Dihydroorotase MoPyr4 is required for development, pathogenicity, and autophagy in rice blast fungus.

Dihydroorotase (DHOase) is the third enzyme in the six enzymatic reaction steps of the endogenous pyrimidine nucleotide de novo biosynthesis pathway, which is a metabolic pathway conserved in both bacteria and eukaryotes. However, research on the biological function of DHOase in plant pathogenic fungi is very limited. In this study, we identified and named MoPyr4, a homologous protein of Saccharomyces cerevisiae DHOase Ura4, in the rice blast fungus Magnaporthe oryzae and investigated its ability to regulate fungal growth, pathogenicity, and autophagy. Deletion of MoPYR4 led to defects in growth, conidiation, appressorium formation, the transfer and degradation of glycogen and lipid droplets, appressorium turgor accumulation, and invasive hypha expansion in M. oryzae, which eventually resulted in weakened fungal pathogenicity. Long-term replenishment of exogenous uridine-5'-phosphate (UMP) can effectively restore the phenotype and virulence of the ΔMopyr4 mutant. Further study revealed that MoPyr4 also participated in the regulation of the Pmk1-MAPK signaling pathway, co-localized with peroxisomes for the oxidative stress response, and was involved in the regulation of the Osm1-MAPK signaling pathway in response to hyperosmotic stress. In addition, MoPyr4 interacted with MoAtg5, the core protein involved in autophagy, and positively regulated autophagic degradation. Taken together, our results suggested that MoPyr4 for UMP biosynthesis was crucial for the development and pathogenicity of M. oryzae. We also revealed that MoPyr4 played an essential role in the external stress response and pathogenic mechanism through participation in the Pmk1-MAPK signaling pathway, peroxisome-related oxidative stress response mechanism, the Osm1-MAPK signaling pathway and the autophagy pathway.

A New Methodology for High Spatiotemporal Resolution Measurements of Air Volatile Organic Compounds: From Sampling to Data Deconvolution.

Monitoring of volatile organic compounds (VOCs) in air is crucial for understanding their atmospheric impacts and advancing their emission reduction plans. This study presents an innovative integrated methodology suitable for achieving semireal-time high spatiotemporal resolution three-dimensional measurements of VOCs from ground to hundreds of meters above ground. The methodology integrates an active AirCore sampler, custom-designed for deployment from unmanned aerial vehicles (UAV), a proton-transfer-reaction mass spectrometry (PTR-MS) for sample analysis, and a data deconvolution algorithm for improved time resolution for measurements of multiple VOCs in air. The application of the deconvolution technique significantly improves the signal strength of data from PTR-MS analysis of AirCore samples and enhances their temporal resolution by 4 to 8 times to 4-11 s. A case study demonstrates that the methodology can achieve sample collection and analysis of VOCs within 45 min, resulting in >120-360 spatially resolved data points for each VOC measured and achieving a horizontal resolution of 20-55 m at a UAV flight speed of 5 m/s and a vertical resolution of 5 m. This methodology presents new possibilities for acquiring 3-dimensional spatial distributions of VOC concentrations, effectively tackling the longstanding challenge of characterizing three-dimensional VOC distributions in the lowest portion of the atmospheric boundary layer.

[Two new pinophol derivatives from endophytic fungus Penicillium herquei JX4 hosted in Ceriops tagal].

An OSMAC strategy was used to study secondary metabolites and anti-inflammatory activities of the endophytic fungus Penicillium herquei JX4 hosted in Ceriops tagal. The PDB ferment of fungus P. herquei JX4 was isolated, purified, and identified by using silica gel column chromatography, gel column chromatography, octadecylsilyl(ODS) column chromatography, and semi-preparative high-performance liquid chromatography. Two new pinophol derivatives, pinophol H(1) and pinophol I(2) were isolated and identified, and they were evaluated in terms of the inhibitory activities against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse macrophage RAW264.7 cells. The results showed that compound 1 had significant inhibitory activity on NO production, with an IC_(50) value of 8.12 µmol·L~(-1).

Sex differences in clinical profile, left ventricular remodeling and cardiovascular outcomes among diabetic patients with heart failure and reduced ejection fraction: a cardiac-MRI-based study.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is associated with a high rate of mortality and morbidity. Evidence has shown that sex differences may be an important contributor to phenotypic heterogeneity in patients with HFrEF. Although diabetes mellitus (DM) frequently coexists with HFrEF and results in a worse prognosis, there remains a need to identify sex-related differences in the characteristics and outcomes of this population. In this study, we aimed to investigate the between-sex differences in clinical profile, left ventricular (LV) remodeling, and cardiovascular risk factors and outcomes in patients with HFrEF concomitant with DM. METHODS: A total of 273 patients with HFrEF concomitant with DM who underwent cardiac MRI were included in this study. Clinical characteristics, LV remodeling as assessed by cardiac MRI, and cardiovascular risk factors and outcomes were compared between sexes. RESULTS: Women were older, leaner and prone to have anemia and hypoproteinemia but less likely to have ischemic etiology. Cardiac MRI revealed that despite similar LVEFs between the sexes, there was more LV concentric remodeling, less impaired global systolic peak strain in longitudinal and circumferential components and a decreased likelihood of late gadolinium enhancement presence in women than in men. During a median follow-up time of 34.6 months, women exhibited better overall survival than men did (log-rank P = 0.042). Multivariable Cox proportional hazards analysis indicated different risk factors for predicting outcomes between sexes, with hypertension [hazard ratio (HR) = 2.05, 95% confidence interval (CI) 1.05 to 4.85, P = 0.041] and hypoproteinemia (HR = 2.27, 95% CI 1.06 to 4.37, P = 0.039) serving as independent determinants of outcomes in women, whereas ischemic etiology (HR = 1.96, 95% CI 1.11 to 3.48, P = 0.021) and atrial fibrillation (HR = 1.86, 95% CI 1.02 to 3.41, P = 0.044) served as independent determinants of outcomes in men. CONCLUSIONS: Among patients with HFrEF concomitant with DM, women displayed different LV remodeling and risk factors and had better survival than men did. Sex-based phenotypic heterogeneity in patients with HFrEF in the context of DM should be addressed in clinical practice.

UiO-66/PIM-1 Mixed-Matrix Membrane for Hexane Isomer Separation.

The separation of high-octane dibranched alkanes from naphtha is critical in the refining of gasoline. To date, research on the membrane-based separation of alkane isomers has been limited, with a particular paucity of investigations into mixed-matrix membranes. Herein, the continuous and dense UiO-66/PIM-1 mixed-matrix membrane, which was prepared through precise control of the interfacial structure, was first applied to the differentiation of C6 alkane isomers. Due to the synergistic combination of UiO-66 with differential adsorption capabilities for alkanes and PIM-1 that possesses a cross-linkable structure, the resulting UiO-66/PIM-1-(20) membrane demonstrated remarkable separation performance and high stability. Pervaporation measurements showed that the mass fraction of 2,2-dimethylbutane in the feed side was increased from 50.0 to 75.8 wt % while an excellent flux of 1700 g m-2 h-1 was maintained over a continuous 40 h period. The UiO-66/PIM-1-(20) membrane, characterized by its facile replication and processing, shows potential for large-scale fabrication. This study offers a new approach to the membrane separation of alkane isomers.

A detailed analysis of 16S rRNA gene sequencing and conventional PCR-based testing for the diagnosis of bacterial pathogens and discovery of novel bacteria.

This study represents the first analysis of the bacterial community in chickens affected by swollen head syndrome, utilizing 16S rRNA gene sequencing. Samples were obtained from clinical laying chickens and were examined for the presence of Avibacterium paragallinarum (APG) and Ornithobacterium rhinotracheale (ORT) using conventional polymerase chain reaction (PCR). From the samples, five APG-positive (APG) and APG-negative (N-APG) samples were chosen, along with five specific pathogen-free chickens, for 16S rRNA gene sequencing. Results showed that APG and ORT were widely detected in the chicken samples with swollen head syndrome (SHS, 9/10), while APG was detected in all five specific pathogen-free (SPF) samples. In contrast, conventional PCR sensitivity was found to be inadequate for diagnosis, with only 35.7% (5/14) and 11.1% (1/9) sensitivity for APG and ORT, respectively, based on 16S rRNA gene sequencing data. Furthermore, 16S rRNA gene sequencing was able to quantify the bacteria in the samples, revealing that the relative abundance of APG in the APG group ranged from 2.7 to 81.3%, while the relative abundance of APG in the N-APG group ranged from 0.1 to 21.0%. Notably, a low level of APG was also detected in all 5 SPF samples. The study also identified a significant number of animal and human common bacterial pathogens, including but not limited to Gallibacterium anatis, Riemerella columbina, Enterococcus cecorum, Mycoplasma synoviae, Helicobacter hepaticus, and Staphylococcus lentus. In conclusion, 16S rRNA gene sequencing is a valuable tool for bacterial pathogen diagnosis and the discovery of novel bacterial pathogens, while conventional PCR is not reliable for diagnosis.

Assessment of subclinical LV myocardial dysfunction in T2DM patients with diabetic peripheral neuropathy: a cardiovascular magnetic resonance study.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most prevalent complication of diabetes, and has been demonstrated to be independently associated with cardiovascular events and mortality. This aim of this study was to investigate the subclinical left ventricular (LV) myocardial dysfunction in type 2 diabetes mellitus (T2DM) patients with and without DPN. METHODS: One hundred and thirty T2DM patients without DPN, 61 patients with DPN and 65 age and sex-matched controls who underwent cardiovascular magnetic resonance (CMR) imaging were included, all subjects had no symptoms of heart failure and LV ejection fraction ≥ 50%. LV myocardial non-infarct late gadolinium enhancement (LGE) was determined. LV global strains, including radial, circumferential and longitudinal peak strain (PS) and peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were evaluated using CMR feature tracking and compared among the three groups. Multivariable linear regression analyses were performed to determine the independent factors of reduced LV global myocardial strains in T2DM patients. RESULTS: The prevalence of non-infarct LGE was higher in patients with DPN than those without DPN (37.7% vs. 19.2%, p = 0.008). The LV radial and longitudinal PS (radial: 36.60 ± 7.24% vs. 33.57 ± 7.30% vs. 30.72 ± 8.68%; longitudinal: - 15.03 ± 2.52% vs. - 13.39 ± 2.48% vs. - 11.89 ± 3.02%), as well as longitudinal PDSR [0.89 (0.76, 1.05) 1/s vs. 0.80 (0.71, 0.93) 1/s vs. 0.77 (0.63, 0.87) 1/s] were decreased significantly from controls through T2DM patients without DPN to patients with DPN (all p < 0.001). LV radial and circumferential PDSR, as well as circumferential PS were reduced in both patient groups (all p < 0.05), but were not different between the two groups (all p > 0.05). Radial and longitudinal PSSR were decreased in patients with DPN (p = 0.006 and 0.003, respectively) but preserved in those without DPN (all p > 0.05). Multivariable linear regression analyses adjusting for confounders demonstrated that DPN was independently associated with LV radial and longitudinal PS (ß = - 3.025 and 1.187, p = 0.014 and 0.003, respectively) and PDSR (ß = 0.283 and - 0.086, p = 0.016 and 0.001, respectively), as well as radial PSSR (ß = - 0.266, p = 0.007). CONCLUSIONS: There was more severe subclinical LV dysfunction in T2DM patients complicated with DPN than those without DPN, suggesting further prospective study with more active intervention in this cohort of patients.

Single-cell transcriptomics across 2,534 microbial species reveals functional heterogeneity in the rumen microbiome.

Deciphering the activity of individual microbes within complex communities and environments remains a challenge. Here we describe the development of microbiome single-cell transcriptomics using droplet-based single-cell RNA sequencing and pangenome-based computational analysis to characterize the functional heterogeneity of the rumen microbiome. We generated a microbial genome database (the Bovine Gastro Microbial Genome Map) as a functional reference map for the construction of a single-cell transcriptomic atlas of the rumen microbiome. The atlas includes 174,531 microbial cells and 2,534 species, of which 172 are core active species grouped into 12 functional clusters. We detected single-cell-level functional roles, including a key role for Basfia succiniciproducens in the carbohydrate metabolic niche of the rumen microbiome. Furthermore, we explored functional heterogeneity and reveal metabolic niche trajectories driven by biofilm formation pathway genes within B. succiniciproducens. Our results provide a resource for studying the rumen microbiome and illustrate the diverse functions of individual microbial cells that drive their ecological niche stability or adaptation within the ecosystem.

Identification and Validation of PKR as a Direct Target for the Novel Sulfonamide-Substituted Tetrahydroquinoline Nonselective Inhibitor of the NLRP3 Inflammasome.

The NLRP3 inflammasome is a critical component of the innate immune system. The persistent abnormal activation of the NLRP3 inflammasome is implicated in numerous human diseases. Herein, sulfonamide-substituted tetrahydroquinoline derivative S-9 was identified as the most promising NLRP3 inhibitor, without obvious cytotoxicity. In vitro, S-9 inhibited the priming and activation stages of the NLRP3 inflammasome. Incidentally, we also observed that S-9 had inhibitory effects on the NLRC4 and AIM2 inflammasomes. To elucidate the multiple anti-inflammatory activities of S-9, photoaffinity probe P-2, which contained a photoaffinity label and a functional handle, was developed for target identification by chemical proteomics. We identified PKR as a novel target of S-9 in addition to NLRP3 by target fishing. Furthermore, S-9 exhibited a significant anti-neuroinflammatory effect in vivo. In summary, our findings show that S-9 is a promising lead compound targeting both PKR and NLRP3 that could emerge as a molecular tool for treating inflammasome-related diseases.

Distinct characteristics of the gut virome in patients with osteoarthritis and gouty arthritis.

BACKGROUND/PURPOSE(S): The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. METHODS: We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. RESULTS: Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. CONCLUSION: Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies.

Correlation of fluid-attenuated inversion recovery sequence vascular hyperintensity in magnetic resonance with collateral circulation and short-term clinical prognosis in acute ischemic stroke.

Background: Accurately assessing the prognosis of patient with large-scale cerebral infarction caused by acute middle cerebral artery (MCA) occlusion in the early stages of onset can help clinicians to actively and effectively intervene, thus reducing mortality and disability rates. This study set out to investigate the predictive value of fluid-attenuated inversion recovery vascular hyperintensity (FVH) on collateral circulation and clinical prognosis. Methods: The clinical data of 70 patients admitted to The First People's Hospital of Lianyungang from January 2018 to December 2021 with acute cerebral infarction due to occlusion of the proximal end of the M1 segment in the MCA were retrospectively collected. All patients had their first onset of disease and did not receive thrombolytic therapy at the time of onset. Subsequently, they underwent endovascular thrombectomy for treatment. The FVH and collateral vessel scores were derived according to patients' fluid-attenuated in version recovery (FLAIR) sequence and time-of-flight magnetic resonance angiography images. Based on the 90-day Modified Rankin Scale (mRS), patients were allocated to a good prognosis group (mRS ≤2) and a poor prognosis group (mRS =3-6). The correlation between the FVH and collateral vessel scores was assessed using the Spearman rank correlation test. Pearson correlation coefficient analysis was used to assess the correlation between FVH and the 90-day mRS together with the infarct size. Univariate analysis, multivariate binary logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were adopted to identify those factors potentially. associated with the prognosis of patients with acute ischemic stroke (AIS). Results: Out of 70 patients with acute unilateral MCA occlusion (MCAO) who met the inclusion criteria, 62 showed positive FVH sign. These 62 patients were divided into a good prognosis group (n=32) and a poor prognosis group (n=30) based on the mRS score 90 days after discharge. The Spearman rank correlation test indicated that FVH was positively correlated with collateral vessel grade (Spearman rho =0.865; P<0.001); meanwhile, Pearson correlation coefficient analysis indicated that FVH score had moderate negative correlation with 90-day mRS score (r=-0.605; P<0.001). The results of multivariate binary logistic regression analysis indicated that collateral vessel grade and FVH score may be associated with the prognosis of patients with AIS, and the area under the curve (AUC) of FVH score was larger than collateral vessel grade (AUC =0.738). Conclusions: There was a positive correlation between FVH score and collateral vessel grade, and FVH score could indicate collateral circulation. FVH score was negatively correlated with 90-day mRS score and infarct volume and thus can predict clinical prognosis.

Rapid solar-driven atmospheric water-harvesting with MAF-4-derived nitrogen-doped nanoporous carbon.

Sorption-based atmospheric water-harvesting (AWH) could help to solve global freshwater scarcity. The search for adsorbents with high water-uptake capacity at low relative humidity, rapid adsorption-desorption kinetics and high thermal conductivity is a critical challenge in AWH. Herein, we report a MAF-4 (aka ZIF-8)-derived nanoporous carbon (NPCMAF-4-800) with multiple N-doped sites, considerable micropore characteristics and inherent photothermal properties, for efficient water production in a relatively arid climate. NPCMAF-4-800 exhibited optimal water-sorption performance of 306 mg g-1 at 40% relative humidity (RH). An excellent sunlight-absorption rate was realized (97%) attributed to its high degree of graphitization. A proof-of-concept device was designed and investigated for the practical harvesting of water from the atmosphere using natural sunlight. NPCMAF-4-800 achieved an unprecedentedly high water production rate of 380 mg g-1 h-1 at 40% RH, and could produce 1.77 L kg-1 freshwater during daylight hours in an outdoor low-humidity climate of ∼25 °C and 40% RH. These findings may shed light on the potential of MOF-derived porous carbons in the AWH field, and inspire the future development of solar-driven water-generation systems.

Limit state equation and failure pressure prediction model of pipeline with complex loading.

Assessing failure pressure is critical in determining pipeline integrity. Current research primarily concerns the buckling performance of pressurized pipelines subjected to a bending load or axial compression force, with some also looking at the failure pressure of corroded pipelines. However, there is currently a lack of limit state models for pressurized pipelines with bending moments and axial forces. In this study, based on the unified yield criterion, we propose a limit state equation for steel pipes under various loads. The most common operating loads on buried pipelines are bending moment, internal pressure, and axial force. The proposed limit state equation for intact pipelines is based on a three-dimensional pipeline stress model with complex load coupling. Using failure data, we investigate the applicability of various yield criteria in assessing the failure pressure of pipelines with complex loads. We show that the evaluation model can be effectively used as a theoretical solution for assessing the failure pressure in such circumstances and for selecting appropriate yield criteria based on load condition differences.

DDAH1 promotes neurogenesis and neural repair in cerebral ischemia.

Choline acetyltransferase (ChAT)-positive neurons in neural stem cell (NSC) niches can evoke adult neurogenesis (AN) and restore impaired brain function after injury, such as acute ischemic stroke (AIS). However, the relevant mechanism by which ChAT+ neurons develop in NSC niches is poorly understood. Our RNA-seq analysis revealed that dimethylarginine dimethylaminohydrolase 1 (DDAH1), a hydrolase for asymmetric NG,NG-dimethylarginine (ADMA), regulated genes responsible for the synthesis and transportation of acetylcholine (ACh) (Chat, Slc5a7 and Slc18a3) after stroke insult. The dual-luciferase reporter assay further suggested that DDAH1 controlled the activity of ChAT, possibly through hypoxia-inducible factor 1α (HIF-1α). KC7F2, an inhibitor of HIF-1α, abolished DDAH1-induced ChAT expression and suppressed neurogenesis. As expected, DDAH1 was clinically elevated in the blood of AIS patients and was positively correlated with AIS severity. By comparing the results among Ddah1 general knockout (KO) mice, transgenic (TG) mice and wild-type (WT) mice, we discovered that DDAH1 upregulated the proliferation and neural differentiation of NSCs in the subgranular zone (SGZ) under ischemic insult. As a result, DDAH1 may promote cognitive and motor function recovery against stroke impairment, while these neuroprotective effects are dramatically suppressed by NSC conditional knockout of Ddah1 in mice.

Impact of Type 2 Diabetes Mellitus on Left Atrioventricular Coupling and Left Atrial Deformation in Patients with Essential Hypertension: An MRI Feature Tracking Study.

BACKGROUND: Hypertension (HTN) and type 2 diabetes mellitus (T2DM) are both associated with left ventricular (LV) and left atrial (LA) structural and functional abnormalities; however, the relationship between the left atrium and ventricle in this population is unclear. PURPOSE: To identify differences between hypertensive patients with and without T2DM as the basis for further investigation the atrioventricular coupling relationship. STUDY TYPE: Cross-sectional, retrospective study. POPULATION: 89 hypertensive patients without T2DM [HTN (T2DM-)] (age: 58.4 +/- 11.9 years, 48 male), 62 hypertensive patients with T2DM [HTN (T2DM+)] (age: 58.5 +/- 9.1 years, 32 male) and 70 matched controls (age: 55.0 +/- 9.6 years, 37 male). FIELD STRENGTH/SEQUENCE: 2D balanced steady-state free precession cine sequence at 3.0 T. ASSESSMENT: LA reservoir, conduit, and booster strain (εs, εe, and εa) and strain rate (SRs, SRe, and SRa), LV radial, circumferential and longitudinal peak strain (PS) and peak systolic strain rate and peak diastolic strain rate (PSSR and PDSR) were derived from LA and LV cine images and compared between groups. STATISTICAL TESTS: Chi-square or Fisher's exact test, one-way analysis of variance, analysis of covariance, Pearson's correlation, multivariable linear regression analysis, and intraclass correlation coefficient. A P value <0.05 was considered significant. RESULTS: Compared with controls, εs, εe, SRe and PS-longitudinal, PDSR-radial, and PDSR-longitudinal were significantly lower in HTN (T2DM-) group, and they were even lower in HTN (T2DM+) group than in both controls and HTN (T2DM-) group. SRs, εa, SRa, as well as PS-radial, PS-circumferential, PSSR-radial, and PSSR-circumferential were significantly lower in HTN (T2DM+) compared with controls. Multivariable regression analyses demonstrated that: T2DM and PS-circumferential and PS-longitudinal (ß = -4.026, -0.486, and -0.670, respectively) were significantly associated with εs; T2DM and PDSR-radial and PDSR-circumferential were significantly associated with εe (ß = -3.406, -3.352, and -6.290, respectively); T2DM and PDSR-radial were significantly associated with SRe (ß = 0.371 and 0.270, respectively); T2DM and PDSR-longitudinal were significantly associated with εa (ß = -1.831 and 5.215, respectively); and PDSR-longitudinal was significantly associated with SRa (ß = 1.07). DATA CONCLUSION: In hypertensive patients, there was severer LA dysfunction in those with coexisting T2DM, which may be associated with more severe LV dysfunction and suggests adverse atrioventricular coupling. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.

Soft Gel Filler Embedded Elastomer with Surfactant Improved Interface for Dielectric Elastomer Actuators.

Stretchable materials are the foundation of dielectric actuators (DEAs) for artificial muscle. However, the inadequate dielectric constant of stretchable materials has always greatly limited the performance of artificial muscle. Recently, soft fillers have been proposed to improve the dielectric property and preserve the stretchability for softness, aiming to avoid the stiffening effect of traditional rigid fillers. As composites, an amount of interfacial region is generated, which remarkably affects composites' performance from dielectrics to mechanics. Herein, we demonstrate that the size effect, interfacial binding, and compatibility have a great impact on soft filler doped composites. Particularly, according to the liquid characteristics of soft fillers, we explore an interfacial modification method using surfactants. Composite breakdown strength is thus enhanced 2.2-fold from that in the control group due to the reduction of mismatch between fillers and matrix. Moreover, surfactants alleviate the well-known stiffening effect in small fillers. The area strain of the composites reaches 10.3 ± 0.4% at a low electric field of 7 MV/m, and a soft micropump is successfully assembled. These findings demonstrate a unique and combined interfacial influence of soft filler doped elastomer, which promotes the advancements of the dielectric elastomer artificial muscle.

New Indole Alkaloids from the Fungus Talaromyces assiutensis JTY2.

Three new indole alkaloids, named talatensindoids A-C (1-3), together with two known biogenetically related indole alkaloids tryptamine (4) and L-tryptophan (5) were isolated from the Talaromyces assiutensis JTY2 based on the guidance of OSMAC approach. The structures of these indole alkaloids were determined by comprehensive spectroscopic analyses. The absolute configuration of 3 was confirmed by X-ray crystallographic analysis. Compound 1 represent the rare example of a chlorine-substituted indole alkaloid from natural products. The inhibitory activity of compounds 1-5 against two phytopathogenic fungi and three phytopathogenic bacteria was evaluated. Compound 1 exhibited broad spectrum antibacterial activities.

Lysophospholipid acyltransferase-mediated formation of saturated glycerophospholipids maintained cell membrane integrity for hypoxic adaptation.

Adaptation to hypoxia has attracted much public interest because of its clinical significance. However, hypoxic adaptation in the body is complicated and difficult to fully explore. To explore previously unknown conserved mechanisms and key proteins involved in hypoxic adaptation in different species, we first used a yeast model for mechanistic screening. Further multi-omics analyses in multiple species including yeast, zebrafish and mice revealed that glycerophospholipid metabolism was significantly involved in hypoxic adaptation with up-regulation of lysophospholipid acyltransferase (ALE1) in yeast, a key protein for the formation of dipalmitoyl phosphatidylcholine [DPPC (16:0/16:0)], which is a saturated phosphatidylcholine. Importantly, a mammalian homolog of ALE1, lysophosphatidylcholine acyltransferase 1 (LPCAT1), enhanced DPPC levels at the cell membrane and exhibited the same protective effect in mammalian cells under hypoxic conditions. DPPC supplementation effectively attenuated growth restriction, maintained cell membrane integrity and increased the expression of epidermal growth factor receptor under hypoxic conditions, but unsaturated phosphatidylcholine did not. In agreement with these findings, DPPC treatment could also repair hypoxic injury of intestinal mucosa in mice. Taken together, ALE1/LPCAT1-mediated DPPC formation, a key pathway of glycerophospholipid metabolism, is crucial for cell viability under hypoxic conditions. Moreover, we found that ALE1 was also involved in glycolysis to maintain sufficient survival conditions for yeast. The present study offers a novel approach to understanding lipid metabolism under hypoxia and provides new insights into treating hypoxia-related diseases.

Insights into Chitin-Degradation Potential of Shewanella khirikhana JW44 with Emphasis on Characterization and Function of a Chitinase Gene SkChi65.

Chitin, a polymer of ß-1,4-linked N-acetylglucosamine (GlcNAc), can be degraded into valuable oligosaccharides by various chitinases. In this study, the genome of Shewanella khirikhana JW44, displaying remarkable chitinolytic activity, was investigated to understand its chitin-degradation potential. A chitinase gene SkChi65 from this strain was then cloned, expressed, and purified to characterize its enzymatic properties and substrate hydrolysis. Genome analysis showed that, of the 14 genes related to chitin utilization in JW44, six belonged to glycoside hydrolase (GH) families because of their functional domains for chitin binding and catalysis. The recombinant chitinase SkChi65, consisting of 1129 amino acids, was identified as a member of the GH18 family and possessed two chitin-binding domains with a typical motif of [A/N]KWWT[N/S/Q] and one catalytic domain with motifs of DxxDxDxE, SxGG, YxR, and [E/D]xx[V/I]. SkChi65 was heterologously expressed as an active protein of 139.95 kDa best at 37 °C with 1.0 mM isopropyl-ß-d-thiogalactopyranoside induction for 6 h. Purified SkChi65 displayed high stability over the ranges of 30-50 °C and pH 5.5-8.0 with optima at 40 °C and pH 7.0. The kinetic parameters Km, Vmax, and kcat of SkChi65 towards colloidal chitin were 27.2 µM, 299.2 µMs-1, and 10,203 s-1, respectively. In addition to colloidal chitin, SkChi65 showed high activity towards glycol chitosan and crystalline chitin. After analysis by thin-layer chromatography, the main products were N,N'-diacetylchitobiose, and GlcNAc with (GlcNAc)2-6 used as substrates. Collectively, SkChi65 could exhibit both exo- and endochitinase activities towards diverse substrates, and strain JW44 has a high potential for industrial application with an excellent capacity for chitin bioconversion.

Hydroxychloroquine-induced hyperpigmentation of the skin and bull's-eye maculopathy in rheumatic patients: a case report and literature review.

Hydroxychloroquine (HCQ) is used as a traditional disease-modifying antirheumatic drugs (DMARDs), for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, it can cause serious adverse reactions, including hyperpigmentation of the skin and bull's-eye macular lesions. Here, we present a case of HCQ-induced hyperpigmentation of the skin and bull's-eye macular lesions in a patient who received HCQ for RA. A 65-year-old female patient developed blurred vision and hyperpigmentation of multiple areas of skin over the body for one month after 3 years of HCQ treatment for RA. Based on clinical presentation, ophthalmological examination and dermatopathological biopsy, a diagnosis of drug-induced cutaneous hyperpigmentation and bullous maculopathy of the right eye was made. After discontinuation of HCQ and treatment with iguratimod tablets, the hyperpigmentation of the patient 's skin was gradually reduced, and the symptoms of blurred vision were not significantly improved. We also reviewed the available literature on HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions and described the clinical features of HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions. In conclusion, clinicians should be aware of early cutaneous symptoms and HCQ-associated ophthalmotoxicity in patients with rheumatic diseases on HCQ sulphate and should actively monitor patients, have them undergo regular ophthalmological examinations and give appropriate treatment to prevent exacerbation of symptoms.