Expression of Plasmodium major facilitator superfamily protein in transporters - Δ Candida identifies a drug transporter.

Aim: To assess the functional relevance of a putative Major Facilitator Superfamily protein (PF3D7_0210300; 'PfMFSDT') as a drug transporter, using Candida glabrata for orthologous protein expression.Methods: Complementary Determining Sequence encoding PfMFSDT was integrated into the genome of genetically engineered C. glabrata strain MSY8 via homologous recombination, followed by assessing its functional relevance as a drug transporter.Results & conclusion: The modified C. glabrata strain exhibited plasma membrane localization of PfMFSDT and characteristics of an Major Facilitator Superfamily transporter, conferring resistance to antifungals, ketoconazole and itraconazole. The nanomolar inhibitory effects of the drugs on the intra-erythrocytic growth of Plasmodium falciparum highlight their antimalarial properties. This study proposes PfMFSDT as a drug transporter, expanding the repertoire of the currently known antimalarial 'resistome'.

[Box: see text].

Anticancer activity of quantum size carbon dots: opportunities and challenges.

Research into the anticancer activity of quantum-sized carbon dots (CDs) has emerged as a promising avenue in cancer research. This CDs delves into the opportunities and challenges associated with harnessing the potential of these nanostructures for combating cancer. Quantum-sized carbon dots, owing to their unique physicochemical properties, exhibit distinct advantages as potential therapeutic agents. Opportunities lie in their tunable size, surface functionalization capabilities, and biocompatibility, enabling targeted drug delivery and imaging in cancer cells. However, we include challenges, a comprehensive understanding of the underlying mechanisms, potential toxicity concerns, and the optimization of synthesis methods for enhanced therapeutic efficacy. A succinct summary of the state of the research in this area is given in this review, emphasizing the exciting possibilities and ongoing challenges in utilizing quantum-sized carbon dots as a novel strategy for cancer treatment.

A Diagnosis of Sheehan's Syndrome: Better Late Than Never.

A middle-aged woman presented with history of fatigue, low mood, swelling of limbs, and facial puffiness. On detailed history taking, she also complained of salt craving, secondary amenorrhea, and loss of libido for almost a decade. Investigations revealed pan-hypopituitarism. She was started on appropriate hormonal therapy which saw a rapid resolution of symptoms within 2 weeks. Sheehan's syndrome may have an acute presentation or chronic. The symptoms may be subtle like fatigue or overt like hypotension and syncope. A high degree of suspicion of Sheehan's syndrome is essential for its timely management, and goes a long way in preserving the quality of life.

Naringin: A flavanone with a multifaceted target against sepsis-associated organ injuries.

BACKGROUND: Sepsis causes multiple organ dysfunctions and raises mortality and morbidity rates through a dysregulated host response to infection. Despite the growing research interest over the last few years, no satisfactory treatment exists. Naringin, a naturally occurring bioflavonoid with vast therapeutic potential in citrus fruits and Chinese herbs, has received much attention for treating sepsis-associated multiple organ dysfunctions. PURPOSE: The review describes preclinical evidence of naringin from 2011 to 2024, particularly emphasizing the mechanism of action mediated by naringin against sepsis-associated specific injuries. The combination therapy, safety profile, drug interactions, recent advancements in formulation, and future perspectives of naringin are also discussed. METHODS: In vivo and in vitro studies focusing on the potential role of naringin and its mechanism of action against sepsis-associated organ injuries were identified and summarised in the present manuscript, which includes contributions from 2011 to 2024. All the articles were extracted from the Medline database using PubMed, Science Direct, and Web of Science with relevant keywords. RESULTS: Research findings revealed that naringin modulates many signaling cascades, such as Rho/ROCK and PPAR/STAT1, PIP3/AKT and KEAP1/Nrf2, and IkB/NF-kB and MAPK/Nrf2/HO-1, to potentially protect against sepsis-induced intestinal, cardiac, and lung injury, respectively. Furthermore, naringin treatment exhibits anti-inflammatory, anti-apoptotic, and antioxidant action against sepsis harm, highlighting naringin's promising effects in septic settings. Naringin could be employed as a treatment against sepsis, based on studies on combination therapy, synergistic effects, and toxicological investigation that show no reported severe side effects. CONCLUSION: Naringin might be a promising therapeutic approach for preventing sepsis-induced multiple organ failure. Naringin should be used alongside other therapeutic therapies with caution despite its great therapeutic potential and lower toxicity. Nonetheless, clinical studies are required to comprehend the therapeutic benefits of naringin against sepsis.

Dual Role of TRPV1 Channels in Cerebral Stroke: An Exploration from a Mechanistic and Therapeutic Perspective.

Transient receptor potential vanilloid subfamily member 1 (TRPV1) has been strongly implicated in the pathophysiology of cerebral stroke. However, the exact role and mechanism remain elusive. TPRV1 channels are exclusively present in the neurovascular system and involve many neuronal processes. Numerous experimental investigations have demonstrated that TRPV1 channel blockers or the lack of TRPV1 channels may prevent harmful inflammatory responses during ischemia-reperfusion injury, hence conferring neuroprotection. However, TRPV1 agonists such as capsaicin and some other non-specific TRPV1 activators may induce transient/slight degree of TRPV1 channel activation to confer neuroprotection through a variety of mechanisms, including hypothermia induction, improving vascular functions, inducing autophagy, preventing neuronal death, improving memory deficits, and inhibiting inflammation. Another factor in capsaicin-mediated neuroprotection could be the desensitization of TRPV1 channels. Based on the summarized evidence, it may be plausible to suggest that TPRV1 channels have a dual role in ischemia-reperfusion-induced cerebral injury, and thus, both agonists and antagonists may produce neuroprotection depending upon the dose and duration. The current review summarizes the dual function of TRPV1 in ischemia-reperfusion-induced cerebral injury models, explains its mechanism, and predicts the future.

Role of infrastructure and operation in disease prevalence in dairy farms: groundwork for disease prevention-based antibiotic stewardship.

Attempts at regulating misuse of antibiotics in the dairy industry have been ineffective, especially in low- and middle-income countries, who also typically have high burden of preventable infectious disease, we propose a disease prevention-based approach to minimize the need and in turn consumption of antibiotics in dairy farms. Since the immediate environment of the animals is key to disease prevalence, we targeted the infrastructure- and operation-related factors in dairy farms and their link with prevalence of most common diseases and symptoms. We conducted four focused group discussions and a cross-sectional survey in 378 dairy farms to investigate disease prevalence and associated infrastructural (housing system, and manger shape), and operational (waste management, feed management, and type of cleaning agent) parameters. The most common diseases (Mastitis and secondary infections related to Foot-and-mouth disease) and symptoms (fever and diarrhoea) in the focus area were linked with the infrastructural and operational factors on the dairy farm with higher disease prevalence reported in dairy farms, where the animals were exposed to variations in diurnal temperatures or were hard to clean. We further used ML classifiers - Neural Network (NN), k-Nearest Neighbour (kNN), Support Vector Machine (SVM), Decision Tree (DT), and Random Forest (RF) - to corroborate the relationship between infrastructure and operations of the dairy farms and disease prevalence- The DT classifier on randomly sampled data could predict the prevalence of the two most common diseases (accuracy = 92%, F1-score = 0.919) Our results open new avenues for cost-effective interventions such as use of curve-edged mangers, use of rubber mats on floors, not reusing leftover feed etc. in dairy farms to prevent the most common diseases and symptoms in dairy farms and reduce the need and consumption of antibiotics.

Outcome of Total Surgical Debridement of Covid Associated Rhino-Orbito-Cerebral Mucormycosis Based on a New Surgical Staging System: A Cohort Study.

To propose a surgical staging system with management protocol for post-covid Rhino-orbito-cerebral mucormycosis (ROCM) with central skull base osteomyelitis. A prospective cohort study of a total of 193 post-covid ROCM patients was conducted between May 2021 and January 2022 at a tertiary care centre. Patients were assessed radiologically and staged from I to V. Follow up period was 16 months and the surgical outcome in terms of recurrent disease was assessed. A total of 193 patients (129 primary and 64 revision) were studied. Maxilla was found to be the epicenter of anterior disease (69.3%) and pterygoid wedge was noted to be the epicenter of posterior disease (85.6%). More than 65% of our patients, at the time of presentation, presented with involvement of the central skull base. Intracranial disease was noted in 13.9% of patients and the mortality rate was 6.2%. This staging system provides a systematic step-by-step protocol for the management of ROCM, with emphasis on meticulous disease clearance at the central skull base.

Insights into the interface of NiCo2O4 spinel /LaCoO3 perovskite nano-composite for CO and soot oxidation.

In the quest for the development of thermally stable, highly active and low-cost catalysts for use in catalyzed diesel particulate filter, nano-composites are new areas of research. Therefore, we reported the easy synthesis of spinel NiCo2O4/perovskite LaCoO3 nano-composite, and its individual oxides NiCo2O4 and LaCoO3 for comparison. The detailed insights into the physio-chemical characteristics of formed NiCo2O4/ LaCoO3 nano-composite were done based on various characterization analysis such as X-ray diffraction (XRD), Fourier transform infrared (FT-IR), N2 physiosorption, scanning electron microscopy-energy dispersive spectroscopy (SEM-EDX), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The characterization analysis of NiCo2O4/LaCoO3 revealed the successful formation of a chemical interface possessing strong interfacial interaction, resulting in desirable physicochemical characteristics such as small crystallite size, abundant mesoporosity, high specific surface area and activation of surface lattice oxygen. Owing to the desirable characteristics, the activity results over NiCo2O4/LaCoO3 nano-composite showed the excellent CO oxidation performance and high soot oxidation activity, recyclability and thermal stability. This work mainly attempts to emphasize the effectiveness of the facile, inexpensive and conventionally used precipitation method for the successful formation of highly efficient nano-composites.

Spatially activated conserved auxin-transcription factor regulatory module controls de novo root organogenesis in rice.

MAIN CONCLUSION: This study reveals that the process of crown root development and auxin-induced de novo root organogenesis during in vitro plantlet regeneration share a common auxin-OsWOX10 regulatory module in rice. In the fibrous-type root system of rice, the crown roots (CR) are developed naturally from the shoot tissues. Generation of robust auxin response, followed by activation of downstream cell fate determinants and signaling pathways at the onset of crown root primordia (CRP) establishment is essential for new root initiation. During rice tissue culture, embryonic calli are induced to regenerate shoots in vitro which undergo de novo root organogenesis on an exogenous auxin-supplemented medium, but the mechanism underlying spatially restricted root organogenesis remains unknown. Here, we reveal the dynamics of progressive activation of genes involved in auxin homeostasis and signaling during initiation and outgrowth of rice crown root primordia. By comparative global dataset analysis, we identify the crown root primordia-expressed genes whose expression is also regulated by auxin signaling. In-depth spatio-temporal expression pattern analysis shows that the exogenous application of auxin induces a set of key transcription factors exclusively in the spatially positioned CRP. Further, functional analysis of rice WUSCHEL-RELATED HOMEOBOX 10 (OsWOX10) during in vitro plantlet regeneration from embryogenic calli shows that it promotes de novo root organogenesis from regenerated shoots. Expression of rice OsWOX10 also induces adventitious roots (AR) in Arabidopsis, independent of homologous endogenous Arabidopsis genes. Together, our findings reveal that a common auxin-transcription factor regulatory module is involved in root organogenesis under different conditions.

Assessment of the differential trade-off between growth, subsistence, and productivity of two popular Indian hybrid mango varieties under elevated ozone exposure.

The multifunctionality of plants is well known to be compromised in the areas experiencing higher concentrations of tropospheric ozone (O3). Mango (Mangifera indica L.) cultivation is essential to the economy of tropical regions, including India. Mango, widely grown in suburban and rural areas, experiences production loss due to air pollutants. Ozone, the most important phytotoxic gas in mango growing areas, warrants an investigation of its effects. Therefore, we assessed the differential sensitivity of mango saplings (two-year-old hybrid and regular-bearing mango varieties, Amrapali and Mallika) at two levels of O3: ambient and elevated (ambient + 20 ppb) using open-top chambers from September 2020 to July 2022. Under elevated O3, both varieties showed similar seasonal responses (winter and summer) for all the growth parameters but differed in their height-diameter allocation pattern. A decrease in stem diameter and an increase in plant height were observed in Amrapali, whereas Mallika showed a reverse response. Early emergence of phenophases was noticed during the reproductive growth of both varieties under elevated O3 exposure. However, these changes were more pronounced in Amrapali. Stomatal conductance was more negatively affected in Amrapali than in Mallika under elevated O3 during both seasons. Furthermore, leaf morpho-physiological traits (leaf nitrogen concentration, leaf area, leaf mass per area, and photosynthetic nitrogen use efficiency) and inflorescence parameters responded variably in both varieties under elevated O3 stress. A decrease in photosynthetic nitrogen use efficiency, further enhanced yield loss which was more pronounced in Mallika than in Amrapali under elevated O3 exposure. The results of this study could be useful in selecting a better-performing variety based on its productivity, which will be economically more beneficial in achieving the goal of sustainable production at the anticipated high O3 levels under a climate change scenario.

Targeting an essential Plasmodium cold shock protein to block growth and transmission of malaria parasite.

Cold shock proteins are characterized by the presence of one or more cold shock domains that bestow them with nucleic acid binding ability. Although cold shock proteins are well characterized in bacteria, plants and humans, there is no information on their existence and role in malaria parasite. Here, we have identified and delineated the function of a cold shock protein of Plasmodium falciparum (Pf) 'PfCoSP'. We demonstrate that PfCoSP exhibits nucleic acid binding properties and regulates gene expression. PfCoSP promotes microtubule assembly by interacting with Pf α/ß tubulin. We identified a human cold shock protein LIN28A inhibitor 'LI71' as a binding partner of PfCoSP which inhibited PfCoSP-DNA and α/ß tubulin interactions and, also inhibited the development of asexual blood stages and gametocyte stage of malaria parasite. Because PfCoSP is essential for parasite survival, characterization of its interacting partners may form the basis for development of future anti-malarials.

Lateral root branching: evolutionary innovations and mechanistic divergence in land plants.

The root system architecture in plants is a result of multiple evolutionary innovations over time in response to changing environmental cues. Dichotomy and endogenous lateral branching in the roots evolved in lycophytes lineage but extant seed plants use lateral branching instead. This has led to the development of complex and adaptive root systems, with lateral roots playing a key role in this process exhibiting conserved and divergent features in different plant species. The study of lateral root branching in diverse plant species can shed light on the orderly yet distinct nature of postembryonic organogenesis in plants. This insight provides an overview of the diversity in lateral root (LR) development in various plant species during the evolution of root system in plants.

Natural polyphenols: a promising bioactive compounds for skin care and cosmetics.

The physiological and morphological aspects of skin suffer from frequent change. Numerous internal and external factors have direct impact on inducing various skin problems like inflammation, aging, cancer, oxidative stress, hyperpigmentation etc. The use of plant polyphenols as a photo-ecting agent is gaining popularity nowadays. Polyphenols are known to enhance endogenic antioxidant system of skin thereby preventing various skin diseases. The biological activity of plant polyphenols is dependent on their physicochemical properties for overcoming the epidermal barriers to reach the specific receptor. Several evidences have reported the vital role polyphenols in mitigating adverse skin problems and reverting back the healthy skin condition. The interest in plant derived skin care products is emerging due to the changing notion of people to shift their focus towards use of plant-based products. The present review draws an attention to uncover the protective role of polyphenols in prevention of various skin problems. Several in vitro and in vivo studies have been summarized that claims the efficacious nature of plant extract having dermatological significance.

Auxin-Responsive (Phospho)proteome Analysis Reveals Key Biological Processes and Signaling Associated with Shoot-Borne Crown Root Development in Rice.

The rice root system is primarily composed of shoot-borne adventitious/crown roots (ARs/CRs) that develop from the coleoptile base, and therefore, it is an excellent model system for studying shoot-to-root trans-differentiation process. We reveal global changes in protein and metabolite abundance and protein phosphorylation in response to an auxin stimulus during CR development. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) analyses of developing crown root primordia (CRP) and emerged CRs identified 334 proteins and 12 amino acids, respectively, that were differentially regulated upon auxin treatment. Gene ontology enrichment analysis of global proteome data uncovered the biological processes associated with chromatin conformational change, gene expression and cell cycle that were regulated by auxin signaling. Spatial gene expression pattern analysis of differentially abundant proteins disclosed their stage-specific dynamic expression pattern during CRP development. Further, our tempo-spatial gene expression and functional analyses revealed that auxin creates a regulatory module during CRP development and activates ethylene biosynthesis exclusively during CRP initiation. Further, the phosphoproteome analysis identified 8,220 phosphosites, which could be mapped to 1,594 phosphoproteins and of which 66 phosphosites were differentially phosphorylated upon auxin treatment. Importantly, we observed differential phosphorylation of the cyclin-dependent kinase G-2 (OsCDKG;2) and cell wall proteins, in response to auxin signaling, suggesting that auxin-dependent phosphorylation may be required for cell cycle activation and cell wall synthesis during root organogenesis. Thus, our study provides evidence for the translational and post-translational regulation during CR development downstream of the auxin signaling pathway.

Genetic and Hormonal Blueprint of Shoot-Borne Adventitious Root Development in Rice and Maize.

The evolution of root architecture in plants was a prerequisite for the absorption of water and minerals from the soil, and thus a major determinant of terrestrial plant colonization. Cereals have a remarkably complex root system consisting of embryonic primary roots and post-embryonic lateral roots and shoot-borne adventitious roots. Among grass species, rice adventitious roots (also called crown roots) are developed from compressed nodes at the stem base, whereas in maize, besides crown roots, several aboveground brace roots are also formed, thus adventitious root types display species-specific diversity. Despite being the backbone for the adult root system in monocots, adventitious roots are the least studied of all the plant organs. In recent times, molecular genetics, genomics and proteomics-based approaches have been utilized to dissect the mechanism of post-embryonic meristem formation and tissue patterning. Adventitious root development is a cumulative effect of the actions and interactions of crucial genetic and hormonal regulators. In this review, we provide a comprehensive view of the key regulators involved during the different stages of adventitious root development in two important crop plants, rice and maize. We have reviewed the roles of major phytohormones, microRNAs and transcription factors and their crosstalk during adventitious root development in these cereal crops.

Implications of Foliar Particulate Matter Deposition on the Physiology and Nutrient Allocation of Dominant Perennial Species of the Indo-Gangetic Plains.

The ramifications of different concentrations of foliar particulate matter on the physiology, nutrient stoichiometry, allocation pattern, and their corresponding re-translocation rates were investigated for evergreen (Mangifera indica and Psidium guajava), semi-evergreen (Ficus religiosa and Azadirachta indica), and deciduous (Dalbergia sissoo) tree species in a simulation experiment over an exposure period of 2 years. Physiological parameters (Pn, gs, Ci, E, and WUE), nutrient stoichiometry (C: N) in different plant parts, and their allocation pattern for five macro- (C, N, K, Mg, Ca) and five (Zn, Ni, Mn, Cu, Fe) micro-elements at two different concentrations of particulate matter (ambient and elevated) with respect to control (no particulate load) were assessed. Significant differences in nutrient concentrations and their re-translocation rates were observed between the treatments in evergreen species compared to deciduous species. The photosynthetic rate significantly declined with an increase in foliar deposition of particulate matter. Higher variations in C, N, K, Mg, and Zn levels were found compared to other elements under particulate matter stress and the ratio of C/N showed a slight decline in mature leaves except in deciduous tree species. The nutrient stoichiometry revealed that the deciduous species were more tolerant whereas the re-translocation efficiency was maximum for the semi-evergreen tree species. The nutrient allocation was found greater in foliage compared to branch in evergreen and was opposite in semi-evergreen and deciduous tree species. The element re-translocation rate indicated an inconsistent behavior in nutrient recycling under the particulate matter load depending upon the tree species. The study entrenched a critical change in nutrient re-translocation and allocation pattern under the particulate stress in different parts of the tree, suggesting a novel approach for screening the tree species for sustainable plantation and planning of urban areas.

Species-specific function of conserved regulators in orchestrating rice root architecture.

Shoot-borne adventitious/crown roots form a highly derived fibrous root system in grasses. The molecular mechanisms controlling their development remain largely unknown. Here, we provide a genome-wide landscape of transcriptional signatures - tightly regulated auxin response and in-depth spatio-temporal expression patterns of potential epigenetic modifiers - and transcription factors during priming and outgrowth of rice (Oryza sativa) crown root primordia. Functional analyses of rice transcription factors from WUSCHEL-RELATED HOMEOBOX and PLETHORA gene families reveal their non-redundant and species-specific roles in determining the root architecture. WOX10 and PLT1 regulate both shoot-borne crown roots and root-borne lateral roots, but PLT2 specifically controls lateral root development. PLT1 activates local auxin biosynthesis genes to promote crown root development. Interestingly, O. sativa PLT genes rescue lateral root primordia outgrowth defects of Arabidopsis plt mutants, demonstrating their conserved role in root primordia outgrowth irrespective of their developmental origin. Together, our findings unveil a molecular framework of tissue transdifferentiation during root primordia establishment, leading to the culmination of robust fibrous root architecture. This also suggests that conserved factors have evolved their transcription regulation to acquire species-specific function.

State-of-the-Art in CRISPR Technology and Engineering Drought, Salinity, and Thermo-tolerant crop plants.

KEY MESSAGE: Our review has described principles and functional importance of CRISPR-Cas9 with emphasis on the recent advancements, such as CRISPR-Cpf1, base editing (BE), prime editing (PE), epigenome editing, tissue-specific (CRISPR-TSKO), and inducible genome editing and their potential applications in generating stress-tolerant plants. Improved agricultural practices and enhanced food crop production using innovative crop breeding technology is essential for increasing access to nutritious foods across the planet. The crop plants play a pivotal role in energy and nutrient supply to humans. The abiotic stress factors, such as drought, heat, and salinity cause a substantial yield loss in crop plants and threaten food security. The most sustainable and eco-friendly way to overcome these challenges are the breeding of crop cultivars with improved tolerance against abiotic stress factors. The conventional plant breeding methods have been highly successful in developing abiotic stress-tolerant crop varieties, but usually cumbersome and time-consuming. Alternatively, the CRISPR/Cas genome editing has emerged as a revolutionary tool for making efficient and precise genetic manipulations in plant genomes. Here, we provide a comprehensive review of the CRISPR/Cas genome editing (GE) technology with an emphasis on recent advances in the plant genome editing, including base editing (BE), prime editing (PE), epigenome editing, tissue-specific (CRISPR-TSKO), and inducible genome editing (CRISPR-IGE), which can be used for obtaining cultivars with enhanced tolerance to various abiotic stress factors. We also describe tissue culture-free, DNA-free GE technology, and some of the CRISPR-based tools that can be modified for their use in crop plants.

Treasuring the computational approach in medicinal plant research.

Medicinal plants serve as a valuable source of secondary metabolites since time immemorial. Computational Research in 21st century is giving more attention to medicinal plants for new drug design as pharmacological screening of bioactive compound was time consuming and expensive. Computational methods such as Molecular Docking, Molecular Dynamic Simulation and Artificial intelligence are significant Insilico tools in medicinal plant research. Molecular docking approach exploits the mechanism of potential phytochemicals into the target active site to elucidate its interactions and biological therapeutic properties. MD simulation illuminates the dynamic behavior of biomolecules at atomic level with fine quality representation of biomolecules. Dramatical advancement in computer science is illustrating the biological mechanism via these tools in different diseases treatment. The advancement comprises speed, the system configuration, and other software upgradation to insights into the structural explanation and optimization of biomolecules. A probable shift from simulation to artificial intelligence has in fact accelerated the art of scientific study to a sky high. The most upgraded algorithm in artificial intelligence such as Artificial Neural Networks, Deep Neural Networks, Neuro-fuzzy Logic has provided a wide opportunity in easing the time required in classical experimental strategy. The notable progress in computer science technology has paved a pathway for understanding the pharmacological functions and creating a roadmap for drug design and development and other achievement in the field of medicinal plants research. This review focus on the development and overview in computational research moving from static molecular docking method to a range of dynamic simulation and an advanced artificial intelligence such as machine learning.