Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

BACKGROUND: New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with molnupiravir started within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed Covid-19 and at least one risk factor for severe Covid-19 illness. Participants in the trial were randomly assigned to receive 800 mg of molnupiravir or placebo twice daily for 5 days. The primary efficacy end point was the incidence hospitalization or death at day 29; the incidence of adverse events was the primary safety end point. A planned interim analysis was performed when 50% of 1550 participants (target enrollment) had been followed through day 29. RESULTS: A total of 1433 participants underwent randomization; 716 were assigned to receive molnupiravir and 717 to receive placebo. With the exception of an imbalance in sex, baseline characteristics were similar in the two groups. The superiority of molnupiravir was demonstrated at the interim analysis; the risk of hospitalization for any cause or death through day 29 was lower with molnupiravir (28 of 385 participants [7.3%]) than with placebo (53 of 377 [14.1%]) (difference, -6.8 percentage points; 95% confidence interval [CI], -11.3 to -2.4; P = 0.001). In the analysis of all participants who had undergone randomization, the percentage of participants who were hospitalized or died through day 29 was lower in the molnupiravir group than in the placebo group (6.8% [48 of 709] vs. 9.7% [68 of 699]; difference, -3.0 percentage points; 95% CI, -5.9 to -0.1). Results of subgroup analyses were largely consistent with these overall results; in some subgroups, such as patients with evidence of previous SARS-CoV-2 infection, those with low baseline viral load, and those with diabetes, the point estimate for the difference favored placebo. One death was reported in the molnupiravir group and 9 were reported in the placebo group through day 29. Adverse events were reported in 216 of 710 participants (30.4%) in the molnupiravir group and 231 of 701 (33.0%) in the placebo group. CONCLUSIONS: Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19. (Funded by Merck Sharp and Dohme; MOVe-OUT ClinicalTrials.gov number, NCT04575597.).

Alleviating salinity stress in canola (Brassica napus L.) through exogenous application of salicylic acid.

Canola, a vital oilseed crop, is grown globally for food and biodiesel. With the enormous demand for growing various crops, the utilization of agriculturally marginal lands is emerging as an attractive alternative, including brackish-saline transitional lands. Salinity is a major abiotic stress limiting growth and productivity of most crops, and causing food insecurity. Salicylic acid (SA), a small-molecule phenolic compound, is an essential plant defense phytohormone that promotes immunity against pathogens. Recently, several studies have reported that SA was able to improve plant resilience to withstand high salinity. For this purpose, a pot experiment was carried out to ameliorate the negative effects of sodium chloride (NaCl) on canola plants through foliar application of SA. Two canola varieties Faisal (V1) and Super (V2) were assessed for their growth performance during exposure to high salinity i.e. 0 mM NaCl (control) and 200 mM NaCl. Three levels of SA (0, 10, and 20 mM) were applied through foliar spray. The experimental design used for this study was completely randomized design (CRD) with three replicates. The salt stress reduced the shoot and root fresh weights up to 50.3% and 47% respectively. In addition, foliar chlorophyll a and b contents decreased up to 61-65%. Meanwhile, SA treatment diminished the negative effects of salinity and enhanced the shoot fresh weight (49.5%), root dry weight (70%), chl. a (36%) and chl. b (67%). Plants treated with SA showed an increased levels of both enzymatic i.e. (superoxide dismutase (27%), peroxidase (16%) and catalase (34%)) and non-enzymatic antioxidants i.e. total soluble protein (20%), total soluble sugar (17%), total phenolic (22%) flavonoids (19%), anthocyanin (23%), and endogenous ascorbic acid (23%). Application of SA also increased the levels of osmolytes i.e. glycine betaine (31%) and total free proline (24%). Salinity increased the concentration of Na+ ions and concomitantly decreased the K+ and Ca2+ absorption in canola plants. Overall, the foliar treatments of SA were quite effective in reducing the negative effects of salinity. By comparing both varieties of canola, it was observed that variety V2 (Super) grew better than variety V1 (Faisal). Interestingly, 20 mM foliar application of SA proved to be effective in ameliorating the negative effects of high salinity in canola plants.

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.

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.

Molecular characterization, spatio-temporal expression patterns of crtc2 gene and its immune roles in yellow catfish (Pelteobagrus fulvidraco).

cAMP response element binding (CREB) protein 2 (CRTC2) is a transcriptional coactivator of CREB and plays an important role in the immune system. Thus far, the physiological roles of Crtc2 in teleost are still poorly understood. In this study, the crtc2 gene was identified and characterized from yellow catfish (Pelteobagrus fulvidraco; therefore, the gene is termed as pfcrtc2), and its evolutionary and molecular characteristics as well as potential immunity-related roles were investigated. Our results showed that the open reading frame of pfcrtc2 was 2346 bp in length, encoding a protein with 781 amino acids. Gene structure analysis revealed its existence of 14 exons and 13 introns. A phylogenetic analysis proved that the tree of crtc2 was clustered into five groups, exhibiting a similar evolutionary topology with species evolution. Multiple protein sequences alignment demonstrated high conservation of the crtc2 in various vertebrates with similar structure. Syntenic and gene structural comparisons further established that crtc2 was highly conserved, implying its similar roles in diverse vertebrates. Tissue distribution pattern detected by quantitative real-time PCR showed that the pfcrtc2 gene was almost expressed in all detected tissues except for eyes, with the highest expression levels in the gonad, indicating that Crtc2 may play important roles in various tissues. In addition, pfcrtc2 was transcribed at all developmental stages in yellow catfish, showing the highest expression levels at 12 h after fertilization. Finally, the transcriptional profiles of crtc2 were significantly increased in yellow catfishes injected with Aeromonas hydrophila or Poly I:C, which shared a consistent change pattern with four immune-related genes including IL-17A, IL-10, MAPKp38, and NF-κBp65, suggesting pfCrtc2 may play critical roles in preventing both exogenous bacteria and virus invasion. In summary, our findings lay a solid foundation for further studies on the functions of pfcrtc2, and provide novel genetic loci for developing new strategies to control disease outbreak in teleost.

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.

Mettl1 knockdown alleviates cardiac I/R injury in mice by inactivating the Mettl1-CYLD-P53 positive feedback loop.

The N7-methylguanosine (m7G) methyltransferase Mettl1 has been recently implicated in cardiac repair and fibrosis. In this study we investigated the role of Mettl1 in mouse cardiomyocytes injury and the underlying mechanisms. Cardiac ischemia/reperfusion (I/R) I/R model was established in mice by ligation of the left anterior descending coronary artery (LAD) for 45 min followed by reperfusion for 24 h. We showed the mRNA and protein levels of Mettl1 were significantly upregulated in mouse I/R hearts and H2O2-treated neonatal mouse cardiomyocytes (NMCMs). Mettl1 knockdown markedly ameliorated cardiac I/R injury, evidenced by decreased infarct size, apoptosis, and improved cardiac function. Overexpression of Mettl1 triggered cardiomyocytes apoptosis in vivo and in vitro. By performing RNA sequencing combined with m7G methylated RNA sequencing in Mettl1-overexpressing mouse hearts, we revealed that Mettl1 catalyzed m7G modification of the deubiquitinase cylindromatosis (CYLD) mRNA to increase the expression of CYLD, which enhanced the stability of P53 via abrogating its ubiquitination degradation. Vice versa, P53 served as a transcriptional factor to positively regulate Mettl1 expression during I/R injury. Knockdown of CYLD mitigated cardiomyocytes apoptosis induced by Mettl1 overexpression or oxidative stress. From the available drug-targets databases and literature, we identified 4 small molecule inhibitors of m7G modification. Sinefungin, one of the Mettl1 inhibitors exerted profound protection against cardiac I/R injury in vivo and in vitro. Collectively, this study has identified Mettl1 as a key regulator of cardiomyocyte apoptosis, and targeting the Mettl1-CYLD-P53 positive feedback circuit may represent a novel therapeutic avenue for alleviating cardiac I/R injury.

Intersecting planetary health: Exploring the impacts of environmental stressors on wildlife and human health.

This comprehensive review articulates critical insights into the nexus of environmental stressors and their health impacts across diverse species, underscoring significant findings that reveal profound effects on both wildlife and human health systems. Central to our examination is the role of pollutants, climate variables, and pathogens in contributing to complex disease dynamics and physiological disruptions, with particular emphasis on immune and endocrine functions. This research brings to light emerging evidence on the severe implications of environmental pressures on a variety of taxa, including predatory mammals, raptorial birds, seabirds, fish, and humans, which are pivotal as indicators of broader ecosystem health and stability. We delve into the nuanced interplay between environmental degradation and zoonotic diseases, highlighting novel intersections that pose significant risks to biodiversity and human populations. The review critically evaluates current methodologies and advances in understanding the morphological, histopathological, and biochemical responses of these organisms to environmental stressors. We discuss the implications of our findings for conservation strategies, advocating for a more integrated approach that incorporates the dynamics of zoonoses and pollution control. This synthesis not only contributes to the academic discourse but also aims to influence policy by aligning with the Global Goals for Sustainable Development. It underscores the urgent need for sustainable interactions between humans and their environments, which are critical for preserving biodiversity and ensuring global health security. By presenting a detailed analysis of the interdependencies between environmental stressors and biological health, this review highlights significant gaps in current research and provides a foundation for future studies aimed at mitigating these pressing issues. Our study is significant as it proposes integrative and actionable strategies to address the challenges at the intersection of environmental change and public health, marking a crucial step forward in planetary health science.

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.

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.

Interaction of titanium dioxide nanoparticles with PVC-microplastics and chromium counteracts oxidative injuries in Trachyspermum ammi L. by modulating antioxidants and gene expression.

The emergence of polyvinyl chloride (PVC) microplastics (MPs) as pollutants in agricultural soils is increasingly alarming, presenting significant toxic threats to soil ecosystems. Ajwain (Trachyspermum ammi L.), a plant of significant medicinal and culinary value, is increasingly subjected to environmental stressors that threaten its growth and productivity. This situation is particularly acute given the well-documented toxicity of chromium (Cr), which has been shown to adversely affect plant biomass and escalate risks to the productivity of such economically and therapeutically important species. The present study was conducted to investigate the individual effects of different levels of PVC-MPs (0, 2, and 4 mg L-1) and Cr (0, 150, and 300 mg kg-1) on various aspects of plant growth. Specifically, we examined growth and biomass, photosynthetic pigments, gas exchange attributes, oxidative stress responses, antioxidant compound activity (both enzymatic and nonenzymatic), gene expression, sugar content, nutritional status, organic acid exudation, and Cr accumulation in different parts of Ajwain (Trachyspermum ammi L.) seedlings, which were also exposed to varying levels of titanium dioxide (TiO2) nanoparticles (NPs) (0, 25, and 50 µg mL-1). Results from the present study showed that the increasing levels of Cr and PVC-MPs in soils significantly decreased plant growth and biomass, photosynthetic pigments, gas exchange attributes, sugars, and nutritional contents from the roots and shoots of the plants. Conversely, increasing levels of Cr and PVC-MPs in the soil increased oxidative stress indicators in term of malondialdehyde, hydrogen peroxide, and electrolyte leakage, and also increased organic acid exudation pattern in the roots of T. ammi seedlings. Interestingly, the application of TiO2-NPs counteracted the toxicity of Cr and PVC-MPs in T. ammi seedlings, leading to greater growth and biomass. This protective effect is facilitated by the NPs' ability to sequester reactive oxygen species, thereby reducing oxidative stress and lowering Cr concentrations in both the roots and shoots of the plants. Our research findings indicated that the application of TiO2-NPs has been shown to enhance the resilience of T. ammi seedlings to Cr and PVC-MPs toxicity, leading to not only improved biomass but also a healthier physiological state of the plants. This was demonstrated by a more balanced exudation of organic acids, which is a critical response mechanism to metal stress.

Phytoremediation efficiency of poplar hybrid varieties with diverse genetic backgrounds in soil contaminated by multiple toxic metals (Cd, Hg, Pb, and As).

Fifteen poplar varieties were used in a field trial to investigate the phytoremediation efficiency, stress resistance, and wood property of poplar hybrid varieties with diverse genetic backgrounds under the composite pollution of heavy metals. The coefficient of variation and clone repeatability for growth traits and Cd concentration were large. The Cd accumulation of poplar varieties 107 and QHQ reached 1.9 and 1.7 mg, respectively, followed by QHB, Ti, 69, and Pa, in which Cd accumulation reached 1.3 mg. Most of the intra-specific hybrid varieties (69, QH1, SL4, T3, and ZL46) had low Cd concentrations and small biomass, resulting in weak Cd accumulation and low phytoremediation efficiency for Cd-polluted soil. By contrast, the inter-sectional and inter-specific hybrid varieties exhibited better growth performance and accumulated higher concentrations of heavy metals than the intra-specific hybrids. The bioconcentration factor and translocation factor of Hg, As, and Pb were less than 1, indicating that poplars have low phytoremediation efficiency for these heavy metals. The hybrids between section Aigeiros and Tacamahaca (QHQ and QHB) and the inter-specific hybrid 107 within section Aigeiros were more resistant to composite heavy metal stress than the other poplar varieties were partially because of their high levels of free proline that exceeded 93 µg·g-1 FW. According to the correlation analysis of the concentrations of the different heavy metals, the poplar roots absorbed different heavy metals in a cooperative manner, indicating that elite poplar varieties with superior capacity for accumulating diverse heavy metals can be bred feasibly. Compared with the intra-specific hybrid varieties, the inter-sectional (QHQ and QHB) and inter-specific (107) hybrid varieties had higher pollution remediation efficiency, larger biomass, higher cellulose content, and lower lignin content, which is beneficial for pulpwood. Therefore, breeding and extending inter-sectional (QHQ and QHB) and inter-specific hybrid varieties can improve the phytoremediation of composite pollution.

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.

Microwave seed priming and ascorbic acid assisted phytoextraction of heavy metals from surgical industry effluents through spinach.

The prevalence of inorganic pollutants in the environment, including heavy metals (HMs), necessitates a sustainable and cost-effective solution to mitigate their impacts on the environment and living organisms. The present research aimed to assess the phytoextraction capability of spinach (Spinach oleracea L.), under the combined effects of ascorbic acid (AA) and microwave (MW) irradiation amendments, cultivated using surgical processing wastewater. In a preliminary study, spinach seeds were exposed to MW radiations at 2.45 GHz for different durations (15, 30, 45, 60, and 90 seconds). Maximum germination was observed after the 30 seconds of radiation exposure. Healthy spinach seeds treated with MW radiations for 30 s were cultivated in the sand for two weeks, after which juvenile plants were transferred to a hydroponic system. Surgical industry wastewater in different concentrations (25 %, 50 %, 75 %, 100 %) and AA (10 mM) were provided to both MW-treated and untreated plants. The results revealed that MW-treatment significantly enhanced the plant growth, biomass, antioxidant enzyme activities and photosynthetic pigments, while untreated plants exhibited increased reactive oxygen species (ROS) and electrolyte leakage (EL) compared with their controls. The addition of AA to both MW-treated and untreated plants improved their antioxidative defense capacity under HMs-induced stress. MW-treated spinach plants, under AA application, demonstrated relatively higher concentrations and accumulation of HMs including lead (Pb), cadmium (Cd) and nickel (Ni). Specifically, MW-treated plants with AA amendment showed a significant increase in Pb concentration by 188 % in leaves, Cd by 98 %, and Ni by 102 % in roots. Additionally, the accumulation of Ni increased by 174 % in leaves, Cd by 168 % in roots, and Pb by 185 % in the stem of spinach plant tissues compared to MW-untreated plants. These findings suggested that combining AA with MW irradiation of seeds could be a beneficial strategy for increasing the phytoextraction of HMs from wastewater and improving overall plant health undergoing HMs stress.

Region-Controlled Framework Interface Mediated Anion Exchange Chemical Transformation to Designed Metal Phosphosulfide Heteronanostructures.

Postsynthetic chemical transformation provides a powerful platform for creating heteronanostructures (HNs) with well-defined materials and interfaces that generate synergy or enhancement. However, it remains a synthetic bottleneck for the precise construction of HNs with increased degrees of complexity and more elaborate functions in a predictable manner. Herein, we define a general transformative protocol for metal phosphosulfide HNs based on tunable hexagonal Cu1.81S frameworks with corner-, edge- and face-controlled growth of Co2P domains. The region-controlled Cu1.81S-Co2P framework interfaces can serve as "kinetic barriers" in mediating the direction and rate between P and S anion exchange reactions, thus leading to a family of morphology and phase designed Cu3P1-xSx-Co2P HNs with hollow (branched, dotted and crown), porous and core-shell architectures. This study reveals the internal transformation mechanism between metal sulfide and phosphide nanocrystals, and opens up a new way for the rational synthesis of metastable HNs that are otherwise inaccessible.

Recirculating frass from food waste bioconversion using black soldier fly larvae: Impacts on process efficiency and product quality.

Biowaste generation is increasing worldwide and inadequate disposal has strong negative impacts on food systems and ecosystems. Biodigestion of biowaste using black soldier fly (Hermetia illucens) larvae (BSFL) generates valuable by-products such as animal feed (larval biomass) and organic fertiliser (frass). However, the latter is typically unstable immediately after waste conversion and is thus unsafe for use as a fertilizer in terms of maturity. This study evaluated recirculation of frass within bioconversion of post-consumer food waste (FW) as a dietary component for BSFL to improve the quality of the subsequent frass obtained. Frass was introduced at increasing inclusion levels replacing food waste (2.5-100% on wet-weight basis) as part of the larvae's feeding substrate. Bioconversion efficiency and material reduction were significantly reduced by frass inclusion, while larval yield per experimental unit remained unchanged. When considering only the waste component in the larval diet, larval yield (dry-weight basis) ranged between 207 (0% frass inclusion) and 403 (40% frass inclusion) kg tonne FW-1, thus increasing by up to 94% at higher frass inclusion. With increasing dietary inclusion rate of frass from 0% to 100%, crude protein content of larval biomass increased by 41%, while fat content was reduced by 32%. The recirculated frass (obtained after including frass in the larval diet) had elevated concentrations of P, K, S, Na and B and around 6% lower organic matter content, demonstrating a higher degree of decomposition. Frass inclusion in the larval diet generated recirculated frass that were more stable and mature, as indicated by self-heating capacity, CO2 and NH3 volatilisation, seed germination bioassays and other parameters. It was concluded that frass recirculation improves waste bioconversion efficiency in relation to food waste unit, as well as larval biomass and frass quality, ensuring safer use as a fertilizer.

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.

Long noncoding RNA 02027 inhibits proliferation, migration and invasion of hepatocellular carcinoma via miR-625-3p/PDLIM5 pathway.

BACKGROUND: Long non-coding RNAs have been established to promote or inhibit the oncogenic and tumorigenic potential of various cancers, acting as competing endogenous RNAs (ceRNAs) for specific microRNAs. The primary objective of the study was to investigate the underlying mechanism by which the LINC02027/miR-625-3p/PDLIM5 axis affects proliferation, migration and invasion in hepatocellular carcinoma (HCC). METHODS: The differentially expressed gene was selected based on gene sequencing and bioinformation database analysis of HCC and adjacent non-tumor tissues. The expression of LINC02027 in HCC tissues and cells and its regulatory effect on the development of HCC were detected by colony formation, cell counting kit-8 assays, wound healing assays, Transwell assays and subcutaneous tumorigenesis assays in nude mice. According to the results of database prediction, quantitative real-time polymerase chain reaction and dual-luciferase reporter assay, the downstream microRNA and target gene were searched. Finally, HCC cells were transfected with lentivirus and used for cell function assays in vitro and in vivo. RESULTS: Downregulation of LINC02027 was detected in HCC tissues and cell lines and was associated with poor prognosis. The overexpression of LINC02027 suppressed the proliferation, migration and invasion of HCC cells. Mechanistically, LINC02027 inhibited epithelial-to-mesenchymal transition. As a ceRNA, LINC02027 inhibited the malignant ability of HCC by competitively binding to miR-625-3p to regulate the expression of PDLIM5. CONCLUSIONS: The LINC02027/miR-625-3p/PDLIM5 axis inhibits the development of HCC.

Cell-specific NFIA upregulation promotes epileptogenesis by TRPV4-mediated astrocyte reactivity.

BACKGROUND: The astrocytes in the central nervous system (CNS) exhibit morphological and functional diversity in brain region-specific pattern. Functional alterations of reactive astrocytes are commonly present in human temporal lobe epilepsy (TLE) cases, meanwhile the neuroinflammation mediated by reactive astrocytes may advance the development of hippocampal epilepsy in animal models. Nuclear factor I-A (NFIA) may regulate astrocyte diversity in the adult brain. However, whether NFIA endows the astrocytes with regional specificity to be involved in epileptogenesis remains elusive. METHODS: Here, we utilize an interference RNA targeting NFIA to explore the characteristics of NFIA expression and its role in astrocyte reactivity in a 4-aminopyridine (4-AP)-induced seizure model in vivo and in vitro. Combined with the employment of a HA-tagged plasmid overexpressing NFIA, we further investigate the precise mechanisms how NIFA facilitates epileptogenesis. RESULTS: 4-AP-induced NFIA upregulation in hippocampal region is astrocyte-specific, and primarily promotes detrimental actions of reactive astrocyte. In line with this phenomenon, both NFIA and vanilloid transient receptor potential 4 (TRPV4) are upregulated in hippocampal astrocytes in human samples from the TLE surgical patients and mouse samples with intraperitoneal 4-AP. NFIA directly regulates mouse astrocytic TRPV4 expression while the quantity and the functional activity of TRPV4 are required for 4-AP-induced astrocyte reactivity and release of proinflammatory cytokines in the charge of NFIA upregulation. NFIA deficiency efficiently inhibits 4-AP-induced TRPV4 upregulation, weakens astrocytic calcium activity and specific astrocyte reactivity, thereby mitigating aberrant neuronal discharges and neuronal damage, and suppressing epileptic seizure. CONCLUSIONS: Our results uncover the critical role of NFIA in astrocyte reactivity and illustrate how epileptogenic brain injury initiates cell-specific signaling pathway to dictate the astrocyte responses.

Mycorrhizal symbiosis reprograms ion fluxes and fatty acid metabolism in wild jujube during salt stress.

Chinese jujube (Ziziphus jujuba) is an important fruit tree in China, and soil salinity is the main constraint affecting jujube production. It is unclear how arbuscular mycorrhizal (AM) symbiosis supports jujube adaptation to salt stress. Herein, we performed comparative physiological, ion flux, fatty acid (FA) metabolomic, and transcriptomic analyses to examine the mechanism of AM jujube responding to salt stress. AM seedlings showed better performance during salt stress. AM symbiosis altered phytohormonal levels: indole-3-acetic acid and abscisic acid contents were significantly increased in AM roots and reduced by salt stress. Mycorrhizal colonization enhanced root H+ efflux and K+ influx, while inducing expression of plasma membrane-type ATPase 7 (ZjAHA7) and high-affinity K+ transporter 2 (ZjHAK2) in roots. High K+/Na+ homeostasis was maintained throughout salt exposure. FA content was elevated in AM leaves as well as roots, especially for palmitic acid, oleic acid, trans oleic acid, and linoleic acid, and similar effects were also observed in AM poplar (Populus. alba × Populus. glandulosa cv. 84K) and Medicago truncatula, indicating AM symbiosis elevating FA levels could be a conserved physiological effect. Gene co-expression network analyses uncovered a core gene set including 267 genes in roots associated with AM symbiosis and conserved transcriptional responses, for example, FA metabolism, phytohormone signal transduction, SNARE interaction in vesicular transport, and biotin metabolism. In contrast to widely up-regulated genes related to FA metabolism in AM roots, limited genes were affected in leaves. We propose a model of AM symbiosis-linked reprogramming of FA metabolism and provide a comprehensive insight into AM symbiosis with a woody species adaptation to salt stress.