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This paper aims to study the flow of a non-Newtonian fluid of Reiner-Rivlin type between two co-axial porous circular cylinders. The inner cylinder moves with a transient velocity while the outer one is fixed.

Results are presented for the measurement of large-scale anisotropies in the arrival directions of ultra–high-energy cosmic rays detected at the Pierre Auger Observatory during 19 yr of operation, prior to AugerPrime, the upgrade of the observatory. The 3D dipole amplitude and direction are reconstructed above 4 EeV in four energy bins. Besides the established dipolar anisotropy in R.A. above 8 EeV, the Fourier amplitude of the 8–16 EeV energy bin is now also above the 5 σ discovery level. No time variation of the dipole moment above 8 EeV is found, setting an upper limit to the rate of change of such variations of 0.3% yr ^−1 at the 95% confidence level. Additionally, the results for the angular power spectrum are shown, demonstrating no other statistically significant multipoles. The results for the equatorial dipole component down to 0.03 EeV are presented, using for the first time a data set obtained with a trigger that has been optimized for lower energies. Finally, model predictions are discussed and compared with observations, based on two source emission scenarios obtained in the combined fit of spectrum and composition above 0.6 EeV.

This study investigates the photophysical behaviour of Mn/Fe and Mn/Sn co-doped CsPbCl 3 perovskite nanocrystals (NCs) to explore carrier dynamics and dopant interactions. Using gated photoluminescence (PL) and temperature-dependent measurements, we elucidate the impact of dopant chemistry on exciton behaviour, focusing on vibrationally assisted delayed fluorescence (VADF) and energy transfer mechanisms. The efficiency of VADF is influenced by factors such as the bandgap, temperature, quantum confinement, and host composition. In Mn/Fe co-doped NCs, Fe-induced trap states introduce additional radiative pathways, resulting in a unique emission around 515 nm. In contrast, in Mn/Sn co-doped NCs, Sn captures photoexcited carriers, preventing the VADF process and leading to non-radiative decay. The findings provide key insights into dopant-dopant interactions and the mechanisms governing carrier transfer, enhancing our understanding of these materials for future optoelectronic applications., (© 2025 Wiley-VCH GmbH.)

Regioselective and enantioselective C-H functionalization is a valuable method for synthesizing chiral and complex molecules. However, it often requires large amounts of toxic oxidants and high temperature, making it environmentally and economically adverse. Additionally, these traditional approaches generally suffer from regioselectivity and enantioselectivity issues. To overcome these limitations, a new mechanism is needed to control both of these simultaneously. Herein, we report the first Pd catalyzed regioselective distal and atroposelective olefination of simple arenes/biaryls via an electrooxidative reaction pathway. This unique electro-oxidative strategy with Pd(II) catalysis demonstrates unprecedented access to 'regio-resolved' reactions, furnishing chiral molecule synthesis under dynamic kinetic resolution without the conventional requirement of metal-based oxidants and thermal energy. Both electroanalytical studies and DFT calculations suggest the involvement of a Pd(II)/Pd(IV) catalytic cycle via a crucial Pd(III) intermediate that initiates both the distal and atroposelective olefination reactions., (© 2025 Wiley-VCH GmbH.)

In the lush tea estates of Northeast India, the growth of the tea plant (Camellia sinensis L.) hinges on the intricate dance of soil properties. This present study delves into the soil characteristics of sixteen tea estates, situated spanning the verdant landscapes of Assam and the enchanting Darjeeling hills in West Bengal. We meticulously analyzed soil pH, organic carbon (OC) content, texture, available nitrogen, phosphorus, potassium, sulfur, exchangeable calcium, and magnesium using rigorous standard methods. In our analysis, we also investigated various forms of soil acidity. These include exchangeable acidity (EA), exchangeable aluminum (EAl), exchangeable hydrogen (EH), extractable acidity (ExtA), hydrolytic acidity (HA), non-exchangeable aluminum (NEA), pH-dependent acidity (pHDA), total acidity (TA), and total potential acidity (TPA). The findings revealed that most of the estates have soil with acidity levels below 4.50 rendering it unsuitable for tea cultivation. The various acidity fractions exhibited specific ranges for different soil components, with pH-dependent acidity emerging as the primary contributor to TPA, and EAl, exerting the most significant influence on TA in the soils being investigated. The study also demonstrated a strong inverse relationship between pH and all forms of acidity, except for non-exchangeable acidity and hydrolytic acidity. Furthermore, the presence of OC was found to have a substantial impact on soil acidity, displaying a notably strong positive association with EA, pHDA, and TPA. Canonical correlation analysis (CCA) revealed the relationship between soil acidity and its physical and chemical properties. The principal component analysis (PCA) showed that the first six PCs accounted for over 80% of the variability, with PC-1, PC-2, and PC-3 describing 31.86, 20.78, and 14.13% respectively. These results highlight the urgent need for soil amendments and better field management practices to combat soil acidity for sustainable tea cultivation., Competing Interests: Declarations. Ethics approval: The authors declare that the submitted manuscript is original. They also acknowledge that the current research has been conducted ethically and that the final shape of the research has been agreed upon by all the authors. Consent to participate: The authors consent to participate in this research study. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This work estimates Michaelis-Menten kinetics parameters for nutrient transport under varying flow rates in the soft roots of Indian mustard ( Brassica juncea ) using a plant fluidic device. To find the metallic components within the roots, inductively coupled plasma mass spectrometry (ICP-MS) analysis was performed. The flow rate-dependent metabolic changes were examined using Raman spectral analysis. In addition, three-dimensional numerical simulations were conducted to assess mechanical stresses resulting from the concentration difference that enhances osmotic pressure and flow loading at the root-liquid interface. Convection, the primary mode of nutrient transport in flowing media, was observed to reduce nutrient uptake at higher flow rates. In contrast, diffusion became more prevalent in areas where the complex root structure restricted the flow field. The concentration gradient between the upstream and downstream regions of the root caused nutrient diffusion from downstream to upstream. As seen, an increase in flow rate resulted in a decrease in root length due to the reduction of advantageous metabolites, which led to lower average mechanical stress and osmotic pressure loading. Additionally, osmotic pressure at the root-liquid interface was found to increase over time. Numerical simulations revealed that the average internal mechanical stress was substantially greater when osmotic pressure was considered. This emphasizes the importance of accounting for osmotic pressure when assessing mechanical stress in roots. This study uses a fluidic device that replicates hydroponic conditions for the first time in order to evaluate the convection-dependent Michaelis-Menten kinetics of nutrient uptake in plant roots.

We present measurements of the atmospheric depth of the shower maximum X_{max}, inferred for the first time on an event-by-event level using the surface detector of the Pierre Auger Observatory. Using deep learning, we were able to extend measurements of the X_{max} distributions up to energies of 100 EeV (10^{20}  eV), not yet revealed by current measurements, providing new insights into the mass composition of cosmic rays at extreme energies. Gaining a 10-fold increase in statistics compared to the fluorescence detector data, we find evidence that the rate of change of the average X_{max} with the logarithm of energy features three breaks at 6.5±0.6(stat)±1(syst)  EeV, 11±2(stat)±1(syst)  EeV, and 31±5(stat)±3(syst)  EeV, in the vicinity to the three prominent features (ankle, instep, suppression) of the cosmic-ray flux. The energy evolution of the mean and standard deviation of the measured X_{max} distributions indicates that the mass composition becomes increasingly heavier and purer, thus being incompatible with a large fraction of light nuclei between 50 and 100 EeV.

Antiretroviral therapy (ART) improves the quality of life for those living with the human immunodeficiency virus type one (HIV-1). However, poor compliance reduces ART effectiveness and leads to immune compromise, viral mutations, and disease co-morbidities. Here we develop a drug formulation in which a lipid-based nanoparticle (LBNP) carrying rilpivirine (RPV) is decorated with the C-C chemokine receptor type 5 (CCR5) targeting peptide. This facilitates extended drug persistence within myeloid cells. Particle delivery to viral reservoirs is tracked by positron emission tomography. The CCR5-mediated LBNP cell uptake and retention reduce HIV-1 replication in human monocyte-derived macrophages and infected humanized mice (hu mice). Focused ultrasound with microbubbles mediated blood brain barrier (BBB) disruption allows the CCR5-targeted LBNP to penetrate the BBB and reach brain myeloid cells. These findings offer a role for CCR5-targeted therapeutics in antiretroviral delivery to optimize HIV suppression., Competing Interests: Competing interests: The authors declare that Dr. Howard Gendelman co-founder of Exavir Therapeutics, Inc. The biotechnology company is developing ultra-long-acting drugs. The drugs in development are not linked to those created in the current report. All other authors declare no competing interests., (© 2025. The Author(s).)

Room temperature stirring of a mixture of chalcogenated arylhydrazones and ninhydrin in dichloromethane (DCM) in the presence of acid leads to the formation of pyrazole-fused isocoumarins, substituted with a diarylsulphide/diarylselenide moiety. On the other hand, refluxing the same mixture in the protic polar solvent ethanol with acid produces diarylsulphide/diarylselenide containing ninhydrin hydrazones. Further study reveals that, like ninhydrin, isatin can also generate the corresponding chalcogenated hydrazones at the C-3 position under similar reaction conditions.

In vivo, molecular imaging is prevalent for biology research and therapeutic practice. Among advanced imaging technologies, photoacoustic (PA) imaging and sensing is gaining interest around the globe due its exciting features like high resolution and good (~ few cm) penetration depth. PA imaging is a recent development in ultrasonic technology that generates acoustic waves by absorbing optical energy. However, poor light penetration through tissue continues to be the key obstacle in the field. The NPs as contrast agents can assist in overcoming tissue penetration depth as NPs can produce high signal to noise (SNR) PA signal which aids reconstruction of high resolution of the PA images in deep tissue sights. Subsequently, NPs are very effective in PA based targeted and precise theranostic applications. This article detail about various NPs (organic, inorganic and hybrid) used in PA imaging and spectroscopy applications including various disease diagnosis, therapy and theranostic. It also features optical property, advantages and limitations of various NPs utilised in PA techniques which would comprehend readers about the potential of NPs in evolving PA technique from laboratory to clinical modality in future., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The orientation and function of smooth muscle in the cervix may contribute to the important biomechanical properties that change during pregnancy. Thus, this study examined the three-dimensional structure, smooth muscle phenotype, and mechanical and contractile functions of the upper and lower cervix of nongravid (not pregnant) and gravid (pregnant) mice. In gravid cervix, we uncovered region-specific changes in the structure and organization of fiber tracts. We also detected a greater proportion of contractile smooth muscle cells (SMCs), but an equal proportion of synthetic SMCs, in the upper versus lower cervix. Furthermore, we revealed that the lower cervix had infrequent spontaneous contractions, distension had a minimal effect on contractility, and the upper cervix had forceful contractions in response to labor-inducing agents (oxytocin and prostaglandin E 2 ). These findings identify regional differences in cervix contractility related to contractile SMC content and fiber organization, which could be targeted with diagnostic technologies and for therapeutic intervention.

RNA interference has emerged as a promising therapeutic strategy to tackle acute kidney injury (AKI). Development of targeted delivery systems is highly desired for selective renal delivery of RNA and improved therapeutic outcomes in AKI. Inulin is a plant polysaccharide traditionally employed to measure glomerular filtration rate. Here, we describe the synthesis of inulin modified with α-cyclam-p-toluic acid (CPTA) to form a novel renal-targeted polymer, Inulin-CPTA (IC), which is capable of selective siRNA delivery to the injured kidneys. We show that conjugating CPTA to inulin imparts IC with targeting properties for cells that overexpress the C-X-C chemokine receptor 4 (CXCR4). Self-assembled IC/siRNA nanoparticles (polyplexes) demonstrated rapid accumulation in the injured kidneys with selective uptake and prolonged retention in injured renal tubules overexpressing the CXCR4 receptor. Tumor-suppressor protein p53 contributes significantly to the pathogenesis of AKI. siRNA-induced silencing of p53 has shown therapeutic potential in several preclinical studies, making it an important target in the treatment of AKI. Systemically administered nanoparticles formulated using IC and siRNA against p53 selectively accumulated in the injured kidneys and potently silenced p53 expression. Selective p53 knockdown led to positive therapeutic outcomes in mice with cisplatin-induced AKI, as seen by reduced tubular cell death, renal injury, inflammation, and overall improved renal function. These findings indicate that IC is a promising new carrier for renal-targeted delivery of RNA for the treatment of AKI., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Duchenne muscular dystrophy (DMD) gene encodes dystrophin, a large multidomain protein. Its nonfunctionality leads to dystrophinopathies like DMD and Becker muscular dystrophy, for which no cure is yet available. A few therapies targeted towards specific mutations can extend the lifespan of patients, although with limited efficacy and high costs, emphasizing the need for more general treatments. Dystrophin's complex structure with poorly understood domains and the presence of multiple isoforms with varied expression patterns in different tissues pose challenges in therapeutic development. The C-terminal (CT) domain of dystrophin is less understood in terms of its structure-function, although it has been shown to perform important functional roles by interacting with another cytosolic protein, dystrobrevin. Dystrophin and dystrobrevin stabilize the sarcolemma membrane by forming a multiprotein complex called dystrophin-associated glycoprotein complex that is destabilized in DMD. Dystrobrevin has two major isoforms, alpha and beta, with tissue-specific expression patterns. Here, we characterize the CT domain of dystrophin and its interactions with the two dystrobrevin isoforms. We show that the CT domain is nonglobular and shows reversible urea denaturation as well as thermal denaturation. It interacts with dystrobrevin isoforms differentially, with differences in binding affinity and the mode of interaction. We further show that the amino acid differences in the CT region of dystrobrevin isoforms contribute to these differences. These results have implications for the stability of dystrophin-associated glycoprotein complex in different tissues and explain the differing symptoms associated with DMD patients affecting organs beyond the skeletal muscles., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Developing a water-soluble, oxygen-tolerant, and acid-stable synthetic H 2 production catalyst is vital for renewable energy infrastructure. To access such an effective catalyst, we strategically incorporated enzyme-inspired, multicomponent outer coordination sphere elements around the cobaloxime (Cl-Co-X) core with suitable axial coordination (X). Our cobaloximes with axial imidazole or L-histidine coordination in photocatalytic HAT including the construction of anilines via a non-canonical cross-coupling approach is found superior compared to commonly used cobaloxime catalysts. The reversible Co(II)/Co(I) process is influenced by the axial N ligand's nature. Imidazole/L-histidine with a higher pKa promptly produces H 2 upon irradiation, leading to the improved reactivity compared to previously employed axial (di)chloride or pyridine analogue., (© 2024 Wiley-VCH GmbH.)

Metal hexacyanoferrates (MHCF) are a class of inorganic adsorbents used for wastewater management due to the presence of interstitial sites for capturing heavy metal ions. In present work, we are reporting the synthesis of magnetic nanocomposite of Fe 3 O 4 /graphene oxide/potassium copper hexacyanoferrate via wet chemical and coprecipitation approach. Potassium copper hexacyanoferrate (KCuHCF) and Graphene oxide (GO) both are marvelous adsorbents but their nano-size becomes a major obstacle in their separation process after the adsorption of the radionuclides. Thus, our synthesized nanocomposite Fe 3 O 4 /GO/KCuHCF enhances the recovery of KCuHCF even after radioactive Cs + adsorption with adsorption capacity of 18 mg g -1 coinciding well with the Langmuir adsorption isotherm mechanism. The synthesized adsorbent is characterized thoroughly using UV-Visible spectroscopy, FT-IR, TGA, XPS, Raman spectroscopy, TEM-EDAX and XRD. This synthesized nanocomposite is used for the batch extraction of radioactive Cs + from low level radioactive waste (LLW). The extraction kinetics followed pseudo-second-order kinetics mechanism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The recent success of gene therapy during the COVID-19 pandemic has underscored the importance of effective and safe delivery systems. Complementing lipid-based delivery systems, polymers present a promising alternative for gene delivery. Significant advances have been made in the recent past, with multiple clinical trials progressing beyond phase I and several companies actively working on polymeric delivery systems which provides assurance that polymeric carriers can soon achieve clinical translation. The massive advantage of structural tunability and vast chemical space of polymers is being actively leveraged to mitigate shortcomings of traditional polycationic polymers and improve the translatability of delivery systems. Tailored polymeric approaches for diverse nucleic acids and for specific subcellular targets are now being designed to improve therapeutic efficacy. This review describes the recent advances in polymer design for improved gene delivery by polyplexes and covalent polymer-nucleic acid conjugates. The review also offers a brief note on novel computational techniques for improved polymer design. The review concludes with an overview of the current state of polymeric gene therapies in the clinic as well as future directions on their translation to the clinic., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Malaria is a worldwide health concern, but a great majority of cases occur in tropical countries like India. With almost 95% of Indian population living in malaria endemic regions, India contributes to most of the global malaria cases and deaths, outside of African countries. Despite significant advances towards malaria control and eradication, mortality associated with severe malaria remains particularly high. Changing epidemiology, vulnerable patient population, overlapping symptomatology, and limited availability of parenteral preparations of artemisinin derivatives pose significant challenges in management of severe malaria. Further, the dearth of large-scale randomized trials from the developing countries makes it difficult to establish evidence-based guidelines pertaining to their situation. Thus, this position paper aims to provide guidance to critical care physicians across the country on managing patients with severe malaria in intensive care units (ICUs)., How to Cite This Article: Hegde A, Chhallani AK, Gupta B, Kadapatti K, Karnad D, Maheshwarappa HM, et al . ISCCM Position Statement on the Management of Severe Malaria in Intensive Care Unit. Indian J Crit Care Med 2024;28(S2):S59-S66., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2024; The Author(s).)

Lysine acetylation (AcK) is a prominent post-translational modification in eye lens crystallins. We have observed that AcK formation is preferred in some lysine residues over others in crystallins. In this study, we have investigated the role of thiols in such AcK formation. Upon incubation with acetyl-CoA (AcCoA), αA-Crystallin, which contains two cysteine residues, showed significantly higher levels of AcK than αB-Crystallin, which lacks cysteine residues. Incubation with thiol-rich γS-Crystallin resulted in higher AcK formation in αB-Crystallin from AcCoA. External free thiol (glutathione and N-acetyl cysteine) increased the AcK content in AcCoA-incubated αB-Crystallin. Reductive alkylation of cysteine residues significantly decreased ( p < 0.001) the AcCoA-mediated AcK formation in αA-Crystallin. Introduction of cysteine residues within ∼5 Å of lysine residues (K92C, E99C, and V169C) in αB-Crystallin followed by incubation with AcCoA resulted in a 3.5-, 1.3- and 1.3-fold increase in the AcK levels when compared to wild-type αB-Crystallin, respectively. Together, these results suggested that AcK formation in α-Crystallin is promoted by the proximal cysteine residues and protein-free thiols through an S → N acetyl transfer mechanism.

Background: While short-term outcomes of total knee arthroplasty (TKA) have been extensively studied, there is a need for longstanding assessments to understand the enduring impact of the procedure on patient well-being., Methods: A retrospective cohort research to rate the longstanding functional outcomes and quality of life (QoL) in those undergoing primary TKA. Patient-reported outcomes, including SF-36 and EQ-5D scores, were collected at multiple time points postoperatively (1, 5, and 10 years). Objective assessments of functional parameters, i.e., range of motion, gait analysis, and quadriceps strength, were also recorded., Results: Current findings demonstrate significant improvements in functional outcomes post-TKA, with sustained benefits observed over a 10-year period. Range of motion, gait parameters, and quadriceps strength showed consistent enhancements postoperatively. Moreover, QoL measures, as reflected by SF-36 and EQ-5D scores, exhibited substantial improvements following TKA and remained elevated throughout the follow-up period., Conclusion: This research highlights the enduring effectiveness of TKA in improving both functional outcomes and QoL in patients with advanced knee arthritis., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Background: "Proximal humerus fractures [PHFs]" are common orthopedic injuries, often requiring surgical intervention for optimal outcomes. However, the choice of surgical approach remains controversial, with varying outcomes reported in the literature., Methods: A retrospective research was overseen among subjects who had surgery for PHFs. Three surgical approaches were compared: "Open Reduction Internal Fixation (ORIF)", "Hemiarthroplasty [HA]", and "Reverse Shoulder Arthroplasty [RSA]". Demographic data, fracture characteristics, surgical details, and postoperative outcomes were analyzed., Results: ORIF confirmed smaller operative time and shorter complication levels compared to HA and RSA. Complications included surgical site infection, implant-related issues, and reoperation. Age, fracture type, and surgeon experience influenced the choice of surgical approach., Conclusion: This research provides valuable insights into the outcomes of different surgical approaches for PHFs. ORIF may offer advantages in select cases, but individualized treatment decisions are necessary. Further research is warranted to refine treatment algorithms and optimize patient outcomes., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Antiretroviral therapy (ART) improves the quality of life for those living with the human immunodeficiency virus type one (HIV-1). However, poor compliance reduces ART effectiveness and leads to immune compromise, viral mutations, and disease co-morbidities. A novel drug formulation is made whereby a lipid nanoparticle (LNP) carrying rilpivirine (RPV) is decorated with the C-C chemokine receptor type 5 (CCR5). This facilitates myeloid drug depot deposition. Particle delivery to viral reservoirs is tracked by positron emission tomography. The CCR5-mediated RPV LNP cell uptake and retention reduce HIV-1 replication in human monocyte-derived macrophages and infected humanized mice. Focused ultrasound allows the decorated LNP to penetrate the blood-brain barrier and reach brain myeloid cells. These findings offer a role for CCR5-targeted therapeutics in antiretroviral delivery to optimize HIV suppression., Competing Interests: Additional Declarations: Yes there is potential Competing Interest. Howard Gendelman is the co-founder of Exavir Therapeutics, Inc, a company formed to develop LA ART.

The effects of human activities are becoming clearer every year, with multiple reports of struggling and eroded ecosystems resulting in new threats of plant and animal extinctions throughout the world. It has been speculated that roadside tea-growing soils impact on metal dynamics from soil to tea plants and subsequently to tea infusion which may be threatened by increasingly unpredictable and dangerous surroundings. Furthermore, heavy metals released from vehicles on the national highway (NH) could be a source of metal contamination in roadside tea soils and tea plants. This study was articulated to realize the effect of NH on a buildup of selected metals (Cu, Cd, Fe, Mn, Ni, and Zn) in made tea along with repeated tea infusion. In general, metal concentration was found significantly higher in made tea prepared from the young shoots collected from the vicinity of NH. The results also showed that distance from the NH and infusion process significantly influenced to content of the analysed metal in tea infusions. The mean average daily intake (ADI) and hazard quotient (HQ) values of analysed tea samples were found in the orderMn˃Fe˃Zn˃Cu˃Ni˃Cd and Mn˃Cu˃Zn˃Fe˃Ni˃Cd, respectively. The HQ values of all analysed metals were found << 1, indicating that ingestion of tea infusion with analysed heavy metals should not cause a danger to human health. However, this study further demonstrates the consumption of tea infusion prepared from made tea around the vicinity of NH may contribute to a significantly higher quantity of metal intake in the human body. From the hierarchical cluster analysis, it has been observed that there are three homogenous groups of analysed heavy metals., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Moringa oleifera Lam. is a pan-tropical plant well known to the ancient world for its extensive therapeutic benefits in the Ayurvedic and Unani medical systems. The ancient world was familiar with this tree, but it has only lately been rediscovered as a multifunctional species with a huge range of possible therapeutic applications. It is a folk remedy for skin diseases, edema, sore gums, etc. This review comprises the history, ethnomedicinal applications, botanical characteristics, geographic distribution, propagation, nutritional and phytochemical profile, dermatological effects, and commercially available cosmeceuticals of Moringa oleifera Lam.Compilation of all the presented data has been done by employing various search engines like Science Direct, Google, PubMed, Research Gate, EBSCO, SciVal, SCOPUS, and Google Scholar.Studies on phytochemistry claim the presence of a variety of substances, including fatty acids, phenolic acids, sterols, oxalates, tocopherols, carotenoids, flavonoids, flavonols glycosides, tannins, terpenoids, terpene, saponins, phylates, alkaloids, glucosinolates, glycosides, and isothiocyanate. The pharmacological studies have shown the efficacy of Moringa oleifera Lam. as an antibacterial, antifungal, anti-inflammatory, antioxidant, anti-atopic dermatitis, antipsoriatic, promoter of wound healing, effective in treating herpes simplex virus, photoprotective, and UV protective. As a moisturizer, conditioner, hair growth promoter, cleanser, antiwrinkle, anti-aging, anti-acne, scar removal, pigmentation, and control for skin infection, sores, as well as sweating, it has also been utilized in a range of cosmeceuticals.he Moringa oleifera Lam. due to its broad range of phytochemicals can be proven boon for the treatment of dermatological disorders., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: Escherichia coli and Staphylococcus aureus are two of the most common bacterial species responsible for sepsis. While it is observed that they have disparate clinical phenotypes, the signaling differences elicited by each bacteria that drive this variance remain unclear. Therefore, we used human whole blood exposed to heat-killed E. coli or S. aureus and measured the transcriptomic signatures. Relative to unstimulated control blood, heat-killed bacteria exposure led to significant dysregulation (upregulated and downregulated) of >5,000 genes for each experimental condition, with a slight increase in gene alterations by S. aureus. While there was significant overlap regarding proinflammatory pathways, Gene Ontology overrepresentation analysis of the most altered genes suggested biological processes like macrophage differentiation and ubiquinone biosynthesis were more unique to heat-killed S. aureus, compared with heat-killed E. coli exposure. Using Ingenuity Pathway Analysis, it was demonstrated that nuclear factor erythroid 2-related factor 2 signaling, a main transcription factor in antioxidant responses, was predominately upregulated in S. aureus exposed blood relative to E. coli. Furthermore, the use of pharmacologics that preferentially targeted the nuclear factor erythroid 2-related factor 2 pathway led to differential cytokine profiles depending on the type of bacterial exposure. These findings reveal significant inflammatory dysregulation between E. coli and S. aureus and provide insight into the targeting of unique pathways to curb bacteria-specific responses., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

The success of long-acting (LA) drug delivery systems (DDSs) is linked to their biocompatible polymers. These are used for extended therapeutic release. For treatment or prevention of human immune deficiency virus type one (HIV-1) infection, LA DDSs hold promise for improved regimen adherence and reduced toxicities. Current examples include Cabenuva, Apretude, and Sunlenca. Each is safe and effective. Alternative promising DDSs include implants, prodrugs, vaginal rings, and microarray patches. Each can further meet patients' needs. We posit that the physicochemical properties of the formulation chemical design can optimize drug release profiles. We posit that the strategic design of LA DDS polymers will further improve controlled drug release to simplify dosing schedules and improve regimen adherence.

We show, for the first time, radio measurements of the depth of shower maximum (X&#95;{max}) of air showers induced by cosmic rays that are compared to measurements of the established fluorescence method at the same location. Using measurements at the Pierre Auger Observatory we show full compatibility between our radio and the previously published fluorescence dataset, and between a subset of air showers observed simultaneously with both radio and fluorescence techniques, a measurement setup unique to the Pierre Auger Observatory. Furthermore, we show radio X&#95;{max} resolution as a function of energy and demonstrate the ability to make competitive high-resolution X&#95;{max} measurements with even a sparse radio array. With this, we show that the radio technique is capable of cosmic-ray mass composition studies, both at Auger and at other experiments.

White Rabbit (WR) is an optical fibre-based time-frequency synchronization technology typically used in timekeeping laboratories for distributing time-frequency signals from a reference clock to distant locations. The accuracy of the received signals at the user end can be affected by random noise processes present in the WR network due to the internal electronic components of WR devices. In this paper, we investigate the presence of random noise processes in the WR network. We then study their statistical properties and model the distribution based on experimentally recorded measurements. According to our study, the probability density function (PDF) follows a Gaussian mixture model (GMM) with varying distribution parameters, and the correlation analysis indicates a strong correlation of the phase noise process over the temporal samples. Furthermore, the developed phase noise models have also been verified by comparing them against additional experimental data. Finally, we present the methodology to generate the phase noise process using computer simulations with the PDF and correlation models developed in this work to help algorithm developers and equipment manufacturers make use of our results.

Heterogeneous response to Enzalutamide, a second-generation androgen receptor signaling inhibitor, is a central problem in castration-resistant prostate cancer (CRPC) management. Genome-wide systems investigation of mechanisms that govern Enzalutamide resistance promise to elucidate markers of heterogeneous treatment response and salvage therapies for CRPC patients. Focusing on the de novo role of MYC as a marker of Enzalutamide resistance, here we reconstruct a CRPC-specific mechanism-centric regulatory network, connecting molecular pathways with their upstream transcriptional regulatory programs. Mining this network with signatures of Enzalutamide response identifies NME2 as an upstream regulatory partner of MYC in CRPC and demonstrates that NME2-MYC increased activities can predict patients at risk of resistance to Enzalutamide, independent of co-variates. Furthermore, our experimental investigations demonstrate that targeting MYC and its partner NME2 is beneficial in Enzalutamide-resistant conditions and could provide an effective strategy for patients at risk of Enzalutamide resistance and/or for patients who failed Enzalutamide treatment., (© 2024. The Author(s).)

Metal-free catalysts for various organic transformations are of high demand now. In this study, we present a new carbon dot as an efficient metal-free nanophotocatalyst for carrying out a series of organic bond formation reactions. Using a single photocatalyst carbon dot, Csp 2 -Csp 2 , Csp 2 -B, Csp 2 -S, Csp 2 -Se, and C-P bond formation reactions were performed with a high yield of the corresponding products. Moreover, Csp 2 -H activation of the aromatic ring was achieved by merging the carbon dot photocatalyst with a transition metal. Interestingly, these carbon nanodot-based catalysts show good recyclability a few times without any significant loss of catalytic activity. The development of catalytic systems based on carbon dots has its merits vested in the advantageous properties of this nanomaterial, such as a robust chemical nature and cheap cost of preparation. This report demonstrates that a carbon dot indeed holds the potential to replace expensive metal-based catalysts as well as organic dyes in five different photoredox reactions.

Diagnosing and then treating disease defines theranostics. The approach holds promise by facilitating targeted disease outcomes. The simultaneous analysis of finding the presence of disease pathophysiology while providing a parallel in treatment is a novel and effective strategy for seeking improved medical care. We discuss how theranostics improves disease outcomes is discussed. The chapter reviews the delivery of targeted therapies. Bioimaging techniques are highlighted as early detection and tracking systems for microbial infections, degenerative diseases, and cancers., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The design of supramolecular hydrogels comprising aligned domains is important for the fabrication of biomimetic materials and applications in optoelectronics. One way to access such materials is by the self-assembly of small molecules into long fibres, which can be aligned using an external stimulus. Out-of-equilibrium supramolecular gels can also be designed, where pre-programmed changes of state can be induced by the addition of chemical fuels. Here we exploit these dynamic properties to form materials with aligned domains through a 'forging' approach: an external force is used to rearrange the underlying network from random to aligned fibres as the system undergoes a pre-programmed gel-to-sol-to-gel transition. We show that we can predictably organize the supramolecular fibres, leading to controllable formation of materials with aligned domains through a high degree of temporal control., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

With hundreds of coronaviruses (CoVs) identified in bats that can infect humans, it is essential to understand how CoVs that affected the human population have evolved. Seven known CoVs have infected humans, of which three CoVs caused severe disease with high mortalities: severe acute respiratory syndrome (SARS)-CoV emerged in 2002, Middle East respiratory syndrome-CoV in 2012, and SARS-CoV-2 in 2019. SARS-CoV and SARS-CoV-2 belong to the same family, follow the same receptor pathway, and use their receptor-binding domain (RBD) of spike protein to bind to the angiotensin-converting enzyme 2 (ACE2) receptor on the human epithelial cell surface. The sequence of the two RBDs is divergent, especially in the receptor-binding motif that directly interacts with ACE2. We probed the biophysical differences between the two RBDs in terms of their structure, stability, aggregation, and function. Since RBD is being explored as an antigen in protein subunit vaccines against CoVs, determining these biophysical properties will also aid in developing stable protein subunit vaccines. Our results show that, despite RBDs having a similar three-dimensional structure, they differ in their thermodynamic stability. RBD of SARS-CoV-2 is significantly less stable than that of SARS-CoV. Correspondingly, SARS-CoV-2 RBD shows a higher aggregation propensity. Regarding binding to ACE2, less stable SARS-CoV-2 RBD binds with a higher affinity than more stable SARS-CoV RBD. In addition, SARS-CoV-2 RBD is more homogenous in terms of its binding stoichiometry toward ACE2 compared to SARS-CoV RBD. These results indicate that SARS-CoV-2 RBD differs from SARS-CoV RBD in terms of its stability, aggregation, and function, possibly originating from the diverse receptor-binding motifs. Higher aggregation propensity and decreased stability of SARS-CoV-2 RBD warrant further optimization of protein subunit vaccines that use RBD as an antigen by inserting stabilizing mutations or formulation screening., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Presbyopia is the progressive loss of the ability of the lens to focus on nearby objects due to its increased stiffness. It occurs in the mid-40s and continues to worsen until the mid-60s. The age-associated increase in protein cross-linking in the lens leads to protein aggregation and water insolubility, especially in the nuclear region, contributing to lens stiffness. This study reports the development of aggrelyte-2A (methyl S -acetyl- N -(3,3-dimethylbutanoyl) cysteinate, a derivative of our previously reported aggrelyte-2) for reversing the stiffness of aged lenses. Aggrelyte-2A showed minimal toxicity in cultured mouse lens epithelial cells (up to 2000 µM) and human lens epithelial cells (up to 250 µM). Lenses from aged mice (age: 24-25 months) treated with 1 mM aggrelyte-2A for 24 h, and human lenses (age: 47-67 years) treated with 250 µM aggrelyte-2A for 48 h showed 11-14% reductions in stiffness, accompanied by an increase in acetyllysine in lens proteins, and free-thiols in the lens. Topical application of aggrelyte-2A (40 mM, 5 µl twice daily for 4 weeks) on mouse eyes significantly reduced lens stiffness. The topical application showed no toxicity to the lens, cornea, or retina, as revealed by morphological examination, H&E staining, and optical coherence tomography. These data suggest that aggrelyte-2A could be developed as a presbyopia-reversing therapeutic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Panja, Nam, Gaikwad, Rankenberg and Nagaraj.)

Background While medical education is vital for producing competent physicians, its rigorous curriculum can harm students' mental well-being. This study focuses on assessing psychological stress in first-year medical students in Eastern India and aims to identify its primary causes. Methods This cross-sectional study involved 125 first-year MBBS students in a tertiary care medical teaching institution in eastern India. They completed the Medical Student Stressor Questionnaire (MSSQ-40) questionnaire to measure stress and provided academic records to be reviewed.  Results Among the 125 students included in the study, male students demonstrated greater academic and interpersonal stress. The findings revealed that a substantial proportion (79%) of the student population experienced high to severe levels of academic stress, followed by 88% who reported moderate to high levels of social-related stress. Furthermore, it was observed that those students who experienced high to severe stress across all six domains tended to perform poorly during the initial half of their academic year. Conclusion The high levels of stress experienced by medical students can have significant implications for their academic performance. However, the nature of our study limits us to only highlight the existence of a correlation between the two. Future studies on the same should be conducted to assess the causal relation between these factors., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Panja et al.)

Introduction: Chronological aging is a well-recognized diagnostic and prognostic factor in multiple cancer types, yet the role of biological aging in manifesting cancer progression has not been fully explored yet., Methods: Given the central role of chronological aging in prostate cancer and AML incidence, here we investigate a tissue-specific role of biological aging in prostate cancer and AML progression. We have employed Cox proportional hazards modeling to associate biological aging genes with cancer progression for patients from specific chronological aging groups and for patients with differences in initial cancer aggressiveness., Results: Our prostate cancer-specific investigations nominated four biological aging genes (CD44, GADD45B, STAT3, GFAP) significantly associated with time to disease progression in prostate cancer in Taylor et al. patient cohort. Stratified survival analysis on Taylor dataset and validation on an independent TCGA and DKFZ PRAD patient cohorts demonstrated ability of these genes to predict prostate cancer progression, especially for patients with higher Gleason score and for patients younger than 60 years of age. We have further tested the generalizability of our approach and applied it to acute myeloid leukemia (AML). Our analysis nominated three AML-specific biological aging genes (CDC42EP2, CDC42, ALOX15B) significantly associated with time to AML overall survival, especially for patients with favorable cytogenetic risk score and for patients older than 56 years of age., Discussion: Comparison of the identified PC and AML markers to genes selected at random and to known markers of progression demonstrated robustness of our results and nominated the identified biological aging genes as valuable markers of prostate cancer and AML progression, opening new avenues for personalized therapeutic management and potential novel treatment investigations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ramakrishnan, Datta, Panja, Patel, Liu, Craige, Chu, Jean-Marie, Oladoja, Kim and Mitrofanova.)

Tocklai vegetative (TV) cultivars are extensively planted in the tea-growing regions of Northeast India. The present investigation explores the impact of season on the total polyphenol (TP) content and the antioxidant activity of thirty-one TV cultivars (TV1-TV31) and four other commercially popular cultivars, namely, Betjan, Kharijan, S.3A/3, and T.3E/3. The TP content of the cultivars was observed to be highest in the monsoon season, with values ranging from 230.57 to 283.53 mg g -1 . In the pre-monsoon season and autumn, the TP content ranged from 197.87 to 256.77 mg g -1 and from 169.97 to 223.50 mg g -1 , respectively. Antioxidant activity was measured through DPPH, ABTS, FRAP, and lipid peroxidation inhibition assays. The cultivars showed the highest antioxidant activity in the monsoon in tandem with TP content. A bivariate correlation indicated a highly significant ( p ≤ 0.01) positive correlation of antioxidant activity with TP content (R 2 = 0.83-0.96).

Electrochemically promoted transition metal-catalyzed C-H functionalization has emerged as a promising area of research over the last few decades. However, development in this field is still at an early stage compared to traditional functionalization reactions using chemical-based oxidizing agents. Recent reports have shown increased attention on electrochemically promoted metal-catalyzed C-H functionalization. From the standpoint of sustainability, environmental friendliness, and cost effectiveness, electrochemically promoted oxidation of a metal catalyst offers a mild, efficient, and atom-economical alternative to traditional chemical oxidants. This Review discusses advances in the field of transition metal-electrocatalyzed C-H functionalization over the past decade and describes how the unique features of electricity enable metal-catalyzed C-H functionalization in an economic and sustainable way., (© 2023 Wiley-VCH GmbH.)

Herein, we have developed a nanocomposite catalyst for organic transformation. The catalysts are synthesized based on CuO/ZnO/ZrO 2 materials through the coprecipitation method followed by calcination in air at 500 °C for 5 h. The physicochemical characterization using TGA, XRD, SEM and N 2 -physisorption at -196 °C was carried out for all the prepared catalysts. Nanocomposite catalyst with Cu/Zn=1 : 1 showed the smallest particle size and largest surface area among all the other investigated catalysts. Under ideal reaction conditions, this new heterogenous catalyst has demonstrated its excellent efficacy for the oxidation of benzylic alcohol and can be successfully used in up to three catalytic cycles with little loss of catalytic activity., (© 2023 Wiley-VCH GmbH.)

The term "C-H functionalisation" incorporates C-H activation followed by its transformation. In a single line, this can be defined as the conversion of carbon-hydrogen bonds into carbon-carbon or carbon-heteroatom bonds. The catalytic functionalisation of C-H bonds using transition metals has emerged as an atom-economical technique to engender new bonds without activated precursors which can be considered as a major drawback while attempting large-scale synthesis. Replacing the transition-metal-catalysed approach with a metal-free strategy significantly offers an alternative route that is not only inexpensive but also environmentally benign to functionalize C-H bonds. Recently metal free synthetic approaches have been flourishing to functionalize C-H bonds, motivated by the search for greener, cost-effective, and non-toxic catalysts. In this review, we will highlight the comprehensive and up-to-date discussion on recent examples of ground-breaking research on green and sustainable metal-free C-H bond functionalisation.

Aging proteins in the lens become increasingly aggregated and insoluble, contributing to presbyopia. In this study, we investigated the ability of aggrelyte-2 (N,S-diacetyl-L-cysteine methyl ester) to reverse the water insolubility of aged human lens proteins and to decrease stiffness in cultured human and mouse lenses. Water-insoluble proteins (WI) of aged human lenses (65-75 years) were incubated with aggrelyte-2 (500 μM) for 24 or 48 h. A control compound that lacked the S-acetyl group (aggrelyte-2C) was also tested. We observed 19%-30% solubility of WI upon treatment with aggrelyte-2. Aggrelyte-2C also increased protein solubility, but its effect was approximately 1.4-fold lower than that of aggrelyte-2. The protein thiol contents were 1.9- to 4.9-fold higher in the aggrelyte-2- and aggrelyte-2C-treated samples than in the untreated samples. The LC-MS/MS results showed N ε -acetyllysine (AcK) levels of 1.5 to 2.1 nmol/mg protein and 0.6 to 0.9 nmol/mg protein in the aggrelyte-2- and aggrelyte-2C-treated samples. Mouse (C57BL/6J) lenses (incubated for 24 h) and human lenses (incubated for 72 h) with 1.0 mM aggrelyte-2 showed significant decreases in stiffness with simultaneous increases in soluble proteins (human lenses) and protein-AcK levels, and such changes were not observed in aggrelyte-2C-treated lenses. Mass spectrometry of the solubilized protein revealed AcK in all crystallins, but more was observed in α-crystallins. These results suggest that aggrelyte-2 increases protein solubility and decreases lens stiffness through acetylation and disulfide reduction. Aggrelyte-2 might be useful in treating presbyopia in humans., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Combination therapy targeting multiple therapeutic targets is a favorable strategy to achieve better therapeutic outcomes in cancer and inflammatory diseases. Codelivery is a subfield of drug delivery that aims to achieve combined delivery of diverse therapeutic cargoes within the same delivery system, thereby ensuring delivery to the same site and providing an opportunity to tailor the release kinetics as desired. Among the wide range of materials being investigated in the design of codelivery systems, lipids have stood out on account of their low toxicity, biocompatibility, and ease of formulation scale-up. This review highlights the advances of the last decade in lipid-based codelivery systems focusing on the codelivery of drug-drug, drug-nucleic acid, nucleic acid-nucleic acid, and protein therapeutic-based combinations for targeted therapy in cancer and inflammatory diseases., (© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Black root rot disease of Cicer arietinum L. is accountable for substantial loss in chickpea production worldwide. Endophytic Bacillus siamensis CNE6 has previously shown multifaceted plant growth-promoting, broad-spectrum antifungal, and chickpea plant-colonizing potential. In the present study, the strain Bacillus siamensis CNE6 was used for controlling black root rot disease caused by Fusarium solani CRP1 in chickpea. CNE6 showed strong antagonistic potential against CRP1 both in vivo and in vitro . Scanning electron microscopic studies indicated cellular deformation of CRP1 due to production of β-glucanase, protease, and other secondary metabolites. A total of five compounds were detected from the cell-free supernatant (CFS) of the ethyl acetate (EA) fraction of CNE6 through gas chromatography-mass spectrometry analysis. A confocal microscopic study demonstrated strong inhibition of biofilm formation of the pathogen CRP1 by the EA fraction of CFS of CNE6. Molecular docking analysis revealed that one compound, (2E)-6-methoxy-2-[(4-methoxyphenyl)methylidene]-2,3-dihydro-1-benzofuran-3-one, may inhibit the activity of lanosterol 14-alpha demethylase, which is involved in ergosterol biosynthesis and beta-tubulin assembling. In vivo experiments also showed the efficacy of CNE6 for increasing chickpea growth as well as upregulation of four defense genes ( CHI1 , PAMP , PR2B , and TF1082 ) upon pathogenic challenge. Thus, our results strongly suggest a positive role for CNE6 as a prospective biocontrol agent for combating Fusarium solani in chickpea. IMPORTANCE The present work was undertaken to explore an effective biocontrol agent against the destructive black root rot disease of chickpea. We have used an efficient bacterial endophyte, CNE6, which can colonize in the chickpea root system, produce secondary metabolites and enzymes to degrade pathogenic cellular integrity, inhibit pathogenic establishment by rupturing biofilm formation, and induce host immunity upon treatment. Interaction of the bacterial metabolite was also observed with lanosterol 14-alpha demethylase, which is an important component in fungal membrane functioning. Being an endophyte, Bacillus siamensis CNE6 fulfills a suitable criterion as a biocontrol agent to control black root rot disease in chickpea and has huge prospects for use commercially.

Smart healthcare is an integral part of a smart city, which provides real time and intelligent remote monitoring and tracking services to patients and elderly persons. In the era of an extraordinary public health crisis due to the spread of the novel coronavirus (2019-nCoV), which caused the deaths of millions and affected a multitude of people worldwide in different ways, the role of smart healthcare has become indispensable. Any modern method that allows for speedy and efficient monitoring of COVID19-affected patients could be highly beneficial to medical staff. Several smart-healthcare systems based on the Internet of Medical Things (IoMT) have attracted worldwide interest in their growing technical assistance in health services, notably in predicting, identifying and preventing, and their remote surveillance of most infectious diseases. In this paper, a real time health monitoring system for COVID19 patients based on edge computing and fuzzy logic technique is proposed. The proposed model makes use of the IoMT architecture to collect real time biological data (or health information) from the patients to monitor and analyze the health conditions of the infected patients and generates alert messages that are transmitted to the concerned parties such as relatives, medical staff and doctors to provide appropriate treatment in a timely fashion. The health data are collected through sensors attached to the patients and transmitted to the edge devices and cloud storage for further processing. The collected data are analyzed through fuzzy logic in edge devices to efficiently identify the risk status (such as low risk, moderate risk and high risk) of the COVID19 patients in real time. The proposed system is also associated with a mobile app that enables the continuous monitoring of the health status of the patients. Moreover, once alerted by the system about the high risk status of a patient, a doctor can fetch all the health records of the patient for a specified period, which can be utilized for a detailed clinical diagnosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier Ltd. All rights reserved.)

We use a pH-driven annealing process to convert between co-assembled and self-sorted networks in multicomponent gels. The initially formed gels at low pH are co-assembled, with the two components coexisting within the same self-assembled structures. We use an enzymatic approach to increase the pH, resulting in a gel-to-sol transition, followed by a hydrolysis to lower the pH once again. As the pH decreases, a self-sorted network is formed by a two-stage gelation process determined by the pK a of each component. This approach can be expanded to layered systems to generate many varied systems by changing composition and rates of pH change, adapting their microstructure and so allowing access to a far greater range of morphologies and complexity than can be achieved in single component systems., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)