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Introduction Deep mycoses acquired by penetrating trauma to the skin can have varied and sometimes atypical morphological presentations resulting in diagnostic dilemmas and delay in treatment onset. Histopathology can be a useful tool in not only diagnosing but also differentiating various deep mycoses. Aims and Objectives To observe various morphological presentations and histopathological features of deep fungal infections. Materials and Methods A retrospective multi-centric study was conducted from 2010 to 2020 at 16 centres. The cases with diagnoses of various deep mycoses were included in the study. The patients presenting with cutaneous manifestations were included in the study. Their demographic details, history, presenting signs and symptoms, morphological presentations, histopathological features and treatment details were collected from the case sheets. Results A total of 124 cases were found from the case records. The most common type was chromoblastomycosis (42) followed by mycetoma (28) and rhinosporidiosis (17). The mean age was 43.76 ± 5.44 years. The average duration of symptoms before presentation was between 2 months to 10 years (average 2.5 ± 1.33 years). Male to female ratio was 1:0.7. Prior history of trauma was recorded in 36% of cases. Chromoblastomycosis cases presented with verrucous to atrophic plaques with black dots on the surface and histopathology findings included pesudoepitheliomatous hyperplasia, epithelioid cell granulomas, copper penny bodies within granulomas and abscesses. Rhinosporidiosis cases had polypoid grape-like lesions in the nose and eyes most commonly with histopathology findings of abundant thick-walled sporangia in dermis packed with thousands of spores. Eumycetoma patients had pigmented, indurated swelling with multiple sinuses discharging black granules and histopathology showed dermal abscesses and foreign body granulomatous reaction with PAS-positive hyphae. Histoplasmosis patients presented with few to multiple nodulo-pustular lesions on skin and palatal ulcers while small basophilic bodies packed in the cytoplasm of histiocytes were noted in histopathology. Phaeohyphomycosis cases presented as deep-seated cystic lesions and biopsy revealed deepithelialized cysts in the dermis or hypodermis with lumen showing necro inflammatory debris and fungal hyphae. Sporotrichosis cases had erythematous, tender nodules and papules either as single lesions or as multiple lesions arranged in a linear fashion and histopathology showed pseudoepitheliomatous hyperplasia of epidermis, loose to well-defined epithelioid cell granulomas and microabscesses. Spores were found in two cases. Cryptococcosis patient had multiple umbilicated lesions resembling giant molluscum contagiosum loose epithelioid cell granulomas and medium-sized spores lying in both intra and extracellularly on histopathology. Penicilliosis patients had nodulo-pustular lesions and histopathology showed an admixture of histiocytes, epithelioid cells, plasma cells, lymphocytes and polymorphs in the dermis with the presence of yeast-like spores in the cytoplasm of histiocytes and epithelioid cells. Entomophthoromycosis cases presented with asymptomatic subcutaneous firm swelling with loss of skin pinchability. Conclusion Though clinical findings of deep fungal infections are characteristic similar morphology and atypical presentations can be sometimes confusing. Histopathology is useful for confirming the diagnosis.

Abstract Combining safety objectives with stability objectives is crucial for safety-critical systems. Existing studies generally unified these two objectives by constructing Lyapunov-type barrier functions. However, insufficient analysis of key set relationships within the system may render the proposed safety and stability conditions conservative, and these studies also did not provide how to use such conditions to design safety-stability control strategies. This paper proposed a feasible and constructive design to achieve stabilization of safety-critical systems by a relaxed converse Lyapunov-barrier approach. By analyzing the relationships between a series of sets associated with the safety-critical system, the stability and safety conditions can be appropriately relaxed. Then, with the help of relaxed converse control Lyapunov-barrier functions (RCCLBFs), a theoretical result was obtained for the stability of affine nonlinear systems with safety constraints. Subsequently, a constructive method was developed for a second-order strict-feedback system to transform the process of solving RCCLBFs into a Lyapunov-like stabilization problem. Finally, the proposed safety-stability control method is exerted on a robotic system and demonstrated by simulations.

Zinc and cadmium pollutants cause a significant environmental effect that cannot be ignored. Due to their considerable amount in an aqueous environment, industries are seeking suitable adsorbents that are environmentally friendly and inexpensive for removing metals from wastewater before disposing of them in surface waters. This research employed original MXene (MX) and chitosan-modified MXene (CSMX) to extract zinc (Zn(II)) and cadmium (Cd(II)) metal ions from water-based solutions. The composite material produced was analyzed using techniques such as X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Brunauer-Emmett-Teller (BET). The effects of contact duration, pH of the solution, and initial concentration of metal ions on the adsorption process of Zn(II) and Cd(II) onto both MX and CSMX composites were investigated. MX and prepared CSMX composite presented a high adsorption capacity for both studied heavy metals, which were 91.55 and 73.82 mg/g for Zn(II) and Cd(II) onto MX, 106.84 and 93.07 mg/g for Cd(II) and Zn(II) onto CSMX composite, respectively. Furthermore, the maximum competitive adsorption capacities for Zn(II) onto MX and CSMX composites are 77.29 and 93.47 mg/g, and for are Cd(II) 60.30 and 79.66 mg/g, respectively. Hence, the removal capacities for both single and competitive metal ions were superior to CSMX composite. However, the adsorption capacities after five successive regeneration sequences were only dropped by 13.2% for Zn(II) and 17.4% for Cd(II) onto the CSMX composite compared to the first cycle. These results confirm that both metals could be efficiently terminated from wastewater, which makes the prepared CSMX composite a favorable candidate adsorbent in practical applications.

Abstract Background Plasmodium falciparum oocysts undergo growth and maturation in a unique setting within the mosquito midgut, firmly situated between the epithelium and the basal lamina. This location exposes them to specific nutrient exchange and metabolic processes while in direct contact with the mosquito haemolymph. The limited availability of in vitro culture systems for growth of the various P. falciparum mosquito stages hampers study of their biology and impedes progress in combatting malaria. Methods An artificial in vitro environment was established to mimic this distinctive setting, transitioning from a 2D culture system to a 3D model capable of generating fully mature oocysts that give rise to in vitro sporozoites. Results A two-dimensional (2D) chamber slide was employed along with an extracellular matrix composed of type IV collagen, entactin, and gamma laminin. This matrix facilitated development of the optimal medium composition for cultivating mature P. falciparum oocysts in vitro. However, the limitations of this 2D culture system in replicating the in vivo oocyst environment prompted a refinement of the approach by optimizing a three-dimensional (3D) alginate matrix culture system. This new system offered improved attachment, structural support, and nutrient exchange for the developing oocysts, leading to their maturation and the generation of sporozoites. Conclusions This technique enables the in vitro growth of P. falciparum oocysts and sporozoites.

In its highly developed form, the evolving three-dimensional (3D) bioprinting technology aims to create 3D structures with living cells to mimic real tissue and organ functions. It would offer significant benefits across research, personalized medicine, and multiple other applications when adequately developed for human medicine. Presently, more technological activities are witnessed in North America, followed by Europe, Asia Pacific countries, Israel among the Middle East countries, and some South American countries. Around 75 commercial companies are active in 3D bioprinting, with only about a dozen making significant commercial progress. This number is expected to rise phenomenally as breakthroughs in manufacturing and the safe use of 3D bioprinted tissues and organs emerge. Legal frameworks for 3D bioprinting will likely be established, incorporating additions to existing drug laws once countries like the United States of America authorize using 3D bioprinted products in personalized medicine. The demand for 3D bioprinting products is rising based on expectations of future benefits. Therefore, intense research and development activities are ongoing, resulting in demands for the supply of research materials. The legal framework still needs to be put in place for the commercial use of 3D bioprinted tissues and organs in personalized medicine; therefore, laws are to be created for their safe use. This review provides a flavor of the evolution of 3D bioprinting startup companies globally using these technologies.

Abstract Cd(II) is a potentially toxic heavy metal having carcinogenic activity. It is becoming widespread in the soil and groundwater by various natural and anthropological activities. This is inviting its immediate removal. The present study is aimed at developing a Cd(II) resistant strain isolated from contaminated water body and testing its potency in biological remediation of Cd(II) from aqueous environment. The developed resistant strain was characterized by SEM, FESEM, TEM, EDAX, FT-IR, Raman Spectral, XRD and XPS analysis. The results depict considerable morphological changes had taken place on the cell surface and interaction of Cd(II) with the surface exposed functional groups along with intracellular accumulation. Molecular contribution of critical cell wall component has been evaluated. The developed resistant strain had undergone Cd(II) biosorption study by employing adsorption isotherms and kinetic modeling. Langmuir model best fitted the Cd(II) biosorption data compared to the Freundlich one. Cd(II) biosorption by the strain followed a pseudo second order kinetics. The physical parameters affecting biosorption were also optimized by employing response surface methodology using central composite design. The results depict remarkable removal capacity 75.682 ± 0.002% of Cd(II) by the developed resistant strain from contaminated aqueous medium using 500 ppm of Cd(II). Quantitatively, biosorption for Cd(II) by the newly developed resistant strain has been increased significantly (p

We consider a probe U(1) Maxwell-Chern-Simons theory in 5-dimensions, and analyze the vector perturbations around a classical charged black-brane background. We solve the equations of motion for these perturbations in a derivative expansion. By computing the boundary current, we find that time and spatial derivatives can be interpreted as the induced electric and magnetic field respectively, and the Chern-Simons term contributes to a nonzero divergence of the boundary current which indicates a quantum anomaly. Using holography, we construct a two-derivative effective action for the vector perturbations. By complexifying the radial coordinate, and using appropriate transformation, we construct the full solution on the complexified bulk contour. By computing the on-shell action for the full Schwinger-Keldysh geometry, we obtain the Keldysh functional. We find that the single boundary on-shell action mixes parity, whereas the Keldysh functional does not depend on the Chern-Simons term up to the quadratic orders in derivative expansion.

Background Cardiovascular disease and cancer share a common risk factor: chronic stress/allostatic load (AL). A 1‐point increase in AL is linked to up to a 30% higher risk of major cardiac events (MACE) in patients with prostate cancer. However, AL's role in MACE in breast cancer, lung cancer, or colorectal cancer remains unknown. Methods and Results Patients ≥18 years of age diagnosed with the mentioned 3 cancers of interest (2010–2019) and followed up at a large, hybrid academic‐community practice were included in this retrospective cohort study. AL was modeled as an ordinal measure (0–11). Adjusted Fine–Gray competing risks regressions estimated the impact of AL precancer diagnosis on 2‐year MACE (a composite of heart failure, ischemic stroke, acute coronary syndrome, and atrial fibrillation). The effect of AL changes over time on MACE was calculated via piecewise Cox regression (before, and 2 months, 6 months, and 1 year after cancer diagnosis). Among 16 467 patients, 50.5% had breast cancer, 27.9% had lung cancer, and 21.4% had colorectal cancer. A 1‐point elevation in AL before breast cancer diagnosis corresponded to a 10% heightened associated risk of MACE (adjusted hazard ratio, 1.10 [95% CI, 1.06–1.13]). Similar findings were noted in lung cancer (adjusted hazard ratio, 1.16 [95% CI, 1.12–1.20]) and colorectal cancer (adjusted hazard ratio, 1.13 [95% CI, 1.08–1.19]). When considering AL as a time‐varying exposure, the peak associated MACE risk occurred with a 1‐point AL rise between 6 and 12 months post‐ breast cancer, lung cancer, and colorectal cancer diagnosis. Conclusions AL warrants investigation as a potential marker in these patients to identify those at elevated cardiovascular risk and intervene accordingly.

Abstract Introduction The study aimed to evaluate comparability in terms of efficacy, safety and immunogenicity of Sun’s ranibizumab biosimilar with reference ranibizumab in patients with neovascular age-related macular degeneration (nAMD). Methods This prospective, randomised, double-blind, two-group, parallel-arm, multicentre, phase 3 comparative study included patients with nAMD ≥ 50 years, randomised (in a 2:1 ratio) in a double-blind manner to receive 0.5 mg (0.05 mL) intravitreal injection of either Sun’s ranibizumab or reference ranibizumab in the study eye every 4 weeks until week 16 (total of four doses). Results Primary endpoint results demonstrated equivalence in the proportion of patients who lost fewer than 15 letters from baseline best-corrected visual acuity (BCVA) to the end of week 16 (99% of patients in Sun’s ranibizumab and 100% in reference ranibizumab; p > 0.9999), with the proportional difference (90% confidence interval) at −1% (−2.51, +0.61) lying within a pre-specified equivalence margin. Visual acuity improved by 15 or more letters in 43% of Sun’s ranibizumab group and 37% of the reference ranibizumab group (p = 0.4267). The mean increase in BCVA was 15.7 letters in Sun’s ranibizumab group and 14.6 letters in the reference ranibizumab group (p

Abstract Considering the importance of sustainable nuclear energy, effective management of radioactive nuclear waste, such as sequestration of radioiodine has inflicted a significant research attention in recent years. Despite the fact that materials have been reported for the adsorption of iodine, development of effective adsorbent with significantly improved segregation properties for widespread practical applications still remain exceedingly difficult due to lack of proper design strategies. Herein, utilizing unique hybridization synthetic strategy, a composite crystalline aerogel material has been fabricated by covalent stepping of an amino-functionalized stable cationic discrete metal-organic polyhedra with dual-pore containing imine-functionalized covalent organic framework. The ultralight hybrid composite exhibits large surface area with hierarchical macro-micro porosity and multifunctional binding sites, which collectively interact with iodine. The developed nano-adsorbent demonstrate ultrahigh vapor and aqueous-phase iodine adsorption capacities of 9.98 g.g−1 and 4.74 g.g−1, respectively, in static conditions with fast adsorption kinetics, high retention efficiency, reusability and recovery.

Ensemble learning (EL) has become an essential technique in machine learning that can significantly enhance the predictive performance of basic models, but it also comes with an increased cost of computation. The primary goal of the proposed approach is to present a general integrative framework that allows for applying active learning (AL) which makes use of only limited budget by selecting optimal instances to achieve comparable predictive performance within the context of ensemble learning. The proposed framework is based on two distinct approaches: (i) AL is implemented following a full scale EL, which we call the ensemble learning on top of active learning (ELTAL), and (ii) apply the AL while using the EL, which we call the active learning during ensemble learning (ALDEL). Various algorithms for ELTAL and ALDEL are presented using Stacking and Boosting with various algorithm-specific query strategies. The proposed active learning algorithms are numerically illustrated with the Support Vector Machine (SVM) model using simulated data and two real-world applications, evaluating their accuracy when only a small number instances are selected as compared to using full data. Our findings demonstrate that: (i) the accuracy of a boosting or stacking model, using the same uncertainty sampling, is higher than that of the SVM model, highlighting the strength of EL; (ii) AL can enable the stacking model to achieve comparable accuracy to the SVM model using the full dataset, with only a small fraction of carefully selected instances, illustrating the strength of active learning.

The hygroscopic motion of plants has inspired the development of moisture‐activated soft actuators. These actuators driven by ambient moisture sources are of great research interest in robotics and self‐regulating textiles. However, these actuators often have slow motion and can only perform bending and twisting motions. Herein, a cellulose film‐based fast‐morphing and motion‐programmable soft actuator is presented that can generate caterpillar‐like movement. The cellophane films reported here bend almost instantaneously under changing humidity, with a large bending curvature, high repeatability, and negligible hysteresis. Different actuation modes are studied using both coated and uncoated cellophane films. The uncoated cellophane film can continuously move on a moist substrate through autonomous bending–rolling–flipping (or oscillating) cycles. A facile strategy is used here to control the rolling direction and facilitate the flipping motion by offsetting its center of gravity during deformation by adding appropriate weights on the end of the actuator. The coated cellophane film is used to fabricate motion‐programmable actuators through heat‐laminating. Several actuator structures are designed and fabricated and their diverse moisture‐induced motions are demonstrated.

Yellow stem borer [Scirpophaga incertulas (Walker)], is a major pest of low-land rice (Oryza sativa L.), causing 30–40% yield losses. The use of biological control agents to suppress yellow stem borer (YSB) population and damage across Asia includes inundative releases of the egg parasitoid, Trichogramma japonicum Ashmead. However, information on the time and number of parasitoids’ releases are lacking to control YSB in summer low-land rice. Therefore, an experiment was conducted during summer seasons of 2018 and 2019 at ICAR-National Institute of Biotic Stress Management, Raipur, Chhattisgarh to standardize the time and number of T. japonicum releases for effective biocontrol of YSB. Experiment consisted of 3 different treatment schedules, viz. T1, Four releases of T. japonicum at weekly intervals on the 7th, 14th, 21st, 28th days after planting (DAT); T2, Four releases of T. japonicum at weekly intervals on the 14th, 21st, 28th, 35th DAT; T3, Four releases of T. japonicum at weekly intervals on the 21st, 28th, 35th, 42nd DAT; and T4, Control (no release of wasps). Significant reduction of YSB-induced damage symptoms was observed in the treatment schedule (T2) consisting of four releases of T. japonicum (@50,000 wasps/ha/release) at weekly intervals on the 14th, 21st, 28th, 35th DAT of rice which significantly reduced the dead heart (9.1%, 45.83% reduction over control) and the white ear (1.8%, 47.05% reduction over control), as compared to untreated control plots (T4) (16.8% dead heart, 3.4% white ear) in summer 2018. Similarly, in summer 2019, the reduction in dead heart and white ear by the treatment (T2) was 43.35% and 46.15% over control, respectively. The significant reduction of YSB-induced damages corresponded with the increased grain yield in (T2) from 2018–19 i.e. 12.74–20.18% across the seasons. The results suggest that the (T2) augmentative releases provided ecologically viable bio-control of YSB during the summer seasons in low-land rice.

Summary: The translocation of polymers is omnipresent in inherently crowded biological systems. We investigate the dynamics of polymer translocation through a pore in free and crowded environments using Langevin dynamics simulation. We observed a location-dependent translocation rate of monomers showcasing counterintuitive behavior in stark contrast to the bead velocity along the polymer backbone. The free energy calculation of asymmetrically placed polymers indicates a critical number of segments to direct receiver-side translocation. For one-sided crowding, we have identified a critical crowding size revealing a nonzero probability of translocation toward the crowded-side. Moreover, we have observed that shifting the polymer toward the crowded-side compensates for one-sided crowding, yielding an equal probability akin to a crowder-free system. In two-sided crowding, a slight variation in crowder size and packing fraction induces a polymer to switch its translocation direction. These conspicuous yet counter-intuitive phenomena are rationalized by minimalistic theoretical arguments based on osmotic pressure and radial entropic forces.

Climate change impacts such as climate-amplified weather events are increasing in intensity, frequency, and severity. Despite climate change affecting areas all around the world, the adverse impacts of climate change are unequally distributed, causing specific populations to be more susceptible to the impacts of climate change. Addressing climate inequalities in health research requires a climate justice approach, which prioritizes recognitional, distributional, and procedural justice in research and intervention design. Pregnant individuals are particularly vulnerable to climate change impacts since pregnancy represents a time of both psychological and physiological change that can be extremely sensitive to the environment. Nevertheless, there are few studies examining the association between pregnancy health and climate justice. This review evaluates the status of climate change impacts and pregnancy health outcomes through recognitional, distributive, and procedural justice definitions. We identify four themes already present in the literature: 1. Vulnerable Populations Within an Already Vulnerable Population, 2. Need for More Ecological-level Studies, 3. Addressing the Structural Factors that Drive Climate Injustice, and 4. Community-Centered Solutions Moving Forward. Our findings emphasize the importance of transdisciplinary, participatory, and multisectoral collaboration to improve climate-related pregnancy health interventions.

Background The temporal progression states of the molecular and structural substrate in atrial fibrillation (AF) are not well understood. We hypothesized that these can be detected by AF electrograms and magnetic resonance imaging parametric mapping. Methods and Results AF was induced in 43 dogs (25–35 kg, ≥1 year) by rapid atrial pacing (RAP) (3–33 weeks, 600 beats/min), and 4 controls were used. We performed high‐resolution epicardial mapping (UnEmap, 6 atrial regions, both atria, 130 electrodes, distance 2.5 mm) and analyzed electrogram cycle length, dominant frequency, organization index, and peak‐to‐peak bipolar voltage. Implantable telemetry recordings were used to quantify parasympathetic nerve activity over RAP time. Magnetic resonance imaging native T1, postcontrast T1, T2 mapping, and extracellular volume fraction were assessed (1.5T, Siemens) at baseline and AF. In explanted atrial tissue, DNA oxidative damage (8‐hydroxy‐2′‐deoxyguanosine staining) and percentage of fibrofatty tissue were quantified. Cycle length and organization index decreased (R=0.5, P

As cancer therapies increase in effectiveness and patients' life expectancies improve, balancing oncologic efficacy while reducing acute and long-term cardiovascular toxicities has become of paramount importance. To address this pressing need, the Cardiology Oncology Innovation Network (COIN) was formed to bring together domain experts with the overarching goal of collaboratively investigating, applying, and educating widely on various forms of innovation to improve the quality of life and cardiovascular healthcare of patients undergoing and surviving cancer therapies. The COIN mission pillars of innovation, collaboration, and education have been implemented with cross-collaboration among academic institutions, private and public establishments, and industry and technology companies. In this report, we summarize proceedings from the first two annual COIN summits (inaugural in 2020 and subsequent in 2021) including educational sessions on technological innovations for establishing best practices and aligning resources. Herein, we highlight emerging areas for innovation and defining unmet needs to further improve the outcome for cancer patients and survivors of all ages. Additionally, we provide actionable suggestions for advancing innovation, collaboration, and education in cardio-oncology in the digital era.

Purpose Vemifltration units are sludge-free, noise-free and low- or no-electricity-requiring systems of operation. The aim of this study was to emphasize wastewater treatment by vermifiltration technology using waste-eater earthworms to highlight the benefits of clean and nutritive vermifiltered water (vermiaqua) uses in agriculture to the farmers. Methods Wastewater sample was filtered through fabricated vermifiltration unit to study physio-chemical and biological properties of vermiaqua and uniform-sized Allium cepa (Onion) bulbs were kept for root germination at different concentrations (10â1, 10â3, 10â5, 10â7, 10â9) of wastewater and vermiaqua at room temperature for 5 days to study impacts of vermiaqua on morphological and cytological characteristics of onion. Results Vermiaqua was odorless, pale yellow in appearance, lower in turbidity and highly nutritive as ammonia and nitrate contents were highly increased. In E. coli-free vermiaqua, BOD5 loads were also reduced by 91%. Almost all vermiaquatreated root germinations were âacceleratedâ, whereas all wastewater-treated root germinations were âretardedâ. The highest number of germinated roots was counted at 10â5 concentration of vermiaqua, whereas at the same concentration of wastewater no germination was observed. Many types of chromosomal abnormalities were observed at metaphase and anaphase stages of wastewater-treated roots, whereas the single type of chromosomal abnormality was observed at anaphase stage of vermiaqua-treated roots. Conclusions Earthworms upgraded the performance of fabricated systems having integrated methods (biological, chemical and physical) of wastewater purification. Morphological and cytological studies revealed vermiaqua highly promoted the root germination without any chromosomal abnormalities.

BackgroundParkinson's Disease (PD) affects movement and cognition, and physiotherapy, particularly treadmill gait training, has potential in addressing movement dysfunctions in PD. However, treadmill training falls short in addressing cognitive aspects and adherence. Virtual reality (VR) and gamification can enhance motor and cognitive retraining and improve adherence. People with Parkinson's Disease (PWPD) have decreased motor skill learning efficiency, but tDCS can improve motor and cognitive learning.Methods78 participants with PD will be randomly allocated in a 1:1:1 ratio to one of three groups: (1) treadmill + Gamified Virtual Reality Environment (GVRE) + tDCS training group; (2) treadmill + GVRE training group or (3) treadmill training group. Participants will follow a 6-week, 12-session treadmill gait training plan, gradually increasing session duration from 20 to 45 minutes. Participants in (1) and (2) will undergo a GVRE training protocol, with (1) also receiving tDCS for the first 20 minutes of each session. Assessments will occur at baseline, post-intervention, and at a 6-week follow-up. The primary outcome measure will be gait speed during single and dual-task performance. Secondary measures will include additional gait parameters, executive tests for cognitive performance, and clinical outcomes for disease stage, cognitive status, and physical condition.DiscussionThis randomized clinical trial presents an innovative neurorehabilitation protocol that aims to improve gait and cognition in PWPD. The study also examines how tDCS can enhance motor and cognitive training. Results could contribute to enhancing the motor and cognitive state of PWPD through a GVRE and tDCS-based neurorehabilitation protocol.Trial registrationNCT05243394. 28/02/2024 -v3.2.

Malaria remains a global health challenge with significant mortality and morbidity annually, with resistant parasite strains complicating treatment efforts. There is an acute need for novel antimalarial drugs that can put a stop to the future public health crisis caused by the multi-drug resistance strains of the Plasmodium parasite . However, the discovery of these new components is very challenging in the context of the generation of multi-drug resistance properties of malaria. The novel drugs also need to have several properties involving enhanced therapeutic prospects, successful treatment capabilities, and novel mechanisms of action that will forestall the resistance. To successfully achieve this aim researchers are trying to focus on exploring promising malaria targets. Various approaches have been made for the development of drugs for malaria including the remodelling of existing drugs and the development of novel inhibitors which acts on new targets. Advancement in the study provides more information on the biology of parasites and the new targets which help in the development of novel drugs. The present review focuses on the study of novel targets of malaria parasites and subsequent inhibitors of those particular targets. Some of these targets include malarial protease, various transporter proteins, enzymes involved in the synthesis of DNA, and nucleic acids like dihydroorotate dehydrogenase, dihydrofolate reductase, apicoplast and dihydropteroate synthase. Other potential targets are also included in this review such as isoprenoid biosynthesis, farnesyl transferase of parasite, P. falciparum translational elongation factor 2, and phosphatidyl inositol 4 kinase. These promising targets have also been summed up along with their corresponding inhibitors for combating multi-drug resistance malaria., Competing Interests: Conflict of interestNo conflict of interest to declare. This manuscript and its subheadings are related to the journal., (© Indian Society for Parasitology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objectives: This study discusses the experience at our centre with treating traumatic thoracolumbar fractures using percutaneous pedicle screw fixation., Methods: We reviewed the case notes and imaging retrospectively between January 2013 and June 2019., Results: A total of 257 patients were included, 123 males and 134 females aged between 17 and 70; the mean age was 47.6 years. The majority of injuries were from fall from significant height. The fractures involved the thoracic and lumbar vertebra in 98 and 151 of the cases respectively. Percutaneous pedicle screw fixation was performed either one or two levels above and below the fracture depending on the level of injury. Forty two cases were treated with additional short pedicle screws at the level of fracture. More than 15% (39) of the patients presented with a neurological deficit; more than 80% (32) of those showed post-operative improvement in their neurology as per Frankel Grading system. The mean operative time was 117 min ± 45 min; mean length of hospital stay was 7.2 days ± 3.8 days, with significant improvement in pain., Conclusions: Percutaneous pedicle screw fixation is a safe surgical option with comparable outcomes to open surgery and a potential reduction in perioperative morbidity.

Developing sustainable and multifunctional materials is imperative for advancing anti-counterfeiting measures, sensing technologies, and intelligent packaging solutions. Concurrently, materials based on carbon dots (CDs) and cellulose nanocrystals (CNCs) are becoming established in such applications. Therefore, herein, we present the fabrication and characterization of water-based CDs and CNCs from Vigna mungo (black lentil: BL). The carbon dots (CD BL ) were doped with nitrogen (NCD BL ) and sulfur (SCD BL ). These CDs were then utilized as anti-counterfeit inks and multifunctional sensor films when loaded in a biodegradable CNC BL matrix. These CD BL , SCD BL , and NCD BL exhibited diameters of 3.7, 5.3, and 5.5 nm, respectively, with bandgap values ranging from 3.65 eV to 2.95 eV. For anti-counterfeiting, CDs/CNC BL -based inks were applied to white sheets, rendering them invisible under normal lighting conditions and visible under UV light (365 nm). NCD BL exhibited sensitivity towards pH changes (2-12), demonstrating the sensing potential of NCD BL /CNC BL films for monitoring food freshness. Additionally, NCD BL /CNC BL -based films have exhibited effective control over microbial load due to nitrogen doping. These films biodegrade within 29 days when buried in soil after use. This innovative approach presents multifunctional films that address critical needs in sensing, anti-counterfeiting, and intelligent packaging and opens new avenues for creating eco-friendly, multifunctional materials.

Purpose: Histone methyltransferases are enzymes that selectively methylate lysine or arginine residues on both histone and non-histone proteins, categorized into lysine methyltransferases and arginine methyltransferases. Notably, EZH2 and PRMT5 are known for catalyzing trimethylation of H3 at K27 and symmetric dimethylation of H4 at R3, respectively. These methylation events are recognized as characteristic histone-repressive marks in cancer. The over expression of PRMT5 and EZH2 were reported in various cancers and recognized as a drug target. The study aims to explore the inhibitory potential of phytocompound, Epigallocatechin-3-gallate (EGCG), against PRMT5 and EZH2 in the breast cancer model., Methods: Screening of an array of phytocompounds was conducted through a combination of in-silico and in-vitro assays. Interactions between EGCG and human PRMT5: MEP50 and EZH2 were evaluated using molecular docking. Binding efficiency was validated, by Surface Plasmon Resonance studies and inhibitory potential was accessed by in vitro methylation followed by western blots, ELISA, and cell-based assays. In-vivo efficacy of EGCG was carried on cell line derived mice xenograft model., Results: EGCG demonstrated robust interactions with PRMT5:MEP50 complex and EZH2, particularly within the SAM binding site. Surface Plasmon Resonance analysis revealed strong binding affinity in nanomolar concentrations, particularly with PRMT5-MEP50 compared to EZH2. In-vitro assays confirmed EGCG's ability to inhibit PRMT5 and EZH2, leading to a decrease in their catalytic products, namely H4R3me2s and H3K27me3, respectively. EGCG treatment induced both autophagy and apoptosis invitro. In-vivo studies demonstrated significant reductions in tumor size and the proliferation marker ki67, accompanied by a decrease in histone repressive marks., Conclusion: The findings suggest that EGCG effectively inhibits PRMT5 and EZH2, underscoring its potential for combined therapeutic strategies in cancer treatment., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024. Published by Elsevier Inc.)

The present investigation is subjected to comprehensive phytoestrogen analysis from Senna occidentalis pre-winter and winter seasonal pods using LC-MS and NMR. The analysis of the extracts revealed the presence of many phytoestrogens. Furthermore, molecular docking studies were employed for the investigation of the in-silico interactions between the isolated phytoestrogens and PPAR-α. The results of the molecular docking study demonstrated that among the identified compounds, PPAR-α exhibited the highest binding affinity, with a binding energy of -8.5 kcal/mol. It was closely followed by kaempferol, myricetin, quercetin, and apigenin, with binding energies of -8.5 kcal/mol, -7.8 kcal/mol, -7.6 kcal/mol, and -7.3 kcal/mol, respectively. These findings indicate that the compounds may interact with PPAR-α, potentially altering its activity. The study reveals the presence of various phytochemicals and their potential interaction with PPAR-α, underscoring their promise for drug development. The notable binding affinities observed with PPAR-α hint at their prospective use in therapeutic interventions.