Enriched soil amendments influenced soil fertility, herbage yield and bioactive principle of medicinal plant (Cassia angustifolia Vahl.) grown in two different soils.

High cost of chemical fertilizers and poor nutrient content in conventional organic sources (manure, compost, charcoal etc.) can be addressed through development of enriched organic amendments. However, there is a need to evaluate enriched organic amendments as a potential alternative of chemical fertilizers. Therefore, an effort was made to prepare enriched organic amendments through blending distillation waste of aromatic plant biomass (DWB) with naturally available low-grade rock phosphate (RP) and waste mica (WM). Enrich compost (ENC) was produced from DWB in a natural composting process, blended with mineral powder, whereas biochar fortified mineral (BFM) was prepared by blending biochar, derived from DWB through hydrothermal reaction, with mineral powder. The main aims of the present study were to investigate the impacts of ENC and BFM applications on soil properties, and herbage yield and quality of a medicinal herb Senna (Cassia angustifolia Vahl.). The performances of ENC and BFM at two different rates (2.5 and 5 t ha-1) were compared with the application of conventional farmyard manure (FYM, 5 t ha-1) and chemical fertilizers (CF, NPK 60-40-20 kg ha-1) in two different soils in a pot experiment. Both, ENC and EBC improved soil quality and fertility by increasing soil organic carbon, available nutrients, microbial biomass and enzyme activity. The ENC and BFM increased total herbage yields by 21 and 16.3 % compared to FYM. In both soils, the CF treatment produced the maximum dry herbage yields (32.7-37.4 g pot-1), which however were comparable to ENC (31.9-33.7 g pot-1) and BFM (30.7-35.1 g pot-1) treatments. Bioactive compound (sennoside) production in senna was significantly improved by ENC and BFM compared to CF. The present study indicates that ENC and BFM could not only help to overcome the limitation of conventional FYM, but also have the potentials to substitute costly chemical fertilizers, particularly in medicinal plant cultivation.

Inhaled particulate accumulation with age impairs immune function and architecture in human lung lymph nodes.

Older people are particularly susceptible to infectious and neoplastic diseases of the lung and it is unclear how lifelong exposure to environmental pollutants affects respiratory immune function. In an analysis of human lymph nodes (LNs) from 84 organ donors aged 11-93 years, we found a specific age-related decline in lung-associated, but not gut-associated, LN immune function linked to the accumulation of inhaled atmospheric particulate matter. Increasing densities of particulates were found in lung-associated LNs with age, but not in the corresponding gut-associated LNs. Particulates were specifically contained within CD68+CD169- macrophages, which exhibited decreased activation, phagocytic capacity, and altered cytokine production compared with non-particulate-containing macrophages. The structures of B cell follicles and lymphatic drainage were also disrupted in lung-associated LNs with particulates. Our results reveal that the cumulative effects of environmental exposure and age may compromise immune surveillance of the lung via direct effects on immune cell function and lymphoid architecture.

Biochar-microorganism interactions for organic pollutant remediation: Challenges and perspectives.

Numerous harmful chemicals are introduced every year in the environment through anthropogenic and geological activities raising global concerns of their ecotoxicological effects and decontamination strategies. Biochar technology has been recognized as an important pillar for recycling of biomass, contributing to the carbon capture and bioenergy industries, and remediation of contaminated soil, sediments and water. This paper aims to critically review the application potential of biochar with a special focus on the synergistic and antagonistic effects on contaminant-degrading microorganisms in single and mixed-contaminated systems. Owing to the high specific surface area, porous structure, and compatible surface chemistry, biochar can support the proliferation and activity of contaminant-degrading microorganisms. A combination of biochar and microorganisms to remove a variety of contaminants has gained popularity in recent years alongside traditional chemical and physical remediation technologies. The microbial compatibility of biochar can be improved by optimizing the surface parameters so that toxic pollutant release is minimized, biofilm formation is encouraged, and microbial populations are enhanced. Biocompatible biochar thus shows potential in the bioremediation of organic contaminants by harboring microbial populations, releasing contaminant-degrading enzymes, and protecting beneficial microorganisms from immediate toxicity of surrounding contaminants. This review recommends that biochar-microorganism co-deployment holds a great potential for the removal of contaminants thereby reducing the risk of organic contaminants to human and environmental health.

Revamping highly weathered soils in the tropics with biochar application: What we know and what is needed.

Fast weathering of parent materials and rapid mineralization of organic matter because of prevalent climatic conditions, and subsequent development of acidity and loss/exhaustion of nutrient elements due to intensive agricultural practices have resulted in the degradation of soil fertility and productivity in the vast tropical areas of the world. There is an urgent need for rejuvenation of weathered tropical soils to improve crop productivity and sustainability. For this purpose, biochar has been found to be more effective than other organic soil amendments due to biochar's stability in soil, and thus can extend the benefits over long duration. This review synthesizes information concerning the present status of biochar application in highly weathered tropical soils highlighting promising application strategies for improving resource use efficiency in terms of economic feasibility. In this respect, biochar has been found to improve crop productivity and soil quality consistently through liming and fertilization effects in low pH and infertile soils under low-input conditions typical of weathered tropical soils. This paper identifies several advance strategies that can maximize the effectiveness of biochar application in weathered tropical soils. However, strategies for the reduction of costs of biochar production and application to increase the material's use efficiency need future development. At the same time, policy decision by linking economic benefits with social and environmental issues is necessary for successful implementation of biochar technology in weathered tropical soils. This review recommends that advanced biochar strategies hold potential for sustaining soil quality and agricultural productivity in tropical soils.

The Role of 18F-FDG PET/CT in Predicting the Neoadjuvant Treatment Response in Patients with Locally Advanced Breast Cancer.

Purpose: Patients with locally advanced breast cancer (LABC) should be treated with neoadjuvant chemotherapy (NAC). Pathological complete response (pCR) is related to better disease-free survival (DFS). The best strategy for assessing the efficacy of NAC has not been established yet, but several studies have shown that 18F-FDG PET/CT is a potential imaging tool for assessing pCR. The aim of this study is to investigate the merits of 18F-FDG PET/CT imaging in predicting pCR in both axillary and breast tissue and to establish a threshold maximum standard uptake value (SUVmax) for predicting the response after completion of NAC. Methods: A total of 186 LABC patients, treated with an NAC regimen according to tumor subtype, were retrospectively analyzed in this study. All patients underwent 18F-FDG PET/CT imaging before and after completion of NAC. PET parameters were measured in the most FDG avid breast tissue and axillary lymph nodes. We analyzed the correlation between the tumor SUVmax of the PET/CT response and the pCR after surgery. DFS was also evaluated with respect to pCR. Results: Higher pCR rates were significantly associated with a higher tumor grade, an initial Ki-67 ≥20% (p = 0.03 and p = 0.003, respectively), a triple-negative subtype (32.9%), and a human epidermal growth factor receptor 2 (HER-2)-positive subtype (24.7%) (p < 0.001). There was a significant correlation between the pCR and a complete response in 18F-FDG PET/CT (p < 0.001). The overall sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 18F-FDG PET/CT to determine the pCR after NAC were 100%, 72.2%, 85%, 75.2%, and 100%, respectively. We demonstrated a 1.1 cutoff SUVmax for breast tumors after NAC (OR: 3.94, 95% CI: 1.14-5.05, p = 0.004), the 18F-FDG PET/CT response to NAC (OR: 0.50, 95% CI: 0.25-0.99, p = 0.003), and the molecular subtype of breast tumors (OR: 0.58, 95% CI: 0.38-0.88, p = 0.011). Conclusion: Our results confirm that 18F-FDG PET/CT is a useful method for predicting the NAC response in LABC.

SARS-CoV-2 infection generates tissue-localized immunological memory in humans.

Adaptive immune responses to SARS-CoV-2 infection have been extensively characterized in blood; however, most functions of protective immunity must be accomplished in tissues. Here, we report from examination of SARS-CoV-2 seropositive organ donors (ages 10 to 74) that CD4+ T, CD8+ T, and B cell memory generated in response to infection is present in the bone marrow, spleen, lung, and multiple lymph nodes (LNs) for up to 6 months after infection. Lungs and lung-associated LNs were the most prevalent sites for SARS-CoV-2­specific memory T and B cells with significant correlations between circulating and tissue-resident memory T and B cells in all sites. We further identified SARS-CoV-2­specific germinal centers in the lung-associated LNs up to 6 months after infection. SARS-CoV-2­specific follicular helper T cells were also abundant in lung-associated LNs and lungs. Together, the results indicate local tissue coordination of cellular and humoral immune memory against SARS-CoV-2 for site-specific protection against future infectious challenges.

Tissue-specific immunity for a changing world.

Our immune system has evolved to protect us from pathogens and maintain homeostasis through localization in diverse tissue sites throughout the body. Immune responses are orchestrated by T cells, which direct pathogen clearance at the infection site and establish tissue-resident memory T cells (TRMs) for protection immunity. Here, we discuss how tissue immune responses are influenced by various stressors (e.g., metabolic, environmental, aging) that are rapidly changing due to climate fluctuations and globalization. We propose potential strategies for targeting tissue immunity to mitigate future pathogenic and environmental challenges and areas of investigation that can elucidate mechanisms for adapting and restoring homeostasis.

Valorization of Java citronella (Cymbopogon winterianus Jowitt) distillation waste as a potential source of phenolics/antioxidant: influence of extraction solvents.

Solid residues obtained after essential oil extraction from Cymbopogon winterianus Jowitt (Java citronella) was explored as a potential source of phenolics/antioxidant. Both the non-distilled plant materials and their solid residues were extracted with Soxhlet extraction method using solvents of various polarity viz. petroleum ether, chloroform, ethyl acetate, acetone, ethanol, methanol, water and various combination of (50% and 75%) of methanol, ethanol, and acetone in water. Different antioxidant assays like 2,2-diphenyl-1- picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), superoxide anion (SO) radical scavenging assay, ferric-reducing antioxidant power (FRAP) and iron chelating ability along with total phenol (TPC) and flavonoid content (TFC) was measured to evaluate the extract. Compared to distilled materials, the non-distilled plant materials had significantly higher TPC/TFC content and also exhibited higher antioxidant activities. 50% aqueous methanol showed the highest extractive yield, whereas 75% aqueous methanol exhibited the highest TPC and TFC content. The 50% or 75% aqueous methanolic extract also exhibited the highest DPPH, ABTS and SO scavenging activity and ferric-reducing antioxidant power activity. However, ethyl acetate and 75% aqueous acetone extract of non-distilled and distilled plant materials, respectively showed the highest iron chelating activity. The half maximal effective concentration (IC50 = µg/mL) for DPPH, ABTS, SO and metal chelating ability in non-distilled plant extract ranged from 64-387, 92-761, 285-870, and 164-924, respectively, and corresponding value of distilled materials ranged from 144-865, 239-792, 361-833 and 374-867, respectively. The EC50 (µg/mL) for FRAP assay ranged from 118-840 and 151-952 for non-distilled and distilled materials, respectively. The findings of this study indicate the potential of these by-products as a natural antioxidants source.

Environmentally safe release of plant available potassium and micronutrients from organically amended rock mineral powder.

The staggering production of rock dusts and quarry by-products of mining activities poses an immense environmental burden that warrants research for value-added recycling of these rock mineral powders (RMP). In this study, an incubation experiment was conducted to determine potassium (K) and micronutrients (Zn, Cu, Fe and Mn) release from a quarry RMP to support plant nutrition. Four different size fractions of the RMP were incubated with organic amendments (cow dung and legume straw) under controlled conditions for 90 days. Samples were collected at different intervals (7, 15, 30, 45, 60 and 90 days) for the analysis of available K and micronutrients in the mineral-OM mixtures and leachates. There was a significant (p <0.05) increase in pH of leachates from the mineral-OM mixtures. The K release was significantly higher from the finer size fraction of RMP. About 18.7% Zn added as RMP was released during the incubation period. Zn release increased from 4.7 to 23.2% as the particle size of RMP decreased. Similarly, Cu release from RMP increased from 2.9 to 21.6%, with a decrease in the particle size. Fe and Mn recovery from RMP recorded 11.2 and 6.6%, respectively. Combined application of OM and RMP showed significantly higher nutrient release than other treatments. This study indicates that effective blending of RMP with organic amendments could be a potential source of K and micronutrients in agriculture without posing a risk of toxic element contamination to the soil.

Repurposing distillation waste biomass and low-value mineral resources through biochar-mineral-complex for sustainable production of high-value medicinal plants and soil quality improvement.

High cost of synthetic fertilizers and their hazardous effects catapult the exploration of alternative nutrient formulations and soil amendments. This study aimed to synthesize a novel biochar-mineral-complex (BMC), and evaluate its nutrient supplying and soil improvement performances. In a hydrothermal reaction, the BMC was prepared using a biochar derived from distillation waste of Lemongrass (Cymbopogon flexuosus) and farmyard manure, for the first time via fortification with low-grade rock phosphate and waste mica. The BMC showed improved physico-chemical properties and nutrient availability than the pristine biochar. When applied to a deeply weathered acidic soil, the BMC significantly (P < 0.05) improved the herbage and bioactive compound (sennoside) yields of a medicinal plant (senna; Cassia angustifolia Vahl.) compared to the pristine biochar, farmyard manure, vermicompost, and chemical fertilizers. The BMC also improved the soil quality by increasing nutrient and carbon contents, and microbial activities. Soil quality improvement facilitated greater nutrient uptake in senna plants under BMC compared to the pristine biochar, and conventional organic and chemical fertilizer treatments. This study thus encourages the development of BMC formulations not only to overcome the limitation of sole biochar application to soils, but also to phaseout chemical fertilizers in agriculture. Moreover, BMC could bestow resilience and sustainability to crop production via value-added recycling of waste biomass and low-grade mineral resources.

Identification of a nerve-associated, lung-resident interstitial macrophage subset with distinct localization and immunoregulatory properties.

Tissue-resident macrophages are a diverse population of cells that perform specialized functions including sustaining tissue homeostasis and tissue surveillance. Here, we report an interstitial subset of CD169+ lung-resident macrophages that are transcriptionally and developmentally distinct from alveolar macrophages (AMs). They are primarily localized around the airways and are found in close proximity to the sympathetic nerves in the bronchovascular bundle. These nerve- and airway-associated macrophages (NAMs) are tissue resident, yolk sac derived, self-renewing, and do not require CCR2+ monocytes for development or maintenance. Unlike AMs, the development of NAMs requires CSF1 but not GM-CSF. Bulk population and single-cell transcriptome analysis indicated that NAMs are distinct from other lung-resident macrophage subsets and highly express immunoregulatory genes under steady-state and inflammatory conditions. NAMs proliferated robustly after influenza infection and activation with the TLR3 ligand poly(I:C), and in their absence, the inflammatory response was augmented, resulting in excessive production of inflammatory cytokines and innate immune cell infiltration. Overall, our study provides insights into a distinct subset of airway-associated pulmonary macrophages that function to maintain immune and tissue homeostasis.

Prognostic Significance of Metastatic Lymph Node Ratio in Patients with pN3 Gastric Cancer Who Underwent Curative Gastrectomy.

BACKGROUND: Lymph node involvement is an important prognostic factor in patients with gastric cancer. The aim of this study was to determine the prognostic significance of metastatic lymph node ratio (MLNR) and compare it to the number of lymph node metastasis in pN3 gastric cancer. METHODS: We retrospectively analyzed 207 patients with pN3 gastric cancer who had undergone radical gastrectomy. Prognostic factors and MLNR were evaluated by univariate and multivariate analysis. RESULTS: An MLNR of 0.75 was found to be the best cut-off value to determine the prognosis of patients with pN3 gastric cancer (p = 0.001). The MLNR was significantly higher in patients with large-sized and undifferentiated tumors, vascular, lymphatic and perineural invasion, and total gastrectomy. In multivariate analysis, MLNR (p = 0.041), tumor differentiation (p = 0.046), and vascular invasion (p = 0.012) were found to be independent prognostic factors for disease-free survival, while both MLNR (p < 0.001) and pN stage (p = 0.002) were independent prognostic indicators, as was tumor size, for overall survival. There was significant difference with respect to the recurrence patterns between MLNR groups. Lymph node and peritoneal recurrences were significantly higher in patients with MLNR > 0.75 compared to the MLNR < 0.75 group (p < 0.05). However, recurrence patterns were similar between pN3a and pN3b. CONCLUSION: Our results showed that MLNR was a useful indicator to determine the prognosis and recurrence patterns of patients with radically resected gastric cancer. Moreover, MLNR is a beneficial and reliable technique for evaluating lymph node metastasis.

CD169+ macrophages orchestrate innate immune responses by regulating bacterial localization in the spleen.

The spleen is an important site for generating protective immune responses against pathogens. After infection, immune cells undergo rapid reorganization to initiate and maintain localized inflammatory responses; however, the mechanisms governing this spatial and temporal cellular reorganization remain unclear. We show that the strategic position of splenic marginal zone CD169+ macrophages is vital for rapid initiation of antibacterial responses. In addition to controlling initial bacterial growth, CD169+ macrophages orchestrate a second phase of innate protection by mediating the transport of bacteria to splenic T cell zones. This compartmentalization of bacteria within the spleen was essential for driving the reorganization of innate immune cells into hierarchical clusters and for local interferon-γ production near sites of bacterial replication foci. Our results show that both phases of the antimicrobial innate immune response were dependent on CD169+ macrophages, and, in their absence, the series of events needed for pathogen clearance and subsequent survival of the host was disrupted. Our study provides insight into how lymphoid organ structure and function are related at a fundamental level.

MRF-ANN: a machine learning approach for automated ER scoring of breast cancer immunohistochemical images.

Molecular pathology, especially immunohistochemistry, plays an important role in evaluating hormone receptor status along with diagnosis of breast cancer. Time-consumption and inter-/intraobserver variability are major hindrances for evaluating the receptor score. In view of this, the paper proposes an automated Allred Scoring methodology for estrogen receptor (ER). White balancing is used to normalize the colour image taking into consideration colour variation during staining in different labs. Markov random field model with expectation-maximization optimization is employed to segment the ER cells. The proposed segmentation methodology is found to have F-measure 0.95. Artificial neural network is subsequently used to obtain intensity-based score for ER cells, from pixel colour intensity features. Simultaneously, proportion score - percentage of ER positive cells is computed via cell counting. The final ER score is computed by adding intensity and proportion scores - a standard Allred scoring system followed by pathologists. The classification accuracy for classification of cells by classifier in terms of F-measure is 0.9626. The problem of subjective interobserver ability is addressed by quantifying ER score from two expert pathologist and proposed methodology. The intraclass correlation achieved is greater than 0.90. The study has potential advantage of assisting pathologist in decision making over manual procedure and could evolve as a part of automated decision support system with other receptor scoring/analysis procedure.

Pregnane X Receptor Regulates Pathogen-Induced Inflammation and Host Defense against an Intracellular Bacterial Infection through Toll-like Receptor 4.

The nuclear pregnane X receptor (PXR) plays a central role in regulating xenobiotic metabolism. We now report a novel role for PXR as a critical negative regulator of innate immunity after infection. Pxr(-/-) mice exhibited remarkably elevated pro-inflammatory cytokine and chemokine production following infection with Listeria monocytogenes (Lm). Despite the more robust innate immune response, Pxr(-/-) mice were highly susceptible to Lm infection. Surprisingly, disruption of the Toll-like receptor 4 (TLR4) but not TLR2 signaling restored the inflammation to normal levels and the ability to clear Lm in Pxr(-/-) mice. Mechanistically, the heightened inflammation in Pxr(-/-) mice resulted in the death of inflammatory monocytes that led to the enhanced susceptibility to Lm infection. These data demonstrated that PXR regulated pathogen-induced inflammation and host defense against Lm infection through modulating the TLR4 pathway. In summary, we discovered an apical role for PXR in regulating innate immunity. In addition, we uncovered a remarkable negative impact of the TLR4 pathway in controlling the quality of the inflammatory response and host defense against a gram-positive bacterial infection.

Validation of a QuEChERS-based gas chromatographic method for analysis of pesticide residues in Cassia angustifolia (senna).

A simple multi-residue method based on modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) approach was established for the determination of 17 organochlorine (OC), 15 organophosphorous (OP) and 7 synthetic pyrethroid (SP) pesticides in an economically important medicinal plant of India, Senna (Cassia angustifolia), by gas chromatography coupled to electron capture and flame thermionic detectors (GC/ECD/FTD) and confirmation of residues was done on gas chromatograph coupled with mass spectrometry (GC-MS). The developed method was validated by testing the following parameters: linearity, limit of detection (LOD), limit of quantification (LOQ), matrix effect, accuracy-precision and measurement uncertainty; the validation study clearly demonstrated the suitability of the method for its intended application. All pesticides showed good linearity in the range 0.01-1.0 µg mL(-1) for OCs and OPs and 0.05-2.5 µg mL(-1) for SPs with correlation coefficients higher than 0.98. The method gave good recoveries for most of the pesticides (70-120%) with intra-day and inter-day precision < 20% in most of the cases. The limits of detection varied from 0.003 to 0.03 mg kg(-1), and the LOQs were determined as 0.01-0.049 mg kg(-1). The expanded uncertainties were <30%, which was distinctively less than a maximum default value of ±50%. The proposed method was successfully applied to determine pesticide residues in 12 commercial market samples obtained from different locations in India.

Border Patrol Gone Awry: Lung NKT Cell Activation by Francisella tularensis Exacerbates Tularemia-Like Disease.

The respiratory mucosa is a major site for pathogen invasion and, hence, a site requiring constant immune surveillance. The type I, semi-invariant natural killer T (NKT) cells are enriched within the lung vasculature. Despite optimal positioning, the role of NKT cells in respiratory infectious diseases remains poorly understood. Hence, we assessed their function in a murine model of pulmonary tularemia--because tularemia is a sepsis-like proinflammatory disease and NKT cells are known to control the cellular and humoral responses underlying sepsis. Here we show for the first time that respiratory infection with Francisella tularensis live vaccine strain resulted in rapid accumulation of NKT cells within the lung interstitium. Activated NKT cells produced interferon-γ and promoted both local and systemic proinflammatory responses. Consistent with these results, NKT cell-deficient mice showed reduced inflammatory cytokine and chemokine response yet they survived the infection better than their wild type counterparts. Strikingly, NKT cell-deficient mice had increased lymphocytic infiltration in the lungs that organized into tertiary lymphoid structures resembling induced bronchus-associated lymphoid tissue (iBALT) at the peak of infection. Thus, NKT cell activation by F. tularensis infection hampers iBALT formation and promotes a systemic proinflammatory response, which exacerbates severe pulmonary tularemia-like disease in mice.

Catalytic pyrolysis of waste furniture sawdust for bio-oil production.

In this study, the catalytic pyrolysis of waste furniture sawdust in the presence of ZSM-5, H-Y and MCM-41 (10 wt % of the biomass sample) was carried out in order to increase the quality of the liquid product at the various pyrolysis temperatures of 400, 450, 500 and 550(o)C. In the non-catalytic work, the maximum oil yield was obtained as 42% at 500(o)C in a fixed-bed reactor system. In the catalytic work, the maximum oil yield was decreased to 37.48, 30.04 and 29.23% in the presence of ZSM-5, H-Y and MCM-41, respectively. The obtained pyrolysis oils were analyzed by various spectroscopic and chromatographic techniques. It was determined that the use of a catalyst decreased acids and increased valuable organics found in the bio-oil. The removal of oxygen from bio-oil was confirmed with the results of the elemental analysis and gas chromatography-mass spectrometry.

NK cells gain higher IFN-γ competence during terminal differentiation.

NK cells are the main cells of the innate immune system that produce IFN-γ, and they express this cytokine at early stages of maturation in response to cytokine stimulation. Conversely, acquisition of IFN-γ-competence in CD4(+) T helper cells requires a differentiation process from naïve toward type 1 (Th1) cells, which is associated with epigenetic remodeling at the IFNG locus. In the present study, we show that the ability of NK cells to produce IFN-γ in response to activating receptor (actR) engagement is gradually acquired during terminal differentiation and is accompanied by progressively higher NF-κB activation in response to actR triggering. Moreover, during the differentiation process NK cells gradually display increasing expression of IFNG and TBX21 (encoding T-bet) transcripts and demethylation at the IFNG promoter. This study provides new insights in the molecular mechanisms underlying NK-cell ability to express IFN-γ upon actR engagement. Thus, we propose that in order to efficiently produce IFN-γ in response to infected or transformed cells, NK cells gain Th1-like features, such as higher IFN-γ competence and epigenetic remodeling of the IFNG promoter, during their terminal differentiation.