Pretreatment of chitin depolymerization by expansin-like protein to improve hydrolysis efficiency.

Chitin is a polysaccharide similar to cellulose that contains abundant hydrogen bonds. Expansin-like proteins disrupt hydrogen bond networks, causing cellulose to swell and accelerating its degradation. We examined the effects of pretreatment with two expansin-like proteins, CxEXL22 (Arthrobotrys sp. CX1) and HcEXL (Hahella chejuensis), on chitin depolymerisation and enzymatic degradation. The efficiency of chitin degradation increased more than two-fold after pretreatment with expansin-like proteins. Following pretreatment with expansin-like proteins, chitin had a lower crystallinity index, greater d-spacing and crystallite size, and weaker hydrogen bonds, and the loosened porous microfibrils were more exposed than in untreated chitin. The rupture characterisation of crystalline chitin indicated that expansin-like proteins loosened the hydrogen bonds of the chitin polysaccharide chains, causing significant depolymerisation to expose more porous structures and enhance chitin accessibility.

Mendelian randomization study on insulin resistance and risk of hypertension and cardiovascular disease.

Observational studies have suggested that insulin resistance (IR) is associated with hypertension and various cardiovascular diseases. However, the presence of a causal relationship between IR and cardiovascular disease remains unclear. Here, we applied Mendelian randomization (MR) approaches to address the causal association between genetically determined IR and the risk of cardiovascular diseases. Our primary genetic instruments comprised 53 SNPs associated with IR phenotype from a GWAS of up to 188,577 participants. Genetic association estimates for hypertension and venous thromboembolism (VTE) were extracted from UK Biobank, estimates for atrial fibrillation (AF) were extracted from the hitherto largest GWAS meta-analysis on AF, estimates for heart failure were extracted from HERMES Consortium, estimates for peripheral artery disease (PAD) and aortic aneurysm were extracted from the FinnGen Study. The main analyses were performed using the random-effects inverse-variance weighted approach, and complemented by sensitivity analyses and multivariable MR analyses. Corresponding to 55% higher fasting insulin adjusted for body mass index, 0.46 mmol/L lower high-density lipoprotein cholesterol and 0.89 mmol/L higher triglyceride, one standard deviation change in genetically predicted IR was associated with increased risk of hypertension (odds ratio (OR) 1.06, 95% CI 1.04-1.08; P = 1.91 × 10-11) and PAD (OR 1.90, 95% CI 1.43-2.54; P = 1.19 × 10-5). Suggestive evidence was obtained for an association between IR and heart failure (OR per SD change in IR: 1.19, 95% CI 1.01-1.41, P = 0.041). There was no MR evidence for an association between genetically predicted IR and atrial fibrillation, VTE, and aortic aneurysm. Results were widely consistent across all sensitivity analyses. In multivariable MR, the association between IR and PAD was attenuated after adjustment for lipids (P = 0.347) or BMI (P = 0.163). Our findings support that genetically determined IR increases the risk of hypertension and PAD.

Triamcinolone acetonide suppressed scar formation in mice and human hypertrophic scar fibroblasts in a dose-dependent manner.

A hypertrophic scar is a complex medical problem. The study of triamcinolone acetonide for the treatment of scars is necessary. The 7mm full-thickness skin wounds were created on the back of BALA/c mice to construct the animal scar model. The different doses of triamcinolone acetonide injection or normal saline were injected into the wound on the 15th, 30th and 45th day after the operation. The skin histopathological changes of mice were observed by Hematoxylin-Eosin (H&E) staining. The proteins and mRNA expression level of scar-biomarkers (COL1, COL3, α-SMA) in mice scar tissue were detected by western blot and qRT-PCR. Besides, the effect of triamcinolone acetonide on the proliferation, invasion, and migration of human hypertrophic scar fibroblast (hHSFs) in vitro was also explored by cck-8, transwell and wound healing assays. After triamcinolone acetonide was injected into the wound, the proportion of scar was significantly reduced, and the treatment effect was concentration-dependently. H&E staining showed that the skin histopathological of mice was improved dose-dependently after injecting the low/middle/high-dosage of triamcinolone acetonide. The proteins and mRNA expression levels of COL1, COL3, and α-SMA were reduced dose-dependently in mice scar tissue. Furthermore, triamcinolone acetonide dose-dependently suppressed the proliferation, invasion, and migration of hHSFs in vitro. Together, triamcinolone acetonide suppressed scar formation in mice and human hypertrophic scar fibroblasts in a dose-dependent manner, phenotypically and mechanistically. The research and further exploration of triamcinolone acetonide in treating scar formation may find new effective treatment methods for the scar.

Factors influencing immunogenicity and safety of SARS-CoV-2 vaccine in liver transplantation recipients: a systematic review and meta-analysis.

Background: This review summarizes the factors influencing the efficacy and safety of the COVID-19 vaccine in LTR through meta-analysis, hoping to provide strategies for vaccine use. Methods: Electronic databases were screened for studies on mRNA vaccines in LTR. The primary outcome was the pooled seroconversion rate, and the secondary outcome was the incidence of adverse events+breakthrough infections. Subgroup analyses were made based on BMI, associated comorbidities, presence of baseline leukopenia, time since transplant, and drugs used. Result: In total, 31 articles got included. The pooled seroconversion rate after at least two doses of SARS-CoV-2 vaccination was 72% (95% CI [0.52-0.91). With significant heterogeneity among studies I2 = 99.9%, the seroconversion rate was about 72% (95%CI [0.66-0.75]), from the studies reporting two doses of vaccine slightly higher around 75%(95%CI [0.29-1.22]) from studies reporting three doses. The pooled seroconversion rate within the lower to normal BMI group was 74% (95% CI [0.22-1.27], Pi=0.005) against 67% (95% CI [0.52-0.81], Pi=0.000) in the high BMI group. The pooled seroconversion rate in the ''positive leukopenia'' group was the lowest, 59%. Leukopenia could influence the vaccine seroconversion rate in LTR. From the time since transplant analysis after setting seven years as cut off point, the pooled seroconversion rate after at least two doses of COVID-19 vaccination was 53% (95% CI [0.18-0.83], P=0.003, I2 = 99.6%) in <7years group and 83% (95% CI [0.76-0.90], P=0.000 I2 = 95.7%) in > 7years group. The only time since transplantation had reached statistical significance to be considered a risk factor predictor of poor serological response (OR=1.27 95%CI [1.03-1.55], P=0.024). The breakthrough infection rate after vaccination was very low2% (95% CI 0.01-0.03, I2 = 63.0%), and the overall incidence of adverse events, which included mainly pain at the injection site and fatigue, was 18% (95%CI [0.11-0.25], I2 = 98.6%, Pi=0.000). Conclusion: The seroconversion rate in LTR vaccinated with at least two doses of mRNA COVID-19 vaccine could be significantly affected by the vaccine type, immunosuppressant used, BMI, leukopenia, associated comorbidities, and time since transplantation. Nevertheless, booster doses are still recommended for LTR.

First report of the ectomycorrhizal fungal community associated with two herbaceous plants in Inner Mongolia, China.

Ectomycorrhizal (EM) fungi play a vital role in ensuring plant health, plant diversity, and ecosystem function. However, the study on fungal diversity and community assembly of EM fungi associated with herbaceous plants remains poorly understood. Thus, in our study, Carex pediformis and Polygonum divaricatum in the subalpine meadow of central Inner Mongolia, China were selected for exploring EM fungal diversity and community assembly mechanisms by using llumina MiSeq sequencing of the fungal internal transcribed spacer 2 region (ITS2). We evaluated the impact of soil, climatic, and spatial variables on EM fungal diversity and community turnover. Deterministic vs. stochastic processes for EM fungal community assembly were quantified using ß-Nearest taxon index scores. The results showed that a total of 70 EM fungal OTUs belonging to 21 lineages were identified, of which Tomentella-Thelephora, Helotiales1, Tricholoma, Inocybe, Wilcoxina were the most dominant EM fungal lineages. EM fungal communities were significantly different between the two herbaceous plants and among the two sampling sites, and this difference was mainly influenced by soil organic matter (OM) content and mean annual precipitation (MAP). The neutral community model (NCM) explained 45.7% of the variations in EM fungi community assembly. A total of 99.27% of the ß-Nearest Taxa Index (ßNTI) value was between -2 and 2. These results suggest that the dominant role of stochastic processes in shaping EM fungal community assembly. In addition, RCbray values showed that ecological drift in stochastic processes dominantly determined community assembly of EM fungi. Overall, our study shed light on the EM fungal diversity and community assembly associated with herbaceous plants in the subalpine region of central Inner Mongolia for the first time, which provided a better understanding of the role of herbaceous EM fungi.

Bright white electroluminescence from polycrystalline dysprosium-doped yttrium gallium garnet nanofilms fabricated by atomic layer deposition on silicon.

Bright white emission is obtained under electrical excitation from dysprosium doped Y3Ga5O12 garnet (YGG:Dy) nanofilms fabricated by atomic layer deposition on silicon substrates. Electroluminescence (EL) composed of yellow (580 nm) and blue (482 and 492 nm) emission corresponds to the CIE chromaticity coordinates of (0.3568, 0.3807) and a CCT of ∼4700 K and can be used for lighting and displays. The crystallization and micro-morphology of polycrystalline YGG:Dy nanolaminates are explored by adjusting the annealing temperature, Y/Ga ratio, Ga2O3 interlayer thickness and Dy2O3 dopant cycle. The near-stoichiometric device annealed at 1000 °C presents optimal EL performance with the maximum external quantum efficiency and the optical power density reaching 6.35% and 18.13 mW cm-2, respectively. The EL decay time is estimated to be 273.05 µs, with a large excitation section of 8.33 × 10-15 cm2. The conduction mechanism is confirmed to be the Poole-Frenkel mode under operation electric fields and the impact-excitation of Dy3+ ions by energetic electrons results in emission. Bright white emission from Si-based YGG:Dy devices can provide a new route to developing integrated light sources and display applications.

Atomic layer deposition of Er-doped yttrium aluminum gallium garnet nanofilms with tunable crystallization and electroluminescence properties.

Polycrystalline erbium-doped Y3(AlxGa1-x)5O12 (Er-YAGG) nanofilms with various Al/Ga compositions are deposited on silicon using atomic layer deposition followed by annealing at different temperatures. The Al/Ga ratios and the corresponding annealing temperatures required for crystallization are confirmed by investigating the diffraction patterns and micro-morphologies. The co-alloying of Al and Ga compositions controllably changes the lattice constant and impacts the grain growth. The crystal-field splitting of doped Er3+ ions is also modified, manifesting different electroluminescence (EL) spectra that also indicate the crystallization of garnet matrices. The EL performance of a device based on the Y3Al2Ga3O12 nanofilm (1.39 at% Er dopant) annealed at 900 °C is improved due to the adjustment of morphology and microstructural perturbations that are beneficial for radiative transition. The optimal EL device exhibits a low onset voltage of ∼25 V and a maximum external quantum efficiency of 3.29%. The excitation cross-section under electrical pumping is estimated to be 1.18 × 10-15 cm2. The carrier transport of these co-alloyed Er-YAGG devices conforms to the Poole-Frenkel mechanism. Both the EL decay lifetime and the device operation time increase with the incorporation of Ga within the Er-YAGG nanofilms. These Er-YAGG devices with tunable optoelectronic properties manifest promising potential for the engineering of light sources compatible with CMOS technology.

Management of the Uncinate Process in No-Touch Laparoscopic Pancreaticoduodenectomy.

Laparoscopic pancreatoduodenectomy (LPD) is a demanding abdominal operation that necessitates meticulous surgical skills and teamwork. The management of the pancreatic uncinate process is one of the most important and difficult processes in LPD because of its deep anatomical location and difficult exposure. Complete resection of the uncinate process and mesopancreas has become the cornerstone of LPD. In particular, it is even more difficult to avoid positive surgical margins and incomplete lymph node dissection when the tumor is located in the uncinate process. No-touch LPD, which is an ideal oncological operation process fitting the "tumor-free" principle, has been reported by our group previously. This article introduces the management of the uncinate process in no-touch LPD. Based on the multi-angle arterial approach, in this protocol, the median-anterior and left-posterior approaches to the SMA are used to correctly deal with the important vascular structure, the inferior pancreaticoduodenal artery (IPDA), in order to ensure the safe and complete excision of the uncinate process and mesopancreas. For the achievement of the no-touch isolation technique in LPD, the pancreatic head and the blood supply to the duodenal region must be severed at the very early stage of the operation; after that, the tumor can be isolated intact, resection can be performed in situ, and finally, the tissue can be removed en bloc. This paper aims to show the distinctive ways to manage the uncinate process in no-touch LPD and investigate the viability and safety of this approach. Moreover, the technique may increase the R0 resection rate.

Along with cyclic electron flow and non-photochemical quenching, water-to-water cycle is involved uniquely in alleviating Zn stress-caused photodamage in Melia azedarach.

Zinc (Zn) is a widespread industrial pollutant that has detrimental effects on plant growth and development. Photoprotective properties ensure plant survival during stress by protecting the photosynthetic apparatus. This occurs via numerous mechanisms, including non-photochemical quenching (NPQ), cyclic electron flow (CEF) and the water-to-water cycle (WWC). However, whether and how Zn stress affects the photoprotective properties of plants to enhance the tolerance of Zn toxicity remains unknown. In this study, we treated Melia azedarach plants with different Zn concentrations ranging from 200 to 1000 mg kg-1. We then analyzed the activities of two leaf photosynthetic pigment components-photosystems I and II (PSI and PSII)-and the relative expression levels of their subunit genes. As expected, we found that Zn treatment decreases photosynthesis and increases photodamage in M. azedarach leaves. The Zn treatments exacerbated a variety of photodamage phenotypes in photosystem activities and altered the expression levels of key photosystem complex genes and proteins. Furthermore, our results demonstrated that PSI was more seriously damaged than PSII under Zn stress. Subsequently, we compared differences in photodamage in the NPQ, CEF and WWC photoprotection pathways under Zn stress and found that each exerted a protective function again photodamage under 200 mg kg-1 Zn stress. The NPQ and CEF may also play major protective roles in the avoidance of irreversible photodamage and helping to ensure survival under higher (i.e., 500 and 1000 mg kg-1) levels of Zn stress. Thus, our study revealed that NPQ- and CEF-based photoprotection mechanisms are more effective than WWC in M. azedarach upon Zn stress.

An Insight into the Essential Role of Carbohydrate-Binding Modules in Enzymolysis of Xanthan.

To date, due to the low accessibility of enzymes to xanthan substrates, the enzymolysis of xanthan remains deficient, which hinders the industrial production of functional oligoxanthan. To enhance the enzymatic affinity against xanthan, the essential role of two carbohydrate binding modules-MiCBMx and PspCBM84, respectively, derived from Microbacterium sp. XT11 and Paenibacillus sp. 62047-in catalytic properties of endotype xanthanase MiXen were investigated for the first time. Basic characterizations and kinetic parameters of different recombinants revealed that, compared with MiCBMx, PspCBM84 dramatically increased the thermostability of endotype xanthanase, and endowed the enzyme with higher substrate affinity and catalytic efficiency. Notably, the activity of endotype xanthanase was increased by 16 times after being fused with PspCBM84. In addition, the presence of both CBMs obviously enabled endotype xanthanase to produce more oligoxanthan, and xanthan digests prepared by MiXen-CBM84 showed better antioxidant activity due to the higher content of active oligosaccharides. The results of this work lay a foundation for the rational design of endotype xanthanase and the industrial production of oligoxanthan in the future.

Narrow UVB-Emitted YBO3 Phosphor Activated by Bi3+ and Gd3+ Co-Doping.

Y0.9(GdxBi1-x)0.1BO3 phosphors (x = 0, 0.2, 0.4, 0.6, 0.8, and 1.0, YGB) were obtained via high-temperature solid-state synthesis. Differentiated phases and micro-morphologies were determined by adjusting the synthesis temperature and the activator content of Gd3+ ions, verifying the hexagonal phase with an average size of ~200 nm. Strong photon emissions were revealed under both ultraviolet and visible radiation, and the effectiveness of energy transfer from Bi3+ to Gd3+ ions was confirmed to improve the narrow-band ultraviolet-B (UVB) (6PJ→8S7/2) emission of Gd3+ ions. The optimal emission was obtained from Y0.9Gd0.08Bi0.02BO3 phosphor annealed at 800 °C, for which maximum quantum yields (QYs) can reach 24.75% and 1.33% under 273 nm and 532 nm excitations, respectively. The optimal QY from the Gd3+-Bi3+ co-doped YGB phosphor is 75 times the single Gd3+-doped one, illustrating that these UVB luminescent phosphors based on co-doped YBO3 orthoborates possess bright UVB emissions and good excitability under the excitation of different wavelengths. Efficient photon conversion and intense UVB emissions indicate that the multifunctional Gd3+-Bi3+ co-doped YBO3 orthoborate is a potential candidate for skin treatment.

Degradation of atrazine in river sediment by dielectric barrier discharge plasma (DBDP) combined with a persulfate (PS) oxidation system: response surface methodology, degradation mechanisms, and pathways.

Single degradation systems based on dielectric barrier discharge plasma (DBDP) or persulfate (PS) oxidation cannot achieve the desired goals (high degradation efficiency, high mineralization rate, and low product toxicity) of degrading atrazine (ATZ) in river sediment. In this study, DBDP was combined with a PS oxidation system (DBDP/PS synergistic system) to degrade ATZ in river sediment. A Box-Behnken design (BBD) including five factors (discharge voltage, air flow, initial concentration, oxidizer dose, and activator dose) and three levels (- 1, 0, and 1) was established to test a mathematical model by response surface methodology (RSM). The results confirmed that the degradation efficiency of ATZ in river sediment was 96.5% in the DBDP/PS synergistic system after 10 min of degradation. The experimental total organic carbon (TOC) removal efficiency results indicated that 85.3% of ATZ is mineralized into CO2, H2O, and NH4+, which effectively reduces the possible biological toxicity of the intermediate products. Active species (sulfate (SO4•-), hydroxy (•OH), and superoxide (•O2-) radicals) were found to exert positive effects in the DBDP/PS synergistic system and illustrated the degradation mechanism of ATZ. The ATZ degradation pathway, composed of 7 main intermediates, was clarified by Fourier transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GC-MS). This study indicates that the DBDP/PS synergistic system is a highly efficient, environmentally friendly, novel method for the remediation of river sediment containing ATZ pollution.

Bergenin alleviates Diabetic Retinopathy in STZ-induced rats.

Diabetic retinopathy (DR) is the key cause of blindness and visual impairment in diabetes patients around the world. The high levels of oxidative stress in diabetes patients cause diabetic retinopathy. In addition to being an antioxidant, Bergenin also works as an immunosuppressant, an anti-inflammatory, and anticarcinogenic against hepatocarcinoma. This study examined the effects of Bergenin on diabetic retinopathy rats, using Streptozotocin (STZ) intraperitoneally to induce diabetes in rats. The animals were divided into four groups (n = 6), including a normal control (Group I), diabetic control (Group II), Bergenin (25 mg/kg) (Group III), and metformin (350 mg/kg) (Group IV). As previously mentioned, each animal received treatment for 60 days. To induce DR, rats were administered STZ (60 mg/kg) intraperitoneally for 60 days. Standard methods were utilized to measure the body weight of rats, blood glucose levels. We measured lipid profiles (Triglycerides, cholesterol, LDL, and HDL), inflammatory markers, and antioxidant levels with their respective kits. Analysis of retinal tissue morphometry and MMP-9, VEGF, and MCP-1 levels in serum was performed. Our research examined the expression levels of target genes (TNF-α, IL-1ß, and IL-6) using RT-PCR analysis. STZ-induced animals that were treated with Bergenin had less food intake, lower blood glucose, and improved body weight. Bergenin significantly suppressed levels of pro-inflammatory cytokines, cholesterol, TG, LDL, AI, MMP-9, VEGF, and MCP-1 and increased the level of HDL and antioxidant enzymes in STZ-induced DR rats. As well as increasing antioxidant levels, reducing retinal thickness, and increasing cell numbers, Bergenin also lessened DR remarkably. The results of this study demonstrated that Bergenin effectively inhibited STZ-induced DR in rats.

Inhibition of Chitosan with Different Molecular Weights on Barley-Borne Fusarium graminearum during Barley Malting Process for Improving Malt Quality.

There are many Fusarium graminearum contaminations in barley that are often associated with malt and beer quality issues. Thus, it is important to find a biological antifungal agent to prevent the growth of F. graminearum during malting. Minimum inhibition concentration (MIC) of chitosan for mycelial growth and spore germination of F. graminearum was 2.6 g/L and 1.6 g/L, respectively, indicating that the F. graminearum strain was highly sensitive toward chitosan. Chitosan with a molecular weight of 102.7 kDa was added at 0.5 g/kg during the first steeping stage, resulting in the maximum inhibition rate of F. graminearm in barley. The biomass of F. graminearm and deoxynivalenol content in the infected barley at the end of germination with 0.5 g/kg chitosan treatment were decreased by 50.7% and 70.5%, respectively, when compared with the infected barley without chitosan. Chitosan could remove the negative effects of F. graminearm infection on barley germination and malt quality, which makes the application of chitosan during the steeping process as a potential antifungal agent in the malting process to protect from F. graminearum infection.

Fatty acid-binding protein 5 aggravates pulmonary artery fibrosis in pulmonary hypertension secondary to left heart disease via activating wnt/ß-catenin pathway.

INTRODUCTION: Pulmonary hypertension secondary to left heart disease (PH-LHD) is a common and fatal disease. However, no effective therapeutic targets have been identified. OBJECTIVES: Here, we set out to illustrate the functional role and underlying mechanisms of fatty acid-binding protein 5 (FABP5) in PH-LHD development. METHODS: We performed a systematic analysis of datasets GSE84704 and GSE16624 to identify differentially expressed genes and then constructed protein-protein interaction network for significant modules. Potential target genes in the modules were validated by RT-qPCR and western blot in a PH-LHD mouse model. PH-LHD or sham mice were treated with FABP5 antagonist SBFI-26 or DMSO for 28 days. The role of FABP5 on cardiac function was determined by echocardiography, its impact on pulmonary vascular remodelling were evaluated with right heart catheter, histological analysis and western blot. In vitro, primary pulmonary adventitial fibroblasts were used to investigate the pro-fibrotic mechanisms involving in FABP5. RESULTS: FABP5 was the only one dramatically upregulated along with increased protein expression in the established PH-LHD mouse model. Inhibition of FABP5 by SBFI-26 injection abrogated pulmonary artery remodelling in PH-LHD and improved cardiac function. In vitro, SBFI-26 or FABP5 siRNA blunted the TGF-ß1-induced fibrotic response in cultured pulmonary adventitial fibroblasts. Mechanistically, FABP5 knockdown inhibited GSK3ß phosphorylation and increased ß-catenin phosphorylation. The wnt/ß-catenin agonist SKL2001 diminished the antifibrotic effect of FABP5 knockdown on pulmonary adventitial fibroblasts under TGF-ß1 stimulation. CONCLUSION: FABP5 is an important mediator of pulmonary artery remodelling and a potential therapeutic target for PH-LHD.

Polycrystalline Er-doped Y3Ga5O12 nanofilms fabricated by atomic layer deposition on silicon at a low temperature and the exploration on electroluminescence performance.

Polycrystalline erbium-doped Y3Ga5O12 garnet (YGG) nanofilms are deposited by atomic layer deposition on Si substrates after annealing down to 800 °C, based on which ∼1.53 µm electroluminescence (EL) devices are fabricated. The optimal EL performance depends on the adjustment of Y/Ga ratio and Ga2O3 interlayer thickness within the nanolaminates, which exert no prominent impact on the crystallization and film morphology of YGG nanofilms. EL spectra reveal that the crystalline structure after annealing impacts the surrounding environment of Er3+ ions, leading to different emission peaks. These silicon-based devices present a low turn-on voltage of ∼25 V, while the external quantum efficiency and maximum optical power density reach 2.51% and 10.03 mW cm-2, respectively. The EL is ascribed to the impact-excitation of doped Er3+ ions in polycrystalline YGG nanofilms by energetic electrons, the conduction mechanism of which is confirmed to be the Poole-Frenkel mode. These prototype devices possess excellent stability and can operate for up to 49 hours under continuous current injection, verifying the improvement of device performance by the utilization of gallium in the fabrication of garnet nanofilms. The Si-based YGG:Er EL devices are of promising potential for integrated optoelectronic applications.

Exploration of dilated cardiomyopathy for biomarkers and immune microenvironment: evidence from RNA-seq.

BACKGROUND: The pathogenic mechanism of dilated cardiomyopathy (DCM) remains to be defined. This study aimed to identify hub genes and immune cells that could serve as potential therapeutic targets for DCM. METHODS: We downloaded four datasets from the Gene Expression Omnibus (GEO) database: GSE141910, GSE3585, GSE42955 and GSE79962. Weighted gene coexpression network analysis (WGCNA) and differential expression analysis were performed to identify gene panels related to DCM. Meanwhile, the CIBERSORT algorithm was used to estimate the immune cells in DCM tissues. Multiple machine learning approaches were used to screen the hub genes and immune cells. Finally, the diagnostic value of the hub genes was assessed by receiver operating characteristic (ROC) analysis. An experimental mouse model of dilated cardiomyopathy was used to validate the bioinformatics results. RESULTS: FRZB and EXT1 were identified as hub biomarkers, and the ROC curves suggested an excellent diagnostic ability of the above genes for DCM. In addition, naive B cells were upregulated in DCM tissues, while eosinophils, M2 macrophages, and memory CD4 T cells were downregulated in DCM tissues. The increase in two hub genes and naive B cells was validated in animal experiments. CONCLUSION: These results indicated that FRZB and EXT1 could be used as promising biomarkers, and eosinophils, M2 macrophages, resting memory CD4 T cells and naive B cells may also affect the occurrence of DCM.

Development of bacterial resistance induced by low concentration of two-dimensional black phosphorus via mutagenesis.

The wide use of nano-antibacterial materials has triggered concerns over the development of nanomaterials-associated bacterial resistance. Two-dimensional (2D) black phosphorus (BP) as a new class of emerging 2D nanomaterial has displayed excellent antibacterial performance. However, whether bacteria repeatedly exposed to 2D BP can develop resistance is not clear. We found that wild type E. coli K-12 MG 1655 strains can increase resistance to 2D-BP nanosheets after repeated exposure with subinhibitory concentration of 2D-BP nanosheets. Adaptive morphogenesis including the reinforced barrier function of cell membrane were observed in the resistant bacteria, which enhanced the resistance of bacteria to 2D-BP nanosheets. The whole-genome sequencing analysis showed that the three mutation genes including dmdA, mntP, and gyrA genes were observed in the 2D-BP resistant strains, which controlled catabolism, membrane structure, and DNA replication, respectively. Furthermore, transcriptional sequencing confirmed that these genes related to metabolization, membrane structure, and cell motility were upregulated in the 2D-BP resistant bacteria. The development of resistance to 2D-BP in bacteria mainly attributed to the changes in energy metabolism and membrane structure of bacteria caused by gene mutations. In addition, the up-regulated function of cell motility also helped the bacteria to develop resistance by escaping external stimuli. The results provided new evidence for understanding an important effect of nano-antibacterial materials on the development of bacterial resistance.

Preparation of ß-cyclodextrin/dopamine hydrochloride-graphene oxide and its adsorption properties for sulfonamide antibiotics.

To develop high-efficiency antibiotic adsorbents, ß-cyclodextrin and dopamine hydrochloride were used to modify graphene oxide to prepare a new type of ternary composite material (ß-cyclodextrin/dopamine hydrochloride-graphene oxide, CD-DGO). The material was characterized using scanning electron microscopy, Fourier infrared spectrometry, transmission electron microscopy, and specific surface area optical analysis. Two typical sulfonamides antibiotics (sulfamethoxazole, sulfadiazine) adsorption capacity were evaluated in terms of the dosage of composite materials, the ratio of each component, and the pH of the solution. We analyzed the adsorption characteristics via adsorption kinetics and adsorption isotherms, and then investigated the stability of the adsorbent through desorption and regeneration of the adsorbent. The results show that the adsorption effect of sulfonamides antibiotics is best at pH = 2; the adsorption kinetics conform to the pseudo-second-order kinetic model, and the adsorption equilibrium follows the Langmuir adsorption isotherm; the maximum adsorption capacity of CD-DGO for sulfamethoxazole and sulfadiazine is 144 mg·g-1 and 152 mg·g-1, respectively. The material has good reusability, and the dominant force in the adsorption process is the π-π electron conjugation effect with hydrogen bonding. This offers a theoretical basis for the treatment of sulfonamides antibiotics water pollution.

Prognostic nomogram for predicting cancer-specific survival in patients with resected hilar cholangiocarcinoma: a large cohort study.

Background: The aim of the study was to establish and validate a novel prognostic nomogram of cancer-specific survival (CSS) in resected hilar cholangiocarcinoma (HCCA) patients. Methods: A training cohort of 536 patients and an internal validation cohort of 270 patients were included in this study. The demographic and clinicopathological variables were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate Cox regression analysis were performed in the training cohort, followed by the construction of nomogram for CSS. The performance of the nomogram was assessed by concordance index (C-index) and calibration plots and compared with the American Joint Committee on Cancer (AJCC) staging systems. Decision curve analysis (DCA) was applied to measure the predictive power and clinical value of the nomogram. Results: The nomogram incorporating age, tumor size, tumor grade, lymph node ratio (LNR) and T stage parameters was with a C-index of 0.655 in the training cohort, 0.626 in the validation cohort, compared with corresponding 0.631, 0.626 for the AJCC 8th staging system. The calibration curves exhibited excellent agreement between CSS probabilities predicted by nomogram and actual observation in the training cohort and validation cohort. DCA indicated that this nomogram generated substantial clinical value. Conclusions: The proposed nomogram provided a more accurate prognostic prediction of CSS for individual patients with resected HCCA than the AJCC 8th staging system, which might be served as an effective tool to stratify resected HCCA patients with high risk and facilitate optimizing therapeutic benefit.