Selective Oxidation of Vitamin D3 Enhanced by Long-Range Effects of a Substrate Channel Mutation in Cytochrome P450BM3 (CYP102A1).

Vitamin D deficiency affects nearly half the population, with many requiring or opting for supplements with vitamin D3(VD3), the precursor of vitamin D (1α,25-dihydroxyVD3). 25-HydroxyVD3, the circulating form of vitamin D, is a more effective supplement than VD3 but its synthesis is complex. We report here the engineering of cytochrome P450BM3(CYP102A1) for the selective oxidation of VD3 to 25-hydroxyVD3. Long-range effects of the substrate-channel mutation Glu435Ile promoted binding of the VD3 side chain close to the heme, enhancing VD3 oxidation activity that reached 6.62 g of 25-hydroxyVD3 isolated from a 1-litre scale reaction (69.1% yield; space-time-yield 331 mg/L/h).

Efficacy and safety of casirivimab and imdevimab for preventing and treating COVID-19: a systematic review and meta-analysis.

Background: The ongoing global epidemic of coronavirus disease 2019 (COVID-19) has created a serious public health problem. The selection of safe and effective therapeutic agents is of paramount importance. This systematic review aims to evaluate the efficacy and safety of the combination of casirivimab and imdevimab in the treatment of global cases of COVID-19. Methods: To identify randomized controlled trials (RCTs) investigating the combined administration of casirivimab and imdevimab for COVID-19 management, a comprehensive search was conducted across multiple databases including PubMed, Web of Science, Embase, and the Cochrane Library from their inception to September 10, 2022. Data on the efficacy and safety of casirivimab and imdevimab were extracted. Subgroup analyses and sensitivity analyses were performed. Results: A total of 851 articles were searched. Twelve studies were finally included in the meta-analysis, with 27,179 participants. Dichotomous and continuous variables were presented as odds ratios (ORs) and weighted mean differences (WMDs) with their 95% confidence intervals (CIs), respectively. Compared to placebo or alternative medications, the combination of casirivimab and imdevimab reduced viral load (WMD: -0.73, 95% CI: -1.09 to -0.38, P<0.01), all-cause mortality (OR =0.90, 95% CI: 0.82-0.99, P=0.03), the incidence of any serious adverse events (OR =0.80, 95% CI: 0.67-0.95, P=0.01), the incidence of Grade 3 or more severe adverse events (OR =0.76, 95% CI: 0.62-0.92, P=0.01), the likelihood of contracting COVID-19, the incidence of hospitalization, emergency room visits, and mortality (OR =0.54, 95% CI: 0.32-0.93, P=0.03). Conclusions: The monoclonal antibody combination of casirivimab and imdevimab is effective in treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as they can reduce viral load, all-cause mortality, infection rates, and the incidence of clinical outcomes of special interest after treatment, while maintaining a favorable safety profile.

Isolation, molecular identification, and genomic analysis of Mangrovibacter phragmitis strain ASIOC01 from activated sludge harboring the bioremediation prowess of glycerol and organic pollutants in high-salinity.

The physiological and genotypic characteristics of Mangrovibacter (MGB) remain largely unexplored, including their distribution and abundance within ecosystems. M. phragmitis (MPH) ASIOC01 was successfully isolated from activated sludge (AS), which was pre-enriched by adding 1,3-dichloro-2-propanol and 3-chloro-1,2-propanediol as carbon sources. The new isolate, MPH ASIOC01, exhibited resilience in a medium containing sodium chloride concentration up to 11% (with optimal growth observed at 3%) and effectively utilizing glycerol as their sole carbon source. However, species delimitation of MGBs remains challenging due to high 16S rRNA sequence similarity (greater than 99% ANI) among different MGBs. In contrast, among the housekeeping gene discrepancies, the tryptophan synthase beta chain gene can serve as a robust marker for fast species delimitation among MGBs. Furthermore, the complete genome of MPH ASIOC01 was fully sequenced and circlized as a single contig using the PacBio HiFi sequencing method. Comparative genomics revealed genes potentially associated with various phenotypic features of MGBs, such as nitrogen-fixing, phosphate-solubilizing, cellulose-digesting, Cr-reducing, and salt tolerance. Computational analysis suggested that MPH ASIOC01 may have undergone horizontal gene transfer events, possibly contributing unique traits such as antibiotic resistance. Finally, our findings also disclosed that the introduction of MPH ASIOC01 into AS can assist in the remediation of wastewater chemical oxygen demand, which was evaluated using gas chromatograph-mass spectrometry. To the best of our knowledge, this study offers the most comprehensive understanding of the phenotypic and genotypic features of MGBs to date.

Akkermansia muciniphila outer membrane protein regulates recruitment of CD8+ T cells in lung adenocarcinoma and through JAK-STAT signalling pathway.

As a Gram-negative anaerobic bacterium, Akkermansia muciniphila (AKK) participates in the immune response in many cancers. Our study focused on the factors and molecular mechanisms of AKK affecting immune escape in lung adenocarcinoma (LUAD). We cultured AKK bacteria, prepared AKK outer membrane protein Amuc_1100 and constructed a subcutaneous graft tumour mouse model. A549, NCI-H1395 cells and mice were respectively treated with inactivated AKK, Amuc_1100, Ruxolitinib (JAK inhibitor) and RO8191 (JAK activator). CD8+ T cells that penetrated the membrane were counted in the Transwell assay. The toxicity of CD8+ T cells was evaluated by lactate dehydrogenase assay. Western blot was applied to determine JAK/STAT-related protein and PD-L1 expression, whilst CCL5, granzyme B and INF-γ expression were assessed through enzyme-linked immunosorbent assay (ELISA). The proportion of tumour-infiltrating CD8+ T cells and the levels of granzyme B and INF-γ were determined by flow cytometry. AKK markedly accelerated A549 and NCI-H1395 recruiting CD8+ T cells and enhanced CD8+ T cell toxicity. Amuc_1100 purified from AKK exerted the same promoting effects. Besides, Amuc_1100 dramatically suppressed PD-L1, p-STAT and p-JAK expression and enhanced CCL5, granzyme B and INF-γ expression. Treatment with Ruxolitinib accelerated A549 and NCI-H1395 cells recruiting CD8+ T cells, enhanced CD8+ T cell toxicity, CCL5, granzyme B and INF-γ expression, and inhibited PD-L1 expression. In contrast, the RO8191 treatment slowed down the changes induced by Amuc_1100. Animal experiments showed that Amuc_1100 was found to increase the number of tumour-infiltrating CD8+ T cells, increase the levels of granzyme B and INF-γ and significantly inhibit the expression of PD-L1, p-STAT and p-JAK, which exerted an antitumour effect in vivo. In conclusion, through inhibiting the JAK/STAT signalling pathway, AKK outer membrane protein facilitated the recruitment of CD8+ T cells in LUAD and suppressed the immune escape of cells.

The A53T mutation in α-synuclein enhances pro-inflammatory activation in human microglia upon inflammatory stimulus.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease, following Alzheimer's. It is characterized by the aggregation of α-synuclein into Lewy bodies and Lewy neurites in the brain. Microglia-driven neuroinflammation may contribute to neuronal death in PD, however the exact role of microglia remains unclear and has been understudied. The A53T mutation in the gene coding for α-synuclein has been linked to early-onset PD, and exposure to A53T-mutant human α-synuclein increases the potential for inflammation of murine microglia. To date, its effect has not been studied in human microglia. METHODS: Here, we used 2-dimensional cultures of human iPSC-derived microglia and transplantation of these cells into the mouse brain to assess the cell-autonomous effects of the A53T mutation on human microglia. RESULTS: We found that A53T-mutant human microglia had an intrinsically increased propensity towards pro-inflammatory activation upon inflammatory stimulus. Additionally, transplanted A53T mutant microglia showed a strong decrease in catalase expression in non-inflammatory conditions, and increased oxidative stress. CONCLUSIONS: Our results indicate that A53T mutant human microglia display cell-autonomous phenotypes that may worsen neuronal damage in early-onset PD.

Q-ADER: An Effective Q-Learning for Recommendation With Diminishing Action Space.

Deep reinforcement learning (RL) has been widely applied to personalized recommender systems (PRSs) as they can capture user preferences progressively. Among RL-based techniques, deep Q-network (DQN) stands out as the most popular choice due to its simple update strategy and superior performance. Typically, many recommendation scenarios are accompanied by the diminishing action space setting, where the available action space will gradually decrease to avoid recommending duplicate items. However, existing DQN-based recommender systems inherently grapple with a discrepancy between the fixed full action space inherent in the Q-network and the diminishing available action space during recommendation. This article elucidates how this discrepancy induces an issue termed action diminishing error in the vanilla temporal difference (TD) operator. Due to this discrepancy, standard DQN methods prove impractical for learning accurate value estimates, rendering them ineffective in the context of diminishing action space. To mitigate this issue, we propose the Q-learning-based action diminishing error reduction (Q-ADER) algorithm to modify the value estimate error at each step. In practice, Q-ADER augments the standard TD learning with an error reduction term which is straightforward to implement on top of the existing DQN algorithms. Experiments are conducted on four real-world datasets to verify the effectiveness of our proposed algorithm.

Elastic-Plastic Fully π-Conjugated Polymer with Excellent Energy Dissipation Capacity for Ultra-Deep-Blue Flexible Polymer Light-Emitting Diodes with CIEy = 0.04.

Emerging intrinsically flexible fully π-conjugated polymers (FπCPs) are a promising functional material for flexible optoelectronics, attributed to their potential interchain interpenetration and entanglement. However, the challenge remains in obtaining elastic-plastic FπCPs with intrinsic robust optoelectronic property and excellent long-term and cycling deformation stability simultaneously for applications in deep-blue flexible polymer light-emitting diodes (PLEDs). This study, demonstrates a series of elastic-plastic FπCPs (P1-P4) with an excellent energy dissipation capacity via side-chain internal plasticization for the ultra-deep-blue flexible PLEDs. First, the freestanding P1 film exhibited a maximum fracture strain of 34.6%. More interestingly, the elastic behavior is observed with a low strain (≤10%), and the stretched film with a high deformation (>10%) attributed to plastic processing revealed the robust capacity to realize energy absorption and release. The elastic-plastic P1 film exhibits outstanding ultra-deep-blue emission, with an efficiency of 56.38%. Subsequently, efficient PLEDs are fabricated with an ultra-deep-blue emission of CIE (0.16, 0.04) and a maximum external quantum efficiency of 1.73%. Finally, stable and efficient ultra-deep-blue electroluminescence are obtained from PLEDs based on stretchable films with different strains and cycling deformations, suggesting excellent elastic-plastic behavior and deformation stability for flexible electronics.

Development and validation of a model for predicting the early occurrence of RF in ICU-admitted AECOPD patients: a retrospective analysis based on the MIMIC-IV database.

BACKGROUND: This study aims to construct a model predicting the probability of RF in AECOPD patients upon hospital admission. METHODS: This study retrospectively extracted data from MIMIC-IV database, ultimately including 3776 AECOPD patients. The patients were randomly divided into a training set (n = 2643) and a validation set (n = 1133) in a 7:3 ratio. First, LASSO regression analysis was used to optimize variable selection by running a tenfold k-cyclic coordinate descent. Subsequently, a multifactorial Cox regression analysis was employed to establish a predictive model. Thirdly, the model was validated using ROC curves, Harrell's C-index, calibration plots, DCA, and K-M curve. RESULT: Eight predictive indicators were selected, including blood urea nitrogen, prothrombin time, white blood cell count, heart rate, the presence of comorbid interstitial lung disease, heart failure, and the use of antibiotics and bronchodilators. The model constructed with these 8 predictors demonstrated good predictive capabilities, with ROC curve areas under the curve (AUC) of 0.858 (0.836-0.881), 0.773 (0.746-0.799), 0.736 (0.701-0.771) within 3, 7, and 14 days in the training set, respectively and the C-index was 0.743 (0.723-0.763). Additionally, calibration plots indicated strong consistency between predicted and observed values. DCA analysis demonstrated favorable clinical utility. The K-M curve indicated the model's good reliability, revealed a significantly higher RF occurrence probability in the high-risk group than that in the low-risk group (P < 0.0001). CONCLUSION: The nomogram can provide valuable guidance for clinical practitioners to early predict the probability of RF occurrence in AECOPD patients, take relevant measures, prevent RF, and improve patient outcomes.

Inflammation-Responsive Mesoporous Silica Nanoparticles with Synergistic Anti-inflammatory and Joint Protection Effects for Rheumatoid Arthritis Treatment.

PURPOSE: Joint destruction is a major burden and an unsolved problem in rheumatoid arthritis (RA) patients. We designed an intra-articular mesoporous silica nanosystem (MSN-TP@PDA-GlcN) with anti-inflammatory and joint protection effects. The nanosystem was synthesized by encapsulating triptolide (TP) in mesoporous silica nanoparticles and coating it with pH-sensitive polydopamine (PDA) and glucosamine (GlcN) grafting on the PDA. The nano-drug delivery system with anti-inflammatory and joint protection effects should have good potency against RA. METHODS: A template method was used to synthesize mesoporous silica (MSN). MSN-TP@PDA-GlcN was synthesized via MSN loading with TP, coating with PDA and grafting of GlcN on PDA. The drug release behavior was tested. A cellular inflammatory model and a rat RA model were used to evaluate the effects on RA. In vivo imaging and microdialysis (MD) system were used to analyze the sustained release and pharmacokinetics in RA rats. RESULTS: TMSN-TP@PDA-GlcN was stable, had good biocompatibility, and exhibited sustained release of drugs in acidic environments. It had excellent anti-inflammatory effects in vitro and in vivo. It also effectively repaired joint destruction in vivo without causing any tissue toxicity. In vivo imaging and pharmacokinetics experiments showed that the nanosystem prolonged the residence time, lowered the Cmax value and enhanced the relative bioavailability of TP. CONCLUSIONS: These results demonstrated that MSN-TP@PDA-GlcN sustained the release of drugs in inflammatory joints and produced effective anti-inflammatory and joint protection effects on RA. This study provides a new strategy for the treatment of RA.

A target-triggered strand displacement-assisted target recycling based on carbon dots-based fluorescent probe and MSNs@PDA nanoparticles for miRNA amplified detection and fluorescence imaging.

A target-triggered strand displacement-assisted target recycling based on carbon dots-based fluorescent probe and mesoporous silica nanoparticles@polydopamine (MSNs@PDA) was established to detect miRNA. The surface of MSNs rich in mesopores was coated with a layer of PDA, which can adsorb and quench the fluorescence of single-stranded Fuel DNA with fluorescent carbon dots (CDs) modified at the end through fluorescence resonance energy transfer (FRET). After adding double-stranded DNA-gold nanoparticles (dsDNA-AuNPs) and target let-7a, it will trigger two toehold-mediated strand displacement reactions (TSDR), leading to the recovery of fluorescence and the recycling of target let-7a (excitation wavelength: 380 nm; emission wavelength: 458 nm). The recovery value of fluorescence is proportional to the logarithm of the target microRNA let-7a concentration, thus realizing the sensitivity amplification detection of disease markers. The MSNs@PDA@Fuel DNA-CDs/dsDNA-AuNPs nanoplatform based on the strategy of "on-off-on" and TSDR cyclic amplification may hold great potential as an effective and safe nanoprobe for accurate fluorescence imaging of diseases related to miRNA with low abundances.

N-ethyl-N-nitrosourea (ENU)-induced C-terminal truncation of Runx3 results in autoimmune colitis associated with Th17/Treg imbalance.

Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory intestinal disease that affects people around the world. The primary cause of IBD is an imbalance in the host immune response to intestinal flora. Several human genes, including IL10, STAT3, IRGM, ATG16L1, NOD2 and RUNX3, are associated with inappropriate immune responses in IBD. It has been reported that homozygous Runx3-knockout (ko) mice spontaneously develop colitis. However, the high mortality rate in these mice within the first two weeks makes it challenging to study the role of Runx3 in colitis. To address this issue, a spontaneous colitis (SC) mouse model carrying a C-terminal truncated form of Runx3 with Tyr319stop point mutation has been generated. After weaning, SC mice developed spontaneous diarrhea and exhibited prominent enlargement of the colon, accompanied by severe inflammatory cell infiltration. Results of immunofluorescence staining showed massive CD4+ T cell infiltration in the inflammatory colon of SC mice. Colonic IL-17A mRNA expression and serum IL-17A level were increased in SC mice. CD4+ T cells from SC mice produced stronger IL-17A than those from wildtype mice in Th17-skewing conditions in vitro. In addition, the percentages of Foxp3+ Treg cells as well as the RORγt+Foxp3+ Treg subset, known for its role in suppressing Th17 response in the gut, were notably lower in colon lamina propria of SC mice than those in WT mice. Furthermore, transfer of total CD4+ T cells from SC mice, but not from wildtype mice, into Rag1-ko host mice resulted in severe autoimmune colitis. In conclusion, the C-terminal truncated Runx3 caused autoimmune colitis associated with Th17/Treg imbalance. The SC mouse model is a feasible approach to investigate the effect of immune response on spontaneous colitis.

Commonly used software tools produce conflicting and overly-optimistic AUPRC values.

The precision-recall curve (PRC) and the area under the precision-recall curve (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluate 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in more than 3000 published studies. We find the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results.

A nomogram to predict cryptococcal meningitis in patients with pulmonary cryptococcosis.

Background: The most serious manifestation of pulmonary cryptococcosis is complicated with cryptococcal meningitis, while its clinical manifestations lack specificity with delayed diagnosis and high mortality. The early prediction of this complication can assist doctors to carry out clinical interventions in time, thus improving the cure rate. This study aimed to construct a nomogram to predict the risk of cryptococcal meningitis in patients with pulmonary cryptococcosis through a scoring system. Methods: The clinical data of 525 patients with pulmonary cryptococcosis were retrospectively analyzed, including 317 cases (60.38 %) with cryptococcal meningitis and 208 cases (39.62 %) without cryptococcal meningitis. The risk factors of cryptococcal meningitis were screened by univariate analysis, LASSO regression analysis and multivariate logistic regression analysis. Then the risk factors were incorporated into the nomogram scoring system to establish a prediction model. The model was validated by receiver operating characteristic (ROC) curve, decision curve analysis (DCA) and clinical impact curve. Results: Fourteen risk factors for cryptococcal meningitis in patients with pulmonary cryptococcosis were screened out by statistical method, including 6 clinical manifestations (fever, headache, nausea, psychiatric symptoms, tuberculosis, hematologic malignancy) and 8 clinical indicators (neutrophils, lymphocytes, glutamic oxaloacetic transaminase, T cells, helper T cells, killer T cells, NK cells and B cells). The AUC value was 0.978 (CI 96.2 %∼98.9 %), indicating the nomogram was well verified. Conclusion: The nomogram scoring system constructed in this study can accurately predict the risk of cryptococcal meningitis in patients with pulmonary cryptococcosis, which may provide a reference for clinical diagnosis and treatment of patients with cryptococcal meningitis.

The association between ultra-processed food intake and age-related hearing loss: a cross-sectional study.

OBJECTIVES: This study aimed to explore the association between ultra-processed foods and age-related hearing loss. METHODS: Cross-sectional analyses based on data from a nationally representative sample of 1075 adults aged over 50 in the US was performed. The odds ratios (ORs) and 95% confidence intervals (CIs) for hearing loss according to ultra-processed foods intake quartiles were calculated using a multiple adjusted logistic regression model. Restricted cubic spline model was used to flexibly model potential nonlinear relations between ultra-processed foods intake and possibility of hearing loss. We also explored statistical interactions and conducted subgroup analyses where they were found to be significant. RESULTS: Ultra-processed foods intake was significantly correlated with high-frequency hearing loss. After controlling for all covariables, individuals in the fourth quartile of Ultra-processed foods consumption had a 2.8 times higher chance of developing high-frequency hearing loss than individuals in the first quartile of Ultra-processed foods consumption. We also found that the association was more significant in non-Hispanic whites. CONCLUSIONS: This study discovered an association between Ultra-processed foods intake and the incidence of high-frequency hearing loss, which was more significant in non-Hispanic whites.

Construction and validation of a nomogram model to predict the poor prognosis in patients with pulmonary cryptococcosis.

Background: Patients with poor prognosis of pulmonary cryptococcosis (PC) are prone to other complications such as meningeal infection, recurrence or even death. Therefore, this study aims to analyze the influencing factors in the poor prognosis of patients with PC, so as to build a predictive nomograph model of poor prognosis of PC, and verify the predictive performance of the model. Methods: This retrospective study included 410 patients (78.1%) with improved prognosis of PC and 115 patients (21.9%) with poor prognosis of PC. The 525 patients with PC were randomly divided into the training set and validation set according to the ratio of 7:3. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm was used to screen the demographic information, including clinical characteristics, laboratory test indicators, comorbidity and treatment methods of patients, and other independent factors that affect the prognosis of PC. These factors were included in the multivariable logistic regression model to build a predictive nomograph. The receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA) were used to verify the accuracy and application value of the model. Results: It was finally confirmed that psychological symptoms, cytotoxic drugs, white blood cell count, hematocrit, platelet count, CRP, PCT, albumin, and CD4/CD8 were independent predictors of poor prognosis of PC patients. The area under the curve (AUC) of the predictive model for poor prognosis in the training set and validation set were 0.851 (95% CI: 0.818-0.881) and 0.949, respectively. At the same time, calibration curve and DCA results confirmed the excellent performance of the nomogram in predicting poor prognosis of PC. Conclusion: The nomograph model for predicting the poor prognosis of PC constructed in this study has good prediction ability, which is helpful for improving the prognosis of PC and further optimizing the clinical management strategy.

Commonly used software tools produce conflicting and overly-optimistic AUPRC values.

The precision-recall curve (PRC) and the area under it (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluated 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in >3,000 published studies. We found the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results.

The Effect of Colloidal Nanoparticles on Phase Separation of Block and Heteroarm Star Copolymers Confined between Polymer Brushes.

The effect of colloidal nanoparticles on the phase changes of the amphiphilic AB linear diblock, A1A2B, and A2B heteroarm star copolymers confined between two polymer brush substrates was investigated by using a real-space self-consistent field theory. By changing the concentrations of nanoparticles and polymer brushes, the phase structure of the amphiphilic AB copolymer transforms from lamellar to core-shell hexagonal phase to cylinder phase. The pattern of A2B heteroarm star copolymer changes from core-shell hexagonal phases to lamellar phases and the layer decreases when increasing the density of the polymer brushes. The results showed that the phase behavior of the system is strongly influenced by the polymer brush architecture and the colloidal nanoparticle numbers. The colloidal nanoparticles and the soft confined surface of polymer brushes make amphiphilic AB copolymers easier to form ordered structures. The dispersion of the nanoparticles was also investigated in detail. The soft surfaces of polymer brushes and the conformation of the block copolymers work together to force the nanoparticles to disperse evenly. It will give helpful guidance for making some new functional materials by nano etching technology, nano photoresist, and nanoprinting.

Relationship Between Systemic Immune-Inflammation Index and Risk of Respiratory Failure and Death in COPD: A Retrospective Cohort Study Based on the MIMIC-IV Database.

Purpose: Chronic obstructive pulmonary disease (COPD) concurrent with respiratory failure (RF) is devastating, and may result in death and disability. Systemic immune-inflammation index (SII) is a new prognostic biomarker linked to unfavorable outcomes of acute coronary syndrome, ischemic stroke, and heart failure. Nonetheless, its role in COPD is rarely investigated. Consequently, this study intends to assess the accuracy of SII in predicting the prognosis of COPD. Patients and Methods: The clinical information was retrospectively acquired from the Medical Information Mart for Intensive Care-IV database. The outcomes encompassed the incidence of RF and mortality. The relationship between different SII and outcomes was examined utilizing the Cox proportional-hazards model and restricted cubic splines. Kaplan-Meier analysis was employed for all-cause mortality. Results: The present study incorporated 1653 patients. During hospitalization, 697 patients (42.2%) developed RF, and 169 patients (10.2%) died. And 637 patients (38.5%) died during long-term follow-up. Higher SII increased the risk of RF (RF: HR: 1.19, 95% CI 1.12-1.28, P<0.001), in-hospital mortality (HR: 1.22, 95% CI 1.07-1.39, P=0.003), and long-term follow-up mortality (HR: 1.12, 95% CI 1.05-1.19, P<0.001). Kaplan-Meier analysis suggested a significantly elevated risk of all-cause death (log-rank P<0.001) in patients with higher SII, especially during the short-term follow-up period of 21 days. Conclusion: SII is closely linked to an elevated risk of RF and death in COPD patients. It appears to be a potential predictor of the prognosis of COPD patients, which is helpful for the risk stratification of this population. However, more prospective studies are warranted to consolidate our conclusion.

Triphenylamine Spirofunctionalized Light-Emitting Conjugated Polymer with an Ultradeep-Blue Narrowband Emission for Large-Area Printed Display.

Emerging printed large-area polymer light-emitting diodes (PLEDs) are essential for manufacturing flat-panel displays and solid lighting devices. However, it is challenging to obtain large-area and stable ultradeep-blue PLEDs because of the lack of light-emitting conjugated polymers (LCPs) with robust deep-blue emissions, excellent morphological stabilities, and high charging abilities. Here, a novel unsymmetrically substituted polydiarylfluorene (POPSAF) is obtained with stable narrowband emission for large-area printed displays via triphenylamine (TPA) spirofunctionalization of LCPs. POPSAF films show narrowband and stable ultradeep-blue emission with a full width at half maximum (FWHM) of 36 nm, associated with their intrachain excitonic behavior without obvious polaron formation. Compared to controlled poly[4-(octyloxy)-9,9-diphenylfluoren-2,7-diyl]-co-[5-(octyloxy)-9,9-diphenylfluoren-2,7-diyl] (PODPF), excellent charge transport is observed in the POPSAF films because of the intrinsic hole transport ability of the TPA units. Large-area PLEDs are fabricated via blade-coating with an emission area of 9 cm2, which exhibit uniform ultradeep-blue emission with an FWHM of 36 nm and corresponding Commission internationale de l'éclairage (CIE) coordinates of (0.155, 0.072). These findings are attributed to the synergistic effects of robust emission, stable morphology, and printing capacity. Finally, preliminary printed passive matrix (PM) PLED displays with 20 × 20 pixels monochromes are fabricated, confirmed the effectiveness of spirofunctionalization in optoelectronics.

LncRNA HCG11 enhances the chemosensitivity of non-small cell lung cancer cells to Gemcitabine via miR-17-5p/p21 axis.

BACKGROUND: This study investigated the inhibitory effects of lncRNA HLA Complex Group 11 (HCG11) on non-small cell lung cancer (NSCLC) and the molecular mechanisms. RESEARCH DESIGN AND METHODS: Bioinformatics analysis was conducted to determine the downstream targeted gene miR-17-5p/p21 and predict their binding sites. qRT-PCR and Western blot were used to detect expression levels, and dual luciferase and RIP assays were adopted to verify binding relationship. RESULTS: The lncRNA HCG11/miR-17-5p/p21 axis was found to regulate drug resistance, proliferation, apoptosis, and cell cycle of A549 and A549-Gemcitabine (GEM) cells. HCG11 acted as a ceRNA binding to miR-17-5p, which repressed p21 expression in turn. In vivo experiments demonstrated that HCG11 hindered tumor growth. Therefore, lncRNA HCG11, by targeting the miR-17-5p/p21 axis, suppressed GEM resistance and malignant progression of NSCLC cells. CONCLUSIONS: This study provides a reference for investigating the potential value of lncRNA HCG11 in the diagnosis of NSCLC and finding potential targets against clinical chemotherapeutic resistance in NSCLC.