Oral microbiota diversity in moderate to severe plaque psoriasis, nail psoriasis and psoriatic arthritis.

Gaining a comprehensive understanding of the role played by the oral microbiome in moderate to severe plaque psoriasis and its potential implications for disease management and development holds significant importance. With the objective of exploring correlations between the oral microbiota and severe psoriasis, this study involved 72 severe psoriasis patients and 16 healthy individuals, whose clinical manifestations and living habits were carefully recorded. Cutting-edge techniques such as 16S rRNA gene sequencing and bioinformatics analysis were employed to compare the microbial flora, investigating dynamic changes among severe plaque psoriasis patients, psoriatic arthritis patients and healthy individuals. The findings revealed noteworthy patterns including increased levels of Aggregatibacter in the psoriatic arthritis group, accompanied by a decrease in the level of Prevotella. Moreover, the enrichment o Capnocytandophaga (P = 0.009), Campylobacter (P = 0.0022), and Acetobacter (P = 0.0292) was notably more substantial in the psoriasis group compared to the control group, whereas certain bacterial species such as Bacteroides (P = 0.0049), Muribaculaceae (P = 0.0048) demonstrated decreased enrichment. Additionally, the psoriatic arthritis group exhibited significantly higher levels of Ralstonia, Bifidobacterium and Micromonospora. Based on these findings, it can be inferred that individuals with lower levels of Prevotella and higher levels of Corynebacterium may be more susceptible to psoriasis exacerbation.

Integrated analysis of remote sensing with meteorological and health data for allergic rhinitis forecasting in Tianjin.

Long time series of vegetation monitoring can be carried out by remote sensing data, the level of urban greening is objectively described, and the spatial characteristics of plant pollen are indirectly understood. Pollen is the main allergen in patients with seasonal allergic rhinitis. Meteorological factors affect the release and diffusion of pollen. Therefore, studying of the complex relationship between meteorological factors and allergic rhinitis is essential for effective prevention and treatment of the disease. In this study, we leverage remote sensing data for a comprehensive decade-long analysis of urban greening in Tianjin, which exhibits an annual increase in vegetative cover of 0.51 per annum, focusing on its impact on allergic rhinitis through changes in pollen distribution. Utilizing high-resolution imagery, we quantify changes in urban Fractional Vegetation Coverage (FVC) and its correlation with pollen types and allergic rhinitis cases. Our analysis reveals a significant correlation between FVC trends and pollen concentrations, with a surprising value of 0.71, highlighting the influence of urban greenery on allergenic pollen levels. We establish a robust connection between the seasonal patterns of pollen outbreaks and allergic rhinitis consultations, with a noticeable increase in consultations during high pollen seasons. our findings indicate a higher allergenic potential of herbaceous compared to woody vegetation. This nuanced understanding underscores the importance of pollen sensitivity, alongside concentration, in driving allergic rhinitis incidents. Utilizing a Generalized Linear Model, significant features influencing the number of visits for allergic rhinitis (P < 0.05) were identified. Both GLM and LSTM models were employed to forecast the visitation volumes for rhinitis during the spring and summer-autumn of 2022. Upon validation, it was found that the R² values between the simulated and actual values for both GLM and LSTM models surpassed the 95% confidence threshold. Moreover, the R² values for the summer-autumn seasons (GLM: 0.56, LSTM: 0.72) were higher than those for spring (GLM: 0.22, LSTM: 0.47). Comparing the errors between the simulated and actual values of GLM and LSTM models, LSTM exhibited higher simulation precision in both spring and summer-autumn seasons, demonstrating superior simulation performance. Overall, our study pioneers the integration of remote sensing with meteorological and health data for allergic rhinitis forecasting. This integrative approach provides valuable insights for public health planning, particularly in urban settings, and lays the groundwork for advanced, location-specific allergenic pollen forecasting and mitigation strategies.

Formation processes and mechanisms of a fault-controlled colluvial landslide in the Qinling-Daba Mountains, China.

Faults play a crucial role in shaping the formation and damage patterns of landslides in the mountainous region, particularly in Qinling-Daba (Qinba) area in China. On 6 October 2022, following a 4-day rainfall event totaling 221.5 mm, a landslide occurred in Hanwang Town, Shaanxi Province. The left boundary of the landslide coincided with a fault, which influence the formation and movement development of the landslide. To further understand and quantified the formation process and damage mechanism of the landslide, a comprehensive study was conducted, incorporating field investigations, local rainfall data, and various methods including unmanned aerial vehicles (UAVs), numerical simulations, and laboratory test. The results indicate that fault dictate the formation of the Lijiaping landslide by influencing the mechanical strength of the rock mass and the catchment topography in the landslide area. Due to fault, the rock mass in the landslide area is high fragmentation, with a softening coefficient of about 0.52. Weathering resulted in numerous residual and slope sediments in the landslide area, providing ample material for the landslide. Meanwhile, the fault activity led to a wedge-shaped topography in the landslide area, with an average Terrain Wetness Index (TWI) of 3.43, significantly higher than the Hanwang Township average of 1.47. This creates a hydrogeological structure favorable for landslides. Numerical simulations revealed that the maximum velocity of the landslide reached 5.05 m/s and the maximum displacement was 53.18 m, both occurring in the central part of the landslide. These findings offer crucial scientific insights for understanding and preventing similar geological hazards.

Alleviative effects of C60 fullerene nanoparticles on arsenate transformation and toxicity to Danio rerio.

Widely-used C60 fullerene nanoparticles (C60) result in their release into the aquatic environment, which may affect the distribution and toxicity of pollutants such as arsenic (As), to aquatic organism. In this study, arsenate (As(V)) accumulation, speciation and subcellular distribution was determined in Danio rerio (zebrafish) intestine, head and muscle tissues in the presence of C60. Meanwhile we compared how single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs), graphene oxide (GO) and graphene (GN) nanoparticles alter the behaviors of As(V). Results showed that C60 significantly inhibited As accumulation and toxicity in D. rerio, due to a decrease in total As and monomethylarsonic acid (MMA) and As(V) species concentrations, a lower relative distribution in the metal-sensitive fraction (MSF). It was attributed that C60 may coat As(V) ion channels and consequently, affect the secretion of digestive enzymes in the gut, favoring As excretion and inhibiting As methylation. Similarly, MWCNTs reduced the species concentration of MMA and As(V) in the intestines, low GSH (glutathione) contents in the intestine. Due to the disparity of other carbon-based nanomaterial morphologies, SWCNTs, GO and GN exhibited the various effects on the toxicity of As(V). In addition, the possible pathway of arsenobetaine (AsB) biosynthesis included migration from the intestine to muscle in D. rerio, with the precursor of AsB likely to be 2-dimethylarsinylacetic acid (DMAA). The results of this study suggest that C60 is beneficial for controlling As(V) pollution and reducing the impact of As(V) biogeochemical cycles throughout the ecosystem.

The efficacy of acupuncture for trigeminal neuralgia: an overview of systematic reviews.

Background: Many systematic reviews (SRs) and meta-analysis (MAs) have reported the efficacy of acupuncture treatment for primary trigeminal neuralgia (PTN), but the quality of evidence is unknown and therefore needs to be evaluated comprehensively. Methods: Eight electronic databases were searched from their inception until January 5, 2024. The methodological quality, reporting quality, and risk of bias of the included SRs were assessed by the assessment of multiple systematic reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Reviews (ROBIS) tool, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The quality of evidence for outcome measures was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: We identified 13 SRs/MAs met inclusion criteria. According to the results of the AMSTAR-2, six were rated as critically low quality and seven as low quality. According to ROBIS assessment, 8 SRs/MAs were classified as low risk, and 5 SRs/MAs were found to be high risk. The PRISMA report still has some reporting deficiencies in aspects such as protocol and registration, search strategy, risk of bias, additional analyzes and funding. According to the GRADE system, no high-quality evidence was found, 1 was of moderate quality, 4 were of low quality, and 8 were of critical low quality. Conclusion: Based on the evidence collected, acupuncture shows promise as a treatment for PTN patients. However, it is important to note that the included SRs/MAs generally have low methodological quality and evidence quality. Therefore, caution must be exercised when interpreting this conclusion. To enhance future research in this area, it is recommended to adequately report methodological details and adhere to guidelines for conducting SRs/MAs.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024499280.

Design and Evaluation of a Rapid Monolithic Manufacturing Technique for a Novel Vision-Based Tactile Sensor: C-Sight.

Tactile sensing has become indispensable for contact-rich dynamic robotic manipulation tasks. It provides robots with a better understanding of the physical environment, which is a vital supplement to robotic vision perception. Compared with other existing tactile sensors, vision-based tactile sensors (VBTSs) stand out for augmenting the tactile perception capabilities of robotic systems, owing to superior spatial resolution and cost-effectiveness. Despite their advantages, VBTS production faces challenges due to the lack of standardised manufacturing techniques and heavy reliance on manual labour. This limitation impedes scalability and widespread adoption. This paper introduces a rapid monolithic manufacturing technique and evaluates its performance quantitatively. We further develop and assess C-Sight, a novel VBTS sensor manufactured using this technique, focusing on its tactile reconstruction capabilities. Experimental results demonstrate that the monolithic manufacturing technique enhances VBTS production efficiency significantly. Also, the fabricated C-Sight sensor exhibits its reliable tactile perception and reconstruction capabilities, proofing the validity and feasibility of the monolithic manufacturing method.

Wnt-5a-Receptor Tyrosine Kinase-Like Orphan Receptor 2 Signaling Provokes Metastatic Colonization and Angiogenesis in Renal Cell Carcinoma, and the Axis Activation Is Suppressed by Prunetin.

Wnt-5a is a protein that is encoded by the WNT5A gene and is a ligand for the receptor tyrosine kinase-like orphan receptor 2 (ROR2). However, its biological impact on clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, the prognostic significance of concurrent WNT5A and ROR2 expression levels was observed to predict unfavorable overall survival and disease-specific survival. High Wnt-5a expression was detected in a ccRCC cell line panel but not in HK-2 cells, a normal proximal tubular cell line. Inhibition of DNA methyltransferase by 5-azacytidine in 786-O and Caki-2 cells resulted in Wnt-5a up-regulation, indicating potential epigenetic modification. Furthermore, the results revealed the repression of cell movement in vitro and metastatic colonization in vivo on WNT5A and ROR2 knockdown. The suppressions of angiogenesis in vivo and tubular-like structure formation in endothelial cells in vitro were also observed after silencing WNT5A and ROR2 expression. In addition, alteration in the downstream gene signature of the Wnt-5a-ROR2 signaling was discovered to be similar to that in metastasis-associated gene 1-ß-catenin axis. Moreover, prunetin treatment was found to reverse the gene signature derived from Wnt-5a-ROR2 signaling activation and to abolish ccRCC cell migration and proliferation. Overall, this study demonstrates the clinical and functional significance of the Wnt-5a-ROR2 axis and identifies prunetin as a potential precision medicine for patients with ccRCC harboring aberrant Wnt-5a-ROR2 signaling pathways.

A real-world study of tyrosine kinase inhibitors plus anti-PD-1 immunotherapy with or without chemoembolization for hepatocellular carcinoma patients with main portal vein invasion.

BACKGROUND: Although systemic therapies are recommended for hepatocellular carcinoma (HCC) patients with main portal vein (MPV) invasion and preserved liver function, the outcome is limited. In the real-world, chemoembolization is a commonly used local treatment for advanced HCC. PURPOSE: To evaluate whether the additional chemoembolization treatment yields survival benefits compared to systemic therapy for HCC patients with MPV invasion and preserved liver function (Child-Pugh score ≤ B7) in a real-world study from multiple centers. PATIENTS AND METHODS: Between January 2020 and December 2022, 91 consecutive HCC patients with MPV invasion who received either systemic medical therapy (i.e., tyrosine kinase inhibitors (TKIs) plus anti-PD-1 immunotherapy, S group, n = 43) or in combination with chemoembolization treatment (S-T group, n = 48) from five centers were enrolled in the study. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and treatment response. Adverse events (AEs) related to treatment were also recorded. Survival curves were constructed with the Kaplan-Meier method and compared using the log-rank test. RESULTS: The baseline characteristics were comparable between the two groups. The mean number of chemoembolization sessions per patient was 2.1 (range 1-3). The median OS was 10.0 months and 8.0 months in the S-T group and S group, respectively (P = 0.254). The median PFS between the two groups was similar (4.0 months vs. 4.0 months, P = 0.404). The disease control rate between the S-T and S groups were comparable (60.4% vs. 62.8%, P = 0.816). Although no chemoembolization-related deaths occurred, 13 grade 3-4 AEs occurred in the S-T group. CONCLUSIONS: The results of the real-world study demonstrated that additional chemoembolization treatment did not yield survival benefits compared to TKIs plus anti-PD-1 immunotherapy for the overall patients with advanced HCC and MPV invasion.

Effects of Polyphenol-Rich Foods on Lipids and Oxidative Stress Status in Patients with Hyperlipidemia: A Systematic Review of Randomized Controlled Trials.

Background: Hyperlipidemia has been demonstrated to be an autonomous predictor of numerous cardiovascular and cerebrovascular ailments, and research indicates that polyphenols have preventive and therapeutic effects on hyperlipidemia. Nevertheless, the impact of polyphenol-rich foods on blood lipids and oxidative stress status in patients with hyperlipidemia remains inconclusive. Objective: To examine the impact of polyphenol-rich foods on lipid levels and oxidative stress in individuals with hyperlipidemia. Methods: To retrieve papers published from the establishment of the database through October 9, 2023, eight databases were searched: the Chinese National Knowledge Infrastructure, the China Biomedical Literature Database, the Wanfang Database, the China Science and Technology Journal Database, PubMed, the Cochrane Library, Embase, and the Web of Science. The quality of include studies was assessed using the Cochrane Risk of Bias in Randomized Trials tool, v2. Results: The study involved 13 surveys encompassing 640 patients diagnosed with hyperlipidemia. The scope of the food surveys included 12 commonly consumed food groups and medicinal and food homologous substances. All 13 studies reported the effects of polyphenol-rich foods on blood lipids, with significant improvements observed in blood lipid levels for 9 types of foods. Eight studies examined the impact on oxidative stress, and six foods demonstrated a significant reduction in oxidative stress levels. The observed effects were found to be influenced by factors such as dosage, duration of intervention, and gender. Conclusion: Foods abundant in polyphenols play a crucial role in the prevention and treatment of hyperlipidemia by counteracting oxidative stress and regulating metabolic disorders. The confirmation of certain positive effects by several studies notwithstanding, discrepancies in results arise from various factors, necessitating further large-scale, prospective, well-designed randomized controlled studies to address this issue.

Exploration on OCT biomarker candidate related to macular edema caused by diabetic retinopathy and retinal vein occlusion in SD-OCT images.

To improve the understanding of potential pathological mechanisms of macular edema (ME), we try to discover biomarker candidates related to ME caused by diabetic retinopathy (DR) and retinal vein occlusion (RVO) in spectral-domain optical coherence tomography images by means of deep learning (DL). 32 eyes of 26 subjects with non-proliferative DR (NPDR), 77 eyes of 61 subjects with proliferative DR (PDR), 120 eyes of 116 subjects with branch RVO (BRVO), and 17 eyes of 15 subjects with central RVO (CRVO) were collected. A DL model was implemented to guide biomarker candidate discovery. The disorganization of the retinal outer layers (DROL), i.e., the gray value of the retinal tissues between the external limiting membrane (ELM) and retinal pigment epithelium (RPE), the disrupted and obscured rate of the ELM, ellipsoid zone (EZ), and RPE, was measured. In addition, the occurrence, number, volume, and projected area of hyperreflective foci (HRF) were recorded. ELM, EZ, and RPE are more likely to be obscured in RVO group and HRFs are observed more frequently in DR group (all P ≤ 0.001). In conclusion, the features of DROL and HRF can be possible biomarkers related to ME caused by DR and RVO in OCT modality.

Short-term culture for rapid identification by mass spectrometry and automated antimicrobial susceptibility testing from positive bottles.

BACKGROUND: Early and appropriate antibiotic treatment improves the clinical outcome of patients with sepsis. There is an urgent need for rapid identification (ID) and antimicrobial susceptibility testing (AST) of bacteria that cause bloodstream infection (BSI). Rapid ID and AST can be achieved by short-term incubation on solid medium of positive blood cultures using MALDI-TOF mass spectrometry (MS) and the BD M50 system. The purpose of this study is to evaluate the performance of rapid method compared to traditional method. METHODS: A total of 124 mono-microbial samples were collected. Positive blood culture samples were short-term incubated on blood agar plates and chocolate agar plates for 5 ∼ 7 h, and the rapid ID and AST were achieved through Zybio EXS2000 MS and BD M50 System, respectively. RESULTS: Compared with the traditional 24 h culture for ID, this rapid method can shorten the cultivation time to 5 ∼ 7 h. Accurate organism ID was achieved in 90.6% of Gram-positive bacteria (GP), 98.5% of Gram-negative bacteria (GN), and 100% of fungi. The AST resulted in the 98.5% essential agreement (EA) and 97.1% category agreements (CA) in NMIC-413, 99.4% EA and 98.9% CA in PMIC-92, 100% both EA and CA in SMIC-2. Besides, this method can be used for 67.2% (264/393) of culture bottles during routine work. The mean turn-around time (TAT) for obtaining final results by conventional method is approximately 72.6 ± 10.5 h, which is nearly 24 h longer than the rapid method. CONCLUSIONS: The newly described method is expected to provide faster and reliable ID and AST results, making it an important tool for rapid management of blood cultures (BCs). In addition, this rapid method can be used to process most positive blood cultures, enabling patients to receive rapid and effective treatment.

Glaucoma Detection through a Novel Hyperspectral Imaging Band Selection and Vision Transformer Integration.

Conventional diagnostic methods for glaucoma primarily rely on non-dynamic fundus images and often analyze features such as the optic cup-to-disc ratio and abnormalities in specific retinal locations like the macula and fovea. However, hyperspectral imaging techniques focus on detecting alterations in oxygen saturation within retinal vessels, offering a potentially more comprehensive approach to diagnosis. This study explores the diagnostic potential of hyperspectral imaging for glaucoma by introducing a novel hyperspectral imaging conversion technique. Digital fundus images are transformed into hyperspectral representations, allowing for a detailed analysis of spectral variations. Spectral regions exhibiting differences are identified through spectral analysis, and images are reconstructed from these specific regions. The Vision Transformer (ViT) algorithm is then employed for classification and comparison across selected spectral bands. Fundus images are used to identify differences in lesions, utilizing a dataset of 1291 images. This study evaluates the classification performance of models using various spectral bands, revealing that the 610-780 nm band outperforms others with an accuracy, precision, recall, F1-score, and AUC-ROC all approximately at 0.9007, indicating its superior effectiveness for the task. The RGB model also shows strong performance, while other bands exhibit lower recall and overall metrics. This research highlights the disparities between machine learning algorithms and traditional clinical approaches in fundus image analysis. The findings suggest that hyperspectral imaging, coupled with advanced computational techniques such as the ViT algorithm, could significantly enhance glaucoma diagnosis. This understanding offers insights into the potential transformation of glaucoma diagnostics through the integration of hyperspectral imaging and innovative computational methodologies.

Use of MRI Radiomics Models in Evaluating the Low HER2 Expression in Breast Cancer.

OBJECTIVE: To investigate the magnetic resonance imaging (MRI) radiomics models in evaluating the human epidermal growth factor receptor 2(HER2) expression in breast cancer.

Materials and Methods: The MRI data of 161 patients with invasive ductal carcinoma (non-special type) of breast cancer were retrospectively collected, and the MRI radiomics models were established based on the MRI imaging features of the fat suppression T2 weighted image (T2WI) sequence, dynamic contrast-enhanced (DCE)-T1WIsequence and joint sequences. The T-test and the least absolute shrinkage and selection operator (LASSO) algorithm were used for feature dimensionality reduction and screening, respectively, and the random forest (RF) algorithm was used to construct the classification model.

Results: The model established by the LASSO-RF algorithm was used in the ROC curve analysis. In predicting the low expression state of HER2 in breast cancer, the radiomics models of the fat suppression T2WI sequence, DCE-T1WI sequence, and the combination of the two sequences showed better predictive efficiency. In the receiver operating characteristic (ROC) curve analysis for the verification set of low, negative, and positive HER2 expression, the area under the ROC curve (AUC) value was 0.81, 0.72, and 0.62 for the DCE-T1WI sequence model, 0.79, 0.65 and 0.77 for the T2WI sequence model, and 0.84, 0.73 and 0.66 for the joint sequence model, respectively. The joint sequence model had the highest AUC value.

Conclusions: The MRI radiomics models can be used to effectively predict the HER2 expression in breast cancer and provide a non-invasive and early assistant method for clinicians to formulate individualized and accurate treatment plans.

Value of orthogonal axial MR images in preoperative T staging of gastric cancer.

PURPOSE: To assess the value of orthogonal axial images (OAI) of MRI in gastric cancer T staging. METHODS: This retrospective study enrolled 133 patients (median age, 63 [range, 24-85] years) with gastric adenocarcinoma who underwent both CT and MRI followed by surgery. MRI lacking or incorporating OAI and CT images were evaluated, respectively. Diagnostic performance (accuracy, sensitivity, and specificity) for each T stage, overall diagnostic accuracy and rates of over- and understaging were quantified employing pathological T stage as a reference standard. The McNemar's test was performed to compare the overall accuracy. RESULTS: Among patients with pT1-pT4 disease, MRI with OAI (accuracy: 88.7-94.7%, sensitivity: 66.7-93.0%, specificity: 91.5-100.0%) exhibited superior diagnostic performance compared to MRI without OAI (accuracy: 81.2-88.7%, sensitivity: 46.2-83.1%, specificity: 85.5-99.1%) and CT (accuracy: 88.0-92.5%, sensitivity: 53.3-90.1%, specificity: 88.7-98.1%). The overall accuracy of MRI with OAI was significantly higher (83.5%) than that of MRI without OAI (67.7%) (p < .001). However, there was no significant difference in the overall accuracy of MRI with OAI and CT (78.9%) (p = .35). The over- and understaging rates of MRI with OAI (12.0, 4.5%) were lower than those of MRI without OAI (21.8, 10.5%) and CT (12.8, 8.3%). CONCLUSION: OAI play a pivotal role in the T staging of gastric cancer. MRI incorporating OAI demonstrated commendable performance for gastric cancer T-staging, with a slight tendency toward its superiority over CT.

Novel CCR3-targeted cyclic peptides as potential therapeutic agents for age-related macular degeneration via inhibiting angiogenesis and reducing retinal photoreceptor damage.

The prolonged intravitreal administration of anti-vascular endothelial growth factor (VEGF) drugs is prone to inducing aberrant retinal vascular development and causing damage to retinal neurons. Hence, we have taken an alternative approach by designing and synthesizing a series of cyclic peptides targeting CC motif chemokine receptor 3 (CCR3). Based on the binding mode of the N-terminal region in CCR3 protein to CCL11, we used computer-aided identification of key amino acid sequence, conformational restriction through different cyclization methods, designed and synthesized a series of target cyclic peptides, and screened the preferred compound IB-2 through affinity. IB-2 exhibits excellent anti-angiogenic activity in HRECs. The apoptosis level of 661W cells demonstrated a significant decrease with the escalating concentration of IB-2. This suggests that IB-2 may have a protective effect on photoreceptor cells. In vivo experiments have shown that IB-2 significantly reduces retinal vascular leakage and choroidal neovascularization (CNV) area in a laser-induced mouse model of CNV. These findings indicate the potential of IB-2 as a safe and effective therapeutic agent for AMD, warranting further development.

Mechanical Strain Induces and Increases Vesicular Release Monitored by Microfabricated Stretchable Electrodes.

Exocytosis involving the fusion of intracellular vesicles with cell membrane, is thought to be modulated by the mechanical cues in the microenvironment. Single-cell electrochemistry can offer unique information about the quantification and kinetics of exocytotic events; however, the effects of mechanical force on vesicular release have been poorly explored. Herein, we developed a stretchable microelectrode with excellent electrochemical stability under mechanical deformation by microfabrication of functionalized poly(3,4-ethylenedioxythiophene) conductive ink, which achieved real-time quantitation of strain-induced vesicular exocytosis from a single cell for the first time. We found that mechanical strain could cause calcium influx via the activation of Piezo1 channels in chromaffin cell, initiating the vesicular exocytosis process. Interestingly, mechanical strain increases the amount of catecholamines released by accelerating the opening and prolonging the closing of fusion pore during exocytosis. This work is expected to provide revealing insights into the regulatory effects of mechanical stimuli on vesicular exocytosis.

Transforming Adolescent Smiles: Correcting Skeletal Mandibular Retrusion and Bimaxillary Protrusion with Clear Aligners.

Maxillary protrusion combined with mandibular retraction is a highly prevalent but extremely complex maxillofacial deformity that can have a serious negative impact on patients' facial aesthetics and mental health. The traditional orthodontic treatment strategy often involves extracting 4 first premolars and conventional fixed techniques, combined with mini-implant screws, to retract the anterior teeth and improve facial protrusion. In recent years, an invisible orthodontic technique, without brackets, has become increasingly popular. However, while an invisible aligner has been used in some cases with reasonable results, there remain significant challenges in achieving a perfect outcome. This case report presents an adolescent patient with bimaxillary protrusion and mandibular retrognathia. Based on the characteristics of the invisible aligners and the growth characteristics of the adolescent's teeth and jawbone, we designed precise three-dimensional tooth movement and corresponding resistance/over-correction for each tooth, while utilizing the patient's jawbone growth potential to promote rapid development of the mandible, accurately and efficiently correcting bimaxillary protrusion and skeletal mandibular retrognathia. The patient's facial aesthetics, especially the lateral morphology, have been greatly improved, and various aesthetic indicators have also shown significant changes, and to the patient's great benefit, invasive mini-implant screws were not used during the treatment. This case highlights the advantages of using invisible aligners in adolescent maxillary protrusion combined with mandibular retraction patients. Furthermore, comprehensive and accurate design combined with good application of growth potential can also enable invisible orthodontic technology to achieve perfect treatment effects in tooth extractions, providing clinical guidance for orthodontists.

Shenling Baizhu powder alleviates non-alcoholic fatty liver disease by modulating autophagy and energy metabolism in high-fat diet-induced rats.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has emerged as a burgeoning health problem worldwide, but no specific drug has been approved for its treatment. Shenling Baizhu powder (SL) is extensively used to treat NAFLD in Chinese clinical practice. However, the therapeutic components and pharmacological mechanisms of SL against NAFLD have not been thoroughly investigated. PURPOSE: This study aimed to investigate the pharmacological impact and molecular mechanism of SL on NAFLD. METHODS: First, we established an animal model of NAFLD by high-fat diet (HFD) feeding, and evaluated the therapeutic efficacy of SL on NAFLD by physiological, biochemical, pathological, and body composition analysis. Next, the effect of SL on autophagic flow in NAFLD rats was evaluated by ultrastructure, immunofluorescence staining, and western blotting. Moreover, an integrated strategy of targeted energy metabolomics and network pharmacology was performed to characterize autophagy-related genes and explore the synergistic effects of SL active compounds. UPLC-MS/MS, molecular docking combined with in vivo and in vitro experiments were conducted to verify the key compounds and genes. Finally, a network was established among SL-herb-compound-genes-energy metabolites-NAFLD, which explains the complicated regulating mechanism of SL on NAFLD. RESULTS: We discovered that SL decreased hepatic lipid accumulation, hepatic steatosis, and insulin resistance, and improved systemic metabolic disorders and pathological abnormalities. Subsequently, an integrated strategy of targeted energy metabolomics and network pharmacology identified quercetin, ellagic acid, kaempferol, formononetin, stigmasterol, isorhamnetin and luteolin as key compounds; catalase (CAT), AKT serine/threonine kinase 1 (AKT), nitric oxide synthase 3 (eNOS), NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase 1 (HO-1) and hypoxia-inducible factor 1 subunit alpha (HIF-1α) were identified as key genes; while nicotinamide adenine dinucleotide phosphate (NADP) and succinate emerged as key energy metabolites. Mechanistically, we revealed that SL may exert its anti-NAFLD effect by inducing autophagy activation and forming a comprehensive regulatory network involving key compounds, key genes, and key energy metabolites, ultimately alleviating oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction. CONCLUSION: Our study demonstrated the therapeutic effect of SL in NAFLD models, and establishes a basis for the development of potential products from SL plant materials for the treatment of NAFLD.

Long-term outcomes of intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection (IOCCRC): a randomized, multicenter, prospective, phase III trial.

BACKGROUND: We aimed to compare combined intraoperative chemotherapy and surgical resection with curative surgical resection alone in colorectal cancer patients. METHODS: We performed a multicenter, open-label, randomized, phase III trial. All eligible patients were randomized and assigned to intraoperative chemotherapy and curative surgical resection or curative surgical resection alone (1:1). Survival actualization after long-term follow-up was performed in patients analyzed on an intention-to-treat basis. RESULTS: From January 2011 to January 2016, 696 colorectal cancer patients were enrolled and randomly assigned to intraoperative chemotherapy and radical surgical resection (n=341) or curative surgical resection alone (n=344). Intraoperative chemotherapy with surgical resection showed no significant survival benefit over surgical resection alone in colorectal cancer patients (3-year DFS: 91.1% vs. 90.0%, P=0.328; 3-year OS: 94.4% vs. 95.9%, P=0.756). However, colon cancer patients benefitted from intraoperative chemotherapy, with a relative 4% reduction in liver and peritoneal metastasis (HR=0.336, 95% CI: 0.148-0.759, P=0.015) and a 6.5% improvement in 3-year DFS (HR=0.579, 95% CI: 0.353-0.949, P=0.032). Meanwhile, patients with colon cancer and abnormal pretreatment CEA levels achieved significant survival benefits from intraoperative chemotherapy (DFS: HR=0.464, 95% CI: 0.233-0.921, P=0.029 and OS: (HR=0.476, 95% CI: 0.223-1.017, P=0.049). CONCLUSIONS: Intraoperative chemotherapy showed no significant extra prognostic benefit in total colorectal cancer patients who underwent radical surgical resection; however, in colon cancer patients with abnormal pretreatment serum CEA levels (> 5 ng/ml), intraoperative chemotherapy could improve long-term survival.

[Source and Cause Analysis of High Concentration of Inorganic Aerosol During Two Typical Pollution Processes in Winter over Tianjin].

Inorganic aerosol is the main component of haze days in winter over Tianjin. In this study, two typical high concentrations of secondary inorganic aerosol (SIA) processes, defined as CASE1 and CASE2, were selected during polluted days in January 2020 over Tianjin, and the effects of meteorological factors, regional transport, and chemical processes were comprehensively investigated combined with observations and numerical models (WRF-NAQPMS). The average SIA concentrations in CASE1 and CASE2 were 76.8 µg·m-3 and 66.0 µg·m-3, respectively, and the nitrate concentration was higher than that of sulfate and ammonium, which were typical nitrate-dominated pollution processes. Meteorological conditions played a role in inorganic aerosol formation. The temperature of approximately -6-0℃ and 2-4℃ and the relative humidity of 50%-60% and 80%-100% would be suitable conditions for the high SIA concentration (>80 µg·m-3) in CASE1, whereas the temperature of approximately 2-4℃ and the relative humidity of 60%-70% would be suitable in CASE2. The average contribution rates of external sources to SIA in the CASE1 and CASE2 processes were 62.3% and 22.1%, which were regional transport-dominant processes and local emission-dominant processes, respectively. The contribution of the local emission of CASE1 to nitrate and sulfate was 16.2 µg·m-3 and 8.2 µg·m-3, respectively, higher than that of external sources (31.7 µg·m-3 and 8.8 µg·m-3). the local contribution of CASE2 to nitrate and sulfate was 29.3 µg·m-3 and 25.1 µg·m-3, respectively, whereas the contribution from external sources was 8.1 µg·m-3 and 9.4 µg·m-3, respectively. The quantitative result indicated that local formation and regional transport resulted in higher nitrate concentration than sulfate in CASE1, in contrast to only local sources in CASE2. The gas phase reaction was the main source of inorganic aerosol formation, contributing 48.9% and 57.8% in CASE1 and CASE2, respectively, whereas the heterogeneous reactions were also important processes, with contribution rates of 48.1% and 42.2% to SIA. The effect of aqueous phase reaction was negligible.