The interplay of co-infections in shaping COVID-19 severity: Expanding the scope beyond SARS-CoV-2.

High mortality has been reported in severe cases of COVID-19. Emerging reports suggested that the severity is not only due to SARS-CoV-2 infection, but also due to coinfections by other pathogens exhibiting symptoms like COVID-19. During the COVID-19 pandemic, simultaneous respiratory coinfections with various viral (Retroviridae, Flaviviridae, Orthomyxoviridae, and Picoviridae) and bacterial (Mycobacteriaceae, Mycoplasmataceae, Enterobacteriaceae and Helicobacteraceae) families have been observed. These pathogens intensify disease severity by potentially augmenting SARSCoV-2 replication, inflammation, and modulation of signaling pathways. Coinfection emerges as a critical determinant of COVID-19 severity, principally instigated by heightened pro-inflammatory cytokine levels, as cytokine storm. Thereby, in co-infection scenario, the severity is also driven by the modulation of inflammatory signaling pathways by both pathogens possibly associated with interleukin, interferon, and cell death exacerbating the severity. In the current review, we attempt to understand the role of co- infections by other pathogens and their involvement in the severity of COVID-19.

MiRNA-3163 limits ovarian cancer stem-like cells via targeting SOX-2 transcription factor.

Cancer stem cells (CSCs) are pivotal in both cancer progression and the acquisition of drug resistance. MicroRNAs (miRNAs) play a crucial role in modulating CSC properties and are being explored as potential targets for therapeutic interventions. MiR-3163 is primarily known for its tumor suppressive properties in various human malignancies, with lower expression reported across different cancer types. However, its role in regulating the ovarian CSC phenotype and the underlying mechanism remain largely unknown. Here, we report a remarkable downregulation of miR-3163 in ovarian cancer stem-like cells (CSLCs). Enforced expression of miR-3163 in ovarian adherent and CSLCs, significantly disrupts the stemness phenotype. Moreover, downregulation of miR-3163 expression in ovarian cancer cells (OV2008 and OVCAR-3) inhibits the stem-like cells characterized by CD44+CD117+ expression. Sphere formation assay results reveal that overexpression of miR-3163 in ovarian cancer cells significantly inhibits spheroid formation ability, confirming the regulatory properties of miR-3163 on ovarian CSLCs. Mechanistic investigation reveals that miR-3163 depletes ovarian CSLCs via targeting SOX-2. Furthermore, we establish SOX-2 as a direct target of miR-3163 through dual-luciferase assay. Taken together, our study demonstrates that overexpression of miR-3163 could be a promising strategy for efficiently eradicating the CSC population to prevent chemoresistance and tumor relapse in ovarian cancer patients.

SARS-CoV-2 envelope protein induces necroptosis and mediates inflammatory response in lung and colon cells through receptor interacting protein kinase 1.

SARS-CoV-2 Envelope protein (E) is one of the crucial components in virus assembly and pathogenesis. The current study investigated its role in the SARS-CoV-2-mediated cell death and inflammation in lung and gastrointestinal epithelium and its effect on the gastrointestinal-lung axis. We observed that transfection of E protein increases the lysosomal pH and induces inflammation in the cell. The study utilizing Ethidium bromide/Acridine orange and Hoechst/Propidium iodide staining demonstrated necrotic cell death in E protein transfected cells. Our study revealed the role of the necroptotic marker RIPK1 in cell death. Additionally, inhibition of RIPK1 by its specific inhibitor Nec-1s exhibits recovery from cell death and inflammation manifested by reduced phosphorylation of NFκB. The E-transfected cells' conditioned media induced inflammation with differential expression of inflammatory markers compared to direct transfection in the gastrointestinal-lung axis. In conclusion, SARS-CoV-2 E mediates inflammation and necroptosis through RIPK1, and the E-expressing cells' secretion can modulate the gastrointestinal-lung axis. Based on the data of the present study, we believe that during severe COVID-19, necroptosis is an alternate mechanism of cell death besides ferroptosis, especially when the disease is not associated with drastic increase in serum ferritin.

Direct Ink Writing of Carbon-Doped Polymeric Composite Ink: A Review on Its Requirements and Applications.

Direct Ink Writing (DIW) opens new possibilities in three-dimensional (3D) printing of carbon-based polymeric ink. This is due to its ability in design flexibility, structural complexity, and environmental sustainability. This area requires exhaustive study because of its wide application in different manufacturing sectors. The present article is related to the variant emerging 3D printing techniques and DIW of carbonaceous materials. Carbon-based materials, extensively used for various applications in 3D printing, possess impressive chemical stability, strength, and flexible nanostructure. Fine printable inks consist predominantly of uniform solutions of carbon materials, such as graphene, graphene oxide (GO), carbon fibers (CFs), carbon nanotubes (CNTs), and solvents. It also contains compatible polymers and suitable additives. This review article elaborately discusses the fundamental requirements of DIW in structuring carbon-doped polymeric inks viz. ink formulation, required ink rheology, extrusion parameters, print fidelity prediction, layer bonding examination, substrate selection, and curing method to achieve fine functional composites. A detailed description of its application in the fields of electronics, medical, and mechanical segments have also been focused in this study.

Numerical and Experimental Mechanical Analysis of Additively Manufactured Ankle-Foot Orthoses.

Growing age and different conditions often require the replacement of orthoses, and FDM-based 3D printing can produce them quickly with less investment. In today's market for orthotics, these characteristics are highly desired. Therefore, this study is fully focused on the optimization and strength analysis of FDM 3D-printed ankle-foot orthoses (AFO) fabricated using PLA and PLA reinforced with carbon fiber (PLA-C). An increase in ankle plantar-flexor force can be achieved by reinforcing thermoplastic AFOs with CFs. Specially designed mechanical strength tests were conducted at the UTM to generate force-displacement curves for stored elastic energy and fracture studies. The mechanical behavior of both AFOs was predicted with the help of an FEA. The model predictions were validated by comparing them with mechanical strength testing conducted under the same loading and boundary conditions as the FEA. In both the prediction and experimental analysis, the PLA-C-based AFOs were stiffer and could withstand greater loads than the PLA-based AFOs. An area of high stress in the simulation and a fracture point in experimentation were both found at the same location. Furthermore, these highly accurate models will allow the fabrication of AFOs to be improved without investing time and resources on trials.

Surface Topography Analysis of Mg-Based Composites with Different Nanoparticle Contents Disintegrated Using Abrasive Water Jet.

This study investigated the effect of abrasive water jet kinematic parameters, such as jet traverse speed and water pressure, on the surface of magnesium-based metal matrix nanocomposites (Mg-MMNCs) reinforced with 50 nm (average particle size) Al2O3 particles at concentrations of 0.66 and 1.11 wt.%. The extent of grooving caused by abrasive particles and irregularities in the abrasive waterjet machined surface with respect to traverse speed (20, 40, 250 and 500 mm/min), abrasive flow rate (200 and 300 g/min) and water pressure (100 and 400 MPa) was investigated using surface topography measurements. The results helped to identify the mode of material disintegration during the process. The nanoindentation results show that material softening was decreased in nanocomposites with higher reinforcement content due to the presence of a sufficient amount of nanoparticles (1.11 wt.%), which protected the surface from damage. The values of selected surface roughness profile parameters-average roughness (Ra), maximum height of peak (Rp) and maximum depth of valleys (Rv)-reveal a comparatively smooth surface finish in composites reinforced with 1.11 wt.% at a traverse speed of 500 mm/min. Moreover, abrasive waterjet machining at high water pressure (400 MPa) produced better surface quality due to sufficient material removal and effective cleaning of debris from the machining zone as compared to a low water pressure (100 MPa), low traverse speed (5 mm/min) and low abrasive mass flow rate (200 g/min).

Development and validation of a Questionnaire to study practices and diversities in Plexus and Peripheral nerve blocks.

BACKGROUND AND AIMS: Regional anaesthesia techniques are a part of perioperative medicine that affects both perioperative and long-term outcomes. We have a paucity of the data on the usage and practices of plexus and peripheral nerve blocks (PNBs). To the best of our knowledge, this is the first effort to validate a survey for plexus and PNBs. Subsequently, this questionnaire could be used for the survey to look for the trends and disparities in PNB practices and further to develop a national registry in the future. METHODS: Thirty questions were prepared after evidence-based search and reviewed by experts for suggestions. Changes were done and the questionnaire with the grading sheet was sent to 19 experts. The responses were analysed to calculate the content validity index (CVI) item-wise (I-CVI), scale-wise (S-CVI), and modified kappa statistics. The I-CVI of 0.78 and an S-CVI/average of 0.90 was taken as acceptable with more than six experts. RESULTS: Fourteen experts out of 19 assessed and graded the questions as per the provided sheet and submitted suggestions through the mail. Question reframing, option reconsideration, and change from single to multiple choices were incorporated as per the suggestions of the experts. Mean I-CVI for relevance, simplicity, clarity, and ambiguity was 0.99, 0.98, 0.98, and 0.99, respectively. S-CVI/average was 0.98, 0.97, 0.98, and 0.99 for relevance, simplicity, clarity, and ambiguity, respectively. CONCLUSION: We conclude that this questionnaire has met the content validity criteria and can be used to study plexus and PNBs practices.

Role of graphene in biosensor and protective textile against viruses.

Coronavirus disease (COVID-19) is a recently discovered infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Graphene is an emerging material due to its extraordinary performance in the field of electronics and antimicrobial textiles. Special attention devoted to graphene oxide-based materials due to its surface to volume ratio is very high which make it easy to attach biomolecules by simple adsorption or by crosslinking between reactive groups and the graphene surface. In response to the COVID-19 pandemic, we have summarized the recent developments of graphene and its derivatives with possible virus detection and textile applications. Moreover, graphene strain sensors can be executed on high-performance textiles and high-throughput drug efficacy screening.

The prevalence of dyslipidemia in patients with diabetes mellitus of ayurveda Hospital.

BACKGROUND: Dyslipidemia is one of the major risk factors for cardiovascular disease in diabetes mellitus. Early detection and treatment of dyslipidemia in type-2 diabetes mellitus can prevent risk for atherogenic cardiovascular disorder. The rationale of this study was to detect the lipid abnormality in diabetic patients. METHODS: Necessary data was collected from the medical archives of 150 patients (73 female and 77 male) with diabetes mellitus registered in Department of pathology and biochemistry of a Ayurveda hospital established at Kolkata, India. RESULTS: The mean ages of female and male subjects were 51.8 ± 10.8 and 53.2 ± 11.3 years respectively. The range and mean value of FBS in females were 113-342 mg/dl and 157.7 ± 6.3 mg/dl, while the range and mean value of PPBS in females were 135-560 mg/dl and 275.5 ± 12.3 mg/dl respectively. Results showed that range and mean value of FBS in males were 111-462 mg/dl and 160.8 ± 7.4 mg/dl, while the range and mean value of PPBS in males were 136-598 mg/dl and 302.1 ± 12.6 mg/dl respectively. Results of serum lipids showed that the mean values for total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) in female patients were 202.2 ± 5.9 mg/dl, 168.3 ± 8.2 mg/dl, 44.9 ± 1.3 mg/dl, 123.6 ± 5.2 mg/dl and 33.7 ± 1.7 mg/dl respectively. The mean values for TC, TG, HDL-C, LDL-C and VLDL-C in male patients were 182.5 ± 4.8 mg/dl, 128.1 ± 10.8 mg/dl, 40.8 ± 1.2 mg/dl, 105.4 ± 4.8 mg/dl and 36.2 ± 2.2 respectively. FBS showed significant positive correlation with PPBS, cholesterol, TG, and VLDL-C. PPBS also demonstrated direct and significant correlations with TG and VLDL-C. CONCLUSIONS: The study showed common lipid abnormalities during diabetes induced dyslipidemia i.e., hypercholesterolemia, hypertriglyceridemia and elevated LDL-C. This study suggests the dominance of hyperlipidemia over increased prevalence of dyslipidemia.

Sucrose and raffinose family oligosaccharides (RFOs) in soybean seeds as influenced by genotype and growing location.

Sucrose content in soybean seeds is desired to be high because as a sweetness-imparting component, it helps in wider acceptance of soy-derived food products. Conversely, galactosyl derivatives of sucrose, that is, raffinose and stachyose, which are flatulence-inducing components, need to be in low concentration in soybean seeds not only for augmenting utilization of the crop in food uses but also for delivering soy meal with improved metabolizable energy for monogastric animals. In the present study, analysis of 148 soybean genotypes for sucrose and total raffinose family oligosaccharides (RFOs) contents revealed a higher variation (4.80-fold) for sucrose than for RFOs content (2.63-fold). High-performance liquid chromatography analyses revealed ranges of 0.64-2.53 and 2.09-7.1 mmol/100 g for raffinose and stachyose contents, respectively. As information concerning the environmental effects on the sucrose and RFOs content in soybean seeds is not available, we also investigated a set of seven genotypes raised at widely different geographical locations for these quality traits. Sucrose content was found to be significantly higher at cooler location (Palampur); however, differences observed for raffinose and stachyose contents across the growing locations were genotype-dependent. The results suggest that soybean genotypes grown at cooler locations may be better suited for processing soy food products with improved taste and flavor.

Gamma irradiation induced enhancement in isoflavones, total phenol, anthocyanin and antioxidant properties of varying seed coat colored soybean.

Three Indian soybean genotypes, namely, Kalitur, Hara soya and NRC37 with black, green and yellow colored seed coat respectively were gamma irradiated at a dose of 0.5, 2.0, and 5.0 kGy. The total isoflavones and total phenol content (TPC) in all the genotypes increased significantly at a dose of 0.5 and 2 kGy respectively. The anthocyanin content was high in Kalitur, while other genotypes showed no detectable amounts of it. The hydroxyl radical scavenging activity (HRSA), DPPH free radical scavenging activity (FRSA) and total antioxidant power (TAP) were highest in Kalitur with black seed coat color. However, maximum enhancement in antioxidant properties was found in NRC37 with yellow followed by Hara soya with green seed coat color at a dose of 0.5 and 2.0 kGy. It was also observed that the 3 soybean genotypes showed an increase in antioxidant constituents and antioxidative properties at lower doses of 0.5 and 2.0 kGy while, the antioxidant effects of soy seeds were either decreased or remained constant at a higher dose of 5.0 kGy. It is suggested that mild gamma irradiation enhanced the antioxidant constituents and, hence, antioxidant potential of soybean seeds.

Relative changes in tocopherols, isoflavones, total phenolic content, and antioxidative activity in soybean seeds at different reproductive stages.

Immature seeds of soybean are becoming increasingly popular as a snack/vegetable to harness the health benefits of soybean. They are shelled from the immature pods picked from the mother plant at different reproductive stages. Information concerning changes in antioxidant constituents and antioxidant capacity during reproductive phases of soybean seeds is scarce. The aim of the present study was to determine whether immature seeds picked at different reproductive stages differ in tocopherol, isoflavone, total phenolic contents, free radical scavenging activity, and total antioxidative capacity. Seeds shelled from the soybean pods picked at three reproductive stages (R5, R6, and R7) as well as at full maturity were subjected to high-performance liquid chromatography analyses for tocopherol and isoflavone contents. Significantly higher values (P<0.05) were observed for tocopherols and isoflavones in immature seeds picked at late reproductive stages. At the first reproductive stage, that is, R5 stage, delta-tocopherol was the predominant form of tocopherol, whereas in subsequent reproductive stages as well as at complete maturity stage, the gamma-isomer contributed maximum proportion to the total tocopherol content. Genistein was, in general, the major form of isoflavone at all reproductive stages. Reduction in free radical scavenging activity, total antioxidant capacity, and total phenolic content in late-picked seeds concomitant with increased concentration of tocopherol and isoflavone isomers was observed. The results show that bioactive constituents other than isoflavones and tocopherols may decline with the advancement of maturity.