Parkinson's disease-risk protein TMEM175 is a proton-activated proton channel in lysosomes.

Lysosomes require an acidic lumen between pH 4.5 and 5.0 for effective digestion of macromolecules. This pH optimum is maintained by proton influx produced by the V-ATPase and efflux through an unidentified "H+ leak" pathway. Here we show that TMEM175, a genetic risk factor for Parkinson's disease (PD), mediates the lysosomal H+ leak by acting as a proton-activated, proton-selective channel on the lysosomal membrane (LyPAP). Acidification beyond the normal range potently activated LyPAP to terminate further acidification of lysosomes. An endogenous polyunsaturated fatty acid and synthetic agonists also activated TMEM175 to trigger lysosomal proton release. TMEM175 deficiency caused lysosomal over-acidification, impaired proteolytic activity, and facilitated α-synuclein aggregation in vivo. Mutational and pH normalization analyses indicated that the channel's H+ conductance is essential for normal lysosome function. Thus, modulation of LyPAP by cellular cues may dynamically tune the pH optima of endosomes and lysosomes to regulate lysosomal degradation and PD pathology.

Usp14 deficiency removes α-synuclein by regulating S100A8/A9 in Parkinson's disease.

Ubiquitin-proteasome system dysfunction triggers α-synuclein aggregation, a hallmark of neurodegenerative diseases, such as Parkinson's disease (PD). However, the crosstalk between deubiquitinating enzyme (DUBs) and α-synuclein pathology remains unclear. In this study, we observed a decrease in the level of ubiquitin-specific protease 14 (USP14), a DUB, in the cerebrospinal fluid (CSF) of PD patients, particularly females. Moreover, CSF USP14 exhibited a dual correlation with α-synuclein in male and female PD patients. To investigate the impact of USP14 deficiency, we crossed USP14 heterozygous mouse (USP14+/-) with transgenic A53T PD mouse (A53T-Tg) or injected adeno-associated virus (AAV) carrying human α-synuclein (AAV-hα-Syn) in USP14+/- mice. We found that Usp14 deficiency improved the behavioral abnormities and pathological α-synuclein deposition in female A53T-Tg or AAV-hα-Syn mice. Additionally, Usp14 inactivation attenuates the pro-inflammatory response in female AAV-hα-Syn mice, whereas Usp14 inactivation demonstrated opposite effects in male AAV-hα-Syn mice. Mechanistically, the heterodimeric protein S100A8/A9 may be the downstream target of Usp14 deficiency in female mouse models of α-synucleinopathies. Furthermore, upregulated S100A8/A9 was responsible for α-synuclein degradation by autophagy and the suppression of the pro-inflammatory response in microglia after Usp14 knockdown. Consequently, our study suggests that USP14 could serve as a novel therapeutic target in PD.

Machine learning-based identification of a cell death-related signature associated with prognosis and immune infiltration in glioma.

Accumulating evidence suggests that a wide variety of cell deaths are deeply involved in cancer immunity. However, their roles in glioma have not been explored. We employed a logistic regression model with the shrinkage regularization operator (LASSO) Cox combined with seven machine learning algorithms to analyse the patterns of cell death (including cuproptosis, ferroptosis, pyroptosis, apoptosis and necrosis) in The Cancer Genome Atlas (TCGA) cohort. The performance of the nomogram was assessed through the use of receiver operating characteristic (ROC) curves and calibration curves. Cell-type identification was estimated by using the cell-type identification by estimating relative subsets of known RNA transcripts (CIBERSORT) and single sample gene set enrichment analysis methods. Hub genes associated with the prognostic model were screened through machine learning techniques. The expression pattern and clinical significance of MYD88 were investigated via immunohistochemistry (IHC). The cell death score represents an independent prognostic factor for poor outcomes in glioma patients and has a distinctly superior accuracy to that of 10 published signatures. The nomogram performed well in predicting outcomes according to time-dependent ROC and calibration plots. In addition, a high-risk score was significantly related to high expression of immune checkpoint molecules and dense infiltration of protumor cells, these findings were associated with a cell death-based prognostic model. Upregulated MYD88 expression was associated with malignant phenotypes and undesirable prognoses according to the IHC. Furthermore, high MYD88 expression was associated with poor clinical outcomes and was positively related to CD163, PD-L1 and vimentin expression in the in-horse cohort. The cell death score provides a precise stratification and immune status for glioma. MYD88 was found to be an outstanding representative that might play an important role in glioma.

BeEAM vs. BEAM: evaluating conditioning regimens for autologous stem cell transplantation in patients with relapsed or refractory DLBCL.

PURPOSE: To evaluate whether BeEAM is an alternative to BEAM for autologous stem cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). METHODS: Data of 60 patients with relapsed or refractory DLBCL who underwent ASCT from January 2018 to June 2023 in our center, including 30 patients in the BeEAM group and 30 patients in the BEAM group, were retrospectively analyzed. The time to hematopoietic reconstitution, treatment-related adverse events, number of hospitalization days, hospitalization cost, and survival benefit were compared between the two groups. RESULTS: The clinical characteristics of the patients did not significantly differ between the two groups. The median number of reinfused CD34 + cells was 5.06 × 106/kg and 5.17 × 106/kg in the BeEAM and BEAM groups, respectively, which did not significantly different (p = 0.8829). In the BeEAM and BEAM groups, the median time to neutrophil implantation was 10.2 and 10.27 days, respectively (p = 0.8253), and the median time to platelet implantation was 13.23 and 12.87 days, respectively (p = 0.7671). In the BeEAM and BEAM groups, the median hospitalization duration was 30.37 and 30.57 days, respectively (p = 0.9060), and the median hospitalization cost was RMB 83,425 and RMB 96,235, respectively (p = 0.0560). The hospitalization cost was lower in the BeEAM group. The most common hematologic adverse events were grade ≥ 3 neutropenia and thrombocytopenia, whose incidences were similar in the two groups. The most common non-hematologic adverse events were ≤ grade 2 and the incidences of these events did not significantly differ between the two groups. Median overall survival was not reached in either group, with predicted 5-year overall survival of 72.5% and 60% in the BeEAM and BEAM groups, respectively (p = 0.5872). Five-year progression-free survival was 25% and 20% in the BeEAM and BEAM groups, respectively (p = 0.6804). CONCLUSION: As a conditioning regimen for relapsed or refractory DLBCL, BeEAM has a desirable safety profile and is well tolerated, and its hematopoietic reconstitution time, number of hospitalization days, and survival benefit are not inferior to those of BEAM. BeEAM has a lower hospitalization cost and is an alternative to BEAM.

Low-frequency repetitive transcranial magnetic stimulation alters the individual functional dynamical landscape.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive approach to modulate brain activity and behavior in humans. Still, how individual resting-state brain dynamics after rTMS evolves across different functional configurations is rarely studied. Here, using resting state fMRI data from healthy subjects, we aimed to examine the effects of rTMS to individual large-scale brain dynamics. Using Topological Data Analysis based Mapper approach, we construct the precise dynamic mapping (PDM) for each participant. To reveal the relationship between PDM and canonical functional representation of the resting brain, we annotated the graph using relative activation proportion of a set of large-scale resting-state networks (RSNs) and assigned the single brain volume to corresponding RSN-dominant or a hub state (not any RSN was dominant). Our results show that (i) low-frequency rTMS could induce changed temporal evolution of brain states; (ii) rTMS didn't alter the hub-periphery configurations underlined resting-state brain dynamics; and (iii) the rTMS effects on brain dynamics differ across the left frontal and occipital lobe. In conclusion, low-frequency rTMS significantly alters the individual temporo-spatial dynamics, and our finding further suggested a potential target-dependent alteration of brain dynamics. This work provides a new perspective to comprehend the heterogeneous effect of rTMS.

New insight into identifying sediment phosphorus sources in multi-source polluted urban river: Effect of environmental-induced microbial community succession on stability of microbial source tracking results.

Identifying sediment phosphorus sources, the key to control eutrophication, is hindered in multi-source polluted urban rivers by the lack of appropriate methods and data resolution. Community-based microbial source tracking (MST) offers new insight, but the bacterial communities could be affected by environmental fluctuations during the migration with sediments, which might induce instability of MST results. Therefore, the effects of environmental-induced community succession on the stability of MST were compared in this study. Liangxi River, a highly eutrophic urban river, was selected as the study area where sediment phosphorus sources are difficult to track because of multi-source pollution and complicated hydrodynamic conditions. Spearman correlation analysis (P < 0.05) was conducted to recognize a close relationship between sediment, bacterial communities and phosphorus, verifying the feasibility of MST for identify sediment phosphorus sources. Two distinct microbial community fingerprints were constructed based on whether excluded 113 vulnerable species, which were identified by analyzing the differences of microorganisms across a concentration gradient of exogenous phosphorus input in microbial environmental response experiment. Because of the lower unknown proportion and relative standard deviations, MST results were more stable and reliable when based on the fingerprints excluding species vulnerable to phosphorus. This study presents a novel insight on how to identify sediment phosphorus sources in multi-source polluted urban river, and would help to develop preferential control strategies for eutrophication management.

Influence of rapid vertical mixing on bacterial community assembly in stratified water columns.

Water column mixing homogenizes thermal and chemical gradients which are known to define distribution of microbial communities and influence the prevailing biogeochemical processes. Little is however known about the effects of rapid water column mixing on the vertical distribution of microbial communities in stratified reservoirs. To address this knowledge gap, physicochemical properties and microbial community composition from 16 S rRNA amplicon sequencing were analyzed before and after mixing of vertically stratified water-column bioreactors. Our results showed that α-diversity of bacterial communities decreased from bottom to surface during periods of thermal stratification. After an experimental mixing event, bacterial community diversity experienced a significant decrease throughout the water column and network connectivity was disrupted, followed by slow recovery. Significant differences in composition were seen for both total (DNA) and active (RNA) bacterial communities when comparing surface and bottom layer during periods of stratification, and when comparing samples collected before mixing and after re-stratification. The dominant predicted community assembly processes for stratified conditions were deterministic while such processes were less important during recovery from episodic mixing. Water quality characteristics of stratified water were significantly correlated with bacterial community diversity and structure. Furthermore, structural equation modeling analyses showed that changes in sulfur may have the greatest direct effect on bacterial community composition. Our results imply that rapid vertical mixing caused by episodic weather extremes and hydrological operations may have a long-term effect on microbial communities and biogeochemical processes.

Preparation of O-g-C3N4 nanowires/Bi2O2CO3 porous plate composite photocatalysts for the efficient degradation of tetracycline hydrochloride in wastewater.

Both g-C3N4 and Bi2O2CO3 are good photocatalysts for the removal of antibiotic pollutants, but their morphological modulation and catalytic performance need to be further improved. In this study, the calcination-hydrothermal method is used to prepare a O-g-C3N4@Bi2O2CO3 (CN@BCO) composite photocatalyst from dicyandiamide and bismuth nitrate. The prepared catalyst is characterized through various methods, including X-ray diffraction (XRD) and transmission electron microscopy (TEM). Further, the effects of different parameters, such as catalyst concentration and initial pH of the reaction solution, on its photocatalytic activity are investigated. The results show that the CN@BCO sample achieves an optimal degradation rate of 98.1% for tetracycline hydrochloride (TCH) with a concentration of 20 mg/L and a removal rate of 69.4% for total organic carbon (TOC) at 40 min. The quenching experiments show that ·O2-, h+, and ·OH participate in the photocatalytic process, with ·O2- being the most dominant active species. The toxicity of the predicted TCH degradation intermediates is analyzed using Toxicity Estimation Software Tool (TEST). Overall, the CN@BCO composite exhibits excellent photocatalytic performance, making it a promising candidate for environmental purification and wastewater treatment.

Dietary intake of α-ketoglutarate ameliorates α-synuclein pathology in mouse models of Parkinson's disease.

Parkinson's disease (PD) is a progressive movement disorder characterized by dopaminergic (DA) neuron degeneration and the existence of Lewy bodies formed by misfolded α-synuclein. Emerging evidence supports the benefits of dietary interventions in PD due to their safety and practicality. Previously, dietary intake of α-ketoglutarate (AKG) was proved to extend the lifespan of various species and protect mice from frailty. However, the mechanism of dietary AKG's effects in PD remains undetermined. In the present study, we report that an AKG-based diet significantly ameliorated α-synuclein pathology, and rescued DA neuron degeneration and impaired DA synapses in adeno-associated virus (AAV)-loaded human α-synuclein mice and transgenic A53T α-synuclein (A53T α-Syn) mice. Moreover, AKG diet increased nigral docosahexaenoic acid (DHA) levels and DHA supplementation reproduced the anti-α-synuclein effects in the PD mouse model. Our study reveals that AKG and DHA induced microglia to phagocytose and degrade α-synuclein via promoting C1q and suppressed pro-inflammatory reactions. Furthermore, results indicate that modulating gut polyunsaturated fatty acid metabolism and microbiota Lachnospiraceae_NK4A136_group in the gut-brain axis may underlie AKG's benefits in treating α-synucleinopathy in mice. Together, our findings propose that dietary intake of AKG is a feasible and promising therapeutic approach for PD.

Identification of potential cell death-related biomarkers for diagnosis and treatment of osteoporosis.

BACKGROUND: This study aimed to identify potential biomarkers for the diagnosis and treatment of osteoporosis (OP). METHODS: Data sets were downloaded from the Gene Expression Omnibus database, and differentially programmed cell death-related genes were screened. Functional analyses were performed to predict the biological processes associated with these genes. Least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), and random forest (RF) machine learning algorithms were used to screen for characteristic genes, and receiver operating characteristics were used to evaluate the diagnosis of disease characteristic gene values. Gene set enrichment analysis (GSEA) and single-sample GSEA were conducted to analyze the correlation between characteristic genes and immune infiltrates. Cytoscape and the Drug Gene Interaction Database (DGIdb) were used to construct the mitochondrial RNA-mRNA-transcription factor network and explore small-molecule drugs. Reverse transcription real-time quantitative PCR (RT-qPCR) analysis was performed to evaluate the expression of biomarker genes in clinical samples. RESULTS: In total, 25 differential cell death genes were identified. Among these, two genes were screened using the LASSO, SVM, and RF algorithms as characteristic genes, including BRSK2 and VPS35. In GSE56815, the area under the receiver operating characteristic curve of BRSK2 was 0.761 and that of VPS35 was 0.789. In addition, immune cell infiltration analysis showed that BRSK2 positively correlated with CD56dim natural killer cells and negatively correlated with central memory CD4 + T cells. Based on the data from DGIdb, hesperadin was associated with BRSK2, and melagatran was associated with VPS35. BRSK2 and VPS35 were expectably upregulated in OP group compared with controls (all p < 0.05). CONCLUSIONS: BRSK2 and VPS35 may be important diagnostic biomarkers of OP.

Metformin Protects Against Acute Kidney Injury Induced by Lipopolysaccharide via Up-Regulating the MCPIP1/SIRT1 Pathway.

In the present study, we aimed to explore the effect and underlying mechanism of metformin on lipopolysaccharide (LPS)-induced acute kidney injury (AKI). A total of 24 BALB/C mice were randomly divided into four groups: control group, LPS group and metformin group (50 or 100 mg/kg). The histological changes and cell apoptosis in kidney tissues were detected by hematoxylin-eosin staining and terminal-deoxynucleotidyl transferase-mediated nick end labeling assay, respectively. Enzyme-linked immunosorbent assay was applied to determine serum levels of blood urea nitrogen (BUN), kidney injury molecule-1 (Kim-1), creatinine (Cre), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß). Western blotting analysis were carried out to confirm the expressions of monocyte chemotactic protein-inducible protein 1 (MCPIP1), silent information regulator sirtuin 1 (SIRT1), and NF-κB p65 (acetyl K310). Compared with the control group, the mice in LPS group had glomerular capillary dilatation, renal interstitial edema, tubular cell damage and apoptosis. The serum levels of BUN, KIM-1, Cre, TNF-α, and IL-1ß in LPS group were significantly higher than those in control group. Moreover, LPS also elevated the expressions of MCPIP1 and NF-κB p65 (acetyl K310) but decreased the expression of SIRT1 in kidney tissues. However, metformin distinctly decreased LPS-induced renal dysfunction, the serum levels of BUN, KIM-1, Cre, TNF-α, and IL-1ß. In addition, metformin markedly increased the expressions of MCPIP1 and SIRT1 but decreased the expression of NF-κB p65 (acetyl K310) in kidney tissues. Metformin prevented LPS-induced AKI by up-regulating the MCPIP1/SIRT1 signaling pathway and subsequently inhibiting NF-κB-mediated inflammation response.

Choriocarcinoma That Had Transferred to the Right Inferior Pulmonary Vein and Left Atrium: A Case Report.

Here, we present a case of choriocarcinoma with metastasis only to the right inferior pulmonary vein and heart, which is unusual, as the skipping of lung metastasis is extremely rare. The 34-year-old patient presented with cough and hemoptysis. The diagnosis was challenging due to the absence of gynecological abnormalities and elevated ß-HCG levels, only revealing a cardiac mass upon imaging. While no abnormalities were found through gynecological ultrasound or gynecological examination, the serum human chorionic gonadotropin ß subunit (ß-HCG) level was abnormally raised. Echocardiography showed a left atrial myxoma with a size of approximately 6.3×1.81 cm. A left atrial mass resection was performed during cardiac surgery, where it was found that the left atrial mass had originated from the right inferior pulmonary vein. It was approximately 6×3×3 cm in size, with a flesh-red color and firm tissue. Postoperative pathology and immunohistochemistry indicated choriocarcinoma. The cardiac surgery unearthed a mass originating from the right inferior pulmonary vein. Its size and characteristics, along with the chemotherapy regimens that followed, are crucial details for understanding treatment approaches for such atypical cases. Highlight the patient's recovery post-treatment and the effectiveness of the chemotherapy regimen. This offers insights into the potential for successful treatment outcomes in atypical choriocarcinoma cases. The patient underwent chemotherapy regimens with etoposide, cisplatin (EP) ,etoposide, and methotrexate, and dactinomycin alternating with cyclophosphamide and vincristine (EMACO). A satisfactory result was achieved. This case enhances understanding of choriocarcinoma metastasis patterns. It underscores the need for a multidisciplinary approach in diagnosing and managing such rare presentations.

Exogenous Melatonin Enhances Dihydrochalcone Accumulation in Lithocarpus litseifolius Leaves via Regulating Hormonal Crosstalk and Transcriptional Profiling.

Dihydrochalcones (DHCs) constitute a specific class of flavonoids widely known for their various health-related advantages. Melatonin (MLT) has received attention worldwide as a master regulator in plants, but its roles in DHC accumulation remain unclear. Herein, the elicitation impacts of MLT on DHC biosynthesis were examined in Lithocarpus litseifolius, a valuable medicinal plant famous for its sweet flavor and anti-diabetes effect. Compared to the control, the foliar application of MLT significantly increased total flavonoid and DHC (phlorizin, trilobatin, and phloretin) levels in L. litseifolius leaves, especially when 100 µM MLT was utilized for 14 days. Moreover, antioxidant enzyme activities were boosted after MLT treatments, resulting in a decrease in the levels of intracellular reactive oxygen species. Remarkably, MLT triggered the biosynthesis of numerous phytohormones linked to secondary metabolism (salicylic acid, methyl jasmonic acid (MeJA), and ethylene), while reducing free JA contents in L. litseifolius. Additionally, the flavonoid biosynthetic enzyme activities were enhanced by the MLT in leaves. Multiple differentially expressed genes (DEGs) in RNA-seq might play a crucial role in MLT-elicited pathways, particularly those associated with the antioxidant system (SOD, CAT, and POD), transcription factor regulation (MYBs and bHLHs), and DHC metabolism (4CL, C4H, UGT71K1, and UGT88A1). As a result, MLT enhanced DHC accumulation in L. litseifolius leaves, primarily by modulating the antioxidant activity and co-regulating the physiological, hormonal, and transcriptional pathways of DHC metabolism.

Efficient extraction performance and mechanisms of Cd2+ and Pb2+ in water by novel dicationic ionic liquids.

Ten novel hydrophobic dicationic ionic liquids (DILs) were synthesized and applied for the extraction of heavy metals in aqueous solutions. Their physicochemical properties were measured at ambient temperature, and the leaching behaviors of the as-prepared DILs in water were assessed by TOC analysis. Metal extraction experiments were carried out to evaluate the extraction performances of the DILs. It was found that the extraction rates of up to 0.45 and 0.53 mg·(g·min)-1 were achieved with 100 mg DILs for 5 mL of 5 mg/L Cd2+ and Pb2+ solutions. Besides, the extraction efficiencies of Cd2+ and Pb2+ were respectively up to 95.48% and 98.46%, when the volumes of the simulated wastewater were expanded by a factor of 20 at a constant extraction phase ratio (1000 mg DILs for 50 mL of 5 mg/L Cd2+ or Pb2+ solutions). The reusability of the novel DILs was successfully proved by the back-extraction experiments with 0.5 M HNO3. Finally, taking Cd2+ extraction as an example, the extraction mechanism based on FTIR analysis and quantum chemical calculations showed that both S and O atoms in the anions of DILs had physical and quasi-chemical interactions with Cd2+, which were stronger than the electrostatic attraction.

Inflammation plays a critical role in damage to the bronchiolar epithelium induced by Trueperella pyogenes in vitro and in vivo.

Trueperella pyogenes can cause severe pulmonary disease in swine, but the mechanism of pathogenesis is not well defined. T. pyogenes-induced damage to porcine bronchial epithelial cells (PBECs), porcine precision-cut lung slices (PCLS), and respiratory epithelium of mice remains unknown. In this study, we used T. pyogenes 20121 to infect PBECs in air-liquid interface conditions and porcine PCLS. T. pyogenes could adhere to, colonize, and induce cytotoxic effect on PBECs and the luminal surface of bronchi in PCLS, which damaged the bronchiolar epithelium. Moreover, bronchiolar epithelial cells showed extensive degeneration in the lungs of infected mice. Furthermore, western blot showed that the NOD-like receptor (NLR)/C-terminal caspase recruitment domain (ASC)/caspase-1 axis and nuclear factor-kappa B pathway were involved in inflammation in PCLS and lungs of mice, which also confirms that porcine PCLS provide a platform to analyze the pulmonary immune response. Meanwhile, the levels of p-c-Jun N-terminal kinase, p-extracellular signal-regulated kinase, and p-protein kinase B (AKT) were increased significantly, which indicated the mitogen-activated protein kinase and Akt pathways were also involved in inflammation in T. pyogenes-infected mice. In addition, we used T. pyogenes 20121 to infect tumor necrosis factor-alpha (tnf-α-/-) mice, and the results indicated that apoptosis and injury in respiratory epithelium of infected tnf-α-/- mice were alleviated. Thus, the pro-inflammatory cytokine TNF-α played a role in apoptosis and the respiratory epithelium injury in mouse lungs. Collectively, our study provides insight into the inflammatory injury induced by T. pyogenes and suggests that blocking NLR may be a potential therapeutic strategy against T. pyogenes infection.

Engineering Low-Cost Organic Cathode for Aqueous Rechargeable Battery and Demonstrating the Proton Intercalation Mechanism for Pyrazine Energy Storage Unit.

Seeking organic cathode materials with low cost and long cycle life that can be employed for large-scale energy storage remains a significant challenge. This work has synthesized an organic compound, triphenazino[2,3-b](1,4,5,8,9,12-hexaazatriphenylene) (TPHATP), with as high as 87.16% yield. This compound has a highly π-conjugated and rigid molecular structure, which is synthesized by capping hexaketocyclohexane with three molecules of 2,3-diaminophenazine derived from low-cost o-phenylenediamine, and is used as a cathode material for assembling aqueous rechargeable zinc ion batteries. Both experiments and DFT calculations demonstrate that the redox mechanism of TPHATP is predominantly governed by H+ storage. The Zn-intercalation product of nitride-type compound, is too unstable to form in water. Moreover, the TPHATP cathode exhibits a capacity of as high as 318.3 mAh g-1 at 0.1 A g-1 , and maintained a stable capacity of 111.9 mAh g-1 at a large current density of 10 A g-1 for 5000 cycles with only a decay of 0.000512% per cycle. This study provides new insights into understanding pyrazine as an active redox group and offers a potential affordable aqueous battery system for grid-scale energy storage.

Nonmetallic Nitrogen-Doped MnO2 as Highly Efficient Oxygen Electrocatalyst for Rechargeable Zinc-Air Batteries.

Zinc-air batteries (ZABs) have been considered as one of the most promising energy storage devices to solve the problem of energy crisis and environmental pollution. In this work, we reported the synthesis of nitrogen-doped MnO2 (N-MnO2 ) to replace the noble metal electrocatalysts for air cathode in ZABs. The doped N atoms here introduced more Mn3+ and oxygen vacancies for MnO2 , enhancing charge transfer property and accelerating surface intermediate product during the oxygen reduction reaction (ORR). Hence, the best N-MnO2 achieved remarkable electrocatalytic activities towards ORR (half-wave potential of 0.797 V vs. RHE), and reversible oxygen overpotential of around 0.842 V, which is better than or comparable to the Pt/C and Mn-based catalysts reported recently. Moreover, the homemade ZABs based on N-MnO2 showed the maximum power density of 132.8 mW cm-2 and excellent cyclic stability.

Establishment of Agrobacterium-mediated transformation system to Juglans sigillata Dode 'Qianhe-7'.

An efficient genetic transformation system is of great significance for verifying gene function and improving plant breeding efficiency by gene engineering. In this study, a stable Agrobacterium mediated genetic transformation system of Juglans sigillata Dode 'Qianhe-7' was investigated using callus and negative pressure-assisted and ultrasonic-assisted transformation selection. The results showed that the axillary shoot leaves were suitable to induce callus and the callus proliferation rate could reach 516.27% when induction calli were cultured on DKW medium containing 0.5 mg L-1 indole-3-butyric acid, 1.2 mg L-1 2,4-dichlorophenoxyacetic acid and 0.5 mg L-1 kinetin for 18 d. In addition, negative pressure infection was the optimal infection method with the lowest browning rate (0.00%), high GFP conversion rate (16.67%), and better growth status. To further prove the feasibility of this genetic transformation system, the flavonol synthetase (JsFLS5) gene was successfully transformed into the into leaf-derived callus of 'Qianhe-7'. JsFLS5 expression and the content of total flavonoids in transformed callus were improved significantly compared with the untransformed callus, which proved that we had an efficient and reliable genetic transformation system using leaf-derived callus of Juglans sigillata.

Biochar alleviates the crop failure of rice production induced by low-nitrogen cultivation mode by regulating the soil microbes taxa composition.

To improve the nitrogen utilization efficiency and a series of environmental problems caused by excessive application of nitrogen fertilizer, actual agricultural production often reduced the usage ratio of nitrogen fertilizer. However, the reduction in nitrogen fertilizer not only affects the soil microenvironment but also leads to adverse effects on rice yield. Due to its unique properties, biochar can regulate soil nutrient distribution and significantly affect soil microbial community structure/functions. To further understand the effects of different levels of biochar on soil nutrient indicators, soil microorganisms and crop growth under the nitrogen-reduction condition, our experiment with four groups was set up as followed: 0%, 2.5% and 5% biochar application rates with 99 kg/hm2 nitrogen fertilizer and one control group (the actual fertilizer standard used in the field:110 kg/hm2) without no exogenous biochar supplement. The rice yield and soil nutrient indexes were observed, and the differences between groups were analyzed based on multiple comparisons. 16S ribosomal RNA and ITS sequencing were used to analyze the community structure of soil bacteria and fungi. Redundancy analysis was performed to obtain the correlation relationships between microbial community marker species, soil nutrient indexes, and rice yield. Path analysis was used to determine the mechanism by which soil nutrient indexes affect rice yield. The results showed that a higher application rate of biochar led to a significant increased trend in the soil pH, organic matter and total nitrogen content. In addition, a high concentration of biochar under nitrogen-reduction condition decreased the soil bacterial diversity but elevated the fungal diversity. Different concentrations of biochar resulted in these changes in the relative abundance of soil bacteria/fungi but did not alter the dominant species taxa. Taken together, appropriate usage for biochar under the nitrogen-reduction background could induce alteration in soil nutrient indicators, microbial communities and crop yields. These results provide a theoretical basis for exploring scientific, green and efficient fertilization strategies in the rice cultivation industry. Notably, the interaction relationship between rhizosphere microorganisms in rice and soil microbial taxa are not yet clear, so further research on its detailed effects on rice production is needed. In addition, the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for the physiological functions of the soil microbes could only predict the potential metabolic pathways. Therefore, the next-generation metagenome techonology might be performed to explore detailed metabolic differences and accurate taxa alteration at the "species" level.

IL-17A promotes endothelial cell senescence by up-regulating the expression of FTO through activating JNK signal pathway.

Endothelial aging is a sign of vascular aging that predisposes patients to vascular disease. We explored the effects of IL-17A on endothelial cell aging and determined the potential underlying mechanisms. In human umbilical vein endothelial cells, IL-17A promoted senescence, evidenced as increased positive staining of senescence-associated ß-galactosidase, increased proportion of cells arrested at G0/G1 stage, and upregulated p21 and p16 expression. IL-17A increased the expression of the m6A methylase FTO. We then investigated the relationship between FTO and endothelial cell aging. After interfering with FTO expression by siRNA, we observed that FTO induced endothelial cell aging. An increase in the expression of p-Jun N-terminal kinases (JNK) increased after IL-17A treatment indicated, that the JNK signaling pathway affected FTO expression. Moreover, the addition of the JNK signaling pathway inhibitor SP600125 blocked the effect of IL-17A on FTO expression. In conclusion, our findings revealed that IL-17A can promote endothelial cell aging by activating the JNK signaling pathway and upregulating FTO expression. This discovery can help in the identification of new therapeutic targets against endothelial cell aging and related vascular complications.