VHL suppresses autophagy and tumor growth through PHD1-dependent Beclin1 hydroxylation.

The Von Hippel-Lindau (VHL) protein, which is frequently mutated in clear-cell renal cell carcinoma (ccRCC), is a master regulator of hypoxia-inducible factor (HIF) that is involved in oxidative stresses. However, whether VHL possesses HIF-independent tumor-suppressing activity remains largely unclear. Here, we demonstrate that VHL suppresses nutrient stress-induced autophagy, and its deficiency in sporadic ccRCC specimens is linked to substantially elevated levels of autophagy and correlates with poorer patient prognosis. Mechanistically, VHL directly binds to the autophagy regulator Beclin1, after its PHD1-mediated hydroxylation on Pro54. This binding inhibits the association of Beclin1-VPS34 complexes with ATG14L, thereby inhibiting autophagy initiation in response to nutrient deficiency. Expression of non-hydroxylatable Beclin1 P54A abrogates VHL-mediated autophagy inhibition and significantly reduces the tumor-suppressing effect of VHL. In addition, Beclin1 P54-OH levels are inversely correlated with autophagy levels in wild-type VHL-expressing human ccRCC specimens, and with poor patient prognosis. Furthermore, combined treatment of VHL-deficient mouse tumors with autophagy inhibitors and HIF2α inhibitors suppresses tumor growth. These findings reveal an unexpected mechanism by which VHL suppresses tumor growth, and suggest a potential treatment for ccRCC through combined inhibition of both autophagy and HIF2α.

Highly pathogenic PRRSV upregulates IL-13 production through nonstructural protein 9-mediated inhibition of N6-methyladenosine demethylase FTO.

Porcine reproductive and respiratory syndrome virus (PRRSV), a highly infectious virus, causes severe losses in the swine industry by regulating the inflammatory response, inducing tissue damage, suppressing the innate immune response, and promoting persistent infection in hosts. Interleukin-13 (IL-13) is a cytokine that plays a critical role in regulating immune responses and inflammation, particularly in immune-related disorders, certain types of cancer, and numerous bacterial and viral infections; however, the underlying mechanisms of IL-13 regulation during PRRSV infection are not well understood. In this study, we demonstrated that PRRSV infection elevates IL-13 levels in porcine alveolar macrophages. PRRSV enhances m6A-methylated RNA levels while reducing the expression of fat mass and obesity associated protein (FTO, an m6A demethylase), thereby augmenting IL-13 production. PRRSV nonstructural protein 9 (nsp9) was a key factor for this modulation. Furthermore, we found that the residues Asp567, Tyr586, Leu593, and Asp595 were essential for nsp9 to induce IL-13 production via attenuation of FTO expression. These insights delineate PRRSV nsp9's role in FTO-mediated IL-13 release, advancing our understanding of PRRSV's impact on host immune and inflammatory responses.

PRODeepSyn: predicting anticancer synergistic drug combinations by embedding cell lines with protein-protein interaction network.

Although drug combinations in cancer treatment appear to be a promising therapeutic strategy with respect to monotherapy, it is arduous to discover new synergistic drug combinations due to the combinatorial explosion. Deep learning technology holds immense promise for better prediction of in vitro synergistic drug combinations for certain cell lines. In methods applying such technology, omics data are widely adopted to construct cell line features. However, biological network data are rarely considered yet, which is worthy of in-depth study. In this study, we propose a novel deep learning method, termed PRODeepSyn, for predicting anticancer synergistic drug combinations. By leveraging the Graph Convolutional Network, PRODeepSyn integrates the protein-protein interaction (PPI) network with omics data to construct low-dimensional dense embeddings for cell lines. PRODeepSyn then builds a deep neural network with the Batch Normalization mechanism to predict synergy scores using the cell line embeddings and drug features. PRODeepSyn achieves the lowest root mean square error of 15.08 and the highest Pearson correlation coefficient of 0.75, outperforming two deep learning methods and four machine learning methods. On the classification task, PRODeepSyn achieves an area under the receiver operator characteristics curve of 0.90, an area under the precision-recall curve of 0.63 and a Cohen's Kappa of 0.53. In the ablation study, we find that using the multi-omics data and the integrated PPI network's information both can improve the prediction results. Additionally, the case study demonstrates the consistency between PRODeepSyn and previous studies.

Catalytic CO Oxidation on the Cu+-Ov-Ce3+ Interface Constructed by an Electrospinning Method for Enhanced CO Adsorption at Low Temperature.

It is crucial to eliminate CO emissions using non-noble catalysts. Cu-based catalysts have been widely applied in CO oxidation, but their activity and stability at low temperatures are still challenging. This study reports the preparation and application of an efficient copper-doped ceria electrospun fiber catalyst prepared by a facile electrospinning method. The obtained 10Cu-Ce fiber catalyst achieved complete CO oxidation at a temperature as low as 90 °C. However, a reference 10Cu/Ce catalyst prepared by the impregnation method needed 110 °C to achieve complete CO oxidation under identical reaction conditions. Asymmetric oxygen vacancies (ASOV) at the interface between copper and cerium were constructed, to effectively absorb gas molecules involved in the reaction, leading to the enhanced oxidation of CO. The exceptional ability of the 10Cu-Ce catalyst to adsorb CO is attributed to its unique structure and surface interaction phase Cu+-Ov-Ce3+, as demonstrated by a series of characterizations and DFT calculations. This novel approach of using electrospinning offers a promising technique for developing low-temperature and non-noble metal-based catalysts.

Genetic and biological properties of H7N9 avian influenza viruses detected after application of the H7N9 poultry vaccine in China.

The H7N9 avian influenza virus (AIV) that emerged in China have caused five waves of human infection. Further human cases have been successfully prevented since September 2017 through the use of an H7N9 vaccine in poultry. However, the H7N9 AIV has not been eradicated from poultry in China, and its evolution remains largely unexplored. In this study, we isolated 19 H7N9 AIVs during surveillance and diagnosis from February 2018 to December 2019, and genetic analysis showed that these viruses have formed two different genotypes. Animal studies indicated that the H7N9 viruses are highly lethal to chicken, cause mild infection in ducks, but have distinct pathotypes in mice. The viruses bound to avian-type receptors with high affinity, but gradually lost their ability to bind to human-type receptors. Importantly, we found that H7N9 AIVs isolated in 2019 were antigenically different from the H7N9 vaccine strain that was used for H7N9 influenza control in poultry, and that replication of these viruses cannot, therefore, be completely prevented in vaccinated chickens. We further revealed that two amino acid mutations at positions 135 and 160 in the HA protein added two glycosylation sites and facilitated the escape of the H7N9 viruses from the vaccine-induced immunity. Our study provides important insights into H7N9 virus evolution and control.

Nanopore Single-molecule Analysis of Biomarkers: Providing Possible Clues to Disease Diagnosis.

Biomarker detection has attracted increasing interest in recent years due to the minimally or non-invasive sampling process. Single entity analysis of biomarkers is expected to provide real-time and accurate biological information for early disease diagnosis and prognosis, which is critical to the effective disease treatment and is also important in personalized medicine. As an innovative single entity analysis method, nanopore sensing is a pioneering single-molecule detection technique that is widely used in analytical bioanalytical fields. In this review, we overview the recent progress of nanopore biomarker detection as new approaches to disease diagnosis. In highlighted studies, nanopore was focusing on detecting biomarkers of different categories of communicable and noncommunicable diseases, such as pandemic Covid-19, AIDS, cancers, neurologic diseases, etc. Various sensitive and selective nanopore detecting strategies for different types of biomarkers are summarized. In addition, the challenges, opportunities, and direction for future development of nanopore-based biomarker sensors are also discussed.

Multi-pulse dynamic patterns in a mode-locked erbium-doped fiber laser based on an Sb2S3-PVA saturable absorber.

Multi-pulse dynamic patterns have been experimentally documented in a passively mode-locked (PML) erbium-doped fiber (EDF) laser using an Sb2S3-PVA saturable absorber (SA). The fundamental mode-locking operation, with a repetition rate of ∼3.22 MHz, a pulse width of ∼2.5 ps, a signal-to-noise ratio (SNR) of ∼50 dB and a peak power over 200 W, was achieved under a pump power from 280 to 360 mW with appropriate polarization states introduced by the polarization controllers (PCs). By rotating the orientation of the intra-cavity PCs carefully and slowly at a pump power of 350 mW, it was found that a multi-pulse bunch was transformed gradually from a single-pulse to a twelve-pulse bunch, with several intermediate transition states of multi-pulse bunches being observed. In addition, other characteristic modes including disordered multi-pulses and soliton rains have been experimentally observed by meticulously adjusting the polarization states of PCs at a pump power of 350 mW. Our systematic study clearly demonstrates that Sb2S3has potential as an effective SA for generating different operation states of multi-pulses in PML anomalous-dispersion EDF lasers.

Integrating multiple references for single-cell assignment.

Efficient single-cell assignment is essential for single-cell sequencing data analysis. With the explosive growth of single-cell sequencing data, multiple single-cell sequencing data sources are available for the same kind of tissue, which can be integrated to further improve single-cell assignment; however, an efficient integration strategy is still lacking due to the great challenges of data heterogeneity existing in multiple references. To this end, we present mtSC, a flexible single-cell assignment framework that integrates multiple references based on multitask deep metric learning designed specifically for cell type identification within tissues with multiple single-cell sequencing data as references. We evaluated mtSC on a comprehensive set of publicly available benchmark datasets and demonstrated its state-of-the-art effectiveness for integrative single-cell assignment with multiple references.

Prevalence of Body Somatic Deformities in Plastic Surgery Patients: A Systematic Review with Meta-analysis.

BACKGROUND: Plastic surgery is a surgical specialty that focuses on restoring, reconstructing, or changing the human body. Somatic deformities (SD) are defined by a distorted impression of one's own body image and are rather frequent. The majority of people with SD have some level of social and vocational impairment, with obsessive concerns about appearance leading to compulsive behaviors and, in more severe situations, suicidal thoughts. OBJECTIVE: The current study aims to confirm the prevalence of SD in plastic surgery patients using a systematic review of the literature and a meta-analysis. METHODOLOGY: We have searched for electronic databases with MeSH terms, and the studies for analysis were selected based on inclusion and exclusion criteria and quality assessment. The study was conducted as per the PRISMA guidelines. The pooled prevalence was calculated using fixed and random effect model. The publication bias was assessed qualitatively (funnel plot) as well as quantitatively (Begg, Egger and Harbord tests). All analysis was done using Stats Direct (version 3). RESULTS: The pooled prevalence of somatic deformities in plastic surgery with 95% confidence interval using random effect model was found to be 0.19 [0.12, 0.27] which indicates a significant association of somatic deformities in plastic surgery. The heterogeneity among studies was found to be high as indicated by Cochran Q (P < 0.0001) and I2 tests (98.6%). The qualitative and quantitative analysis has also shown significant involvement of publication bias. CONCLUSION: Based on available evidence, there is a significant association of somatic deformities in plastic surgery. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Can Anti-inflammatory Drugs used in Plastic Surgery Procedures Increase the Risk of Hematoma?

BACKGROUND: Anti-inflammatory drugs are commonly used to lower inflammation which is linked to a variety of disorders. It acts by inhibiting cyclooxygenase-mediated prostaglandin synthesis at the molecular level. Hematoma is related with the use of anti-inflammatory medications. However, the specific link is still unknown. Thus, the main objective of the study is to find out the association of hematoma with ant-inflammatory drugs. MATERIAL AND METHODS: The relevant studies were searched in PubMed and screened based on inclusion and exclusion criteria. The quality of full-text studies was assessed using suitable Newcastle-Ottawa Scale. The overall estimate was calculated in terms of odds ratio with 95% confidence interval. The random effect model was used. The qualitative analysis of publication bias was done through funnel plot. RESULTS: The overall estimate measures [OR 1.01 (0.50, 2.06)] have shown non-significant risk of hematoma with use of anti-inflammatory drugs in plastic surgery as compared to non-anti-inflammatory drugs. The heterogeneity among studies was found to be 34%. The subgroup analysis of individual drugs was not done due to availability of a smaller number of studies. CONCLUSION: Based on available data, there is no significant risk of hematoma with use of anti-inflammatory drugs in plastic surgery. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The relationship among knowledge, attitude, and behavior of workers on food safety in Taiwan's Company A.

In recent years, consumer awareness of food safety has been increasing, and food workers with professional food safety knowledge, attitude, and practical implementation are essential for maintaining the quality of food as well as preventing foodborne diseases. This study evaluates the knowledge, attitude, and implementation of food safety practices among employees in a food company in Taiwan. The employees were both who had received food safety knowledge and training and had yet to receive it. Data collection was carried out through 68 questionnaires, and analysis methods, including descriptive statistical analysis and multiple regression analysis, have performed. Before the first stage of education and training, 100% of the employees knew that food factories must conduct regular water quality testing. Still, the error rate for personal hygiene and safety was the highest. The second part has the highest average food safety attitude and the concept of food preservation. The third part of personnel behavior was to avoid cross-contamination. After the second stage of education and training of personnel in food safety knowledge, the attitude and behavior have been greatly improved. The findings of this study can be used as a reference for food suppliers to develop employee education and training.

Noise-like pulse generation in an Nd-doped single-mode all-fiber mode-locked Raman laser operating at 0.93 µm.

Based on the Nd-doped single-mode fiber (SMF) as the gain medium and SMF as the Raman medium, an all-fiber mode-locked Raman laser operating at 0.93 µm waveband was demonstrated for the first time. A mandrel with a diameter of 10 mm was employed to introduce bending losses to suppress the dominant emission of Nd-doped fiber at 1.06 µm. A noise-like pulse with a pulse width of 194.70 fs, a repetition rate of 1.73 MHz and a single pulse energy of 2.03 nJ was obtained in the mode-locked Raman laser with a Stokes wavelength of 932.59 nm. Such an ultrafast all-fiber Raman laser operating at 0.93 µm has the advantages of low cost, simple structure and compactness, and can be used as an ideal light source for the two-photon microscopy.

Modeling for extracavity-pumped terahertz parametric oscillators.

This paper presents a modeling method for extracavity-pumped terahertz parametric oscillators (TPO) based on stimulated polariton scattering, in which the pumping beam is from a different laser, and the Stokes beam oscillates in its cavity. After suitable approximations and assumptions, the average THz wave amplitude in the nonlinear crystal is expressed as a function of the fundamental and Stokes wave amplitudes. Then the rate equation for the Stokes wave is obtained based on the Stokes wave increment within a cavity roundtrip timescale. After solving the Stokes wave rate equation, the Stokes wave temporal evolution is considered as a known parameter, and the properties of the residual fundamental and terahertz waves are obtained by numerically solving the coupled wave equations. This modeling method is applied to an extracavity-pumped TPO based on MgO:LiNbO3 crystal. The simulation results are basically consistent with the experimental results. The main reasons causing the deviations of the simulation results from the experimental results are analyzed. To the best of our knowledge, this is the first time to perform the modeling for extracavity-pumped Q-switched TPOs.

Dual-mode optical thermometry design in K3YSi2O7:Eu multi-site phosphor.

In this study, a dual-mode optical thermometer is designed based on radiative transitions from Eu3+ and Eu2+ ions at different K3YSi2O7 lattice sites. In the luminescence-intensity-ratio strategy, a ratiometric signal composed of Eu3+:5D0→7F1 and Eu3+:5D0→7F2 emissions at 593 and 616 nm, respectively, is employed. Meanwhile, the intensity ratio of the 593-nm emission under O2-→Eu3+ charge transfer excitation (λex = 249 nm) to that upon Eu2+:4f7→4f65d1 excitation (λex = 349 nm) is selected as a thermometric parameter in the single-band-ratio approach. The study findings show that combining the two strategies is conducive to the improvements in sensing-sensitive and anti-interference performance.

Effects of norfloxacin, copper, and their interactions on microbial communities in estuarine sediment.

The discharge of antibiotics and metals in estuaries is of great concern since they threaten microbial communities that are critical for maintaining ecosystem function. To understand single and combined effects of norfloxacin (0-20 µg g-1) and copper (40 µg g-1) on microbial ecology in estuaries, we evaluated changes in bacteria population, inhibition rates, and microbial composition in estuarine sediments over a 28-day period. Bacteria population significantly decreased following single and combined exposure to norfloxacin and copper throughout the incubation period, except on Day 28 in treatments exposed to copper, 20 µg g-1 norfloxacin, or both. These three treatment groups had lower Shannon diversity and Simpson's indices on Day 28 than other treatments and the controls suggesting recovery in bacteria population did not correspond with recovery in richness and evenness. Furthermore, functional predictions revealed that the effect of time and contaminants were significantly different on some microbial community functions on Day 28, especially the combination of Cu and high concentration NFX, including aerobic chemoheterotrophy, methanol oxidation and methylotrophy. Thus, norfloxacin and copper had significant adverse effects on microbial communities in estuarine sediments; however, the combined effects were variable and depended on exposure duration and antibiotic concentration.

Generation of bright-dark soliton pairs based on a ferromagnetic insulator Cr2Si2Te6 as a modulator in an Er-doped fiber laser.

In this work, a saturable absorber (SA) based on Cr2Si2Te6 (CST), with a modulation depth of 14.90% and saturation intensity of 4.81MW/cm2, was prepared by a liquid phase stripping method. Its nonlinear optical properties and application in obtaining mode-locked pulse output of bright-dark solitons are studied. When the pump power was 1250 mW, the maximum output power was 26.60 mW; the energy of the single pulse was 15.02 nJ, and the repetition rate was 1.77 MHz. Our results provided evidence that CST can be used as an excellent SA for a mode-locked laser and demonstrated that ferromagnetic insulators can be used for the study of bright-dark soliton pairs.

Passively mode-locked Er-doped fiber laser based on a ferromagnetic insulator Cr2Si2Te6 as a saturable absorber.

In our work, a new-type, to the best of our knowledge, ferromagnetic insulator and its nonlinear optical absorption characteristics and related ultrafast modulation applications were investigated. Cr2Si2Te6 saturable absorbers (SAs) with a modulation depth and a saturable intensity of 9.7% and 3.5MW/cm2 were fabricated. By adjusting the pump power to 120 mW and optimizing the polarization state, traditional soliton operations were obtained successfully; the corresponding duration of pulse and the fundamental repetition rate were ∼1.33ps and 6.70 MHz, and the signal-to-noise ratio was 50 dB. The experimental results reveal that Cr2Si2Te6 with excellent saturable absorption characteristics can be used as a SA to obtain ultrafast pulse lasers.

Diterpenoid Caesalmin C Delays Aß-Induced Paralysis Symptoms via the DAF-16 Pathway in Caenorhabditis elegans.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the world. However, there is no effective drug to cure it. Caesalmin C is a cassane-type diterpenoid abundant in Caesalpinia bonduc (Linn.) Roxb. In this study, we investigated the effect of caesalmin C on Aß-induced toxicity and possible mechanisms in the transgenic Caenorhabditis elegans AD model. Our results showed that caesalmin C significantly alleviated the Aß-induced paralysis phenotype in transgenic CL4176 strain C. elegans. Caesalmin C dramatically reduced the content of Aß monomers, oligomers, and deposited spots in AD C. elegans. In addition, mRNA levels of sod-3, gst-4, and rpt-3 were up-regulated, and mRNA levels of ace-1 were down-regulated in nematodes treated with caesalmin C. The results of the RNAi assay showed that the inhibitory effect of caesalmin C on the nematode paralysis phenotype required the DAF-16 signaling pathway, but not SKN-1 and HSF-1. Further evidence suggested that caesalmin C may also have the effect of inhibiting acetylcholinesterase (AchE) and upregulating proteasome activity. These findings suggest that caesalmin C delays the progression of AD in C. elegans via the DAF-16 signaling pathway and that it could be developed into a promising medication to treat AD.

Cryptotanshinone Alleviates Oxidative Stress and Reduces the Level of Abnormally Aggregated Protein in Caenorhabditis elegans AD Models.

Alzheimer's disease (AD) is one of the leading causes of dementia. As the first common neurodegenerative disease, there are no effective drugs that can reverse the progression. The present study is to report the anti-AD effect of cryptotanshinone (CTS), a natural product isolated from Salvia castanea. It is found that it can alleviate AD-like features associated with Aß1-42 toxicity in muscle cells as well as neuronal cells of Caenorhabditis elegans (C. elegans). Further studies showed that CTS reduced the level of reactive oxygen species (ROS) in nematodes, up-regulated the expression of sod-3, and enhanced superoxide dismutase activity. Cryptotanshinone reduced the level of Aß monomers and highly toxic oligomers in C. elegans while inhibiting the abnormal aggregation of polyglutamine protein. In addition, CTS upregulated the expression of hsp-16.2 and downregulated the expression of ace-2. These results suggested that CTS could alleviate oxidative stress and reduce the level of abnormally aggregated proteins and has the potential to be developed as an anti-AD drug candidate.

Passively Mode-Locked Er-Doped Fiber Laser Based on Sb2S3-PVA Saturable Absorber.

In this paper, antimony trisulfide (Sb2S3) was successfully prepared with the liquid phase exfoliation method and embedded into polyvinyl alcohol (PVA) as a saturable absorber (SA) in a passively mode-locked Er-doped fiber laser for the first time. Based on Sb2S3-PVA SA with a modulation depth of 4.0% and a saturable intensity of 1.545 GW/cm2, a maximum average output power of 3.04 mW and maximum peak power of 325.6 W for the stable mode-locked pulses was achieved with slope a efficiency of 0.87% and maximum single pulse energy of 0.81 nJ at a repetition rate of 3.47 MHz under a pump power of 369 mW. A minimum pulse width value of 2.4 ps with a variation range less than 0.1 ps, and a maximum signal to noise ratio (SNR) of 54.3 dB indicated reliable stability of mode-locking, revealing promising potentials of Sb2S3 as a saturable absorber in ultrafast all-fiber lasers.