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Scheme illustration of Antibody-antibiotic conjugates (AAC) target S. aureus and mediate endocytosis to kill bacteria after entry into the cell. The proposed mechanism suggests that S. aureus-AAC complex mediates endocytosis through the antibody Fcγ receptor, and cathepsin cleaves the intracellular AAC-linker to release vancomycin. Subsequently, vancomycin completed the elimination of S. aureus in the cell. [Display omitted] • S. aureus exists in the synovial fluid of patients in the form of a "Trojan horse", avoiding antibiotic treatment and mediating infection recurrence. • The main host cell types of MRSA in implant infection in mice are macrophages, osteoclasts, synoviocytes and osteoblasts. • The modified SpA antibody (M0662) from a clinical strain has a high affinity with SpA surface antigen of S. aureus (KD < 10-3nM). • AAC captures extracellular S. aureus and acts as a "biological bomb" to rapidly eliminate S. aureus in the cell. • Application of AACs in the implant infection model significantly improved the bactericidal effect of vancomycin and blocked bacterial biofilm formation. Treating orthopedic implant-associated infections, especially those caused by Staphylococcus aureus (S. aureus) , remains a significant challenge. S. aureus has the ability to invade host cells, enabling it to evade both antibiotics and immune responses during infection, which may result in clinical treatment failures. Therefore, it is critical to identify the host cell type of implant-associated intracellular S. aureus infections and to develop a strategy for highly targeted delivery of antibiotics to the host cells. Introduced an antibody-antibiotic conjugate (AAC) for the targeted elimination of intracellular S. aureus. The AAC comprises of a human monoclonal antibody (M0662) directly recognizes the surface antigen of S. aureus , Staphylococcus protein A, which is conjugated with vancomycin through cathepsin-sensitive linkers that are cleavable in the proteolytic environment of the intracellular phagolysosome. AAC, vancomycin and vancomycin combined with AAC were used in vitro intracellular infection and mice implant infection models. We then tested the effect of AAC in vivo and in vivo by fluorescence imaging, in vivo imaging, bacterial quantitative analysis and bacterial biofilm imaging. In vitro, it was observed that AAC captured extracellular S. aureus and co-entered the cells, and subsequently released vancomycin to induce rapid elimination of intracellular S. aureus. In the implant infection model, AAC significantly improved the bactericidal effect of vancomycin. Scanning electron microscopy showed that the application of AAC effectively blocked the formation of bacterial biofilm. Further histochemical and micro-CT analysis showed AAC significantly reduced the level of bone marrow density (BMD) and bone volume fraction (BV/TV) reduction caused by bacterial infection in the distal femur of mice compared to vancomycin treatment alone. The application of AAC in an implant infection model showed that it significantly improved the bactericidal effects of vancomycin and effectively blocked the formation of bacterial biofilms, without apparent toxicity to the host. [ABSTRACT FROM AUTHOR]

Left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) are referred to as left bundle branch area pacing. This study investigated whether long-term clinical outcomes differ in patients undergoing LBBP, LVSP, and biventricular pacing (BiVP) for cardiac resynchronization therapy (CRT). Consecutive patients with reduced left ventricular ejection fraction (LVEF <50%) undergoing CRT were prospectively enrolled if they underwent successful LBBP, LVSP, or BiVP. The primary composite end point was all-cause mortality or heart failure hospitalization. Secondary end points included all-cause mortality, heart failure hospitalization, and echocardiographic measures of reverse remodeling. A total of 259 patients (68 LBBP, 38 LVSP, and 153 BiVP) were observed for a mean duration of 28.8 ± 15.8 months. LBBP was associated with a significantly reduced risk of the primary end point by 78% compared with both BiVP (7.4% vs 41.2%; adjusted hazard ratio [aHR], 0.22 [0.08–0.57]; P =.002) and LVSP (7.4% vs 47.4%; aHR, 0.22 [0.08–0.63]; P =.004]. The adjusted risk of all-cause mortality was significantly higher in LVSP than in BiVP (31.6% vs 7.2%; aHR, 3.19 [1.38–7.39]; P =.007) but comparable between LBBP and BiVP (2.9% vs 7.2%; aHR, 0.33 [0.07–1.52], P =.155). Propensity score adjustment also obtained similar results. LBBP showed a higher rate of echocardiographic response (ΔLVEF ≥10%: 60.0% vs 36.2% vs 16.1%; P <.001) than BiVP or LVSP. LBBP yielded long-term clinical outcomes superior to those of BiVP and LVSP. The role of LVSP for CRT needs to be reevaluated because of its high mortality risk. [Display omitted] [ABSTRACT FROM AUTHOR]

Src homology 2 domain-containing tyrosine phosphatase 2 (SHP2) is an essential tyrosine phosphatase that is pivotal in regulating various cellular signaling pathways such as cell growth, differentiation, and survival. The activation of SHP2 has been shown to have a therapeutic effect in colitis and Parkinson's disease. Thus, the identification of SHP2 activators and a complete understanding of their mechanism is required. We used a two-step screening assay to determine a novel allosteric activator of SHP2 that stabilizes it in an open conformation. Oleanolic acid was identified as a suitable candidate. By binding to R362, K364, and K366 in the active center of the PTP domain, oleanolic acid maintained the active open state of SHP2, which facilitated the binding between SHP2 and its substrate. This oleanolic acid-activated SHP2 hindered Th17 differentiation by disturbing the interaction between STAT3 and IL-6R α and inhibiting the activation of STAT3. Furthermore, via the activation of SHP2 and subsequent attenuation of the STAT3–Th17 axis, oleanolic acid effectively mitigated colitis in mice. This protective effect was abrogated by SHP2 knockout or administration of the SHP2 inhibitor SHP099. These findings underscore the potential of oleanolic acid as a promising therapeutic agent for treating inflammatory bowel diseases. Oleanolic acid prevents SHP2 deactivation by binding to it in its open conformation. The resultant activation of SHP2 by oleanolic acid suppresses Th17 differentiation and significantly alleviates colitis in mice. [Display omitted] [ABSTRACT FROM AUTHOR]

This study focuses on the development and characterization of a novel composite material based on flue gas desulfurization (FGD) gypsum modified with functionalized nanocellulose. The incorporation of 0.1 wt% nanocellulose into the FGD gypsum matrix resulted in significant improvements in mechanical strength, water resistance, and thermal insulation properties. The flexural and compressive strength of the optimized composite increased by 32 % and 27 %, respectively, compared to the control sample. The water absorption decreased by 22 %, and the softening coefficient increased from 0.72 to 0.85, indicating enhanced water resistance. The thermal conductivity of the composite was reduced by 31 %, showcasing its potential as an energy-efficient building material. SEM analysis revealed a refined microstructure with improved interfacial bonding between the nanocellulose and gypsum matrix, while FTIR spectroscopy confirmed the presence of chemical interactions between the components. The moisture buffering capacity of the composite was also superior, with a 38 % higher moisture buffering value than the control sample. These findings highlight the potential of functionalized nanocellulose as a reinforcing agent in FGD gypsum-based composites, offering a promising solution for the development of high-performance, eco-friendly building materials. [ABSTRACT FROM AUTHOR]

To study the multilevel coupled vibration of a naval gun under the foundation motion excitation of the ship, a mechanical-electrical-hydraulic coupled dynamic model of the naval gun including the follow-up systems' influence was established. The subprogram for calculating the ship foundation motion was written by the harmonic superposition method, and the motion in the 3 and 5-scale sea waves was reconstructed, respectively. Based on the multidisciplinary simulation, the transmission characteristics of the ship's foundation motion excitation along the naval gun and the influence of the tooth arc arrangement on the stabilization accuracy of the naval gun are analyzed. The results show that: the foundation motion excitation of the ship will aggravate the imbalance of the contact forces at the left and right trunnions of the cradle. A bilateral symmetrical arrangement scheme of the tooth arcs can reduce the contact forces' imbalance at the trunnions and reduce the adverse influence on the stabilization accuracy of the naval gun. The relevant research provides theoretical support and technical guidance for the structural design or verification of the naval gun. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate research hotspots and trends in the field of periodontitis and drug delivery systems from the perspective of bibliometrics. Publications related to periodontitis and drug delivery systems between 2001 and 2023 were retrieved from the Web of Science Core Collection database. Bibliometric analysis was conducted using VOSviewer, CiteSpace, and the R package "bibliometrix." A total of 299 articles from 46 countries, primarily India and China, were included in the analysis, and the number of articles related to periodontitis and drug delivery systems were found to be increasing annually. Silpakorn University, the Government Dental College and Research Institute, and the Indian Institute of Technology were identified as the main research institutions investigating the topic, while the Journal of Periodontology emerged as the most popular and co-cited journal in this field. Among the authors of these articles, Thawatchai Phaechamud published the most papers and Gary Greenstein was the most co-cited author. The development of more suitable treatment methods for periodontitis and materials for developing drug delivery systems is a major focus in this research field, with "implants," "efficacy," "nanoparticles," and "mucoadhesive" being the main emerging research hotspots. To the best of our knowledge, this is the first comprehensive bibliometric study summarizing research trends and developments in the field of periodontitis and drug delivery systems. This information elucidates the latest research frontiers and can assist in conceptualizing new directions in research on periodontitis and drug delivery systems. [ABSTRACT FROM AUTHOR]

• Epilepsy surgery in infants (<12 months) is safe and effective. In this study, 76.7 % (33/43) achieved Engel I at the last postoperative follow-up, which is higher than the average previously reported. • The presence of hypsarrhythmia on preoperative interictal electroencephalogram (EEG), positron emission tomography (PET) features of the lesion area, and diagnosis of an epileptic syndrome were the main factors affecting the postoperative clinical outcomes. • Significant developmental improvements in infants (< 12 months) with drug-resistant epilepsy can be achieved after curative surgery. To investigate the clinical outcomes and safety of surgery in infants (< 12 months of age) with drug-resistant epilepsy, clarify surgical indications, and select appropriate surgical methods. This was a retrospective analysis of infants with drug-resistant epilepsy who underwent epilepsy surgery and were followed up for > 6 months at the Epilepsy Center of Shenzhen Children's Hospital. Clinical data included etiology, seizure type, surgical procedure, preoperative auxiliary examinations, pathological findings, and intraoperative and postoperative complications. Clinical outcomes were assessed based on postoperative seizure frequency, antiseizure medicines (ASMs) use, and neurocognitive development. Intraoperative blood loss, operative duration, postoperative complications, and duration of intensive care were evaluated to assess the safety of epilepsy surgery. Univariate and logistic analyses were performed to explore the factors influencing prognosis. Epilepsy surgery was performed on 44 infants with drug-resistant epilepsy, including 7 patients who underwent two operations. The age of seizure onset ranged from 1 day to 11 months (median: 1 month, interquartile range (IQR): 0.1–3.8), the disease course was 1–11 months (median: 4 months, IQR: 2–7), and the age at surgery was 6.9 ± 3.6 months. Twenty-three patients underwent hemispherectomy (52.3 %), and two underwent subtotal hemispherectomy. Five patients underwent multilobar disconnection, five underwent frontal lobotomy, and the remaining nine underwent focal resection. The surgical duration was 7.5 ± 2 h. Intraoperative blood loss ranged from 50 to 1800 ml (median: 275 ml, IQR: 200–500), with all patients receiving an intraoperative blood transfusion of 0.5–6 U (median: 1.5 U, IQR: 1.5–3). The intensive care unit stay was 1–4 days (median: 1 day, IQR: 1–2). The postoperative complication rate was 13.6 % (6/44; two cases of hydrocephalus with intracranial infection, two isolated hydrocephalus, and two subdural hematomas). Excluding one child who died of severe lung infection approximately one year after surgery and one child lost to follow-up after surgery, all other cases were regularly followed up for 10 –49 months (median: 30 months, IQR: 16.5–36). After surgery, patients were treated with 0–3 ASMs (median: 1 ASM, IQR: 0–2); 27.9 % (12/43) stopped taking ASMs and 51.2 % (22/43) had reduced number of ASMs. Engel I was achieved in 76.7 % (33/43) of the patients at the last follow-up. In 17 cases with complete developmental quotient follow-up data, the preoperative and postoperative developmental quotient means were 28.8 ± 21 and 43.2 ± 20.1, showing statistically significant differences (p<0.05) Epilepsy surgery in infants under 12 months of age is safe and effective. Early preoperative evaluation is crucial for identifying structural lesions and suitable candidates for surgery among infants with drug-resistant epilepsy. The timeliness of surgery is essential for achieving favorable clinical outcomes. [ABSTRACT FROM AUTHOR]

Tranexamic acid (TXA) is acknowledged for reducing blood loss and transfusion requirements in various surgical specialties, yet its role in orthognathic procedures is less defined. Our study seeks to fill this knowledge gap by reviewing the available data and summarising the efficacy and clinical outcomes of TXA in orthognathic surgery. We performed a systematic review and meta-analysis, searching five databases for studies until 16 April, 2023. Our key outcome measures were intraoperative blood loss, postoperative bleeding, and transfusion rate. Previous weaknesses in systematic review and meta-analyses (SRMA) were identified using Assessing the Methodological Quality of Systematic Reviews-2 (AMSTAR-2). The risk of bias was evaluated with the RoB-2 tool. A total of 15 studies were included, involving a combined total of 1060 patients. Compared with the control, the TXA group demonstrated significant reductions in intraoperative blood loss (mean difference −135.60 mL; p < 0.00001; 95% CI, −177.51 to −93.70 mL), Hb level drop (mean difference: 2.67 [−0.63, 5.98]), and improved surgical field visibility [p < 0.00001. (MD −0.99) (CI −1.11 to −0.86)]. No significant differences were observed in postoperative haematocrit levels (mean difference: −0.42 [−2.19, 1.35]; p = 0.003; I2 = 75%), operation duration (p = 0.21), or duration of hospital stay (p = 0.63) between TXA and control groups. In orthognathic surgery, TXA effectively minimises blood loss, demonstrating both safety and efficiency. Well-designed, larger studies and comparisons with other haemostatic agents could solidify TXA evidence. [ABSTRACT FROM AUTHOR]

Numerous studies have investigated bird diversity-environment relationships in agricultural landscapes. While many studies have emphasized the importance of natural/semi-natural elements and their diversity within or surrounding farmlands, it remains unclear how crop diversity impacts birds. There is also a significant gap in our knowledge regarding the effects of temporal changes in crop composition on bird diversity. Using small farmlands in a sub-tropical city of China, we examined how spatial and temporal variation of crops and other local farmland features was linked to species diversity of birds and their traits. In small peri‑urban agricultural areas of Guangzhou, we collected bird and crop/non-crop data approximately bimonthly from December 2021 to October 2022. Overall crop diversity and seasonal crop changes were indexed by alpha diversity (Shannon-Wiener index) and beta diversity, respectively. Both alpha and beta crop diversities were positively associated with Shannon-Wiener diversity of birds. Alpha crop diversity also tended to have a positive impact on species richness. Percent cover of woody vegetation showed a positive effect on all three bird diversity indices, i.e., species richness, Shannon-Wiener diversity, and evenness. Percent cover of rice affected species richness positively and evenness negatively, whereas the effects of percent cover of corn were the opposite. In a fourth-corner analysis, the abundance of plant/seed-eating birds was negatively associated with alpha crop diversity, whereas the abundance of ground-foraging birds was positively associated with beta crop diversity. These patterns indicate that seasonally dynamic crop changes as well as local crop diversity can influence bird diversity and traits in small farmlands. They also suggest that natural/semi-natural woody vegetation, such as trees and shrubs, play a critical role in enhancing species diversity of birds in farmlands dominated by herbaceous edible crops. [ABSTRACT FROM AUTHOR]

• Most studies (13/20) supported unhealthy food environments as a risk factor of CVD. • Healthy food environments were positively linked with CVD in 3 out of 7 studies. • The relationship between comprehensive food environments and CVD was inconsistent. • Future studies should examine food environments and CVD in developing countries. Cardiovascular disease (CVD) is the leading cause of death worldwide, particularly affecting low- and middle-income countries. Food environments may be linked with the risk of CVD; however, current study findings regarding their relationship are inconsistent. A systematic review of their associations is needed to guide interventions to improve cardiovascular health. This systematic review aimed to comprehensively assess the relationship between food environments and CVD outcomes, including incidence, hospitalization, mortality, and recurrence rates. According to PRISMA guidelines, a systematic search was conducted until 28th March 2024, using eight databases, including PubMed, Embase, Ovid, CINAHL, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Data. The review quality was assessed according to the Agency for Healthcare Research and Quality (AHRQ) and Newcastle-Ottawa Scale (NOS). The included studies were categorized based on their exposure factors into unhealthy, healthy, and comprehensive food environments, encompassing facilities that offer healthy and unhealthy foods. The findings were narratively synthesized according to this classification. A total of 23 studies, encompassing 13 cross-sectional studies and 10 cohort-longitudinal studies, were included in this review. Among the 20 studies on unhealthy food environments, 13 found a positive association with CVD outcomes. Of the seven studies on healthy food environments, 3 found a negative association with CVD outcomes. Additionally, 4 out of 8 studies on comprehensive food environments found a significant but inconsistent association with CVD outcomes. This study suggested that unhealthy food environments are probably associated with CVD outcomes. At the same time, there is currently no conclusive evidence to indicate a relationship between healthy food environments or comprehensive food environments and CVD outcomes. [ABSTRACT FROM AUTHOR]

To assess the effects of moxibustion on immune reconstitution inflammatory syndrome (IRIS) in patients with acquired immune deficiency syndrome (AIDS) by tracking T-cell subsets over a 48-week prospective cohort study. Patients with AIDS who had low viral loads and weakened immune systems were divided into a moxibustion group and a non-moxibustion group. The non-moxibustion group received standard western treatment, including 48 weeks of antiretroviral therapy (ART). The moxibustion group received ART combined with moxibusion therapy, administered three times weekly. Each treatment lasted 10 weeks, with four courses completed over 48 weeks, separated by 2-week breaks. At different time points, plasma levels of CD4+, CD8+, CD45RA+, CD45RO+, CD4+CD28+, CD8+CD38+, and CD4+CD38+ were compared between the two groups. A total of 200 eligible patients were included and divided into two groups, with 100 in the non-moxibustion group and 100 in the moxibustion group. At Week 24, the CD4+T cell count was (180.71 ± 79.62) cells/μL in the non-moxibustion group and (218.22 ± 82.02) cells/μL in the moxibustion group. By Week 36, the counts were (204.83 ± 96.78) cells/μL and (239.35±81.90) cells/μL, respectively. At Weeks 24 and 48, the CD8+ T cell and CD45RO+ counts were higher in the moxibustion group than in the non-moxibustion group (P < 0.05). By Week 48, the CD45RA+ count was also higher in the moxibustion group (P < 0.05). At Week 24, the CD4+CD25+ count was lower in the moxibustion group than in the non-moxibustion group (P < 0.05). Moxibustion enhances immune function in patients with AIDS and IRIS by regulating T-HIVcell subsets and increasing CD4+ and CD8+ T lymphocyte counts. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR), the major mechanism by which various cancers develop specific resistance to therapeutic agents, has set up enormous obstacles to many forms of tumor chemotherapy. Traditional cocktail therapy administration, based on the combination of multiple drugs for anti-MDR chemotherapy, often suffers from inconsistent in vivo pharmacokinetic behaviors that cannot act synchronously on the lesions, leading to limited pharmacodynamic outcomes. Despite the emergence of nanomedicines, which has improved chemotherapeutic drugs' bioavailability and therapeutic effect on clinical application, these monotherapy-based nano-formulations still show poor progression in overcoming MDR. Herein, a "one stone and three birds" nanococktail integrated by a cocrystal@protein-anchoring strategy was purposed for triple-payload delivery, which paclitaxel-disulfiram cocrystal-like nanorods (NRs) were anchored with the basic protein drug Cytochrome c (Cyt C), followed by hyaluronic-acid modification. In particular, NRs were utilized as carrier-like particles to synchronously deliver biomacromolecule Cyt C into tumor cells and then promote cell apoptosis. Of note, on A549/Taxol drug-resistant tumor-bearing mice, the system with extraordinarily high encapsulation efficiency demonstrated prolonged in vivo circulation and increased tumor-targeting accumulation, significantly reversing tumor drug resistance and improving therapeutic efficacy. Our mechanistic study indicated that the system induced the apoptosis of Taxol-resistant tumor cells through the signal axis P-glycoprotein/Cyt C/caspase 3. Collectively, this nanococktail strategy offers a promising approach to improve the sensitivity of tumor cells to chemotherapeutic drugs and strengthen intractable drug-resistant oncotherapy. Cocrystal@protein-anchoring nanococktail (HA-HNRplex) triple-payload delivery platform used a "one stone and three birds" strategy to synchronously transport PTX, DSF and Cyt C for treating multidrug resistance cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

To investigate the association between cardiovascular risk estimated using the Framingham Risk Score (FRS) and carotid stiffening determined using ultrafast pulse wave velocity (ufPWV) measurements in apparently healthy individuals. We enrolled 1034 apparently healthy participants without known cardiovascular disease who underwent ufPWV measurements. Clinical and laboratory findings, carotid intima–media thickness (cIMT), pulse wave velocity at the beginning of systole (PWV-BS), and pulse wave velocity at the end of systole (PWV-ES) were assessed. In FRS assessments based on major cardiovascular risk factors (CVRFs), participants were assigned into three risk categories: low risk (<10%, n = 679), intermediate risk (10–20%, n = 191), and high risk (>20%, n = 164); the low-risk category was further subdivided into three subcategories: < 1% (n = 58), 1%− 5% (n = 374) and > 5% (n = 247). Multivariate logistic regression analyses with crude and adjusted odds ratios (ORs) were used to evaluate the association of carotid stiffening and FRS-based risk stratification. Carotid stiffening indicated by PWV-BS and PWV-ES differed notably between the FRS-estimated low-risk vs. intermediate-risk and high-risk categories, but only PWV-ES differed notably among the low-risk subcategories (all p < 0.010), and correlated notably with the FRS-estimated risk most obviously in low-risk participants (r = 0.517). In participants with cIMT < 0.050 cm, only PWV-ES differed significantly among the FRS-estimated risk categories (all p < 0.001). Increased PWV-BS (adjusted OR: 1.49; p = 0.003) and PWV-ES (adjusted OR: 1.29; p = 0.007) were both associated with FRS categories independent of conventional CVRFs in low- vs. intermediate-risk categories, but not in low- vs. high-risk categories (all p > 0.050). In vivo imaging of carotid stiffening by ufPWV measurements is independently linked to FRS categories, and ufPWV indices may help stratify differing levels of cardiovascular risk in apparently healthy young people. Data generated or analyzed during the study are available from the corresponding author by reasonable request. • Carotid stiffening quantified by ufPWV measurements differed notably among FRS-estimated risk categories and low-risk subcategories. • ufPWV indices correlated notably with FRS-estimated risk and major CVRFs. • PWV-ES increased steeply with higher FRS categories, even with normal cIMT. • ufPWV indices were associated with cardiovascular risk stratification independently in low- vs. intermediate-risk populations. • ufPWV may be a promising quantitative predictor for cardiovascular risk stratification in apparently healthy young people. [ABSTRACT FROM AUTHOR]

Oral aphthous ulcers are common mucosal lesions that cause pain and discomfort. There are diverse biomaterials and drug treatments for oral ulcers used in both research and clinical settings. However, the complex oral environment often results in low adhesion and short drug retention times, which lead to poor drug availability and treatment outcomes. In this study, a mussel-inspired adhesive hydrogel was developed by grafting catechol onto hyaluronic acid (C-HA), and dopamine was added for oxidative pre-polymerization to form modified hyaluronic acid (M-HA), which remarkably increased the adhesion of the hydrogels. Then, M-HA was interpenetrated into the gelatin methacryloyl (GelMA) network. Chlorhexidine gluconate (CHG) was then incorporated into the hydrogel to enhance its availability and therapeutic effect through its sustained-release capability. The GelMA/M-HA hydrogel demonstrated strong adhesion to wet tissues, antibacterial and anti-inflammatory properties, and good biocompatibility. In both rat oral ulcers and infected wounds, the adhesive hydrogel significantly accelerated the healing of the ulcers and infected wounds. These results indicated that this adhesive hydrogel offers a promising new strategy for the treatment of oral ulcers in clinical practice. Oral ulcers are a common and high-incidence mucosal condition that seriously affect people's daily lives, often making it difficult for patients to chew and speak. However, a dynamic oral environment with various types of bacteria influences drug availability and treatment effects in clinical settings. To address this challenge, an adhesive, mussel-inspired, drug-loaded hydrogel was constructed using natural macromolecules (hyaluronic acid and gelatin) with good biocompatibility. Chlorhexidine gluconate (CHG), with its broad-spectrum antibacterial activity, has been incorporated to synergistically promote oral ulcer healing. The splendid adhesion, antibacterial, and therapeutic effects of this hydrogel demonstrated a new strategy for treating oral ulcers. [Display omitted] [ABSTRACT FROM AUTHOR]

Limited studies have evaluated the global burden, trends, and cross-country inequalities for urinary tract infections (UTIs) in adolescents and young adults (AYAs). Age-standardized incidence rate, age-standardized mortality rate, and age-standardized Disability-Adjusted Life Years (DALYs) rate were used to describe the UTI burden. The estimated annual percentage changes were calculated to evaluate the temporal trends from 1990 to 2019. The slope index of inequality and concentration index were utilized to quantify the distributive inequalities. From 1990 to 2019, a significant increase in age-standardized incidence rate (estimated annual percentage change =0.22%, 95% confidence interval 0.19%-0.26%) was found for UTIs in AYAs, and the increasing trend was more pronounced in males than females. Significant decreases in age-standardized mortality rate and age-standardized DALY rate were found in females but not in males. The slope index of inequality changed from 21.80 DALYs per 100,000 in 1990 to 20.91 DALYs per 100,000 in 2019 for UTIs in AYAs. Moreover, the concentration index showed -0.23 in 1990 and -0.14 in 2019. Countries with lower sociodemographic development levels shouldered a disproportionately higher UTI burden. UTIs remain an ongoing health burden for AYAs globally, with substantial heterogeneities found across countries, sex, and age groups. • Urinary tract infections (UTIs) remain an ongoing health burden globally. • Studies on global burden and inequalities for UTIs in young population are limited. • UTI showed an increasing incidence trend from 1990 to 2019 in the 15 to 39 age groups. • UTI burden is substantially higher in lower than in higher socioeconomic groups. [ABSTRACT FROM AUTHOR]

To unravel the heterogeneity and function of microenvironmental neutrophils during intervertebral disc degeneration (IDD). Single-cell RNA sequencing (scRNA-seq) was utilized to dissect the cellular landscape of neutrophils in intervertebral disc (IVD) tissues and their crosstalk with nucleus pulposus cells (NPCs). The expression levels of macrophage migration inhibitory factor (MIF) and ACKR3 in IVD tissues were detected. The MIF/ACKR3 axis was identified and its effects on IDD were investigated in vitro and in vivo. We sequenced here 71520 single cells from 5 control and 9 degenerated IVD samples using scRNA-seq. We identified a unique cluster of neutrophils abundant in degenerated IVD tissues that highly expressed MIF and was functionally enriched in extracellular matrix organization (ECMO). Cell-to-cell communication analyses showed that this ECMO-neutrophil subpopulation was closely interacted with an effector NPCs subtype, which displayed high expression of ACKR3. Further analyses revealed that MIF was positively correlated with ACKR3 and functioned via directly binding to ACKR3 on effector NPCs. MIF inhibition attenuated degenerative changes of NPCs and extracellular matrix, which could be partially reversed by ACKR3 overexpression. Clinically, a significant correlation of high MIF/ACKR3 expression with advanced IDD grade was observed. Furthermore, we also found a positive association between MIF+ ECMO-neutrophil counts and ACKR3+ effector NPCs density as well as higher expression of the MIF/ACKR3 signaling in areas where these two cell types were neighbors. These data suggest that ECMO-neutrophil promotes IDD progression by their communication with NPCs via the MIF/ACKR3 axis, which may shed light on therapeutic strategies. [ABSTRACT FROM AUTHOR]

Three novel sesterterpenoids glasesterterpenoids A−C (1 − 3), featuring an unprecedented 7-cyclohexyldecahydronaphthalene carbon skeleton, were isolated from the root of Lindera glauca (L. glauca). Their structures were elucidated by quantum chemical calculations and spectroscopic methods. The biogenetic pathway for 1 − 3 is proposed. In the bioassay, glasesterterpenoid C exhibited DNA topoisomerase 1 (Top1) inhibitory activity compared with the positive control, camptothecin. These findings represent the first examples of sesterterpenoids with a 7-cyclohexyldecahydronaphthalene carbon skeleton from the root of L. glauca. [ABSTRACT FROM AUTHOR]

Tumor relapse and metastasis are the major causes of mortality associated with urothelial cancer. In the tumor microenvironment, negative regulatory molecules and various immune cell subtypes suppress antitumor immunity. The inflammatory microenvironment, associated with neutrophils and neutrophil extracellular traps (NETs), promotes tumor metastasis. However, no drugs are currently available to specifically inhibit neutrophils and NETs. In this study, we first demonstrated that icaritin (ICT), a Chinese herbal remedy that is a first-line treatment for advanced and incurable hepatocellular carcinoma, reduces NETs caused by suicidal NETosis and prevents neutrophil infiltration in the tumor microenvironment. Mechanistically, ICT binds to and inhibits the expression of PADI2 in neutrophils, thereby suppressing PADI2-mediated histone citrullination. Moreover, ICT inhibits ROS generation, suppresses the MAPK signaling pathway, and inhibits NET-induced tumor metastasis. Simultaneously, ICT inhibits tumoral PADI2-mediated histone citrullination, which consequently suppresses the transcription of neutrophil-recruiting genes such as GM-CSF and IL-6. The downregulation of IL-6 expression, in turn, forms a regulatory feedback loop through the JAK2/STAT3/IL-6 axis. Through a retrospective study of clinical samples, we found a correlation between neutrophils, NETs, UCa prognosis, and immune evasion. Combining ICT with immune checkpoint inhibitors may have synergistic effects. In summary, our study demonstrated that ICT could be a novel inhibitor of NETs and a novel UCa treatment. ICT inhibits the tumor recruitment of neutrophils, suppresses PADI2-mediated histone citrullination and ROS production in neutrophils, consequently inhibiting the NETs formation. [Display omitted] [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis, is a common metabolic liver disease worldwide. Currently, satisfactory drugs for NAFLD treatment remain lacking. Obesity and diabetes are the leading causes of NAFLD, and compounds with anti-obesity and anti-diabetic activities are considered suitable candidates for treating NAFLD. In this study, biochemical and histological assays revealed that a natural lignan schisanhenol (SAL) effectively decreased lipid accumulation and improved hepatic steatosis in free fatty acid (FFA)-treated HepG2 cells and high-fat diet (HFD)-induced NAFLD mice. Further, molecular analyses, microRNA (miRNA)-seq, and bioinformatics analyses revealed that SAL may improve NAFLD by targeting the miR-802/adenosine monophosphate-activated protein kinase (AMPK) pathway. Liver-specific overexpression of miR-802 in NAFLD mice significantly impaired SAL-mediated liver protection and decreased the protein levels of phosphorylated (p)-AMPK and PRKAB1. Dual-luciferase assay analysis further confirmed that miR-802 inhibits hepatic AMPK expression by binding to the 3' untranslated region of mouse Prkab1 or human PRKAA1. Additionally, genetic silencing of PRKAA1 blocked SAL-induced AMPK pathway activation in FFA-treated HepG2 cells. The results demonstrate that SAL is an effective drug candidate for treating NAFLD through regulating miR-802/AMPK-mediated lipid metabolism. A natural compound, schisanhenol (SAL), exerts anti-NAFLD effects by inhibiting miR-802 and activating the AMPK signaling pathway to regulate lipid homeostasis. [Display omitted] [ABSTRACT FROM AUTHOR]

With the escalating prevalence of global heat waves, heat stroke has become a prominent health concern, leading to substantial liver damage. Unlike other forms of liver injury, heat stroke-induced damage is characterized by heat cytotoxicity and heightened inflammation, directly contributing to elevated mortality rates. While clinical assessments have identified elevated bilirubin levels as indicative of Kupffer cell dysfunction, their specific correlation with heat stroke liver injury remains unclear. Our hypothesis proposes the involvement of Kupffer cell ferroptosis during heat stroke, initiating IL-1 β -mediated inflammation. Using single-cell RNA sequencing of murine macrophages, a distinct and highly susceptible Kupffer cell subtype, Clec4F+/CD206+, emerged, with heme oxygenase 1 (HMOX-1) playing a pivotal role. Mechanistically, heat-induced HMOX-1, regulated by early growth response factor 1, mediated ferroptosis in Kupffer cells, specifically in the Clec4F+/CD206+ subtype (KC2), activating phosphatidylinositol 4-kinase beta and promoting PI4P production. This cascade triggered NLRP3 inflammasome activation and maturation of IL-1 β. These findings underscore the critical role of targeted therapy against HMOX-1 in ferroptosis within Kupffer cells, particularly in Clec4F+/CD206+ KCs. Such an approach has the potential to mitigate inflammation and alleviate acute liver injury in the context of heat stroke, offering a promising avenue for future therapeutic interventions. This study elucidates the intricate molecular mechanisms underpinning heat stroke-induced liver injury, highlighting the diverse responses of Kupffer cell (KC) subsets and the pivotal role of HMOX-1 in orchestrating ferroptosis in KCs, particularly in KC2, and NLRP3 inflammasome activation. [Display omitted] [ABSTRACT FROM AUTHOR]

The effectiveness of tumor treatment using reactive oxygen species as the primary therapeutic medium is hindered by limitations of tumor microenvironment (TME), such as intrinsic hypoxia in photodynamic therapy (PDT) and overproduction of reducing glutathione (GSH) in chemodynamic therapy (CDT). Herein, we fabricate metal-polyphenol self-assembled nanodots (Fe@BDP NDs) guided by second near-infrared (NIR-II) fluorescence imaging. The Fe@BDP NDs are designed for synergistic combination of type-I PDT and CDT-amplified ferroptosis. In a mildly acidic TME, Fe@BDP NDs demonstrate great Fenton activity, leading to the generation of highly toxic hydroxyl radicals from overproduced hydrogen peroxide in tumor cells. Furthermore, Fe@BDP NDs show favorable efficacy in type-I PDT, even in tolerating tumor hypoxia, generating active superoxide anion upon exposure to 808 nm laser irradiation. The significant efficiency in reactive oxygen species (ROS) products results in the oxidation of sensitive polyunsaturated fatty acids, accelerating lethal lipid peroxidation (LPO) bioprocess. Additionally, Fe@BDP NDs illustrate an outstanding capability for GSH depletion, causing the inactivation of glutathione peroxidase 4 and further promoting lethal LPO. The synergistic type-I photodynamic and chemodynamic cytotoxicity effectively trigger irreversible ferroptosis by disrupting the intracellular redox homeostasis. Moreover, Fe@BDP NDs demonstrate charming NIR-II fluorescence imaging capability and effectively accumulated at the tumor site, visualizing the distribution of Fe@BDP NDs and the treatment process. The chemo/photo-dynamic-amplified ferroptotic efficacy of Fe@BDP NDs was evidenced both in vitro and in vivo. This study presents a compelling approach to intensify ferroptosis via visualized CDT and PDT. In this study, we detailed the fabrication of metal-polyphenol self-assembled nanodots (Fe@BDP NDs) guided by second near-infrared (NIR-II) fluorescence imaging, aiming to intensify ferroptosis via the synergistic combination of type-I PDT and CDT. In a mildly acidic TME, Fe@BDP NDs exhibited significant Fenton activity, resulting in the generation of highly toxic •OH from overproduced H 2 O 2 in tumor cells. Fe@BDP NDs possessed a remarkable capability for GSH depletion, resulting in the inactivation of glutathione peroxidase 4 (GPX4) and further accelerating lethal LPO. This study presented a compelling approach to intensify ferroptosis via visualized CDT and PDT. [Display omitted] [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a kind of multifactorial ocular surface disease that displays ocular discomfort, visual disturbance, and tear film instability. Oxidative stress is a fundamental pathogenesis in DED. An imbalance between the reactive oxygen species (ROS) level and protective enzyme action will lead to oxidative stress, cell dysfunction, tear hyperosmolarity, and inflammation. Herein, a multifunctional cerium oxide nanozyme with high ocular surface retention property was designed to neutralize over-accumulated ROS and restore redox balance. Cerium oxide nanozymes were fabricated via branched polyethylenimine-graft-poly (ethylene glycol) nucleation and dispersion, followed by phenylboronic acid (PBA) functionalization (defined as Ce@PB). Due to the dynamic chemical bonding formation between the PBA segment and the cis-diol groups in the mucin layer of the tear film, Ce@PB nanozymes possess good adhesive capability to the ocular surface, thus extending the drug's retention time. On the other hand, Ce@PB nanozymes could mimic the cascade processes of superoxide dismutase and catalase to maintain intracellular redox balance. In vitro and in vivo studies suggest that such multifunctional nanozymes possess good biocompatibility and hemocompatibility. More importantly, Ce@PB nanozymes treatment in the animal model could repair corneal epithelial defect, increase the number of goblet cells and promote tear secretion, thus achieving an effective treatment for DED. • PBA-functionalized bPEI-g-PEG-based cerium oxide (Ce@PB) nanozymes were designed and fabricated. • The Ce@PB nanozymes have superoxide dismutase (SOD) and catalase (CAT) enzyme-like activity scavenging excessive intracellular reactive oxygen species (ROS). • The Ce@PB nanozymes demonstrate extended retention on the ocular surface and can effectively treat dry eye disease. [Display omitted] [ABSTRACT FROM AUTHOR]

The global climate issue is becoming increasingly serious, and studying the energy transition (ET) has proven to be an effective solution to this problem. The essence of climate mitigation is to address the issue of ensuring the public health (pH) of human beings. Still, the definitions of ET in existing literature are inconsistent, and Many researches overlook the definitions of ET in official documents and discuss the relationship between ET and pH. Therefore, this research utilizes panel data from 107 countries over the period 2000–2020 to construct an energy transition indicator based on the definition from the World Economic Forum (WEF). It also examines the link between ET and pH using a two-way fixed effects regression. In the current turbulent international environment, this paper also investigates this link in the context of composite risk control (CRC), financial risk control (FRC), economic risk control (ERC), and political risk control (PRC). The results show that ET can significantly improve pH, a conclusion that remains significant after being subjected to a range of robustness tests. The study exploring the mechanism impact on the relationship between ET and pH shows that CRC, FRC, ERC, and PRC all strengthen the effect of ET on pH, and the mechanism effect varies considerably between high-income and low- and middle-income countries (LMICs); ET is more significantly affected by the mechanism in LMICs than in high-income countries. Furthermore, this paper illustrates that ET does not differ by gender in improving pH among infants, while there are gender differences in adults by using the instrumental variable regression and GMM regression to mitigate the endogenous and heteroscedasticity issue for heterogeneity test. The study in this paper can not only inspire policy researchers on which aspects to promote ET, but also provide a direction for improving pH. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Extensive research is currently directed at identifying novel targets for its diagnosis and treatment. We investigated the biological functions and clinical significance of mucin-type N-acetylglucosaminyltransferase 3 (GCNT3) in HCC. Variations in the mRNA expression of GCNT3 were examined in normal and HCC tissues. Cell function assays and animal models characterized the effects of GCNT3 on the proliferation, invasion, and migration abilities of HCC cells. Western blot and immunofluorescence analyses were performed to explore further the specific mechanisms whereby GCNT3 affects HCC progression. There is a strong correlation between GCNT3 overexpression and tumor formation and metastasis in vivo and in vitro. GCNT3 acted as a regulator of the synthesis of mucin-type O-glycans by interacting with mucin 13 (MUC13) to regulate its expression levels, activating the GSK3β/β-catenin signaling pathway. The activation of GSK3β/β-catenin signaling by GCNT3 was mitigated by MUC13 knockdown. In clinical HCC specimens, GCNT3 expression was upregulated in HCC tissues compared to non-tumor tissues. Further, there was a significant correlation between high GCNT3 expression and poor patient survival. GCNT3 regulated tumor progression in HCC through the MUC13/GSK3-β/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated T H 2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. Real-time reverse transcription–quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5 -knockout mice were used to establish a nasal polyp model with T H 2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5 -deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions. [ABSTRACT FROM AUTHOR]

Medulloblastoma (MB) and Ependymoma (EM) in children, share similarities in age group, tumor location, and clinical presentation. Distinguishing between them through clinical diagnosis is challenging. This study aims to explore the effectiveness of using radiomics and machine learning on multiparametric magnetic resonance imaging (MRI) to differentiate between MB and EM and validate its diagnostic ability with an external set. Axial T2 weighted image (T2WI) and contrast-enhanced T1weighted image (CE-T1WI) MRI sequences of 135 patients from two centers were collected as train/test sets. Volume of interest (VOI) was manually delineated by an experienced neuroradiologist, supervised by a senior. Feature selection analysis and the least absolute shrinkage and selection operator (LASSO) algorithm identified valuable features, and Shapley additive explanations (SHAP) evaluated their significance. Five machine-learning classifiers-extreme gradient boosting (XGBoost), Bernoulli naive Bayes (Bernoulli NB), Logistic Regression (LR), support vector machine (SVM), linear support vector machine (Linear SVC) classifiers were built based on T2WI (T2 model), CE-T1WI (T1 model), and T1 + T2WI (T1 + T2 model). A human expert diagnosis was developed and corrected by senior radiologists. External validation was performed at Sun Yat-Sen University Cancer Center. 31 valuable features were extracted from T2WI and CE-T1WI. XGBoost demonstrated the highest performance with an area under the curve (AUC) of 0.92 on the test set and maintained an AUC of 0.80 during external validation. For the T1 model, XGBoost achieved the highest AUC of 0.85 on the test set and the highest accuracy of 0.71 on the external validation set. In the T2 model, XGBoost achieved the highest AUC of 0.86 on the test set and the highest accuracy of 0.82 on the external validation set. The human expert diagnosis had an AUC of 0.66 on the test set and 0.69 on the external validation set. The integrated T1 + T2 model achieved an AUC of 0.92 on the test set, 0.80 on the external validation set, achieved the best performance. Overall, XGBoost consistently outperformed in different classification models. The combination of radiomics and machine learning on multiparametric MRI effectively distinguishes between MB and EM in childhood, surpassing human expert diagnosis in training and testing sets. [ABSTRACT FROM AUTHOR]

To evaluate the image quality of low-dose CT colonography (CTC) using deep learning-based reconstruction (DLR) compared to iterative reconstruction (IR). Adults included in the study were divided into four groups according to body mass index (BMI). Routine-dose (RD: 120 kVp) CTC images were reconstructed with IR (RD-IR); low-dose (LD: 100 kVp) images were reconstructed with IR (LD-IR) and DLR (LD-DLR). The subjective image quality was rated on a 5-point scale by two radiologists independently. The parameters for objective image quality included noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The Friedman test was used to compare the image quality among RD-IR, LD-IR and LD-DLR. The Kruskal Wallis test was used to compare the results among different BMI groups. A total of 270 volunteers (mean age: 47.94 years ± 11.57; 115 men) were included. The effective dose of low-dose CTC was decreased by approximately 83.18% (5.18 mSv ± 0.86 vs. 0.86 mSv ± 0.05, P < 0.001). The subjective image quality score of LD-DLR was superior to that of LD-IR (3.61 ± 0.56 vs. 2.70 ± 0.51, P < 0.001) and on par with the RD- IR's (3.61 ± 0.56 vs. 3.74 ± 0.52, P = 0.486). LD-DLR exhibited the lowest noise, and the maximum SNR and CNR compared to RD-IR and LD-IR (all P < 0.001). No statistical difference was found in the noise of LD-DLR images between different BMI groups (all P > 0.05). Compared to IR, DLR provided low-dose CTC with superior image quality at an average radiation dose of 0.86 mSv, which may be promising in future colorectal cancer screening. [ABSTRACT FROM AUTHOR]

Laparoscopic hepatectomy (LH) has become a common surgery for the treatment of liver tumor. To evaluate the surgical quality of laparoscopic hepatectomy under the context of precision surgery with Textbook outcome (TO), a comprehensive and holistic assessment approach. A total of 1056 patients who underwent laparoscopic hepatectomy from May 2016 and December 2022 were enrolled in the study. All the patients were performed hepatectomy. The rate of TO and factors associated with achieving TO were examined. Among the 1056 patients, 75 % patients achieved TO. The main reason limited patients achieving textbook outcomes was prolonged length of hospital stay (LOS). The univariate analysis indicated that age>65, ASA classification ≥3, liver cirrhosis, tumor size > 3 cm, tumor number ≥2, type of primary cancer, and IWATE DSS were significantly associated with non-achievement of TO. The multivariate analysis indicated that the ASA classification ≥3 and advanced difficulty level in IWATE DSS independent factors associated with achieving TO. Reaching TO can significantly prolong the postoperative recurrence time and overall survival time of hepatocellular carcinoma patients. In the context of precision surgery, 75 % patients undergoing laparoscopic hepatectomy achieved a TO. Patients who achieved TO had significantly improved survival. [ABSTRACT FROM AUTHOR]

Gallstones are common and associated with substantial health and economic burden. We aimed to comprehensively evaluate the prevalence and incidence of gallstones in the 21st century. We systematically searched PubMed and Embase to identify studies reporting the prevalence and/or incidence of gallstones between January 1, 2000, and November 18, 2023. Pooled prevalence and incidence were calculated using DerSimonian and Laird's random-effects model. We performed subgroup analyses and meta-regression based on age, sex, geographic location, population setting, and modality of detection to examine sources of heterogeneity. Based on 115 studies with 32,610,568 participants, the pooled prevalence of gallstones was 6.1% (95% CI, 5.6–6.5). Prevalence was higher in females vs males (7.6% vs 5.4%), in South America vs Asia (11.2% vs 5.1%), in upper-middle-income countries vs high-income countries (8.9% vs 4.0%), and with advancing age. On sensitivity analysis of population-based studies, the prevalence of gallstones was 5.5% (95% CI, 4.1–7.4; n = 44 studies), and when limiting subgroup analysis to imaging-based detection modalities, the prevalence was 6.7% (95% CI, 6.1–7.3; n = 101 studies). Prevalence has been stable over the past 20 years. Based on 12 studies, the incidence of gallstones was 0.47 per 100 person-years (95% CI, 0.37–0.51), without differences between males and females, and with increasing incidence in more recent studies. Globally, 6% of the population have gallstones, with higher rates in females and in South America. The incidence of gallstones may be increasing. Our findings call for prioritizing research on the prevention of gallstones. [ABSTRACT FROM AUTHOR]

• A teach-back education program based on BCW was proven effective to mitigate the perioperative pain among patients with lung cancer. • It could also reduce the use of PCA and increase patients' satisfaction, demonstrating it as a cost-effective method in pain management. To assess the effect of a teach-back educational intervention using Behavior Change Wheel (BCW) framework on perioperative pain among patients with lung cancer. A prospective quasi-experimental study was conducted in 88 patients with lung cancer from a tertiary hospital in China. According to the order of admission, they were allocated to either control group or intervention group, with 44 patients in each group. Patients in the control group received routine nursing care, while patients in the intervention group were given a teach-back education program based on BCW framework. The visual analog scale (VAS) was adopted to evaluate patients' pain on the day of surgery (T0), 1 (T1), 2 (T2), and 3 (T3) days after surgery. We also recorded the use of patient-controlled analgesia (PCA), the length of hospital stay, and the degree of patients' satisfaction. Rest pain, pain when coughing, and pain during activity that patients in the intervention group experienced were significantly less severe than those in the control group on T0 and T1. The pain when coughing in the intervention group was also significantly milder on T2 and T3. In addition, the number of self-control time, use duration, and total dose of PCA were significantly lower in the intervention group. Moreover, patients' satisfaction of nursing service was significantly higher in the intervention group. A teach-back education program based on BCW framework was effective in pain management among the perioperative patients with lung cancer. This study demonstrates the application of teach-back method and the BCW in the development of patient education intervention to mitigate perioperative pain. [ABSTRACT FROM AUTHOR]

The prospect of employing chemoimmunotherapy targeted towards the endoplasmic reticulum (ER) presents an opportunity to amplify the synergistic effects of chemotherapy and immunotherapy. In this study, we initially validated celastrol (CEL) as an inducer of immunogenic cell death (ICD) by promoting ER stress and autophagy in colorectal cancer (CRC) cells. Subsequently, an ER-targeted strategy was posited, involving the codelivery of CEL with PD-L1 small interfering RNAs (siRNA) using KDEL peptide-modified exosomes derived from milk (KME), to enhance chemoimmunotherapy outcomes. Our findings demonstrate the efficient transportation of KME to the ER via the Golgi-to-ER pathway. Compared to their non-targeting counterparts, KME exhibited a significant augmentation of the CEL-induced ICD effect. Additionally, it facilitated the release of danger signaling molecules (DAMPs), thereby stimulating the antigen-presenting function of dendritic cells and promoting the infiltration of T cells into the tumor. Concurrently, the ER-targeted delivery of PD-L1 siRNA resulted in the downregulation of both intracellular and membrane PD-L1 protein expression, consequently fostering the proliferation and activity of CD8+ T cells. Ultimately, the ER-targeted formulation exhibited enhanced anti-tumor efficacy and provoked anti-tumor immune responses against orthotopic colorectal tumors in vivo. Collectively, a robust ER-targeted delivery strategy provides an encouraging approach for achieving potent cancer chemoimmunotherapy. ER-targeted delivery amplified celastrol-induced immunogenic cell death and bolstered the therapeutic impact of PD-L1 siRNA to remodel the immunosuppressive microenvironment, thereby augmenting the anti-tumor efficacy in colorectal cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Emotional regulation involves managing attention, affect, and behavior, and is essential for long-term health and well-being, including positive school adjustment. The purpose of this secondary data analysis from the Durham Child Health and Development Study was to explore how parent and teacher reported emotional regulation behaviors related to school adjustment outcomes (social skills, academic performance, and academic achievement) during early childhood. Parent and teacher reports on emotional regulation behaviors showed mixed concordance, however they correlated with critical aspects of school adjustment. Clinical and practical implications are discussed, including the role of psychiatric nurses in promoting positive emotional regulation and school adjustment outcomes across settings. [ABSTRACT FROM AUTHOR]

• This was the first meta-analysis comparing fusion rate of different MCs; • MCs decreased the fusion rate at the 3- and 6-month follow-ups; • MCs-2 and MCs-3 decrease the fusion rate in PLIF. To compare the fusion rates of spinal interbody fusion in patients with modic changes (MCs). This meta-analysis was registered at PROSPERO, and the project number was CRD42024538023. This network meta-analysis was conducted according to the PRISMA 2020 statement. The PubMed, Embase, Web of Science Core Collection, ClinicalTrials.gov and Cochrane Library databases were searched from inception to March 28, 2024 for potential studies. STATA 13.0 and Review Manager 5.3 were used to perform the meta-analysis. Seven studies with a total of 1162 patients or segments assigned to four groups according to MCs grade were identified. The fusion rate in the non-modic changes (NMCs) was significantly greater than that in the MCs at the 3-month (p = 0.0001) and 6-month (p = 0.002) follow-ups. No significant difference was detected in the fusion rate at 12-month (p = 0.34) and final follow-ups (p = 0.41). No significant difference was found in cervical fusion (p = 0.88) or transforaminal lumbar interbody fusion (TLIF) (p = 0.51). The fusion rate of NMCs was significantly greater than that of MCs in posterior lumbar interbody fusion (PLIF) (p < 0.00001). No significant differences were identified among the four groups in the overall comparison, cervical fusion or TLIF subgroups. The fusion rate in the NMCs was significantly greater than that in the MCs-2 and MCs-3 in the PLIF. MCs decreased the fusion rate at the 3- and 6-month follow-ups. MCs-2 and MCs-3 decrease the fusion rate in PLIF. [ABSTRACT FROM AUTHOR]

This study aimed to perform a bibliometric analysis examining contributing countries and collaborative networks, authors and collaborative relationships, the performance of the institutions, and cocited journals and references in 3 major orthodontic journals (American Journal of Orthodontics and Dentofacial Orthopedics , European Journal of Orthodontics , and Angle Orthodontist) over two 10-year periods (2002-2011 and 2012-2021). In this study, 4432 publications in the first decade and 4012 publications in the second decade were quantitatively analyzed and visualized using visualization software such as VOSviewer (Leiden University, Leiden, Netherlands), CiteSpace (Drexel University, Philadelphia, Pa), and Scimago Graphica (SCImago Lab, Spain). Institutions in the United States had the highest number of publications through the 2 decades, whereas Brazil, South Korea, and China achieved significant improvements in performance in the second decade compared with the first. Closer collaborative networks among scholars were revealed in the second decade. The cocitation analysis of the journals showed that highly cited journals included more professional orthodontic journals in the second decade than in the first decade. Bibliometric analysis of publications in 3 major orthodontic journals over two 10-year periods revealed a trend of diversification in countries and institutions participating in publishing, international collaborations, and collaboration networks among authors in the field of orthodontics during the 2 decades. • We analyzed publications in 3 major orthodontic journals in 2002-2011 and 2012-2021. • Institutions in the United States were the most productive country in the 2 decades. • Academic orthodontic departments at universities contributed more publications. • Professional journals on orthodontics were cited more frequently from 2012 to 2021. [ABSTRACT FROM AUTHOR]

• We developed immersive virtual reality (IVR) system to enable students to engage in exploratory learning. • To verify the effect of IVR on assisted learning, we conducted a mixed-methods study. • IVR course stimulates students' curiosity, which reduces the difficulty and cost of learning and improves their performance. • IVR exploratory teaching can be developed in a customized manner, and adapted to other disciplines or other geriatric nursing interventions. This study aimed to enhance understanding, engagement, and learning efficiency in the course "The Care of Common Diseases of Older Adults" using a developed Immersive Virtual Reality(IVR) system. A mixed-methods study with 32 students was conducted. The quantitative part involved a randomized controlled trial, and the qualitative part included thematic interviews with students and teachers. The intervention group using the IVR system showed significant improvements in positivity and performance evaluation scores ( P < 0.05) compared to the control group. Negative affect scores also decreased significantly ( P < 0.05). Qualitative data from interviews supported the quantitative findings, highlighting increased curiosity, learning enthusiasm, and academic performance. IVR significantly enhances learning by stimulating curiosity and active participation, making education more accessible and improving student performance. Future IVR enhancements should focus on user-friendliness and empathetic feedback in adult care. [ABSTRACT FROM AUTHOR]

[Display omitted] Rhinitis is a prevalent, chronic nasal condition associated with asthma. However, its developmental trajectories remain poorly characterized. We sought to describe the course of rhinitis from infancy to adolescence and the association between identified phenotypes, asthma-related symptoms, and physician-diagnosed asthma. We collected rhinitis data from questionnaires repeated across 22 time points among 688 children from infancy to age 11 years and used latent class mixed modeling (LCMM) to identify phenotypes. Once children were between ages 5 and 12, a study physician determined asthma diagnosis. We collected information on the following asthma symptoms: any wheeze, exercise-induced wheeze, nighttime coughing, and emergency department visits. For each, we used LCMM to identify symptom phenotypes. Using logistic regression, we described the association between rhinitis phenotype and asthma diagnosis and each symptom overall and stratified by atopic predisposition and sex. LCMM identified 5 rhinitis trajectory groups: never/infrequent; transient; late onset, infrequent; late onset, frequent; and persistent. LCMM identified 2 trajectories for each symptom, classified as frequent and never/infrequent. Participants with persistent and late onset, frequent phenotypes were more likely to be diagnosed with asthma and to have the frequent phenotype for all symptoms (P <.01). We identified interaction between seroatopy and rhinitis phenotype for physician-diagnosed asthma (P =.04) and exercise-induced wheeze (P =.08). Severe seroatopy was more common among children with late onset, frequent and persistent rhinitis, with nearly 25% of these 2 groups exhibiting sensitivity to 4 or 5 of the 5 allergens tested. In this prospective, population-based birth cohort, persistent and late onset, frequent rhinitis phenotypes were associated with increased risk of asthma diagnosis and symptoms during adolescence. [ABSTRACT FROM AUTHOR]

Biliary atresia is the most common cause of obstructive jaundice in infants and conventional cholangiography is the current diagnostic gold standard. Fluorescent cholangiography with indocyanine green can enhance biliary tree visualization during surgery because it is exclusively excreted into the bile ducts and eventually into the intestine. Therefore, we hypothesized that indocyanine green presence in stool could confirm bile duct patency in infants. A prospective single center cohort study was performed on infants (age ≤ 12 months) with and without jaundice after obtaining IRB approval. Indocyanine green was administered intravenously (0.1 mg/kg). Soiled diapers collected post-injection were imaged for fluorescence. After indocyanine green administration, fluorescence was detected in soiled diapers for control patients (n = 4 , x = 14 h22 m post-injection) and jaundiced patients without biliary atresia (n = 11 , x = 13 h28 m post-injection). For biliary atresia patients (n = 7), post-injection soiled diapers before and after Kasai portoenterostomy were collected. Fluorescence was not detected in stool from 6 of 7 biliary atresia patients. As a test, indocyanine green detection in stool was 97% accurate for assessing biliary patency. Fluorescent Imaging for Indocyanine Green (FIInd Green) in stool is a fast and accurate approach to assess biliary patency non-invasively in infants. Level III. [ABSTRACT FROM AUTHOR]

Bacterial infections pose a global concern due to high fatality rates, particularly with the rise of drug-resistant bacteria and biofilm formation. There is an urgent need for innovative strategies to combat this issue. A study on chemodynamic therapy (CDT) using nanozymes in conjunction with photothermal therapy (PTT) has displayed potential in addressing drug-resistant bacterial infections. However, the effectiveness of this combined approach is limited by inadequate light absorption. This work suggests the NiOx nanoparticles enriched with oxygen vacancies enhance CDT and PTT to overcome this challenge. The presence of oxygen vacancies in NiOx can reduce the energy gap between its valence band and conduction band, facilitating oxygen adsorption. NiOx has exhibited notable antibacterial properties and complete eradication of biofilms in both laboratory and animal trials. In animal abscess models, NiOx demonstrated antibacterial and anti-inflammatory effects in the initial stages, while also promoting wound healing and tissue regeneration by influencing immune factors and encouraging collagen deposition and neovascularization. With positive biosafety and biocompatibility profiles, the oxygen vacancy-enhanced CDT and PTT therapy proposed in this article hold promise for effective sterilization, deep biofilm removal, and treatment of infections caused by drug-resistant bacteria. This study constructs oxygen vacancies NiOx nanoparticles (NiOx NPs) to improve the efficacy of photothermal therapy and chemodynamic therapy. The presence of oxygen vacancies in NiOx NPs helps bridge the energy gap between its valence band and conduction band, facilitating oxygen adsorption and improving catalytic efficiency. In both in vivo and in vitro antibacterial experiments, NiOx NPs demonstrate effective antibacterial and anti-inflammatory properties. Furthermore, it aids in wound healing and tissue regeneration by modulating immune factors, collagen deposition, and angiogenesis. This approach presents a promising collaborative strategy for utilizing nickel-based defective nanomaterials in combating deep drug-resistant bacterial infections. [Display omitted] [ABSTRACT FROM AUTHOR]

Therapeutic resistance is an essential challenge for nanotherapeutics. Herein, a narrow bandgap RuI 3 nanoplatform has been constructed firstly to synergize radiotherapy (RT), photothermal therapy (PTT), and thermoelectric dynamic therapy (TEDT) for tumor eradication. Specifically, the photothermal performance of RuI 3 can ablate tumor cells while inducing TEDT. Noteworthy, the thermoelectric effect is found firstly in RuI 3 , which can spontaneously generate an electric field under the temperature gradient, prompting carrier separation and triggering massive ROS generation, thus aggravating oxidative stress level and effectively inhibiting HSP-90 expression. Moreover, RuI 3 greatly enhances X-ray deposition owing to its high X-ray attenuation capacity, resulting in a pronounced computed tomography imaging contrast and DNA damage. In addition, RuI 3 possesses both catalase-like and glutathione peroxidase-like properties, which alleviate tumor hypoxia and reduce antioxidant resistance, further exacerbating 1O 2 production during RT and TEDT. This integrated therapy platform combining PTT, TEDT, and RT significantly inhibits tumor growth. RuI 3 nanoparticles were synthesized for the first time. RuI 3 exhibited the highest photothermal properties among iodides, and the photothermal conversion efficiency was 53.38 %. RuI 3 was found to have a thermoelectric effect, and the power factor could be comparable to that of most conventional thermoelectric materials. RuI 3 possessed both catalase-like and glutathione peroxidase-like properties, which contributed to enhancing the effect of radiotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) is reshaping clinical practice in dentistry. This study aims to provide a comprehensive overview of global trends and research hotspots on the application of AI to dentistry. Studies on AI in dentistry published between 2000 and 2023 were retrieved from the Web of Science Core Collection. Bibliometric parameters were extracted and bibliometric analysis was conducted using VOSviewer, Pajek, and CiteSpace software. A total of 651 publications were identified, 88.7 % of which were published after 2019. Publications originating from the United States and China accounted for 34.5 % of the total. The Charité Medical University of Berlin was the institution with the highest number of publications, and Schwendicke and Krois were the most active authors in the field. The Journal of Dentistry had the highest citation count. The focus of AI in dentistry primarily centered on the analysis of imaging data and the dental diseases most frequently associated with AI were periodontitis, bone fractures, and dental caries. The dental AI applications most frequently discussed since 2019 included neural networks, medical devices, clinical decision support systems, head and neck cancer, support vector machine, geometric deep learning, and precision medicine. Research on AI in dentistry is experiencing explosive growth. The prevailing research emphasis and anticipated future development involve the establishment of medical devices and clinical decision support systems based on innovative AI algorithms to advance precision dentistry. This study provides dentists with valuable insights into this field. [ABSTRACT FROM AUTHOR]

The prosperity of e-commerce has made our lives more convenient, but the logistics behind it has been silently paying. The e-commerce industry is expanding at an unprecedented rate, and with it comes explosive growth in logistics demand, especially in the warehouse distribution link. In order to meet this demand, the warehouse distribution system needs to be improved both in terms of technology and efficiency. This rapid development also brings a series of problems. First of all is the problem of logistics congestion. Due to the surge in orders, especially during peak shopping periods, logistics centers are often under great pressure. This not only affects the speed of delivery, but can also lead to damage or loss of goods. The purpose of this paper is to find an effective method to optimize the logistics warehouse allocation system of e-commerce, and to provide an efficient and reliable logistics optimization scheme for e-commerce enterprises. In this paper, data analysis and simulation methods are used to analyze. The experimental results show that PSO has the largest improvement in the order clerk operation efficiency (13%) and the smallest improvement in the order status (1%). [ABSTRACT FROM AUTHOR]