Integrated Approaches Revealed the Therapeutic Mechanisms of Zuojin Pill Against Gastric Mucosa Injury in a Rat Model with Chronic Atrophic Gastritis.

Background: The Zuojin Pill (ZJP) is widely used for treating chronic atrophic gastritis (CAG) in clinical practice, effectively ameliorating symptoms such as vomiting, pain, and abdominal distension in patients. However, the underlying mechanisms of ZJP in treating CAG has not been fully elucidated. Purpose: This study aimed to clarify the characteristic function of ZJP in the treatment of CAG and its potential mechanism. Methods: The CAG model was established by alternant administrations of ammonia solution and sodium deoxycholate, as well as an irregular diet. Therapeutic effects of ZJP on body weight, serum biochemical indexes and general condition were analyzed. HE staining and AB-PAS staining were analyzed to characterize the mucosal injury and the thickness of gastric mucosa. Furthermore, network pharmacology and molecular docking were used to predict the regulatory mechanism and main active components of ZJP in CAG treatment. RT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to measure the expression levels of apoptosis-related proteins, gastric mucosal barrier-associated proteins and PI3K/Akt signaling pathway proteins. Results: The results demonstrated that ZJP significantly improved the general state of CAG rats, alleviated weight loss and gastric histological damage and reduced the serum biochemical indicators. Network pharmacology and molecular docking found that ZJP in treating CAG by inhibiting inflammation, suppressing apoptosis, and protecting the gastric mucosal barrier via the PI3K/Akt signaling pathway. Further experiments confirmed that ZJP obviously modulated the expression of key proteins involved in gastric mucosal cell apoptosis, such as Bax, Bad, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, Cytochrome C, Bcl-2, and Bcl-xl. Moreover, ZJP significantly reversed the protein expression of Occludin, ZO-1, Claudin-4 and E-cadherin. Conclusion: Our study revealed that ZJP treats CAG by inhibiting the PI3K/Akt signaling pathway. This research provided a scientific basis for the rational use of ZJP in clinical practice.

Proton pump inhibitors stabilize the expression of PD-L1 on cell membrane depending on the phosphorylation of GSK3ß.

BACKGROUND: Preclinical and clinical evidence indicates that proton pump inhibitors (PPIs) may indirectly diminish the microbiome diversity, thereby reducing the effectiveness of immune checkpoint inhibitors (ICIs). Conversely, recent publications have shown that PPIs could potentially enhance the response to ICIs. The precise mechanism through which PPIs modulate the ICIs remains unclear. In this study, we discovered a novel molecular function of PPIs in regulating immune invasion, specifically through inducing PD-L1 translocation in various tumor cells. METHODS: C57BL/6 mice subcutaneous transplantation model is used to verify the potential efficacy of PPIs and PD-L1 antibody. Western blotting analysis and phosphorylated chip are used to verify the alteration of PD-L1-related pathways after being treated with PPIs. The related gene expression is performed by qRT-PCR and luciferase reporter analysis. We also collected 60 clinical patients diagnosed with esophageal cancer or reflux esophagitis and then detected the expression of PD-L1 in the tissue samples by immunohistochemistry. RESULTS: We observed that the IC50 of tumor cells in response to PPIs was significantly higher than that of normal epithelial cells. PPIs significantly increased the expression of PD-L1 on cell membrane at clinically relevant concentrations. Furthermore, pre-treatment with PPIs appeared to synergize the efficiency of anti-PD-L1 antibodies in mouse models. However, PPI administration did not alter the transcription or total protein level of PD-L1 in multiple tumor cells. Using a phosphorylated protein chip, we identified that PPIs enhanced the phosphorylation of GSK3ß, then leading to PD-L1 protein translocation to the cell membranes. The capacity of PPIs to upregulate PD-L1 was negated following GSK3ß knockout. Furthermore, our clinical data showed that the PPIs use resulted in increased PD-L1 expression in esophageal cancer patients. CONCLUSION: We mainly address a significant and novel mechanism that the usage of PPIs could directly induce the expression of PD-L1 by inducing GSK3ß phosphorylation and facilitate primary tumor progression and metastasis.

Probiotic-derived amphiphilic exopolysaccharide self-assembling adjuvant delivery platform for enhancing immune responses.

Enhancing immune response activation through the synergy of effective antigen delivery and immune enhancement using natural, biodegradable materials with immune-adjuvant capabilities is challenging. Here, we present NAPSL.p that can activate the Toll-like receptor 4 (TLR4) pathway, an amphiphilic exopolysaccharide, as a potential self-assembly adjuvant delivery platform. Its molecular structure and unique properties exhibited remarkable self-assembly, forming a homogeneous nanovaccine with ovalbumin (OVA) as the model antigen. When used as an adjuvant, NAPSL.p significantly increased OVA uptake by dendritic cells. In vivo imaging revealed prolonged pharmacokinetics of NAPSL. p-delivered OVA compared to OVA alone. Notably, NAPSL.p induced elevated levels of specific serum IgG and isotype titers, enhancing rejection of B16-OVA melanoma xenografts in vaccinated mice. Additionally, NAPSL.p formulation improved therapeutic effects, inhibiting tumor growth, and increasing animal survival rates. The nanovaccine elicited CD4+ and CD8+ T cell-based immune responses, demonstrating the potential for melanoma prevention. Furthermore, NAPSL.p-based vaccination showed stronger protective effects against influenza compared to Al (OH)3 adjuvant. Our findings suggest NAPSL.p as a promising, natural self-adjuvanting delivery platform to enhance vaccine design across applications.

Thermal degradation of greenhouse gas SF6 at realistic temperatures: Insights from atomic-scale CVHD simulations.

Sulfur hexafluoride (SF6), recognized as a potent greenhouse gas with significant contributions to climate change, presents challenges in understanding its degradation processes. Molecular dynamics simulations are valuable tools for understanding modes of decomposition while the traditional approaches face limitations in time scale and require unrealistically high temperatures. The collective variable-driven hyperdynamics (CVHD) approach has been introduced to directly depict the pyrolysis process for SF6 gas at practical application temperatures, as low as 1600 K for the first time. Achieving an unprecedented acceleration factor of up to 107, the method extends the simulation time scale to milliseconds and beyond while maintaining consistency with experimental and theoretical models. The differences in the reaction process between simulations conducted at actual and elevated temperatures have been noted, providing insights into SF6 degradation pathways. The work provides a basis for the further studies on the thermal degradation of pollutants.

Improving Microstructural Estimation in Time-Dependent Diffusion MRI With a Bayesian Method.

BACKGROUND: Accurately fitting diffusion-time-dependent diffusion MRI (td-dMRI) models poses challenges due to complex and nonlinear formulas, signal noise, and limited clinical data acquisition. PURPOSE: Introduce a Bayesian methodology to refine microstructural fitting within the IMPULSED (Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion) model and optimize the prior distribution within the Bayesian framework. STUDY TYPE: Retrospective. POPULATION: Involving 69 pediatric patients (median age 6 years, interquartile range [IQR] 3-9 years, 61% male) with 41 low-grade and 28 high-grade gliomas, of which 76.8% were identified within the brainstem or cerebellum. FIELD STRENGTH/SEQUENCE: 3 T, oscillating gradient spin-echo (OGSE) and pulsed gradient spin-echo (PGSE). ASSESSMENT: The Bayesian method's performance in fitting cell diameter ( d $$ d $$ ), intracellular volume fraction ( f in $$ {f}_{in} $$ ), and extracellular diffusion coefficient ( D ex $$ {D}_{ex} $$ ) was compared against the NLLS method, considering simulated and experimental data. The tumor region-of-interest (ROI) were manually delineated on the b0 images. The diagnostic performance in distinguishing high- and low-grade gliomas was assessed, and fitting accuracy was validated against H&E-stained pathology. STATISTICAL TESTS: T-test, receiver operating curve (ROC), area under the curve (AUC) and DeLong's test were conducted. Significance considered at P < 0.05. RESULTS: Bayesian methodology manifested increased accuracy with robust estimates in simulation (RMSE decreased by 29.6%, 40.9%, 13.6%, and STD decreased by 29.2%, 43.5%, and 24.0%, respectively for d $$ d $$ , f in $$ {f}_{in} $$ , and D ex $$ {D}_{ex} $$ compared to NLLS), indicating fewer outliers and reduced error. Diagnostic performance for tumor grade was similar in both methods, however, Bayesian method generated smoother microstructural maps (outliers ratio decreased by 45.3% ± 19.4%) and a marginal enhancement in correlation with H&E staining result (r = 0.721 for f in $$ {f}_{in} $$ compared to r = 0.698 using NLLS, P = 0.5764). DATA CONCLUSION: The proposed Bayesian method substantially enhances the accuracy and robustness of IMPULSED model estimation, suggesting its potential clinical utility in characterizing cellular microstructure. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Epileptic Seizure Prediction Using Spatiotemporal Feature Fusion on EEG.

Electroencephalography (EEG) plays a crucial role in epilepsy analysis, and epileptic seizure prediction has significant value for clinical treatment of epilepsy. Currently, prediction methods using Convolutional Neural Network (CNN) primarily focus on local features of EEG, making it challenging to simultaneously capture the spatial and temporal features from multi-channel EEGs to identify the preictal state effectively. In order to extract inherent spatial relationships among multi-channel EEGs while obtaining their temporal correlations, this study proposed an end-to-end model for the prediction of epileptic seizures by incorporating Graph Attention Network (GAT) and Temporal Convolutional Network (TCN). Low-pass filtered EEG signals were fed into the GAT module for EEG spatial feature extraction, and followed by TCN to capture temporal features, allowing the end-to-end model to acquire the spatiotemporal correlations of multi-channel EEGs. The system was evaluated on the publicly available CHB-MIT database, yielding segment-based accuracy of 98.71%, specificity of 98.35%, sensitivity of 99.07%, and F1-score of 98.71%, respectively. Event-based sensitivity of 97.03% and False Positive Rate (FPR) of 0.03/h was also achieved. Experimental results demonstrated this system can achieve superior performance for seizure prediction by leveraging the fusion of EEG spatiotemporal features without the need of feature engineering.

Reviving Static Charts into Live Charts.

Data charts are prevalent across various fields due to their efficacy in conveying complex data relationships. However, static charts may sometimes struggle to engage readers and efficiently present intricate information, potentially resulting in limited understanding. We introduce "Live Charts," a new format of presentation that decomposes complex information within a chart and explains the information pieces sequentially through rich animations and accompanying audio narration. We propose an automated approach to revive static charts into Live Charts. Our method integrates GNN-based techniques to analyze the chart components and extract data from charts. Then we adopt large natural language models to generate appropriate animated visuals along with a voice-over to produce Live Charts from static ones. We conducted a thorough evaluation of our approach, which involved the model performance, use cases, a crowd-sourced user study, and expert interviews. The results demonstrate Live Charts offer a multi-sensory experience where readers can follow the information and understand the data insights better. We analyze the benefits and drawbacks of Live Charts over static charts as a new information consumption experience.

Quaternary Ammonium Assisted Synthesis of Melanin-like Poly(l-DOPA) Nanoparticles with a Boosted Photothermal Effect.

Poly(levodopa) nanoparticles (P(l-DOPA) NPs) are another kind of melanin mimetic besides well-established polydopamine nanoparticles (PDA NPs). Due to the presence of carboxyl groups, the oxidative polymerization of l-DOPA to obtain particles was not as efficient as that of dopamine. Several established methods toward P(l-DOPA) NP fabrication do not combine convenience, morphological regularity, size controllability, low cost, and adaptability to metal-free application scenarios. In this work, P(l-DOPA) NPs were successfully prepared in hot water with the assistant of organic quaternary ammonium, due to the extra physical cross-linking mediated by cations. The employed physical interactions could also be affected by quaternary ammonium structure (i.e., number of cation heads, length of alkyl chain) to achieve different polymerization acceleration effects. The obtained P(l-DOPA) NPs retained superior photothermal properties and outperformed PDA-based melanin materials. Furthermore, P(l-DOPA) NPs were used in photothermal tumor therapy and showed better efficacy. This study offers new insights into the synthesis of melanin-like materials, as well as new understanding of the interaction between quaternary ammonium and bioinspired polyphenolic materials.

A comparative study of satellite altimetry-based and DEM-based methods for estimating lake water volume changes.

This study compared two different methods, the satellite altimetry-based and DEM (digital elevation model)-based, for estimating lake water volume changes. We focused on 34 lakes in China as the testing sites to compare the two methods for lake water volume changes from 2005 to 2020. The satellite altimetry-based method used water levels provided by the DAHITI (Database for Hydrological Time Series of Inland Waters) data and surface areas derived from Landsat imagery. The DEM-based method used the SRTM DEM data in combination with Landsat-derived lake extents. Our results showed a high degree of consistency in lake water volume changes estimated between the two methods (R2 > 0.90), but each method has its limitations. In terms of temporal coverage, the satellite altimetry-based method with the DAHITI data is limited by missing water level data in certain periods. The performance of the DEM-based method in extracting lake shore boundaries in regions with flat terrains (slope <1.5°) is not satisfactory. The DEM-based method has complete regional applicability (100%) in the Tibetan Plateau (TP) Lake Region, yet its effectiveness drops significantly in the Xinjiang and Eastern China Plain Lake Regions, with applicability rates of 50 and 40%, respectively.

A Fuzzy-PI Clock Servo with Window Filter for Compensating Queue-Induced Delay Asymmetry in IEEE 1588 Networks.

Clock synchronization is one of the popular research topics in Distributed Measurement and Control Systems (DMCSs). In most industrial fields, such as Smart Grid and Flight Test, the highest requirement for synchronization accuracy is 1 µs. IEEE 1588 Precision Time Protocol-2008 (PTPv2) can theoretically achieve sub-microsecond accuracy, but it relies on the assumption that the forward and backward delays of PTP packets are symmetrical. In practice, PTP packets will experience random queue delays in switches, making the above assumption challenging to satisfy and causing poor synchronization accuracy. Although using switches supporting the Transparent Clock (TC) can improve synchronization accuracy, these dedicated switches are generally expensive. This paper designs a PTP clock servo for compensating Queue-Induced Delay Asymmetry (QIDA), which can be implemented based on ordinary switches. Its main algorithm comprises a minimum window filter with drift compensation and a fuzzy proportional-integral (PI) controller. We construct a low-cost hardware platform (the cost of each node is within USD 10) to test the performance of the clock servo. In a 100 Mbps network with background (BG) traffic of less than 70 Mbps, the maximum absolute time error (max |TE|) does not exceed 0.35 µs, and the convergence time is about half a minute. The accuracy is improved hundreds of times compared with other existing clock servos.

The contribution of small heterodimer partner to the occurrence and progression of cholestatic liver injury.

BACKGROUND AND AIM: Small heterodimer partner (SHP, encoded by NR0B2) plays an important role in maintaining bile acid homeostasis. The loss of the hepatic farnesoid X receptor (FXR)/SHP signal can cause severe cholestatic liver injury (CLI). FXR and SHP have overlapping and nonoverlapping functions in bile acid homeostasis. However, the key role played by SHP in CLI is unclear. METHODS: In this study, an alpha-naphthylisothiocyanate (ANIT)-induced cholestasis mouse model was established. The effect of SHP knockout (SHP-KO) on liver and ileal pathology was evaluated. 16S rRNA gene sequencing analysis combined with untargeted metabolomics was applied to reveal the involvement of SHP in the pathogenesis of CLI. RESULTS: The results showed that ANIT (75 mg/kg) induced cholestasis in WT mice. No significant morphological changes were found in the liver and ileal tissue of SHP-KO mice. However, the serum metabolism and intestinal flora characteristics were significantly changed. Moreover, compared with the WT + ANIT group, the serum levels of ALT and AST in the SHP-KO + ANIT group were significantly increased, and punctate necrosis in the liver tissue was more obvious. The ileum villi showed obvious shedding, thinning, and shortening. In addition, SHP-KO-associated differential intestinal flora and differential biomarkers were significantly associated. CONCLUSION: In this study, we elucidated the serum metabolic characteristics and intestinal flora changes related to the aggravation of CLI in SHP-KO mice induced by ANIT.

Advances of Transition Metal-Based Electrochemical Non-enzymatic Glucose Sensors for Glucose Analysis: A Review.

Glucose concentration is a crucial parameter for assessing human health. Over recent years, non-enzymatic electrochemical glucose sensors have drawn considerable attention due to their substantial progress. This review explores the common mechanism behind the transition metal-based electrocatalytic oxidation of glucose molecules through classical electrocatalytic frameworks like the Pletcher model and the Hydrous Oxide-Adatom Mediator model (IHOAM), as well as the redox reactions at the transition metal centers. It further compiles the electrochemical characterization techniques, associated formulas, and their ensuing conclusions pertinent to transition metal-based non-enzymatic electrochemical glucose sensors. Subsequently, the review covers the latest advancements in the field of transition metal-based active materials and support materials used in non-enzymatic electrochemical glucose sensors in the last decade (2014-2023). Additionally, it presents a comprehensive classification of representative studies according to the active metal catalysts components involved.

Expeditious Synthesis of Gwanakoside A and the Chloronaphthol Glycoside Congeners.

The synthesis of gwanakoside A, a chlorinated naphthol bis-glycoside, and its analogues was achieved through stepwise chlorination and donor-equivalent controlled regioselective phenol glycosylation with glycosyl N-phenyltrifluoroacetimidates as donors. Gwanakoside A displayed considerable inhibitory effects against various cancer cells and Staphylococcus aureus strains.

UV absorption enhanced polydopamine coating.

Mussel-inspired polydopamine (PDA) coatings have gained significant attention in various fields, including biomedicine, energy, detection, and UV protection, owing to their versatile and promising properties. Among these properties, UV shielding stands out as a key feature of PDA coatings. Nevertheless, the current methods for tuning the UV-shielding properties of PDA coatings are quite limited, and only rely on thickness adjustment, which might involve additional issues like color and visible light transmittance to the coating layer. In this study, we propose a facile and modular approach to enhance the UV absorption of PDA coatings by incorporating thiol-heterocycle (TH) derivatives. Both pre- and post-modification strategies can effectively impede the formation of conjugated structures within PDA, leading to enhanced UV absorption within the PDA layers. More importantly, these strategies can improve the UV absorption of PDA coatings while reducing the visible light absorption. Furthermore, this method enabled efficient regulation of the UV absorption of PDA coatings by altering the ring type (benzene ring or pyridine ring) and substituent on the ring (methoxyl group or hydrogen atom). These PDA coatings with enhanced UV absorption demonstrate great promise for applications in UV protection, antibacterial activity, wound healing and dye degradation.

Access to pyrrolines and fused diaziridines by selective radical addition to homoallylic diazirines.

Pyrroline derivatives are common in bioactive natural products and therapeutic agents. We report here a synthesis of pyrrolines and fused diaziridines by divergent radical cyclization of homoallylic diazirines, which can serve as an internal radical trap and a nitrogen source. This reaction proceeds by selective radical addition to C[double bond, length as m-dash]C or N[double bond, length as m-dash]N bonds followed by intramolecular cyclization. Frontier molecular orbital analysis provides a deep insight into the origin of the selectivity. The reaction demonstrates a new cyclization mode, broad functional group compatibility and high product diversity, and reveals a much broader chemical space for diazirine studies.

Developing an AI-empowered head-only ultra-high-performance gradient MRI system for high spatiotemporal neuroimaging.

Recent advances in neuroscience requires high-resolution MRI to decipher the structural and functional details of the brain. Developing a high-performance gradient system is an ongoing effort in the field to facilitate high spatial and temporal encoding. Here, we proposed a head-only gradient system NeuroFrontier, dedicated for neuroimaging with an ultra-high gradient strength of 650 mT/m and 600 T/m/s. The proposed system features in 1) ultra-high power of 7MW achieved by running two gradient power amplifiers using a novel paralleling method; 2) a force/torque balanced gradient coil design with a two-step mechanical structure that allows high-efficiency and flexible optimization of the peripheral nerve stimulation; 3) a high-density integrated RF system that is miniaturized and customized for the head-only system; 4) an AI-empowered compressed sensing technique that enables ultra-fast acquisition of high-resolution images and AI-based acceleration in q-t space for diffusion MRI (dMRI); and 5) a prospective head motion correction technique that effectively corrects motion artifacts in real-time with 3D optical tracking. We demonstrated the potential advantages of the proposed system in imaging resolution, speed, and signal-to-noise ratio for 3D structural MRI (sMRI), functional MRI (fMRI) and dMRI in neuroscience applications of submillimeter layer-specific fMRI and dMRI. We also illustrated the unique strength of this system for dMRI-based microstructural mapping, e.g., enhanced lesion contrast at short diffusion-times or high b-values, and improved estimation accuracy for cellular microstructures using diffusion-time-dependent dMRI or for neurite microstructures using q-space approaches.

Optimal design of radial tire section layout based on thermal fatigue life improving.

The design of tire fatigue life was optimized by combining approximate model and finite element simulation, and compared with the tire endurance test results. The design variables are selected through sensitivity analysis of materials in various regions of the tire, and the thermal fatigue life of the tire is used as the objective function, and the approximate relationship between the design variables and the objective function is fitted based on the approximate model method, and the approximate model is optimized using genetic algorithm to find the optimal solution. The fatigue life of the tire is improved by about 25 %.

Circular RNA HIPK2 Promotes A1 Astrocyte Activation after Spinal Cord Injury through Autophagy and Endoplasmic Reticulum Stress by Modulating miR-124-3p-Mediated Smad2 Repression.

Glial scarring formed by reactive astrocytes after spinal cord injury (SCI) is the primary obstacle to neuronal regeneration within the central nervous system, making them a promising target for SCI treatment. Our previous studies have demonstrated the positive impact of miR-124-3p on neuronal repair, but it remains unclear how miR-124-3p is involved in autophagy or ER stress in astrocyte activation. To answer this question, the expression of A1 astrocyte-related markers at the transcriptional and protein levels after SCI was checked in RNA-sequencing data and verified using quantitative polymerase chain reaction (qPCR) and Western blotting in vitro and in vivo. The potential interactions among circHIPK2, miR-124-3p, and Smad2 were analyzed and confirmed by bioinformatics analyses and a luciferase reporter assay. In the end, the role of miR-124-3p in autophagy, ER stress, and SCI was investigated by using Western blotting to measure key biomarkers (C3, LC3, and Chop) in the absence or presence of corresponding selective inhibitors (siRNA, 4-PBA, TG). As a result, SCI caused the increase of A1 astrocyte markers, in which the upregulated circHIPK2 directly targeted miR-124-3p, and the direct downregulating effect of Smad2 by miR-124-3p was abolished, while Agomir-124 treatment reversed this effect. Injury caused a significant change of markers for ER stress and autophagy through the circHIPK2/miR-124-3p/Smad2 pathway, which might activate the A1 phenotype, and ER stress might promote autophagy in astrocytes. In conclusion, circHIPK2 may play a functional role in sequestering miR-124-3p and facilitating the activation of A1 astrocytes through regulating Smad2-mediated downstream autophagy and ER stress pathways, providing a new perspective on potential targets for functional recovery after SCI.

Epidemiology and genotypes analysis of human papillomavirus infection in Beijing, China.

BACKGROUND: This study aimed to investigate the epidemiology of high-risk human papillomavirus (HPV) in the female population in Beijing, China, and identify the relationship between HPV genotypes and host factors. METHODS: HPV testing was performed on women aged 15-89 (mean age 38.0 ± 10.9 years) from Beijing in 2020. High-risk HPV genotyping real-time polymerase chain reaction was used to determine HPV genotypes. The overall prevalence, age-specific prevalence, genotype distribution, and the correlation between HPV genotypes and cervical cytology were analyzed. RESULTS: Among the 25,344 study participants, the single and double infection rates were 18.8% (4,777/25,344) and 4.2% (1,072/25,344), respectively. A total of 6,119 HPV-positive individuals were found to have 91.6% negative results for intraepithelial lesion or malignancy (NILM), 5.8% atypical squamous cells of undetermined significance (ASC-US), 0.9% low-grade squamous intraepithelial lesion (LSIL), and 1.7% high-grade squamous intraepithelial lesion (HSIL). In single HPV infections, the HPV16 genotype was highly associated with cervical cytology severity (χ2 trend = 172.487, P < 0.001). Additionally, HPV infection rates increased gradually with age, and statistical differences were observed across age groups (χ2 = 180.575; P < 0.001). High-risk HPV genotypes were highly prevalent in women below 25 years of age and those aged 55-59 years. Cluster analysis revealed that the 13 HPV genotypes could be roughly divided into two groups in a single infection; however, patterns of infection consistent with biological characteristics were not observed. CONCLUSION: High-risk HPV was found in 24.1% of outpatients, with HPV52, HPV58, HPV16, HPV39, and HPV51 being the most common high-risk genotypes. Single high-risk HPV infection was predominant. HPV16, HPV39, HPV51, and HPV52 were associated with cervical lesion progression. HPV16 infection was especially worrying since it aggravates cervical lesions. Because the infection rates of the 13 HPV genotypes differed by age, the peak HPV infection rate should not guide vaccination, screening, and prevention programs. Instead, these initiatives should be tailored based on the regional HPV distribution characteristics. Moreover, it was determined that Beijing's populace needed to receive treatment for HPV39 infection.

Robust and Multifunctional Therapeutic Nanoparticles against Peritonitis-Induced Sepsis.

Apart from bacterial growth and endotoxin generation, the excessive production of reactive radicals linked with sepsis also has a substantial impact on triggering an inflammatory response and further treatment failure. Hence, the rational design and fabrication of robust and multifunctional nanoparticles (NPs) present a viable means of overcoming this dilemma. In this study, we used antibiotic polymyxin B (PMB) and antioxidant natural polyphenolic protocatechualdehyde (PCA) to construct robust and multifunctional NPs for sepsis treatment, leveraging the rich chemistries of PCA. The PMB release profile from the NPs demonstrated pH-responsive behavior, which allowed the NPs to exhibit effective bacterial killing and radical scavenging properties. Data from in vitro cells stimulated with H2O2 and lipopolysaccharide (LPS) showed the multifunctionalities of NPs, including intracellular reactive oxygen species (ROS) scavenging, elimination of the bacterial toxin LPS, inhibiting macrophage M1 polarization, and anti-inflammation capabilities. Additionally, in vivo studies further demonstrated that NPs could increase the effectiveness of sepsis treatment by lowering the bacterial survival ratio, the expression of the oxidative marker malondialdehyde (MDA), and the expression of inflammatory cytokine TNF-α. Overall, this work provides ideas of using those robust and multifunctional therapeutic NPs toward enhanced sepsis therapy efficiency.