Effects of Cadmium Stress on Tartary Buckwheat Seedlings.

Cadmium (Cd) is a naturally occurring toxic heavy metal that adversely affects plant germination, growth, and development. While the effects of Cd have been described on many crop species including rice, maize, wheat and barley, few studies are available on cadmium's effect on Tartary buckwheat which is a traditional grain in China. We examined nine genotypes and found that 30 µM of Cd reduced the root length in seedlings by between 4 and 44% and decreased the total biomass by 7 to 31%, compared with Cd-free controls. We identified a significant genotypic variation in sensitivity to Cd stress. Cd treatment decreased the total root length and the emergence and growth of lateral roots, and these changes were significantly greater in the Cd-sensitive genotypes than in tolerant genotypes. Cd resulted in greater wilting and discoloration in sensitive genotypes than in tolerant genotypes and caused more damage to the structure of root and leaf cells. Cd accumulated in the roots and shoots, but the concentrations in the sensitive genotypes were significantly greater than in the more tolerant genotypes. Cd treatment affected nutrient uptake, and the changes in the sensitive genotypes were greater than those in the tolerant genotypes, which could maintain their concentrations closer to the control levels. The induction of SOD, POD, and CAT activities in the roots and shoots was significantly greater in the tolerant genotypes than in the sensitive genotypes. We demonstrated that Cd stress reduced root and shoot growth, decreased plant biomass, disrupted nutrient uptake, altered cell structure, and managed Cd-induced oxidative stress differently in the sensitive and tolerant genotypes of Tartary buckwheat.

Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney, and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways.

BACKGROUND: Jianpi Gushen Huayu Decoction (JPGS) has been used to clinically treat diabetic nephropathy (DN) for many years. However, the protective mechanism of JPGS in treating DN remains unclear. AIM: To evaluate the therapeutic effects and the possible mechanism of JPGS on DN. METHODS: We first evaluated the therapeutic potential of JPGS on a DN mouse model. We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics. Furthermore, we examined the effects of JPGS on c-Jun N-terminal kinase (JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3). RESULTS: The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress. Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice. A total of 51 differential metabolites were screened. Pathway analysis results indicated that nine pathways significantly changed between the control and model groups, while six pathways significantly altered between the model and JPGS groups. Pathways related to cysteine and methionine metabolism; alanine, tryptophan metabolism; aspartate and glutamate metabolism; and riboflavin metabolism were identified as the key pathways through which JPGS affects DN. Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors. CONCLUSION: JPGS could markedly treat mice with streptozotocin (STZ)-induced DN, which is possibly related to the regulation of several metabolic pathways found in kidneys. Furthermore, JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathway-mediated apoptosis in DN mice.

Ginsenoside Rd Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Inflammation and Apoptosis through PI3K/Akt Signaling Pathway.

Myocardial ischemia/reperfusion (I/R) injury is the leading cause of death worldwide. Ginsenoside Rd (GRd) has cardioprotective properties but its efficacy and mechanism of action in myocardial I/R injury have not been clarified. This study investigated GRd as a potent therapeutic agent for myocardial I/R injury. Oxygen-glucose deprivation and reperfusion (OGD/R) and left anterior descending (LAD) coronary artery ligation were used to establish a myocardial I/R injury model in vitro and in vivo. In vivo, GRd significantly reduced the myocardial infarct size and markers of myocardial injury and improved the cardiac function in myocardial I/R injury mice. In vitro, GRd enhanced cell viability and protected the H9c2 rat cardiomyoblast cell line from OGD-induced injury GRd. The network pharmacology analysis predicted 48 potential targets of GRd for the treatment of myocardial I/R injury. GO and KEGG enrichment analysis indicated that the cardioprotective effects of GRd were closely related to inflammation and apoptosis mediated by the PI3K/Akt signaling pathway. Furthermore, GRd alleviated inflammation and cardiomyocyte apoptosis in vivo and inhibited OGD/R-induced apoptosis and inflammation in cardiomyocytes. GRd also increased PI3K and Akt phosphorylation, suggesting activation of the PI3K/Akt pathway, whereas LY294002, a PI3K inhibitor, blocked the GRd-induced inhibition of OGD/R-induced apoptosis and inflammation in H9c2 cells. The therapeutic effect of GRd in vivo and in vitro against myocardial I/R injury was primarily dependent on PI3K/Akt pathway activation to inhibit inflammation and cardiomyocyte apoptosis. This study provides new evidence for the use of GRd as a cardiovascular drug.

Jian-Pi-Gu-Shen-Hua-Yu Decoction Alleviated Diabetic Nephropathy in Mice through Reducing Ferroptosis.

Background: Diabetic nephropathy (DN), one of the most frequent complications of diabetes mellitus, is a leading cause of end-stage renal disease. However, the current treatment methods still cannot effectively halt the progression of DN. Jian-Pi-Gu-Shen-Hua-Yu (JPGS) decoction can be used for the treatment of chronic kidney diseases such as DN, but the specific mechanism of action has not been fully elucidated yet. Purpose: The aim of this study is to clarify whether JPGS alleviates the progression of diabetic nephropathy by inhibiting ferroptosis. Materials and Methods: We established a DN mouse model to investigate the therapeutic effect of JPGS in a DN mouse model. Subsequently, we examined the effects of JPGS on ferroptosis- and glutathione peroxidase 4 (GPX4) pathway-related indices. Finally, we validated whether JPGS inhibited ferroptosis in DN mice via the GPX4 pathway using GPX4 inhibitor and ferroptosis inhibitors. Results: The results indicate that JPGS has a therapeutic effect on DN mice by improving kidney function and reducing inflammation. Additionally, JPGS treatment decreased iron overload and oxidative stress levels while upregulating the expression of GPX4 pathway-related proteins. Moreover, JPGS demonstrated a similar therapeutic effect as Fer-1 in the context of DN treatment, and RSL3 was able to counteract the therapeutic effect of JPGS and antiferroptotic effect. Conclusion: JPGS has significant therapeutic and anti-inflammatory effects on DN mice, and its mechanism is mainly achieved by upregulating the expression of GPX4 pathway-related proteins, thereby alleviating iron overload and ultimately reducing ferroptosis.

Identification and Fungicide Screening of Fungal Species Associated with Walnut Anthracnose in Shaanxi and Liaoning Provinces, China.

Walnut is cultivated around the world for its precious woody nut and edible oil. Recently, walnut infected by Colletotrichum spp. resulted in a great yield and quality loss. In August and September 2014, walnut fruits with anthracnose were sampled from two commercial orchards in Shaanxi and Liaoning provinces, and five representative isolates were used in this study. To identify the pathogen properly, four genes per region (internal transcribed spacer, glyceraldehyde-3-phosphate dehydrogenase, actin, and chitin synthase) were sequenced and used in phylogenetic studies. Based on multilocus phylogenetic analysis, five isolates clustered with Colletotrichum fioriniae, including its ex-type, with 100% bootstrap support. The results of multilocus phylogenetic analyses, morphology, and pathogenicity confirmed that C. fioriniae was one of the walnut anthracnose pathogens in China. All 13 fungicides tested inhibited mycelial growth and spore germination. Flusilazole, fluazinam, prochloraz, and pyraclostrobin showed the strongest suppressive effects on the mycelial growth than the others, the average EC50 values ranged from 0.09 to 0.40 µg/ml, and there was not any significant difference (P < 0.05). Pyraclostrobin, thiram, and azoxystrobin were the most effective fungicides on spore germination (P < 0.05), and the EC50 values ranged from 0.01 to 0.44 µg/ml. Pyraclostrobin, azoxystrobin, fluazinam, flusilazole, mancozeb, thiram, and prochloraz exhibited a good control effect on walnut anthracnose caused by C. fioriniae, and preventive activities were greater than curative activities. Pyraclostrobin at 250 a.i. µg/ml and fluazinam at 500 a.i. µg/ml provided the highest preventive and curative efficacy, and the values ranged from 81.3 to 82.2% and from 72.9 to 73.6%, respectively. As a consequence, mancozeb and thiram could be used at the preinfection stage, and pyraclostrobin, azoxystrobin, flusilazole, fluazinam, and prochloraz could be used at the early stage for effective prevention and control of walnut anthracnose caused by C. fioriniae. The results will provide more significant instructions for controlling the disease effectively in northern China.

Overexpression of IlHMA2, from Iris lactea, Improves the Accumulation of and Tolerance to Cadmium in Tobacco.

Long-distance transport cadmium (Cd) from roots to shoots is a key factor for Cd phytoremediation. Our previous study indicated that heavy metal P1B2-ATPases, IlHMA2, was involved in improving the accumulation of Cd via mediated long-distance transport Cd, contributing to the phytoremediation in Cd accumulator Iris lactea. However, whether the overexpression of IlHMA2 could enhance the accumulation and tolerance to Cd remains unclear in plants. Here, we generated transgenic tobacco overexpressing IlHMA2 and tested its effect on the translocation and accumulation of Cd and zinc (Zn), as well as the physio-biochemical characteristics under 50 mg/L Cd exposure. The overexpression of IlHMA2 significantly increased Cd concentrations in xylem saps, resulting in enhanced root-to-shoot Cd translocation compared with wild-type. Meanwhile, overexpressing IlHMA2 promoted Zn accumulations, accompanied by elevating proline contents and antioxidant enzyme activity (SOD, POD, and CAT) to diminish the overproduction of ROS in transgenic tobacco. These pieces of evidence suggested that higher Zn concentrations and lower ROS levels could tremendously alleviate Cd toxicity for transgenic tobacco, thereby improving the growth and tolerance. Overall, the overexpression of IlHMA2 could facilitate Cd accumulation and enhance its tolerance in tobacco exposed to Cd contaminations. This would provide a valuable reference for improving Cd phytoremediation efficiency.

Reduced 2,4-dienoyl-CoA reductase 1 is served as an unfavorable biomarker and is related to immune infiltration in cervical cancer.

BACKGROUND: Worldwide, cervical cancer (CC) remains the most prevalent malignancy of the female reproductive system, posing a threat to women's life and health, and increasing the medical and economic burden on society. Therefore, the search for tumor biomarkers for CC remains an important research direction. Immunotherapy has significantly improved patient outcomes, and genes related to tumor immune infiltration have been clinically relevant and highly reproducible biomarkers that affect the prognosis and response to treatment of CC. 2,4-dienoyl-CoA reductase 1 (DECR1) was considered to be an oncogene in a previous study, but relationship between DECR1 and immune infiltration was not mentioned. Our study aimed to reveal the clinical value of DECR1 in CC and to investigate its relationship with immune infiltration. METHODS: Human Protein Atlas was used to identify the localization of DECR1. The Ualcan database, TCGA, and IHC were used to assess the prognostic value of DECR1. GSEA was used to assess the possible signaling pathways of DECR1 in CC. The TIMER database was applied to reveal the relevance between DECR1 and immune infiltration. GEPIA was conducted to detect the co-relationship among DECR1, immune markers, and typical molecules of apoptosis. RESULTS: DECR1 was mainly distributed in the cytoplasm and overlapped with the endoplasmic reticulum. DECR1 was downregulated in CC compared to adjacent tissue. Survival analysis showed that patients with lower expression of DECR1 have a worse prognosis in CC. GSEA suggested that DECR1 was closely related to apoptosis signaling. TIMER showed that DECR1 was positively correlated with CD8+ T cell and CD4+ T cell but not with B cell in CC. CONCLUSION: DECR1 may be a potential cancer suppressor in CC and may be involved in apoptotic pathways and associated with immune infiltration.

San-Huang-Yi-Shen capsule ameliorates diabetic nephropathy in mice through inhibiting ferroptosis.

Diabetic nephropathy (DN) is one of the main complications of diabetes. However, effective therapy to block or slow down the progression of DN is still lacking. San-Huang-Yi-Shen capsule (SHYS) has been shown to significantly improve renal function and delay the progression of DN. However, the mechanism of SHYS on DN is still unclear. In this study, we established a mouse model of DN. Then, we investigated the anti-ferroptotic effects of SHYS including the reduction of iron overload and the activation of cystine/GSH/GPX4 axis. Finally, we used a GPX4 inhibitor (RSL3) and ferroptosis inhibitor (ferrostatin-1) to determine whether SHYS ameliorates DN through inhibiting ferroptosis. The results showed that SHYS treatment was effective for mice with DN in terms of improving renal function, and reducing inflammation and oxidative stress. Besides, SHYS treatment reduced iron overload and upregulated the expression of cystine/GSH/GPX4 axis-related factors in kidney. Moreover, SHYS exhibited similar therapeutic effect on DN as ferrostatin-1, RSL3 could abolish the therapeutic and anti- ferroptotic effects of SHYS on DN. In conclusion, SHYS can be used to treat mice with DN. Furthermore, SHYS could inhibit ferroptosis in DN through reducing iron overload and upregulating the expression of cystine/GSH/GPX4 axis.

Promoted dissipation and detoxification of atrazine by graphene oxide coexisting in water.

The herbicide atrazine (ATZ) has a detrimental effect on the health of aquatic ecosystems and has become a global concern in recent years. But the understanding of its persistence and potential toxicity under combined pollution, especially in the coexistence of other emerging pollutants, remains limited. In this work, the dissipation and transformation of ATZ in combination with graphene oxide (GO) in water were investigated. Results showed that dissipation rates of ATZ dramatically increased by 15-95% with half-lives shortened by 15-40% depending on initial concentrations of ATZ, and the products were mainly toxic chloro-dealkylated intermediates (deethylatrazine (DEA) and deisopropylatrazine (DIA)), but their contents were significantly lower under the coexistence of GO compared to ATZ alone. In the presence of GO, the nontoxic dechlorinated metabolite hydroxyatrazine (HYA) was detected earlier than 2-9 days, and ATZ transformation into HYA was increased by 6-18% during 21-day incubation periods. This study indicated that the coexistence of GO enhanced the dissipation and detoxification of ATZ. From a remediation standpoint, GO-induced hydrolytic dechlorination of ATZ can reduce its ecological toxicity. But the environmental risks of ATZ for aquatic ecosystem under the coexistence of GO should still be given the necessary prominence due to the potential hazard of ATZ adsorbed on GO and the predominant degradation products (DEA and DIA).

RTP4, a Biomarker Associated with Diagnosing Pulmonary Tuberculosis and Pan-Cancer Analysis.

Background: Pulmonary tuberculosis (PTB) is a global epidemic of infectious disease; the purpose of our study was to explore new potential biomarkers for the diagnosis of pulmonary tuberculosis and to use the biomarkers for further pan-cancer analysis. Methods: Four microarray gene expression sets were downloaded from the GEO public databases and conducted for further analysis. Healthy control (HC) samples and samples of pulmonary tuberculosis (PTB) were calculated with enrichment scores in folate biosynthesis pathways. The scores acted as a new phenotype combined with clinical information (control or PTB) for subsequent analysis. Weight gene coexpression network analysis (WGCNA) was used to seek the modules mostly related to PTB and folate biosynthesis in training sets. Twenty-nine coexistence genes were screened by intersecting the genes in the green-yellow module of GSE28623 and the brown module of GSE83456. We used the protein-protein interaction network analysis to narrow the gene range to search for hub genes. Then, we downloaded the unified and standardized pan-cancer data set from the UCSC database for correlations between biomarkers and prognosis and tumor stage differences. Results: Eventually, RTP4 was selected as a biomarker. To verify the reliability of this biomarker, an area under the ROC (AUC) was calculated in gene sets (GSE28623, GSE83456, and GSE34608). Lastly, to explore the difference in RTP4 expression before and after antituberculosis treatment, the GSE31348 gene set was enrolled to compare the expressions in weeks 0 and 26. The results showed significant differences between these two time points (p < 0.001). RTP4 was significantly upregulated in the pulmonary tuberculosis group compared to the healthy control group in three gene sets and downregulated after antituberculosis therapy in one gene set. These results suggest that RTP4 can be used as a potential biomarker in diagnosing tuberculosis. The results of pan-cancer analysis showed that high expression of RTP4 in 4 tumor types was positively correlated with poor prognosis and high expression of RTP4 in 6 tumor types was negatively correlated with poor prognosis. We found significant differences in the expression of the RTP4 gene at different stages in 5 types of tumors. Conclusion: RTP4 might be a new potential biomarker for diagnosing pulmonary tuberculosis.

Effects of Graphene Oxide on the Growth and Photosynthesis of the Emergent Plant Iris pseudacorus.

The extensive applications of graphene oxide (GO) inevitably lead to entry into the natural aquatic environment. However, information on its toxicity to emergent plants is still lacking. In this study, an emergent plant, Iris pseudacorus, was exposed to GO (1, 20, 80, and 140 mg·L-1) under hydroponic conditions for 15 weeks. Changes in plant growth were assessed by analyzing plant biomass and photosynthetic pigment contents; the photosynthesis response was verified by measuring chlorophyll a fluorescence; and the nutrient levels of the plant were evaluated. Results showed that GO at 20-140 mg·L-1 significantly increased plant dry weight by 37-84% and photosynthetic pigment contents by 26-178%, and 80 mg·L-1 was the optimal concentration. PSII activity, adjustment capacities of electron transport in PSII, the grouping or energetic connectivity between PSII units, light energy conversion efficiency, photosynthesis performance indexes (by 11-51%), and contents of several nutrient elements (N, Fe, and Cu) were increased by 49-69%, 34-84%, and 11-38%, respectively. These findings indicate that GO can enhance plant growth by promoting plant photosynthesis performance and improving plant nutrient levels, and has great application potential in promoting the growth and development of this emergent plant as a phytoremediation agent.

Salt Restriction and Angiotensin-Converting Enzyme Inhibitor Improve the Responsiveness of the Small Artery in Salt-Sensitive Hypertension.

For salt-sensitive hypertension (SSH), salt restriction and angiotensin-converting enzyme (ACE) inhibitors are essential treatments, but their effect on the function of resistance arteries is unclear. Here, we present an intravital study to detect the effect of salt restriction and ACE inhibitors on the function of the mesenteric small artery (MSA) in SSH. Dahl salt-sensitive rats were randomized into the following groups: ACE inhibitor gavage, salt restriction, ACE inhibitor combined with salt restriction, and high-salt diet. After a 12-week intervention, the mesenteric vessels maintained their perfusion in vivo, and the changes in the diameter and blood perfusion of the MSAs to norepinephrine (NE) and acetylcholine (ACh) were detected. Switching from a high-salt diet to a low-salt diet (i.e., salt restriction) attenuated the vasoconstriction of the MSAs to NE and promoted the vasodilatation to ACh, while ACE inhibitor improved the vasodilatation more obviously. Pathologically, changes in local ACE, AT1R, and eNOS expression were involved in these processes induced by a high-salt diet. Our study suggests that salt restriction and ACE inhibitor treatment improve high salt intake-induced MSA dysfunction in SSH, and salt restriction is a feasible and effective treatment. Our findings may provide a scientific basis for the treatment of hypertension.

First report of jujube anthracnose caused by Colletotrichum siamense in China.

Jujube (Zizyphus jujuba Mill.), a native small deciduous tree of China, is widely cultivated in China, Korea, India, Japan, Europe, and the United States (Chen et al. 2020). The fruit have been commonly consumed as healthy food supplements and traditional Chinese medicine for over 2000 years (Li et al. 2007). In August 2019, anthracnose-like leaf spot symptoms were observed on jujube plants in Xiaomenya Village, Jinan City, Shandong Province, China (36°27'39″N, 117°3'13″E), with over 30% leaf disease incidence. The spots were circular, sunken, brown in the center and with dark brown edges. As the spots enlarged and coalesced, it resulted in leaf perforation and early defoliation. Sometimes acervuli were observed on the lesions (Fig. S1a, b). To identify the causal agent, 20 diseased leaves were sampled, the margins of the lesions were cut into pieces (5 × 5 mm), sterilized and cultured following the protocol described previously (Wan et al. 2020) at 25 ℃ for 5 days. Twelve monospore isolates showing identical colony morphology were obtained. Three representative isolates, JNZG11, JNZG311, JNZG313, were used for further study. When grown on PDA the colony color was initially white and then turned pale-gray to gray in 5-day-old cultures. On the reverse, colonies were brown-black with an orange pigmentation near the center. Aerial mycelium was cottony, dense, white to pale-gray. Conidia were hyaline, 1-celled, smooth-walled, subcylindrical, oblong, attenuated with slightly rounded ends, (11.1-) 12.7-13.3 (-17.8) ×(-4.4) 5.2-5.5 (-6.3) µm (n=50). Appressoria were dark-brown, oval or irregular, (7.3-) 8.6-9.2 (-9.8) ×(-5.1) 5.8-6.9 (-7.0) µm (n=50) (Fig. S1c-g). The morphology resembled those of Colletotrichum gloeosporioides species complex (Cannon et al. 2012). For accurate identification, the sequences of the ribosomal internal transcribed spacer (ITS), actin (ACT), ß-tub2 (TUB2), calmodulin (CAL), chitin synthase (CHS-1), and glyceraldehyde-3phosphate dehydrogenase (GAPDH) of the 3 isolates were sequenced (Weir et al. 2012), and deposited into GenBank (Accession Nos. see Table 1). The six loci (ITS, GAPDH, ACT, CHS-1, CAL, and TUB2) were concatenated and the aligned sequences (1904 bp) were 99.7% homologous to ex-type C. siamense ICMP18578. The sequences of 38 Colletotrichum species (44 isolates) were downloaded from GenBank for phylogenetic analyses. In the maximum likelihood phylogenetic tree generated, the highest log likelihood was -8798.90 and the three isolates were all in the C. siamense clade (bootstrap support 94 %) (Fig. S2). To complete Koch's postulates, 60 healthy, mature jujube leaves on 12 branches (5 leaves per branch) (variety 'Zhongqiuhong') were inoculated with 20 µL of spore suspension (106 conidia/mL) or sterile water as a control. The branches were placed in sterile beakers containing a small amount of sterile water sealed with plastic wrap and maintained at 28 °C, 12 h light/dark. Five days after inoculation, all treated leaves showed the typical anthracnose symptom, similar to that observed in the field (Fig. S1h). The same fungus was re-isolated from the margins of the lesions using the aforementioned methods. Whereas no fungus were isolated from the controls. Previously, C. siamense has been reported to infect Z. mauritiana in China (Shu et al. 2020). To our knowledge, this is the first report of C. siamense causing anthracnose on Z. jujuba in China. This finding provides crucial information for the effective management of this disease.

Potential therapeutic value of necroptosis inhibitor for the treatment of COVID-19.

The coronavirus disease 2019 (COVID-19), caused by a novel virus of the beta-coronavirus genus (SARS-CoV-2), has spread rapidly, posing a significant threat to global health. There are currently no drugs available for effective treatment. Severe cases of COVID-19 are associated with hyperinflammation, also known as cytokine storm syndrome. The reduce inflammation are considered promising treatments for COVID-19. Necroptosis is a type of programmed necrosis involved in immune response to viral infection, and severe inflammatory injury. Inhibition of necroptosis is pivotal in preventing associated inflammatory responses. The expression of key regulators of the necroptosis pathway is generally up-regulated in COVID-19, indicating that the necroptosis pathway is activated. Thus, necroptosis inhibitors are expected to be novel therapeutic candidates for the treatment of COVID-19.Better knowledge of the necroptosis pathway mechanism is urgently required to solve the remaining mysteries surrounding the role of necroptosis in COVID-19. In this review, we briefly introduce the pathogenesis of necroptosis, the relationship between necroptosis, cytokine storm, and COVID-19 also summarizes the progress of inhibitors of necroptosis. This research provides a timely and necessary suggest of the development of necroptosis inhibitors to treat COVID-19 and clinical transformation of inhibitors of necroptosis.

Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial-mesenchymal transition in clear-cell renal cell carcinoma.

RUNX3 is a transcription factor and tumor suppressor that is silenced or inactivated in diverse tumors. The effect of RUNX3 on the epithelial-mesenchymal transition in clear-cell renal cell carcinoma (CCRCC) remains unclear. We determined the expression of RUNX3 and E-cadherin in tumor tissues and adjacent normal tissues of 30 CCRCC patients; established cultured CCRCC cells with the overexpression of RUNX3; and examined the in vivo tumorigenic function of RUNX3 in a nude mouse xenograft model of CCRCC. RUNX3 and E-cadherin were downregulated in human CCRCC samples. Cell lines with RUNX3 overexpression had reduced cell proliferation, invasion, and migration, a prolonged cell cycle, increased apoptosis, and increased expression of E-cadherin. In the nude mouse xenograft model of CCRCC, tumors with the overexpression of RUNX3 had smaller volumes and weights and had increased expression of E-cadherin. In conclusion, RUNX3 overexpression increased the level of E-cadherin and inhibited the proliferation, invasion, and migration of CCRCC in vitro and in vivo. RUNX3 has potential use as a biomarker for prognostic monitoring of CCRCC and as a therapeutic target for the treatment of this cancer.

On the Quantization of AB Phase in Nonlinear Systems.

Self-intersecting energy band structures in momentum space can be induced by nonlinearity at the mean-field level, with the so-called nonlinear Dirac cones as one intriguing consequence. Using the Qi-Wu-Zhang model plus power law nonlinearity, we systematically study in this paper the Aharonov-Bohm (AB) phase associated with an adiabatic process in the momentum space, with two adiabatic paths circling around one nonlinear Dirac cone. Interestingly, for and only for Kerr nonlinearity, the AB phase experiences a jump of π at the critical nonlinearity at which the Dirac cone appears and disappears (thus yielding π-quantization of the AB phase so long as the nonlinear Dirac cone exists), whereas for all other powers of nonlinearity, the AB phase always changes continuously with the nonlinear strength. Our results may be useful for experimental measurement of power-law nonlinearity and shall motivate further fundamental interest in aspects of geometric phase and adiabatic following in nonlinear systems.

San-Huang-Yi-Shen Capsule Ameliorates Diabetic Kidney Disease through Inducing PINK1/Parkin-Mediated Mitophagy and Inhibiting the Activation of NLRP3 Signaling Pathway.

San-Huang-Yi-Shen capsule (SHYS) has been used in the treatment of diabetic kidney disease (DKD) in clinics. However, the mechanism of SHYS on DKD remains unclear. In this study, we used a high-fat diet combined with streptozocin (STZ) injection to establish a rat model of DKD, and different doses of SHYS were given by oral gavage to determine the therapeutic effects of SHYS on DKD. Then, we studied the effects of SHYS on PINK1/Parkin-mediated mitophagy and the activation of NLRP3 inflammasome to study the possible mechanisms of SHYS on DKD. Our result showed that SHYS could alleviate DKD through reducing the body weight loss, decreasing the levels of fasting blood glucose (FBG), and improving the renal function, insulin resistance (IR), and inhibiting inflammatory response and oxidative stress in the kidney. Moreover, transmission electron microscopy showed SHYS treatment improved the morphology of mitochondria in the kidney. In addition, western blot and immunoflourescence staining showed that SHYS treatment induced the PINK1/Parkin-mediated mitophagy and inhibited the activation of NLRP3 signaling pathway. In conclusion, our study demonstrated the therapeutic effects of SHYS on DKD. Additionally, our results indicated that SHYS promoted PINK1/Parkin-mediated mitophagy and inhibited NLRP3 inflammasome activation to improve mitochondrial injury and inflammatory responses.

Thoracoscopic Clockwise Lobectomy May Be a Stylized Procedure for Treating Children with Congenital Lung Malformations.

Background: Thoracoscopic lobectomy is a challenging procedure in children with congenital lung malformations (CLMs). This study aims to evaluate the safety and efficacy of thoracoscopic clockwise lobectomy (TCL) in CLMs in children and its potential to be a stylized procedure. Methods: All patients with CLMs who received TCL from 2015 to 2019 in our hospital were retrospectively reviewed. Clinical information was extracted from medical records, including patient demographics, operative details, and outcomes. Results: A total of 184 patients with a median age of 6.8 months (range, 3-156) and a median weight of 9 kg (range, 6-45) received TCL. Lesions were all located in the lower lobe and included congenital pulmonary airway malformation (n = 133), intralobar sequestration (n = 44), bronchiectasis (n = 4), and congenital lobar emphysema (n = 3). The mean (±standard deviation [SD]) operating time was 46 ± 7.5 minutes (range, 35-113). The mean (±SD) blood loss was 3.5 ± 0.8 mL (range, 1-60). Three patients converted to thoracotomy, and 162 patients did not have a chest tube placed. The postoperative course was uneventful in all patients except 2 patients who developed air leaks and 23 patients who developed a mild fever. The median length of postoperative hospital stay was 2 days. A total of 163 patients were followed up for more than 1 year without any complications. Conclusion: TCL is suitable for lower lobectomy and is safe and effective in standard and complicated thoracoscopic lobectomy. It could be recommended as a stylized procedure in treating children with CLMs.

ROS scavenging and ion homeostasis is required for the adaptation of halophyte Karelinia caspia to high salinity.

The halophyte Karelinia caspia has not only fodder and medical value but also can remediate saline-alkali soils. Our previous study showed that salt-secreting by salt glands is one of main adaptive strategies of K. caspia under high salinity. However, ROS scavenging, ion homeostasis, and photosynthetic characteristics responses to high salinity remain unclear in K. caspia. Here, physio-biochemical responses and gene expression associated with ROS scavenging and ions transport were tested in K. caspia subjected to 100-400 mM NaCl for 7 days. Results showed that both antioxidant enzymes (SOD, APX) activities and non-enzymatic antioxidants (chlorogenic acid, α-tocopherol, flavonoids, polyamines) contents were significantly enhanced, accompanied by up-regulating the related enzyme and non-enzymatic antioxidant synthesis gene (KcCu/Zn-SOD, KcAPX6, KcHCT, KcHPT1, Kcγ-TMT, KcF3H, KcSAMS and KcSMS) expression with increasing concentrations of NaCl. These responses are beneficial for removing excess ROS to maintain a stable level of H2O2 and O2 - without lipid peroxidation in the K. caspia response to high salt. Meanwhile, up-regulating expression of KcSOS1/2/3, KcNHX1, and KcAVP was linked to Na+ compartmentalization into vacuoles or excretion through salt glands in K. caspia. Notably, salt can improve the function of PSII that facilitate net photosynthetic rates, which is helpful to growing normally in high saline. Overall, the findings suggested that ROS scavenging systems and Na+/K+ transport synergistically contributed to redox equilibrium, ion homeostasis, and the enhancement of PSII function, thereby conferring high salt tolerance.

Activated platelet membrane nanovesicles recruit neutrophils to exert the antitumor efficiency.

Platelets play a crucial role in the recruitment of neutrophils, mediated by P-selectin, CCL5, and ICAM-2. In this study, we prepared platelet membrane nanovesicles from activated platelets. Whether activated platelet membrane nanovesicles can recruit neutrophils has not been reported, nor has their role in antitumor immunity. The results of SDS-PAGE showed that the platelet membrane nanovesicles retained almost all the proteins of platelets. Western blotting showed that both the activated platelets and the platelet membrane nanovesicles expressed P-selectin, ICAM-2, and CCL5. In vivo results of a mouse model of breast cancer-transplanted tumor showed that tumor volume reduced significantly, Ki-67-positive tumor cells decreased, and TUNEL-positive tumor cells increased in tumors after treatment with activated platelet membrane nanovesicles (aPNs). After treatment with aPNs, not only the number of neutrophils, CD8+, CD4+ T cells, and B cells increased, but also IL-12, TNF-α, and IFN-γ levels elevated significantly in tumor tissues.