Immunogenic Material Vaccine for Cancer Immunotherapy by Structure-Dependent Immune Cell Trafficking and Modulation.

Inherently immunogenic materials offer enormous prospects in enhancing vaccine efficacy. However, the understanding and improving material adjuvanticity remain elusive. Herein how the structural presentation of immunopotentiators in a material governs the dynamic dialogue between innate and adaptive immunity for enhanced cancer vaccination is reported. The immunopotentiator manganese into six differing structures that resemble the architectures of two types of pathogens (spherical viruses or rod-like bacteria) is precisely manipulated. The results reveal that innate immune cells accurately sense and respond to the architectures, of which two outperformed material candidates (151 nm hollow spheres and hollow microrods with an aspect ratio of 4.5) show higher competence in creating local proinflammatory environment with promoted innate immune cell influx and stimulation on dendritic cells (DCs). In combination with viral peptides, model proteins, or cell lysate antigens, the outperformed microrod material remarkably primes antigen-specific CD8 cytolytic T cells. In prophylactic and therapeutic regimens, the microrod adjuvanted vaccines display optimal aptitude in tumor suppression in four aggressive murine tumor models, by promoting the infiltration of heterogeneous cytolytic effector cells while decreasing suppressive immunoregulatory populations in tumors. This study demonstrates that a rationally selected architecture of immunogenic materials potentially advances the clinical reality of cancer vaccination.

Residents' KABP and Social Support Statuses Under Normalized COVID-19 Pandemic Prevention and Control: A Cross-Sectional Study.

OBJECTIVES: To investigate the status quo of residents' knowledge, attitude, belief, and practice (KABP) and social support and the correlation of KABP with social support under normalized coronavirus disease (COVID-19) pandemic prevention and control. METHODS: A questionnaire was designed based on the KABP model, and an online survey was conducted among residents in September 2022. SPSS software (version 25.0) was used to analyze the data. Two independent sample t-tests, one-way analysis of variance (ANOVA), multivariate linear regression analysis, and Pearson's correlation analysis were conducted. RESULTS: In total, 326 valid questionnaires were obtained. The scoring rates of residents' KABP and social support were 68.1%, 92.2%, 89.3%, 75.3%, and 62.6%, respectively. Main factors influencing residents' knowledge included gender, nationality, education level, practice, and social support; those influencing attitude were belief and practice; those influencing belief were place of residence, attitude, and practice; those influencing practice were knowledge, attitude, belief, and social support; and those influencing social support were marital status, place of residence, knowledge, and practice. Social support was positively correlated with knowledge and practice. CONCLUSIONS: This study provides a scientific foundation for the current normalized prevention and control of COVID-19 and is conducive to health managers to better carry out prevention and control related health education for specific groups.

Comparison of esophageal cancer survival after neoadjuvant chemoradiotherapy plus surgery versus definitive chemoradiotherapy: A systematic review and meta-analysis.

Surgery after neoadjuvant chemoradiotherapy remains the gold standard for the treatment of resectable esophageal cancer (EC); however, chemoradiotherapy without surgery has been recommended in specific cases. The aim of this meta-analysis is to analyse the survival between surgeries after neoadjuvant chemoradiotherapy compared with definitive chemoradiotherapy in order to provide a theoretical basis for clinically individualised differential treatment. We conducted an initial search of MEDLINE (PubMed), the Cochrane Library, and Embase for English-only articles that compared treatment regimens and provided survival data. According to the final I2 value of the two survival indicators, the random effect model or fixed effect model was used to calculate the overall hazard ratio (HR) and 95% confidence intervals (CI). Cochrane's Q test was used to judge the heterogeneity of the studies, and a funnel plot was used to evaluate for publication bias. A sensitivity analysis was performed to verify the stability of the included studies. A total of 38 studies involving 29161 patients (neoadjuvant therapy: 15401, definitive chemoradiotherapy: 13760) were included in the analysis. The final pooled results (HR = 0.74, 95% CI: 0.67-0.82) showed a statistically significant increase in overall survival with neoadjuvant chemoradiotherapy plus surgery compared with definitive chemoradiotherapy. Subgroup analyses were performed to determine the effects of heterogeneity, additional treatment regimens, study types, and geographic regions, as well as histologic differences, complications, and recurrence, on the overall results. For people with esophageal cancer that can be removed, neoadjuvant chemoradiotherapy combined with surgery improves survival compared to definitive chemoradiotherapy. However, more research is needed to confirm these results and help doctors make decisions about treatment.

Thiopyran-Fused Mono and Double Helicenes with Low Band Gaps via Simultaneous Ring Expansion and 6-endo Cyclizations.

Mono and double helicenes (M5, M6, D5, and D6) containing six-membered thiopyran rings have been successfully prepared via simultaneous ring expansion and 6-endo cycloisomerizations from the corresponding precursors with five-membered thiophene rings. Although D5 and D6 exhibit similar chemical structures, they demonstrate completely different helical structures because of their distinct steric clashes caused by the incorporated methyl groups. Moreover, all of the thiopyran-fused helicenes exhibit broad absorption bands covering the visible and near-infrared regions.

A computational and experimental study of cis-trans isomeric pesticides based on collision-induced dissociation of high-resolution mass spectrometry.

RATIONALE: Pesticide isomers are widely available in agricultural production and may vary widely in biological activity, potency, and toxicity. Chromatographic and mass spectrometric analysis of pesticide isomers is challenging due to structural similarities. METHODS: Based on liquid chromatography time-of-flight mass spectrometry, identification of cis-trans isomeric pesticides was achieved through retention time, characteristic fragment ions, and relative abundance ratio. Furthermore, theoretical and basic research has been conducted on the differences in characteristic fragment ions and their relative abundance ratios of cis-trans isomers. On the one hand, the cleavage pathways of six cis-trans isomers were elucidated through collision-induced dissociation to explain different fragment ions of the isomers. On the other hand, for those with the same fragment ions but different abundance ratios, energy-resolved mass spectrometry combined with computational chemical density functional theory in terms of kinetics, thermodynamics, and bond lengths was employed to explain the reasons for the differences in characteristic fragment ions and their abundance ratios. RESULTS: A high-resolution mass spectrometry method was developed for the separation and analysis of cis-trans isomers of pesticides in traditional Chinese medicine Radix Codonopsis, and six pesticide isomers were distinguished by retention time, product ions, and relative abundance ratios. The limits of quantification of the six pesticides were up to 10 µg/kg, and the linear ranges of them were 10-200 µg/kg, with coefficients of determination (R2) > 0.99, which demonstrated the good linearity of the six pesticides. The recoveries of the pesticides at spiked concentrations of 10, 20, and 100 µg/kg reached 70-120% with relative standard deviations ≤20%. CONCLUSIONS: It was demonstrated that the application of the method was well suited for accurate qualitative and quantitative analysis for isomers with different structures, which could avoid false-negative results caused by ignoring other isomers effectively.

Joint association of sedentary behavior and physical activity with pulmonary function.

BACKGROUND: Sedentary behavior may influence the respiratory health, but the joint effects of sedentary behavior and physical activity on pulmonary function remains poorly elucidated. We aimed to estimate the association between sedentary behavior and physical activity with pulmonary function. METHODS: A total of 12,343 participants aged 12-79 years were analyzed from the U.S. NHANES 2007-2012. Participants were categorized into 16 groups according to the cross-tabulation of sedentary behavior time (0-4.0, 4.1-8.0, 8.1-12.0, and > 12.0 h/day) and moderate or vigorous physical activity (MVPA) (0, 1-149, 150-299, and ≥ 300 min/week). Generalized linear models were used to test the association of sedentary behavior and MVPA with pulmonary function. RESULTS: Participants with sedentary behavior > 4.0 h/day were negatively related to FEV1 (forced expiratory volume in 1 s) (ß ranging from -0.015 to -0.009, p < 0.05). Compared with the reference group (0 min of MVPA and > 12.0 h/day of sedentary behavior), the negative association of sedentary behavior ≤ 8.0 h/day with FEV1 may be reduced through appropriate MVPA (ß ranging from 0.019 to 0.030, p < 0.05). For sedentary behavior > 8.0 h/day, even MVPA ≥ 300 min/week may not decrease the negative relationships. Similar results were also observed in FVC (forced vital capacity) (ß ranging from 0.018 to 0.030, p < 0.05). In participants aged ≥ 45 years, the associations were more notable. CONCLUSION: This study indicated the sedentary behavior ≤ 4.0 h/day was a relatively healthy lifestyle for pulmonary function. Only below 8.0 h/day of sedentary behavior, the negative association with pulmonary function may be reduced through appropriate MVPA.

YTHDF1's Regulatory Involvement in Breast Cancer Prognosis, Immunity, and the ceRNA Network.

YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), an m6A reader, has a role in the development and progression of breast cancer as well as the immunological microenvironment. The networks of competing endogenous RNA in cancer have received much attention in research. In tumor gene therapy, the regulatory networks of m6A and competing endogenous RNA are increasingly emerging as a new route. We evaluated the relationship between the YTHDF1 expression, overall survival, and clinicopathology of breast cancer using TCGA, PrognoScan, and other datasets. We used Western blot to demonstrate that YTHDF1 is substantially expressed in breast cancer tissues. Furthermore, we explored YTHDF1's functions in the tumor mutational burden, microsatellite instability, and tumor microenvironment. Our findings indicate that YTHDF1 is a critical component of the m6A regulatory proteins in breast cancer and may have a particular function in the immunological microenvironment. Crucially, we investigated the relationship between YTHDF1 and the associated competitive endogenous RNA regulatory networks, innovatively creating three such networks (Dehydrogenase/Reductase 4-Antisense RNA 1-miR-378g-YTHDF1, HLA Complex Group 9-miR-378g-YTHDF1, Taurine Up-regulated 1-miR-378g-YTHDF1). Furthermore, we showed that miR-378g could inhibit the expression of YTHDF1, and that miR-378g/YTHDF1 could impact MDA-MB-231 proliferation. We speculate that YTHDF1 may serve as a biomarker for poor prognosis and differential diagnosis, impact the growth of breast cancer cells via the ceRNA network axis, and be a target for immunotherapy against breast cancer.

Association between postoperative pathological results and non-sentinel nodal metastasis in breast cancer patients with sentinel lymph node-positive breast cancer.

OBJECTIVE: For patients with 1-2 positive sentinel lymph nodes (SLN) identified by biopsy, the necessity of axillary lymph node dissection (ALND) remains a matter of debate. The primary aim of this study was to investigate the association between postoperative pathological factors and non-sentinel lymph node (NSLN) metastases in Chinese patients diagnosed with sentinel node-positive breast cancer. METHODS: This research involved a total of 280 individuals with SLN-positive breast cancer. The relationship between postoperative pathological variables and non-sentinel lymph node metastases was scrutinized using univariate, multivariate, and stratified analysis. RESULTS: Among the 280 patients with a complete count of SLN positives, 126 (45.0%) exhibited NSLN metastasis. Within this group, 45 cases (35.71%) had 1 SLN positive, while 81 cases (64.29%) demonstrated more than 1 SLN positive. Multivariate logistic regression analysis revealed that HER2 expression status (OR 2.25, 95% CI 1.10-4.60, P = 0.0269), LVI (OR 6.08, 95% CI 3.31-11.14, P < 0.0001), and the number of positive SLNs (OR 4.17, 95% CI 2.35-7.42, P < 0.0001) were positively correlated with NSLNM. CONCLUSION: In our investigation, the risk variables for NSLN metastasis included LVI, HER2 expression, and the quantity of positive sentinel lymph nodes. However, further validation is imperative, including this institution, distinct institutions, and diverse patient populations.

2D Hierarchical Microbarcodes with Expanded Storage Capacity for Optical Multiplex and Information Encryption.

The design of nanosegregated fluorescent tags/barcodes by geometrical patterning with precise dimensions and hierarchies could integrate multilevel optical information within one carrier and enhance microsized barcoding techniques for ultrahigh-density optical data storage and encryption. However, precise control of the spatial distribution in micro/nanosized matrices intrinsically limits the accessible barcoding applications in terms of material design and construction. Here, crystallization forces are leveraged to enable a rapid, programmable molecular packing and rapid epitaxial growth of fluorescent units in 2D via crystallization-driven self-assembly. The fluorescence encoding density, scalability, information storage capacity, and decoding techniques of the robust 2D polymeric barcoding platform are explored systematically. These results provide both a theoretical and an experimental foundation for expanding the fluorescence storage capacity, which is a longstanding challenge in state-of-the-art microbarcoding techniques and establish a generalized and adaptable coding platform for high-throughput analysis and optical multiplexing.

Lymphovascular invasion is a significant risk factor for non-sentinel nodal metastasis in breast cancer patients with sentinel lymph node (SLN)-positive breast cancer: a cross-sectional study.

BACKGROUND: A connection between lymphovascular invasion and axillary lymph node metastases in breast cancer has been observed, but the findings are inconsistent and primarily based on research in Western populations. We investigated the association between lymphovascular invasion and non-sentinel lymph node (non-SLN) metastasis in breast cancer patients with sentinel lymph node (SLN) metastasis in western China. METHODS: This study comprised 280 breast cancer patients who tested positive for SLN through biopsy and subsequently underwent axillary lymph node dissection (ALND) at The People's Hospital of Guangxi Zhuang Autonomous Region between March 2013 and July 2022. We used multivariate logistic regression analyses to assess the association between clinicopathological characteristics and non-SLN metastasis. Additionally, we conducted further stratified analysis. RESULTS: Among the 280 patients with positive SLN, only 126 (45%) exhibited non-SLN metastasis. Multivariate logistic regression demonstrated that lymphovascular invasion was an independent risk factor for non-SLN in breast cancer patients with SLN metastasis (OR = 6.11; 95% CI, 3.62-10.32, p < 0.05). The stratified analysis yielded similar results. CONCLUSIONS: In individuals with invasive breast cancer and 1-2 positive sentinel lymph nodes, lymphovascular invasion is the sole risk factor for non-SLN metastases. This finding aids surgeons and oncologists in devising a plan for local axillary treatment, preventing both over- and undertreatment.

Simultaneous Screening and Quantification of 479 Pesticides in Green Tea by LC-QTOF-MS.

A high-throughput screening and quantification method for 479 pesticides in green tea was established based on solid-phase extraction combined with liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Pesticides were extracted from samples using an optimized SPE (TPT cartridges) procedure. LC-QTOF-MS in All Ions MS/MS scan mode acquired full MS data for quantification and product ion spectra for identification. LC-QTOF-MS quantification was achieved using matrix-matched standard calibration curves to achieve the optimal method accuracy. The method performance characteristics included the linearity, overall recovery, precision, and measurement uncertainty being evaluated. The validation results exhibited a good sensitivity with the LOQs of 5-55 µg/kg, which was satisfactory for their MRLs in China or the EU. The recoveries of more than 92.7% of the 479 pesticides in green tea were 70-120% at the three spiked levels with a precision of ≤20%. Finally, this method was employed to analyze 479 pesticides in 95 tea samples from markets in China. The test results of the tea samples showed that tolfenpyrad, buprofezin, and pyridaben were found with lower concentrations. The method has effectively improved the determination efficiency of pesticide residue screening by high-resolution mass spectrometry in green tea.

Tuning the Functionality of Self-Assembled 2D Platelets in the Third Dimension.

The decoration of 2D nanostructures using heteroepitaxial growth is of great importance to achieve functional assemblies employed in biomedical, electrical, and mechanical applications. Although the functionalization of polymers before self-assembly has been investigated, the exploration of direct surface modification in the third dimension from 2D nanostructures has, to date, been unexplored. Here, we used living crystallization-driven self-assembly to fabricate poly(ε-caprolactone)-based 2D platelets with controlled size. Importantly, surface modification of the platelets in the third dimension was achieved by using functional monomers and light-induced polymerization. This method allows us to selectively regulate the height and fluorescence properties of the nanostructures. Using this approach, we gained unprecedented spatial control over the surface functionality in the specific region of complex 2D platelets.

Stereocomplex-Driven Morphological Transition of Coil-Rod-Coil Poly(lactic acid)-Based Cylindrical Nanoparticles.

The stereocomplexation of poly(lactic acid) (PLA) enantiomers opens up an avenue for the formation of new materials with enhanced performance, specifically regarding their mechanical and thermal resistance and resistance to hydrolysis. Despite these useful features, the study of the stereocomplexation between block copolymers based on PLA in solution is limited, and a comprehensive understanding of this phenomenon is urgently needed. Herein, triblock copolymers of poly(N-hydroxyethyl acrylamide) and PL(or D)LA in which PLA was midblock (PHEAAmy-b-PL(D)LAx-b-PHEAAmy) were synthesized and assembled into cylindrical micelles via crystallization-driven self-assembly . The stereocomplexation between enantiomeric micelles facilitates the morphological transition, and the transformation process was investigated in detail by varying the aging temperature, block composition, and solvent. It was found that the solubility of the copolymers played a vital role in determining the occurrence and the speed of the chain exchange between the micelles and the unimers, which thereafter has a significant impact on the shape transition. These results lead to a deeper understanding of the stereocomplex-driven morphological transition process and provide valuable guidance for further optimization of the transition under physiological conditions as a new category of stimuli-responsive systems for biomedical applications.

Age has a U-shaped relationship with breast cancer outcomes in women: a cohort study.

Background and Objectives: Age is a significant determinant of susceptibility to breast cancer. Currently, the available evidence regarding the non-linear correlation between the age of diagnosis and the prognosis of breast cancer patients is contradictory. Insufficient data currently exist regarding the influence of age at diagnosis on the prognosis of breast cancer. The objective of our investigation was to examine the relationship between age at diagnosis and overall survival (OS), breast cancer-specific survival (BCSS), and disease-free survival (DFS). Methods: This retrospective cohort study included 1054 patients diagnosed with breast cancer between March 7, 2013 and December 31, 2019. The hazard ratios (HRs) and 95% confidence interval (CI) for OS, BCSS, DFS were assessed using Cox proportional hazard ratio models and restricted cubic splines (RCS). Results: The study included 1054 breast cancer patients who met the criteria. With a median follow-up of 4.86 years, 71 patients (6.74%) died and 144 patients (13.66%) relapsed. After multivariable adjustment, age showed a U-shaped association with OS, BCSS, and DFS, with significantly higher risk at two ends, with age inflection points of 44, 44, and 41 years for OS, BCSS, and DFS, respectively. For OS, Quartile 1 (HR, 2.09; 95% CI: 0.90-4.84), Quartile 3 (HR, 2.44; 95% CI: 1.05-5.65) and Quartile 4 (HR, 3.38; 95% CI: 1.51-7.54) had poorer OS compared with Quartile 2. Similar results were found for BCSS and DFS. Conclusions: This study confirmed a U-shaped association between age at diagnosis and breast cancer outcome.

Regulating the surface topography of CpG nanoadjuvants via coordination-driven self-assembly for enhanced tumor immunotherapy.

Immunoadjuvants play a key role in enhancing the efficacy of therapeutic tumor vaccines for treating malignant and recurrent cancers. However, due to the bottleneck in the rational design and mechanistic understanding of novel adjuvants, currently available immunoadjuvants in clinical practice are very limited. To boost adjuvant design and development, herein we propose a surface topography regulatory strategy for constructing novel adjuvants with improved adjuvant properties. One of the licensed adjuvants with a well-defined molecular mechanism of immune activation, cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs), was used as the material framework. We constructed immunostimulatory CpG nanoparticles (CpG NPs) with different surface topographies by coordination-driven self-assembly between CpG ODNs and ferrous ions. These self-assembled CpG NPs combine the biological and physical activation abilities of innate immunity and can be used as adjuvants of tumor antigens for malignant tumor immunotherapy. The experimental results showed that these CpG NPs could rapidly enter innate immune cells and remold the tumor microenvironment (TME) to enhance anti-tumor immunotherapy via (i) inducing proinflammatory cytokine production; (ii) promoting the transformation of macrophages from immunosuppressed M2 types into immunoactivated M1 types; (iii) amplifying the antigen presentation of mature dendritic cells (DCs), and (iv) activating T cells in tumor sites. Among the prepared nanostructures, pompon-shaped nanoparticles (NPpo) showed the strongest adjuvant properties and anti-tumor immunotherapeutic effect as the adjuvant of ovalbumin in melanoma-bearing mice. Overall, this work provides an effective strategy for designing novel adjuvants for activating the immunosuppressed TME to enable better cancer immunotherapy.

Effect of preoperative peripheral blood platelet volume index on prognosis in patients with invasive breast cancer.

Aim: This study was designed to investigate the prognostic value of the platelet volume index in patients with invasive breast cancer (IBC). Methods: A total of 524 patients with IBC were enrolled in this study, with a median follow-up time of 6.76 years. The relationship between platelet volume indices and breast cancer prognosis was analyzed. Results: There is a strong correlation between a higher platelet distribution width-to-platelet count ratio (PDW/P) and poorer disease-free survival (DFS) in patients with IBC. The DFS rate was significantly lower among individuals with elevated PDW/P ratios compared with those with lower ratios. Conclusion: The PDW/P ratio is an independent risk factor for predicting DFS in patients with IBC.

Pan-mediastinal neoplasm diagnosis via nationwide federated learning: a multicentre cohort study.

BACKGROUND: Mediastinal neoplasms are typical thoracic diseases with increasing incidence in the general global population and can lead to poor prognosis. In clinical practice, the mediastinum's complex anatomic structures and intertype confusion among different mediastinal neoplasm pathologies severely hinder accurate diagnosis. To solve these difficulties, we organised a multicentre national collaboration on the basis of privacy-secured federated learning and developed CAIMEN, an efficient chest CT-based artificial intelligence (AI) mediastinal neoplasm diagnosis system. METHODS: In this multicentre cohort study, 7825 mediastinal neoplasm cases and 796 normal controls were collected from 24 centres in China to develop CAIMEN. We further enhanced CAIMEN with several novel algorithms in a multiview, knowledge-transferred, multilevel decision-making pattern. CAIMEN was tested by internal (929 cases at 15 centres), external (1216 cases at five centres and a real-world cohort of 11 162 cases), and human-AI (60 positive cases from four centres and radiologists from 15 institutions) test sets to evaluate its detection, segmentation, and classification performance. FINDINGS: In the external test experiments, the area under the receiver operating characteristic curve for detecting mediastinal neoplasms of CAIMEN was 0·973 (95% CI 0·969-0·977). In the real-world cohort, CAIMEN detected 13 false-negative cases confirmed by radiologists. The dice score for segmenting mediastinal neoplasms of CAIMEN was 0·765 (0·738-0·792). The mediastinal neoplasm classification top-1 and top-3 accuracy of CAIMEN were 0·523 (0·497-0·554) and 0·799 (0·778-0·822), respectively. In the human-AI test experiments, CAIMEN outperformed clinicians with top-1 and top-3 accuracy of 0·500 (0·383-0·633) and 0·800 (0·700-0·900), respectively. Meanwhile, with assistance from the computer aided diagnosis software based on CAIMEN, the 46 clinicians improved their average top-1 accuracy by 19·1% (0·345-0·411) and top-3 accuracy by 13·0% (0·545-0·616). INTERPRETATION: For mediastinal neoplasms, CAIMEN can produce high diagnostic accuracy and assist the diagnosis of human experts, showing its potential for clinical practice. FUNDING: National Key R&D Program of China, National Natural Science Foundation of China, and Beijing Natural Science Foundation.

Stretchable and Self-Healable Fiber-Shaped Conductors Suitable for Harsh Environments.

Fiber-shaped conductors with high electrical conductivity, stretchability, and durability have attracted increasing attention due to their potential for integration into arbitrary wearable forms. However, these fiber conductors still suffer from low reliability and short life span, particularly in harsh environments. Herein, a conductive, environment-tolerant, stretchable, and healable fiber conductor (CESH), which consists of a self-healable and stretchable organohydrogel fiber core, a conductive and buckled silver nanowire coating, and a self-healable and waterproof protective sheath, is reported. Such a multilayer core-sheath design not only offers high stretchability (≈2400%), high electrical conductivity (1.0 × 106 S m-1 ), outstanding self-healing ability and durability, but also possesses unprecedented tolerance in harsh environments including wide working temperature (-60-20 °C), arid (≈10 % RH (RH: room humidity)), and underwater conditions. As proof-of-concept demonstrations, CESHs are integrated into various wearable formats as interconnectors to steadily perform the electric function under different mechanical deformations and harsh conditions. Such a new type of multifunctional fiber conductors can bridge the gap in stretchable and self-healing fiber technologies by providing ultrastable electrical conductance and excellent environmental tolerance, which can greatly expand the range of applications for fiber conductors.