Efficacy and safety of generic pomalidomide plus low-dose dexamethasone in relapsed or refractory multiple myeloma: a multicenter, open-label, single-arm trial.

This multicenter, open-label, single-arm trial (ClinicalTrials.gov, NCT05236621) was conducted to confirm the efficacy and safety of generic pomalidomide plus dexamethasone in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Total 79 eligible RRMM patients were planned to be included. Patients were treated with generic pomalidomide (4 mg daily on days 1-21, orally) and low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally; 20 mg for patients aged > 75 years) in 28-day cycles until disease progression with a maximum treatment duration of 2 years. The primary endpoint is the overall response rate (ORR) assessed by the independent review committee per the 2016 International Myeloma Working Group guidelines. A total of 85 eligible patients were included in this study from 32 centers in China, with a median age of 62.0 (range, 39-76) years, a median prior line of therapy of 4 (range, 1-16), and 41.2% patients with high-risk cytogenetics. The ORR was 38.8% (95% confidence interval (CI), 28.44-50.01). The disease control rate was 67.1% (95% CI, 56.02-76.87), meanwhile, the median progression-free survival was 5.55 months (95% CI, 3.68-7.52). Among the treatment-related adverse events (TRAEs), infective pneumonia (17.6%) was the most frequent non-hematologic adverse event, while a decrease in neutrophil count (52.9%) was the most common grade ≥ 3 TRAE. The study results indicated that the generic pomalidomide demonstrated consistent efficacy and a safety profile similar to the branded pomalidomide when combined with low-dose dexamethasone in Chinese RRMM patients.Registration number ClinicalTrials.gov NCT05236621, retrospectively registered on February 11, 2022.

Rational design of NiO/Ti3C2Tx nanocomposites with enhanced triethylamine sensing performance.

MXenes with excellent conductivity and abundant surface functional groups have displayed great advantages as platforms for sensing materials. NiO also has drawn much attention for gas detection due to its unique merits of excellent catalytic activity. Herein, NiO nanoparticles are incorporated with multilayer Ti3C2Tx-MXene to develop excellent triethylamine sensors. Due to the larger specific surface area and formed p-p heterojunctions, the response of the NiO/Ti3C2Tx gas sensor is endowed with a response value of 950% to 50 ppm triethylamine gas and is much higher than that of the pristine NiO sensor. Moreover, the NiO/Ti3C2Tx sensor displays a fast response time of 8 s (50 ppm triethylamine), excellent reproducibility, and reliable long-term stability. This study proves that NiO/Ti3C2Tx sensors have potential for the effective detection of triethylamine gas.

Room-temperature highly sensitive triethylamine detection by few-layer Nb2CTxMXene nanosheets.

MXene, a class of two-dimensional materials that are emerging as rising stars in the field of materials, are receiving much attention in sensing. Ti3C2TxMXene, the most maturely researched MXene, is widely used in energy, biomedical, laser, and microwave shielding applications and has also been expanded to gas sensing and wearable electronics applications. Compared with Ti3C2Tx, Nb2CTxMXene is more difficult to etch and has higher resistances at room temperature; so, few studies have been reported on their use in the sensing field. Based on the preparation of few-layer Nb2CTxMXene by intercalation, this study thoroughly examined their gas-sensing properties. The successfully prepared few-layer Nb2CTxshowed good selectivity and high sensitivity to triethylamine at room temperature, with response values up to 47.2% for 50 ppm triethylamine and short response/recovery time (22/20 s). This study opens an important path for the design of novel Nb-based MXene sensors for triethylamine gas detection.

Preparation of a high-performance H2S gas sensor based on CuO/Co3O4composite derived from bimetallic MOF.

The bimetallic metal-organic frameworks (MOFs), Cu/Co-MOF, was synthesized through a solvothermal method and calcined to obtain CuO/Co3O4composites. By adjusting the molar ratio between Cu and Co ions, a composite material of CuO/Co3O4(Cu:Co = 1:1) was developed and showed excellent sensing capabilities, and the response reached as high as 196.3 for 10 ppm H2S detection. Furthermore, the optimal operating temperature as low as 40 °C was found. In comparison with the sensors prepared by pristine CuO and pristine Co3O4, the sensor based on CuO/Co3O4composite exhibited a significant response. Additionally, the sensor can detect H2S gas down to 300 ppb. The gas sensing mechanism is discussed in depth from the perspective of p-p heterojunction formation between the p-type CuO and p-type Co3O4. The as-prepared CuO/Co3O4composite-based sensor is expected to find practical application in the low-power monitoring of H2S.

Integrating Mendelian Randomization with Single-cell Sequencing Data Reveals the Causal Effect and Related Mechanisms of Smoking on Parkinson's Disease.

INTRODUCTION: Smoking (nicotine) has been reported to possibly be neuroprotective and conducive to patients with early Parkinson's disease (PD). However, the causal effect of smoking on PD and the molecular mechanisms of smoking-related genes (SRGs) are vague. METHODS: First, genome-wide association study summary data on smoking (ukb-b-6244) and PD (ieu-b-7) were retrieved from the Integrative Epidemiology Unit OpenGWAS database for Mendelian randomization (MR) analysis. Sensitivity analyses were performed to validate the results of the MR analyses. Subsequently, a differential analysis of PD patients and controls was performed to identify differentially expressed SRGs (DE-SRGs). Finally, the expression of DE-SRGs was analyzed in annotated cell types. RESULTS: The MR analysis revealed that smoking was a protective factor causally related to PD (P=0.008, odds ratio=0.288). Furthermore, a total of five DE-SRGs enriched in Toll-like receptor signaling pathways were identified in GSE7621 dataset. Regarding single-cell analysis of GSE184950 dataset, a total of nine cell types were annotated. The expression of LRRN1 in oligodendrocyte progenitor cells and oligodendrocytes, respectively, differed significantly between PD patients and controls. CONCLUSIONS: Our study supported a causal relationship between smoking and PD and found that five SRGs (MAPK8IP1, LRRN1, LINC00324, HIST1H2BK, and YOD1) enriched in Toll-like receptor signaling pathways might be beneficial in PD. In addition, single-cell sequencing indicated that four SRGs were differentially expressed in different cell types. All four genes except MAPK8IP1 were significantly correlated with the 10 genes calculated by scPagwas. Thus, this evidence provides a theoretical basis for further research on the effect of nicotine (smoking) on PD. IMPLICATIONS: In order to explore the potential etiology and pathogenesis of Parkinson's disease, this study combined Mendelian randomization, transcriptomics and single-cell sequencing analysis to explore the association between exposure factors and Parkinson's disease, observe and confirm the relationship and mechanism between the two from the perspective of genetics, and provide more reliable evidence for causal inference.

Cathepsin G promotes arteriovenous fistula maturation by positively regulating the MMP2/MMP9 pathway.

BACKGROUND: Arteriovenous fistula (AVF) is currently the preferred vascular access for hemodialysis patients. However, the low maturation rate of AVF severely affects its use in patients. A more comprehensive understanding and study of the mechanisms of AVF maturation is urgently needed. METHODS AND RESULTS: In this study, we downloaded the publicly available datasets (GSE119296 and GSE220796) from the Gene Expression Omnibus (GEO) and merged them for subsequent analysis. We screened 84 differentially expressed genes (DEGs) and performed the functional enrichment analysis. Next, we integrated the results obtained from the degree algorithm provided by the Cytohubba plug-in, Molecular complex detection (MCODE) plug-in, weighted gene correlation network analysis (WGCNA), and Least absolute shrinkage and selection operator (LASSO) logistic regression. This integration allowed us to identify CTSG as a hub gene associated with AVF maturation. Through the literature search and Pearson's correlation analysis, the genes matrix metalloproteinase 2 (MMP2) and MMP9 were identified as potential downstream effectors of CTSG. We then collected three immature clinical AVF vein samples and three mature samples and validated the expression of CTSG using immunohistochemistry (IHC) and double-immunofluorescence staining. The IHC results demonstrated a significant decrease in CTSG expression levels in the immature AVF vein samples compared to the mature samples. The results of double-immunofluorescence staining revealed that CTSG was expressed in both the intima and media of AVF veins. Moreover, the expression of CTSG in vascular smooth muscle cells (VSMCs) was significantly higher in the mature samples compared to the immature samples. The results of Masson's trichrome and collagen I IHC staining demonstrated a higher extent of collagen deposition in the media of immature AVF veins compared to the mature. By constructing an in vitro CTSG overexpression model in VSMCs, we found that CTSG upregulated the expression of MMP2 and MMP9 while downregulating the expression of collagen I and collagen III. Furthermore, CTSG was found to inhibit VSMC migration. CONCLUSIONS: CTSG may promote AVF maturation by stimulating the secretion of MMP2 and MMP9 from VSMCs and reducing the extent of medial fibrosis in AVF veins by inhibiting the secretion of collagen I and collagen III.

Matched Stochastic Resonance Enhanced Underwater Passive Sonar Detection under Non-Gaussian Impulsive Background Noise.

Remote passive sonar detection with low-frequency band spectral lines has attracted much attention, while complex low-frequency non-Gaussian impulsive noisy environments would strongly affect the detection performance. This is a challenging problem in weak signal detection, especially for the high false alarm rate caused by heavy-tailed impulsive noise. In this paper, a novel matched stochastic resonance (MSR)-based weak signal detection model is established, and two MSR-based detectors named MSR-PED and MSR-PSNR are proposed based on a theoretical analysis of the MSR output response. Comprehensive detection performance analyses in both Gasussian and non-Gaussian impulsive noise conditions are presented, which revealed the superior performance of our proposed detector under non-Gasussian impulsive noise. Numerical analysis and application verification have revealed the superior detection performance with the proposed MSR-PSNR detector compared with energy-based detection methods, which can break through the high false alarm rate problem caused by heavy-tailed impulsive noise. For a typical non-Gasussian impulsive noise assumption with α=1.5, the proposed MSR-PED and MSR-PSNR can achieve approximately 16 dB and 22 dB improvements, respectively, in the detection performance compared to the classical PED method. For stronger, non-Gaussian impulsive noise conditions corresponding to α=1, the improvement in detection performance can be more significant. Our proposed MSR-PSNR methods can overcome the challenging problem of a high false alarm rate caused by heavy-tailed impulsive noise. This work can lay a solid foundation for breaking through the challenges of underwater passive sonar detection under non-Gaussian impulsive background noise, and can provide important guidance for future research work.

Integration of Hollow Microneedle Arrays with Jellyfish-Shaped Electrochemical Sensor for the Detection of Biomarkers in Interstitial Fluid.

This study integrates hollow microneedle arrays (HMNA) with a novel jellyfish-shaped electrochemical sensor for the detection of key biomarkers, including uric acid (UA), glucose, and pH, in artificial interstitial fluid. The jellyfish-shaped sensor displayed linear responses in detecting UA and glucose via differential pulse voltammetry (DPV) and chronoamperometry, respectively. Notably, the open circuit potential (OCP) of the system showed a linear variation with pH changes, validating its pH-sensing capability. The sensor system demonstrates exceptional electrochemical responsiveness within the physiological concentration ranges of these biomarkers in simulated epidermis sensing applications. The detection linear ranges of UA, glucose, and pH were 0~0.8 mM, 0~7 mM, and 4.0~8.0, respectively. These findings highlight the potential of the HMNA-integrated jellyfish-shaped sensors in real-world epidermal applications for comprehensive disease diagnosis and health monitoring.

Proteasomal inhibitors induce myeloma cell pyroptosis via the BAX/GSDME pathway.

Proteasomes are overexpressed in multiple myeloma (MM) and proteasomal inhibitors (PIs) have been widely used for the treatment of MM. PIs are reported to induce MM cell apoptosis but impair necroptosis. In the present study, we found that PIs MG132 and bortezomib induce MM cell pyroptosis, a novel type of cell death, in a GSDME-dependent manner. Lack of GSDME totally blocks PI-induced pyroptosis. Interestingly, we found that Caspase-3/6/7/9 are all involved in pyroptosis triggered by PIs because the specific inhibitor of each caspase ablates GSDME activation. PIs markedly reduce mitochondrial membrane potential. Moreover, PIs disrupt the interaction of Bcl-2 and BAX, induce cytochrome c release from mitochondria to cytosol and activate GSDME. Furthermore, we found that overexpression of an N-terminal portion of GSDME suffices to release cytochrome c from mitochondria and to activate Caspase-3/9, suggesting N-GSDME might penetrate the mitochondrial membrane. Consistent with Bcl-2 inhibition, BAX can induce MM cell pyroptosis in a GSDME-dependent manner. In accordance with these findings, inhibition of Bcl-2 synergizes with PIs to induce MM cell pyroptosis. Therefore, the present study indicates that PIs trigger MM cell pyroptosis via the mitochondrial BAX/GSDME pathway and provides a rationale for combined treatment of MM with Bcl-2 and proteasome inhibitors to increase therapeutic efficiency via induction of pyroptosis.

An IPSO-FW-WSVM Method for Stock Trading Signal Forecasting.

Trading signal detection is a very popular yet challenging research topic in the financial investment area. This paper develops a novel method integrating piecewise linear representation (PLR), improved particle swarm optimization (IPSO) and a feature-weighted support vector machine (FW-WSVM) to analyze the nonlinear relationships between trading signals and the stock data hidden in historical data. First, PLR is applied to generate numerous trading points (valleys or peaks) based on the historical data. These turning points' prediction is formulated as a three-class classification problem. Then, IPSO is utilized to find the optimal parameters of FW-WSVM. Lastly, we conduct a series of comparative experiments between IPSO-FW-WSVM and PLR-ANN on 25 stocks with 2 different investment strategies. The experiment results show that our proposed method achieves higher prediction accuracy and profitability, which indicates the IPSO-FW-WSVM method is effective in the prediction of trading signals.

Cu2O/Ti3C2Txnanocomposites for detection of triethylamine gas at room temperature.

Triethylamine gas is one of the harmful volatile organic compounds for human health and the ecological environment. Therefore, in order to prevent the detrimental effects of triethylamine gas, it has greatly requirement to be accurately detected. Unfortunately, Cu2O has a low triethylamine gas response and slow recovery. Because of this, we prepared Cu2O/Ti3C2Txnanocomposites by a facile ultrasonication technique. Cu2O is uniformly dispersed on the surface and interlayers of multilayer Ti3C2Txto form a stable hybrid heterostructure. The optimized Cu2O/Ti3C2Txnanocomposite sensor's response to 10 ppm triethylamine at room temperature is 181.6% (∣Rg-Ra∣/Ra × 100%). It is 3.5 times higher than the original Cu2O nanospheres (52.1%). Moreover, due to the characteristics of high carrier migration rate and excellent conductivity of Ti3C2Tx, the response recovery rate (1062 s/74 s) of Cu2O/Ti3C2Txcomposites is greatly improved than pristine Cu2O (3169 s/293 s). In addition, Cu2O/Ti3C2Txnanocomposites sensor also shows excellent repeatability, outstanding selectivity, and long-term stability. Thus, the Cu2O/Ti3C2Txnanocomposites sensor has broad application prospects for detecting triethylamine gas at room temperature.

First report of Alternaria alternata causing leaf yellow spot on Ginger (Zingiber officinale Roscoe) in Laifeng, China.

Ginger (Zingiber officinale Roscoe) is a highly important commercial crop in China, which is widely cultivated for its medicinal and nutritional qualities. Fengtou ginger is a variety mainly grown in Central China. From June to September of 2021, leaf yellow spot symptoms were observed on ginger plants var. Fengtou in commercial fields, localized in Laifeng county (29.37゜N, 109.31゜E), Hubei Province, China. Early symptoms were small yellow spots (approximately 0.2 cm) on leaves, but these spots gradually expanded, and the middle turn brown. The incidence of yellow spot on plants was 15% to 35%. To identify the causal agent of the disease, 15 symptomatic leaves were collected on from plants in the field. From each ginger leaf, small fragments (2 to 4 mm) were cut from the margin of the lesions and surface disinfected with 75% ethanol and 2% sodium hypochlorite for 30 s and 60 s, respectively, and rinsed three times with sterile water (Zhong et al. 2022). The disinfected small fragments were placed on Rose Bengal Agar medium at 25 ℃. After 3 to 5 days of incubation, a total of 11 isolates from leaf samples were obtained, of which 8 showed a radial mycelial growth that was grayish and then darkened. Conidiophores were brown and branched. Conidia were multicellular, obclavate to obpyriform within 9.1-22.6 µm (average 14.3 µm) in length and 6.0-13.5 µm (average 7.9 µm) in width (n=30). The isolates were identified as Alternaria sp. according to their morphological characteristics (Simmons 2007). For further molecular identification, genomic DNAs of two representative isolates (isolate 1 and isolate 4) were extracted and amplificated using a set of primers ITS1/ITS4 (White et al. 1990), RPB2-5F/RPB2-7R (Liu et al. 1999) and gpd1/gpd2 (Berbee et al. 1999), for the internal transcribed spacer (ITS)-rDNA region, partial RNA polymerase II largest subunit (RPB2), and Glyceraldehyde 3-phosphate (GADPH), respectively. The sequences were submitted to GenBank with submission Nos. OM701795 and OM701794 for ITS-rDNA; OM864662 and OM864663 for RPB2; OM864664 and OM864665 for the GADPH gene. A BLAST analysis in GenBank showed 100% identity with A. alternata for ITS (GenBank No. MN907440), RPB2 (GenBank No. KP057228) and GADPH (GenBank No. MK637444), respectively. A pathogenicity test was performed on potted healthy plants of ginger var. Fengtou of 2.5-month-old in a greenhouse. A total of five plants were sprayed with a conidial suspension (105 spores/mL) of each isolate on leaves until runoff (3 to 5 ml per plant) occurred. Five plants were sprayed with sterile water. The plants were grown in a greenhouse at 25 ℃. Eight days after inoculation, the symptoms similar to diseased leaves in the field appeared on the inoculated leaves, while the controls remained healthy. The fugus re-isolated from infected tissues was morphologically and molecularly identical to the original isolates of A. alternata, which fulfill the Koch's postulates. To our knowledge, this is the first report of A. alternata causing yellow spot on ginger in China. The work will be beneficial to develop effective management methods for preventing and treating this disease and avoid yield and economic loss of ginger in China.

Flexible fabric gas sensors based on reduced graphene-polyaniline nanocomposite for highly sensitive NH3detection at room temperature.

A flexible fabric gas sensor for the detection of sub-ppm-level NH3is reported in this paper. The reduced graphene oxide (rGO)-polyaniline (PANI) nanocomposite was successfully coated on cotton thread via anin situpolymerization technique. The morphology, microstructure and composition were analyzed by field-emission scanning electron microscope, x-ray diffraction, Fourier transform infrared spectroscopy and Raman spectroscopy. Furthermore, we have studied the responses of the rGO-PANI nanocomposite-based flexible sensors for the detection of NH3varying from 1-100 ppm, operated at 22 °C. At the optimized concentration of rGO, the response of these sensors increased by 4-5 times in comparison with the pristine rGO and PANI. These flexible sensors exhibited fast response, remarkable long-term stability, good selectivity and a low detection limit. The sensing mechanism for the high sensing performance has been thoroughly discussed and it is mainly due to the distinctive 1D fiber structure, the formation of a p-p heterojunction between the rGO nanosheets and PANI. The rGO-PANI composite-based fabric sensor with low power consumption is a potential flexible electronic device for the detection of NH3.

Host genetics and the rumen microbiome jointly associate with methane emissions in dairy cows.

Cattle and other ruminants produce large quantities of methane (~110 million metric tonnes per annum), which is a potent greenhouse gas affecting global climate change. Methane (CH4) is a natural by-product of gastro-enteric microbial fermentation of feedstuffs in the rumen and contributes to 6% of total CH4 emissions from anthropogenic-related sources. The extent to which the host genome and rumen microbiome influence CH4 emission is not yet well known. This study confirms individual variation in CH4 production was influenced by individual host (cow) genotype, as well as the host's rumen microbiome composition. Abundance of a small proportion of bacteria and archaea taxa were influenced to a limited extent by the host's genotype and certain taxa were associated with CH4 emissions. However, the cumulative effect of all bacteria and archaea on CH4 production was 13%, the host genetics (heritability) was 21% and the two are largely independent. This study demonstrates variation in CH4 emission is likely not modulated through cow genetic effects on the rumen microbiome. Therefore, the rumen microbiome and cow genome could be targeted independently, by breeding low methane-emitting cows and in parallel, by investigating possible strategies that target changes in the rumen microbiome to reduce CH4 emissions in the cattle industry.

Automatic Modulation Classification Based on Deep Feature Fusion for High Noise Level and Large Dynamic Input.

Automatic modulation classification (AMC) is playing an increasingly important role in spectrum monitoring and cognitive radio. As communication and electronic technologies develop, the electromagnetic environment becomes increasingly complex. The high background noise level and large dynamic input have become the key problems for AMC. This paper proposes a feature fusion scheme based on deep learning, which attempts to fuse features from different domains of the input signal to obtain a more stable and efficient representation of the signal modulation types. We consider the complementarity among features that can be used to suppress the influence of the background noise interference and large dynamic range of the received (intercepted) signals. Specifically, the time-series signals are transformed into the frequency domain by Fast Fourier transform (FFT) and Welch power spectrum analysis, followed by the convolutional neural network (CNN) and stacked auto-encoder (SAE), respectively, for detailed and stable frequency-domain feature representations. Considering the complementary information in the time domain, the instantaneous amplitude (phase) statistics and higher-order cumulants (HOC) are extracted as the statistical features for fusion. Based on the fused features, a probabilistic neural network (PNN) is designed for automatic modulation classification. The simulation results demonstrate the superior performance of the proposed method. It is worth noting that the classification accuracy can reach 99.8% in the case when signal-to-noise ratio (SNR) is 0 dB.

Macrophage-derived sulfur dioxide is a novel inflammation regulator.

Macrophage-mediated inflammation is a key pathophysiological component of cardiovascular diseases, but the underlying mechanisms by which the macrophage regulates inflammation have been unclear. In our study, we, for the first time, showed an endogenous sulfur dioxide (SO2) production in RAW267.4 macrophages by using HPLC and SO2-specific fluorescent probe assays. Moreover, the endogenous SO2 generating enzyme aspartate aminotransferase (AAT) was found to be expressed by the macrophages. Furthermore, we showed that AAT2 knockdown triggered spontaneous macrophage-mediated inflammation, as represented by the increased TNF-α and IL-6 levels and the enhanced macrophage chemotaxis; these effects could be reversed by the treatment with a SO2 donor. Mechanistically, AAT2 knockdown activated the NF-κB signaling pathway in macrophages, while SO2 successfully rescued NF-κB activation. In contrast, forced AAT2 expression reversed AngII-induced NF-κB activation and subsequent macrophage inflammation. Moreover, treatment with a SO2 donor also alleviated macrophage infiltration in AngII-treated mouse hearts. Collectively, our data suggest that macrophage-derived SO2 is an important regulator of macrophage activation and it acts as an endogenous "on-off switch" in the control of macrophage activation. This knowledge might enable a new therapeutic strategy for cardiovascular diseases.

Negative auto-regulation of sulfur dioxide generation in vascular endothelial cells: AAT1 S-sulfenylation.

Recently, endogenous sulfur dioxide (SO2) has been found to exert an important function in the cardiovascular system. However, the regulatory mechanism for SO2 generation has not been entirely clarified. Hence, we aimed to explore the possible auto-regulation of endogenous SO2 generation and its mechanisms in vascular endothelial cells. We showed that SO2 did not affect the protein expression of aspartate aminotransferase 1 (AAT1), a major SO2 synthesis enzyme, but significantly inhibited AAT activity in primary human umbilical vein endothelial cells (HUVECs) and porcine purified AAT1 protein. An AAT1 enzymatic kinetic study showed that SO2 reduced the Vmax (1.89 ± 0.10 vs 2.55 ± 0.12, µmol/mg/min, P < 0.05) and increased the Km (35.97 ± 9.54 vs 19.33 ± 1.76 µmol/L, P < 0.05) values. Furthermore, SO2 induced S-sulfenylation of AAT1 in primary HUVECs and purified AAT1 protein. LC-MS/MS analysis indicated that SO2 sulfenylated AAT1 at Cys192. Mechanistically, thiol reductant DTT treatment or C192S mutation prevented SO2-induced AAT1 sulfenylation and the subsequent inhibition of AAT activity in purified AAT1 protein and primary HUVECs. Our findings reveal, for the first time, a mechanism of auto-regulation of SO2 generation through sulfenylation of AAT1 at Cys192 to suppress AAT activity in vascular endothelial cells. These findings will greatly deepen the understanding of regulatory mechanisms in the cardiovascular homeostasis.

Flexible inorganic CsPbI3 perovskite nanocrystal-PMMA composite films with enhanced stability in air and water for white light-emitting diodes.

Perovskite nanocrystals are a new type of fluorescent material with the advantages of facile preparation process, bright tunable color with high quantum yield. They are ideal candidates for optoelectronic devices such as light-emitting diode (LED) and display. However, for practical applications of iodine-based perovskite nanocrystals, the photostability remains a great challenge because of their sensitivity to environmental factors such as oxygen, humidity etc. In this paper, we improve the photostability of CsPbI3 by introducing the polymethyl methacrylate (PMMA) as a matrix to form flexible perovskite/PMMA composite films. The composite films maintain good photoluminescence quantum yield for 25 d in air and 4 d in water. Furthermore, these films are flexible and can sustain multiple bending and folding while maintaining their photoluminescence properties. This photostability against mechanical deformation allows for the development of flexible devices. As an example, flexible white light-emitting diodes (WLED) were produced with chromaticity coordination (0.31, 0.32), color temperature 6735 K and good stability over time.

Predictive ability of host genetics and rumen microbiome for subclinical ketosis.

Subclinical metabolic disorders such as ketosis cause substantial economic losses for dairy farmers in addition to the serious welfare issues they pose for dairy cows. Major hurdles in genetic improvement against metabolic disorders such as ketosis include difficulties in large-scale phenotype recording and low heritability of traits. Milk concentrations of ketone bodies, such as acetone and ß-hydroxybutyric acid (BHB), might be useful indicators to select cows for low susceptibility to ketosis. However, heritability estimates reported for milk BHB and acetone in several dairy cattle breeds were low. The rumen microbial community has been reported to play a significant role in host energy homeostasis and metabolic and physiologic adaptations. The current study aims at investigating the effects of cows' genome and rumen microbial composition on concentrations of acetone and BHB in milk, and identifying specific rumen microbial taxa associated with variation in milk acetone and BHB concentrations. We determined the concentrations of acetone and BHB in milk using nuclear magnetic resonance spectroscopy on morning milk samples collected from 277 Danish Holstein cows. Imputed high-density genotype data were available for these cows. Using genomic and microbial prediction models with a 10-fold resampling strategy, we found that rumen microbial composition explains a larger proportion of the variation in milk concentrations of acetone and BHB than do host genetics. Moreover, we identified associations between milk acetone and BHB with some specific bacterial and archaeal operational taxonomic units previously reported to have low to moderate heritability, presenting an opportunity for genetic improvement. However, higher covariation between specific microbial taxa and milk acetone and BHB concentrations might not necessarily indicate a causal relationship; therefore further validation is needed before considering implementation in selection programs.

Knockdown of PSMC3IP suppresses the proliferation and xenografted tumorigenesis of hepatocellular carcinoma cell.

Hepatocellular carcinoma (HCC) is the fifth most frequent malignancy and the second leading cause of cancer-related death worldwide. Proteasome 26S subunit ATPase 3 interacting protein (PSMC3IP) is an oncogene in breast cancer, while its role in HCC remains unclear. Here, we found that PSMC3IP was critical for the cell proliferation and tumorigenic capacity of HCC cells. Upregulation of PSMC3IP was observed in HCC specimens, and high PSMC3IP expression predicted poor overall survival of HCC patients. In vitro, knockdown of PSMC3IP blunted the proliferation and colony formation of BEL-7404 and SMMC-7721 cells. Likewise, PSMC3IP silencing suppressed the xenografted tumor development of BEL-7404 cells. Mechanistically, apoptosis was enhanced after PSMC3IP knockdown in both BEL-7404 and SMMC-7721 cells. At the molecular level, TP53 and GNG4 were upregulated and eukaryotic translation initiation factor 4E (EIF4E) and insulin like growth factor 1 receptor (IGF1R) were downregulated in shPSMC3IP compared with shCtrl BEL-7404 cells. Therefore, targeting PSMC3IP maybe a promising strategy for HCC.