Inoculum Sources of Puccinia striiformis f. sp. tritici for Stripe Rust Epidemics on the Eastern Coast of China.

Stripe rust, a fungal disease caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most destructive diseases affecting wheat production areas worldwide. In recent years in China, wheat stripe rust has caused huge yield losses throughout the vast Huang-Huai-Hai region, including the eastern coast regions, especially Shandong province. The aim of the present study was to explore the population structure and potential inoculum sources of the pathogen in this region. A total of 234 Pst isolates in 2021 were collected and isolated from seven provinces and identified for virulence phenotypes using 19 Chinese differentials and for genotypes using 17 single-nucleotide polymorphism-based Kompetitive allele-specific PCR markers. The virulence phenotype tests identified predominant races CYR34 (18.0%) and CYR32 (16.0%) in Shandong, which were similar to the results in Henan province, also with the predominant races CYR34 (21.9%) and CYR32 (18.8%). Based on the virulence data of phenotyping, the Pst populations in Shandong, Hubei, and Henan were similar. The genotypic analysis revealed remarkable gene flows among the Shandong, Hubei, Henan, Yunnan, and Guizhou populations, showing a migration of Pst from the southwestern oversummering regions to Shandong through the winter spore production regions. Genetic structure analysis also indicated an additional migration route from the northwestern oversummering regions through winter spore production regions to Shandong. The results are useful for understanding stripe rust epidemiology in the eastern coast region and improving control of the disease throughout the country.

Interpretable machine learning models for early prediction of acute kidney injury after cardiac surgery.

OBJECTIVE: Postoperative acute kidney injury (PO-AKI) is a common complication after cardiac surgery. We aimed to evaluate whether machine learning algorithms could significantly improve the risk prediction of PO-AKI. METHODS: The retrospective cohort study included 2310 adult patients undergoing cardiac surgery in a tertiary teaching hospital, China. Postoperative AKI and severe AKI were identified by the modified KDIGO definition. The sample was randomly divided into a derivation set and a validation set based on a ratio of 4:1. Exploiting conventional logistic regression (LR) and five ML algorithms including decision tree, random forest, gradient boosting classifier (GBC), Gaussian Naive Bayes and multilayer perceptron, we developed and validated the prediction models of PO-AKI. We implemented the interpretation of models using SHapley Additive exPlanation (SHAP) analysis. RESULTS: Postoperative AKI and severe AKI occurred in 1020 (44.2%) and 286 (12.4%) patients, respectively. Compared with the five ML models, LR model for PO-AKI exhibited the largest AUC (0.812, 95%CI: 0.756, 0.860, all P < 0.05), sensitivity (0.774, 95%CI: 0.719, 0.813), accuracy (0.753, 95%CI: 0.719, 0.781) and Youden index (0.513, 95%CI: 0.451, 0.573). Regarding severe AKI, GBC algorithm showed a significantly higher AUC than the other four ML models (all P < 0.05). Although no significant difference (P = 0.173) was observed in AUCs between GBC (0.86, 95%CI: 0.808, 0.902) and conventional logistic regression (0.803, 95%CI: 0.746, 0.852), GBC achieved greater sensitivity, accuracy and Youden index than conventional LR. Notably, SHAP analyses showed that preoperative serum creatinine, hyperlipidemia, lipid-lowering agents and assisted ventilation time were consistently among the top five important predictors for both postoperative AKI and severe AKI. CONCLUSION: Logistic regression and GBC algorithm demonstrated moderate to good discrimination and superior performance in predicting PO-AKI and severe AKI, respectively. Interpretation of the models identified the key contributors to the predictions, which could potentially inform clinical interventions.

Resting-state functional magnetic resonance imaging study comparing tremor-dominant and postural instability/gait difficulty subtypes of Parkinson's disease.

PURPOSE: The symptom-specific intrinsic neural mechanisms underlying Parkinson's disease (PD) subtypes (tremor dominant [TD] and postural instability gait difficulty [PIGD]) remain unclarified. We examined spontaneous brain activity patterns in TD and PIGD. MATERIAL AND METHODS: We included 49 patients with PD (21 with TD/28 with PIGD) and 32 healthy controls (HCs) in this study. We conducted analysis of variance and post-hoc analyses of the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values of the three groups, with age, sex, and gray matter volume as covariates, and a relationship analysis of the ALFF and ReHo values with clinical variables. RESULTS: In comparison with HCs, PIGD PD patients had increased ALFF values in the right middle occipital gyrus and left superior occipital gyrus and decreased values primarily in the bilateral inferior frontal gyrus (triangular part). TD PD patients had lower ALFF values in the right inferior frontal gyrus (triangular part) and left insula. In comparison to TD PD patients, PIGD PD patients had higher ALFF values in the left middle occipital gyrus and left superior occipital gyrus. In contrast to HCs, TD PD patients demonstrated a reduction of ReHo values in the left middle temporal gyrus, and PIGD patients showed a decrease of ReHo values in the left inferior temporal gyrus. CONCLUSION: ALFF values increased in the occipital gyrus of the PIGD PD patients, thus providing evidence of a compensatory mechanism of altered motor function in comparison with the TD PD patients.

Discovery of 2-(isoxazol-5-yl)phenyl 3,4-dihydroxybenzoate as a potential inhibitor for the Wnt/ß-catenin pathway.

Carnosic acid could disrupt the ß-catenin/BCL9 protein-protein interaction and inhibit ß-catenin dependent transcription, thereby reduce the incidence of colorectal cancer induced by abnormal activation of Wnt/ß-catenin signalling pathway. However, its activity was weak (IC50 for SW480: 28.2 ± 2.05 µM) and total synthesis was difficult. During the structural simplification of natural products, S0 was revealed to be the basic pharmacophore of carnosic acid. Subsequent structural optimization of S0 led to the discovery of S11 as a possible anticancer agent with prominent proliferation inhibition effect (IC50 for SW480: 9.56 ± 0.91 µM) and best selectivity index (SI = 3.0) against Wnt hyperactive cancer cells. Futher mechanism investigation through TOP/FOP dual luciferase reporter assay, immunofluorescence, co-immunoprecipitation, microscale thermophoresis, downstream oncoprotein expression and cell apoptosis showed that compound S11 could significantly inhibit the proliferation of SW480 cells via obvioudsly decreasing the nucleus translocation of ß-catenin and effectively disrupting ß-catenin/BCL9 protein-protein interaction. Additionally, cell migration, molecule docking, in vitro stability and solubility assays were also conducted. Overall, S11 was worthy of in-depth study as a potential inhibitor for the Wnt/ß-catenin pathway and its discovery also proved that the structural simplification of natural products was still one of the effective methods to find new lead compounds or candidate drugs.

Enhanced liquid phase exfoliation of graphene in water using an insoluble bis-pyrene stabiliser.

Stabilisers, such as surfactants, polymers and polyaromatic molecules, offer an effective way to produce graphene dispersions in water by Liquid Phase Exfoliation (LPE) without degrading the properties of graphene. In particular, pyrene derivatives provide better exfoliation efficiency than traditional surfactants and polymers. A stabiliser is expected to be relatively soluble in order to disperse hydrophobic graphene in water. Here, we show that exfoliation can also be achieved with insoluble pyrene stabilisers if appropriately designed. In particular, bis-pyrene stabilisers (BPSs) functionalised with pyrrolidine provide a higher exfoliation efficiency and percentage of single layers compared to traditional pyrene derivatives under the same experimental conditions. This is attributed to the enhanced interactions between BPS and graphene, provided by the presence of two pyrene binding groups. This approach is therefore attractive not only to produce highly concentrated graphene, but also to use graphene to disperse insoluble molecules in water. The enhanced adsorption of BPS on graphene, however, is reflected in higher toxicity towards human epithelial bronchial immortalized cells, limiting the use of this material for biomedical applications.

Prediction of all-cause mortality in coronary artery disease patients with atrial fibrillation based on machine learning models.

BACKGROUND: Machine learning (ML) can include more diverse and more complex variables to construct models. This study aimed to develop models based on ML methods to predict the all-cause mortality in coronary artery disease (CAD) patients with atrial fibrillation (AF). METHODS: A total of 2037 CAD patients with AF were included in this study. Three ML methods were used, including the regularization logistic regression, random forest, and support vector machines. The fivefold cross-validation was used to evaluate model performance. The performance was quantified by calculating the area under the curve (AUC) with 95% confidence intervals (CI), sensitivity, specificity, and accuracy. RESULTS: After univariate analysis, 24 variables with statistical differences were included into the models. The AUC of regularization logistic regression model, random forest model, and support vector machines model was 0.732 (95% CI 0.649-0.816), 0.728 (95% CI 0.642-0.813), and 0.712 (95% CI 0.630-0.794), respectively. The regularization logistic regression model presented the highest AUC value (0.732 vs 0.728 vs 0.712), specificity (0.699 vs 0.663 vs 0.668), and accuracy (0.936 vs 0.935 vs 0.935) among the three models. However, no statistical differences were observed in the receiver operating characteristic (ROC) curve of the three models (all P > 0.05). CONCLUSION: Combining the performance of all aspects of the models, the regularization logistic regression model was recommended to be used in clinical practice.

Structural and Functional Thalamic Changes in Parkinson's Disease With Mild Cognitive Impairment.

BACKGROUND: The thalamus is a key node of deep gray matter and previous studies have demonstrated that it is involved in the modulation of cognition. PURPOSE: To investigate the volume changes of the thalamus and its subregions and altered thalamus functional connectivity patterns in Parkinson's disease (PD) patients with and without mild cognitive impairment (MCI). STUDY TYPE: Prospective. POPULATION: Thirty-three patients with MCI (PD-MCI), 36 PD patients having no cognitive impairment (PD-NCI), 21 healthy controls (HCs). SEQUENCE: 3.0T MRI scanner; 3D T1 -weighted fast spoiled gradient recalled echo (3D T1 -FSPGR); resting-state fMRI ASSESSMENT: Voxel-based morphometry (VBM) was performed to calculate the volume of the thalamus and its subregions. The left and right total thalamus were considered seeds and seed-based functional connectivity (FC) was analyzed. Additionally, correlations between volumes and cognitive performance and between FC values and cognitive performance were examined separately. STATISTICAL TEST: Analysis of covariance (ANCOVA); two-sample t-tests; partial correlation analysis. RESULTS: The volumes of the total thalamus (PD-MCI vs. PD-NCI vs. HCs: 18.39 ± 1.67 vs. 19.63 ± 1.79 vs. 19.47 ± 1.35) and its subregions were significantly reduced in PD-MCI as compared to PD-NCI (total thalamus: P = 0.002) and HCs (total thalamus: P = 0.012). Compared with PD-NCI, PD-MCI showed increased FC between the thalamus and bilateral middle cingulate cortex and left posterior cingulate cortex, and decreased FC between thalamus and the left superior occipital gyrus, left cuneus, left precuneus, and left middle occipital gyrus. Volumes of thalamus and the subregions, as well as the FC of thalamus with the identified regions, were significantly correlated (P < 0.05, FDR-corrected) with neuropsychological scores in PD patients. DATA CONCLUSION: We noted volume loss and altered FC of thalamus in PD-MCI patients, and these changes were correlated with global cognitive performance. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICIENCY: Stage 2 J. Magn. Reson. Imaging 2020;52:1207-1215.

Synthesis and antifungal activity of imidazo[1,2-b]pyridazine derivatives against phytopathogenic fungi.

A series of 3,6-disubstituted imidazo[1,2-b]pyridazine derivatives have been synthesized and characterized with spectroscopic analyses. The antifungal activities of these compounds against nine phytopathogenic fungi were evaluated by the mycelium growth rate method. The in vitro antifungal bioassays indicated that most of compounds displayed excellent and broad-spectrum antifungal activities. Especially, compounds 4a, 4c, 4d, 4l and 4r exhibited 1.9-25.5 fold more potent than the commercially available fungicide hymexazol against Corn Curvalaria Leaf Spot (CL), Alternaria alternate (AA), Pyricularia oryzae (PO) and Alternaria brassicae (AB) strains. Structure-activity relationship analysis showed that the enhanced antifungal activity is significantly affected by the substituents on the benzene ring and pyridazine ring.

Antithrombotic therapy in coronary artery disease patients with atrial fibrillation.

BACKGROUND: Coronary artery disease (CAD) and atrial fibrillation (AF) frequently coexist in clinical practice, making it challenging for the treating physician to choose anticoagulation and antiplatelet therapies. The aim of this study was to investigate antithrombotic strategies and assess related adverse outcomes in stable coronary artery disease (SCAD) and acute coronary syndrome (ACS) patients with AF when the CHA2DS2-VASc score was ≥2. METHODS: We performed a retrospective study and collected data from a computer-based patient record management system in Zhengzhou University People's Hospital in China. In total, 2978 patients with a hospital discharge diagnosis of CAD and concomitant AF who met the inclusion criteria were enrolled from January 1, 2012 to December 31, 2016, and data from 2050 patients were finally analysed. The χ2 test was used to compare the incidences of clinical endpoints between the SCAD+AF group and the ACS + AF group. Multivariable Cox regression analysis was performed to identify independent predictive factors of adverse outcomes in both groups. RESULTS: Oral anticoagulant (OAC) monotherapy was the most common antithrombotic therapy in SCAD+AF patients (49.55%), while double antiplatelet therapy (DAPT) was the most common treatment in ACS + AF patients (54.19%) at discharge. OAC monotherapy significantly increased and the use of single antiplatelet therapy (SAPT) decreased during follow-up (34 ± 13 months) when compared to their use at discharge in the SCAD+AF group (all p < 0.001). In the ACS + AF group, the proportion of patients using DAPT decreased notably, while the proportions of patients using SAPT and dual therapy (DT) combining OAC with SAPT increased significantly during follow-up (all p < 0.001) compared to the proportions at discharge. According to multivariable Cox regression analysis, age, hypertension and prior stroke were independent risk factors for ischaemic stroke in the SCAD+AF group and ACS + AF group (all p < 0.05). OAC was an independent protective factor for ischaemic stroke in both groups (all p < 0.05). Previous bleeding independently increased the risk of haemorrhage in both groups (all p < 0.01). CONCLUSIONS: In this study, the proportion of anticoagulant-antiplatelet combined therapy was low in ACS + AF patients with high stroke risk. In clinical practice, the awareness of anticoagulation needs to be strengthened regarding patients with CAD and AF.

Quinone-catalyzed oxidative deformylation: synthesis of imines from amino alcohols.

A new method for imine synthesis by way of quinone-catalyzed oxidative deformylation of 1,2-amino alcohols is reported. A wide range of readily accessible amino alcohols and primary amines can be reacted to provide N-protected imine products. The methodology presented provides a novel organocatalytic approach for imine synthesis and demonstrates the synthetic versatility of quinone-catalyzed oxidative C-C bond cleavage.

[Survey on the early reperfusion therapy status in patients with ST-segment elevation myocardial infarction hospitalized in tertiary and secondary hospitals in Henan province].

OBJECTIVE: To observe the early reperfusion therapy status for patients with ST elevation acute myocardial infarction (STEMI) hospitalized in tertiary and secondary hospitals in Henan province. METHODS: Baseline data, early reperfusion treatment and in-hospital mortality of STEMI patients hospitalized in 17 hospitals in Henan province (8 tertiary hospitals, 9 secondary hospitals) from June 2011 to June 2012 were obtained using a uniformed questionnaire. RESULTS: One thousand six hundred and eighty six patients were enrolled, of which 886 patients were hospitalized in tertiary hospitals and 880 patients were early hospitalized in secondary hospitals. Six hundred and fifty four patients (38.8%, 654/1 686) underwent early reperfusion therapy (543 with thrombolysis and 111 with primary percutaneous coronary intervention (PCI)). There was no difference in the proportion of early reperfusion therapy between tertiary and secondary hospitals (40.1% (355/886) vs. 37.4% (299/800), P = 0.257). The median time from symptom onset to first medical contact, door-to-needle and door-to-balloon was 132 min, 18 min and 60 min, respectively. The median time from symptom onset to first medical contact (150 min vs. 120 min, P = 0.001), door-to-needle (30 min vs. 18 min, P = 0.003) and symptom onset-to-thrombolysis (3.5 h vs. 2.7 h, P = 0.001) were significantly longer in tertiary hospitals than in secondary hospitals. No difference was found in median time of door-to-balloon, symptom onset-to-primary PCI or symptom onset-to-elected PCI between tertiary and secondary hospitals (all P > 0.05). The proportion of door-to-needle ≤ 30 min was lower in tertiary hospitals than in secondary hospitals (46.4% (84/181) vs. 62.2% (153/246), P = 0.001). However, there was no difference in the proportion of door-to-balloon ≤ 90 min between tertiary and secondary hospitals (58.8% (60/102) vs. 57.1% (4/7), P = 1.000). In-hospital mortality was also similar between tertiary and secondary hospitals (5.8% (51/886) vs. 5.5% (44/800), P = 0.820). CONCLUSIONS: Early reperfusion rate is low, and thrombolysis is the main early reperfusion therapy in both tertiary and secondary hospitals in Henan province. Tertiary hospitals did not take advantage of their primary PCI capability. There is great room for improvement in early reperfusion therapy in tertiary and secondary hospitals.

Effect of preoperative moderate-dose statin and duration on acute kidney injury after cardiac surgery: a retrospective cohort study.

BACKGROUND: The impact of preoperative statin use on postoperative acute kidney injury (AKI) is uncertain. We aimed to examine the association of statin therapy before cardiac surgery with postoperative AKI. METHODS: The retrospective cohort study consisted of 1581 patients undergoing cardiac surgery. Postoperative AKI were identified by the modified KDIGO definition. Propensity-score matching was employed to control for selection bias, and logistic regression was used to control for confounders. Subgroup and interaction analyses were performed to evaluate the robustness of the findings. RESULTS: The overall incidence of postoperative AKI and severe AKI were 42.19% and 12.27%, respectively. Preoperative moderate-dose statin was significantly associated with a reduced incidence of postoperative AKI (28.9% vs 43.0%, OR (95%CI): 0.54 (0.38, 0.77), p < 0.001) and severe AKI (6.9% vs 13.7%, OR (95%CI): 0.46 (0.26, 0.83), p = 0.009). The beneficial effect on postoperative AKI persisted after adjusting for major confounding factors (OR (95%CI): 0.47 (0.34, 0.66)). Decreased risk of postoperative AKI was observed in patients with preoperative statin duration of 7 ∼ 14 days (OR (95%CI): 0.41 (0.25, 0.65)) and over 14 days (OR (95%CI): 0.43 (0.28, 0.65)), but not in those with preoperative statin duration of <7 days. Similar favorable effects were noted in most subgroup patients, except for those with high-risk factors such as diabetes mellitus, previous congestive cardiac failure, arrhythmia, preoperative ACEI/ARB, aortic cross-clamping or IABP. CONCLUSION: Preoperative moderate-dose statin was significantly related to a decreased risk of postoperative AKI, especially in patients who received statins for a longer duration. Further large-scale multicenter randomized controlled trials are needed to ascertain the impact of statin dose, duration, and timing on postoperative AKI in cardiac surgery patients.

Synergistic enhancement of chemisorption and catalytic conversion in lithium-sulfur batteries via Co3Fe7/Co5.47N separator mediator.

Lithium-sulfur batteries (LSBs) show considerable potential in next-generation high performance batteries, but the heavy shuttle effect and sluggish redox kinetics of polysulfide hinder their further applications. In this paper, to address these shortcomings of LSBs, Co3Fe7/Co5.47N heterostructure were prepared and constructed from their Fe-Co Prussian blue analogue precursors under the condition of high temperature pyrolysis. The obtained Co3Fe7/Co5.47N display excellent immobilization-diffusion-conversion performance for polysulfides by synergistic effect in successfully hindering the shuttle effect of polysulfides. When the Co3Fe7/Co5.47N heterostructure were applied to modify the commercial polypropylene (PP) separator, the batteries displayed fantastic rate capacity and cycling stability. Specifically, the Co3Fe7/Co5.47N-PP batteries exhibit an extremely satisfactory initial specific capacity of 1430 m Ah/g at 0.5C, wonderful rate capacity of around 780 m Ah/g at 3C and superior per cycle decaying rate of 0.08 % for 500 cycles at 0.5C. When the current density reaches to 2C, the batteries still exhibit 501 m Ah/g after 900 cycles with 0.015 % per cycle decay rate. Besides, even in the high loading of sulfur (3.0 mg cm-2) at 0.5C, the superior cycling stability (0.075 % per cycle decay rate after 200 cycles) and high specific capacity (741 mAh/g after 200 cycles) can still be performed. Thus, this work provides a facile method for high-powered and long-life Li-S batteries with eminent entrapping-conversion processes of polysulfides.

Vernicia fordii leaf extract inhibited anthracnose growth by downregulating reactive oxygen species (ROS) levels in vitro and in vivo.

Background: Colletotrichum fructicola is a predominant anthracnose species in Camellia oleifera, causing various adverse effects. Traditional intercropping Vernicia fordii with C. oleifera may enhance anthracnose resistance, but the mechanism remains elusive. Methods: We utilized UPLC-MS/MS and acid-base detection to identify the major antimicrobial alkaloid components in the V. fordii leaf extract. Subsequently, by adding different concentrations of V. fordii leaf extract for cultivating C. fructicola, with untreated C. fructicola as a control, we investigated the impact of the V. fordii leaf extract, cell wall integrity, cell membrane permeability, MDA, and ROS content changes. Additionally, analysis of key pathogenic genes of C. fructicola confirmed that the V. fordii leaf extract inhibits the growth of the fungus through gene regulation. Results: This study discovered the alkaloid composition of V. fordii leaf extract by UPLC-MS/MS and acid-base detection, such as trigonelline, stachydrine, betaine, and O-Phosphocholine. V. fordii leaf extract successfully penetrated C. fructicola mycelia, damaged cellular integrity, and increased ROS and MDA levels by 1.75 and 2.05 times respectively, thereby inhibiting C. fructicola proliferation. By analyzing the key pathogenic genes of C. fructicola, it was demonstrated that the antifungal function of V. fordii leaf extract depends mainly on the regulation of RAB7 and HAC1 gene expression. Therefore, this study elucidates the mechanism of V. fordii -C. oleifera intercropping in strengthening anthracnose resistance in C. oleifera, contributing to efficient C. oleifera cultivation.

The influence of motor learning methods on motor performance stability: The moderating effect of reinvestment propensity.

Different motor learning methods (explicit or analogy learning) show different effects on motor performance stability, and reinvestment propensity plays an important role in motor performance stability. This study aimed to explore whether reinvestment propensity, that is, movement self-consciousness (MS-C) and conscious motor processing (CMP) as two dimensions, played a moderating role in the relationship between motor learning methods and motor performance stability. A total of 78 participants were randomly assigned to either the explicit or analogy learning group and their reinvestment propensity was measured. We recorded the number of golf putt goals in both the practice phase and the test phases (including a retention test and a stress test). In the moderating analysis, participants' reinvestment propensity was the moderating variable, and the dependent variable was motor performance stability (i.e., the difference between the two test phases). Results showed that motor performance was significantly different between practicing blocks, which indicated that the motor performance of learners was gradually increasing. The significant interaction between learning methods and the test phase on motor performance was detected, suggesting under stress, analogy learning was more likely to maintain the stability of motor performance, while explicit learning impaired the stability of motor performance. The CMP played a significant moderating role in the relationship between motor learning methods and motor performance stability. The result indicated that for learners with low CMP, the motor performance stability of analogy learning was better than explicit learning, while there was no significant difference in the stability of motor performance between the two learning methods for learners with high reinvestment propensity. No significant evidence was found that MS-C played a moderating role in the relationship between motor learning methods and motor performance stability. These findings expand the theoretical framework of motor skill learning and provide theoretical support for motor performance stability.

An HIV-1 CRISPR-Cas9 membrane trafficking screen reveals a role for PICALM intersecting endolysosomes and immunity.

HIV-1 hijacks host proteins involved in membrane trafficking, endocytosis, and autophagy that are critical for virus replication. Molecular details are lacking but are essential to inform on the development of alternative antiviral strategies. Despite their potential as clinical targets, only a few membrane trafficking proteins have been functionally characterized in HIV-1 replication. To further elucidate roles in HIV-1 replication, we performed a CRISPR-Cas9 screen on 140 membrane trafficking proteins. We identified phosphatidylinositol-binding clathrin assembly protein (PICALM) that influences not only infection dynamics but also CD4+ SupT1 biology. The knockout (KO) of PICALM inhibited viral entry. In CD4+ SupT1 T cells, KO cells exhibited defects in intracellular trafficking and increased abundance of intracellular Gag and significant alterations in autophagy, immune checkpoint PD-1 levels, and differentiation markers. Thus, PICALM modulates a variety of pathways that ultimately affect HIV-1 replication, underscoring the potential of PICALM as a future target to control HIV-1.

Resting-state functional connectivity of the occipital cortex in different subtypes of Parkinson's disease.

AIMS: To examine whether functional connectivity (FC) of the occipital gyrus differs between patients with Parkinson's disease (PD) motor subtypes and healthy controls (HCs). METHODS: We enrolled 30 PD patients exhibiting tremor dominance (TD), 43 PD patients with postural instability and gait disturbance (PIGD), and 42 HCs. The occipital gyrus was partitioned into six areas of interest, as seed points, via the Anatomical Automatic Labeling template to compare the FC of the three groups and analyze the relationship of FC with clinical scales. RESULTS: Compared with the PIGD group, the TD group showed increased FC between the left superior occipital gyrus (SOG.L) and right median cingulate and paracingulate gyri (DCG.R)/right paracentral lobule/bilateral inferior parietal, but supramarginal and angular gyri; the left middle occipital gyrus (MOG.L) and left posterior cingulate gyrus (PCG.L); the MOG.R and SOG.L/right calcarine fissure and surrounding cortex/DCG.R/PCG.L/right cuneus; the left inferior occipital gyrus (IOG.L) and right caudate nucleus; and the IOG.R and PCG.L. CONCLUSION: Differentiated FC between the occipital gyrus and other brain areas within the PD motor subtypes, which may serve as neural markers to distinguish between patients with TD and PIGD PD.

KLK10/LIPH/PARD6B/SLC52A3 are promising molecular biomarkers for the prognosis of pancreatic cancer through a ceRNA network.

Pancreatic adenocarcinoma (PAAD) remains challenging to diagnose and treat clinically due to its difficult early diagnosis, low surgical resection rate, and high risk of postoperative recurrence and metastasis. SMAD4 is a classical mutated gene in pancreatic cancer and is lost in up to 60%-90 % of PAAD patients, and its mutation often predicts a poor prognosis and treatment resistance. In this study, based on the expression profile data in The Cancer Genome Atlas database, we identified a ceRNA network composed of 2 lncRNAs, 1 miRNA, and 4 mRNAs through differential expression analysis and survival prognosis analysis. Among them, high expression of KLK10/LIPH/PARD6B/SLC52A3 influenced the prognosis and overall survival of PAAD patients. We confirmed the high expression of these target genes in pancreatic tissue of pancreatic-specific SMAD4-deficient mice. In addition, immune infiltration analysis showed that the high expression of these target genes affects the tumor immune environment and contributes to the progression of PAAD. Abnormal overexpression of these target genes may be caused by hypermethylation. In conclusion, we found that KLK10/LIPH/PARD6B/SLC52A3 is a potential prognostic marker for PAAD based on a competing endogenous RNA-mediated mechanism and revealed the potential pathogenic mechanism by which deficient expression of SMAD4 promotes pancreatic cancer progression, which provides a new pathway and theoretical basis for targeted therapy or improved prognosis of pancreatic cancer. These data will help reveal potential therapeutic targets for pancreatic cancer and improve the prognosis of pancreatic cancer patients.

The power and the promise of CAR-mediated cell immunotherapy for clinical application in pancreatic cancer.

BACKGROUND: Pancreatic cancer, referred to as the "monarch of malignancies," is a neoplastic growth mostly arising from the epithelial cells of the pancreatic duct and acinar cells. This particular neoplasm has a highly unfavorable prognosis due to its marked malignancy, inconspicuous initial manifestation, challenging early detection, rapid advancement, and limited survival duration. Cellular immunotherapy is the ex vivo culture and expansion of immune effector cells, granting them the capacity to selectively target malignant cells using specialized techniques. Subsequently, these modified cells are reintroduced into the patient's organism with the purpose of eradicating tumor cells and providing therapeutic intervention for cancer. PRESENT SITUATION: Presently, the primary cellular therapeutic modalities employed in the treatment of pancreatic cancer encompass CAR T-cell therapy, TCR T-cell therapy, NK-cell therapy, and CAR NK-cell therapy. AIM OF REVIEW: This review provides a concise overview of the mechanisms and primary targets associated with various cell therapies. Additionally, we will explore the prospective outlook of cell therapy in the context of treating pancreatic cancer.

The power and the promise of synthetic lethality for clinical application in cancer treatment.

Synthetic lethality is a phenomenon wherein the simultaneous deficiency of two or more genes results in cell death, while the deficiency of any individual gene does not lead to cell death. In recent years, synthetic lethality has emerged as a significant topic in the field of targeted cancer therapy, with certain drugs based on this concept exhibiting promising outcomes in clinical trials. Nevertheless, the presence of tumor heterogeneity and the intricate DNA repair mechanisms pose challenges to the effective implementation of synthetic lethality. This review aims to explore the concepts, development, and ethical quandaries surrounding synthetic lethality. Additionally, it will provide an in-depth analysis of the clinical application and underlying mechanism of synthetic lethality.