene was expressed in follicular cells and oocytes at all the development stages of both in vivo developed and in vitro cultured follicles. Higher KISS1R gene expression was supported by culture medium containing KP along with other hormones and growth factors. Accordingly, it is suggested that one of the mechanisms through which KP and other growth factors and hormones influence the ovarian follicular development in mammals is through the upregulation of expression of the KP receptor gene.

Apoptotic effect of Bulbine Natalensis and Chlorophytum Comosum in myelogenous Leukemia K562 cell line / Efeito apoptótico da natalensia bulbina e do clorofito comoso na linhagem celular mielogênea da leucemia K562

Abstract Bulbine natalensis and Chorophytum comosum are potential medicinal source for the treatment of cancers. Chronic myeloid leukaemia is a hematopoietic stem cells disorder treated by tyrosine kinase inhibitors but often cause recurrence of the leukaemia after cessation of therapy, hence require alternative treatment. This study determines the anti-cancer effect of leaf, root and bulb methanolic and aqueous extracts of B. natalensis and C. comosum in chronic human myelogenous leukaemia (K562) cell line by MTT, Hoechst bis-benzimide nuclear and annexin V stain assays. The root methanolic extract of B. natalensis and C. comosum showed a high cytotoxicity of 8.6% and 16.7% respectively on the K562 cell line at 1,000 μg/ml concentration. Morphological loss of cell membrane integrity causing degradation of the cell and fragmentation were observed in the root methanolic extract of both plants. A high apoptosis (p < 0.0001) was induced in the K562 cells by both leaf and root extracts of the C. comosum compared to the B. natalensis. This study shows both plants possess apoptotic effect against in vitro myelogenous leukaemia which contributes to the overall anti-cancer properties of B. natalensis and C. comosum to justify future therapeutic applications against chronic myelogenous leukaemia blood cancer.

Resumo Bulbine natalensis Baker e Chorophytum comosum (Thunb.) Jacques são potenciais fontes medicinais para o tratamento de cânceres. A Leucemia Mieloide Crônica (LMC) é um distúrbio das células-tronco hematopoiéticas que é tratado com inibidores da tirosina quinase, mas frequentemente, causa recorrência da leucemia após a interrupção da terapia, portanto, requer um tratamento alternativo. Este estudo determinou o efeito anticancerígeno de extratos metanólicos e aquosos de folha, raiz e bulbo de B. natalensis e C. comosum na linhagem celular de leucemia mieloide humana crônica (K562) por ensaios de MTT, Hoechst bis-benzimida nuclear e anexina V. O extrato metanólico da raiz de B. natalensis e C. comosum apresentou alta citotoxidade de 8,6% e 16,7% respectivamente, na linhagem celular K562 com a concentração de 1,000 μg / ml. Perda morfológica da integridade da membrana celular causando degradação dos núcleos, citoplasma e encolhimento celular foi observada no extrato metanólico da raiz de ambas as plantas. Uma alta apoptose (p <0,0001) foi induzida nas células K562 por extratos de folhas e raízes de C. comosum em comparação com B. natalensis. Este estudo mostrou que ambas as plantas possuem efeito apoptótico contra leucemia mieloide in vitro que contribui para as propriedades anticâncer gerais de B. natalensis e C. comosum para justificar futuras aplicações terapêuticas contra câncer de sangue de LMC.

Apoptotic effect of Bulbine Natalensis and Chlorophytum Comosum in myelogenous Leukemia K562 cell line

Abstract Bulbine natalensis and Chorophytum comosum are potential medicinal source for the treatment of cancers. Chronic myeloid leukaemia is a hematopoietic stem cells disorder treated by tyrosine kinase inhibitors but often cause recurrence of the leukaemia after cessation of therapy, hence require alternative treatment. This study determines the anti-cancer effect of leaf, root and bulb methanolic and aqueous extracts of B. natalensis and C. comosum in chronic human myelogenous leukaemia (K562) cell line by MTT, Hoechst bis-benzimide nuclear and annexin V stain assays. The root methanolic extract of B. natalensis and C. comosum showed a high cytotoxicity of 8.6% and 16.7% respectively on the K562 cell line at 1,000 g/ml concentration. Morphological loss of cell membrane integrity causing degradation of the cell and fragmentation were observed in the root methanolic extract of both plants. A high apoptosis (p 0.0001) was induced in the K562 cells by both leaf and root extracts of the C. comosum compared to the B. natalensis. This study shows both plants possess apoptotic effect against in vitro myelogenous leukaemia which contributes to the overall anti-cancer properties of B. natalensis and C. comosum to justify future therapeutic applications against chronic myelogenous leukaemia blood cancer.

Resumo Bulbine natalensis Baker e Chorophytum comosum (Thunb.) Jacques são potenciais fontes medicinais para o tratamento de cânceres. A Leucemia Mieloide Crônica (LMC) é um distúrbio das células-tronco hematopoiéticas que é tratado com inibidores da tirosina quinase, mas frequentemente, causa recorrência da leucemia após a interrupção da terapia, portanto, requer um tratamento alternativo. Este estudo determinou o efeito anticancerígeno de extratos metanólicos e aquosos de folha, raiz e bulbo de B. natalensis e C. comosum na linhagem celular de leucemia mieloide humana crônica (K562) por ensaios de MTT, Hoechst bis-benzimida nuclear e anexina V. O extrato metanólico da raiz de B. natalensis e C. comosum apresentou alta citotoxidade de 8,6% e 16,7% respectivamente, na linhagem celular K562 com a concentração de 1,000 g / ml. Perda morfológica da integridade da membrana celular causando degradação dos núcleos, citoplasma e encolhimento celular foi observada no extrato metanólico da raiz de ambas as plantas. Uma alta apoptose (p 0,0001) foi induzida nas células K562 por extratos de folhas e raízes de C. comosum em comparação com B. natalensis. Este estudo mostrou que ambas as plantas possuem efeito apoptótico contra leucemia mieloide in vitro que contribui para as propriedades anticâncer gerais de B. natalensis e C. comosum para justificar futuras aplicações terapêuticas contra câncer de sangue de LMC.

One-Pot Solvothermal Synthetic Route of a Zinc Oxide Nanoparticle-Decorated Reduced Graphene Oxide Nanocomposite: An Advanced Material with a Novel Anticancer Theranostic Approach.

This study focuses on a one-pot solvothermal synthetic route for the preparation of uniformly decorated zinc oxide nanoparticles on the surface of reduced graphene oxide (rGO/ZnO-NC) by using Andrographis paniculata leaf aqueous extract as an eco-friendly reducing agent. After characterizing the samples by different physical and chemical techniques, the anticancer activity of the synthesized rGO/ZnO-NC was examined on two human cancerous cell lines (HCT116 and A549) and one normal cell line (hMSCs). The MTT assays revealed that rGO/ZnO-NC exhibited dose-dependent cytotoxicity at a maximum concentration range of 10 ppm and the viability of the cells was drastically decreased to 95-96%. Measurement of reactive oxygen species (ROS) generation and Annexin V-FTIC staining assay revealed that rGO/ZnO-NC induced apoptosis in HCT116 and A549 cell lines. Thus, this study shows that the green-synthesized rGO/ZnO-NC has great potential in developing an efficacious novel therapeutic agent for cancers.

Ceftazidime-avibactam alone or in combination with Aztreonam versus Polymyxins in the management of carbapenem-Resistant Klebsiella pneumoniae nosocomial Infections (CAPRI study): a retrospective cohort study from South India.

INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections commonly cause hospital-acquired infections. The study aimed to compare the outcomes of CRKP infections between patients receiving ceftazidime avibactam +/- aztreonam and polymyxins in a hospital setting with a high prevalence of New Delhi Metallo Beta Lactamase production. METHODS: We conducted a retrospective cohort study from January 2020 to September 2022 in critically ill adult patients admitted to a non-COVID-19 medical intensive care unit with CRKP infection. The patients were followed up for a total of 30 days or death, whichever was later. RESULTS: Of a total of 106 patients included in the study, 65 patients received polymyxins and 41 patients received ceftazidime-avibactam +/- aztreonam. Higher 30-day mortality was noted in the polymyxin group (56.9% vs. 29.2%, P = 0.005). The mean time to event (mortality) in ceftazidime-avibactam +/- aztreonam was 23.9 + 1.5 days which was significantly higher compared to polymyxins (17.9 + 1.2 days, p = 0.006). On Cox regression analysis, after adjusting for the covariates, the hazard ratio for time to event with the use of polymyxin was 2.02 (95% CI: 1.03-3.9). CONCLUSION: Ceftazidime-avibactam + aztreonam is possibly associated with better clinical outcomes in patients infected with CRKP.

Biofabricated Palladium Nanoparticle-Decorated Reduced Graphene Oxide Nanocomposite Using the Punica granatum (Pomegranate) Peel Extract: Investigation of Potent In Vivo Hepatoprotective Activity against Acetaminophen-Induced Liver Injury in Wistar Albino Rats.

Acute acetaminophen (APAP) toxicity is a predominant clinical problem, which causes serious liver injury in both humans and experimental animals. This study presents the histological and biochemical factor and antioxidant enzyme level changes induced by an acute acetaminophen overdose in Wistar albino rat livers to elucidate the effective hepatoprotective potential of biofabricated palladium nanoparticle-decorated reduced graphene oxide nanocomposites (rGO/PdNPs-NC) compared to silymarin. After detailed characterization of the hepatoprotective potential of the synthesized rGO/PdNPs-NC, the rats were divided into eight groups (n = 6): control group (normal saline, 1 mL/kg b.w.), silymarin, Punica granatum (pomegranate) peel extract, PdNPs, reduced graphene oxide (rGO-PG), and reduced graphene oxide palladium nanocomposites (rGO/PdNPs-NC, low and high doses) for 7 successive days. The acetaminophen (APAP)-treated group was administered a single dose of acetaminophen (2 g/kg b.w.) on the 8th day. The histopathological results showed that the acetaminophen overdose group exhibited massive intrahepatic hemorrhagic necrosis around the centrilobular region with hepatocytes with vacuolization and swollen cytoplasm found in the liver architecture. This hepatopotential was further assessed by various biochemical parameters such as SGOT, SGPT, ALB, ALP, LDH, direct bilirubin, total bilirubin, and total protein. Also, the antioxidant parameters such as SOD, CAT, MDA, GSH, GRD, and GST were assayed. Rats of groups 7 and 8 showed a significant decrease in SGOT, SGPT, ALP, LDH, direct bilirubin, and total bilirubin (p < 0.001), while a significant increase in the final total protein and ALB as compared to group 2 rats (p < 0.001) was observed. The antioxidant parameters exhibited that rats of groups 7 and 8 showed a significant (p < 0.001) increase in the level of SOD, CAT, GSH, GRD, and GST without affecting the MDA as compared to group 2 rats. Also, the hepatoprotective potential of rGO/PdNPs-NC (low and high doses) was comparable to that of the standard reference drug silymarin. The present study reveals that the rGO/PdNPs-NC possesses significant hepatoprotective activity and acts as an effective and promising curative agent against acetaminophen-induced hepatotoxicity.

COVID-19 Associated Mucormycosis.

Mucormycosis is a life-threatening opportunistic fungal infection seen in immunocompromised states. Rising incidence of mucormycosis among Coronavirus Disease-2019 infected individuals is an increasing concern in India. The disease which was endemic has blown out to become an epidemic. The purpose of this research is to study the epidemiology, management and outcome of Coronavirus Disease-2019 Associated Mucormycosis (CAM) cases. Additionally, the role of diabetes and steroids in the causation of CAM was determined. A hospital-based observational study was conducted at a tertiary care centre involving cases with rhino-orbital mucormycosis with recent history of COVID-19 infection. Out of 205,166(81%) cases had Diabetes Mellitus as a comorbid condition. Among them, 75(36.6%) cases were diagnosed with diabetes during COVID-19 treatment. 161/205(78.5%) cases received corticosteroids during COVID-19 treatment. Corticosteroids were notindicated in 43(26.7%) cases. 177/205(85.4%) cases were alive at the end of 12 weeks. 8 out of 10 deaths were seen in cases having diabetes. As the incidence of mucormycosis is increasing, better awareness among general population about the disease, early diagnosis and multidisciplinary approach is required to improve prognosis.

Surgical Efficacy of Mastoidectomy in Chronic Otitis Media: Squamosal Type.

Chronic Otitis Media-Squamosal type is an erosive process, which when confined to ossicular chain causes varying degrees of hearing impairment. As the disease progresses to involve surrounding vital structures, it causes various complications like facial palsy, vertigo, mastoid abscess, which are more common than the other intracranial complications, and require a definitive surgical intervention i.e., mastoidectomy at the earliest. A retrospective study on 60 patients who had been operated for squamosal type were analysed for the demographics, symptomatology, intraoperative extent of cholesteatoma, type of mastoidectomy done, various graft materials used for reconstruction, post operatively for graft uptake, hearing improvement and the results were analysed using ChOLE classification of cholesteatoma. Although Intact Canal Wall mastoidectomy had improved post op PTA values, there was no significant difference in the Air-Bone gap closure when Intact Canal Wall mastoidectomy was compared to Canal Wall Down Mastoidectomy.

Reversal of uniocular blindness with corticosteroids in a solid organ transplant recipient with cryptococcal meningitis and immune reconstitution syndrome (IRIS): A case report.

Cryptococcal meningitis is a life-threatening infection commonly seen in patients with advanced HIV infection and solid organ transplant recipients. We report a case of cryptococcal meningitis with immune reconstitution syndrome (IRIS) who presented to us with a headache and complete loss of vision in the left eye. He was managed with antifungals and a short course of steroids, and he regained vision completely. In the hospital, he developed complications including tacrolimus toxicity, fluconazole-induced QT prolongation, and flucytosine-induced thrombocytopenia. Our case demonstrates the importance of a multidisciplinary approach in the management of complex cases like cryptococcal meningitis in solid organ transplant recipients.

Disease modeling and pharmacological rescue of autosomal dominant Retinitis Pigmentosa associated with RHO copy number variation.

Retinitis pigmentosa (RP), a heterogenous group of inherited retinal disorder causes slow progressive vision loss with no effective treatments available. Mutations in the rhodopsin gene (RHO), account for ~25% cases of autosomal dominant RP (adRP). In this study, we describe the disease characteristics of the first ever reported mono-allelic copy number variation (CNV) in RHO as a novel cause of adRP. We (1) show advanced retinal degeneration in a male patient (60-70 year old) harboring four transcriptionally active intact copies of rhodopsin, (2) recapitulated the clinical phenotypes using retinal organoids, and (3) assessed the utilization of a small molecule, Photoregulin3 (PR3), as a clinically viable strategy to target and modify disease progression in RP patients associated with RHO-CNV. Patient retinal organoids showed photoreceptors dysgenesis, with rod photoreceptors displaying stunted outer segments with occasional elongated cilia-like projections (microscopy); increased RHO mRNA expression (qRT-PCR and bulk RNA-sequencing); and elevated levels and mislocalization of rhodopsin protein (RHO) within the cell body of rod photoreceptors (western blotting and immunohistochemistry) over the extended (300-days) culture time period when compared against control organoids. Lastly, we utilized PR3 to target NR2E3, an upstream regulator of RHO, to alter RHO expression and observed a partial rescue of RHO protein localization from the cell body to the inner/outer segments of rod photoreceptors in patient organoids. These results provide a proof-of-principle for personalized medicine and suggest that RHO expression requires precise control. Taken together, this study supports the clinical data indicating that adRP due to RHO-CNV develops due protein overexpression overloading the photoreceptor post-translational modification machinery.

A Novel Psychosocial Intervention for Motivational Negative Symptoms in Schizophrenia: Combined Motivational Interviewing and CBT.

OBJECTIVE: Negative symptoms are a primary cause of disability in schizophrenia for which there are no established pharmacotherapies. This study evaluated a novel psychosocial intervention that combined two evidence-based practices-motivational interviewing and cognitive-behavioral therapy (MI-CBT)-for the treatment of motivational negative symptoms. METHODS: Seventy-nine participants with schizophrenia and moderate to severe negative symptoms were included in a randomized controlled trial comparing the 12-session MI-CBT treatment with a mindfulness control condition. Participants were assessed at three time points through the study period, which included 12 weeks of active treatment and 12 weeks of follow-up. The primary outcome measures were motivational negative symptoms and community functioning; the secondary outcomes included a posited biomarker of negative symptoms: pupillometric response to cognitive effort. RESULTS: Compared with the control group, participants in the MI-CBT group showed significantly greater improvements in motivational negative symptoms over the acute treatment period. Their gains relative to baseline were maintained at follow-up, although the differential benefit relative to control subjects was attenuated. There were nonsignificant effects toward improvements in community functioning and differential change in the pupillometric markers of cognitive effort. CONCLUSIONS: The results show that combining motivational interviewing with CBT yields improvements in negative symptoms, a feature of schizophrenia generally thought of as resistant to intervention. Motivational negative symptoms not only responded to the novel treatment, but the gains were maintained over the follow-up period. Implications for future studies and for improving the generalization of the negative symptom gains to daily functioning domains are discussed.

Fabrication and Characterization Techniques of In Vitro 3D Tissue Models.

The culturing of cells in the laboratory under controlled conditions has always been crucial for the advancement of scientific research. Cell-based assays have played an important role in providing simple, fast, accurate, and cost-effective methods in drug discovery, disease modeling, and tissue engineering while mitigating reliance on cost-intensive and ethically challenging animal studies. The techniques involved in culturing cells are critical as results are based on cellular response to drugs, cellular cues, external stimuli, and human physiology. In order to establish in vitro cultures, cells are either isolated from normal or diseased tissue and allowed to grow in two or three dimensions. Two-dimensional (2D) cell culture methods involve the proliferation of cells on flat rigid surfaces resulting in a monolayer culture, while in three-dimensional (3D) cell cultures, the additional dimension provides a more accurate representation of the tissue milieu. In this review, we discuss the various methods involved in the development of 3D cell culture systems emphasizing the differences between 2D and 3D systems and methods involved in the recapitulation of the organ-specific 3D microenvironment. In addition, we discuss the latest developments in 3D tissue model fabrication techniques, microfluidics-based organ-on-a-chip, and imaging as a characterization technique for 3D tissue models.

Efficient One-Pot Solvothermal Synthesis and Characterization of Zirconia Nanoparticle-Decorated Reduced Graphene Oxide Nanocomposites: Evaluation of Their Enhanced Anticancer Activity toward Human Cancer Cell Lines.

This study mainly deals with an effective one-pot solvothermal synthetic pathway for the preparation of uniformly dispersed zirconium oxide nanoparticles on the flattened rough surface of reduced graphene oxide (ZrO2/rGO NCs) using the aqueous leaf extract of Andrographis paniculata. After obtaining detailed information on the preparation and characterization, the anticancer activity of the synthesized ZrO2/rGO nanocrystals (NCs) was evaluated on two human cancer cell lines (A549 and HCT116) along with one normal human cell line (hMSC). The 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide assays revealed that ZrO2/rGO NCs exhibited a dose-dependent cytotoxicity pattern. The cell viability (%) drastically decreases up to 96-98% after exposure to an optimal concentration of 10 ppm nanocomposites. Analysis of both the reactive oxygen species generation and the Annexin V-FTIC staining assays reveal that ZrO2/rGO NCs have the ability to induce apoptosis in A549 and HCT116 cell lines. Thus, the green synthesis of ZrO2/rGO NCs shows potential in developing efficient therapeutic agents for cancer therapy.

Post COVID-19 Mucormycosis-The Horizon.

Objective: Acute Invasive Fungal Rhinosinusitis is a rare condition which recently has gained attention due to its increased occurrence in the post COVID-19 patients past the second wave. The current study retrospectively evaluates the occurrence of Acute Invasive Fungal Rhinosinusitis (Mucormycosis) in post COVID-19 (Corona Virus Disease-19) patients. Methods: A descriptive study included patients diagnosed with Acute Invasive Fungal Rhinosinusitis (Mucormycosis) after recent COVID-19 infection. 110 patients were evaluated retrospectively with histopathological confirmation of Mucormycosis. Surgical treatment was restricted to patients who tested Real Time Polymerase Chain Reaction (RT PCR) negative for COVID-19 except for three patients who were tested positive. Antifungal agents were given to patients following surgery. Results: A total of 110 patients with a mean age of 48.42 years were included. The most common risk factor was diabetes mellitus (88.2%). Sino-nasal, orbital, palatal and intracranial involvement were 57.9%, 48.5%, 12.7% and 5.6% respectively. Histopathological confirmation revealed mucormycosis. The most common reported symptoms were periorbital oedema (20.5%), headache (20.3%), gingival swelling (18.5%) facial pain (18.4%) and facial swelling (18.2%). All the patients were treated with surgical debridement and antifungal medications. The overall survival rate was 95.32%. Conclusion: Acute Invasive Fungal Rhinosinusitis is a life-threatening opportunistic infection. Patients with moderate to severe COVID-19 infection are more susceptible to it. Uncontrolled diabetes mellitus and intake of corticosteroids increase the risk of developing Acute Invasive Fungal Rhinosinusitis. Early diagnosis and timely management can improve survival rates of the patients.

A Review on Psychrophilic ß-D-Galactosidases and Their Potential Applications.

The majority of the Earth's ecosystem is frigid and frozen, which permits a vast range of microbial life forms to thrive by triggering physiological responses that allow them to survive in cold and frozen settings. The apparent biotechnology value of these cold-adapted enzymes has been targeted. Enzymes' market size was around USD 6.3 billion in 2017 and will witness growth at around 6.8% CAGR up to 2024 owing to shifting consumer preferences towards packaged and processed foods due to the rising awareness pertaining to food safety and security reported by Global Market Insights (Report ID-GMI 743). Various firms are looking for innovative psychrophilic enzymes in order to construct more effective biochemical pathways with shorter reaction times, use less energy, and are ecologically acceptable. D-Galactosidase catalyzes the hydrolysis of the glycosidic oxygen link between the terminal non-reducing D-galactoside unit and the glycoside molecule. At refrigerated temperature, the stable structure of psychrophile enzymes adjusts for the reduced kinetic energy. It may be beneficial in a wide variety of activities such as pasteurization of food, conversion of biomass, biological role of biomolecules, ambient biosensors, and phytoremediation. Recently, psychrophile enzymes are also used in claning the contact lens. ß-D-Galactosidases have been identified and extracted from yeasts, fungi, bacteria, and plants. Conventional (hydrolyzing activity) and nonconventional (non-hydrolytic activity) applications are available for these enzymes due to its transgalactosylation activity which produce high value-added oligosaccharides. This review content will offer new perspectives on cold-active ß-galactosidases, their source, structure, stability, and application.

Determination of the ursolic and oleanolic acids content with the antioxidant capacity in apple peel extract of various cultivars.

Apples are rich sources of ursolic acid (UA) and oleanolic acid (OA) which are the major and most prominent triterpenes in the peel of an apple. Pentacyclic triterpenes are ideal nutraceuticals due to their ability to reduce the risk of many life-threatening diseases such as cancer, cardiovascular and diabetes. This study was to determine the content of UA and OA in the apple peel extract from different cultivars grown in South Africa as well as the correlation of their content level with antioxidant capacity. Quantitative analysis of UA and OA in apple peels from three cultivars; red delicious (RD), royal gala (RG) and granny smith (GS) apples was carried out using HPLC and their antioxidant capacity was analyzed using the DPPH assay. The RD showed the highest content of UA and OA (248.02 ± 0.08 µg/ml and 110.00 ± 0.08 µg/ml respectively) in the apple peel extract and also displayed a significantly high level of antioxidant capacity (97.3 ± 0.40%; p < 0.0001) compared to the RG and GS cultivars. A strong positive correlation was noted between the UA, OA and antioxidant capacities of all the cultivars. Only the RD cultivar showed a significant correlation though; UA (r = 0.9570; p = 0.0027) and OA (r = 0.8503; p = 0.0319). This study demonstrated that the RD and RG apple peels possess the highest UA and OA content which invariably increases their antioxidant activities compared to GS apple. Thus, both apple cultivars would be useful and recommended for food consumption and nutraceuticals values to improve human health.