Screening of Short-Chain Antimicrobial Peptide LKARI with Broad-Spectrum Bactericidal Properties and Its Application in Promoting Wound Healing.

Due to the extensive use of antibiotics, many highly resistant bacteria and extensively resistant bacteria have been produced. In recent years, the increase of drug-resistant bacteria and the resulting proliferation of drug-resistant bacteria have increased the incidence of hospital-acquired infections and caused great harm to human health. Antimicrobial peptides (AMPs) are considered to be an innovative antibiotic and belong to the latest advances in this field. We designed a polypeptide and verified its low minimum inhibitory concentration and broad-spectrum activity against Gram-positive bacteria, Gram-negative bacteria, and fungi in microbiology and pharmacology. Several experiments have confirmed that the screened antimicrobial peptides have significant antidrug resistance and also show significant therapeutic properties in the treatment of systemic bacterial infections. In addition, through our experimental research, it was proved that the antibacterial hydrogel composed of poly(vinyl alcohol), sodium alginate, and antimicrobial peptides had excellent antibacterial properties and showed good wound healing ability.

The Role of Natural Products from Herbal Medicine in TLR4 Signaling for Colorectal Cancer Treatment.

The toll-like receptor 4 (TLR4) signaling pathway constitutes an intricate network of protein interactions primarily involved in inflammation and cancer. This pathway triggers intracellular signaling cascades, modulating transcription factors that regulate gene expression related to immunity and malignancy. Previous studies showed that colon cancer patients with low TLR4 expression exhibit extended survival times and the TLR4 signaling pathway holds a significant role in CRC pathogenesis. In recent years, traditional Chinese medicines (TCMs) have garnered substantial attention as an alternative therapeutic modality for CRC, primarily due to their multifaceted composition and ability to target multiple pathways. Emerging evidence indicates that specific TCM products, such as andrographolide, rosmarinic acid, baicalin, etc., have the potential to impede CRC development through the TLR4 signaling pathway. Here, we review the role and biochemical processes of the TLR4 signaling pathway in CRC, and natural products from TCMs affecting the TLR4 pathway. This review sheds light on potential treatment strategies utilizing natural TLR4 inhibitors for CRC, which contributes to the advancement of research and accelerates their clinical integration into CRC treatment.

A Short Review of Advances in MOF Glass Membranes for Gas Adsorption and Separation.

The phenomenon of melting in metal-organic frameworks (MOFs) has recently garnered attention. Crystalline MOF materials can be transformed into an amorphous glassy state through melt-quenching treatment. The resulting MOF glass structure eliminates grain boundaries and retains short-range order while exhibiting long-range disorder. Based on these properties, it emerges as a promising candidate for high-performance separation membranes. MOF glass membranes exhibit permanent and accessible porosity, allowing for selective adsorption of different gas species. This review summarizes the melting mechanism of MOFs and explores the impact of ligands and metal ions on glassy MOFs. Additionally, it presents an analysis of the diverse classes of MOF glass composites, outlining their structures and properties, which are conducive to gas adsorption and separation. The absence of inter-crystalline defects in the structures, coupled with their distinctive mechanical properties, renders them highly promising for industrial gas separation applications. Furthermore, this review provides a summary of recent research on MOF glass composite membranes for gas adsorption and separation. It also addresses the challenges associated with membrane production and suggests future research directions.

Cloning and functional characterization of the peptide deformylase encoding gene EuPDF1B from Eucommia ulmoides Oliv.

Peptide deformylase can catalyse the removal of formyl groups from the N-terminal formyl methionine of the primary polypeptide chain. The peptide deformylase genes of a few herbaceous plants have been studied to some extent, but the peptide deformylase genes of woody plants have not been studied. In this study, we isolated EuPDF1B from Eucommia ulmoides Oliv. The full-length sequence of EuPDF1B is 1176 bp long with a poly-A tail and contains an open reading frame of 831 bp that encodes a protein of 276 amino acids. EuPDF1B was localized to the chloroplast. qRT‒PCR analysis revealed that this gene was expressed in almost all tissues tested but mainly in mature leaves. Moreover, the expression of EuPDF1B was enhanced by ABA, MeJA and GA and inhibited by shading treatment. The expression pattern of EuPDF1B was further confirmed in EuPDF1Bp: GUS transgenic tobacco plants. Among all the transgenic tobacco plants, EuPDF1Bp-3 showed the highest GUS histochemical staining and activity in different tissues. This difference may be related to the presence of enhancer elements in the region from - 891 bp to - 236 bp of the EuPDF1B promoter. In addition, the expression of the chloroplast gene psbA and the net photosynthetic rate, fresh weight and height of tobacco plants overexpressing EuPDF1B were greater than those of the wild-type tobacco plants, suggesting that EuPDF1B may promote the growth of transgenic tobacco plants. This is the first time that PDF and its promoter have been cloned from woody plants, laying a foundation for further analysis of the function of PDF and the regulation of its expression.

An Explainable Artificial Intelligence Model to Predict Malignant Cerebral Edema after Acute Anterior Circulating Large-Hemisphere Infarction.

INTRODUCTION: Malignant cerebral edema (MCE) is a serious complication and the main cause of poor prognosis in patients with large-hemisphere infarction (LHI). Therefore, the rapid and accurate identification of potential patients with MCE is essential for timely therapy. This study utilized an artificial intelligence-based machine learning approach to establish an interpretable model for predicting MCE in patients with LHI. METHODS: This study included 314 patients with LHI not undergoing recanalization therapy. The patients were divided into MCE and non-MCE groups, and the eXtreme Gradient Boosting (XGBoost) model was developed. A confusion matrix was used to measure the prediction performance of the XGBoost model. We also utilized the SHapley Additive exPlanations (SHAP) method to explain the XGBoost model. Decision curve and receiver operating characteristic curve analyses were performed to evaluate the net benefits of the model. RESULTS: MCE was observed in 121 (38.5%) of the 314 patients with LHI. The model showed excellent predictive performance, with an area under the curve of 0.916. The SHAP method revealed the top 10 predictive variables of the MCE such as ASPECTS score, NIHSS score, CS score, APACHE II score, HbA1c, AF, NLR, PLT, GCS, and age based on their importance ranking. CONCLUSION: An interpretable predictive model can increase transparency and help doctors accurately predict the occurrence of MCE in LHI patients not undergoing recanalization therapy within 48 h of onset, providing patients with better treatment strategies and enabling optimal resource allocation.

Macrophage-Targeting DNA Nanomaterials: A Future Direction of Biological Therapy.

DNA can be used for precise construction of complex and flexible micro-nanostructures, including DNA origami, frame nucleic acids, and DNA hydrogels. DNA nanomaterials have good biocompatibility and can enter macrophages via scavenger receptor-mediated endocytosis. DNA nanomaterials can be uniquely and flexibly designed to ensure efficient uptake by macrophages, which represents a novel strategy to regulate macrophage function. With the development of nanotechnology, major advances have been made in the design and manufacturing of DNA nanomaterials for clinical therapy. In diseases accompanied by macrophage disturbances including tumor, infectious diseases, arthritis, fibrosis, acute lung injury, and atherosclerosis, DNA nanomaterials received considerable attention as potential treatments. However, we lack sufficient information to guarantee precise targeting of macrophages by DNA nanomaterials, which precludes their therapeutic applications. In this review, we summarize recent studies of macrophage-targeting DNA nanomaterials and discuss the limitations and challenges of this approach with regard to its potential use as a biological therapy.

[Incidence and risk factors of deep vein thrombosis in patients with rheumatoid arthritis].

OBJECTIVE: To investigate the incidence and risk factors of deep vein thrombosis (DVT) in patients with rheumatoid arthritis (RA). METHODS: The clinical data of RA patients who were hospi-talized in the Department of Rheumatology and Immunology of Aerospace Center Hospital from May 2015 to September 2021 was retrospectively analyzed, including demographic characteristics, concomitant diseases, laboratory examinations (blood routine, biochemistry, coagulation, inflammatory markers, rheumatoid factor, antiphospholipid antibodies and lupus anticoagulant, etc.) and treatment regimens. The patients were compared according to the presence or absence of DVT, and the t test, Mann-Whitney U test or Chi-square test were applied to screen for relevant factors for DVT, followed by Logistic regression analysis to determine risk factors for DVT in patients with RA. RESULTS: The incidence of DVT in the RA patients was 9.6% (31/322); the median age of RA in DVT group was significantly older than that in non-DVT group [64 (54, 71) years vs. 50 (25, 75) years, P < 0.001]; the level of disease activity score using 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) in DVT group was higher than that in non-DVT group [5.2 (4.5, 6.7) vs. 4.5(4.5, 5.0), P < 0.001]; the incidence of hypertension, chronic kidney disease, fracture or surgery history within 3 months, and varicose veins of the lower extremities in DVT group was higher than that in non-DVT group (P < 0.001). The levels of hemoglobin and albumin in DVT group were significantly lower than that in non-DVT group (P=0.009, P=0.004), while the D-dimer level and rheumatoid factor positive rate in DVT group were significantly higher than that in non-DVT group (P < 0.001). The use rate of glucocorticoid in DVT group was higher than that in non-DVT group (P=0.009). Logistic regression analysis showed that the age (OR=1.093, P < 0.001), chronic kidney disease (OR=7.955, P=0.005), fracture or surgery history within 3 months (OR=34.658, P=0.002), DAS28-ESR (OR=1.475, P=0.009), and the use of glucocorticoid (OR=5.916, P=0.003) were independent risk factors for DVT in RA patients. CONCLUSION: The incidence of DVT in hospitalized RA patients was significantly increased, in addition to traditional factors, such as age and chronic kidney disease, increased DAS28-ESR level and the use of glucocorticoid were also independent risk factors for DVT.

Olink proteomics analysis uncovers inflammatory proteins in patients with different states of bipolar disorder.

STUDY DESIGN: A prospective study. BACKGROUND: This study aims to investigate the relationship between different states of bipolar disorder (BD) and plasma inflammatory proteins, which may be used as their biomarkers. MATERIALS AND METHODS: We totally collected admission plasma from 16 healthy subjects and 32 BD patients, including 16 patients with BD manic episodes (BD-M) and 16 patients with BD depressive episodes (BD-D). Ten samples in each group were analyzed by proximity extension assays of 92 inflammation-related proteins, and all samples were verified by ELISA. Receiver-operating characteristic (ROC) curve analysis was performed to identify the diagnostic ability and cut-off values of potential biomarkers. RESULTS: Our findings showed that BD patients had significantly higher levels of IL6, MCP-1, TGF-α, IL8, and IL10-RB in comparison with healthy subjects, and their cut-off values were 0.531 pg/ml, 0.531 pg/ml, 0.469 pg/ml, 0.406 pg/ml, and 0.406 pg/ml, respectively. The levels of IL6, MCP-1, TGF-α, and IL8 in BD-M patients were significantly greater than in healthy individuals, and their cut-off values were 0.813 pg/ml, 0.688 pg/ml, 0.438 pg/ml, and 0.625 pg/ml, respectively. Moreover, we found cut-off values of 0.500 pg/mL and 0.688 ng/mL for TGF-α and ß-NGF, respectively, even though the levels in the BD-D group were much higher than in the control group. Furthermore, BD-M patients had significantly higher levels of IL6, FGF-19, IFN-γ, and IL-17C in comparison with BD-D patients. Likewise, 0.687 pg/ml, 0.500 pg/ml, 0.438 pg/ml, and 0.375 pg/ml were their cut-off values, respectively. Our findings also showed that the combination of these proteins had the highest diagnostic accuracy. CONCLUSIONS: Our findings showed that plasma inflammatory proteins were related to BD and its subtypes, which may be utilized as potential biomarkers of different stages of BD. Furthermore, we also found their cut-off values and their combinations to have the highest diagnostic accuracy, providing clinicians with a new method to rapidly differentiate BD and its subtypes and manage early targeted interventions.

Chemical Characterization of Honeysuckle Polyphenols and Their Alleviating Function on Ultraviolet B-Damaged HaCaT Cells by Modulating the Nrf2/NF-κB Signaling Pathways.

Scientific evidence attests that the epidermis receives excessive ultraviolet B (UVB) radiation, triggering the generation of substantial quantities of reactive oxygen species (ROS), which disrupted the delicate equilibrium of oxidation-reduction, leading to oxidative stress and inflammation. The historical use of honeysuckle polyphenols (HPs) has garnered our attention due to their efficacy in inhibiting oxidative damage. In this study, HPs were prepared from honeysuckle flowers employing an ultrasonic-assisted extraction method and quantitatively analyzed by a LC-MS/MS, and the mechanisms underlying HPs' antioxidative and anti-inflammatory effects on a UVB-irradiated HaCaT cell model were systematically investigated. The results showed that HPs had a significant cellular repair effect on UVB-irradiated HaCaT cells (p < 0.001). The mechanism of action indicated that HPs could allow Nrf2 to enter the nucleus by regulating the dissociation of Nrf2 from Keap1, which further increases the activity of downstream proteases (SOD and CAT), increases ROS scavenging, and reduces the intracellular malondialdehyde (MDA) level. In addition, HPs could down-regulate Toll-like receptor 4 (TLR4) and inhibit NF-κB (P65) dissociating from IκBα, resulting in a decrease in NF-κB (P65) entry into the nucleus and a decrease in inflammatory factors (TNF-α, IL-6, and IL-1ß). In addition, four key compounds in HPs, including chlorogenic acid, quercetin, isorhamnetin, and luteolin, were selected to verify the mechanism of HPs repairing UVB damage using molecular docking techniques. The experiment suggested that four key active compounds could effectively occupy the Kelch homologue (Kelch) structural domain of Keap1, competitively bind with Nrf2, and facilitate the promotion of Nrf2 binding, ultimately enhancing the translocation of Nrf2 into the nucleus. In addition, four key active compounds could effectively interact with NF-κB (P65) through hydrogen bonding, van der Waals forces, and electrostatic forces to inhibit its entry into the nucleus. In summary, HPs can effectively repair the damage of HaCaT cells by UVB radiation and can be used to develop health and cosmetic products for the treatment of UV radiation-induced diseases.

An Umbrella Insight into the Phytochemistry Features and Biological Activities of Corn Silk: A Narrative Review.

Corn silk (Zea mays L.) is the stigma of an annual gramineous plant named corn, which is distributed in many regions worldwide and has a long history of medicinal use. In recent years, with the sustainable development of traditional Chinese medicine, studies of corn silk based on modern technologies, such as GC-MS, LC-MS, and other analytical means, have offered more comprehensive analyses. Phytochemistry studies have shown that the main bioactive components in corn silk include flavonoids, polyphenols, phenolic acids, fatty acids, and terpenoids. Pharmacological studies have shown that corn silk extract has various pharmacological effects, such as reducing blood lipids, lowering blood pressure, regulating blood sugar levels, anti-inflammatory effects, and anti-oxidation effects. In this paper, the related research on corn silk from the past few years is summarized to provide a theoretical reference for the further development and utilization of corn silk.

Comprehensive pan-cancer analysis unveils the significant prognostic value and potential role in immune microenvironment modulation of TRIB3.

TRIB3, a pseudokinase, was previously studied within only some specific cancer types, leaving its comprehensive functions in pan-cancer contexts largely unexplored. Here, we performed an integrated analysis of TRIB3 expression, prognosis, genetic alterations, functional enrichment and tumor immune-related characteristics in 33 cancer types. Our results showed that TRIB3 exhibits high expression levels across 24 different cancer types and correlates closely with unfavorable prognoses. Meanwhile, TRIB3 shows mutations in a wide spectrum of 22 distinct cancer types, with the predominant mutation types being missense mutations and gene amplifications, and significant changes in DNA methylation levels in 14 types of cancer. We further discovered that TRIB3 expression is significantly associated with cancer immune-related genome mutations, such as tumor mutational burden (TMB), microsatellite instability (MSI) and DNA mismatch repair (MMR), and infiltration of immunosuppressive cells, such as CD4+ Th2 cells and myeloid-derived suppressor cells (MDSCs), into the tumor microenvironment. These results indicated that the expression of TRIB3 might reshape the tumor immune microenvironment (TIME) and lead to immunosuppressive "cold" tumors. In addition, our results confirmed that the loss of function of TRIB3 inhibits cell proliferation, promotes apoptosis, and leads to significant enrichment of "hot" tumor-related immune pathways, at least in breast cancer cells, which further supports the important role of TRIB3 in cancer prognosis and TIME regulation. Together, this pan-cancer investigation provided a comprehensive understanding of the critical role of TRIB3 in human cancers, and suggested that TRIB3 might be a promising prognostic biomarker and a potential target for cancer immunotherapy.

Cancer pain intensity and perceived social support in palliative care: 1-week prospective study.

OBJECTIVES: Pain is a complex and multidimensional experience affected by psychosocial factors. Perceived social support (PSS) has been considered as a positive psychosocial resource for effective regulation of cancer patients' well-being. Our study examined the relationship between PSS and pain intensity under 1-week palliative care. METHODS: A prospective study was conducted of terminal cancer inpatients (N=84) recruited from the hospice ward. Pain intensity was assessed on admission and 1 week later, and patients completed self-report questionnaires assessing PSS at admission. The repeated designed analysis of variance was used to explore the correlate of PSS with cancer pain. RESULTS: Pain intensity decreased after 1 week (t=2.303, p=0.024), and 47.62% gained pain relief. For pain intensity, there was a significant PSS group×time interaction effect detected (F=4.544, p=0.036). Pain intensity in the high PSS group was significantly reduced 1 week later (p=0.008), while the change of pain intensity was not significant in the low PSS group (p=0.609). CONCLUSIONS: PSS at admission predicted the 1-week development of pain intensity. Identifying PSS of terminal cancer patients leads to early interventions that are more effective in improving pain management of palliative care.

Channel Gating in Kalium Channelrhodopsin Slow Mutants.

Kalium channelrhodopsin 1 from Hyphochytrium catenoides (HcKCR1) is the first discovered natural light-gated ion channel that shows higher selectivity to K+ than to Na+ and therefore is used to silence neurons with light (optogenetics). Replacement of the conserved cysteine residue in the transmembrane helix 3 (Cys110) with alanine or threonine results in a >1,000-fold decrease in the channel closing rate. The phenotype of the corresponding mutants in channelrhodopsin 2 is attributed to breaking of a specific interhelical hydrogen bond (the "DC gate"). Unlike CrChR2 and other ChRs with long distance "DC gates", the HcKCR1 structure does not reveal any hydrogen bonding partners to Cys110, indicating that the mutant phenotype is likely caused by disruption of direct interaction between this residue and the chromophore. In HcKCR1_C110A, fast photochemical conversions corresponding to channel gating were followed by dramatically slower absorption changes. Full recovery of the unphotolyzed state in HcKCR1_C110A was extremely slow with two time constants 5.2 and 70 min. Analysis of the light-minus-dark difference spectra during these slow processes revealed accumulation of at least four spectrally distinct blue light-absorbing photocycle intermediates, L, M1 and M2, and a UV light-absorbing form, typical of bacteriorhodopsin-like channelrhodopsins from cryptophytes. Our results contribute to better understanding of the mechanistic links between the chromophore photochemistry and channel conductance, and provide the basis for using HcKCR1_C110A as an optogenetic tool.

Preparation and application of hemostatic microspheres containing biological macromolecules and others.

Bleeding from uncontrollable wounds can be fatal, and the body's clotting mechanisms are unable to control bleeding in a timely and effective manner in emergencies such as battlefields and traffic accidents. For irregular and inaccessible wounds, hemostatic materials are needed to intervene to stop bleeding. Hemostatic microspheres are promising for hemostasis, as their unique structural features can promote coagulation. There is a wide choice of materials for the preparation of microspheres, and the modification of natural macromolecular materials such as chitosan to enhance the hemostatic properties and make up for the deficiencies of synthetic macromolecular materials makes the hemostatic microspheres multifunctional and expands the application fields of hemostatic microspheres. Here, we focus on the hemostatic mechanism of different materials and the preparation methods of microspheres, and introduce the modification methods, related properties and applications (in cancer therapy) for the structural characteristics of hemostatic microspheres. Finally, we discuss the future trends of hemostatic microspheres and research opportunities for developing the next generation of hemostatic microsphere materials.

Large-scale loss-of-function perturbations reveal a comprehensive epigenetic regulatory network in breast cancer.

OBJECTIVE: Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression; however, the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive. It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets. METHODS: We employed high-throughput sequencing-based high-throughput screening (HTS2) to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators. Then, bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer. RESULTS: Utilizing these gene expression signatures, we classified the epigenetic regulators into five distinct clusters, each characterized by specific functions. We discovered functional similarities between BAZ2B and SETMAR, as well as CLOCK and CBX3. Moreover, we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation. Notably, we constructed an epigenetic regulatory network based on the gene expression signatures, which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer. CONCLUSIONS: Our work deciphered the extensive regulation among hundreds of epigenetic regulators. The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.

Structural basis of peptide secretion for Quorum sensing by ComA.

Quorum sensing (QS) is a crucial regulatory mechanism controlling bacterial signalling and holds promise for novel therapies against antimicrobial resistance. In Gram-positive bacteria, such as Streptococcus pneumoniae, ComA is a conserved efflux pump responsible for the maturation and secretion of peptide signals, including the competence-stimulating peptide (CSP), yet its structure and function remain unclear. Here, we functionally characterize ComA as an ABC transporter with high ATP affinity and determined its cryo-EM structures in the presence or absence of CSP or nucleotides. Our findings reveal a network of strong electrostatic interactions unique to ComA at the intracellular gate, a putative binding pocket for two CSP molecules, and negatively charged residues facilitating CSP translocation. Mutations of these residues affect ComA's peptidase activity in-vitro and prevent CSP export in-vivo. We demonstrate that ATP-Mg2+ triggers the outward-facing conformation of ComA for CSP release, rather than ATP alone. Our study provides molecular insights into the QS signal peptide secretion, highlighting potential targets for QS-targeting drugs.

Novel Ca-Chelating Peptides from Protein Hydrolysate of Antarctic Krill (Euphausia superba): Preparation, Characterization, and Calcium Absorption Efficiency in Caco-2 Cell Monolayer Model.

Antarctic krill (Euphausia superba) is the world's largest resource of animal proteins and is thought to be a high-quality resource for future marine healthy foods and functional products. Therefore, Antarctic krill was degreased and separately hydrolyzed using flavourzyme, pepsin, papain, and alcalase. Protein hydrolysate (AKH) of Antarctic krill prepared by trypsin showed the highest Ca-chelating rate under the optimized chelating conditions: a pH of 8.0, reaction time of 50 min, temperature of 50 °C, and material/calcium ratio of 1:15. Subsequently, fourteen Ca-chelating peptides were isolated from APK by ultrafiltration and a series of chromatographic methods and identified as AK, EAR, AEA, VERG, VAS, GPK, SP, GPKG, APRGH, GVPG, LEPGP, LEKGA, FPPGR, and GEPG with molecular weights of 217.27, 374.40, 289.29, 459.50, 275.30, 300.36, 202.21, 357.41, 536.59, 328.37, 511.58, 516.60, 572.66, and 358.35 Da, respectively. Among fourteen Ca-chelating peptides, VERG presented the highest Ca-chelating ability. Ultraviolet spectrum (UV), Fourier Transform Infrared (FTIR), and scanning electron microscope (SEM) analysis indicated that the VERG-Ca chelate had a dense granular structure because the N-H, C=O and -COOH groups of VERG combined with Ca2+. Moreover, the VERG-Ca chelate is stable in gastrointestinal digestion and can significantly improve Ca transport in Caco-2 cell monolayer experiments, but phytate could significantly reduce the absorption of Ca derived from the VERG-Ca chelate. Therefore, Ca-chelating peptides from protein hydrolysate of Antarctic krill possess the potential to serve as a Ca supplement in developing healthy foods.

Development and validation of a nomogram for the risk prediction of malignant cerebral edema after acute large hemispheric infarction involving the anterior circulation.

Background: Malignant cerebral edema (MCE) is a life-threatening complication of large hemisphere infarction (LHI). Therefore, a fast, accurate, and convenient tool for predicting MCE can guide triage services and facilitate shared decision-making. In this study, we aimed to develop and validate a nomogram for the early prediction of MCE risk in acute LHI involving the anterior circulation and to understand the potential mechanism of MCE. Methods: This retrospective study included 312 consecutive patients with LHI from 1 January 2019 to 28 February 2023. The patients were divided into MCE and non-MCE groups. MCE was defined as an obvious mass effect with ≥5 mm midline shift or basal cistern effacement. Least absolute shrinkage and selection operator (LASSO) and logistic regression were performed to explore the MCE-associated factors, including medical records, laboratory data, computed tomography (CT) scans, and independent clinic risk factors. The independent factors were further incorporated to construct a nomogram for MCE prediction. Results: Among the 312 patients with LHI, 120 developed MCE. The following eight factors were independently associated with MCE: Glasgow Coma Scale score (p = 0.007), baseline National Institutes of Health Stroke Scale score (p = 0.006), Alberta Stroke Program Early CT Score (p < 0.001), admission monocyte count (p = 0.004), white blood cell count (p = 0.002), HbA1c level (p < 0.001), history of hypertension (p = 0.027), and history of atrial fibrillation (p = 0.114). These characteristics were further used to establish a nomogram for predicting prognosis. The nomogram achieved an AUC-ROC of 0.89 (95% CI, 0.82-0.96). Conclusion: Our nomogram based on LASSO-logistic regression is accurate and useful for the early prediction of MCE after LHI. This model can serve as a precise and practical tool for clinical decision-making in patients with LHI who may require aggressive therapeutic approaches.

cGAS-STING signaling pathway promotes hypoxia-induced renal fibrosis by regulating PFKFB3-mediated glycolysis.

Hypoxia has long been considered to play an active role in the progression of fibrosis in chronic kidney disease, but its specific mechanism is not fully understood. The stimulator of interferon genes (STING) has been a research hotspot in the fields of tumor, immunity, and infection in recent years, and its role in immune and inflammatory responses related to kidney disease has gradually attracted attention. This study mainly explores the role and mechanism of STING in hypoxia-related renal fibrosis. To address this issue, we stimulated human proximal tubular epithelial (HK-2) cells with hypoxia for 48 h to construct cell models. Meanwhile, C57BL/6J male mice were used to establish a renal fibrosis model induced by renal ischemia-reperfusion injury (IRI). In our present study, we found that the GMP-AMP synthase (cGAS)-STING signaling pathway can promote the progression of renal fibrosis after hypoxic exposure, and this effect is closely related to 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3)-mediated glycolysis. Furthermore, inhibition of both STING and its downstream interferon regulatory factor 3 (IRF3) reversed elevated PFKFB3 expression, thereby attenuating hypoxia-induced renal fibrosis. Taken together, our data suggest that the cGAS-STING-IRF3-PFKFB3 signaling pathway activated under hypoxia may provide new ideas and targets for the treatment of early renal fibrosis.

Dimensions of spiritual well-being in relation to physical and psychological symptoms: a cross-sectional study of advanced cancer patients admitted to a palliative care unit.

OBJECTIVES: Advanced cancer patients face various symptoms, which can cause physical and psychological distress. As a multidimensional construct, spiritual well-being (SWB) may be an inner resource for dealing with these problems. Our study explored the impact of different dimensions of SWB on physical and psychological symptoms in advanced cancer patients admitted to a palliative care unit. METHODS: This cross-sectional study was conducted among 108 advanced cancer patients in the Hospice Ward, Shengjing Hospital of China Medical University. Patients completed questionnaires on SWB and cancer-related symptoms (insomnia, fatigue, pain, depression and anxiety) at the time of admission. Linear regression analysis was applied to determine the relationship between SWB (meaning, peace and faith) and symptom distress. RESULTS: SWB accounted for an additional variance of cancer-related symptoms (17.8% to 44.4%). Meaning was negatively associated with insomnia (ß = -0.516, p < 0.001) and fatigue (ß = -0.563, p < 0.001). Peace and faith were related to lower psychological symptoms, while meaning represented a positive effect on anxiety (ß = 0.275, p = 0.036). Higher peace was associated with lower cancer pain (ß = -0.422, p < 0.001). CONCLUSIONS: Our findings suggested that achieving peace and faith appeared to function consistently as a positive resource for advanced cancer patients on depression, anxiety and pain, while meaning may serve to facilitate or hinder positive adjustment. Future studies should focus on the potential clinical implications by identifying the distinct dimension of SWB as symptom management targets in the palliative care practice.