Advancements in Human Norovirus Cultivation in Human Intestinal Enteroids.

Human noroviruses (HuNoVs) are a significant cause of both epidemic and sporadic acute gastroenteritis worldwide. The lack of a reproducible culture system for HuNoVs was a major obstacle in studying virus replication and pathogenesis for almost a half-century. This barrier was overcome with our successful cultivation of multiple HuNoV strains in human intestinal enteroids (HIEs), which has significantly advanced HuNoV research. We previously optimized culture media conditions and generated genetically-modified HIE cultures to enhance HuNoV replication in HIEs. Building upon these achievements, we now present additional advancements to this culture system, which involve testing different media, unique HIE lines, and additional virus strains. HuNoV infectivity was evaluated and compared in new HIE models, including HIEs generated from different intestinal segments of individual adult organ donors, HIEs made from human embryonic stem cell-derived human intestinal organoids that were transplanted into mice (H9tHIEs), genetically-engineered (J4 FUT2 knock-in [ KI ], J2 STAT1 knock-out [ KO ]) HIEs, as well as HIEs derived from a patient with common variable immunodeficiency (CVID) and from infants. Our findings reveal that small intestinal HIEs, but not colonoids, from adults, H9tHIEs, HIEs from a CVID patient, and HIEs from infants support HuNoV replication with segment and strain-specific differences in viral infection. J4 FUT2-KI HIEs exhibit the highest susceptibility to HuNoV infection, allowing the cultivation of a broader range of GI and GII HuNoV strains than previously reported. Overall, these results contribute to a deeper understanding of HuNoVs and highlight the transformative potential of HIE cultures in HuNoV research. Importance: Human noroviruses (HuNoVs) are very contagious and cause significant acute gastroenteritis globally, but studying them has been hindered by the lack of a reproducible culture system for nearly 50 years. This barrier was overcome by successfully cultivating multiple HuNoV strains in human intestinal enteroids (HIEs), advancing HuNoV research. We previously optimized culture conditions and developed genetically modified HIEs to enhance HuNoV replication. In this study, we tested different media, unique HIE lines, and additional virus strains, evaluating HuNoV infectivity in new HIE models. These models include HIEs from various intestinal segments of adult donors, human embryonic stem cell-derived HIEs transplanted into mice (H9tHIEs), genetically-engineered HIEs (J4 FUT2 knock-in [ KI ], J2 STAT1 knock-out [ KO ]), HIEs from a common variable immunodeficiency (CVID) patient, and from infants. Our findings show that adult small intestinal HIEs, H9tHIEs, CVID patient HIEs, and infant HIEs support HuNoV replication with segment and strain-specific differences. J4 FUT2-KI HIEs exhibited the highest susceptibility, allowing cultivation of a broader range of HuNoV strains. These results enhance the understanding of HuNoVs and highlight the transformative potential of HIE cultures in HuNoV research.

A novel strategy to elicit enduring anti-morphine immunity and relief from addiction by targeting Acr1 protein nano vaccine through TLR-2 to dendritic cells.

Morphine addiction poses a significant challenge to global healthcare. Current opioid substitution therapies, such as buprenorphine, naloxone and methadone are effective but often lead to dependence. Thus, exploring alternative treatments for opioid addiction is crucial. We have developed a novel vaccine that presents morphine and Pam3Cys (a TLR-2 agonist) on the surface of Acr1 nanoparticles. This vaccine has self-adjuvant properties and targets TLR-2 receptors on antigen-presenting cells, particularly dendritic cells. Our vaccination strategy promotes the proliferation and differentiation of morphine-specific B-cells and Acr1-reactive CD4 T-cells. Additionally, the vaccine elicited the production of high-affinity anti-morphine antibodies, effectively eliminating morphine from the bloodstream and brain in mice. It also reduced the expression of addiction-associated µ-opioid receptor and dopamine genes. The significant increase in memory CD4 T-cells and B-cells indicates the vaccine's ability to induce long-lasting immunity against morphine. This vaccine holds promise as a prophylactic measure against morphine addiction.

Unveiling the ion sensing capabailities of 'click' derived chalcone-tailored 1,2,3-triazolic isomers for Pb(ii) and Cu(ii) ions: DFT analysis.

In this study, two novel chalcone-derived 1,2,3-triazole-appended positional isomers (probe 6 and probe 9) were synthesized via the 'CuAAC' (Cu(i) - catalysed alkyne azide cycloaddition) methodology for the purpose of metal ion detection. The synthesized probes underwent characterization utilizing standard spectroscopic methodologies including FTIR, NMR (1H and 13C), and mass spectrometry. Subsequently, the sensing capabilities of these probes were explored using UV-Vis and fluorescence spectroscopy, wherein their selective recognition potential was established for Pb(ii) and Cu(ii), both of which can pose serious health hazards when prevalent in the environment above permissible limits. Both the probes exhibited fairly low limits of detection (LoD), determined as 5.69 µM and 6.55 µM in the case of probe 6 for Pb(ii) and Cu(ii) respectively; whereas the probe 9 exhibited an LoD of 5.06 µM and 7.52 µM for Pb(ii) and Cu(ii), respectively. The job's plot for the probe demonstrates the formation of a 1 : 1 complex between the metal and ligand. Furthermore, the interaction of the free probes with the metal ions in the metal-ligand complex was elucidated through 1H NMR analysis and validated theoretically using Density Functional Theory (DFT) simulations with the B3LYP/6-311G++(d,p) and B3LYP/LANL2DZ basis sets for geometry optimization of the probes and their corresponding metal complexes. These findings offer a reliable approach to Cu(ii) and Pb(ii) ion detection and can be further used for the potential applications in environmental monitoring and analytical chemistry.

Case-area targeted interventions during a large-scale cholera epidemic: A prospective cohort study in Northeast Nigeria.

BACKGROUND: Cholera outbreaks are on the rise globally, with conflict-affected settings particularly at risk. Case-area targeted interventions (CATIs), a strategy whereby teams provide a package of interventions to case and neighboring households within a predefined "ring," are increasingly employed in cholera responses. However, evidence on their ability to attenuate incidence is limited. METHODS AND FINDINGS: We conducted a prospective observational cohort study in 3 conflict-affected states in Nigeria in 2021. Enumerators within rapid response teams observed CATI implementation during a cholera outbreak and collected data on household demographics; existing water, sanitation, and hygiene (WASH) infrastructure; and CATI interventions. Descriptive statistics showed that CATIs were delivered to 46,864 case and neighbor households, with 80.0% of cases and 33.5% of neighbors receiving all intended supplies and activities, in a context with operational challenges of population density, supply stock outs, and security constraints. We then applied prospective Poisson space-time scan statistics (STSS) across 3 models for each state: (1) an unadjusted model with case and population data; (2) an environmentally adjusted model adjusting for distance to cholera treatment centers and existing WASH infrastructure (improved water source, improved latrine, and handwashing station); and (3) a fully adjusted model adjusting for environmental and CATI variables (supply of Aquatabs and soap, hygiene promotion, bedding and latrine disinfection activities, ring coverage, and response timeliness). We ran the STSS each day of our study period to evaluate the space-time dynamics of the cholera outbreaks. Compared to the unadjusted model, significant cholera clustering was attenuated in the environmentally adjusted model (from 572 to 18 clusters) but there was still risk of cholera transmission. Two states still yielded significant clusters (range 8-10 total clusters, relative risk of 2.2-5.5, 16.6-19.9 day duration, including 11.1-56.8 cholera cases). Cholera clustering was completely attenuated in the fully adjusted model, with no significant anomalous clusters across time and space. Associated measures including quantity, relative risk, significance, likelihood of recurrence, size, and duration of clusters reinforced the results. Key limitations include selection bias, remote data monitoring, and the lack of a control group. CONCLUSIONS: CATIs were associated with significant reductions in cholera clustering in Northeast Nigeria despite operational challenges. Our results provide a strong justification for rapid implementation and scale-up CATIs in cholera-response, particularly in conflict settings where WASH access is often limited.

Exploring novel insights into the molecular mechanisms underlying Bisphenol A-induced toxicity: A persistent threat to human health.

Bisphenol A (BPA) is a ubiquitous industrial chemical used in the production of polycarbonate plastics and epoxy resins, found in numerous consumer products. Despite its widespread use, its potential adverse health effects have raised significant concerns. This review explores the molecular mechanisms and evidence-based literature underlying BPA-induced toxicities and its implications for human health. BPA is an endocrine-disrupting chemical (EDC) which exhibits carcinogenic properties by influencing various receptors, such as ER, AhR, PPARs, LXRs, and RARs. It induces oxidative stress and contributes to cellular dysfunction, inflammation, and DNA damage, ultimately leading to various toxicities including but not limited to reproductive, cardiotoxicity, neurotoxicity, and endocrine toxicity. Moreover, BPA can modify DNA methylation patterns, histone modifications, and non-coding RNA expression, leading to epigenetic changes and contribute to carcinogenesis. Overall, understanding molecular mechanisms of BPA-induced toxicity is crucial for developing effective strategies and policies to mitigate its adverse effects on human health.

Leucaena leucocephala succinate based polyelectrolyte complexes for colon delivery of synbiotic in management of inflammatory bowel disease.

Polyelectrolyte complexes (PECs) formed by the interaction between oppositely charged polymers have emerged as promising carriers for accomplishing colon-specific release. In this study, we have explored the potential of polyelectrolyte complexes between a succinate derivative of Leucaena leucocephala galactomannan and cationic guar gum for colon delivery of synbiotic. The PECs were prepared using a polyelectrolyte complexation method and characterized. The PECs exhibited excellent stability, with high encapsulation efficiency for both probiotics (95.53 %) and prebiotics (83.33 %). In vitro studies demonstrated enhanced survivability and proliferation of the encapsulated probiotics in the presence of prebiotics (93.29 %). The SEM images revealed a smooth and firm structure with reduced number of pores when both prebiotic and probiotic were encapsulated together. The treatment with synbiotic PECs in acetic acid induced IBD rats significantly relieves colitis symptoms as was evident from colon/body ratio, DAI score and histopathology studies. An increase in the protein and reduced glutathione levels and reduction in superoxide dismutase activity was observed in colitic rats that received synbiotic treatment as compared to colitic rats. Overall, this study highlights the potential of Leucaena leucocephala succinate-cationic guar gum PECs as a promising system for colon-specific synbiotic delivery, with implications for improved gut health and the treatment of various gastrointestinal disorders.

Time-encoded electrical detection of trace RNA biomarker by integrating programmable molecular amplifier on chip.

One of the serious challenges facing modern point-of-care (PoC) molecular diagnostic platforms relate to reliable detection of low concentration biomarkers such as nucleic acids or proteins in biological samples. Non-specific analyte-receptor interactions due to competitive binding in the presence of abundant molecules, inefficient mass transport and very low number of analyte molecules in sample volume, in general pose critical hurdles for successful implementation of such PoC platforms for clinical use. Focusing on these specific challenges, this work reports a unique PoC biosensor that combines the advantages of nanoscale biologically-sensitive field-effect transistor arrays (BioFET-arrays) realized in a wafer-scale top-down nanofabrication as high sensitivity electrical transducers with that of sophisticated molecular programs (MPs) customized for selective recognition of analyte miRNAs and amplification resulting in an overall augmentation of signal transduction strategy. The MPs realize a programmable universal molecular amplifier (PUMA) in fluidic matrix on chip and provide a biomarker-triggered exponential release of small nucleic acid sequences easily detected by receptor-modified BioFETs. A common miRNA biomarker LET7a was selected for successful demonstration of this novel biosensor, achieving limit of detection (LoD) down to 10 fM and wide dynamic ranges (10 pM-10 nM) in complex physiological solutions. As the determination of biomarker concentration is implemented by following the electrical signal related to analyte-triggered PUMA in time-domain instead of measuring the threshold shifts of BioFETs, and circumvents direct hybridization of biomarkers at transducer surface, this new strategy also allows for multiple usage (>3 times) of the biosensor platform suggesting exceptional cost-effectiveness for practical use.

Clicking in harmony: exploring the bio-orthogonal overlap in click chemistry.

In the quest to scrutinize and modify biological systems, the global research community has continued to explore bio-orthogonal click reactions, a set of reactions exclusively targeting non-native molecules within biological systems. These methodologies have brought about a paradigm shift, demonstrating the feasibility of artificial chemical reactions occurring on cellular surfaces, in the cell cytosol, or within the body - an accomplishment challenging to achieve with the majority of conventional chemical reactions. This review delves into the principles of bio-orthogonal click chemistry, contrasting metal-catalyzed and metal-free reactions of bio-orthogonal nature. It comprehensively explores mechanistic details and applications, highlighting the versatility and potential of this methodology in diverse scientific contexts, from cell labelling to biosensing and polymer synthesis. Researchers globally continue to advance this powerful tool for precise and selective manipulation of biomolecules in complex biological systems.

Assessing the Global Impact of Ambient Air Pollution on Cancer Incidence and Mortality: A Comprehensive Meta-Analysis.

PURPOSE: This study aims to examine the association between exposure to major ambient air pollutants and the incidence and mortality of lung cancer and some nonlung cancers. METHODS: This meta-analysis used PubMed and EMBASE databases to access published studies that met the eligibility criteria. Primary analysis investigated the association between exposure to air pollutants and cancer incidence and mortality. Study quality was assessed using the Newcastle Ottawa Scale. Meta-analysis was conducted using R software. RESULTS: The meta-analysis included 61 studies, of which 53 were cohort studies and eight were case-control studies. Particulate matter 2.5 mm or less in diameter (PM2.5) was the exposure pollutant in half (55.5%), and lung cancer was the most frequently studied cancer in 59% of the studies. A pooled analysis of exposure reported in cohort and case-control studies and cancer incidence demonstrated a significant relationship (relative risk [RR], 1.04 [95% CI, 1.02 to 1.05]; I2, 88.93%; P < .05). A significant association was observed between exposure to pollutants such as PM2.5 (RR, 1.08 [95% CI, 1.04 to 1.12]; I2, 68.52%) and nitrogen dioxide (NO2) (RR, 1.03 [95% CI, 1.01 to 1.05]; I2, 73.52%) and lung cancer incidence. The relationship between exposure to the air pollutants and cancer mortality demonstrated a significant relationship (RR, 1.08 [95% CI, 1.07 to 1.10]; I2, 94.77%; P < .001). Among the four pollutants, PM2.5 (RR, 1.15 [95% CI, 1.08 to 1.22]; I2, 95.33%) and NO2 (RR, 1.05 [95% CI, 1.02 to 1.08]; I2, 89.98%) were associated with lung cancer mortality. CONCLUSION: The study confirms the association between air pollution exposure and lung cancer incidence and mortality. The meta-analysis results could contribute to community cancer prevention and diagnosis and help inform stakeholders and policymakers in decision making.

Spring applied phosphorus loss with cover crops in no-till terraced field.

Cover crops (CC) can improve phosphorus (P) cycling by reducing water related P losses and contributing to P nutrition of a rotational crop. This is particularly important in claypan soils with freeze-thaw cycles in early spring in the Midwest U.S. This 4-year study (2019-2022) examined the impact of CC monoculture and mix of CC species on P losses from a fertilizer application, and determined the P balance in soil compared to no cover crop (noCC). The CC mix consisted of wheat (Triticum aestivum L.), radish (Raphanus raphanistrum subsp. Sativus), and turnip (Brassica rapa subsp. Rapa) (3xCCmix) in 2019 and 2021 before corn, and cereal rye (Secale cereale L.) was planted as monoculture before soybean in 2020 and 2022. The 3xCCmix had no effect on total phosphorus (TP) and dissolved reactive phosphorus (PO4-P) concentration or load in 2019 and 2021. Cereal rye reduced TP and PO4-P load 70% and 73%, respectively, compared to noCC. The variation in soil moisture, temperature, and net precipitation from fertilizer application until CC termination affected available soil P pools due to variability in CC species P uptake, residue decomposition, and P loss in surface water runoff. Overall, the P budget calculations showed cereal rye had 2.4 kg ha-1 greater P uptake compared to the 3xCCmix species which also reduced P loss in water and had greater differences in soil P status compared to noCC. This study highlights the benefit of CCs in reducing P loss in surface runoff and immobilizing P through plant uptake. However, these effects were minimal with 3xCCmix species and variability in crop residue decomposition from different CC species could affect overall P-soil balance.

Underutilized fruit lasoda (Cordia myxa L.): Review on bioactive compounds, antioxidant potentiality and applications in health bioactivities and food.

Underutilized fruits are thought to be nutrient and antioxidant gold mines. Despite their high nutritive value, therapeutic properties, and ability to grow in adverse soil and climatic conditions, they have received little attention. However, these underutilized fruits are an important component of traditional foods, particularly in arid and semiarid regions of Rajasthan. Lasoda (Cordia myxa) contains numerous phytochemicals that contribute to its antioxidant potential, including tannins, flavonoids, phenolic acids, xanthones, terpenes, and saponins. The primary goal of this review is to emphasize the importance of extracting bioactive compounds from lasoda and evaluating their antioxidant potential. Furthermore, this review emphasizes the major areas for the application of lasoda and its extract as prospective positive health agents that can be used in the preparation of functional foods. The use of lasoda may also improve the value of bakery products and meat quality and prevent postharvest losses. This review is a pilot article that can aid in the nutritional profiling of Cordia fruits and seeds, and it provides information on the effective and efficient use of this underutilized fruit in the food and nutraceutical industries.

Role of microRNAs and their putative mechanism in regulating potato (Solanum tuberosum L.) life cycle and response to various environmental stresses.

The exponentially increasing population and the demand for food is inextricably linked. This has shifted global attention to improving crop plant traits to meet global food demands. Potato (Solanum tuberosum L.) is a major non-grain food crop that is grown all over the world. Currently, some of the major global potato research work focuses on the significance of microRNAs (miRNAs) in potato. miRNAs are a type of non-coding RNAs that regulate the gene expression of their target mRNA genes by cleavage and/or their translational inhibition. This suggests an essential role of miRNAs in a multitude of plant biological processes, including maintenance of genome integrity, plant growth, development and maturation, and initiation of responses to various stress conditions. Therefore, engineering miRNAs to generate stress-resistant varieties of potato may result in high yield and improved nutritional qualities. In this review, we discuss the potato miRNAs specifically known to play an essential role in the various stages of the potato life cycle, conferring stress-resistant characteristics, and modifying gene expression. This review highlights the significance of the miRNA machinery in plants, especially potato, encouraging further research into engineering miRNAs to boost crop yields and tolerance towards stress.

Exploring fine tuning between phytohormones and ROS signaling cascade in regulation of seed dormancy, germination and seedling development.

In higher plants, seed is a propagule which ensures dissemination and survival of species. Developmental phases of a seed comprise embryogenesis, maturation and germination paving a way to its final fate i.e. seedling establishment. The final stage of seed maturation is marked by dehydration, acquisition of dessication tolerance and induction of dormancy. A precise Abscisic acid (ABA) to Gibberellins (GA) ratio, accumulation of miRNA 156, low level of reactive oxygen species (ROS) and enzyme inactivity govern seed dormancy. This also prevent pre harvest sprouting of the seeds. Overtime, stored seed mRNAs and proteins are degraded through oxidation of specific nucleotides in response to ROS accumulation. This degradation alleviates seed dormancy and transforms a dormant seed into a germinating seed. At this stage, ABA catabolism and degradation accompanied by GA synthesis contribute to low ABA to GA ratio. GA as well as ROS acts downstream, to mobilize reserve food materials, rupture testa, enhance imbibition and protrude radicle. All these events mark seed germination. Further, seedling is established under the governance of auxin and light. ABA and GA are master regulators while auxin, cytokinins, ethylene, jasmonic acid, brassinosteroids act through interdependent pathways to tightly regulate seed dormancy, germination and seedling establishment. In this review, the role of phytohormones and ROS in accordance with environmental factors in governing seed dormancy, promoting seed germination and thus, establishing a seedling is discussed in detail.

The acidic C-terminal tail of DNA Gyrase of Salmonella enterica serovar Typhi controls DNA relaxation in an acidic environment.

The intracellular bacteria, Salmonella Typhi adapts to acidic conditions in the host cell by resetting the chromosomal DNA topology majorly controlled by DNA Gyrase, a Type II topoisomerase. DNA Gyrase forms a heterodimer A2B2 complex, which manages the DNA supercoiling and relaxation in the cell. DNA relaxation forms a part of the regulatory mechanism to activate the transcription of genes required to survive under hostile conditions. Acid-induced stress attenuates the supercoiling activity of the DNA Gyrase, resulting in DNA relaxation. Salmonella DNA becomes relaxed as the bacteria adapt to the acidified intracellular environment. Despite comprehensive studies on DNA Gyrase, the mechanism to control supercoiling activity needs to be better understood. A loss in supercoiling activity in E. coli was observed upon deletion of the non-conserved acidic C-tail of Gyrase A subunit. Salmonella Gyrase also contains an acidic tail at the C-terminus of Gyrase A, where its deletion resulted in reduced supercoiling activity compared to wild-type Gyrase. Interestingly, we also found that wild-type Gyrase compromises supercoiling activity at acidic pH 2-3, thereby causing DNA relaxation. The absence of a C-tail displayed DNA supercoiling to some extent between pH 2-9. Hence, the C-tail of Gyrase A might be one of the controlling factors that cause DNA relaxation in Salmonella at acidic pH conditions. We propose that the presence of the C-tail of GyraseA causes acid-mediated inhibition of the negative supercoiling activity of Gyrase, resulting in relaxed DNA that attracts DNA-binding proteins for controlling the transcriptional response.

Synthesis of unsymmetrical 2,3,7,8-tetrabromo meso-5,10,11,16-tetraaryl- triphyrin(2.1.1) and its use in the synthesis of sterically crowded 2,3,5,7,8,10,11,16-octaarylated triphyrin(2.1.1)s.

Triphyrin(2.1.1) is a 14π aromatic contracted congener of an 18π aromatic porphyrin(1.1.1.1). An unsymmetrical 2,3,7,8-tetrabromo meso-tetraaryl triphyrin(2.1.1) containing four bromides at the ß-pyrrole carbons of two out of three pyrrole rings of the triphyrin core was synthesized for the first time in 90% yield by treating meso-tetraaryl triphyrin(2.1.1) with five equivalents of N-bromosuccinimide in 1,2-dichloroethane (DCE) under reflux for 8 h. The X-ray structure revealed that the triphyrin(2.1.1) macrocycle was significantly distorted in 2,3,7,8-tetrabromo meso-tetraaryl triphyrin compared to planar meso-tetraaryl triphyrin. A series of novel sterically crowded 2,3,5,7,8,10,11,16-octaaryl triphyrin(2.1.1)s were synthesized by coupling 2,3,7,8-tetrabromo meso-tetraaryl triphyrin with six different aryl boronic acids under Suzuki-Miyaura coupling conditions. NMR, absorption, electrochemical and theoretical studies revealed that the structure and electronic properties were drastically altered in the 2,3,5,7,8,10,11,16-octaaryl triphyrin(2.1.1) series due to the presence of four additional aryl groups at the ß-pyrrole carbons which caused steric crowding at the periphery of the triphyrin core resulting in a decrease in effective π-conjugation in the triphyrin(2.1.1)s.

Association of COVID with Mycosis in General.

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 is a respiratory disease which created havoc worldwide, was accompanied by another peculiar, otherwise rare, secondary fungal infection Mucormycosis which was observed at exceptionally high incidence in India during the second wave of COVID-19. The article explores possible links between the two infectious diseases to understand a higher-than-normal occurrence of Mucormycosis in COVID-19 patients. Coronavirus enters the patients through ACE-2 and many other receptors like- NRP-1, TfR, CD-126, and CD-26. Virus bind to cells possessing these receptors and affect their proper functioning, disturbing homeostatic metabolism and resulting in conditions like hyperglycemia, Diabetic Ketoacidosis (DKA), low serum pH, iron overload, anemia, hypoxia, and immunosuppression as explained in the article. All these outcomes provide a very supportive environment for the attack and spread of Mucormycosis fungi. The major receptor for Mucormycosis in humans is the GRP-78. Its expression is upregulated by coronavirus entry and by hyperferritinemia, hyperglycemia, and acidic conditions prevalent in COVID patients, thus providing an easy entry for the fungal species. Upregulation of GRP-78 furthermore damages pancreatic ß-cells and intensifies hyperglycemia, showing quite a synergic relationship. Inordinate rise of Mucormycosis cases in India might be explained by facts like- India possessing a large proportion of diabetic patients, emergence of a very deadly strain of coronavirus- Delta strain, higher doses of steroids and antibodies used to treat patients against this strain, overburdened health care services, sudden much higher need of oxygen supply and use of industrial oxygen could explain the Mucormycosis outbreak observed in India during the second wave of COVID-19. OBJECTIVE: The present review discusses the functional interdependence between COVID-19 and Mucormycosis and summarizes the possible synergic links between COVID and Mucormycosis. CONCLUSION: The receptors and metabolic pathways affected by COVID-19 result in severe physiological conditions- hyperglycemia, DKA, anemia, iron overload, immunosuppression, and hypoxia. All these conditions not only increase the expression of GRP-78, the major receptor for entry of fungi but also play a crucial role in providing quality media for Mucormycosis fungus to establish and grow. Hence explains the fungal epidemic observed in India during the second wave of COVID-19 in India.

Subclinical circulation of Chicken infectious anaemia virus- A Sero-molecular study.

Chicken infectious anaemia-an important immunosuppressive viral disease of chicken-gained much attention in the recent past. Based on huge mortality and production loss observed in the fast-growing poultry sector, the present study aimed to find out the current status of the chicken infectious anaemia virus (CIAV), among chicken flocks in the Punjab state of India by sero-molecular study. The sera from the blood samples were tested for anti-CIAV antibodies by indirect ELISA and also compared with haematological parameters. DNA from sero-positive samples underwent PCR amplification, sequencing and phylogenetic analysis of the most conserved genomic region (VP3 gene) to detect viraemia in asymptomatic birds. The serological study using indirect ELISA showed a high sero-positivity of 77.27% in chicken flocks. Additionally, the present study also revealed the high molecular evidence (72.54%) of CIAV in apparently healthy birds. Genetic analysis showed that all CIAVs have conserved VP3 genes without any nucleotide substitutions, indicating presence of CIAV and its subclinical circulation among apparently healthy flocks. The wide distribution of CIAV among birds may be the reason for huge mortality and production loss. Further, it is suggested that studies be conducted to find out the co-involvement of CIAV with other immunosuppressive microbial agents and the immunosuppressive effect of CIAV in apparently healthy birds. Also, its role in vaccine failure and outbreaks of various other avian diseases needs to be explored.

Gut microbiome-associated predictors as biomarkers of response to advanced therapies in inflammatory bowel disease: a systematic review.

Loss of response to therapy in inflammatory bowel disease (IBD) has led to a surge in research focusing on precision medicine. Three systematic reviews have been published investigating the associations between gut microbiota and disease activity or IBD therapy. We performed a systematic review to investigate the microbiome predictors of response to advanced therapy in IBD. Unlike previous studies, our review focused on predictors of response to therapy; so the included studies assessed microbiome predictors before the proposed time of response or remission. We also provide an update of the available data on mycobiomes and viromes. We highlight key themes in the literature that may serve as future biomarkers of treatment response: the abundance of fecal SCFA-producing bacteria and opportunistic bacteria, metabolic pathways related to butyrate synthesis, and non-butyrate metabolomic predictors, including bile acids (BAs), amino acids, and lipids, as well as mycobiome predictors of response.

Cu(i)-catalysed 1,2,3-triazole stitched chalcomer assembly as Pb(ii) and Cu(ii) ion sensor: DFT and docking scrutiny.

Herein, a 1,2,3-triazole derivative (CBT), synthesized using the Copper(i) catalyzed Alkyne Azide Cycloaddition (CuAAC) procedure, based on a chalcone skeleton has been reported, that was implemented as an effective sensor for Pb(ii) and Cu(ii) ions. The synthesized CBT was characterized using spectroscopic techniques such as FTIR, NMR (1H and 13C), and mass spectrometry. The sensing behaviour of CBT was analyzed using UV-Vis spectroscopy, demonstrating selective sensing for Pb(ii) and Cu(ii) ions, competitively. The correlation plot revealed the detection limit for Pb(ii) and Cu(ii) ions to be 100 µM and 110 µM respectively. In addition, DFT simulations and molecular electrostatic potential (MEP) studies scrutinized the binding strategy of the free CBT and its orientation towards the metal ions in the metal-ligand complex. The probe CBT was predicted via the online platform Way2drug for its pharmacological properties, investigating the possibility to inhibit early atherosclerosis. CBT was subsequently docked to the TRIB1 protein using AutoDock Vina and demonstrated a high binding affinity with a value of -6.2 kcal mol-1.