Laser-induced fibers and copper phthalocyanine modified laser-induced graphene electrodes for sensitive and selective electrochemical detection of nitrite.

We have recently reported laser-induced fibers (LIF) as a promising nanomaterial that possesses good electrochemical activity and are easily manufacturable. In this paper, for the first time, the application of LIF as functionalization materials on laser-induced graphene (LIG) electrodes for the detection of nitrate is demonstrated. The as-fabricated LIF surfaces on Kapton were extracted by ultrasonication as a dispersion and were used to modify the surface of the LIG electrode. An enhancement in active surface area from 0.669 cm2 for bare LIG to 0.83 cm2 for LIF-modified LIG was observed. Similarly, the heterogeneous electron transfer rate increased from 0.190 to 0.346 cm s-1 for LIF/LIG electrodes. The electrochemical detection of nitrite was achieved by modifying the LIG with a nanocomposite of LIF and copper phthalocyanine (CuPc). The presence of CuPc provided the desired catalytic activity towards the oxidation of nitrite, and the LIF enhanced the electron transfer to the electrode. Such a synergetic combination of the LIF embedded with CuPc enabled reaching a low limit of detection (LoD) of 0.12 µM, a large linear range from 10 to 10 000 µM and good selectivity in the presence of potential interferants. The sensor had a long shelf life of 30 days and good analytical capability to detect nitrite in mineral, tap, and groundwater. The potential of LIF is largely unexplored and the findings reported here on the fibers would open manifold opportunities for realizing novel applications.

Integrative alternative splicing analysis reveals new prognosis signature in B-cell acute lymphoblastic leukemia.

The dysregulation of alternative splicing (AS) is increasingly recognized as a pivotal player in the pathogenesis, progression, and treatment resistance of B-cell acute lymphoblastic leukemia (B-ALL). Despite its significance, the clinical implications of AS events in B-ALL remain largely unexplored. This study developed a prognostic model based on 18 AS events (18-AS), derived from a meticulous integration of bioinformatics methodologies and advanced machine learning algorithms. The 18-AS signature observed in B-ALL distinctly categorized patients into different groups with significant differences in immune infiltration, V(D)J rearrangement, drug sensitivity, and immunotherapy outcomes. Patients classified within the high 18-AS group exhibited lower immune infiltration scores, poorer chemo- and immune-therapy responses, and worse overall survival, underscoring the model's potential in refining therapeutic strategies. To validate the clinical applicability of the 18-AS, we established an SF-AS regulatory network and identified candidate drugs. More importantly, we conducted in vitro cell proliferation assays to confirm our analysis, demonstrating that the High-18AS cell line (SUP-B15) exhibited significantly enhanced sensitivity to Dasatinib, Dovitinib, and Midostaurin compared to the Low-18AS cell line (REH). These findings reveal AS events as novel prognostic biomarkers and therapeutic targets, advancing personalized treatment strategies in B-ALL management.

Structural Changes and Differences in Intrinsic Photoluminescence of Four Cationic Two-Dimensional Lead Halide Frameworks Modulated by Synthesis Temperature.

Luminescent hybrid organolead halide materials with cationic inorganic frameworks and high chemical inertness have demonstrated broad application prospects in the visible light region. However, the corresponding relationship between structural changes and luminescence properties in such materials needs further clarification. Here, for the first time, we have successfully synthesized [Pb2X3](PDAH)(H2O) (X = Cl or Br, PDAH = C7H4NO4) single crystals via a facile hydrothermal method and then obtained [Pb11X14](PDA)4 (X = Cl or Br, PDA = C7H3NO4) at higher temperatures. The different synthesis temperatures resulted in significant differences in the luminescence properties of the two groups of structures. X-ray crystallography revealed the different degrees of distortion of the PbII centers' coordination environment between the two structures, which would significantly affect the electron-phonon coupling process under excited states and ultimately affect the emission properties originating from self-trapped excitons (STEs) of the two materials. In addition, density functional theory (DFT) calculations indicate that the two structures have different band gap characteristics due to the different proportions of inorganic and organic components, which also affect the optoelectronic properties of the two groups of materials. It is also worth mentioning that the broadband orange-light emission of [Pb11Br14](PDA)4 with a high photoluminescence quantum efficiency (PLQE) of 86% endows it with potential applications in WLEDs.

An Extremely Rare Case of Collision Tumor: A Craniopharyngioma Coexists Pilocytic Astrocytoma.

A 21-year-old man presented with a 2-day history of cephalalgia and a 1-day history of nausea and vomiting. Neuroradiologic imaging revealed a lesion in the third ventricle accompanied by hydrocephalus. After undergoing a ventriculoperitoneal shunt procedure, the patient experienced relief from symptoms. One-month post-shunt, we excised the tumor. Histopathological examination identified it as a rare collision tumor, composed of a mixture of craniopharyngioma and pilocytic astrocytoma. This is an exceedingly rare type of tumor, with no similar cases reported in the existing literature.

Necroptosis plays a role in TL1A-induced airway inflammation and barrier damage in asthma.

BACKGROUND: Airway epithelial cell (AEC) necroptosis contributes to airway allergic inflammation and asthma exacerbation. Targeting the tumor necrosis factor-like ligand 1 A (TL1A)/death receptor 3 (DR3) axis has a therapeutic effect on asthmatic airway inflammation. The role of TL1A in mediating necroptosis of AECs challenged with ovalbumin (OVA) and its contribution to airway inflammation remains unclear. METHODS: We evaluated the expression of the receptor-interacting serine/threonine-protein kinase 3(RIPK3) and the mixed lineage kinase domain-like protein (MLKL) in human serum and lung, and histologically verified the level of MLKL phosphorylation in lung tissue from asthmatics and OVA-induced mice. Next, using MLKL knockout mice and the RIPK3 inhibitor GSK872, we investigated the effects of TL1A on airway inflammation and airway barrier function through the activation of necroptosis in experimental asthma. RESULTS: High expression of necroptosis marker proteins was observed in the serum of asthmatics, and necroptosis was activated in the airway epithelium of both asthmatics and OVA-induced mice. Blocking necroptosis through MLKL knockout or RIPK3 inhibition effectively attenuated parabronchial inflammation, mucus hypersecretion, and airway collagen fiber accumulation, while also suppressing type 2 inflammatory factors secretion. In addition, TL1A/ DR3 was shown to act as a death trigger for necroptosis in the absence of caspases by silencing or overexpressing TL1A in HBE cells. Furthermore, the recombinant TL1A protein was found to induce necroptosis in vivo, and knockout of MLKL partially reversed the pathological changes induced by TL1A. The necroptosis induced by TL1A disrupted the airway barrier function by decreasing the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin, possibly through the activation of the NF-κB signaling pathway. CONCLUSIONS: TL1A-induced airway epithelial necroptosis plays a significant role in promoting airway inflammation and barrier dysfunction in asthma. Inhibition of the TL1A-induced necroptosis pathway could be a promising therapeutic strategy.

Targeting lysyl oxidase like 2 attenuates OVA-induced airway remodeling partly via the AKT signaling pathway.

BACKGROUND: Airway epithelium is an important component of airway structure and the initiator of airway remodeling in asthma. The changes of extracellular matrix (ECM), such as collagen deposition and structural disturbance, are typical pathological features of airway remodeling. Thus, identifying key mediators that derived from airway epithelium and capable of modulating ECM may provide valuable insights for targeted therapy of asthma. METHODS: The datasets from Gene Expression Omnibus database were analyzed to screen differentially expressed genes in airway epithelium of asthma. We collected bronchoscopic biopsies and serum samples from asthmatic and healthy subjects to assess lysyl oxidase like 2 (LOXL2) expression. RNA sequencing and various experiments were performed to determine the influences of LOXL2 knockdown in ovalbumin (OVA)-induced mouse models. The roles and mechanisms of LOXL2 in bronchial epithelial cells were explored using LOXL2 small interfering RNA, overexpression plasmid and AKT inhibitor. RESULTS: Both bioinformatics analysis and further experiments revealed that LOXL2 is highly expressed in airway epithelium of asthmatics. In vivo, LOXL2 knockdown significantly inhibited OVA-induced ECM deposition and epithelial-mesenchymal transition (EMT) in mice. In vitro, the transfection experiments on 16HBE cells demonstrated that LOXL2 overexpression increases the expression of N-cadherin and fibronectin and reduces the expression of E-cadherin. Conversely, after silencing LOXL2, the expression of E-cadherin is up-regulated. In addition, the remodeling and EMT process that induced by transforming growth factor-ß1 could be enhanced and weakened after LOXL2 overexpression and silencing in 16HBE cells. Combining the RNA sequencing of mouse lung tissues and experiments in vitro, LOXL2 was involved in the regulation of AKT signaling pathway. Moreover, the treatment with AKT inhibitor in vitro partially alleviated the consequences associated with LOXL2 overexpression. CONCLUSIONS: Taken together, the results demonstrated that epithelial LOXL2 plays a role in asthmatic airway remodeling partly via the AKT signaling pathway and highlighted the potential of LOXL2 as a therapeutic target for airway remodeling in asthma.

Gasdermin D silencing alleviates airway inflammation and remodeling in an ovalbumin-induced asthmatic mouse model.

Emerging evidence demonstrates that pyroptosis has been implicated in the pathogenesis of asthma. Gasdermin D (GSDMD) is the pyroptosis executioner. The mechanism of GSDMD in asthma remains unclear. The aim of this study was to elucidate the potential role of GSDMD in asthmatic airway inflammation and remodeling. Immunofluorescence staining was conducted on airway epithelial tissues obtained from both asthma patients and healthy controls (HCs) to evaluate the expression level of N-GSDMD. ELISA was used to measure concentrations of cytokines (IL-1ß, IL-18, IL-17A, and IL-10) in serum samples collected from asthma patients and healthy individuals. We demonstrated that N-GSDMD, IL-18, and IL-1ß were significantly increased in samples with mild asthma compared with those from the controls. Then, wild type and Gsdmd-knockout (Gsdmd-/-) mice were used to establish asthma model. We performed histopathological staining, ELISA, and flow cytometry to explore the function of GSDMD in allergic airway inflammation and tissue remodeling in vivo. We observed that the expression of N-GSDMD, IL-18, and IL-1ß was enhanced in OVA-induced asthma mouse model. Gsdmd knockout resulted in attenuated IL-18, and IL-1ß production in both bronchoalveolar lavage fluid (BALF) and lung tissue in asthmatic mice. In addition, Gsdmd-/- mice exhibit a significant reduction in airway inflammation and remodeling, which might be associated with reduced Th17 inflammatory response and M2 polarization of macrophages. Further, we found that GSDMD knockout may improve asthmatic airway inflammation and remodeling through regulating macrophage adhesion, migration, and macrophage M2 polarization by targeting Notch signaling pathway. These findings demonstrate that GSDMD deficiency profoundly alleviates allergic inflammation and tissue remodeling. Therefore, GSDMD may serve as a potential therapeutic target against asthma.

Study of equivalent circuit of GaN based laser chip and packaged laser.

High-speed GaN-based lasers play a pivotal role in visible light communication (VLC) systems; however, the causes of the limited modulation response of our fabricated laser diode (LD) are not fully understood. Accordingly, we constructed an equivalent circuit model for both the LD and its packaging. This model enabled us to analyze the series resistance and parallel capacitance of the LD at different injection currents. Experiments and simulations were performed to investigate the intrinsic responses of the LD. The series resistance and parallel capacitance are responsible for S21 roll-off at low frequencies. Determination of the packaging design parameters on the modulation response of a transistor outline (TO)-can packaged LD was investigated which is important to achieve the impedance match in the future. The value of each discrete component was determined by fitting the scattering parameters of the equivalent circuit model to the packaged LD. Reducing the series resistance and parallel capacitance improved the modulation response. Our study firstly illustrates the design and manufacture of violet-blue-green laser transmitters with a large modulation bandwidth for ultra-high-speed VLC from the point of the impedance influence.

Differential Characteristics of the Metabolic Profiles and Microbial Community between Superior and Normal Grades of Nongxiangxing-daqu.

Nongxiangxing-daqu (NXDQ), as a saccharification and fermentation agent, directly affects the flavor and yield of fresh Nongxiangxing Baijiu (NXBJ). The difference in fermentation temperature owing to the artificial turning operation leads to the formation of superior (S) and normal (N) grades of NXDQ. Here, aiming to explore the discriminant characteristics of two grades of NXDQ, we studied the physicochemical properties, volatile compounds and microbial communities using HS-SPME-GC/MS and high-throughput sequencing technology. The NXDQ grades presented different physicochemical properties. Staphylococcus, Weissella, Lactobacillus and Thermoascus were dominant in the S grade (S-NXDQ), while Bacillus, Thermoactinomyces and Aspergillus were predominant in the N grade (N-NXDQ). Higher alcohols, aldehydes and ketones positively correlated with the bacterial biomarkers could be used as metabolic biomarkers for N-NXDQ; the S-NXDQ had a higher abundance of key enzymes involved in lactic acid and ethanol fermentation, while N-NXDQ had a higher abundance of key enzymes involved in amino acid synthesis and long-chain fatty acid and lipid metabolism. N-NXDQ and S-NXDQ had different microbial and metabolic biomarkers. These findings provide insight into the discriminant characteristics of different grades of NXDQ, a theoretical basis for rational evaluation of NXDQ, and effective information for quality improvement of daqu.

Multifaceted experiments and photothermal simulations based analysis of laser induced graphene and its fibers.

The interaction of CO2 laser with polyimide results in the formation of laser-induced graphene (LIG) and other morphological transitions based on laser parameters, such as Laser-induced fibers (LIF) on the surface. However, a fundamental investigation of LIF, its properties and potential have not been explored until now. We aim therefore to provide novel insights into the LIF by characterization of its structural, electrical, electrochemical, and mechanical properties. Four different morphologies were identified depending on the laser parameters and the temperature required for their formation were quantified by FEM model. Minimum temperatures of 1800 K were required to form LIG and around 2600 to 5000 K to form LIF. High heterogeneity of the LIF along thickness due to temperature gradients, and the existence of sheet structures underneath the fibers were identified. Due to the loosely bound nature of fibers, LIF dispersion was prepared by ultrasonication to functionalize the carbon electrode for electrochemical characterization. The modification with LIF on the electrodes enhanced the electrochemical response of the electrode towards standard redox couple which confirmed the conductive nature of the fibers. This work provides a solid basis for the versatile tuning of the behavior and properties of LIF for potential applications.

Circular RNA HIPK2 Promotes A1 Astrocyte Activation after Spinal Cord Injury through Autophagy and Endoplasmic Reticulum Stress by Modulating miR-124-3p-Mediated Smad2 Repression.

Glial scarring formed by reactive astrocytes after spinal cord injury (SCI) is the primary obstacle to neuronal regeneration within the central nervous system, making them a promising target for SCI treatment. Our previous studies have demonstrated the positive impact of miR-124-3p on neuronal repair, but it remains unclear how miR-124-3p is involved in autophagy or ER stress in astrocyte activation. To answer this question, the expression of A1 astrocyte-related markers at the transcriptional and protein levels after SCI was checked in RNA-sequencing data and verified using quantitative polymerase chain reaction (qPCR) and Western blotting in vitro and in vivo. The potential interactions among circHIPK2, miR-124-3p, and Smad2 were analyzed and confirmed by bioinformatics analyses and a luciferase reporter assay. In the end, the role of miR-124-3p in autophagy, ER stress, and SCI was investigated by using Western blotting to measure key biomarkers (C3, LC3, and Chop) in the absence or presence of corresponding selective inhibitors (siRNA, 4-PBA, TG). As a result, SCI caused the increase of A1 astrocyte markers, in which the upregulated circHIPK2 directly targeted miR-124-3p, and the direct downregulating effect of Smad2 by miR-124-3p was abolished, while Agomir-124 treatment reversed this effect. Injury caused a significant change of markers for ER stress and autophagy through the circHIPK2/miR-124-3p/Smad2 pathway, which might activate the A1 phenotype, and ER stress might promote autophagy in astrocytes. In conclusion, circHIPK2 may play a functional role in sequestering miR-124-3p and facilitating the activation of A1 astrocytes through regulating Smad2-mediated downstream autophagy and ER stress pathways, providing a new perspective on potential targets for functional recovery after SCI.

Suppression of SPARC Ameliorates Ovalbumin-induced Airway Remodeling via TGFß1/Smad2 in Chronic Asthma.

PURPOSE: Airway remodeling is a critical feature of asthma. Secreted protein acidic and rich in cysteine (SPARC), which plays a cardinal role in regulating cell-matrix interactions, has been implicated in various fibrotic diseases. However, the effect of SPARC in asthma remains unknown. METHODS: We studied the expression of SPARC in human bronchial epithelial cells and serum of asthmatics as well as in the lung tissues of chronic asthma mice. The role of SPARC was examined by using a Lentivirus-mediated SPARC knockdown method in the ovalbumin (OVA)-induced asthma mice. The biological processes regulated by SPARC were identified using RNA sequencing. The function of SPARC in the remodeling process induced by transforming growth factor ß1 (TGFß1) was conducted by using SPARC small interfering RNA (siRNA) or recombinant human SPARC protein in 16HBE cells. RESULTS: We observed that SPARC was up-regulated in human bronchial epithelia of asthmatics and the asthmatic mice. The levels of serum SPARC in asthmatics were also elevated and negatively correlated with the forced expiratory volume in one second (FEV1) to forced vital capacity ratio (FVC) (r = -0.485, P < 0.01) and FEV1 (%predicted) (r = -0.425, P = 0.001). In the chronic asthmatic mice, Lentivirus-mediated SPARC knockdown significantly decreased airway remodeling and airway hyper-responsiveness. According to gene set enrichment analysis, negatively enriched pathways found in the OVA + short hairpin-SPARC group included ECM organization and collagen formation. In the lung function studies, knockdown of SPARC by siRNA reduced the expression of remodeling-associated biomarkers, cell migration, and contraction by blocking the TGFß1/Smad2 pathway. Addition of human recombinant SPARC protein promoted the TGFß1-induced remodeling process, cell migration, and contraction in 16HBE cells via the TGFß1/Smad2 pathway. CONCLUSIONS: Our studies provided evidence for the involvement of SPARC in the airway remodeling of asthma via the TGFß1/Smad2 pathway.

Transcription factor 12-mediated self-feedback regulatory mechanism is required in DUX4 fusion leukaemia.

BACKGROUND: IGH::DUX4 is frequently observed in 4% B-cell acute lymphoblastic leukaemia patients. Regarding the IGH::DUX4-driven transactivation and alternative splicing, which are the main reasons behind this acute leukaemia outbreak, it remains unclear how transcriptional cofactors contribute to this oncogenic process. Further investigation is required to elucidate their specific role in leukaemogenesis. METHODS: In order to investigate the cofactors of IGH::DUX4, integrated mining of Chromatin immunoprecipitation (ChIP)-sequencing and RNA-sequencing of leukaemia cells and patient samples were conducted. Furthermore, to elucidate the synergistic interaction between transcription factor 12 (TCF12) and IGH::DUX4, knockdown and knockout experiment, mammalian two-hybridisation assay, co-immunoprecipitation and in situ proximity ligation assays were carried out. Additionally, to further investigate the direct interaction between TCF12 and IGH::DUX4, AI-based structural simulations were utilised. Finally, to validate the synergistic role of TCF12 in promoting IGH::DUX4 leukaemia, cell proliferation, apoptosis and drug sensitivity experiments were performed. RESULTS: In this study, we observed that the IGH::DUX4 target gene TCF12 might be an important cofactor/helper for this oncogenic driver. The co-expression of IGH::DUX4 and TCF12 resulted in enhanced DUX4-driven transactivation. Supportively, knockdown and knockout of TCF12 significantly reduced expression of IGH::DUX4-driven target genes in leukaemia REH (a precursor B-cell leukaemia cell line) and NALM-6 cells (a precursor B-cell leukaemia cell line). Consistently, in TCF12 knockout cells, the expression of structure-based TCF12 mutant, but not wild-type TCF12, failed to restore the TCF12-IGH::DUX4 crosstalk and the synergistic transactivation. More importantly, the breakdown in TCF12-IGH::DUX4 cooperation impaired IGH::DUX4-driven leukaemia cell survival, caused sensitivity to the chemotherapy. CONCLUSIONS: Altogether, these results helped to define a previously unrecognised TCF12-mediated positive self-feedback regulatory mechanism in IGH::DUX4 leukaemia, which holds the potential to function as a pivotal drug target for the management of this particular form of leukaemia. HIGHLIGHTS: Transcription factor 12 (TCF12) is a new novel cofactor in IGH::DUX4 transcriptional complexes/machinery. TCF12 mediates a positive self-feedback regulatory mechanism in IGH::DUX4-driven oncogenic transaction. IGH::DUX4-TCF12 structure/cooperation might represent a potent target/direction in future drug design against B-cell acute lymphoblastic leukaemia.

Transcription factor abnormalities in B-ALL leukemogenesis and treatment.

The biological regulation of transcription factors (TFs) and repressor proteins is an important mechanism for maintaining cell homeostasis. In B cell acute lymphoblastic leukemia (B-ALL) TF abnormalities occur at high frequency and are often recognized as the major driving factor in carcinogenesis. We provide an in-depth review of molecular mechanisms of six major TF rearrangements in B-ALL, including DUX4-rearranged (DUX4-R), MEF2D-R, ZNF384-R, ETV6-RUNX1 and TCF3-PBX1 fusions, and KMT2A-R. In addition, the therapeutic options and prognoses for patients who harbor these TF abnormalities are discussed. This review aims to provide an up-to-date panoramic view of how TF-based oncogenic fusions might drive carcinogenesis and impact on potential therapeutic exploration of B-ALL treatments.

Age is Not the Most Important Factor in the Prognosis of Femoral Neck Fracture: An Analysis of Long-Term Clinical Follow-Up.

Objective: The prognosis of femoral neck fractures is affected by factors including age and type of fracture. This study aimed to explore the associations among postsurgical outcomes of internal fixation for femoral neck fracture (healing rate, necrosis rate, and joint function score) and age and type of fracture. Methods: We retrospectively analyzed 297 cases of femoral neck fracture treated with internal fixation between February 2008 and October 2018. The postoperative femoral neck nonunion rate (a measure of healing) and femoral head necrosis rate were determined by x-ray and computed tomography. The Harris hip score (a measure of joint function and pain) was calculated. The effects of age and fracture type on these factors were analyzed. Results: There was no significant difference in the rate of femoral head necrosis and postoperative joint function scores among the different age groups. There was a significant difference in the postoperative rate of femoral head necrosis by Garden (P = .001) and Pauwels (P = .01) fracture types. No significant differences were noted for the Harris hip score for fractures characterized by the Pauwels classification (P = .09). However, the Harris hip scores differed significantly among groups for fractures categorized by the Garden classification (P = .001). Conclusions: Fracture type but not age is closely related to femoral head necrosis and Harris hip score after internal fixation of femoral neck fractures.

Metal-Stabilized Thiyl Radicals Design Inspired by Elemental Periodic Extension Notion for Ligand-Based Alkene Addition.

Inspired by alkene addition to the Ru and Re tris(thiolate) complexes via carbon-sulfur bond formation/cleavage reactions along with a periodic extension catalysis notion, a comparative study of the electronic structures, mechanisms, and reactivities for ethylene addition to the Os and Tc tris(thiolate) complexes was performed by DFT and high-level ab initio quantum calculations. The oxidized Os and Tc complexes were revealed to exhibit sufficient radical characters on the ligands to support their reaction with ethylene, whereas neutral Tc tris(thiolate) complex featuring little thiyl radical character renders no reactivity toward ethylene. Differential reactivities of these tris(thiolate) complexes was deemed to derive from the synergy of the thiyl radical character, the electronegativity, the row, and the charge. Extending from Ru and Re tris(thiolate) complexes to their Os and Tc counterparts can help us to get insightful rationales that would promote further research on alkene addition to metal-stabilized thiyl radicals.

[Study of hospitalization risk indicators for intensive care unit patients evaluated by intelligent calculation method].

OBJECTIVE: To explore the characteristics of the changes in risk score for intensive care unit (ICU) patients during hospitalization by the intelligent calculation method, and to provide evidence for the risk prevention. METHODS: In this retrospective study, ICU patients of the Fifth Central Hospital in Tianjin from November 3, 2021 to March 28, 2022 were enrolled and divided into ≥ 14 days group, 10-13 days group, 7-9 days group, and 3-6 days group according to the ICU length of stay. Risk scores assessed by the intelligent calculation method of the ICU patients were collected, including nutritional risk screening 2002 (NRS 2002), Caprini score and Padua score. NRS 2002 score for all patients, Caprini score for surgical patients and Padua score for internal medicine patients were selected. Trends in change of each score were compared between patients admitted to ICU 1, 3, 7 (if necessary), 10 (if necessary), and 14 days (if necessary). RESULTS: A total of 138 patients were involved, including 79 males and 59 females, with an average age of (61.71±18.86) years and an average hospital stay of [6.00 (4.00, 9.25)] days. (1) in the group with ICU length of stay ≥ 14 days (21 cases): there was no significant change in the NRS 2002 scores of the patients within 10 days, but the NRS 2002 score was significantly decreased in 14 days as compared with 1 day [3.00 (2.50, 3.50) vs. 4.00 (3.00, 5.00), P < 0.05]; both Caprini and Padua score were increased with prolonged hospital stay and compared with 1 day, the scores at the other time points were significantly increased, especially at 14 days [Caprini score: 5.00 (3.25,7.00) vs. 2.50 (1.25, 5.50), Padua score: 6.00 (6.00, 7.00) vs. 3.00 (1.00, 3.00), both P < 0.05]. (2) in the group with ICU length of stay from 10-13 days (15 cases): with the prolonged hospital stay, there was no significant change in NRS 2002 score, but both Caprini and Padua score were increased at 3, 7, 10 days, especially at 10 days [Caprini score: 3.00 (2.00, 4.75) vs. 2.00 (0.25, 2.75), Padua score: 5.00 (3.50, 6.00) vs. 2.00 (0.50, 4.00), both P < 0.05]. (3) in the group with ICU length of stay from 7-9 days (23 cases): compared with 1 day, the NRS 2002 score at 3 days and7 days were decreased, but the Caprini and Padua score were increased, especially at 7 days [NRS 2002 score: 2.00 (1.00, 4.00) vs. 2.00 (2.00, 4.00), Caprini score: 3.00 (2.00, 5.50) vs. 2.00 (0.25, 3.00), Padua score: 5.00 (4.00, 6.00) vs. 2.00 (0,2.00),all P < 0.05]. (4) in the group with ICU length of stay from 3-6 days (79 cases): compared with 1 day, the NRS 2002 score at 3 days was decreased [NRS 2002 score: 2.00 (1.00, 3.00) vs. 2.00 (1.00, 3.00), P < 0.05], Caprini and Padua score were significantly increased [Caprini score: 3.00 (2.00, 4.00) vs. 2.00 (1.00, 3.00), Padua score: 5.00 (4.00, 5.00) vs. 2.00 (1.00, 3.00), both P < 0.05]. CONCLUSIONS: Based on dynamic assessment of intelligent calculation methods, the risk of thrombosis in ICU patients increased with hospital length of stay, and the nutritional risk was generally flat or reducing in different hospitalization periods.

Disulfiram alleviates acute lung injury and related intestinal mucosal barrier impairment by targeting GSDMD-dependent pyroptosis.

BACKGROUND: Pyroptosis was implicated in acute lung injury (ALI). Disulfiram is reported as an effective pyroptosis inhibitor by inhibiting gasdermin D(GSDMD). However, the function of pyroptosis executor GSDMD and treatment of disulfiramon on ALI, especially whether it was involved in ALI-associated intestinal mucosal barrier impairment remains unclear. This study aims to explore the role of pyroptosis and disulfiram' treatment on ALI and related intestinal mucosal barrier impairment. METHODS: First, we established lipopolysaccharide (LPS)-induced ALI models in wild-type and Gsdmd knockout (Gsdmd-/-), to detect the effect of pyroptosis on ALI-related intestinal mucosal barrier impairment. Furthermore, we used wild-type mice treated with disulfiram to investigate the treatment of disulfiram on ALI and related intestinal mucosal barrier impairment. RESULTS: The data showed that GSDMD-mediated pyroptosis was activated in both lung and intestinal mucosa tissues in LPS-induced ALI, and deficiency of Gsdmd ameliorated LPS-induced ALI and related intestinal mucosal barrier damage. We also disclosed that disulfiram inhibited the pyroptosis level, and alleviated ALI and related intestinal mucosal barrier impairment induced by LPS. CONCLUSION: These findings suggested the role of GSDMD-mediated pyroptosis and the potential application treatment of disulfiram in ALI and related intestinal mucosal barrier damage.

Comparative analysis of the microbiotas and physicochemical properties inside and outside medium-temperature Daqu during the fermentation and storage.

Medium-temperature Daqu (MT-Daqu), a saccharification-fermentation agent and aroma-producing agent, is used to produce Chinese strong-flavor Baijiu. Many related studies have been published; however, less is known about microbial community and quality properties inside and outside the MT-Daqu from fermentation to storage. Here, along with determining the physicochemical index, the microbial community of MT-Daqu was investigated using both culture-dependent and culture-independent methods during 31 days of fermentation and 4 months of storage. Volatile compounds of mature MT-Daqu were analyzed using headspace solid-phase microextraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS). The results indicated obvious variation in the microbial community due to the changes in environmental conditions, and the physicochemical indices shifted from fluctuations in the fermentation period to relative stability after storage for 3 months. Moreover, the microbial counts and physicochemical indices of the inner layers of MT-Daqu differed from those of the outer layers. The dominant communities, including the bacterial phyla Firmicutes, Proteobacteria, and Actinobacteria and the fungal phyla Ascomycota and Mucoromycota, showed different abundances in the two parts of the mature MT-Daqu, and different microbial communities were enriched in both parts. Additionally, pyrazines and alcohols were the most abundant volatile aroma compounds in the mature MT-Daqu.