Can high-yielding maize system decrease greenhouse gas emissions largely while simultaneously enhancing economic and ecosystem benefits through the "Rhizobiont" concept? Evidence from field.

Ensuring high grain yields while minimizing environmental costs is a pressing imperative aligned with the Sustainable Development Goals (SDGs). In this study, we sought to establish a high-yielding maize system (HYMS) by implementing the innovative "Rhizobiont" concept for nutrient management, while substantially reducing greenhouse gas emissions. A 2-yr field study was conducted in a station of China Agriculture University (Wuqiao) with six treatments. The HYMS was established to achieve a harmonious equilibrium among genetic factors, environmental conditions, and management practices. HYMS demonstrated a significant boost in grain yield, averaging 12,706.6 kg ha-1 in 2021 and 13,676.4 kg ha-1 in 2022. These represented substantial increases of 25.6 % and 25.5 %, respectively, when compared to the current farmers practices (CP). More importantly, the N rate in HYMS was optimized to 148.2 kg ha-1 in 2021 and 138.0 kg ha-1 in 2022 with the implementation of the "Rhizobiont" concept. This represented a remarkable reduction of 35.5 % to 39.9 % in N application compared to CP. As a direct consequence, the measured cumulative emissions of greenhouse gases such as CO2, N2O, and CH4 in HYMS were notably decreased, showing reductions of 24.1 %, 36.0 %, and 7.0 %, respectively, compared to CP. Furthermore, the carbon intensity in HYMS was significantly reduced by 43.7 %. These considerable reductions in fertilizer use translated into tangible economic benefits (EB) and ecosystem economic benefit (EEB) in HYMS. EB was found to be 90.9 % higher, while EEB was 117.9 % higher than CP. These findings underscore the vast potential of HYMS and the "Rhizobiont" concept in promoting sustainable agriculture, with far-reaching implications for global food security and the well-being of smallholder farmers.

CT-based identification of pediatric non-Wilms tumors using convolutional neural networks at a single center.

BACKGROUND: Deep learning (DL) is more and more widely used in children's medical treatment. In this study, we have developed a computed tomography (CT)-based DL model for identifying undiagnosed non-Wilms tumors (nWTs) from pediatric renal tumors. METHODS: This study collected and analyzed the preoperative clinical data and CT images of pediatric renal tumor patients diagnosed by our center from 2008 to 2020, and established a DL model to identify nWTs noninvasively. RESULTS: A total of 364 children who had been confirmed by histopathology with renal tumors from our center were enrolled, including 269 Wilms tumors (WTs) and 95 nWTs. For DL model development, all cases were randomly allocated to training set (218 cases), validation set (73 cases), and test set (73 cases). In the test set, the DL model achieved area under the curve of 0.831 (95% CI: 0.712-0.951) in discriminating WTs from nWTs, with the accuracy, sensitivity, and specificity of 0.781, 0.563, and 0.842, respectively. The sensitivity of our model was higher than a radiologist with 15 years of experience. CONCLUSIONS: We presented a DL model for identifying undiagnosed nWTs from pediatric renal tumors, with the potential to improve the image-based diagnosis. IMPACT: Deep learning model was used for the first time to identify pediatric renal tumors in this study. Deep learning model can identify non-Wilms tumors from pediatric renal tumors. Deep learning model based on computed tomography images can improve tumor diagnosis rate.

Nucleus-selective codelivery of proteins and drugs for synergistic antitumor therapy.

Subcellular organelle targeted transport is of great significance for accurately delivering drugs to active sites for better pharmacological effects, but there are still a lot of challenges due to transport problems. In addition, the killing effect of one kind of drug on cells is limited. Therefore, it is necessary to develop a multifunctional nanoplatform that can co-deliver synergistic therapeutic agents. Here, we prepare a simple amphiphilic nanocarrier (LC) with rapid endosomal escape ability for nucleus-selective delivery of hydrophilic active protein deoxyribonuclease I (DNase I) and hydrophobic anticancer drug doxorubicin (DOX). LC has been applied to effectively encapsulate DNase I just by simply mixing their aqueous solutions together. In addition, DOX modified with adamantane groups via a redox-responsive linker is incorporated into the architecture of DNase I nanoformulations through host-guest interaction. This multi-component nanoplatform can quickly escape from the endolysosomes into the cytoplasm and make DNase I and DOX highly accumulate in the nucleus and consequently induce strong synergistic anticancer efficacy both in vitro and in vivo. This work illustrates a new platform for codelivery of proteins and drugs that target subcellular compartments for functions.

Self-Assembly of Intelligent Nanoplatform for Endogenous H2S-Triggered Multimodal Cascade Therapy of Colon Cancer.

The specific in situ generation and activation of therapeutic agents with high spatiotemporal precision is expected to revolutionize cancer treatment. Here, we develop an intelligent nanoplatform (termed as NP-Cu), which is constructed by assembling photosensitizer chlorin e6 (Ce6), hypoxia-responsive prodrug banoxantrone (AQ4N) with clickable dibenzocyclooctyne (DIBO) functionalized lysine (D-K), and cyclen-Cu2+ complex, for improving combination anticancer therapy. Cyclen-Cu2+ complex-induced photodynamic therapy (PDT) quenching in NP-Cu can be effectively and selectively activated by tumor-overproduced hydrogen sulfide (H2S). More importantly, the reaction of endogenous H2S with Cu2+ can generate photothermal agent copper sulfide (CuS) for photothermal therapy (PTT). Furthermore, with the activation of PTT and PDT, intracellular hypoxic stress is amplified to trigger AQ4N-associated chemodynamic therapy (CDT), leading to light-enhanced cascade therapy of PDT, PTT and CDT. Therefore, we present a simple and practical strategy for developing pathological stimuli responsive combination therapy, which has the potential of advancing precision cancer medicine.

Decabromodiphenyl ether-induced PRKACA hypermethylation contributed to glycolipid metabolism disorder via regulating PKA/AMPK pathway in rat and L-02 cells.

BDE-209 is the most prevalent congener of polybrominated diphenyl ethers and has high bioaccumulation in humans and animals. BDE-209 has been reported to disrupt glycolipid metabolism, but the mechanisms are still unclear. In this study, we found that BDE-209 induced liver tissue injury and hepatotoxicity, increased the glucose and total cholesterol levels in the serum of rats, and increased glucose and triglyceride levels in L-02 cells. BDE-209 exposure changed the PKA, p-PKA, AMPK, p-AMPK, ACC, and FAS expression in rats' liver and L-02 cells. Moreover, BDE-209 induced PRKACA-1 hypermethylation in L-02 cells. AMPK activator (AICAR) inhibited the changes of p-AMPK, ACC, and FAS expression and elevation of glucose and triglyceride levels induced by BDE-209. DNA methylation inhibitor (5-Aza-CdR) reversed BDE-209 induced alters of PKA/AMPK/ACC/FAS signaling pathway. These results demonstrated that BDE-209 could disrupt the glycolipid metabolism by causing PRKACA-1 hypermethylation to regulate the PKA/AMPK signaling pathway in hepatocytes.

Imaging features and differences among the three primary malignant non-Wilms tumors in children.

BACKGROUND: The pathology, treatment and prognosis of malignant non-Wilms tumors (NWTs) are different, so it is necessary to differentiate these types of tumors. The purpose of this study was to review the clinical and imaging features of malignant NWTs and features of tumor metastasis. METHODS: We retrospectively analyzed the CT images of 65 pediatric patients with NWTs from March 2008 to July 2020, mainly including clear cell sarcoma of the kidney (CCSK), malignant rhabdomyoma tumor of the kidney (MRTK) and renal cell carcinoma (RCC). Available pretreatment contrast-enhanced abdominal CT examinations were reviewed. The clinical features of the patients, imaging findings of the primary mass, and locoregional metastasis patterns were evaluated in correlation with pathological and surgical findings. RESULTS: The study included CCSK (22 cases), MRTK (27 cases) and RCC (16 cases). There were no significant differences observed among the sex ratios of CCSK, MRTK and RCC (all P > 0.05). Among the three tumors, the onset age of MRTK patients was the smallest, while that of RCC patients was the largest (all P < 0.05). The tumor diameter of CCSK was larger than that of MRTK and RCC (all P < 0.001). For hemorrhage and necrosis, the proportion of MRTK patients was larger than that of the other two tumors (P = 0.017). For calcification in tumors, the proportion of calcification in RCC was highest (P = 0.009). Only MRTK showed subcapsular fluid (P < 0.001). In the arterial phase, the proportion of slight enhancement in RCC was lower than that in the other two tumors (P = 0.007), and the proportion of marked enhancement was the highest (P = 0.002). In the venous phase, the proportion of slight enhancement in RCC was lower than that in the other two tumors (P < 0.001). Only CCSK had bone metastasis. There was no liver and lung metastasis in RCC. CONCLUSIONS: NWTs have their own imaging and clinical manifestations. CCSK can cause vertebral metastasis, MRTK can cause subcapsular effusion, and RCC tumor density is usually high and calcification. These diagnostic points can play a role in clinical diagnosis.

Decabromodiphenyl ether disturbs hepatic glycolipid metabolism by regulating the PI3K/AKT/GLUT4 and mTOR/PPARγ/RXRα pathway in mice and L02 cells.

Decabromodiphenyl ether (BDE-209) is a persistent environmental pollutant that poses great risks to human health and has been associated with glucose and lipid metabolism. However, the mechanisms by which BDE-209 disturbs glycolipid metabolism in the liver remain unclear. Therefore, this study sought to confirm the effects of BDE-209 on glycolipid metabolism in mice livers and L02 cells to elucidate potential mechanisms of action. In vivo BDE-209 exposure caused histological damage and lipid accumulation, elevated glucose, low-density lipoprotein, total cholesterol, and triglyceride levels, and decreased glycogen and high-density lipoprotein levels in mice livers. Moreover, in vitro BDE-209 exposure not only induced L02 cells cytotoxicity (i.e., reduced cell viability and increased LDH leakage and ROS generation) but also increased glucose and triglyceride concentrations in L02 cells. Furthermore, IGF-1, an activator of the PI3K-AKT pathway, markedly inhibited BDE-209-induced glucose concentration increase in L02 cells and antagonized the inhibitory effect of BDE-209 on the PI3K/AKT/GLUT4 pathway by counteracting the changes in the expression levels of p-IRS, AKT, PI3K, p-AKT, and GLUT4. Moreover, GW9662, a PPARγ inhibitor, blocked lipid accumulation and the upregulation of the mTOR/PPARγ/RXRα pathway in L02 cells induced by BDE-209 by relieving the increases in p-mTOR, PPARγ, and RXRα protein expression levels. In summary, this study revealed that BDE-209 disrupted glycolipid metabolism by inhibiting the PI3K/AKT/GLUT4 pathway and activating the mTOR/PPARγ/RXRα pathway.

Ultrasonic manifestation of urethral polyp in a girl: a case report.

Urethral polyp, a rare condition, occurs frequently in boys but seldom in young girls. In this report, we describe a case of a six-year-old female patient who experienced dysuria for eight days. Color ultrasound of the patient's urinary system revealed a solid nodule 14×9 mm in size at the opening of the urethra in the trigonal area of the bladder. The nodule was connected to the urethra's posterior wall, and no blood flow signal could be detected. The primary diagnosis was urethral mass. A F7 ureteroscope was used as the cystourethroscope and was inserted into the bladder via the external opening of the urethra. Biopsy forceps were used to remove pathological lesions from the uplifted mucosa and submucosa. The postoperative pathological report was urethral polyp. When a child experiences intermittent urine retention, intermittent hematuria, and intermittent lower urinary tract symptoms, urethral polyp should be considered first.

Endosulfan induces cardiotoxicity through apoptosis via unbalance of pro-survival and mitochondrial-mediated apoptotic pathways.

Although the associations between endosulfan and adverse cardiovascular health have been reported, the toxic effects and underlying mechanism of endosulfan on the heart are not well understood. In this study, we examined the cardiotoxicity induced by endosulfan using Wistar rats and human cardiomyocytes (AC16) cells. Wistar rats were divided into control group (received corn oil alone) and three concentrations of endosulfan groups (1, 5 and 10 mg/kg·bw) by gavage. The AC16 cells were treated with three various concentrations (0, 1.25, 5, and 20 µg/mL) of endosulfan. The results showed that endosulfan induced cytotoxicity through damaging myocardial structure, decreasing the viability of cardiomyocytes, and elevating the serum levels of cardiac troponin I, heart fatty acid binding protein, aspartate aminotransferase, and reactive oxygen species (p < 0.05). Moreover, measurement of mitochondrial function showed that endosulfan could significantly decrease adenosine triphosphate levels and cytochrome c oxidase IV expression in AC16 cells (p < 0.05). In addition, endosulfan obviously inhibited Bcl-2 expression, activated the expressions of cytochrome c/Caspase-9/Caspase-3 signaling pathway, and induced the apoptosis of AC16 cells (p < 0.05). Furthermore, endosulfan significantly increased the expression of Bim, and inhibited the expressions of PI3K/Akt/FoxO3a signaling pathways in cardiomyocytes (p < 0.05). These results suggest that endosulfan may induce cardiotoxicity by inducing myocardial apoptosis resulting from activation of mitochondria-mediated apoptosis pathway and inhibition of pro-survival signaling pathways, which might be helpful in elucidating the mechanism of cardiac dysfunction induced by endosulfan.

Fine particulate matters induce apoptosis via the ATM/P53/CDK2 and mitochondria apoptosis pathway triggered by oxidative stress in rat and GC-2spd cell.

Fine particulate matters (PM2.5) have been associated with male reproductive toxicity because it can penetrate into the lung's gas-exchange region, and spread to the whole body via circulatory system. Previous studies have shown that PM2.5 could induce DNA damage and apoptosis by reactive oxygen species (ROS). The aim of the present study is to determine the exact mechanism and role of apoptosis induced by PM2.5 in spermatocyte cells. Male Sprague-Dawley (SD) rats were treated with normal saline (control group) or PM2.5 with the doses of 1.8, 5.4 and 16.2 mg/kg bw. via intratracheal instillation every 3 days for 30 days. Mouse spermatocyte-derived cells (GC-2spd cells) were treated with various concentrations (0, 50, 100, 200 µg/mL) of PM2.5 for 24 h. The results showed that exposure to PM2.5 resulted in injury of testicular tissue and impaired mitochondria integrity in GC-2spd cells. Moreover, PM2.5 induced DNA damage and apoptosis in GC-2spad cells via ROS generation, and the ATM/P53/CDK2 and mitochondria apoptosis pathway autophagy signal pathway were activated. N-Acetyl-L-cysteine (NAC), a well-known antioxidant, ameliorated DNA damage, and inhibited apoptosis. These findings demonstrated PM2.5 might induce apoptosis via the mitochondrial apoptosis pathway through causing DNA damage resulting from oxidative stress, and finally caused spermatogenesis disorder.

The effects of decabromodiphenyl ether on glycolipid metabolism and related signaling pathways in mice.

Decabromodiphenyl ether (BDE-209), an addictive type flame retardant, is widely found in environments, and could affect the glycolipid metabolism. The present study was designed to investigate the potential mechanism of BDE-209 affecting glycolipid metabolism. Forty mice were randomly divided into four groups, and they were exposed to BDE-209 at dosages of 0, 7.5, 25 and 75 mg kg-1·d-1 for 28 d, respectively. The results showed that BDE-209 increased the serum levels of glucose, insulin, and triglyceride, also decreased the level of high-density lipoprotein, and damaged the structures of liver and adipose tissue in mice. BDE-209 significantly increased the protein expression of p-IRS, markedly decreased the expressions of PI3K, p-AKT, and GLUT4, significantly improved the lipid metabolism related factor expressions of p-mTOR, mTOR, PPARγ and RXRɑ, also inhibited the activity of antioxidant enzymes in the liver of mice. These results suggested that BDE-209 could affect glucose metabolism and inhibiting PI3K/AKT/GLUT4 signaling pathway resulting from improving the p-IRS expression, and interfered with lipid metabolism through activate mTOR/PPARγ/RXRα resulting from oxidative stress in mice.

Computed Tomography and Magnetic Resonance Imaging Manifestations of Spinal Monostotic Fibrous Dysplasia.

AIM: The purpose of the study was to analyze and summarize the computed tomography (CT) and magnetic resonance imaging (MRI) findings of spinal monostotic fibrous dysplasia (MFD) as well as evaluate the clinical value of CT and MRI in MFD diagnosis. MATERIALS AND METHODS: CT (n = 4) and MRI (n = 5) images of six patients with pathologically confirmed spinal MFD were examined. The assessed image features included location, shape, rib involvement, vertebral collapse, margin, attenuation, and sclerotic rim on CT, as well as signal intensity, dark signal rim, and enhancement pattern on MRI. RESULTS: In total, four of six patients underwent CT scanning. The most common findings on CT scanning were expansile lesions (n = 4), sclerotic rims (n = 4), and ground-glass opacity (GGO) (n = 4). In total, five of six patients underwent MRI. The lesions were low-signal intensity (n = 2), low-to-isointense signal intensity (n = 1), and low-signal intensity with several isointense portions (n = 2) on T1-weighted imaging (T1WI). The lesions were low-signal intensity (n = 1), isointense to high intensity (n = 1), and isointense signal intensity with several high portions (n = 3) on T2WI. A dark signal rim was found in most cases on T1WI and T2WI (n = 4). The lesions (n = 2) showed obvious enhancement. CONCLUSIONS: The CT and MRI manifestations of spinal MFD have the following characteristics: expansile lesion, GGO, sclerotic rim, and no obvious soft-tissue mass. The combined use of CT and MRI examinations is necessary for patients with suspected spinal MFD.

Fine particle matter disrupts the blood-testis barrier by activating TGF-ß3/p38 MAPK pathway and decreasing testosterone secretion in rat.

Fine particle matter (PM) is correlated with male reproductive dysfunction in animals and humans, but the underlying mechanisms remain unknown. To investigate the toxic mechanism of PM, 32 male Sprague-Dawley (SD) rats were exposed to saline or PM2.5 with the doses of 1.8, 5.4, and 16.2 mg/kg.b.w. via intratracheal instillation, respectively, one time every 3 days, in total times for 30 days. Sperm concentration, hormone level, the expressions of BTB-associated protein and the mitogen-activated protein kinase (MAPK) pathway, tumor necrosis factor α and transforming growth factor ß3 levels were detected. The results showed a decrease in sperm number, testosterone and luteinizing hormone levels and altered ultrastructure of BTB in testis of rat after exposure to PM2.5 . The protein levels of N-Cadherin, Occludin, Claudin-11, and Connexin-43 were significantly decreased in the testes. TGF-ß3 content in testes showed increase, with the p-p38/p38 MAPK ratio also increasing after PM2.5 exposure. These results demonstrate that PM2.5 restrained the expressions of BTB-associated proteins through activating TGF-ß3/p38 MAPK pathway and decreasing testosterone secretion, and therefore lead to the damage of BTB resulting in the decrease of sperm quality, which might be the potential reasons for its negative effects on spermatogenesis and male reproduction.