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Purpose: The current study aimed to assess the protective performance of helmets equipped with multi-directional impact protection system (MIPS) under various oblique impact loads. Methods: Initially, a finite element model of a bicycle helmet with MIPS was developed based on the scanned geometric parameters of an actual bicycle helmet. Subsequently, the validity of model was confirmed using the KASK WG11 oblique impact test method. Three different impact angles (30°, 45°, and 60°) and 2 varying impact speeds (5 m/s and 8 m/s) were employed in oblique tests to evaluate protective performance of MIPS in helmets, focusing on injury assessment parameters such as peak linear acceleration (PLA) and peak angular acceleration (PAA) of the head. Results: The results demonstrated that in all impact simulations, both assessment parameters were lower during impact for helmets equipped with MIPS compared to those without. The PAA was consistently lower in the MIPS helmet group, whereas the difference in PLA was not significant in the no-MIPS helmet group. For instance, at an impact velocity of 8 m/s and a 30° inclined anvil, the MIPS helmet group exhibited a PAA of 3225 rad/s2 and a PLA of 281 g. In contrast, the no-MIPS helmet group displayed a PAA of 8243 rad/s2 and a PLA of 292 g. Generally, both PAA and PLA parameters decreased with the increase of anvil angles. At a 60° anvil angles, PAA and PLA values were 664 rad/s2 and 20.7 g, respectively, reaching their minimum. Conclusion: The findings indicated that helmets incorporating MIPS offer enhanced protection against various oblique impact loads. When assessing helmets for oblique impacts, the utilization of larger angle anvils and rear impacts might not adequately evaluate protective performance during an impact event. These findings will guide advancements in helmet design and the refinement of oblique impact test protocols.

Summary: Hydrodesulfurization (HDS) is a commonly used route for producing clean fuels in modern refinery. Herein, ammonium/amine-intercalated MoS2 catalysts with various content of 1T phase and S vacancies have been successfully synthesized. Along with the increment of 1T phase and S vacancies of MoS2, the initial reaction rate of the HDS of dibenzothiophene (DBT) can be improved from 0.09 to 0.55 μmol·gcat−1·s−1, accounting for a remarkable activity compared to the-state-of-the-art catalysts. In a combinatory study via the activity evaluation and catalysts characterization, we found that the intercalation species of MoS2 played a key role in generating more 1T phase and S vacancies through the ‘intercalation-deintercalation’ processes, and the hydrogenation and desulfurization of HDS can be significantly promoted by 1T phase and S vacancies on MoS2, respectively. This study provides a practically meaningful guidance for developing more advanced HDS catalysts by the intercalated MoS2-derived materials with an in-depth understanding of structure-function relationships.

This study investigated the bactericidal effects of ultraviolet (UV) radiation, a high-voltage electric field (HVEF), and their combination on Escherichia coli. The results indicated that UV and combined disinfection were more effective with longer exposure, leading to significant reductions in microbial activity. Specifically, the single UV disinfection alone reduced activity by 3.3 log after 5 min, while combined disinfection achieved a 4.2 log reduction. In contrast, short-term HVEF treatment did not exhibit significant bactericidal effects, only achieving a reduction of 0.17 log in 5 min. Furthermore, prolonged exposure to both UV disinfection and an HVEF was found to damage cell membranes, ultimately causing cell death, while shorter durations did not. Despite rapid cell count decreases, flow cytometry did not detect apoptotic or necrotic cells, likely due to rapid cell rupture. This study suggests that combining UV radiation and an HVEF could be a promising approach for inhibiting bacterial reproduction, with HVEF enhancing UV effects. These findings provide insights for using combined HVEF and UV disinfection in food safety and preservation.

1,8-Cineole, the main component of volatile oil in aromatic plants, has diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer properties. Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM). Here, we investigated the protective effect of 1,8-cineole on DR and found that 1,8-cineole treatment could alter the expression of several genes in both high glucose (HG)-induced ARPE-19 cells and retinal tissues of DM mice, as well as inhibit ferroptosis. Subsequent investigations into the molecular mechanisms underlying this inhibition revealed that expression of thioredoxin-interacting protein (TXNIP) was significantly upregulated while that of peroxisome proliferator-activated receptor γ (PPAR-γ) was significantly downregulated in HG-induced ARPE-19 cells, and treatment with 1,8-cineole could effectively reverse these changes. Treatment with a PPAR-γ pharmacological agonist (rosiglitazone), alone or combined with 1,8-cineole, significantly inhibited the transcription of TXNIP and ferroptosis in HG-induced ARPE-19 cells. Conversely, pretreatment with GW9662, a PPAR-γ inhibitor, upregulated the transcription and expression of TXNIP in HG-induced ARPE-19 cells; 1,8-cineole failed to reverse this upregulated expression. To explore these relationships, we constructed a PPAR-γ adenovirus shRNA to elucidate the effect of 1,8-cineole on the negative regulation of TXNIP by PPAR-γ. Taken together, the present findings indicate that HG-induced ferroptosis in retinal tissue plays an essential role in the pathogenesis of DR, which can be ameliorated by 1,8-cineole.

Abstract Background Sepsis is a heterogeneous syndrome, and the identification of clinical subphenotypes is essential. Although organ dysfunction is a defining element of sepsis, subphenotypes of differential trajectory are not well studied. We sought to identify distinct Sequential Organ Failure Assessment (SOFA) score trajectory-based subphenotypes in sepsis. Methods We created 72-h SOFA score trajectories in patients with sepsis from four diverse intensive care unit (ICU) cohorts. We then used dynamic time warping (DTW) to compute heterogeneous SOFA trajectory similarities and hierarchical agglomerative clustering (HAC) to identify trajectory-based subphenotypes. Patient characteristics were compared between subphenotypes and a random forest model was developed to predict subphenotype membership at 6 and 24 h after being admitted to the ICU. The model was tested on three validation cohorts. Sensitivity analyses were performed with alternative clustering methodologies. Results A total of 4678, 3665, 12,282, and 4804 unique sepsis patients were included in development and three validation cohorts, respectively. Four subphenotypes were identified in the development cohort: Rapidly Worsening (n = 612, 13.1%), Delayed Worsening (n = 960, 20.5%), Rapidly Improving (n = 1932, 41.3%), and Delayed Improving (n = 1174, 25.1%). Baseline characteristics, including the pattern of organ dysfunction, varied between subphenotypes. Rapidly Worsening was defined by a higher comorbidity burden, acidosis, and visceral organ dysfunction. Rapidly Improving was defined by vasopressor use without acidosis. Outcomes differed across the subphenotypes, Rapidly Worsening had the highest in-hospital mortality (28.3%, P-value

Leaf chlorophyll content (LCC) significantly correlates with crop growth conditions, nitrogen content, yield, etc. It is a crucial indicator for elucidating the senescence process of plants and can reflect their growth and nutrition status. This study was carried out based on a potato nitrogen and potassium fertilizer gradient experiment in the year 2022 at Keshan Farm, Qiqihar Branch of Heilongjiang Agricultural Reclamation Bureau. Leaf hyperspectral and leaf chlorophyll content data were collected at the potato tuber formation, tuber growth, and starch accumulation periods. The PROSPECT-4 radiative transfer model was employed to construct a look-up table (LUT) as a simulated data set. This was accomplished by simulating potato leaves’ spectral reflectance and chlorophyll content. Then, the active learning (AL) technique was used to select the most enlightening training samples from the LUT based on the measured potato data. The Gaussian process regression (GPR) algorithm was finally employed to construct the inversion models for the chlorophyll content of potato leaves for both the whole and single growth periods based on the training samples selected by the AL method and the ground measured data of the potatoes. The R2 values of model validation accuracy for the potato whole plantation period and three single growth periods are 0.742, 0.683, 0.828, and 0.533, respectively with RMSE values of 4.207, 4.364, 2.301, and 3.791 µg/cm2. Compared with the LCC inversion accuracy through LUT with a cost function, the validation accuracies of the GPR_PROSPECT-AL hybrid model were improved by 0.119, 0.200, 0.328, and 0.255, and the RMSE were reduced by 3.763, 2.759, 0.118, and 5.058 µg/cm2, respectively. The study results indicate that the hybrid method combined with the radiative transfer model and active learning can effectively select informative training samples from a data pool and improve the accuracy of potato LCC estimation, which provides a valid tool for accurately monitoring crop growth and growth health.

Accurate and high-throughput identification of the initial anthesis of soybean varieties is important for the breeding and screening of high-quality soybean cultivars in field trials. The objectives of this study were to identify the initial day of anthesis (IADAS) of soybean varieties based on remote sensing multispectral time-series images acquired by unmanned aerial vehicles (UAVs), and analyze the differences in the initial anthesis of the same soybean varieties between two different climatic regions, Shijiazhuang (SJZ) and Xuzhou (XZ). First, the temporal dynamics of several key crop growth indicators and spectral indices were analyzed to find an effective indicator that favors the identification of IADAS, including leaf area index (LAI), above-ground biomass (AGB), canopy height (CH), normalized-difference vegetation index (NDVI), red edge chlorophyll index (CIred edge), green normalized-difference vegetation index (GNDVI), enhanced vegetation index (EVI), two-band enhanced vegetation index (EVI2) and normalized-difference red-edge index (NDRE). Next, this study compared several functions, like the symmetric gauss function (SGF), asymmetric gauss function (AGF), double logistic function (DLF), and fourier function (FF), for time-series curve fitting, and then estimated the IADAS of soybean varieties with the first-order derivative maximal feature (FDmax) of the CIred edge phenology curves. The relative thresholds of the CIred edge curves were also used to estimate IADAS, in two ways: a single threshold for all of the soybean varieties, and three different relative thresholds for early, middle, and late anthesis varieties, respectively. Finally, this study presented the variations in the IADAS of the same soybean varieties between two different climatic regions and discussed the probable causal factors. The results showed that CIred edge was more suitable for soybean IADAS identification compared with the other investigated indicators because it had no saturation during the whole crop lifespan. Compared with DLF, AGF and FF, SGF provided a better fitting of the CIred edge time-series curves without overfitting problems, although the coefficient of determination (R2) and root mean square error (RMSE) were not the best. The FDmax of the SGF-fitted CIred edge curve (SGF_CIred edge) provided good estimates of the IADAS, with an RMSE and mean average error (MAE) of 3.79 days and 3.00 days, respectively. The SGF-fitted_CIred edge curve can be used to group the soybean varieties into early, middle and late groups. Additionally, the accuracy of the IADAS was improved (RMSE = 3.69 days and MAE = 3.09 days) by using three different relative thresholds (i.e., RT50, RT55, RT60) for the three flowering groups compared to when using a single threshold (RT50). In addition, it was found that the IADAS of the same soybean varieties varied greatly when planted in two different climatic regions due to the genotype–environment interactions. Overall, this study demonstrated that the IADAS of soybean varieties can be identified efficiently and accurately based on UAV remote sensing multispectral time-series data.

Abstract Background Currently, there are relatively few studies on the effects of changes in oestrogen and androgen levels on prostatic microvessel density (MVD). This article aimed to study the changes in prostatic MVD in Sprague-Dawley (SD) rats after castration under the effect of oestrogen/androgen at different concentrations. Methods Male SD rats aged 3–4 months were randomly divided into a control group, a castration group, and groups with different concentrations of oestrogen/androgen treatment after castration. Dihydrotestosterone (DHT) and oestradiol (E) were administered daily by subcutaneous injection for one month. All the rats were killed by cervical dislocation after one month, and the serum DHT and E concentrations of the rats in each group were measured by ELISA. Prostate tissue specimens were immunohistochemically stained with monoclonal antibodies against CD34 and factor VIII for MVD. Results Compared with the control group, the MVD decreased significantly in the castration group (P

The separation of SiC and Si3N4 inclusions from solar cell Si scraps to the slag phase during slag refining is essential to the recovery and production of high-purity Si. This study characterized the SiC and Si3N4 inclusions in solar cell Si scraps, which formed large clusters with complex shapes. According to the experimental and theoretical investigations, the inclusions with large diameters were found to be conducive to passing through the Si/slag interface and then being retained in the slag phase. The favorable conditions such as positive overall wettability, high operating temperature, low viscosity slag, and prolonged-time can promote the small inclusion removal from molten Si scraps.

The heat treatment process is a vital step for manufacturing high-speed railway spring fasteners. In this study, orthogonal experiments were carried out to obtain reliable optimised heat treatment parameters through a streamlined number of experiments. Results revealed that a better comprehensive mechanical performance could be obtained under the following combination of heat treatment parameters: quenching temperature of 850 °C, holding time of 35 min, medium of 12% polyalkylene glycol (PAG) aqueous solution, tempering temperature of 460 °C, and holding time of 60 min. As one of the most important testing criteria, fatigue performance would be improved with increasing strength. Additionally, a high ratio of martensite to ferrite is proven to improve the fatigue limit more significantly. After this heat treatment process, the metallographic microstructure and mechanical properties satisfy the technical requirements for the high-speed railway practical operation. These findings provide a valuable reference for the practical forming process of spring fasteners.

The differential diagnosis of renal tumors and abscesses is crucial owing to their different treatments. Although antibacterial administration and radiological examination are excellent means for distinction, misdiagnosis is common and may lead to severe consequences, such as the need for nephrectomy. Here, we report a case involving a 52-year-old Asian woman with a renal mass for which a differential diagnosis was challenging. The mass persisted after administration of intravenous antibiotic therapy for 1 month. A computed tomography scan indicated an inflammatory lesion, whereas magnetic resonance imaging suggested a diagnosis of a tumor. Despite these indications, a right renal abscess was suspected during robot-assisted laparoscopic surgery, and nephron-sparing surgery was performed, which allowed confirmation of the final pathological result by biopsy specimen. Postoperatively, the mass gradually decreased in size after antibiotic therapy for a further month. This case, in which a renal abscess mimicked a tumor and the patient almost underwent a nephrectomy, highlights the need for caution in establishing therapeutic schedules for patients with inaccurate diagnoses. The management strategies for such patients must be reviewed and improved.

Abstract Drug resistance is a crucial obstacle to achieve satisfactory chemotherapeutic effects. Numerous studies have shown that the PI3K/Akt signaling pathway plays a significant role in various processes of cellular events and tumor progression, while few studies have focused on the PI3K/Akt signaling pathway in drug resistance of endothelial cells. The present study aims to explore the relationship of PI3K/Akt signaling and cellular resistance to anticancer drugs in human microvessel endothelial cells (HMEC-1). We established stable sunitinib-resiatant human microvessel endothelial cells (HMEC-su) after long-term exposure to sunitinib (a small-molecule tyrosine kinase receptor inhibitor) for 12 months. HMEC-su showed significant alternations of cell morphology and exhibited a 2.32-fold higher IC50 of sunitinib than parental HMEC-1 cells. Expression of P-glycoprotein (P-gp) and breast cancer-resistance protein (ABCG2) which mediates drug efflux, increased significantly in HMEC-su lines compared with HMEC-1 cells by western blots assay. Our study further demonstrates that LY294002 (blocking the PI3K/Akt pathway) enhances the sensibility of HMEC-su to suntinib and inhibits the gene transcription and protein expression of P-gp, ABCG2 in HMEC-su cells. In conclusion, these results indicate that LY294002 could reverse P-gp and ABCG2 mediated-drug resistance to sunitinib in HMEC-su cells by inhibiting PI3K/Akt signaling.

OBJECTIVES:. Older age is a key risk factor for adverse outcomes in critically ill patients with COVID-19. However, few studies have investigated whether preexisting comorbidities and acute physiologic ICU factors modify the association between age and death. DESIGN:. Multicenter cohort study. SETTING:. ICUs at 68 hospitals across the United States. PATIENTS:. A total of 5,037 critically ill adults with COVID-19 admitted to ICUs between March 1, 2020, and July 1, 2020. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The primary exposure was age, modeled as a continuous variable. The primary outcome was 28-day inhospital mortality. Multivariable logistic regression tested the association between age and death. Effect modification by the number of risk factors was assessed through a multiplicative interaction term in the logistic regression model. Among the 5,037 patients included (mean age, 60.9 yr [± 14.7], 3,179 [63.1%] male), 1,786 (35.4%) died within 28 days. Age had a nonlinear association with 28-day mortality (p for nonlinearity

The adverse effects of plastic on adult animal and human health have been receiving increasing attention. However, its potential toxicity to fetuses has not been fully elucidated. Herein, biodistribution of polystyrene (PS) particles was determined after the maternal mice were orally given PS micro- and/or nano-particles with and without surface modifications during gestational days 1 to 17. The results showed that PS microplastics (MPs) and nanoparticles (NPs) mainly emerged in the alimentary tract, brain, uterus, and placenta in maternal mice, and only the latter infiltrated into the fetal thalamus. PS NPs and carboxyl-modified NPs induced differentially expressed genes mainly enriched in oxidative phosphorylation and GABAergic synapse. Maternal administration of PS particles during gestation led to anxiety-like behavior of the progenies and their γ-aminobutyric acid (GABA) reduction in the prefrontal cortex and amygdala at Week 8. N-Acetylcysteine (NAC), an antioxidant, alleviated PS particles-induced oxidative injury in the fetal brain and rescued the anxiety-like behavior of the progenies. Additionally, PS nanoparticles caused excessive ROS and apoptosis in neuronal cell lines, which were prevented by glutathione supplementation. These results suggested that PS particles produced a negative effect on fetuses by inducing oxidative injury and suppressing GABA synthesis in their brain. The findings contribute to estimating the risk for PS particles to human and animal health.

To improve the quality of products produced from microforming, various nanolubricants have been applied in the field of micromanufacturing in recent years. In this paper, the effects of glycerol-based lubricant containing TiO2 NPs (NPs) on micro deep drawing (MDD) of austenitic stainless steel (ASS) SUS301 were studied, and the lubrication mechanism involved was discussed. The MDD experiments were conducted with the SUS301 foils under dry, 1, 2, and 4 wt% TiO2 NP lubrication conditions. The results show that the use of the TiO2 nanolubricants can significantly improve the quality of the drawn cups in terms of decreased wrinkling and surface roughness. Besides, the concentration of TiO2 NPs influences lubricity by reducing friction during the MDD process. The peak drawing force is the lowest when 2 wt% nanolubricant is applied, which drops to 72.54 N from 77.38 N under dry conditions. The micro cup drawn under 2 wt% TiO2 nanolubricant has the best quality among those obtained under all the lubrication conditions. The lubrication mechanisms are derived from the mending effects of TiO2 NPs and the formation of thin lubricant films associated with the open lubricant pockets (OLPs) and close lubricant pocket (CLPs) theory in the MDD. The CLPs function as reservoirs that retain lubricants to counteract the load pressure, whereas the OLPs lead to lubricant leakage due to the higher flow resistance. It was found that the lubricant film and NPs are insufficient at a low concentration (1 wt%), while the lubrication performance can be enhanced with increased NP concentration. However, there exist apparent agglomerations on the surface of the produced micro cup when using 4 wt% nanolubricant, which greatly deteriorates the lubricant performance in the MDD process. It is concluded that the lubricant containing 2 wt% TiO2 NPs demonstrates the best lubrication performance during the MDD of ASS SUS301.

The gradual development of online teaching has become an important field of personnel training in universities, strengthening the quality of online teaching has become a new task for the development of higher education in our country. In view of the challenges faced by online teaching in universities in quality assurance, quality control and quality management, based on the requirements of applying TQM theory to online teaching in universities in an all-round, whole process and full participation, starting from establishing online teaching quality assurance mechanism, optimizing online teaching quality control system and improving online teaching quality supervision measures, the quality of online teaching in universities is effectively improved.[1] Help our country higher education cause reform and development.

Purpose To evaluate the association between body mass index (BMI) and clinical outcomes other than death in patients hospitalised and intubated with COVID-19.Methods This is a single-centre cohort study of adults with COVID-19 admitted to New York Presbyterian Hospital-Weill Cornell Medicine from 3 March 2020 through 15 May 2020. Baseline and outcome variables, as well as lab and ventilatory parameters, were generated for the admitted and intubated cohorts after stratifying by BMI category. Linear regression models were used for continuous, and logistic regression models were used for categorical outcomes.Results The study included 1337 admitted patients with a subset of 407 intubated patients. Among admitted patients, hospital length of stay (LOS) and home discharge was not significantly different across BMI categories independent of demographic characteristics and comorbidities. In the intubated cohort, there was no difference in in-hospital events and treatments, including renal replacement therapy, neuromuscular blockade and prone positioning. Ventilatory ratio was higher with increasing BMI on days 1, 3 and 7. There was no significant difference in ventilator free days (VFD) at 28 or 60 days, need for tracheostomy, hospital LOS, and discharge disposition based on BMI in the intubated cohort after adjustment.Conclusions In our COVID-19 population, there was no association between obesity and morbidity outcomes, such as hospital LOS, home discharge or VFD. Further research is needed to clarify the mechanisms underlying the reported effects of BMI on outcomes, which may be population dependent.

The synergistic effect of electrostatically enhanced fibrous filtration originates from the charging characteristics of aerosol particles and electret fibers in an electric field. Two electrostatically enhanced fibrous filter systems are designed in this study to investigate the mechanism of the effects of the charging characteristics of oily aerosol on the filtration efficiency. We investigate the charging characteristics and their effects on the filtration efficiency of dioctyl-phthalate (DOP) aerosol particles of various sizes by setting different filter systems and electric field intensities. The experimental results show that the charge of DOP particles increases with the strength of the electric field, and the average charge increases with the particle size. The maximum charge of DOP particles reaches 4760 eC/P, and the filtration efficiency of the coupled system improves when DOP particles are amply charged. For 0.25 μm DOP particles as the most penetrating particle size, the system had good long-term stability, and the filtration efficiency is approximately 72% higher than that of the fiber acting alone. Meanwhile, the problem of oily aerosol deposition reducing the electret filtration efficiency is solved, providing a basis for long-term filtration and oily aerosol purification by electret fiber.

Summary: Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.

OBJECTIVES:. Critically ill patients with coronavirus disease 2019 have variable mortality. Risk scores could improve care and be used for prognostic enrichment in trials. We aimed to compare machine learning algorithms and develop a simple tool for predicting 28-day mortality in ICU patients with coronavirus disease 2019. DESIGN:. This was an observational study of adult patients with coronavirus disease 2019. The primary outcome was 28-day inhospital mortality. Machine learning models and a simple tool were derived using variables from the first 48 hours of ICU admission and validated externally in independent sites and temporally with more recent admissions. Models were compared with a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 using the area under the receiver operating characteristic curve and calibration. SETTING:. Sixty-eight U.S. ICUs. PATIENTS:. Adults with coronavirus disease 2019 admitted to 68 ICUs in the United States between March 4, 2020, and June 29, 2020. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The study included 5,075 patients, 1,846 (36.4%) of whom died by day 28. eXtreme Gradient Boosting had the highest area under the receiver operating characteristic curve in external validation (0.81) and was well-calibrated, while k-nearest neighbors were the lowest performing machine learning algorithm (area under the receiver operating characteristic curve 0.69). Findings were similar with temporal validation. The simple tool, which was created using the most important features from the eXtreme Gradient Boosting model, had a significantly higher area under the receiver operating characteristic curve in external validation (0.78) than the Sequential Organ Failure Assessment score (0.69), National Early Warning Score (0.60), and CURB-65 (0.65; p < 0.05 for all comparisons). Age, number of ICU beds, creatinine, lactate, arterial pH, and Pao2/Fio2 ratio were the most important predictors in the eXtreme Gradient Boosting model. CONCLUSIONS:. eXtreme Gradient Boosting had the highest discrimination overall, and our simple tool had higher discrimination than a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 on external validation. These models could be used to improve triage decisions and clinical trial enrichment.

Compared with the young, the elderly (age greater than or equal to 60 years old) vulnerable road users (VRUs) face a greater risk of injury or death in a traffic accident. A contributing vulnerability is the aging processes that affect their brain structure. The purpose of this study was to investigate the injury mechanisms and establish head AIS 4+ injury tolerances for the elderly VRUs based on various head injury criteria. A total of 30 elderly VRUs accidents with detailed injury records and video information were selected and the VRUs’ kinematics and head injuries were reconstructed by combining a multi-body system model (PC-Crash and MADYMO) and the THUMS (Ver. 4.0.2) FE models. Four head kinematic-based injury predictors (linear acceleration, angular velocity, angular acceleration, and head injury criteria) and three brain tissue injury criteria (coup pressure, maximum principal strain, and cumulative strain damage measure) were studied. The correlation between injury predictors and injury risk was developed using logistical regression models for each criterion. The results show that the calculated thresholds for head injury for the kinematic criteria were lower than those reported in previous literature studies. For the brain tissue level criteria, the thresholds calculated in this study were generally similar to those of previous studies except for the coup pressure. The models had higher (>0.8) area under curve values for receiver operator characteristics, indicating good predictive power. This study could provide additional support for understanding brain injury thresholds in elderly people.

The combination of chemotherapy with natural products is a common strategy to enhance anticancer effects while alleviating the dose-dependent adverse effects of cancer treatment. Oxymatrine (OMT) has been extensively reported as having anticancer activity. Doxorubicin (DOX) is a chemotherapeutic DNA-damaging agent used for the treatment of carcinoma. In this study, we investigated whether synergistic effects exist with the combination treatment with OMT and DOX using human colorectal cancer cell (CRC) lines and the potential mechanisms involved in in vitro and in vivo activities. The MTT and colony formation assay results showed that compared to either OMT or DOX monotherapy, the combination of OMT + DOX markedly inhibited the growth of HT-29 and SW620 cells. Wound healing assays showed significant inhibition of cell migration with co-treatment, supported by the change in E-cadherin and N-cadherin expressions in Western blotting. Furthermore, flow cytometry analysis revealed that OMT + DOX co-treatment enhanced cell apoptosis as a result of ROS generation, whereas NAC attenuated OMT + DOX–induced apoptosis. Similarly, the apoptosis-related proteins (cleaved caspase-3, cleaved caspase-9, and the ratio of Bax/Bcl-2) were determined by Western blotting, which showed that the expressions of these markers were notably increased in the co-treatment group. Furthermore, co-administration of a low dose of DOX and OMT inhibited xenograft tumor growth in a dose-dependent manner. TUNEL assay and Ki67 staining images indicated more apoptosis and less proliferation occurred in OMT plus DOX-treated xenograft tumors. Meanwhile, the combination strategy decreased cardiotoxicity, which is the most serious side effect of DOX. RNA sequencing was performed to explore the precise molecular alterations involved in the combination group. Among the numerous differentially expressed genes, downregulated FHL-2 and upregulated cleaved SPTAN1 were validated in both mRNA and protein levels of HT-29 and SW620 cells. These two proteins might play a pivotal role involving in OMT + DOX synergistic activity. Overall, OMT in combination with DOX presented an outstanding synergistic antitumor effect, indicating that this beneficial combination may offer a potential therapy for CRC patients.

Pulmonary emphysema is a fatal lung disease caused by the progressive thinning, enlargement and destruction of alveoli that is closely related to inflammation and oxidative stress. Oxymatrine (OMT), as a bioactive constituent of traditional Chinese herbal Sophora flavescens, has great potential to alleviate pulmonary emphysema via its anti-inflammatory and antioxidative activities. Pulmonary administration is the most preferable way for the treatment of lung diseases. To improve the in vivo stability and pulmonary retention of OMT, OMT-loaded liposome with carboxymethyl chitosan (CMCS) modification was developed. The CMCS was modified on the surface of OMT liposomes via electrostatic attraction and covalent conjugation to obtain Lipo/OMT@CMCS and CMCS-Lipo/OMT, respectively. A porcine pancreatic elastase (PPE)-induced emphysema mice model was established to evaluate the alleviation effects of OMT on alveolar expansion and destruction. CMCS-modified liposomal OMT exhibited superior ameliorative effects on emphysema regardless of the preparation methods, and higher sedimentation and longer retention in the lung were observed in the CMCS-Lipo group. The mechanisms of OMT on emphysema were related to the downregulation of inflammatory cytokines and the rebalancing of antioxidant/oxidation via the Nrf2/HO-1 and NF-κB/IκB-α signaling pathways, leading to reduced cell apoptosis. Moreover, the OMT liposomal preparations further enhanced its anti-inflammatory and antioxidative effects. In conclusion, pulmonary administration of OMT is a potential strategy for the treatment of emphysema and the therapeutic effects can be further improved by CMCS-modified liposomes.

α2-Adrenegic receptors (α2Rs) are important presynaptic modulators of central noradrenergic function (auto receptors) and postsynaptic mediators of many of the widespread effects of catecholamines and related drugs. Studies have shown that ruminants (such as goats and cattle) express special α2DR subtypes in addition to α2BR and α2CR. Real-time quantitative PCR and Western blotting were used to investigate the distribution and density of α2R in different nuclei of the goat central nervous system, selected regions of the spinal cord (L4-L6), and in various peripheral tissues. α2-AR subtype-specific antibodies were injected intrathecally and intracerebroventricularly into the tested goats to block the corresponding subtype of receptors. Pain threshold and physiological parameters were evaluated to explore the functional characteristics of α2BR, α2CR and α2DR in goats. Our results suggest that the expression of the mRNAs and proteins of all three α2R subtypes are widely but unevenly distributed in the goat CNS and peripheral tissues. Furthermore, α2DR plays a more important role in α2R-mediated analgesia in goats than α2BR and α2CR, whereas α2CR activation exerts a greater effect on body temperature than α2BR and α2DR.

To identify the water softening mechanisms that caused landslides in Panzhihua Airport, China, property and saturation tests of the mudstones extracted from a representative landslide were proposed. In this paper, water saturation tests were carried out on samples of carbonaceous mudstone collected from the east side of the No. 12 landslide at the airport. A number of different analytical techniques and mechanical tests were used to determine changes in chemical composition, mineral assemblages, and mudstone structural characteristics, including shear strength, after the mudstone had been softened. Three kinds of changes caused by water and three mudstone softening stages are proposed. The results show that the water has a significant influence on the properties of the mudstone, so the stability of the mudstone in the watery period is a big threat to the upper structure. A model for water immersion mudstone strength softening is developed. The model incorporates a permeability coefficient, the hydraulic gradient, and time; the model can be used to determine the mudstone’s shear strength and internal friction angle. This study provides a reference for the study of rock softened by water immersion.

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A low-cost titanium alloy (Ti–5Al–2Fe–3Mo wt.%) was designed and fabricated by blended elemental powder metallurgy (BEPM) process. The high-temperature deformation behavior of the powder metallurgical Ti–5Al–2Fe–3Mo wt.% (PM-TiAlFeMo) alloy was investigated by hot compression tests at temperatures ranging from 700 to 1000 °C and strain rates ranging from 0.001 to 10 s−1. The flow curves were employed to develop the Arrhenius-type constitutive model in consideration of effects of deformation temperature, strain rate, and flow stress. The value of activation energy (Q) was determined as 413.25 kJ/mol. In order to describe the workability and predict the optimum hot processing parameters of the PM-TiAlFeMo alloy, the processing map has been established based on the true stress–true strain curves and power dissipation efficiency map. Moreover, microstructure observations match well with the analyses about deformation mechanisms, revealing that dynamic recovery and dynamic recrystallization are dominant softening mechanisms at relatively high temperatures. However, the kinking and breaking of microstructure prefer to occur at relatively low temperatures.

As one of the most common malignancies worldwide, Hepatocellular carcinoma (HCC) has been treated by Sorafenib, which is the first approved target drug by FDA for advanced HCC. However, drug resistance is one of the obstacles to its application. As a typical characteristic of most solid tumors, hypoxia has become a key cause of resistance to chemotherapy and radiotherapy. It is important to elucidate the underlying mechanisms of Sorafenib resistance under hypoxia. In this study, the morphological changes of hepatocellular carcinoma cells were observed by Live Cell Imaging System and Transmission Electron Microscope; Sorafenib was found to induce necroptosis in liver cancer. Under hypoxia, the distribution of necroptosis related proteins was changed, which contributed to Sorafenib resistance. HSP90α binds with the necrosome complex and promotes chaperone-mediated autophagy (CMA) degradation, which leads necroptosis blocking and results in Sorafenib resistance. The patient-derived tumor xenograft (PDX) model has been established to investigate the potential therapeutic strategies to overcome Sorafenib resistance. 17-AAG inhibited HSP90α and presented obvious reversal effects of Sorafenib resistance in vivo and in vitro. All the results emphasized that HSP90α plays a critical role in Sorafenib resistance under hypoxia and 17-AAG combined with Sorafenib is a promising therapy for hepatocellular carcinoma.

The pricing problem of geometric average Asian option under fractional Brownian motion is studied in this paper. The partial differential equation satisfied by the option’s value is presented on the basis of no-arbitrage principle and fractional formula. Then by solving the partial differential equation, the pricing formula and call-put parity of the geometric average Asian option with dividend payment and transaction costs are obtained. At last, the influences of Hurst index and maturity on option value are discussed by numerical examples.

Geometric-average Asian option pricing model with monotonous transaction cost rate under fractional Brownian motion was established. The method of partial differential equations was used to solve this model and the analytical expressions of the Asian option value were obtained. The numerical experiments show that Hurst exponent of the fractional Brownian motion and transaction cost rate have a significant impact on the option value.

Background & Aims: This meta-analysis was performed to compare the efficacy and safety of a triple therapy, involving transcatheter arterial chemoembolization (TACE) + apatinib combined with a programmed-cell death protein-1 (PD-1) inhibitor versus TACE + apatinib, a dual therapy with apatinib and PD-1 inhibitor, and TACE alone for the treatment of advanced primary hepatocellular carcinoma (HCC). Methods: A computerized systematic search of databases, such as PubMed, Embase, the Cochrane Library, CNKI, Wanfang Data, and VIP e-Journals was performed to retrieve studies comparing TACE + apatinib combined with a PD-1 inhibitor versus a non-triple therapy for the treatment of advanced primary HCC. The literature search, quality assessment, and data extraction were performed independently by two researchers. Stata 16.0 software was employed to analyze the data. Heterogeneity was assessed utilizing the I2 statistic and p-value, followed by conducting sensitivity analysis. Results: A total of 2,352 patients were enrolled from 8 studies, including 900 patients in the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor, 877 patients in the TACE + apatinib group, 52 patients in the apatinib + a PD-1 inhibitor group, and 112 patients in the TACE group. The results revealed that the objective response rate (ORR) was significantly higher in the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor than that in the non-triple therapy group [odds ratio (OR)=2.47, 95% confidence interval (95%CI): 1.61-3.78]. Besides, disease control rate (DCR) was greater in the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor than that in the non-triple therapy group (OR=1.87, 95%CI: 1.44-2.44). Patients in the triple therapy group experienced a significant extension of overall survival (OS) (HR=0.42, 95%CI: 0.36-0.49). In addition, there was no significant difference in the overall rate of adverse events (AEs) between the two groups (OR=1.05, 95%CI: 0.89-1.22). Conclusions: Compared with the non-triple therapy group, the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor outperformed in terms of tumor response and long-term survival with manageable AEs. [ABSTRACT FROM AUTHOR]