Analysis of alterations in serum vitamins and correlations with gut microbiome, microbial metabolomics in patients with sepsis.

BACKGROUND: Vitamins are essential micronutrients that play key roles in many biological pathways associated with sepsis. The gut microbiome plays a pivotal role in the progression of sepsis and may contribute to the onset of multi-organ dysfunction syndrome (MODS). The aim of this study was to investigate the changes in serum vitamins, and their correlation with intestinal flora and metabolomic profiles in patients with sepsis. METHODS: The serum levels of vitamins were determined by Ultra Performance Liquid Chromatography (UPLC). 16S rRNA gene sequencing and Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) targeted metabolomics were used for microbiome and metabolome analysis. RESULTS: In the training cohort: After univariate, multivariate (OPLS-DA) and Spearman analyses, it was concluded that vitamin levels of 25 (OH) VD3 and (VD2 + VD3), as well as vitamins A and B9, differed significantly among healthy controls (HC), non-septic critical patients (NS), and sepsis patients (SS) (P < 0.05). The validation cohort confirmed the differential vitamin findings from the training cohort. Moreover, analyses of gut flora and metabolites in septic patients and healthy individuals revealed differential flora, metabolites, and metabolic pathways that were linked to alterations in serum vitamin levels. We found for the first time that vitamin B9 was negatively correlated with g_Sellimonas. CONCLUSION: Sepsis patients exhibited significantly lower levels of 25 (OH) VD3 and (VD2 + VD3), vitamins A and B9, which hold potential as predictive markers for sepsis prognosis. The changes in these vitamins may be associated with inflammatory factors, oxidative stress, and changes in gut flora.

Energy-Efficient Sleep Apnea Detection Using a Hyperdimensional Computing Framework Based on Wearable Bracelet Photoplethysmography.

OBJECTIVE: Sleep apnea syndrome (SAS) is a common sleep disorder, which has been shown to be an important contributor to major neurocognitive and cardiovascular sequelae. Considering current diagnostic strategies are limited with bulky medical devices and high examination expenses, a large number of cases go undiagnosed. To enable large-scale screening for SAS, wearable photoplethysmography (PPG) technologies have been used as an early detection tool. However, existing algorithms are energy-intensive and require large amounts of memory resources, which are believed to be the major drawbacks for further promotion of wearable devices for SAS detection. METHODS: In this paper, an energy-efficient method of SAS detection based on hyperdimensional computing (HDC) is proposed. Inspired by the phenomenon of chunking in cognitive psychology as a memory mechanism for improving working memory efficiency, we proposed a one-dimensional block local binary pattern (1D-BlockLBP) encoding scheme combined with HDC to preserve dominant dynamical and temporal characteristics of pulse rate signals from wearable PPG devices. RESULTS: Our method achieved 70.17% accuracy in sleep apnea segment detection, which is comparable with traditional machine learning methods. Additionally, our method achieves up to 67× lower memory footprint, 68× latency reduction, and 93× energy saving on the ARM Cortex-M4 processor. CONCLUSION: The simplicity of hypervector operations in HDC and the novel 1D-BlockLBP encoding effectively preserve pulse rate signal characteristics with high computational efficiency. SIGNIFICANCE: This work provides a scalable solution for long-term home-based monitoring of sleep apnea, enhancing the feasibility of consistent patient care.

Establishment of transgenic fluorescent mice for labeling synapses and screening synaptogenic adhesion molecules.

Synapse is the fundamental structure for neurons to transmit information between cells. The proper synapse formation is crucial for developing neural circuits and cognitive functions of the brain. The aberrant synapse formation has been proved to cause many neurological disorders, including autism spectrum disorders and intellectual disability. Synaptic cell adhesion molecules (CAMs) are thought to play a major role in achieving mechanistic cell-cell recognition and initiating synapse formation via trans-synaptic interactions. Due to the diversity of synapses in different brain areas, circuits and neurons, although many synaptic CAMs, such as Neurexins (NRXNs), Neuroligins (NLGNs), Synaptic cell adhesion molecules (SynCAMs), Leucine-rich-repeat transmembrane neuronal proteins (LRRTMs), and SLIT and NTRK-like protein (SLITRKs) have been identified as synaptogenic molecules, how these molecules determine specific synapse formation and whether other molecules driving synapse formation remain undiscovered are unclear. Here, to provide a tool for synapse labeling and synaptic CAMs screening by artificial synapse formation (ASF) assay, we generated synaptotagmin-1-tdTomato (Syt1-tdTomato) transgenic mice by inserting the tdTomato-fused synaptotagmin-1 coding sequence into the genome of C57BL/6J mice. In the brain of Syt1-tdTomato transgenic mice, the tdTomato-fused synaptotagmin-1 (SYT1-tdTomato) signals were widely observed in different areas and overlapped with synapsin-1, a widely-used synaptic marker. In the olfactory bulb, the SYT1-tdTomato signals are highly enriched in the glomerulus. In the cultured hippocampal neurons, the SYT1-tdTomato signals showed colocalization with several synaptic markers. Compared to the wild-type (WT) mouse neurons, cultured hippocampal neurons from Syt1-tdTomato transgenic mice presented normal synaptic neurotransmission. In ASF assays, neurons from Syt1-tdTomato transgenic mice could form synaptic connections with HEK293T cells expressing NLGN2, LRRTM2, and SLITRK2 without immunostaining. Therefore, our work suggested that the Syt1-tdTomato transgenic mice with the ability to label synapses by tdTomato, and it will be a convenient tool for screening synaptogenic molecules.

Overexpression of SPP1 is a prognostic indicator of immune infiltration in lung adenocarcinoma.

OBJECTIVE: The extracellular phosphoprotein, secreted phosphoprotein 1 (SPP1), plays a crucial role in various tumors and regulating the immune system. This study aimed to evaluate its prognostic value and relationship to immune infiltration in lung adenocarcinoma (LUAD). METHODS: In the TCGA and GEO datasets, the information on clinic and transcriptome analysis of SPP1 in non-small-cell lung cancer (NSCLC) was examined accordingly. The association of SPP1 expression with overall survival and clinicopathologic characteristics was investigated by univariate and multivariate analysis. CancerSEA database was utilized to investigate the role of SPP1 at the cellular level by single-cell analysis. Additionally, the CIBERSORT algorithm was utilized to assess the correlation among the immune cells that infiltrated. RESULTS: NSCLC tissues exhibited a notable rise in SPP1 expression compared with that of normal tissues. Furthermore, the overexpression of SPP1 was substantially associated with clinicopathological features and unfavorable survival outcomes in individuals with LUAD, whereas no such correlation was observed in lung squamous cell carcinoma. Immune cells that infiltrate tumors and their corresponding genes were associated with SPP1 expression levels in LUAD. CONCLUSIONS: SPP1 is a reliable indicator for assessing LUAD immune infiltration status and prognosis. With this approach, SPP1 can help earlier LUAD diagnosis and act as a possible immunotherapy target.

Supervised and unsupervised machine learning approaches for monitoring subvisible particles within an aluminum-salt adjuvanted vaccine formulation.

Suspensions of protein antigens adsorbed to aluminum-salt adjuvants are used in many vaccines and require mixing during vial filling operations to prevent sedimentation. However, the mixing of vaccine formulations may generate undesirable particles that are difficult to detect against the background of suspended adjuvant particles. We simulated the mixing of a suspension containing a protein antigen adsorbed to an aluminum-salt adjuvant using a recirculating peristaltic pump and used flow imaging microscopy to record images of particles within the pumped suspensions. Supervised convolutional neural networks (CNNs) were used to analyze the images and create "fingerprints" of particle morphology distributions, allowing detection of new particles generated during pumping. These results were compared to those obtained from an unsupervised machine learning algorithm relying on variational autoencoders (VAEs) that were also used to detect new particles generated during pumping. Analyses of images conducted by applying both supervised CNNs and VAEs found that rates of generation of new particles were higher in aluminum-salt adjuvant suspensions containing protein antigen than placebo suspensions containing only adjuvant. Finally, front-face fluorescence measurements of the vaccine suspensions indicated changes in solvent exposure of tryptophan residues in the protein that occurred concomitantly with new particle generation during pumping.

Identification of Mudanjiang Phlebovirus in the Daxing'anling Region of China.

Mudanjiang phlebovirus (MJPV) is a newly discovered phlebovirus, initially detected from Ixodes persulcatus ticks in China in 2022. In this study, by next-generation sequencing (NGS) on a wide variety of ticks and wild small animals in China, we detected MJPV from I. persulcatus and Meriones meridianus. Additionally, we conducted RT-PCR and sequencing on 1815 adult ticks and 805 wild small mammals collected from eight provinces in China between 2017 and 2021. MJPV RNA-positive results were found in 0.22% (4/1815) of tick samples, as well as in 0.12% (1/805) of rodent samples. All positive detections were obtained from Heilongjiang and Inner Mongolia. Sequencing analysis revealed nucleotide similarities ranging from 98.23% to 99.11%, as well as amino acid similarities ranging from 99.12% to100%, between the current MJPV strain and previously reported strains of MJPV. Phylogenetic tree analysis demonstrated that the previously reported MJPV strain along with our two variants clustered together with other tick-borne phenuiviruses, indicating their close relationship within this viral group. This study represents the first detection of MJPV infection in wild rodents, expanding the known host range for this virus in the endemic regions.

In Situ Observation of Cellular Structure Changes in and Chain Segregations of Anabaena sp. PCC 7120 on TiO2 Films under a Photocatalytic Device.

Cyanobacteria outbreaks are serious water pollution events, causing water crises around the world. Photocatalytic disinfection, as an effective approach, has been widely used to inhibit blue algae growth. In this study, a tiny reaction room containing a TiO2 film was designed to fulfill in situ optical observation of the destruction process of a one-dimensional multicellular microorganism, Anabaena sp. PCC 7120, which is also a typical bacterial strain causing water blooms. It was found that the fragment number increased exponentially with the activation time. The fracture mechanics of the algae chains were hypothesized to be the combining functions of increased local tensile stress originated from the cell contracting as well as the oxidative attacks coming from reactive oxygen species (ROSs). It was assumed that the oxidative species were the root cause of cellular structure changes in and chain fractures of Anabaena sp. PCC 7120 in the photocatalytic inactivation activity.

Facile Synthesis of Cu-Doped ZnO Nanoparticles for the Enhanced Photocatalytic Disinfection of Bacteria and Fungi.

In this study, Cu-doped ZnO was prepared via the facile one-pot solvothermal approach. The structure and composition of the synthesized samples were characterized by XRD (X-ray diffraction), TEM (transmission electron microscopy), and XPS (X-ray photoelectron spectroscopy) analyses, revealing that the synthesized samples consisted of Cu-doped ZnO nanoparticles. Ultraviolet-visible (UV-vis) spectroscopy analysis showed that Cu-doping significantly improves the visible light absorption properties of ZnO. The photocatalytic capacity of the synthesized samples was tested via the disinfection of Escherichia coli, with the Cu-ZnO presenting enhanced disinfection compared to pure ZnO. Of the synthesized materials, 7% Cu-ZnO exhibited the best photocatalytic performance, for which the size was ~9 nm. The photocurrent density of the 7% Cu-ZnO samples was also significantly higher than that of pure ZnO. The antifungal activity for 7% Cu-ZnO was also tested on the pathogenic fungi of Fusarium graminearum. The macroconidia of F. graminearum was treated with 7% Cu-ZnO photocatalyst for 5 h, resulting in a three order of magnitude reduction at a concentration of 105 CFU/mL. Fluorescence staining tests were used to verify the survival of macroconidia before and after photocatalytic treatment. ICP-MS was used to confirm that Cu-ZnO met national standards for cu ion precipitation, indicating that Cu-ZnO are environmentally friendly materials.

Predicting Colloidal Stability of High-Concentration Monoclonal Antibody Formulations in Common Pharmaceutical Buffers Using Improved Polyethylene Glycol Induced Protein Precipitation Assay.

Colloidal stability is an important consideration when developing high concentration mAb formulations. PEG-induced protein precipitation is a commonly used assay to assess the colloidal stability of protein solutions. However, the practical usefulness and the current theoretical model for this assay have yet to be verified over a large formulation space across multiple mAbs and mAb-based modalities. In the present study, we used PEG-induced protein precipitation assays to evaluate colloidal stability of 3 mAbs in 24 common formulation buffers at 20 and 5 °C. These prediction assays were conducted at low protein concentration (1 mg/mL). We also directly characterized high concentration (100 mg/mL) formulations for cold-induced phase separation, turbidity, and concentratibility by ultrafiltration. This systematic study allowed analysis of the correlation between the results of low concentration assays and the high concentration attributes. The key findings of this study include the following: (1) verification of the usefulness of three different parameters (Cmid, µB, and Tcloud) from PEG-induced protein precipitation assays for ranking colloidal stability of high concentration mAb formulations; (2) a new method to implement PEG-induced protein precipitation assay suitable for high throughput screening with low sample consumption; (3) improvement in the theoretical model for calculating robust thermodynamic parameters of colloidal stability (µB and εB) that are independent of specific experimental settings; (4) systematic evaluation of the effects of pH and buffer salts on colloidal stability of mAbs in common formulation buffers. These findings provide improved theoretical and practical tools for assessing the colloidal stability of mAbs and mAb-based modalities during formulation development.

Machine learning-identified stemness features and constructed stemness-related subtype with prognosis, chemotherapy, and immunotherapy responses for non-small cell lung cancer patients.

AIM: This study aimed to explore a novel subtype classification method based on the stemness characteristics of patients with non-small cell lung cancer (NSCLC). METHODS: Based on the Cancer Genome Atlas database to calculate the stemness index (mRNAsi) of NSCLC patients, an unsupervised consensus clustering method was used to classify patients into two subtypes and analyze the survival differences, somatic mutational load, copy number variation, and immune characteristics differences between them. Subsequently, four machine learning methods were used to construct and validate a stemness subtype classification model, and cell function experiments were performed to verify the effect of the signature gene ARTN on NSCLC. RESULTS: Patients with Stemness Subtype I had better PFS and a higher somatic mutational burden and copy number alteration than patients with Stemness Subtype II. In addition, the two stemness subtypes have different patterns of tumor immune microenvironment. The immune score and stromal score and overall score of Stemness Subtype II were higher than those of Stemness Subtype I, suggesting a relatively small benefit to immune checkpoints. Four machine learning methods constructed and validated classification model for stemness subtypes and obtained multiple logistic regression equations for 22 characteristic genes. The results of cell function experiments showed that ARTN can promote the proliferation, invasion, and migration of NSCLC and is closely related to cancer stem cell properties. CONCLUSION: This new classification method based on stemness characteristics can effectively distinguish patients' characteristics and thus provide possible directions for the selection and optimization of clinical treatment plans.

Ze-Qi decoction inhibits non-small cell lung cancer growth and metastasis by modulating the PI3K/Akt/p53 signaling pathway.

Background: The Ze-Qi decoction (ZQD) is a traditional Chinese herbal formula commonly applied to treat lung cancer in China. This study aimed to assess the effective ingredients and molecular mechanisms of ZQD in treating non-small cell lung cancer (NSCLC) based on network pharmacology combined with experimental validation. Methods: Network pharmacology, bioinformatics, and molecular docking analyses were conducted to explore the mechanism of ZQD for treating NSCLC, which was further confirmed by animal experiments. Results: In total, 117 bioactive ingredients and 499 target proteins of ZQD were identified. Network pharmacology revealed 7 core active ingredients and 74 core target proteins. Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the PI3K/Akt and p53 signaling pathways may be crucial in NSCLC treatment. Molecular docking analysis revealed that the seven crucial bioactive ingredients complexed with PI3K, Akt, and p53. The animal experiment results validated that ZQD treatment promoted cell apoptosis and cell cycle arrest, thereby inhibiting NSCLC growth and metastasis. Furthermore, ZQD treatment caused a significant increase in p53 and Bax, while leading to a distinct reduction in p-PI3K (Tyr317), p-Akt (Ser473), VEGFA, CD31, MMP2, MMP9, Bcl2, and CDK2. Conclusions: ZQD inhibited the growth and metastasis of NSCLC subcutaneous tumors in C57BL/6J mice via the PI3K/Akt/p53 signaling pathway.

An effective disease diagnostic model related to pyroptosis in ischemic cardiomyopathy.

Pyroptosis is involved in ischemic cardiomyopathy (ICM). The study aimed to investigate the pyroptosis-related genes and clarify their diagnostic value in ICM. The bioinformatics method identified the differential pyroptosis genes between the normal control and ICM samples from online datasets. Then, protein-protein interaction (PPI) and function analysis were carried out to explore the function of these genes. Following, subtype analysis was performed using ConsensusClusterPlus, functions, immune score, stromal score, immune cell proportion and human leukocyte antigen (HLA) genes between subtypes were investigated. Moreover, optimal pyroptosis genes were selected using the least absolute shrinkage and selection operator (LASSO) analysis to construct a diagnostic model and evaluate its effectiveness using receiver operator characteristic (ROC) analysis. Twenty-one differential expressed pyroptosis genes were identified, and these genes were related to immune and pyroptosis. Subtype analysis identified two obvious subtypes: sub-1 and sub-2. And LASSO identified 13 optimal genes used to construct the diagnostic model. The diagnostic model in ICM diagnosis with the area under ROC (AUC) was 0.965. Our results suggested that pyroptosis was tightly associated with ICM.

Non-immune cell components in tumor microenvironment influencing lung cancer Immunotherapy.

Lung cancer (LC) is one of the leading causes of cancer-related deaths worldwide, with a significant morbidity and mortality rate, endangering human life and health. The introduction of immunotherapies has significantly altered existing cancer treatment strategies and is expected to improve immune responses, objective response rates, and survival rates. However, a better understanding of the complex immunological networks of LC is required to improve immunotherapy efficacy further. Tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs) are significantly expressed by LC cells, which activate dendritic cells, initiate antigen presentation, and activate lymphocytes to exert antitumor activity. However, as tumor cells combat the immune system, an immunosuppressive microenvironment forms, enabling the enactment of a series of immunological escape mechanisms, including the recruitment of immunosuppressive cells and induction of T cell exhaustion to decrease the antitumor immune response. In addition to the direct effect of LC cells on immune cell function, the secreting various cytokines, chemokines, and exosomes, changes in the intratumoral microbiome and the function of cancer-associated fibroblasts and endothelial cells contribute to LC cell immune escape. Accordingly, combining various immunotherapies with other therapies can elicit synergistic effects based on the complex immune network, improving immunotherapy efficacy through multi-target action on the tumor microenvironment (TME). Hence, this review provides guidance for understanding the complex immune network in the TME and designing novel and effective immunotherapy strategies for LC.

Fixators dynamization for delayed union and non-union of femur and tibial fractures: a review of techniques, timing and influence factors.

The optimal balance between mechanical environment and biological factors is crucial for successful bone healing, as they synergistically affect bone development. Any imbalance between these factors can lead to impaired bone healing, resulting in delayed union or non-union. To address this bone healing disorder, clinicians have adopted a technique known as "dynamization" which involves modifying the stiffness properties of the fixator. This technique facilitates the establishment of a favorable mechanical and biological environment by changing a rigid fixator to a more flexible one that promotes bone healing. However, the dynamization of fixators is selective for certain types of non-union and can result in complications or failure to heal if applied to inappropriate non-unions. This review aims to summarize the indications for dynamization, as well as introduce a novel dynamic locking plate and various techniques for dynamization of fixators (intramedullary nails, steel plates, external fixators) in femur and tibial fractures. Additionally, Factors associated with the effectiveness of dynamization are explored in response to the variation in dynamization success rates seen in clinical studies.

Experimental Study: The Effect of Pore Shape, Geometrical Heterogeneity, and Flow Rate on the Repetitive Two-Phase Fluid Transport in Microfluidic Porous Media.

Geologic subsurface energy storage, such as porous-media compressed-air energy storage (PM-CAES) and underground hydrogen storage (UHS), involves the multi-phase fluid transport in structurally disordered or heterogeneous porous media (e.g., soils and rocks). Furthermore, such multi-phase fluid transport is likely to repeatedly occur due to successive fluid injections and extractions, thus, resulting in cyclic drainage-imbibition processes. To complement our preceding study, we conducted a follow-up study with microfluidic pore-network devices with a square solid shape (Type II) to further advance our understanding on the effect of the pore shape (aspect ratio, Type I: 5-6 > Type II: ~1), pore-space heterogeneity (coefficient of variation, COV = 0, 0.25, and 0.5), and flow rates (Q = 0.01 and 0.1 mL/min) on the repetitive two-phase fluid flow in general porous media. The influence of pore shape and pore-space heterogeneity were observed to be more prominent when the flow rate was low (e.g., Q = 0.01 mL/min in this study) on the examined outcomes, including the drainage and imbibition patterns, the similarity of those patterns between repeated steps, the sweep efficiency and residual saturation of the nonwetting fluid, and fluid pressure. On the other hand, a higher flow rate (e.g., Q = 0.1 mL/min in this study) appeared to outweigh those factors for the Type II structure, owing to the low aspect ratio (~1). It was also suggested that the flow morphology, sweep efficiency, residual saturation, and required pressure gradient may not severely fluctuate during the repeated drainage--imbibition processes; instead, becoming stabilized after 4-5 cycles, regardless of the aspect ratio, COV, and Q. Implications of the study results for PM-CAES and UHS are discussed as a complementary analysis at the end of this manuscript.

In vivo flow cytometry reveals an anti-metastatic effect of Rujifang in triple-negative breast cancer.

Breast cancer is the most common cancer, and triple-negative breast cancer (TNBC) has the highest metastasis and mortality rate among all breast cancer subtypes. Rujifang is a traditional Chinese medicine formula with many years of clinical application in breast cancer treatment. Here, we aim to investigate the effects of Rujifang on circulating tumor cell (CTC) dynamics and the tumor microenvironment in a ZsGreen/luciferase double-labeled TNBC orthotopic model. We report that the number of CTCs monitored by in vivo flow cytometry (IVFC) strongly correlates with disease progression. Rujifang treatment decreased the number of CTCs and suppressed the distant metastasis of TNBC. Moreover, immunofluorescence analysis revealed that Rujifang treatment could affect the tumor microenvironment by downregulating Kindlin-1, which has been reported to promote metastasis of TNBC. Our study provides evidence of the anti-metastatic effect of Rujifang against TNBC in an animal model using fluorescent cell lines. The results suggest the potential therapeutic value of Rujifang as an anti-metastatic drug, however, further clinical trials are needed to validate these findings in humans.

2-Oxoglutarate contributes to the effect of foliar nitrogen on enhancing drought tolerance during flowering and grain yield of soybean.

Drought severely affects the growth and yield of soybean plants especially during the flowering period. To investigate the effect of 2-oxoglutarate (2OG) in combination with foliar nitrogen (N) at flowering stage on drought resistance and seed yield of soybean under drought stress. This experiment was conducted in 2021 and 2022 on drought-resistant variety (Hefeng 50) and drought-sensitive variety (Hefeng 43) soybean plants treated with foliar N (DS + N) and 2-oxoglutarate (DS + 2OG) at flowering stage under drought stress. The results showed that drought stress at flowering stage significantly increased leaf malonaldehyde (MDA) content and reduced soybean yield per plant. However, superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activities were significantly increased by foliar N treatment, and 2-oxoglutarate synergistically with foliar N treatment (DS + N + 2OG) was more beneficial to plant photosynthesis. 2-oxoglutarate significantly enhanced plant N content, glutamine synthetase (GS) and glutamate synthase (GOGAT) activity. Furthermore, 2-oxoglutarate increased the accumulation of proline and soluble sugars under drought stress. Under drought stress, soybean seed yield was increased by DS + N + 2OG treatment by 16.48-17.10% and 14.96-18.84% in 2021 and 2022, respectively. Thus, the combination of foliar N and 2-oxoglutarate better mitigated the adverse effects of drought stress and could better compensate for the yield loss of soybean under drought stress.

Clinical efficacy of low-dose glucocorticoid therapy for critically ill patients with severe fever with thrombocytopenia syndrome: A retrospective cohort study.

OBJECTIVES: To determine whether glucocorticoids can improve clinical outcomes of severe fever with thrombocytopenia syndrome (SFTS) patients, and how to identify patients who may benefit from the treatment. METHODS: A retrospective study was performed to include patients with confirmed SFTS from designated hospitals. The effect of glucocorticoids in reducing case fatality rate (CFR) and improving clinical recovery was evaluated by multivariate logistic regression models. RESULTS: A total of 2478 eligible patients were analyzed, of whom 331 received glucocorticoids. An integrated parameter (L-index) based on Log10(lactate dehydrogenase*blood urea nitrogen/lymphocyte count) was constructed to discriminate disease severity. In patients with L-index >3.823 indicating severe SFTS, significantly reduced CFR was observed in patients receiving low-moderate glucocorticoid doses with ≤60 mg daily methylprednisolone or equivalent (odds ratio [OR] 0.46, 95% confidence interval [CI], 0.23-0.88), but not in patients receiving high doses. In patients with L-index ≤3.823 indicating mild SFTS, glucocorticoid treatment was significantly associated with increased CFR (OR 3.34, 95% CI, 1.35-9.51), and mainly attributable to high-dose glucocorticoids (OR 2.83, 95% CI, 1.72-4.96). Disaggregated data analysis revealed a significant effect only in patients ≤65 years old, male, and early admission within 7 days after onset, but not in their counterparts. CONCLUSION: Glucocorticoids are not recommended for mild patients defined by L-index <3.823; however, patients with severe SFTS may benefit from low-moderate doses of glucocorticoids.

Inhibition of Non-small Cell Lung Cancer by Ferroptosis and Apoptosis Induction through P53 and GSK-3ß/Nrf2 Signal Pathways using Qingrehuoxue Formula.

This study aimed to elucidate the effects of Qingrehuoxue Formula (QRHXF) on NSCLC and its underlying mechanisms. Nude mouse model of subcutaneous tumors was established. QRHXF and erastin were administered orally and intraperitoneally, respectively. Mice's body weight and subcutaneous tumor volumes were measured. The effects of QRHXF on epithelial-mesenchymal transition (EMT), tumor-associated angiogenesis and matrix metalloproteinases (MMPs) were assessed. Importantly, we also analysed the anti-NSCLC of QRHXF form the aspect of ferroptosis and apoptosis and investigate its underlying mechanisms. The safety of QRHXF in mice was also evaluated. QRHXF slowed down the speed of tumor growth and visibly inhibited tumor growth. The expression levels of CD31, VEGFA, MMP2 and MMP9 were prominently suppressed by QRHXF. Furthermore, QRHXF appeared to remarkably inhibite cell proliferation and EMT by decreasing Ki67, N-cadherin and vimentin expression but elevating E-cadherin expression. There were more apoptotic cells in QRHXF group's tumor tissues, and QRHXF treatment increased BAX and cleaved-caspased 3 levels but decreased Bcl-2 levels. QRHXF significantly increased the accumulation of ROS, Fe2+, H2O2, and MDA while reduced GSH levels. SLC7A11 and GPX4 protein levels were considerably suppressed by QRHXF treatment. Moreover, QRHXF triggered ultrastructural changes in the mitochondria of tumor cells. The levels of p53 and p-GSK-3ß were upregulated, whereas that of Nrf2 was downregulated in the groups treated with QRHXF. QRHXF displayed no toxicity in mice. QRHXF activated ferroptosis and apoptosis to suppress NSCLC cell progression via p53 and GSK-3ß/Nrf2 signaling pathways.

Microstructure and Properties of Ti-Zr-Mo Alloys Fabricated by Laser Directed Energy Deposition.

The binary Ti-Zr congruent alloys have been a potential candidate for laser-directed energy deposition owing to an excellent combination of high structural stability and good formability. To solve its insufficient strength, a new series of Ti-Zr-Mo alloys with different Mo contents were designed based on a cluster model and then made by laser-directed energy deposition on a high-purity titanium substrate. The effect of Mo content on the microstructure and properties of the L-DEDed alloys was investigated. The consequences exhibit that the microstructure of all designed alloys is featured with near-equiaxed ß grains without obvious texture. However, increasing Mo content induces a gradual refinement of the grain and a steady decrease in the lattice constant, which effectively improves the hardness, strength, wear and corrosion resistance of the designed alloys, but slightly weakens ductility and formability. From the viewpoint of both properties and forming quality, the Ti60.94Zr36.72Mo2.34 (at.%) alloy owns a proper match in mechanical, tribological, chemical, and forming properties, which is widely used in aeroengine components.