TLR4 sensitizes plasmacytoid dendritic cells for antiviral response against SARS-CoV-2 coronavirus.

Plasmacytoid dendritic cells are a rare subset of dendritic cells that exhibit antiviral functions in response to toll-like receptor 7/8 stimulations. Alternative toll-like receptors such as TLR4 have been known to be active in plasmacytoid dendritic cells for immune regulatory functions. However, it is unclear whether these toll-like receptors differentially activate plasmacytoid dendritic cells as compared with canonical toll-like receptor 7/8 stimulation. Here, we assessed alternative plasmacytoid dendritic cell activation states mediated by toll-like receptors other than endosomal toll-like receptors via the RNA sequencing approach. We found that toll-like receptor 4 stimulation induced a high degree of similarity in gene expression pattern to toll-like receptor 7/8 stimulation in plasmacytoid dendritic cells. Despite high resemblance to toll-like receptor 7/8, we discovered unique genes that were activated under toll-like receptor 4 activation only, as well as genes that were induced at a higher magnitude in comparison to toll-like receptor 7/8 activation. In comparison between toll-like receptor 4-activated plasmacytoid dendritic cells and conventional dendritic cells, we revealed that plasmacytoid dendritic cells and conventional dendritic cells expressed distinct gene sets, whereby conventional dendritic cells mostly favored antigen presentation functions for adaptive immune response regulation while plasmacytoid dendritic cells leaned toward immune response against infectious diseases. Last, we determined that toll-like receptor 4 activation sensitized plasmacytoid dendritic cells against SARS-CoV-2 (COVID-19) single-stranded RNA by enhancing antiviral-related responses and type I interferon production. These findings provided greater insights into the toll-like receptor 4 activation state in plasmacytoid dendritic cells, which can be beneficial for alternative therapeutic interventions involving plasmacytoid dendritic cells for various diseases.

Evolution of China's interaction with Middle Eastern countries under the Belt and Road Initiative.

The Middle East holds a critical strategic position in global politics, economy, and military affairs, serving as a pivotal hub for the advancement of the Belt and Road Initiative (BRI) through both land and sea routes. Since the proposal of BRI, China's cooperation with Middle Eastern countries has steadily deepened. Consequently, examining the evolution of China's interaction with Middle Eastern nations over the past decade is of paramount significance for future development. This study utilizes the GDELT database to construct formulas for measuring event impact and bilateral relationship intensity. It analyzes the temporal development and spatial patterns of China's interaction with Middle Eastern countries while also examining the types of interactive relationships between China and individual countries in the Middle East under the principle of reciprocity. The findings indicate that the overall interaction between China and Middle Eastern countries remains stable. Cooperative relationships have transitioned from a "single cooperation" approach to a "dual cooperation" model involving Iran and Saudi Arabia. Moreover, the development trajectory has shifted from an imbalanced "north-high, south-low" pattern towards equilibrium, resulting in a general decline in conflict relations and a decrease in inter-country disparities. The prevalent type of interaction between countries is characterized by balance.

Comparative transcriptome analysis of genes involved in paradormant bud release response in 'Summer Black' grape.

Grapevines possess a hierarchy of buds, and the fruitful winter bud forms the foundation of the two-crop-a-year cultivation system, yielding biannual harvests. Throughout its developmental stages, the winter bud sequentially undergoes paradormancy, endodormancy, and ecodormancy to ensure survival in challenging environmental conditions. Releasing the endodormancy of winter bud results in the first crop yield, while breaking the paradormancy of winter bud allows for the second crop harvest. Hydrogen cyanamide serves as an agent to break endodormancy, which counteracting the inhibitory effects of ABA, while H2O2 and ethylene function as signaling molecules in the process of endodormancy release. In the context of breaking paradormancy, common agronomic practices include short pruning and hydrogen cyanamide treatment. However, the mechanism of hydrogen cyanamide contributes to this process remains unknown. This study confirms that hydrogen cyanamide treatment significantly improved both the speed and uniformity of bud sprouting, while short pruning proved to be an effective method for releasing paradormancy until August. This observation highlights the role of apical dominance as a primary inhibitory factor in suppressing the sprouting of paradormant winter bud. Comparative transcriptome analysis revealed that the sixth node winter bud convert to apical tissue following short pruning and established a polar auxin transport canal through the upregulated expression of VvPIN3 and VvTIR1. Moreover, short pruning induced the generation of reactive oxygen species, and wounding, ethylene, and H2O2 collectively acted as stimulating signals and amplified effects through the MAPK cascade. In contrast, hydrogen cyanamide treatment directly disrupted mitochondrial function, resulting in ROS production and an extended efficacy of the growth hormone signaling pathway induction.

SIRT1-dependent deacetylation of Txnip H3K9ac is critical for exenatide-improved diabetic kidney disease.

Glucagon-like peptide 1 receptor agonist exenatide (exendin-4) has potential protective capabilities against diabetic kidney disease (DKD). However, the underlying mechanism has not been fully elucidated. The expression of thioredoxin-interacting protein (Txnip) is upregulated during DKD progression by histone acetylation. Sirtuin 1 (SIRT1) is a deacetylase and is decreased in DKD, which indicates that it may regulate Txnip in this disease. Here, we used whole-body heterozygous Sirt1 knockout (Sirt1+/-) and kidney-specific Sirt1 knockout (KSK) mice to investigate whether SIRT1 regulates Txnip via histone deacetylation in DKD and exenatide-alleviated DKD. Exenatide substantially improved renal pathological damage, decreased the albumin-to-creatinine ratio (ACR), upregulated SIRT1 expression, and downregulated Txnip expression in kidneys of high-fat diet-treated C57BL/6J mice. However, these effects diminished in Sirt1+/- and KSK mice under exenatide treatment. The downregulation of Txnip expression by exendin-4 in high-glucose-treated SV40 MES13 cells was hampered during Sirt1 knockdown. These results demonstrate that kidney SIRT1 is indispensable in exenatide-improved DKD and downregulation of Txnip expression. Exendin-4 mechanistically downregulated Txnip histone 3 lysine 9 acetylation (H3K9ac) in a SIRT1-dependent manner and decreased spliced X-box binding protein 1 (XBP1s) recruitment to the Txnip promoter. These findings provide epigenetic evidence elucidating the specific mechanism for exenatide-mediated DKD alleviation and highlight the importance of Txnip as a promising therapeutic target for DKD.

In vitro activity of ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam alone or in combination with polymyxin B against carbapenem resistant Acinetobacter baumannii.

Nosocomial infection caused by Carbapenem-Resistant Acinetobacter baumannii (CR-A. baumannii) has become a challenge in clinical practice. Acting as the last resort antibacterial agents for the treatment of CR-A. baumannii infection, polymyxins have high risk of nephrotoxicity and poor clinical efficacy. Ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam are three ß-lactam/ß-lactamase inhibitor combination complexes that newly approved by the Food and Drug Administration for the treatment of carbapenem-resistant Gram-negative bacterial infection. In this study, we analyzed the in vitro activity of those novel antibacterial agents alone or in combination with polymyxin B against the CR-A. baumannii obtained from a Chinese tertiary hospital. Our results suggest that those novel antibacterial agents should not be used alone for the treatment of CR-A. baumannii infection, as they cannot prevent the regrowth of bacteria at the clinical achievable blood concentration. Imipenem/relebactam and meropenem/vaborbactam should not be used as the substitutes of imipenem and meropenem for polymyxin B based combination therapy against CR-A. baumannii, since they have no edge over imipenem and meropenem on antibacterial activity when in combination with polymyxin B. Ceftazidime/avibactam may be more suitable than ceftazidime for polymyxin B based combination therapy against CR-A. baumannii, as it has a higher synergistic rate with polymyxin B, and the antibacterial activity of ceftazidime/avibactam is much higher than that of ceftazidime when tested in combination with polymyxin B. Ceftazidime/avibactam may also be the better choice than imipenem and meropenem for polymyxin B based combination therapy against CR-A. baumannii, as it has a higher synergistic rate with polymyxin B.

A Novel Drug with Potential to Treat Hyperbilirubinemia and Prevent Liver Damage Induced by Hyperbilirubinemia: Carbon Dots Derived from Platycodon grandiflorum.

Platycodon grandiflorum (PG) is a traditional Chinese medicine with a long history, but its active compounds have not been reported. In this study, novel carbon dots (CDs), PG-based CDs (PGC-CDs), were discovered and prepared from PG via calcinations and characterized by transmission electron microscopy; high-resolution transmission electron microscopy; X-ray diffraction, fluorescence, ultraviolet-visible, and Fourier-transform infrared spectrometers; X-ray photoelectron spectroscopy; and high-performance liquid chromatography. In addition, the safety and antioxidant activity of PGC-CDs was evaluated by RAW264.7 cells and LO2 cells. The therapeutic effects of PGC-CDs on hyperbilirubinemia and liver protection were evaluated in a bilirubin-induced hyperbilirubinemia mice model. The experiment confirmed that the diameter range of PGC-CDs was from 1.2 to 3.6 nm. PGC-CDs had no toxicity to RAW264.7 cells and LO2 cells at a concentration of 3.91 to 1000 µg/mL and could reduce the oxidative damage of cells caused by H2O2. PGC-CDs could inhibit the increase levels of bilirubin and inflammation factors and increase the levels of antioxidants and survival rate, demonstrating that PGC-CDs possessed anti-inflammatory and anti-oxidation activity. PGC-CDs may reduce the content of bilirubin, so as to reduce a series of pathological lesions caused by bilirubin, which has potential in treating hyperbilirubinemia and preventing liver damage induced by hyperbilirubinemia.

Development and validation of a risk prediction model for the recurrence of foot ulcer in type 2 diabetes in China: A longitudinal cohort study based on a systematic review and meta-analysis.

AIMS: To develop and validate a risk prediction model for Chinese patients with type 2 diabetes with the recurrence of diabetic foot ulcers (DFUs) based on a systematic review and meta-analysis. METHODS: A prospective analysis was performed with 1333 participants and followed up for 60 months. Three models were analysed using a derived cohort. The risk factors were screened using meta-analysis and logistic regression, and the missing variables were interpolated by multiple imputation. The internal validation was performed using the bootstrap procedure, and the validation cohort was applied to the external validation. The performance of the model was evaluated in the area under the discrimination Receiver Operating Characteristic Curve (ROC). Calibration and discrimination methods were used for the validation cohort. The variables were selected according to their clinical and statistical importance to construct the nomograms. RESULTS: Three models were developed and validated. Model 1 included seven social and clinical indicators like sex, diabetes mellitus duration, previous DFU, location of ulcer, smoking, history of amputation, and foot deformity. Model 2 included four more indicators besides those in Model 1, which were statin agents used, antiplatelet agents used, systolic blood pressure, and body mass index. Model 3 added further laboratory indicators to Model 2, such as LDL-C, HbA1C, fibrinogen, and blood urea nitrogen. In the derivation cohort, 20.1% (206/1027) participants with DFU recurred as compared to the validation cohort, which was 38.2% (117/306). The areas under the curve in the derivation cohort for Models 1-3 were 0.781 (0.744-0.817), 0.843 (0.813-0.873), and 0.899 (0.876-0.922), respectively. The Youden indexes for Models 1-3 were 0.430, 0.559, and 0.653, respectively. Model 3 showed the highest sensitivity and specificity. All models performed well for both discrimination and calibration. CONCLUSIONS: Models 1-2 were non-invasive, which indicate their role in general screening for patients at a high risk of recurrence of DFU. However, Model 3 offers a more specific screening due to its best performance in predicting the risk of DFU recurrence amongst the three models.

Synthesis Strategies and Applications for Pitch-Based Anode: From Industrial By-Products to Power Sources.

It is significant for saving energy to manufacture superb-property batteries. Carbon is one of the most competitive anode materials in batteries, but it is hard for commercial graphite anodes to meet the increasingly higher energy-storage requirements. Moreover, the price of other better-performing carbon materials (such as graphene) is much higher than graphite, which is not conducive to massive production. Pitch, the cheap by-product in the petroleum and coal industries, has high carbon content and yield, making it possible for commercialization. Developing pitch-based anodes can not only lower raw material costs but also realize the pitch's high value-added utilization. We comprehensively reviewed the latest synthesis strategies of pitch-derived materials and then introduced their application and research progress in lithium, sodium, and potassium ion batteries (LIBs, SIBs, and PIBs). Finally, we summarize and suggest the pitch's development trend for anodes and in other fields.

Lifestyle and Social Factors Exacerbated on the Prevalence of Mood Disorders and Functional Dyspepsia Among Neonatal Nurses in China.

Background: Nursing is a high-stress occupation that can have an impact on mental health, particularly for neonatal nurses. Job-related stress factors and work-related behaviors have played a critical role in nurses' mental health. This study aimed to explore the prevalence of mood disorders and the impact of social factors, lifestyle on mood disorders among neonatal nurses. Methods: A total of 260 participants comprising neonatal nurses and nurses who work in neonatal intensive care units (NICU) were recruited. Data were collected using a validated generalized anxiety disorder questionnaire, patient health questionnaire-9, Pittsburgh sleep quality index, and social factors and lifestyle assessments. Results: In total, 49.23% of neonatal nurses exhibited mood disorders, particularly a combination of depression and anxiety. Female, poor interpersonal relationships and unhappy marital status, preference for smoking, alcohol, irregular diet, and poor sleep were common in neonatology nurses who exhibited mood disorders; preference for coffee and tea were lower in neonatology nurses without mood disorders (all P < 0.05). Interpersonal relationships, marital status, irregular diet, and poor sleep were independent factors associated with mood disorders among neonatal nurses (all P < 0.05). Mood disorders presented as functional dyspepsia (FD) among 50.78% of the participants (P < 0.05). Poor sleep and preference for smoking were common among neonatal nurses who had FD with mood disorders (all P < 0.05). Furthermore, the preference for sugary beverages was lower in participants with FD and mood disorders (P < 0.05). Poor sleep was independently associated with FD with mood disorders in neonatology nurses (P < 0.05). Conclusion: Prevalence of anxiety and depression was higher among neonatal nurses. Furthermore, most cases of mood disorders presented as FD. Thus, social factors and lifestyle have an impact on mood disorders which can manifest through somatic symptoms.

An Immunological Perspective of Circulating Tumor Cells as Diagnostic Biomarkers and Therapeutic Targets.

Immune modulation is a hallmark of cancer. Cancer-immune interaction shapes the course of disease progression at every step of tumorigenesis, including metastasis, of which circulating tumor cells (CTCs) are regarded as an indicator. These CTCs are a heterogeneous population of tumor cells that have disseminated from the tumor into circulation. They have been increasingly studied in recent years due to their importance in diagnosis, prognosis, and monitoring of treatment response. Ample evidence demonstrates that CTCs interact with immune cells in circulation, where they must evade immune surveillance or modulate immune response. The interaction between CTCs and the immune system is emerging as a critical point by which CTCs facilitate metastatic progression. Understanding the complex crosstalk between the two may provide a basis for devising new diagnostic and treatment strategies. In this review, we will discuss the current understanding of CTCs and the complex immune-CTC interactions. We also present novel options in clinical interventions, targeting the immune-CTC interfaces, and provide some suggestions on future research directions.

The association between estimated glomerular filtration rate and prognosis in patients with diabetic foot osteomyelitis.

We aimed to explore the association between estimated glomerular filtration rate (eGFR) and prognosis in patients with diabetic foot osteomyelitis (DFO). Three hundred twenty-one DFO inpatients were enrolled and classified into four groups according to the eGFRs as follows: normal (≥90), mildly reduced (60-89), moderately reduced (30-59) and severely reduced (<30). These patients were followed-up for 6 months to observe the outcomes, including ulcer healing and amputation. The associations between eGFR and the outcomes were analysed by univariate and multivariate logistic regression models. Compared with patients with normal eGFR, patients with severely reduced eGFR group had higher risk of healing failure (OR = 4.72, 95% CI: 1.44-15.48), total amputation (OR = 4.50, 95% CI: 1.18-17.13) and minor amputation (OR = 4.05, 95% CI: (1.04-15.87). Severely reduced eGFR in patients with DFO was an independent predictor for amputation and healing failure.

Highly Potent Inhibition of Tyrosinase by Mulberrosides and the Inhibitory Mechanism in Vitro.

Many stilbene glycosides can alleviate skin hyperpigmentation due to their inhibitory effect on tyrosinase. Mulberrosides in Morus alba L. are stilbene glycosides. In the present study, the inhibition of tyrosinase by five mulberrosides (S1-5), isolated from Morus alba L. was investigated and compared, and the inhibitory mechanism was explored. These five mulberrosides exhibited obvious inhibitory effects on tyrosinase only in a concentration-dependent manner, without time-dependence, indicating that they are reversible inhibitors of tyrosinase. S2, S1 and S5 inhibited tyrosinase activity with IC50 values of 28.93, 75.94 and 151.72 µM, respectively, and were more active than kojic acid (IC50 =169.13 µM). Kinetic studies revealed that S1, S2 and S4 were competitive inhibitors, while S3 and S5 were mixed inhibitors. Analysis of the fluorescent spectra showed that mulberrosides S1, S2 and S4 quenched the intrinsic fluorescence intensity of tyrosinase. A molecular docking study indicated that the interaction of tyrosinase with mulberrosides was reflected by compound scores as follows: S2>S5>S1>S3/S4>kojic acid, and hydroxy groups in the side chain of mulberrosides may play a crucial role in the binding of the enzyme. Our results suggest that mulberrosides in Morus alba L. could be further developed as whitening agents for enhanced performance against hyperpigmentation.

Effects of Additives on Coke Reactivity and Sulfur Transformation during Co-pyrolysis of Long Flame Coal and High-Sulfur Coking Coal.

A silica-aluminum-based mineral (GL) was selected for inspecting the effects of interactions of minerals in coal blends on the coke reactivity index (CRI) and sulfur transformation during co-pyrolysis of long flame coal and high-sulfur coking coal. Results indicate a good compatibility for the supply of active hydrogen, decomposition of sulfur, and regulation of reactivity. The experimental values of sulfur content in different coal blend cokes are lower than the calculated values, which can be determined as a result of the directional regulation effect of long flame coal on sulfur transformation. The addition of GL in coal blends significantly reduces the CRI of the corresponding coke, and the effect of GL on coke reactivity is also verified by a 10 kg coke oven experiment. When increasing the ratio of long flame coal, the sulfur fixation in the solid phase has a tendency to be enhanced by alkaline minerals. Also, GL plays a role in reducing the capture of sulfur free radicals by alkaline minerals, which improves the sulfur removal during pyrolysis of coal blends and then reduces the sulfur content in coke. This work provides a reference for using silica-aluminum-based minerals to reduce the capture of sulfur and catalytic effect on coke reactivity.

Development and validation of an incidence risk prediction model for early foot ulcer in diabetes based on a high evidence systematic review and meta-analysis.

OBJECTIVES: To develop and validate a model for predicting the risk of early diabetic foot ulcer (DFU) based on systematic review and meta-analysis. METHODS: Data were analyzed from the risk factors of DFU with their corresponding risk ratio (RR) by meta-analysis. The DFU prediction model included statistically significant risk factors from the meta-analysis, all of which were scored by its weightings, and the prediction model was externally validated using a validation cohort from China. The occurrence of early DFU was defined as patients with type 2 diabetes who were free of DFU at baseline and diagnosed with DFU at follow-up. Evaluation of model performance was based on the area under the discrimination receiver operating characteristic curve (ROC), with optimal cutoff point determined by calculation of sensitivity and specificity. Kaplan-Meier curve were performed tocompare the cumulative risk of different groups. RESULTS: Our meta-analysis confirmed a cumulative incidence of approximately 6.0% in 46,521 patients with diabetes. The final risk prediction model included Sex, BMI, HbA1c, Smoker, DN, DR, DPN, Intermittent Claudication, Foot care, and their RRs were 1.87, 1.08, 1.21, 1.77, 2.97, 2.98, 2.76, 3.77, 0.38, respectively. The total score of all risk factors was 80 points according to their weightings. The prediction model showed good discrimination with AUC = 0.798 (95 %CI 0.738-0.858). At the optimal cut-off value of 46.5 points, the sensitivity, specificity and Youden index were 0.769, 0.798 and 0.567, respectively. The final model stratified the validation cohort into low, low-intermediate, high-intermediate and high-risk groups; Compared with low-risk group, the RR with 95 %CI of developing DFU in high-intermediate and high-risk group were 17.23 (5.12-58.02), p < 0.01 and 46.11 (5.16-91.74), p < 0.01, respectively. CONCLUSION: We have developed a simple tool to facilitates early identification of patients with diabetes at high risk of developing DFU based on scores. This simple tool may improve clinical decision-making and potentially guide early intervention.

Carbon nitride grafted waste-derived carbon as sustainable materials for lithium-sulfur batteries.

The synthesis of a sustainable material through carbon nitride (C3N4) chemically grafted on waste-derived carbon including carbonizing coals (PM), melamine-urea-formaldehyde resins (MUF-C-1100), and luffa cylindrical sponges (SG), respectively, and its application as sulfur cathode in lithium-sulfur (Li-S) batteries were demonstrated. The Li-S cell assembled by the sulfur (S) cathode with component from C3N4grafted coal-derived carbon (PM-CN) possesses a specific capacity of 1269.8 mA h g-1at 0.05 C. At 1 C, the initial specific capacity of PM cathode is only 380.0 mA h g-1, comparable to the PM-CN5 cathode of 681.9 mA h g-1, and PM-CN10 cathode of 580.7 mA h g-1, respectively. And, PM-CN 5 cathode presents the capacity retention of 75.9% with a coulomb efficiency (C.E.) of 97.3% after 200 cycles. The MUF-CN cathode gives a specific capacity of 1335.6 mA h g-1at 0.05 C, and the capacity retention of 66.7% with a C. E. of 93.6% after 300 cycles at 0.5 C. The SG-CN cathode had a specific capacity of 953.9 mA h g-1at 0.05 C, and capacity retention of 95.1% with a C. E. of 98.2% after 125 cycles at 1 C. The remarkable improved performances were mainly ascribed to the sustainable materials as S host with micro-meso pore and C3N4structure providing the strong affinity N sites to lithium polysulfides (LiPSs). This work provides an attractive approach for the preparation of sustainable materials by rational design of grafting C3N4to waste-derived carbons with functions as S cathode materials for high-performance Li-S batteries.

Catalytic Upgrading of Coal Pyrolysis Volatiles by Porous Carbon Materials Derived from the Blend of Biochar and Coal.

A suite of carbon materials is prepared from biochar and coal at three different blending ratios with 10, 20, and 30% biochar by mass. These carbon materials are activated by steam to obtain porous structures. The effect of the inactivated and activated carbon materials on the cracking of coal pyrolysis volatiles is evaluated. The results indicate that the inactivated carbon materials are beneficial to improve the yield of light oil with a boiling point below 170 °C. The steam-activated carbon materials are more conducive to cracking tar pitch than the inactivated carbon materials due to the increased defects in carbon structure. However, it is also easy to form more coke deposits. More components rich in hydrogen are cracked to generate radicals that could combine with the phenols' precursor over carbon materials, and the content of phenols in tar is increased. The carbon materials prepared from biochar and coal using this method show distinct advantages as filter media in the granular bed duster. It can improve the quality of tar along with reducing the dust content in tar.

Effect of hydrogen-rich gas from char gasification on rapid pyrolysis products of low rank coal in a downer pyrolyzer.

For guiding a novel integrated process of low-rank coal pyrolysis and gasification with char gasification gas as a heat carrier, this study investigated the effect of simulated coal gas from char gasification (SCGG) on rapid pyrolysis products of low rank coal from 550 to 700 °C in a downer pyrolyzer. Results indicated that the component of SCGG directly affected the distribution and composition of pyrolysis products. Compared with N2, SCGG facilitated the formation of tar below 600 °C. H2 in SCGG and that from water gas shift reaction (WGS: CO + H2O → CO2 + H2) increased the tar yield by reacting with solid-phase free radicals in coal and inhibiting the secondary reaction of gas-phase volatile radicals. Also, CO2 in SCGG raised the tar yield due to its promotion to coal cracking. When the pyrolysis temperature exceeded 600 °C, the reforming reactions of nascent tar with steam occurred, resulting in a reduced tar yield. SCGG could distinctly reduce the coke yield (coke-S) and pitch content in tar due to the inhibiting effect of H2 from SCGG and WGS on the polycondensation reactions of volatile radicals and reforming reactions of nascent tar. The chemical composition analysis of tar by GC × GC-MS demonstrated that compared with under N2, the contents of phenols, oxygenated compounds, and heterocyclic compounds in tar under SCGG were decreased while the content of aromatics was the opposite mainly due to hydrogenation and reforming reactions of nascent tar. Also, the H/C and O/C ratios of char under the action of SCGG were higher than those under N2 at the same temperature.

Liraglutide protects against high-fat diet-induced kidney injury by ameliorating apoptosis.

BACKGROUND: Obesity is associated with the development and progression of chronic kidney disease. Emerging evidence suggests that glucagon-like peptide-1 receptor agonist could reduce renal damage and albuminuria. Sirtuin 1 (SIRT1) was considered as a crucial regulator in metabolism-related kidney disease. Herein, the role of SIRT1 in liraglutide-ameliorated high-fat diet (HFD)-induced kidney injury was illustrated. METHODS: Male C57BL/6 mice were fed HFD for 20 weeks to induce kidney injury that was then treated with liraglutide for 8 weeks to estimate its protective effect on the kidney. Also, the mechanism of the drug in SV40 MES 13 (SV40) mouse mesangial cells was elucidated. RESULTS: Liraglutide treatment ameliorated HFD-induced metabolic disorders, including hyperglycemia, increasing body weight, and insulin resistance. In addition, kidney weight, urine albumin-to-creatinine, and kidney morphological changes such as vacuolated tubules, glomerulomegaly, thickened glomerular basement membrane, and tubulointerstitial fibrosis were also significantly ameliorated. Furthermore, apoptotic cells and apoptosis markers were downregulated in the kidney of liraglutide-treated mice. In addition, the expression of SIRT1 protein was upregulated, whereas thioredoxin-interacting protein (TXNIP), which serves as a mediator of oxidative stress and apoptosis in metabolism disease, was downregulated by liraglutide. In SV40 cells, the effect of liraglutide on reversing the upregulation of cleaved caspase-3 induced by high glucose (30 mM) was hampered when SIRT1 was knocked down; also, the downregulation of TXNIP by liraglutide was blocked. CONCLUSIONS: Liraglutide might have a beneficial effect on metabolism-related kidney damage by inhibiting apoptosis via activation of SIRT1 and suppression of TXNIP pathway.

Citron C-05 inhibits both the penetration and colonization of Xanthomonas citri subsp. citri to achieve resistance to citrus canker disease.

Citrus canker, caused by Xanthomonas citri subsp. citri (Xcc), is a serious bacterial disease that affects citrus production worldwide. Citron C-05 (Citrus medica) is the only germplasm in the Citrus genus that has been identified to exhibit strong resistance to Xcc. However, it has not been determined when, where, and how Xcc is restricted in the tissues of Citron C-05 during the infection process. In the present study, we investigated the spatiotemporal growth dynamics of an eGFP-labeled virulent Xcc (eGFP-Xcc) strain in Citron C-05 along with five susceptible biotypes (i.e., lemon, pummelo, sour orange, sweet orange, and ponkan mandarin) upon inoculation via the spraying or leaf infiltration of a bacterial suspension. The results from extensive confocal laser scanning microscopy analyses showed that while Xcc grew rapidly in plants of all five susceptible genotypes, Xcc was severely restricted in the epidermal and mesophyll cell layers of the leaves of Citron C-05 in the early stage of infection. Not surprisingly, resistance against Xcc in Citron C-05 was found to be associated with the production of reactive oxygen species and hypersensitive response-like cell death, as well as greater upregulation of several defense-related genes, including a pathogenesis-related gene (PR1) and a glutathione S-transferase gene (GST1), compared with sweet orange as a susceptible control. Taken together, our results not only provide further valuable details of the spatiotemporal dynamics of the host entry, propagation, and spread of Xcc in both resistant and susceptible citrus plants but also suggest that resistance to Xcc in Citron C-05 may be attributed to the activation of multiple defense mechanisms.

Transcriptome analysis of metabolisms related to fruit cracking during ripening of a cracking-susceptible grape berry cv. Xiangfei (Vitis vinifera L.).

BACKGROUND: Grape is an economically valuable fruit around the world. However, some cultivars are prone to fruit cracking during ripening, leading to severe losses. OBJECTIVE: We aimed to find important metabolisms related to fruit cracking during ripening process. METHODS: RNA-Sequence and analysis was applied to the pericarp of cracking-susceptible 'Xiang Fei' at 1 (W1), 2 (W2) and 3 weeks (W3) after veraison on Illumina HiSeq xten; RESULTS: Compared with W1, the berry cracking rate increased significantly in W2 and W3. Through transcriptomic analysis, a total of 22,609 genes were expressed in the grape pericarp, among which 805 and 2758 genes were significantly differentially regulated in W1-vs.-W2 and W1-vs.-W3 comparison, respectively. Besides, 304 and 354 genes were up- and down-regulated in both comparisons. The significantly enriched GO terms of both W1-W2 and W1-W3 are related to cell wall and wax biosynthesis. And lipid metabolism, which are involved in the top 20 enriched KEGG pathways of both comparisons, was related to wax biosynthesis. Further, GO enrichment analysis of differentially expressed genes (DEGs) with same regulatory changes also indicated that the continuously up-regulated DEGs are significantly enriched in cell wall component biosynthesis and hydrolase. CONCLUSION: These findings suggested that genes related to cell wall metabolism and cuticle biosynthesis may play important roles in regulating grape berry cracking. Our results provide a reference for further studies on the molecular mechanism underlying fruit cracking.