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Abstract Colloidal quantum dots (CQDs) are promising optoelectronic materials for solution‐processed thin film optoelectronic devices. However, the large surface area with abundant surface defects of CQDs and trap‐assisted non‐radiative recombination losses at the interface between CQDs and charge‐transport layer limit their optoelectronic performance. To address this issue, an interface heterojunction strategy is proposed to protect the CQDs interface by incorporating a thin layer of polyethyleneimine (PEIE) to suppress trap‐assisted non‐radiative recombination losses. This thin layer not only acts as a protective barrier but also modulates carrier recombination and extraction dynamics by forming heterojunctions at the buried interface between CQDs and charge‐transport layer, thereby enhancing the interface charge extraction efficiency. This enhancement is demonstrated by the shortened lifetime of carrier extraction from 0.72 to 0.46 ps. As a result, the resultant PbS CQD solar cells achieve a power‐conversion‐efficiency (PCE) of 13.4% compared to 12.2% without the heterojunction.

Food waste jeopardizes food security and causes economic and resource losses. Household food waste is the most significant source of global food waste and urgently needs to be reduced. Based on the China Health and Nutrition Survey (CHNS), our study estimates the daily food waste data of 6,418 sample observations across China and the dietary preference scores of their household heads. Using a count regression model, our study explores the relationship between dietary preference and household food waste in Chinese households, and further explores the moderating function of household refrigerator use. The study has found that: (1) improving dietary preference score can significantly reduce household food waste ratio, and robustness tests support this finding. (2) There is a positive moderating effect of refrigerator use in the process of how dietary preference influence food waste. (3) Heterogeneity analysis shows that the impact of dietary preference on household food waste varies by gender and age of the household head, household size, economic level, urban–rural type, and north–south region. Our study provides evidence that improving dietary preference can reduce household food waste in China, which has certain implications for waste reduction in other developing countries.

Objectives: Effective exclusion of low-risk symptomatic outpatient cases for colorectal cancer (CRC) remains diagnostic challenges. We aimed to develop a self-reported symptom-based decision-making model for application in outpatient scenarios. Methods: In total, 8233 symptomatic cases at risk for CRC, as judged by outpatient physicians, were involved in this study at seven medical centers. A decision-making model was constructed using 60 self-reported symptom parameters collected from the questionnaire. Further internal and external validation cohorts were built to evaluate the discriminatory power of the CRC model. The discriminatory power of the CRC model was assessed by the C-index and calibration plot. After that, the clinical utility and user experience of the CRC model were evaluated. Results: Nine symptom parameters were identified as valuable predictors used for modeling. Internal and external validation cohorts verified the adequate discriminatory power of the CRC model. In the clinical application step, all 17 physicians found the model easy to grasp, 99.9 % of the patients were satisfied with the survey form. Application of this model detected all CRC cases. The total consistency ratio of outpatient cases undergoing colonoscopy was 81.4 %. None of the low-risk patients defined by the CRC model had been diagnosed with CRC. Conclusion: This multicenter study developed and validated a simple and user-friendly decision-making model covering self-reported information. The CRC model has been demonstrated to perform well in terms of rapid outpatient decision-making scenarios and clinical utility, particularly because it can better rule out low-risk outpatient cases.

BackgroundDisulfidptosis and ferroptosis are forms of programmed cell death that may be associated with the pathogenesis of periodontitis. Our study developed periodontitis-associated biomarkers combining disulfidptosis and ferroptosis, which provides a new perspective on the pathogenesis of periodontitis.MethodsFirstly, we obtained the periodontitis dataset from public databases and found disulfidptosis- and ferroptosis-related differentially expressed transcripts based on the disulfidptosis and ferroptosis transcript sets. After that, transcripts that are tissue biomarkers for periodontitis were found using three machine learning methods. We also generated transcript subclusters from two periodontitis microarray datasets: GSE16134 and GSE23586. Furthermore, three transcripts with the best classification efficiency were further screened. Their expression and classification efficacy were validated using qRT-PCR. Finally, periodontal clinical indicators of 32 clinical patients were collected, and the correlation between three transcripts above and periodontal clinical indicators was analyzed.ResultsWe identified six transcripts that are tissue biomarkers for periodontitis, the top three transcripts with the best classification, and delineated two expression patterns in periodontitis.ConclusionsOur study found that disulfidptosis and ferroptosis were associated with immune responses and may involve periodontitis genesis.

ObjectiveTo quantitatively study the measurement data related to the bony posterior cranial fossa and explore the correlation between bony posterior cranial fossa morphology and the occurrence of hemifacial spasm.MethodsA total of 50 patients with hemifacial spasm who attended the Department of Neurosurgery of China-Japan Friendship Hospital from October 2021 to February 2022 were included, and 60 patients with minor head trauma excluding skull fracture and intracranial abnormalities were included as controls. Cranial multilayer spiral CTs (MSCTs) were performed in both groups, and multiplanar reconstruction (MPR) was used as a postprocessing method to measure data related to the posterior cranial fossa in both groups.ResultsCompared with the control group, the anteroposterior diameter (labeled AB) and the height (labeled BE) of the bony posterior cranial fossa, the anteroposterior diameter of the foramen magnum (labeled BC), the length of the clivus (labeled AB), and the length of the posterior occipital (labeled CD) in the HFS group were all reduced, and the differences were statistically significant. BE is positively correlated with AB and CD, with a stronger correlation observed between BE and AB (r = 0.487, p

BackgroundType 1 diabetes mellitus (T1DM) is a chronic metabolic disease that seriously jeopardizes human physical and mental health and reduces quality of life. Intestinal flora is one of the critical areas of exploration in T1DM research.ObjectiveThis study aims to explore the research hotspot and development trend of T1DM and intestinal flora to provide research direction and ideas for researchers.MethodsWe used the Web of Science (WOS) Core Collection and searched up to 18 November 2023, for articles on studies of the correlation between T1DM and intestinal flora. CiteSpace, VOSviewers and R package “bibliometrix” were used to conduct this bibliometric analysis.ResultsEventually, 534 documents met the requirements to be included, and as of 18 November 2023, there was an upward trend in the number of publications in the field, with a significant increase in the number of articles published after 2020. In summary, F Susan Wong (UK) was the author with the most publications (21), the USA was the country with the most publications (198), and the State University System of Florida (the United States) was the institution with the most publications (32). The keywords that appeared more frequently were T cells, fecal transplants, and short-chain fatty acids. The results of keywords with the most robust citation bursts suggest that Faecalibacterium prausnitzii and butyrate may become a focus of future research.ConclusionIn the future, intestinal flora will remain a research focus in T1DM. Future research can start from Faecalibacterium prausnitzii and combine T cells, fecal bacteria transplantation, and short-chain fatty acids to explore the mechanism by which intestinal flora affects blood glucose in patients with T1DM, which may provide new ideas for the prevention and treatment of T1DM.

Aims: This study explored the molecular and biologic mechanisms underlying the association between circadian rhythm disorders (CRD) and increased risk for hepatocellular carcinoma (HCC). Background: CRD are linked to increased risk for HCC, but the molecular and biologic mechanisms underlying this association are limited.ObjectiveThe study constructed and validated a CRD related gene model as an independent prognostic factor for HCC, providing insight into the molecular mechanisms linking CRD to increased HCC risk and identifying potential indicators for the efficacy of immunotherapy and anticancer drugs. This helps provide important clues for personalized treatment strategies for HCC patients. Methods: Gene sets correlated with circadian rhythm were obtained from the Molecular Signatures Database (MSigDB) to intersect with differentially expressed genes (DEGs) between tumor samples and control samples in The Cancer Genome Atlas (TCGA) and HCCDB18 from Hepatocellular Carcinoma Cell DataBase (HCCDB). The CRD related gene model was developed by univariate Cox and stepwise multivariate analysis. Immune checkpoint blockade (ICB) therapy and anticancer drugs were analyzed using the tumor immune dysfunction and exclusion (TIDE) and pRRophetic, respectively. Seurat determined the cell type of HCC by analyzing single-cell data, and malignant cells were identified using Copykat. To detect the mRNA levels of genes in the CRD related gene model, quantitative real-time polymerase chain reaction (qRT-PCR) was carried out. Results: The activity of circadian rhythm in HCC tissue was significantly lower than that in control tissue. Subsequently, EZH2, IMPDH2, TYMS and SERPINE1 were selected to construct the CRD related gene model, which was an independent factor for HCC prognosis. Notably, low-risk patients had lower levels of immune cell infiltration and lower TIDE scores compared to high-risk patients with HCC, indicating that patients with a low risk may derive more benefit from immunotherapy. IMPDH2, TYMS and SERPINE1 expressed significantly higher in malignant cells than in benign epithelial cells. Conclusions: This study presents a CRD related gene model to reveal the molecular perspective of the dependent mechanism of the association between CRD and cancer, which provides a potential indicator for understanding the preclinical efficacy of ICB and anticancer drugs.

Polystyrene nanoplastics (PS-NPs), emerging and increasingly pervasive environmental contaminants, have the potential to cause persistent harm to organisms. Although previous reports have documented local accumulation and adverse effects in a variety of major organs after PS-NPs exposure, the impact of PS-NPs exposure on erectile function remains unexplored. Herein, we established a rat model of oral exposure to 100 nm PS-NPs for 28 days. To determine the best dose range of PS-NPs, we designed both low-dose and high-dose PS-NPs groups, which correspond to the minimum and maximum human intake doses, respectively. The findings indicated that PS-NPs could accumulate within the corpus cavernosum and high dose but not low dose of PS-NPs triggered erectile dysfunction. Moreover, the toxicological effects of PS-NPs on erectile function include fibrosis in the corpus cavernous, endothelial dysfunction, reduction in testosterone levels, elevated oxidative stress and apoptosis. Overall, this study revealed that PS-NPs exposure can cause erectile dysfunction via multiple ways, which provided new insights into the toxicity of PS-NPs.

Efficient transfer of energy is an important issue addressed by numerous scholars in the literature and various methods have been proposed for enhancing the heat transfer efficiency in heat exchangers. Among many different heat exchangers, helical tubes are one of the most prevalent types of heat exchangers which have many applications in industry. In a case study, effect of twisting technique on the heat transfer in a helical tube with oval cross section has been investigated numerically and the results have been compared with simple circular cross section helical tube. Effect of cross section aspect ratio and twisting ratio in different flow Reynolds numbers has been considered. Results have been presented in terms of Nusselt number, friction factor, PEC, entropy generation and contours of velocity, streamlines and temperature. Results indicate that twisting technique can significantly enhance the heat transfer and all cases have PEC values of above unit which indicates superiority of this method. Also the velocity contours and streamlines indicate that using twisting technique result in higher mixing in the flow which is the reason for higher heat transfer characteristics in twisted oval helical tubes.

With the increasing prevalence of metabolic disorders, hyperglycemia has become a common risk factor that endangers people's lives and the need for new drug solutions is burgeoning. Trans-2, 4-dimethoxystilbene (TDMS), a synthetic stilbene, has been found as a novel hypoglycemic small molecule from glucose consumption test. Normal C57BL/6 J mice, mouse models of type 1 diabetes mellitus and diet-induced obesity subjected to TDMS gavage were found with lower glycemic levels and better glycemic control. TDMS significantly improved the symptoms of polydipsia and wasting in type 1 diabetic mice, and could rise their body temperature at the same time. It was found that TDMS could promote the expression of key genes of glucose metabolism in HepG2, as do in TDMS-treated liver, while it could improve the intestinal flora and relieve intestinal metabolic dysbiosis in hyperglycemic models, which in turn affected its function in the liver, forming the gut-liver axis. We further fished PPARγ by virtual screening that could be promoted by TDMS both in-vitro and in-vivo, which was regulated by upstream signaling of AMPKα phosphorylation. As a novel hypoglycemic small molecule, TDMS was proven to be promising with its glycemic improvements and amelioration of diabetes symptoms. It promoted glucose absorption and utilization by the liver and improved the intestinal flora of diabetic mice. Therefore, TDMS is expected to become a new hypoglycemic drug that acts through gut-liver axis via AMPKα-PPARγ signaling pathway in improving glycemic metabolism, bringing new hope to patients with diabetes and glucose metabolism disorders.

Cities are increasingly vital in global carbon mitigation efforts, yet few have specifically tailored carbon neutrality pathways. Furthermore, out-of-boundary indirect greenhouse gas (GHG) emissions, aside from those related to electricity and heat imports, are often overlooked in existing pathways, despite their significance in comprehensive carbon mitigation strategies. Addressing this gap, here we introduce an integrated analysis framework focusing on both production and consumption-related GHG emissions. Applied to Wuyishan, a service-oriented city in Southern China, this framework provides a holistic view of a city's carbon neutrality pathway, from a full-scope GHG emission perspective. The findings reveal the equal importance of carbon reduction within and outside the city's boundaries, with out-of-boundary emissions accounting for 42% of Wuyishan's present total GHG emissions. This insight highlights the necessity of including these external factors in GHG accounting and mitigation strategy development. This framework serves as a practical tool for cities, particularly in developing countries, to craft effective carbon neutrality roadmaps that encompass the full spectrum of GHG emissions.

Abstract Habitat fragmentation has led to a reduction in the geographic distribution of species, making small populations vulnerable to extinction due to environmental, demographic, and genetic factors. The wild plant Chieniodendron hainanense, a species with extremely small populations, is currently facing endangerment and thus requires urgent conservation efforts. Understanding its genetic diversity is essential for uncovering the underlying mechanisms of its vulnerability and for developing effective conservation strategies. In our study, we analyzed 35 specimens from six different populations of C. hainanense using genotyping-by-sequencing (GBS) and single nucleotide polymorphism (SNP) methodologies. Our findings indicate that C. hainanense has limited genetic diversity. The observed heterozygosity across the populations ranged from 10.79 to 14.55%, with an average of 13.15%. We categorized the six populations of C. hainanense into two distinct groups: (1) Diaoluoshan and Baishaling, and (2) Wuzhishan, Huishan, Bawangling, and Jianfengling. The genetic differentiation among these populations was found to be relatively weak. The observed loss of diversity is likely a result of the effects of natural selection.

C21H27NO4, triclinic, P 1‾ $\overline{1}$ (no. 2), a = 7.5904(17) Å, b = 10.394(2) Å, c = 12.651(3) Å, α = 73.270(4)°, β = 85.888(4)°, γ = 86.078(4)°, V = 952.2(4) Å3, Z = 2, R gt(F) = 0.0469, wR ref(F 2) = 0.1545, T = 296(2) K.

C20H22N2O4, monoclinic, P21/n (no. 14), a = 11.4033(15) Å, b = 14.2998(16) Å, c = 11.6486(16) Å, β = 91.197(8)°, V = 1899.1(4) Å3, Z = 4, Rgt(F) = 0.0513, wRref(F2) = 0.1542, T = 296.2 K.

Abstract Introduction The necessity for tuberculosis preventive treatment (TPT) and routine T-SPOT.TB monitoring in patients with psoriasis and tuberculosis infection (TBI) undergoing interleukin (IL)-17A inhibitor therapy remains uncertain. This study aims to evaluate the long-term safety of IL-17A inhibitors administered without TPT and analyze changes in T-SPOT.TB among these patients. It also identifies risk factors for TBI in patients with psoriasis. Methods This single-center prospective study enrolled adult patients with plaque psoriasis and TBI receiving IL-17A inhibitors. TBI was defined as positive T-SPOT.TB results (≥ 6 spots) without symptoms or evidence of active tuberculosis (ATB). TPT administration was based on contraindications, tuberculosis risk factors, and patient preferences. The primary endpoint was the incidence of ATB over 2 years. Secondary outcomes included T-SPOT.TB changes and TBI risk factors. Results Of the 129 patients with psoriasis and TBI enrolled in the study, 97 (75.2%) did not receive TPT, while 32 (24.8%) did. Among them, 109 patients (84.5%) completed the 2-year follow-up. During the 235 person-years of observation, no ATB cases were identified. Median T-SPOT.TB values showed no significant changes from baseline to year 2 in both the non-TPT (20 vs. 17 spots, p = 0.975) and TPT groups (55 vs. 58 spots, p = 0.830). T-SPOT.TB reversed in 14 patients (12.8%), mostly in the non-TPT group. Moreover, for TBI risk factor analysis, a cohort of 212 patients with psoriasis with negative baseline T-SPOT.TB was evaluated, revealing a TBI prevalence of 37.8%. Logistic regression analysis highlighted age ≥ 45 years (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.50–3.99, p

The formation and evolution mechanisms of coal mine water quality are intricate, significantly influenced by multiple processes such as hydrodynamics, hydrochemistry, and biodegradation. A comprehensive investigation and elucidation of the mechanisms is theoretically crucial for the prevention and remediation of coal mine water pollution. The hydrogeological prototype of a goaf in a coal mine in the Ordos Basin is choosen, and a laboratorial physical model and a coupled hydrodynamic-chemical-biodegradation (HCB) milti-field numerical model for the goaf are established, focusing the water level rises and biogeochemistry processes. The research results demonstrate the significance of multi-field coupling effects on mine water quality. The water level filling up results shows that the matrix-fracture dual-porosity model effectively matches the water level in the goaf with a simulation error of 9.9%, which is much more accurate than the theoretical and the single-porosity model predictions. The simulation results of the hydrochemical field are relatively consistent with the experiments, with relative errors of 3.0%, 21.0%, and 6.2% for \begin{document}${\mathrm{SO}}_4^{2-} $\end{document}, \begin{document}${\mathrm{HCO}}_3^- $\end{document}, and pH, respectively. Results from different time periods indicate that water-rock reactions and microbial activities are not significant during the water storage process. After the goaf is filled up, the hydrodynamics almost stagnate, but the hydrochemical and microbial fields are relatively active. The pyrite oxidation reactions in the No.2 and No.3 coal seams increase the concentration of \begin{document}${\mathrm{SO}}_4^{2-} $\end{document} by about 24.6%. In the later stage, the water environment in the goaf evolves into weakly acidic and anaerobic reducing conditions, and the microbial degradation becomes prominent, reducing the \begin{document}${\mathrm{SO}}_4^{2-} $\end{document} concentration from its peak by 6.1%. A certain “self-purification” ability of mine water in the goaf after closure has been confirmed. By adjusting the microbial metabolic rate constant, the proportion of \begin{document}${\mathrm{SO}}_4^{2-} $\end{document} degradation can be induced up to 61.6%. In actual engineering scenarios, this target can be achieved through some strategies such as supplementing enough dissolved carbon nutrient substance and artificially establishing a closed anaerobic environment. This study expands the multi-field coupling laboratorial experiments and numerical modeling techniques to the formation and evolution of water quality in coal mine water in a goaf, and the constructive conclusions can provide theoretical guidance for the prevention and remediation of coal mine water pollution.

Abstract Dilated perivascular spaces (PVS) have emerged as a pathological hallmark in various neurological conditions, including Parkinson’s disease (PD). Levodopa-induced dyskinesia (LID), an intractable motor complication of PD, remains enigmatic regarding the distribution patterns of PVS. Our objective was to scrutinize the percent PVS (pPVS) changes within PD patients with LID (PD-LID). In total, 132 individuals were enrolled, including PD-LID (n = 42), PD patients without LID (PD-nLID, n = 45), and healthy controls (HCs, n = 45). Employing an automated approach for PVS quantification based on structural magnetic resonance imaging, we comprehensively evaluated total pPVS in subcortical white matter globally and regionally. A significant increase in global pPVS was observed in PD patients versus HCs, particularly evident in PD-LID relative to HCs. Within the PD-LID group, elevated pPVS was discerned in the right inferior frontal gyrus region (rIFG) (pars opercularis), contrasting with PD-nLID and HCs. Moreover, PD patients exhibited increased pPVS in bilateral superior temporal regions compared to HCs. Notably, pPVS in the rIFG positively correlated with dyskinetic symptoms and could well identify LID. Our findings unveiled PVS alternations in subcortical white matter in PD-LID at both global and regional levels, highlighting the increased pPVS in rIFG as a prospective imaging marker for LID.

Abstract This study investigates the impact of macroprudential policies on ecological footprint (EF) in the top 11 largest countries. This study uses country-level panel data from these countries, covering the period from 1992 to 2020. Findings indicate that macroprudential policies alleviates ecological footprint in the sample. Macroprudential policies primarily reduce the ecological footprint before medium quantile (50%) while the environmental benefits of the policies end in the later quantiles. Moreover, environmental policy stringency (EPS) amplifies the positive influence of macroprudential policies on environmental sustainability. Estimate results stay the same with basic regression results in the post-global financial crisis (GFC) period while the impact is positive in the pre-GFC period. Finally, other robust tests validate the findings reported in basic regression model. This study suggests that governments should customize various types of macroprudential policies while also considering environmental concerns. The achievement of a sustainable environment can be facilitated by the combined effects of macroprudential policies and EPS.

Objective To explore the interaction between microRNA-23 （miR-23） and mitochondrial fission protein 1 （FIS1） in human kidney-2 （HK-2） cells and examine the effect of miR-23 on inflammatory response and oxidative stress by targeting FIS1. Methods HK-2 cells were cultured in vitro and induced by lipopolysaccharide （LPS） for modeling of sepsis. Dual luciferase reporter assay was utilized for verifying the interaction between miR-23 and FIS1. HK-2 cells were randomized into groups of miR-23 mimic/inhibitor and eukaryotic expression vector and small interfering RNA of FIS1 alone or in a combination. Cell proliferation was detected by cell counting kit-8 （CCK-8） assay and apoptosis and reactive oxygen species （ROS） were examined by flow cytometry. Malondialdehyde （MDA） was detected by MDA kit and the levels of tumor necrosis factor t （TNF-α）, interleukin （IL）-1β and IL-6/10 were measured by enzyme-linked immunosorbent assay（ELISA）. ResultsThe miR-23 mRNA in HK-2 cells induced by LPS was (0.60±0.12) folds that of control group(P

Perchlorate (\begin{document}${\mathrm{ClO}}_4^- $\end{document}) is a new persistent pollutant with small molecular weight, rapid diffusion, and high stability. It is widely found in the environment, especially in the areas where fireworks are produced and set off intensively. Perchlorate impacts the normal function of thyroid gland; its environmental pollution attracted wide attention and has become a research hotspot in the field of environmental science in recent years. Column experiments using river sand from polluted site as the experiment material were conducted to study on the mechanism and influencing factors of the attenuation of perchlorate stimulated by sulfur. The effects of groundwater, iron oxides, and nitrate (\begin{document}${\mathrm{NO}}_3^- $\end{document}) were investigated in this study. The results show that sulfur is able to stimulate \begin{document}${\mathrm{ClO}}_4^- $\end{document} attenuation, which mainly depends on microbial degradation, and it is limited by the lack of essential inorganic salts and other nutrients for microorganisms. Iron oxides have a buffering effect on the decrease of pH, but have a limited stimulating effect on the \begin{document}${\mathrm{ClO}}_4^- $\end{document} attenuation in the column. Groundwater significantly enhanced sulfur-stimulated \begin{document}${\mathrm{ClO}}_4^- $\end{document} attenuation and microbial acid production. The degradation of nitrate (\begin{document}${\mathrm{NO}}_3^- $\end{document}) in groundwater is preferred to that of \begin{document}${\mathrm{ClO}}_4^- $\end{document}; when \begin{document}${\mathrm{NO}}_3^- $\end{document} concentration is less than about 10 mg/L, \begin{document}${\mathrm{ClO}}_4^- $\end{document} begins to be reducted significantly. Sulfur has the potential as the PRB reaction medium for in-situ remediation of pollutants such as \begin{document}${\mathrm{ClO}}_4^- $\end{document} and \begin{document}${\mathrm{NO}}_3^- $\end{document}. This study provides a theoretical basis and data support for the practical application of environmental remediation.

Abstract Feature selection is a critical component of machine learning and data mining to remove redundant and irrelevant features from a dataset. The Chimp Optimization Algorithm (CHoA) is widely applicable to various optimization problems due to its low number of parameters and fast convergence rate. However, CHoA has a weak exploration capability and tends to fall into local optimal solutions in solving the feature selection process, leading to ineffective removal of irrelevant and redundant features. To solve this problem, this paper proposes the Enhanced Chimp Hierarchy Optimization Algorithm for adaptive lens imaging (ALI-CHoASH) for searching the optimal classification problems for the optimal subset of features. Specifically, to enhance the exploration and exploitation capability of CHoA, we designed a chimp social hierarchy. We employed a novel social class factor to label the class situation of each chimp, enabling effective modelling and optimization of the relationships among chimp individuals. Then, to parse chimps’ social and collaborative behaviours with different social classes, we introduce other attacking prey and autonomous search strategies to help chimp individuals approach the optimal solution faster. In addition, considering the poor diversity of chimp groups in the late iteration, we propose an adaptive lens imaging back-learning strategy to avoid the algorithm falling into a local optimum. Finally, we validate the improvement of ALI-CHoASH in exploration and exploitation capabilities using several high-dimensional datasets. We also compare ALI-CHoASH with eight state-of-the-art methods in classification accuracy, feature subset size, and computation time to demonstrate its superiority.

Abstract Background Cancer‐related pain is one of the common priority symptoms in advanced lung cancer patients at the end‐of‐life (EOL). Alleviating pain is undoubtedly a critical component of palliative care in lung cancer. Our study was initiated to examined trends in opioid prescription‐level outcomes as potential indicators of undertreated pain in China. Methods This study used data on 1330 patients diagnosed with lung cancer of urban city medical insurance in China who died between 2014 and 2017. Opioid prescription‐level outcomes were determined by annual trends of the proportion of patients filling an opioid prescription, the total dose of opioids filled by decedents, and morphine milligram equivalents per day (MMED) at the EOL (defined as the 60 days before death). We further analyzed monthly changes in the number of opioid prescriptions filled, MMED, and mean daily dose of opioids per prescription (MDDP) of the last 60 days of life by year at death and age, respectively. Results A total of 959 patients with exact dates of death were included, with 432 cases (45.06%; 95% CI: 44.36%–45.77%) receiving at least one opioid prescription at the EOL. The declining trends were shown in the proportion of patients filling any opioid prescription, the total dose of opioids filled by decedents and MMED, with an annual decrease of 0.341% (p = 0.01), 104.23 mg (p = 0.011) and 2.84 mg (p = 0.014), respectively. Within the 31–60 days to the 0–30 days of life, the MMED declined 6.08 mg (95% CI: −7.14 to −5.03; p = 0.000351), while the number of opioid prescriptions rose 0.66 (95% CI: 0.160–1.16; p = 0.025). Like the MMED, the MDDP fell 4.11 mg (95% CI: −5.86 to −2.37; p = 0.005) within the last month before death compared to the previous month. Conclusion Terminal lung cancer populations in urban China have experienced reduced access to opioids at the EOL. The clinicians did not prescribe a satisfactory dose of opioids per prescription, while the patients suffered increasing pain in the last 30 days of life. Sufficient opioid analgesic administration should be advocated for lung cancer patients during the EOL period.

Abstract Background Following China’s official designation as malaria-free country by WHO, the imported malaria has emerged as a significant determinant impacting the malaria reestablishment within China. The objective of this study is to explore the application prospects of machine learning algorithms in imported malaria risk assessment of China. Methods The data of imported malaria cases in China from 2011 to 2019 was provided by China CDC; historical epidemic data of malaria endemic country was obtained from World Malaria Report, and the other data used in this study are open access data. All the data processing and model construction based on R, and map visualization used ArcGIS software. Results A total of 27,088 malaria cases imported into China from 85 countries between 2011 and 2019. After data preprocessing and classification, clean dataset has 765 rows (85 * 9) and 11 cols. Six machine learning models was constructed based on the training set, and Random Forest model demonstrated the best performance in model evaluation. According to RF, the highest feature importance were the number of malaria deaths and Indigenous malaria cases. The RF model demonstrated high accuracy in forecasting risk for the year 2019, achieving commendable accuracy rate of 95.3%. This result aligns well with the observed outcomes, indicating the model’s reliability in predicting risk levels. Conclusions Machine learning algorithms have reliable application prospects in risk assessment of imported malaria in China. This study provides a new methodological reference for the risk assessment and control strategies adjusting of imported malaria in China.

Abstract As hypothetical topological defects in the geometry of spacetime, vortex strings could have played many roles in cosmology, and their distinct features can provide observable clues about the early universe’s evolution. A key feature of vortex strings is that they can interact with Weyl fermionic modes and support massless chiral-anomaly states along strings. To date, despite many attempts to detect vortex strings in astrophysics or to emulate them in artificially created systems, observation of these vortex-string chiral modes remains experimentally elusive. Here we report experimental observations of vortex-string chiral modes using a metamaterial system. This is implemented by inhomogeneous perturbation of Yang-monopole phononic metamaterials. The measured linear dispersion and modal profiles confirm the existence of topological modes bound to and propagating along the string with the chiral anomaly. Our work provides a platform for studying diverse cosmic topological defects in astrophysics and offers applications as topological fibres in communication techniques.

Abstract Background Bloodstream infections (BSI) are highly prevalent in hospitalized patients requiring intensive care. They are among the most serious infections and are highly associated with sepsis or septic shock, which can lead to prolonged hospital stays and high healthcare costs. This study aimed at establishing an easy-to-use nomogram for predicting the prognosis of patients with BSI. Methods In retrospective study, records of patients with BSI admitted to the intensive care unit (ICU) over the period from Jan 1st 2016 to Dec 31st 2021 were included. We used data from two different China hospitals as development cohort and validation cohort respectively. The demographic and clinical data of patients were collected. Based on all baseline data, k-means algorithm was applied to discover the groups of BSI phenotypes with different prognostic outcomes, which was confirmed by Kaplan-Meier analysis and compared using log-rank tests. Univariate Cox regression analyses were used to estimate the risk of clusters. Random forest was used to identified discriminative predictors in clusters, which were utilized to construct nomogram based on multivariable logistic regression in the discovery cohort. For easy clinical applications, we developed a bloodstream infections clustering (BSIC) score according to the nomogram. The results were validated in the validation cohort over a similar period. Results A total of 360 patients in the discovery cohort and 310 patients in the validation cohort were included in statistical analyses. Based on baseline variables, two distinct clusters with differing prognostic outcomes were identified in the discovery cohort. Population in cluster 1 was 211 with a ICU mortality of 17.1%, while population in cluster 2 was 149 with an ICU mortality of 41.6% (p

Abstract. Background:. While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD. Methods:. We evaluated phenotypic associations using data from the United Kingdom Biobank (N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DMadjBMI]: Ncase/Ncontrol = 50,409/523,897) and for CAD (Ncase/Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM (Ncase/Ncontrol = 180,834/1,159,055). Results:. Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed (rg = 0.39, P = 1.43 × 10–75), which was largely independent of BMI (T2DMadjBMI–CAD: rg = 0.31, P = 1.20 × 10–36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11–1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07–1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10–1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04–1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9–83.4%) and 90.4% (95% CI: 29.3–151.5%), respectively. Conclusion:. Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Abstract Sequential immunotherapy has shown certain advantages in malignancy. Here, we aim to evaluate the efficacy of sequential anti-CTLA-4 and anti-PD-1 treatment for recurrent or metastatic nasopharyngeal carcinoma patients (R/M NPC). We retrospectively analysis 2 phase I trial of ipilimumab and camrelizumab in Chinese R/M NPC patients. These patients were initially treated with ipilimumab, a CTLA4 blockade, followed by anti-PD-1 treatment. We observed a durable tumor remission in these patients (mPFS: 12.3 months; mDoR: 20.9 months). Multimodal investigations of biopsy samples disclosed remodeling of tumor-immune microenvironment triggered by ipilimumab. In responders, we found increased tumoral PD-L1/PD-L2 expression and T-cell infiltration after ipilimumab treatment, accompanied by reduced stroma and malignant cell components. In contrast, non-responders exhibited increased B-cell infiltration and increased peripheral CD19 + B cells, suggesting a defective transition from memory B cells to plasma cells. This study proposes that sequential therapy can potentially enhance treatment efficacy in chemotherapy-resistant NPC patients and provides insights into how preexisting anti-CTLA4 blockade can influence subsequent anti-PD-1 efficacy by remodeling the TME. Additionally, our results highlight the need for therapeutic strategies targeting naïve/memory B cells.

Abstract Background Primary caregivers of hemodialysis patients suffer from varying degrees of stress from their patients. Caring for hemodialysis patients can expose caregivers to many problems, leading to an increased burden of care and even impacting the quality of care. The purpose of our study was to examine whether family resilience could be a mediating variable moderating the relationship between patient coping styles and caregiver burden. Methods The study was a cross-sectional and descriptive-analytical study that interviewed 173 pairs of hemodialysis patients and their caregivers at a blood purification center in a public hospital in China. The Brief Coping Styles Scale (Chinese version) was used to assess individuals’ coping styles for disease and treatment. From the caregiver’s perspective, the Family Resilience Assessment Scale (Chinese version) was used to understand the resilience of families, and the Zarit Caregiver Burden Scale was used to capture the caregiver’s subjective experience of burden. Statistical analyses were conducted using SPSS version 23 and Amos version 26 to analyze the relationships between variables to examine for correlation and construct mediated effects models. Results Coping styles showed a significant positive correlation with family resilience (r = 0.347, P

Abstract Inflammatory arthritis (IA) is a common rheumatic adverse event following immune checkpoint inhibitors treatment. The clinical disparities between IA and rheumatoid arthritis (RA) imply disease heterogeneity and distinct mechanisms, which remain elusive. Here, we profile CD45+ cells from the peripheral blood or synovial fluid (SF) of patients with PD-1-induced IA (PD-1-IA) or RA using single-cell RNA sequencing. We report the predominant expansion of IL1B hi myeloid cells with enhanced NLRP3 inflammasome activity, in both the SF and peripheral blood of PD-1-IA, but not RA. IL1B hi macrophages in the SF of PD-1-IA shared similar inflammatory signatures and might originate from peripheral IL1B hi monocytes. Exhausted CD8+ T cells (Texs) significantly accumulated in the SF of patients with PD-1-IA. IL1B hi myeloid cells communicated with CD8+ Texs possibly via the CCR1-CCL5/CCL3 and CXCL10-CXCR3 axes. Collectively, these results demonstrate different cellular and molecular pathways in PD-1-IA and RA and highlight IL1B hi macrophages as a possible therapeutic target in PD-1-IA.

Abstract Plant diversity effects on community productivity often increase over time. Whether the strengthening of diversity effects is caused by temporal shifts in species-level overyielding (i.e., higher species-level productivity in diverse communities compared with monocultures) remains unclear. Here, using data from 65 grassland and forest biodiversity experiments, we show that the temporal strength of diversity effects at the community scale is underpinned by temporal changes in the species that yield. These temporal trends of species-level overyielding are shaped by plant ecological strategies, which can be quantitatively delimited by functional traits. In grasslands, the temporal strengthening of biodiversity effects on community productivity was associated with increasing biomass overyielding of resource-conservative species increasing over time, and with overyielding of species characterized by fast resource acquisition either decreasing or increasing. In forests, temporal trends in species overyielding differ when considering above- versus belowground resource acquisition strategies. Overyielding in stem growth decreased for species with high light capture capacity but increased for those with high soil resource acquisition capacity. Our results imply that a diversity of species with different, and potentially complementary, ecological strategies is beneficial for maintaining community productivity over time in both grassland and forest ecosystems.

In this paper, the main literature related to 4DCT imaging and reconstruction techniques over the past 20 years is reviewed, and the contents are summarized. This paper provides a systematic and comprehensive introduction to 4DCT research from five perspectives: the concept of 4DCT, scanning mode and imaging method, reconstruction algorithm, application, research status, and future development expectations. In this study, five types of reconstruction algorithms are summarized, and the advantages, disadvantages, and research difficulties of each algorithm are briefly evaluated. Finally, we conduct a brief statistical analysis on the cited works from the perspective of reconstruction methods, revealing the research progress and future research trends of 4DCT reconstruction algorithms.

Researching target recognition methods for 3D computed tomography (CT) images is important for improving the reliability and stability of the security inspection quality in advanced security CT scanning equipment. This article systematically reviews the latest research progress and developmental trends in target recognition of CT images for security purposes. Not only representative academic research achievements of recent years in this field are summarized and reviewed, but also relevant industrial patents are included for the first time. For literature classification, in addition to two common taxonomies, a new taxonomy is proposed, and the retrieved representative literature is classified with multiple labels. In summarizing and analyzing the research achievements in this field, three important characteristics were identified, and the origins were analyzed. Finally, some suggestions are put forward for future research directions in this field.

Abstract Cardiac macrophage contributes to the development of cardiac fibrosis, but factors that regulate cardiac macrophages transition and activation during this process remains elusive. Here we show, by single-cell transcriptomics, lineage tracing and parabiosis, that cardiac macrophages from circulating monocytes preferentially commit to macrophage-to-myofibroblast transition (MMT) under angiotensin II (Ang II)-induced hypertension, with accompanying increased expression of the RNA N6-methyladenosine demethylases, ALKBH5. Meanwhile, macrophage-specific knockout of ALKBH5 inhibits Ang II-induced MMT, and subsequently ameliorates cardiac fibrosis and dysfunction. Mechanistically, RNA immunoprecipitation sequencing identifies interlukin-11 (IL-11) mRNA as a target for ALKBH5-mediated m6A demethylation, leading to increased IL-11 mRNA stability and protein levels. By contrast, overexpression of IL11 in circulating macrophages reverses the phenotype in ALKBH5-deficient mice and macrophage. Lastly, targeted delivery of ALKBH5 or IL-11 receptor α (IL11RA1) siRNA to monocytes/macrophages attenuates MMT and cardiac fibrosis under hypertensive stress. Our results thus suggest that the ALKBH5/IL-11/IL11RA1/MMT axis alters cardiac macrophage and contributes to hypertensive cardiac fibrosis and dysfunction in mice, and thereby identify potential targets for cardiac fibrosis therapy in patients.

Abstract Glioblastoma, IDH-Wild type (GBM, CNS WHO Grade 4) is a highly heterogeneous and aggressive primary malignant brain tumor with high morbidity, high mortality, and poor patient prognosis. The global burden of GBM is increasing notably due to limited treatment options, drug delivery problems, and the lack of characteristic molecular targets. OTU deubiquitinase 4 (OTUD4) is a potential predictive factor for several cancers such as breast cancer, liver cancer, and lung cancer. However, its function in GBM remains unknown. In this study, we found that high expression of OTUD4 is positively associated with poor prognosis in GBM patients. Moreover, we provided in vitro and in vivo evidence that OTUD4 promotes the proliferation and invasion of GBM cells. Mechanism studies showed that, on the one hand, OTUD4 directly interacts with cyclin-dependent kinase 1 (CDK1) and stabilizes CDK1 by removing its K11, K29, and K33-linked polyubiquitination. On the other hand, OTUD4 binds to fibroblast growth factor receptor 1 (FGFR1) and reduces FGFR1’s K6 and K27-linked polyubiquitination, thereby indirectly stabilizing CDK1, ultimately influencing the activation of the downstream MAPK signaling pathway. Collectively, our results revealed that OTUD4 promotes GBM progression via OTUD4-CDK1-MAPK axis, and may be a prospective therapeutic target for GBM treatment.

Abstract Scutellarin is widely distributed in Scutellaria baicalensis, family Labiatae, and Calendula officinalis, family Asteraceae, and belongs to flavonoids. Scutellarin has a wide range of pharmacological activities, it is widely used in the treatment of cerebral infarction, angina pectoris, cerebral thrombosis, coronary heart disease, and other diseases. It is a natural product with great research and development prospects. In recent years, with in-depth research, researchers have found that wild scutellarin also has good therapeutic effects in anti-tumor, anti-inflammatory, anti-oxidation, anti-virus, treatment of metabolic diseases, and protection of kidney. The cancer treatment involves glioma, breast cancer, lung cancer, renal cancer, colon cancer, and so on. In this paper, the sources, pharmacological effects, in vivo and in vitro models of scutellarin were summarized in recent years, and the current research status and future direction of scutellarin were analyzed. Graphical Abstract

AIM: To determine the teaching effects of a real-time three dimensional (3D) visualization system in the operating room for early-stage phacoemulsification training. METHODS: A total of 10 ophthalmology residents of the first-year postgraduate were included. All the residents were novices to cataract surgery. Real-time cataract surgical observations were performed using a custom-built 3D visualization system. The training lasted 4wk (32h) in all. A modified International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubric (ICO-OSCAR) containing 4 specific steps of cataract surgery was applied. The self-assessment (self) and expert-assessment (expert) were performed through the microsurgical attempts in the wet lab for each participant. RESULTS: Compared with pre-training assessments (self 3.2±0.8, expert 2.5±0.6), the overall mean scores of post-training (self 5.2±0.4, expert 4.7±0.6) were significantly improved after real-time observation training of 3D visualization system (P

The high-temperature wear resistance plays an important role for Ti–6Al–4V alloy components working in extreme environments, especially vital for avoiding unexpected failure. However, the reasonable method of surface modification should meet the requirement of improving in wear resistance and less decreasing in mechanical properties simultaneously, which brings a great challenge. In the present research, the laser shock peening (LSP) technique was applied to optimize the superficial layer of Ti–6Al–4V alloy by different processing. The microstructure, elastic modulus, nano-hardness and high-temperature tribology properties of the LSP processed Ti–6Al–4V were investigated to reveal the improving effect. The results demonstrate the LSP processing transforms the dual-size grain structure to relative homogeneous grain structure and forms the gradient nano-structure in superficial layer. With the increasing of LSP processing numbers, the density of geometrically necessary dislocation (GND) decreases obviously, but the density of statistically stored dislocation (SSD) rises significantly, which promotes the increase of total dislocation density compared with the as-received (AR) alloy. Due to the crystal evolution, the Ti–6Al–4V alloy with three-times LSP processing has the lowest wear rate which is less than half of the as-received state. The observations on worn surface and adjacent cross-sectional microstructure reveal the severe scratching and many inner microcracks in the AR sample but the slight scraping and few inner microcracks in the three-times LSP processed sample. Considering the elevated nano-hardness and elastic modulus, the improved tribological properties should be mainly attributed to the optimized microstructure and dislocation state by LSP processing. The present research provides a more reasonable method to improve the high-temperature wear properties of Ti–6Al–4V alloy.

The oxidation behavior of a medium carbon Cr–Mn–Si alloyed steel was investigated under a mold flux melt environment exposed to different high temperatures of 1175–1425 °C, and holding time of 5–85 min. The results showed that the thicknesses of oxide layers contained Cr–Mn–Si oxide particles significantly increased from 10 to 183 μm with the increasing of oxidation temperature and holding time. The selective oxidation of Cr, Mn and Si elements in the grain boundaries is caused by the diffusion of free oxygen (O2−) migrating from mold flux to steel matrix, which leads to the growth of oxide layer thicknesses. Moreover, the oxidation rate constant (kp) of the Cr–Mn–Si alloyed steel was revealed under the mold flux environment at the temperatures of 1175–1375 °C. In addition, it was found that the growth kinetics of oxide particles in the oxide layer consists of a rapid growth stage and a slow-steady growth stage, and the growth of oxide particles is co-controlled by the diffusion of O2− within the steel matrix and the competing oxidation reactions involving Fe, Cr, Mn, and Si elements.

Abstract Objectives The concurrent impact of COVID-19 and influenza on disease burden is a topic of great concern. This discussion delves into the epidemiological characteristics of seasonal influenza activity in Shanghai within the context of the SARS-CoV-2 epidemic. Methods From 2017 to 2023, a total of 11,081 patients having influenza-like illness (ILI) were included in this study for influenza virus detection. Reverse transcription polymerase chain reaction (RT-PCR) assays were conducted according to standardised protocols to identify the types and subtypes of influenza viruses. The positivity rate of the influenza virus among the sampled ILI cases served as a surrogate measure for estimating various influenza seasonal characteristics, such as periodicity, duration, peak occurrences, and the prevalent subtypes or lineages. Epidemiological aspects across different years and age groups were subjected to comprehensive analysis. For categorical variables, the Chi-square test or Fisher's exact test was employed, as deemed appropriate. Results A total of 1553 (14.0%) tested positive for influenza virus pathogens. The highest positivity rate for influenza was observed in adults aged 25–59 years (18.8%), while the lowest rate was recorded in children under 5 years (3.8%). The influenza circulation patterns in Shanghai were characterised: (1) 2 years exhibited semiannual periodicity (2017–2018, 2022–2023); (2) 3 years displayed annual periodicity (2018–2019, 2019–2020, and 2021–2022); and (3) during 2020–2021, epidemic periodicities of seasonal influenza viruses disappeared. In terms of influenza subtypes, four subtypes were identified during 2017–2018. In 2018–2019 and 2019–2020, A/H3N2, A/H1N1, and B/Victoria were circulating. Notably, one case of B/Victoria was detected in 2020–2021. The epidemic period of 2021–2022 was attributed to B/Victoria, and during 2022–2023, the influenza A virus was the dominant circulating strain. Conclusions The seasonal epidemic period and the predominant subtype/lineage of influenza viruses around the SARS-CoV-2 epidemic period in Shanghai city are complex. This underscores the necessity for vigilant influenza control strategies amidst the backdrop of other respiratory virus pandemics.

Artificial helical microswimmers with shape-morphing capacities and adaptive locomotion have great potential for precision medicine and noninvasive surgery. However, current reconfigurable helical microswimmers are hampered by their low-throughput fabrication and limited adaptive locomotion. Here, a rotary holographic processing strategy (a helical femtosecond laser beam) is proposed to produce stimuli-responsive helical microswimmers (

The coastal environment functional zoning in Zhejiang Province plays an important role in the protection of the coastal environment and the adjustment of the coastal resources exploitation and utilization, and has become an important basis for the coastal environment supervision. However, under the optimization of territorial spatial planning and high-quality development of marine economy, it has showed a significant lag. This paper analyzed its main problems through the experience of the coastal environment functional zoning in Zhejiang Province in compiling, adjusting, monitoring and evaluating. On this basis, policy recommendations for the management were put forward, including the important principle of ecological priority and bottom-line constraint, the orderly connection to the Zhejiang Province′s territorial spatial planning, the scientific control measures of different zones, the integration of various marine planning and protection objectives, and the sound management boundaries based on land-sea coordination.

Objectives Investigate the impact of daily occupational walking steps on the progression of papillary thyroid cancer (PTC), a topic hitherto underresearched. Material and Methods The authors analyzed the data from 800 individuals with PTC across stages 0–IV. Participants were evenly divided into 2 distinct occupational groups: office workers and construction workers (N = 400 each). Data included comprehensive records of daily walking steps, demographic information, and clinical indicators. Pearson’s correlation coefficients or analysis of variance (ANOVA) were employed to assess the linkage between daily walking steps and PTC risk and stage, as well as associated biochemical markers. Results The analysis revealed a significant inverse relationship between daily walking steps and PTC risk. A higher frequency of daily steps was associated with reduced chances of PTC onset and a lower diagnostic stage of the disease. This protective effect of physical activity was particularly pronounced in the construc- tion worker cohort. Subsequent evaluations showed that construction workers who consistently logged higher daily steps had markedly lower levels of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, thyroid peroxidase antibody, thyroglobulin antibody, and thy- roglobulin (Tg). Notably, daily walking steps exhibited a strong inverse correlation with body mass index (BMI), age, PTC volumes, and levels of TSH and Tg across both occupational groups (ρ < –0.37). The increase in daily steps was associated with the reduction in PTC stages (p < 0.001). Conclusions The research underscores the potential benefits of increased daily walking steps, suggesting that they may play a protective role in reducing PTC risk and moderating its progression. Int J Occup Med Environ Health. 2024;37(1):58–71

Abstract This research explores the potential of multimodal fusion for the differential diagnosis of early-stage lung adenocarcinoma (LUAD) (tumor sizes < 2 cm). It combines liquid biopsy biomarkers, specifically extracellular vesicle long RNA (evlRNA) and the computed tomography (CT) attributes. The fusion model achieves an impressive area under receiver operating characteristic curve (AUC) of 91.9% for the four-classification of adenocarcinoma, along with a benign-malignant AUC of 94.8% (sensitivity: 89.1%, specificity: 94.3%). These outcomes outperform the diagnostic capabilities of the single-modal models and human experts. A comprehensive SHapley Additive exPlanations (SHAP) is provided to offer deep insights into model predictions. Our findings reveal the complementary interplay between evlRNA and image-based characteristics, underscoring the significance of integrating diverse modalities in diagnosing early-stage LUAD.

Abstract The advent of SARS-CoV-2 variants with defined mutations that augment pathogenicity and/or increase immune evasiveness continues to stimulate global efforts to improve vaccine formulation and efficacy. The extraordinary advantages of lipid nanoparticles (LNPs), including versatile design, scalability, and reproducibility, make them ideal candidates for developing next-generation mRNA vaccines against circulating SARS-CoV-2 variants. Here, we assess the efficacy of LNP-encapsulated mRNA booster vaccines encoding the spike protein of SARS-CoV-2 for variants of concern (Delta, Omicron) and using a predecessor (YN2016C isolated from bats) strain spike protein to elicit durable cross-protective neutralizing antibody responses. The mRNA-LNP vaccines have desirable physicochemical characteristics, such as small size (~78 nm), low polydispersity index (90%). We employ in vivo bioluminescence imaging to illustrate the capacity of our LNPs to induce robust mRNA expression in secondary lymphoid organs. In a BALB/c mouse model, a three-dose subcutaneous immunization of mRNA-LNPs vaccines achieved remarkably high levels of cross-neutralization against the Omicron B1.1.529 and BA.2 variants for extended periods of time (28 weeks) with good safety profiles for all constructs when used in a booster regime, including the YN2016C bat virus sequences. These findings have important implications for the design of mRNA-LNP vaccines that aim to trigger durable cross-protective immunity against the current and newly emerging variants.