Advances in the biosynthesis of tetraacetyl phytosphingosine, a key substrate of ceramides.

Ceramides, formed by the dehydration of long-chain fatty acids with phytosphingosine and its derivatives, are widely used in skincare, cosmetics, and pharmaceuticals. Due to the exceedingly low concentration of phytosphingosine in plant seeds, relying on the extraction method is highly challenging. Currently, the primary method for obtaining phytosphingosine is the deacetylation of tetraacetyl phytosphingosine (TAPS) derived from fermentation. Wickerhamomyces ciferrii, an unconventional yeast from the pods of Dipteryx odorata, is the only known microorganism capable of naturally secreting TAPS, which is of great industrial value. In recent years, research and applications focused on modifying W. ciferrii for TAPS overproduction have increased rapidly. This review first describes the discovery history, applications, microbial synthesis pathway of TAPS. Research progress in using haploid breeding, mutagenesis breeding, and metabolic engineering to improve TAPS production is then summarized. In addition, the future prospects of TAPS production using the W. ciferrii platform are discussed in light of the current progress, challenges, and trends in this field. Finally, guidelines for future researches are also emphasized.

Investigating solvent effects on synthesizing novel cobalt hydroxide and fluoride complex from Co(BF4)2 as active materials of the battery supercapacitor hybrid.

Metal-organic framework (MOF) derivatives with tunable pore structure and improved conductivity are intensively designed as electroactive materials. Incorporating structure directing agents (SDA) is beneficial for designing MOF derivatives with excellent electrochemical performances. Ammonium fluoroborate has been reported as an effective SDA, coupled with cobalt salt and 2-methylimidazole, to synthesize zeolitic imidazolate framework-67 (ZIF-67) derivatives for charge storage. However, the synthetic environment for growing cobalt-based active materials is relatively complex. In this study, cobalt tetrafluoroborate (Co(BF4)2) is proposed as a novel cobalt precursor, supplementing cobalt ions and acting as the SDA in a single chemical, to synthesize the cobalt-based electroactive material of energy storage electrodes. Interactions between solvent molecules and solutes play significant roles on the morphology, composition, and electrochemical performance of active materials. Deionized water, methanol and ethanol are used as precursor solvents to understand their effects on material and electrochemical properties. The optimal electrode presents a specific capacitance of 608.3 F/g at 20 mV/s, attributed to the highest electrochemical surface area and evident compositions of cobalt fluoride and hydroxide. A battery supercapacitor hybrid achieves the maximum energy density of 45 Wh/kg at 429 W/kg. The CF retention of 100% and Coulombic efficiency of 99% are achieved after 10,000 cycles.

Atomically dispersed iron sites from eco-friendly microbial mycelium as highly efficient hydrogenation catalyst.

Iron, one of the most abundant elements on earth and an essential element for living organisms, plays a crucial role in our daily metabolism. In the field of catalysis, the development of high-performance catalysts based on less toxic iron element is also of significant importance for green chemistry and a sustainable future. To construct Fe-based heterogeneous catalysts with excellent hydrogenation performance, precise modulation of the atomic coordination structure is a key strategy for enhancing catalytic activity. In this study, we present an in-situ coating method for applying a zeolitic imidazolate framework (ZIF) onto the surface of fungal hyphae. The asymmetric coordination structure of Fe1-N3P1 was precisely tailored by utilizing the phosphorus source from the fungus and the nitrogen source in the ZIFs. Detailed characterizations and density functional theory calculations revealed that the incorporation of ZIFs not only increased the specific surface area of catalysts, but also facilitated the dispersion of Fe2P nanoparticles into the Fe1-N3P1 center, making the lowest reaction energy barrier and resulting in the best performance for nitrobenzene hydrogenation when compared to the Fe2P nanoparticles and clusters. This research introduces a novel design concept for constructing asymmetric monoatomic configuration based on the inherent characteristics of natural microorganisms and the exogenous porous coordination polymers.

A contactless in situ EFISH method for measuring electrostatic potential profile of semiconductor/electrolyte junctions.

In photoelectrochemical cells, promising devices for directly converting solar energy into storable chemical fuels, the spatial variation of the electrostatic potential across the semiconductor-electrolyte junction is the key parameter that determines the cell performance. In principle, electric field induced second harmonic generation (EFISH) provides a contactless in situ spectroscopic tool to measure the spatial variation of electrostatic potential. However, the total second harmonic generation (SHG) signal contains the contributions of the EFISH signals of semiconductor space charge layer and the electric double layer, in addition to the SHG signal of the electrode surface. The interference of these complex quantities hinders their analysis. In this work, to understand and deconvolute their contributions to the total SHG signals, bias-dependent SHG measurements are performed on the rutile TiO2(100)-electrolyte junction as a function of light polarization and crystal azimuthal angle (angle of the incident plane relative to the crystal [001] axis). A quadratic response between SHG intensity and the applied potential is observed in both the accumulation and depletion regions of TiO2. The relative phase difference and amplitude ratio are extracted at selected azimuthal angles and light polarizations. At 0° azimuthal angle and s-in-p-out polarization, the SHG intensity minimum has the best match with the TiO2 flatband potential due to the orthogonal relative phase difference between bias-dependent and bias-independent SHG terms. We further measure the pH-dependent flatband potential and probe the photovoltage under open circuit conditions using the EFISH technique, demonstrating the capability of this contactless method for measuring electrostatic potential at semiconductor-electrolyte junctions.

Three new species of Colletotrichum (Glomerellales, Glomerellaceae) associated with walnut (Juglansregia) anthracnose from China.

Colletotrichum species are significant pathogens of various economic plant hosts worldwide. In this study, 45 Colletotrichum isolates were obtained from symptomatic walnut leaves of walnut anthracnose in Shaanxi and Sichuan Provinces. In conjunction with morphological evidence and multi-gene phylogenetic analyses of internal transcribed spacer (ITS), actin (act), chitin synthase 1 (chs1), glyceraldehyde-3-phosphate dehydrogenase (gapdh) and beta-tubulin (tub2) sequences support the introduction of three new species, namely Colletotrichumcordae, C.guangyuanense and C.juglandium. Five species of Colletotrichum were identified to be C.fioriniae of the C.acutatum species complex, C.karsti of the C.boninense species complex, C.gloeosporioides, C.mengyinense and C.siamense of the C.gloeosporioides species complex. The three new species are described and illustrated in this paper and compared with taxa in the Colletotrichumgloeosporioides species complex. The current results improve the understanding of Colletotrichum species causing walnut anthracnose in China.

The Influence of High-Concentrate Diet Supplemented with Tannin on Growth Performance, Rumen Fermentation, and Antioxidant Ability of Fattening Lambs.

This experiment aimed to study the effects of tannin supplementation on growth performance, rumen fermentation characteristics, apparent digestibility and serum biochemistry, and antioxidant and immune indexes in fattening lambs. A total of 36 male Hu sheep lambs (body weight = 15.83 ± 0.48 kg and days of age = 55 ± 2 d) were fed a high-concentrate diet and randomly divided into one of three groups of 12 animals each: control with no tannin (CON) and tannin treatments (TA1, 3 g/d per lamb; TA2, 6 g/d per lamb). The feeding experiment lasted for 60 d. The results showed that the average daily gain and ruminal propionate content of lambs in the TA1 group were higher (p < 0.05) than those in the CON group. Lambs fed tannin had significantly increased (p < 0.05) microbial protein and decreased (p < 0.05) ammonia nitrogen concentrations in the rumen. In addition, the crude protein and neutral detergent fiber digestibility of the TA2 group were significantly decreased (p < 0.05) as compared with the TA1 and CON groups, respectively. The serum concentrations of triglyceride, immunoglobulin A, and catalase and the total antioxidant capacity were higher (p < 0.05) in the TA1 group that those in the CON group, whereas an opposite trend of urea nitrogen, interleukin-1ß, and malondialdehyde was found between the two groups. Also, tannin supplementation increased (p < 0.05) Lactobacillus and decreased (p < 0.05) Salmonella counts in the feces of lambs. Taken together, tannin supplementation can improve the growth performance, immunity, and antioxidant ability of fattening lambs fed a high-concentrate diet.

Akkermansia Muciniphila supplementation improves hyperlipidemia, cardiac function, and gut microbiota in high fat fed apolipoprotein E-deficient mice.

Hyperlipidemia, obesity and gut dysbiosis are pivotal risk factors for atherosclerotic cardiovascular disease (ACVD). Supplementation of Akkermansia muciniphila (AKK) has also been proven to be effective in the prevention and treatment of obesity and other metabolic disorders. Here we found that AKK was more abundant in healthy control than ACVD patients via metagenomic sequencing on fecal samples. Subsequently, we investigated the role and underlying mechanism of AKK on obesity-associated atherosclerosis. AKK intervention partially reversed the exacerbation of atherosclerotic lesion formation in ApoE-/- mice by improving dyslipidemia. Interestingly, replenishment with AKK significantly enhanced cardiac function and reduced the body weight. It also reduced pro-inflammatory cytokine IL-6 and increased anti-inflammatory IL-10 in the circulation. Additionally, AKK colonization dramatically regulated gut microbiota and increased the abundance of Lactobacillaceae. Our findings have provided novel insights into the therapeutic potential of AKK as a beneficial microbe for treating atherosclerotic-associated cardiovascular diseases.

Selective and stable visible-light-prompted scavenger-free photoelectrochemical strategy based on a ternary ErVO4/P@g-C3N4/SnS2 nanocomposite for the detection of lead ions in different water samples.

Lead ions (Pb2+) are heavy metal environmental pollutants that can significantly impact biological health. In this study, the synthesis of a ternary nanocomposite, ErVO4/P@g-C3N4/SnS2, was achieved using a combination of hydrothermal synthesis and mechanical grinding. The as-fabricated photoelectrochemical (PEC) sensor was found to be an ideal substrate for Pb2+ detection with high sensitivity and reliability. The ErVO4/P@g-C3N4/SnS2/FTO was selected as the substrate because of its remarkable and reliable photocurrent response. The Pb2+ sensor exhibited a low detection limit of 0.1 pM and a broad linear range of 0.002-0.2 nM. Moreover, the sensor exhibited outstanding stability, selectivity, and reproducibility. In real-time applications, it exhibited stable recovery and a low relative standard deviation, ensuring reliable and accurate measurements. The as-prepared PEC sensor was highly stable for the detection of Pb2+ in different water samples. This promising characteristic highlights its significant potential for use in the detection of environmental pollutants.

ECM-mimicking composite hydrogel for accelerated vascularized bone regeneration.

Bioactive hydrogel materials have great potential for applications in bone tissue engineering. However, fabrication of functional hydrogels that mimic the natural bone extracellular matrix (ECM) remains a challenge, because they need to provide mechanical support and embody physiological cues for angiogenesis and osteogenesis. Inspired by the features of ECM, we constructed a dual-component composite hydrogel comprising interpenetrating polymer networks of gelatin methacryloyl (GelMA) and deoxyribonucleic acid (DNA). Within the composite hydrogel, the GelMA network serves as the backbone for mechanical and biological stability, whereas the DNA network realizes dynamic capabilities (e.g., stress relaxation), thereby promoting cell proliferation and osteogenic differentiation. Furthermore, functional aptamers (Apt19S and AptV) are readily attached to the DNA network to recruit bone marrow mesenchymal stem cells (BMSCs) and achieve sustained release of loaded vascular endothelial growth factor towards angiogenesis. Our results showed that the composite hydrogel could facilitate the adhesion of BMSCs, promote osteogenic differentiation by activating focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/ß-Catenin signaling pathway, and eventually enhance vascularized bone regeneration. This study shows that the multifunctional composite hydrogel of GelMA and DNA can successfully simulate the biological functions of natural bone ECM and has great potential for repairing bone defects.

Multicenter radio-multiomic analysis for predicting breast cancer outcome and unravelling imaging-biological connection.

Radiomics offers a noninvasive avenue for predicting clinicopathological factors. However, thorough investigations into a robust breast cancer outcome-predicting model and its biological significance remain limited. This study develops a robust radiomic model for prognosis prediction, and further excavates its biological foundation and transferring prediction performance. We retrospectively collected preoperative dynamic contrast-enhanced MRI data from three distinct breast cancer patient cohorts. In FUSCC cohort (n = 466), Lasso was used to select features correlated with patient prognosis and multivariate Cox regression was utilized to integrate these features and build the radiomic risk model, while multiomic analysis was conducted to investigate the model's biological implications. DUKE cohort (n = 619) and I-SPY1 cohort (n = 128) were used to test the performance of the radiomic signature in outcome prediction. A thirteen-feature radiomic signature was identified in the FUSCC cohort training set and validated in the FUSCC cohort testing set, DUKE cohort and I-SPY1 cohort for predicting relapse-free survival (RFS) and overall survival (OS) (RFS: p = 0.013, p = 0.024 and p = 0.035; OS: p = 0.036, p = 0.005 and p = 0.027 in the three cohorts). Multiomic analysis uncovered metabolic dysregulation underlying the radiomic signature (ATP metabolic process: NES = 1.84, p-adjust = 0.02; cholesterol biosynthesis: NES = 1.79, p-adjust = 0.01). Regarding the therapeutic implications, the radiomic signature exhibited value when combining clinical factors for predicting the pathological complete response to neoadjuvant chemotherapy (DUKE cohort, AUC = 0.72; I-SPY1 cohort, AUC = 0.73). In conclusion, our study identified a breast cancer outcome-predicting radiomic signature in a multicenter radio-multiomic study, along with its correlations with multiomic features in prognostic risk assessment, laying the groundwork for future prospective clinical trials in personalized risk stratification and precision therapy.

Advancements in NADH Oxidase Nanozymes: Bridging Nanotechnology and Biomedical Applications.

Nicotinamide adenine dinucleotide (NADH) oxidase (NOX) is key in converting NADH to NAD+, crucial for various biochemical pathways. However, natural NOXs are costly and unstable. NOX nanozymes offer a promising alternative with potential applications in bio-sensing, antibacterial treatments, anti-aging, and anticancer therapies. This review provides a comprehensive overview of the types, functional mechanisms, biomedical applications, and future research perspectives of NOX nanozymes. It also addresses the primary challenges and future directions in the research and development of NOX nanozymes, underscoring the critical need for continued investigation in this promising area. These challenges include optimizing the catalytic efficiency, ensuring biocompatibility, and achieving targeted delivery and controlled activity within biological systems. Additionally, the exploration of novel materials and hybrid structures holds great potential for enhancing the functional capabilities of NOX nanozymes. Future research directions can involve integrating advanced computational modeling with experimental techniques to better understand the underlying mechanisms and to design more effective nanozyme candidates. Collaborative efforts across disciplines such as nanotechnology, biochemistry, and medicine will be essential to unlock the full potential of NOX nanozymes in future biomedical applications.

Novel design of nickel cobalt boride nanosheets-decorated molybdenum disulfide hollow spheres as efficient battery-type materials of hybrid supercapacitors.

Transition metal borides (TMBs) with high theoretical capacitances and excellent electronic properties have attracted much attention as a promising active material of supercapacitors (SCs). However, TMB nanoparticles are prone to conduct self-aggregation, which significantly deteriorates the electrochemical performance and structural stability. To address the severe self-aggregation in TMBs and improve the active material utilization, it is imperative to provide a conductive substrate that promotes the dispersion of TMB during growths. In this work, sheet-like nickel cobalt boride (NCB) was grown on molybdenum disulfide (MoS2) hollow spheres (H-MoS2) by using simple template growth and chemical reduction methods. The resultant NCB/H-MoS2-50 was observed with uniform NCB nanosheets structure on the surface of the H-MoS2 and stronger MB bonding. After optimizing the loading amount of H-MoS2, the optimal composite (NCB/H-MoS2-50) modified nickel foam (NF) exhibits a superior specific capacity (1302 C/g) than that of the NCB electrode (957 C/g) at 1 A/g. Excellent rate capability of 84.8% (1104 C/g at 40 A/g) is also achieved by the NCB/H-MoS2-50 electrode. The extraordinary electrochemical performance of NCB/H-MoS2-50 is credited to the unique nanosheet-covered hollow spheres structure for facilitating ion diffusion and versatile charge storage mechanisms from the pseudocapacitive behavior of H-MoS2 and the Faradaic redox behavior of NCB. Furthermore, a hybrid SC is assembled with NCB/H-MoS2-50 and activated carbon (AC) electrodes (NCB/H-MoS2-50//AC), which operates in a potential window up to 1.7 V and delivers a high energy density of 76.8 W h kg-1 at a power density of 850 W kg-1. A distinguished cycling stability of 93.2% over 20,000 cycles is also obtained for NCB/H-MoS2-50//AC. These findings disclose the significant potential of NCB/H-MoS2-50 as a highly performed battery-type material of SCs.

Effects of grape seed extract supplementation on the growth performance, nutrients digestion and immunity of weaned lambs.

Grape seed extract (GSE) has a variety of biological functions. At present, there has been limited information on the utilization of GSE as a feed additive in weaned lambs. The aim of this experiment was to study the potential influence of dietary supplementation with GSE on the growth performance, rumen fermentation characteristics, apparent digestibility, blood parameters and immunity in weaned lambs. In total, 30 male Hu sheep lambs with similar body weight (15.43 ± 0.49 kg) and age (48 ± 2 days) were randomly divided into two treatments: control (CON, fed basal ration) and GSE [fed basal ration and 0.6 g/d GSE (main compositions: proanthocyanidin 50%, catechin 24%, gallic acid 16% and epicatechin 6%) per lamb]. The feeding experiment lasted for 60 d. Results showed that GSE supplementation significantly increased (p = 0.008) the average daily gain of lambs. Compared with CON group, the ruminal propionate and butyrate concentrations were significantly increased (p < 0.05) in GSE group, whereas the ammonia nitrogen was decreased (p = 0.007). Also, the crude protein, neutral detergent fiber and ether extract digestibility of GSE group were higher (p < 0.05) than those of CON group. The serum contents of glucose, triglyceride, immunoglobulin G, glutathione peroxidase and total antioxidant capacity were significantly increased (p < 0.05) in GSE group when compared to those in CON group. However, an opposite trend of urea nitrogen, non-esterified fatty acid, interleukin-1ß, itumor necrosis factor-α and malondialdehyde was observed between the two groups. Additionally, supplementation of GSE increased (p < 0.05) the Lactobacillus and decreased (p < 0.05) the Escherichia coli and Salmonella counts in the feces of lambs. In summary, GSE supplementation can improve growth performance, nutrient digestion and immunity of weaned lambs.

Transcriptomic analysis and validation study of key genes and the HIF­1α/HO­1 pathway associated with ferroptosis in neutrophilic asthma.

Ferroptosis, as a unique form of cell death caused by iron overload and lipid peroxidation, is involved in the pathogenesis of various inflammatory diseases of the airways. Inhibition of ferroptosis has become a novel strategy for reducing airway epithelial cell death and improving airway inflammation. The aim of the present study was to analyze and validate the key genes and signaling pathways associated with ferroptosis by bioinformatic methods combined with experimental analyzes in vitro and in vivo to aid the diagnosis and treatment of neutrophilic asthma. A total of 1,639 differentially expressed genes (DEGs) were identified in the transcriptome dataset. After overlapping with ferroptosis-related genes, 11 differentially expressed ferroptosis-related genes (DE-FRGs) were obtained. A new diagnostic model was constructed by these DE-FRGs from the transcriptome dataset with those from the GSE108417 dataset. The receiver operating characteristic curve analysis indicated that the area under the curve had good diagnostic performance (>0.8). As a result, four key DE-FRGs (CXCL2, HMOX1, IL-6 and SLC7A5) and biological pathway [hypoxia-inducible factor 1 (HIF-1) signaling pathway] associated with ferroptosis in neutrophilic asthma were identified by the bioinformatics analysis combined with experimental validation. The upstream regulatory network of key DE-FRGs and target drugs were predicted and the molecular docking results from screened 37 potential therapeutic drugs revealed that the 13 small-molecule drugs exhibited a higher stable binding to the primary proteins of key DE-FRGs. The results suggested that four key DE-FRGs and the HIF-1α/heme oxygenase 1 pathway associated with ferroptosis have potential as novel markers or targets for the diagnosis or treatment of neutrophilic asthma.

Manganese inhibits HBV transcription and promotes HBsAg degradation at non-toxic levels.

Chronic hepatitis B virus (HBV) infection continues to pose a significant global health challenge. However, therapeutic measures for a cure are lacking in clinical practice. Manganese, an essential trace element, has garnered attention due to its potential to activate innate immune pathways and its significant role in antiviral and antitumor immunity. Yet, the specific impact of manganese on chronic hepatitis B has been largely unexplored. Our research reveals that manganese substantially inhibits HBV replication in hepatocellular carcinoma cells at non-toxic levels. This suppression occurs independently of well-known anti-HBV innate immune pathways, such as the cGAS-STING pathway. Mechanistically, manganese decreases HBV transcription by diminishing the levels of liver-specific transcription factors. Furthermore, it activates the mTOR pathway, enhancing HBsAg ubiquitination through the upregulation of the ubiquitin ligase ß-TrCP and increasing proteasome activity via the augmentation of its subunits, leading to a ubiquitin-dependent degradation of HBsAg. Significantly, our study also uncovers a notable clinical correlation between manganese levels and chronic hepatitis B infection. These findings position manganese as a critical element in diminishing HBV replication, offering a new direction in the management of chronic hepatitis B.

Engineering Yarrowia lipolytica for Efficient Synthesis of Geranylgeraniol.

Geranylgeraniol (GGOH) is a crucial component in fragrances and essential oils, and a valuable precursor of vitamin E. It is primarily extracted from the oleoresin of Bixa orellana, but is challenged by long plant growth cycles, severe environmental pollution, and low extraction efficiency. Chemically synthesized GGOH typically comprises a mix of isomers, making the separation process both challenging and costly. Advancements in synthetic biology have enabled the construction of microbial cell factories for GGOH production. In this study, Yarrowia lipolytica was engineered to efficiently synthesize GGOH by expressing heterologous phosphatase genes, enhancing precursor supplies of farnesyl diphosphate, geranylgeranyl pyrophosphate, and acetyl-CoA, and downregulating the squalene synthesis pathway by promoter engineering. Additionally, optimizing fermentation conditions and reducing reactive oxygen species significantly increased the GGOH titer to 3346.47 mg/L in a shake flask. To the best of our knowledge, this is the highest reported GGOH titer in shaking flasks to date, setting a new benchmark for terpenoid production.

Facile Combination of Bismuth Vanadate with Nickel Tellurium Oxide for Efficient Photoelectrochemical Catalysis of Water Oxidation Reactions.

Bismuth vanadate (BVO) having suitable band edges is one of the effective photocatalysts for water oxidation, which is the rate-determining step in the water splitting process. Incorporating cocatalysts can reduce activation energy, create hole sinks, and improve photocatalytic ability of BVO. In this work, the visible light active nickel tellurium oxide (NTO) is used as the cocatalyst on the BVO photoanode to improve photocatalytic properties. Different NTO amounts are deposited on the BVO to balance optical and electrical contributions. Higher visible light absorbance and effective charge cascades are developed in the NTO and BVO composite (NTO/BVO). The highest photocurrent density of 6.05 mA/cm2 at 1.23 V versus reversible hydrogen electrode (VRHE) and the largest applied bias photon-to-current efficiency (ABPE) of 2.13% are achieved for NTO/BVO, while BVO shows a photocurrent density of 4.19 mA/cm2 at 1.23 VRHE and ABPE of 1.54%. Excellent long-term stability under light illumination is obtained for NTO/BVO with photocurrent retention of 91.31% after 10,000 s. The photoelectrochemical catalytic mechanism of NTO/BVO is also proposed based on measured band structures and possible interactions between NTO and BVO. This work has depicted a novel cocatalytic BVO system with a new photocharging material and successfully achieves high photocurrent densities for catalyzing water oxidation.

[Effect of Selinexor on Proliferation and Apoptosis of Acute Myeloid Leukemia Kasumi-1 Cells].

OBJECTIVE: To investigate the effects of selinexor, a inhibitor of nuclear export protein 1 (XPO1) on the proliferation inhibition and apoptosis of Kasumi-1 cells in acute myeloid leukemia (AML). METHODS: MTS method was used to detect the inhibitory effect of different concentrations of selinexor on the proliferation of Kasumi-1 cells at different time points. The apoptosis rate and cell cycle changes after treatment with different concentration of selinexor were detected by flow cytometry. RESULTS: Selinexor inhibited the growth of Kasumi-1 cells at different time points in a concentration-dependent manner (r 24 h=0.7592, r 48 h=0.9456, and r 72 h=0.9425). Selinexor inhibited Kasumi-1 cells growth in a time-dependent manner (r =0.9057 in 2.5 µmol/L group, r =0.9897 in 5 µmol/L group and r =0.9994 in 10 µmol/L group). Selinexor could induce apoptosis of Kasumi-1 cells in a dose-dependent manner (r =0.9732), and the apoptosis of Kasumi-1 cells was more obvious with the increase of drug concentration. The proportion of G0/G1 phase was significantly increased and the proportion of S phase was significantly decreased after the treatment of Kasumi-1 cells by selinexor. With the increase of drug concentration, the proportion of Kasumi-1 cells cycle arrest in G0/G1 phase was increased and the cell synthesis was decreased. CONCLUSION: Selinexor can promote the death of tumor cells by inhibiting Kasumi-1 cells proliferation, inducing apoptosis and blocking cell cycle.

Upregulation of Metrnl improves diabetic kidney disease by inhibiting the TGF-ß1/Smads signaling pathway: A potential therapeutic target.

PURPOSE: This study comprises an investigation of the role of meteorin-like (Metrnl) in an experimental model of diabetic kidney disease (DKD). METHODS: Twenty-four db/db mice were randomly assigned to one of the following groups: DKD, DKD + Metrnl-/-, and DKD + Metrnl+/+. Plasma Metrnl concentrations were measured using ELISA. Kidney tissues were examined via western blotting, qRT-PCR, and immunohistochemistry to determine the expression levels of inflammatory factors. Electron microscopy was employed to observe stained kidney sections. RESULTS: Compared with the NC group, FBG, BW, and UACR were elevated in the DKD and Metrnl-/- groups, with severe renal pathological injury, decreased serum Metrnl concentration, decreased renal Metrnl expression, and increased expression levels of TNF-α, TGF-ß1, TGF-R1, pSmad2, pSmad3, and α-SMA. In contrast, the Metrnl+/+ group showed decreased FBG and UACR, BUN, TC and TG, increased HDL-C and serum Metrnl concentration, increased renal Metrnl expression, and decreased expression of TNF-α, TGF-ß1, TGF-R1, pSmad2, pSmad3, and α-SMA, compared to the DKD and Metrnl-/- groups. A Pearson bivariate correlation analysis revealed a negative correlation between UACR and Metrnl, and a positive correlation between UACR and TGF-ß1. CONCLUSION: Upregulation of renal Metrnl expression can improve renal injury by downregulating the expression of molecules in the TGF-ß1/Smads signaling pathway in the renal tissues of type 2 diabetic mice; and by reducing the production of fibrotic molecules such as α-SMA.

Diversity and Pathogenicity of Six Diaporthe Species from Juglans regia in China.

Walnut (Juglans regia L.) is cultivated extensively in China for its substantial economic potential as a woody oil species. However, many diseases caused by Diaporthe greatly affect the health of Juglans regia trees. The present study revealed the presence of Diaporthe species from Juglans regia. A total of six species of Diaporthe were isolated from twigs of Juglans regia in three provinces in China, including two known species (Diaporthe gammata and D. tibetensis) and four novel species (D. chaotianensis, D. olivacea, D. shangluoensis and D. shangrilaensis). Phylogenetic relationships of the new species were determined by multilocus phylogenetic analyses based on partial sequences of the internal transcribed spacer (ITS) region, calmodulin (cal) gene, histone H3 (his3) gene, translation elongation factor 1-α (tef1-α) gene and ß-tubulin (tub2) gene. Pathogenicity tests indicated that all Diaporthe species obtained in this study were confirmed as pathogens of Juglans regia. This study deepens the understanding of species associated with several disease symptoms in Juglans regia and provides useful information for effective disease control.