Revealing the Mechanism Underlying 3D-AFM Imaging of Suspended Structures by Experiments and Simulations.

The invention of 3D atomic force microscopy (3D-AFM) has enabled visualizing subnanoscale 3D hydration structures. Meanwhile, its applications to imaging flexible molecular chains have started to be experimentally explored. However, the validity and principle of such imaging have yet to be clarified by comparing experiments and simulations or cross-observations with an alternative technique. Such studies are impeded by the lack of an appropriate model. Here, this difficulty is overcome by fabricating 3D carbon nanotube (CNT) structures flexible enough for 3D-AFM, large enough for scanning electron microscopy (SEM), and simple enough for simulations. SEM and 3D-AFM observations of the same model provide unambiguous evidence to support the possibility of imaging overlapped nanostructures, such as suspended CNT and underlying platinum (Pt) nanodots. Langevin dynamics simulations of such 3D-AFM imaging clarify the imaging mechanism, where the flexible CNT is laterally displaced to allow the AFM probe access to the underlying structures. These results consistently show that 3D-AFM images are affected by the friction between the CNT and AFM nanoprobe, yet it can be significantly suppressed by oscillating the cantilever. This study reinforces the theoretical basis of 3D-AFM for imaging various 3D self-organizing systems in diverse fields, from life sciences to interface sciences.

Resurgence of Dengue Virus Serotype 2: Findings from the 2023 Bangladesh Outbreak.

Bangladesh experienced the largest and deadliest dengue outbreak in 2023, after the virus had reappeared in the country 2 decades earlier. A total of 1,705 people died in Bangladesh, representing the highest case fatality rate (0.5%) due to dengue in the world for that year. The severity of dengue infection is to some extent related to the emergence of new circulating serotypes. To identify the possible predominant serotype in 2023, the reverse transcription polymerase chain reaction-based identification technique was used on stored serum samples of suspected dengue patients during the period between July and December 2023. The overall result of molecular serotyping showed that dengue virus (DENV-2) reappeared as the predominant serotype (74.1%), followed by a moderate number of samples with DENV-1 (19.8%) and DENV-3 (6.1%), in 2023. However, DENV-1 was found to be dominant in a few rural areas of Cox's Bazar districts. During the 2019 outbreak, DENV-3 was the dominant serotype, which seemed to be replaced by the DENV-2 serotype; this may have impacted the increased case fatality in 2023.

Human health risk assessment of heavy metals in vegetables of Bangladesh.

This study aims to evaluate the heavy metal concentration in fifteen species of vegetables as well as associated health risk. Atomic absorption spectrometry is used to assess heavy metals. The mean concentrations of Pb, Cd, Cr, Ni and Fe in vegetables were 4.78, 0.713, 9.266, 0.083, 5.06 mg/kg/fw exceeding the reference value of FAO/WHO indicating unsafe to consumption. Based on principal component analysis, the Pb, Cr, Ni and Fe are from same sources. Health risk was estimated in terms of estimated daily intake (EDI), target hazard quotient, hazard index (HI) and cancer risk (CR). The EDI values of metals except Cr were found to be lower than maximum tolerable daily intake (MTDI). The total THQs of metals were > 1 indicating non-carcinogenic health risk. The individual HI values for vegetables except potato (0.831) and total HI values were found to be > 1 (94.747). The TCR of Pb, Cd and Cr were > 1.0E-04 which indicating carcinogenic risk. Fruit and pod vegetables contribute much in carcinogenic risk for Pb and Cr whereas fruit, root and stems vegetables for Cd. The study revealed potential human health risk associated with the consumption of different types of vegetables in Bangladeshi adult population that might assist the regulatory bodies to develop new strategies to minimize the risk to human.

Collision Tumor of the Ovary: Adult Granulosa Cell Tumor and Mesonephric-like Adenocarcinoma.

Collision tumors of the ovaries are rare, with only a few reports in the literature. Adult granulosa cell tumors are a relatively common primary tumor component of previously reported collision tumors. The combination of serous and mucinous tumors with adult granulosa cell tumors has been reported in several cases. On the other hand, mesonephric-like adenocarcinomas are rare neoplasms that commonly arise in the uterine corpus and ovaries. In this report, we present the case of a collision tumor composed of an adult granulosa cell tumor and mesonephric-like adenocarcinoma of the ovary in a 63-year-old woman. The initial magnetic resonance imaging findings showed a cystic mass with an internal hemorrhage, which suggested an adult granulosa cell tumor, and a solid mass with different enhancements. Microscopically, the tumor had two distinct components: An adult granulosa cell tumor and a mesonephric-like adenocarcinoma. Recognizing collision tumors consisting of slow-growing and aggressive tumors may prove beneficial in future diagnostic and treatment strategies.

Model simplification and sensitivity analysis of chemical species for oxidation behavior in multi route complex chemical mechanism.

This study employs a Model Reduction Technique (MRT) to simplify the four-step catalytic carbon monoxide (CO) oxidation reaction. The C-matrix method identifies key elements, key/non key components, and key reactions, while the Intrinsic Low-Dimensional Manifold (ILDM) pinpoints a Slow-Invariant Manifold (SIM) important for understanding key species behavior. Sensitivity analysis can be considered for measuring the efficiency of the chemical species in detailed mechanism. This systematic approach contributes to optimizing and controlling complex reactions offering broad application potential. In addition to the mathematical proof, the validation of the given chemical model is rectified. The comparison between the slow invariant manifold of both reaction routes is reported and the computational based results performed in this study are obtained through MATLAB.

Effectiveness of ultrasonography in the diagnosis of temporomandibular joint disorders: A systematic review and meta-analysis.

BACKGROUND: Temporomandibular disorders (TMDs) pose diagnostic challenges, and selecting appropriate imaging modalities is crucial for accurate assessment. This study aimed to compare the diagnostic accuracy and efficacy of ultrasonography (US) and magnetic resonance imaging (MRI) in identifying TMDs. METHODS: A comprehensive meta-analysis was conducted, including studies that compared US and MRI for TMJ disorder assessments. Fixed-effects models were utilized to calculate pooled odds ratios (ORs) and relative risks (RRs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the chi-squared test and I2 statistic. Newcastle-Ottawa scale was used to assess the methodological quality of the studies included. RESULTS: Six studies were included, involving a total of 281 participants. The meta-analysis demonstrated that MRI was statistically somewhat better than US in identifying TMJ disorders. The summary OR was 0.64 (95% CI: 0.46-0.90), and the summary RR was 0.80 (95% CI: 0.68-0.95). Heterogeneity among the studies was low (χ2 = 2.73, df = 5, p = .74; I2 = 0%). Demographic variables revealed variations in sample size, gender ratio and mean age across the studies. CONCLUSION: This meta-analysis provides evidence that MRI may be more effective than US in diagnosing TMDs. However, the study is limited by the small number of included studies and variations in demographic variables and study designs. Future research with larger samples and standardised protocols is essential to confirm and strengthen these findings. Understanding the diagnostic accuracy of MRI and US for TMJ disorders will aid clinicians in making informed decisions for effective TMJ disorder assessments and patient management.

Patient Satisfaction Following Orthodontic Treatment: A Systematic Review.

Patient-reported outcome measures (PROMs) have become increasingly important in orthodontic treatment as they reflect patients' perceptions of treatment outcomes. Understanding patient satisfaction with orthodontic treatment is crucial for improving healthcare delivery and patient-centered care. This systematic review aimed to critically appraise the evidence regarding patient satisfaction after orthodontic treatment, exploring the effects of different treatment types, patient demographics, and other factors on satisfaction levels. Eight electronic bibliographic databases were searched without publication time or language restrictions, including PubMed®, Scopus®, the Cochrane Central Register of Controlled Trials, Web of Science™, Embase®, Google™ Scholar, Trip, and OpenGrey. A manual search was conducted on the references in the included papers. Eligibility criteria were established based on the Population, Intervention, Comparison, Outcomes, and Study (PICOS) framework. Studies were included if they reported patient satisfaction levels following orthodontic treatment using standardized questionnaires. Two reviewers independently collected and analyzed the data. The risk of bias was assessed using Cochrane's risk of bias tool (RoB2) for randomized clinical trials, and the methodologic quality for cohort and cross-sectional studies was assessed using the modified version of the Newcastle-Ottawa scale. Fourteen studies employed various questionnaires and timings to gauge post-orthodontic treatment satisfaction. Patient satisfaction levels were generally high, with most studies reporting satisfaction rates above 91%. Fixed orthodontic appliances were associated with higher satisfaction levels compared to removable appliances. While age and gender did not significantly influence satisfaction, the quality of care and doctor-patient relationships were crucial factors in patient satisfaction. This systematic review proves that patient satisfaction with orthodontic treatment is generally high, with fixed appliances and positive doctor-patient relationships contributing to higher satisfaction levels. However, the quality of the evidence was moderate to low, highlighting the need for further high-quality clinical studies in this area.

Haemonchus contortus, an obligatory haematophagus worm infection in small ruminants: Population genetics and genetic diversity.

Haemonchus contortus, a stomach worm, is prevalent in ruminants worldwide. They particularly hamper profitable small ruminant production. Here, we estimate the genetic variation of H. contortus collected from slaughtered goats and sheep from various geographic zones of Bangladesh using multiple genes. To perform this, adult parasites were isolated from the abomasum of slaughtered animals (sheep and goats). Among them, 79 male H. contortus were identified by microscopy. Following the extraction of DNA, ITS-2 and cox1 genes were amplified and subsequently considered for sequencing. After alignment and editing, sequences were analyzed to find out sequence variation, diversity pattern of genes, and population genetics of isolates. Among the sequence data, the analyses identified 19 genotypes of ITS-2 and 77 haplotypes of cox1 genes. The diversity of nucleotides was 0.0103 for ITS-2 and 0.029 for cox1 gene. The dendogram constructed by the genotype and haplotype sequences of H. contortus revealed that two populations were circulating in Bangladesh without any demarcation of host and geographic regions. Analysis of population genetics demonstrated a high flow of genes (89.2 %) within the population of the worm in Bangladesh. The Fst value showed very little amount of genetic difference among the worm populations of Bangladesh but marked genetic variation between different continents. The findings are expected to help explain the risks of anthelmintic resistance and the transmission pattern of the parasite, and also provide a control strategy against H. contortus.

Knowledge and attitude regarding obstructive sleep apnoea among medical and dental practitioners working in North-Eastern Peninsular Malaysia: A comparative cross-sectional study.

BACKGROUND: Obstructive Sleep Apnea (OSA) is a temporary airflow obstruction during periods of sleep. Patients with OSA often suffer from poor work performance, compromised sleep quality, and low quality of life which may lead to a life-threatening event. Adequate knowledge and a positive attitude toward OSA among medical and dental practitioners are crucial to the initial diagnosis and treatment. OBJECTIVE: This study aimed to identify the differences in knowledge and attitude toward OSA between medical and dental practitioners working in North-Eastern Peninsular Malaysia. METHODS: A comparative cross-sectional study was performed from February 2020 to February 2021. A total of fifty-two medical practitioners and fifty-two dental practitioners working at university-based outpatient clinics, government health clinics, and oral health clinics located in Kelantan State of Malaysia participated in the study, and data were collected by the structured questionnaire including sociodemographic inquiry and OSAKA questionnaire by non-probability stratified random sampling. The Mann-Whitney U test was used to compare knowledge and attitude scores between the two groups. RESULTS: The mean age of the respondents was 34.6 years. The current study shows that 92.3% of medical doctors and 96.1% of dental doctors were able to correctly answer the question "Most of the patients with OSA snore" a significant finding in our study. Only 1% of medical professionals could answer seventeen questions correctly with a median score of 11, and only 1% of dental professionals could answer sixteen questions correctly with a median score of 9. None of them could provide an accurate answer to all the knowledge questions. Medical and dental practitioners exhibited different knowledge levels on OSA (z- statistics=-4.39, U = 827.00 with p <  0.05, and effect size, r = 0.61). However, no significant differences were found in total knowledge score by gender (p-value>0.05), ethnicity (p-value>0.05), total service years (p-value>0.05), and training attended. In addition, significant differences in attitude levels between medical and dental practitioners have been observed (z-statistics=-3.42, U = 725.00 with p <  0.05, and effect size, r = 0.47). Nevertheless, no significant differences have been seen in total attitude score by ethnicity (p-value >  0.05), total service years (p-value >  0.05), attending training on OSA (p-value >  0.05), and professional status (p-value >  0.05) except gender (p-value <  0.05). CONCLUSION: A Significant difference is evident concerning knowledge and attitude toward OSA diagnosis and management between medical and dental practitioners working in North-Eastern Peninsular Malaysia. Medical practitioners in this study recorded a higher knowledge and attitude score compared to dental practitioners.

Complete mitogenome and intra-family comparative mitogenomics showed distinct position of Pama Croaker Otolithoides pama.

The Pama Croaker, Otolithoides pama, is an economically important fish species in Bangladesh. Intra-family similarities in morphology and typical barcode sequences of cox1 create ambiguities in its identification. Therefore, morphology and the complete mitochondrial genome of O. pama, and comparative mitogenomics within the family Sciaenidae have been studied. Extracted genomic DNA was subjected to Illumina-based short read sequencing for De-Novo mitogenome assembly. The complete mitogenome of O. pama (Accession: OQ784575.1) was 16,513 bp, with strong AC biasness and strand asymmetry. Relative synonymous codon usage (RSCU) among 13 protein-coding genes (PCGs) of O. pama was also analyzed. The studied mitogenomes including O. pama exhibited consistent sizes and gene orders, except for the genus Johnius which possessed notably longer mitogenomes with unique gene rearrangements. Different genetic distance metrics across 30 species of Sciaenidae family demonstrated 12S rRNA and the control region (CR) as the most conserved and variable regions, respectively, while most of the PCGs undergone a purifying selection. Different phylogenetic trees were congruent with one another, where O. pama was distinctly placed. This study would contribute to distinguishing closely related fish species of Sciaenidae family and can be instrumental in conserving the genetic diversity of O. pama.

Tilting and Distortion in the Multiferroic Aurivillius Phase Bi6Ti3Fe1.5Mn0.5O18.

Aurivillius structured Bi6Ti3Fe1.5Mn0.5O18 (B6TFMO) has emerged as a rare room temperature multiferroic, exhibiting reversible magnetoelectric switching of ferroelectric domains under cycled magnetic fields. This layered oxide presents exceptional avenues for advancing data storage technologies owing to its distinctive ferroelectric and ferrimagnetic characteristics. Despite its immense potential, a comprehensive understanding of the underlying mechanisms driving multiferroic behavior remains elusive. Herein, we employ atomic resolution electron microscopy to elucidate the interplay of octahedral tilting and atomic-level structural distortions within B6TFMO, associating these phenomena with functional properties. Fundamental electronic features at varying bonding environments within this complex system are scrutinized using electron energy loss spectroscopy (EELS), revealing that the electronic nature of the Ti4+ cations within perovskite BO6 octahedra is influenced by position within the Aurivillius structure. Layer-by-layer EELS analysis shows an ascending crystal field splitting (Δ) trend from outer to center perovskite layers, with an average increase in Δ of 0.13 ± 0.06 eV. Density functional theory calculations, supported by atomic resolution polarization vector mapping of B-site cations, underscore the correlation between the evolving nature of Ti4+ cations, the extent of tetragonal distortion and ferroelectric behavior. Integrated differential phase contrast imaging unveils the position of light oxygen atoms in B6TFMO for the first time, exposing an escalating degree of octahedral tilting toward the center layers, which competes with the magnitude of BO6 tetragonal distortion. The observed octahedral tilting, influenced by B-site cation arrangement, is deemed crucial for juxtaposing magnetic cations and establishing long-range ferrimagnetic order in multiferroic B6TFMO.

Black Seed Oil-Based Curcumin Nanoformulations Ameliorated Cuprizone-Induced Demyelination in the Mouse Hippocampus.

Multiple sclerosis (MS) is a neurodegenerative disease characterized by the demyelination of nerves, axonal damage, and neuroinflammation. Cognition impairment, pain, and loss of mobility are some of the usual complications of MS. It has been postulated that the overproduction of proinflammatory cytokines and reactive oxygen species (ROS) are the main factors that contribute to MS pathology. Among various animal models, the cuprizone model is the most widely used model for investigating MS-related pathology. We assessed the effects of cuprizone along with the protective effects of some black seed oil-based nanoformulations of curcumin with and without piperine, in mice hippocampus in terms of the changes in antioxidant enzymes, transcription factors, and cytokines during demyelination and remyelination processes. The results of behavioral studies point toward impairment in working memory following the feeding of cuprizone for 5 weeks. However, in treatment groups, mice seemed to prevent the toxic effects of cuprizone. Nanoformulations used in this study were found to be highly effective in lowering the amount of ROS as indicated by the levels of antioxidant enzymes like catalase, superoxide dismutase, glutathione, and glutathione peroxidase. Moreover, nanoformulations CCF and CCPF were observed resisting the toxic effects of cuprizone. We observed greater expression of NFκB-p65 in the CPZ group than in the control group. CCF nanoformulation had a better inhibitory effect on NFκB-p65 than other formulations. Histological examination of the hippocampus was also conducted. Nanoformulations used here were found effective in reversing MS-related pathophysiology and hence have the potential to be applied as adjuvant therapy for MS treatment.

Efficient Synthesis of Thiazole-Fused Bisnoralcohol Derivatives as Potential Therapeutic Agents.

Thiazole derivatives are known for a wide range of therapeutic properties. Bisnoralcohol is an inexpensive natural product obtained by the biodegradation of sterols. This article describes an efficient synthesis of a library of thiazole-fused bisnoralcohol derivatives. These novel compounds have been studied for their antineoplastic and antibacterial properties, which led to the discovery of hit compounds with therapeutic potential. The antibacterial compound is noncytotoxic and nonhemolytic against cancer cell lines and sheep red blood cells, respectively. Several of the antineoplastic compounds showed activity against human cancer cell lines with growth inhibition at submicromolar concentration.

Mechanistic insight into the mode of inhibition of dietary flavonoids; targeting macrophage migration inhibitory factor.

Introduction: The Macrophage Migration Inhibitory Factor (MIF), a key pro-inflammatory mediator, is responsible for modulating immune responses. An array of inflammatory and autoimmune diseases has been linked to the dysregulated activity of MIF. The significance in physiological as well as pathophysiological phenomena underscores the potential of MIF as an attractive target with pharmacological relevance. Extensive research in past has uncovered a number of inhibitors, while the ISO-1, or (S, R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester being recognized as a benchmark standard so far. Recent work by Yang and coworkers identified five promising dietary flavonoids, with superior activity compared to the standard ISO-1. Nevertheless, the exact atomic-level inhibitory mechanism is still elusive. Methods: To improve the dynamic research, and rigorously characterize, and compare molecular signatures of MIF complexes with ISO-1 and flavonoids, principal component analysis (PCA) was linked with molecular dynamics (MD) simulations and binding free energy calculations. Results: The results suggest that by blocking the tautomerase site these small molecule inhibitors could modify the MIF activity by disrupting the intrinsic dynamics in particular functional areas. The stability matrices revealed the average deviation values ranging from 0.27-0.32 nm while the residue level fluctuations indicated that binding of the selected flavonoids confer enhanced stability relative to the ISO-1. Furthermore, the gyration values extracted from the simulated trajectories were found in the range of 1.80-1.83 nm. Discussion: Although all the tested flavonoids demonstrated remarkable results, the one obtained for the potent inhibitors, particularly Morin and Amentoflavone exhibited a good correlation with biological activity. The PCA results featured relatively less variance and constricted conformational landscape than others. The stable ensembles and reduced variation in turns might be the possible reasons for their outstanding performance documented previously. The results from the present exploration provide a comprehensive understanding of the molecular complexes formed by flavonoids and MIF, shedding light on their potential roles and impacts. Future studies on MIF inhibitors may benefit from the knowledge gathered from this investigation.

Improved Diagnostic Accuracy of Thyroid Fine-Needle Aspiration Cytology with Artificial Intelligence Technology.

Background: Artificial intelligence (AI) is increasingly being applied in pathology and cytology, showing promising results. We collected a large dataset of whole slide images (WSIs) of thyroid fine-needle aspiration cytology (FNA), incorporating z-stacking, from institutions across the nation to develop an AI model. Methods: We conducted a multicenter retrospective diagnostic accuracy study using thyroid FNA dataset from the Open AI Dataset Project that consists of digitalized images samples collected from 3 university hospitals and 215 Korean institutions through extensive quality check during the case selection, scanning, labeling, and reviewing process. Multiple z-layer images were captured using three different scanners and image patches were extracted from WSIs and resized after focus fusion and color normalization. We pretested six AI models, determining Inception ResNet v2 as the best model using a subset of dataset, and subsequently tested the final model with total datasets. Additionally, we compared the performance of AI and cytopathologists using randomly selected 1031 image patches and reevaluated the cytopathologists' performance after reference to AI results. Results: A total of 10,332 image patches from 306 thyroid FNAs, comprising 78 malignant (papillary thyroid carcinoma) and 228 benign from 86 institutions were used for the AI training. Inception ResNet v2 achieved highest accuracy of 99.7%, 97.7%, and 94.9% for training, validation, and test dataset, respectively (sensitivity 99.9%, 99.6%, and 100% and specificity 99.6%, 96.4%, and 90.4% for training, validation, and test dataset, respectively). In the comparison between AI and human, AI model showed higher accuracy and specificity than the average expert cytopathologists beyond the two-standard deviation (accuracy 99.71% [95% confidence interval (CI), 99.38-100.00%] vs. 88.91% [95% CI, 86.99-90.83%], sensitivity 99.81% [95% CI, 99.54-100.00%] vs. 87.26% [95% CI, 85.22-89.30%], and specificity 99.61% [95% CI, 99.23-99.99%] vs. 90.58% [95% CI, 88.80-92.36%]). Moreover, after referring to the AI results, the performance of all the experts (accuracy 96%, 95%, and 96%, respectively) and the diagnostic agreement (from 0.64 to 0.84) increased. Conclusions: These results suggest that the application of AI technology to thyroid FNA cytology may improve the diagnostic accuracy as well as intra- and inter-observer variability among pathologists. Further confirmatory research is needed.

Immunoglobulin G4-related disease mimicking an appendiceal neoplasm: a case report.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by chronic activation of the immune system and a tendency to form tumorous lesions. IgG4-RD is frequently characterized by the presence of tumor-like masses affecting multiple organs and is easily mistaken for a malignant neoplasm. However, IgG4-RD affecting the appendix is extremely rare, with only seven cases reported previously. We report the case of a woman in her early 60s who presented with insidious abdominal pain and radiological findings mimicking appendiceal neoplasms. After diagnosing appendiceal neoplasms, surgery was performed. The patient had a serum IgG4 concentration of <1.35 g/L, which did not satisfy one of the three revised comprehensive diagnostic criteria for IgG4-RD. A pathological examination was conducted, and the patient was diagnosed with appendiceal IgG4-RD. To the best of our knowledge, there have been no previously reported cases of IgG4-RD affecting the appendix in patients with low serum IgG4 concentrations. This report may prove beneficial for the future understanding of IgG4-RD and for the revision of diagnostic and treatment strategies.

Results of a nationally representative seroprevalence survey of chikungunya virus in Bangladesh.

There is an increasing global burden from chikungunya virus (CHIKV). Bangladesh reported a major epidemic in 2017, however, it was unclear if there had been prior widespread transmission. We conducted a nationally representative seroprevalence survey in 70 randomly selected communities immediately prior to the epidemic. We found 69/2,938 (2.4%) of sampled individuals were seropositive to CHIKV. Being seropositive to dengue virus (aOR 3.13 [95% CIs: 1.86-5.27]), male sex (aOR 0.59 [95% CIs: 0.36-0.99]), and community presence of Aedes aegypti mosquitoes (aOR: 1.80, 95% CI: 1.05-3.07) were significantly associated with CHIKV seropositivity. Using a spatial prediction model, we estimated that across the country, 4.99 (95% CI: 4.89 - 5.08) million people had been previously infected. These findings highlight high population susceptibility prior to the major outbreak and that previous outbreaks must have been spatially isolated.

Impact of mutations in SARS-CoV-2 recombinant sub-variant XBB.1.16 on the binding affinity with human ACE2 receptor.

Despite the waning threat of the COVID-19 pandemic, its detrimental impact on global health persists. Regardless of natural immunity or immunity obtained through vaccination, emerging variants of the virus continue to undergo mutations and propagate globally. The persistent mutations in SARS-CoV-2, along with the subsequent formation of recombinant sub-variants has become a challenge for researchers and health professionals, raising concerns about the efficacy of current vaccines. Gaining a better understanding of the biochemical interactions between the Spike Protein (RBD) of SARS-CoV-2 variants and the human ACE2 receptor can prove to be beneficial in designing and developing antiviral therapeutics that are equally effective against all strains and emerging variants. Our objective in this study was to investigate the interfacial binding pattern of the SARS-CoV-2 RBD-ACE2 complex of the Wild Type (WT), Omicron, and the Omicron recombinant sub-variant XBB.1.16. We aimed to examine the atomic level factors and observe how mutations influence the interaction between the virus and its host using Molecular Dynamics simulation, MM/GBSA energy calculations, and Principal Component Analysis. Our findings reveal a higher degree of structural deviation and flexibility in XBB.1.16 compared to WT and Omicron. PCA indicated a wider cluster and significant flexibility in the movements of XBB.1.16 which can also be observed in free energy landscapes, while the normal mode analysis revealed converging motions within the RBD-ACE2 complexes which can facilitate the interaction between them. A pattern of decreased binding affinity was observed in case of XBB.1.16 when compared to the WT and Omicron. These observed deviations in XBB.1.16 when compared to its parent lineage Omicron, and WT can be attributed to the mutations specific to it. Collectively, these results enhance our understanding of the impact of mutations on the interaction between this strain and the host, taking us one step closer to designing effective antiviral therapeutics against the continually mutating strains.

Withaferin A alleviates inflammation in animal models of arthritis by inhibiting the NF-κB pathway and cytokine release.

Withaferin A, a steroid lactone from Withania somnifera, exhibits anti-inflammatory, immunomodulatory, and antioxidant properties. This study investigated the effects of withaferin A on collagen-induced arthritis (CIA) rats, focusing on NF-κB p65 regulation and cytokine release. Withaferin A (50 mg/kg b.wt., orally) or methotrexate (0.25 mg/kg b.wt., i.p., as a reference drug) was given to CIA rats daily for 20 days postarthritis induction. Joints were removed from nonarthritic and arthritic rats to assess the levels of NO, MPO, interleukin (IL)-1ß, IL-6, IL-10, TNF-α, COX-2, and NF-κB via ELISA. Furthermore, the mRNA expression of IL-1ß, IL-10, TNF-α, COX-2, iNOS, and NF-κB was also assessed through qPCR. Treatment with withaferin A significantly inhibited the levels of inflammatory cytokines and the transcription factor NF-κB; suppressed the expression of IL-1ß, IL-10, TNF-α, COX-2, iNOS, and NF-κB in the joint tissue of CIA rats; and reduced cartilage and bone destruction, as shown by H&E staining. To confirm the results obtained from biochemical and molecular studies and to determine the molecular target of withaferin A, we performed a molecular simulation of the potential targets of withaferin A, which identified the NF-κB pathway as its target. These results suggested that withaferin A effectively attenuated rheumatoid arthritis progression by inhibiting the activation of the NF-κB pathway and the downstream secretion of inflammatory cytokines.