Immunosuppressive effects of morphine on macrophage polarization and function.

Macrophages play a pivotal role in safeguarding against a broad spectrum of infections, from viral, bacterial, fungal to parasitic threats and contributing to the immune defense against cancer. While morphine's immunosuppressive effects on immune cells are extensively documented, a significant knowledge gap exists regarding its influence on macrophage polarization and differentiation. Hence, we conducted a study that unveils that prior exposure to morphine significantly impedes the differentiation of bone marrow cells into macrophages. Furthermore, the polarization of macrophages toward the M1 phenotype under M1-inducing conditions experiences substantial impairment, as evidenced by the diminished expression of CD80, CD86, CD40, iNOS, and MHCII. This correlates with reduced expression of M1 phenotypical markers such as iNOS, IL-1ß, and IL-6, accompanied by noticeable morphological, size, and phagocytic alterations. Further, we also observed that morphine affected M2 macrophages. These findings emphasize the necessity for a more comprehensive understanding of the impact of morphine on compromising macrophage function and its potential ramifications for therapeutic approaches.

Quinoline Derivatives as Promising Scaffolds for Antitubercular Activity: A Comprehensive Review.

BACKGROUND: Heterocyclic compounds and their derivatives play a significant role in the design and development of novel quinoline drugs. Among the various pharmacologically active heterocyclic compounds, quinolines stand out as the most significant rings due to their broad pharmacological roles, specifically antitubercular activity, and their presence in plant-based compounds. Quinoline is characterized by a benzene ring fused to a pyridine ring, with both rings sharing two adjacent carbon atoms. Other names, such as benzpyridine, benzopyridine, and 1-azanaphthalene also know it. The importance of quinoline lies in its incorporation as a key component in various natural compounds found in medicinal plant families like Fumariaceae, Berberidaceae, Rutaceae, Papavaraceae, and others. OBJECTIVE: This article is expected to have a significant impact on the advancement of effective antitubercular medications. Through harnessing the potent activity of quinoline derivatives, the research aims to make valuable contributions to combating tuberculosis more efficiently and ultimately reducing the global burden of this infectious disease. METHODS: Numerous nitrogen-containing heterocyclic compounds exhibit significant potential as antitubercular agents. These chemicals have fused aromatic nitrogen-heterocyclic nuclei that can change the number of electrons they have, which can change their chemical, physical, and biological properties. This versatility arises from their ability to bind to receptors in multiple modes, a critical aspect of drug pharmacological screening. Among these compounds, quinoline stands out as it incorporates a stable fusion of a benzene ring with a pyridine nucleus. Quinolines have demonstrated a diverse range of pharmacological activities, including but not limited to anti-tubercular, antitumor, anticoagulant, anti-inflammatory, antioxidant, antiviral, antimalarial, anti-HIV, and antimicrobial effects. RESULTS: Some molecules, such as lone-paired nitrogen species, include pyrrole, pyrazole, and quinoline. These molecules contain oxygen and take part in metabolic reactions with other molecules inside the cell. However, an excessive accumulation of reactive nitrogen species can lead to cytotoxicity, resulting in damage to essential biological macromolecules. Among these compounds, quinoline stands out as the oldest and most effective one, exhibiting a wide range of beneficial properties such as antitubercular, antimicrobial, anti-inflammatory, antioxidant, analgesic, and anticonvulsant activities. Notably, naturally occurring quinoline compounds, such as quinine, have proven to be potent antimalarial drugs. CONCLUSION: This review highlights quinoline derivatives' antitubercular potential, emphasizing recent research advancements. Utilizing IC50 values, the study underscores the efficacy of various quinoline substitutions, hybrids, and electron-withdrawing groups against MTB H37Rv. Continued research is essential for developing potent, low-toxicity quinoline derivatives to combat tuberculosis.

Green synthesis of silver nanoparticles employing hamdard joshanda extract: putative antimicrobial potential against gram positive and gram negative bacteria.

The bio-mediated synthesis of nanoparticles offers a sustainable and eco-friendly approach. In the present study, silver nanoparticles (AgNPs) were synthesized using Joshanda extract, a commercially available herbal formulation derived from a traditional medicinal plant, as a reducing and stabilizing agent. The as-synthesized AgNPs were characterized using UV-Vis spectroscopy, dynamic light scattering (DLS), X-ray Diffraction (XRD) study, and Fourier-transform infrared (FTIR) analysis. UV-Vis spectroscopy exhibited a prominent absorption peak at 430 nm, confirming the formation of AgNPs. DLS analysis revealed the size distribution of the nanoparticles, ranging from 80 to 100 nm, and zeta potential measurements indicated a surface charge of - 14.4 mV. The XRD analysis provide evidence for the presence of a face-centered cubic structure within the silver nanoparticles. FTIR analysis further elucidated the interaction of bioactive compounds from the Joshanda extract with the AgNPs' surface. Strong peaks at 765-829 cm-1 indicated C-Cl stretching vibrations of alkyl halides, while the stretching of alkenes C=C was observed at 1641 cm-1. Moreover, the presence of alcohols and phenol (OH) groups was identified at 3448 cm-1, suggesting their involvement in nanoparticle stabilization. The antimicrobial potential of the synthesized AgNPs was evaluated against both gram-negative Pseudomonas aeruginosa and gram-positive Streptococcus mutans using zone of inhibition assays. The AgNPs exhibited remarkable inhibitory effects against both types of bacteria. Additionally, AgNPs-treated groups demonstrated a significant increase in reactive oxygen species (ROS) levels, indicating potential of as-synthesized AgNPs in disruption of the target microbial membranes. Furthermore, the as-synthesized AgNPs exhibited notable anti-biofilm properties by effectively hindering the development of mature biofilms. This study highlights the efficient green synthesis of AgNPs using Joshanda extract and also provides insights into their physico-chemical properties of as-synthesized nanoparticles. The demonstrated antimicrobial activity against both gram-negative and gram-positive bacteria, along with biofilm inhibition potential, underscores the promising applications of the as-synthesized AgNPs in the field of biomedical and environmental sciences. The study bridges traditional knowledge with contemporary nanotechnology, offering a novel avenue for the development of eco-friendly antimicrobial agents.

Heavily Ossified Soft Tissue Chondroma of Plantar Foot and the Significance of Radiological Imaging: A Case Report.

Soft tissue chondroma is a relatively rare, slowly growing, benign cartilaginous tumor. This solitary mass can imitate chondrosarcomas in radiologic and histological characteristics. The diagnosis is hard to establish on clinical presentation and relies on careful radiological examination. The lesion is equally prevalent in both genders and primarily affects people in their forties and sixties. They may occur in any part of the body; however, they are most commonly observed in hand and foot. We report the case of a 61-year-old female who presented with heavily ossified soft tissue chondroma within the plantar fascia of her left foot. A conclusive diagnosis was established via histopathological examination. The chondroma was marginally excised, and the postoperative period was uneventful.

Therapeutic Application, Phytoactives and Pharmacology of Tinospora cordifolia: An Evocative Review.

Tinospora cordifolia (Guduchi or Gurjo), a herbaceous vine or climbing deciduous shrub, is consider as an important medicine in the Ayurvedic system of medication, which is available in India, China, Myanmar, Bangladesh and Srilanka. Menispermaceae is the family of this compound. T. cordifolia have a variety of properties to treat various ailments such as fevers, jaundice, diabetes, dysentery, urinary infections, and skin diseases. This compound has been subjected to many chemicals, pharmacological, pre-clinical, or clinical investigations and some new therapeutic potential effects have been indicated. This review aims to summarize the critical information concerning in areas of chemical constituents, chemical structure, and pharmacokinetic activities such as anti-diabetic, anticancer, immune-modulatory, antivirus (especially in silico study about COVID-19), antioxidant, antimicrobial, hepatoprotective and its effect on cardiovascular and neurological disorders as well as rheumatoid arthritis. This traditional herb needs more experimental study on the clinical, pre-clinical study, and clinical efficacy of these compounds for the prevention and treatment of COVID-19 and needs large-scale clinical studies to prove the clinical efficacy of this compound, especially in stress-related diseases and other neuronal disorders.

Potential of siRNA-Bearing Subtilosomes in the Treatment of Diethylnitrosamine-Induced Hepatocellular Carcinoma.

Therapeutics, based on small interfering RNA (siRNA), have demonstrated tremendous potential for treating cancer. However, issues such as non-specific targeting, premature degradation, and the intrinsic toxicity of the siRNA, have to be solved before they are ready for use in translational medicines. To address these challenges, nanotechnology-based tools might help to shield siRNA and ensure its specific delivery to the target site. Besides playing a crucial role in prostaglandin synthesis, the cyclo-oxygenase-2 (COX-2) enzyme has been reported to mediate carcinogenesis in various types of cancer, including hepatocellular carcinoma (HCC). We encapsulated COX-2-specific siRNA in Bacillus subtilis membrane lipid-based liposomes (subtilosomes) and evaluated their potential in the treatment of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Our findings suggested that the subtilosome-based formulation was stable, releasing COX-2 siRNA in a sustained manner, and has the potential to abruptly release encapsulated material at acidic pH. The fusogenic property of subtilosomes was revealed by FRET, fluorescence dequenching, content-mixing assay, etc. The subtilosome-based siRNA formulation was successful in inhibiting TNF-α expression in the experimental animals. The apoptosis study indicated that the subtilosomized siRNA inhibits DEN-induced carcinogenesis more effectively than free siRNA. The as-developed formulation also suppressed COX-2 expression, which in turn up-regulated the expression of wild-type p53 and Bax on one hand and down-regulated Bcl-2 expression on the other. The survival data established the increased efficacy of subtilosome-encapsulated COX-2 siRNA against hepatocellular carcinoma.

A Review of Electrospun Nanofiber Interleaves for Interlaminar Toughening of Composite Laminates.

Recently, polymeric nanofiber veils have gained lot of interest for various industrial and research applications. Embedding polymeric veils has proven to be one of the most effective ways to prevent delamination caused by the poor out-of-plane properties of composite laminates. The polymeric veils are introduced between plies of a composite laminate, and their targeted effects on delamination initiation and propagation have been widely studied. This paper presents an overview of the application of nanofiber polymeric veils as toughening interleaves in fiber-reinforced composite laminates. It presents a systematic comparative analysis and summary of attainable fracture toughness improvements based on electrospun veil materials. Both Mode I and Mode II tests are covered. Various popular veil materials and their modifications are considered. The toughening mechanisms introduced by polymeric veils are identified, listed, and analyzed. The numerical modeling of failure in Mode I and Mode II delamination is also discussed. This analytical review can be used as guidance for veil material selection, for estimation of the achievable toughening effect, for understanding the toughening mechanism introduced by veils, and for the numerical modeling of delamination.

Electrical Heaters for Anti/De-Icing of Polymer Structures.

The problem of icing for surfaces of engineering structures requires attention more and more every year. Active industrialization in permafrost zones is currently underway; marine transport in Arctic areas targets new goals; the requirements for aerodynamically critical surfaces of wind generators and aerospace products, serving at low temperatures, are increasing; and fiber-reinforced polymer composites find wide applicability in these structural applications demanding the problem of anti/de-icing to be addressed. The traditional manufacturing approaches are superimposed with the new technologies, such as 3D printers and robotics for laying heat wires or cheap and high-performance Thermal Sprayed methods for metallic cover manufacturing. Another next step in developing heaters for polymer structures is nano and micro additives to create electrically conductive heating networks within. In our study, we review and comparatively analyze the modern technologies of structure heating, based on resistive heating composites.

Amphotericin B Nano-Assemblies Circumvent Intrinsic Toxicity and Ensure Superior Protection in Experimental Visceral Leishmaniasis with Feeble Toxic Manifestation.

In spite of its high effectiveness in the treatment of both leishmaniasis as well as a range of fungal infections, the free form of the polyene antibiotic amphotericin B (AmB) does not entertain the status of the most preferred drug of choice in clinical settings. The high intrinsic toxicity of the principal drug could be considered the main impedance in the frequent medicinal use of this otherwise very effective antimicrobial agent. Taking into consideration this fact, the pharma industry has introduced many novel dosage forms of AmB to alleviate its toxicity issues. However, the limited production, high cost, requirement for a strict cold chain, and need for parenteral administration are some of the limitations that explicitly compel professionals to look for the development of an alternate dosage form of this important drug. Considering the fact that the nano-size dimensions of drug formulation play an important role in increasing the efficacy of the core drug, we employed a green method for the development of nano-assemblies of AmB (AmB-NA). The as-synthesized AmB-NA manifests desirable pharmacokinetics in the treated animals. The possible mechanistic insight suggested that as-synthesized AmB-NA induces necrosis-mediated cell death and severe mitochondrial dysfunction in L. donovani promastigotes by triggering depolarization of mitochondrial membrane potential. In vivo studies demonstrate a noticeable decline in parasite burden in the spleen, liver, and bone marrow of the experimental BALB/c mice host. In addition to successfully suppressing the Leishmania donovani, the as-formed AmB-NA formulation also modulates the host immune system with predominant Th1 polarization, a key immune defender that facilitates the killing of the intracellular parasite.

Crosstalk between SARS-CoV-2 Infection and Neurological Disorders: A Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent responsible for coronavirus disease (COVID-19), is an issue of global concern since March 2020. The respiratory manifestations of COVID-19 have widely been explained in the last couple of months of the pandemic. Initially, the virus was thought to be restricted to the pulmonary system; however, as time progressed and cases increased during the second wave of COVID-19, the virus affected other organs, including the nervous system. The neurological implication of SARS-CoV-2 infection is mounting, as substantiated by various reports, and in the majority of COVID-19 patients with neurological symptoms, the penetration of SARS-CoV-2 in the central nervous system (CNS) is likely. SARS-CoV-2 can enter the nervous system by exploiting the routes of olfactory mucosa, olfactory and sensory nerve endings, or endothelial and nerve tissues, thus crossing the neural-mucosal interface in the olfactory mucosa in the nose. Owing to multifactorial and complex pathogenic mechanisms, COVID-19 adds a large-scale risk to the entire nervous system. A thorough understanding of SARSCoV- 2 neurological damage is still vague; however, our comprehension of the virus is rapidly developing. The present comprehensive review will gain insights and provide neurological dimensions of COVID-19 and their associated anomalies. The review presents the entry routes of SARS-CoV-2 into the CNS to ascertain potential targets in the tissues owing to infection. We also discuss the molecular mechanisms involved, the array of clinical symptoms, and various nervous system diseases following the attack of SARS-CoV-2.

Metal Release and Cytotoxicity of Different Orthodontic Bracket-Wire Combinations: An In Vitro Study.

Aim: To quantify and compare the metal ions released from different bracket-wire combinations and to assess their cytotoxicity. Materials and Methods: A total of 360 fabricated sectional fixed orthodontic appliances were divided into 6 groups. The first three groups consisted of stainless-steel brackets with stainless-steel, snickel-titanium (NiTi), and titanium-molybdenum alloy (TMA) archwires, and the other three groups were fabricated using ceramic brackets (polycrystalline alumina) with stainless-steel, NiTi, and TMA archwires. These appliances were immersed in artificial saliva (pH 6.5 ± 0.5, 37°C), for 1 week, 2 weeks, and 1 month. The nickel and chromium ions released in the artificial saliva were quantified using a flame atomic absorption spectrometer, and cytotoxicity assessment was performed using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay on human cervical cancer cell line. Results: The stainless-steel bracket groups displayed a significantly greater release of nickel and chromium ions compared to the ceramic bracket groups (P < 0.05). However, no significant differences were identified when comparing the three archwire types within the stainless-steel/ceramic bracket groups. At the end of 1 month, the % cell viability demonstrated by the appliances was in the decreasing order of stainless-steel-TMA > ceramic-stainless steel > stainless-steel-NiTi > ceramic-NiTi > stainless-steel-stainless steel > ceramic-TMA. Conclusion: Considerably greater release of nickel and chromium ions was observed from the appliances utilizing stainless-steel brackets compared to those employing ceramic brackets. However, no remarkable difference in the levels of nickel and chromium ions was observed when comparing the three archwires: stainless steel, NiTi, and TMA. In the cytotoxicity assessment, the ceramic-TMA combination displayed the highest level of cytotoxicity, while the stainless-steel-TMA combination displayed the least cytotoxicity.

ANCA-Negative EGPA With Pulmonary, Cutaneous, and Neurological Manifestations in a 25-Year-Old Male: A Case Report.

Eosinophilic granulomatosis with polyangiitis is a systemic vasculitis characterized by the presence of asthma, hyper-eosinophilia, and necrotizing vasculitis with extravascular eosinophilic granulomas. We report the case of a 25-year-old male who presented to the outpatient department complaining of joint aches and numbness in the hands and legs. Physical examination revealed erythematous blanchable macular rashes on palms and soles. Raynaud's phenomenon was also observed. Lab workup revealed elevated WBC count and peripheral blood eosinophilia. Antibody tests were positive only for anti-nuclear antibodies. A diagnosis of eosinophilic granulomatosis with polyangiitis including peripheral neuropathy, arthralgia, rash, and pulmonary manifestations was established. The patient was started on a therapeutic regimen of corticosteroids and immunosuppressants, which halted the progression of the disease. Peripheral neuropathy and arthralgia also improved.

Schwannoma of the Ascending Colon in a 22-Year-Old Male: A Case Report.

Schwannoma of the ascending colon is an extremely rare neoplasm that is often discovered incidentally in the asymptomatic older population on surveillance colonoscopy. We present the case of a symptomatic 22-year-old male presenting with one month of discomfort in the right lower abdominal quadrant, abdominal bloating, and hematochezia. A sessile polyp measuring 0.5 cm was identified in the ascending colon on the colonoscopy. The polyp was completely resected using cold snare polypectomy. Histological examination of the resected polyp with hematoxylin-eosin staining revealed small nodules of bland spindle cells with focal nuclear condensation. The lesional cells tested positive for S-100 and SOX-10 on immunohistochemical analysis, establishing the diagnosis of benign schwannoma. Since this lesion was submucosal, its diagnosis required an endoscopic biopsy that could only be performed on the mucosa. It was difficult to distinguish it from other mesenchymal tumors (gastrointestinal stromal tumor or leiomyoma), and this makes the differential diagnosis exceedingly challenging. If the immunohistochemistry is positive for S-100 and negative for C-KIT, CD-34, actin, and desmin, it aids in diagnosis. These tumors have non-specific radiological features and are asymptomatic.

Recent Studies on Thermally Conductive 3D Aerogels/Foams with the Segregated Nanofiller Framework.

As technology advances toward ongoing circuit miniaturization and device size reduction followed by improved power density, heat dissipation is becoming a key challenge for electronic equipment. Heat accumulation can be prevented if the heat from electrical equipment is efficiently exported, ensuring a device's lifespan and dependability and preventing otherwise possible mishaps or even explosions. Hence, thermal management applications, which include altering the role of aerogels from thermally insulative to thermally conductive, have recently been a hot topic for 3D-aerogel-based thermal interface materials. To completely comprehend three-dimensional (3D) networks, we categorized and comparatively analyzed aerogels based on carbon nanomaterials, namely fibers, nanotubes, graphene, and graphene oxide, which have capabilities that may be fused with boron nitride and impregnated for better thermal performance and mechanical stability by polymers, including epoxy, cellulose, and polydimethylsiloxane (PDMS). An alternative route is presented in the comparative analysis by carbonized cellulose. As a result, the development of structurally robust and stiff thermally conductive aerogels for electronic packaging has been predicted to increase polymer thermal management capabilities. The latest trends include the self-organization of an anisotropic structure on several hierarchical levels within a 3D framework. In this study, we highlight and analyze the recent advances in 3D-structured thermally conductive aerogels, their potential impact on the next generation of electronic components based on advanced nanocomposites, and their future prospects.

Illuminating the Molecular Intricacies of Exosomes and ncRNAs in Cardiovascular Diseases: Prospective Therapeutic and Biomarker Potential.

Cardiovascular diseases (CVDs) are one of the leading causes of death worldwide. Accumulating evidences have highlighted the importance of exosomes and non-coding RNAs (ncRNAs) in cardiac physiology and pathology. It is in general consensus that exosomes and ncRNAs play a crucial role in the maintenance of normal cellular function; and interestingly it is envisaged that their potential as prospective therapeutic candidates and biomarkers are increasing rapidly. Considering all these aspects, this review provides a comprehensive overview of the recent understanding of exosomes and ncRNAs in CVDs. We provide a great deal of discussion regarding their role in the cardiovascular system, together with providing a glimpse of ideas regarding strategies exploited to harness their potential as a therapeutic intervention and prospective biomarker against CVDs. Thus, it could be envisaged that a thorough understanding of the intricacies related to exosomes and ncRNA would seemingly allow their full exploration and may lead clinical settings to become a reality in near future.

Exosome-encapsulated ncRNAs: Emerging yin and yang of tumor hallmarks.

Tumorigenesis is a multifaceted process, where multiple physiological traits serving as cancer's distinctive characteristics are acquired. "Hallmarks of cancer" is a set of cognitive abilities acquired by human cells that are pivotal to their tumor-forming potential. With limited or no protein-coding ability, non-coding RNAs (ncRNAs) interact with their target molecules and yield significant regulatory effects on several cell cycle processes. They play a "yin" and "yang" role, thereby functioning both as oncogenic and tumor suppressor and considered important in the management of various types of cancer entities. ncRNAs serve as important post-transcriptional and translational regulators of not only unrestricted expansion and metastasis of tumor cells but also of various biological processes, such as genomic mutation, DNA damage, immune escape, and metabolic disorder. Dynamical attributes such as increased proliferative signaling, migration, invasion, and epithelial-mesenchymal transition are considered to be significant determinants of tumor malignancy, metastatic dissemination, and therapeutic resistance. Furthermore, these biological attributes engage tumor cells with immune cells within the tumor microenvironment to promote tumor formation. We elaborate the interaction of ncRNAs with various factors in order to regulate cancer intra/intercellular signaling in a specific tumor microenvironment, which facilitates the cancer cells in acquiring malignant hallmarks. Exosomes represent a means of intercellular communication and participate in the maintenance of the tumor hallmarks, adding depth to the intricate, multifactorial character of malignant neoplasia. To summarize, ncRNAs have a profound impact on tumors, affecting their microcirculation, invasiveness, altered metabolism, microenvironment, and the capacity to modify the host immunological environment. Though the significance of ncRNAs in crosstalk between the tumor and its microenvironment is being extensively explored, we intend to review the hallmarks in the light of exosome-derived non-coding RNAs and their impact on the tumor microenvironment.

Synthesis of steroidal dihydropyrazole derivatives using green ZnO NPs and evaluation of their anticancer and antioxidant activity.

Zinc oxide nanoparticles (ZnO NPs) were synthesized by a green method using Azadirachta indica leaf extract. The structure of the prepared ZnO (NPs) were characterized by FT-IR, XRD, SEM-EDX and TEM analyses. The biosynthesized ZnO (NPs) were then used as a catalyst for the synthesis of steroidal dihydropyrazole derivatives through a one-pot multicomponent reaction involving phenyl acetylene and hydrazine derivatives. The anticancer activity of newly synthesized compounds were evaluated against three cancer cell lines namely HeLa (human cervical carcinoma), Hep3B (human hepatocellular carcinoma) and MCF7 (human breast adenocarcinoma) by MTT assay. The tested compounds were found to be active against all cancer cell lines and less toxic towards normal peripheral blood mononuclear cells (PBMCs). Antioxidant activity have also been investigated via free radical scavenging ability using DPPH, FRAP and ABTS assay. The tested compounds were found to exhibit moderate to good antioxidant activity which increases with increase in the concentration of steroidal dihydropyrazoles. Among all the tested steroidal dihydropyrazoles, compound 17 is found to be most active.

Effect of Date Palm (Phoenix dactylifera) Phytochemicals on Aß1-40 Amyloid Formation: An in-silico Analysis.

Alzheimer's disease (AD) is a neurodegenerative disease and the most prevalent form of dementia. The generation of oxygen free radicals and oxidative damage is believed to be involved in the pathogenesis of AD. It has been suggested that date palm, a plant rich in phenolic compounds and flavonoids, can provide an alternative treatment to fight memory loss and cognitive dysfunction due to its potent antioxidant activity. Thus, we studied the effect of flavonoids present in date palm on Aß1-40 amyloid formation using molecular docking and molecular dynamics simulation. AutoDock. Myricetin was used as a positive control drug. The flavonoids Diosmetin, Luteolin, and Rutin were found to be potent inhibitors of aggregation (docking energies ≤ -8.05 kcal mol-1) targeting Aß1-40 fibrils (both 2LMO and 6TI5), simultaneously. Further screening by physicochemical properties and drug-likeness analysis suggested that all flavonoids except Rutin followed Lipinski's rule of five. Rutin was, thus, taken as a negative control (due to its violation of Lipinski's rule) to compare its dynamics with Diosmetin. Diosmetin exhibited the highest positive scores for drug likeness. Since Luteolin exhibited moderate drug-likeness and better absorption properties, it was also included in molecular dynamics simulation. Molecular dynamics of shortlisted compounds (Rutin, Diosmetin, and Luteolin) were performed for 200 ns, and the results were analyzed by monitoring root mean square deviations (RMSD), root mean square fluctuation (RMSF) analysis, the radius of gyration (Rg), and solvent accessible surface area (SASA). The results proved the formation of a stable protein-compound complex. Based on binding energies and non-bonded interactions, Rutin and Luteolin emerged as better lead molecules than Diosmetin. However, high MW (610.5), lowest absorption rate (16.04%), and more than one violation of Lipinski's rule make Rutin a less likely candidate as an anti-amyloidogenic agent. Moreover, among non-violators of Lipinski's rule, Diosmetin exhibited a greater absorption rate than Luteolin as well as the highest positive scores for drug-likeness. Thus, we can conclude that Diosmetin and Luteolin may serve as a scaffold for the design of better inhibitors with higher affinities toward the target proteins. However, these results warrant in-vitro and in-vivo validation before practical use.

Scalable Fabrication of Thermally Conductive Layered Nacre-like Self-Assembled 3D BN-Based PVA Aerogel Framework Nanocomposites.

In this study, three-dimensional (3D) polyvinyl alcohol (PVA)/aligned boron nitride (BN) aerogel framework nanocomposites with high performance were fabricated by a facile strategy. The boron nitride powder was initially hydrolyzed and dispersed with a chemically crosslinked plasticizer, diethyl glycol (DEG), in the PVA polymer system. The boron nitride and DEG/PVA suspensions were then mixed well with different stoichiometric ratios to attain BN/PVA nanocomposites. Scanning electron microscopy revealed that BN platelets were well dispersed and successfully aligned/oriented in one direction in the PVA matrix by using a vacuum-assisted filtration technique. The formed BN/PVA aerogel cake composite showed excellent in-plane and out-of-plane thermal conductivities of 0.76 W/mK and 0.61 W/mK with a ratio of BN/PVA of (2:1) in comparison with 0.15 W/mK for the pure PVA matrix. These high thermal conductivities of BN aerogel could be attributed to the unidirectional orientation of boron nitride nanoplatelets with the post-two days vacuum drying of the specimens at elevated temperatures. This aerogel composite is unique of its kind and displayed such high thermal conductivity of the BN/PVA framework without impregnation by any external polymer. Moreover, the composites also presented good wettability results with water and displayed high electrical resistivity of ~1014 Ω cm. These nanocomposites thus, with such exceptional characteristics, have a wide range of potential uses in packaging and electronics for thermal management applications.

Mucormycosis and COVID-19 pandemic: Clinical and diagnostic approach.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is yet to be controlled worldwide, especially in India. The second wave of coronavirus disease 2019 (COVID-19) led to panic and confusion in India, owing to the overwhelming number of the population that fell prey to this highly infectious virus of recent times. In the second wave of COVID-19, the patients had to fight both the virus and opportunistic infections triggered by fungi and bacteria. Repeated use of steroids, antibiotics, and oxygen masks during the management of severely and critically ill COVID-19 patients nurtured opportunistic infections such as mucormycosis. Despite mucormycosis being a decades-old disease, it has gained notice of its widespread occurrence in COVID-19 patients throughout India. Instances of mucormycosis are usually unearthed in immunocompromised individuals and are caused by the inhalation of filamentous fungi, either from the natural environment or through supportive care units. In the recent outbreak during the second wave of COVID-19 in India, it has been seen to cause secondary infection as it grows along with the treatment of COVID-19. Furthermore, COVID-19 patients with comorbidities such as diabetes were more likely to have the mucormycosis co-infection because of their challenged immune systems' inability to fight it. Despite the hype, mucormycosis still remains neglected and least studied, which is predominantly due to all focus on diagnostics, vaccine, and therapeutic research. In this review, we emphasize mainly on the association of mucormycosis in COVID-19 patients. We also present the molecular mechanism of mucormycosis for a better understanding of the fungal infections in patients who have recently been infected with SARS-CoV-2. Better understanding of fungal pathogens, immediate diagnosis, and management of the infections are crucial in COVID-19 patients, as high mortalities have been recorded in co-infected patients despite recovery from COVID-19.