Janus kinase inhibition (JAKi) therapy in refractory anti-synthetase syndrome: A retrospective cohort study.

OBJECTIVES: To evaluate the efficacy and safety of Janus kinase inhibitors (JAKi) in the treatment of refractory anti-synthetase syndrome (ASS) in real-world clinical settings. METHODS: The medical records of all refractory ASS patients who were treated with JAKi from October 2020 to June 2023 were retrospectively reviewed. RESULTS: Twenty patients were included, and all (100 %) patients had interstitial lung disease (ILD). After treatment with JAKi, 14 (70 %) of the refractory ASS patients showed significant improvement in clinical manifestations, including arthritis (56.3 % vs. 6.3 %, p = 0.002), rash (77.8 % vs. 27.8 %, p = 0.012), shortness of breath (55.6 % vs. 16.7 %, p = 0.039), cough (61.1 % vs. 11.1 %, p = 0.012). Improvement was noted for myalgia (50 % vs. 11.1 %, p = 0.016) and muscular weakness (61.1 % vs. 11.1 %, p = 0.012), while creatine kinase (CK) levels, which were abnormally elevated in five patients prior treatment, were significantly lowered (1096 ± 1042.98 IU/L vs. 199.2 ± 144.66 IU/L, p = 0.043). A decrease in levels of inflammatory markers, including erythrocyte sedimentation rate (ESR) (p = 0.001) and C-reactive protein (CRP) (p = 0.023) was observed in the patients. In ASS-ILD, the CT score reduced (188.75 ± 69.67 vs. 156.35 ± 74.62, p = 0.001). Furthermore, the glucocorticoid dose significantly reduced (21.42 ± 13.26 mg vs. 11.32 ± 8.59 mg; p = 0.001). CONCLUSIONS: JAKi were effective in most refractory ASS patients as evidenced by improved skin rash, myositis, and ILD. However, larger prospective controlled studies are required to evaluate its efficacy.

Fluorinated hydroxyapatite conditions a favorable osteo-immune microenvironment via triggering metabolic shift from glycolysis to oxidative phosphorylation.

BACKGROUND: Biological-derived hydroxyapatite is widely used as a bone substitute for addressing bone defects, but its limited osteoconductive properties necessitate further improvement. The osteo-immunomodulatory properties hold crucial promise in maintaining bone homeostasis, and precise modulation of macrophage polarization is essential in this process. Metabolism serves as a guiding force for immunity, and fluoride modification represents a promising strategy for modulating the osteoimmunological environment by regulating immunometabolism. In this context, we synthesized fluorinated porcine hydroxyapatite (FPHA), and has demonstrated its enhanced biological properties and osteogenic capacity. However, it remains unknown whether and how FPHA affects the immune microenvironment of the bone defects. METHODS: FPHA was synthesized and its composition and structural properties were confirmed. Macrophages were cultured with FPHA extract to investigate the effects of FPHA on their polarization and the related osteo-immune microenvironment. Furthermore, total RNA of these macrophages was extracted, and RNA-seq analysis was performed to explore the underlying mechanisms associated with the observed changes in macrophages. The metabolic states were evaluated with a Seahorse analyzer. Additionally, immunohistochemical staining was performed to evaluate the macrophages response after implantation of the novel bone substitutes in critical size calvarial defects in SD rats. RESULTS: The incorporation of fluoride ions in FPHA was validated. FPHA promoted macrophage proliferation and enhanced the expression of M2 markers while suppressing the expression of M1 markers. Additionally, FPHA inhibited the expression of inflammatory factors and upregulated the expression of osteogenic factors, thereby enhancing the osteogenic differentiation capacity of the rBMSCs. RNA-seq analysis suggested that the polarization-regulating function of FPHA may be related to changes in cellular metabolism. Further experiments confirmed that FPHA enhanced mitochondrial function and promoted the metabolic shift of macrophages from glycolysis to oxidative phosphorylation. Moreover, in vivo experiments validated the above results in the calvarial defect model in SD rats. CONCLUSION: In summary, our study reveals that FPHA induces a metabolic shift in macrophages from glycolysis to oxidative phosphorylation. This shift leads to an increased tendency toward M2 polarization in macrophages, consequently creating a favorable osteo-immune microenvironment. These findings provide valuable insights into the impact of incorporating an appropriate concentration of fluoride on immunometabolism and macrophage mitochondrial function, which have important implications for the development of fluoride-modified immunometabolism-based bone regenerative biomaterials and the clinical application of FPHA or other fluoride-containing materials.

GbyE: an integrated tool for genome widely association study and genome selection based on genetic by environmental interaction.

BACKGROUND: The growth and development of organism were dependent on the effect of genetic, environment, and their interaction. In recent decades, lots of candidate additive genetic markers and genes had been detected by using genome-widely association study (GWAS). However, restricted to computing power and practical tool, the interactive effect of markers and genes were not revealed clearly. And utilization of these interactive markers is difficult in the breeding and prediction, such as genome selection (GS). RESULTS: Through the Power-FDR curve, the GbyE algorithm can detect more significant genetic loci at different levels of genetic correlation and heritability, especially at low heritability levels. The additive effect of GbyE exhibits high significance on certain chromosomes, while the interactive effect detects more significant sites on other chromosomes, which were not detected in the first two parts. In prediction accuracy testing, in most cases of heritability and genetic correlation, the majority of prediction accuracy of GbyE is significantly higher than that of the mean method, regardless of whether the rrBLUP model or BGLR model is used for statistics. The GbyE algorithm improves the prediction accuracy of the three Bayesian models BRR, BayesA, and BayesLASSO using information from genetic by environmental interaction (G × E) and increases the prediction accuracy by 9.4%, 9.1%, and 11%, respectively, relative to the Mean value method. The GbyE algorithm is significantly superior to the mean method in the absence of a single environment, regardless of the combination of heritability and genetic correlation, especially in the case of high genetic correlation and heritability. CONCLUSIONS: Therefore, this study constructed a new genotype design model program (GbyE) for GWAS and GS using Kronecker product. which was able to clearly estimate the additive and interactive effects separately. The results showed that GbyE can provide higher statistical power for the GWAS and more prediction accuracy of the GS models. In addition, GbyE gives varying degrees of improvement of prediction accuracy in three Bayesian models (BRR, BayesA, and BayesCpi). Whatever the phenotype were missed in the single environment or multiple environments, the GbyE also makes better prediction for inference population set. This study helps us understand the interactive relationship between genomic and environment in the complex traits. The GbyE source code is available at the GitHub website ( https://github.com/liu-xinrui/GbyE ).

Qijiao Shengbai Capsule alleviated leukopenia by interfering leukotriene pathway: Integrated network study of multi-omics.

BACKGROUND: Leukopenia could be induced by chemotherapy, which leads to bone marrow suppression and even affects the therapeutic progression of cancer. Qijiao Shengbai Capsule (QSC) has been used for the treatment of leukopenia in clinic, but its bioactive components and mechanisms have not yet been elucidated clearly. PURPOSE: This study aimed to elucidate the molecular mechanisms of QSC in treating leukopenia. STUDY DESIGN: Serum pharmacochemistry, multi-omics, network pharmacology, and validation experiment were combined to study the effect of QSC in murine leukopenia model. METHODS: First, UPLC-QTOF-MS was used to clarify the absorbed components of QSC. Then, cyclophosphamide (CTX) was used to induce mice model with leukopenia, and the therapeutic efficacy of QSC was assessed by an integrative approach of multi-omics and network pharmacology strategy. Finally, molecular mechanisms and potential therapeutic targets were identified by validated experiments. RESULTS: 121 compounds absorbed in vivo were identified. QSC significantly increase the count of white blood cells (WBCs) in peripheral blood of leukopenia mice with 15 days treatment. Multi-omics and network pharmacology revealed that leukotriene pathway and MAPK signaling pathway played crucial roles during the treatment of leukopenia with QSC. Six targets (ALOX5, LTB4R, CYSLTR1, FOS, JUN, IL-1ß) and 13 prototype compounds were supposed to be the key targets and potential active components, respectively. The validation experiment further confirmed that QSC could effectively inhibit the inflammatory response induced by leukopenia. The inhibitors of ALOX5 activity can significantly increase the number of WBCs in leukopenia mice. Molecular docking of ALOX5 suggested that calycosin, daidzein, and medicarpin were the potentially active compounds of QSC. CONCLUSION: Leukotriene pathway was found for the first time to be a key role in the development of leukopenia, and ALOX5 was conformed as the potential target. QSC may inhibit the inflammatory response and interfere the leukotriene pathway, it is able to improve hematopoiesis and achieve therapeutic effects in the mice with leukopenia.

Saxibacter everestensis gen. nov., sp. nov., A Novel Member of the Family Brevibacteriaceae, Isolated from the North Slope of Mount Everest.

We isolated and analyzed a novel, Gram-stain-positive, aerobic, rod-shaped, non-motile actinobacterium, designated as strain ZFBP1038T, from rock sampled on the north slope of Mount Everest. The growth requirements of this strain were 10-37 °C, pH 4-10, and 0-6% (w/v) NaCl. The sole respiratory quinone was MK-9, and the major fatty acids were anteiso-C15:0 and iso-C17:0. Peptidoglycan containing meso-diaminopimelic acid, ribose, and glucose were the major cell wall sugars, while polar lipids included diphosphatidyl glycerol, phosphatidyl glycerol, an unidentified phospholipid, and an unidentified glycolipid. A phylogenetic analysis based on 16S rRNA gene sequences showed that strain ZFBP1038T has the highest similarity with Spelaeicoccus albus DSM 26341 T (96.02%). ZFBP1038T formed a distinct monophyletic clade within the family Brevibacteriaceae and was distantly related to the genus Spelaeicoccus. The G + C content of strain ZFBP1038T was 63.65 mol% and the genome size was 4.05 Mb. Digital DNA-DNA hybridization, average nucleotide identity, and average amino acid identity values between the genomes of strain ZFBP1038T and representative reference strains were 19.3-25.2, 68.0-71.0, and 52.8-60.1%, respectively. Phylogenetic, phenotypic, and chemotaxonomic characteristics as well as comparative genome analyses suggested that strain ZFBP1038T represents a novel species of a new genus, for which the name Saxibacter gen. nov., sp. nov. was assigned with the type strain Saxibacter everestensis ZFBP1038T (= EE 014 T = GDMCC 1.3024 T = JCM 35335 T).

Novel endotypes of antisynthetase syndrome identified independent of anti-aminoacyl transfer RNA synthetase antibody specificity that improve prognostic stratification.

OBJECTIVES: To systemically analyse the heterogeneity in the clinical manifestations and prognoses of patients with antisynthetase syndrome (ASS) and evaluate the transcriptional signatures related to different clinical phenotypes. METHODS: A total of 701 patients with ASS were retrospectively enrolled. The clinical presentation and prognosis were assessed in association with four anti-aminoacyl transfer RNA synthetase (ARS) antibodies: anti-Jo1, anti-PL7, anti-PL12 and anti-EJ. Unsupervised machine learning was performed for patient clustering independent of anti-ARS antibodies. Transcriptome sequencing was conducted in clustered ASS patients and healthy controls. RESULTS: Patients with four different anti-ARS antibody subtypes demonstrated no significant differences in the incidence of rapidly progressive interstitial lung disease (RP-ILD) or prognoses. Unsupervised machine learning, independent of anti-ARS specificity, identified three endotypes with distinct clinical features and outcomes. Endotype 1 (RP-ILD cluster, 23.7%) was characterised by a high incidence of RP-ILD and a high mortality rate. Endotype 2 (dermatomyositis (DM)-like cluster, 14.5%) corresponded to patients with DM-like skin and muscle symptoms with an intermediate prognosis. Endotype 3 (arthritis cluster, 61.8%) was characterised by arthritis and mechanic's hands, with a good prognosis. Transcriptome sequencing revealed that the different endotypes had distinct gene signatures and biological processes. CONCLUSIONS: Anti-ARS antibodies were not significant in stratifying ASS patients into subgroups with greater homogeneity in RP-ILD and prognoses. Novel ASS endotypes were identified independent of anti-ARS specificity and differed in clinical outcomes and transcriptional signatures, providing new insights into the pathogenesis of ASS.

UPLC-Q-TOF/MS based metabolite profiling and quality marker constituents screening of root, stem and rhizome extracts of Ilex asprella.

OBJECTIVE: The root of Ilex asprella (RIA) is a popular plant resource for treating inflammation-related diseases. The purpose of this study was to identify the secondary metabolites, to compare anti-inflammatory effects and to determine the quality marker components among root, stem and rhizome sections of IA. METHODS: Chemical fingerprints of stem, root and rhizome of IA was determined by high performance liquid chromatography (HPLC). A reliable method using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was established for comprehensively determining the chemical constituents of the plants. Anti-inflammatory activities of IA and its ingredients were screened by in vivo mouse ear swelling and in vitro LPS-induced release of NO from RAW264.7 cells experiments. RESULTS: Root, stem and rhizome of IA have shown high similarity in chemical fingerprints. Totally 149 compounds were characterized in IA, including triterpenoids, triterpenoid saponins, phenolic acids and lignans. 44 of them were identified based on co-occurring Mass2Motifs, including 19 unreported ones, whilst 17 were tentatively confirmed by comparison with reference compounds. No significant anti-inflammatory activity difference among root, stem and rhizome parts of IA was found. Ilexsaponin B2, protocatechualdehyde, isochlorogenic acid B and quinic acid, were screened out as quality marker compounds in IA. CONCLUSION: A sensitive and rapid strategy was established to evaluate the differences on secondary metabolites of different parts of IA for the first time, and this study may contribute to the quality evaluation of medicinal herbs and provide theoretically data support for further analysis of different parts of IA.

Superhydrophobic magnetic Fe3O4 polyurethane sponges for oil-water separation and oil-spill recovery.

The effective and affordable separation of oil and water, a crucial process in the safe handling of environmental disasters such as crude oil spills and recovery of valuable resources, is a highly sought-after yet challenging task. Herein, superhydrophobic PU sponge was fabricated for the fast and cost-effective adsorptive separation of oil and different organic solvents from water. Octadecyltrichlorosilane (OTS)-functionalized Fe3O4@SiO2 core-shell microspheres were dip-coated on the surface of porous materials via a dip-coating process, thereby endowing them with superhydrophobicity. Owing to the hydrophobic interaction between OTS molecules and oil and increased capillary force in the micropores, the resulting superhydrophobic sponge served as a selective oil-sorbent scaffold for absorbing oil from oil-water mixtures, including oil-water suspensions and emulsions. Remarkably, after the recovery of the adsorbed oil via mechanical extrusion, these superhydrophobic materials could be reused multiple times and maintain their oil-water separation efficacy even after 10 oil-water separation cycles.

Balance between the CMC/ACP Nanocomplex and Blood Assimilation Orchestrates Immunomodulation of the Biomineralized Collagen Matrix.

Calcium phosphate-based biomineralized biomaterials have broad application prospects. However, the immune response and foreign body reactions elicited by biomineralized materials have drawn substantial attention recently, contrary to the immune microenvironment optimization concept. Therefore, it is important to clarify the immunomodulation properties of biomineralized materials. Herein, we prepared the biomineralized collagen matrix (BCM) and screened the key immunomodulation factor carboxymethyl chitosan/amorphous calcium phosphate (CMC/ACP) nanocomplex. The immunomodulation effect of the BCM was investigated in vitro and in vivo. The BCM triggered evident inflammatory responses and cascade foreign body reactions by releasing the CMC/ACP nanocomplex, which activated the potential TLR4-MAPK/NF-κB pathway, compromising the collagen matrix biocompatibility. By contrast, blocking the CMC/ACP nanocomplex release via the blood assimilation process of the BCM mitigated the inflammation and foreign body reactions, enhancing biocompatibility. Hence, the immunomodulation of the BCM was orchestrated by the balance between the CMC/ACP nanocomplex and the blood assimilation process. Controlling the release of the CMC/ACP nanocomplex to accord the biological effects of ACP with the temporal regenerative demands is key to developing advanced biomineralized materials.

A novel UV-resistant bacterium Sphingomonas endolithica sp. nov., and genomic analysis, isolated from the north slope of Mount Everest.

Gram-stain-negative, aerobic, rod-shaped, non-motile bacterium strain ZFBP2030T was isolated from a rock on the North slope of Mount Everest. This strain contained a unique ubiquinone-10 (Q-10) as a predominant respiratory quinone. Among the tested fatty acids, the strain contained summed feature 8, C14:0 2OH, and C16:0, as major cellular fatty acids. The polar lipid profile contained phosphatidyl glycerol, phosphatidyl ethanolamine, three unidentified phospholipids, two unidentified aminolipids, and six unidentified lipids. The cell-wall peptidoglycan was a meso-diaminopimelic acid, and cell-wall sugars were ribose and galactose. Phylogenetic analyses based on 16S rRNA gene sequence revealed that strain ZFBP2030T was a member of the genus Sphingomonas, exhibiting high sequence similarity to the 16S rRNA gene sequences of Sphingomonas aliaeris DH-S5T (97.9%), Sphingomonas alpina DSM 22537T (97.3%) and Sphingomonas hylomeconis CCTCC AB 2013304T (97.0%). The 16S rRNA gene sequence similarity between ZFBP2030T and other typical strains was less than 97.0%. The average amino acid identity values, average nucleotide identity, and digital DNA-DNA hybridization values between strain ZFBP2030T and its highest sequence similarity strains were 56.9-79.9%, 65.1-82.2%, and 19.3-25.8%, respectively. The whole-genome size of the novel strain ZFBP2030T was 4.1 Mbp, annotated with 3838 protein-coding genes and 54 RNA genes. Moreover, DNA G + C content was 64.7 mol%. Stress-related functions predicted in the subsystem classification of the strain ZFBP2030T genome included osmotic, oxidative, cold/heat shock, detoxification, and periplasmic stress responses. The overall results of this study clearly showed that strain ZFBP2030T is a novel species of the genus Sphingomonas, for which the name Sphingomonas endolithica sp. nov. is proposed. The type of strain is ZFBP2030T (= EE 013T = GDMCC 1.3123T = JCM 35386T).

The predictive value of baseline symptom score and the peripheral CD4CD8 double-positive T cells in patients with AECOPD.

BACKGROUND: Accurate prediction of acute exacerbation helps select patients with chronic obstructive pulmonary disease (COPD) for individualized therapy. The potential of lymphocyte subsets to function as clinical predictive factors for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) remains uncertain. METHODS: In this single-center prospective cohort study with a 2-year follow-up, 137 patients aged 51 to 79 with AECOPD were enrolled. We examined the prognostic indicators of AECOPD by analyzing lymphocyte subsets and baseline symptom score. Furthermore, a predictive model was constructed to anticipate the occurrence of respiratory failure in patients experiencing AECOPD. RESULTS: The COPD Assessment Test (CAT) score combined with home oxygen therapy and CD4+CD8+ T cells% to predict respiratory failure in AECOPD patients were the best (the area under the curves [AUC] = 0.77, 95% CI: 0.70-0.86, P < 0.0001, sensitivity: 60.4%, specificity: 86.8%). The nomogram model, the C index, calibration plot, decision curve analysis, and clinical impact curve all indicate the model's good predictive performance. The observed decrease in the proportions of CD4+CD8+ T cells appears to be correlated with more unfavorable outcomes. CONCLUSIONS: The nomogram model, developed to forecast respiratory failure in patients with AECOPD, utilizing variables such as home oxygen therapy, CAT score, and CD4+CD8+ T cells%, demonstrated a high level of practicality in clinical settings. CD4+CD8+ T cells serve as a reliable and readily accessible predictor of AECOPD, exhibiting greater stability compared to other indices. It is less susceptible to subjective influences from patients or physicians. This model facilitated personalized estimations, enabling healthcare professionals to make informed decisions regarding preventive interventions.

Prevalence of post-traumatic stress disorder among residents of Shanghai standardized training programs during the COVID-19 outbreak: a cross-sectional study.

Background: The COVID-19 pandemic may have increased the prevalence of psychiatric disorders, such as anxiety, depressive disorders, and post-traumatic stress disorder (PTSD), among healthcare workers. Purpose: This study aims to investigate the prevalence of PTSD and its risk factors among residents in the standardized residency training programs (SRTPs) in Shanghai during the COVID-19 outbreak. Participants and methods: An online cross-sectional survey was conducted between December 17, 2021, and January 7, 2022, among SRPT residents from 15 hospitals in Shanghai, China. Questionnaires comprising general information, medical-related traumatic event experiences, the PTSD Checklist (PCL-5), and the perceived social support scale (PSSS) were distributed to the participants using the online Questionnaire Star electronic system. Results: We included 835 valid responses for the analysis. In total, 654 residents (78.3%) had experienced at least one traumatic event, and 278 residents (33.3%) were found to have PTSD symptoms. The age 26-30 years old, female sex, and increased resident working hours were identified as the risk factors for PTSD (p < 0.05), and perceived social support had a significant negative association with PTSD (p < 0.05). Conclusion: During the COVID-19 pandemic, there was a high prevalence of PTSD among SRTPs residents in Shanghai. The age 26-30 years old, female sex, and increased resident working hours were identified as risk factors for PTSD, while perceived social support was identified as a protective factor against PTSD. The present findings can be applied in STRPs management and provide useful information for designing special interventions and protocols for SRTPs residents.

Phosphorylated Fish Gelatin and the Quality of Jelly Gels: Gelling and Microbiomics Analysis.

Phosphorylated fish gelatin (PFG) exhibited preferable physical and chemical properties than fish gelatin (FG) in our previous study. To investigate the application values of PFG, the effects of different ratios (2:1, 1:1 and 1:2) of FG(PFG)/κ carrageenan (κC) on the quality of jelly gels (JGs) were investigated. The sensory quality of PFG:κC (1:2)/FG:κC (1:2) was found to be superior based on sensory evaluations, which was also verified with the results for texture, rheology, etc. Moreover, the structural changes in JGs were related to the introduction of phosphoric acid groups into the molecular chain of gelatin and the protein-polysaccharide interactions. According to the storage results, PFG jelly had better storage quality, higher hardness and chewiness values than those of FG jelly. High-throughput sequencing of JG microbial analysis showed that the addition of PFG changed the amount of microorganisms, microbial species abundance and the microbial composition of JGs, which were also closely related to the storage quality of JGs. In conclusion, the applications of PFG have promising potential to improve the quality of confectionery.

Optimized osteogenesis of porcine bone-derived xenograft through surface coating of magnesium-doped nanohydroxyapatite.

As one of the key factors influencing the outcome of guided bone regeneration, the currently used xenografts possess insufficient capability in osteogenesis. With the aim of improving the osteogenic performance of xenografts, porcine bone-derived hydroxyapatite (PHA) was prepared and subsequently coated by magnesium-doped nano hydroxyapatite (nMgHA, 10%, 20%, and 30% of Mg/Ca + Mg) through a straightforward and cost-efficient approach. The physiochemical and biological properties of nMgHA/PHAs were examinedin vitroandin vivo. The inherent three-dimensional (3D) porous framework with the average pore size of 300 µm was well preserved in nMgHA/PHAs. Meanwhile, excess magnesium released from the so-called 'surface pool' of PHA was verified. In contrast, slower release of magnesium at lower concentrations was detected for nMgHA/PHAs. Significantly more newly-formed bone and microvessels were observed in 20%nMgHA/PHA than the other specimens. With the limitations of the present study, it could be concluded that PHA coated by 20%nMgHA may have the optimized osteogenic performance due to the elimination of the excess magnesium from the 'surface pool', the preservation of the inherent 3D porous framework with the favorable pore size, and the release of magnesium at an appropriate concentration that possessed osteoimmunomodulatory effects on macrophages.

Optimal cut-off MoCA score for screening for mild cognitive impairment in elderly individuals in China: A systematic review and meta-analysis.

AIM: To evaluate the optimal cut-off MoCA score for elderly individuals with MCI. DESIGN: A systematic review and meta-analysis. METHOD: Articles were retrieved from PubMed, Ovid, Embase, The Cochrane Library, PsycINFO, CBM, CNKI, WanFang and CQVIP and were assessed by using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Figures of the assessment were made by using Review Manager 5.3, and a meta-analysis of the data was conducted by using Bivariate Random-effects Meta-Analysis (BRMA) via Stata 14.0. RESULTS: Seventeen articles were retrieved from the database, and when the cut-offs were 24/25 and 25/26, they represented the same diagnostic value; in addition, the AUC was 0.96, which demonstrated high predictive validity for mild cognitive impairment screening. However, the sensitivity was higher with 25/26 (se=0.95, sp=0.80), whereas the specificity was higher with 24/25 (se=0.92, sp=0.89).

Using complete blood count, serum immunoglobulins G/A/M and complement C3/C4 levels to predict the risk of COPD acute exacerbation: 2-year follow-up in a single-center prospective cohort study.

Autoimmunity is present in patients with stable chronic obstructive pulmonary disease (COPD), playing a role in indirect and direct ways. We aimed to explore whether autoimmunity could play a role in COPD exacerbations and construct autoimmunity-related prediction models. This prospective, longitudinal, observational cohort study enrolled 155 patients with acute COPD exacerbations (AECOPD) followed for at least two years. The laboratory parameters, including complete blood count, serum immunoglobulins G/A/M and complement C3/C4 levels, were collected at enrollment. We studied the demographic characteristics, clinical characteristics and laboratory parameters to identify independent risk factors and build predictive models. The results showed that lower lymphocyte count was associated with noninvasive ventilation (NIV) in patients with AECOPD (the odds ratio [OR] 0.25, the 95% confidence interval [CI]: 0.08-0.81, P = 0.02). Lymphocyte count performed well with an area under the curves (AUC) of 0.75 (P < 0.0001, sensitivity: 78.1%, specificity: 62.3%, cutoff value [Cov] ≤ 1.1). The C index, calibration plot, decision curve analysis (DCA) and bootstrap repetitions indicated that this clinical prediction model based on lymphocyte count for NIV in patients with AECOPD performed well. Having prior home oxygen therapy (OR: 2.82, 95% CI: 1.25-6.36, P = 0.013) and higher COPD Assessment Test (CAT) scores (OR: 1.14, 95% CI: 1.03-1.25, P = 0.011) were associated with the increased risk for respiratory failure. For predicting respiratory failure, CAT scores and home oxygen therapy combined had an AUC-ROC of 0.73 (P < 0.0001). This clinical prediction model based on lymphocyte count may help to assist in treatment decisions for NIV in patients with AECOPD. Lower complement C3 seems to be associated with worse outcomes in patients with AECOPD.

Tailoring the multiscale mechanics of tunable decellularized extracellular matrix (dECM) for wound healing through immunomodulation.

With the discovery of the pivotal role of macrophages in tissue regeneration through shaping the tissue immune microenvironment, various immunomodulatory strategies have been proposed to modify traditional biomaterials. Decellularized extracellular matrix (dECM) has been extensively used in the clinical treatment of tissue injury due to its favorable biocompatibility and similarity to the native tissue environment. However, most reported decellularization protocols may cause damage to the native structure of dECM, which undermines its inherent advantages and potential clinical applications. Here, we introduce a mechanically tunable dECM prepared by optimizing the freeze-thaw cycles. We demonstrated that the alteration in micromechanical properties of dECM resulting from the cyclic freeze-thaw process contributes to distinct macrophage-mediated host immune responses to the materials, which are recently recognized to play a pivotal role in determining the outcome of tissue regeneration. Our sequencing data further revealed that the immunomodulatory effect of dECM was induced via the mechnotrasduction pathways in macrophages. Next, we tested the dECM in a rat skin injury model and found an enhanced micromechanical property of dECM achieved with three freeze-thaw cycles significantly promoted the M2 polarization of macrophages, leading to superior wound healing. These findings suggest that the immunomodulatory property of dECM can be efficiently manipulated by tailoring its inherent micromechanical properties during the decellularization process. Therefore, our mechanics-immunomodulation-based strategy provides new insights into the development of advanced biomaterials for wound healing.

GraphPLBR: Protein-Ligand Binding Residue Prediction With Deep Graph Convolution Network.

The intermolecular interactions between proteins and ligands occur through site-specific amino acid residues in the proteins, and the identification of these key residues plays a critical role in both interpreting protein function and facilitating drug design based on virtual screening. In general, the information about the ligands-binding residues on proteins is unknown, and the detection of the binding residues by the biological wet experiments is time consuming. Therefore, many computational methods have been developed to identify the protein-ligand binding residues in recent years. We propose GraphPLBR, a framework based on Graph Convolutional Neural (GCN) networks, to predict protein-ligand binding residues (PLBR). The proteins are represented as a graph with residues as nodes through 3D protein structure data, such that the PLBR prediction task is transformed into a graph node classification task. A deep graph convolutional network is applied to extract information from higher-order neighbors, and initial residue connection with identity mapping is applied to cope with the over-smoothing problem caused by increasing the number of graph convolutional layers. To the best of our knowledge, this is a more unique and innovative perspective that utilizes the idea of graph node classification for protein-ligand binding residues prediction. By comparing with some state-of-the-art methods, our method performs better on several metrics.

Superiority of integrated cervicothoracic immobilization in the setup of lung cancer patients treated with supraclavicular station irradiation.

Objective: To investigate the superiority of the integrated cervicothoracic immobilization devices (ICTID) on the mobility of the supraclavicular station in lung cancer patients requiring both primary lung lesion and positive supraclavicular lymph nodes irradiation. Methods: One hundred patients with lung cancer were prospectively enrolled in the study. The following four different fixation methods are used for CT simulation positioning: thoracoabdominal flat immobilization device fixation with arms lifting (TAFID group), head-neck-shoulder immobilization device fixation with arms on the body sides (HNSID group), ICTID fixation with arms on the body sides (ICTID arms-down group), and n ICTID fixation with arms lifting (ICTID arms-up group). Cone-beam computed tomography (CBCT) images are taken daily or weekly before treatment, to assess anatomical changes during the radiotherapy course. Results: The translation errors in X (left-right direction), Y (head-foot direction), and Z (abdomen-back direction) directions of the ICTID arms-up, TAFID, ICTID arms-down and HNSID groups were (0.15 ± 0.18) cm, (0.15 ± 0.16) cm, (0.16 ± 0.16) cm, and (0.15 ± 0.20) cm; (0.15 ± 0.15) cm, (0.21 ± 0.25) cm, (0.28 ± 0.23) cm, and (0.27 ± 0.21) cm; (0.13 ± 0.14) cm, (0.15 ± 0.14) cm, (0.17 ± 0.13) cm, and (0.16 ± 0.14) cm, respectively. Among them, the ICTID arms-up group had the minimal setup errors in X direction than those in ICTID arms-down (p=0.001) and HNSID groups (p=0.001), and in Y direction than those in TAFID (p<0.001), and in Z direction than those in ICTID arms-down (p<0.001) and TAFID groups (p=0.034). For the rotational errors of the four groups in the directions of sagittal plane, transverse plane, and coronal plane, the ICTID arms-up group had the smallest setup errors in the sagittal plane than that of TAFID groups and similar rotation setup errors with those of the other three groups. Conclusion: For patients requiring radiation of primary lung lesion and positive supraclavicular lymph nodes, an integrated frame fixation device is preferred the ICTID arms-up methods provide the smallest set up error and satisfied repeatability of body position, compared with TAFID and HNSID.

Identification of the anti-inflammatory quality markers of Chrysanthemi Flos (Juhua) using spectrum-effect relationships combined with bioactivity re-evaluation.

Chrysanthemi Flos (Juhua), an edible herbal medicine that possesses efficacies of dispersing wind, clearing heat and detoxifying. Studies have demonstrated that the health benefits of Chrysanthemi Flos are largely attributable to its anti-inflammatory effects. However, the correlation between the compounds monitored by the current quality control methods and the anti-inflammatory effects of Chrysanthemi Flos is unclear. In order to better control the quality of Chrysanthemi Flos, the identification of anti-inflammatory quality markers (Q-markers) of Chrysanthemi Flos was performed. The chemical components of Chrysanthemi Flos were profiled by HPLC fingerprints combined with chemometrics methods. Simultaneously, the anti-inflammatory activities of 10 batches of water extracts of Chrysanthemi Flos were evaluated in lipopolysaccharide-activated RAW 264.7 macrophages cells. Gray correlation analysis was performed to assess the relationship between the anti-inflammatory activity and chemical properties. The results showed that 13 common peaks were closely correlated with the anti-inflammatory effect, and further bioactivity re-evaluation confirmed that 10 known compounds exerted a strong anti-inflammatory effect. The quantitative analysis of the 10 Q-markers showed that the 25 batches of samples could be discriminated into different zones according to their producing areas. Conclusively, the present work identified 10 anti-inflammatory Q-markers of Chrysanthemi Flos using spectrum-effect relationships combined with bioactivity re-evaluation.