Structural analysis and blood-enriching effects comparison based on biological potency of Angelica sinensis polysaccharides.

Angelica sinensis is a long-standing medicine used by Chinese medical practitioners and well-known for its blood-tonic and blood-activating effects. Ferulic acid, ligustilide, and eugenol in Angelica sinensis activate the blood circulation; however, the material basis of their blood-tonic effects needs to be further investigated. In this study, five homogeneous Angelica sinensis polysaccharides were isolated, and their sugar content, molecular weight, monosaccharide composition, and infrared characteristics determined. Acetylphenylhydrazine (APH) and cyclophosphamide (CTX) were used as inducers to establish a blood deficiency model in mice, and organ indices, haematological and biochemical parameters were measured in mice. Results of in vivo hematopoietic activity showed that Angelica sinensis polysaccharide (APS) could elevate erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), and interleukin-3 (IL-3) serum levels, reduce tumor necrosis factor-α (TNF-α) level in mice, and promote hematopoiesis in the body by regulating cytokine levels. Biological potency test results of the in vitro blood supplementation indicated strongest tonic activity for APS-H2O, and APS-0.4 has the weakest haemopoietic activity. The structures of APS-H2O and APS-0.4 were characterized, and the results showed that APS-H2O is an arabinogalactan glycan with a main chain consisting of α-1,3,5-Ara(f), α-1,5- Ara(f), ß-1,4-Gal(p), and ß-1,4-Gal(p)A, and two branched chains of ß-t-Gal(p) and α-t-Glc(p) connected to each other in a (1→3) linkage to α-1,3,5-Ara(f) on the main chain. APS-0.4 is an acidic polysaccharide with galacturonic acid as the main chain, consisting of α-1,4-GalA, α-1,2-GalA, α-1,4-Gal, and ß-1,4-Rha. In conclusion, APS-H2O can be used as a potential drug for blood replenishment in patients with blood deficiency, providing a basis for APS application in clinical treatment and health foods, as well as research and development of new polysaccharide-based drugs.

Metal nanowire-based transparent electrode for flexible and stretchable optoelectronic devices.

High-quality transparent electrodes are indispensable components of flexible optoelectronic devices as they guarantee sufficient light transparency and electrical conductivity. Compared to commercial indium tin oxide, metal nanowires are considered ideal candidates as flexible transparent electrodes (FTEs) owing to their superior optoelectronic properties, excellent mechanical flexibility, solution treatability, and higher compatibility with semiconductors. However, certain key challenges associated with material preparation and device fabrication remain for the practical application of metal nanowire-based electrodes. In this review, we discuss state-of-the-art solution-processed metal nanowire-based FTEs and their applications in flexible and stretchable optoelectronic devices. Specifically, the important properties of FTEs and a cost-benefit analysis of existing technologies are introduced, followed by a summary of the synthesis strategy, key properties, and fabrication technologies of the nanowires. Subsequently, we explore the applications of metal-nanowire-based FTEs in different optoelectronic devices including solar cells, photodetectors, and light-emitting diodes. Finally, the current status, future challenges, and emerging strategies in this field are presented.

Skin microbiome profiling reveals the crucial role of microbial metabolites in anti-photoaging.

BACKGROUND: Skin microbiota is essential for health maintenance. Photoaging is the primary environmental factor that affects skin homeostasis, but whether it influences the skin microbiota remains unclear. OBJECTIVE: The objective of this study is to investigate the relationship between photoaging and skin microbiome. METHODS: A cohort of senior bus drivers was considered as a long-term unilateral ultraviolet (UV) irradiated population. 16S rRNA amplicon sequencing was conducted to assess skin microbial composition variations on different sides of their faces. The microbiome characteristics of the photoaged population were further examined by photoaging guinea pig models, and the correlations between microbial metabolites and aging-related cytokines were analyzed by high-throughput sequencing and reverse transcription polymerase chain reaction. RESULTS: Photoaging decreased the relative abundance of microorganisms including Georgenia and Thermobifida in human skin and downregulated the generation of skin microbe-derived antioxidative metabolites such as ectoin. In animal models, Lactobacillus and Streptobacillus abundance in both the epidermis and dermis dropped after UV irradiation, resulting in low levels of skin antioxidative molecules and leading to elevated expressions of the collagen degradation factors matrix metalloproteinase (MMP)-1 and MMP-2 and inflammatory factors such as interleukin (IL)-1ß and IL-6. CONCLUSIONS: Skin microbial characteristics have an impact in photoaging and the loss of microbe-derived antioxidative metabolites impairs skin cells and accelerates the aging process. Therefore, microbiome-based therapeutics may have potential in delaying skin aging.

The construction of machine learning-based predictive models for high-quality embryo formation in poor ovarian response patients with progestin-primed ovarian stimulation.

OBJECTIVE: To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms. METHODS: A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children's Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group (N = 1950) and the non-high-quality cleavage embryo group (N = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group (N = 124) and the non-high-quality blastocyst group (N = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly. RESULTS: Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636-0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759-0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741-0.884). CONCLUSION: We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions.

TGF-ß1 mediates hypoxia-preconditioned olfactory mucosa mesenchymal stem cells improved neural functional recovery in Parkinson's disease models and patients.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear. METHODS: We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients. RESULTS: A functional assay identified that transforming growth factor-ß1 (TGF-ß1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-ß1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD. CONCLUSIONS: These findings provide compelling evidence for the involvement of TGF-ß1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-ß1 may be used alone or combined with hOM-MSCs therapy for treating PD.

Structural insights into the binding of nanobodies to the staphylococcal enterotoxin B.

Staphylococcal Enterotoxin Type B (SEB), produced by Staphylococcus aureus bacteria, is notorious for inducing severe food poisoning and toxic shock syndrome. While nanobody-based treatments hold promises for combating SEB-induced diseases, the lack of structural information between SEB and nanobodies has hindered the development of nanobody-based therapeutics. Here, we present crystal structures of SEBNb3, SEBNb6, SEBNb8, SEBNb11, and SEB-Nb20 at resolutions ranging from 1.59 Što 2.33 Å. Crystallographic analysis revealed that Nb3, Nb8, Nb11, and Nb20 bind to SEB at the T-cell receptor (TCR) interface, while Nb6 binds at the major histocompatibility complex (MHC) interface, suggesting their potential to inhibit SEB function by disrupting interactions with TCR or MHC molecules. Molecular biological analyses confirmed the thermodynamic and kinetic parameters of Nb3, Nb5, Nb6, Nb8, Nb11, Nb15, Nb18, and Nb20 to SEB. The competitive inhibition was further confirmed by cell-based experiments demonstrating nanobody neutralization. These findings elucidate the structural basis for developing specific nanobodies to neutralize SEB threats, providing crucial insights into the underlying mechanisms and offering significant assistance for further optimization towards future therapeutic strategies.

A Novel Ultrasound Method of Evaluating Dynamic Extrusion of Lateral Meniscus in Healthy Population: Different Patterns of Dynamic Extrusion Revealed Between Lateral and Medial Meniscus.

OBJECTIVES: To establish a reliable ultrasound (US) method of evaluating dynamic extrusion of lateral meniscus in healthy population, and to investigate the pattern of dynamic meniscus extrusion (ME) in lateral meniscus under loading conditions. METHODS: The lateral ME was examined via US method in unloaded, double-leg standing, and single-leg standing positions. Two different US measurement methods were compared to the magnetic resonance imaging (MRI) results to determine the optimal measurement methods. The US results obtained by different researchers were tested for interobserver consistency and the results obtained by the same researcher on two separate days were tested for intraobserver consistency. The patterns of dynamic extrusion were compared between medial and lateral sides. RESULTS: A total of healthy 44 volunteers were included in the study, with 86 knees assessed by US, and 25 knees evaluated by MRI. The US evaluation of dynamic lateral ME demonstrated excellent interobserver and intraobserver reliability. The US measurements using method A were consistent with the MRI results with no significant difference (P = .861, intraclass correlation coefficient [ICC] = 0.868), while method B underestimated the lateral ME compared to MRI (P = .001, ICC = 0.649). Lateral ME decreased slightly from unloaded (1.0 ± 0.8 mm) to single-leg standing position (0.8 ± 0.8 mm), whereas medial ME increased significantly in both double-leg and single-leg standing positions (2.4 ± 0.7 mm, 2.6 ± 0.7 mm). CONCLUSION: A novel US evaluation method of lateral ME was established with reliable and accurate results compared to the MRI. Lateral ME in healthy populations decreased slightly as the loadings increased, which was different from the pattern of dynamic extrusion in medial meniscus.

Do social economic status modify the association between air pollution and depressive or anxiety symptoms? A big sample cross-sectional study from the rural areas of Central China.

BACKGROUND: Fewer studies have examined the relationship between air pollution and depressive or anxiety symptoms in rural residents. Social economic status (SES), as an important indicator of the current state of socioeconomic development, we know little about how it modifies the relationship between air pollution and symptoms of depression or anxiety. METHODS: The patient health questionnaire (PHQ-2) and generalized anxiety scale (GAD-2) were used to learn about the prevalence of depressive and anxiety symptoms, the social economic status of the participants was categorized into two levels: lower and higher, and a binary logistic regression model was used to analyze the relationship between air pollution and residents' symptoms of depression or anxiety. RESULTS: A total of 10,670 adults were enrolled in this study, of which a total of 1292 participants suffered from depressive symptoms and 860 suffered from anxiety symptoms. Short-term exposure to PM2.5 and O3, singly or in combination, may be associated with the onset of depression symptoms, and there was a significant interaction between SES and exposure to PM2.5 or O3. Residents of areas with higher SES may have a lower risk of suffering from anxiety symptoms after O3 exposure compared to participants living in lower SES. LIMITATIONS: The study was a cross-sectional study, which may have lowered the quality level of the evidence. CONCLUSIONS: Short-term PM2.5 and O3 exposure may be associated with an increased prevalence risk of depressive symptoms. Higher levels of SES may reduce the adverse effects of air pollution on depressive or anxiety symptoms.

Isolation and characterization of a novel Bacillus cereus bacteriophage vBce-DP7.

Foodborne pathogens have become a major concern for public health. Bacillus cereus, a representative foodborne pathogen, is particularly challenging due to its ability to cause food poisoning and its resilient spores that are difficult to completely eradicate. Therefore, it is crucial to develop measures to prevent and control B. cereus. Bacteriophages, which are high specific towards their host strains and cannot infect eukaryotes, have proven to be effective in combating foodborne pathogens and are safe for human use. In this study, we isolated and characterized a novel bacteriophage named vBce-DP7 that specifically targets B. cereus strains belonging to three different sequence types (STs). Phage vBce-DP7 is a lytic one and has a short latent time of only 15 minutes. Moreover, it exhibited a good temperature tolerance, retaining high activity across a broad range of 4 - 55 °C. Additionally, its activity remains unaffected within a wide pH range spanning from 2 - 10. Interestingly, with only 4% genetic similarity with known bacteriophages, vBce-BP7 shows a possible classification on a family level though it shares many similar functional proteins with Salasmaviridae bacteriophages. Taken together, vBce-BP7 demonstrates its significant potential for further exploration in terms of phage diversity and its application in controlling B. cereus.

Dual-recognition colorimetric platform based on porous Au@Pt nanozymes for highly sensitive washing-free detection of Staphylococcus aureus.

A dual-recognition strategy is reported to construct a one-step washing and highly efficient signal-transduction tag system for high-sensitivity colorimetric detection of Staphylococcus aureus (S. aureus). The porous (gold core)@(platinum shell) nanozymes (Au@PtNEs) as the signal labels show highly efficient peroxidase mimetic activity and are robust. For the sake of simplicity the detection involved the use of a vancomycin-immobilized magnetic bead (MB) and aptamer-functionalized Au@PtNEs for dual-recognition detection in the presence of S. aureus. In addition, we designed a magnetic plate to fit the 96-well microplate to ensure consistent magnetic properties of each well, which can quickly remove unreacted Au@PtNEs and sample matrix while avoiding tedious washing steps. Subsequently, Au@PtNEs catalyze hydrogen peroxide (H2O2) to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) generating a color signal. Finally, the developed Au@PtNEs-based dual-recognition washing-free colorimetric assay displayed a response in the range of S. aureus of 5 × 101-5 × 105 CFU/mL, and the detection limit was 40 CFU/mL within 1.5 h. In addition, S. aureus-fortified samples were analyzed to further evaluate the performance of the proposed method, which yielded average recoveries ranging from 93.66 to 112.44% and coefficients of variation (CVs) within the range 2.72-9.01%. These results furnish a novel horizon for the exploitation of a different mode of recognition and inexpensive enzyme-free assay platforms as an alternative to traditional enzyme-based immunoassays for the detection of other Gram-positive pathogenic bacteria.

Impact of a 12-wk physical conditioning program on the aerobic capacity of aviation cadets.

BACKGROUND: Flight cadets need to have good physical fitness to cope with the challenges of flying missions. The continuous development of science and technology has led to the constant upgrading of fighter jets and the improvement of their performance, which has resulted in new and higher requirements for the physical fitness of flight personnel. The traditional physical training mode, method, and assessment have been used for many years and do not meet current fitness needs. AIM: To investigate the impact of a 12-wk comprehensive anti-G fitness training program on the aerobic capacity of aviation cadets and to evaluate its effectiveness. METHODS: Fifty-five cadets were randomly assigned to control and experimental groups using a randomized, single-blind design. The control group maintained their existing training regimen, while the experimental group participated in a 12-wk comprehensive training intervention. The training program comprised strength training twice per week, high-intensity interval training three times per week, and supplemental nutritional and psychological support. Maximal oxygen uptake (VO2max), lower limb strength, and hemoglobin levels were measured at baseline, at 6 wk and 12 wk post-intervention. RESULTS: Repeated measures analysis of variance revealed significant differences of both VO2max and relative VO2 in both groups across time points (P < 0.05). However, no significant time-group interaction was observed (P > 0.05). Paired t-tests comparing baseline and 12-wk results showed that VO2max and relative VO2 were significantly higher in the experimental group than the control group (P < 0.05). This suggests that the training program effectively enhanced the aerobic capacity of the experimental group. Key indicators of aerobic capacity, bilateral lower limb strength and hemoglobin levels, were also significantly different over time and between groups (P < 0.05). No significant differences were noted in heart-rate metrics (P > 0.05). CONCLUSION: A 12-wk comprehensive anti-G fitness training program significantly improved the aerobic capacity of aviation cadets, thereby enhancing their overall capacity and laying a physiological foundation for enduring high-G flights.

Remote ischemic conditioning prevents ischemic cerebrovascular events in children with moyamoya disease: a randomized controlled trial.

BACKGROUND: Moyamoya disease (MMD) is a significant cause of childhood stroke and transient ischemic attacks (TIAs). This study aimed to assess the safety and efficacy of remote ischemic conditioning (RIC) in children with MMD. METHODS: In a single-center pilot study, 46 MMD patients aged 4 to 14 years, with no history of reconstructive surgery, were randomly assigned to receive either RIC or sham RIC treatment twice daily for a year. The primary outcome measured was the cumulative incidence of major adverse cerebrovascular events (MACEs). Secondary outcomes included ischemic stroke, recurrent TIA, hemorrhagic stroke, revascularization rates, and clinical improvement assessed using the patient global impression of change (PGIC) scale during follow-up. RIC-related adverse events were also recorded, and cerebral hemodynamics were evaluated using transcranial Doppler. RESULTS: All 46 patients completed the final follow-up (23 each in the RIC and sham RIC groups). No severe adverse events associated with RIC were observed. Kaplan-Meier analysis indicated a significant reduction in MACEs frequency after RIC treatment [log-rank test (Mantel-Cox), P = 0.021]. At 3-year follow-up, two (4.35%) patients had an ischemic stroke, four (8.70%) experienced TIAs, and two (4.35%) underwent revascularization as the qualifying MACEs. The clinical improvement rate in the RIC group was higher than the sham RIC group on the PGIC scale (65.2% vs. 26.1%, P < 0.01). No statistical difference in cerebral hemodynamics post-treatment was observed. CONCLUSIONS: RIC is a safe and effective adjunct therapy for asymptomatic children with MMD. This was largely due to the reduced incidence of ischemic cerebrovascular events.

Finite element analysis of endoscopic cross-overtop decompression for single-segment lumbar spinal stenosis based on real clinical cases.

Introduction: For severe degenerative lumbar spinal stenosis (DLSS), the conventional percutaneous endoscopic translaminar decompression (PEID) has some limitations. The modified PEID, Cross-Overtop decompression, ensures sufficient decompression without excessive damage to the facet joints and posterior complex integrity. Objectives: To evaluate the biomechanical properties of Cross-Overtop and provide practical case validation for final decision-making in severe DLSS treatment. Methods: A finite element (FE) model of L4-L5 (M0) was established, and the validity was verified against prior studies. Endo-ULBD (M1), Endo-LOVE (M2), and Cross-Overtop (M3) models were derived from M0 using the experimental protocol. L4-L5 segments in each model were evaluated for the range of motion (ROM) and disc Von Mises stress extremum. The real clinical Cross-Overtop model was constructed based on clinical CT images, disregarding paraspinal muscle influence. Subsequent validation using actual FE analysis results enhances the credibility of the preceding virtual FE analysis. Results: Compared with M0, ROM in surgical models were less than 10°, and the growth rate of ROM ranged from 0.10% to 11.56%, while those of disc stress ranged from 0% to 15.75%. Compared with preoperative, the growth rate of ROM and disc stress were 2.66%-11.38% and 1.38%-9.51%, respectively. The ROM values in both virtual and actual models were less than 10°, verifying the affected segment stability after Cross-Overtop decompression. Conclusion: Cross-Overtop, designed for fully expanding the central canal and contralateral recess, maximizing the integrity of the facet joints and posterior complex, does no significant effect on the affected segmental biomechanics and can be recommended as an effective endoscopic treatment for severe DLSS.

Enhancing Adhesion and Reducing Ohmic Contact through Nickel-Silicon Alloy Seed Layer in Electroplating Ni/Cu/Ag.

Due to the lower cost compared to screen-printed silver contacts, the Ni/Cu/Ag contacts formed by plating have been continuously studied as a potential metallization technology for solar cells. To address the adhesion issue of backside grid lines in electroplated n-Tunnel Oxide Passivating Contacts (n-TOPCon) solar cells and reduce ohmic contact, we propose a novel approach of adding a Ni/Si alloy seed layer between the Ni and Si layers. The metal nickel layer is deposited on the backside of the solar cells using electron beam evaporation, and excess nickel is removed by H2SO4:H2O2 etchant under annealing conditions of 300-425 °C to form a seed layer. The adhesion strength increased by more than 0.5 N mm-1 and the contact resistance dropped by 0.5 mΩ cm2 in comparison to the traditional direct plating Ni/Cu/Ag method. This is because the resulting Ni/Si alloy has outstanding electrical conductivity, and the produced Ni/Si alloy has higher adhesion over direct contact between the nickel-silicon interface, as well as enhanced surface roughness. The results showed that at an annealing temperature of 375 °C, the main compound formed was NiSi, with a contact resistance of 1 mΩ cm-2 and a maximum gate line adhesion of 2.7 N mm-1. This method proposes a new technical solution for cost reduction and efficiency improvement of n-TOPCon solar cells.

Distinct time trends in colorectal cancer incidence in countries with SDI levels from 1990 to 2019: an age-period-cohort analysis for the Global Burden of Disease 2019 study.

Introduction: The burden of colorectal cancer (CRC) plays a pivotal role in the global cancer epidemic. Our study reported the incidence trends in CRC and the associated effects of age, period, and birth cohort in 204 countries and territories over the past 30 years. Methods: The incidence data of CRC were extracted from the Global Burden of Disease Study (GBD) 2019. We performed the age-period-cohort (APC) model to estimate the overall annual percentage change (net drift) in the incidence rate, the annual percentage change by age group (local drift), and the relative risk (period and cohort effects) of the period and cohort in CRC during 1990-2019. This approach allows examining and distinguishing age, period, and cohort effects in incidence and potentially distinguishing colorectal cancer gaps in prevention and screening. Results: In 2019, the incidence of CRC was 2.17 (95% UI 2.00-2.34) million, of which China, the United States of America, and Japan had the highest incidence population, accounting for 45.9% of the global population. The age-standardized incidence rate (ASIR) was 26.7 (95% UI 28.9-24.6) per 100,000 people, of which 30 countries had an incidence rate greater than 40.0 per 100,000 people. From 1990 to 2019, the middle SDI region had the largest increase in incidence rate, with a net drift of 2.33% (95% CI 2.2-2.46%, p < 0.001). Globally, the incidence population was concentrated in the age group of 50-69 years, and the age group of 30-34 years had the largest increase in incidence rate (local drift 1.19% (95% CI 1.01-1.37%)). At the same time, the sex and age distributions of CRC incidence had significant heterogeneity across regions and countries. In the past 30 years, the incidence rate in 31 countries has been well controlled (net drift <0), and most of them were concentrated in high-and high-middle-SDI regions, such as Australia, Czechia, and Belgium, and the relative risk of incidence generally improved over time and consecutive young birth cohorts. CRC incidence showed an unfavorable trend (net drift ≥1%) in 89 countries, of which 27 countries were more significant (net drift >2%), mostly concentrated in the middle SDI region, such as China, Mexico, and Brazil, and the risk of period and birth cohort was unfavorable. Conclusion: Globally, the incidence of CRC has shown an overall upward trend over the past 30 years, with the exception of some countries with higher SDI values. Significant age-period-cohort differences were observed in the risk of incidence in CRC worldwide. Effective prevention and control policies need to take into account the age-period-cohort effect characteristics of different regions.

Health screenings in college health centers: Variations in practice.

Objective: The purpose of this study was to examine the routine screening of female students in college health centers for six priority health-related behaviors and experiences (tobacco use, alcohol use, eating disorders [EDs], obesity, anxiety and depression, intimate partner violence/sexual violence [IPV/SV]), and to identify variations in practice. Participants: A nationally representative sample of 1,221 healthcare providers (HCPs), including nurse practitioners, physicians, and physician assistants, from 471 U.S. college health centers. Methods: HCPs completed surveys (on-line or paper) and reported on routine screening of female college students. Results: HCPs reported consistently high rates (75-85%) of screening for tobacco use, alcohol use, and anxiety/depression. Rates of screening for IPV/SV, obesity and EDs were much lower. Nurse practitioners reported the highest IPV/SV screening rates. Conclusions: College health centers present unique opportunities for screening, case-finding and intervening to reduce long-term sequelae. Providers are well-positioned to lead initiatives to improve screening practices.

Comparison of gasless transaxillary endoscopic thyroidectomy, endoscopic thyroidectomy via areola approach and conventional open thyroidectomy in patients with unilateral papillary thyroid carcinoma.

BACKGROUND: Gasless transaxillary endoscopic thyroidectomy (GTET) and endoscopic thyroidectomy via the areola approach (ETA) have emerged as minimally invasive surgical techniques for managing papillary thyroid carcinoma (PTC). This study aimed to assess the surgical efficacy of endoscopic thyroidectomy (ET) as compared to conventional open thyroidectomy (COT) in PTC patients. METHODS: Between 2020 and 2022, 571 PTC patients underwent unilateral thyroidectomy accompanied by ipsilateral central lymph node dissection. This cohort comprised 72 patients who underwent GTET, 105 ETA, and 394 COT. The analysis encompassed a comprehensive examination of patient clinicopathologic characteristics and postoperative complaints. Furthermore, the learning curve of GTET was evaluated using the cumulative summation (CUSUM) method. RESULTS: Patients in the ET group exhibited a lower mean age and a higher proportion of female individuals. Operation time in the ET group was significantly longer. No significant differences were observed in the incidence of postoperative complications among the three groups. With regard to postoperative complaints reported three months after surgery, GTET demonstrated superior alleviation of anterior chest discomfort and swallowing difficulties. Patients who underwent ET reported significantly higher cosmetic satisfaction levels. Additionally, the learning curve of GTET was 27 cases, and the operation time during the mature phase of the learning curve exhibited a significant reduction when compared to ETA. CONCLUSIONS: The findings of this study affirm the safety and feasibility of employing GTET and ETA for the surgical management of PTC. GTET presents an attractive surgical option, particularly for patients with unilateral PTC who place a premium on cosmetic outcomes.

TSFAN: tensorized spatial-frequency attention network with domain adaptation for cross-session EEG-based biometric recognition.

Objective.Electroencephalogram (EEG) signals are promising biometrics owning to their invisibility, adapting to the application scenarios with high-security requirements. However, It is challenging to explore EEG identity features without the interference of device and state differences of the subject across sessions. Existing methods treat training sessions as a single domain, affected by the different data distribution among sessions. Although most multi-source unsupervised domain adaptation (MUDA) methods bridge the domain gap between multiple source and target domains individually, relationships among the domain-invariant features of each distribution alignment are neglected.Approach.In this paper, we propose a MUDA method, Tensorized Spatial-Frequency Attention Network (TSFAN), to assist the performance of the target domain for EEG-based biometric recognition. Specifically, significant relationships of domain-invariant features are modeled via a tensorized attention mechanism. It jointly incorporates appropriate common spatial-frequency representations of pairwise source and target but also cross-source domains, without the effect of distribution discrepancy among source domains. Additionally, considering the curse of dimensionality, our TSFAN is approximately represented in Tucker format. Benefiting the low-rank Tucker Network, the TSFAN can scale linearly in the number of domains, providing us the great flexibility to extend TSFAN to the case associated with an arbitrary number of sessions.Main results.Extensive experiments on the representative benchmarks demonstrate the effectiveness of TSFAN in EEG-based biometric recognition, outperforming state-of-the-art approaches, as verified by cross-session validation.Significance.The proposed TSFAN aims to investigate the presence of consistent EEG identity features across sessions. It is achieved by utilizing a novel tensorized attention mechanism that collaborates intra-source transferable information with inter-source interactions, while remaining unaffected by domain shifts in multiple source domains. Furthermore, the electrode selection shows that EEG-based identity features across sessions are distributed across brain regions, and 20 electrodes based on 10-20 standard system are able to extract stable identity information.

A novel inhalable nanobody targeting IL-4Rα for the treatment of asthma.

BACKGROUND: Inhalable biologics represent a promising approach to improve the efficacy and safety of asthma treatment. Although several mAbs targeting IL-4 receptor α chain (IL-4Rα) have been approved or are undergoing clinical trials, the development of inhalable mAbs targeting IL-4Rα presents significant challenges. OBJECTIVE: Capitalizing on the distinctive advantages of nanobodies (Nbs) in maintaining efficacy during storage and administration, we sought to develop a novel inhalable IL-4Rα Nb for effectively treating asthma. METHODS: Three IL-4Rα immunized Nb libraries were used to generate specific and functional IL-4Rα Nbs. LQ036, a bivalent Nb comprising 2 HuNb103 units, was constructed with a high affinity and specificity for human IL-4Rα. The efficacy, pharmacokinetics, and safety of inhaled LQ036 were evaluated in B-hIL4/hIL4RA humanized mice. RESULTS: LQ036 inhibited secreted embryonic alkaline phosphatase reporter activity, inhibited TF-1 cell proliferation, and suppressed phosphorylated signal transducer and activator of transduction 6 in T cells from patients with asthma. Crystal structure analysis revealed a binding region similar to dupilumab but with higher affinity, leading to better efficacy in blocking the signaling pathway. HuNb103 competed with IL-4 and IL-13 for IL-4Rα binding. Additionally, LQ036 significantly inhibited ovalbumin-specific IgE levels in serum, CCL17 levels in bronchoalveolar lavage fluid, bronchial mucous cell hyperplasia, and airway goblet cell hyperplasia in B-hIL4/hIL4RA humanized mice. Inhaled LQ036 exhibited favorable pharmacokinetics, safety, and tissue distribution, with higher concentrations observed in the lungs and bronchi. CONCLUSIONS: These findings from preclinical studies establish the safety and efficacy of inhaled LQ036, underscoring its potential as a pioneering inhalable biologic therapy for asthma.