Alternaria alternata species complex impairing solanaceous vegetables in Northern parts of India: an emerging problem in Solanum lycopersicum L.

Severe incidence of Alternaria spp. was observed in the three solanaceous vegetables viz. tomato, potato and brinjal grown in National Capital Region of Delhi and Haryana. The symptomatic plants exhibited necrotic brown lesions on the leaves initiating from the lower older leaves and extending to stem, affecting the whole plant. Subsequently, black sooty sporulation was observed in fruits of tomato and brinjal crop. During the survey, tomato crop was most susceptible with 98.99% incidence, followed by brinjal with 82.36% and potato with 61.19% incidence. The mean plant disease index varied between 9.98% and 65.99% among the three crops. Isolation and characterization of the causal agent from symptomatic plants revealed association of small-spored Alternaria spp. in all crops. Further, morphological and Internal Transcribed Spacer (ITS) sequencing phylogenetic analysis ascertained the fungus belong to Alternaria section of Alternaria genus. As tomato was found most susceptible, host plant resistance was explored among 197 tomato germplasm/breeding lines under epiphytotic conditions. It was found that 08 accessions exhibited moderate resistance against pathogen. The findings in the study suggest that small-spored Alternaria is an emerging problem in the solanaceous vegetables and warrants attention for effective management of the disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04059-7.

Discovery, lead identification and exploration of potential oxadiazole derivatives in targeting STAT3 as anti-cancer agents.

Oxadiazoles an important heterocyclic scaffold of medicinal importance in the field of drug discovery. In the study, a library of oxadiazole based compounds was selected for screening against STAT-3 as anti-cancer target. STAT3 is a potential target of interest in cancer therapy. A total of 544 screened library of compounds was subjected to molecular docking against STAT-3 (6NJS and 6NQU). The compounds with good dock score and binding interations were further subjected to in-silico ADME analysis followed by toxicity estimation. A total of 141 hits were selected against 6NJS and 50 hits against 6NQU and further screened for kinetic properties and drug likeliness. The compounds were screened on the basis of physico-chemical properties, solubility, gastrointestinal absorption, BBB permeability, synthetic accessibility, Lipinski and other violations. Best compounds obtained after ADME analysis were further subjected for toxicity analysis. Carcinogenecity, mutagenicity, Ames and other important parameters were considered for toxicity based screening. The best leads thus obtained (compound 114 and 40) were further subjected to molecular dynamics against the respective target proteins. MD simulations were run to access the stability of C-114 and C-40 along with the dynamic behaviour of both complexes for about 100 ns and shows good stability with the proteins.

Retraction: Recent application of visible-light induced radicals in C-S bond formation.

[This retracts the article DOI: 10.1039/D0RA03086D.].

Retraction: Recent advances in visible-light graphitic carbon nitride (g-C3N4) photocatalysts for chemical transformations.

[This retracts the article DOI: 10.1039/D2RA01797K.].

Deciphering the defense response in tomato against Sclerotium rolfsii by Trichoderma asperellum strain A10 through gene expression analysis.

Biological control agents are preferred over chemicals for managing plant diseases, with Trichoderma species being particularly effective against soil-borne pathogens. This study examines the use of a highly antagonistic strain, Trichoderma asperellum A10, and a virulent strain, Sclerotium rolfsii Sr38, identified and confirmed through ITS, ß-tubulin (T. asperellum), TEF 1α, and RPB2 (S. rolfsii) sequences. In vitro and in planta experiments compared the antagonistic potential of A10 with other antagonistic fungi and fungicides against S. rolfsii. A10 achieved 94.66% inhibition of S. rolfsii in dual culture assays. In greenhouse trials with tomato variety Pusa Ruby, A10 showed significant pre- and post-inoculation effectiveness, with disease inhibition of 86.17 and 80.60%, respectively, outperforming T. harzianum, Propiconazole, and Carbendazim. Additionally, microbial priming with A10 was explored to enhance plant defense responses. Pre-treatment of tomato plants with T. asperellum A10 led to significant upregulation of several defense-related genes, including PR1, PR2, PR3, PR5, PR12, thioredoxin peroxidase, catalase, polyphenol oxidase, phenylalanine ammonia lyase, isochorismate synthase, laccase, prosystemin, multicystatin, WRKY31, MYC2, lipoxygenase A, lipoxygenase C, proteinase inhibitor I, proteinase inhibitor II, and ethylene response 1 associated with various signaling pathways such as salicylic acid (SA)-mediated and jasmonic acid/ethylene (JA/ET)-mediated responses. This upregulation was particularly evident at 48 h post-inoculation in A10-primed plants challenged with S. rolfsii, inducing resistance against collar rot disease. This study underscores the effectiveness of T. asperellum A10 in controlling collar rot and highlights its potential for inducing resistance in plants through microbial priming, providing valuable insights into sustainable disease management strategies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04040-4.

Type I interferon signaling induces melanoma cell-intrinsic PD-1 and its inhibition antagonizes immune checkpoint blockade.

Programmed cell death 1 (PD-1) is a premier cancer drug target for immune checkpoint blockade (ICB). Because PD-1 receptor inhibition activates tumor-specific T-cell immunity, research has predominantly focused on T-cell-PD-1 expression and its immunobiology. In contrast, cancer cell-intrinsic PD-1 functional regulation is not well understood. Here, we demonstrate induction of PD-1 in melanoma cells via type I interferon receptor (IFNAR) signaling and reversal of ICB efficacy through IFNAR pathway inhibition. Treatment of melanoma cells with IFN-α or IFN-ß triggers IFNAR-mediated Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling, increases chromatin accessibility and resultant STAT1/2 and IFN regulatory factor 9 (IRF9) binding within a PD-1 gene enhancer, and leads to PD-1 induction. IFNAR1 or JAK/STAT inhibition suppresses melanoma-PD-1 expression and disrupts ICB efficacy in preclinical models. Our results uncover type I IFN-dependent regulation of cancer cell-PD-1 and provide mechanistic insight into the potential unintended ICB-neutralizing effects of widely used IFNAR1 and JAK inhibitors.

Light-driven photocatalysis as an effective tool for degradation of antibiotics.

Antibiotic contamination has become a severe issue and a dangerous concern to the environment because of large release of antibiotic effluent into terrestrial and aquatic ecosystems. To try and solve these issues, a plethora of research on antibiotic withdrawal has been carried out. Recently photocatalysis has received tremendous attention due to its ability to remove antibiotics from aqueous solutions in a cost-effective and environmentally friendly manner with few drawbacks compared to traditional photocatalysts. Considerable attention has been focused on developing advanced visible light-driven photocatalysts in order to address these problems. This review provides an overview of recent developments in the field of photocatalytic degradation of antibiotics, including the doping of metals and non-metals into ultraviolet light-driven photocatalysts, the formation of new semiconductor photocatalysts, the advancement of heterojunction photocatalysts, and the building of surface plasmon resonance-enhanced photocatalytic systems.

Prognostic biomarkers of intracerebral hemorrhage identified using targeted proteomics and machine learning algorithms.

Early prognostication of patient outcomes in intracerebral hemorrhage (ICH) is critical for patient care. We aim to investigate protein biomarkers' role in prognosticating outcomes in ICH patients. We assessed 22 protein biomarkers using targeted proteomics in serum samples obtained from the ICH patient dataset (N = 150). We defined poor outcomes as modified Rankin scale score of 3-6. We incorporated clinical variables and protein biomarkers in regression models and random forest-based machine learning algorithms to predict poor outcomes and mortality. We report Odds Ratio (OR) or Hazard Ratio (HR) with 95% Confidence Interval (CI). We used five-fold cross-validation and bootstrapping for internal validation of prediction models. We included 149 patients for 90-day and 144 patients with ICH for 180-day outcome analyses. In multivariable logistic regression, UCH-L1 (adjusted OR 9.23; 95%CI 2.41-35.33), alpha-2-macroglobulin (aOR 5.57; 95%CI 1.26-24.59), and Serpin-A11 (aOR 9.33; 95%CI 1.09-79.94) were independent predictors of 90-day poor outcome; MMP-2 (aOR 6.32; 95%CI 1.82-21.90) was independent predictor of 180-day poor outcome. In multivariable Cox regression models, IGFBP-3 (aHR 2.08; 95%CI 1.24-3.48) predicted 90-day and MMP-9 (aOR 1.98; 95%CI 1.19-3.32) predicted 180-day mortality. Machine learning identified additional predictors, including haptoglobin for poor outcomes and UCH-L1, APO-C1, and MMP-2 for mortality prediction. Overall, random forest models outperformed regression models for predicting 180-day poor outcomes (AUC 0.89), and 90-day (AUC 0.81) and 180-day mortality (AUC 0.81). Serum biomarkers independently predicted short-term poor outcomes and mortality after ICH. Further research utilizing a multi-omics platform and temporal profiling is needed to explore additional biomarkers and refine predictive models for ICH prognosis.

Characterizing genetic diversity of Sclerotium rolfsii isolates by biomapping of mycelial compatibility groupings and multilocus sequence analysis.

Genetic diversity in Sclerotium rolfsii is useful for understanding its population structure, identifying different mycelial compatibility groups (MCGs), and developing targeted strategies for disease management in affected crops. In our study, a comprehensive genetic analysis was conducted on 50 isolates of S. rolfsii, collected from various geographic regions and host plants. Two specific genes, TEF1α and RPB2, were utilized to assess the genetic diversity and relationships among these isolates. Notably, out of 1225 pairings examined, only 154 exhibited a compatible reaction, while the majority displayed antagonistic reactions, resulting in the formation of a barrier zone. The isolates were grouped into 10 distinct MCGs. These MCGs were further characterized using genetic sequencing. TEF1α sequences distinguished the isolates into 17 distinct clusters, and RPB2 sequences classified them into 20 clusters. Some MCGs shared identical gene sequences within each gene, while others exhibited unique sequences. Intriguingly, when both TEF1α and RPB2 sequences were combined, all 10 MCGs were effectively differentiated, even those that appeared identical with single-gene analysis. This combined approach provided a comprehensive understanding of the genetic diversity and relationships among the S. rolfsii isolates, allowing for precise discrimination between different MCGs. The results shed light on the population structure and genetic variability within this plant pathogenic fungus, providing valuable insights for disease management and control strategies. This study highlights the significance of comprehending the varied virulence characteristics within S. rolfsii isolates, categorizing them into specific virulence groups based on disease severity index (DSI) values. The association with MCGs provides additional insights into the genetic underpinnings of virulence in this pathogen. Furthermore, the identification of geographical patterns in virulence implies the influence of region-specific factors, with potential implications for disease control and crop protection strategies.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [G. M. Sandeep] Last name [Kumar]. Author 2 Given name: [Praveen Kumar] Last name [Singh]. Also, kindly confirm the details in the metadata are correct.I confirm that the given names are accurate and presented in the correct sequence.

Development of immunochromatographic strip assay to detect recent infection of Japanese encephalitis virus in swine population.

Japanese Encephalitis (JE) is a mosquito borne re-emerging viral zoonotic disease. Sero-conversion in swine occurs 2-3 weeks before human infection, thus swine act as a suitable sentinel for predicting JE outbreaks in humans. The present study was undertaken with the objective of developing immunochromatographic strip (ICS) assay to detect recent infection of Japanese Encephalitis virus (JEV) in swine population. The two formats of ICS assay were standardized. In the first format, gold nanoparticles (GNP) were conjugated with goat anti-pig IgM (50 µg/ml) followed by spotting of recombinant NS1 protein (1 mg/ml) of JEV on NCM as test line and protein G (1 mg/ml) as control line. In the format-II, GNP were conjugated with rNS1 protein (50 µg/ml) followed by spotting of Goat anti-pig IgM (1 mg/ml) as test line and IgG against rNS1 (1 mg/ml) as control line. To decrease the non- specific binding, blocking of serum and nitrocellulose membrane (NCM) was done using 5% SMP in PBS-T and 1% BSA, respectively. Best reaction conditions for the assay were observed when 10 µl of GNP conjugate and 50 µl of 1:10 SMP blocked sera was reacted on BSA blocked NCM followed by reaction time of 15 mins. Samples showing both test and control line were considered positive whereas samples showing only control line were considered negative. A total of 318 field swine sera samples were screened using indirect IgM ELISA and developed ICS assay. Relative diagnostic sensitivity and specificity of format-I was 81.25% and 93.0% whereas of format-II was 87.50% and 62.93%, respectively. Out of 318 samples tested, 32 were positive through IgM ELISA with sero-positivity of 10.06% while sero-positivity with format-I of ICS was 8.1%. Owing to optimal sensitivity and higher specificity of format-I, it was validated in three different labs and the kappa agreement ranged from 0.80 to 1, which signifies excellent repeatability of the developed assay to test field swine sera samples for detecting recent JEV infection.

An HLA-E-targeted TCR bispecific molecule redirects T cell immunity against Mycobacterium tuberculosis.

Peptides presented by HLA-E, a molecule with very limited polymorphism, represent attractive targets for T cell receptor (TCR)-based immunotherapies to circumvent the limitations imposed by the high polymorphism of classical HLA genes in the human population. Here, we describe a TCR-based bispecific molecule that potently and selectively binds HLA-E in complex with a peptide encoded by the inhA gene of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis in humans. We reveal the biophysical and structural bases underpinning the potency and specificity of this molecule and demonstrate its ability to redirect polyclonal T cells to target HLA-E-expressing cells transduced with mycobacterial inhA as well as primary cells infected with virulent Mtb. Additionally, we demonstrate elimination of Mtb-infected cells and reduction of intracellular Mtb growth. Our study suggests an approach to enhance host T cell immunity against Mtb and provides proof of principle for an innovative TCR-based therapeutic strategy overcoming HLA polymorphism and therefore applicable to a broader patient population.

A clinic-pathological research explored the significance of ascorbic acid and iron levels in serum and saliva in premalignant disorder patients at Kanpur, Uttar Pradesh.

Context: Oral submucous fibrosis (OSMF), or OSMF, is a well-known, potentially premalignant condition of the oral cavity. Monitoring OSMF widespread effects necessitate interventions in at-risk individuals, ideally before the disease becomes aggressive. Ascorbic acid and iron, for instance, are significant micronutrients in the pathogenesis of OSMF. Aims: This study aimed to investigate the significance of ascorbic acid and iron levels in serum and saliva in patients with premalignant disorder (OSMF) and to correlate variations in ascorbic acid and iron levels with histopathological grading. Settings and Design: The present study was conducted on 195 patients over a period of 10 months. Subjects and Methods: These patients were divided into two groups, Group I (n = 88, Control), Group II (n = 107, clinically diagnosed and histopathologically confirmed cases of OSMF). Serum and salivary ascorbic acid were analyzed by the dintrophenyl hydrazine method, whereas serum and salivary iron were analyzed by the dipyridyl method. Statistical Analysis Used: Paired t-test and Fisher test were used to compare between the mean and to find the level of significance P value. Results: The serum and salivary ascorbic acid levels consistently decreased with the progression of histopathological grading of OSMF. Serum and salivary iron levels were also decreased in OSMF patients, and it came as significant. Conclusions: Excess collagen synthesis during OSMF may have been promoted with ascorbic acid and iron. As a reason, serum and salivary monitoring may be significant in detecting and diagnosing OSMF early on.

Percutaneous elevation of proximal tibia depressed fractures using modified new instrument.

Proximal tibia depression fracture often occur isolated or in conjunction with complex fracture presentations and elevation of such depression is required to retard arthritis in long term. Conventional open reduction by sub meniscal approach has many percutaneous alternatives from arthroscopy assisted reduction to balloon tibioplasty. Few authors even reported usage of PCL jig and percutaneous pins to elevate, while the primary author has previously described an instrument to elevate the depressed fragment percutaneously. With the shortcomings of the same instrument, authors have designed modifications in the same to address anterior and posterior extensions of depression without widening the metaphyseal window. In this article, we describe the size and concept of the modified design and its efficacy to address depression injuries.

Recent advances of decatungstate photocatalyst in HAT process.

The decatungstate anion (W10O324-) appears to exhibit especially interesting properties as a photocatalyst. Because of its unique photocatalytic properties, it is now recognised as a promising tool in organic chemistry. This study examines recent advances in decatungstate chemistry, primarily concerned with synthetic and, to some degree, mechanistic challenges. In this short review we have selected to give a number of illustrative examples that demonstrate the various applications of decatungstate in the hydrogen atom transfer (HAT) process.

Chronic Morphine Treatment and Antiretroviral Therapy Exacerbate HIV-Distal Sensory Peripheral Neuropathy and Induce Distinct Microbial Alterations in the HIV Tg26 Mouse Model.

Distal Sensory Peripheral Neuropathy (DSP) is a common complication in HIV-infected individuals, leading to chronic pain and reduced quality of life. Even with antiretroviral therapy (ART), DSP persists, often prompting the use of opioid analgesics, which can paradoxically worsen symptoms through opioid-induced microbial dysbiosis. This study employs the HIV Tg26 mouse model to investigate HIV-DSP development and assess gut microbiome changes in response to chronic morphine treatment and ART using 16S rRNA sequencing. Our results reveal that chronic morphine and ART exacerbate HIV-DSP in Tg26 mice, primarily through mechanical pain pathways. As the gut microbiome may be involved in chronic pain persistence, microbiome analysis indicated distinct bacterial community changes between WT and Tg26 mice as well as morphine- and ART-induced microbial changes in the Tg26 mice. This study reveals the Tg26 mouse model to be a relevant system that can help elucidate the pathogenic mechanisms of the opioid- and ART-induced exacerbation of HIV-associated pain. Our results shed light on the intricate interplay between HIV infection, ART, opioid use, and the gut microbiome in chronic pain development. They hold implications for understanding the mechanisms underlying HIV-associated pain and microbial dysbiosis, with potential for future research focused on prevention and treatment strategies.

Altered gut microbiome drives heightened pain sensitivity in a murine model of metastatic triple-negative breast cancer.

The microbiota residing in the gut environment is essential for host homeostasis. Increasing evidence suggests that microbial perturbation (dysbiosis) regulates cancer initiation and progression at local and distant sites. Here, we have identified microbial dysbiosis with the depletion of commensal bacteria as a host-intrinsic factor associated with metastatic dissemination to the bone. Using a mouse model of triple-negative mammary cancer, we demonstrate that a pre-established disruption of microbial homeostasis using an antibiotic cocktail increases tumor growth, enhanced circulating tumor cells, and subsequent dissemination to the bone. We found that the presence of pathogenic bacteria and loss of commensal bacteria in an antibiotic-induced gut environment is associated with sustained inflammation. Increased secretion of G-CSF and MMP-9 in intestinal tissues, followed by increased neutrophil infiltration and severe systemic inflammation in tumor-bearing mice, indicates the direct consequence of a dysbiotic microbiome. Increased neutrophil infiltration to the bone metastatic niche facilitates extravasation and transendothelial migration of tumor cells. It provides a novel, pre-established, and favorable environment to form an immunosuppressive pre-metastatic niche. The presence of tumor cells in immunosuppressive metastatic tumor niche disrupts the balance between osteoblasts and osteoclasts, promotes osteoclast differentiation, and remodels the bone structure. Excessive bone resorption by osteoclasts causes bone degradation and ultimately causes extreme pain in a bone metastatic mouse model. In clinical settings, bone metastasis is associated with intractable severe pain that severely compromises the quality of life in these patients.

Development of pathophysiologically relevant models of sickle cell disease and ß-thalassemia for therapeutic studies.

Ex vivo cellular system that accurately replicates sickle cell disease and ß-thalassemia characteristics is a highly sought-after goal in the field of erythroid biology. In this study, we present the generation of erythroid progenitor lines with sickle cell disease and ß-thalassemia mutation using CRISPR/Cas9. The disease cellular models exhibit similar differentiation profiles, globin expression and proteome dynamics as patient-derived hematopoietic stem/progenitor cells. Additionally, these cellular models recapitulate pathological conditions associated with both the diseases. Hydroxyurea and pomalidomide treatment enhanced fetal hemoglobin levels. Notably, we introduce a therapeutic strategy for the above diseases by recapitulating the HPFH3 genotype, which reactivates fetal hemoglobin levels and rescues the disease phenotypes, thus making these lines a valuable platform for studying and developing new therapeutic strategies. Altogether, we demonstrate our disease cellular systems are physiologically relevant and could prove to be indispensable tools for disease modeling, drug screenings and cell and gene therapy-based applications.

Correction: Visible-light acridinium-based organophotoredox catalysis in late-stage synthetic applications.

[This corrects the article DOI: 10.1039/D3RA01364B.].

Tumor cell-intrinsic PD-1 promotes Merkel cell carcinoma growth by activating downstream mTOR-mitochondrial ROS signaling.

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer. Inhibitors targeting the programmed cell death 1 (PD-1) immune checkpoint have improved MCC patient outcomes by boosting antitumor T cell immunity. Here, we identify PD-1 as a growth-promoting receptor intrinsic to MCC cells. In human MCC lines and clinical tumors, RT-PCR-based sequencing, immunoblotting, flow cytometry, and immunofluorescence analyses demonstrated PD-1 gene and protein expression by MCC cells. MCC-PD-1 ligation enhanced, and its inhibition or silencing suppressed, in vitro proliferation and in vivo tumor xenograft growth. Consistently, MCC-PD-1 binding to PD-L1 or PD-L2 induced, while antibody-mediated PD-1 blockade inhibited, protumorigenic mTOR signaling, mitochondrial (mt) respiration, and ROS generation. Last, pharmacologic inhibition of mTOR or mtROS reversed MCC-PD-1:PD-L1-dependent proliferation and synergized with PD-1 checkpoint blockade in suppressing tumorigenesis. Our results identify an MCC-PD-1-mTOR-mtROS axis as a tumor growth-accelerating mechanism, the blockade of which might contribute to clinical response in patients with MCC.

Novel applications of photobiocatalysts in chemical transformations.

Photocatalysis has proven to be an effective approach for the production of reactive intermediates under moderate reaction conditions. The possibility for the green synthesis of high-value compounds using the synergy of photocatalysis and biocatalysis, benefiting from the selectivity of enzymes and the reactivity of photocatalysts, has drawn growing interest. Mechanistic investigations, substrate analyses, and photobiocatalytic chemical transformations will all be incorporated in this review. We seek to shed light on upcoming synthetic opportunities in the field by precisely describing mechanistically unique techniques in photobiocatalytic chemistry.