Ecotoxicological effects of triclosan on Lemna minor: bioconcentration, growth inhibition and oxidative stress.

Triclosan (TCS), an emerging pollutant, is a notable contributor to adverse impacts on aquatic organisms due to its widespread use during COVID-19 and hydrophobic properties. There is extensive documented literature on TCS toxicity in commercially important fish species; however, studies on aquatic plants remain limited. In this prelude, the present study aims to evaluate the effect of TCS on Lemna minor, a commercially important aquatic plant species for 7 days. The results showed dose-dependent significant alterations in growth, pigments and stress enzymes of L. minor at varied concentrations of TCS (1 to 8 mg L-1). Median inhibitory concentration (IC50) was found to be 4.813 mg L-1. Total chlorophyll and carotenoid levels decreased 73.11 and 81.83%, respectively after 7 days of TCS exposure. A significant increase in catalase and superoxide dismutase activity was observed in TCS exposed groups as compared to the control. Bioconcentration factor was found to be in the range of 5.855 to 37.129 signifying TCS ability to accumulate and transfer through the food chain. Scanning electron microscopy (SEM) analysis showed deformation in the cell surface and alteration of stroma morphology of TCS exposed groups. Furthermore, the Fourier transform infrared spectroscopy (FTIR) study also revealed that higher concentrations of TCS could cause alteration in the functional groups in the plant. This study demonstrates that TCS negatively impacts the growth and metabolism of primary producers, offering crucial insights into its interactions with aquatic plants and establishing baseline information essential for crafting effective mitigation strategies for TCS contamination in aquatic environments.

De Novo Design of Integrin α5ß1 Modulating Proteins for Regenerative Medicine.

Integrin α5ß1 is crucial for cell attachment and migration in development and tissue regeneration, and α5ß1 binding proteins could have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo α5ß1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of α5ß1. When immobilized onto titanium surfaces and throughout 3D hydrogels, the NeoNectins outperform native fibronectin and RGD peptide in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed fibronectin and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine.

Synthesis and Biological Evaluation of Amino Acid and Peptide Conjugates of 5-Bromovaleric Acid.

BACKGROUND: Among various carboxylic acid derivatives, valeric acid or pentanoic acid is found to be widely distributed in nature. It is a straight-chain alkyl carboxylic acid containing five carbon atoms. Due to the therapeutic value of valeric acid, it is used as a versatile nucleus in the pharmaceutical field. Valeric acid derivatives are associated with a broad spectrum of biological activities, like anticonvulsant, antiplatelet, antidiabetic, and plant growth activities. AIM: It has previously been revealed that peptide derivatives of carboxylic acids are accountable for enhanced antimicrobial activity. Therefore, it was hypothesized that coupling peptides with valeric acid would increase the antimicrobial properties of the target compounds. So, the objective of the present study was to synthesize peptide derivatives of 5-bromovaleric acid and evaluate their antibacterial and antifungal activities. METHODS: 5-bromovaleric acid was synthesized by the reaction of cyclopentanone and hydrogen peroxide in the presence of copper bromide and sodium bromide. Additionally, 5-bromovaleric acid was coupled with amino acid methyl esters, dipeptides, tripeptides, and tetrapeptides in the presence of dicyclohexylcarbodimide (DCC) and N-methylmorpholine (NMM) as a base under continuous stirring for 36 hours to produce its peptide derivatives. RESULTS: The results obtained showed that 5-bromovaleric acid possesses more potent antibacterial activity than N-terminal 5-bromovaleric acid conjugates of selected di-, tri, and tetra peptide Cterminal methyl esters against ciprofloxacin as a standard. The selected dipeptide and tripeptide Nterminal 5-bromovaleric acid-conjugated C-terminal methyl ester derivatives were more active than the selected tetrapeptide methyl ester analogue. Using fluconazole as a reference, the antifungal efficacy of 5-bromovaleric acid against C. albicans and A. niger declined as it was combined with C-terminal methyl esters of selected dipeptides, tripeptides, and tetrapeptides. CONCLUSION: The novel selected peptide derivatives had less antibacterial and antifungal action than the parent 5-bromovaleric acid. Antibacterial and antifungal investigations showed that 5- bromopentanoic acid peptide derivatives might impair antimicrobial efficacy. Further, attaching 5- bromopentanoic acid to di, tri, and tetra peptides did not boost their antibacterial potential.

Ecotoxicological risk assessment of triclosan, an emerging pollutant in a riverine and estuarine ecosystems: A comparative study.

Triclosan (TCS), an antibacterial biocide, pervades water and sediment matrices globally, posing a threat to aquatic life. In densely populated cities like Mumbai, rivers and coastal bodies demand baseline TCS data for ecotoxicological assessment due to the excessive use of personal care products comprising TCS. This pioneering study compares spatiotemporal TCS variations and risks in freshwater and marine ecosystems employing multivariate analysis of physicochemical parameters. Over five months (January to May 2022), Mithi River exhibited higher TCS concentrations (water: 1.68 µg/L, sediment: 3.19 µg/kg) than Versova Creek (water: 0.49 µg/L, sediment: 0.69 µg/kg). Principal component analysis revealed positive correlations between TCS and physicochemical parameters. High-risk quotients (>1) underscore TCS threats in both water bodies. This study furnishes crucial baseline data, emphasizing the need for effective treatment plans for TCS in effluent waters released into the adjacent aquatic systems.

Enhanced identification of endocrine disruptors through integration of science-based regulatory practices and innovative methodologies: The MERLON Project.

The prevalence of hormone-related health issues caused by exposure to endocrine disrupting chemicals (EDCs) is a significant, and increasing, societal challenge. Declining fertility rates together with rising incidence rates of reproductive disorders and other endocrine-related diseases underscores the urgency in taking more action. Addressing the growing threat of EDCs in our environment demands robust and reliable test methods to assess a broad variety of endpoints relevant for endocrine disruption. EDCs also require effective regulatory frameworks, especially as the current move towards greater reliance on non-animal methods in chemical testing puts to test the current paradigm for EDC identification, which requires that an adverse effect is observed in an intact organism. Although great advances have been made in the field of predictive toxicology, disruption to the endocrine system and subsequent adverse health effects may prove particularly difficult to predict without traditional animal models. The MERLON project seeks to expedite progress by integrating multispecies molecular research, new approach methodologies (NAMs), human clinical epidemiology, and systems biology to furnish mechanistic insights and explore ways forward for NAM-based identification of EDCs. The focus is on sexual development and function, from foetal sex differentiation of the reproductive system through mini-puberty and puberty to sexual maturity. The project aims are geared towards closing existing knowledge gaps in understanding the effects of EDCs on human health to ultimately support effective regulation of EDCs in the European Union and beyond.

Chronic toxicity of sediment-bound triclosan on freshwater walking catfish Clarias magur: Organ level accumulation and selected enzyme biomarker responses.

Triclosan (TCS) is a biocide widely used in personal care and medicinal products. TCS persists in sediments and has been detected worldwide, making sediments a vital route of TCS exposure to aquatic organisms. This experiment explored the bioaccumulation and toxicological effects of TCS-contaminated sediment. The study revealed that the half-life of TCS in the sediment-water system was 21.52 days. Exposure of Clarias magur juveniles to 0.4 and 0.8 mg kg-1 TCS-spiked sediment resulted in high Biota-Sediment Accumulation Factor (BSAF) with the highest bioaccumulation in the liver (29.62-73.61 mg kg-1), followed by gill (9.22-17.57 mg kg-1), kidney (5.04-9.76 mg kg-1), muscle (2.63-4.87 mg kg-1) and brain (1.53-3.20 mg kg-1). Furthermore, a concentration-dependent increase in oxidative stress biomarkers such as superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) was documented during 45 days of exposure in gill, liver, kidney, muscle, and brain tissues of exposed fish. A similar increasing trend was also recorded for liver transaminase enzymes such as glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) during the experimental period compared to control. Serum biochemical analysis revealed a significant time and concentration-dependent increase in serum glucose, serum GOT, and serum GPT, while serum total protein and albumin decreased significantly during exposure. These findings demonstrate high bioaccumulative and toxic nature of TCS in fish, promoting multiple physiological and biochemical dysfunctions through sediment exposure. The study underscores the urgent need for strengthened regulations and robust monitoring of triclosan across various environmental matrices, including sediment, to mitigate the detrimental impacts of TCS effectively.

Impact of coconut kernel extract on carcinogen-induced skin cancer model: Oxidative stress, C-MYC proto-oncogene and tumor formation.

This study aimed at analysing the effects of coconut (Cocos nucifera L.) kernel extract (CKE) on oxidative stress, C-MYC proto-oncogene, and tumour formation in a skin cancer model. Tumorigenesis was induced by dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA). In vitro antioxidant activity of CKE was assessed using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2), total phenolic and flavonoid content assays. CKE showed a higher antioxidant activity then ascorbic acid (*P < 0.05, ****P < 0.0001). HPLC and NMR study of the CKE revealed the presence of lauric acid (LA). Following the characterization of CKE, mice were randomly assigned to receive DMBA/TPA Induction and CKE treatment at different doses (50, 100, and 200 mg/kg) of body weight. LA 100 mg/kg of body weight used as standard. Significantly, the CKE200 and control groups' mice did not develop tumors; however, the CKE100 and CKE50 treated groups did develop tumors less frequently than the DMBA/TPA-treated mice. Histopathological analysis revealed that the epidermal layer in DMBA-induced mice was thicker and had squamous pearls along with a hyperplasia/dysplasia lesion, indicating skin squamous cell carcinoma (SCC), whereas the epidermal layers in CKE200-treated and control mice were normal. Additionally, the CKE treatment demonstrated a significant stimulatory effect on the activities of reactive oxygen species (ROS), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), as well as an inhibitory effect on lipid peroxidase (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001) and c-MYC protein expression (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001). In conclusion, CKE prevents the growth of tumors on mouse skin by reducing oxidative stress and suppressing c-MYC overexpression brought on by DMBA/TPA induction. This makes it an effective dietary antioxidant with anti-tumor properties.

Study of risk factors for injuries due to cardiopulmonary resuscitation with special focus on the role of the heart: A machine learning analysis of a prospective registry with multiple sources of information (ReCaPTa Study).

Background: The study of thoracic injuries and biomechanics during CPR requires detailed studies that are very scarce. The role of the heart in CPR biomechanics has not been determined. This study aimed to determine the risk factors importance for serious ribcage damage due to CPR. Methods: Data were collected from a prospective registry of out-of-hospital cardiac arrest between April 2014 and April 2017. This study included consecutive out-of-hospital CPR attempts undergoing an autopsy study focused on CPR injuries. Cardiac mass ratio was defined as the ratio of real to expected heart mass. Pearson's correlation coefficient was used to select clinically relevant variables and subsequently classification tree models were built. The Gini index was used to determine the importance of the associated serious ribcage damage factors. The LUCAS® chest compressions device forces and the cardiac mass were analyzed by linear regression. Results: Two hundred CPR attempts were included (133 manual CPR and 67 mechanical CPR). The mean age of the sample was 60.4 ± 13.5, and 56 (28%) were women. In all, 65.0% of the patients presented serious ribcage damage. From the classification tree build with the clinically relevant variables, age (0.44), cardiac mass ratio (0.26), CPR time (0.22), and mechanical CPR (0.07), in that order, were the most influential factors on serious ribcage damage. The chest compression forces were greater in subjects with higher cardiac mass. Conclusions: The heart plays a key role in CPR biomechanics being cardiac mass ratio the second most important risk factor for CPR injuries.

A chemical magnet: Approaches to guide precise protein localization.

Small molecules that chemically induce proximity between two proteins have been widely used to precisely modulate protein levels, stability, and activity. Recently, several studies developed novel strategies that employ heterobifunctional molecules that co-opt shuttling proteins to control the spatial localization of a target protein, unlocking new potential within this domain. Together, these studies lay the groundwork for novel targeted protein relocalization modalities that can rewire the protein circuitry and interactome to influence biological outcomes.

Self-healable, Tolerant Superaerophobic Coating for Improving Electrochemical Hydrogen Production.

Gas-evolving electrodes often suffer from the blocking of catalytic active sites-due to unwanted and unavoidable adhesion of generated gas bubbles, which elevates the overpotential for the electrochemical hydrogen evolution reaction (HER)- by raising the resistance of the electrode. Here, a catalyst-free and self-healable superaerophobic coating having ultra-low bubble adhesion is introduced for achieving significantly depleted overpotentials of 209 and 506 mV at both low (50 mA cm-2) and high (500 mA cm-2) current densities, respectively, compared to a bare nickel-foam electrode. The optimized coating ensured an early detachment of the generated tiny (0.8 ± 0.1 mm) gas bubble-and thus, prevented the undesired rise in resistance of the coated electrode. The systematic association of physical (i.e., ionic interactions, H-bonding, etc.) cross-linkage, ß-amino ester type covalent cross-linkage and reinforced halloysite nano clay enables the design of such functional material embedded with essential characteristics-including improved mechanical (toughness of 63.7 kJ m-3, and tensile modulus of 26 kPa) property and chemical (extremes of pH (1 and 14), salinity, etc.) stability, rapid (<10 min) self-healing ability (even at alkaline condition) and desired bubble-wettability (bubble contact angle of 158.2 ± 0.2°) with ultralow force (4.2 ± 0.4 µN) of bubble adhesion.

An Unobtrusive Fall Detection System Using Ceiling-mounted Ultra-wideband Radar.

Falls are among the most devastating events that can happen to an older person. Automatic fall detection systems aim to solve this problem by alerting carers and family the moment a fall occurs. This paper presents the development of an unobtrusive fall detection system using ultra-wideband (UWB) radar. The proposed system employed a ceiling-mounted UWB radar to avoid object occlusion and allow for flexible implementation. An innovative pre-processing method was developed to effectively enhance motion and reduce noise from raw UWB data. We designed a trial protocol composed of common types of falls in older population and activities of daily living (ADL). A fall detection algorithm based on convolutional neural networks was developed with simulated falls and ADLs obtained from ten participants following the trial protocol in a clear and cluttered living environment. The fall detection system achieved an accuracy of 93.97%, with a sensitivity of 95.58% and specificity of 92.68%.

Pathogenicity of white spot syndrome virus (WSSV) after multiple passages in mud crab, Scylla olivacea.

White spot syndrome virus (WSSV) is a highly virulent shrimp pathogen with a broad host range. Among the hosts, though mud crab, Scylla olivacea is reported to be more susceptible to WSSV than S. serrata and S. paramamosain, a detailed study on the pathogenicity and genome stability of the virus after multiple passages has yet to be reported. Firstly, to test the pathogenicity of the virus, WSSV was intramuscularly injected into healthy shrimp, Penaeus vannamei. Experimentally infected P. vannamei showed the first mortality at 36 h post-injection (hpi), followed by 100 % cumulative mortality in 7 days post-injection (dpi). However, S. olivacea injected with the WSSV inoculum derived from infected shrimp showed the first mortality at 48 hpi and a cumulative mortality of 70 % at the end of the ten days experiment. Subsequently, WSSV was sequentially passaged five times in Scylla olivacea to find out any change in the virulence of the virus in each passage. S. olivacea groups injected with 1st, second, third and fourth passages derived from the crab recorded the first mortality between 48 and 56 hpi and the cumulative mortality of 60 to 70 % at the end of the ten days experiment. Injection of WSSV inoculum in P. vannamei derived from multiple passages in S. olivaceae revealed the retention of the pathogenicity of the virus. Shrimp groups injected with WSSV derived from different passages showed first mortality between 24 and 36 hpi and cumulative mortality of 100 % between 6 and 7 dpi. The average viral load in the shrimp groups injected with WSSV inoculum derived from shrimp was 3.6 × 108, whereas in shrimp injected with the inoculum derived from 1st, third and fifth passages from crab showed 4.0 × 108, 4.7 × 108 and 4.3 × 108 copies per 100 ng DNA. Histological examination of the gill and stomach tissue of shrimp injected with inoculum prepared from shrimp as well as the inoculum derived from 1st, third and fifth passages in S. olivacea revealed characteristic pathological manifestations of the WSSV infection in gill and stomach tissues such as hypertrophied nuclei, Cowdry A-type inclusions as well as massive basophilic intranuclear inclusions. Further, to study the genome stability, the primers targeting highly variable regions of the WSSV genome (ORF94, ORF125, ORF75, variable region (VR) 14/15 and VR 23/24) were used to amplify WSSV derived from different passages and the amplified PCR products were sequenced. The sequence analysis revealed the WSSV genome stability after multiple passages in mud crab, S. olivacea.

Perceptions of primary and secondary care clinicians treating diabetic foot: A pan India study and quantitative analysis.

AIM: The study quantifies clinicians' perceptions and challenges during different stages of diabetic foot treatment. Diabetic neuropathy (DN), which is a major consequence of diabetes, significantly increases the risk of lower limb amputation. This can be prevented to a large extent by foot care, early detection, and lesion treatment. METHODS: Ninety-two Indian clinicians of various demographics, medical specializations, and experiences were interviewed. Diabetic foot treatment by primary and secondary care clinicians was assessed. This study evaluates aspects related to patient awareness, compliance, and shortcomings of current diagnostic techniques. RESULTS: A two-sample Mann-Whitney statistical method was used to infer the perceptions of clinicians on hypothesis questions. Primary and secondary care clinicians' perceptions differed for the hypotheses related to objective assessment (p-value = 0.001), operator variability (p-value = 0.03), and patient compliance (p-value = 0.047). Conversely, both groups held comparative perspectives for the awareness (p-value = 0.369) and examination time (p-value = 0.276) hypotheses. CONCLUSIONS: All clinicians strongly supported the need for an objective assessment to reduce the misdiagnosis of DN. Further, DNis often underdiagnosed due to a lack of awareness and knowledgeamong people with diabetes. Secondary care clinicians acknowledged a need for trained operators to reduce reliability errors. These insights provide directions for future research in this field.

Biochar for Improving Growth Performance of Shrimp and Environmental Quality in an Inland Saline Culture System.

The current study, which lasted 45 days, was designed to find a more effective way to use the vast resources of salt-affected land and ground saline water for aquaculture. Biochar made from agrowaste was used as a sediment amendment. The 100 g of biochar was applied to 25 kg of sediment (i.e., 9.0 ton ha-1) in 300L capacity fiber reinforced plastic, and Penaeus vannamei (P. vannamei) (2.74 ± 0.03 g) was stocked at 90 juveniles m-2 in inland ground saline water of salinity 10 ppt fortified with potassium levels that are 50% equivalent to those of seawater. Among different treatments, T1 indicates paddy straw biochar (PSB) application in sediment; T2 indicates sediment amended with KOH-activated PSB; T3 indicates sugar cane bagasse biochar (SBB) application in sediment; and T4 indicates sediment amended with KOH-activated SBB. Compared to the control the potassium (K+), alkalinity, total hardness, calcium/magnesium ratio, and pH of the water increased significantly (P ≤ 0.05) in treatments where biochar was used as an amendment in sediment. The T3 treatment had the best Ca/Mg ratio (1.00:3.12). In water, the magnitude of increase in K+ concentration from high to low followed the order: T2 > T4 > T1 > T3 > control. The concentration of NH4+-N in water was found to be increasing in control, whereas in the rest of the treatments, it decreased significantly from day 1, until the end of the experiment. Compared to control, the bulk density was decreased, and sediment cation exchange capacity and water holding capacity were increased significantly in treatments where biochar was used as an amendment. The soil microbial parameter measured in terms of soil enzyme dehydrogenase was significantly different among treatments at the end of the experiment. Weight gain (%), specific growth rate (SGR), survival (%), and feed conversion ratio of P. vannamei varied significantly in T1, T2, T3, and T4 compared to the control. The SGR (2.38b ± 0.05% day-1) and weight gain (%) in T2, and survival (96.1b ± 2.0%) in T3 treatment were found to be the highest at the end of the experiment. When biochar was mixed with sediment in the inland saline system, an improvement was seen in sediment quality, water quality, and growth characteristics of P. vannamei.

Cas phosphorylation regulates focal adhesion assembly.

Integrin-mediated cell attachment rapidly induces tyrosine kinase signaling. Despite years of research, the role of this signaling in integrin activation and focal adhesion assembly is unclear. We provide evidence that the Src-family kinase (SFK) substrate Cas (Crk-associated substrate, p130Cas, BCAR1) is phosphorylated and associated with its Crk/CrkL effectors in clusters that are precursors of focal adhesions. The initial phospho-Cas clusters contain integrin ß1 in its inactive, bent closed, conformation. Later, phospho-Cas and total Cas levels decrease as integrin ß1 is activated and core focal adhesion proteins including vinculin, talin, kindlin, and paxillin are recruited. Cas is required for cell spreading and focal adhesion assembly in epithelial and fibroblast cells on collagen and fibronectin. Cas cluster formation requires Cas, Crk/CrkL, SFKs, and Rac1 but not vinculin. Rac1 provides positive feedback onto Cas through reactive oxygen, opposed by negative feedback from the ubiquitin proteasome system. The results suggest a two-step model for focal adhesion assembly in which clusters of phospho-Cas, effectors and inactive integrin ß1 grow through positive feedback prior to integrin activation and recruitment of core focal adhesion proteins.

Assessment of toxicity potential of neglected Mithi River water from Mumbai megacity, India, in zebrafish using embryotoxicity, teratogenicity, and genotoxicity biomarkers.

The Mithi River begins at Vihar Lake and flows through the industrial hub of the city of Mumbai, India, and merges with the Arabian Sea at Mahim Creek. The current study was carried out to assess the ecotoxicological effects of the Mithi River surface water in zebrafish (Danio rerio) embryos. Water samples were collected from ten sampling sites (S1 to S10) located along the course of the Mithi River. The toxicity of water samples was assessed using a zebrafish embryo toxicity test (ZFET). Water samples were diluted from all sites at 1:0, 1:2, 1:4, 1:8, 1:16, 1:32, 1:64, and 1:128 times. The lowest and highest LDil 20 values for 96 h were estimated as 9.16 and 74.18 respectively for the S2 and S5 sites. The results of embryotoxicity and teratogenicity assays indicated a significant difference (p < 0.0001) between embryos exposed to control and sampling sites (except S1) for various endpoints such as mortality, egg coagulation, pericardial edema, yolk sac edema, tail bend, and skeletal deformities. The histopathological analysis revealed various lesions, ascertaining the toxic effects of water samples. The comet assay revealed significantly higher DNA damage (except S1) in embryos exposed to sites S5 and S6 with OTM values of 4.46 and 2.48 respectively. The results indicated that the Mithi River is polluted with maximum pollution load at the middle stretches. The study further indicated that the pollutants in the Mithi River (except S1) could potentially be hazardous to the aquatic organisms; therefore, continuous biomonitoring of the river is needed for its revival.

Management of compromised residual alveolar ridges using hollow denture with three-dimensional printed spacer and specialized impression technique.

Impression making in compromised residual alveolar ridge is a regular challenge in rehabilitating patients with conventional removable complete dentures. In patients who cannot afford implant-supported dentures, specialized impression technique is a viable and justified option for fabrication of complete dentures. More often, the stability of denture in such patients becomes a deciding factor between failure and success. Furthermore, increased interarch space may result in increased height of maxillary and/or mandibular dentures with corresponding increase in weight, which further compromises the retention and stability of the prosthesis. This article describes an amalgamation of Hobkirk's impression technique in a case of resorbed maxillary residual alveolar ridge with a flabby anterior segment and fabrication of hollow maxillary dentures using a "three-dimensional printed dental spacer" with a "double-flask technique." The weight of the final prosthesis was reduced therefore contributing to improved retention and stability of the final prosthesis.

Mechanism of Immune Evasion in Mosquito-Borne Diseases.

In recent decades, mosquito-borne illnesses have emerged as a major health burden in many tropical regions. These diseases, such as malaria, dengue fever, chikungunya, yellow fever, Zika virus infection, Rift Valley fever, Japanese encephalitis, and West Nile virus infection, are transmitted through the bite of infected mosquitoes. These pathogens have been shown to interfere with the host's immune system through adaptive and innate immune mechanisms, as well as the human circulatory system. Crucial immune checkpoints such as antigen presentation, T cell activation, differentiation, and proinflammatory response play a vital role in the host cell's response to pathogenic infection. Furthermore, these immune evasions have the potential to stimulate the human immune system, resulting in other associated non-communicable diseases. This review aims to advance our understanding of mosquito-borne diseases and the immune evasion mechanisms by associated pathogens. Moreover, it highlights the adverse outcomes of mosquito-borne disease.

Effect of Low-Level Laser Therapy on Early Wound Healing and Levels of Inflammatory Mediators in Gingival Crevicular Fluid Following Open Flap Debridement.

Introduction Low-level laser therapy (LLLT) has a beneficial effect on pain relief and wound healing. This study aims at a clinical evaluation of early wound healing and a biochemical evaluation of inflammatory mediators in gingival crevicular fluid (GCF) following LLLT with an open flap debridement (OFD) in periodontal therapy. Material and methods This randomized controlled trial included 40 chronic periodontitis patients with bilateral attachment loss, pocket depths of 5 mm affecting at least two quadrants, and radiographic evidence of horizontal bone loss. 120 control sites were randomly selected to receive OFD, and contralateral 120 test sites received bio-stimulation with a diode laser (890 nm) after OFD. The wound healing index was recorded at the 1st and 2nd weeks, and clinical parameters such as the plaque index, gingival index, pocket probing depth, clinical attachment level, and GCF inflammatory mediators were evaluated at baseline, 3, and 6 months. Results From the start of the study to 6 months later, there was a statistically significant drop in plaque index, gingival index, probing pocket depth, and gain clinical attachment levels in both groups. However, when the two groups were compared, there were no significant differences at any time intervals. GCF inflammatory mediators tumor necrosis factor (TNF) alpha and matrix metalloproteinases (MMP-8) decrease, and osteoprotegerin (OPG) levels increase in both the test group and control group from baseline to 3 months and 6 months. In intergroup comparisons, there was a statistically significant reduction in the test group as compared to the control group at 6 months. There was a decline in gingival crevicular fluid - interleukin-6 (GCF IL-6) levels from baseline to 3 months and 6 months in both the groups but when analysed statistically, the results were not significant on intergroup and intragroup comparison at any time interval. The Landry Wound Healing Index values in the 1st and 2nd weeks were showing statistically significant improved healing in the test group as compared to the control group. There was significantly better wound healing at sites where a diode laser was used. Conclusion LLLT increases early wound healing after periodontal surgical procedures.

Inducible nitric oxide synthase deficiency promotes murine-ß-coronavirus induced demyelination.

BACKGROUND: Multiple sclerosis (MS) is characterized by neuroinflammation and demyelination orchestrated by activated neuroglial cells, CNS infiltrating leukocytes, and their reciprocal interactions through inflammatory signals. An inflammatory stimulus triggers inducible nitric oxide synthase (NOS2), a pro-inflammatory marker of microglia/macrophages (MG/Mφ) to catalyze sustained nitric oxide production. NOS2 during neuroinflammation, has been associated with MS disease pathology; however, studies dissecting its role in demyelination are limited. We studied the role of NOS2 in a recombinant ß-coronavirus-MHV-RSA59 induced neuroinflammation, an experimental animal model mimicking the pathological hallmarks of MS: neuroinflammatory demyelination and axonal degeneration. OBJECTIVE: Understanding the role of NOS2 in murine-ß-coronavirus-MHV-RSA59 demyelination. METHODS: Brain and spinal cords from mock and RSA59 infected 4-5-week-old MHV-free C57BL/6 mice (WT) and NOS2-/- mice were harvested at different disease phases post infection (p.i.) (day 5/6-acute, day 9/10-acute-adaptive and day 30-chronic phase) and compared for pathological outcomes. RESULTS: NOS2 was upregulated at the acute phase of RSA59-induced disease in WT mice and its deficiency resulted in severe disease and reduced survival at the acute-adaptive transition phase. Low survival in NOS2-/- mice was attributed to (i) high neuroinflammation resulting from increased accumulation of macrophages and neutrophils and (ii) Iba1 + phagocytic MG/Mφ mediated-early demyelination as observed at this phase. The phagocytic phenotype of CNS MG/Mφ was confirmed by significantly higher mRNA transcripts of phagocyte markers-CD206, TREM2, and Arg1 and double immunolabelling of Iba1 with MBP and PLP. Further, NOS2 deficiency led to exacerbated demyelination at the chronic phase as well. CONCLUSION: Taken together the results imply that the immune system failed to control the disease progression in the absence of NOS2. Thus, our observations highlight a protective role of NOS2 in murine-ß-coronavirus induced demyelination.