Ionic and nano calcium to reduce cadmium and arsenic toxicity in plants: Review of mechanisms and potentials.

Contamination of agricultural soils with heavy metal(loid)s like arsenic (As) and cadmium (Cd) is an ever increasing concern for crop production, quality, and global food security. Numerous in-situ and ex-situ remediation approaches have been developed to reduce As and Cd contamination in soils. However, field-scale applications of conventional remediation techniques are limited due to the associated environmental risks, low efficacy, and large capital investments. Recently, calcium (Ca) and Ca-based nano-formulations have emerged as promising solutions with the large potential to mitigate As and Cd toxicity in soil for plants. This review provides comprehensive insights into the phytotoxic effects of As and Cd stress/toxicity and discusses the applications of Ca-based ionic and nano-agrochemicals to alleviate As and Cd toxicity in important crops such as rice, wheat, maize, and barley. Further, various molecular and physiological mechanisms induced by ionic and nano Ca to mitigate As and Cd stress/toxicity in plants are discussed. This review also critically analyzes the efficiency of these emerging Ca-based approaches, both ionic and nano-formulations, in mitigating As and Cd toxicity in comparison to conventional remediation techniques. Additionally, future perspectives and ecological concerns of the remediation approaches encompassing ionic and nano Ca have been discussed. Overall, the review provides an updated and in-depth knowledge for developing sustainable and effective strategies to address the challenges posed by As and Cd contamination in agricultural crops.

Comparative simulation of green finance-driven oil production and expulsion: Technological innovation with Expulsinator and traditional pyrolysis in near-natural conditions.

This study explores the impact of green finance and technological innovation on oil production and expulsion by comparing the Expulsinator with traditional pyrolysis methods. The Expulsinator introduces a novel approach to simulating compound production and expulsion in natural settings, utilizing hydrous decomposition in an open pass-on mode and lithostatic compression on an intact starting point disc with an undamaged mineral framework and chemical kerogen network. In contrast, traditional decomposition methods, while valuable for assessing production dynamics, are less suitable for studying primary emigration and expulsion due to sampling damage, improper pressure settings, closed-mode burning, or waterless pyrolysis. This study aims to assess the efficacy of energy production and expulsion emulation by the Expulsinator, driven by green finance initiatives, and compare it with traditional decomposition methods. Production and evacuation behaviors were evaluated using Rock Evaluation pyrolysis, HyPy, and covered small container pyrolysis (CSVP). The Expulsinator exhibited higher asphalt discharge than CSVP, attributed to increased bitumen cross-linking during traditional pyrolysis, which favors pyrobitumen formation. Variations in alkane quantities and structures were observed due to ejection impacts and production dynamics, especially delayed ejection from chromatography. Expulsinator hydrous CSVP ratios remained at 65 %, while TOC ratios exceeded 81 %. Lower gas production was observed compared to CSVP, with higher Expulsinator TOC conversion explained by the rapid removal of produced products in the open setup to prevent reformation. The Expulsinator provides valuable data on oil and gas production suitable for computational modeling tasks, highlighting the role of green finance and technological innovation in advancing sustainable energy solutions.

Synthesis of surficial-modified green biochar catalyst generated by biogas residue biochar and potential application for catalytic ozonation degradation of ciprofloxacin.

This study synthesized novel, green, and easily recoverable surface-modified economical catalysts via hydrothermal treatment (HT) successfully, utilizing biogas residue biochar (BRB), a food waste product from anaerobic fermentation, pyrolyzed at 500 °C for 50 min. Using autoclaves, a total of six solutions were prepared, each having 1 g fine-grinded BRB, surficial modified by adding glycerol (GL) (10 or 20 mL) and SDI water (70 or 60 mL), and heated in an oven at 240 °C, 180 °C, and 120 °C for 24 h. Afterward, the catalysts showed the potential for degradation of widely used emerging pollutants like ciprofloxacin. Taking advantage of catalytic surface modification, the catalytic ozonation degradation was more effective than that of a single ozonation. However, under similar conditions, catalyst amount 0.20 g, ozone dose 15 mg L-1, and ciprofloxacin 80 mg L-1, the performance of the 10 mL GL-180 °C catalyst was excellent. It showed a 92.45%-94.41% optimum removal rate in the 8-10 min interval. After five continuous cycles, the 10 mL GL-180 °C catalyst exhibited excellent stability and reusability. XPS, FT-IR, BET, XRD, and SEM before and after the reaction confirmed the successful synthesis and degradation mechanism. A possible degradation pathway was unrevealed based on a liquid chromatography-mass spectrometer (LC-MS) and scavenger test, proving the significant roles of superoxide radicals (O2•-), hydroxyl radicals (•OH), and singlet oxygen (1O2). Further, Electron paramagnetic resonance (EPR) analysis confirmed the presence of active oxygen species. Subsequently, 10 mL GL-180 °C showed promising degradation for the actual water environment, such as groundwater (73.55%) and river water (64.74%). This work provides a valuable economic strategy to convert biogas residue biochar into a low-cost catalyst for organic pollutant decomposition.

Influence of elastomeric and steel ligatures on periodontal health during fixed appliance orthodontic treatment: a systematic review and meta-analysis.

INTRODUCTION: Metallic and elastomeric ligatures are widely used in orthodontics to secure the archwire within the bracket slots, but elastomeric ligatures have traditionally been associated with increased microbial colonization, which could adversely affect periodontal health. AIM: This systematic review compares the periodontal effects of elastomeric and steel ligatures used for orthodontic fixed appliances. METHODS: Unrestricted literature search of 7 databases (MEDLINE, Scopus, Web of Science, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Virtual Health Library) up to July 2023 were performed for randomized / non-randomized clinical studies on humans comparing the two ligation methods during fixed-appliance therapy. After duplicate study selection, data extraction, and risk-of-bias assessment with the Risk of Bias (RoB) 2 or the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) tool, random-effects meta-analyses of Mean Differences (MD) or Standardized Mean Differences (SMD) and their 95% confidence intervals (CIs) were carried out, followed by assessment of certainty of existing evidence with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: A total of 11 studies (3 randomized / 8 non-randomized) with 354 patients (mean age 14.7 years and 42% male) were included. No statistically significant differences were seen for plaque index (5 studies; SMD = 0.48; 95% CI = -0.03 to 1.00; P = 0.07), gingival index (2 studies; MD = 0.01; 95% CI = -0.14 to 0.16; P = 0.89), probing pocket depth (2 studies; MD = 0; 95% CI = -0.17 to 0.16; P = 0.97), or Streptococcus mutans counts (4 studies; SMD = 0.40; 95% CI=-0.41 to 1.20; P = 0.21). Elastomeric ligatures were associated with moderately increased total bacterial load (3 studies; SMD = 0.43; 95% CI = 0.10 to 0.76; P = 0.03). Confidence in these estimates was low in all instances due to the inclusion of non-randomized studies with high risk of bias. CONCLUSIONS: Existing low quality evidence indicates that ligature method does not seem to influence the periodontal health during fixed treatment, even if elastomeric ligatures are associated with a moderate increase of bacterial load. REGISTRATION: PROSPERO (CRD42023444383).

Genome-wide characterization and functional analysis of the melon TGA gene family in disease resistance through ectopic overexpression in Arabidopsis thaliana.

TGA-binding (TGA) transcription factors, characterized by the basic region/leucine zipper motif (bZIP), have been recognized as pivotal regulators in plant growth, development, and stress responses through their binding to the as-1 element. In this study, the TGA gene families in melon, watermelon, cucumber, pumpkin, and zucchini were comprehensively characterized, encompassing analyses of gene/protein structures, phylogenetic relationships, gene duplication events, and cis-acting elements in gene promoters. Upon transient expression in Nicotiana benthamiana, the melon CmTGAs, with typical bZIP and DOG1 domains, were observed to localize within the nucleus. Biochemical investigation revealed specific interactions between CmTGA2/3/5/8/9 and CmNPR3 or CmNPR4. The CmTGA genes exhibited differential expression patterns in melon plants in response to different hormones like salicylic acid, methyl jasmonate, and ethylene, as well as a fungal pathogen, Stagonosporopsis cucurbitacearum that causes gummy stem blight in melon. The overexpression of CmTGA3, CmTGA8, and CmTGA9 in Arabidopsis plants resulted in the upregulation of AtPR1 and AtPR5 expression, thereby imparting enhanced resistance to Pseudomonas syringae pv. Tomato DC3000. In contrast, the overexpression of CmTGA7 or CmTGA9 resulted in a compromised resistance to Botrytis cinerea, coinciding with a concomitant reduction in the expression levels of AtPDF1.2 and AtMYC2 following infection with B. cinerea. These findings shed light on the important roles of specific CmTGA genes in plant immunity, suggesting that genetic manipulation of these genes could be a promising avenue for enhancing plant immune responses.

Comparison of Soft Tissue Chin Thickness in Adult Patients With Various Mandibular Divergence Patterns.

Objective This study aimed to compare the soft tissue chin (STC) thickness at different levels in patients presenting for orthodontic treatment with different vertical facial types. Materials and methods This comparative cross-sectional study was conducted at Sharif Medical & Dental College, Lahore, Pakistan, on 195 subjects. Patients presenting for orthodontic treatment, both genders, aged from 18 to 32 years, and Pakistani nationals were included. Patients with any craniofacial deformity, syndrome, cleft lip and palate, previous orthodontic or orthognathic treatment, and multiple missing teeth and prostheses in edentulous areas were excluded. Vertical facial patterns and STC thickness were recorded from pre-treatment lateral cephalograms. One-way analysis of variance (ANOVA) was applied to compare STC among various vertical facial patterns. Post-hoc analysis was done using the Tukey test. Results There were 126 females (64.62%) and 69 males (35.38%). The mean age was 21.66 ± 3.44 years. All three soft tissue chin thickness distances significantly differed among vertical facial patterns (p<0.001). Multiple comparisons show that the distance between soft and hard tissue pogonion was insignificant between low and normal angle facial heights (p=0.5). Similarly, no significant difference was observed for the distance between soft and hard tissue menton in low and normal angle subjects (p=0.4). The rest of the multiple comparisons were statistically significant (p<0.05). Conclusion The STC thickness is significantly associated with vertical facial divergence. While planning orthognathic surgery or genioplasty of the mandible, due consideration should be given to vertical divergence of the face to avoid unwanted facial changes.

Modulation of rhizosphere microbial community and metabolites by bio-functionalized nanoscale silicon oxide alleviates cadmium-induced phytotoxicity in bayberry plants.

Cadmium (Cd) is an extremely toxic heavy metal that can originate from industrial activities and accumulate in agricultural soils. This study investigates the potential of biologically synthesized silicon oxide nanoparticles (Bio-SiNPs) in alleviating Cd toxicity in bayberry plants. Bio-SiNPs were synthesized using the bacterial strain Chryseobacterium sp. RTN3 and thoroughly characterized using advanced techniques. A pot experiment results demonstrated that Cd stress substantially reduced leaves biomass, photosynthesis efficiency, antioxidant enzyme activity, and induced oxidative damage in bayberry (Myrica rubra) plants. However, Bio-SiNPs application at 200 mg kg-1 significantly enhanced plant biomass, chlorophyll content (26.4 %), net photosynthetic rate (8.6 %), antioxidant enzyme levels, and mitigated reactive oxygen species production under Cd stress. Bio-SiNPs modulated key stress-related phytohormones by increasing salicylic acid (13.2 %) and abscisic acid (13.7 %) contents in plants. Bio-SiNPs augmented Si deposition on root surfaces, preserving normal ultrastructure in leaf cells. Additionally, 16S rRNA gene sequencing demonstrated that Bio-SiNPs treatment favorably reshaped structure and abundance of specific bacterial groups (Proteobacteria, Actinobacteriota, and Acidobacteriota) in the rhizosphere. Notably, Bio-SiNPs application significantly modulated the key metabolites (phenylacetaldehyde, glycitein, maslinic acid and methylmalonic acid) under both normal and Cd stress conditions. Overall, this study highlights that bio-nanoremediation using Bio-SiNPs enhances tolerance to Cd stress in bayberry plants by beneficially modulating biochemical, microbial, and metabolic attributes.

Combining VPS34 inhibitors with STING agonists enhances type I interferon signaling and anti-tumor efficacy.

An immunosuppressive tumor microenvironment promotes tumor growth and is one of the main factors limiting the response to cancer immunotherapy. We have previously reported that inhibition of vacuolar protein sorting 34 (VPS34), a crucial lipid kinase in the autophagy/endosomal trafficking pathway, decreases tumor growth in several cancer models, increases infiltration of immune cells and sensitizes tumors to anti-programmed cell death protein 1/programmed cell death 1 ligand 1 therapy by upregulation of C-C motif chemokine 5 (CCL5) and C-X-C motif chemokine 10 (CXCL10) chemokines. The purpose of this study was to investigate the signaling mechanism leading to the VPS34-dependent chemokine increase. NanoString gene expression analysis was applied to tumors from mice treated with the VPS34 inhibitor SB02024 to identify key pathways involved in the anti-tumor response. We showed that VPS34 inhibitors increased the secretion of T-cell-recruitment chemokines in a cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes protein (STING)-dependent manner in cancer cells. Both pharmacological and small interfering RNA (siRNA)-mediated VPS34 inhibition increased cGAS/STING-mediated expression and secretion of CCL5 and CXCL10. The combination of VPS34 inhibitor and STING agonist further induced cytokine release in both human and murine cancer cells as well as monocytic or dendritic innate immune cells. Finally, the VPS34 inhibitor SB02024 sensitized B16-F10 tumor-bearing mice to STING agonist treatment and significantly improved mice survival. These results show that VPS34 inhibition augments the cGAS/STING pathway, leading to greater tumor control through immune-mediated mechanisms. We propose that pharmacological VPS34 inhibition may synergize with emerging therapies targeting the cGAS/STING pathway.

Biogenic silicon nanoparticles mitigate cadmium (Cd) toxicity in rapeseed (Brassica napus L.) by modulating the cellular oxidative stress metabolism and reducing Cd translocation.

Nano-enabled strategies have emerged as promising alternatives to resolve heavy metals (HMs) related harms in an eco-friendly manner. Here, we explored the potential of biogenic silicon nanoparticles (SiNPs) in alleviating cadmium (Cd) stress in rapeseed (Brassica napus L.) plants by modulating cellular oxidative repair mechanisms. Biogenic SiNPs of spherical shapes with size ranging between 14 nm and 35 nm were synthesized using rice straw extract and characterized through advanced characterization techniques. A greenhouse experiment results showed that SiNPs treatment at 250 mg kg-1 significantly improved growth parameters, including fresh weight (33.3 %) and dry weight (32.6 %) of rapeseed plants than Cd-treated control group. Photosynthesis and leaf gas exchange parameters were also positively influenced by SiNPs treatment, indicating enhanced photosynthetic efficiency. Additionally, SiNPs treatment at 250 mg kg-1 increased the activities of antioxidant enzymes such as superoxide dismutase (19.1 %), peroxidase (33.4 %), catalase (14.4 %), and ascorbate peroxidase (33.8 %), which may play a crucial role in ROS scavenging and reduction in Cd-induced oxidative stress. TEM analysis revealed that SiNPs treatment effectively mitigated Cd-induced damage to leaf ultrastructure, while qPCR analysis showed that SiNPs treatment changed the expressions of the antioxidant defense and stress related genes. Moreover, SiNPs treatment significantly influenced the Cd accumulation and Si contents in plants. Overall, our findings revealed that biogenic SiNPs have great potential to serve as a sustainable, eco-friendly, and non-toxic alternative for the remediation of Cd toxicity in rapeseed plants.

Salicylic acid-doped iron nano-biostimulants potentiate defense responses and suppress Fusarium wilt in watermelon.

INTRODUCTION: Chemo- and bio-genic metallic nanoparticles (NPs), as a novel nano-enabled strategy, have demonstrated a great potential in crop health management. OBJECTIVE: The current study aimed to explore the efficacy of advanced nanocomposites (NCs), integrating biogenic (bio) metallic NPs and plant immunity-regulating hormones, in crop disease control. METHODS: Iron (Fe) NPs were biosynthesized using cell-free supernatant of a Fe-resistant strains, Bacillus marisflavi ZJ-4. Further, salicylic acid-coated bio-FeNPs (SI) NCs were prepared via co-precipitation method under alkaline conditions. Both bio-FeNPs and SINCs were characterized using basic analytical techniques, including Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction analysis, and scanning/transmission electron microscopy. RESULTS: Bio-FeNPs and SINCs had variable shapes with average sizes of 72.35 nm and 65.87 nm, respectively. Under greenhouse conditions, bio-FeNPs and SINCs improved the agronomic traits of the watermelon plants, and SINCs outperformed bio-FeNPs, providing the maximum growth promotion of 32.5%. Soil-drenching with bio-FeNPs and SINCs suppressed Fusarium oxysporum f. sp. niveum-caused Fusarium wilt in watermelon, and SINCs provided better protection than bio-FeNPs, through inhibiting the fungal invasive growth within host plants. SINCs improved the antioxidative capacity and primed a systemic acquired resistance (SAR) response via activating the salicylic acid signaling pathway genes. These findings indicate that SINCs can reduce the severity of Fusarium wilt in watermelon by modulating antioxidative capacity and potentiating SAR to restrict in planta fungal invasive growth. CONCLUSION: This study provides new insights into the potential of bio-FeNPs and SINCs as biostimulants and bioprotectants for growth promotion and Fusarium wilt suppression, ensuring sustainable watermelon production.

Transcriptomic and proteomic profiling reveals toxicity and molecular action mechanisms of bioengineered chitosan­iron nanocomposites against Xanthomonas oryzae pv. oryzae.

Bacterial leaf blight (BLB) pathogen, Xanthomonas oryzae pv. oryzae (Xoo) is the most devastating bacterial pathogen, which jeopardizes the sustainable rice (Oryza sativa L.) production system. The use of antibiotics and conventional pesticides has become ineffective due to increased pathogen resistance and associated ecotoxicological concerns. Thus, the development of effective and sustainable antimicrobial agents for plant disease management is inevitable. Here, we investigated the toxicity and molecular action mechanisms of bioengineered chitosan­iron nanocomposites (BNCs) against Xoo using transcriptomic and proteomic approaches. The transcriptomic and proteomics analyses revealed molecular antibacterial mechanisms of BNCs against Xoo. Transcriptomic data revealed that various processes related to cell membrane biosynthesis, antioxidant stress, DNA damage, flagellar biosynthesis and transcriptional regulator were impaired upon BNCs exposure, which clearly showing the interaction of BNCs to Xoo pathogen. Similarly, proteomic profiling showed that BNCs treatment significantly altered the levels of functional proteins involved in the integral component of the cell membrane, catalase activity, oxidation-reduction process and metabolic process in Xoo, which is consistent with the results of the transcriptomic analysis. Overall, this study suggested that BNCs has great potential to serve as an eco-friendly, sustainable, and non-toxic alternative to traditional agrichemicals to control the BLB disease in rice.

Assessment of quality of life (QOL) in cancer patients attending oncology unit of a Teaching Hospital in Bangladesh.

BACKGROUND: The quality of life (QoL) of a cancer patient is their perception of their physical, functional, psychological, and social well-being. QoL is one of the most important factors to consider when treating someone with cancer and during follow-up. The aim of this study was to understand the state of QoL among cancer patients in Bangladesh and to determine the factors that affect it. METHODS: This cross-sectional study was conducted on 210 cancer patients who attended the oncology unit of Delta Medical College & Hospital, Dhaka during the period between 1 May 2022 and 31 August 2022. Data were collected using the Bengali version of the European Organization for Research and Treatment of Cancer (EORTC) questionnaire. RESULTS: The study reported a high number of female cancer patients (67.6%), who were married, Muslims by religion, and non-residents of Dhaka. Breast cancer was more common among women (31.43%), while lung and upper respiratory tract cancer was more prevalent among men (19.05%). The majority of the patients (86.19%) were diagnosed with cancer in the past year. The overall mean score for functional scales was higher for physical functioning (54.92) whereas it was lower for social functioning (38.89). The highest score on the symptom scale was for financial problems (63.02), while the lowest was for diarrhea (33.01). The overall QoL score of cancer patients in the study was 47.98 and it was lower for males (45.71) compared to females (49.10). CONCLUSIONS: The overall QoL was poor among Bangladeshi cancer patients compared to those in developed countries. A low QoL score was observed for social and emotional functions. Financial difficulty was the main reason behind the lower QoL score on the symptom scale.

Lower Limb Salvage For Tumours Around The Knee Using Oncological Resections And Megaprosthetic Reconstructions.

BACKGROUND: This descriptive case series documented the clinical presentation of tumours around the knee in our population and explored the outcome of lower limb salvage with oncological resections and megaprosthetic reconstructions. The variables analysed included return of knee function, disease free survival and any complications observed over a follow up period of 5-years. METHODS: The study spanned over a period of 13-years. It included adult patients of all genders who presented with tumours around the knee and underwent tumour resections followed by megaprosthetic reconstructions at our institute. RESULTS: Out of 73 patients, there were 43 (58.90%) males and 30 (41.09%) females. Their ages ranged between 16-53 years with a mean of 32.97±10.68 years. The tumours included giant cell tumours (n=41), osteosarcomas (n=24), Spindle cell sarcoma (n=5), chondrosarcoma (n=2) and Ewing's sarcoma (n=1). The average postoperative musculoskeletal tumour society (MSTS) score was 84.65%. Various complications encountered included superficial infections/ delayed wound healing among 9 (12.32%) patients, local recurrence in 6 (8.21%), deep infections among 5 (6.84%) and transient palsy of peroneal nerve in 3 (4.10%) cases. There was aseptic loosening and traumatic disruption of extensor mechanism one each (1.36%). There were 7 (9.58%) mortalities in our series. CONCLUSIONS: Giant cell tumours and osteosarcomas were the most frequent tumours observed around the knee. The tumours affected relatively younger population. Safe oncological resections of the tumours followed by megaprosthetic reconstructions provided reasonable outcome in the majority of patients.

The ß-carboline Harmine improves the therapeutic benefit of anti-PD1 in melanoma by increasing the MHC-I-dependent antigen presentation.

Harmine is a dual-specificity tyrosine-regulated kinase 1A (DYRK1A) inhibitor that displays a number of biological and pharmacological properties. Also referred to as ACB1801 molecule, we have previously reported that harmine increases the presentation of major histocompatibility complex (MHC)-I-dependent antigen on melanoma cells. Here, we show that ACB1801 upregulates the mRNA expression of several proteins of the MHC-I such as Transporter Associated with antigen Processing TAP1 and 2, Tapasin and Lmp2 (hereafter referred to as MHC-I signature) in melanoma cells. Treatment of mice bearing melanoma B16-F10 with ACB1801 inhibits the growth and weight of tumors and induces a profound modification of the tumor immune landscape. Strikingly, combining ACB1801 with anti-PD1 significantly improves its therapeutic benefit in B16-F10 melanoma-bearing mice. These results suggest that, by increasing the MHC-I, ACB1801 can be combined with anti-PD1/PD-L1 therapy to improve the survival benefit in cancer patients displaying a defect in MHC-I expression. This is further supported by data showing that i) high expression levels of TAP1, Tapasin and Lmp2 was observed in melanoma patients that respond to anti-PD1; ii) the survival is significantly improved in melanoma patients who express high MHC-I signature relative to those expressing low MHC-I signature; and iii) high expression of MHC-I signature in melanoma patients was correlated with increased expression of CD8 and NK cell markers and overexpression of proinflammatory chemokines involved in the recruitment of CD8+ T cells.

Miso: A traditional nutritious & health-endorsing fermented product.

Consumer demand for fermented foods with a well-balanced nutrient profile has been increasing owing to their ability to prevent chronic diseases as well as their functional, nutritional, and nutraceutical benefits. Among those functional foods, miso is a well-known traditional fermented food with a distinctive savory flavor and aroma that is most commonly used as a seasoning in miso soup. Among different fermented products, miso is derived from soybeans and grains as a result of the activities of Koji enzymes and beneficial microbes. Additionally, the microbial community of miso is thought to be crucial in enhancing its distinct flavor and texture as well as its nutritional properties. Despite the importance of microorganisms in the production of miso, there has been relatively little research done to characterize and describe the nutritional and medicinal potential of miso. In this review, the potential therapeutic properties, i.e., anticancer, antimicrobial, and antiobesity, of miso have been discussed comprehensively. This review envisions the production technology, its history, microbial population, nutritional properties, and the potential health benefits of miso associated with its consumption.

Pharmacological investigation of brucine anti-ulcer potential.

Gastric ulcer is one of the most common chronic gastrointestinal diseases characterized by a significant defect in the mucosal barrier. The current study has been conducted to evaluate the brucine anti-ulcer effect. Brucine has binding energy values ranging from -2.99 to -8.11 kcal/mol against chosen targets, according to in silico research. Brucine exhibits an inhibitory effect against Helicobacter pylori. In vivo findings revealed that brucine (3 mg/kg) showed effective results in healing ethanol-induced ulcer lesions of the gastric region in rats. Brucine showed an inhibitory effect against H+/K+-ATPase. Levels of glutathione, glutathione-s-transferase, and catalase were enhanced in the gastric rat tissue with the use of brucine, while a significant decrease in lipid peroxide levels was seen. Histopathological evaluation showed improvement in cellular architecture and a decrease in inflammatory indicators like cyclooxygenase, tumor necrosis factor, and nuclear factor kappa B expression, validated through immunohistochemistry, enzyme-linked immunosorbent assay, and Western blot techniques. In the reverse transcription-polymerase chain reaction, brucine decreased H+/K+-ATPase mRNA levels. This study reveals that brucine possesses stable binding affinities against selected targets. Brucine exhibits an anti-ulcer effect, mediated via anti-H. pylori, H+/K+-ATPase inhibition, and antioxidant and anti-inflammatory pathways.

SNAI1-dependent upregulation of CD73 increases extracellular adenosine release to mediate immune suppression in TNBC.

Triple-negative subtype of breast cancer (TNBC) is hallmarked by frequent disease relapse and shows highest mortality rate. Although PD-1/PD-L1 immune checkpoint blockades have recently shown promising clinical benefits, the overall response rate remains largely insufficient. Hence, alternative therapeutic approaches are warranted. Given the immunosuppressive properties of CD73-mediated adenosine release, CD73 blocking approaches are emerging as attractive strategies in cancer immunotherapy. Understanding the precise mechanism regulating the expression of CD73 is required to develop effective anti-CD73-based therapy. Our previous observations demonstrate that the transcription factors driving epithelial-to-mesenchymal transition (EMT-TF) can regulate the expression of several inhibitory immune checkpoints. Here we analyzed the role of the EMT-TF SNAI1 in the regulation of CD73 in TNBC cells. We found that doxycycline-driven SNAI1 expression in the epithelial -like TNBC cell line MDA-MB-468 results in CD73 upregulation by direct binding to the CD73 proximal promoter. SNAI1-dependent upregulation of CD73 leads to increased production and release of extracellular adenosine by TNBC cells and contributes to the enhancement of TNBC immunosuppressive properties. Our data are validated in TNBC samples by showing a positive correlation between the mRNA expression of CD73 and SNAI1. Overall, our results reveal a new CD73 regulation mechanism in TNBC that participates in TNBC-mediated immunosuppression and paves the way for developing new treatment opportunities for CD73-positive TNBC.

Exogenous calcium oxide nanoparticles alleviate cadmium toxicity by reducing Cd uptake and enhancing antioxidative capacity in barley seedlings.

Heavy metal contamination is a serious environmental issue that jeopardize global food production and safety, while cadmium (Cd) is a most widely distributed heavy metal in the earth's crust and highly toxic to organisms. The available strategies of fighting against heavy metal contamination are not commonly used due to their ineffectiveness and time- or cost-consuming. Recently, nanotechnology-based ameliorative strategies have emerged as a potential alternative to physic-chemical techniques. In the current study, we used two barley genotypes, LJZ (Cd sensitive) and Pu-9 (Cd tolerant), to study the effects of exogenous calcium oxide nanoparticles (CaO NPs) in alleviating Cd stress. Cd exposure to barley plants led to significant reduction in morph-physiological, nutrient contents, photosynthetic rate, and large accumulation of Cd in plant tissues. However, CaO NPs application significantly increased plant biomass, activities of anti-oxidative enzymes (i.e., ascorbate peroxidase, catalase, superoxide dismutase, and glutathione reductase) and the content of non-enzymatic antioxidants (ascorbate and glutathione) accompanied by great reduction of malondialdehyde (MDA) and hydrogen peroxide contents under Cd stress. Furthermore, CaO NPs increased the expression levels of genes associated with anti-oxidative enzymes. The alleviation of Cd stress by CaO NPs is more obvious in Pu-9 than LJZ. It may be suggested that CaO NPs can be used as a potential chemical to alleviate Cd uptake and toxicity of the crops planted in the Cd-contaminated soil.

Mitochondria preserve an autarkic one-carbon cycle to confer growth-independent cancer cell migration and metastasis.

Metastasis is the most common cause of death in cancer patients. Canonical drugs target mainly the proliferative capacity of cancer cells, which leaves slow-proliferating, persistent cancer cells unaffected. Metabolic determinants that contribute to growth-independent functions are still poorly understood. Here we show that antifolate treatment results in an uncoupled and autarkic mitochondrial one-carbon (1C) metabolism during cytosolic 1C metabolism impairment. Interestingly, antifolate dependent growth-arrest does not correlate with decreased migration capacity. Therefore, using methotrexate as a tool compound allows us to disentangle proliferation and migration to profile the metabolic phenotype of migrating cells. We observe that increased serine de novo synthesis (SSP) supports mitochondrial serine catabolism and inhibition of SSP using the competitive PHGDH-inhibitor BI-4916 reduces cancer cell migration. Furthermore, we show that sole inhibition of mitochondrial serine catabolism does not affect primary breast tumor growth but strongly inhibits pulmonary metastasis. We conclude that mitochondrial 1C metabolism, despite being dispensable for proliferative capacities, confers an advantage to cancer cells by supporting their motility potential.

A 32-Bit Single Quadrant Angle-Controlled Chipless Tag for Radio Frequency Identification Applications.

A 32-bit chipless RFID tag operating in the 4.5-10.9 GHz band is presented in this paper. The tag has a unique multiple-arc-type shape consisting of closely packed 0.2 mm wide arcs of different radii and lengths. The specific tag geometry provides multiple resonances in frequency domain of an RCS plot. A frequency domain coding technique has also been proposed to encode the tag's RCS signature into a 32-bit digital identification code. The tag has an overall dimension of 17.9 × 17.9 mm2, resulting in a high code density of 9.98 bits/cm2 and spectral efficiency of 5 bits/GHz. The proposed tag is built on a low loss substrate bearing a very small footprint, thereby making it extremely suitable for large-scale product identification purposes in future chipless RFID tag systems.