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Galectin-9 (Gal-9) is a tandem-repeat galectin with diverse roles in immune homeostasis, inflammation, malignancy, and autoimmune diseases. In cancer, Gal-9 displays variable expression patterns across different tumor types. Its interactions with multiple binding partners, both intracellularly and extracellularly, influence key cellular processes, including immune cell modulation and tumor microenvironment dynamics. Notably, Gal-9 binding to cell-specific glycoconjugate ligands has been implicated in both promoting and suppressing tumor progression. Here, we provide insights into Gal-9 and its involvement in immune homeostasis and cancer biology with an emphasis on multiple myeloma (MM) pathophysiology, highlighting its complex and context-dependent dual functions as a pro- and anti-tumorigenic molecule and its potential implications for therapy in MM patients.

Sterility mosaic disease (SMD) is an emerging biotic risk to the cultivation of pigeonpea throughout the Indian subcontinent. The prevalence and distribution of SMD documented from diverse agro-climatic zones are still poorly known. In this investigation, we determined the spatial distribution of SMD covering major pigeonpea-growing states of Southern India namely, Karnataka, Telangana, Tamil Nadu, Maharashtra, and Andhra Pradesh by considering 2 years of exploratory survey data. Geospatial approaches were employed to determine the SMD incidence levels at unvisited locations using neighboring observations. The results indicated enormous variability in disease incidence ranging from 0 to 82.64% and 0 to 36.84%, respectively, in Kharif 2021–22 and 2022–23 in pigeonpea-growing states. Spatial autocorrelation analysis and Ripley’s K function established the presence of average clustering over sampling locations. Two main clusters were identified via agglomerative hierarchical cluster analysis. From the Local Moran’s I spatial autocorrelation (LISA) analysis, most of the districts were clustered together at (I25%) above the threshold level and must be closely monitored to restrict and minimize further disease spread across the studied areas in Southern India. In pigeonpea, this is the first study in India that attempted to understand the spatial pattern of SMD using geostatistical methodologies. The results of the study will aid in the design and dissemination of specific management practices and curb the further spread of SMD.

IntroductionRecent studies have indicated considerable health risks associated with the consumption of artificial sweeteners. Neotame is a relatively new sweetener in the global market however there is still limited data on the impact of neotame on the intestinal epithelium or the commensal microbiota.MethodsIn the present study, we use a model of the intestinal epithelium (Caco-2) and microbiota (Escherichia coli and Enterococcus faecalis) to investigate how physiologically-relevant exposure of neotame impacts intestinal epithelial cell function, gut bacterial metabolism and pathogenicity, and gut epithelium-microbiota interactions.ResultsOur findings show that neotame causes intestinal epithelial cell apoptosis and death with siRNA knockdown of T1R3 expression significantly attenuating the neotame-induced loss to cell viability. Similarly, neotame exposure results in barrier disruption with enhanced monolayer leak and reduced claudin-3 cell surface expression through a T1R3-dependent pathway. Using the gut bacteria models, E. coli and E. faecalis, neotame significantly increased biofilm formation and metabolites of E. coli, but not E. faecalis, reduced Caco-2 cell viability. In co-culture studies, neotame exposure increased adhesion capacity of E. coli and E. faecalis onto Caco-2 cells and invasion capacity of E. coli. Neotame-induced biofilm formation, E.coli-specific Caco-2 cell death, adhesion and invasion was identified to be meditated through a taste-dependent pathway.DiscussionOur study identifies novel pathogenic effects of neotame on the intestinal epithelium or bacteria alone, and in co-cultures to mimic the gut microbiome. These findings demonstrate the need to better understand food additives common in the global market and the molecular mechanisms underlying potential negative health impacts.

IntroductionThis study aimed to evaluate the implications of supplementary nutrition during the mid-to-late pregnancy on various parameters in Hanwoo cows and their subsequent neonatal calves.Materials and methodsEight Hanwoo cows in their first parity were divided into two groups. The control group (C, 100%) received 3kg of concentrate and 5kg of rice straw throughout the pregnancy period, while the treatment group (T, 150%) increased their diet during mid-to-late pregnancy. Both performance assessments and blood metabolite analyses were performed for the pregnant cows. Neonatal calves were subjected to morphometric evaluations, blood sampling, and detailed morphometric analyses of carcasses and gastrointestinal components.ResultsPerformance indices of the cows showed that both Pregnancy Period (PregP) and Body Condition Score (BCS) were significantly improved with supplemental feeding (p

Fungicidal application has been the common and prime option to combat fruit rot disease (FRD) of arecanut (Areca catechu L.) under field conditions. However, the existence of virulent pathotypes, rapid spreading ability, and improper time of fungicide application has become a serious challenge. In the present investigation, we assessed the efficacy of oomycete-specific fungicides under two approaches: (i) three fixed timings of fungicidal applications, i.e., pre-, mid-, and post-monsoon periods (EXPT1), and (ii) predefined different fruit stages, i.e., button, marble, and premature stages (EXPT2). Fungicidal efficacy in managing FRD was determined from evaluations of FRD severity, FRD incidence, and cumulative fallen nut rate (CFNR) by employing generalized linear mixed models (GLMMs). In EXPT1, all the tested fungicides reduced FRD disease levels by >65% when applied at pre- or mid-monsoon compared with untreated control, with statistical differences among fungicides and timings of application relative to infection. In EXPT2, the efficacy of fungicides was comparatively reduced when applied at predefined fruit/nut stages, with statistically non-significant differences among tested fungicides and fruit stages. A comprehensive analysis of both experiments recommends that the fungicidal application can be performed before the onset of monsoon for effective management of arecanut FRD. In conclusion, the timing of fungicidal application based on the monsoon period provides better control of FRD of arecanut than an application based on the developmental stages of fruit under field conditions.

Infections caused by Mycoplasma synoviae are major welfare and economic concerns in poultry industries worldwide. These infections cause chronic respiratory disease and/or synovitis in chickens and turkeys leading to reduced production and increased mortality rates. The live attenuated vaccine strain MS-H (Vaxsafe® MS), commonly used for protection against M. synoviae infection in many countries, contains 32 single nucleotide variations compared to its wildtype parent strain, 86079/7NS. Genomic analysis of vaccine strains reisolated from flocks following the administration of MS-H has identified reversions to the original 86079/7NS sequence in the obgE, oppF and gapdh genes. Here, three MS-H field reisolates containing the 86079/7NS genotype in obgE (AS2), obgE and oppF (AB1), and obgE, oppF and gapdh (TS4), as well as the vaccine MS-H and the parental strain 86079/7NS were experimentally inoculated to chickens. The strains were assessed for their ability to infect and elicit immune responses in the recipient chickens, as well as in naïve in-contact chickens. Despite the loss of temperature sensitivity phenotype and colonization of the reisolates in the lower respiratory tract, there was no significant differences detected in the microscopic mucosal thickness of the middle or lower trachea of the inoculated chickens. Concurrent reversions in ObgE, OppF and GAPDH proteins were associated with higher gross air sac lesion scores and increased microscopic upper-tracheal mucosal thickness in chickens directly inoculated with the reisolates following intratracheal administration of a virulent strain of infectious bronchitis virus. The gross air sac lesions of the chickens in-contact with those inoculated with reisolates were not significantly different to those of chickens in-contact with MS-H inoculated chickens, suggesting that horizontal transmission of the reisolates in the poultry flock will not lead to higher pathogenicity or clinical signs. These results suggest a significant role of GAPDH and/or cumulative effect of ObgE, OppF and GAPDH on M. synoviae pathogenicity. Future experiments will be required to investigate the effect of single mutations in gapdh or oppF gene on pathogenicity of M. synoviae.

BackgroundDuring the second wave of the COVID-19 pandemic in India, the Ministry of Ayush conducted a community study to provide therapeutic care to patients with asymptomatic, mild, and moderate COVID-19 in home isolation based on the empirical evidence generated on the efficacy of AYUSH-64 in COVID-19.ObjectiveTo document disease characteristics, care-seeking behavior, and outcomes in patients with asymptomatic, mild, or moderate COVID-19 in home isolation who used AYUSH-64 for COVID-19.MethodsCross-sectional analysis of the data generated through a community study conducted in India from 08 May to 31 August 2021 was performed to study the disease characteristics, care-seeking behavior during home isolation, clinical outcomes, adverse events, and the association between various risk factors and clinical recovery during the study period. The data were collected through semi-structured questionnaires, available in electronic data collection format at the baseline, 7, 14, and 21 days. A logistic regression was performed to explore the relationship between relevant variables and clinical recovery.ResultsData from 64,642 participants were analyzed for baseline assessment, and final analysis was done for 49,770 participants. The mean age of the enrolled participants was 38.8 ± 11.7 years, and 8.4% had co-morbidities. AYUSH-64 was utilized as an add-on to the standard care by 58.3% of participants. Comparable clinical outcomes were observed in participants utilizing AYUSH-64 either as a standalone or as an add-on to standard care, in terms of clinical recovery, disease progression, the requirement for oxygen supplementation, hospitalization, ICU admission, and need for ventilator support. Younger age, having no co-morbidities or substance abuse, and having been vaccinated were associated with early clinical recovery than those who were older and not vaccinated.ConclusionsThe study findings suggest that AYUSH-64 use, either standalone or as an adjunct to standard care, in asymptomatic, mild, or moderate COVID-19 is associated with good clinical outcomes. Ayush services and interventions can be effectively integrated into the mainstream public health architecture to serve public health goals.

Pre-harvest sprouting (PHS) is one of the primary problems associated with seed dormancy in rice (Oryza sativa L.). It causes yield loss and reduces grain quality under unpredictable humid conditions at the ripening stage, thus affecting the economic value of the rice crop. To resolve this issue, understanding the molecular mechanism underlying seed dormancy in rice is important. Recent studies have shown that seed dormancy is affected by a large number of genes associated with plant hormone regulation. However, understanding regarding the effect of heat stress on seed dormancy and plant hormones is limited. This study compared the transcriptome and small RNAome of the seed embryo and endosperm of two contrasting japonica rice accessions, PHS susceptible (with low seed dormancy) and PHS resistant (with high seed dormancy), at three different maturation stages. We found that 9,068 genes and 35 microRNAs (miRNAs) were differentially expressed in the embryo, whereas 360 genes were differentially expressed in the endosperm. Furthermore, we identified and verified the candidate genes associated with seed dormancy and heat stress-related responses in rice using quantitative real-time PCR. We newly discovered eight hormone-related genes, four heat shock protein-related genes, and two miRNAs potentially involved in PHS. These findings provide a strong foundation for understanding the dynamics of transcriptome and small RNAome of hormone- and heat stress-related genes, which affect PHS during seed maturation.

The phloem sap tapped from unopened inflorescence (spadix) of coconut palm using a novel collecting device, “coco-sap chiller,” has been branded Kalparasa® (henceforth as Kalparasa in the text) to distinguish its properties not found in sap harvested by traditional methods. To know its hitherto unidentified microbiome profile, we employed high-throughput sequencing to uncover the bacteriome and mycobiome in fresh and 12-h fermented samples. Fresh Kalparasa had a pH of 7.2, which dropped to 4.5 after 12 h, signifying fermentation of the sap. Diversity analysis indicated fresh Kalparasa having higher bacterial species than the fermented one. Contrary to this, fresh sap had lower fungal/yeast diversity than the fermented sample. Fresh Kalparasa had relatively higher abundance of probiotic-type Leuconostoc genus followed by equal proportions of Gluconobacter, Acetobacter, and Fructobacillus. The 12-h fermented Kalparasa showed a significant increase in Gluconobacter with a sharp decrease in Leuconostoc. Mycobiome data revealed fresh Kalparasa to be preponderant in Saccharomyces and Hanseniaspora genera of yeasts while the fermented sap had higher representation of Hanseniaspora and Cortinarius and lesser Saccharomyces. This suggested that the fermentation of Kalparasa was probably driven by symbiotic culture of bacteria and yeasts (SCOBY), particularly acetic acid bacteria and non-Saccharomyces yeasts. The bacteriome-function predictions highlighted the enrichment of glycerophospholipid, ABC transporters, purine, and pyrimidine metabolisms. Based on our findings, Kalparasa containing large population of Leuconostoc mesenteroides, Fructobacillus fructosus, Saccharomyces cerevisiae, and Hanseniaspora guilliermondii can be promoted as a healthy “unfermented” plant edible food containing live probiotic-type microbiome during its consumption.

The fine-tuning of inorganic phosphate (Pi) for enhanced use efficiency has long been a challenging subject in agriculture, particularly in regard to rice as a major crop plant. Among ribonucleases (RNases), the RNase T2 family is broadly distributed across kingdoms, but little has been known on its substrate specificity compared to RNase A and RNase T1 families. Class I and class II of the RNase T2 family are defined as the S-like RNase (RNS) family and have showed the connection to Pi recycling in Arabidopsis. In this study, we first carried out a phylogenetic analysis of eight rice and five Arabidopsis RNS genes and identified mono-specific class I and dicot-specific class I RNS genes, suggesting the possibility of functional diversity between class I RNS family members in monocot and dicot species through evolution. We then compared the in silico expression patterns of all RNS genes in rice and Arabidopsis under normal and Pi-deficient conditions and further confirmed the expression patterns of rice RNS genes via qRT-PCR analysis. Subsequently, we found that most of the OsRNS genes were differentially regulated under Pi-deficient treatment. Association of Pi recycling by RNase activity in rice was confirmed by measuring total RNA concentration and ribonuclease activity of shoot and root samples under Pi-sufficient or Pi-deficient treatment during 21 days. The total RNA concentrations were decreased by < 60% in shoots and < 80% in roots under Pi starvation, respectively, while ribonuclease activity increased correspondingly. We further elucidate the signaling pathway of Pi starvation through upregulation of the OsRNS genes. The 2-kb promoter region of all OsRNS genes with inducible expression patterns under Pi deficiency contains a high frequency of P1BS cis-acting regulatory element (CRE) known as the OsPHR2 binding site, suggesting that the OsRNS family is likely to be controlled by OsPHR2. Finally, the dynamic transcriptional regulation of OsRNS genes by overexpression of OsPHR2, ospho2 mutant, and overexpression of OsPT1 lines involved in Pi signaling pathway suggests the molecular basis of OsRNS family in Pi recycling via RNA decay under Pi starvation.

Microsatellites are ubiquitously distributed, polymorphic repeat sequence valuable for association, selection, population structure and identification. They can be mined by genomic library, probe hybridization and sequencing of selected clones. Such approach has many limitations like biased hybridization and selection of larger repeats. In silico mining of polymorphic markers using data of various genotypes can be rapid and economical. Available tools lack in some or other aspects like: targeted user defined primer generation, polymorphism discovery using multiple sequence, size and number limits of input sequence, no option for primer generation and e-PCR evaluation, transferability, lack of complete automation and user-friendliness. They also lack the provision to evaluate published primers in e-PCR mode to generate additional allelic data using re-sequenced data of various genotypes for judicious utilization of previously generated data. We developed the tool (PolyMorphPredict) using Perl, R, Java and launched at Apache which is available at http://webtom.cabgrid.res.in/polypred/. It mines microsatellite loci and computes primers from genome/transcriptome data of any species. It can perform e-PCR using published primers for polymorphism discovery and across species transferability of microsatellite loci. Present tool has been evaluated using five species of different genome size having 21 genotypes. Though server is equipped with genomic data of three species for test run with gel simulation, but can be used for any species. Further, polymorphism predictability has been validated using in silico and in vitro PCR of four rice genotypes. This tool can accelerate the in silico microsatellite polymorphism discovery in re-sequencing projects of any species of plant and animal for their diversity estimation along with variety/breed identification, population structure, MAS, QTL and gene discovery, traceability, parentage testing, fungal diagnostics and genome finishing.

Cold stress is very detrimental to crop production. However, only a few genes in rice have been identified with known functions related to cold tolerance. To meet this agronomic challenge more effectively, researchers must take global approaches to select useful candidate genes and find the major regulatory factors. We used five Gene expression omnibus series data series of Affymetrix array data, produced with cold stress-treated samples from the NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/), and identified 502 cold-inducible genes common to both japonica and indica rice cultivars. From them, we confirmed that the expression of two randomly chosen genes was increased by cold stress in planta. In addition, overexpression of OsWRKY71 enhanced cold tolerance in ‘Dongjin,’ the tested japonica cultivar. Comparisons between japonica and indica rice, based on calculations of plant survival rates and chlorophyll fluorescence, confirmed that the japonica rice was more cold-tolerant. Gene Ontology enrichment analysis indicate that the ‘L-phenylalanine catabolic process,’ within the Biological Process category, was the most highly overrepresented under cold-stress conditions, implying its significance in that response in rice. MapMan analysis classified ‘Major Metabolic’ processes and ‘Regulatory Gene Modules’ as two other major determinants of the cold-stress response and suggested several key cis-regulatory elements. Based on these results, we proposed a model that includes a pathway for cold stress-responsive signaling. Results from our functional analysis of the main signal transduction and transcription regulation factors identified in that pathway will provide insight into novel regulatory metabolism(s), as well as a foundation by which we can develop crop plants with enhanced cold tolerance.

Water deficiencies are one of the most serious challenges to crop productivity. To improve our understanding of soil moisture stress, we performed RNA-Seq analysis using roots from 4-week-old rice seedlings grown in soil that had been subjected to drought conditions for 2–3 d. In all, 1,098 genes were up-regulated in response to soil moisture stress for 3 d, which causes severe damage in root development after recovery, unlikely that of 2 d. Comparison with previous transcriptome data produced in drought condition indicated that more than 68% of our candidate genes were not previously identified, emphasizing the novelty of our transcriptome analysis for drought response in soil condition. We then validated the expression patterns of two candidate genes using a promoter-GUS reporter system in planta and monitored the stress response with novel molecular markers. An integrating omics tool, MapMan analysis, indicated that RING box E3 ligases in the ubiquitin-proteasome pathways are significantly stimulated by induced drought. We also analyzed the functions of 66 candidate genes that have been functionally investigated previously, suggesting the primary roles of our candidate genes in resistance or tolerance relating traits including drought tolerance (29 genes) through literature searches besides diverse regulatory roles of our candidate genes for morphological traits (15 genes) or physiological traits (22 genes). Of these, we used a T-DNA insertional mutant of rice phytochrome B (OsPhyB) that negatively regulates a plant's degree of tolerance to water deficiencies through the control of total leaf area and stomatal density based on previous finding. Unlike previous result, we found that OsPhyB represses the activity of ascorbate peroxidase and catalase mediating reactive oxygen species (ROS) processing machinery required for drought tolerance of roots in soil condition, suggesting the potential significance of remaining uncharacterized candidate genes for manipulating drought tolerance in rice.

Human respiratory syncytial virus (RSV) is a lung tropic virus causing severe airway diseases including bronchiolitis and pneumonia among infants, children and immuno-compromised individuals. RSV triggers transforming growth factor-beta(TGF-beta) production from lung epithelial cells and TGF-beta facilitates RSV infection of these cells. However, it is still unknown whether RSV infected myeloid cells like macrophages produce TGF-beta and the role of TGF-beta if any during RSV infection of these cells. Our study revealed that RSV infected macrophages produce TGF-beta and as a consequence these cells activate TGF-beta dependent SMAD-2/3 signaling pathway. Further mechanistic studies illustrated a role of autophagy in triggering TGF-beta production from RSV infected macrophages. In an effort to elucidate the role of TGF-beta and SMAD-2/3 signaling during RSV infection, we surprisingly unfolded the requirement of TGF-beta---SMAD2/3 signaling in conferring optimal innate immune antiviral response during RSV infection of macrophages. Type-I interferon (e.g. interferon-beta or IFN-beta) is a critical host factor regulating innate immune antiviral response during RSV infection. Our study revealed that loss of TGF-beta---SMAD2/3 signaling pathway in RSV infected macrophages led to diminished expression and production of IFN-beta. Inhibiting autophagy in RSV infected macrophages also resulted in reduced production of IFN-beta. Thus, our studies have unfolded the requirement of autophagy---TGF-beta---SMAD2/3 signaling network for optimal innate immune antiviral response during RSV infection of macrophages.

Adipose tissue is known to secrete hormones actively and produces many biologically active proteins called adipocytokines. Typically, obesity is followed by low-grade inflammation, which is characterized by increased circulating levels of pro-inflammatory cytokines. Macrophages play a role in the inflammatory process by secreting many cytokines such as tumour necrosis factor-alpha, interleukin-6, resistin and retinol binding protein-4. These cytokines and chemokines participate in low grade pro-inflammatory processes leading to insulin resistance, metabolic impairment and cardiovascular diseases. More metabolic regulators, such as fibroblast growth factor (FGF)21, FGF19, FGF1, vaspin and visfatin have now been discovered but their exact roles in human diseases are still unclear. This review focuses on recent research regarding the role of adipokines and new metabolic factors in metabolic derangement or cardiovascular disease.