PLCL/SF/NGF nerve conduit loaded with RGD-TA-PPY hydrogel promotes regeneration of sciatic nerve defects in rats through PI3K/AKT signalling pathways.

Peripheral nerve defect are common clinical problem caused by trauma or other diseases, often leading to the loss of sensory and motor function in patients. Autologous nerve transplantation has been the gold standard for repairing peripheral nerve defects, but its clinical application is limited due to insufficient donor tissue. In recent years, the application of tissue engineering methods to synthesize nerve conduits for treating peripheral nerve defect has become a current research focus. This study introduces a novel approach for treating peripheral nerve defects using a tissue-engineered PLCL/SF/NGF@TA-PPy-RGD conduit. The conduit was fabricated by combining electrospun PLCL/SF with an NGF-loaded conductive TA-PPy-RGD gel. The gel, synthesized from RGD-modified tannic acid (TA) and polypyrrole (PPy), provides growth anchor points for nerve cells. In vitro results showed that this hybrid conduit could enhance PC12 cell proliferation, migration, and reduce apoptosis under oxidative stress. Furthermore, the conduit activated the PI3K/AKT signalling pathway in PC12 cells. In a rat model of sciatic nerve defect, the PLCL/SF/NGF@TA-PPy-RGD conduit significantly improved motor function, gastrocnemius muscle function, and myelin sheath axon thickness, comparable to autologous nerve transplantation. It also promoted angiogenesis around the nerve defect. This study suggests that PLCL/SF/NGF@TA-PPy-RGD conduits provide a conducive environment for nerve regeneration, offering a new strategy for peripheral nerve defect treatment, this study provided theoretical basis and new strategies for the research and treatment of peripheral nerve defect.

Investigation of the distribution of inguinal lymph nodes and delineation of the inguinal clinical target volume using 18F-FDG PET/CT.

OBJECTIVE: Radiotherapy is a crucial treatment modality for pelvic cancers, but uncertainties persist in defining the clinical target volume (CTV) for the inguinal lymphatic drainage region. Suboptimal CTV delineation may compromise treatment efficacy and result in subpar disease control. This study aimed to investigate and map the distribution of lymph node metastases (LNM) in the groin area to facilitate an improved and detailed CTV definition using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). METHODS: Inguinal LNM in patients with biopsy-proven pelvic malignancies were identified using 18F-FDG PET/CT scan. The longitudinally nearest axial plane was determined based on six typical bony landmarks, and the axial direction relative to the femoral artery of LNM was recorded. The distances from the LNM to the nearest edge of the femoral artery were measured on the axial plane. An optimal margin to cover 95% of LNM was estimated to develop contouring recommendations. RESULTS: In this study, 500 positive LNM were identified by 18F-FDG PET/CT among 185 patients with primary pelvic malignancies. Relative to the femoral artery, lymph nodes were distributed laterally (10:00-11:00, n = 35), anteriorly (12:00-1:00, n = 213), and medially (2:00-4: 00, n = 252). For CTV delineation, the recommended distances from the femoral artery on the SFH were lateral 19 mm, anterior 19 mm, and medial 25 mm; on the SGT were lateral 26 mm, anterior 20 mm, and medial 25 mm; on the SPS were lateral 28 mm, anterior 29 mm, and medial 26 mm; on the IPS were anterior 29 mm and medial 28 mm; on the IIT were anterior 27 mm and medial 27 mm; on the ILT were anterior 25 mm and medial 23 mm. Use interpolation to contour the area between six axial slices, including any radiographically suspicious LNM. CONCLUSIONS: Using 18F-FDG PET/CT, we investigated the distribution pattern of inguinal LNM and propose a more comprehensive guideline for inguinal CTV delineation.

Cu(II)-Mediated Sulfonylation of (Hetero)arenes with TosMIC Using Monodentate Directing Groups.

Monodentate chelation-assisted direct ortho-C-H sulfonylation of (hetero)arenes using TosMIC as the novel sulfonylating reagent has been developed. A broad range of substrates, including indolines, indoles, 2-phenylpyridines, and others were well tolerated to afford the corresponding products in moderate to good yields. Mechanistic studies revealed that the sulfonyl radical might be involved. Inspired by the above discovery, preliminary para-C-H sulfonylation of naphthalene substrate was also successfully realized. The current protocol featured with cheap metal catalysis, good functional group compatibility, and operational convenience.

Valtrate Suppresses TNFSF14-Mediated Arrhythmia After Myocardial Ischemia-Reperfusion by Inducing N-linked Glycosylation of LTßR to Regulate MGA/MAX/c-Myc/Cx43.

ABSTRACT: Myocardial ischemia-reperfusion (MIR)-induced arrhythmia remains a major cause of death in patients with cardiovascular diseases. The reduction of Cx43 has been known as a major inducer of arrhythmias after MIR, but the reason for the reduction of Cx43 remains largely unknown. The aim of this study was to find the key mechanism underlying the reduction of Cx43 after MIR and to screen out an herbal extract to attenuate arrhythmia after MIR. The differentially expressed genes in the peripheral blood mononuclear cell (PBMCs) after MIR were analyzed using the data from several gene expression omnibus data sets, followed by the identification in PBMCs and the serum of patients with myocardial infarction. Tumor necrosis factor superfamily protein 14 (TNFSF14) was increased in PBMCs and the serum of patients, which might be associated with the injury after MIR. The toxic effects of TNFSF14 on cardiomyocytes were investigated in vitro . Valtrate was screened out from several herbal extracts. Its protection against TNFSF14-induced injury was evaluated in cardiomyocytes and animal models with MIR. Recombinant TNFSF14 protein not only suppressed the viability of cardiomyocytes but also decreased Cx43 by stimulating the receptor LTßR. LTßR induces the competitive binding of MAX to MGA rather than the transcriptional factor c-Myc, thereby suppressing c-Myc-mediated transcription of Cx43. Valtrate promoted the N-linked glycosylation modification of LTßR, which reversed TNFSF14-induced reduction of Cx43 and attenuated arrhythmia after MIR. In all, valtrate suppresses TNFSF14-induced reduction of Cx43, thereby attenuating arrhythmia after MIR.

AnWRKY29 and AnHSP90 synergistically modulate trehalose levels in a desert shrub leaves during osmotic stress.

Trehalose, a biological macromolecule with osmotic adjustment properties, plays a crucial role during osmotic stress. As a psammophyte, Ammopiptanthus nanus relies on the accumulation of organic solutes to respond to osmotic stress. We utilized virus-induced gene silencing technology for the first time in the desert shrub A. nanus to confirm the central regulatory role of AnWRKY29 in osmotic stress, as it controls the transcription of AnTPS11 (trehalose-6-phosphate synthase 11). Further investigation has shown that AnHSP90 may interact with AnWRKY29. The AnHSP90 gene is sensitive to osmotic stress, underscoring its pivotal role in orchestrating the response to such adverse conditions. By directly targeting the W-box element within the AnTPS11 promoter, AnWRKY29 effectively enhances the transcriptional activity of AnTPS11, which is facilitated by AnHSP90. This discovery highlights the critical role of AnWRKY29 and AnHSP90 in enabling organisms to adapt to and cope effectively with osmotic stress, which can be a crucial factor in A. nanus survival and overall ecological resilience. Collectively, uncovering the molecular mechanisms underlying the osmotic responses of A. nanus is paramount for comprehending and augmenting the osmotic tolerance mechanisms of psammophyte shrub plants.

SIRT6 alleviates senescence induced by Porphyromonas gingivalis in human gingival fibroblasts.

OBJECTIVE: Bidirectional influences between senescence and inflammation are newly discovered. This study aimed to clarify the roles and mechanism of Porphyromonas gingivalis (P. gingivalis) in exacerbating senescence in human gingival fibroblasts (HGFs). DESIGN: Subgingival plaque and gingivae were collected from twenty-four periodontitis patients and eighteen periodontally healthy subjects. Quantities of P. gingivalis in subgingival plaque were explored using real-time PCR and the expressions of p53, p21 and SIRT6 in gingivae were detected by IHC. Moreover, senescence in HGFs was induced by P. gingivalis lipopolysaccharide (LPS) and the expressions of senescence-related ß-galactosidase (SA-ß-gal), p53, p21 and senescence-associated secretory phenotype (IL-6 and IL-8) with or without treatment by SIRT6 activator UBCS039 were explored by IHC, western blot and ELISA, respectively. In addition, the levels of SIRT6, Nrf2, HO-1 and reactive oxygen species (ROS) were examined by western blot and flow cytometry. RESULTS: Quantities of P. gingivalis in subgingival plaque and semi-quantitative scores of p53 and p21 in gingivae of periodontitis patients were increased compared with healthy controls (p < 0.05), while SIRT6 score in periodontitis patients was decreased (p < 0.001). Quantities of P. gingivalis were positively correlated with p53 and p21 scores (0.6 < r < 0.9, p < 0.01), and negatively correlated with SIRT6 score (-0.9 < r<-0.6, p < 0.01). Moreover, P. gingivalis LPS increased the levels of SA-ß-gal, p53, p21, IL-6, IL-8 and ROS and decreased the levels of SIRT6, Nrf2 and HO-1 in HGFs, which was rescued by UBCS039 (p < 0.05). CONCLUSIONS: P. gingivalis LPS could induce senescence of HGFs, which could be reversed by SIRT6 via Nrf2-HO-1 signaling pathway.

Effects of mind-body exercise on knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effect of mind-body exercise on improving knee osteoarthritis (KOA) and thereby informing osteoarthritis exercise rehabilitation. METHODS: The China National Knowledge Infrastructure (CNKI), Wanfang, PubMed/Medline, Cochrane Library, Web of Science, EBSCO, Embase, Scopus, and ProQuest databases were searched to identify randomized controlled trials (RCTs) that involved tai chi, yoga, and baduanjin interventions for KOA. The search period ranged from inception to October 25, 2022. The methodological quality of the included studies was evaluated by the Cochrane risk of bias assessment tool, and the included data were statistically analyzed and plotted using Review Manager 5.3 and Stata 14.0 software. RESULTS: We included 17 articles with a total of 1122 patients. Compared with the control group, mind-body exercise significantly improved patient pain (standardized mean difference (SMD) = -0.65, 95% confidence interval (CI) [-0.87, -0.42], p < 0.00001), stiffness (SMD = -0.75, 95% CI [-1.05, -0.45], p < 0.00001), physical function (SMD = -0.82, 95% CI [-1.03, -0.62], p < 0.00001), mental health (SMD = 0.31, 95% CI [0.11, 0.51], p = 0.002), and depression (SMD = -0.32, 95% CI [-0.50, -0.15], p = 0.0003). In terms of motor ability, mind-body exercise significantly increased the 6-min walking distance (SMD = 18.45, 95% CI [5.80, 31.10], p = 0.004) and decreased timed up and go test time (SMD = -1.15, 95% CI [-1.71, -0.59], p < 0.0001). CONCLUSIONS: The current study showed that mind-body exercise is safe and effective for KOA patients. However, given the methodological limitations of the included studies, additional high-quality evidence is needed to support the conclusions of this study.

Predicting quetiapine dose in patients with depression using machine learning techniques based on real-world evidence.

BACKGROUND: Being one of the most widespread, pervasive, and troublesome illnesses in the world, depression causes dysfunction in various spheres of individual and social life. Regrettably, despite obtaining evidence-based antidepressant medication, up to 70% of people are going to continue to experience troublesome symptoms. Quetiapine, as one of the most commonly prescribed antipsychotic medication worldwide, has been reported as an effective augmentation strategy to antidepressants. The right quetiapine dose and personalized quetiapine treatment are frequently challenging for clinicians. This study aimed to identify important influencing variables for quetiapine dose by maximizing the use of data from real world, and develop a predictive model of quetiapine dose through machine learning techniques to support selections for treatment regimens. METHODS: The study comprised 308 depressed patients who were medicated with quetiapine and hospitalized in the First Hospital of Hebei Medical University, from November 1, 2019, to August 31, 2022. To identify the important variables influencing the dose of quetiapine, a univariate analysis was applied. The prediction abilities of nine machine learning models (XGBoost, LightGBM, RF, GBDT, SVM, LR, ANN, DT) were compared. Algorithm with the optimal model performance was chosen to develop the prediction model. RESULTS: Four predictors were selected from 38 variables by the univariate analysis (p < 0.05), including quetiapine TDM value, age, mean corpuscular hemoglobin concentration, and total bile acid. Ultimately, the XGBoost algorithm was used to create a prediction model for quetiapine dose that had the greatest predictive performance (accuracy = 0.69) out of nine models. In the testing cohort (62 cases), a total of 43 cases were correctly predicted of the quetiapine dose regimen. In dose subgroup analysis, AUROC for patients with daily dose of 100 mg, 200 mg, 300 mg and 400 mg were 0.99, 0.75, 0.93 and 0.86, respectively. CONCLUSIONS: In this work, machine learning techniques are used for the first time to estimate the dose of quetiapine for patients with depression, which is valuable for the clinical drug recommendations.

APOE ε4-associated downregulation of the IL-7/IL-7R pathway in effector memory T cells: Implications for Alzheimer's disease.

INTRODUCTION: The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive. METHODS: The present study enrolled 54 patients diagnosed with late-onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). RESULTS: Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells. DISCUSSION: These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy. HIGHLIGHTS: The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL-7/IL-7R signal pathways enriches T cells.

Whole-Genome Sequences of 13 Chinese Indigenous Pinewood Nematodes, Bursaphelenchus xylophilus.

The pinewood nematode (Bursaphelenchus xylophilus, PWN) induces pine wilt disease in Pinaceae plants, causing severe destruction to pine forests. Previous studies report that by 2023, 663 cities across 18 provinces in China had been infested by the PWN, necessitating immediate control measures. To identify the genetic variations associated with the PWN's adaptation to new environments, we conducted whole-genome sequencing (WGS) on 13 indigenous PWN samples from two distinct geographic zones within China, specifically Anhui, Liaoning, and Jiangxi provinces. We identified genetic variants and analyzed the genetic structure of these populations, followed by functional gene enrichment analyses. Our findings reveal genetic variants associated with secretion, immune system function, membrane processes, metabolism, catabolism, and cell wall regulation, supporting the hypothesis that the PWN genome has been shaped by local ecosystems.

[Impact of Liparis nervosa extract on neuroinflammation mediated by LPS-induced BV-2 microglial cells and its bioactive components analysis].

To investigate the impact and potential mechanisms of extracts from different parts of Liparis nervosa on neuroinflammation by lipopolysaccharide(LPS)-induced BV-2 microglial cells. The materials of L. nervosa were subjected to crushing, ethanol extraction, and concentration to obtain an alcohol extract. Subsequently, the extract was further extracted to obtain petroleum ether extract, ethyl acetate extract, N-butanol extract, and aqueous phase extract. The ethyl acetate extract was separated into distillate(1)-(6)using D101 macroporous resin column chromatography. The experiment was divided into control group, LPS model group, L. nervosa extract group, and LPS + L. nervosa group. LPS was utilized to induce a neuroinflammatory cell model in BV-2 microglial cells. The Griess test was utilized for detecting the production of nitric oxide(NO) in the cell supernatant. Cell viability was detected by MTT assay. The release of interleukin-6(IL-6) and tumor necrosis factor alpha(TNF-α) in the cell supernatant was quantified using ELISA.RT-qPCR was utilized to assess the m RNA levels of pro-inflammatory cytokines inducible nitric oxide synthase(iNOS), cyclooxygenase-2(COX-2), interleukin( IL)-6, IL-1ß, and TNF-α. The protein expression of i NOS, COX-2, nuclear factor kappa-B p65(p65), p-p65, extracellular signal-regulated kinase(ERK), p-ERK, c-jun N-terminal kinase(JNK), p-JNK, p38 mitogen-activated protein kinase(p38), and p-p38 MAPK(p-p38) were also evaluated by Western blot. The chemical composition of active substances in L. nervosa was analyzed using the UHPLC-Q-Exactive Orbitrap technology and literature comparison. Our findings indicate that extracts from different parts of L. nervosa exhibit a significant reduction in the release of NO from LPS-induced BV-2 microglial cells.Specifically, the ethyl acetate extract demonstrates the most notable inhibitory effect without causing cell toxicity. Additionally, the distillate(6) extracted from the ethyl acetate exhibits a reduction in the m RNA and protein levels of i NOS, COX-2, IL-6, IL-1ß, and TNF-α in a dose-dependent manner, and it inhibits the protein expression of p-p65, p-ERK, p-p38, and p-JNK in LPS-induced BV-2 microglial cells. A total of 79 compounds in the distillate(6) were identified by mass spectrometry, including 12 confirmed compounds with anti-inflammatory effects. This study confirmed the remarkable efficacy of L. nervosa extract in the treatment of neuroinflammation, which may be achieved through the inhibition of NF-κB and MAPK signaling pathways.

Ultra-High Metal-Ion Selectivity Induced by Intramolecular Cation-π Interactions for the One-Pot Synthesis of Precise Heterometallic Architectures.

Heterometallic supramolecules, known for their unique synergistic effects, have shown broad applications in photochemistry, host-guest chemistry, and catalysis. However, there are great challenges to precisely construct heterometallic supramolecules rather than a statistical mixture, due to the limited metal-ion selectivity of coordination units. In particular, heterometallic architectures precisely encoded with different metal ions usually fail to form in a one-pot method when only one type of coordinated motif exists due to its poor metal-ion selectivity. Herein, we propose an effective intramolecular cation-π (ICπ) strategy and successfully constructed the heterometallic supramolecule Zn2Cu4L34 by the one-pot self-assembly of tritopic terpyridyl ligand L3 with Zn(II) and Cu(II), following a clear self-assembly mechanism in which only thermodynamic dimers ZnL12 and Cu2L22 were constructed with model ligands L1, L2, Zn(II) and Cu(II) with perfect self-sorting and an ultra-high metal-selectivity feature. The successful construction of the heterometallic supramolecule Zn2Cu4L34, in which the definite sequence of metal ions Zn(II) and Cu(II) is encoded in the one-pot method, will offer a novel approach to precisely construct heterometallic architectures.

Novel, high accuracy models for hepatocellular carcinoma prediction based on longitudinal data and cell-free DNA signatures.

BACKGROUND & AIMS: Current hepatocellular carcinoma (HCC) risk scores do not reflect changes in HCC risk resulting from liver disease progression/regression over time. We aimed to develop and validate two novel prediction models using multivariate longitudinal data, with or without cell-free DNA (cfDNA) signatures. METHODS: A total of 13,728 patients from two nationwide multicenter prospective observational cohorts, the majority of whom had chronic hepatitis B, were enrolled. aMAP score, as one of the most promising HCC prediction models, was evaluated for each patient. Low-pass whole-genome sequencing was used to derive multi-modal cfDNA fragmentomics features. A longitudinal discriminant analysis algorithm was used to model longitudinal profiles of patient biomarkers and estimate the risk of HCC development. RESULTS: We developed and externally validated two novel HCC prediction models with a greater accuracy, termed aMAP-2 and aMAP-2 Plus scores. The aMAP-2 score, calculated with longitudinal data on the aMAP score and alpha-fetoprotein values during an up to 8-year follow-up, performed superbly in the training and external validation cohorts (AUC 0.83-0.84). The aMAP-2 score showed further improvement and accurately divided aMAP-defined high-risk patients into two groups with 5-year cumulative HCC incidences of 23.4% and 4.1%, respectively (p = 0.0065). The aMAP-2 Plus score, which incorporates cfDNA signatures (nucleosome, fragment and motif scores), optimized the prediction of HCC development, especially for patients with cirrhosis (AUC 0.85-0.89). Importantly, the stepwise approach (aMAP -> aMAP-2 -> aMAP-2 Plus) stratified patients with cirrhosis into two groups, comprising 90% and 10% of the cohort, with an annual HCC incidence of 0.8% and 12.5%, respectively (p <0.0001). CONCLUSIONS: aMAP-2 and aMAP-2 Plus scores are highly accurate in predicting HCC. The stepwise application of aMAP scores provides an improved enrichment strategy, identifying patients at a high risk of HCC, which could effectively guide individualized HCC surveillance. IMPACT AND IMPLICATIONS: In this multicenter nationwide cohort study, we developed and externally validated two novel hepatocellular carcinoma (HCC) risk prediction models (called aMAP-2 and aMAP-2 Plus scores), using longitudinal discriminant analysis algorithm and longitudinal data (i.e., aMAP and alpha-fetoprotein) with or without the addition of cell-free DNA signatures, based on 13,728 patients from 61 centers across mainland China. Our findings demonstrated that the performance of aMAP-2 and aMAP-2 Plus scores was markedly better than the original aMAP score, and any other existing HCC risk scores across all subsets, especially for patients with cirrhosis. More importantly, the stepwise application of aMAP scores (aMAP -> aMAP-2 -> aMAP-2 Plus) provides an improved enrichment strategy, identifying patients at high risk of HCC, which could effectively guide individualized HCC surveillance.

Hourglass-Shaped Nanocages with Concaved Structures Based on Selective Self-Complementary Coordination Ligands and Tunable Hierarchical Self-Assembly.

Three-dimensional (3D) structures constructed via coordination-driven self-assemblies have recently garnered increasing attention due to the challenges in structural design and potential applications. In particular, developing new strategy for the convenient and precise self-assemblies of 3D supramolecular structures is of utmost interest. Introducing the concept of self-coordination ligands, herein the design and synthesis of two meta-modified terpyridyl ligands with selective self-complementary coordination moiety are reported and their capability to assemble into two hourglass-shaped nanocages SA and SB is demonstrated. Within these 3D structures, the meta-modified terpyridyl unit preferably coordinates with itself to serve as concave part. By changing the arm length of the ligands, hexamer (SA) and tetramer (SB) are obtained respectively. In-depth studies on the assembly mechanism of SA and SB indicate that the dimers could be formed first via self-complementary coordination and play crucial roles in controlling the final structures. Moreover, both SA and SB can go through hierarchical self-assemblies in solution as well as on solid-liquid interface, which are characterized by transmission electron microscope (TEM) and scanning tunneling microscopy (STM). It is further demonstrated that various higher-order assembly structures can be achieved by tuning the environmental conditions.

Transcriptomics and co-expression network analysis revealing candidate genes for the laccase activity of Trametes gibbosa.

BACKGROUND: Trametes gibbosa, which is a white-rot fungus of the Polyporaceae family found in the cold temperate zone, causes spongy white rot on wood. Laccase can oxidize benzene homologs and is one of the important oxidases for white rot fungi to degrade wood. However, the pathway of laccase synthesis in white rot fungi is unknown. RESULTS: The peak value of laccase activity reached 135.75 U/min/L on the 9th day. For laccase activity and RNA-seq data, gene expression was segmented into 24 modules. Turquoise and blue modules had greater associations with laccase activity (positively 0.94 and negatively -0.86, respectively). For biology function, these genes were concentrated on the cell cycle, citrate cycle, nicotinate, and nicotinamide metabolism, succinate dehydrogenase activity, flavin adenine dinucleotide binding, and oxidoreductase activity which are highly related to the laccase synthetic pathway. Among them, gene_8826 (MW199767), gene_7458 (MW199766), gene_61 (MW199765), gene_1741 (MH257605), and gene_11087 (MK805159) were identified as central genes. CONCLUSION: Laccase activity steadily increased in wood degradation. Laccase oxidation consumes oxygen to produce hydrogen ions and water during the degradation of wood. Some of the hydrogen ions produced can be combined by Flavin adenine dinucleotide (FAD) to form reduced Flavin dinucleotide (FADH2), which can be transmitted. Also, the fungus was starved of oxygen throughout fermentation, and the NADH and FADH2 are unable to transfer hydrogen under hypoxia, resulting in the inability of NAD and FAD to regenerate and inhibit the tricarboxylic acid cycle of cells. These key hub genes related to laccase activity play important roles in the molecular mechanisms of laccase synthesis for exploring industrial excellent strains.

Preoperative Frailty Assessment Predicts Postoperative Mortality, Delirium and Pneumonia in Elderly Lung Cancer Patients: A Retrospective Cohort Study.

BACKGROUND: The purpose of this study was to investigate the predictive value of the 5-factor modified frailty index (mFI-5) for postoperative mortality, delirium and pneumonia in patients over 65 years of age undergoing elective lung cancer surgery. METHODS: Data were collected from a single-center retrospective cohort study conducted in a general tertiary hospital from January 2017 to August 2019. In total, the study included 1372 elderly patients aged over 65 who underwent elective lung cancer surgery. They were divided into frail group (mFI-5, 2-5), prefrail group (mFI-5, 1) and robust group (mFI-5, 0) on the basis of mFI-5 classification. The primary outcome was postoperative 1-year all-cause mortality. Secondary outcomes were postoperative pneumonia and postoperative delirium. RESULTS: Frailty group had the highest incidence of postoperative delirium (frailty 31.2% versus prefrailty 1.6% versus robust 1.5%, p < 0.001), postoperative pneumonia (frailty 23.5% versus prefrailty 7.2% versus robust 7.7%, p < 0.001), and postoperative 1-year mortality (frailty 7.0% versus prefrailty 2.2% versus robust 1.9%. p < 0.001). Frail patients have significantly longer length of hospitalization than those in the robust group and prefrail patients (p < 0.001). Multivariate analysis showed a clear link between frailty and increased risk of postoperative delirium (aOR 2.775, 95% CI 1.776-5.417, p < 0.001), postoperative pneumonia (aOR 3.291, 95% CI 2.169-4.993, p < 0.001) and postoperative 1-year mortality (aOR 3.364, 95% CI, 1.516-7.464, p = 0.003). CONCLUSIONS: mFI-5 has potential clinical utility in predicting postoperative death, delirium and pneumonia incidence in elderly patients undergoing radical lung cancer surgery. Frailty screening of patients (mFI-5) may provide benefits in risk stratification, targeted intervention efforts, and assist physicians in clinical decision-making.

A machine learning model for predicting blood concentration of quetiapine in patients with schizophrenia and depression based on real-world data.

AIMS: This study aimed to establish a prediction model of quetiapine concentration in patients with schizophrenia and depression, based on real-world data via machine learning techniques to assist clinical regimen decisions. METHODS: A total of 650 cases of quetiapine therapeutic drug monitoring (TDM) data from 483 patients at the First Hospital of Hebei Medical University from 1 November 2019 to 31 August 2022 were included in the study. Univariate analysis and sequential forward selection (SFS) were implemented to screen the important variables influencing quetiapine TDM. After 10-fold cross validation, the algorithm with the optimal model performance was selected for predicting quetiapine TDM among nine models. SHapley Additive exPlanation was applied for model interpretation. RESULTS: Four variables (daily dose of quetiapine, type of mental illness, sex and CYP2D6 competitive substrates) were selected through univariate analysis (P < .05) and SFS to establish the models. The CatBoost algorithm with the best predictive ability (mean [SD] R2  = 0.63 ± 0.02, RMSE = 137.39 ± 10.56, MAE = 103.24 ± 7.23) was chosen for predicting quetiapine TDM among nine models. The mean (SD) accuracy of the predicted TDM within ±30% of the actual TDM was 49.46 ± 3.00%, and that of the recommended therapeutic range (200-750 ng mL-1 ) was 73.54 ± 8.3%. Compared with the PBPK model in a previous study, the CatBoost model shows slightly higher accuracy within ±100% of the actual value. CONCLUSIONS: This work is the first real-world study to predict the blood concentration of quetiapine in patients with schizophrenia and depression using artificial intelligent techniques, which is of significance and value for clinical medication guidance.

Construction of 1,3,5-Triazine-Based Prisms and Their Enhanced Solid-State Emissions.

In this study, two trigonal prisms based on the 1,3,5-triazine motif (SA and SB), distinguished by hydrophobic groups, were prepared by the self-assembly of tritopic terpyridine ligands and Zn(II) ions. SA and SB exhibited high luminescence efficiencies in the solid state, overcoming the fluorescence quenching of the 1,3,5-triazine group caused by π-π interactions. Notably, SA and SB exhibited different luminescence behaviors in the solution state and aggregation state. SB with 12 alkyl chains exhibited extremely weak fluorescence in a dilute solution, but its fluorescence intensity and photoluminescence quantum yield (PLQY) were significantly enhanced in the aggregated state (with the increase in the water fraction), especially in the solid state. Different from the gradually enhanced efficiency of SB, the PLQY of SA gradually decreased with the increase in aggregation but still maintained a high luminescence efficiency. These two complexes exhibited different modes to solve the fluorescence quenching of 1,3,5-triazine in the solid state. The hierarchical self-assembly of SB exhibited nanorods owing to the hydrophobic interactions of alky chains, while SA aggregated into spheres under the influence of π-π interactions.

Amine-Imine Nickel Catalysts with Pendant O-Donor Groups for Ethylene (Co)Polymerization.

The introduction of a secondary interaction is an efficient strategy to modulate transition-metal-catalyzed ethylene (co)polymerization. In this contribution, O-donor groups were suspended on amine-imine ligands to synthesize a series of nickel complexes. By adjusting the interaction between the nickel metal center and the O-donor group on the ligands, these nickel complexes exhibited high activities for ethylene polymerization (up to 3.48 × 106 gPE·molNi-1·h-1) with high molecular weight up to 5.59 × 105 g·mol-1 and produced good polyethylene elastomers (strain recovery (SR) = 69-81%). In addition, these nickel complexes can catalyze the copolymerization of ethylene with vinyl acetic acid, 6-chloro-1-hexene, 10-undecylenic, 10-undecenoic acid, and 10-undecylenic alcohol to prepare the functionalized polyolefins.

Science in China: 30 years on.

Three decades after introducing market reforms and opening up to the rest of the world, China has become a major economic power. As the country prepares to show the world its sporting might, its competitiveness in life sciences may still need a boost.