A plant NLR receptor employs ABA central regulator PP2C-SnRK2 to activate antiviral immunity.

Defence against pathogens relies on intracellular nucleotide-binding, leucine-rich repeat immune receptors (NLRs) in plants. Hormone signaling including abscisic acid (ABA) pathways are activated by NLRs and play pivotal roles in defence against different pathogens. However, little is known about how hormone signaling pathways are activated by plant immune receptors. Here, we report that a plant NLR Sw-5b mimics the behavior of the ABA receptor and directly employs the ABA central regulator PP2C-SnRK2 complex to activate an ABA-dependent defence against viral pathogens. PP2C4 interacts with and constitutively inhibits SnRK2.3/2.4. Behaving in a similar manner as the ABA receptor, pathogen effector ligand recognition triggers the conformational change of Sw-5b NLR that enables binding to PP2C4 via the NB domain. This receptor-PP2C4 binding interferes with the interaction between PP2C4 and SnRK2.3/2.4, thereby releasing SnRK2.3/2.4 from PP2C4 inhibition to activate an ABA-specific antiviral immunity. These findings provide important insights into the activation of hormone signaling pathways by plant immune receptors.

Soil quality and ecosystem multifunctionality after 13-year of organic and nitrogen fertilization.

Organic and mineral fertilization increase crop productivity, but their combined effects on soil quality index (SQI) and ecosystem multifunctionality (EMF, defined as the capacity of soils to simultaneously provide multiple functions and services) are not clear. We conducted a 13-year field trial in North China Plain to examine how five maize-derived organic fertilizers (straw, manure, compost, biogas residue, and biochar) at equal C input rate (3.2 t C ha-1), with or without nitrogen (N) fertilization influenced topsoil (0-15 cm) physico-chemical properties, activities of enzymes responsible for carbon (C), N, and phosphorus (P) cycling, as well as SQI and soil EMF. Organic fertilizers with or without N increased SQI by 51-187 % and EMF by 31-351 % through the enhancement of soil physical (mean weight diameter of soil aggregates) and chemical properties (C, N, and P contents) as well as C, N, and P acquisition enzyme activities, albeit the biochar effects were of minor importance. N application increased EMF compared to soil without N. Soil quality increased with EMF. Random forest analysis revealed that microbial biomass C and N, available P, permanganate oxidizable C, dissolved organic C and N, mean weight diameter of aggregates, hot water extractable C, and electrical conductivity were the main contributions to soil EMF. We conclude that application of maize-derived organic fertilizers, especially compost and straw, with optimal N fertilization is a plausible strategy to increase SQI and EMF under a wheat/maize system.

Clinical significance of regional constructive and wasted work in patients receiving cardiac resynchronization therapy.

Background: Previous studies have shown that global constructive work (CW) and wasted work (WW) predict response to cardiac resynchronization therapy (CRT). This study evaluated the predictive value of regional CW and WW for reverse remodeling and clinical outcomes after CRT. Methods: We performed a prospective study involving 134 CRT candidates with left bundle branch block and left ventricular ejection fraction ≤35%. Global and regional CW and WW were calculated using pressure-strain loop analysis. CRT response was defined by reverse remodeling as a reduction of ≥15% in left ventricular end-systolic volume after six months. Results: At six-month follow-up, 92 (69%) patients responded to CRT. Of the regional CW and WW measures, lateral wall (LW) CW and septal WW were most strongly and significantly correlated with reverse remodeling. At multivariate analysis, LW CW and septal WW were both independent determinants of reverse remodeling. When LW CW and septal WW were included in the model, global CW and WW were not independently associated with reverse remodeling. LW CW and septal WW predicted reverse remodeling with an area under the curve (AUC) of 0.783 (95% CI: 0.700-0.866) and 0.737 (95% CI: 0.644-0.831), respectively. Using both variables increased the AUC to 0.832 (95% CI: 0.755-0.908). Both LW CW ≤878 mmHg% (HR 2.01; 95% CI: 1.07-3.79) and septal WW ≤181 mmHg% (HR 2.60; 95% CI: 1.38-4.90) were significant predictors of combined death and HF hospitalization at two-year follow-up. Conclusion: LW CW and septal WW before CRT are important determinants of reverse remodeling and clinical outcomes.

Silymarin Synergizes with Antiviral Therapy in Hepatitis B Virus-Related Liver Cirrhosis: A Propensity Score Matching Multi-Institutional Study.

Hepatitis B virus (HBV)-related liver cirrhosis (HBV-LC) presents a substantial mortality and hepatocellular carcinoma (HCC) risk. While antiviral therapy (AVT) is the standard, complete HBV clearance remains elusive and may not reduce the risk of death in patients with decompensated cirrhosis. Silymarin, a centuries-old herbal remedy, has shown promise against HBV infection and as an antifibrosis therapy. This study explores the potential of silymarin combined with AVT to reduce mortality and HCC incidence in patients with HBV-LC. This research, spanning from 2001 to 2019, entailed a multi-institutional retrospective cohort study which included 8447 HBV-LC patients all undergoing AVT. After applying inclusion and exclusion criteria, the study comprised two cohorts: a case cohort receiving silymarin alongside AVT for at least 30 days, and a control cohort on AVT alone. Propensity score matching, based on baseline parameters including HBV-DNA levels, comorbidity, and an important LC medication, namely, non-selective ß-blockers, was employed to ensure balanced groups, resulting in 319 patients in each cohort for subsequent analyses. Overall mortality was the primary outcome, with HCC occurrence as a secondary outcome. Among 319 patients in both cohorts, the case cohort exhibited significant improvements in the international normalized ratio (INR), model for end-stage liver disease (MELD) score and the Charlson comorbidity index (CCI) one year after the index date. A competing risk survival analysis demonstrated superior one-year and two-year mortality outcomes in the case cohort. However, no significant impact on one-year and two-year HCC occurrence was observed in either cohort. The combination of silymarin and AVT in HBV-LC patients demonstrated a synergistic effect, leading to decreased overall mortality and an improved comorbidity index. While the incidence of HCC remained unchanged, our results suggested promising potential for further clinical trials investigating the synergistic role of silymarin in the treatment of HBV-LC.

Optimizing biochar application for enhanced cotton and sugar beet production in Xinjiang: a comprehensive study.

BACKGROUND: Optimizing biochar application is vital for enhancing crop production and ensuring sustainable agricultural production. A 3-year field experiment was established to explore the effects of varying the biochar application rate (BAR) on crop growth, quality, productivity and yields. BAR was set at 0, 10, 50 and 100 t ha-1 in 2018; 0, 10, 25, 50 and 100 t ha-1 in 2019; and 0, 10, 25 and 30 t ha-1 in 2020. Crop quality and growth status and production were evaluated using the dynamic technique for order preference by similarity to ideal solution with the entropy weighted method (DTOPSIS-EW), principal component analysis (PCA), membership function analysis (MFA), gray relation analysis (GRA) and the fuzzy Borda combination evaluation method. RESULTS: Low-dose BAR (≤ 25 t ha-1 for cotton; ≤ 50 t ha-1 for sugar beet) effectively increased biomass, plant height, leaf area index (LAI), water and fertility (N, P and K) productivities, and yield. Biochar application increased the salt absorption and sugar content in sugar beet, with the most notable increases being 116.45% and 20.35%, respectively. Conversely, BAR had no significant effect on cotton fiber quality. The GRA method was the most appropriate for assessing crop growth and quality. The most indicative parameters for reflecting cotton and sugarbeet growth and quality status were biomass and LAI. The 10 t ha-1 BAR consistently produced the highest scores and was the most economically viable option, as evaluated by DTOPSIS-EW. CONCLUSION: The optimal biochar application strategy for improving cotton and sugar beet cultivation in Xinjiang, China, is 10 t ha-1 biochar applied continuously. © 2024 Society of Chemical Industry.

Enhanced extraction of heavy metals from gypsum-based hazardous waste by nanoscale sulfuric acid film at ambient conditions.

Low-cost, low-energy extraction of heavy metal(loid)s (HMs) from hazardous gypsum cake is the goal of the metallurgical industry to mitigate environmental risks and carbon emissions. However, current extracting routes of hydrometallurgy often suffer from great energy inputs and substantial chemical inputs. Here, we report a novel solid-like approach with low energy consumption and chemical input to extract HMs by thin films under ambient conditions. Through constructing a nanoscale sulfuric acid film (NSF) of ∼50 nm thickness on the surface of arsenic-bearing gypsum (ABG), 99.6% of arsenic can be removed, surpassing the 50.3% removal in bulk solution. In-situ X-ray diffraction, infrared spectral, and ab initio molecular dynamics (AIMD) simulations demonstrate that NSF plays a dual role in promoting the phase transformation from gypsum to anhydrite and in changing the ionic species to prevent re-doping in anhydrite, which is not occurred in bulk solutions. The potential of the NSF is further validated in extracting other heavy metal(loid)s (e.g., Cu, Zn, and Cr) from synthetic and actual gypsum cake. With energy consumption and costs at 1/200 and 1/10 of traditional hydrometallurgy separately, this method offers an efficient and economical pathway for extracting HMs from heavy metal-bearing waste and recycling industrial solid waste.

How do sphingosine-1-phosphate affect immune cells to resolve inflammation?

Inflammation is an important immune response of the body. It is a physiological process of self-repair and defense against pathogens taken up by biological tissues when stimulated by damage factors such as trauma and infection. Inflammation is the main cause of high morbidity and mortality in most diseases and is the physiological basis of the disease. Targeted therapeutic strategies can achieve efficient toxicity clearance at the inflammatory site, reduce complications, and reduce mortality. Sphingosine-1-phosphate (S1P), a lipid signaling molecule, is involved in immune cell transport by binding to S1P receptors (S1PRs). It plays a key role in innate and adaptive immune responses and is closely related to inflammation. In homeostasis, lymphocytes follow an S1P concentration gradient from the tissues into circulation. One widely accepted mechanism is that during the inflammatory immune response, the S1P gradient is altered, and lymphocytes are blocked from entering the circulation and are, therefore, unable to reach the inflammatory site. However, the full mechanism of its involvement in inflammation is not fully understood. This review focuses on bacterial and viral infections, autoimmune diseases, and immunological aspects of the Sphks/S1P/S1PRs signaling pathway, highlighting their role in promoting intradial-adaptive immune interactions. How S1P signaling is regulated in inflammation and how S1P shapes immune responses through immune cells are explained in detail. We teased apart the immune cell composition of S1P signaling and the critical role of S1P pathway modulators in the host inflammatory immune system. By understanding the role of S1P in the pathogenesis of inflammatory diseases, we linked the genomic studies of S1P-targeted drugs in inflammatory diseases to provide a basis for targeted drug development.

[Effect of Using Hydrogen Peroxide for Periodic Disinfection Combined With Continuous Disinfection to Control Contamination in Dental Unit Waterline]. / è¿‡æ°§åŒ–æ°¢å®šæœŸæ¶ˆæ¯’ç»“åˆæŒç»­æ¶ˆæ¯’å¯¹å£è ”ç»¼åˆæ²»ç–—å°æ°´è·¯æ±¡æŸ“æŽ§åˆ¶çš„æœ‰æ•ˆæ€§è§‚å¯Ÿ.

Objective: To observe the effect of using hydrogen peroxide in periodic disinfection combining with continuous disinfection of dental unit waterlines and to provide references for the selection of waterway disinfection measures. Methods: A total of 4 dental units in a hospital of stomatology were selected through convenience sampling. The dental unit waterlines received periodic disinfection once every 4 weeks in addition to continuous disinfection (When the dental units were not used for more than 3 days, an additional periodic disinfection would be performed.). Periodic disinfection referred to filling up the waterlines with a disinfectant solution (1.4% hydrogen peroxide) by using the waterline disinfection device that came with the dental unit, immersing for 24 hours, and then emptying out the disinfectant solution. Continuous disinfection referred to using hydrogen peroxide at a concentration of 0.014% as dental treatment water and using it to flush the waterlines for 2 minutes before any dental treatment in the morning and to flush the waterlines for 30 seconds after each dental treatment. The study lasted for 25 weeks, with periodic disinfection being performed for 7 times and continuous disinfection carried out for the rest of the dental treatment time. During the 25 weeks, water samples were collected from air/water syringes and high-speed handpieces. Then, the water samples were incubated and the bacterial concentration and the qualification rates were calculated accordingly. When the bacterial concentration≤100 CFU/ mL, the water samples were considered to be qualified. Waterline tubes of 1 cm were collected before and after the 25 weeks of disinfection with hydrogen peroxide. Biofilms in the waterline tube were observed under scanning electron microscope. Results: A total of 352 water samples were collected. Eight water samples were collected before disinfection with hydrogen peroxide, with the median of bacterial concentration being 3140 CFU/mL. On the first day of disinfection with hydrogen peroxide, the median bacterial concentration in dental treatment water was 7.5 CFU/mL. There was a significant difference between the bacterial concentration of the water samples before the disinfection and that after the disinfection (P=0.012). A total of 344 water samples were collected after the disinfection, with the median bacterial concentrations for air/water syringes and high-speed handpieces being 11 CFU/mL and 11CFU/mL and the qualified rates being 83.7% and 82.0%, respectively. There was no significant difference in bacterial concentration or the qualification rates. During week 1 through week 9 of the disinfection, the qualification rates of the dental treatment water always exceeded 80% in 8 weeks, with week 3 being the exception. In the two four-week disinfection periods of week 14 through week 17 and week 18 through week 21, the qualification rate was maintained at above 80% for only the first two weeks and started to decrease from the third week. Biofilm morphology was observed under scanning electron microscope. Before the disinfection, the biofilm was found to be a dense structure and the mixture of a large number of bacteria. After 25 weeks of the disinfection, the biofilm structure appeared to be loose and did not show consistent characteristics of a large number of bacteria retained. Conclusion: Periodic disinfection combined with continuous disinfection using hydrogen peroxide can effectively control contamination in dental unit waterlines. But the cycles of periodic disinfection and the concentration of hydrogen peroxide for continuous disinfection should be further discussed according to the actual clinical situation.

Andrographolide regulates H3 histone lactylation by interfering with p300 to alleviate aortic valve calcification.

BACKGROUND AND PURPOSE: Our previous studies have found that andrographolide (AGP) alleviates calcific aortic valve disease (CAVD), but the underlying mechanism is unclear. This study explores the molecular target and signal mechanisms of AGP in inhibiting CAVD. EXPERIMENTAL APPROACH: The anti-calcification effects of the aortic valve with AGP treatment were evaluated by alizarin red staining in vitro and ultrasound and histopathological assessment of a high-fat (HF)-fed ApoE-/- mouse valve calcification model. A correlation between the H3 histone lactylation (H3Kla) and calcification was detected. Molecular docking and surface plasmon resonance (SPR) experiments were further used to confirm p300 as a target for AGP. Overexpression (oe) and silencing (si) of p300 were used to verify the inhibitory effect of AGP targeting p300 on the H3Kla in vitro and ex vivo. KEY RESULTS: AGP significantly inhibited calcium deposition in valve interstitial cells (VICs) and ameliorated aortic valve calcification. The multi-omics analysis revealed the glycolysis pathway involved in CAVD, indicating that AGP interfered with lactate production by regulating lactate dehydrogenase A (LDHA). In addition, lactylation, a new post-translational modification, was shown to have a role in promoting aortic valve calcification. Furthermore, H3Kla and H3K9la site were shown to correlate with Runx2 expression inhibition by AGP treatment. Importantly, we found that p300 transferase was the molecular target of AGP in inhibiting H3Kla. CONCLUSIONS AND IMPLICATIONS: Our findings, for the first time, demonstrated that AGP alleviates calcification by interfering with H3Kla via p300, which might be a powerful drug to prevent CAVD.

Neuronal CFL1 upregulation in head and neck squamous cell carcinoma enhances tumor-nerve crosstalk and promotes tumor growth.

Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer type, marked by a pronounced nerve density within the tumor microenvironment and a high rate of perineural invasion (PNI). Growing evidence suggests that the nervous system plays a vital role in HNSCC progression. Yet, the mechanisms governing cancer-nerve interactions remain largely elusive. Our research revealed that cofilin-1 (CFL1) is significantly overexpressed in HNSCC and correlates with both PNI and unfavorable prognosis. Utilizing multiplex fluorescent immunohistochemistry, we have localized CFL1 chiefly to the nerves adjacent to tumor sites. Significantly, it is the elevated expression of CFL1 in neuronal structures, rather than in the tumor cells, that aligns with diminished patient survival rates. We observed that HNSCC cells induced the expression of neuronal CFL1 and that the conditional knockout of neuronal CFL1 impedes tumor-nerve interactions. Both Gene Ontology functional enrichment analyses and Gene Set Enrichment Analysis demonstrate that CFL1 expression in HNSCC is associated with specific biological processes, including "RIBOSOME," "PROTEASOME," and "cadherin binding." In summary, HNSCC promotes the expression of CFL1 in nerves, which is essential for cancer-nerve interactions. The neuronal CFL1 is associated with PNI and may be a potential molecular prognostic marker of poor survival in HNSCC.

Incidences, risk factors, and clinical correlates of severe QT prolongation after the use of quetiapine or haloperidol.

BACKGROUND: Case reports suggest that quetiapine or haloperidol use is associated with severe QT prolongation (SQTP) and torsades de pointes. OBJECTIVE: The purpose of this study was to examine the incidences, risk factors, and outcomes of SQTP in quetiapine and haloperidol users. METHODS: This study accessed electronic medical records from a multicenter health-care hospital system in Taiwan and included patients who received quetiapine or haloperidol therapy and had both baseline and follow-up electrocardiograms. SQTP was defined as a posttreatment corrected QT (QTc) interval exceeding 500 ms or an increase in QTc interval of >60 ms compared with the baseline value. We analyzed the risk factors and outcomes of SQTP using multivariate logistic regression. RESULTS: Mean increases in QTc interval were +8.3 ± 51.8 and +8.9 ± 44.0 ms after the administration of quetiapine (n = 8832) and haloperidol (n = 2341). Among these users, 1149 (13.0%) and 333 (14.2%) developed SQTP, respectively. Common risk factors for SQTP included old age, heart failure, hypokalemia, amiodarone use, and baseline QTc interval. SQTP in quetiapine users was significantly associated with ventricular arrhythmias (odds ratio 2.84; 95% confidence interval 1.95-4.13) and sudden cardiac death (odds ratio 2.29; 95% confidence interval 1.44-3.66). CONCLUSION: More than 10% of patients receiving quetiapine or haloperidol therapy developed SQTP, and many of them were exposed to risk factors for SQTP. SQTP in quetiapine users was significantly associated with increased risks of ventricular arrhythmias and sudden cardiac death. Clinicians should be vigilant for ventricular arrhythmias in quetiapine users who have risk factors for SQTP.

Trend analysis of quality indicators in palliative home care among terminally ill cancer and non-cancer patients in Taiwan: a 6-year observational study.

PURPOSE: Palliative home care services (PHCS) have been emerging for years. However, limited data exist regarding quality indicators for pain control, unplanned hospital readmissions, and household deaths among terminal cancer and non-cancer patients receiving PHCS. METHODS: We conducted a retrospective collection and recording of data from 1242 terminally ill cancer and non-cancer patients receiving PHCS. The data were obtained from the Hospice-Palliative Clinical Database (HPCD) of Taichung Veterans General Hospital (TCVGH) for the period from 2016 to 2021. T test and chi-square test were applied for characteristics and the quality indicators among cancer and non-cancer groups. Chi-square test was used for trend analysis of the number of patients receiving PHCS and the quality indicators among cancer and non-cancer groups throughout the study period. RESULTS: A total of 1242 terminally ill cancer and non-cancer patients who had received PHCS were documented by TCVGH from the years 2016 to 2021, including 221 non-cancer patients and 1021 cancer patients having an average age of 70. The number of terminally ill cancer and non-cancer patients receiving PHCS has increased annually since 2016. Another finding was that age was a statistically significant factor impacting quality indicators. On the other hand, compared to non-cancer patients, cancer patients had a higher likelihood of receiving treatment with analgesics when needed. Their odds of needing analgesics more than three times within 4 days after PHCS enrollment were significantly elevated [OR 4.188, 95% CI (1.002, 17.51)]. CONCLUSION: The results of this 6-year observational study indicate a substantial increase in the number of terminal cancer and non-cancer patients receiving PHCS over the past decade. Furthermore, aging plays an important role in life quality of terminal cancer and non-cancer patients.

Serum vitamin C levels and their correlation with chronic kidney disease in adults: a nationwide study.

INTRODUCTION: Inflammation and oxidative stress play significant roles in the development of chronic kidney disease (CKD). Given the recognized antioxidant properties of vitamin C, our study aimed to explore the correlation between CKD and serum vitamin C levels. METHODS: Data were gathered from the 2017-2018 National Health and Nutrition Examination Survey. Participants below 18 years of age, pregnant individuals, those lacking essential data for CKD diagnosis, or individuals with incomplete serum vitamin C data were excluded. Subgroup and weighted multivariable logistic regression analyses were performed to assess the potential correlation between serum vitamin C and CKD. RESULTS: Our study comprised 4969 participants, revealing an overall CKD prevalence of 15.0%. The results indicated that individuals with reduced serum vitamin C levels were more likely to be male, possess lower educational attainment, have a diminished poverty-income ratio, engage in heavy drinking, and be current smokers. Additionally, they exhibited a higher prevalence of obesity and diabetes. Significantly, participants in the third quartile group experienced a 37.0%, 47.0%, and 46.6% decrease in the risk of developing albuminuria, low estimated glomerular filtration rate (eGFR), and CKD, respectively. Subgroup analysis demonstrated that individuals between 65 and 80 years of age showed a statistically reduced risk of developing CKD and low eGFR when their serum vitamin C levels fell in the third and fourth quartile groups. CONCLUSIONS: Our findings reveal a correlation between elevated serum vitamin C levels and a decreased risk of developing albuminuria, low eGFR, and CKD. Appropriately increasing serum vitamin C levels may hold promise in protecting renal function, particularly among older individuals.

Aurora B promotes the CENP-T-CENP-W interaction to guide accurate chromosome segregation in mitosis.

Accurate chromosome segregation in mitosis depends on kinetochores that connect centromeric chromatin to spindle microtubules. Centromeres are captured by individual microtubules via a kinetochore constitutive centromere-associated network (CCAN) during chromosome segregation. CCAN contains 16 subunits, including CENP-W and CENP-T. However, the molecular recognition and mitotic regulation of the CCAN assembly remain elusive. Here, we revealed that CENP-W binds to the histone fold domain and an uncharacterized N-terminal region of CENP-T. Aurora B phosphorylates CENP-W at Thr60, which enhances the interaction between CENP-W and CENP-T to ensure robust metaphase chromosome alignment and accurate chromosome segregation in mitosis. These findings delineate a conserved signaling cascade that integrates protein phosphorylation with CCAN integrity for the maintenance of genomic stability.

Sulfur vacancy-enhanced In2S3-x hollow microtubes for photocatalytic Cr (VI) and tetracycline removal.

Morphological regulation and defect engineering are efficient methods for photocatalytic technology by improving photon absorption and electron dissociation. Herein, In2S3-x hollow microtubes with S-vacancies (MIS) were fabricated via a simple solvothermal reaction using In-based metal-organic frameworks (In-MOFs) as a precursor. Experimental results demonstrate that the hollow structure and optimal S-vacancies can jointly accelerate the photocatalytic reaction, attributed to a larger specific surface area, more active sites, and faster electron transfer efficiency. The champion MIS(2) displayed significantly better photocatalytic activity for Cr(VI) reduction and tetracycline (TC) degradation. The Cr(VI) reduction rate by MIS(2) is 3.67 and 2.82 times higher than those of optimal In2S3 template-free (HIS(2)) and MIS(1) with poor S-vacancies, respectively. The removal efficiency of TC by MIS(2) is 1.37 and 1.15 times higher than those of HIS(2) and MIS(1). Further integration of MIS(2) with aerogel simplifies the recovery process significantly.

A novel iron sulfide phase with remarkable hydroxyl radical generation capability for contaminants degradation.

The hydroxyl radical (·OH) stands as one of the most potent oxidizing agents, capable of engaging in non-selective and instantaneous reactions with contaminants in water. Herein, we present a novel iron sulfide phase (S-FeS) characterized by an unprecedented structure, accompanied by its remarkable hydroxyl radical generation capability and contaminant degradation efficiency surpassing that of the conventional metastable iron sulfide phase, namely, the Mackinawite (FeS). In comparison to FeS, S-FeS exhibits enhanced degradation kinetics and higher efficacy in the removal of methylene blue, ciprofloxacin, and trivalent arsenic. Utilizing density functional theory (DFT) calculations, we postulate the mechanism for the exceptional contaminant degradation performance of S-FeS to be attributed to the increased exposure of the highly reactive (110) crystal facets. This research uncovers a new metastable phase that expands the polymorphisms within the iron sulfide family and showcases its capability for driving the oxygen reduction reaction.

Diagnostic yield and novel candidate genes by next generation sequencing in 166 children with intrahepatic cholestasis.

BACKGROUND AND AIMS: Cholestatic liver disease is a leading referral to pediatric liver transplant centers. Inherited disorders are the second most frequent cause of cholestasis in the first month of life. METHODS: We retrospectively characterized the genotype and phenotype of 166 participants with intrahepatic cholestasis, and re-analyzed phenotype and whole-exome sequencing (WES) data from patients with previously undetermined genetic etiology for newly published genes and novel candidates. Functional validations of selected variants were conducted in cultured cells. RESULTS: Overall, we identified disease-causing variants in 31% (52/166) of our study participants. Of the 52 individuals, 18 (35%) had metabolic liver diseases, 9 (17%) had syndromic cholestasis, 9 (17%) had progressive familial intrahepatic cholestasis, 3 (6%) had bile acid synthesis defects, 3(6%) had infantile liver failure and 10 (19%) had a phenocopy of intrahepatic cholestasis. By reverse phenotyping, we identified a de novo variant c.1883G > A in FAM111B of a case with high glutamyl transpeptidase (GGT) cholestasis. By re-analyzing WES data, two patients were newly solved, who had compound heterozygous variants in recently published genes KIF12 and USP53, respectively. Our additional search for novel candidates in unsolved WES families revealed four potential novel candidate genes (NCOA6, CCDC88B, USP24 and ATP11C), among which the patients with variants in NCOA6 and ATP11C recapitulate the cholestasis phenotype in mice models. CONCLUSIONS: In a single-center pediatric cohort, we identified monogenic variants in 22 known human intrahepatic cholestasis or phenocopy genes, explaining up to 31% of the intrahepatic cholestasis patients. Our findings suggest that re-evaluating existing WES data from well-phenotyped patients on a regular basis can increase the diagnostic yield for cholestatic liver disease in children.

Positive regulation of the PhcB neighbouring regulator PrhX on expression of the type III secretion system and pathogenesis in Ralstonia solanacearum.

Ralstonia solanacearum PhcB and PhcA control a quorum-sensing (QS) system that globally regulates expression of about one third of all genes, including pathogenesis genes. The PhcB-PhcA QS system positively regulates the production of exopolysaccharide (EPS) and negatively regulates hrp gene expression, which is crucial for the type III secretion system (T3SS). Both EPS and the T3SS are essential for pathogenicity. The gene rsc2734 is located upstream of a phcBSR operon and annotated as a response regulator of a two-component system. Here, we demonstrated that RSc2734, hereafter named PrhX, positively regulated hrp gene expression via a PrhA-PrhIR-PrhJ-HrpG signalling cascade. Moreover, PrhX was crucial for R. solanacearum to invade host roots and grow in planta naturally. prhX expression was independent of the PhcB-PhcA QS system. PrhX did not affect the expression of phcB and phcA and the QS-dependent phenotypes, such as EPS production and biofilm formation. Our results provide novel insights into the complex regulatory network of the T3SS and pathogenesis in R. solanacearum.

Interfacial Engineering of Fluorinated TiO2 Nanosheets with Abundant Oxygen Vacancies for Boosting the Hydrogen Storage Performance of MgH2.

The interaction between fluorinated surface in the partially reduced nano-crystallite titanium dioxide (TiO2-x (F)) and MgH2 is studied for the first time. Compared with pristine MgH2 (416 °C), the onset desorption temperature of MgH2 +5 wt.% TiO2-x (F) composite can be dramatically lowered to 189 °C. In addition, the composite exhibits remarkable dehydrogenation kinetics, which can release 6.0 wt.% hydrogen thoroughly within 6 min at 250 °C. The apparent activation energy for dehydriding is decreased from 268.42 to 119.96 kJ mol-1 . Structural characterization and theoretical calculations indicate that the synergistic effect between multivalent Ti species, and the in situ formed MgF2 and MgF2-x Hx is beneficial for improving the hydrogen storage performance of MgH2 . Moreover, oxygen vacancies can accelerate the electron transportation and facilitate hydrogen diffusion. The study provides a novel perspective on the modification of MgH2 by fluorinated transition metal oxide catalyst.