Phyto-treatment of tannery industry effluents under combined application of citric acid and chromium-reducing bacterial strain through Lemna minor L.: A lab scale study.

Contamination of agricultural soils with heavy metals (HMs) poses a significant environmental threat, especially because industrial discharges often irrigate agricultural lands. A prominent source of HM(s) pollution occurs from tannery effluents containing high concentrations of chromium (Cr) in both Cr3+ and Cr6+ forms along with other toxic materials. Cr is known for its carcinogenic and mutagenic properties in biological systems. Microbe-assisted phytoremediation has emerged as a promising and environmentally friendly approach for detoxifying Cr-contaminated environments. This study aimed to evaluate the performance of citric acid (CA) and a Cr-reducing bacterial strain (Staphylococcus aureus) on the phytoextraction potential of Lemna minor within a Constructed Wetland System treated with tannery wastewater. Various combinations of tannery wastewater (0, 50, and 100 %), CA (0, 5 and 10 mM), and microbial inoculants were applied to the test plants. The mitigative effects of Staphylococcus aureus strain K1 were examined in combination with different concentrations of CA (0, 5, 10 mM). Data on growth and yield attributes highlighted the beneficial effects of bacterial inoculation and CA in ameliorating Cr toxicity in L. minor, as evidenced by increased foliar chlorophyll and carotenoid contents, enhanced antioxidant enzyme activities (SOD, POD, APX, CAT), and improved nutrient uptake. Specifically, CA application resulted in an enhancement of Cr ranging from 12% to 15% and 23%-31% in concentration, and 134%-141% and 322%-337% in Cr accumulation, respectively. When combined with the S. aureus inoculation treatment, CA application (5 and 10 mM) further increased the concentration and accumulation of Cr in L. minor. The enhancement in Cr ranged from 12% to 23% and 27%-41% in concentration, 68%-75%, and 179%-185% in accumulation, respectively. These results demonstrated that L. minor is an effective choice for environmentally friendly Cr remediation due to its continued ability to grow in polluted wastewater. This study suggested that microbial-assisted phytoextraction combined with chelating agents such as CA could be a practical and effective approach for remediating tannery effluents.

Ameliorating effects of natural herbal supplements against water-borne induced toxicity of heavy metals on Nile tilapia, (Oreochromis niloticus).

The efficacy of herbal supplements in mitigating heavy metals (HMs) toxicity was investigated using a widely grown fish, the Nile tilapia (Oreochromis niloticus). The experiment was conducted over two phases: during the stress phase, the experimental fishes were exposed to sub-lethal concentrations of HMs, including lead, cadmium, zinc, and copper for 15 days; following which during the feeding phase, herbal supplements were given for 70 days to ameliorate their effects. Seven groups were established: the control negative group (CON-ve), control positive group (CON+ve, without any treatment), and five groups with supplementation of 1% turmeric (TUR), cinnamon (CIN), ginger (GIN), garlic (GAR), and their mixture (MIX), respectively. A total of 315 fishes were distributed evenly in experimental tanks (15 fishes per tank, in triplicates). The results revealed that exposure to HMs led to significant (p < 0.05) alterations in all the tested parameters, i.e., liver damage and growth reduction. The herbal supplements, especially the MIX groups, ameliorated the harmful effects of HMs and restored fish growth, digestibility, carcass composition, and liver health. In conclusion, the study demonstrated that the herbal supplements were effective in reducing the HMs-linked toxicity in Nile tilapia. Future studies pertaining to the mechanisms facilitated by the various herbal bioactive substances-linked tolerance to HMs in fishes are warranted.

Assessing anticancer, antidiabetic, and antioxidant capacities in green-synthesized zinc oxide nanoparticles and solvent-based plant extracts.

Cancer and diabetes represent significant challenges in the field of biomedicine, with major and global impacts on public health. Acacia nilotica, commonly called 'gum arabic tree,' is recognized for its unique biomedical properties. The current study aimed to investigate the pharmacological potential of A. nilotica-based zinc-oxide nanoparticles (ZnO-NPs) in comparison to the ethanol and methanol-based extracts against cancer, diabetes, and oxidative stress. Green synthesis of ZnO-NPs was performed using barks of Acacia nilotica. Different techniques for the characterization of ZnO-NPs, including UV-Visible spectroscopy, Scanning Electron Microscopy, Fourier Transmission Infrared (FT-IR) spectroscopy, and X-ray Diffraction (XRD), were utilized. The morphological analysis of ZnO-NPs revealed that the fine NPs have mean particle sizes of 15 ± 1.5 nm. For the solvent based-extraction, leaves and barks were utilized and dissolved into ethanol and methanol for further processing. The MTT assay revealed that the optimum concentration of ZnO-NPs to inhibit the proliferation of liver cancer cell line HepG2 was 100 µg/mL where 67.0 % inhibition was observed; and both ethanol- and methanol-based extracts showed optimum inhibition at 100 µg/mL. The DPPH assay further demonstrated that 250 µg/mL of ZnO-NPs and 1000 µg/mL of both ethanol- and methanol-based extracts, as the optimum concentration for antioxidant activity (with 73.1 %, 68.9 % and 68.2 % inhibition respectively). The α-Glucosidase inhibition assay revealed that 250 µg/mL of ZnO-NPs and 10 µg/mL of both ethanol- and methanol-based extracts as the optimum concentration for antidiabetic activity (with 95 %, 93.7 % and 93.4 % inhibition respectively). The study provided interesting insights into the efficacy and reliability of ZnO-NPs for potential pharmacological application. Further research should be focused on examining specific pathways and the safety of ZnO-NPs in comparison to solvent-based extracts.

RING finger protein 5 protects against acute myocardial infarction by inhibiting ASK1.

BACKGROUND: Myocardial infarction (MI) is a major disease with high morbidity and mortality worldwide. However, existing treatments are far from satisfactory, making the exploration of potent molecular targets more imperative. The E3 ubiquitin ligase RING finger protein 5 (RNF5) has been previously reported to be involved in several diseases by regulating ubiquitination-mediated protein degradation. Nevertheless, few reports have focused on its function in cardiovascular diseases, including MI. METHODS: In this study, we established RNF5 knockout mice through precise CRISPR-mediated genome editing and utilized left anterior descending coronary artery ligation in 9-11-week-old male C57BL/6 mice. Subsequently, serum biochemical analysis and histopathological examination of heart tissues were performed. Furthermore, we engineered adenoviruses for modulating RNF5 expression and subjected neonatal rat cardiomyocytes to oxygen-glucose deprivation (OGD) to mimic ischemic conditions, demonstrating the impact of RNF5 manipulation on cellular viability. Gene and protein expression analysis provided insights into the molecular mechanisms. Statistical methods were rigorously employed to assess the significance of experimental findings. RESULTS: We found RNF5 was downregulated in infarcted heart tissue of mice and NRCMs subjected to OGD treatment. RNF5 knockout in mice resulted in exacerbated heart dysfunction, more severe inflammatory responses, and increased apoptosis after MI surgery. In vitro, RNF5 knockdown exacerbated the OGD-induced decline in cell activity, increased apoptosis, while RNF5 overexpression had the opposite effect. Mechanistically, it was proven that the kinase cascade initiated by apoptosis signal-regulating kinase 1 (ASK1) activation was closely regulated by RNF5 and mediated RNF5's protective function during MI. CONCLUSIONS: We demonstrated the protective effect of RNF5 on myocardial infarction and its function was dependent on inhibiting the activation of ASK1, which adds a new regulatory component to the myocardial infarction associated network and promises to enable new therapeutic strategy.

Effects of 6-methoxybenzoxazolinone (6-MBOA) on animals: state of knowledge and open questions.

6-methoxybenzoxazolinone (6-MBOA) is a secondary plant metabolite predominantly found in monocotyledonous plants, especially Gramineae. In damaged tissue, 2-ß-D-glucopyranosyloxy-4-hydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA-Glc) is hydrolyzed to DIMBOA, which spontaneously decomposes into 6-MBOA. It is commonly detected in plants consumed by voles and livestock and can also be present in cereal-based products. Discovered in 1955, this compound is renowned for its ability to trigger animal reproduction. However, there is a lack of research on its functional and mechanistic properties, leaving much of their potential unexplored. This review aimed to comprehensively summarize the effects of 6-MBOA on animal reproduction and human health, as well as its defensive role against herbivores. Studies have shown that 6-MBOA effectively inhibits the digestion, development, growth, and reproduction of insects. 6-MBOA may act as a partial agonist of melatonin and exert a regulatory role in mammalian reproduction, resulting in either promoting or inhibiting effects. 6-MBOA has been theorized to possess anti-tumor, anti-AIDS, anti-anxiety, and weight-loss effects in humans. However, insufficient attention has been paid to its defense properties against mammalian herbivores, and the mechanisms underlying its effects on mammalian reproduction remain unclear. In addition, research on its impact on human health is still in its preliminary stages. The review emphasizes the need for further systematic and comprehensive research on 6-MBOA to fully understand its diverse functions. Elucidating the effects of 6-MBOA on animal reproduction, adaptation, and human health would advance our understanding of plant-herbivore coevolution and the influence of environmental factors on animal population dynamics. Furthermore, this knowledge could potentially promote its application in human health and animal husbandry.

Evaluating the phytotoxicological effects of bulk and nano forms of zinc oxide on cellular respiration-related indices and differential gene expression in Hordeum vulgare L.

The increasing use of nanoparticles is driving the growth of research on their effects on living organisms. However, studies on the effects of nanoparticles on cellular respiration are still limited. The remodeling of cellular-respiration-related indices in plants induced by zinc oxide nanoparticles (nnZnO) and its bulk form (blZnO) was investigated for the first time. For this purpose, barley (Hordeum vulgare L.) seedlings were grown hydroponically for one week with the addition of test compounds at concentrations of 0, 0.3, 2, and 10 mg mL-1. The results showed that a low concentration (0.3 mg mL-1) of blZnO did not cause significant changes in the respiration efficiency, ATP content, and total reactive oxygen species (ROS) content in leaf tissues. Moreover, a dose of 0.3 mg mL-1 nnZnO increased respiration efficiency in both leaves (17 %) and roots (38 %). Under the influence of blZnO and nnZnO at medium (2 mg mL-1) and high (10 mg mL-1) concentrations, a dose-dependent decrease in respiration efficiency from 28 % to 87 % was observed. Moreover, the negative effect was greater under the influence of nnZnO. The gene transcription of the subunits of the mitochondria electron transport chain (ETC) changed mainly only under the influence of nnZnO in high concentration. Expression of the ATPase subunit gene, atp1, increased slightly (by 36 %) in leaf tissue under the influence of medium and high concentrations of test compounds, whereas in the root tissues, the atp1 mRNA level decreased significantly (1.6-2.9 times) in all treatments. A dramatic decrease (1.5-2.4 times) in ATP content was also detected in the roots. Against the background of overexpression of the AOX1d1 gene, an isoform of alternative oxidase (AOX), the total ROS content in leaves decreased (with the exception of 10 mg mL-1 nnZnO). However, in the roots, where the pressure of the stress factor is higher, there was a significant increase in ROS levels, with a maximum six-fold increase under 10 mg mL-1 nnZnO. A significant decrease in transcript levels of the pentose phosphate pathway and glycolytic enzymes was also shown in the root tissues compared to leaves. Thus, the disruption of oxidative phosphorylation leads to a decrease in ATP synthesis and an increase in ROS production; concomitantly reducing the efficiency of cellular respiration.

Harnessing plant extracts for eco-friendly synthesis of iron nanoparticle (Fe-NPs): Characterization and their potential applications for ameliorating environmental pollutants.

Iron-nanoparticles (Fe-NPs) are increasingly been utilized in environmental applications due to their efficacy and strong catalytic activities. The novelty of nanoparticle science had attracted many researchers and especially for their green synthesis, which can effectively reuse biological resources during the polymerization reactions. Thus, the synthesis of Fe-NPs utilizing plant extracts could be considered as the eco-friendly, simple, rapid, energy-efficient, sustainable, and cost-effective. The green synthesis route can be recognized as a practical, valuable, and economically effective alternative for large-scale production. During the production process, some biomolecules present in the extracts undergo metal salts reduction, which can serve as both a capping and reducing mechanism, enhancing the reactivity and stability of green-synthesized Fe-NPs. The diversity of species provided a wide range of potential sources for green synthesis of Fe-NPs. With improved understanding of the specific biomolecules involved in the bioreduction and stabilization processes, it will become easier to identify and utilize new, potential plant materials for Fe-NPs synthesis. Newly synthesized Fe-NPs require different characterization techniques such as transmission electron microscope, ultraviolet-visible spectrophotometry, and X-ray absorption fine structure, etc, for the determination of size, composition, and structure. This review described and assessed the recent advancements in understanding green-synthesized Fe-NPs derived from plant-based material. Detailed information on various plant materials suitable of yielding valuable biomolecules with potential diverse applications in environmental safety. Additionally, this review examined the characterization techniques employed to analyze Fe-NPs, their stability, accumulation, mobility, and fate in the environment. Holistically, the review assessed the applications of Fe-NPs in remediating wastewaters, organic residues, and inorganic contaminants. The toxicity of Fe-NPs was also addressed; emphasizing the need to refine the synthesis of green Fe-NPs to ensure safety and environmental friendliness. Moving forward, the future challenges and opportunities associated with the green synthesis of Fe-NPs would motivate novel research about nanoparticles in new directions.

Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial.

BACKGROUND: The autologous anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M has been approved for the treatment of relapsed and refractory multiple myeloma in many countries across the world under the name ciltacabtagene autoleucel. LEGEND-2 was the first-in-human trial of LCAR-B38M and yielded deep and durable therapeutic responses. Here, we reported the outcomes in LEGEND-2 after a minimal 5-year follow-up. METHODS: Participants received an average dose of 0.5 × 106 cells/kg LCAR-B38M in split or single unfractionated infusions after cyclophosphamide-based lymphodepletion therapy. Investigator-assessed response, survival, safety and pharmacokinetics were evaluated. RESULTS: Seventy-four participants enrolled and had a median follow-up of 65.4 months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 21.0% and 49.1%, with progressive flattening of the survival curves over time. Patients with complete response (CR) had longer PFS and OS, with 5-year rates of 28.4% and 65.7%, respectively. Twelve patients (16.2%) remained relapse-free irrespective of baseline high-risk cytogenetic abnormality and all had normal humoral immunity reconstituted. An ongoing CR closely correlated with several prognostic baseline indices including favorable performance status, immunoglobulin G subtype, and absence of extramedullary disease, as well as a combination cyclophosphamide and fludarabine preconditioning strategy. Sixty-two (83.8%) suffered progressive disease (PD) and/or death; however, 61.1% of PD patients could well respond to subsequent therapies, among which, the proteasome inhibitor-based regimens benefited the most. Concerning the safety, hematologic and hepatic function recovery were not significantly different between non-PD and PD/Death groups. A low rate of second primary malignancy (5.4%) and no severe virus infection were observed. The patients who tested positive for COVID-19 merely presented self-limiting symptoms. In addition, a sustainable CAR T population of one case with persistent remission was delineated, which was enriched with indolently proliferative and lowly cytotoxic CD4/CD8 double-negative functional T lymphocytes. CONCLUSIONS: These data, representing the longest follow-up of BCMA-redirected CAR T-cell therapy to date, demonstrate long-term remission and survival with LCAR-B38M for advanced myeloma. TRIAL REGISTRATION: LEGEND-2 was registered under the trial numbers NCT03090659, ChiCTRONH-17012285.

Residual efficiency of iron-nanoparticles and different iron sources on growth, and antioxidants in maize plants under salts stress: life cycle study.

Exogenous application of iron (Fe) may alleviate salinity stress in plants growing in saline soils. This comparative study evaluated the comparative residual effects of iron nanoparticles (FNp) with two other Fe sources including iron-sulphate (FS) and iron-chelate (FC) on maize (Zea mays L.) crop grown under salt stress. All three Fe sources were applied at the rate of 15 and 25 mg/kg of soil before the sowing of wheat (an earlier crop; following the sequence of crop rotation) and no further Fe amendments were added later for the maize crop. Results revealed that FNp application at 25 mg/kg (FNp-2) substantially increased maize height, root length, root dry weight, shoot dry weight, and grain weightby 80.7%, 111.1%, 45.7%, 59.5%, and 77.2% respectively, as compared to the normal controls; and 62.6%, 81.3%, 65.1%, 78%, and 61.2% as compared to salt-stressed controls, respectively. The FNp-2 treatment gave higher activities of antioxidant enzymes, such as superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase compared to salt stressed control (50.6%, 51%, 48.5%, and 49.2%, respectively). The FNp-2 treatment also produced more photosynthetic pigments and better physiological markers: higher chlorophyll a contents by 49.9%, chlorophyll b contents by 67.2%, carotenoids by 62.5%, total chlorophyll contents by 50.3%, membrane stability index by 59.1%, leaf water relative contents by 60.3% as compared to salt stressed control. The highest Fe and Zn concentrations in maize roots, shoots, and grains were observed in FNp treatment as compared to salts stressed control. Higher application rates of Fe from all the sources also delivered better outcomes in alleviating salinity stress in maize compared to their respective low application rates. The study demonstrated that FNp application alleviated salinity stress, increased nutrient uptake and enhanced the yield of maize grown on saline soils.

Synergistic interplay between melatonin and hydrogen sulfide enhances cadmium-induced oxidative stress resistance in stock (Matthiola incana L.).

Ornamental crops particularly cut flowers are considered sensitive to heavy metals (HMs) induced oxidative stress condition. Melatonin (MLT) is a versatile phytohormone with the ability to mitigate abiotic stresses induced oxidative stress in plants. Similarly, signaling molecules such as hydrogen sulfide (H2S) have emerged as potential options for resolving HMs related problems in plants. The mechanisms underlying the combined application of MLT and H2S are not yet explored. Therefore, we evaluated the ability of individual and combined applications of MLT (100 µM) and H2S in the form of sodium hydrosulfide (NaHS), a donor of H2S, (1.5 mM) to alleviate cadmium (Cd) stress (50 mg L-1) in stock (Matthiola incana L.) plants by measuring various morpho-physiological and biochemical characteristics. The results depicted that Cd-stress inhibited growth, photosynthesis and induced Cd-associated oxidative stress as depicted by excessive ROS accumulation. Combined application of MLT and H2S efficiently recovered all these attributes. Furthermore, Cd stress-induced oxidative stress markers including electrolyte leakage, malondialdehyde, and hydrogen peroxide are partially reversed in Cd-stressed plants by MLT and H2S application. This might be attributed to MLT or H2S induced antioxidant plant defense activities, which effectively reduce the severity of oxidative stress indicators. Overall, MLT and H2S supplementation, favorably regulated Cd tolerance in stock; yet, the combined use had a greater effect on Cd tolerance than the independent application.

An Evidence-Based Medical Review on Promoting Gastrointestinal Function Recovery After Colorectal Cancer Surgery.

Objective: The objective of this study was to search for, evaluate, and summarize data related to a faster postoperative recovery in patients with colorectal cancer (CRC) based on literature from China as well as internationally. This will serve as an evidence-based foundation for the clinical implementation of enhanced postoperative recovery of gastrointestinal function in patients with CRC. Methods: Based on the hierarchical "6S" evidence model, we conducted a systematic search of computerized decision-support systems, guideline websites, as well as domestic and international databases for evidence, guidelines, expert consensus statements, clinical decision-making, best practices, evidence summaries, and systematic reviews of interventions focusing on accelerating gastrointestinal function rehabilitation after CRC surgery. The time limit for the search was from the date of creation of the database to January 2023. Two researchers evaluated the quality of the literature that was included, and we extracted data and summarized the evidence from those publications that fulfilled the quality criteria. Results: The review included a total of 21 publications, comprising 6 guidelines, 6 systematic reviews, 3 expert consensus statements, 4 randomized controlled trials, and 2 evidence summaries. We summarized 51 best evidence findings across five areas: organizational management, preoperative risk assessment, education, intraoperative monitoring, and postoperative management. Conclusion: There is a wide variety and wealth of information available on interventions to promote enhanced postoperative recovery of gastrointestinal function in patients with CRC. The use of evidence is discussed, keeping in mind the practical situation in China.

Biochar impacts on carbon dioxide, methane emission, and cadmium accumulation in rice from Cd-contaminated soils; A meta-analysis.

Climate change and cadmium (Cd) contamination pose severe threats to rice production and food security. Biochar (BC) has emerged as a promising soil amendment for mitigating these challenges. To investigate the BC effects on paddy soil upon GHG emissions, Cd bioavailability, and its accumulation, a meta-analysis of published data from 2000 to 2023 was performed. Data Manager 5.3 and GetData plot Digitizer software were used to obtain and process the data for selected parameters. Our results showed a significant increase of 18% in soil pH with sewage sludge BC application, while 9% increase in soil organic carbon (SOC) using bamboo chips BC. There was a significant reduction in soil bulk density (8%), but no significant effects were observed for soil porosity, except for wheat straw BC which reduced the soil porosity by 6%. Sewage sludge and bamboo chips BC significantly reduced carbon dioxide (CO2) by 7-8% while municipal biowaste reduced methane (CH4) emissions by 2%. In the case of heavy metals, sunflower seedshells-derived materials and rice husk BC significantly reduced the bioavailable Cd in paddy soils by 24% and 12%, respectively. Cd uptake by rice roots was lowered considerably by the addition of kitchen waste (22%), peanut hulls (21%), and corn cob (15%) based BC. Similarly, cotton sticks, kitchen waste, peanut hulls, and rice husk BC restricted Cd translocation from rice roots to shoots by 22%, 27%, 20%, and 19%, respectively, while sawdust and rice husk-based BC were effective for reducing Cd accumulation in rice grains by 25% and 13%. Regarding rice yield, cotton sticks-based BC significantly increased the yield by 37% in Cd-contaminated paddy soil. The meta-analysis demonstrated that BC is an effective and multi-pronged strategy for sustainable and resilient rice cultivation by lowering greenhouse gas emissions and Cd accumulation while improving yields under the increasing threat of climate change.

Construction of disulfidptosis-based immune response prediction model with artificial intelligence and validation of the pivotal grouping oncogene c-MET in regulating T cell exhaustion.

Background: Given the lack of research on disulfidptosis, our study aimed to dissect its role in pan-cancer and explore the crosstalk between disulfidptosis and cancer immunity. Methods: Based on TCGA, ICGC, CGGA, GSE30219, GSE31210, GSE37745, GSE50081, GSE22138, GSE41613, univariate Cox regression, LASSO regression, and multivariate Cox regression were used to construct the rough gene signature based on disulfidptosis for each type of cancer. SsGSEA and Cibersort, followed by correlation analysis, were harnessed to explore the linkage between disulfidptosis and cancer immunity. Weighted correlation network analysis (WGCNA) and Machine learning were utilized to make a refined prognosis model for pan-cancer. In particular, a customized, enhanced prognosis model was made for glioma. The siRNA transfection, FACS, ELISA, etc., were employed to validate the function of c-MET. Results: The expression comparison of the disulfidptosis-related genes (DRGs) between tumor and nontumor tissues implied a significant difference in most cancers. The correlation between disulfidptosis and immune cell infiltration, including T cell exhaustion (Tex), was evident, especially in glioma. The 7-gene signature was constructed as the rough model for the glioma prognosis. A pan-cancer suitable DSP clustering was made and validated to predict the prognosis. Furthermore, two DSP groups were defined by machine learning to predict the survival and immune therapy response in glioma, which was validated in CGGA. PD-L1 and other immune pathways were highly enriched in the core blue gene module from WGCNA. Among them, c-MET was validated as a tumor driver gene and JAK3-STAT3-PD-L1/PD1 regulator in glioma and T cells. Specifically, the down-regulation of c-MET decreased the proportion of PD1+ CD8+ T cells. Conclusion: To summarize, we dissected the roles of DRGs in the prognosis and their relationship with immunity in pan-cancer. A general prognosis model based on machine learning was constructed for pan-cancer and validated by external datasets with a consistent result. In particular, a survival-predicting model was made specifically for patients with glioma to predict its survival and immune response to ICIs. C-MET was screened and validated for its tumor driver gene and immune regulation function (inducing t-cell exhaustion) in glioma.

Peroxiredoxin 3 regulates breast cancer progression via ERK-mediated MMP-1 expression.

Peroxiredoxin 3 (PRDX3), a mitochondrial hydrogen peroxide scavenger, is known to be upregulated during tumorigenesis and cancer progression. In this study, we provide evidence for the first time that PRDX3 could regulate cellular signaling pathways associated with Matrix Metalloproteinase-1 (MMP-1) expression and activity in breast cancer progression. We show that shRNA-mediated gene silencing of PRDX3 inhibits cell migration and invasion in two triple-negative breast cancer cell lines. Reciprocal experiments show that PRDX3 overexpression promotes invasion and migration of the cancer cells, processes which are important in the metastatic cascade. Notably, this phenomenon may be attributed to the activation of MMP-1, which is observed to be upregulated by PRDX3 in the breast cancer cells. Moreover, immunohistochemical staining of breast cancer tissues revealed a positive correlation between PRDX3 and MMP-1 expression in both epithelial and stromal parts of the tissues. Further pathway reporter array and luciferase assay demonstrated that activation of ERK signaling is responsible for the transcriptional activation of MMP-1 in PRDX3-overexpressed cells. These findings suggest that PRDX3 could mediate cancer spread via ERK-mediated activation of MMP-1. Targeted inhibition of ERK signaling may be able to inhibit tumor metastasis in triple-negative breast cancer.

Identification of MGMT promoter methylation as a specific lipid metabolism biomarker, reveals the feasibility of atorvastatin application in glioblastoma.

BACKGROUND: Glioblastoma is one of the deadliest tumors, and limited improvement in managing glioblastoma has been achieved in the past decades. The unmethylated promoter area of 6-O-Methylguanine-DNA Methyltransferase (MGMT) is a significant biomarker for recognizing a subset of glioblastoma that is resistant to chemotherapy. Here we identified MGMT methylation can also work as a specific biomarker to classify the lipid metabolism patterns between methylated and unmethylated glioblastoma and verify the potential novel therapeutic strategy for unmethylated MGMT glioblastoma. METHODS: Liquid Chromatograph Mass Spectrometer has been applied for non-targeted metabolome and targeted lipidomic profiling to explore the metabolism pattern correlated with MGMT promoter methylation. Transcriptome has been performed to explore the biological differences and the potential mechanism of lipid metabolism in glioblastoma samples. In vivo and ex vivo assays were performed to verify the anti-tumor activity of atorvastatin in the administration of glioblastoma. RESULTS: Multi-omics assay has described a significant difference in lipid metabolism between MGMT methylated and unmethylated glioblastoma. Longer and unsaturated fatty acyls were found enriched in MGMT-UM tumors. Lipid droplets have been revealed remarkably decreased in MGMT unmethylated glioblastoma. In vivo and ex vivo assays revealed that atorvastatin and also together with temozolomide showed significant anti-tumor activity, and atorvastatin alone was able to achieve better survival and living conditions for tumor-hosting mice. CONCLUSIONS: MGMT promoter methylation status might be a well-performed biomarker of lipid metabolism in glioblastoma. The current study can be the basis of further mechanism studies and implementation of clinical trials, and the results provide preclinical evidence of atorvastatin administration in glioblastoma, especially for MGMT unmethylated tumors.

Mobile Health System for Meeting Health Information Needs in Patients With Head and Neck Cancer Undergoing Radiotherapy: Development and Feasibility Study.

Patients with head and neck cancer undergoing radiotherapy encounter physical and psychosocial challenges, indicating unmet needs. Mobile health technology can potentially support patients. This single-armed feasibility study included 30 patients with head and neck cancer undergoing radiotherapy. Patients were asked to use the Health Enjoy System, a mobile health support system that provides a disease-related resource for 1 week. We assessed the usability of the system and its limited efficacy in meeting patients' health information needs. The result showed that the system was well received by patients and effectively met their health information needs. They also reported free comments on the system's content, backend maintenance, and user engagement. This study supplies a foundation for further research to explore the potential benefits of the Health Enjoy System in supporting patients with head and neck cancer.

Effects of agro based organic amendments on growth and cadmium uptake in wheat and rice crops irrigated with raw city effluents: Three years field study.

Cadmium (Cd) accumulates in the vegetative tissues of rice and wheat crops, posing a serious threat in the food chain. A long-term field experiment was conducted to investigate the effects of rice husk biochar (RHB), farm manure (FM), press mud (PrM), and poultry manure (PM) on the growth, yield, and economics of wheat and rice crops grown with sewage water. The results showed that RHB increased wheat plant height (27%, 66%, 70%), spike-length (33%, 99%, 56%), straw yield (21%, 51%, 49%), and grain yield (42%, 63%, 65%) in year-1, year-2, and year-3, than respective controls. For rice crop, RHB showed the maximum increase in plant height (64%, 92%, 96%), spike length (55%, 95%, 90%), straw yield (34%, 53%, 55%), and grain yield (46%, 66%, 69%) each year (2019-2021), compared to their respective controls. The Cd immobilization was increased by the application of RHB while other treatments followed FM > PrM > PM > control in each year of wheat and rice crops. For year-1, benefit-cost ratio remained maximum with the application of FM while for the 2nd and 3rd years in sequence, RHB proved more economical than other treatments and consistently produced wheat and rice with lower Cd concentration than FM, PrM, and PM in grains. This long-term experiment suggested that the application of organic amendments consistently increased biomass of rice and wheat and decreased the Cd concentration in tissues. The RHB remained more effective compared with FM, PrM, and PM in terms of yield, low Cd accumulation and economics of rice and wheat crops.

Effect of an artificial intelligence-assisted system on endoscopic diagnosis of superficial oesophageal squamous cell carcinoma and precancerous lesions: a multicentre, tandem, double-blind, randomised controlled trial.

BACKGROUND: Despite the usefulness of white light endoscopy (WLE) and non-magnified narrow-band imaging (NBI) for screening for superficial oesophageal squamous cell carcinoma and precancerous lesions, these lesions might be missed due to their subtle features and interpretation variations among endoscopists. Our team has developed an artificial intelligence (AI) system to detect superficial oesophageal squamous cell carcinoma and precancerous lesions using WLE and non-magnified NBI. We aimed to evaluate the auxiliary diagnostic performance of the AI system in a real clinical setting. METHODS: We did a multicentre, tandem, double-blind, randomised controlled trial at 12 hospitals in China. Eligible patients were aged 18 years or older and underwent sedated upper gastrointestinal endoscopy for screening, investigation of gastrointestinal symptoms, or surveillance. Patients were randomly assigned (1:1) to either the AI-first group or the routine-first group using a computerised random number generator. Patients, pathologists, and statistical analysts were masked to group assignment, whereas endoscopists and research assistants were not. The same endoscopist at each centre did tandem upper gastrointestinal endoscopy for each eligible patient on the same day. In the AI-first group, the endoscopist did the first examination with the assistance of the AI system and the second examination without it. In the routine-first group, the order of examinations was reversed. The primary outcome was the miss rate of superficial oesophageal squamous cell carcinoma and precancerous lesions, calculated on a per-lesion and per-patient basis. All analyses were done on a per-protocol basis. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2100052116) and is completed. FINDINGS: Between Oct 19, 2021, and June 8, 2022, 5934 patients were randomly assigned to the AI-first group and 5912 to the routine-first group, of whom 5865 and 5850 were eligible for analysis. Per-lesion miss rates were 1·7% (2/118; 95% CI 0·0-4·0) in the AI-first group versus 6·7% (6/90; 1·5-11·8) in the routine-first group (risk ratio 0·25, 95% CI 0·06-1·08; p=0·079). Per-patient miss rates were 1·9% (2/106; 0·0-4·5) in AI-first group versus 5·1% (4/79; 0·2-9·9) in the routine-first group (0·37, 0·08-1·71; p=0·40). Bleeding after biopsy of oesophageal lesions was observed in 13 (0·2%) patients in the AI-first group and 11 (0·2%) patients in the routine-first group. No serious adverse events were reported by patients in either group. INTERPRETATION: The observed effect of AI-assisted endoscopy on the per-lesion and per-patient miss rates of superficial oesophageal squamous cell carcinoma and precancerous lesions under WLE and non-magnified NBI was consistent with substantial benefit through to a neutral or small negative effect. The effectiveness and cost-benefit of this AI system in real-world clinical settings remain to be further assessed. FUNDING: National Natural Science Foundation of China, 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University, and Chengdu Science and Technology Project. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Comparative Transcriptome Analysis Identifies Desmoglein-3 as a Potential Oncogene in Oral Cancer Cells.

The role of desmoglein-3 (DSG3) in oncogenesis is unclear. This study aimed to uncover molecular mechanisms through comparative transcriptome analysis in oral cancer cells, defining potential key genes and associated biological processes related to DSG3 expression. Four mRNA libraries of oral squamous carcinoma H413 cell lines were sequenced, and 599 candidate genes exhibited differential expression between DSG3-overexpressing and matched control lines, with 12 genes highly significantly differentially expressed, including 9 upregulated and 3 downregulated. Genes with known implications in cancer, such as MMP-13, KRT84, OLFM4, GJA1, AMOT and ADAMTS1, were strongly linked to DSG3 overexpression. Gene ontology analysis indicated that the DSG3-associated candidate gene products participate in crucial cellular processes such as junction assembly, focal adhesion, extracellular matrix formation, intermediate filament organisation and keratinocyte differentiation. Validation of RNA-Seq was performed through RT-qPCR, Western blotting and immunofluorescence analyses. Furthermore, using transmission electron microscopy, we meticulously examined desmosome morphology and revealed a slightly immature desmosome structure in DSG3-overexpressing cells compared to controls. No changes in desmosome frequency and diameter were observed between the two conditions. This study underscores intricate and multifaceted alterations associated with DSG3 in oral squamous carcinoma cells, implying a potential oncogenic role of this gene in biological processes that enable cell communication, motility and survival.