A dual-channel fluorescent probe targeting lysosomes for differential detection of Cys/Hcy and GSH: Applications in food, pharmaceutical analysis and bioimaging.

Thiols function as antioxidants in food, prolonging shelf life and enhancing flavor. Moreover, thiols are vital biomolecules involved in enzyme activity, cellular signal transduction, and protein folding among critical biological processes. In this paper, the fluorescent probe PYL-NBD was designed and synthesized, which utilized the fluorescent molecule pyrazoline, the lysosome-targeted morpholine moiety, and the sensing moiety NBD. Probe PYL-NBD was tailored for the recognition of biothiols through single-wavelength excitation, yielding distinct fluorescence emission signals: blue for Cys, Hcy, and GSH; green for Cys, Hcy. Probe PYL-NBD exhibited rapid reaction kinetics (<10 min), distinct fluorescence response signals, and low detection limits (15.7 nM for Cys, 14.4 nM for Hcy, and 12.6 nM for GSH). Probe PYL-NBD enabled quantitative determination of Cys content in food samples and L-cysteine capsules. Furthermore, probe PYL-NBD had been successfully applied for confocal imaging with dual-channel detection of biothiols in various biological specimens, including HeLa cells, zebrafish, tumor sections, and Arabidopsis thaliana.

Alzheimer's disease-linked risk alleles elevate microglial cGAS-associated senescence and neurodegeneration in a tauopathy model.

The strongest risk factors for late-onset sporadic Alzheimer's disease (AD) include the ε4 allele of apolipoprotein E (APOE), the R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2), and female sex. Here, we combine APOE4 and TREM2R47H (R47H) in female P301S tauopathy mice to identify the pathways activated when AD risk is the strongest, thereby highlighting detrimental disease mechanisms. We find that R47H induces neurodegeneration in 9- to 10-month-old female APOE4 tauopathy mice. The combination of APOE4 and R47H (APOE4-R47H) worsened hyperphosphorylated tau pathology in the frontal cortex and amplified tauopathy-induced microglial cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling and downstream interferon response. APOE4-R47H microglia displayed cGAS- and BAX-dependent upregulation of senescence, showing association between neurotoxic signatures and implicating mitochondrial permeabilization in pathogenesis. By uncovering pathways enhanced by the strongest AD risk factors, our study points to cGAS-STING signaling and associated microglial senescence as potential drivers of AD risk.

A metabolomics approach reveals the pharmacological effects and mechanisms of Cistanche tubulosa stems and its combination with fluoxetine on depression in comorbid with sexual dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried succulent stems of Cistanche tubulosa (Schenk) Wight are utilized in traditional medicine for tonifying kidney yang, which have shown to be effective in alleviating depression-like behavior or male sexual dysfunction, respectively. However, the pharmacological effects and mechanisms of C. tubulosa and its combinations in the treatment of depression in comorbid with sexual dysfunction remain unclear. AIM OF THE STUDY: This study aims to elucidate the pharmacological effects and mechanisms of C. tubulosa aqueous extract (CTE) and its combination with fluoxetine (FLX) on depression in comorbid with sexual dysfunction. MATERIALS AND METHODS: A mouse model of depression in comorbid with sexual dysfunction was created using the chronic unpredictable mild stress (CUMS) procedure. The therapeutic effects of CTE and its combination with FLX were assessed using depressive-like and mating behavior experiments, histopathological analysis, and hypothalamic pituitary gonadal (HPG) axis function evaluation. The mechanisms were explored by integrated serum and testicular metabolomics combined with network correlation analysis. RESULTS: CTE was confirmed to significantly improve depressive-like behaviors, reduce mating abilities, testicular histopathological damage, and HPG axis hormone secretion disorders in CUMS mice. Subsequently, mechanism exploration findings indicated that CTE might exert its effect by regulating potential efficacy-related biomarkers (isobutyrylglycine, citric acid, D-galactose) to improve several metabolic pathways centered around steroid hormone biosynthesis and tricarboxylic acid (TCA) cycle. Furthermore, the combination of CTE and FLX exhibited stronger antidepressant effects than FLX alone, and ameliorated the exacerbated sexual dysfunction induced by FLX. These effects were achieved through the regulation of potential efficacy-related biomarkers (17α-hydroxypregnenolone, tetrahydrodeoxy-corticosterone, sphingosine, cortol, thymine, and L-histidine), thereby improving disorders in glycerophospholipid and histidine metabolism. CONCLUSION: In conclusion, the amelioration effects of CTE and its combination with FLX on depression in comorbid with sexual dysfunction were confirmed for the first time. This key mechanism may be achieved by modulating the level of potential efficacy-related biomarkers, and then emphatically intervene in steroid hormone biosynthesis, TCA cycle, glycerophospholipid and histidine metabolism. The study offers a new perspective for the development and utilization of C. tubulosa.

From Proline to Chlorantraniliprole Mimics: Computer-Aided Design, Simple Preparation, and Excellent Insecticidal Profiles.

Chlorantraniliprole (CHL), a favored agricultural insecticide, is renowned for its high efficiency and broad-spectrum effectiveness against lepidoptera insects. However, the urgency for new insecticide development is underscored by the intricate multistep preparation process and modest overall yields of CHL, along with the escalating challenge of insect resistance. In response, we have crafted CHL mimics from proline employing computer-aided drug design. Molecular docking analysis of CHL's interactions with the ryanodine receptor (RyR) revealed that the nitrogen atom within the pyrazole moiety does not engage in pivotal interactions. Its removal may not abolish bioactivity entirely but could substantially simplify the synthetic process, thereby enhancing atom economy. This revelation prompted the exclusion of nitrogen and the subsequent formation of a pyrrole ring, enabling the meticulous design of synthetic pathways characterized by cost-effective precursors, streamlined synthesis, the avoidance of toxic reagents, minimal instrumentation, and high yields in the pursuit of innovative RyR modulators. Among these modulators, A1 and B1, obtained with yields exceeding 60%, showcased exceptional insecticidal potency, with LC50 values spanning from 0.12 to 1.47 mg L-1 against P. xylostella and M. separate. The inhibitory effects of these two compounds on insect detoxification enzymes imply a reduced likelihood of eliciting resistance in comparison to CHL, a finding further corroborated by their insecticidal potency against resistant pests. Moreover, molecular docking, MD simulations, and DFT calculations provided valuable structural insights, potentially unraveling the superior insecticidal activity of these two molecules, and thus paving the way for developing more potent insecticides.

Altered Brain Structure in Hemifacial Spasm Patients: A Multimodal Brain Structure Study.

Objective: Hemifacial spasm (HFS) is a clinical neurosurgical disease, which brain structural alterations caused by HFS remain a topic of debate. We evaluated changes in brain microstructure associated with HFS and observed their relevance to clinical characteristics. Methods: We enrolled 72 participants. T1-weighted structural and diffusion tensor images were collected from all participants using 3.0T magnetic resonance equipment. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to identify changes in gray matter volume (GMV) and disruptions in white matter (WM) integrity. The severity of the spasms was graded using the Cohn scale. Results: VBM analysis revealed that the GMV was significantly reduced in the left Thalamus and increased GMV in the right Cerebellum IV-V of the HFS group. TBSS analysis showed that FA in the left superior longitudinal fasciculus (SLF) of the HFS group was significantly increased. GMV in the thalamus showed a negative correlation with disease duration and Cohn grade, while FA in the left SLF had a positive correlation with both the disease duration and Cohn grade. Conclusion: We identified regions with altered GMV in HFS patients. Additionally, we determined that FA in the left SLF might serve as a significant neural indicator of HFS.

Development and application of an artificial intelligence-assisted endoscopy system for diagnosis of Helicobacter pylori infection: a multicenter randomized controlled study.

BACKGROUND: The early diagnosis and treatment of Heliobacter pylori (H.pylori) gastrointestinal infection provide significant benefits to patients. We constructed a convolutional neural network (CNN) model based on an endoscopic system to diagnose H. pylori infection, and then examined the potential benefit of this model to endoscopists in their diagnosis of H. pylori infection. MATERIALS AND METHODS: A CNN neural network system for endoscopic diagnosis of H.pylori infection was established by collecting 7377 endoscopic images from 639 patients. The accuracy, sensitivity, and specificity were determined. Then, a randomized controlled study was used to compare the accuracy of diagnosis of H. pylori infection by endoscopists who were assisted or unassisted by this CNN model. RESULTS: The deep CNN model for diagnosis of H. pylori infection had an accuracy of 89.6%, a sensitivity of 90.9%, and a specificity of 88.9%. Relative to the group of endoscopists unassisted by AI, the AI-assisted group had better accuracy (92.8% [194/209; 95%CI: 89.3%, 96.4%] vs. 75.6% [158/209; 95%CI: 69.7%, 81.5%]), sensitivity (91.8% [67/73; 95%CI: 85.3%, 98.2%] vs. 78.6% [44/56; 95%CI: 67.5%, 89.7%]), and specificity (93.4% [127/136; 95%CI: 89.2%, 97.6%] vs. 74.5% [114/153; 95%CI: 67.5%, 81.5%]). All of these differences were statistically significant (P < 0.05). CONCLUSION: Our AI-assisted system for diagnosis of H. pylori infection has significant ability for diagnostic, and can improve the accuracy of endoscopists in gastroscopic diagnosis. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Daping Hospital (10/07/2020) (No.89,2020) and was registered with the Chinese Clinical Trial Registration Center (02/09/2020)   ( www.chictr.org.cn ; registration number: ChiCTR2000037801).

Intratumoral and peritumoral radiomics combined with computed tomography features for predicting the invasiveness of lung adenocarcinoma presenting as a subpleural ground-glass nodule with a consolidation-to-tumor ratio ≤50.

Background: Preoperative accurate judgment of the degree of invasiveness in subpleural ground-glass lung adenocarcinoma (LUAD) with a consolidation-to-tumor ratio (CTR) ≤50% is very important for the choice of surgical timing and planning. This study aims to investigate the performance of intratumoral and peritumoral radiomics combined with computed tomography (CT) features for predicting the invasiveness of LUAD presenting as a subpleural ground-glass nodule (GGN) with a CTR ≤50%. Methods: A total of 247 patients with LUAD from our hospital were randomly divided into two groups, i.e., the training cohort (n=173) and the internal validation cohort (n=74) (7:3 ratio). Furthermore, 47 patients from three other hospitals were collected as the external validation cohort. In the training cohort, the differences in clinical-radiological features were compared using univariate and multivariate analyses. The gross tumor volume (GTV) and gross peritumoral tumor volume (GPTV5, GPTV10, and GPTV15) radiomics models were constructed based on intratumoral and peritumoral (5, 10, and 15 mm) radiomics features. Additionally, the radscore of the best radiomics model and clinical risk factors were used to construct a combined model and the predictive efficacy of the model was evaluated in the validation cohorts. Finally, the receiver operating characteristics (ROC) curve and area under the curve (AUC) value were used to evaluate the discriminative ability of the model. Results: Tumor size and CTR were independent risk factors for predicting the invasiveness of LUAD. The GPTV10 model outperformed the other radiomics models, with AUC values of 0.910, 0.870, and 0.887 in the three cohorts. The AUC values of the combined model were 0.912, 0.874, and 0.892. Conclusions: A nomogram based on GPTV10-radscore, tumor size, and CTR exhibited high predictive efficiency for predicting the invasiveness of LUAD.

3D hot spot construction on the hydrophobic interface with SERS tags for quantitative detection of pesticide residues on food surface.

The overuse of pesticides results in excessive pesticide residues, posing a potential threat to human health. Herein, this work proposes a SERS substrate for the quantitative analysis of pesticide residues on food surfaces. Au cores are assembled on PS microspheres, followed by the modification of Raman internal standards (1,4-BDT) on the gold core surface and the growth of the Au shell. After incubating the analytes with PS@Au@1,4-BDT@Au particles, the mixture is dropped on the hydrophobic gold film for drying before detection. The SERS substrates exhibited high sensitivity and stability, with a detection limit of 10-12 M and an RSD of less than 7 %. Combined with a portable Raman spectrometer, the SERS detection of pesticide residues on three kinds of food surfaces is carried out, with a sensitivity of 10-11 M, meeting the US MRLs regulations. Therefore, this strategy may possess significant potential for future food safety.

Metabolomics Revealed the Tolerance and Growth Dynamics of Arbuscular Mycorrhizal Fungi (AMF) to Soil Salinity in Licorice.

Several studies have been devoted to seeking some beneficial plant-related microorganisms for a long time, and on this basis, it has been found that arbuscular mycorrhizal fungi (AMF) have a considerable positive impact on plant health as a biological fungal agent. In this study, we focused on the effects of different AMF on the growth dynamics and root configuration of licorice under saline and alkali conditions. The metabolites of licorice under different AMF were assessed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Funneliformis mosseae (Fm) and Rhizophagus intraradices (Ri) were added as different AMF treatments, while the sterilized saline-alkali soil was treated as a control. Samples were taken in the R1 period (15 d after AMF treatment) and the R2 period (45 d after AMF treatment). The results showed that the application of AMF significantly increased the root growth of licorice and significantly increased the biomass of both shoot and root. A total of 978 metabolites were detected and divided into 12 groups including lipids, which accounted for 15.44%; organic acids and their derivatives, at 5.83%; benzene compounds and organic heterocyclic compounds, at 5.42%; organic oxides, at 3.78%; and ketones, accounting for 3.17%. Compared with the control, there were significant changes in the differential metabolites with treatment inoculated with AMF; the metabolic pathways and biosynthesis of secondary metabolites were the main differential metabolite enrichment pathways in the R1 period, and those in the R2 period were microbial metabolism in diverse environments and the degradation of aromatic compounds. In conclusion, the use of AMF as biofertilizer can effectively improve the growth of licorice, especially in terms of the root development and metabolites, in saline-alkali soil conditions.

CT-based whole lung radiomics nomogram for identification of PRISm from non-COPD subjects.

BACKGROUND: Preserved Ratio Impaired Spirometry (PRISm) is considered to be a precursor of chronic obstructive pulmonary disease. Radiomics nomogram can effectively identify the PRISm subjects from non-COPD subjects, especially when during large-scale CT lung cancer screening. METHODS: Totally 1481 participants (864, 370 and 247 in training, internal validation, and external validation cohorts, respectively) were included. Whole lung on thin-section computed tomography (CT) was segmented with a fully automated segmentation algorithm. PyRadiomics was adopted for extracting radiomics features. Clinical features were also obtained. Moreover, Spearman correlation analysis, minimum redundancy maximum relevance (mRMR) feature ranking and least absolute shrinkage and selection operator (LASSO) classifier were adopted to analyze whether radiomics features could be used to build radiomics signatures. A nomogram that incorporated clinical features and radiomics signature was constructed through multivariable logistic regression. Last, calibration, discrimination and clinical usefulness were analyzed using validation cohorts. RESULTS: The radiomics signature, which included 14 stable features, was related to PRISm of training and validation cohorts (p < 0.001). The radiomics nomogram incorporating independent predicting factors (radiomics signature, age, BMI, and gender) well discriminated PRISm from non-COPD subjects compared with clinical model or radiomics signature alone for training cohort (AUC 0.787 vs. 0.675 vs. 0.778), internal (AUC 0.773 vs. 0.682 vs. 0.767) and external validation cohorts (AUC 0.702 vs. 0.610 vs. 0.699). Decision curve analysis suggested that our constructed radiomics nomogram outperformed clinical model. CONCLUSIONS: The CT-based whole lung radiomics nomogram could identify PRISm to help decision-making in clinic.

Biosynthesis of nonnutritive monosaccharide d-allulose by metabolically engineered Escherichia coli from nutritive disaccharide sucrose.

Sucrose is a commonly utilized nutritive sweetener in food and beverages due to its abundance in nature and low production costs. However, excessive intake of sucrose increases the risk of metabolic disorders, including diabetes and obesity. Therefore, there is a growing demand for the development of nonnutritive sweeteners with almost no calories. d-Allulose is an ultra-low-calorie, rare six-carbon monosaccharide with high sweetness, making it an ideal alternative to sucrose. In this study, we developed a cell factory for d-allulose production from sucrose using Escherichia coli JM109 (DE3) as a chassis host. The genes cscA, cscB, cscK, alsE, and a6PP were co-expressed for the construction of the synthesis pathway. Then, the introduction of ptsG-F and knockout of ptsG, fruA, ptsI, and ptsH to reprogram sugar transport pathways resulted in an improvement in substrate utilization. Next, the carbon fluxes of the Embden-Meyerhof-Parnas and the pentose phosphate pathways were regulated by the inactivation of pfkA and zwf, achieving an increase in d-allulose titer and yield of 154.2% and 161.1%, respectively. Finally, scaled-up fermentation was performed in a 5 L fermenter. The titer of d-allulose reached 11.15 g/L, with a yield of 0.208 g/g on sucrose.

HKDC1 promotes liver cancer stemness under hypoxia via stabilizing ß-catenin.

BACKGROUND AND AIMS: Hexokinases (HKs), a group of enzymes catalyzing the first step of glycolysis, have been shown to play important roles in liver metabolism and tumorigenesis. Our recent studies identified HKDC1 as a top candidate associated with liver cancer metastasis. We aimed to compare its cell type specificity with other HKs upregulated in liver cancer and investigate the molecular mechanisms underlying its involvement in liver cancer metastasis. APPROACH AND RESULTS: We found that, compared to HK1 and HK2, the other two commonly upregulated HKs in liver cancer, HKDC1 was most strongly associated with the metastasis potential of tumors and organoids derived from two liver cancer mouse models we previously established. RNA in situ hybridization and single-cell RNA-seq analysis revealed that HKDC1 was specifically upregulated in malignant cells in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) patient tumors, whereas HK1 and HK2 were widespread across various tumor microenvironment lineages. An unbiased metabolomic profiling demonstrated that HKDC1 overexpression in HCC cells led to metabolic alterations distinct from those from HK1 and HK2 overexpression, with HKDC1 particularly impacting the tricarboxylic acid (TCA) cycle. HKDC1 was prometastatic in HCC orthotopic and tail vein injection mouse models. Molecularly, HKDC1 was induced by hypoxia and bound to glycogen synthase kinase 3ß to stabilize ß-catenin, leading to enhanced stemness of HCC cells. CONCLUSIONS: Overall, our findings underscore HKDC1 as a prometastatic HK specifically expressed in the malignant compartment of primary liver tumors, thereby providing a mechanistic basis for targeting this enzyme in advanced liver cancer.

Single-Cell RNA Sequencing Revealing that MMP12+ Macrophages are Associated with Cancer Liver Metastasis.

AIM: We aimed to explore the MMP12+ macrophages function in liver metastasis of Colorectal cancer [CRC]. BACKGROUND: CRC has a high incidence, and a great many patients develop liver metastases. Some studies have found that macrophages may participate in the liver metastasis of CRC. OBJECTIVE: This study aimed to determine the factors and major signaling pathways of MMP12+ macrophages affecting liver metastasis of CRC. METHODS: The single-cell RNA sequencing [scRNA-seq] data of CRC and bulk transcriptome data were downloaded. After filtering scRNA-seq data, dimensionality reduction and clustering were performed to identify different cell subgroups. The FindAll- Markers function was used to calculate the differentially expressed genes in each cell subgroup, and the genes in the promising set were uploaded to the DAVID database to analyze the biological processes to which these genes were enriched. Differentially expressed genes among macrophage subgroups were selected by the AverageExpression function. Then, the CIBERSORT algorithm was used to compute the proportion of each macrophage subgroup in each bulk tissue and determine the most significant macrophage subgroup. The dynamic changes of gene expression in macrophage subgroup were computed by Pseudotime. Finally, CellChat was applied to investigate the effect of the macrophage subgroup on epithelial cells and the ligand-receptor effect of B cells and T cells. RESULTS: Clustering scRNA-seq data showed a larger proportion of macrophages in liver metastases. The proportion of MMP12+ macrophage subtypes increased gradually among normal, tumor, and liver metastasis groups, and MMP12+ macrophages were associated with angiogenesis, cell migration, and inhibited T cell proliferation. The Pseudotime showed higher expression levels of genes related to angiogenesis and enhanced TGF-ß signaling pathway and the negative regulation of T cell proliferation with the occurrence of liver metastasis in MMP12+ macrophages. MMP12+ macrophages can promote the proliferation of epithelial cells and inhibit the activation of T cells and B cells. CONCLUSION: MMP12+ macrophages promoted liver metastasis of CRC by influencing angiogenesis, TGF-ß signaling pathway expression, and regulation of T cells and B cells.

Comparative analysis of the complete mitogenomes of Camellia sinensis var. sinensis and C. sinensis var. assamica provide insights into evolution and phylogeny relationship.

Introduction: Among cultivated tea plants (Camellia sinensis), only four mitogenomes for C. sinensis var. assamica (CSA) have been reported so far but none for C. sinensis var. sinensis (CSS). Here, two mitogenomes of CSS (CSSDHP and CSSRG) have been sequenced and assembled. Methods: Using a combination of Illumina and Nanopore data for the first time. Comparison between CSS and CSA mitogenomes revealed a huge heterogeneity. Results: The number of the repetitive sequences was proportional to the mitogenome size and the repetitive sequences dominated the intracellular gene transfer segments (accounting for 88.7%- 92.8% of the total length). Predictive RNA editing analysis revealed that there might be significant editing in NADH dehydrogenase subunit transcripts. Codon preference analysis showed a tendency to favor A/T bases and T was used more frequently at the third base of the codon. ENc plots analysis showed that the natural selection play an important role in shaping the codon usage bias, and Ka/Ks ratios analysis indicated Nad1 and Sdh3 genes may have undergone positive selection. Further, phylogenetic analysis shows that six C. sinensis clustered together, with the CSA and CSS forming two distinct branches, suggesting two different evolutionary pathway. Discussion: Altogether, this investigation provided an insight into evolution and phylogeny relationship of C. sinensis mitogenome, thereby enhancing comprehension of the evolutionary patterns within C. sinensis species.

Nature of back slopping kombucha fermentation process: insights from the microbial succession, metabolites composition changes and their correlations.

Kombucha, a fermented tea prepared with a symbiotic culture of bacteria and yeast (SCOBY), offers a unique and unpredictable home-brewed fermentation process. Therefore, the need for a controlled kombucha fermentation process has become evident, which requiring a thorough understanding of the microbial composition and its relationship with the metabolites produced. In this study, we investigated the dynamics of microbial communities and metabolites over a 12-day fermentation period of a conventional kombucha-making process. Our findings revealed similarities between the microbial communities in the early (0-2 days) and late (10-12 days) fermentation periods, supporting the principle of back-slopping fermentation. Untargeted metabolite analysis unveiled the presence of harmful biogenic amines in the produced kombucha, with concentrations increasing progressively throughout fermentation, albeit showing relatively lower abundance on days 8 and 12. Additionally, a contrasting trend between ethanol and caffeine content was observed. Canonical correspondence analysis highlighted strong positive correlations between specific bacterial/yeast strains and identified metabolites. In conclusion, our study sheds light on the microbial and metabolite dynamics of kombucha fermentation, emphasizing the importance of microbial control and quality assurance measures in the production process.

An integrated machine learning model enhances delayed graft function prediction in pediatric renal transplantation from deceased donors.

BACKGROUND: Kidney transplantation is the optimal renal replacement therapy for children with end-stage renal disease; however, delayed graft function (DGF), a common post-operative complication, may negatively impact the long-term outcomes of both the graft and the pediatric recipient. However, there is limited research on DGF in pediatric kidney transplant recipients. This study aims to develop a predictive model for the risk of DGF occurrence after pediatric kidney transplantation by integrating donor and recipient characteristics and utilizing machine learning algorithms, ultimately providing guidance for clinical decision-making. METHODS: This single-center retrospective cohort study includes all recipients under 18 years of age who underwent single-donor kidney transplantation at our hospital between 2016 and 2023, along with their corresponding donors. Demographic, clinical, and laboratory examination data were collected from both donors and recipients. Univariate logistic regression models and differential analysis were employed to identify features associated with DGF. Subsequently, a risk score for predicting DGF occurrence (DGF-RS) was constructed based on machine learning combinations. Model performance was evaluated using the receiver operating characteristic curves, decision curve analysis (DCA), and other methods. RESULTS: The study included a total of 140 pediatric kidney transplant recipients, among whom 37 (26.4%) developed DGF. Univariate analysis revealed that high-density lipoprotein cholesterol (HDLC), donor after circulatory death (DCD), warm ischemia time (WIT), cold ischemia time (CIT), gender match, and donor creatinine were significantly associated with DGF (P < 0.05). Based on these six features, the random forest model (mtry = 5, 75%p) exhibited the best predictive performance among 97 machine learning models, with the area under the curve values reaching 0.983, 1, and 0.905 for the entire cohort, training set, and validation set, respectively. This model significantly outperformed single indicators. The DCA curve confirmed the clinical utility of this model. CONCLUSIONS: In this study, we developed a machine learning-based predictive model for DGF following pediatric kidney transplantation, termed DGF-RS, which integrates both donor and recipient characteristics. The model demonstrated excellent predictive accuracy and provides essential guidance for clinical decision-making. These findings contribute to our understanding of the pathogenesis of DGF.

[Long-term efficacy of oblique lateral interbody fusion combined with vertebral screw fixation for the treatment of lumbar specific infection].

OBJECTIVE: To explore medium and long term efficacy of oblique lateral interbody fusion (OLIF) in treating lumbar specific infection. METHODS: From October 2017 to January 2021, 24 patients with lumbar specific infection were treated by OLIF combined with vertebral screw internal fixation, including 15 males and 9 females, aged from 27 to 61 years old with an average of (43.0±15.0) years old;the courses of disease ranged from 6 to 24 months with an average of (14.0±7.0) months;7 patients with L2-L3, 12 patients with L3-L4 and 5 patients with L4-L5;19 patients with tuberculosis infection and 5 patients with brucella infection. The amount of intraoperative blood loss, operative time and complications were recorded, and erythrocyte sedimentation rate(ESR), C-reactive protein (CRP), visual analogue scale (VAS), Japanese Orthopaedic Association(JOA) score and American Spinal Injury Association (ASIA) rating were compared before and one month after opertaion. RESULTS: All patients were followed up from 9 to 24 months with an average of (13.0±6.0) months. Operative time was (132.5±21.4) min, and intraoperative blood loss was (227.3±43.1) ml. ESR and CRP were decreased from (82.34±18.62) mmol·h-1 and (53.08±21.84) mg·L-1 before operation to (33.52±17.31) mmol·h-1 and (15.48±8.36) mg·L-1 at one month after operation, respectively (P<0.05). VAS was decreased from (7.52±1.36) before opertaion to (1.74±0.87) at one month after operation (P<0.05). JOA was increased from (17.86±3.95) before operation to (24.72±3.19) at one month after operation (P<0.05). Four patients had neurological symptoms before operation, and were classified to grade D according to ASIA classification, who were recovered to grade E at 1 month after operation. One patient was suffered from psoas major muscle injury after operation, and returned to normal at 3 weeks. One patient was suffered from abdominal distension and difficulty in defecation, and relieved after gastrointestinal decompression and enema. No complications such as abdominal organ injury and poor wound healing occurred in all patients. CONCLUSION: OLIF combined with vertebral screw internal fixation is a new minimally invasive surgical method for the treatment of lumbar specific infection, especially the lesion located on the middle lumbar vertebra. It has advantages of less trauma, short operation time, less blood loss, convenient operation, complete removal of the lesion, safety and effectiveness, and has good medium-and long-term efficacy for lumbar specific infection.

Effects of personalized music listening on post-stroke cognitive impairment: A randomized controlled trial.

BACKGROUND AND PURPOSE: Previous studies have suggested that music listening has the potential to positively affect cognitive functions and mood in individuals with post-stroke cognitive impairment (PSCI), with a preference for self-selected music likely to yield better outcomes. However, there is insufficient clinical evidence to suggest the use of music listening in routine rehabilitation care to treat PSCI. This randomized control trial (RCT) aims to investigate the effects of personalized music listening on mood improvement, activities of daily living (ADLs), and cognitive functions in individuals with PSCI. MATERIALS AND METHODS: A total of 34 patients with PSCI were randomly assigned to either the music group or the control group. Patients in the music group underwent a three-month personalized music-listening intervention. The intervention involved listening to a personalized playlist tailored to each individual's cultural, ethnic, and social background, life experiences, and personal music preferences. In contrast, the control group patients listened to white noise as a placebo. Cognitive function, neurological function, mood, and ADLs were assessed. RESULTS: After three months of treatment, the music group showed significantly higher Montreal Cognitive Assessment (MoCA) scores compared to the control group (p=0.027), particularly in the domains of delayed recall (p=0.019) and orientation (p=0.023). Moreover, the music group demonstrated significantly better scores in National Institutes of Health Stroke Scale (NIHSS) (p=0.008), Barthel Index (BI) (p=0.019), and Zarit Caregiver Burden Interview (ZBI) (p=0.008) compared to the control group. No effects were found on mood as measured by the Hamilton Anxiety Rating Scale (HAMA) and the Hamilton Depression Rating Scale (HAMD). CONCLUSION: Personalized music listening promotes the recovery of cognitive and neurological functions, improves ADLs, and reduces caregiver burden in patients with PSCI.

MEIKIN expression and its C-terminal phosphorylation by PLK1 is closely related the metaphase-anaphase transition by affecting cyclin B1 and Securin stabilization in meiotic oocyte.

Oocyte meiotic maturation failure and chromosome abnormality is one of the main causes of infertility, abortion, and diseases. The mono-orientation of sister chromatids during the first meiosis is important for ensuring accurate chromosome segregation in oocytes. MEIKIN is a germ cell-specific protein that can regulate the mono-orientation of sister chromatids and the protection of the centromeric cohesin complex during meiosis I. Here we found that MEIKIN is a maternal protein that was highly expressed in mouse oocytes before the metaphase I (MI) stage, but became degraded by the MII stage and dramatically reduced after fertilization. Strikingly, MEIKIN underwent phosphorylation modification after germinal vesicle breakdown (GVBD), indicating its possible function in subsequent cellular event regulation. We further showed that MEIKIN phosphorylation was mediated by PLK1 at its carboxyl terminal region and its C-terminus was its key functional domain. To clarify the biological significance of meikin degradation during later stages of oocyte maturation, exogenous expression of MEIKIN was employed, which showed that suppression of MEIKIN degradation resulted in chromosome misalignment, cyclin B1 and Securin degradation failure, and MI arrest through a spindle assembly checkpoint (SAC)-independent mechanism. Exogenous expression of MEIKIN also inhibited metaphase II (MII) exit and early embryo development. These results indicate that proper MEIKIN expression level and its C-terminal phosphorylation by PLK1 are critical for regulating the metaphase-anaphase transition in meiotic oocyte. The findings of this study are important for understanding the regulation of chromosome segregation and the prevention meiotic abnormality.