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The rise in global temperature also favors the multiplication of pests and pathogens, which calls into question global food security. Plants have developed special coping mechanisms since they are sessile and lack an immune system. These mechanisms use a variety of secondary metabolites as weapons to avoid obstacles, adapt to their changing environment, and survive in less-than-ideal circumstances. Plant secondary metabolites include phenolic compounds, alkaloids, glycosides, and terpenoids, which are stored in specialized structures such as latex, trichomes, resin ducts, etc. Secondary metabolites help the plants to be safe from biotic stressors, either by repelling them or attracting their enemies, or exerting toxic effects on them. Modern omics technologies enable the elucidation of the structural and functional properties of these metabolites along with their biosynthesis. A better understanding of the enzymatic regulations and molecular mechanisms aids in the exploitation of secondary metabolites in modern pest management approaches such as biopesticides and integrated pest management. The current review provides an overview of the major plant secondary metabolites that play significant roles in enhancing biotic stress tolerance. It examines their involvement in both indirect and direct defense mechanisms, as well as their storage within plant tissues. Additionally, this review explores the importance of metabolomics approaches in elucidating the significance of secondary metabolites in biotic stress tolerance. The application of metabolic engineering in breeding for biotic stress resistance is discussed, along with the exploitation of secondary metabolites for sustainable pest management.

In recent years, the global agricultural system has been unfavorably impacted by adverse environmental changes. These changes in the climate, in turn, have altered the abiotic conditions of plants, affecting plant growth, physiology and production. Abiotic stress in plants is one of the main obstacles to global agricultural production and food security. Therefore, there is a need for the development of novel approaches to overcome these problems and achieve sustainability. Nanotechnology has emerged as one such novel approach to improve crop production, through the utilization of nanoscale products, such as nanofertilizer, nanofungicides, nanoherbicides and nanopesticides. Their ability to cross cellular barriers makes nanoparticles suitable for their application in agriculture. Since they are easily soluble, smaller, and effective for uptake by plants, nanoparticles are widely used as a modern agricultural tool. The implementation of nanoparticles has been found to be effective in improving the qualitative and quantitative aspects of crop production under various biotic and abiotic stress conditions. This review discusses various abiotic stresses to which plants are susceptible and highlights the importance of the application of nanoparticles in combating abiotic stress, in addition to the major physiological, biochemical and molecular-induced changes that can help plants tolerate stress conditions. It also addresses the potential environmental and health impacts as a result of the extensive use of nanoparticles.

Limited treatment options exist for COVID-19 infections; thus, attempts from complementary and alternative systems (CAM) of medicine are being explored as possible therapeutic options. Ayurcov is a formulation made of ingredients mentioned in Ayurveda. These constituents have proven antiviral, detoxifying, immune-modulating, and bio-enhancing properties. The present study was carried out to evaluate the therapeutic effect and safety of Ayurcov in patients with various severity states of COVID-19 infections. A randomized, single blinded, controlled trial was carried out in adults diagnosed with mild-to-moderate, and severe COVID-19 infections confirmed by real time reverse transcriptase polymerase chain reaction (rRTPCR) test. The interventional group received three doses of ‘Ayurcov’. It is constituted of Haridra Churna (Curcuma longa), Go ark (Bos Indicus Distilled Urine), Sphatika (Alum), Sita (Rock Candy), Godugdham (Bos Indicus Milk) milk, Goghritam (Bos Indicus ghee) on Day 1, as an adjuvant to the standard of care, and the control group received only the standard of care. Key outcomes included: proportion of patients and time taken for symptom resolution, reduction in the rRT-PCR Ct values, safety, and functional status until 42 days after discharge. Ninety patients with mild-to-moderate and 30 patients with severe COVID-19 disease were recruited. It was observed that significantly more proportions of patients receiving Ayurcov had symptom relief much earlier than control group. Additionally, the interventional group showed significantly lower rRT-PCR Ct values. However, a shorter time of resolution of symptoms was observed with the interventional group in the mild to moderate category but not with those having severe symptoms. Similarly, a significantly better functional status was observed with interventional group on days 7 and 28 after discharge. Ayurcov was not observed with higher risks of any adverse/serious adverse events. Ayurcov as adjuvant with standard of care was associated with significantly earlier resolution of COVID-19 related symptoms than standard of care alone. •Study medicine is a formulation made of ingredients mentioned in Ayurveda, one of the oldest complementary and alternative systems.•Study design is credible as a randomized, blinded, controlled trial with objective parameters.•Patients receiving study medicine had statistically significant symptom relief much earlier than control group.•Easy to reach out to the general population as it is just one day, cost effective intervention.

Clinical use of 2-deoxystreptamine aminoglycoside antibiotics, which target the bacterial ribosome, is compromised by adverse effects related to limited drug selectivity. Here we present a series of 4′,6′- O -acetal and 4′- O -ether modifications on glucopyranosyl ring I of aminoglycosides. Chemical modifications were guided by measuring interactions between the compounds synthesized and ribosomes harbouring single point mutations in the drug-binding site, resulting in aminoglycosides that interact poorly with the drug-binding pocket of eukaryotic mitochondrial or cytosolic ribosomes. Yet, these compounds largely retain their inhibitory activity for bacterial ribosomes and show antibacterial activity. Our data indicate that 4′- O -substituted aminoglycosides possess increased selectivity towards bacterial ribosomes and little activity for any of the human drug-binding pockets. Aminoglycoside antibiotics target the ribosome but their limited selectivity for the bacterial ribosome can cause side effects in humans. Here, the authors synthesize 4′- O -ether or 4′,6′- O -acetal modifications and show that these compounds possess increased selectivity against bacterial ribosomes.

Background The role of diet in India's rapidly progressing chronic disease epidemic is unclear; moreover, diet may vary considerably across North-South regions. Methods The India Health Study was a multicenter study of men and women aged 35-69, who provided diet, lifestyle, and medical histories, as well as blood pressure, fasting blood, urine, and anthropometric measurements. In each region (Delhi, n = 824; Mumbai, n = 743; Trivandrum, n = 2,247), we identified two dietary patterns with factor analysis. In multiple logistic regression models adjusted for age, gender, education, income, marital status, religion, physical activity, tobacco, alcohol, and total energy intake, we investigated associations between regional dietary patterns and abdominal adiposity, hypertension, diabetes, and dyslipidemia. Results Across the regions, more than 80% of the participants met the criteria for abdominal adiposity and 10 to 28% of participants were considered diabetic. In Delhi, the \"fruit and dairy\" dietary pattern was positively associated with abdominal adiposity [highest versus lowest tertile, multivariate-adjusted OR and 95% CI: 2.32 (1.03-5.23); P trend = 0.008] and hypertension [2.20 (1.47-3.31); P trend < 0.0001]. In Trivandrum, the \"pulses and rice\" pattern was inversely related to diabetes [0.70 (0.51-0.95); P trend = 0.03] and the \"snacks and sweets\" pattern was positively associated with abdominal adiposity [2.05 (1.34-3.14); P trend = 0.03]. In Mumbai, the \"fruit and vegetable\" pattern was inversely associated with hypertension [0.63 (0.40-0.99); P trend = 0.05] and the \"snack and meat\" pattern appeared to be positively associated with abdominal adiposity. Conclusions Cardio-metabolic risk factors were highly prevalent in this population. Across all regions, we found little evidence of a Westernized diet; however, dietary patterns characterized by animal products, fried snacks, or sweets appeared to be positively associated with abdominal adiposity. Conversely, more traditional diets in the Southern regions were inversely related to diabetes and hypertension. Continued investigation of diet, as well as other environmental and biological factors, will be needed to better understand the risk profile in this population and potential means of prevention.

Background Retroviruses selectively package two copies of their unspliced genomes by what appears to be a dimerization-dependent RNA packaging mechanism. Dimerization of human immunodeficiency virus Type-1 (HIV-1) genomes is initiated by “kissing” interactions between GC-rich palindromic loop residues of a conserved hairpin (DIS), and is indirectly promoted by long-range base pairing between residues overlapping the gag start codon (AUG) and an upstream Unique 5′ element (U5). The DIS and U5:AUG structures are phylogenetically conserved among divergent retroviruses, suggesting conserved functions. However, some studies suggest that the DIS of HIV-2 does not participate in dimerization, and that U5:AUG pairing inhibits, rather than promotes, genome dimerization. We prepared RNAs corresponding to native and mutant forms of the 5′ leaders of HIV-1 (NL4-3 strain), HIV-2 (ROD strain), and two divergent strains of simian immunodeficiency virus (SIV; cpz-TAN1 and -US strains), and probed for potential roles of the DIS and U5:AUG base pairing on intrinsic and NC-dependent dimerization by mutagenesis, gel electrophoresis, and NMR spectroscopy. Results Dimeric forms of the native HIV-2 and SIV leaders were only detectable using running buffers that contained Mg 2+ , indicating that these dimers are more labile than that of the HIV-1 leader. Mutations designed to promote U5:AUG base pairing promoted dimerization of the HIV-2 and SIV RNAs, whereas mutations that prevented U5:AUG pairing inhibited dimerization. Chimeric HIV-2 and SIV leader RNAs containing the dimer-promoting loop of HIV-1 (DIS) exhibited HIV-1 leader-like dimerization properties, whereas an HIV-1 NL4-3 mutant containing the SIV cpzTAN1 DIS loop behaved like the SIV cpzTAN1 leader. The cognate NC proteins exhibited varying abilities to promote dimerization of the retroviral leader RNAs, but none were able to convert labile dimers to non-labile dimers. Conclusions The finding that U5:AUG formation promotes dimerization of the full-length HIV-1, HIV-2, SIV cpzUS , and SIV cpzTAN1 5′ leaders suggests that these retroviruses utilize a common RNA structural switch mechanism to modulate function. Differences in native and NC-dependent dimerization propensity and lability are due to variations in the compositions of the DIS loop residues rather than other sequences within the leader RNAs. Although NC is a well-known RNA chaperone, its role in dimerization has the hallmarks of a classical riboswitch.

Background Neurological disorders pose a substantial burden on India’s healthcare system, contributing significantly to disability and mortality. In rural areas, where access to specialists availability is limited, Community Health Officers (CHOs) play a crucial role in bridging the gap in care. However, the lack of structured training programs for CHO’s in neurological disorder management highlights an urgent need for targeted capacity-building interventions. This study evaluates the impact of a structured training program on the knowledge and skills of CHOs in managing common neurological disorders under the Karnataka Brain Health Initiative (KaBHI). Methods The quasi-experimental study was conducted across three districts in Karnataka-Chikkaballapura, Kolar, and Bengaluru South. A total of 295 CHOs participated in a two-hour training program delivered by expert neurologists, covering headache, epilepsy, stroke, and dementia through lectures, discussions, and case-based scenarios. Pre- and post-training knowledge assessments using a standardized multiple-choice questionnaire evaluated the program’s impact. Feedback from participants was collected to assess training quality. Results Of the 295 participants, 280 completed both pre- and post-training assessments. Significant improvements were observed in knowledge scores across all disorders, with a mean score increase from 57.46 ± 16.4 to 75.79 ± 12.9 (mean difference: 18.3, p <0.001). The program was effective regardless of prior clinical experience, indicating its adaptability. Feedback highlighted high satisfaction with the training's structure, content, and delivery. Conclusion This study provides strong evidence that structured training programs can significantly enhance CHOs' ability to diagnose and manage neurological disorders, particularly in resource-limited settings. Beyond immediate knowledge gains, these findings highlight the broader potential for integrating similar capacity-building initiatives for neurological care into national healthcare programs, such as the Ayushman Bharat Mission and Health and Wellness Centers (HWCs). By equipping frontline healthcare providers with specialized skills, such programs can improve early diagnosis, facilitate timely intervention, and enhance patient outcomes, ultimately reducing the burden of neurological disorders at the primary care level. Future phases of KaBHI, implemented state-wide, will focus on ensuring long-term sustainability by refining and expanding this training model to address a wider range of neurological conditions and strengthening its integration into primary healthcare frameworks.

Tuberculous meningitis (TBM) results from dissemination of M. tuberculosis to the cerebrospinal fluid (CSF) and meninges. Ischaemia, hydrocephalus and raised intracranial pressure frequently result, leading to extensive brain injury and neurodisability. The global burden of TBM is unclear and it is likely that many cases are undiagnosed, with many treated cases unreported. Untreated, TBM is uniformly fatal, and even if treated, mortality and morbidity are high. Young age and human immunodeficiency virus (HIV) infection are potent risk factors for TBM, while Bacillus Calmette–Guérin (BCG) vaccination is protective, particularly in young children. Diagnosis of TBM usually relies on characteristic clinical symptoms and signs, together with consistent neuroimaging and CSF parameters. The ability to confirm the TBM diagnosis via CSF isolation of M. tuberculosis depends on the type of diagnostic tests available. In most cases, the diagnosis remains unconfirmed. GeneXpert MTB/RIF and the next generation Xpert Ultra offer improved sensitivity and rapid turnaround times, and while roll-out has scaled up, availability remains limited. Many locations rely only on acid fast bacilli smear, which is insensitive. Treatment regimens for TBM are based on evidence for pulmonary tuberculosis treatment, with little consideration to CSF penetration or mode of drug action required. The World Health Organization recommends a 12-month treatment course, although data on which to base this duration is lacking. New treatment regimens and drug dosages are under evaluation, with much higher dosages of rifampicin and the inclusion of fluoroquinolones and linezolid identified as promising innovations. The inclusion of corticosteroids at the start of treatment has been demonstrated to reduce mortality in HIV-negative individuals but whether they are universally beneficial is unclear. Other host-directed therapies show promise but evidence for widespread use is lacking. Finally, the management of TBM within health systems is sub-optimal, with drop-offs at every stage in the care cascade.

Tuberculous intracranial mass lesions are common in settings with high tuberculosis (TB) incidence and HIV prevalence. The diagnosis of such lesions, which include tuberculoma and tuberculous abscesses, is often presumptive and based on radiological features, supportive evidence of TB elsewhere and response to TB treatment. However, the treatment response is unpredictable, with lesions frequently enlarging paradoxically or persisting for many years despite appropriate TB treatment and corticosteroid therapy. Most international guidelines recommend a 9-12 month course of TB treatment for central nervous system TB when the infecting Mycobacterium tuberculosis ( M.tb ) strain is sensitive to first-line drugs. However, there is variation in opinion and practice with respect to the duration of TB treatment in patients with tuberculomas or tuberculous abscesses. A major reason for this is the lack of prospective clinical trial evidence. Some experts suggest continuing treatment until radiological resolution of enhancing lesions has been achieved, but this may unnecessarily expose patients to prolonged periods of potentially toxic drugs. It is currently unknown whether persistent radiological enhancement of intracranial tuberculomas after 9-12 months of treatment represents active disease, inflammatory response in a sterilized lesion or merely revascularization. The consequences of stopping TB treatment prior to resolution of lesional enhancement have rarely been explored. These important issues were discussed at the 3 rd International Tuberculous Meningitis Consortium meeting. Most clinicians were of the opinion that continued enhancement does not necessarily represent treatment failure and that prolonged TB therapy was not warranted in patients presumably infected with M.tb strains susceptible to first-line drugs. In this manuscript we highlight current medical treatment practices, benefits and disadvantages of different TB treatment durations and the need for evidence-based guidelines regarding the treatment duration of patients with intracranial tuberculous mass lesions.

Tuberculous meningitis (TBM) is the most severe and disabling form of tuberculosis (TB), accounting for around 1-5% of the global TB caseload, with mortality of approximately 20% in children and up to 60% in persons co-infected with human immunodeficiency virus even in those treated. Relatively few centres of excellence in TBM research exist and the field would therefore benefit from greater co-ordination, advocacy, collaboration and early data sharing. To this end, in 2009, 2015 and 2019 we convened the TBM International Research Consortium, bringing together approximately 50 researchers from five continents. The most recent meeting took place on 1 st and 2 nd March 2019 in Lucknow, India. During the meeting, researchers and clinicians presented updates in their areas of expertise, and additionally presented on the knowledge gaps and research priorities in that field. Discussion during the meeting was followed by the development, by a core writing group, of a synthesis of knowledge gaps and research priorities within seven domains, namely epidemiology, pathogenesis, diagnosis, antimicrobial therapy, host-directed therapy, critical care and implementation science. These were circulated to the whole consortium for written input and feedback. Further cycles of discussion between the writing group took place to arrive at a consensus series of priorities. This article summarises the consensus reached by the consortium concerning the unmet needs and priorities for future research for this neglected and often fatal disease.