Association of screen exposure/sedentary behavior and precocious puberty/early puberty.

Background: In recent years, with the development of society, children's daily exposure to screen time has gradually increased. Screen exposure and sedentary behavior have brought a host of harms to children's lives. The aim of this study was to explore the effects of screen exposure and sedentary behavior on precocious puberty and early development. Methods: This is a cross-sectional study in the school-based population. A total of 3,560 children were recruited from Qufu City, Shandong province using multistage stratified cluster random sampling. All study subjects had a physical examination by professional pediatricians in October 2019, and were investigated with health questionnaires. Precocious puberty is defined as development of secondary sexual signs in boys before 9 years or in girls before 8 years. Screen time was calculated as the average of screen time on weekdays and weekend days, and sedentary time was calculated as the average of sedentary time on weekdays and weekend days. After adjusting for potential confounders, logistic regression was used to examine the association between screen exposure and sedentary behavior and early puberty and precocious puberty. Results: Sedentary time was a risk factor for precocious puberty and early development (OR = 1.428, 95% CI = 1.087-1.876) in girls without adjustment. No significant association was found between screen exposure and early puberty and early development both in girls and boys. Conclusions: Excessive sedentary behavior was associated with an increased risk of early puberty, especially in girls, while there was no significant association between screen exposure and early puberty and early development. In addition, further longitudinal investigations are needed to determine the causal relationship between screen exposure, sedentary behavior and precocious puberty.

Primary Sjogren's Syndrome Associated with Lung Adenocarcinoma: Probing the Potential Common Pathogenic Mechanisms and Experimental Verification.

This study aimed to probe the potential common pathogenic mechanisms linking primary Sjogren's syndrome (pSS) and lung adenocarcinoma (LUAD) through bioinformatics analysis and experimental verification. The relevant genes associated with pSS and LUAD were retrieved from the Gene Expression Omnibus (GEO) database and Genecard database. Subsequently, differentially expressed genes (DEGs) associated with pSS and LUAD were screened as pSS-LUAD-DEGs. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed to elucidate the significant biological functions of pSS-LUAD-DEGs. Core targets were identified by constructing the protein-protein interaction (PPI) network, further assessing hub gene diagnostic accuracy through Receiver Operating Characteristic (ROC) curve analyses. In this study, NOD/Ltj mice served as pSS animal models and were stimulated with particulate matter 2.5 (PM2.5) to generate an inflammatory reaction. Quantitative real-time polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and western blotting were employed for relevant molecular biology experiment verification. The results revealed through KEGG and GO enrichment analyses indicate that inflammation plays a critical role in linking pSS and LUAD. IL6, CCNA2, JAK2, IL1B, ASPM, CCNB2, NUSAP1, and CEP55 were determined as key targets of pSS-LUAD. BALB/c mice and NOD/Ltj mice exhibited enhanced expression of inflammatory cytokines IL-6 and IL-1ß in lung tissues following 21 days of stimulation with PM2.5, activating the JAK2/STAT3 signaling pathway and up-regulating the expression of tumor-associated genes CCNA2, CCNB2, and CEP55, with NOD/Ltj mice exhibiting more pronounced changes than BALB/c mice. This protocol demonstrates that carcinogenesis induced by the pulmonary inflammatory microenvironment may be a key reason for the high incidence of LUAD in pSS patients. Additionally, blocking-related mechanisms may help prevent the occurrence of LUAD in pSS patients.

Study on risk factors of impaired fasting glucose and development of a prediction model based on Extreme Gradient Boosting algorithm.

Objective: The aim of this study was to develop and validate a machine learning-based model to predict the development of impaired fasting glucose (IFG) in middle-aged and older elderly people over a 5-year period using data from a cohort study. Methods: This study was a retrospective cohort study. The study population was 1855 participants who underwent consecutive physical examinations at the First Affiliated Hospital of Soochow University between 2018 and 2022.The dataset included medical history, physical examination, and biochemical index test results. The cohort was randomly divided into a training dataset and a validation dataset in a ratio of 8:2. The machine learning algorithms used in this study include Extreme Gradient Boosting (XGBoost), Support Vector Machines (SVM), Naive Bayes, Decision Trees (DT), and traditional Logistic Regression (LR). Feature selection, parameter optimization, and model construction were performed in the training set, while the validation set was used to evaluate the predictive performance of the models. The performance of these models is evaluated by an area under the receiver operating characteristic (ROC) curves (AUC), calibration curves and decision curve analysis (DCA). To interpret the best-performing model, the Shapley Additive exPlanation (SHAP) Plots was used in this study. Results: The training/validation dataset consists of 1,855 individuals from the First Affiliated Hospital of Soochow University, yielded significant variables following selection by the Boruta algorithm and logistic multivariate regression analysis. These significant variables included systolic blood pressure (SBP), fatty liver, waist circumference (WC) and serum creatinine (Scr). The XGBoost model outperformed the other models, demonstrating an AUC of 0.7391 in the validation set. Conclusions: The XGBoost model was composed of SBP, fatty liver, WC and Scr may assist doctors with the early identification of IFG in middle-aged and elderly people.

The Distribution of Cervical Transformation Zone and Its Impact on Colposcopic Diagnosis: A Multicenter Study in China.

OBJECTIVE: The value of the transformation zone (TZ) is often overlooked in clinical settings. This study aims to assess TZ distribution, associated factors, and its impact on colposcopic diagnosis. METHODS: χ2 tests were used to analyze demographics, clinical history, and tissue samples to examine the differences in TZ distribution. Factors affecting the TZ were explored using logistic regression, and diagnostic indicators were calculated. RESULTS: A total of 5,302 individual datasets were finally included. TZ1, TZ2, and TZ3 accounted for 31.6%, 38.5%, and 30.0%, respectively. Age is the most important factor that influences the location of the TZ. The proportion of TZ3 steadily increased with age, comprising over 55% in women over 50. The colposcopic diagnostic performance shows that high-grade squamous intraepithelial lesion or worse (HSIL+) sensitivity of TZ3 (58.1%, 95% confidence interval [CI] = 52.9-63.4) is significantly lower than that of TZ1 (69.8%, 95% CI = 65.5-74.1) and TZ2 (73.2%, 95% CI = 69.7-76.8). The HSIL+ specificity of TZ3 (96.3, 95% CI = 95.3-97.4) was higher than that of TZ1 (96.3, 95% CI = 95.2-97.3) and TZ2 (92.5, 95% CI = 91.1-93.9). The HSIL+ positive predictive value (81.3%, 95% CI = 76.4-86.2) and negative predictive value (89.3%, 95% CI = 87.6-90.9) for TZ3 are high, with no significant differences when compared with TZ1 and TZ2. CONCLUSIONS: Age predominantly influences TZ location, with TZ3 being most frequently found in women over 50. While TZ3 poses a higher risk of missed diagnosis during colposcopy, it remains clinically valuable in identifying diseased and nondiseased status. Increasing colposcopists' awareness of TZ importance is needed in clinical practice.

Decafluorinated and Perfluorinated Warped Nanographenes: Synthesis, Structural Analysis, and Properties.

Fluorination is a useful approach for tailoring the physicochemical properties of nanocarbon materials. However, owing to the violent reactivity of fluorination, achieving edge-perfluorination of nanographene while maintaining its original π-conjugated structure is challenging. Instead of using traditional fluorination, here, we employed a bottom-up strategy involving fluorine preinstallation and synthesized decafluorinated and perfluorinated warped nanographenes (DFWNG and PFWNG, respectively) through a 10-fold Suzuki-Miyaura coupling followed by a harsh Scholl reaction, whereby precisely edge-perfluorinated nanographene with an intact π-conjugated structure was achieved for the first time. X-ray crystallography confirmed the intact π-conjugated structure and more twisted saddle-shaped geometry of PFWNG compared to that of DFWNG. Dynamic study revealed that the 26-ring carbon framework of PFWNG is less flexible than that of DFWNG and the pristine WNG, enabling chirality resolution of PFWNG and facilitating the achievement of CD spectra at -10 °C. The edge-perfluorination of PFWNG resulted in improved solubility, lower lowest unoccupied molecular orbital, and a surface electrostatic potentials/dipole moment direction opposite those of the pristine WNG. Likely owing to its intact π-conjugated structure, PFWNG exhibits comparable electron mobility with well-known PC61BM. Furthermore, perfluorination improves thermal stability and hydrophobicity, making PFWNG suitable for use as a thermostable/hydrophobic n-type semiconductor material. In the future, this fluorination strategy can be used to synthesize other perfluorinated nanocarbon materials, such as perfluorinated graphene nanoribbons and porous nanocarbon.

Polymer homologue-mediated formation of hydrogel microneedles for controllable transdermal drug delivery.

Poly(ethylene glycol) diacrylate (PEGDA) microneedles (MNs) are hydrogel-based devices that achieve controlled drug delivery kinetics by adjusting the crosslinking density. However, the biosafety of many crosslinking agents used to regulate crosslinking density is not ideal. To avoid crosslinking agents and simplify the preparation process, using two types of polymer homologues with different number-average molecular weights, we have successfully developed a series of PEGDA MNs with controllable crosslinking density (abbreviated as TP-X MNs). The research showed that the mechanical properties and drug release behavior of TP-X MNs could be tuned by simply controlling the weight proportion of two different PEGDA components in MNs. Ex vivo drug delivery experiments indicated that all TP-X MNs exhibited a sustained release profile, and their control range of 336-hour accumulative release rates was from 6.24% to 40.93%. Moreover, we prepared a novel dual-layer PEDGA MN, which can customize the drug loading and release rate in each layer of MN. This work demonstrates a new way to develop hydrogel MNs with adjustable crosslink density and broadens the applications of PEGDA MN in the biomedical field.

Structurally Compact Penta(N,N-diphenylamino)corannulene as Dopant-free Hole Transport Materials for Stable and Efficient Perovskite Solar Cells.

Hole transport materials (HTMs) are essential for improving the stability and efficiency of perovskite solar cells (PSCs). In this study, we have designed and synthesized a novel organic small molecule HTM, cor-(DPA)5, characterized by a bowl-shaped core with symmetric five diphenylamine groups. Compared to already-known HTMs, the bowl-shaped and relatively compact structure of cor-(DPA)5 facilitates intermolecular π-π interactions, promotes film formations, and enhances charge transport. Consequently, the cor-[DPA(2)]5 HTM exhibits high charge mobility, exceptional hydrophobicity, and a significantly elevated glass transition temperature. Superior to previously reported HTMs such as spiro-OMeTAD and cor-OMePTPA, our newly synthesized cor-(DPA)5 HTM is free from any ionic dopants. As a result, the dopant-free cor-[DPA(2)]5-based PSC demonstrates an impressive efficiency of 24.01%, and exhibits outstanding operational stability. It retains 96% after continuous exposure to 1 sun irradiation for 800 hours under MPP (maximum power point) tracking in ambient air. These findings present a structurally compact novel HTM and exemplify a new approach to the molecular design of HTM for the development of stable and effective PSCs.

Nanoparticle-mediated synergistic disruption of tumor innervation and redox homeostasis for potent antineoplastic therapy.

Innervation is closely linked to several biological processes that promote tumor growth, making it an increasingly promising therapeutic target. In this study, biomimetic hollow MnO2 nanocarriers camouflaged with tumor cell membranes (HMLC) are developed to encapsulate lidocaine, an innervation inhibitor, for effective antineoplastic therapy. This approach aims to suppress nerve fiber growth and induce intracellular redox imbalance. Benefiting from the tumor-homing effect, HMLC accumulates in cancerous tissue during circulation and is endocytosed by tumor cells through homologous membrane fusion. Once inside the cells, MnO2 can be degraded by the overproduced glutathione and H2O2, leading to the tumor-specific release of Mn2+ and lidocaine. The Mn2+-mediated Fenton-like reaction promotes the accumulation of reactive oxygen species, and the resulting oxidative stress, combined with glutathione depletion, exacerbates redox imbalance. Simultaneously, the released lidocaine downregulates nerve growth factor and neuronatin. The reduction in nerve growth factor significantly inhibits nerve fiber formation and infiltration in tumor tissue, while the decrease in neuronatin reduces intracellular Ca2+, which helps prevent metastasis. Overall, this strategy highlights the potential of nanoparticle-based tumor innervation disruptors in antineoplastic therapy.

PoIL8-L, a teleost interleukin-8 like, enhances leukocyte cellular vitality and host defense against bacterial infections in Japanese flounder (Paralichthys olivaceus).

Interleukin-8 (IL-8), a CXC chemokine, exerts pivotal effect on cell migration, inflammatory response, and immune regulation. In this study, we examined the immunological characteristics of an IL-8 like homologue (PoIL8-L) in Japanese flounder (Paralichthys olivaceus). PoIL8-L contains a conserved chemokine CXC domain and 105 amino acid residues. PoIL8-L expression in tissues was constitutive, and significantly regulated by V. havieri or E. tarda infection. In vitro, rPoIL8-L could bind to eight tested bacteria, exhibited bacteriostatic and bactericidal effects against certain bacteria, and could bind to the targeted bacterial Ⅳ pilin protein rPilA of E. tarda. Furthermore, rPoIL8-L could attach to peripheral blood leukocytes, and enhance their immune genes expression, respiratory burst, chemotaxis, proliferation, acid phosphatase activity, and phagocytic activity. Additionally, rPoIL8-L induce neutrophils to extrude neutrophil extracellular traps. In vivo, rPoIL8-L could promote host resistance to E. tarda infection. In summary, these findings provide fresh perspectives on the immunological antibacterial properties of IL-8 in teleost.

Chinese colposcopists' attitudes toward the colposcopic artificial intelligence auxiliary diagnostic system (CAIADS): A nation-wide, multi-center survey.

Objective: The objective of this study was to assess the attitudes toward the Colposcopic Artificial Intelligence Auxiliary Diagnostic System (CAIADS) of colposcopists working in mainland China. Methods: A questionnaire was developed to collect participants' sociodemographic information and assess their awareness, attitudes, and acceptance toward the CAIADS. Results: There were 284 respondents from 24 provinces across mainland China, with 55% working in primary care institutions. Participant data were divided into two subgroups based on their colposcopy case load per year (i.e. ≥50 cases; <50 cases). The analysis showed that participants with higher loads had more experience working with CAIADS and were more knowledgeable about CAIADS and AI systems. Overall, in both groups, about half of the participants understood the potential applications of big data and AI-assisted diagnostic systems in medicine. Although less than one-third of the participants were knowledgeable about CAIADS and its latest developments, more than 90% of the participants were open with the idea of using CAIADS. Conclusions: While a related lack of acknowledgement of CAIADS exists, the participants in general had an open attitude toward CAIADS. Practical experience with colposcopy or CAIADS contributed to participants' awareness and positive attitudes. The promotion of AI tools like CAIADS could help address regional health inequities to improve women's well-being, especially in low- and middle-income countries.

PoCXCL8, a teleost chemokine, exerts direct bactericidal, chemotactic/phagocytic, and NETs releasing properties, promoting host anti-bacterial immunity.

As an important CXC chemokine, CXCL8 plays pleiotropic roles in immunological response. In teleost, CXCL8 is involved in cell migration and bacterial invasion. However, the immune antibacterial function of CXCL8 in Japanese flounder (Paralichthys olivaceus) (PoCXCL8) is largely scarce. In this research, we investigated the antibacterial property and leukocyte activation of PoCXCL8. PoCXCL8 consists of 100 amino acid residues, with a conserved chemokine CXC domain. PoCXCL8 was expressed in various tissues, with the highest level in liver and the lowest level in muscle, and sharply induced by V. harveyi or E. tarda in liver, spleen, and head kidney. In vitro, the recombinant PoCXCL8 (rPoCXCL8) could bind to Bacillus subtilis, Edwardsiella tarda, Escherichia coli, Pseudomonas fluorescens, Vibrio anguillarum, Vibrio harveyi, Staphylococcus aureus, and Micrococcus luteus, affect the growth of E. coli, E. tarda, M. luteus, and P. fluorescens, and have a direct bactericidal effect on E. coli and E. tarda. Moreover, rPoCXCL8 was able to bind the outer membranal protein rPilA of E. tarda. In addition, rPoCXCL8 could bind to PBLs, activating the PBLs activity including chemotaxis, proliferation, phagocytosis, reactive oxygen species, acid phosphatase activity. At same time, rPoCXCL8 could induce neutrophil to generate neutrophil extracellular traps (NETs) and promote the expression of inflammatory genes including IL-1ß, IL6, MMP13, TNF-α, and NF-κB. In flounder, the presence of rPoCXCL8 could enhance the in vivo resistance to E. tarda in liver, spleen, and head kidney. Moreover, the PoCXCL8-deficient could attenuate the fish defense against E. tarda infection in in spleen and head kidney. In conclusion, these results provided new insights into the antibacterial properties of CXCL8 in P. olivaceus.

An assessment of ChatGPT's responses to frequently asked questions about cervical and breast cancer.

BACKGROUND: Cervical cancer (CC) and breast cancer (BC) threaten women's well-being, influenced by health-related stigma and a lack of reliable information, which can cause late diagnosis and early death. ChatGPT is likely to become a key source of health information, although quality concerns could also influence health-seeking behaviours. METHODS: This cross-sectional online survey compared ChatGPT's responses to five physicians specializing in mammography and five specializing in gynaecology. Twenty frequently asked questions about CC and BC were asked on 26th and 29th of April, 2023. A panel of seven experts assessed the accuracy, consistency, and relevance of ChatGPT's responses using a 7-point Likert scale. Responses were analyzed for readability, reliability, and efficiency. ChatGPT's responses were synthesized, and findings are presented as a radar chart. RESULTS: ChatGPT had an accuracy score of 7.0 (range: 6.6-7.0) for CC and BC questions, surpassing the highest-scoring physicians (P < 0.05). ChatGPT took an average of 13.6 s (range: 7.6-24.0) to answer each of the 20 questions presented. Readability was comparable to that of experts and physicians involved, but ChatGPT generated more extended responses compared to physicians. The consistency of repeated answers was 5.2 (range: 3.4-6.7). With different contexts combined, the overall ChatGPT relevance score was 6.5 (range: 4.8-7.0). Radar plot analysis indicated comparably good accuracy, efficiency, and to a certain extent, relevance. However, there were apparent inconsistencies, and the reliability and readability be considered inadequate. CONCLUSIONS: ChatGPT shows promise as an initial source of information for CC and BC. ChatGPT is also highly functional and appears to be superior to physicians, and aligns with expert consensus, although there is room for improvement in readability, reliability, and consistency. Future efforts should focus on developing advanced ChatGPT models explicitly designed to improve medical practice and for those with concerns about symptoms.

Human behavior-based COVID-19 transmission in two dining spaces.

Since December 2019, the COVID-19 pandemic has rapidly disseminated globally, posing significant threats to the world. The dining spaces are high-risk indoor environments for the transmission of SARS-CoV-2, posing challenges for intervention and control. This study, based on surveillance videos from two COVID-19 outbreak cases in restaurants, obtained real data on human behaviors of close contact and surface touch. A respiratory infectious disease transmission model was developed, incorporating four transmission routes: short-range airborne, long-range airborne, fomite and large droplet. The results indicate that diners and staff spent 21.9 %-28.7 % and 17.5 %-27.8 % of their time on speaking, respectively, while spending 85.9 %-90.7 % and 83.4 %-87.6 % of their time on surface touching. The primary transmission routes were short-range (contributing 5.8 %-70.9 %) and long-range airborne (contributing 28.4 %-93.0 %), with fomite and large droplet routes contributing less than 12.0 %. Staff-only mask wearing reduced infection risk by 12.8 %-31.8 %. It is recommended that mandatory mask wearing for staff is necessary, while diners should wear masks as much as possible, and that the equivalent ventilation rate of clean fresh air is suggested to 30.0 m3/ (h·person). This study provides a scientific support to make non-pharmaceutical interventions in dinning spaces.

Neighboring Effect-Initiated Supramolecular Nanocomplex with Sequential Infiltration as Irreversible Apoptosis Inducer for Synergetic Chemo-Immunotherapy.

Chemotherapy-based combination regimens are recommended as first-line treatment for colorectal cancer. However, multidrug resistance (MDR) and limited drug infiltration in tumor microenvironment remain critical challenges. Herein, a pH/redox dual activated supramolecular DAS@CD-OxPt (IV) nanoparticles (NPs) via host-guest molecular recognition to achieve relay drugs delivery of active oxaliplatin (OxPt (IV)) and Src inhibitor dasatinib (DAS) between tumor cells is developed. DAS@CD-OxPt (IV) NPs exhibit prolonged circulation in the blood and intra-tumoral retention. Triggered by the endo/lysosome (pH 5.0), flexible DAS@CD-OxPt (IV) NPs exhibited proton-driven in situ assembly to form nanofiber in tumor cells. Dual chemotherapeutic agents released from DAS@CD-OxPt (IV) NPs synergistically cause irreversible DNA damage by blocking p53-mediated DNA repair. Supramolecular nanofibers can further serve as the "ammunition depot" to continuously release drugs from dying cells and transport them into neighboring tumor cells, leading to domino-like cell death and enhanced immunogenicity. Furthermore, DAS@CD-OxPt (IV) NPs combined with immune checkpoint blockade (ICB) therapy strikingly suppress CT26 tumor growth and pulmonary metastasis.

Proton-activated chloride channel increases endplate porosity and pain in a mouse spine degeneration model.

Chronic low back pain (LBP) can severely affect daily physical activity. Aberrant osteoclast-mediated resorption leads to porous endplates, which allow the sensory innervation that causes LBP. Here, we report that expression of the proton-activated chloride (PAC) channel was induced during osteoclast differentiation in the porous endplates via a RANKL/NFATc1 signaling pathway. Extracellular acidosis evoked robust PAC currents in osteoclasts. An acidic environment of porous endplates and elevated PAC activation-enhanced osteoclast fusion provoked LBP. Furthermore, we found that genetic knockout of the PAC gene Pacc1 significantly reduced endplate porosity and spinal pain in a mouse LBP model, but it did not affect bone development or homeostasis of bone mass in adult mice. Moreover, both the osteoclast bone-resorptive compartment environment and PAC traffic from the plasma membrane to endosomes to form an intracellular organelle Cl channel had a low pH of approximately 5.0. The low pH environment activated the PAC channel to increase sialyltransferase St3gal1 expression and sialylation of TLR2 in the initiation of osteoclast fusion. Aberrant osteoclast-mediated resorption is also found in most skeletal disorders, including osteoarthritis, ankylosing spondylitis, rheumatoid arthritis, heterotopic ossification, and enthesopathy. Thus, elevated Pacc1 expression and PAC activity could be a potential therapeutic target for the treatment of LBP and osteoclast-associated pain.

Ti3C2Tx@PLGA/Icaritin microspheres-modified PLGA/ß-TCP scaffolds modulate Icaritin release to enhance bone regeneration through near-infrared response.

Porous poly (lactic-co-glycolic acid)/ß-tricalcium phosphate/Icaritin (PLGA/ß-TCP/ICT, PTI) scaffold is a tissue engineering scaffold based on PLGA/ß-TCP (PT) containing Icaritin, the main active ingredient of the Chinese medicine Epimedium. Due to its excellent mechanical properties and osteogenic effect, PTI scaffold has the potential to promote bone defect repair. However, the release of ICT from the scaffolds is difficult to control. In this study, we constructed Ti3C2Tx@PLGA/ICT microspheres (TIM) and evaluated their characterization as well as ICT release under near-infrared (NIR) irradiation. We utilized TIM to modify the PT scaffold and performed biological experiments. First, we cultured rat bone marrow mesenchymal stem cells on the scaffold to assess biocompatibility and osteogenic potential under on-demand NIR irradiation. Subsequently, to evaluate the osteogenic properties of TIM-modified scaffoldin vivo, the scaffold was implanted into a femoral condyle defect model. TIM have excellent drug-loading capacity and encapsulation efficiency for ICT, and the incorporation of Ti3C2Txendows TIM with photothermal conversion capability. Under 0.90 W cm-2NIR irradiation, the temperature of TIM maintained at 42.0 ± 0.5 °C and the release of ICT was accelerated. Furthermore, while retaining its original properties, the TIM-modified scaffold was biocompatible and could promote cell proliferation, osteogenic differentiation, and biomineralizationin vitro, as well as the osteogenesis and osseointegrationin vivo, and its effect was further enhanced through the modulation of ICT release under NIR irradiation. In summary, TIM-modified scaffold has the potential to be applied in bone defects repairing.

Distribution and diagnostic value of single and multiple high-risk HPV infections in detection of cervical intraepithelial neoplasia: A retrospective multicenter study in China.

The risk associated with single and multiple human papillomavirus (HPV) infections in cervical intraepithelial neoplasia (CIN) remains uncertain. This study aims to explore the distribution and diagnostic significance of the number of high-risk HPV (hr-HPV) infections in detecting CIN, addressing a crucial gap in our understanding. This comprehensive multicenter, retrospective study meticulously analyzed the distribution of single and multiple hr-HPV, the risk of CIN2+, the relationship with CIN, and the impact on the diagnostic performance of colposcopy using demographic information, clinical histories, and tissue samples. The composition of a single infection was predominantly HPV16, 52, 58, 18, and 51, while HPV16 and 33 were identified as the primary causes of CIN2+. The primary instances of dual infection were mainly observed in combinations such as HPV16/18, HPV16/52, and HPV16/58, while HPV16/33 was identified as the primary cause of CIN2+. The incidence of hr-HPV infections shows a dose-response relationship with the risk of CIN (p for trend <0.001). Compared to single hr-HPV, multiple hr-HPV infections were associated with increased risks of CIN1 (1.44, 95% confidence interval [CI]: 1.20-1.72), CIN2 (1.70, 95% CI: 1.38-2.09), and CIN3 (1.08, 95% CI: 0.86-1.37). The colposcopy-based specificity of single hr-HPV (93.4, 95% CI: 92.4-94.4) and multiple hr-HPV (92.9, 95% CI: 90.8-94.6) was significantly lower than negative (97.9, 95% CI: 97.0-98.5) in detecting high-grade squamous intraepithelial lesion or worse (HSIL+). However, the sensitivity of single hr-HPV (73.5, 95% CI: 70.8-76.0) and multiple hr-HPV (71.8, 95% CI: 67.0-76.2) was higher than negative (62.0, 95% CI: 51.0-71.9) in detecting HSIL+. We found that multiple hr-HPV infections increase the risk of developing CIN lesions compared to a single infection. Colposcopy for HSIL+ detection showed high sensitivity and low specificity for hr-HPV infection. Apart from HPV16, this study also found that HPV33 is a major pathogenic genotype.

A Precise Pulmonary Airway Tree Segmentation Method Using Quasi-Spherical Region Constraint and Tracheal Wall Gap Sealing.

Accurate segmentation of the pulmonary airway tree is crucial for diagnosing lung diseases. To tackle the issues of low segmentation accuracy and frequent leaks in existing methods, this paper proposes a precise segmentation method using quasi-spherical region-constrained wavefront propagation with tracheal wall gap sealing. Based on the characteristic that the surface formed by seed points approximates the airway cross-section, the width of the unsegmented airway is calculated, determining the initial quasi-spherical constraint region. Using the wavefront propagation method, seed points are continuously propagated and segmented along the tracheal wall within the quasi-spherical constraint region, thus overcoming the need to determine complex segmentation directions. To seal tracheal wall gaps, a morphological closing operation is utilized to extract the characteristics of small holes and locate low-brightness tracheal wall gaps. By filling the CT values at these gaps, the method seals the tracheal wall gaps. Extensive experiments on the EXACT09 dataset demonstrate that our algorithm ranks third in segmentation completeness. Moreover, its performance in preventing airway leaks is significantly better than the top-two algorithms, effectively preventing large-scale leak-induced spread.

Loss of the putative Rab GTPase, Ypt7, impairs the virulence of Cryptococcus neoformans.

Small GTPases of the Rab family coordinate multiple membrane fusion and trafficking events in eukaryotes. In fungi, the Rab GTPase, Ypt7, plays a critical role in late endosomal trafficking, and is required for homotypic fusion events in vacuole biogenesis and inheritance. In this study, we identified a putative YPT7 homologue in Cryptococcus neoformans, a fungal pathogen causing life threatening meningoencephalitis in immunocompromised individuals. As part of an ongoing effort to understand mechanisms of iron acquisition in C. neoformans, we established a role for Ypt7 in growth on heme as the sole iron source. Deletion of YPT7 also caused abnormal vacuolar morphology, defective endocytic trafficking and autophagy, and mislocalization of Aph1, a secreted vacuolar acid phosphatase. Ypt7 localized to the vacuolar membrane and membrane contact sites between the vacuole and mitochondria (vCLAMPs), and loss of the protein impaired growth on inhibitors of the electron transport chain. Additionally, Ypt7 was required for robust growth at 39°C, a phenotype likely involving the calcineurin signaling pathway because ypt7 mutants displayed increased susceptibility to the calcineurin-specific inhibitors, FK506 and cyclosporin A; the mutants also had impaired growth in either limiting or high levels of calcium. Finally, Ypt7 was required for survival during interactions with macrophages, and ypt7 mutants were attenuated for virulence in a mouse inhalation model thus demonstrating the importance of membrane trafficking functions in cryptococcosis.

Design, synthesis and anti-HBV activity study of novel HBV capsid assembly modulators.

Capsid assembly modulators (CAMs) have the potential to cure chronic hepatitis B, as demonstrated in clinical trials. Lead compounds NVR3-778 and 5a were found to exist in normal and flipped conformations through induced fit docking. Therefore, we designed and synthesized series I and II compounds by interchanging the amide and sulfonamide bonds of 5a to modify both the tolerance region and solvent-opening region. Among them, compound 4a (EC50 = 0.24 ± 0.10 µM, CC50 > 100 µM) exhibited potent anti-HBV activity with low toxicity, surpassing the lead compounds NVR3-778 (EC50 = 0.29 ± 0.03 µM, CC50 = 20.78 ± 2.29 µM) and 5a (EC50 = 0.50 ± 0.07 µM, CC50 = 48.16 ± 9.15 µM) in HepAD38 cells. Additionally, compared with the lead compound, 4a displayed a stronger inhibitory effect on HBV capsid protein assembly. Molecular dynamics (MD) simulations confirmed that the normal conformation of 4a had relatively stable conformation at different frames of binding modes. Furthermore, 4a showed better metabolic stability in human plasma than positive control drugs. Therefore, compound 4a could be further structurally modified as a potent lead compound.