Identifying Factors Associated with Fast Visual Field Progression in Patients with Ocular Hypertension Based on Unsupervised Machine Learning.

PURPOSE: To identify ocular hypertension (OHT) subtypes with different trends of visual field (VF) progression based on unsupervised machine learning and to discover factors associated with fast VF progression. DESIGN: Cross-sectional and longitudinal study. PARTICIPANTS: A total of 3133 eyes of 1568 ocular hypertension treatment study (OHTS) participants with at least five follow-up VF tests were included in the study. METHODS: We used a latent class mixed model (LCMM) to identify OHT subtypes using standard automated perimetry (SAP) mean deviation (MD) trajectories. We characterized the subtypes based on demographic, clinical, ocular, and VF factors at the baseline. We then identified factors driving fast VF progression using generalized estimating equation (GEE) and justified findings qualitatively and quantitatively. MAIN OUTCOME MEASURE: Rates of SAP mean deviation (MD) change. RESULTS: The LCMM model discovered four clusters (subtypes) of eyes with different trajectories of MD worsening. The number of eyes in clusters were 794 (25%), 1675 (54%), 531 (17%) and 133 (4%). We labeled the clusters as Improvers (cluster 1), Stables (cluster 2), Slow progressors (cluster 3), and Fast progressors (cluster 4) based on their mean of MD decline rate, which were 0.08, -0.06, -0.21, and -0.45 dB/year, respectively. Eyes with fast VF progression had higher baseline age, intraocular pressure (IOP), pattern standard deviation (PSD) and refractive error (RE), but lower central corneal thickness (CCT). Fast progression was associated with being male, heart disease history, diabetes history, African American race, and stroke history. CONCLUSION: Unsupervised clustering can objectively identify OHT subtypes including those with fast VF worsening without human expert intervention. Fast VF progression was associated with higher history of stroke, heart disease and diabetes. Fast progressors were more from African American race , males and had higher incidence of glaucoma conversion. Subtyping can provide guidance for adjusting treatment plans to slow vision loss and improve quality of life of patients with a faster progression course.

Enhanced oral bioavailability of cannabidiol by flexible zein nanoparticles: in vitro and pharmacokinetic studies.

Introduction: Cannabidiol (CBD) has a variety of pharmacological effects including antiepileptic, antispasmodic, anxiolytic and anti-inflammatory among other pharmacological effects. However, since CBD is a terpene-phenolic compound, its clinical application is limited by its poor water solubility, low stability, and low bioavailability. Methods: In this study, we used several strategies to address the above problems. Hydrochloric acid was used to modify zein to improve the molecular flexibility. Flexible zein nanoparticles (FZP-CBD) loaded with CBD was prepared to improve the stability and bioavailability of CBD. The parameters were evaluated in terms of morphology, particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE%), loading capacity (LC%), and storage stability. Simulated gastrointestinal fluid release experiment and bioavailability assay were applied in the evaluation. Results: The simulated gastrointestinal fluid experiment showed that the release rates of FZP-CBD and natural zein nanoparticles (NZP-CBD) loaded with CBD were 3.57% and 89.88%, respectively, after digestion with gastric fluid for 2 h, 92.12% and 92.56%, respectively, after intestinal fluid digestion for 2 h. Compared with NZP-CBD, the C max of FZP-CBD at 3 different doses of CBD was increased by 1.7, 1.3 and 1.5 times respectively, and AUC0-t was increased by 1.4, 1.1 and 1.7 times respectively, bioavailability (F) was increased by 135.9%, 114.9%, 169.6% respectively. Discussion: The experimental results showed that FZP-CBD could protect most of the CBD from being released in the stomach, and then control its release in the intestines, promote the absorption of CBD in the small intestine, and increase the bioavailability of CBD. Therefore, FZP-CBD could improve the utilization value of CBD and provide a new idea for the application of CBD in medicine and pharmacy.

A High-Throughput Method for Accurate Extraction of Intact Rice Panicle Traits.

Rice panicle traits serve as critical indicators of both yield potential and germplasm resource quality. However, traditional manual measurements of these traits, which typically involve threshing, are not only laborious and time-consuming but also prone to introducing measurement errors. This study introduces a high-throughput and nondestructive method, termed extraction of panicle traits (EOPT), along with the software Panicle Analyzer, which is designed to assess unshaped intact rice panicle traits, including the panicle grain number, grain length, grain width, and panicle length. To address the challenge of grain occlusion within an intact panicle, we define a panicle morphology index to quantify the occlusion levels among the rice grains within the panicle. By calibrating the grain number obtained directly from rice panicle images based on the panicle morphology index, we substantially improve the grain number detection accuracy. For measuring grain length and width, the EOPT selects rice grains using an intersection over union threshold of 0.8 and a confidence threshold of 0.7 during the grain detection process. The mean values of these grains were calculated to represent all the panicle grain lengths and widths. In addition, EOPT extracted the main path of the skeleton of the rice panicle using the Astar algorithm to determine panicle lengths. Validation on a dataset of 1,554 panicle images demonstrated the effectiveness of the proposed method, achieving 93.57% accuracy in panicle grain counting with a mean absolute percentage error of 6.62%. High accuracy rates were also recorded for grain length (96.83%) and panicle length (97.13%). Moreover, the utility of EOPT was confirmed across different years and scenes, both indoors and outdoors. A genome-wide association study was conducted, leveraging the phenotypic traits obtained via EOPT and genotypic data. This study identified single-nucleotide polymorphisms associated with grain length, width, number per panicle, and panicle length, further emphasizing the utility and potential of this method in advancing rice breeding.

Novel Stability Criteria of Asynchronously Switched Nonlinear Neutral Time-Delay Systems.

This article investigates the input-to-state stability and integral input-to-state stability for the switched nonlinear neutral systems (SNNSs) with multiple time-varying delays (MTVDs) and asynchronous switching. According to the fact that the switching signals of the controllers and the subsystems are inconsistent, novel stability criteria on the input-to-state stability and integral input-to-state stability properties for SNNSs with MTVDs and the asynchronous switching phenomenon are presented by multiple Lyapunov-Krasovskii functionals, the merging switching signal, and the mode-dependent average dwell time technique. Compared with the existing related works, our results are less conservative. Meanwhile, our proposed works not only investigate the effects of switches and neutral terms on the stability property for SNNSs but also study the case of the systems with MTVDs and asynchronous switching. Finally, two practical examples, including the practical coupled mass-spring-damper-pendulum system, are presented to show the effectiveness of our results.

MSI2 regulates NLK-mediated EMT and PI3K/AKT/mTOR pathway to promote pancreatic cancer progression.

BACKGROUND: The incidence of pancreatic cancer is increasing by years, and the 5-year survival rate is very low. Our team have revealed that Musashi2 (MSI2) could promote aggressive behaviors in pancreatic cancer by downregulating Numb and p53. MSI2 also facilitates EMT in pancreatic cancer induced by EGF through the ZEB1-ERK/MAPK signaling pathway. This study aims to further explore the molecular mechanisms of MSI2-regulated downstream pathways in pancreatic cancer. METHODS: In vitro and in vivo experiments were conducted to investigate the role and mechanism of MSI2 in promoting malignant behaviors of pancreatic cancer through regulation of NLK. RESULTS: Genes closely related to MSI2 were screened from the GEPIA and TCGA databases. We found that NLK showed the most significant changes in mRNA levels with consistent changes following MSI2 interference and overexpression. The high correlation between MSI2 and NLK was also observed at the protein level. Multivariate analysis revealed that both MSI2 and NLK were independent adverse indicators of survival in pancreatic cancer patients, as well as join together. In vitro, silencing or overexpressing NLK altered cell invasion and migration, by regulating EMT and the PI3K-AKT-mTOR pathway. Silencing MSI2 reduced protein expression in the EMT and PI3K-AKT-mTOR pathways, leading to decreased cell invasion and migration abilities, while these effects could be reversed by overexpression of NLK. In vivo, MSI2 silencing inhibited liver metastasis, which could be reversed by overexpressing NLK. Mechanistically, MSI2 directly binds to the translation regulatory region of NLK mRNA at positions 79-87 nt, enhancing its transcriptional activity and exerting post-transcriptional regulatory roles. The analysis of molecular docking showed the close relationship between MSI2 and NLK in pancreatic cancer patients. CONCLUSIONS: Our findings elucidate the regulatory mechanisms of the MSI2-NLK axis in modulating aggressive behaviors of pancreatic cancer cells, which providing new evidence for therapeutic strategies in pancreatic cancer.

Uncovering the Nexus between Urban Heat Islands and Material Stocks of Built Environment in 335 Chinese Cities.

China's unprecedented rapid urbanization has dramatically reshaped the urban built environment, disrupting the thermal balance of cities. This disruption causes the urban heat island (UHI) effect, adversely affecting urban sustainability and public health. Although studies have highlighted the remarkable impacts of the built environment on UHIs, the specific effects of its various structures and components remain unclear. In this study, a multidimensional remote sensing data set was used to quantify the atmospheric UHIs across 335 Chinese cities from 1980 to 2020. In conjunction with stocks of three end-use sectors and three material groups, the impacts of gridded material stocks on UHI variations were analyzed. The findings reveal that building stocks exert a predominant influence in 48% of cities. Additionally, the extensive use of metal and inorganic materials has increased thermal stress in 220 cities, leading to an average UHI increase of 0.54 °C. The effect of organic materials, primarily arising from mobile heat sources, is continuously increasing. Overall, this study elucidates the effect of the functional structure and material composition of urban landscapes on UHIs, highlighting the complexities associated with the influence of the built environment on the urban heat load.

One-Step Reverse Transcriptase qPCR Method for Serum Hepatitis B Virus RNA Quantification.

In recent years, serum hepatitis B virus (HBV) RNA has been identified as a promising noninvasive surrogate biomarker of intrahepatic covalently closed circular DNA (cccDNA), detection of which requires an invasive liver biopsy in patients with chronic HBV infection. It is impractical to detect intrahepatic cccDNA as a routine diagnosis for chronic hepatitis B (CHB) patients in clinical management. Here, we describe a detailed protocol for serum HBV RNA quantification, which can reflect the activity of intrahepatic cccDNA. The procedure includes three major steps: (1) Simultaneous isolation of HBV DNA and RNA from patients' serum, (2) DNase I digestion for removing HBV DNA contamination, and (3) HBV RNA quantification by one-step reverse transcription qPCR.

Discovery, Optimization, and Biological Evaluation of Novel Pyrazol-5-yl-phenoxybenzamide Derivatives as Potent Succinate Dehydrogenase Inhibitors.

The diphenyl ether molecular pharmacophore has played a significant role in the development of fungicidal compounds. In this study, a variety of pyrazol-5-yl-phenoxybenzamide derivatives were synthesized and evaluated for their potential to act as succinate dehydrogenase inhibitors (SDHIs). The bioassay results indicate certain compounds to display a remarkable and broad-spectrum in their antifungal activities. Notably, compound 12x exhibited significant in vitro activities against Valsa mali, Gaeumannomyces graminis, and Botrytis cinerea, with EC50 values of 0.52, 1.46, and 3.42 mg/L, respectively. These values were lower or comparable to those of Fluxapyroxad (EC50 = 12.5, 1.93, and 8.33 mg/L, respectively). Additionally, compound 12x showed promising antifungal activities against Sclerotinia sclerotiorum (EC50 = 0.82 mg/L) and Rhizoctonia solani (EC50 = 1.86 mg/L), albeit lower than Fluxapyroxad (EC50 = 0.23 and 0.62 mg/L). Further in vivo experiments demonstrated compound 12x to possess effective protective antifungal activities against V. mali and S. sclerotiorum at a concentration of 100 mg/L, with inhibition rates of 66.7 and 89.3%, respectively. In comparison, Fluxapyroxad showed inhibition rates of 29.2 and 96.4% against V. mali and S. sclerotiorum, respectively. Molecular docking analysis revealed that compound 12x interacts with SDH through hydrogen bonding, π-cation, and π-π interactions, providing insights into the probable mechanism of action. Furthermore, compound 12x exhibited greater binding energy and SDH enzyme inhibitory activity than Fluxapyroxad (ΔGcal = -46.8 kcal/mol, IC50 = 1.22 mg/L, compared to ΔGcal = -41.1 kcal/mol, IC50 = 8.32 mg/L). Collectively, our results suggest that compound 12x could serve as a promising fungicidal lead compound for the development of more potent SDHIs for crop protection.

Intra-annual vegetation changes and spatial variation in China over the past two decades based on remote sensing and time-series clustering.

Vegetation is an important link between land, atmosphere, and water, making its changes of great significance. However, existing research has predominantly focused on long-term vegetation changes, neglecting the intra-annual variations of vegetation. Hence, this study is based on the Enhanced Vegetation Index (EVI) data from 2000 to 2022, with a time step of 16 days, to analyze the intra-annual patterns of vegetation changes in China. The average intra-annual EVI values for each municipal-level administrative region were calculated, and the time-series k-means clustering algorithm was employed to divide these regions, exploring the spatial variations in China's intra-annual vegetation changes. Finally, the ridge regression and random forest methods were utilized to assess the drivers of intra-annual vegetation changes. The results showed that: (1) China's vegetation status exhibits a notable intra-annual variation pattern of "high in summer and low in winter," and the changes are more pronounced in the northern regions than in the southern regions; (2) the intra-annual vegetation changes exhibit remarkable regional disparities, and China can be optimally clustered into four distinct clusters, which align well with China's temperature and precipitation zones; and (3) the intra-annual vegetation changes demonstrate significant correlations with meteorological factors such as dew point temperature, precipitation, maximum temperature, and sea-level pressure. In conclusion, our study reveals the characteristics, spatial patterns and driving forces of intra-annual vegetation changes in China, which contribute to explaining ecosystem response mechanisms, providing valuable insights for ecological research and the formulation of ecological conservation and management strategies.

Prevalence and molecular characteristics of intestinal pathogenic Escherichia coli isolated from diarrheal pigs in Southern China.

Intestinal pathogenic Escherichia coli (InPEC) is one of the most common causes of bacterial diarrhea in farm animals, including profuse neonatal diarrhea and post weaning diarrhea (PWD) in piglets. In this study, we investigated the prevalence of InPEC and associated primary virulence factors among 543 non-duplicate E. coli isolates from diarrheal pigs from 15 swine farms in southern China. Six major virulence genes associated with InPEC were identified among 69 (12.71 %) E. coli isolates and included est (6.62 %), K88 (4.79 %), elt (3.68 %), eae (1.47 %), stx2 (0.92 %) and F18 (0.55 %). Three pathotypes of InPEC were identified including ETEC (8.10 %), EPEC (1.29 %) and STEC/ETEC (0.92 %). In particular, K88 was only found in ETEC from breeding farms, whereas F18 was only present in STEC/ETEC hybrid from finishing farms. Whole genome sequence analysis of 37 E. coli isolates revealed that InPEC strains frequently co-carried multiple antibiotic resistance gene (ARG). est, elt and F18 were also found to co-locate with ARGs on a single IncFIB/IncFII plasmid. InPEC isolates from different pathotypes also possessed different profiles of virulence genes and antimicrobial resistance genes. Population structure analysis demonstrated that InPEC isolates from different pathotypes were highly heterogeneous whereas those of the same pathotype were extremely similar. Plasmid analysis revealed that K88 and/or est/elt were found on pGX18-2-like/pGX203-2-like and pGX203-1-like IncFII plasmids, while F18 and elt/est, as well as diverse ARGs were found to co-locate on IncFII/IncFIB plasmids with a non-typical backbone. Moreover, these key virulence genes were flanked by or adjacent to IS elements. Our findings indicated that both clonal expansion and horizontal spread of epidemic IncFII plasmids contributed to the prevalence of InPEC and the specific virulence genes (F4, F18, elt and est) in the tested swine farms.

High blood glucose variability may predict poor outcomes in patients with spontaneous cerebellar hemorrhage undergoing surgical operation: a retrospective study.

BACKGROUND: Elevated blood glucose (BG) variability has been reported as an independent risk factor for poor prognosis in a variety of diseases. This study aimed to investigate the association between BG variability and clinical outcomes in patients with spontaneous cerebellar hemorrhage (SCH) undergoing surgical operation. METHODS: This retrospective cohort study of the consecutive patients admitted to the department of Neurosurgery, the Affiliated Hospital of Qingdao University between January 2014 and June 2022 with the diagnosis of SCH underwent surgical intervention. BG analysis was continuously and routinely performed. BG variability was represented by the standard deviation (SD) of the serial measurements within the first 7 days. The general characteristics, imageological information, blood glucose level, and surgical information were reviewed and compared through medical records. RESULTS: A total of 115 patients (65 male and 50 female) were enrolled. Out of all 115 patients, the overall clinical outcomes according to the modified Rankin Scale (mRS) were poor (mRS 3-6) in 31 patients (26.96%) and good (mRS 0-2) in 84 patients (73.04%). Twelve of the 115 patients died during hospitalization, and the mortality rate was 10.43%. Multivariate logistic regression analysis showed that SD of BG (odds ratio (OR), 4.717; 95% confidence interval (CI), 1.054-21.115; P = 0.043), GCS (OR, 0.563; 95% CI, 0.330-0.958; P = 0.034), and hematoma volume (OR, 1.395; 95% CI, 1.118-1.748; P = 0.003) were significant predictors. The area under the ROC curve of SD of BG was 0.911 (95% CI, 0.850-0.973; P < 0.001) with a sensitivity and specificity of 90.3% and 83.3%, respectively, and the cut-off value was 1.736. CONCLUSIONS: High BG Variability is independently correlated with the 6-month poor outcomes in patients with SCH undergoing surgical operation.

PRRX1-OLR1 axis supports CAFs-mediated lung cancer progression and immune suppression.

OBJECTIVE: To investigate the mechanism by which cancer-associated fibroblasts (CAFs) affect the growth and immune evasion of lung cancer cells. METHODS: Initially, datasets comparing CAFs with normal fibroblasts were downloaded from the GEO dataset GSE48397. Genes with the most significant differential expression were selected and validated using clinical data. Subsequently, CAFs were isolated, and the selected genes were knocked down in CAFs. Co-culture experiments were conducted with H1299 or A549 cells to analyze changes in lung cancer cell growth, migration, and immune evasion in vitro and in vivo. To further elucidate the upstream regulatory mechanism, relevant ChIP-seq data were downloaded from the GEO database, and the regulatory relationships were validated through ChIP-qPCR and luciferase reporter assays. RESULTS: OLR1 was significantly overexpressed in CAFs and strongly correlated with adverse prognosis in lung cancer patients. Knockdown of OLR1 markedly inhibited CAFs' support for the growth and immune evasion of lung cancer cells in vitro and in vivo. ChIP-seq results demonstrated that PRRX1 can promote OLR1 expression by recruiting H3K27ac and H3K4me3, thereby activating CAFs. Knockdown of PRRX1 significantly inhibited CAFs' function, while further overexpression of OLR1 restored CAFs' support for lung cancer cell growth, migration, and immune evasion. CONCLUSION: PRRX1 promotes OLR1 expression by recruiting H3K27ac and H3K4me3, activating CAFs, and thereby promoting the growth, migration, and immune evasion of lung cancer cells.

Intracranial seeding of pituitary neuroendocrine tumor: a case report.

Background: Pituitary neuroendocrine tumors (PitNETs) are predominantly benign, though a minority may exhibit invasive tendencies. A diagnosis of metastatic PitNETs, in the absence of malignant histology, hinges on the identification of craniospinal and/or systemic metastases. Only a minority of PitNETs exhibit intracranial seeding. Notably, craniotomy for PitNETs excision is a prominent catalyst for iatrogenic seeding. Case Description: This article presented a compelling case that 15 years following craniotomy for the resection of a somatotroph PitNET, a lesion emerged at the left frontal base within the ethmoid sinus. Subsequent post-operative pathology unveiled a mature plurihormonal pituitary specific transcription factor 1 (PIT-1)-lineage PitNET. Growth hormone (GH) levels decreased significantly from 22.8 ng/mL pre-operation to 2 ng/mL post-operative, and concurrently, prolactin (PRL) levels decreased from 26.7 ng/mL pre-operation to 4.5 ng/mL post-operation. Furthermore, in the follow-up examination conducted 5 months after the operation, both GH and PRL levels were found to be within the normal range for the patient. This robustly suggested that the initial surgical procedure played a key role in the development of the lesion. Conclusions: This underscores the paramount significance of strictly adhering to the non-tumor removal during craniotomy for PitNETs excision. Regardless of apparent complete resection on imaging, it remains imperative to conduct routine follow-up evaluations, encompassing both imaging studies and hormone level assessments.

Real world risk of discontinuing oral anticoagulation after successful catheter ablation for atrial fibrillation.

Background: Many patients with atrial fibrillation (AF) discontinued oral anticoagulation (OAC) therapy after successful catheter ablation. We aimed to determine the real-world risks and consequences of discontinuing OAC use after catheter ablation for AF. Methods: Patients who underwent successful catheter ablation for AF from January 2004 to December 2020 were divided into continued long-term OAC (On-OAC, n = 1062) and discontinued (Off-OAC, n = 1055) groups. The long-term outcomes including thromboembolic events, major bleeding, all-cause mortality and major adverse cardiovascular events (MACE), were compared between the two groups. Results: The CHA2DS2-VASc score was 3.44 ± 1.12. After a mean follow-up of 37.09 months, thromboembolism risk was higher and major bleeding risk was lower in the Off-OAC than in the On-OAC group (Both log-rank P < 0.001). CHA2DS2-VASc score-stratified subgroup analysis showed similar cumulative event rates between the two groups in men and women with scores of 2 and 3 (intermediate risk for stroke), respectively, (P > 0.05), except for a higher major bleeding rate in the On-OAC group (P = 0.002). Patients at high risk for stroke (men and women with scores ≥3 and ≥ 4) had better non-thromboembolic and non-MACE results (Both log-rank P < 0.05). Conclusion: Men with a CHA2DS2-VASc score of 2 and women with a score of 3 had a relatively low incidence of stroke events after successful catheter ablation for AF and may be safe for anticoagulation cessation. Greater benefits from long-term OAC were observed in men with CHA2DS2-VASc score ≥3 and women with score ≥4.

Veno-arterial extracorporeal membrane oxygenation for the treatment of obstructive shock caused by venous air embolism: A case report.

BACKGROUND: Venous air embolism (VAE) is a potentially lethal condition, with a reported incidence rate of about 0.13%, and the true incidence may be higher since many VAE are asymptomatic. The current treatments for VAE include Durant's maneuver, aspiration and removal of air through venous catheters, and hyperbaric oxygen therapy. For critically ill patients, use of cardiotonic drugs and chest compressions remain useful strategies. The wider availability of extracorporeal membrane oxygenation (ECMO) has brought a new option for VAE patients. CASE SUMMARY: A 53-year-old female patient with VAE presented to the emergency clinic due to abdominal pain with fever for 1 d and unconsciousness for 2 h. One day ago, the patient suffered from abdominal pain, fever, and diarrhea. She suddenly became unconscious after going to the toilet during the intravenous infusion of ciprofloxacin 2 h ago, accompanied by nausea and vomiting, during which a small amount of gastric contents were discharged. She was immediately sent to a local hospital, where cranial and chest computed tomography showed bilateral pneumonia as well as accumulated air visible in the right ventricle and pulmonary artery. The condition deteriorated despite endotracheal intubation, rehydration, and other treatments, and the patient was then transferred to our hospital. Veno-arterial ECMO was applied in our hospital, and the patient's condition gradually improved. The patient was successfully weaned from ECMO and extubated after two days. CONCLUSION: ECMO may be an important treatment for patients with VAE in critical condition.

Unraveling the causes of the Seoul Halloween crowd-crush disaster.

As the world steadily recovers from the COVID-19 pandemic, managing large gatherings becomes a critical concern for ensuring crowd safety. The crowd-crush disaster in Seoul in 2022 highlights the need for effective predictive crowd management techniques. In this study, an empirical analysis of this incident is conducted using data from various sources, and model-based simulations are created to replicate hazardous crowd conditions in high-risk areas. In the empirical analysis, mobile device data indicates a significant increase in population above normal levels in the disaster area just hours before the incident occurred. In the simulations, a hydrodynamic model is employed to simulate a bidirectional collision, which quantitatively demonstrates that the average density during the crush reached 7.57 ped/m2 (with a maximum of (9.95)ped/m2). Additionally, the average crowd pressure peaked at 1,063 N/m (with a maximum of 1,961 N/m), and the maximum velocity entropy was 10.99. Based on these findings, it can be concluded that the primary causes of the disaster were the substantial population, bidirectional collision, and escalating panic. The results of controlled simulations under various management strategies are then presented. By implementing effective crowd management techniques, crowd safety can be enhanced through quantitative comparisons of these key indicators.

Effect of microwaves combined with peracetic acid to improve the dewatering performance of residual sludge.

The activated sludge process plays a crucial role in modern wastewater treatment plants. During the treatment of daily sewage, a large amount of residual sludge is generated, which, if improperly managed, can pose burdens on the environment and human health. Additionally, the highly hydrated colloidal structure of biopolymers limits the rate and degree of dewatering, making mechanical dewatering challenging. This study investigates the impact and mechanism of microwave irradiation (MW) in conjunction with peracetic acid (PAA) on the dewatering efficiency of sludge. Sludge dewatering effectiveness was assessed through capillary suction time (CST) and specific resistance to filtration (SRF). Examination of the impact of MW-PAA treatment on sludge dewatering performance involved assessing the levels of extracellular polymeric substances (EPS), employing three-dimensional excitation-emission matrix (3D-EEM), Fourier transform-infrared spectroscopy (FT-IR), and scanning electron microscopy. Findings reveal that optimal dewatering performance, with respective reductions of 91.22% for SRF and 84.22% for CST, was attained under the following conditions: microwave power of 600 W, reaction time of 120 s, and PAA dosage of 0.25 g/g MLSS. Additionally, alterations in both sludge EPS composition and floc morphology pre- and post-MW-PAA treatment underwent examination. The findings demonstrate that microwaves additionally boost the breakdown of PAA into •OH radicals, suggesting a synergistic effect upon combining MW-PAA treatment. These pertinent research findings offer insights into employing MW-PAA technology for residual sludge treatment.

Engineering an enzyme-like catalytic sensor for on-site dual-mode evaluation of total antioxidant capacity.

A novel Fe-MoOx nanozyme, engineered with enhanced peroxidase (POD)-like activity through strategic doping and the creation of oxygen vacancies, is introduced to catalyze the oxidation of TMB with high efficiency. Furthermore, Fe-MoOx is responsive to single electron transfer (SET) and hydrogen atom transfer (HAT) mechanisms related to antioxidants and can serve as a desirable nanozyme for total antioxidant capacity (TAC) determination. The TAC colorimetric platform can reach a low LOD of 0.512 µM in solution and 24.316 µM in the smartphone-mediated RGB hydrogel (AA as the standard). As proof of concept, the practical application in real samples was explored. The work paves a promising avenue to design diverse nanozymes for visual on-site inspection of food quality.

Efficacy and Safety of High-Dose TBS on Post-Stroke Upper Extremity Motor Impairment: A Randomized Controlled Trial.

BACKGROUND: Upper extremity (UE) motor function impairment is a major poststroke complication whose recovery remains one of the most challenging tasks in neurological rehabilitation. This study examined the efficacy and safety of the personalized neuroimaging-guided high-dose theta-burst stimulation (TBS) for poststroke UE motor function recovery. METHODS: Patients after stroke with UE motor impairment from a China rehabilitation center were randomly assigned to receive high-dose intermittent TBS (iTBS) to ipsilesional UE sensorimotor network, continuous TBS (cTBS) to contralesional UE sensorimotor network, or sham stimulation, along with conventional therapy for 3 weeks. The primary outcome was the score changes on the Fugl-Meyer assessment-UE from baseline to 1 and 3 weeks. The secondary outcomes included the response rate on Fugl-Meyer assessment-UE scores posttreatment (≥9-point improvement) and score changes in multidimensional scales measuring UE, lower extremity, and activities and participation. RESULTS: From June 2021 to June 2022, 45 participants were randomized and 43 were analyzed. The iTBS and continuous TBS groups showed significantly greater improvement in Fugl-Meyer assessment-UE (mean improvement, iTBS: 10.73 points; continuous TBS: 10.79 points) than the sham group (2.43 points) and exhibited significantly greater response rates on Fugl-Meyer assessment-UE (iTBS, 60.0%; continuous TBS, 64.3%) than the sham group (0.0%). The active groups consistently exhibited superior improvement on the other 2 UE assessments at week 3. However, only the iTBS group showed greater efficacy on 1 lower extremity assessment than the sham group at week 3. Both active groups showed significant improvements in activities and participation assessments. CONCLUSIONS: The study provides evidence for the efficacy and safety of high-dose TBS in facilitating poststroke UE rehabilitation. REGISTRATION: URL: www.chictr.org.cn; Unique identifier: ChiCTR2100047340.

APG-1252 combined with Cabozantinib inhibits hepatocellular carcinoma by suppressing MEK/ERK and CREB/Bcl-xl pathways.

BACKGROUND AND PURPOSE: Liver cancer is the fourth leading cause of cancer-related death worldwide, with hepatocellular carcinoma (HCC) being the most common type of primary liver cancer. APG-1252 is a small molecule inhibitor targeting Bcl-2 and Bcl-xl. However, its anti-tumor effects in HCC, alone or in combination with Cabozantinib, have not been extensively studied. EXPERIMENTAL: Approach: TCGA database analysis was used to analysis the gene expression levels of Bcl-2 and Bcl-xl in HCC tissues. Western blot was employed to detect the protein expression levels. And the inhibitory effects of APG-1252 and Cabozantinib on the proliferation of HCC cell lines was detected by CCK-8. The effect on the migration and invasion of HCC cells was verified by transwell assay. Huh7 xenograft model in nude mice was used to investigate the combination antitumor effect in vivo. KEY RESULTS: Our study demonstrated that APG-1252 monotherapy inhibited the proliferation and migration ability of HCC cells, and induced HCC cells apoptosis. The combination of APG-1252 and Cabozantinib showed significant synergistic antitumor effects. Furthermore, the in vivo experiment demonstrated that the combination therapy exerted a synergistic effect in delaying tumor growth, notably downregulating MEK/ERK phosphorylation levels. In terms of mechanism, Cabozantinib treatment caused an increase in the phosphorylation levels of CREB and Bcl-xl proteins, while the combination with APG-1252 mitigated this effect, thereby enhanced the antitumor effect of Cabozantinib. CONCLUSION AND IMPLICATIONS: Our findings suggest that APG-1252 in combination with Cabozantinib offers a more effective treatment strategy for HCC patients, warranting further clinical investigation.