Tailoring aberration-free photonic nanojets through the illumination of dielectric cylinders using cylindrical vector beams.

This study explores the manipulation of photonic nanojets (PNJs) via axial illumination of cylindrical dielectric particles with cylindrical vector beams (CVBs). The edge diffraction effect of cylindrical particles is harnessed to achieve the near-field focusing of CVBs, minimizing the spherical aberration's impact on the quality of the PNJ. By discussing how beam width, refractive index, and particle length affect PNJs under radially polarized incidence, a simple and effective approach is demonstrated to generate rod-like PNJs with uniform transmission distances and super-diffraction-limited PNJs with pure longitudinal polarization. Azimuthal polarization, on the other hand, generates tube-like PNJs. These PNJs maintain their performance across scale. Combining edge diffraction with CVBs offers innovative PNJ modulation schemes, paving the way for potential applications in particle trapping, super-resolution imaging, photo-lithography, and advancing mesotronics and related fields.

Scalp acupuncture guidance for identifying the optimal site for transcranial electrical stimulation of the hand.

Transcranial electrical stimulation (tES) often targets the EEG-guided C3/C4 area that may not accurately represent M1 for hand muscles. This study aimed to determine if the neuroanatomy-based scalp acupuncture-guided site (AC) was a more effective spot than the C3 site for neuromodulation. Fifteen healthy subjects received one 20-minute session of high-definition transcranial alternating current stimulation (HD-tACS) intervention (20 Hz at 2 mA) at the AC or C3 sites randomly with a 1-week washout period. Subjects performed ball-squeezing exercises with the dominant hand during the HD-tACS intervention. The AC site was indiscernible from the finger flexor hotspot detected by TMS. At the baseline, the MEP amplitude from finger flexors was greater with less variability at the AC site than at the C3 site. HD-tACS intervention at the AC site significantly increased the MEP amplitude. However, no significant changes were observed after tACS was applied to the C3 site. Our results provide evidence that HD-tACS at the AC site produces better neuromodulation effects on the flexor digitorum superficialis (FDS) muscle compared to the C3 site. The AC localization approach can be used for future tES studies.

New options for endoscopic treatment of gastric varices.

BACKGROUND: Gastric venous bleeding is one of the most common adverse events in liver cirrhosis. The therapeutic effect of isolated gastric varices is relatively clear. However, there is no appropriate clinical and endoscopic treatment for extensive variceal bleeding in the gastric fundus and body. METHODS: In this patient with non-isolated gastric varices, we decided to perform endoscopic multi-point ligation of the obvious varices in the gastric fundus and body. RESULTS: In this patient, endoscopic treatment of gastric varices with bleeding after surgery achieved a significant therapeutic effect. Reexamination of gastroscopy at 3 months after operation showed that multiple scars were formed in the gastric fundus and fundus, and no obvious varices were found. CONCLUSIONS: For patients with non-isolated gastric varices, endoscopic multi-point ligation is a safe and effective treatment option for the varices with obvious gastric fundus and body.

SENP1-Mediated HSP90ab1 DeSUMOylation in Cardiomyocytes Prevents Myocardial Fibrosis by Paracrine Signaling.

Myocardial infarction (MI) triggers a poor ventricular remodeling response, but the underlying mechanisms remain unclear. Here, the authors show that sentrin-specific protease 1 (SENP1) is downregulated in post-MI mice and in patients with severe heart failure. By generating cardiomyocyte-specific SENP1 knockout and overexpression mice to assess cardiac function and ventricular remodeling responses under physiological and pathological conditions. Increased cardiac fibrosis in the cardiomyocyte-specific SENP1 deletion mice, associated with increased fibronectin (Fn) expression and secretion in cardiomyocytes, promotes fibroblast activation in response to myocardial injury. Mechanistically, SENP1 deletion in mouse cardiomyocytes increases heat shock protein 90 alpha family class B member 1 (HSP90ab1) SUMOylation with (STAT3) activation and Fn secretion after ventricular remodeling initiated. Overexpression of SENP1 or mutation of the HSP90ab1 Lys72 ameliorates adverse ventricular remodeling and dysfunction after MI. Taken together, this study identifies SENP1 as a positive regulator of cardiac repair and a potential drug target for the treatment of MI. Inhibition of HSP90ab1 SUMOylation stabilizes STAT3 to inhibit the adverse ventricular remodeling response.

Corrigendum: High-definition transcranial direct current stimulation for upper extremity rehabilitation in moderate-to-severe ischemic stroke: a pilot study.

[This corrects the article DOI: 10.3389/fnhum.2023.1286238.].

Machine learning-based CT radiomics enhances bladder cancer staging predictions: A comparative study of clinical, radiomics, and combined models.

BACKGROUND: Predicting the accurate preoperative staging of bladder cancer (BLCA), which markedly affects treatment decisions and patient outcomes, using traditional clinical parameters is challenging. Nevertheless, emerging studies in radiomics, especially machine learning-based computed tomography (CT) image-based radiomics, hold promise in improving stage prediction accuracy in various tumors. However, the comparative performance and clinical utility of models for BLCA are under investigation. PURPOSE: We aimed to investigate the application value of machine learning-based CT radiomics in preoperative staging prediction by comparing the performance of clinical, radiomics, and clinical-radiomics combined models. METHODS: A retrospective cohort of 105 patients with initial BLCA was randomized into training (70%) and testing (30%) cohorts. Radiomics features were extracted from CT images using the optimal feature filter, followed by the application of the least absolute shrinkage and selection operator algorithm for optimum feature selection. Furthermore, machine learning algorithms were used to establish a radiomics model within the training cohort. Independent risk factors for muscle-invasive BLCA (MIBC) obtained by multivariate logistic regression (LR) analysis were separately used to construct a clinical model. For a clinical-radiomics fusion model, radiomics features were combined with clinical parameters. Performance was evaluated based on receiver operating characteristic curves, calibration curves, decision curve analysis (DCA), and standard performance metrics. RESULTS: Patients exhibited a significantly higher age (p = 0.029), larger tumor size (p = 0.01), and an increased neutrophil-to-lymphocyte ratio (NLR; p = 0.045) in the MIBC group than in the NMIBC group. LR analysis revealed age (p = 0.026), tumor size (p = 0.007), and NLR (p = 0.019) as significant predictors for constructing the clinical model. In the testing cohort, the radiomics model, which used an Support Vector Machine classifier, achieved the highest area under the curve (AUC) value of 0.857. The clinical-radiomics model outperformed the remaining two models, with AUC values of 0.958 and 0.893 in the training and testing cohorts, respectively. DeLong's test indicated significant differences between the three models. Calibration curves showed good agreement, and DCA confirmed the superior clinical utility of the clinical-radiomics model. CONCLUSIONS: Machine learning-based CT radiomics combined with clinical parameters was a promising approach in staging BLCA accurately, which outperformed the individual models. Integrating radiomics features with clinical information holds the potential to improve personalized treatment planning and patient outcomes in BLCA.

Significance and Possible Biological Mechanism for CLDN8 Downregulation in Kidney Renal Clear Cell Carcinoma Tissues.

Background: The clinical role of claudin 8 (CLDN8) in kidney renal clear cell carcinoma (KIRC) remains unclarified. Herein, the expression level and potential molecular mechanisms of CLDN8 underlying KIRC were determined. Methods: High-throughput datasets of KIRC were collected from GEO, ArrayExpress, SRA, and TCGA databases to determine the mRNA expression level of the CLDN8. In-house tissue microarrays and immunochemistry were performed to examine CLDN8 protein expression. A summary receiver operating characteristic curve (SROC) and standardized mean difference (SMD) forest plot were generated using Stata v16.0. Single-cell analysis was conducted to further prove the expression level of CLDN8. A clustered regularly interspaced short palindromic repeats knockout screen analysis was executed to assess the growth impact of CLDN8. Functional enrichment analysis was conducted using the Metascape database. Additionally, single-sample gene set enrichment analysis was implied to explore immune cell infiltration in KIRC. Results: A total of 17 mRNA datasets comprising 1,060 KIRC samples and 452 non-cancerous control samples were included in this study. Additionally, 105 KIRC and 16 non-KIRC tissues were analyzed using in-house immunohistochemistry. The combined SMD was -5.25 (95% confidence interval (CI): -6.13 to -4.37), and CLDN8 downregulation yielded an SROC area under the curve (AUC) close to 1.00 (95% CI: 0.99 - 1.00). CLDN8 downregulation was also confirmed at the single-cell level. Knocking out CLDN8 stimulated KIRC cell proliferation. Lower CLDN8 expression was correlated with worse overall survival of KIRC patients (hazard ratio of CLDN8 downregulation = 1.69, 95% CI: 1.2 - 2.4). Functional pathways associated with CLDN8 co-expressed genes were centered on carbon metabolism obstruction, with key hub genes ACADM, ACO2, NDUFS1, PDHB, SDHD, SUCLA2, SUCLG1, and SUCLG2. Conclusions: CLDN8 is downregulated in KIRC and is considered a potential tumor suppressor. CLDN8 deficiency may promote the initiation and progression of KIRC, potentially in conjunction with metabolic dysfunction.

Early detection of pancreatic cancer in patients with recurrent pancreatitis: A case report.

BACKGROUND: Pancreatic cancer presents a challenge with its low early diagnosis and treatment rates, leading to high metastasis and mortality rates. The median survival time for advanced pancreatic cancer is a mere 3 months. However, there's hope: small pancreatic cancers diagnosed at an early stage (T1) or those less than or equal to 1 cm in diameter boast an impressive 5-year survival rate of nearly 100%. This underscores the critical importance of early pancreatic cancer detection for significantly improving prognosis. CASE SUMMARY: Pancreatic cancer, a malignant tumor of the digestive tract, poses challenges in both diagnosis and treatment due to its occult and atypical clinical symptoms. Clinically, patients with recurrent pancreatitis should be vigilant, as it may be indicative of pancreatic cancer, particularly in middle-aged and elderly patients. Here, we presented the case of a patient who experienced recurrent acute pancreatitis within a span of 2 months. During the initial episode of pancreatitis, routine imaging failed to identify the cause of pancreatic cancer. However, upon recurrence of acute pancreatitis, endoscopic ultrasonography (EUS) revealed a space-occupying lesion approximately 1 cm in size in the pancreatic body. Subsequent EUS coupled with fine-needle aspiration examination demonstrated atypical pancreatic gland epithelium. Ultimately, the patient underwent surgery and was diagnosed with an intraductal papillary mucinous tumor of the pancreas (severe epithelial dysplasia, focal cancer). CONCLUSION: We recommend EUS for patients with recurrent pancreatitis of unknown etiology to exclude early pancreatic cancer.

Physiology, Biochemistry, and Transcriptomics Jointly Reveal the Phytotoxicity Mechanism of Acetochlor on Pisum sativum L.

Acetochlor, as a commonly used pre-emergent herbicide, can be toxic to crops and affect production if used improperly. However, the toxic mechanism of acetochlor on plants is not fully understood. The present study used a combination of transcriptomic analysis and physiological measurements to investigate the effects of short-term (15-day) exposure to different concentrations of acetochlor (1, 10, 20 mg/kg) on the morphology, physiology, and transcriptional levels of pea seedlings, aiming to elucidate the toxic response and resistance mechanisms in pea seedlings under herbicide stress. The results showed that the toxicity of acetochlor to pea seedlings was dose-dependent, manifested as dwarfing and stem base browning with increasing concentrations, especially at 10 mg/kg and above. Analysis of the antioxidant system showed that from the 1 mg/kg treatment, malondialdehyde, superoxide dismutase, peroxidase, and glutathione peroxidase in peas increased with increasing concentrations of acetochlor, indicating oxidative damage. Analysis of the glutathione (GSH) metabolism system showed that under 10 mg/kg treatment, the GSH content of pea plants significantly increased, and GSH transferase activity and gene expression were significantly induced, indicating a detoxification response in plants. Transcriptomic analysis showed that after acetochlor treatment, differentially expressed genes in peas were significantly enriched in the phenylpropane metabolic pathway, and the levels of key metabolites (flavonoids and lignin) were increased. In addition, we found that acetochlor-induced dwarfing of pea seedlings may be related to gibberellin signal transduction. Environ Toxicol Chem 2024;00:1-15. © 2024 SETAC.

Embryo thermal manipulation enhances mitochondrial function in the skeletal muscle of heat-stressed broilers by regulating transient receptor potential V2 expression.

Heat stress induces mitochondrial dysfunction, thereby impeding skeletal muscle development and significantly impacting the economic efficiency of poultry production. This study aimed to investigate the effects of embryo thermal manipulation (TM, 41.5°C, 65% RH, 3 h/d during 16-18th embryonic age) on the mitochondrial function of the pectoralis major (PM) in broiler chickens exposed to thermoneutral (24 ± 1°C, 60% RH) or cyclic heat stress (35 ± 1°C, 60% RH, 12 h/d) from day 22 to 28, and to explore potential mechanisms involving transient receptor potential V2 (TRPV2). Additionally, in vitro experiments were conducted to assess the regulatory effects of TRPV2 pharmacological activation and inhibition on mitochondrial function in primary myotubes. The results revealed that TM had no discernible effect on the body weight and feed intake of broiler chickens under heat stress conditions (P > 0.05). However, it did delay the increase in rectal temperature and accelerate the decrease in serum T3 levels (P < 0.05). Furthermore, TM promoted the development of PM muscle fibers, significantly increasing myofiber diameter and cross-sectional area (P < 0.05). Under heat stress conditions, TM significantly upregulated the expression of mitochondrial electron transport chain (ETC) genes and TRPV2 in broiler PM muscle (P < 0.05), with a clear positive correlation observed between the two (P < 0.05). In vitro, pharmacological activation of TRPV2 not only increased its own expression but also enhanced mitochondrial ETC genes expression and oxidative phosphorylation function by upregulating intracellular calcium ion levels (P < 0.05). Conversely, TRPV2 inhibition had the opposite effect. Overall, this study underscores the potential of prenatal thermal manipulation in regulating postnatal broiler skeletal muscle development and mitochondrial function through the modulation of TRPV2 expression.

Astaxanthin Rescues Memory Impairments in Rats with Vascular Dementia by Protecting Against Neuronal Death in the Hippocampus.

Vascular dementia (VaD) is a cognitive disorder characterized by a decline in cognitive function resulting from cerebrovascular disease. The hippocampus is particularly susceptible to ischemic insults, leading to memory deficits in VaD. Astaxanthin (AST) has shown potential therapeutic effects in neurodegenerative diseases. However, the mechanisms underlying its protective effects in VaD and against hippocampal neuronal death remain unclear. In this study, We used the bilateral common carotid artery occlusion (BCCAO) method to establish a chronic cerebral hypoperfusion (CCH) rat model of VaD and administered a gastric infusion of AST at 25 mg/kg per day for 4 weeks to explore its therapeutic effects. Memory impairments were assessed using Y-maze and Morris water maze tests. We also performed biochemical analyses to evaluate levels of hippocampal neuronal death and apoptosis-related proteins, as well as the impact of astaxanthin on the PI3K/Akt/mTOR pathway and oxidative stress. Our results demonstrated that AST significantly rescued memory impairments in VaD rats. Furthermore, astaxanthin treatment protected against hippocampal neuronal death and attenuated apoptosis. We also observed that AST modulated the PI3K/Akt/mTOR pathway, suggesting its involvement in promoting neuronal survival and synaptic plasticity. Additionally, AST exhibited antioxidant properties, mitigating oxidative stress in the hippocampus. These findings provide valuable insights into the potential therapeutic effects of AST in VaD. By elucidating the mechanisms underlying the actions of AST, this study highlights the importance of protecting hippocampal neurons and suggests potential targets for intervention in VaD. There are still some unanswered questions include long-term effects and optimal dosage of the use in human. Further research is warranted to fully understand the therapeutic potential of AST and its application in the clinical treatment of VaD.

Significant liver histological change is common in HBeAg-positive chronic hepatitis B with normal ALT.

BACKGROUND AND AIMS: Numerous HBeAg-positive chronic hepatitis B (CHB) patients with persistently normal ALT have significant liver histopathology. It is imperative to identify true "immune tolerant" patients. We aimed to evaluate the liver histopathology features of HBeAg-positive CHB patients with normal ALT and the incidence of liver cirrhosis and HCC in CHB patients during follow-up. METHODS: 179 HBeAg-positive CHB patients with normal ALT who performed liver biopsy from 2009 to 2018 were retrospectively analyzed. Liver necroinflammation ≥ G2 and/or liver fibrosis ≥ S2 was defined as significant liver histopathological change. RESULTS: 57.5% patients were in the indeterminate phase with significant liver histological changes. The proportion of the patients with evident liver necroinflammation was higher in the high-normal ALT group (21-40U/L) when compared with the low-normal ALT group (≤ 20 U/L) (51.3% vs. 30.0%, p < 0.05), and patients aged ≥ 40 years had a higher proportion of significant fibrosis than those aged < 40 years (64.5% vs. 39.9%, p < 0.05). The percentages of patients with ≥ S2 and ≥ G2/S2 in the HBV DNA < 107 IU/mL group were higher than those in the HBV DNA ≥ 107 IU/mL group (72.7% vs. 40.1%, p < 0.01; 81.8% vs. 54.1%, p < 0.05). During follow-up, two of immune tolerant patients and four of indeterminate patients developed into cirrhosis, and one of immune tolerant patients and one of indeterminate patients developed into HCC, respectively. CONCLUSIONS: HBeAg-positive CHB patients with high-normal ALT or HBV DNA < 107 IU/mL were tend to be indeterminate. Liver biopsy or noninvasive approaches are recommended to evaluate liver histopathology, and antiviral therapy is recommended for patients with significant liver histopathology.

Research Progress of Flexible Piezoresistive Sensors Based on Polymer Porous Materials.

Flexible piezoresistive sensors are in high demand in areas such as wearable devices, electronic skin, and human-machine interfaces due to their advantageous features, including low power consumption, excellent bending stability, broad testing pressure range, and simple manufacturing technology. With the advancement of intelligent technology, higher requirements for the sensitivity, accuracy, response time, measurement range, and weather resistance of piezoresistive sensors are emerging. Due to the designability of polymer porous materials and conductive phases, and with more multivariate combinations, it is possible to achieve higher sensitivity and lower detection limits, which are more promising than traditional flexible sensor materials. Based on this, this work reviews recent advancements in research on flexible pressure sensors utilizing polymer porous materials. Furthermore, this review examines sensor performance optimization and development from the perspectives of three-dimensional porous flexible substrate regulation, sensing material selection and composite technology, and substrate and sensing material structure design.

Nrf2 deficiency exacerbated pulmonary pyroptosis in maternal hypoxia-induced intrauterine growth restriction offspring mice.

Maternal prenatal hypoxia is an important contributor to intrauterine growth restriction (IUGR), which impedes fetal lung maturation and leads to the development of chronic lung diseases. Although evidence suggests the involvement of pyroptosis in IUGR, the molecular mechanism of pyroptosis is still unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been found to potentially interact with gasdermin D (GSDMD), the key protein responsible for pyroptosis, indicating its crucial role in inhibiting pyroptosis. Therefore, we hypothesized that Nrf2 deficiency is a key molecular responsible for lung pyroptosis in maternal hypoxia-induced IUGR offspring mice. Pregnant WT and Nrf2-/- mice were exposed to hypoxia (10.5% O2) to mimic IUGR model. We assessed body weight, lung histopathology, pulmonary angiogenesis, oxidative stress levels, as well as mRNA and protein expressions related to inflammation in the 2-week-old offspring. Additionally, we conducted a dual-luciferase reporter assay to confirm the targeting relationship between Nrf2 and GSDMD. Our findings revealed that offspring with maternal hypoxia-induced IUGR exhibited reduced birth weight, catch-up growth delay, and pulmonary dysplasia. Furthermore, we observed impaired nuclear translocation of Nrf2 and increased GSDMD-mediated pyroptosis in these offspring with IUGR. Moreover, the dual-luciferase reporter assay demonstrated that Nrf2 could directly inhibit GSDMD transcription; deficiency of Nrf2 exacerbated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR. Collectively, our findings suggest that Nrf2 deficiency induces GSDMD-mediated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR; thus highlighting the potential therapeutic approach of targeting Nrf2 for treating prenatal hypoxia-induced pulmonary dysplasia in offspring.

FAK inhibitors in cancer, a patent review - an update on progress.

INTRODUCTION: Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase over-expressed in various malignancies which is related to various cellular functions such as adhesion, metastasis and proliferation. AREAS COVERED: There is growing evidence that FAK is a promising therapeutic target for designing inhibitors by regulating the downstream pathways of FAK. Some potential FAK inhibitors have entered clinical phase research. EXPERT OPINION: FAK could be an effective target in medicinal chemistry research and there were a variety of FAKIs have been patented recently. Here, we updated an overview of design, synthesis and structure-activity relationship of chemotherapeutic FAK inhibitors (FAKIs) from 2017 until now based on our previous work. We hope our efforts can broaden the understanding of FAKIs and provide new ideas and insights for future cancer treatment from medicinal chemistry point of view.

Machine learning prediction model for gray-level co-occurrence matrix features of synchronous liver metastasis in colorectal cancer.

BACKGROUND: Synchronous liver metastasis (SLM) is a significant contributor to morbidity in colorectal cancer (CRC). There are no effective predictive device integration algorithms to predict adverse SLM events during the diagnosis of CRC. AIM: To explore the risk factors for SLM in CRC and construct a visual prediction model based on gray-level co-occurrence matrix (GLCM) features collected from magnetic resonance imaging (MRI). METHODS: Our study retrospectively enrolled 392 patients with CRC from Yichang Central People's Hospital from January 2015 to May 2023. Patients were randomly divided into a training and validation group (3:7). The clinical parameters and GLCM features extracted from MRI were included as candidate variables. The prediction model was constructed using a generalized linear regression model, random forest model (RFM), and artificial neural network model. Receiver operating characteristic curves and decision curves were used to evaluate the prediction model. RESULTS: Among the 392 patients, 48 had SLM (12.24%). We obtained fourteen GLCM imaging data for variable screening of SLM prediction models. Inverse difference, mean sum, sum entropy, sum variance, sum of squares, energy, and difference variance were listed as candidate variables, and the prediction efficiency (area under the curve) of the subsequent RFM in the training set and internal validation set was 0.917 [95% confidence interval (95%CI): 0.866-0.968] and 0.09 (95%CI: 0.858-0.960), respectively. CONCLUSION: A predictive model combining GLCM image features with machine learning can predict SLM in CRC. This model can assist clinicians in making timely and personalized clinical decisions.

Large pre-trained models for treatment effect estimation: Are we there yet?

Deep learning for causal inference is a promising technique that leverages deep neural networks to infer counterfactuals and estimate treatment effects. Liu et al. proposed CURE (causal treatment effect estimation), a new pre-training and fine-tuning framework for treatment effects estimation using large-scale patient data.

Catalyst-free selective oxidation of C(sp3)-H bonds in toluene on water.

The anisotropic water interfaces provide an environment to drive various chemical reactions not seen in bulk solutions. However, catalytic reactions by the aqueous interfaces are still in their infancy, with the emphasis being on the reaction rate acceleration on water. Here, we report that the oil-water interface activates and oxidizes C(sp3)-H bonds in toluene, yielding benzaldehyde with high selectivity (>99%) and conversion (>99%) under mild, catalyst-free conditions. Collision at the interface between oil-dissolved toluene and hydroxyl radicals spontaneously generated near the water-side interfaces is responsible for the unexpectedly high selectivity. Protrusion of free OH groups from interfacial water destabilizes the transition state of the OH-addition by forming π-hydrogen bonds with toluene, while the H-abstraction remains unchanged to effectively activate C(sp3)-H bonds. Moreover, the exposed free OH groups form hydrogen bonds with the produced benzaldehyde, suppressing it from being overoxidized. Our investigation shows that the oil-water interface has considerable promise for chemoselective redox reactions on water without any catalysts.