Development and evaluation of a chicken embryo fibroblast cell culture based live attenuated Indian strain duck plague vaccine.

Duck plague (DP) is an acute, contagious and fatal disease, caused by duck enteritis virus (DEV), with worldwide distribution causing several outbreaks and posing severe economic losses. The present study was carried out with a goal of development of a live attenuated cell culture based DP vaccine using an Indian strain of DEV and evaluation of its safety, efficacy along with complete genome analysis. The live attenuated DP vaccine (DPvac/IVRI-19) was developed by serial propagation of a virulent isolate of DEV (DEV/India/IVRI-2016) in the chicken embryo fibroblast (CEF) primary cell culture. Adaptation of DEV in CEF cell culture was indicated by more rapid appearance of cytopathic effects (CPE) and gradual increase of virus titre, which reached up to 107.5 TCID50/mL after 41 passages. The safety, immunogenicity and efficacy of the vaccine were determined by immunization trials in ducklings. The DPvac/IVRI-19 was found to be avirulent and completely safe in the ducklings. Further, the vaccine induced both humoral and cell mediated immune responses and afforded 100% protection against the virulent DEV challenge. A comparison of the whole genome of DPvac/IVRI-19 (MZ911871) and DEV/India/IVRI-2016 (MZ824102) revealed significant number of mutations, which might be associated with viral attenuation. Phylogenetic tree of DEV/India/IVRI-2016 revealed its evolutionary relationship with other DEV isolates, but it formed a separate cluster with certain unique mutations. Thus, with the proven safety and 100% efficacy, the DPvac/IVRI-19 is suitable for large scale production with precisely pure form of vaccine and has potential utility at national and global levels.

Emerging Role of Gallium-68 DOTANOC PET/CT Guided Radiofrequency Ablation in the Treatment of Tumor-induced Osteomalacia.

Tumor-induced osteomalacia (TIO) is a rare acquired form of hypophosphatemia that can be cured when the tumor responsible is completely removed. These tumors can be small and located in anatomically challenging areas, rendering surgery both risky and extensive. Radiofrequency ablation (RFA) has been explored as an effective treatment option for such tumors. We present a case of a 35-year-old man exhibiting clinical and biochemical features consistent with TIO. The culprit lesion was not detectable on the whole-body computed tomography (CT) scan. Gallium (Ga-68) DOTANOC positron emission tomography (PET)/CT showed increased uptake in the left acetabulum and magnetic resonance imaging (MRI) confirmed the location of the tumor. Given the risky anatomical location, we opted for less-invasive RFA. Following an unsuccessful attempt at CT-guided RFA of the lesion, we used real-time Ga-68 DOTANOC PET/CT guidance for precise imaging during the ablation procedure. Our patient achieved complete remission both clinically and biochemically after RFA. This response was also evident by the absence of tracer uptake in follow-up imaging. In conclusion, DOTANOC PET/CT-guided RFA can serve as a safe and effective treatment for patients with tumors causing TIO. This modality proves valuable when surgical resection is not a viable option.

Genome and secretome insights: unravelling the lignocellulolytic potential of Myceliophthora verrucosa for enhanced hydrolysis of lignocellulosic biomass.

Lignocellulolytic enzymes from a novel Myceliophthora verrucosa (5DR) strain was found to potentiate the efficacy of benchmark cellulase during saccharification of acid/alkali treated bagasse by ~ 2.24 fold, indicating it to be an important source of auxiliary enzymes. The De-novo sequencing and analysis of M. verrucosa genome (31.7 Mb) revealed to encode for 7989 putative genes, representing a wide array of CAZymes (366) with a high proportions of auxiliary activity (AA) genes (76). The LC/MS QTOF based secretome analysis of M. verrucosa showed high abundance of glycosyl hydrolases and AA proteins with cellobiose dehydrogenase (CDH) (AA8), being the most prominent auxiliary protein. A gene coding for lytic polysaccharide monooxygenase (LPMO) was expressed in Pichia pastoris and CDH produced by M. verrucosa culture on rice straw based solidified medium were purified and characterized. The mass spectrometry of LPMO catalyzed hydrolytic products of avicel showed the release of both C1/C4 oxidized products, indicating it to be type-3. The lignocellulolytic cocktail comprising of in-house cellulase produced by Aspergillus allahabadii strain spiked with LPMO & CDH exhibited enhanced and better hydrolysis of mild alkali deacetylated (MAD) and unwashed acid pretreated rice straw slurry (UWAP), when compared to Cellic CTec3 at high substrate loading rate.

Lycopene as a Therapeutic Agent against Aflatoxin B1-Related Toxicity: Mechanistic Insights and Future Directions.

Aflatoxin (AFT) contamination poses a significant global public health and safety concern, prompting widespread apprehension. Of the various AFTs, aflatoxin B1 (AFB1) stands out for its pronounced toxicity and its association with a spectrum of chronic ailments, including cardiovascular disease, neurodegenerative disorders, and cancer. Lycopene, a lipid-soluble natural carotenoid, has emerged as a potential mitigator of the deleterious effects induced by AFB1 exposure, spanning cardiac injury, hepatotoxicity, nephrotoxicity, intestinal damage, and reproductive impairment. This protective mechanism operates by reducing oxidative stress, inflammation, and lipid peroxidation, and activating the mitochondrial apoptotic pathway, facilitating the activation of mitochondrial biogenesis, the endogenous antioxidant system, and the nuclear factor erythroid 2-related factor 2 (Nrf2)/kelch-like ECH-associated protein 1 (KEAP1) and peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) pathways, as well as regulating the activities of cytochrome P450 (CYP450) enzymes. This review provides an overview of the protective effects of lycopene against AFB1 exposure-induced toxicity and the underlying molecular mechanisms. Furthermore, it explores the safety profile and potential clinical applications of lycopene. The present review underscores lycopene's potential as a promising detoxification agent against AFB1 exposure, with the intent to stimulate further research and practical utilization in this domain.

Nanodisc reconstitution and characterization of amyloid-ß precursor protein C99.

Amyloid precursor protein (APP) plays a pivotal role in the pathology of Alzheimer's disease. Since the fragmentation of the membrane-bound APP that results in the production of amyloid-beta peptides is the starting point for amyloid toxicity in AD, it is important to investigate the structure and dynamics of APP in a near-native lipid-bilayer environment. However, the reconstitution of APP into a stable/suitable membrane-mimicking lipid environment is a challenging task. In this study, the 99-residue C-terminal domain of APP is successfully reconstituted into polymer nanodiscs and characterized using size-exclusion chromatography, mass spectrometry, solution NMR, and magic-angle spinning solid-state NMR. In addition, the feasibility of using lipid-solubilizing polymers for isolating and characterizing APP in native E. coli membrane environment is demonstrated.

Recurrent hypo-attenuated leaflet thickening after TAVR: Clinical implications.

Subclinical bioprosthetic valve thrombosis (BPVT) is a relatively common finding in asymptomatic patients during follow-up imaging. However, its clinical significance is unclear. Data from registries associate BPVT with elevated valve gradients, thromboembolic complications, recurrence, and valve degeneration. Given the dynamic nature of the disease process, management is challenging. The duration of anticoagulation is unpredictable, and the need for frequent monitoring of BPVT, even in subclinical scenarios, is unclear. Our report is shedding the light on the clinical implications BPVT.

Multi-OMICS approaches in cancer biology: New era in cancer therapy.

Innovative multi-omics frameworks integrate diverse datasets from the same patients to enhance our understanding of the molecular and clinical aspects of cancers. Advanced omics and multi-view clustering algorithms present unprecedented opportunities for classifying cancers into subtypes, refining survival predictions and treatment outcomes, and unravelling key pathophysiological processes across various molecular layers. However, with the increasing availability of cost-effective high-throughput technologies (HTT) that generate vast amounts of data, analyzing single layers often falls short of establishing causal relations. Integrating multi-omics data spanning genomes, epigenomes, transcriptomes, proteomes, metabolomes, and microbiomes offers unique prospects to comprehend the underlying biology of complex diseases like cancer. This discussion explores algorithmic frameworks designed to uncover cancer subtypes, disease mechanisms, and methods for identifying pivotal genomic alterations. It also underscores the significance of multi-omics in tumor classifications, diagnostics, and prognostications. Despite its unparalleled advantages, the integration of multi-omics data has been slow to find its way into everyday clinics. A major hurdle is the uneven maturity of different omics approaches and the widening gap between the generation of large datasets and the capacity to process this data. Initiatives promoting the standardization of sample processing and analytical pipelines, as well as multidisciplinary training for experts in data analysis and interpretation, are crucial for translating theoretical findings into practical applications.

Thymol as a Potential Neuroprotective Agent: Mechanisms, Efficacy, and Future Prospects.

Neurodegenerative diseases pose a growing global health challenge, with limited effective therapeutic options. Mitochondrial dysfunction, oxidative stress, neuroinflammation, apoptosis, and autophagy are common underlying mechanisms in these diseases. Thymol is a phenolic monoterpene compound that has gained attention for its diverse biological properties, including antioxidant, anti-inflammatory, and immunomodulatory activities. Thymol supplementation could provide potential neuroprotection and improve cognitive deficits, depressant-like effects, learning, and memory impairments in rodents. Mechanistic investigations reveal that the neuroprotective effects of thymol involve the improvement of oxidative stress, mitochondrial dysfunction, and inflammatory response. Several signaling pathways, including mitochondrial apoptotic, NF-κB, AKT, Nrf2, and CREB/BDNF pathways are also involved. In this review, the neuroprotective effects of thymol, the potential molecular mechanisms, safety, applications, and current challenges toward development as a neuroprotective agent were summarized and discussed. We hope that this review provides valuable insights for the further development of this promising natural product as a promising neuroprotective agent.

A thermostable and inhibitor resistant ß-glucosidase from Rasamsonia emersonii for efficient hydrolysis of lignocellulosics biomass.

The present study reports a highly thermostable ß-glucosidase (GH3) from Rasamsonia emersonii that was heterologously expressed in Pichia pastoris. Extracellular ß-glucosidase was purified to homogeneity using single step affinity chromatography with molecular weight of ~ 110 kDa. Intriguingly, the purified enzyme displayed high tolerance to inhibitors mainly acetic acid, formic acid, ferulic acid, vanillin and 5-hydroxymethyl furfural at concentrations exceeding those present in acid steam pretreated rice straw slurry used for hydrolysis and subsequent fermentation in 2G ethanol plants. Characteristics of purified ß-glucosidase revealed the optimal activity at 80 °C, pH 5.0 and displayed high thermostability over broad range of temperature 50-70 °C with maximum half-life of ~ 60 h at 50 °C, pH 5.0. The putative transglycosylation activity of ß-glucosidase was appreciably enhanced in the presence of methanol as an acceptor. Using the transglycosylation ability of ß-glucosidase, the generated low cost mixed glucose disaccharides resulted in the increased induction of R. emersonii cellulase under submerged fermentation. Scaling up the recombinant protein production at fermenter level using temporal feeding approach resulted in maximal ß-glucosidase titres of 134,660 units/L. Furthermore, a developed custom made enzyme cocktail consisting of cellulase from R. emersonii mutant M36 supplemented with recombinant ß-glucosidase resulted in significantly enhanced hydrolysis of pretreated rice straw slurry from IOCL industries (India). Our results suggest multi-faceted ß-glucosidase from R. emersonii can overcome obstacles mainly high cost associated enzyme production, inhibitors that impair the sugar yields and thermal inactivation of enzyme.

Recent progress in ZnCr and NiCr layered double hydroxides and based photocatalysts for water treatment and clean energy production.

In pursuit of advancing photocatalysts for superior performance in water treatment and clean energy generation, researchers are increasingly focusing on layered double hydroxides (LDHs) which have garnered significant attention due to their customizable properties, morphologies, distinctive 2D layered structure and flexible options for modifying anions and cations. No review has previously delved specifically into ZnCr and NiCr LDH-based photocatalysts and therefore, this review highlights the recent surge in ZnCr and NiCr-based LDHs as potential photocatalysts for their applications in water purification and renewable energy generation. The structural and fundamental characteristics of layered double hydroxides and especially ZnCr-LDHs and NiCr-LDHs are outlined. Further, the various synthesis techniques for the preparation of ZnCr-LDHs, NiCr-LDHs and their composite and heterostructure materials have been briefly discussed. The applicability of ZnCr-LDH and NiCr-LDH based photocatalysts in tackling significant issues in water treatment and sustainable energy generation is the main emphasis of this review. It focuses on photocatalytic degradation of organic pollutants in wastewater, elucidating the principles and advancements for enhancing the efficiency of these materials. It also explores their role in H2 production through water splitting, conversion of CO2 into valuable fuels and NH3 synthesis from N2, shedding light on their potential for clean energy solutions. The insights presented herein offer valuable guidance for researchers working towards sustainable solutions for environmental remediation and renewable energy generation.

Therapeutic detoxification of quercetin for aflatoxin B1-related toxicity: Roles of oxidative stress, inflammation, and metabolic enzymes.

Aflatoxins (AFTs), a type of mycotoxin mainly produced by Aspergillus parasiticus and Aspergillus flavus, could be detected in food, feed, Chinese herbal medicine, grain crops and poses a great threat to public health security. Among them, aflatoxin B1 (AFB1) is the most toxic one. Exposure to AFB1 poses various health risks to both humans and animals, including the development of chronic inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, and cancer. The molecular mechanisms underlying these risks are intricate and dependent on specific contexts. This review primarily focuses on summarizing the protective effects of quercetin, a natural phenolic compound, in mitigating the toxic effects induced by AFB1 in both in vitro experiments and animal models. Additionally, the review explores the molecular mechanisms that underlie these protective effects. Quercetin has been demonstrated to not only have the direct inhibitory action on the production of AFTs from Aspergillus, both also possess potent ameliorative effects against AFB1-induced cytotoxicity, hepatotoxicity, and neurotoxicity. These effects are attributed to the inhibition of oxidative stress, mitochondrial dysfunction, mitochondrial apoptotic pathway, and inflammatory response. It could also directly target several metabolic enzymes (i.e., CYP3As and GSTA1) to reduce the production of toxic metabolites of AFB1 within cells, then reduce AFB1-induced cytotoxicity. In conclusion, this review highlights quercetin is a promising detoxification agent for AFB1. By advancing our understanding of the protective mechanisms offered by quercetin, we aim to contribute to the development of effective detoxification agents against AFB1, ultimately promoting better health outcomes.

Microplastic pollutants in water: A comprehensive review on their remediation by adsorption using various adsorbents.

Microplastics (MPs), as emerging pollutants, have attracted the attention of environmentalists, statespersons, and the scientific community over the last few decades. To address the spread of MPs in the environment, it is imperative to develop various removal techniques and materials that are effective, scalable, and ecologically benign. However, to the best of our knowledge, no review has systematically examined the removal of MPs using adsorption or provided an in-depth discussion on various adsorbents. Adsorption is an inexpensive and effective technology for wastewater treatment. Recently, many researchers have conducted studies on MP remediation using diverse adsorbent materials, such as biochar, activated carbon, sponges, carbon nanotubes, metal-layered oxides, metal-organic frameworks (MOFs), and zeolites. Each adsorbent has advantages and disadvantages. To overcome their disadvantages, researchers have been designing and developing hybrid adsorbents for MP remediation. This review provides insights into these individual adsorbents and also discusses hybrid adsorbents for MP removal. Finally, the review elaborates on future possibilities and ways to enable more efficient, scalable, and environmentally friendly MP cleanup. Overall, this review bridges the gap between contemporary MP remediation using adsorption techniques and adsorbent development.

The SMN-ribosome interplay: a new opportunity for Spinal Muscular Atrophy therapies.

The underlying cause of Spinal Muscular Atrophy (SMA) is in the reduction of survival motor neuron (SMN) protein levels due to mutations in the SMN1 gene. The specific effects of SMN protein loss and the resulting pathological alterations are not fully understood. Given the crucial roles of the SMN protein in snRNP biogenesis and its interactions with ribosomes and translation-related proteins and mRNAs, a decrease in SMN levels below a specific threshold in SMA is expected to affect translational control of gene expression. This review covers both direct and indirect SMN interactions across various translation-related cellular compartments and processes, spanning from ribosome biogenesis to local translation and beyond. Additionally, it aims to outline deficiencies and alterations in translation observed in SMA models and patients, while also discussing the implications of the relationship between SMN protein and the translation machinery within the context of current and future therapies.

Heart Rate Variability in Patients of Ankylosing Spondylitis: A Systematic Review and Meta-Analysis.

Patients with ankylosing spondylitis (AS) have a significantly higher risk of cardiovascular morbidities. The participation of the autonomic nervous system (ANS) in AS is still unknown and inconclusive. Heart rate variability (HRV) is defined as the variability of the time interval between two consecutive heartbeats. This meta-analysis aims to detect the association of HRV and its various parameters with AS patients by comparing them to healthy controls. Research literature was searched in PubMed, Embase, and Cochrane Library databases from inception to April 2022. The Review Manager 5 (RevMan) Version 5.4 software was used to analyze the data. In addition, the protocol of systematic review is registered in the PROSPERO database with ID CRD42022336484. This study includes a total of nine case-control studies with a total of 923 patients; 409 with AS and 514 healthy controls. The root mean square of successive differences between normal heartbeats (RMSSD) [standardized mean difference (SMD); -0.47, 95% CI: -0.69 to -0.25, p < 0.0001], proportion of NN50 (pNN50) (SMD; -0.89, 95% CI: -1.74 to -0.04, p = 0.04) and HRV (SMD; -1.11, 95% CI: -1.53 to 0.69, P < 0.00001) were significantly low in AS cases compared to healthy controls. The HRV value was also significantly low in patients with high Bath ankylosing spondylitis disease activity (BASDAI) index (SMD: -1.45, 95% CI: -2.45 to -0.36, p < 0.009). HRV (parasympathetic activity) was significantly lowered in AS patients compared to healthy controls.

Novel LIPA-Targeted Therapy for Treating Ovarian Cancer.

Ovarian cancer (OCa) is the most lethal form of gynecologic cancer, and the tumor heterogeneities at the molecular, cellular, and tissue levels fuel tumor resistance to standard therapies and pose a substantial clinical challenge. Here, we tested the hypothesis that the heightened basal endoplasmic reticulum stress (ERS) observed in OCa represents an exploitable vulnerability and may overcome tumor heterogeneity. Our recent studies identified LIPA as a novel target to induce ERS in cancer cells using the small molecule ERX-41. However, the role of LIPA and theutility of ERX-41 to treat OCa remain unknown. Expression analysis using the TNMplot web tool, TCGA data sets, and immunohistochemistry analysis using a tumor tissue array showed that LIPA is highly expressed in OCa tissues, compared to normal tissues. ERX-41 treatment significantly reduced the cell viability and colony formation ability and promoted the apoptosis of OCa cells. Mechanistic studies revealed a robust and consistent induction of ERS markers, including CHOP, elF2α, PERK, and ATF4, upon ERX-41 treatment. In xenograft and PDX studies, ERX-41 treatment resulted in a significant reduction in tumor growth. Collectively, our results suggest that ERX-41 is a novel therapeutic agent that targets the LIPA with a unique mechanism of ERS induction, which could be exploited to treat heterogeneity in OCa.

Is preoperative elevated glycated hemoglobin (HbA1c) a risk factor for postoperative shoulder stiffness after posterior-superior rotator cuff repair?

Background: Postoperative shoulder stiffness (POSS) affects a large number of patients undergoing rotator cuff repair (RCR). Diabetes may increase the risk of POSS. Preoperative glycated hemoglobin (HbA1c) is a convenient measure of glucose control in this group. The aim of the present study was to determine a relationship between preoperative HbA1c and POSS in patients undergoing postero-superior RCR. Methods: Two hundred fifty patients with full-thickness postero-superior rotator cuffs who underwent RCR were followed for 6 months. Pre- and post-operative external rotation with arm by the side at 3 and 6 months were measured. Patient demographics, tear characteristics, preoperative HbA1c level, and surgical details were recorded. Patients with subscapularis tears, concomitant instability, partial thickness tears, arthritis, and irreparable rotator cuff tears were excluded. Univariate and multivariate logistic regression were used to determine the association between patient characteristics and POSS at 6 months. Results: At the end of 6 months, 16% (41/250) of patients had POSS. Multivariate analysis demonstrated an elevated preoperative HbA1c level was a statistically significant predictor of POSS at 6 months (odds ratio 7.04, P < .01) after posterior superior RCR. Lower preoperative external rotation (P = .02) and female sex (P < .01) were also risk factors associated with POSS. Age, hand dominance, worker's compensation claim status, etiology, and size of the tear, surgical technique, and additional treatments were not statistically significant predictors. Conclusion: Elevated preoperative HbA1c level is associated with POSS after RCR. Measuring HbA1c preoperatively may assist clinicians to identify patients at risk of POSS. HbA1c is a modifiable parameter that could then be optimized preoperatively in order to improve outcomes.

Sleep quality and obstructive sleep apnea among male patients with lower urinary tract symptoms: A prospective observational study.

Introduction: Apart from nocturia, few reports have been published on the relationship between lower urinary tract symptoms (LUTS) and sleep disturbances in patients visiting urology outpatient clinics. This study assessed the association between our population's LUTS and sleep disturbances. Methods: This was a prospective observational study. A total of 123 male patients with a history of LUTS aged more than 40 years were recruited from urology outpatient clinic. International Prostate Symptom Score was utilized to assess LUTS. To determine the quality of sleep, the Pittsburgh Sleep Quality Index (PSQI) was used. Berlin questionnaire (BQ) was used for screening obstructive sleep apnea. Results: A total of 123 participants were enrolled in this study. The mean age of the participants was 61 ± 11.1 years. Nocturia >3 episodes were significantly more in patients with PSQI >5 (P < 0.05). There was a greater prevalence of severe LUTS in patients with PSQI >5 (P < 0.05). The association between LUTS and BQ score showed an increased prevalence of severe symptoms in patients with high BQ. Patients with PSQI >5 had more severe LUTS (53% of patients) compared to patients with PSQI ≤5 (5% of patients) (P = 0.000). Patients with PSQI >5 had overall poorer quality of life (QOL) scores, with QOL being 5 and 6 in 18% and 4.8% of the patients, respectively. Conclusions: There is a significant association between the prevalence of nocturia, moderate-to-severe LUTS, and the existence of sleep disorders. Therefore, screening for sleep disturbances may be performed on male patients who present with LUTS.

"Deoxy" to be or "Desoxy" not to be-a century-old tale in the history of DNA nomenclature.

This commentary discusses a comprehensive history of the first-ever use of pertinent words directly related to DNA, such as desoxyribose, deoxyribose, desoxyribonucleic acid, and deoxyribonucleic acid. With almost 100 years of the identification and nomenclature of desoxyribose sugar and desoxyribonucleic acid, the term "desoxy" continues to see limited use. We hope that whenever young researchers come across the sporadic occurrence of "desoxy" in any published text, they will not consider it a mistake.