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Abstract Lung cancer is intricately associated with genetic susceptibility, leading to familial clustering among affected individuals. This cross-sectional study aimed to assess the knowledge, attitude, and practice (KAP) toward lung cancer risk among the offspring of lung cancer patients. This study was conducted at Guangdong Provincial People’s Hospital between April 2023 and August 2023. Participants’ demographic characteristics and KAP toward lung cancer risk were collected through questionnaires. A total of 481 valid questionnaires were enrolled, with 243 (50.52%) males, and 242 (50.31%) aged > 40 years old. The mean scores for knowledge, attitude, and practice were 8.54 ± 2.60 (range: 0–13), 25.93 ± 3.16 (range: 7–35), and 17.47 ± 4.30 (range: 5–25), respectively. Structural equation modeling indicated that knowledge exerted a negative direct effect on attitude (β = − 0.417, P = 0.006) but a positive direct effect on practice (β = 0.733, P = 0.025). Additionally, attitudes displayed a negative direct effect on practice (β = − 1.707, P = 0.002). In conclusion, offspring of lung cancer patients exhibited insufficient knowledge, positive attitude, and suboptimal practice toward lung cancer risk.

Gastrointestinal cancer is among the most common cancers worldwide. Immune checkpoint inhibitor-based cancer immunotherapy has become an innovative approach in cancer treatment; however, its efficacy in gastrointestinal cancer is limited by the absence of infiltration of immune cells within the tumor microenvironment. Therefore, it is therefore urgent to develop a novel therapeutic drug to enhance immunotherapy. In this study, we describe a previously unreported potentiating effect of Icariside I (ICA I, GH01), the main bioactive compound isolated from the Epimedium species, on anti-tumor immune responses. Mechanistically, molecular docking and SPR assay result show that ICA I binding with TRPV4. ICA I induced intracellular Ca2+ increasing and mitochondrial DNA release by targeting TRPV4, which triggered cytosolic ox-mitoDNA release. Importantly, these intracellular ox-mitoDNA fragments were taken up by immune cells in the tumor microenvironment, which amplified the immune response. Moreover, our study shows the remarkable efficacy of sequential administration of ICA I and anti-α-PD-1 mAb in advanced tumors and provides a strong scientific rationale for recommending such a combination therapy for clinical trials. ICA I enhanced the anti-tumor effects with PD-1 inhibitors by regulating the TRPV4/Ca2+/Ox-mitoDNA/cGAS/STING axis. We expect that these findings will be translated into clinical therapies, which will benefit more patients with cancer in the near future.

ABSTRACTLactate plays an important role in shaping immune tolerance in tumor microenvironment (TME) and correlates with poor prognosis in various solid tumors. Overcoming the immune resistance in an acidic TME may improve the anti-tumor immunity. Here, this study elucidated that via G-protein-coupled receptor 81 (GPR81), lactate could modulate immune tolerance in TME by recruiting regulatory T cells (Tregs) in vitro and in vivo. A high concentration of lactate was detected in cell supernatant and tissues of gastric cancer (GC), which was modulated by lactic dehydrogenase A (LDHA). GPR81 was the natural receptor of lactate and was overexpressed in different GC cell lines and samples, which correlated with poor outcomes in GC patients. Lactate/GPR81 signaling could promote the infiltration of Tregs into TME by inducing the expression of chemokine CX3CL1. GPR81 deficiency could decrease the infiltration of Tregs into TME, thereby inhibiting GC progression by weakening the inhibition of CD8+T cell function in a humanized mouse model. In conclusion, targeting the lactate/GPR81 signaling may potentially serve as a critical process to overcome immune resistance in highly glycolytic GC.

This research focuses on achieving sustainable development in residential buildings with energy use. Under the influence of the energy crisis and related problems, research on residential buildings for less energy use has great potential. The literature review, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses, and including VOSviewer analysis, shows the research is increasing and meaningful. Solar Decathlon buildings are used as the main objects in this research. The fifth Solar Decathlon Europe energy use technologies are examined through onsite investigation and online searching. The Analytic Hierarchy Process method for multi-criteria decision analysis is used for sustainability assessment. Moreover, the Ladybug and ClimateStudio plugins simulated respectively the annual solar radiation and the best angle for receiving it. The main findings show that 34 kinds of technologies used in these buildings can be classified into two categories in three directions. Passive technologies should be applied and prioritized, but generating renewable energy is also important. Some infrequently used technologies are not insignificant. The research shows that the combination of technologies decides sustainability performance, but the quantity used does not. Furthermore, energy use also needs to be balanced and coordinated in combination with architectural aesthetics. This research on energy use in residential buildings is beneficial for achieving sustainable development.

Aims: Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Interleukin-19 (IL-19), a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. The aim of our study was to investigate the effect of IL-19 on osteoporosis. Methods: Blood and femoral bone marrow suspension IL-19 levels were first measured in the lipopolysaccharide (LPS)-induced bone loss model. Small interfering RNA (siRNA) was applied to knock down IL-19 for further validation. Thereafter, osteoclast production was stimulated with IL-19 in combination with mouse macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The effect of IL-19 was subsequently evaluated using tartrate-resistant acid phosphatase (TRAP) staining and quantitative real-time polymerase chain reaction (RT-qPCR). The effect of IL-19 on osteoprotegerin (OPG) was then assessed using in vitro recombinant IL-19 treatment of primary osteoblasts and MLO-Y4 osteoblast cell line. Finally, transient transfection experiments and chromatin immunoprecipitation (ChIP) experiments were used to examine the exact mechanism of action. Results: In the LPS-induced bone loss mouse model, the levels of IL-19 in peripheral blood serum and femoral bone marrow suspension were significantly increased. The in vivo results indicated that global IL-19 deletion had no significant effect on RANKL content in the serum and bone marrow, but could increase the content of OPG in serum and femoral bone marrow, suggesting that IL-19 inhibits OPG expression in bone marrow mesenchymal stem cells (BMSCs) and thus increases bone resorption. Conclusion: IL-19 promotes bone resorption by suppressing OPG expression in BMSCs in a LPS-induced bone loss mouse model, which highlights the potential benefits and side effects of IL-19 for future clinical applications. Cite this article: Bone Joint Res 2023;12(11):691–701.

The inherent nonpolarity of tetragonal lysozyme crystals excludes a ferroelectricity response. Herein, we present a demonstration of achieving measurable ferroelectricity in tetragonal lysozyme crystals through C60 doping. Ferroelectric characterizations revealed that C60-doped tetragonal lysozyme crystals exhibited typical characteristic ferroelectric hysteresis loops. Crystallographic structural analysis suggested that C60 doping may induce a reduction in the overall symmetry of tetragonal Lys@C60, leading to the observed ferroelectricity response. Moreover, the introduction of C60 facilitates efficient electron transport inside the crystal and influences the polarization of Lys@C60, further contributing to the observed ferroelectricity response. This work verifies that C60 doping can serve as a simple strategy to bestow novel ferroelectric properties to non-ferroelectric lysozyme crystals, potentially rendering them suitable for biocompatible and biodegradable application in implantable and wearable bioelectronics.

Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are considered as the first-line treatment for advanced EGFR mutation-positive non-small cell lung cancer (NSCLC). We aimed to analyze the efficacy of EGFR-TKIs treatment in patients with advanced NSCLC of different smoking habits. Methods: We conducted a search for meta-analyses and systematic reviews on the PubMed, MEDLINE, Embase, and the Cochrane Library to address this knowledge gap. Patients were divided into 2 groups: (1) experimental group: treated with EGFR-TKIs or EGFR-TKIs combined with chemotherapy, immunotherapy, antiangiogenesis, radiotherapy and (2) control group: treated with chemotherapy. Progressive-free survival (PFS) and total survival (OS) were adopted for evaluating the efficacy of EGFR-TKIs between experimental group and control group. Results: Eleven studies including 6760 patients were included in the meta-analysis. The results showed that smoking (including previous and current smoking) significantly reduces the PFS and OS in comparison to non-smoking group in the treatment of NSCLC with EGFR-TKIs. In addition, EGFR-TKIs combined with anti-vascular endothelial growth factor therapy can reduce the risk of disease progression in smokers. Conclusions: Our study indicated that smoking significantly reduced the PFS and OS in comparison to non-smoking group in the treatment of NSCLC with EGFR-TKIs.

Background Knowledge gaps remain in how gender‐related socioeconomic inequality affects sex disparities in cardiovascular diseases (CVD) prevention and outcome. Methods and Results Based on a nationwide population cohort, we enrolled 3 737 036 residents aged 35 to 75 years (2014–2021). Age‐standardized sex differences and the effect of gender‐related socioeconomic inequality (Gender Inequality Index) on sex disparities were explored in 9 CVD prevention indicators. Compared with men, women had seemingly better primary prevention (aspirin usage: relative risk [RR], 1.24 [95% CI, 1.18–1.31] and statin usage: RR, 1.48 [95% CI, 1.39–1.57]); however, women's status became insignificant or even worse when adjusted for metabolic factors. In secondary prevention, the sex disparities in usage of aspirin (RR, 0.65 [95% CI, 0.63–0.68]) and statin (RR, 0.63 [95% CI, 0.61–0.66]) were explicitly larger than disparities in usage of angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers (RR, 0.88 [95% CI, 0.84–0.91]) or β blockers (RR, 0.67 [95% CI, 0.63–0.71]). Nevertheless, women had better hypertension awareness (RR, 1.09 [95% CI, 1.09–1.10]), similar hypertension control (RR, 1.01 [95% CI, 1.00–1.02]), and lower CVD mortality (hazard ratio, 0.46 [95% CI, 0.45–0.47]). Heterogeneities of sex disparities existed across all subgroups. Significant correlations existed between regional Gender Inequality Index values and sex disparities in usage of angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers (Spearman correlation coefficient, r=−0.57, P=0.0013), hypertension control (r=−0.62, P=0.0007), and CVD mortality (r=0.45, P=0.014), which remained significant after adjusting for economic factors. Conclusions Notable sex disparities remain in CVD prevention and outcomes, with large subgroup heterogeneities. Gendered socioeconomic factors could reinforce such disparities. A sex‐specific perspective factoring in socioeconomic disadvantages could facilitate more targeted prevention policy making.

Summary: Most gastric cancer (GC) patients with early stage often have no lymph node (LN) metastases, while LN metastases appear in the advanced stage. However, there are some patients who present with early stage LN metastases and no LN metastases in the advanced stage. To explore the deeper molecular mechanisms involved, we collected clinical samples from early and advanced stage GC with and without LN metastases, as well as metastatic lymph nodes. Herein, we identified a key target, HOXA11, that was upregulated in GC tissues and closely associated with lymphatic metastases. HOXA11 transcriptionally regulates TGFβ1 expression and activates the TGFβ1/Smad2 pathway, which not only promotes EMT development but also induces VEGF-C secretion and lymphangiogenesis. These findings provide a plausible mechanism for HOXA11-modulated tumor in lymphatic metastasis and suggest that HOXA11 may represent a potential therapeutic target for clinical intervention in LN-metastatic gastric cancer.

Gastric cancer (GC) is a serious disease with high morbidity and mortality rates worldwide. Chemotherapy plays a key role in GC treatment, while inevitable drug resistance and systematic side effects hinder its clinical application. Fenton chemistry-based chemodynamic therapy (CDT) has been used as a strategy for cancer ferroptosis, and the CDT efficiency could be enhanced by photothermal therapy (PTT). With the trend of treatment and diagnosis integration, the combination of magnetic resonance imaging (MRI) and CDT/PTT exhibits enormous progress. Herein, we constructed a platform based on PEGylated manganese-containing polydopamine (PDA) nanoparticles, named as PEG-PDA@Mn (PP@Mn) NPs. The PP@Mn NPs were stable and globular. Furthermore, they demonstrated near-infrared (NIR)-triggered PTT and Fenton-like reaction-based CDT effects and T1-weighted MRI capabilities. According to in vitro studies, the PP@Mn NPs trigger ferroptosis in cancer cells by producing abundant reactive oxygen species (ROS) via a Fenton-like reaction combined with PTT. Furthermore, in vivo studies showed that, under MRI guidance, the PP@Mn NPs combined with the PTT at the tumor region, have CDT anti-tumor effect. In conclusion, the PP@Mn NPs could provide an effective strategy for CDT/PTT synergistic ferroptosis therapy for GC.

Abstract We evaluate the accuracy of an original hybrid segmentation pipeline, combining variational and deep learning methods, in the segmentation of CT scans of stented aortic aneurysms, abdominal organs and brain lesions. The hybrid pipeline is trained on 50 aortic CT scans and tested on 10. Additionally, we trained and tested the hybrid pipeline on publicly available datasets of CT scans of abdominal organs and MR scans of brain tumours. We tested the accuracy of the hybrid pipeline against a gold standard (manual segmentation) and compared its performance to that of a standard automated segmentation method with commonly used metrics, including the DICE and JACCARD and volumetric similarity (VS) coefficients, and the Hausdorff Distance (HD). Results. The hybrid pipeline produced very accurate segmentations of the aorta, with mean DICE, JACCARD and VS coefficients of: 0.909, 0.837 and 0.972 in thrombus segmentation and 0.937, 0.884 and 0.970 for stent and lumen segmentation. It consistently outperformed the standard automated method. Similar results were observed when the hybrid pipeline was trained and tested on publicly available datasets, with mean DICE scores of: 0.832 on brain tumour segmentation, and 0.894/0.841/0.853/0.847/0.941 on left kidney/right kidney/spleen/aorta/liver organ segmentation.

Abstract Titanium dioxide (TiO2) nanoparticles (NPs) are one of the topmost widely used metallic oxide nanoparticles. Whether present in naked form or doped with metals or polymers, TiO2 NPs perform immensely important functions. However, the alteration in size and shape by doping results in improving the physical, chemical, and biological behaviour of TiO2 NPs. Hence, the differential effects of various TiO2 nanostructures including nanoflakes, nanoflowers, and nanotubes in various domains of biotechnology have been elucidated by researchers. Recently, the exponential growth of research activities regarding TiO2 NPs has been observed owing to their chemical stability, low toxicity, and multifaceted properties. Because of their enormous abundance, plants, humans, and environment are inevitably exposed to TiO2 NPs. These NPs play a significant role in improving agricultural attributes, removing environmental pollution, and upgrading the domain of nanomedicine. Therefore, the currently ongoing studies about the employment of TiO2 NPs in enhancement of different aspects of agriculture, environment, and medicine have been extensively discussed in this review.

Abstract The emergence of the level 3 automated vehicles (L3 AVs) can enable drivers to be completely disengaged from driving and safely perform other non-driving related tasks, but sometimes their takeover of control of the vehicle is required. The takeover of control is an important human–machine interaction in L3 AVs. However, little research has focused on investigating the effect of gender on takeover performance. In order to fill this research gap, a driving simulator study with 76 drivers (33 females and 43 males) was conducted. The participants took over control from L3 AVs, and the timing and quality of takeover were measured. The results show that although there was no significant difference in most of the measurements adopted to quantify takeover performance between female and male. Gender did affect takeover performance slightly, with women exhibited slightly better performance than men. Compared to men, women exhibited a smaller percentage of hasty takeovers and slightly faster reaction times as well as slightly more stable operation of the steering wheel. The findings highlight that it is important for both genders to recognise they can use and interact with L3 AVs well, and more hands-on experience and teaching sessions could be provided to deepen their understanding of L3 AVs. The design of the car interiors of L3 AVs should also take into account gender differences in the preferences of users for different non-driving related tasks.

BackgroundWe aimed to evaluate the function of the reconstructed anal canal in postoperative anorectal malformations (ARMs) patients through three dimension (3D) high-definition anorectal manometry.MethodsFrom January 2015 to December 2019, 3D manometry was performed as a postoperative functional assessment of patients with ARMs divided into age subgroups based on the time of manometry. Manometric parameters, such as the length of the anorectal high-pressure zone (HPZ-length), the mean resting and squeeze pressure of HPZ (HPZ-rest and HPZ-sqze), recto-anal inhibitory reflex (RAIR), and strength distribution of the anal canal, were collected and compared with age-matched controls. Their functional outcomes were analyzed with SPSS 23.0 software for statistical analysis.Results171 manometric measurements were performed on 142 postoperative patients (3 months∼15 years). The HPZ-rest in all patients was significantly lower than in age-matched controls (p

Contemporary college students are suffering from increasingly serious psychological health problems, such as attention fatigue, psychological stress and negative emotions. A growing body of evidence has revealed that restorative environment design is conducive to psychological health. As the main choice of venue for students’ daily activities, campus common spaces are supposed to be restorative to some extent. Given the above, the author studied 22 common spaces in the South China University of Technology (SCUT) Wushan Campus from the perspective of college students’ behavioral patterns based on theories pertaining to restorative environments, then constructed a structural equation model (SEM) analyzing the psychologically restorative effects exerted by the characteristics of campus common spaces upon college students through a scale design and questionnaire survey. With the analysis of 478 valid questionnaires, the research found that the characteristics of campus common spaces with psychologically restorative effects mainly comprise the architectural environment, landscape environment, rest facilities and activity facilities. Among them, the characteristics of activity facilities and the landscape environment have the greatest impact on psychologically restorative effects, accounting for 33 and 30% of the total effects, respectively; they are followed by those of the architectural environment, which accounts for 21% of the total effects; those of the rest facilities have the least impact, accounting for 16% of the total effects. The research also found that the characteristics of campus common spaces can both directly influence college students’ psychological recovery and produce psychologically restorative effects mediated by college students’ behavioral patterns. The mediation effect of college students’ behavioral patterns accounts for approximately 41% of the total effect of psychological restoration, in which the psychologically restorative effect of dynamic exercise behaviors is 2.5 times that of static leisure behaviors. The research reveals how the characteristics of campus common spaces promote the psychological restoration of college students, and it provides inspiration for healthy environment design in campus common spaces.

Abstract Coronary artery disease (CAD) is one of the major cardiovascular diseases and represents the leading causes of global mortality. Developing new diagnostic and therapeutic approaches for CAD treatment are critically needed, especially for an early accurate CAD detection and further timely intervention. In this study, we successfully isolated human plasma small extracellular vesicles (sEVs) from four stages of CAD patients, that is, healthy control, stable plaque, non‐ST‐elevation myocardial infarction, and ST‐elevation myocardial infarction. Surface‐enhanced Raman scattering (SERS) measurement in conjunction with five machine learning approaches, including Quadratic Discriminant Analysis, Support Vector Machine (SVM), K‐Nearest Neighbor, Artificial Neural network, were then applied for the classification and prediction of the sEV samples. Among these five approaches, the overall accuracy of SVM shows the best predication results on both early CAD detection (86.4%) and overall prediction (92.3%). SVM also possesses the highest sensitivity (97.69%) and specificity (95.7%). Thus, our study demonstrates a promising strategy for noninvasive, safe, and high accurate diagnosis for CAD early detection.

Introduction: The porcine nerve-derived extracellular matrix (ECM) fabricated as films has good performance in peripheral nerve regeneration. However, when constructed as conduits to bridge nerve defects, ECM lacks sufficient mechanical strength.Methods: In this study, a novel electrospun bilayer-structured nerve conduit (BNC) with outer poly (L-lactic acid-co-ε-caprolactone) (PLA-PCL) and inner ECM was fabricated for nerve regeneration. The composition, structure, and mechanical strength of BNC were characterized. Then BNC biosafety was evaluated by cytotoxicity, subcutaneous implantation, and cell affinity tests. Furthermore, BNC was used to bridge 10-mm rat sciatic nerve defect, and nerve functional recovery was assessed by walking track, electrophysiology, and histomorphology analyses.Results: Our results demonstrate that BNC has a network of nanofibers and retains some bioactive molecules, including collagen I, collagen IV, laminin, fibronectin, glycosaminoglycans, nerve growth factor, and brain-derived neurotrophic factor. Biomechanical analysis proves that PLA-PCL improves the BNC mechanical properties, compared with single ECM conduit (ENC). The functional evaluation of in vivo results indicated that BNC is more effective in nerve regeneration than PLA-PCL conduit or ENC.Discussion: In conclusion, BNC not only retains the good biocompatibility and bioactivity of ECM, but also obtains the appropriate mechanical strength from PLA-PCL, which has great potential for clinical repair of nerve defects.

Digestive tract-related cancers account for four of the top ten high-risk cancers worldwide. In recent years, cancer immunotherapy, which exploits the innate immune system to attack tumors, has led to a paradigm shifts in cancer treatment. Gut microbiota modification has been widely used to regulate cancer immunotherapy. Dietary compounds and traditional Chinese medicine (TCM) can alter the gut microbiota and its influence on toxic metabolite production, such as the effect of iprindole on lipopolysaccharide (LPS), and involvement in various metabolic pathways that are closely associated with immune reactions. Therefore, it is an effective strategy to explore new immunotherapies for gastrointestinal cancer to clarify the immunoregulatory effects of different dietary compounds/TCMs on intestinal microbiota. In this review, we have summarized recent progress regarding the effects of dietary compounds/TCMs on gut microbiota and their metabolites, as well as the relationship between digestive cancer immunotherapy and gut microbiota. We hope that this review will act as reference, providing a theoretical basis for the clinical immunotherapy of digestive cancer via gut microbiota modulation.

Background: Little is known of the characteristics, treatment, and outcomes of patients with ST-segment elevation myocardial infarction (STEMI) but without standard modifiable cardiovascular risk factors (SMuRFs, including smoking, hypercholesterolemia, diabetes, and hypertension) in developing countries like China. Moreover, contributors to the excess mortality of such SMuRF-less patients remain unclear. Methods: This study was based on a nationally representative sample of patients presenting with STEMI and admitted to 162 hospitals in 31 provinces across mainland China between 2001 and 2015. We compared clinical characteristics, treatments, and mortality during hospitalization between patients with and without SMuRFs. We also investigated the possible causes of differences in mortality and quantified the contributors to excess mortality. Results: Among 16,541 patients (aged 65 ± 13 years; 30.0% women), 19.9% were SMuRF-less. These patients were older (69 vs. 65 years), experienced more cardiogenic shock and lower blood pressure at admission, and were less likely to be admitted to the cardiac ward compared to patients with SMuRFs. Moreover, SMuRF-less patients received treatment less often, including primary percutaneous coronary intervention (17.3% vs. 28.8%, p < 0.001), dual antiplatelet therapy (59.4% vs. 77.0%, p < 0.001), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (49.9% vs. 68.1%, p < 0.001), and statins (69.9% vs. 85.1%, p < 0.001). They had higher in-hospital mortality (18.5% vs. 10.5%, p < 0.001), with 56.1% of deaths occurring within 24 hours of admission. Although the difference in mortality decreased after adjusting for patient characteristics, it remained significant and concerning (odds ratio (OR) 1.41; 95% confidence interval (CI) 1.25–1.59). Mediation analysis found that, in patients without SMuRFs, underutilization of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and statins contributed to an excess mortality risk of 22.4% and 32.5%, respectively. Conclusions: Attention and action are urgently needed for STEMI patients without SMuRFs, given their high incidence and excess in-hospital mortality. The use of timely and adequate evidence-based treatments should be strengthened.

Climate change has reduced the comfort of community environments, and there is an urgent need to improve the health and well-being of low-income residents through design and technical measures. Therefore, this paper conducts research in the context of an ongoing social housing renovation project in Aosta, Italy, in a cold winter and hot summer Alpine environment. The study combined interviews, field measurements, and multiple software simulations to analyze the home of an older adult experiencing energy deprivation. The study found that the indoor acoustic environment quality meets the requirements of various sound-related standards. Still, the lighting and thermal environment must be designed to reduce glare and western sun exposure, and the air quality could improve. Residents’ demand for renovation is low technology, low cost, and high comfort. Therefore, suggestions for combining active and passive transformation measures and maximizing the use of climate and resources are proposed. The lighting and thermal environment are optimized based on the green wisdom of the Haylofts building of the Walser family in the Alps: increase ventilation and reduce indoor air age to improve air quality. Overall, a comprehensive assessment of extreme climatic conditions facilitates the quantitative and qualitative study and control of social housing environments, improves occupant comfort, and decarbonizes such social building stock.

BackgroundImmune checkpoint inhibitors (ICIs) have been increasingly used for the treatment of advanced gastric cancer (AGC). However, the safety and the short-term outcomes of laparoscopic gastrectomy for patients with AGC after neoadjuvant immunotherapy (NAI) remain unknown.MethodsWe retrospectively analyzed the patients with AGC who underwent laparoscopic surgery after neoadjuvant therapy between 1 January 2019 and 31 October 2021. We further compared the differences in postoperative complications, overall response rate, adverse events, surgical parameters, and postoperative recovery between two cohorts: the NAI group (NAI plus chemotherapy) and the neoadjuvant chemotherapy (NAC) group. Multivariable regression analyses were used to determine the risk factors for the overall response rate.ResultsOverall, 80 patients were enrolled, of whom 30 cases were included in the NAI cohort and 50 were included in the NAC cohort. The overall rate of postoperative complications was 30.0% in both groups (p = 1.000). The overall response rate was 70.0% in the NAI cohort and 40% in the NAC cohort (p = 0.012). The adverse effects were found in 16 cases (53.3%) of the NAI cohort and 23 cases (46.0%) of the NAC cohort (p = 0.645). There was no statistical difference in intraoperative bleeding (50 ml vs. 50 ml, p = 0.983), operation time (320.9 min vs. 303.5 min, p = 0.382), dissected lymph node count (43.5 vs. 40.0, p = 0.364), first postoperative anal aerofluxus (3 days vs. 3 days, p = 0.091), first liquid diet (4 days vs. 5 days, p = 0.213), and postoperative length of stay in the hospital (8 days vs. 7 days, p = 0.508) between the two groups. NAI was estimated to be the independent protective factor [odds ratio (OR) 4.931, 95% confidence interval (CI) (1.385–17.559), p = 0.014] for odds to overall response rate, whereas vessel invasion was found to be the significant risk factor [OR 0.113, 95% CI (0.027–0.475), p = 0.003].ConclusionsLaparoscopic surgery after NAI combined with chemotherapy is a safe therapeutic choice for AGC and may bring better short-term outcomes due to a higher overall response rate.

Talaromyces marneffei (T. marneffei) is one of the most important opportunistic human pathogens endemic in Southeast Asia. Talaromycosis, which was once regarded as an opportunistic infectious disease in patients with acquired immunodeficiency syndrome, is being increasingly reported in HIV-negative populations. Since T. marneffei infection can be localized or disseminated, patients may present with a variety of symptoms. However, mediastinal infection attributed to T. marneffei is extremely rare. We report the case of a 32-year-old female who manifested a large mediastinal mass and was eventually diagnosed as acute T. marneffei mediastinitis. The patient was HIV-negative and had no direct contact with intermediate hosts. We successfully managed to treat the patient with inhaled amphotericin B deoxycholate and observed lesion absorption in subsequent CT examinations. To our knowledge, this is the first published case of T. marneffei mediastinitis and first use of inhaled antifungal monotherapy on patients with T. marneffei infection.

Cuttings accumulation in horizontal drilling of a shale gas well is one of the main reasons for high drilling torque and drag and serious backing pressure and consequently influencing the rate of penetration (ROP), so inhibiting the generation of a cuttings bed and keeping the hole clean is an important prerequisite to ensure the smooth and safe drilling of horizontal section. In order to improve the hole cleaning efficiency of horizontal sections, this paper studied the decay laws of helical flow induced by helix angles and rotation speed of a newly developed cuttings bed remover with V-shaped blades for horizontal wells and their influences on the resuspension distribution of cuttings particles by virtue of the CFD numerical simulation method and Euler–Euler binary-fluid model, combined with the theory of particle dynamics. Then, the parameters such as blade rotation speed and blade helix angle were optimized. And the following research results were obtained. First, with the increase of the rotation speed, cuttings deposit at the bottom of the annulus deflects to a certain degree. And the higher the rotation speed, the more obvious the deflection. Second, annulus pressure drop loss increases with the increase of the helix angle. And this phenomenon is more obvious when the helix angle is larger. Third, the field test results in Well Changning H25-7 of the southern Sichuan Basin show that after the application of the newly developed cuttings bed remover for horizontal wells, the drilling friction is decreased by 33 %, the tripping is smooth without sticking. And in the process of its application, no complex downhole accident happened. Obviously, it provides good hole cleaning to ensure the safe and smooth implementation of the later casing running operation. In conclusion, this newly developed cuttings bed remover can satisfy the demand of cutting bed cleaning and drilling cost reduction and efficiency improvement of horizontal wells, so it is worth popularizing and applying. What's more, it provides guidance and reference for the design of similar cuttings bed removers.

In manufacturing, convolutional neural networks (CNNs) are widely used on image sensor data for data-driven process monitoring and quality prediction. However, as purely data-driven models, CNNs do not integrate physical measures or practical considerations into the model structure or training procedure. Consequently, CNNs’ prediction accuracy can be limited, and model outputs may be hard to interpret practically. This study aims to leverage manufacturing domain knowledge to improve the accuracy and interpretability of CNNs in quality prediction. A novel CNN model, named Di-CNN, was developed that learns from both design-stage information (such as working condition and operational mode) and real-time sensor data, and adaptively weighs these data sources during model training. It exploits domain knowledge to guide model training, thus improving prediction accuracy and model interpretability. A case study on resistance spot welding, a popular lightweight metal-joining process for automotive manufacturing, compared the performance of (1) a Di-CNN with adaptive weights (the proposed model), (2) a Di-CNN without adaptive weights, and (3) a conventional CNN. The quality prediction results were measured with the mean squared error (MSE) over sixfold cross-validation. Model (1) achieved a mean MSE of 6.8866 and a median MSE of 6.1916, Model (2) achieved 13.6171 and 13.1343, and Model (3) achieved 27.2935 and 25.6117, demonstrating the superior performance of the proposed model.

Abstract Increasing studies have found that circular RNAs (circRNAs) are aberrantly expressed and play important roles in the occurrence and development of human cancers. However, the function of circRNAs on environmental carcinogen-induced gastric cancer (GC) progression remains poorly elucidated. In the present study, hsa_circ_0110389 was identified as a novel upregulated circRNA in malignant-transformed GC cells through RNA-seq, and subsequent quantitative real-time PCR verified that hsa_circ_0110389 was significantly increased in GC tissues and cells. High hsa_circ_0110389 expression associates with advanced stages of GC and predicts poor prognosis. Knockdown and overexpression assays demonstrated that hsa_circ_0110389 regulates proliferation, migration, and invasion of GC cells in vitro. In addition, hsa_circ_0110389 was identified to sponge both miR-127-5p and miR-136-5p and SORT1 was validated as a direct target of miR-127-5p and miR-136-5p through multiple mechanism assays; moreover, hsa_circ_0110389 sponged miR-127-5p/miR-136-5p to upregulate SORT1 expression and hsa_circ_0110389 promoted GC progression through the miR-127-5p/miR-136-5p–SORT1 pathway. Finally, hsa_circ_0110389 knockdown suppressed GC growth in vivo. Taken together, our findings firstly identify the role of hsa_circ_0110389 in GC progression, which is through miR-127-5p/miR-136-5p–SORT1 pathway, and our study provides novel insight for the identification of diagnostic/prognostic biomarkers and therapeutic targets for GC.

Abstract X-linked nephrogenic diabetes insipidus (X-linked NDI) is a rare inherited disease mainly caused by lost-of-function mutations in human AVPR2 gene encoding arginine vasopressin receptor 2 (V2R). Our focus of the current study is on exploration of the functional and biochemical properties of Ile324Met (I324M) mutation identified in a pedigree showing as typical recessive X-linked NDI. We demonstrated that I324M mutation interfered with the conformation of complex glycosylation of V2R. Moreover, almost all of the I324M-V2R failed to express on the cell surface due to being captured by the endoplasmic reticulum control system. We further examined the signaling activity of DDAVP-medicated cAMP and ERK1/2 pathways and the results revealed that the mutant receptor lost the ability in response to DDAVP stimulation contributed to the failure of accumulation of cAMP and phosphorylated ERK1/2. Based on the characteristics of molecular defects of I324M mutant, we selected two reagents (SR49059 and alvespimycin) to determine whether the functions of I324M-V2R can be restored and we found that both compounds can significantly “rescue” I324M mutation. Our findings may provide further insights for understanding the pathogenic mechanism of AVPR2 gene mutations and may offer some implications on development of promising treatments for patients with X-linked NDI.

Abstract Background Paclitaxel (PTX) has been suggested to be a promising front-line drug for gastric cancer (GC), while P-glycoprotein (P-gp) could lead to drug resistance by pumping PTX out of GC cells. Consequently, it might be a hopeful way to combat drug resistance by inhibiting the out-pumping function of P-gp. Results In this study, we developed a drug delivery system incorporating PTX onto polyethylene glycol (PEG)-modified and oxidized sodium alginate (OSA)-functionalized graphene oxide (GO) nanosheets (NSs), called PTX@GO-PEG-OSA. Owing to pH/thermal-sensitive drug release properties, PTX@GO-PEG-OSA could induced more obvious antitumor effects on GC, compared to free PTX. With near infrared (NIR)-irradiation, PTX@GO-PEG-OSA could generate excessive reactive oxygen species (ROS), attack mitochondrial respiratory chain complex enzyme, reduce adenosine-triphosphate (ATP) supplement for P-gp, and effectively inhibit P-gp’s efflux pump function. Since that, PTX@GO-PEG-OSA achieved better therapeutic effect on PTX-resistant GC without evident toxicity. Conclusions In conclusion, PTX@GO-PEG-OSA could serve as a desirable strategy to reverse PTX’s resistance, combined with chemo/photothermal/photodynamic therapy. Graphic Abstract

By searching lliteratures till January 5, 2022, we evaluated the role of the mediastinal nodal staging of endobronchial ultrasound-guided fine-needle aspiration (EBUS) and endoscopic ultrasound-guided fine-needle aspiration (EUS) in lung cancer. A total of 20 studies with 2,961 patients were included in this study. The pooled sensitivity, specificity, PLR, and NLR for EBUS were 0.79, 0.97, 27.29, and 0.25, respectively. EUS showed staging performance similar to EBUS. The staging performance was significantly improved when combining EBUS + EUS.

Deep learning methods have achieved outstanding results in many image processing and computer vision tasks, such as image segmentation. However, they usually do not consider spatial dependencies among pixels/voxels in the image. To obtain better results, some methods have been proposed to apply classic spatial regularization, such as total variation, into deep learning models. However, for some challenging images, especially those with fine structures and low contrast, classical regularizations are not suitable. We derived a new regularization to improve the connectivity of segmentation results and make it applicable to deep learning. Our experimental results show that for both deep learning methods and unsupervised methods, the proposed method can improve performance by increasing connectivity and dealing with low contrast and, therefore, enhance segmentation results.

Transient electromagnetic method (TEM) is often used in urban underground space exploration and field geological resource detection. Inversion is the most important step in data interpretation. Because of the volume effect of the TEM, the inversion results are usually multi-solvable. To reduce the multi-solvability of inversion, the constrained inversion of TEM has been studied using the least squares method. The inversion trials were performed using two three-layer theoretical geological models and one four-layer theoretical geological model. The results show that one-dimensional least squares constrained inversion is faster and more effective than unconstrained inversion. The induced electromotive force attenuation curves of the inversion model indicate that the same attenuation curve may be used for different geological conditions. Therefore, constrained inversion using known geological information can more accurately reflect the underground geological information.

Background: Hair follicles harbor a rich autologous stem cell pool and human hair follicle-derived mesenchymal stem cells (hHF-MSCs) have multi-lineage differentiation potential. Many sources of MSCs include hHF-MSCs have been attractive candidates for cell therapy, regenerative medicine and tissue engineering. The present study is to explore the effect of intravenous transplantation of hHF-MSCs on bone mass in osteoporotic mice and its mechanism, and provides prospects for clinical applications for the treatment of osteoporosis with hHF-MSCs.Methods: Physically pull out about 20 hairs with intact hair follicles from the occipital area of the scalp of healthy volunteers, and extract hair follicle-derived fibroblast-like cells. These cells were cultured and characterized in vitro. Intravenous injection of hHF-MSCs was performed on ovariectomy-induced and age-related osteoporotic SCID mice for osteoporosis treatment. The mice were sacrificed 7 weeks after the second injection and samples were collected. The long bones and L1 vertebrae were collected for micro-CT scan, histomorphometry and immunohistochemical analysis. Peripheral serum were collected for ELISA analysis and antibody array.Results: Hair follicle-derived fibroblast-like cells were defined as hHF-MSCs. Intravenous transplantation of hHF-MSCs can better restores trabecular bone mass in osteoporotic mice. The double calcein labeling assay, trap staining of bones and ELISA analysis in peripheral serum showed enhanced bone formation and weakened bone resorption after transplantation. Antibody array and immunohistochemical analysis showed that several cytokines including OPG, Wnt2b, Noggin, VCAM-1 and RANKL might be involved in this process.Conclusion: Human HF-MSCs transplantation can combat trabecular bone loss induced by menopause and aging in mice. And the above mechanism that hHF-MSCs transplantation inhibits bone resorption and promote bone formation is related to OPG, Wnt2b, VCAM-1, Noggin and RANKL.

California cannabis regulations require testing for four pathogenic species of Aspergillus-A. niger, A. flavus, A. fumigatus and A. terreus in cannabis flower and cannabis inhalable products. These four pathogenic species of Aspergillus are important human pathogens and their presence in cannabis flower and cannabis products may pose a threat to human health. In this study, we examined the potential of X-ray irradiation for inactivation of cannabis flower contaminated with any of the four pathogenic species of Aspergillus. We determined that X-ray irradiation at a dose of 2.5 kGy is capable of rendering Aspergillus cells non-viable at low (102 spores/g dried flower), medium (103 spores/g dried flower) and high (104 spores/g dried flower) levels of inoculation. We also showed that X-ray treatment of cannabis flower did not significantly alter the cannabinoid or the terpene profiles of the flower samples. Therefore, X-ray irradiation may be a feasible method for Aspergillus decontamination of cannabis flower. More work is required to determine the consumer safety of irradiated cannabis flower and cannabis products.

Aims/Introduction. Sex steroid hormones play a significant role in the progression of cardiovascular and metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). The aim of this cross-sectional study was to explore the associations of testosterone, androstenedione, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS), with the risk of NAFLD in patients with type 2 diabetes mellitus (T2DM). Materials and Methods. There were 1155 patients with T2DM included in the analysis. Serum levels of total testosterone and the precursors of androgens, including androstenedione, DHEA, and DHEAS, were quantified using liquid chromatography-tandem mass spectrometry assays. Results. The risk of NAFLD decreased as total testosterone concentration increased in men with T2DM. After adjusting for age, current smoking, current drinking, body mass index, duration of T2DM, diastolic blood pressure, total cholesterol, triglycerides, low-density lipoprotein/high-density lipoprotein cholesterol ratio, uric acid, C-reactive protein, and sex hormones in model 4, the adjusted odds ratio (OR) and 95% confidence interval (CI) of NAFLD for tertile3 vs tertile1 was 0.37 (0.17–0.77; P=0.024 for trend). When taken as a continuous variable, this association was still robust in model 4 (OR, 0.58; 95% CI, 0.42–0.80; P0.05). Moreover, women showed no significant associations of total testosterone, androstenedione, DHEA, and DHEAS, with the odds of NAFLD (all P>0.05). Conclusions. Serum total testosterone was independently associated with the risk of NAFLD among men with T2DM. This study highlights the potential role of testosterone as a risk factor for NAFLD in patients with T2DM.

Abstract Background CuS-modified hollow mesoporous organosilica nanoparticles (HMON@CuS) have been preferred as non-invasive treatment for cancer, as near infrared (NIR)-induced photo-thermal effect (PTT) and/or photo-dynamic effect (PDT) could increase cancer cells’ apoptosis. However, the certain role of HMON@CuS-produced-PTT&PDT inducing gastric cancer (GC) cells’ mitochondrial damage, remained unclear. Moreover, theranostic efficiency of HMON@CuS might be well improved by applying multi-modal imaging, which could offer an optimal therapeutic region and time window. Herein, new nanotheranostics agents were reported by Gd doped HMON decorated by CuS nanocrystals (called HMON@CuS/Gd). Results HMON@CuS/Gd exhibited appropriate size distribution, good biocompatibility, l-Glutathione (GSH) responsive degradable properties, high photo-thermal conversion efficiency (82.4%) and a simultaneous reactive oxygen species (ROS) generation effect. Meanwhile, HMON@CuS/Gd could efficiently enter GC cells, induce combined mild PTT (43–45 °C) and PDT under mild NIR power density (0.8 W/cm2). Surprisingly, it was found that PTT might not be the only factor of cell apoptosis, as ROS induced by PDT also seemed playing an essential role. The NIR-induced ROS could attack mitochondrial transmembrane potentials (MTPs), then promote mitochondrial reactive oxygen species (mitoROS) production. Meanwhile, mitochondrial damage dramatically changed the expression of anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (Bax). Since that, mitochondrial permeability transition pore (mPTP) was opened, followed by inducing more cytochrome c (Cyto C) releasing from mitochondria into cytosol, and finally activated caspase-9/caspase-3-depended cell apoptosis pathway. Our in vivo data also showed that HMON@CuS/Gd exhibited good fluorescence (FL) imaging (wrapping fluorescent agent), enhanced T1 imaging under magnetic resonance imaging (MRI) and infrared thermal (IRT) imaging capacities. Guided by FL/MRI/IRT trimodal imaging, HMON@CuS/Gd could selectively cause mild photo-therapy at cancer region, efficiently inhibit the growth of GC cells without evident systemic toxicity in vivo. Conclusion HMON@CuS/Gd could serve as a promising multifunctional nanotheranostic platform and as a cancer photo-therapy agent through inducing mitochondrial dysfunction on GC.

Abstract Effective liner shipping is important for the global seaborne trade. The volume of cargoes transported by liner shipping has been increasing over the past decades. Liner shipping companies face three levels of decision problems, including strategic, tactical, and operational problems. The tactical-level decisions are commonly made every three to 6 months. These decisions include: (1) port service frequency determination; (2) fleet deployment; (3) sailing speed optimization; and (4) vessel schedule design. Most of the concurrent liner shipping studies have addressed the tactical-level decision problems separately. Even though a few studies have proposed joint planning models that capture multiple decision problems at the same time, none of the conducted studies has integrated all the four tactical-level decision problems. To address this gap in the state-of-the-art, this study presents a holistic optimization model that addresses all the tactical-level liner shipping decision problems, aiming to maximize the total profit obtained from liner shipping services. The key route service cost components, found in the liner shipping literature, are considered in this study, which include: (1) vessel operational cost; (2) vessel chartering cost; (3) port handling cost; (4) port late arrival cost; (5) fuel consumption cost; (6) container inventory costs in sea and at ports of call; and (7) emission costs in sea and at ports of call. An exact optimization approach is adopted for the developed mathematical model. The computational experiments, conducted for a set of Asia-North America liner shipping routes, showcase the efficiency of the proposed approach and offer some important managerial insights.

The “factory-in-a-box” concept involves assembling production modules (i.e., factories) in containers and transporting the containers to different customer locations. Such a concept could be highly effective during emergencies, when there is an urgent demand for products (e.g., the COVID-19 pandemic). The “factory-in-a-box” planning problem can be divided into two sub-problems. The first sub-problem deals with the assignment of raw materials to suppliers, sub-assembly decomposition, assignment of sub-assembly modules to manufacturers, and assignment of tasks to manufacturers. The second sub-problem focuses on the transport of sub-assembly modules between suppliers and manufacturers by assigning vehicles to locations, deciding the order of visits for suppliers, manufacturers, and customers, and selecting the appropriate routes within the transportation network. This study addresses the second sub-problem, which resembles the vehicle routing problem, by developing an optimization model and solution algorithms in order to optimize the “factory-in-a-box” supply chain. A mixed-integer linear programming model, which aims to minimize the total cost of the “factory-in-a-box” supply chain, is presented in this study. CPLEX is used to solve the model to the global optimality, while four metaheuristic algorithms, including the Evolutionary Algorithm, Variable Neighborhood Search, Tabu Search, and Simulated Annealing, are employed to solve the model for large-scale problem instances. A set of numerical experiments, conducted for a case study of “factory-in-a-box”, demonstrate that the Evolutionary Algorithm outperforms the other metaheuristic algorithms developed for the model. Some managerial insights are outlined in the numerical experiments as well.

A comprehensive transient electromagnetic interpretation method based on seismic wave impedance inversion has been proposed according to the advantages of seismic and transient electromagnetic exploration methods to mitigate of hidden water inrush disasters in coalmines. Combined seismic wave impedance inversion results and resistivity logging data, the method was used to establish a geo-electric model. The stratigraphic horizon and the stratigraphic electrical characteristics were determined by the wave impedance inversion data and the resistivity logging data respectively. Furthermore, the structure and water-bearing property in the stratum were estimated by the analysis of the difference between the measured transient electromagnetic data and the calculated data from the forward model. The numerical calculation of the fault-containing model shows that the comprehensive interpretation method could determine the water-bearing capability of the fault as well as it tendency. An advantage of this new method is the effective avoidance of the influence of low-impedance overburden on the data interpretation. The practical application can accurately explain the location and the water-bearing property of the disaster-causing factors of the hidden water inrush in the coalmines.

Rare autosomal-recessive variants in tetratricopeptide repeat domain 7A (TTC7A) gene have been shown to cause intestinal and immune disorders of variable severity. Missense mutations in TTC7A gene, usually retaining most of the functional motifs, is associated with relative milder clinical presentations. In this study, we reported a patient who was suffering from severe multiple intestinal atresia (MIA) with combined immunodeficiency (CID) that led to the pyloric diaphragm, ileum atresia, colon stenosis, and multiple episodes of sepsis. In spite of several surgeries and supportive treatment, the patient died of severe sepsis and multiple organ failure at age of 3 months. The whole exome sequencing (WES) of peripheral blood samples identified a novel homozygous TTC7A missense mutation (c. 206T>C, p. L69P), inherited from his parents with consanguineous marriage. In silico analysis revealed that a hydrogen bond present between Gly65 and Leu69 in the wild-type TTC7A was disrupted by the Leu69Pro mutation. Moreover, this homozygous missense mutation led to a reduced TTC7A expression in lymphocytes and intestinal tissues, accompanied by impeded lymphocyte development. Further studies demonstrated that the PI4K-FAM126A-EFR3A pathway was impaired in colon tissues. Our data strongly support the linkage of severe MIA-CID with the missense mutation in TTC7A gene. More knowledge of the TTC7A protein functions will have important therapeutic implications for patients with MIA-CID.

Peroxymonosulfate (PMS) plays an important role in the advanced oxidation process for environmental remediation. In this study, barium titanate (BTO) piezocatalyst was selected for the activation of PMS driven by ultrasonic power. The degradation of Rhodamine B (RhB) by BTO single component, PMS single component, and BTO/PMS double components were investigated. The results indicated that PMS can be efficiently activated by BTO under an ultrasound with an RhB degradation rate of 98% within 20 min. The ultrasound not only promoted the activation of the PMS itself, but the surface charge carriers of BTO induced by the ultrasound also contributed to the activation of PMS. ·O2−, ·OH, and ·SO4− radicals were found to be the main active species that participated in the reaction. In order to verify the reaction’s environmental applicability, amoxicillin (AMX) as a typical environmental pollutant was studied. BTO/PMS displayed 80% removal efficiency of AMX, and the products generated were less toxic as demonstrated by eco-toxicity comparison. This work provides a promising strategy to improve the utilization of ultrasonic energy and apply it to the field of environmental pollutants treatment.

As cities transition from incremental development to stock development, university campuses in suburban areas are progressively becoming urban university campuses. The stability of the boundary between urban university campuses and the city, along with the fact that the campus’s overall spatial capacity is reaching its maximum, makes it impossible for urban university campuses to have future spatial expansions. This article focused on the stock development, renewal, and transformation of urban campuses. From the perspective of urban university campus block morphology hierarchy and using the Wushan Campus of South China University of Technology in Guangzhou as an example, this study utilized urban morphology theory, data mining technology, big data collection, and visualization techniques to measure campus block morphology. Then, K-means clustering was utilized to classify the block form, and historical background research was employed to study the many forms of typical block form. Finally, the campus renewal and transformation guiding principles were introduced, and the control index of block form renewal and transformation was formed, evolving into the university campus block form renewal and transformation design technique. This strategy was used to investigate the general revitalization of college campuses.

This study argues that medical data should be better utilized and attention should be paid to the patient’s visual experience during their journey to the emergency department (ED). Wayfinding in medical settings remains a challenge for patients. One reason is that decision makers do not adequately understand what the patients have seen and been through during their journey in the ED built environment, which leads to inaccurate selection and misplacement of signage. This study claims that there is still room to optimize existing wayfinding design methods. This study selected a representative large-scale general hospital in China, collected the annual healthcare information system (HIS) data of ED patients in 2021, and reproduced the clinical process of ED patients in the form of a probability treemap through categorical analysis. Furthermore, Massmotion was used to simulate the patient’s journey and obtain their vision focus area (VFA). With the VFA and field observation record, the research targeted 17 wall surfaces in the ED built environment. On the basis of the comparative analysis, we found the misplacement of the current signage system and the direction of future optimization. This method can provide a reference for designers during their decision-making process to aim for an efficient wayfinding system.

Effective natural ventilation reduces humidity, cools the space, and enhances thermal comfort. In light of the frequent ventilation issues in the Lingnan area, this research suggests a successful ventilation technique using Jiangmen’s “Yunshan Poetic” Moon Island houses as an example. With its symmetrical architectural layout of townhouses and its primary courtyard villa product, the community typifies the Lingnan area. First off, we discovered that the district’s average temperature is as high as 30.95 °C and its average humidity is as high as 83.592%RH using actual measurements and simulation of heat and humidity data. The district’s buildings’ issues with dampness, peeling walls, and substance mold are primarily caused by poor ventilation. Secondly, the PHOENICS program was used to provide efficient ventilation solutions for the following six aspects: external wind infusion organization, group orientation layout, planar grouping optimization, building façade combination, monolithic building openings, and indoor ventilation block. In order to determine if the technique is effective, the ventilation variables are compared before and after optimization using the Building Ventilation Effectiveness Test and Evaluation Criteria. The study concluded that the building’s architectural characteristics and the local climate have an impact on natural ventilation’s effectiveness. This serves as a guide for both the scientific layout development of future urban settlements and the optimization of ventilation of existing villa buildings in humid and hot areas.

This research explored buildings for carbon neutrality to solve the global warming problem in the Third Solar Decathlon China (SDC). The methods were derived from subjective and objective evaluation aspects based on the competition rules. Then, the results of the concepts, technologies, and prospects of 15 buildings were output. The conclusion was summarized after a discussion as follows: (1) Solving global warming through carbon neutrality is widely required and research into this issue is required now. (2) Research methods were determined via five subjective and five objective contests with multiple sub-contests. (3) Fifteen buildings’ concepts, technologies, and prospects were determined regarding the carbon neutrality aspect. (4) A good architectural design concept was needed before building for carbon neutrality. (5) This research summarized the current development of architecture concepts and technologies in academia and industry. (6) Thirty-five kinds of active and passive technologies were determined, where PV as an active method and modular assembly as a passive method were the most used in this competition. (7) The technologies used with a low frequency, such as wind turbine, Stirling engine, hydrogen fuel cell, UHPC, PCM, and SST walls technologies, also need further attention. (8) The prospect of carbon neutrality, especially for energy production in residential buildings, may shift people’s passive acceptance of carbon neutrality to active energy production. (9) Using ANP to produce the SDC ranking may be considered for more scientific investigations to demonstrate the carbon neutrality effect. (10) The limitations will continue to be researched in the future. Finally, this research aimed to make a contribution to solving the global warming for sustainable development.

During the E-cigarette or Vaping product use Associated Lung Injury (EVALI) outbreak of August 2019 to February 2020, the California Department of Public Health, Food and Drug Laboratory Branch received numerous cannabis vape oil cartridge investigation samples from throughout the state. Many of these products were directly linked to patients; others were collected as part of investigations. We determined the major ingredients and additives in twelve unused cannabis vape oil cartridge samples obtained before (n = 2) and during the EVALI outbreak (n = 10) in California from September 2018 to December 2019. We tested for major constituents in vape oil liquid, vape oil vapor, and vape oil aerosol phases. A nontargeted Gas Chromatography Mass Spectrometry direct injection screening method was developed for vape oils, a headspace heating module used for vape oil vapors and a solid-phase microextraction (SPME) vaping rig for aerosols generated by vaping. We have identified more than 100 terpenes and natural extracts, 19 cannabinoids, and other potential toxic additives such as Vitamin E Acetate, Polyethylene Glycols, and Medium Chain Triglycerides. We determined more terpenes and minor cannabinoids can be produced via vaporizing and aerosolizing the vape oil. Delta9-THC and potential toxic additives were found at lower levels in the vapor and aerosol than in the vape liquid.

Unmanned surface vehicle (USV) has witnessed a rapid growth in the recent decade and has been applied in various practical applications in both military and civilian domains. USVs can either be deployed as a single unit or multiple vehicles in a fleet to conduct ocean missions. Central to the control of USV and USV formations, path planning is the key technology that ensures the navigation safety by generating collision free trajectories. Compared with conventional path planning algorithms, the deep reinforcement learning (RL) based planning algorithms provides a new resolution by integrating a high-level artificial intelligence. This work investigates the application of deep reinforcement learning algorithms for USV and USV formation path planning with specific focus on a reliable obstacle avoidance in constrained maritime environments. For single USV planning, with the primary aim being to calculate a shortest collision avoiding path, the designed RL path planning algorithm is able to solve other complex issues such as the compliance with vehicle motion constraints. The USV formation maintenance algorithm is capable of calculating suitable paths for the formation and retain the formation shape robustly or vary shapes where necessary, which is promising to assist with the navigation in environments with cluttered obstacles. The developed three sets of algorithms are validated and tested in computer-based simulations and practical maritime environments extracted from real harbour areas in the UK.

Melanin, as a natural product, has been used as an extraordinary ingredient for nanomedicine due to its great biocompatibility and light responsive property. In this study, polydopamine (PDA), an analog of melanin, was extracted from dopamine and encapsulated with doxorubicin (DOX). The as-prepared nanoparticles (NPs) with good stability, great biosafety and high near infrared (NIR) responsive property ameliorated the cell uptake of DOX in OS-RC-2/ADR cells, exhibited synergistic chemo/photothermal (PTT)/photodynamic (PDT) effects, induced the release of damage associated molecular patterns (DAMPs), and finally, led to immunogenic cell death (ICD). In general, it was suggested that PDA-DOX NPs with NIR irradiation could serve as a promising agent for tumor therapy.

Bio-based polyamide 56T (PA56T) is a new type of bio-based polyamide regarded as a promising material for sustainable solutions. The stabilization of PA56T compounded with Irganox 1098, Doverphos S9228, or SH3368 was studied by using a rotational rheometer and a circulating air oven at 150 °C. The thermal-oxidative aging resulted in an increase of the yellow color index of the PA56T/GF composites, which due to the carbonyl group as a chromophore group, continuously formatted during the aging process. After 10 days of aging, the mechanical properties and dynamic mechanical properties increase due to the molecular cross-linking and annealing effects. When the aging time is beyond 20 days, the degradation of molecular chain segments dominates, and the mechanical properties of PA56T/GF deteriorate continuously. The addition of antioxidants only slowed this effect and did not change the process of thermal-oxidative aging, which destroys the molecular chain. The results from both methods are consistent after a series of characterizations by FTIR, XRD, and so on. In the case of samples without lubricant, the rotational rheometer has the benefit of being less time-consuming than the accelerated aging experiment.

This paper investigates the modification of dopamine (IDA) and uses it as a crosslinking agent to enhance the mechanical strength and hydrophobicity of room-temperature-vulcanized (RTV) silicone rubber. IDA was successfully synthesized with dopamine and 3-isocyanatopropyltriethoxysilane. The structure of IDA was verified by Fourier transform infrared spectroscopy and ^1 H nuclear magnetic resonance spectroscopy. IDA was introduced into the hydroxyl-terminated polydimethylsiloxane (PDMS) system to prepare RTV silicone rubber, and dibutyltin dilaurate (DBTDL) was used as the catalyst. A combination of the scanning electron microscope, thermal gravimetric analysis, universal testing machine, and contact angle was used to analyze the morphology and properties of RTV silicone rubber. The results demonstrated that the addition of IDA significantly enhanced the thermal stability and mechanical strength of RTV silicone rubber. The mechanical strength of the novel RTV silicone rubber increased by 221%. Moreover, the IDA modified RTV silicone rubber had better hydrophobicity as compared to the PDMS polymer prepared with the traditional crosslinking agent.

Image super-resolution is an image reconstruction technique which attempts to reconstruct a high resolution image from one or more under-sampled low-resolution images of the same scene. High resolution images aid in analysis and inference in a multitude of digital imaging applications. However, due to limited accessibility to high-resolution imaging systems, a need arises for alternative measures to obtain the desired results. We propose a three-dimensional single image model to improve image resolution by estimating the analog image intensity function. In recent literature, it has been shown that image patches can be represented by a linear combination of appropriately chosen basis functions. We assume that the underlying analog image consists of smooth and edge components that can be approximated using a reproducible kernel Hilbert space function and the Heaviside function, respectively. We also extend the proposed method to pansharpening, a technology to fuse a high resolution panchromatic image with a low resolution multi-spectral image for a high resolution multi-spectral image. Various numerical results of the proposed formulation indicate competitive performance when compared to some state-of-the-art algorithms.

Drug resistance is the major challenge facing cancer chemotherapy and nanoscale delivery systems based on natural materials, such as sericin, are a promising means of overcoming drug resistance. Yet, no attempt of introducing synthetic poly(γ-benzyl-L-glutamate) (PBLG) onto sericin polypeptide to fabricate a facile biocompatible and biodegradable micelle has been tried. Here, we prepared a polypeptide-based amphiphilic polymer containing hydrophilic sericin polypeptide backbone and PBLG side chains via ring-opening polymerization (ROP) strategy. The introduction of PBLG side chains remarkably enhances the stability of sericin micelles in water. Meanwhile, the micelles exhibited a high loading capacity and pH-responsive release ability for antitumor drug doxorubicin (DOX), called sericin-PBLG-DOX. Owing to the excellent cell membrane penetration of sericin-PBLG, the cellular uptake of DOX when loaded into micelles was improved. Subsequently, sericin-PBLG-DOX was transferred into perinuclear lysosomes, where the release rate of DOX was accelerated. Compared to the same dose of DOX, sericin-PBLG-DOX could induce a more efficient anti-tumor effect both in vitro and in vivo, and these micelles have promise for future clinical applications in overcoming cancer drug resistance with good biosafety, enhanced cellular uptake, pH-triggered drug release, efficient anti-tumor effects, and minimized systemic toxicity.