Neurotoxic effects of triclosan in adolescent mice: Pyruvate kinase M2 dimer regulated signal transducer and activator of transcription 3 phosphorylation mediated microglia activation and neuroinflammation.

Triclosan (TCS), a commonly used antibacterial agent, is associated with various harmful effects on mammalian neurodevelopment, particularly when exposed prenatally. This study investigated the impact of long-term exposure to TCS on the prefrontal cortex development in adolescent mice. We evaluated the motor ability, motor coordination, and anxiety behavior of mice using open field tests (OFT) and elevated cross maze tests (EPM). An increase in movement distance, number of passes through the central area, and open arm retention time was observed in mice treated with TCS. Hematoxylin eosin staining and Nissl staining also showed significant adverse reactions in the brain tissue of TCS-exposed group. TCS induced microglia activation and increased inflammatory factors expression in the prefrontal cortex. TCS also increased the expression of pyruvate kinase M2 (PKM2), thereby elevating the levels of PKM2 dimer, which entered the nucleus. Treatment with TEPP46 (PKM2 dimer nuclear translocation inhibitor) blocked the expression of inflammatory factors induced by TCS. TCS induced the phosphorylation of nuclear signal transducer and activator of transcription 3 (STAT3) in vivo and in vitro, upregulating the levels of inflammatory cytokines. The results also demonstrated the binding of PKM2 to STAT3, which promoted STAT3 phosphorylation at the Tyr705 site, thereby regulating the expression of inflammatory factors. These findings highlight the role of PKM2-regulated STAT3 phosphorylation in TCS-induced behavioral disorders in adolescents and propose a reliable treatment target for TCS.

Study on Static Mechanical Properties and Numerical Simulation of Coral Aggregate Seawater Shotcrete with Reasonable Mix Proportion.

This study aims to explore the static mechanical characteristics of coral aggregate seawater shotcrete (CASS) using an appropriate mix proportion. The orthogonal experiments consisting of four-factor and three-level were conducted to explore an optimal mix proportion of CASS. On a macro-scale, quasi-static compression and splitting tests of CASS with optimal mix proportion at various curing ages employed a combination of acoustic emission (AE) and digital image correlation (DIC) techniques were carried out using an electro-hydraulic servo-controlled test machine. A comparative analysis of static mechanical properties at different curing ages was conducted between the CASS and ordinary aggregate seawater shotcrete (OASS). On a micro-scale, the numerical specimens based on particle flow code (PFC) were subjected to multi-level microcracks division for quantitive analysis of the failure mechanism of specimens. The results show that the optimal mix proportion of CASS consists of 700 kg/m3 of cementitious materials content, a water-binder ratio of 0.45, a sand ratio of 60%, and a dosage of 8% for the accelerator amount. The tensile failure is the primary failure mechanism under uniaxial compression and Brazilian splitting, and the specimens will be closer to the brittle material with increased curing age. The Brazilian splitting failure caused by the arc-shaped main crack initiates from the loading points and propagates along the loading line to the center. Compared with OASS, the CASS has an approximately equal early and low later strength mainly because of the minerals' filling or unfilling effect on coral pores. The rate of increase in CASS is swifter during the initial strength phase and decelerates during the subsequent stages of strength development. The failure in CASS is experienced primarily within the cement mortar and bonding surface between the cement mortar and aggregate.

Effects of warming on rice production and metabolism process associated with greenhouse gas emissions.

Evaluating the impact of global warming on rice production and greenhouse gas (GHG) emissions is critical for ensuring food security and mitigating the consequences of climate change. Nonetheless, the impacts of warming on crop production, GHG emissions, and microbial mechanisms in the single-cropping rice systems remain unclear. Here, a two-year field experiment was conducted to explore the effects of warming (increased by 2.7-3.0 °C on average) in the rice growing season on crop production and functional microorganisms associated with GHG emissions. Results showed that warming resulted in significant reduction (p < 0.01) in the aboveground biomass and grain yield as well as in grain weight, the number of spikelets per panicle, and the seed-setting rate. However, it caused a significant increase (p < 0.01) in the number of panicles by 15.6 % and 34.9 %, respectively. Furthermore, warming significantly increased (p < 0.01) seasonal methane (CH4) emissions but reduced nitrous oxide (N2O) emissions, particularly in 2022.The relative abundance of genes associated with CH4 metabolism and nitrogen metabolism was increased by 40.7 % and 32.7 %, respectively, in response to warming. Moreover, warming had a positive impact on the abundance of genes related to CH4 production and oxidation processes but did not affect the denitrification processes associated with N2O production. These results showed that warming decreased rice yield and biomass in the single cropping rice system but increased CH4 emissions and global warming potential. Taken together, to address the increasing food demand of a growing population and mitigate the impacts of global warming, it is imperative to duce GHG emissions and enhance crop yields.

Enhanced TfR1 Recognition of Myocardial Injury after Acute Myocardial Infarction with Cardiac Fibrosis via Pre-Degrading Excess Fibrotic Collagen.

The fibrosis process after myocardial infarction (MI) results in a decline in cardiac function due to fibrotic collagen deposition and contrast agents' metabolic disorders, posing a significant challenge to conventional imaging strategies in making heart damage clear in the fibrosis microenvironment. To address this issue, we developed an imaging strategy. Specifically, we pretreated myocardial fibrotic collagen with collagenase I combined with human serum albumin (HSA-C) and subsequently visualized the site of cardiac injury by near-infrared (NIR) fluorescence imaging using an optical contrast agent (CI, CRT-indocyanine green) targeting transferrin receptor 1 peptides (CRT). The key point of this strategy is that pretreatment with HSA-C can reduce background signal interference in the fibrotic tissue while enhancing CI uptake at the heart lesion site, making the boundary between the injured heart tissue and the normal myocardium clearer. Our results showed that compared to that in the untargeted group, the normalized fluorescence intensity of cardiac damage detected by NIR in the targeted group increased 1.28-fold. The normalized fluorescence intensity increased 1.21-fold in the pretreatment group of the targeted groups. These data demonstrate the feasibility of applying pretreated fibrotic collagen and NIR contrast agents targeting TfR1 to identify ferroptosis at sites of cardiac injury, and its clinical value in the management of patients with MI needs further study.

Elucidating Iron Metabolism through Molecular Imaging.

Iron is essential for many physiological processes, and the dysregulation of its metabolism is implicated in the pathogenesis of various diseases. Recent advances in iron metabolism research have revealed multiple complex pathways critical for maintaining iron homeostasis. Molecular imaging, an interdisciplinary imaging technique, has shown considerable promise in advancing research on iron metabolism. Here, we comprehensively review the multifaceted roles of iron at the cellular and systemic levels (along with the complex regulatory mechanisms of iron metabolism), elucidate appropriate imaging methods, and summarize their utility and fundamental principles in diagnosing and treating diseases related to iron metabolism. Utilizing molecular imaging technology to deeply understand the complexities of iron metabolism and its critical role in physiological and pathological processes offers new possibilities for early disease diagnosis, treatment monitoring, and the development of novel therapies. Despite technological limitations and the need to ensure the biological relevance and clinical applicability of imaging results, molecular imaging technology's potential to reveal the iron metabolic process is unparalleled, providing new insights into the link between iron metabolism abnormalities and various diseases.

Triclosan induces liver injury in long-life exposed mice via activation of TLR4/NF-κB/NLRP3 pathway.

Triclosan (TCS) is a widely used synthetic, with broad-spectrum antibacterial properties found in both pharmaceuticals and personal care products. More specifically, it is hepatotoxic in rodents and exhibits differential effects in mice and humans. However, the mechanisms underlying TCS-induced liver toxicity have not been elucidated. This study examined the role of the toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB)/ nod-like receptor protein 3 (NLRP3) pathway in TCS-exposed liver toxicity by established a long-life TCS-exposed mice liver injury model. The 24 C57BL/6 pregnant mice exposed to TCS (0, 50 and 100 mg/kg) every day during the gestation and nursing period. After weaning, the male mice were left to continue administrate with TCS until 8 weeks of age. Then, mice in each group were sacrificed for investigation. Long-life exposure to TCS resulted in a reduction of body weight in growth mice. TCS exposure caused the increase of serum ALT, AST and ALP. The situation of inflammatory cell infiltration, macrophage recruitment and collagen fiber deposition in TCS-exposed mice liver tissues were performed by histological analysis including hematoxylin-eosin, Masson, Sirius red, and immunohistochemistry staining. Protein expression levels in TLR4/NF-κB/NLRP3 pathway was measured through Western blot, and the NLRP3 inflammasome activation was measured using real-time quantitative PCR (RT-qPCR). The results showed that exposure to TCS elevated TLR4, myeloid differentiation factor 88 (Myd88), TNF receptor associated factor 6 (TRAF6), enhanced NF-κB activation, and affected NLRP3 inflammasome activation in mice liver. Collectively, these findings indicate that long-life exposure to TCS-induced mice by upregulating the TLR4-Myd88-TRAF6 pathway, activating the NF-κB signaling cascade, initiating the NLRP3 inflammasome pathway, and ultimately leading to liver injury, including inflammation, hepatocyte pyroptosis and hepatofibrosis. Henceforth, the TLR4/NF-κB/NLRP3 pathway may now provide a theoretical basis and valuable therapeutic targets for overcoming TCS-induced liver toxicity.

Preparation of landscape gardening soil using undersized fraction from aged MSW by EDTA or citric acid coupled with humic acid: Effect assessment, properties, and optimization.

Undersized fraction from aged municipal solid waste (UFAMSW), as a kind of soil-like material, has been proved effective in providing a large amount of organic matter and nutrients for soil and plants. The characteristics and effectiveness of heavy metal pollution removal in UFAMSW attracted tremendous research interest from scientists recently. In this study, the heavy metal removal efficiencies and bioavailability of washing on contaminated UFAMSW were evaluated with three washing reagents including ethylene diamine tetra acetic acid (EDTA), citric acid (CA), and humic acid (HA). The effects of chelating agent concentration, pH, and washing time on metal removal were investigated and response surface methodology (RSM) was employed to optimize the washing conditions. The results indicated that the removal efficiencies of Cu, Zn, and Mn could be 53.68%, 52.12%, and 30.63% by EDTA/HA washing and 42.36%, 39.67% and 28.49% by CA/HA washing, respectively. The European Community Bureau of Reference (BCR) sequential extraction was applied to analyze the fraction change of heavy metals in UFAMSW before and after washing, and it was found that chelating agent combined with HA could contribute to the removal of the exchangeable fraction. Physical and chemical properties of UFAMSW were improved to some extent after washing with mixed HA and chelating agent and could achieve the quality standard of landscape gardening soil. Accordingly, the mixture of HA and other chelating agents could be a promising washing process for preparation of landscape gardening soil using UFAMSW.Implications: Our manuscript studies the removal of heavy metals from the contaminated undersized fraction from aged municipal solid waste (UFAMSW). UFAMSW, as a kind of soil-like material, has been proved effective in providing a large amount of organic matter and nutrients for soil and plants however often limited by heavy metal pollution. The UFAMSW used in this experiment was collected after the excavation and screening-sorting of aged refuse from Changshankou Domestic Waste Sanitary Landfill in Wuhan City, Hubei Province, Southern China. This study investigated the effects of EDTA, CA, HA, mixed EDTA/HA, and mixed CA/HA washing on heavy metal removal (Cu, Zn, and Mn), bioavailability of residual heavy metal and properties. The effects of chelating agent concentration, pH, and washing time on metal removal were investigated and then response surface methodology was employed to optimize the washing conditions. The results showed that washing by CA/HA and EDTA/HA, had a higher removal efficiency of heavy metals (Cu, Zn, and Mn) in UFAMSW compared to single HA. Meanwhile, HA has a higher removal for exchangeable fraction of heavy metals, the exchangeable concentration of Cu, Zn, and Mn in CA/HA and EDTA/HA washed UFAMSW were lower compared with UFAMSW washed by single CA and EDTA. Thus, mixing HA with EDTA or CA makes a less risk to environmental and the removal efficiency is acceptable. Additionally, CA/HA and EDTA/HA washing tend to improve soil physicochemical properties and soil fertility. Thus, mixing HA with different washing agent are potential methods for preparation of landscape gardening soil using UFAMSW.

Engineered Bio-Based Hydrogels for Cancer Immunotherapy.

Immunotherapy represents a revolutionary paradigm in cancer management, showcasing its potential to impede tumor metastasis and recurrence. Nonetheless, challenges including limited therapeutic efficacy and severe immune-related side effects are frequently encountered, especially in solid tumors. Hydrogels, a class of versatile materials featuring well-hydrated structures widely used in biomedicine, offer a promising platform for encapsulating and releasing small molecule drugs, biomacromolecules, and cells in a controlled manner. Immunomodulatory hydrogels present a unique capability for augmenting immune activation and mitigating systemic toxicity through encapsulation of multiple components and localized administration. Notably, hydrogels based on biopolymers have gained significant interest owing to their biocompatibility, environmental friendliness, and ease of production. This review delves into the recent advances in bio-based hydrogels in cancer immunotherapy and synergistic combinatorial approaches, highlighting their diverse applications. It is anticipated that this review will guide the rational design of hydrogels in the field of cancer immunotherapy, fostering clinical translation and ultimately benefiting patients.

Effects of selenium nanoparticles produced by Lactobacillus acidophilus HN23 on lipid deposition in WRL68 cells.

Selenium is an essential trace element for most organisms, protecting cells from oxidative damage caused by free radicals and serving as an adjunctive treatment for non-alcoholic fatty liver disease (NAFLD). In this study, We used the lactic acid bacterium Lactobacillus acidophilus HN23 to reduce tetra-valent sodium selenite into particulate matter, and analyzed it through inductively coupled plasma mass spectrometry (ICP-MS), scanning electron microscopy (SEM), X-ray diffraction energy dispersive spectrometry (EDS), and Fourier transform infrared spectroscopy (FTIR). We found that it consisted of selenium nanoparticles (SeNPs) with a mass composition of 65.8 % zero-valent selenium and some polysaccharide and polypeptide compounds, with particle sizes ranging from 60 to 300 nm. We also detected that SeNPs were much less toxic to cells than selenite. We further used free fatty acids (FFA)-induced WRL68 fatty liver cell model to study the therapeutic effect of SeNPs on NAFLD. The results show that SeNPs are more effective than selenite in reducing lipid deposition, increasing mitochondrial membrane potential (MMP) and antioxidant capacity of WRL68 cells, which is attributed to the chemical valence state of selenium and organic composition in SeNPs. In conclusion, SeNPs produced by probiotics L. acidophilus had the potential to alleviate NAFLD by reducing hepatocyte lipid deposition and oxidative damage. This study may open a new avenue for SeNPs drug development to treat NAFLD.

Efficacy and safety of Qingda granule versus valsartan capsule in Chinese grade 1 hypertensive patients with low-moderate risk: A randomized, double-blind, double dummy, non-inferiority, multi-center trial.

BACKGROUND: The efficacy and safety of Qingda granule (QDG) in managing blood pressure (BP) among grade 1 hypertensive patients with low-moderate risk remain uncertain. METHODS: In the randomized, double-blind, double dummy, non-inferiority and multicenter trial, 552 patients with grade 1 hypertension at low-moderate risk were assigned at a ratio of 1:1 to receive either QDG or valsartan for 4 weeks, followed up by a subsequent 4 weeks. RESULTS: Post-treatment, clinic systolic/diastolic BPs (SBP/DBP) were reduced by a mean change of 9.18/4.04 mm Hg in the QDG group and 9.85/5.05 mm Hg in the valsartan group (SBP P = 0.47, DBP P = 0.16). Similarly, 24-hour, daytime and nighttime BPs were proportional in both groups (P > 0.05) after 4 weeks treatment. After discontinuing medications for 4 weeks, the mean reduction of clinic SBP/DBP were 0.29/0.57 mm Hg in the QDG group compared to -1.59/-0.48 mm Hg in the valsartan group (SBP P = 0.04, DBP P = 0.04). Simultaneously, the 24-hour SBP/DBP were reduced by 0.9/0.31 mm Hg in the QDG group and -1.66/-1.08 mm Hg in the valsartan group (SBP P = 0.006, DBP P = 0.02). And similar results were observed regarding the outcomes of daytime and nighttime BPs. There was no difference in occurrence of adverse events between two groups (P > 0.05). CONCLUSION: QDG proves to be efficacious for grade 1 hypertension at a low-to-medium risk, even after discontinuation of the medication for 4 weeks. These findings provide a promising option for managing grade 1 hypertension and suggest the potential for maintaining stable BP through intermittent administration of QDG. TRIAL REGISTRATION: ChiCTR2000033890.

Photoacoustic Spectroscopy-Based Breath Analysis for SIBO.

Breath hydrogen (H2) and methane (CH4) monitoring play an important role in the diagnosis of gastrointestinal disorders, such as lactose intolerance and small intestinal bacterial overgrowth (SIBO). In this paper, the photoacoustic spectroscopy method is used for H2 gas and CH4 gas detection. We present a novel approach for H2 gas concentration measurement, which is the linear relationship between the resonant frequency of breath carbon dioxide (CO2) and the H2 concentration in a resonant photoacoustic cell. Experimental results show that the minimum detectable limits of H2, CH4, and CO2 are calculated to be 8.86, 0.56, and 145.14 ppm, respectively, which can meet the requirements of breath diagnosis.

Stimulus-responsive proteins involved in multi-process regulation of storage substance accumulation during rice grain filling under elevated temperature.

BACKGROUND: The intensified global warming during grain filling deteriorated rice quality, in particular increasing the frequency of chalky grains which markedly impact market value. The formation of rice quality is a complex process influenced by multiple genes, proteins and physiological metabolic processes. Proteins responsive to stimulus can adjust the ability of plants to respond to unfavorable environments, which may be an important protein involved in the regulation of quality formation under elevated temperature. However, relatively few studies have hindered our further understanding of rice quality formation under elevated temperature. RESULTS: We conducted the actual field elevated temperature experiment and performed proteomic analysis of rice grains at the early stage of grain filling. Starting with the response to stimulus in GO annotation, 22 key proteins responsive to stimulus were identified in the regulation of grain filling and response to elevated temperature. Among the proteins responsive to stimulus, during grain filling, an increased abundance of signal transduction and other stress response proteins, a decreased abundance of reactive oxygen species-related proteins, and an increased accumulation of storage substance metabolism proteins consistently contributed to grain filling. However, the abundance of probable indole-3-acetic acid-amido synthetase GH3.4, probable indole-3-acetic acid-amido synthetase GH3.8 and CBL-interacting protein kinase 9 belonged to signal transduction were inhibited under elevated temperature. In the reactive oxygen species-related protein, elevated temperature increased the accumulation of cationic peroxidase SPC4 and persulfide dioxygenase ETHE1 homolog to maintain normal physiological homeostasis. The increased abundance of alpha-amylase isozyme 3E and seed allergy protein RA5 was related to the storage substance metabolism, which regulated starch and protein accumulation under elevated temperature. CONCLUSION: Auxin synthesis and calcium signal associated with signal transduction, other stress responses, protein transport and modification, and reactive oxygen species-related proteins may be key proteins responsive to stimulus in response to elevated temperature. Alpha-amylase isozyme 3E and seed allergy protein RA5 may be the key proteins to regulate grain storage substance accumulation and further influence quality under elevated temperature. This study enriched the regulatory factors involved in the response to elevated temperature and provided a new idea for a better understanding of grain response to temperature.

A new application of nano-selenium: rescue of CK2 and mitochondria from oxidative stress to prevent cardiac hypertrophy.

Background: Excessive reactive oxygen species (ROS) and subsequent mitochondrial dysfunction are pivotal in initiating cardiac hypertrophy. To explore nano-selenium's (SeNP's) preventive potential against this condition, the authors evaluated chemically synthesized chitosan-SeNPs and biosynthesized Bacillus cereus YC-3-SeNPs in an angiotensin II (Ang II)-induced cardiac hypertrophy model. Methods: This investigation encompassed ROS measurement, mitochondrial membrane potential analysis, transmission electron microscopy, gene and protein expression analyses, protein carbonylation assays, serum antioxidant quantification and histological staining. Results: SeNPs effectively countered Ang II-induced cardiac hypertrophy by reducing ROS, restoring mitochondrial and protein kinase 2α (CK2-α) function, activating antioxidant pathways and enhancing serum antioxidant levels. Conclusion: This finding underscores SeNPs' role in attenuating Ang II-induced myocardial hypertrophy both in vitro and in vivo.

Enlargement of the heart is called cardiac hypertrophy; this is caused by too many reactive oxygen species, which are compounds that damage the mitochondria of cells. The mitochondria provide energy to cells and their disruption can cause a significantly negative effect on cells and the tissues and organs cells make up. Selenium is a type of metal that must be consumed in small amounts to stay healthy; it has antioxidant effects, meaning it can stop reactive oxygen species and potentially prevent cardiac hypertrophy. Nano-selenium (SeNP), consisting of tiny, spherical particles containing selenium, may be a more effective way of delivering selenium as an antioxidant to prevent cardiac hypertrophy. SeNPs were made synthetically and from a type of bacterium called Bacillus cereus; both SeNPs demonstrated antioxidant effects in heart cells taken from chicken embryos and live chickens. These results suggest that SeNPs could be developed into medication to combat cardiac hypertrophy.

Reverse genetic study reveals the molecular targets of chordotonal organ TRPV channel modulators.

Insecticides have been widely used for the control of insect pests that have a significant impact on agriculture and human health. A better understanding of insecticide targets is needed for effective insecticide design and resistance management. Pymetrozine, afidopyropen and flonicamid are reported to target on proteins that located on insect chordotonal organs, resulting in the disruption of insect coordination and the inhibition of feeding. In this study, we systematically examined the susceptibility of six Drosophila melanogaster mutants (five transient receptor potential channels and one mechanoreceptor) to three commercially used insecticides, in order to identify the receptor subunits critical to the insect's response to insecticides. Our results showed that iav1, nan36aand wtrw1 mutants exhibited significantly reduced susceptibility to pymetrozine and afidopyropen, but not to flonicamid. The number of eggs produced by the three mutant females were significantly less than that of the w1118 strain. Meanwhile, the longevity of all male mutants and females of nan36a and wtrw1 mutants was significantly shorter than that of the w1118 strain as the control. However, we observed no gravitaxis defects in wtrw1 mutants and the anti-gravitaxis of wtrw1 mutants was abolished by pymetrozine. Behavioral assays using thermogenetic tools further confirmed the bioassay results and supported the idea that Nan as a TRPV subfamily member located in Drosophila chordotonal neurons, acting as a target of pymetrozine, which interferes with Drosophila and causes motor deficits with gravitaxis defects. Taken together, this study elucidates the interactions of pymetrozine and afidopyropen with TRPV channels, Nan and Iav, and TRPA channel, Wtrw. Our research provides another evidence that pymetrozine and afidopyropen might target on nan, iav and wtrw channels and provides insights into the development of sustainable pest management strategies.

Association between weight change and the predicted 10-year risk for atherosclerosis cardiovascular disease among U.S. older adults: data from National Health and Nutrition Examination Survey 1999-2018.

Background: It remains controversial regarding the association between weight change and cardiovascular disease risk in older adults (aged ≥60 years). This study aimed to evaluate the association between weight change and the predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risks in older adults. Methods: This study used data from the National Health and Nutrition Examination Survey (NHANES). Older adults aged 60-79 years who were free of self-reported ASCVD at the time of the NHANES interview were included. Data were collected from January 1999 to December 2018 and analyzed in March 2022. We focused on the associations between weight change and the 10-year ASCVD risks with the percentage change in weight during short-term (1 year) and long-term (10 years), which categorized as moderate to high weight loss (≥10%), small weight loss (5.1-9.9%), stable weight (±5%), small weight gain (5.1-9.9%), and moderate to high weight gain (≥10%). Results: The number of participants was 1,867 (mean age 67.49 years; 42.10% female) for the long-term interval (10 years) in our analysis, and 1894 for the short-term interval (1 years). We only observed an inverse association between long-term weight loss and the 10-year ASCVD risk in fully adjusted model (loss ≥ 10%: ß = 2.52, 95%CI = 0.98, 4.05; loss 5.1% ~ 9.9%: ß = 2.99, 95% CI = 1.30, 4.68), but all intervals of weight gain ≥5% were not significant associated with higher risk than stable weight. However, in the subgroup analyses, the association between long-term weight loss and the 10-year ASCVD risk was not significant in old-old (aged 75-79), obesity (BMI ≥ 35 kg/m2), intentional weight loss, moderate physical activity and diabetics. Conclusion: Older adults (aged 60-79 years) with weight loss >5% over the past 10 years have excess predicted 10-year ASCVD risk. Our study supports the benefits of stable weight in promoting cardiovascular health in older adults.

Manganese-Enriched Zinc Peroxide Functional Nanoparticles for Potentiating Cancer Immunotherapy.

Immunotherapies have shown high clinical success, however, the therapeutical efficacy is largely restrained by insufficient immune activation and an immunosuppressive microenvironment. Herein, we report tumor microenvironment (TME)-responsive manganese-enriched zinc peroxide nanoparticles (MONPs) for synergistic cancer immunotherapy by inducing the immunogenic death (ICD) of cancer cells and activating the stimulator of the interferon gene (STING) pathway. MONPs especially disassociate upon exposure to acidic tumor tissue and in situ generate •OH for the ICD effect. Moreover, Mn2+ activated the STING and synergistically induced the secretion of type I interferon and inflammatory cytokines for specific T cell responses. Meanwhile, MONPs relieved the immunosuppression of TME through decreasing Tregs and polarizing M2 macrophages to the M1 type to unleash a cascade adaptive immune response. In combination with the anti-PD-1 antibody, MONPs showed superior efficacy in inhibiting tumor growth and preventing lung metastasis. Our study demonstrates the feasibility of functional nanoparticles to amplify STING innate stimulation, showing a prominent strategy for cancer immunotherapy.

Corrigendum: Development and validation of a m6A -regulated prognostic signature in lung adenocarcinoma.

[This corrects the article DOI: 10.3389/fonc.2022.947808.].

Ratoon Rice Cropping Mitigates the Greenhouse Effect by Reducing CH4 Emissions through Reduction of Biomass during the Ratoon Season.

The ratoon rice cropping system (RR) is developing rapidly in China due to its comparable annual yield and lower agricultural and labor inputs than the double rice cropping system (DR). Here, to further compare the greenhouse effects of RR and DR, a two-year field experiment was carried out in Hubei Province, central China. The ratoon season showed significantly lower cumulative CH4 emissions than the main season of RR, the early season and late season of DR. RR led to significantly lower annual cumulative CH4 emissions, but no significant difference in cumulative annual N2O emissions compared with DR. In RR, the main and ratoon seasons had significantly higher and lower grain yields than the early and late seasons of DR, respectively, resulting in comparable annual grain yields between the two systems. In addition, the ratoon season had significantly lower global warming potential (GWP) and greenhouse gas intensity-based grain yield (GHGI) than the main and late seasons. The annual GWP and GHGI of RR were significantly lower than those of DR. In general, the differences in annual CH4 emissions, GWP, and GHGI could be primarily attributed to the differences between the ratoon season and the late season. Moreover, GWP and GHGI exhibited significant positive correlations with cumulative emissions of CH4 rather than N2O. The leaf area index (LAI) and biomass accumulation in the ratoon season were significantly lower than those in the main season and late season, and CH4 emissions, GWP, and GHGI showed significant positive correlations with LAI, biomass accumulation and grain yield in the ratoon and late season. Finally, RR had significantly higher net ecosystem economic benefits (NEEB) than DR. Overall, this study indicates that RR is a green cropping system with lower annual CH4 emissions, GWP, and GHGI as well as higher NEEB.

Mitigating the adverse effect of warming on rice canopy and rhizosphere microbial community by nitrogen application: An approach to counteract future climate change for rice.

The adverse impact of climate change on crop production continues to increase, necessitating the development of suitable strategies to mitigate these effects and improve food security. Several studies have revealed how global warming negatively impacts the grain-filling stage of rice and that this effect could be mitigated by nitrogen; however, the impact of nitrogen application on rice canopy and rhizosphere microbial communities remains unclear. We conducted a study using an open-field warming system. Results showed that warming influenced rice canopy by decreasing aboveground biomass and harvest index, whereas nitrogen application had positive effect on rice production under warming conditions by increasing the plant nitrogen content, biomass, harvest index and soil fertilities. Moreover, soil ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) contents were significantly decreased under warming, which were higher after nitrogen application. Notably, warming and nitrogen fertilizer caused 19 % (P < 0.01) and 7 % (P < 0.05) variations, respectively, in the ß diversity of the microbial community, respectively. The impact of warming was significant on NH4+-N-related microorganisms; however, this impact was weakened by nitrogen application for microbes in the rhizosphere. This study demonstrated that enhanced nitrogen fertilizer can alleviate the adverse impact of warming by weakening its effects on rhizosphere microbes, improving soil fertility, promoting rice nitrogen uptake, and increasing the aboveground biomass and harvest index. These findings provide an important theoretical basis for developing practical, responsive cultivation strategies.

Differences Between Patients With Diabetes Mellitus and Obese Patients in Occurrence of Peri-Prosthetic Joint Infection: A Systemic Review and Meta-Analysis.

Background: To understand the differences between patients with diabetes mellitus and obese patients with respect to the occurrence of peri-prosthetic joint infection (PJI) after lower-extremity joint arthroplasty as well as to identify differences in PJI occurrence at different time periods. Patients and Methods: The Cochrane Library, CINAHL, MEDLINE, and PubMed were searched for literature published between January 2000 and July 2022. Our targets were studies involving patients with PJI who had already been diagnosed as having diabetes mellitus or being obese before receiving lower-extremity joint arthroplasty. Analysis was performed using Comprehensive Meta-Analysis Software (CMA) Version 3 (Biostat, Inc., Englewood, NJ, USA). Results: A total of 53,522 patients with diabetes mellitus and 360,018 obese patients were included. The forest plot for patients with and without diabetes mellitus indicated that patients with diabetes mellitus were more likely to contract PJIs than were patients without diabetes mellitus (odds ratio, 1.84; 95% confidence interval [CI], 1.56-2.16) and that no differences existed among early, delayed, and late PJI occurrence in patients with diabetes mellitus. The forest plot for obese and non-obese patients indicated that obese patients were more likely to contract PJIs than were non-obese patients (odds ratio, 1.86; 95% CI, 1.53-2.14) and that among obese patients, early PJI occurrence was higher than was late PJI occurrence. In addition, the mixed model indicated that obese patients were more likely to develop early PJIs than were patients with diabetes mellitus. Conclusions: Patients with diabetes mellitus and obese patients were more likely to develop PJIs than were patients without diabetes mellitus and non-obese patients, and that obese patients were more likely to develop early PJIs than late PJIs. Also, obese patients were more likely to develop early PJIs than patients with diabetes mellitus.