Structured learning in time-dependent Cox models.

Cox models with time-dependent coefficients and covariates are widely used in survival analysis. In high-dimensional settings, sparse regularization techniques are employed for variable selection, but existing methods for time-dependent Cox models lack flexibility in enforcing specific sparsity patterns (ie, covariate structures). We propose a flexible framework for variable selection in time-dependent Cox models, accommodating complex selection rules. Our method can adapt to arbitrary grouping structures, including interaction selection, temporal, spatial, tree, and directed acyclic graph structures. It achieves accurate estimation with low false alarm rates. We develop the sox package, implementing a network flow algorithm for efficiently solving models with complex covariate structures. sox offers a user-friendly interface for specifying grouping structures and delivers fast computation. Through examples, including a case study on identifying predictors of time to all-cause death in atrial fibrillation patients, we demonstrate the practical application of our method with specific selection rules.

CircPIAS1 promotes hepatocellular carcinoma progression by inhibiting ferroptosis via the miR-455-3p/NUPR1/FTH1 axis.

BACKGROUND: The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development. METHODS: Functional analyses were conducted to assess circPIAS1's impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1's effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms. RESULTS: CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib. CONCLUSION: This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.

Environmental and economic analysis of the transformation of paper mill sludge treatment technologies in China.

Paper mill sludge (PMS) is featured with a high content of cellulose and hemicellulose, and using its characteristics to make paperboard can achieve a high-value utilization of PMS, which has attracted growing interest. In this study, currently prevalent landfill, incineration technologies (generating heat and electricity by incineration), and three paperboard technologies (medium density fiberboard, pulp board, and corrugated paper) were evaluated and compared via life cycle assessment (LCA) and life cycle costing (LCC) methods. LCA results show that the PMS-to-pulp board outperforms others with an energy conservation and emission reduction (ECER) value of - 2.86 × 10-8, while the landfill exhibits the highest overall environmental impact with an ECER value of 4.80 × 10-9. LCC results reveal that the PMS-to-pulp board delivers the highest economic profit with $257.357, while the landfill is the lowest with $ - 35.63. The PMS paperboard technologies are more economically friendly than the incineration technologies due to additional electricity/steam consumption during the PMS pre-drying process in incineration. In addition, different scenarios were set up to explore national GHG emission reduction potential by increasing paperboard technologies application rate and reducing the proportion of landfill and incineration. The scenario analysis suggests that replacing 90% of landfill and incineration ratio with PMS paperboard technologies could tremendously improve the overall emission reduction performance with - 9.08 × 1010 kg CO2 eq. This result indicates that the PMS treatment technology transformation has a significant favorable impact on the achievement of the "carbon neutrality" target.

Ab Initio Study on Electronic Excited States of Monochlorosilylene.

We perform a high-level ab initio study on 20 electronic states of monochlorosilylene (HSiCl) using an internally contracted multireference configuration interaction method including Davidson correction (icMRCI+Q). The spin-orbit coupling (SOC) effect is investigated, leading to splitting of the 20 spin-orbit-free states into 50 spin-orbit-coupled states. Vertical transition energies, oscillator strengths, and potential energy curves are presented with and without considering the SOC effect. Analysis indicates that the SOC effect plays an important role, especially for the high-lying excited states of HSiCl. The state interaction and the dynamics of the electronic states of HSiCl in the ultraviolet region are discussed based on our calculation results. Our study paves the way to understanding the behavior of electronic excited states of monochlorosilylene.

Polysaccharide hydrogel containing silver nanoparticle@catechol microspheres with photothermal, antibacterial and anti-inflammatory activities for infected-wounds repair.

Anti-infection hydrogels have recently aroused enormous attraction, particularly in the treatment of chronic wounds. Herein, silver nanoparticle@catechol formaldehyde resin microspheres (Ag@CFRs) were fabricated by one-step hydrothermal method and subsequently encapsulated in hydrogels which were developed by Schiff base reaction between aldehyde groups in oxidized hyaluronic acid and amino groups in carboxymethyl chitosan. The developed polysaccharide hydrogel exhibited microporous structure, high swelling capacity, favorable mechanical strength, enhanced tissue adhesion and photothermal activities. Additionally, the hydrogel not only ensured long-term and high-efficiency antibacterial performance (99.9 %) toward E. coli and S. aureus, but also realized superior cytocompatibility in vitro. Moreover, based on the triple antibacterial strategies endowed by chitosan, silver nanoparticles and the photothermal properties of catechol microspheres, the composite hydrogel exhibited excellent anti-infection function, significantly downregulated inflammatory factors (TNF-α and IL-1ß) and promoted in vivo infected-wound healing. These results demonstrated that the polysaccharide hydrogel containing Ag@CFRs has great potential for infected-wounds repair.

The protective effect of intranasal immunization with influenza virus recombinant adenovirus vaccine on mucosal and systemic immune response.

Influenza virus is a kind of virus that poses several hazards of animal and human health. Therefore, it is important to develop an effective vaccine to prevent influenza. To this end we successfully packaged recombinant adenovirus rAd-NP-M2e-GFP expressing multiple copies of influenza virus conserved antigens NP and M2e and packaged empty vector adenovirus rAd-GFP. The effect of rAd-NP-M2e-GFP on the activation of dendritic cell (DC) in vitro and in vivo was detected by intranasal immunization. The results showed that rAd-NP-M2e-GFP promoted the activation of DC in vitro and in vivo. After the primary immunization and booster immunization of mice through the nasal immune way, the results showed that rAd-NP-M2e-GFP induced enhanced local mucosal-specific T cell responses, increased the content of SIgA in broncho alveolar lavage fluids (BALF) and triggered the differentiation of B cells in the germinal center. It is proved that rAd-NP-M2e-GFP can significantly elicit mucosal immunity and systemic immune response. In addition, rAd-NP-M2e-GFP could effectively protect mice after H1N1 influenza virus challenge. To lay the foundation and provide reference for further development of influenza virus mucosal vaccine in the future.

Dynamic asymmetric spillovers and connectedness between Chinese sectoral commodities and industry stock markets.

This study investigates the dynamic and asymmetric propagation of return spillovers between sectoral commodities and industry stock markets in China. Using a daily dataset from February 2007 to July 2022, we employ a time-varying vector autoregressive (TVP-VAR) model to examine the asymmetric return spillovers and dynamic connectedness across sectors. The results reveal significant time-varying spillovers among these sectors, with the industry stocks acting as the primary transmitter of information to the commodity market. Materials, energy, and industrials stock sectors contribute significantly to these spillovers due to their close ties to commodity production and processing. The study also identifies significant asymmetric spillovers with bad returns dominating, influenced by major economic and political events such as the 2008 global financial crisis, the 2015 Chinese stock market crisis, the COVID-19 pandemic, and the Russia-Ukraine war. Furthermore, our study highlights the unique dynamics within the Chinese market, where net information spillovers from the stock market to commodities drive the financialization process, which differs from the bidirectional commodity financialization observed in other markets. Finally, portfolio analysis reveals that the minimum connectedness portfolio outperforms other approaches and effectively reflects asymmetries. Understanding these dynamics and sectoral heterogeneities has important implications for risk management, policy development, and trading practices.

Design and preparation of Ti-xFe antibacterial titanium alloys based on micro-area potential difference.

Fe was selected as an alloying element for the first time to prepare a new antibacterial titanium alloy based on micro-area potential difference (MAPD) antibacterial mechanism. The microstructure, the corrosion resistance, the mechanical properties, the antibacterial properties and the cell biocompatibility have been investigated in detail by optical microscopy, scanning electron microscopy, electrochemical testing, mechanical property test, plate count method and cell toxicity measurement. It was demonstrated that heat treatment had a significant on the compressive mechanical properties and the antibacterial properties. Ti-xFe (x = 3,5 and 9) alloys after 850 °C/3 h + 550 °C/62 h heat treatment exhibited strong antimicrobial properties with an antibacterial rate of more than 90% due to the MAPD caused by the redistribution of Fe element during the aging process. In addition, the Fe content and the heat treatment process had a significant influence on the mechanical properties of Ti-xFe alloy but had nearly no effect on the corrosion resistance. All Ti-xFe alloys showed non-toxicity to the MC3T3 cell line in comparison with cp-Ti, indicating that the microzone potential difference had no adverse effect on the corrosion resistance, cell proliferation, adhesion, and spreading. Strong antibacterial properties, good cell compatibility and good corrosion resistance demonstrated that Ti-xFe alloy might be a candidate titanium alloy for medical applications.

Electronic excited states of monobromosilylene molecules including the spin-orbit-coupling.

We employ the internally contracted multireference configuration interaction (icMRCI-F12) with Davidson corrections to explore the electronic states of monobromosilylene molecules (HSiBr). A total of 20 states with energy up to 8.7 eV and the corresponding 50 states after taking the spin-orbit coupling (SOC) effects into account are investigated. The spectroscopic constants of the low-lying states, as well as oscillator strengths, vertical transition energies and potential energy curves (PECs) for all the 20 spin-free states and the 50 spin-orbit-coupled states of HSiBr are presented. The results indicate that the SOC effect significantly affects the dissociation pathways and the PECs of electronic excited states of HSiBr. Based on our calculation results, the interactions between the states and the dissociation of HSiBr in the UV region are discussed. Our study sheds some light on the complex interactions and dynamics of the electronic excited states of HSiBr, which would provide valuable information for future experimental investigations.

Variable selection in high dimensions for discrete-outcome individualized treatment rules: Reducing severity of depression symptoms.

Despite growing interest in estimating individualized treatment rules, little attention has been given the binary outcome setting. Estimation is challenging with nonlinear link functions, especially when variable selection is needed. We use a new computational approach to solve a recently proposed doubly robust regularized estimating equation to accomplish this difficult task in a case study of depression treatment. We demonstrate an application of this new approach in combination with a weighted and penalized estimating equation to this challenging binary outcome setting. We demonstrate the double robustness of the method and its effectiveness for variable selection. The work is motivated by and applied to an analysis of treatment for unipolar depression using a population of patients treated at Kaiser Permanente Washington.

Efficient dynamic tunable metasurface based on Ge2Sb2Te5 in the near infrared band.

For effective wavefront management in the optical infrared range, dynamic all-dielectric metasurfaces, always based on phase transition materials, particularly G e 2 S b 2 T e 5 (GST), can be used. In this paper, we propose a GST-based tunable metasurface by structuring the phase-change material GST. We confirm that the nanopillar we designed has high transmittance in the wavelength band around 1550 nm and can fully cover the 0∼2π phase. Based on these characteristics, we can achieve beam steering and a focusing effect in amorphous phase by elaborately arranging GST nanopillars, while the aforementioned optical phenomena disappear in crystalline phase. Additionally, by arranging the array of vortex phases, we also realize switching the perfect composite vortex beam (PCVB) when changing the crystal state of GST, and simulate the generation of PCVB with different topological charges and sizes in amorphous phase. We believe that our research results can serve as a reference for multifunctional optical surfaces, dynamic optical control, optical communication, and information processing.

Adjustable Trifunctional Mid-Infrared Metamaterial Absorber Based on Phase Transition Material VO2.

In this paper, we demonstrate an adjustable trifunctional absorber that can achieve the conversion of broadband, narrowband and superimposed absorption based on the phase transition material vanadium dioxide (VO2) in the mid-infrared domain. The absorber can achieve the switching of multiple absorption modes by modulating the temperature to regulate the conductivity of VO2. When the VO2 film is adjusted to the metallic state, the absorber serves as a bidirectional perfect absorber with switching capability of wideband and narrowband absorption. The superposed absorptance can be generated while the VO2 layer is converted to the insulating state. Then, we introduced the impedance matching principle to explain the inner mechanism of the absorber. Our designed metamaterial system with a phase transition material is promising for sensing, radiation thermometer and switching devices.

COLEC10 Induces Endoplasmic Reticulum Stress by Occupying GRP78 and Inhibits Hepatocellular Carcinoma.

Collectin subfamily member 10 (COLEC10), a C-type lectin mainly expressed in the liver, is involved in the development of hepatocellular carcinoma (HCC). However, its underlying molecular mechanism in HCC progression remains unknown. In this study, reduced COLEC10 expression in tumor tissues was validated using various HCC cohorts and was associated with poor patient prognosis. COLEC10 overexpression attenuated HCC cell growth and migration abilities in vitro and in vivo. We identified that COLEC10 was a novel interactor of 78-kDa glucose-regulated protein (GRP78), a master modulator of the unfolded protein response in the endoplasmic reticulum (ER). COLEC10 overexpression potentiated ER stress in HCC cells, as demonstrated by elevated expression levels of phosphorylated protein kinase RNA-like ER kinase, phosphorylated inositol-requiring protein 1α, activating transcription factor 4, DNA damage-inducible transcript 3, and X-box-binding protein 1s. The ER in COLEC10-overexpressing cells also showed a dilated and fragmented pattern. Mechanistically, COLEC10 overexpression increases GRP78 occupancy through direct binding by the C-terminal carbohydrate recognition domain in the ER, which released and activated the ER stress transducers protein kinase RNA-like ER kinase and phosphorylated inositol-requiring protein 1α, triggering the unfolded protein response activity. COLEC10-overexpressing HCC cells generated a relatively high reactive oxygen species level and switched to apoptotic cell death under sorafenib-treated conditions. Our study provides the first novel view that COLEC10 inhibits HCC progression by regulating GRP78-mediated ER stress signaling and may serve as a promising therapeutic and prognostic biomarker.

Reduced platelet 5-HT content is associated with rest tremor in Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is highly heterogeneous in manifestations and pathogenesis. Serotonergic neurotransmitter system dysfunction is frequently implicated in PD tremor. Serotonin (5-HT) content in platelets is highly correlated with that in cerebrospinal fluid. In this study, we aimed to understand whether and how platelet 5-HT content reflects tremor in PD. METHOD: A total of 139 Chinese PD patients met with inclusion criteria were recruited. Motor and non-motor scores, and disease severity were evaluated. Patients were classified into subtypes of tremor-dominant (TD) and non-tremor-dominant (NTD). Peripheral platelets were isolated, and platelet 5-HT levels were measured. RESULTS: Platelet 5-HT content was lower in PD patients of TD subtype than in NTD subtype. Multifactor risk analysis showed that this lower content was independently associated with the TD phenotype. Platelet 5-HT level was inversely correlated with total tremor score, rest tremor amplitude score, rest tremor constancy score, and index of rest tremor, but not with postural tremor score, and kinetic tremor score. CONCLUSION: The cross-sectional study demonstrates that reduced platelet 5-HT content is associated with PD rest tremor. Our results support the involvement of serotonergic disturbance in PD rest tremor and indicate that 5-HT reduction can be manifested in peripheral platelets.

The impact of negative emotions and relationship quality on consumers' repurchase intention: An empirical study based on service recovery in China's online travel agencies.

Service failures of online travel agencies (OTAs) occur frequently, which makes the OTA business operation model face huge risks. However, the current academic circles still pay insufficient attention to OTA service recovery. This study obtained research data through scenario experiment method, and analyzed data through SPSS25.0, HLM6.08 and other statistical software to explore the impact mechanism of consumers' repurchase intention in OTA service recovery. The empirical results of this study are as follows: Consumers' negative emotions weaken their relationship with tourism suppliers and OTAs. If the relationship quality between consumers and tourism suppliers is improved, the relationship quality between consumers and OTAs will also be improved. The relationship quality between consumers and OTAs has a positive impact on consumers' repurchase intention, and consumer forgiveness has a positive moderating effect between them. This study provides a consumer psychology perspective for discussing OTA's service recovery, which is conducive to promoting the healthy development of OTA's business operation model and benefiting consumers.

Quantitative comparison of the delignification performance of lignocellulosic biomass pretreatment technologies for enzymatic saccharification.

Pretreatments for delignification are required for the enzymatic saccharification of lignocellulosic biomasses. However, in the current literature, various pretreatment approaches have been applied for the same kinds of biomass. To find the optimum pretreatments for biomaterials containing various lignin contents, in this study, a quantitative comparison was carried out on the delignification performance of 15 categories of pretreatments. In total, 1729 sets of biomass, cellulose, hemicellulose, and lignin recovery data were collected from 214 relevant studies. Box plots and Cate-Nelson-like graphs were applied for analyses. The results showed that alkali, oxidation, organic solvent, and multistep pretreatments generally were better at removing lignin and recovering cellulose. Moreover, among these four categories, alkali pretreatments had the best performance, increasing the saccharification efficiency by approximately five-fold. Considering both delignification performance and saccharification improvement, alkali pretreatments are currently considered to be the optimum pretreatment methods for enzymatic saccharification.

Causative Microorganisms Isolated from Patients with Intra-Abdominal Infections and Their Drug Resistance Profiles: An 11-Year (2011-2021) Single-Center Retrospective Study / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the distribution and antimicrobial susceptibility of causative microorganisms recovered from patients with intra-abdominal infections (IAIs).@*METHODS@#A total of 2,926 bacterial and fungal strains were identified in samples collected from 1,679 patients with IAIs at the Peking Union Medical College Hospital between 2011 and 2021. Pathogenic bacteria and fungi were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing (AST) was performed using the VITEK 2 compact system and the Kirby-Bauer method. AST results were interpreted based on the M100-Ed31 clinical breakpoints of the Clinical and Laboratory Standards Institute.@*RESULTS@#Of the 2,926 strains identified, 49.2%, 40.8%, and 9.5% were gram-negative bacteria, gram-positive bacteria, and fungi, respectively. Escherichia coli was the most prevalent pathogen in intensive care unit (ICU) and non-ICU patients; however, a significant decrease was observed in the isolation of E. coli between 2011 and 2021. Specifically, significant decreases were observed between 2011 and 2021 in the levels of extended-spectrum β-lactamase (ESBL)-producing E. coli (from 76.9% to 14.3%) and Klebsiella pneumoniae (from 45.8% to 4.8%). Polymicrobial infections, particularly those involving co-infection with gram-positive and gram-negative bacteria, were commonly observed in IAI patients. Moreover, Candida albicans was more commonly isolated from hospital-associated IAI samples, while Staphylococcus epidermidis had a higher ratio in community-associated IAIs. Additionally, AST results revealed that most antimicrobial agents performed better in non-ESBL-producers than in ESBL-producers, while the overall resistance rates (56.9%-76.8%) of Acinetobacter baumanmii were higher against all antimicrobial agents than those of other common gram-negative bacteria. Indeed, Enterococcus faecium, Enterococcus faecalis, S. epidermidis, and S. aureus were consistently found to be susceptible to vancomycin, teicoplanin, and linezolid. Similarly, C. albicans exhibited high susceptibility to all the tested antifungal drugs.@*CONCLUSION@#The distribution and antimicrobial susceptibility of the causative microorganisms from patients with IAIs were altered between 2011 and 2021. This finding is valuable for the implementation of evidence-based antimicrobial therapy and provides guidance for the control of hospital infections.

Immunogenicity of engineered probiotics expressing conserved antigens of influenza virus and FLIC flagellin against H9N2 AIVinfection in mice.

Avian influenza virus (AIV)is easy to cause diseases in birds and humans.It causes great economic losses to the poultry farms and leads to public health problems. Using vaccines is the main approach to control the prevalence of AIV. In our previously published article, a recombinant Lactobacillus plantarum (L. plantarum) expressing the NP-M2 peptide ofH9N2 AIV was generated, and its protective effect was evaluated in a chicken model. In this study, the protective effect was estimated in mice model. Humoral and cellular immune response parameters were measured using flow cytometry adding to body weight loss, survival rate, virus load, and histopathological changes in the lung. The obtained results elucidated that, the recombinant L. plantarum can promote the activation of dendritic cells (DC), proliferation of T and B cells adding to eliciting protective secretory IgA (sIgA) and humeral IgG level in mice model. Accordingly, it could be used as a patent vaccine to control the AIV infection.

Lymphography method based on time-autocorrelated optical coherence tomography.

Lymphatic vessels are structurally similar to blood vessels, and the lymphatic fluid flowing within the lymphatic vessels is distributed throughout the body and plays a vital role in the human immune system. Visualization of the lymphatic vessels is clinically important in the diagnosis of tumor cell metastasis and related immune system diseases, but lymph is difficult to image due to its near-transparent nature and low flow rate. In this paper, we present a lymphography method based on time-autocorrelated optical coherence tomography. By using the minimum value difference of the autocorrelation function of the time-varying interference intensity between the lymph and the surrounding tissues, the non-invasive and high-sensitivity imaging of lymph vessels can be achieved. The method proposed in this paper has potential significance for the research and treatment of immune system diseases.

Virtual reality for neurorehabilitation: A bibliometric analysis of knowledge structure and theme trends.

Background: As an emerging technology, virtual reality (VR) has been broadly applied in the medical field, especially in neurorehabilitation. The growing application of VR therapy promotes an increasing amount of clinical studies. In this paper, we present a bibliometric analysis of the existing studies to reveal the current research hotspots and guide future research directions. Methods: Articles and reviews on the related topic were retrieved from the Science Citation Index Expanded of Web of Science Core Collection database. VOSviewer and Citespace software were applied to systematically analyze information about publications, countries, institutions, authors, journals, citations, and keywords from the included studies. Results: A total of 1,556 papers published between 1995 and 2021 were identified. The annual number of papers increased gradually over the past three decades, with a peak publication year in 2021 (n = 276). Countries and institutions from North America and Western European were playing leading roles in publications and total citations. Current hotspots were focused on the effectiveness of VR therapy in cognitive and upper limb motor rehabilitation. The clusters of keywords contained the four targeted neurological diseases of VR, while the burst keywords represented that the latest studies were directed toward more defined types of VR therapy and greater study design. Conclusions: Our study offers information regarding to the current hotspots and emerging trends in the VR for rehabilitation field. It could guide future research and application of VR therapy in neurorehabilitation.