Bacterial exopolysaccharide amendment improves the shelf life and functional efficacy of bioinoculant under salinity stress.

AIM: Bacterial exopolysaccharide (EPS) possesses numerous properties beneficial for the growth of microbes and plants under hostile conditions. The study aimed to develop a bioformulation with bacterial EPS to enhance the bioinoculant's shelf-life and functional efficacy under salinity stress. METHODS AND RESULTS: High EPS-producing and salt-tolerant bacterial strain (SD2) exhibiting auxin-production, phosphate-solubilization, and biofilm-forming ability was selected. EPS-based bioformulation of SD2 improved the growth of three legumes under salt stress, from which pigeonpea was selected for further experiments. SD2 improved the growth and lowered the accumulation of stress markers in plants under salt stress. Bioformulations with varying EPS concentrations (1% and 2%) were stored for 6 months at 4°C, 30°C, and 37°C to assess their shelf-life and functional efficacy. The shelf life and efficacy of EPS-based bioformulation was sustained at higher temperature, enhancing pigeonpea growth under stress after six months of storage in both control and natural conditions. However, the efficacy of non-EPS-based bioformulation declined following four months of storage. The bioformulation modulated bacterial abundance in the plant's rhizosphere under stress conditions. CONCLUSIONS AND IMPACT STATEMENT: The study brings forth a new strategy for developing next-generation bioformulations with higher shelf-life and efficacy for salinity stress management in pigeonpea under saline conditions.

Microbial community and functions involved in smokeless tobacco product: a metagenomic approach.

Smokeless tobacco products (STPs) are attributed to oral cancer and oral pathologies in their users. STP-associated cancer induction is driven by carcinogenic compounds including tobacco-specific nitrosamines (TSNAs). The TSNAs synthesis could enhanced due to the metabolic activity (nitrate metabolism) of the microbial populations residing in STPs, but identifying microbial functions linked to the TSNAs synthesis remains unexplored. Here, we rendered the first report of shotgun metagenomic sequencing to comprehensively determine the genes of all microorganisms residing in the Indian STPs belonging to two commercial (Moist-snuff and Qiwam) and three loose (Mainpuri Kapoori, Dohra, and Gudakhu) STPs, specifically consumed in India. Further, the level of nicotine, TSNAs, mycotoxins, and toxic metals were determined to relate their presence with microbial activity. The microbial population majorly belongs to bacteria with three dominant phyla including Actinobacteria, Proteobacteria, and Firmicutes. Furthermore, the STP-linked microbiome displayed several functional genes associated with nitrogen metabolism and antibiotic resistance. The chemical analysis revealed that the Mainpuri Kapoori product contained a high concentration of ochratoxins-A whereas TSNAs and Zink (Zn) quantities were high in the Moist-snuff, Mainpuri Kapoori, and Gudakhu products. Hence, our observations will help in attributing the functional potential of STP-associated microbiome and in the implementation of cessation strategies against STPs. KEY POINTS: •Smokeless tobacco contains microbes that can assist TSNA synthesis. •Antibiotic resistance genes present in smokeless tobacco-associated bacteria. •Pathogens in STPs can cause infections in smokeless tobacco users.

Seed biopriming as a promising approach for stress tolerance and enhancement of crop productivity: a review.

Chemicals are used extensively in agriculture to increase crop production to meet the nutritional needs of an expanding world population. However, their injudicious application adversely affects the soil's physical, chemical and biological properties, subsequently posing a substantial threat to human health and global food security. Beneficial microorganisms improve plant health and productivity with minimal impact on the environment; however, their efficacy greatly relies on the application technique. Biopriming is an advantageous technique that involves the treatment of seeds with beneficial biological agents. It exhibits immense potential in improving the physiological functioning of seeds, thereby playing a pivotal role in their uniform germination and vigor. Biopriming-mediated molecular and metabolic reprogramming imparts stress tolerance to plants, improves plant health, and enhances crop productivity. Furthermore, it is also associated with rehabilitating degraded land, and improving soil fertility, health and nutrient cycling. Although biopriming has vast applications in the agricultural system, its commercialization and utilization by farmers is still in its infancy. This review aims to critically analyze the recent studies based on biopriming-mediated stress mitigation by alteration in physiological, metabolic and molecular processes in plants. Additionally, considering the necessity of popularizing this technique, the major challenges and prospects linked to the commercialization and utilization of this technique in agricultural systems have also been discussed. © 2023 Society of Chemical Industry.

Alteration of oral bacteriome of smokeless tobacco users and their association with oral cancer.

Smokeless tobacco (SLT) is certainly one of the major risk factors associated with oral cancer. Disruption of oral microbiota-host homeostasis contributes to the progression of oral cancer. Here, we profiled SLT users' oral bacterial composition and inferred their functions by sequencing 16S rDNA V3-V4 region and PICRUSt2, respectively. Oral bacteriome of SLT users (with or without oral premalignant lesions), SLT with alcohol co-users, and non-SLT consumers were compared. Oral bacteriome is shaped primarily by SLT use and the incidence of oral premalignant lesions (OPL). A significantly increased bacterial α-diversity was monitored in SLT users with OPL compared to in SLT users without OPL and non-users, whereas ß-diversity was significantly explained by OPL status. Overrepresented genera were Prevotella, Fusobacterium, Veillonella, Haemophilus, Capnocytophaga, and Leptotrichia in SLT users having OPL. LEfSe analysis identified 16 genera as a biomarker that were differentially abundant in SLT users having OPL. The functional prediction of genes significantly increased for several metabolic pathways, more importantly, were nitrogen metabolism, nucleotide metabolism, energy metabolism, and biosynthesis/biodegradation of secondary metabolites in SLT users having OPL. Furthermore, HPV-16 and EBV, but not HPV-18, were considerably connected with the SLT users having OPL. Overall, this study provides evidence that SLT utilization and OPL development are associated with oral bacteriome dysbiosis indicating the enrichment of bacterial species known for their contribution to oral carcinogenesis. Therefore, delineating the cancer-inducing bacterial population in SLT users will facilitate the future development of microbiome-targeted therapies. KEY POINTS: • SLT consumption significantly elevates oral bacterial diversity. • Prevalent significant genera are Prevotella, Veillonella, and Haemophilus in SLT users with OPL. • SLT promotes the occurrence of the cancer-inducing bacterial population.

Characterization of physiochemical parameters & their effect on microbial content of smokeless tobacco products marketed in north India.

BACKGROUND OBJECTIVES: Smokeless tobacco (SLT) product consumption has profound public health implications for its users. The p H and moisture of SLTs determine the bioavailability of nicotine, the microbial structure dynamics and the amount of microbial conversion of tobacco alkaloids to carcinogenic tobacco-specific nitrosamines. This study aimed to characterize and compare the p H, moisture and alkaloid content of various SLT products. METHODS: Thirty-seven SLT samples including khaini , snus, moist snuff, gul , pan masala , zarda , Mainpuri kapoori and qiwam were collected from the retail market around the National Capital Region in north India and their p H, moisture, nicotine and alkaloid content were measured. The p H and total nicotine were used to calculate the amount of free nicotine, the readily absorbed form, for each product by applying the Henderson-Hasselbalch equation. RESULTS: The investigation showed that the SLTs varied drastically in their p H (5.36 to 10.27), moisture content (4.7 to 51.7%) and alkaloid content (0.82 to 35.87 mg/g). The p H and free nicotine levels of a product were found to be positively correlated, and the highest free nicotine content was reported in snus samples. Further, the moisture content was seen to impact the bacterial and fungal diversity in these samples. INTERPRETATION CONCLUSIONS: Studies to detect the presence of pathogenic microbiological genera as well as potentially toxic constituents are warranted. The use of SLTs as an alternative to cigarette smoking should be discouraged, and cessation programmes must call attention to their detrimental effects and emphasize on benefits of quitting SLT consumption.

Fungal Community Composition and Function Associated with Loose Smokeless Tobacco Products.

Smokeless tobacco products (STPs) contain several microbial communities which are responsible for the formation of carcinogens, like tobacco-specific nitrosamine (TSNAs). A majority of STPs are sold in loose/unpackaged form which can be loaded with a diverse microbial population. Here, the fungal population and mycotoxins level of three popular Indian loose STPs, Dohra, Mainpuri Kapoori (MK), and loose leaf-chewing tobacco (LCT) was examined using metagenomic sequencing of ITS1 DNA segment of the fungal genome and LC-MS/MS, respectively. We observed that Ascomycota was the most abundant phylum and Sterigmatomyces and Pichia were the predominant fungal genera in loose STPs. MK displayed the highest α-diversity being enriched with pathogenic fungi Apiotrichum, Aspergillus, Candida, Fusarium, Trichosporon, and Wallemia. Further, FUNGuild analysis revealed an abundance of saprotrophs in MK, while pathogen-saprotroph-symbiotroph were abundant in Dohra and LCT. The level of a fungal toxin (ochratoxins A) was high in the MK product. This study caution that loose STPs harbor various harmful fungi that can infect their users and deliver fungal toxins or disrupt the oral microbiome of SLT users which can contribute to several oral pathologies.

Delineating the Bacteriome of Packaged and Loose Smokeless Tobacco Products Available in North India.

Smokeless tobacco product (STP) consumption is a significant public health threat across the globe. STPs are not only a storehouse of carcinogens and toxicants but also harbor microbes that aid in the conversion of tobacco alkaloids to carcinogenic tobacco-specific nitrosamines (TSNAs), thereby posing a further threat to the health of its consumers. The present study analyzed the bacterial diversity of popular dry and loose STPs by 16S rRNA gene sequencing. This NGS-based investigation revealed four dominant phyla Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria and identified 549 genera, Prevotella, Bacteroides, and Lactobacillus constituting the core bacteriome of these STPs. The most significantly diverse bacteriome profile was displayed by the loose STP Mainpuri kapoori. The study further predicted the functional attributes of the prevalent genera by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) algorithm. Genes encoding for nitrate and nitrite reduction and transport enzymes, antibiotic resistance, multi-drug transporters and efflux pumps, secretion of endo- and exotoxin, and other pro-inflammatory molecules were identified. The loose STPs showed the highest level of nitrogen metabolism genes which can contribute to the synthesis of TSNAs. This study reveals the bacteriome of Indian domestic loose STPs that stagger behind in manufacturing and storage stringencies. Our results raise an alarm that the consumption of STPs harboring pathogenic genera can potentially lead to the onset of several oral and systemic diseases. Nevertheless, an in-depth correlation analysis of the microbial diversity of STPs and their elicit impact on consumer health is warranted. KEY POINTS: • Smokeless tobacco harbors bacteria that aid in synthesis of carcinogenic nitrosamines. • Most diverse bacteriome profile was displayed by loose smokeless tobacco products. • Pathogenic genera in these products can harm the oral and systemic health of users.

Smokeless tobacco consumption induces dysbiosis of oral mycobiome: a pilot study.

Smokeless tobacco (SLT) alters the oral microbiome of smokeless tobacco users. Dysbiosis of oral bacteriome has been determined; however, the mycobiome of SLT users has not been characterized. The oral mycobiome was assayed by amplification and sequencing of the fungal internal transcribed spacer (ITS1) region from oral swab samples of non-SLT users, SLT users (with or without oral lesions), and SLT with alcohol users. We observed that the richness and diversity of oral mycobiome were significantly decreased in SLT with oral lesions users than in non-users. The ß-diversity analysis showed significant dissimilarity of oral mycobiome between non-users and SLT with oral lesions users. Linear discriminant analysis effect size and random forest analysis of oral mycobiome affirm that the genus Pichia was typical for SLT with oral lesions users. Prevalence of the fungal genus Pichia correlates positively with Starmerella, Mortierella, Fusarium, Calonectria, and Madurella, but is negatively correlated with Pyrenochaeta, Botryosporium, and Alternaria. Further, the determination of oral mycobiome functionality showed a high abundance of pathotroph-saprotroph-symbiotroph and animal pathogen-endophyte-epiphyte-undefined saprotroph at trophic and guild levels, respectively, indicating possibly major changes in normal growth repression of types of fungi. The oral mycobiome in SLT users was identified and comprehensively analyzed for the first time. SLT intake is associated with oral mycobiome dysbiosis and such alterations of the oral mycobiome may contribute to oral carcinogenesis in SLT users. This study will provide a basis for further large-scale investigations on the potential role of the mycobiome in SLT-induced oral cancer. KEY POINTS: • SLT induces dysbiosis of the oral microbiome that can contribute to oral cancer. • Oral mycobiome diversity is noticeably reduced in SLT users having oral lesions. • Occurrence of Pichia can be used as a biomarker for SLT users having oral lesions.

Impact of smokeless tobacco-associated bacteriome in oral carcinogenesis.

Smokeless tobacco products possess a complex community of microorganisms. The microbial community ferment compounds present in the smokeless tobacco products and convert them into carcinogens like tobacco-associated nitrosamines. However, the potential of smokeless tobacco products associated bacteriome to manipulate systemic inflammation and other signaling pathways involved in the etiology of oral cancer will be a risk factor for oral cancer. Further, damage to oral epithelial cells causes a leaky oral layer that leads to increased infiltration of bacterial components like lipopolysaccharide, flagellin, and toxins, etc. The consumption of smokeless tobacco products can cause damage to the oral layer and dysbiosis of oral microbiota. Hence, the enrichment of harmful microbes due to dysbiosis in the oral cavity can produce high levels of bacterial metabolites and provoke inflammation as well as carcinogenesis. Understanding the complex and dynamic interrelation between the smokeless tobacco-linked bacteriome and host oral microbiome may help to unravel the mechanism of oral carcinogenesis stimulated by smokeless tobacco products. This review provides an insight into smokeless tobacco product-associated bacteriome and their potential in the progression of oral cancer. In the future, this will guide in the evolution of prevention and treatment strategies against smokeless tobacco products-induced oral cancer. Besides, it will assist the government organizations for better management and cessation policy building for the worldwide problem of smokeless tobacco addiction.

Global occurrence of deoxynivalenol in food commodities and exposure risk assessment in humans in the last decade: a survey.

Preventing food from fungal infestation has become a cause of great concern as food safety is of particular importance to public health globally. Recently International Agency for Research on Cancer (IARC) and the World Health Organization (WHO) in its 2016 press release has urged to take action against widespread mycotoxin contamination in developing countries. Deoxynivalenol (DON) is a group B trichothecene mycotoxin, produced by common field pathogens such as Fusarium graminearum and Fusarium culmorum, and reported to be the predominant contaminant of food commodities. At present, no detailed/systematic review regarding the global occurrence of DON in various food and grain samples is available in the literature. Considering DON's cosmopolitan behavior and toxicological manifestations, the present review summarizes the region-wise reports and surveys conducted across the globe during the last decade, on the occurrence of DON in the food commodities intended for human consumption. Studies conducted on DON metabolites either in food, urine or blood samples from humans have also been reviewed. The present review indicates that the current exposure levels of DON might pose a health risk for the consumers, especially in growing children, necessitating to take vigilant steps to guarantee food safety.

Yeast strain Debaryomyces hansenii for amelioration of arsenic stress in rice.

Arsenic (As) is a serious threat for environment and human health. Rice, the main staple crop is more prone to As uptake. Bioremediation strategies with heavy metal tolerant rhizobacteria are well known. The main objective of the study was to characterize arsenic-resistant yeast strains, capable of mitigating arsenic stress in rice. Three yeast strains identified as Debaryomyces hansenii (NBRI-Sh2.11), Candida tropicalis (NBRI-B3.4) and Candida dubliniensis (NBRI-3.5) were found to have As reductase activity. D. hansenii with higher As tolerance has As expulsion ability as compared to other two strains. Inoculation of D. hansenii showed improved detoxification through scavenging of reactive oxygen species (ROS) by the modulation of SOD and APX activity under As stress condition in rice. Modulation of defense responsive gene (NADPH, GST, GR) along with arsR and metal cation transporter are the probable mechanism of As detoxification as evident with improved membrane (electrolyte leakage) stability. Reduced grain As (~40% reduction) due to interaction with D. hansenii (NBRI-Sh2.11) further validated it's As mitigation property in rice. To the best of our knowledge D. hansenii has been reported for the first time for arsenic stress mitigation in rice with improved growth and nutrient status of the plant.

Chetomin induces apoptosis in human triple-negative breast cancer cells by promoting calcium overload and mitochondrial dysfunction.

Human triple-negative breast cancer (TNBC) is poorly diagnosed and unresponsive to conventional hormone therapy. Chetomin (CHET), a fungal metabolite synthesized by Chaetomium cochliodes, has been reported as a promising anticancer and antiangiogenic agent but the complete molecular mechanism of its anticancer potential remains to be elucidated. In our study, we explored the anti-neoplastic action of CHET on TNBC cells. Cytotoxicity studies were performed in human TNBC cells viz. MDA-MB-231 and MDA-MB-468 cells by Sulforhodamine B assay. It exhibited antiproliferative response and induced apoptosis in both the cell types. Cell cycle analysis revealed that it increases the sub G0/G1 phase cell population. Modulation of mitochondrial membrane potential, activation of caspase 3/7 and a remarkable increase in the expression of cleaved PARP and increased chromatin condensation was observed after CHET treatment in MDA-MB-231 and MDA-MB-468 cells. Additionally, an elevated level of intracellular Ca2+ played an important role in CHET mediated cell death response. Calcium overload in mitochondria led to release of cytochrome c which in turn triggered caspase-3 mediated cell death. Inhibition of calcium signalling using BAPTA-AM reduced apoptosis confirming the involvement of calcium signalling in CHET induced cell death. Chetomin also inhibited PI3K/mTOR cell survival pathway in human TNBC cells. The overall findings suggest that Chetomin inhibited the growth of human TNBC cells by caspase-dependent apoptosis and modulation of PI3K/mTOR signalling and could be used as a novel chemotherapeutic agent for the treatment of human TNBC in future.

Novel combination of salinomycin and resveratrol synergistically enhances the anti-proliferative and pro-apoptotic effects on human breast cancer cells.

Resveratrol (RES) is a natural polyphenol having anti-proliferative activity against breast cancer cells. RES in combination with other chemo modulatory agents, minimizes toxicity and increases efficacy of the treatment. Salinomycin (SAL), a monocarboxylic polyether ionophore is known for selectively targeting breast cancer stem cells. Purpose of the present study was to investigate whether RES in combination with SAL exerts synergistic anti-proliferative activity on breast cancer cells. We further evaluated the molecular mechanism behind SAL and RES mediated cell death. Cytotoxicity assay was performed to determine 50% inhibitory concentration (IC50) of SAL and RES in different human breast cancer cells (HBCCs). Drug synergism and combination index (CI) were calculated using CompuSyn software and effects of synergistic combinations (CI < 1) involving lower doses of SAL and RES were selected for further studies. This combination significantly induced apoptosis in HBCCs without affecting non tumorigenic human breast epithelial cells MCF-10A. Co-treatment enhanced apoptosis in MCF-7 cells via reactive oxygen species (ROS) mediated mitochondrial dysfunction. Oxidative stress disrupt redox homeostasis which altered antioxidant enzymes viz. CuZn Superoxide dismutase (SOD), MnSOD and catalase. Additionally, combination altered nuclear morphology, enhanced PARP cleavage and led to caspase activation. SAL and RES also synergistically modulated MAPK pathway. Study suggests that SAL and RES offer a novel combination approach for the treatment of breast cancer.

Salinomycin: A new paradigm in cancer therapy.

The primary hurdle in the treatment of cancer is acquisition of resistance by the tumor cells toward multiple drugs and selectively targeting the cancer stem cells. This problem was overcome by the chemotherapeutic property of recently discovered drug salinomycin. Exact mechanism of action of salinomycin is not yet known, but there are multiple pathways by which salinomycin inhibits tumor growth. Salinomycin decreases the expression of adenosine triphosphate-binding cassette transporter in multidrug resistance cells and interferes with Akt signaling pathway, Wnt/ß-catenin, Hedgehog, and Notch pathways of cancer progression. Salinomycin selectively targets cancer stem cells. The potential of salinomycin to eliminate both cancer stem cells and therapy-resistant cancer cells may characterize the compound as a novel and an efficient chemotherapeutic drug.

Accidental ingestion of a hypodermic needle during root canal treatment: a case report.

This atypical case report describes the accidental swallowing of a hypodermic needle by a patient during root canal treatment. The needle was safely removed by gastrointestinal endoscopy after 24 hours, but the incident emphasizes the need for rubber dam placement and proper vigilance during all endodontic and restorative procedures to prevent such events, which can be life-threatening or fatal. This case report also guides clinicians in the steps that must be followed if such an accident occurs.

Prevalence and Predictors of Risky Sexual Behavior Among Young Men in India: Evidence From National Family Health Survey.

Objective: The study examines the prevalence and factors associated with high-risk sexual behavior among sexually active young Indian men. Methods: This study used samples of 14,584 men aged 15 to 29 from the National Family Health Survey (NFHS-5), 2019-21. Results: 14% of men engaged in early sexual debut (<18 years), 68% had unprotected sex, and 4% had multiple sexual partners in the past 12 months. Age, marital status, educational attainment, occupation, wealth quintile, alcohol consumption, internet use, media exposure, and region were significant predictors of risky sexual behavior. Conclusions: We suggest a tailored approach for effective policy design considering risk factors of risky sexual behavior.

Spatial interactions modulate tumor growth and immune infiltration.

Lenia, a cellular automata framework used in artificial life, provides a natural setting to implement mathematical models of cancer incorporating features such as morphogenesis, homeostasis, motility, reproduction, growth, stimuli response, evolvability, and adaptation. Historically, agent-based models of cancer progression have been constructed with rules that govern birth, death and migration, with attempts to map local rules to emergent global growth dynamics. In contrast, Lenia provides a flexible framework for considering a spectrum of local (cell-scale) to global (tumor-scale) dynamics by defining an interaction kernel governing density-dependent growth dynamics. Lenia can recapitulate a range of cancer model classifications including local or global, deterministic or stochastic, non-spatial or spatial, single or multi-population, and off or on-lattice. Lenia is subsequently used to develop data-informed models of 1) single-population growth dynamics, 2) multi-population cell-cell competition models, and 3) cell migration or chemotaxis. Mathematical modeling provides important mechanistic insights. First, short-range interaction kernels provide a mechanism for tumor cell survival under conditions with strong Allee effects. Next, we find that asymmetric interaction tumor-immune kernels lead to poor immune response. Finally, modeling recapitulates immune-ECM interactions where patterns of collagen formation provide immune protection, indicated by an emergent inverse relationship between disease stage and immune coverage.

Spatial interactions modulate tumor growth and immune infiltration.

Direct observation of immune cell trafficking patterns and tumor-immune interactions is unlikely in human tumors with currently available technology, but computational simulations based on clinical data can provide insight to test hypotheses. It is hypothesized that patterns of collagen formation evolve as a mechanism of immune escape, but the exact nature of the interaction between immune cells and collagen is poorly understood. Spatial data quantifying the degree of collagen fiber alignment in squamous cell carcinomas indicates that late stage disease is associated with highly aligned fibers. Here, we introduce a computational modeling framework (called Lenia) to discriminate between two hypotheses: immune cell migration that moves 1) parallel or 2) perpendicular to collagen fiber orientation. The modeling recapitulates immune-ECM interactions where collagen patterns provide immune protection, leading to an emergent inverse relationship between disease stage and immune coverage. We also illustrate the capabilities of Lenia to model the evolution of tumor progression and immune predation. Lenia provides a flexible framework for considering a spectrum of local (cell-scale) to global (tumor-scale) dynamics by defining a kernel cell-cell interaction function that governs tumor growth dynamics under immune predation with immune cell migration. Mathematical modeling provides important mechanistic insights into cell interactions. Short-range interaction kernels provide a mechanism for tumor cell survival under conditions with strong Allee effects, while asymmetric tumor-immune interaction kernels lead to poor immune response. Thus, the length scale of tumor-immune interactions drives tumor growth and infiltration.

Spon1+ inflammatory monocytes promote collagen remodeling and lung cancer metastasis through lipoprotein receptor 8 signaling.

Lung cancer is the leading cause of cancer-related deaths in the world, and non-small cell lung cancer (NSCLC) is the most common subset. We previously found that infiltration of tumor inflammatory monocytes (TIMs) into lung squamous carcinoma (LUSC) tumors is associated with increased metastases and poor survival. To further understand how TIMs promote metastases, we compared RNA-Seq profiles of TIMs from several LUSC metastatic models with inflammatory monocytes (IMs) of non-tumor-bearing controls. We identified Spon1 as upregulated in TIMs and found that Spon1 expression in LUSC tumors corresponded with poor survival and enrichment of collagen extracellular matrix signatures. We observed SPON1+ TIMs mediate their effects directly through LRP8 on NSCLC cells, which resulted in TGF-ß1 activation and robust production of fibrillar collagens. Using several orthogonal approaches, we demonstrated that SPON1+ TIMs were sufficient to promote NSCLC metastases. Additionally, we found that Spon1 loss in the host, or Lrp8 loss in cancer cells, resulted in a significant decrease of both high-density collagen matrices and metastases. Finally, we confirmed the relevance of the SPON1/LRP8/TGF-ß1 axis with collagen production and survival in patients with NSCLC. Taken together, our study describes how SPON1+ TIMs promote collagen remodeling and NSCLC metastases through an LRP8/TGF-ß1 signaling axis.

Locating perpetrators of violence against women in India: An analysis of married men's characteristics associated with intimate partner violence.

Intimate Partner Violence (IPV) against married women is widely prevalent in India. Using recent data from NFHS-5, we analyzed the association between husbands' characteristics and IPV. Separate logistic regression models were developed for three distinct "husband characteristic groups" namely demographic, social and economic groups, and one final model including only statistically significant variables. IPV has been found to be significantly associated with men's age, age gap between husband and wife, men's educational level, religion, caste, region, number of daughters, wife's decision-making autonomy, men's IPV justifying attitude, alcoholism and substance abuse among men, type of work and wealth. We suggest shifting the policy gaze from women and prioritizing men's education, control on substance abuse and alcoholism among men as well as employment opportunities to tackle the violence against women.