Sulfur transfer from the endophytic fungus Serendipita indica improves maize growth and requires the sulfate transporter SiSulT.

A deficiency of the essential macronutrient sulfur leads to stunted plant growth and yield loss; however, an association with a symbiotic fungus can greatly improve nutrient uptake by the host plant. Here, we identified and functionally characterized a high-affinity sulfate transporter from the endophytic fungus Serendipita indica. SiSulT fulfills all the criteria expected of a functional sulfate transporter responding to sulfur limitation: SiSulT expression was induced when S. indica was grown under low-sulfate conditions, and heterologous expression of SiSulT complemented a yeast mutant lacking sulfate transport. We generated a knockdown strain of SiSulT by RNA interference to investigate the consequences of the partial loss of this transporter for the fungus and the host plant (maize, Zea mays) during colonization. Wild-type (WT) S. indica, but not the knockdown strain (kd-SiSulT), largely compensated for low-sulfate availability and supported plant growth. Colonization by WT S. indica also allowed maize roots to allocate precious resources away from sulfate assimilation under low-sulfur conditions, as evidenced by the reduction in expression of most sulfate assimilation genes. Our study illustrates the utility of the endophyte S. indica in sulfur nutrition research and offers potential avenues for agronomically sound amelioration of plant growth in low-sulfate environments.

Recent Advancement of Indocyanine Green Based Nanotheranostics for Imaging and Therapy of Coronary Atherosclerosis.

Atherosclerosis is a vascular intima condition in which any part of the circulatory system is affected, including the aorta and coronary arteries. Indocyanine green (ICG), a theranostic compound approved by the FDA, has shown promise in the treatment of coronary atherosclerosis after incorporation into nanoplatforms. By integration of ICG with targeting agents such as peptides or antibodies, it is feasible to increase its concentration in damaged arteries, hence increasing atherosclerosis detection. Nanotheranostics offers cutting-edge techniques for the clinical diagnosis and therapy of atherosclerotic plaques. Combining the optical properties of ICG with those of nanocarriers enables the improved imaging of atherosclerotic plaques and targeted therapeutic interventions. Several ICG-based nanotheranostics platforms have been developed such as polymeric nanoparticles, iron oxide nanoparticles, biomimetic systems, liposomes, peptide-based systems, etc. Theranostics for atherosclerosis diagnosis use magnetic resonance imaging (MRI), computed tomography (CT), near-infrared fluorescence (NIRF) imaging, photoacoustic/ultrasound imaging, positron emission tomography (PET), and single photon emission computed tomography (SPECT) imaging techniques. In addition to imaging, there is growing interest in employing ICG to treat atherosclerosis. In this review, we provide a conceptual explanation of ICG-based nanotheranostics for the imaging and therapy of coronary atherosclerosis. Moreover, advancements in imaging modalities such as MRI, CT, PET, SPECT, and ultrasound/photoacoustic have been discussed. Furthermore, we highlight the applications of ICG for coronary atherosclerosis.

Biofilm inhibition/eradication: exploring strategies and confronting challenges in combatting biofilm.

Biofilms are complex communities of microorganisms enclosed in a self-produced extracellular matrix, posing a significant threat to different sectors, including healthcare and industry. This review provides an overview of the challenges faced due to biofilm formation and different novel strategies that can combat biofilm formation. Bacteria inside the biofilm exhibit increased resistance against different antimicrobial agents, including conventional antibiotics, which can lead to severe problems in livestock and animals, including humans. In addition, biofilm formation also imposes heavy economic pressure on industries. Hence it becomes necessary to explore newer alternatives to eradicate biofilms effectively without applying selection pressure on the bacteria. Excessive usage of antibiotics may also lead to an increase in the number of resistant strains as bacteria employ an advanced antimicrobial resistance mechanism. This review provides insight into multifaceted technologies like quorum sensing inhibition, enzymes, antimicrobial peptides, bacteriophage, phytocompounds, and nanotechnology to neutralize biofilms without developing antimicrobial resistance (AMR). Furthermore, it will pave the way for developing newer therapeutic agents to deal with biofilms more efficiently.

Key computational findings reveal proton transfer as driving the functional cycle in the phosphate transporter PiPT.

Phosphate is an indispensable metabolite in a wide variety of cells and is involved in nucleotide and lipid synthesis, signaling, and chemical energy storage. Proton-coupled phosphate transporters within the major facilitator family are crucial for phosphate uptake in plants and fungi. Similar proton-coupled phosphate transporters have been found in different protozoan parasites that cause human diseases, in breast cancer cells with elevated phosphate demand, in osteoclast-like cells during bone reabsorption, and in human intestinal Caco2BBE cells for phosphate homeostasis. However, the mechanism of proton-driven phosphate transport remains unclear. Here, we demonstrate in a eukaryotic, high-affinity phosphate transporter from Piriformospora indica (PiPT) that deprotonation of aspartate 324 (D324) triggers phosphate release. Quantum mechanics/molecular mechanics molecular dynamics simulations combined with free energy sampling have been employed here to identify the proton transport pathways from D324 upon the transition from the occluded structure to the inward open structure and phosphate release. The computational insights so gained are then corroborated by studies of D45N and D45E amino acid substitutions via mutagenesis experiments. Our findings confirm the function of the structurally predicted cytosolic proton exit tunnel and suggest insights into the role of the titratable phosphate substrate.

Deciphering soil-plant-animal continuum in relation to trace elements in middle Gangetic plain region of India.

The soil-plant-animal continuum represents an evolving realm in biological research that's why this study was undertaken in the middle Gangetic plain region of India. Trace and ultra-trace elements were analyzed in 100 soil samples, 147 feed and fodder samples, as well as 69 blood and 127 hair samples with the help of inductively coupled plasma optical emission spectroscopy (ICP-OES). The levels of trace and ultra-trace elements in the soil were significantly higher than those in the feed, and similarly, the concentrations in the feed were notably higher than those in the blood of dairy cattle. Blood and hair samples from the cattle showed deficiencies in copper (Cu) and manganese (Mn), with reaching approximately 20% and 50%, respectively. Correlation analysis indicated significant (P < 0.05) associations between the trace and ultra-trace elements in plants and the corresponding elements found in cattle's hair, specifically for iron (Fe) and molybdenum (Mo). Conversely, a significant (P < 0.05) negative correlation was observed between soil composition and cattle's blood, while a positive correlation was evident only in the case of silver content between plant and cattle's hair. Regression analyses revealed positive linear relationships between minerals in soils and plants, as well as between plants and cattle. However, the correlation coefficients were statistically insignificant. The regression equations established to predict mineral concentrations in cattle based on soil and plant mineral contents indicated a positive relationship for both trace and ultra-trace elements, suggesting the potential to measure the mineral status in dairy cattle through this approach.

Nanotheranostics: Molecular Diagnostics and Nanotherapeutic Evaluation by Photoacoustic/Ultrasound Imaging in Small Animals.

Nanotheranostics is a rapidly developing field that integrates nanotechnology, diagnostics, and therapy to provide novel methods for imaging and treating wide categories of diseases. Targeted nanotheranostics offers a platform for the precise delivery of theranostic agents, and their therapeutic outcomes are monitored in real-time. Presently, in vivo magnetic resonance imaging, fluorescence imaging, ultrasound imaging, and photoacoustic imaging (PAI), etc. are noninvasive imaging techniques that are preclinically available for the imaging and tracking of therapeutic outcomes in small animals. Additionally, preclinical imaging is essential for drug development, phenotyping, and understanding disease stage progression and its associated mechanisms. Small animal ultrasound imaging is a rapidly developing imaging technique for theranostics applications due to its merits of being nonionizing, real-time, portable, and able to penetrate deep tissues. Recently, different types of ultrasound contrast agents have been explored, such as microbubbles, echogenic exosomes, gas-vesicles, and nanoparticles-based contrast agents. Moreover, an optical image obtained through photoacoustic imaging is a noninvasive imaging technique that creates ultrasonic waves when pulsed laser light is used to expose an object and creates a picture of the tissue's distribution of light energy absorption on the object. Contrast agents for photoacoustic imaging may be endogenous (hemoglobin, melanin, and DNA/RNA) or exogenous (dyes and nanomaterials-based contrast agents). The integration of nanotheranostics with photoacoustic and ultrasound imaging allows simultaneous imaging and treatment of diseases in small animals, which provides essential information about the drug response and the disease progression. In this review, we have covered various endogenous and exogenous contrast agents for ultrasound and photoacoustic imaging. Additionally, we have discussed various drug delivery systems integrated with contrast agents for theranostic application. Further, we have briefly discussed the current challenges associated with ultrasound and photoacoustic imaging.

Correlation of ultrasound-based TIRADS and the Bethesda system for reporting of thyroid cytopathology: A study in a tertiary care centre.

BACKGROUND: The age-standardised incidence rate of thyroid cancer in India is 1 in 416 in the general population. This increased incidence has mainly been attributed to improved detection methods for small thyroid lesions. Two such methods are the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TIRADS) and the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). AIMS AND OBJECTIVES: To study the correlation between ACR TIRADS and TBSRTC, and between each system and the final histopathological report. MATERIALS AND METHODS: Thyroid cytopathology cases were retrieved for the period January 2019 to July 2022. For each case, the TIRADS score and Bethesda category were noted. Histopathology specimens were also traced. RESULTS: The study comprised 1100 cases, with 955 female and 145 male patients (M:F = 1:6.59), and ages ranging between 7 and 85 years. The TIRADS scoring was available for 1036 cases. Histopathology was available for 231 cases. There was a significant correlation between TIRADS and TBSRTC, with a p-value of 0.000 and a substantial Kappa agreement of 0.688. Both TIRADS and TBSRTC also had significant correlations with the histopathology data, with a p-value of 0.000 for each. The sensitivity values for TBSRTC and TIRADS were 69.4% and 65.8%; specificity, 99.3% and 96.5%; positive predictive value (PPV), 98.3% and 91.8%; and negative predictive value (NPV) 84.7% and 84.4%, respectively. The risk of malignancy (ROM) was also calculated and was found to be high, especially for TBSRTC II, III, IV and V (11.3%, 20%, 61.5%, 97.4% respectively) and TIRADS 2 and 3 (10.3% and 29.6% respectively). CONCLUSION: The TIRADS and TBSRTC systems of categorisation of thyroid lesions are concordant and could help improve the overall survival rate of patients with thyroid malignancies.

Functional characterization of a high-affinity iron transporter (PiFTR) from the endophytic fungus Piriformospora indica and its role in plant growth and development.

Iron (Fe) is a micronutrient required for plant growth and development; however, most Fe forms in soil are not readily available to plants, resulting in low Fe contents in plants and, thereby, causing Fe deficiency in humans. Biofortification through plant-fungal co-cultivation might be a sustainable approach to increase crop Fe contents. Therefore, we aimed to examine the role of a Piriformospora indica Fe transporter on rice Fe uptake under low Fe conditions. A high-affinity Fe transporter (PiFTR) from P. indica was identified and functionally characterized. PiFTR fulfilled all criteria expected of a functional Fe transporter under Fe-limited conditions. Additionally, PiFTR expression was induced when P. indica was grown under low Fe conditions, and PiFTR complemented a yeast mutant lacking Fe transport. A knockdown (KD) P. indica strain was created via RNA interference to understand the physiological role of PiFTR. We observed that the KD-PiFTR-P. indica strain transported a significantly lower amount of Fe to colonized rice (Oryza sativa) than the wild type (WT) P. indica. WT P. indica-colonized rice plants were healthier and performed significantly better than KD-PiFTR-P. indica-colonized rice plants. Our study offers potential avenues for an agronomically sound amelioration of plant growth in low Fe environments.

Tailored calix[4]arene-gold nanoconjugate as a ultra-sensitive immunosensing nanolabel.

The construction of highly sensitive and specific immunosensing nanolabels have attracted tremendous attention in the development of reliable point-of-care disease diagnostics. However, there are still challenges with traditional immunoassays, such as complicated and time-consuming procedure, the use of enzyme label, non-specificity, and require readers for detection. Therefore, we have designed and developed site-directed antibody-immobilized calix[4]arene-gold nanoconjugate based colorimetric immunosensing nanolabel to offer high sensitivity. The prepared nanolabel enabled oriented binding of the antibodies by providing full accessibility of Fab domain for antigen binding. The improved sensitivity of the developed nanolabel was evaluated using vertical flow immunoassay (VFIA) for detecting C-reactive protein (CRP) with a lower detection limit up to 1 ng/ml. Our developed nanolabel was found to be highly specific, easy, quick, and appropriate for onsite detection. The nanolabel is validated with spiked blood samples which exhibited ~90% recovery having a relative error of ~2%. Furthermore, the nanolabel was also used for screening of human blood real samples which showed relative error of ~0.6%. The developed nanolabel can be utilized as a potential nanolabel for the quantitative detection of various biomolecules in clinical samples.

Interplay of hydrogen peroxide and nitric oxide: systemic regulation of photosynthetic performance and nitrogen metabolism in cadmium challenged cyanobacteria.

In the present study, the potential role of hydrogen peroxide (H2O2) and nitric oxide (NO) has been well recorded in the induction of cadmium (Cd) stress tolerance in cyanobacteria. In this regard, H2O2 and SNP (sodium nitroprusside, NO donor), were applied to Nostoc muscorum and Anabaena sp. exposed to Cd (6 µM) stress, to analyze different physiological and biochemical parameters. Results revealed that treatment of Cd reduced the growth, pigment contents, photosynthetic oxygen yield and performance of PS II photochemistry (decreased chlorophyll a fluorescence parameters, i.e., ФPo, Ψo, ФEo, PIABS along with Fv/Fo and increased the energy flux parameters, i.e., ABS/RC, TRo/RC, ETo/RC, DIo/RC along with Fo/Fv. Similarly, uptake of nitrate (NO3 -) and nitrite (NO2 -), as well as the activities of nitrate and ammonia assimilating enzymes along with carbohydrate content, were severely affected by Cd toxicity and notwithstanding this, glutamate dehydrogenase (GDH) activity exhibited reverse trend. Exogenous application of a very low dose (1 µM) of H2O2 (only for 3 h) and NO (SNP; 10 µM) notably counteracted Cd-induced toxicity. Nevertheless, the positive impact of H2O2 got reversed under the treatment of PTIO (NO scavenger) and LNAME (inhibitor of nitric oxide synthase; NOS) while NO could work efficiently even in the presence of NAC (H2O2 scavenger) and DPI (inhibitor of NADPH oxidase); hence indicated towards the H2O2 mediated NO signaling in averting Cd induced toxicity in test cyanobacteria. In conclusion, current finding demonstrated a positive cross-talk between H2O2 and NO for providing tolerance to cyanobacteria against Cd stress.

Emerging diagnostic tools for detection of COVID-19 and perspective.

The COVID-19 caused by a novel coronavirus, named Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has taken a great toll of life affecting lakhs of people around the globe. It was detected initially in Wuhan, China and has spread rapidly to more than 208 countries to date. A range of molecular and immunoassay-based techniques ranging from central laboratory testing to point-of-care tests is urgently needed for the diagnosis and management of COVID-19 patients. Intensive research is going on for the rapid and highly sensitive detection of COVID 19 using varied approach. Hence, this review will focus on the structure of SARS-CoV-2 and recent progress of different detection tool for the detection of COVID-19. This review will also stimulate academics and researcher to update their current technology. Additionally, we also state about the future revolving around the detection of the novel coronavirus. Lately, the way ahead for better management are also put forward.

Highly sensitive vertical flow based point-of-care immunokit for rapid and early detection of human CRP as a cardiovascular risk factor.

Early detection and treatment of cardiovascular disease by identifying markers is important to improve the health of our citizens and simultaneously reduce the cost of health care. Therefore, there is an urgent need for early detection and treatment of asymptomatic cardiovascular disease. Herein, we have developed highly sensitive vertical flow immunokit (VFIK) for the detection of C-reactive protein (CRP), comprising an antibody/citrate conjugated gold nanoparticle in a fixed orientation surface. Our CRP test kit has been optimized with various parameters such as buffer composition, the quantity of captured antibody and sensitivity of the assay. Prominently, our developed CRP test kit is highly sensitive and rapid point of care test (POCT) which is capable to detect CRP with minimal volume (50-60 µl) and time (1-2 min) with diminutive detection up to 10 ng/ml. The reliability of our kit was evaluated and validated with spiked and clinical whole blood samples. The results demonstrated that our developed vertical flow-based point-of-care Immunokit may serve fruitful and semi-quantitative routine diagnostic for the early detection of cardiac disease.

Remarkable decrease in the viscosity of waxy crude oil under an electric field.

Uninterrupted transport of waxy crude oil through pipelines remains a pressing concern for the petroleum industry. When the ambient temperature falls below the pour point of the crude, deposition of wax particles may lead to complete blockage of the pipeline. We demonstrate that the application of a DC electric field to waxy crude below its pour point can effectively break the wax network and also reduce the viscosity by up to two orders of magnitude. We have studied the dynamics of the change in viscosity during and after application of an electric field. Three regimes are observed. First is the induction regime, where viscous stresses dominate and the viscosity remains unchanged. During the intermediate and final regimes, the decrease in viscosity follows first order kinetics with rate constants proportional to the strength of the electric field and to the square of the strength, respectively. Microscopic evidence shows that some network connections break during the intermediate regime, whereas in the final regime, further fragmentation of the pieces of the broken network occurs. This is accompanied by aggregation of fine wax fragments. After cessation of the field, the viscosity increases gradually. The rate and the extent of recovery of viscosity depend only on the value of viscosity at the point of cessation of the field. That the breakage of the network occurs, even in the absence of shear, has been demonstrated. Through measurement of the dielectric constants and conductivities of the crude oil and its component phases, we have shown that the wax network experiences compressive Maxwell stress, which is dominated by the electric field within the wax particles.

The mechanism of phosphatidylcholine-induced interference of PAP (248-286) aggregation.

Seminal amyloids are well known for their role in enhancing HIV infection. Among all the amyloidogenic peptides identified in human semen, PAP248-286 was found to be the most active and was termed as semen-derived enhancer of viral infection (SEVI). Although amyloidogenic nature of the peptide is mainly linked with enhancement of the viral infection, the most active physiological conformation of the aggregated peptide remains inconclusive. Lipids are known to modulate aggregation pathway of a variety of proteins and peptides and constitute one of the most abundant biomolecules in human semen. PAP248-286 significantly differs from the other known amyloidogenic peptides, including Aß and IAPP, in terms of critical concentration, surface charge, fibril morphology, and structural transition during aggregation. Hence, in the present study, we aimed to assess the effect of a lipid, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), on PAP248-286 aggregation and the consequent conformational outcomes. Our initial observation suggested that the presence of the lipid considerably influenced the aggregation of PAP248-286 . Further, ZDOCK and MD simulation studies of peptide multimerization have suggested that the hydrophobic residues at C-terminus are crucial for PAP248-286 aggregation and are anticipated to be major DOPC-interacting partners. Therefore, we further assessed the aggregation behaviour of C-terminal (PAP273-286 ) fragment of PAP248-286 and observed that DOPC possesses the ability to interfere with the aggregation behaviour of both the peptides used in the current study. Mechanistically, we propose that the presence of DOPC causes considerable inhibition of the peptide aggregation by interfering with the peptide's disordered state to ß-sheet transition.

An overview of important ethnomedicinal herbs of Phyllanthus species: present status and future prospects.

The genus Phyllanthus consists of more than 1000 species, of which many are used as traditional medicines. The plant extracts have been used since ancient times, for treating hypertension, diabetes, hepatic, urinary, and sexual disorders, and other common ailments. Modern day scientific investigations have now confirmed pharmacognostic properties of Phyllanthus herbs. The phytochemicals attributing these medicinal properties have been identified in many of the Phyllanthus herbs. The morphologically similar herbs of Phyllanthus grow together and admixture of species during collection for manufacture of herbal medicines is quite common. Hence, along with pharmacognostic and phytochemical studies, appropriate protocols for correct identification of species are also important. As the use of these herbs as green medicines is becoming more popular, it is imperative to assess its genetic diversity and phylogenetic relatedness for future conservation strategies. This review is an attempt to present an overview of the existing studies on pharmacognostics, phytochemistry, species identification, and genetic diversity of Phyllanthus herbs and consequently (i) highlight areas where further research is needed and (ii) draw attention towards extending similar studies in underutilized but potentially important herbs such as P. maderaspatensis, P. kozhikodianus, P. rheedii, P. scabrifolius, and P. rotundifolius.

Two-dimensional Be2P4 as a promising thermoelectric material and anode for Na/K-ion batteries.

Incredibly effective and flexible energy conversion and storage systems hold great promise for portable self-powered electronic devices. Owing to their large surface area, exceptional atomic structures, superior electrical conductivity and good mechanical flexibility, two-dimensional (2D) materials are recognized as an attractive option for energy conversion and storage application. In this work, we examined the stability, electronic, thermoelectric and electrochemical aspects of a novel 2D Be2P4 monolayer by adopting density functional theory (DFT). The Be2P4 monolayer exhibits a direct semiconductor gap of 0.9 eV (HSE06), large Young's modulus (∼198 GPa), high carrier mobility (∼104 cm2 V-1 s-1) and a low excitonic binding energy of 0.11 eV. Our calculated findings suggest that Be2P4 shows a lattice thermal conductivity of 1.02 W m K-1 at 700 K, resulting in moderate thermoelectric performance (ZT ∼ 0.7), encouraging its use in thermoelectric materials. In addition, a higher adsorption energy of -2.28 eV (-2.52 eV) and less diffusion barrier of 0.22 eV (0.17 eV) for Na(K)-ion batteries promote fast ion transport in the Be2P4 monolayer. This material also shows a high specific capacity and superior energy density of 8460 W h kg-1 (8883 W h kg-1) for Na(K)-ion batteries. Thus, our results offer insightful information for investigating potential thermoelectric and flexible anode materials based on the Be2P4 monolayer.

Cytological diagnosis of cutaneous granular cell tumor: Rare tumor with rare presentation.

ABSTRACT: Granular cell tumors (GCTs) are uncommon soft tissue tumors, which are difficult to diagnose merely by clinical examination. Fine-needle aspiration cytology (FNAC), being an effective first-line investigation, plays a significant role in the preoperative diagnosis of GCT. However, the tumor can mimic certain other lesions; hence, a cytopathologist needs to be aware of its characteristic morphology. We report here a case of GCT, presented as a subcutaneous nodule in the first finger web. A differential diagnosis of lipoma/neurofibroma was made clinically. FNAC was done and showed characteristic features of granular cell tumor along with intranuclear inclusions and subsequently, it was confirmed on histopathology.

Construction of coumarin-appended calix[4]arene-based fluorescence sensor for the detection of carbofuran in cabbage.

This study presents a novel approach for the detection of carbofuran (CBF) insecticide by systematically exploring a calix[4]arene-derived fluorescence probe, CouC4S, functionalized with two coumarin-labelled cystamine linkages at the narrow edge of the calix[4]arene platform. The proposed method showed a fluorescence "signal - off" effect when CBF binds with CouC4S by quenching the fluorescence intensity of CouC4S. Its limit of detection was as low as 5.55 µM according to the emission study. The working concentration range for this ligand was observed to be up to 5-65 µM. This method could be applied for the on-spot detection of CBF in real samples such as cabbage by spiking CBFvia in situ experiments, which exhibited a limit of detection of 8.823 ppm. For the further confirmation of CouC4S:CBF binding, cyclic voltammetry, differential pulse voltammetry, powder X-ray diffraction, FT-IR spectroscopy, 1H NMR titration, MALDI-TOF and computational investigations were carried out.

The five homologous CiaR-controlled Ccn sRNAs of Streptococcus pneumoniae modulate Zn-resistance.

Zinc is a vital transition metal for Streptococcus pneumoniae, but is deadly at high concentrations. In S. pneumoniae, elevated intracellular free Zn levels result in mis-metallation of key Mn-dependent metabolic and superoxide detoxifying enzymes resulting in Zn intoxication. Here, we report our identification and characterization of the function of the five homologous, CiaRH-regulated Ccn sRNAs in controlling S. pneumoniae virulence and metal homeostasis. We show that deletion of all five ccn genes (ccnA, ccnB, ccnC, ccnD, and ccnE) from S. pneumoniae strains D39 (serotype 2) and TIGR4 (serotype 4) causes Zn hypersensitivity and an attenuation of virulence in a murine invasive pneumonia model. We provide evidence that bioavailable Zn disproportionately increases in S. pneumoniae strains lacking the five ccn genes. Consistent with a response to Zn intoxication or relatively high intracellular free Zn levels, expression of genes encoding the CzcD Zn exporter and the Mn-independent ribonucleotide reductase, NrdD-NrdG, were increased in the ΔccnABCDE mutant relative to its isogenic ccn+ parent strain. The growth inhibition by Zn that occurs as the result of loss of the ccn genes is rescued by supplementation with Mn or Oxyrase™, a reagent that removes dissolved oxygen. Lastly, we found that the Zn-dependent growth inhibition of the ΔccnABCDE strain was not altered by deletion of sodA, whereas the ccn+ ΔsodA strain phenocopied the ΔccnABCDE strain. Overall, our results indicate that the Ccn sRNAs have a crucial role in preventing Zn intoxication in S. pneumoniae.

The baneful alliance of COVID-19 and mucormycosis: Histopathological concerns.

Background: Mucormycosis, once a rare fungal disease, has now shown a surge in cases, and its epidemiology in India is intriguing. Rising incidence confers the necessity of defining the demography of the population at risk, early diagnosis, and recommendations for the management of mucormycosis in patients with coronavirus disease (COVID-19) infection. Aims: To study the clinico-epidemological profile, risk factors, and histopathological features of COVID-19-associated Mucormycosis (CAM). Setting and Design: This is a retrospective observational study. Material and Methods: Fifty-six biopsy specimens taken from patients of COVID-19 with clinical suspicion of mucormycosis were included. Results: Diabetes mellitus, corticosteroids, and oxygen therapy were the most common risk factors associated with CAM. The mean duration between the onset of symptoms of COVID-19 and onset of CAM was 25.2 ± 15.3 days. Rhino-orbito-cerebral mucormycosis (ROCM) was present in 24.5% of the cases, with a survival rate of 58.3%. Histopathology showed tissue invasion by branching broad-based, pale, fungal hyphae consistent with mucor in 49 (87.5%) cases. Inflammation was acute neutrophilic type in 61.2% of the patients with a survival rate of 63.33%. The survival rate with chronic non-granulomatous and chronic granulomatous was 100% and 81.8%, respectively. Conclusion: Keeping a high index of suspicion for mucormycosis in COVID-19 by all medical fraternities of the health community in the existence of risk factors is the need of the hour for prompt diagnosis. Biopsy of antral necrotic tissue should be performed immediately after suspicion for histopathological study to confirm the diagnosis of mucormycosis and predict prognosis depending on the type of inflammation incited, fungal morphology, load, and necrosis.