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Research into mRNA vaccines is advancing rapidly, with proven efficacy against coronavirus disease 2019 and promising therapeutic potential against a variety of solid tumors. Adjuvants, critical components of mRNA vaccines, significantly enhance vaccine effectiveness and are integral to numerous mRNA vaccine formulations. However, the development and selection of adjuvant platforms are still in their nascent stages, and the mechanisms of many adjuvants remain poorly understood. Additionally, the immunostimulatory capabilities of certain novel drug delivery systems (DDS) challenge the traditional definition of adjuvants, suggesting that a revision of this concept is necessary. This review offers a comprehensive exploration of the mechanisms and applications of adjuvants and self-adjuvant DDS. It thoroughly addresses existing issues mentioned above and details three main challenges of immune-related adverse event, unclear mechanisms, and unsatisfactory outcomes in old age group in the design and practical application of cancer mRNA vaccine adjuvants. Ultimately, this review proposes three optimization strategies which consists of exploring the mechanisms of adjuvant, optimizing DDS, and improving route of administration to improve effectiveness and application of adjuvants and self-adjuvant DDS. [ABSTRACT FROM AUTHOR]

In the built heritage studies, the intricate web of social and selective processes that define heritage is evident. These processes are, in many cases, intertwined with the notion of scale, examplified through the production of heritage sites at the local, national, and transnational scales. While heritage and geography scholars have articulated the role played by scale in heritage-making and argue against a rigid, fixed, and hierarchical understanding of scale, they highlight the constant reproduction of scale. There is, so far, limited explanation of how the perception of scale gets reproduced and how crucial actors manipulate scalar power and resources for heritage making and the reproduction of scale. To fill this gap, this paper delves into mainland China's heritage-making, using the southern Anhui historical villages as an example. Based on intensive 5-month field research, this paper has three findings: 1) The nomination process for a World Heritage Site is notably influenced by politics and selectivity; 2) Diverse stakeholders are pivotal in shaping heritage narratives; 3) Individual contributions to heritage creation directly interact with, and subsequently reshape, 'scale', an entity that is simultaneously discursive and tangible. By integrating the notion of 'scale' into heritage discussions, we illuminate two concurrent processes: creating hierarchies through rule assimilation by interpreting the UNESCO standard internally and evolving socio-spatial dynamics via the manifestation of individual agency with resource manipulation, scale jumping, and reproduction of scale. This approach aligns with the material orientation in human geography and repositions 'scale'. Here, it's not just an epistemological framework but also a tangible force that steers individual perceptions and actions and yields measurable material impacts. [ABSTRACT FROM AUTHOR]

To meet the environmental protection and flame retardancy requirements for epoxy resins (EPs) in certain fields, in this study, a novel triazine-ring-containing DOPO-derived compound (VDPD), derived from vanillin, 2,4-Diamino-6-phenyl-1,3,5-triazine, and 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO), was synthesized using a one-pot method. Flame-retardant epoxy resin (FREP) was prepared by adding various ratios of VDPD to EP and curing with 4,4-diaminodiphenylmethane (DDM). The curing behavior, thermal stability, mechanical properties, and flame-retardant properties of the FREP were examined in various tests. According to the results, when the amount of VDPD added to the EP increased, the glass transition temperature of the FREP decreased linearly, and the flame-retardant properties gradually improved. With a 0.4 wt.% P content, the vertical burning rating of EP/DDM/VDPD-0.4 (according to the theoretical content of VDPD) reached the V-0 level, and the LOI value reached 33.1%. In addition, the results of a CCT showed that the peak heat release rate (PHRR) of EP/DDM/VDPD-0.4 decreased by 32% in comparison with that of the EP. Furthermore, compared with those of the EP, the tensile strength of EP/DDM/VDPD-0.4 decreased from 80.2 MPa to 74.3 MPa, only decreasing by 6 MPa, and the tensile modulus increased. Overall, VDPD can maintain the mechanical properties of EP and effectively improve its flame-retardant properties. [ABSTRACT FROM AUTHOR]

Background: Ubiquitination is a critical post-translational modification which can be reversed with an enzyme family known as deubiquitinating enzymes (DUBs). It has been reported that dysregulation of deubiquitination leads to carcinogenesis. As a member of the DUBs family, proteasome 26 S subunit non-ATPase 7 (PSMD7) serves as an underlying tumour-promoting factor in multiple cancers. However, the clinical significance and biological functions of PSMD7 in pancreatic cancer (PC) remain unclear. Results: In this study, we first reported frequent overexpression of PSMD7 in PC tissues, and high levels of PSMD7 were markedly linked to shorter survival and a malignant phenotype in PC patients. An array of in vitro and in vivo gain/loss-of-function tests revealed that PSMD7 facilitates the progression of PC cells. Additionally, we found that PSMD7 promotes PC cell progression by activating the Notch homolog 1 (Notch1) signalling. Interestingly, in PC cells, the inhibitory effect of PSMD7 knockdown on cellular processes was comparable to that observed upon Notch1 knockdown. Mechanistically, PSMD7 deubiquitinated and stabilised sex determining region Y (SRY)-box 2 (SOX2), a key mediator of Notch1 signalling. The stabilisation of SOX2, mediated by PSMD7, dramatically increased SOX2 protein levels, subsequently activating the Notch1 pathway. Finally, restoration of SOX2 expression abrogated the PSMD7-silenced antitumour effect. Conclusions: Taken together, our work identifies and validates PSMD7 as a promoter of PC progression through augmentation of the Notch1 signalling pathway mediated by SOX2. This finding suggests that PSMD7 holds promise as a potential therapeutic target for the management of this refractory disease. [ABSTRACT FROM AUTHOR]

Global warming may increase potential evapotranspiration (ETp), reducing the water resources in Yangzi River Delta. Therefore, it is important to investigate the trend of ETp there under the background of climate change. To this purpose, the systematic biases in temperature outputs of 24 global climate models (GCMs) under 3 shared socioeconomic pathways—representative concentration pathways (SSPs) emission scenarios (SSP1-2.6, SSP2-4.5, and SSP5-8.5)—are first corrected by using 8 bias correction methods. Then, the trend of ETp in Yangtze River Delta is projected by using 4 ETp calculation formulas (Blaney–Criddle, Hargreaves–Samani, Makkink, and Priestley–Taylor). The uncertainty of the projections is estimated and decomposed by using multi-way analysis of variance frameworks. The influence of uncertainty on the projected change signal is quantified by using the signal-to-noise ratio. The results show that all emission scenarios indicate robust increments of ETp. Specifically, relative to 1971~2000, ETp will increase by 0.14~0.17 mm d−1 (5.7~6.8%) during 2021~2050 and by 0.21~0.41 mm d−1 (8.5~16.7%) during 2061~2090, respectively. During 2021~2050, the uncertainty of ETp projections is dominantly contributed by the main effects of GCM (63%) and the ETp calculation formula (24%). During 2061~2090, it is mainly contributed by the main effect of GCM (36%), followed by the main effects of the emission scenario (34%) and the ETp calculation formula (18%). The ETp projections are generally reliable and robust during the two projection periods. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown an association between gut microbiota and cardiovascular diseases (CVDs). However, the underlying causal relationship remains unclear. This study aims to elucidate the causal relationship between gut microbiota and CVDs and to explore the pathogenic role of gut microbiota in CVDs. Methods: In this two-sample Mendelian randomization study, we used genetic instruments from publicly available genome-wide association studies, including single-nucleotide polymorphisms (SNPs) associated with gut microbiota (n = 14,306) and CVDs (n = 2,207,591). We employed multiple statistical analysis methods, including inverse variance weighting, MR Egger, weighted median, MR pleiotropic residuals and outliers, and the leave-one-out method, to estimate the causal relationship between gut microbiota and CVDs. Additionally, we conducted multiple analyses to assess horizontal pleiotropy and heterogeneity. Results: GWAS summary data were available from a pooled sample of 2,221,897 adult and adolescent participants. Our findings indicated that specific gut microbiota had either protective or detrimental effects on CVDs. Notably, Howardella (OR = 0.955, 95% CI: 0.913–0.999, P =.05), Intestinibacter (OR = 0.908, 95% CI:0.831–0.993, P =.03), Lachnospiraceae (NK4A136 group) (OR = 0.904, 95% CI:0.841–0.973, P =.007), Turicibacter (OR = 0.904, 95% CI: 0.838–0.976, P =.01), Holdemania (OR, 0.898; 95% CI: 0.810–0.995, P =.04) and Odoribacter (OR, 0.835; 95% CI: 0.710–0.993, P =.04) exhibited a protective causal effect on atrial fibrillation, while other microbiota had adverse causal effects. Similar effects were observed with respect to coronary artery disease, myocardial infarction, ischemic stroke, and hypertension. Furthermore, reversed Mendelian randomization analyses revealed that atrial fibrillation and ischemic stroke had causal effects on certain gut microbiotas. Conclusion: Our study underscored the importance of gut microbiota in the context of CVDs and lent support to the hypothesis that increasing the abundance of probiotics or decreasing the abundance of harmful bacterial populations may offer protection against specific CVDs. Nevertheless, further research is essential to translate these findings into clinical practice. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis is a common health concern that affects quality of life. This study aims to examine the online search trends of allergic rhinitis in China before and after the COVID-19 epidemic and to explore the association between the daily air quality and online search volumes of allergic rhinitis in Beijing. Methods: We extracted the online search data of allergic rhinitis-related keywords from the Baidu index database from January 23, 2017 to June 23, 2022. We analyzed and compared the temporal distribution of online search behaviors across different themes of allergic rhinitis before and after the COVID-19 pandemic in mainland China, using the Baidu search index (BSI). We also obtained the air quality index (AQI) data in Beijing and assessed its correlation with daily BSIs of allergic rhinitis. Results: The online search for allergic rhinitis in China showed significant seasonal variations, with two peaks each year in spring from March to May and autumn from August and October. The BSI of total allergic rhinitis-related searches increased gradually from 2017 to 2019, reaching a peak in April 2019, and declined after the COVID-19 pandemic, especially in the first half of 2020. The BSI for all allergic rhinitis themes was significantly lower after the COVID-19 pandemic than before (all p values < 0.05). The results also revealed that, in Beijing, there was a significant negative association between daily BSI and AQI for each allergic rhinitis theme during the original variant strain epidemic period and a significant positive correlation during the Omicron variant period. Conclusion: Both air quality and the interventions used for COVID-19 pandemic, including national and local quarantines and mask wearing behaviors, may have affected the incidence and public concern about allergic rhinitis in China. The online search trends can serve as a valuable tool for tracking real-time public concerns about allergic rhinitis. By complementing traditional disease monitoring systems of health departments, these search trends can also offer insights into the patterns of disease outbreaks. Additionally, they can provide references and suggestions regarding the public's knowledge demands related to allergic rhinitis, which can further be instrumental in developing targeted strategies to enhance population-based disease education on allergic diseases. [ABSTRACT FROM AUTHOR]

The normalized subband adaptive filtering algorithm provides fast convergence rate for colored input signals as compared to the normalized least mean square algorithm, but it suffers from a poor convergence issue in the α -stable noise. In light of this, the normalized subband p-norm (NSPN) algorithm, which is based on the least mean p-power error (MPE) criterion, is proposed in this study. This technique is not only robust against impulsive noise samples, but it also maintains a fast convergence rate when colored input signals are used. In addition to this, we develop both the steady-state and the transient models of the NSPN algorithm and provide some insights. Then, in order to solve the problem of making a choice regarding the order p in the NSPN algorithm, we design an autonomous system and come up with the NSPN algorithm with a variable p-norm (VP-NSPN). In addition, we offer the TFC-based VP-NSPN algorithm with a fast convergence rate and low steady-state misadjustment simultaneously by making use of the tap-weights feedback-based convex combination (TFC) scheme. In conclusion, simulation results on system identification and acoustic echo cancellation are undertaken in order to validate the superiority of the proposed algorithms and validate the usefulness of the theoretical analysis. [ABSTRACT FROM AUTHOR]

Rail freight is a common mode of transportation for bulk commodities and is widely used around the world, with heavy quality and large inertia. Conventional control methods are influenced by the dynamic parameters of the train model. To solve this problem, this paper designs a mayfly algorithm-predictive active disturbance rejection controller (MA-PADRC) for speed tracking and wheel anti-slip control of electric freight trains. This control method reduces dependence on accurate modeling. MA-PADRC integrates the searching ability of MA, predicting ability of Smith estimator and high efficiency of ADRC, and it can accurately estimate the driving disturbance of the freight train. Meanwhile, to prevent wheel slip, an Elman neural network-Kalman filter (ENN-KF) is designed. Through it, the precise observation of anti-slip parameters and the constraint of anti-slip control are realized. The proposed control is validated by simulation of both real and virtual driving speeds. The results show that the proposed control has a strong tracking performance, and can effectively prevent wheel slip and guarantee the safe driving of the freight train with large inertia. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) is a common life-threatening condition in critically ill patients. Itis also an important public health issue because it can cause substantial mortality and health care burden worldwide. The objective of this study was to investigate therisk factors that impact ARDS mortality in a medical center in Taiwan. Methods: This was a single center, observational study thatretrospectively analyzed data from adults in 6 intensive care units (ICUs) at Taichung Veterans General Hospital in Taiwan from 1st October, 2018to30th September, 2019. Patients needing invasive mechanical ventilation and meeting the Berlin definition criteria were included for analysis. Results: A total of 1,778 subjects were screened in 6 adult ICUs and 370 patients fulfilled the criteria of ARDS in the first 24 hours of the ICU admission. Among these patients, the prevalenceof ARDS was 20.8% and the overall hospital mortality rate was 42.2%. The mortality rates of mild, moderate and severe ARDS were 35.9%, 43.9% and 46.5%, respectively. In a multivariate logistic regression model, combination of driving pressure (DP) > 14cmH2O and oxygenation (P/F ratio)≤150 was an independent predictor of mortality (OR2.497, 95% CI 1.201–5.191, p = 0.014). Patients with worse oxygenation and a higher driving pressure had the highest hospital mortality rate(p<0.0001). Conclusions: ARDS is common in ICUs and the mortality rate remains high. Combining oxygenation and respiratory mechanics may better predict the outcomes of these ARDS patients. [ABSTRACT FROM AUTHOR]

Background: Established associated factors for DDH include female sex, breech presentation, family history, congenital malformations, oligohydramnios, and maternal hyperthyroidism. However, evidence for environmental factors that may contribute to DDH is limited and inconsistent. Methods: A systematic review of medical literature was conducted to collect data on environmental factors, including latitude, longitude, average yearly precipitation, average yearly temperature, minimum monthly temperature, and maximum monthly temperature, from all institutions that published articles on DDH. Univariate linear regression analysis was used to examine the correlation between environmental factors and DDH incidence, while multiple regression analysis was conducted to identify significant associated factors for DDH incidence. Results: Data from a total of 93 unique manuscripts were analyzed, revealing a significant negative correlation between DDH incidence and temperature, including average yearly temperature (r = -0.27, p = 0.008), minimum monthly temperature (r = -0.28, p = 0.006), and maximum monthly temperature (r = -0.23, p = 0.029). Additionally, there was a significant positive correlation between DDH incidence and latitude (r = 0.27, p = 0.009), and a significant negative correlation between DDH incidence and average yearly precipitation (r = -0.29, p = 0.004). In the final multiple regression analysis, temperature, including average yearly temperature, minimum monthly temperature, and maximum monthly temperature, were identified as significant associated factors for DDH incidence. Conclusion: The findings of this study suggest an association between cold weather and DDH incidence. Further research should explore the link between cold weather and DDH incidence, offering insights into potential interventions for cold climates. [ABSTRACT FROM AUTHOR]

In today's rapidly changing economy, efficient lifestyle has become the current situation of most mobile product users. With the development of performance tools and technologies, a fast lifestyle has brought more wealth and opportunities to users. The slow pace and fluctuating time are indirect income losses, which cause user anxiety to some extent. When the waiting time exceeds the user's waiting threshold, users would experience negative emotions, such as boredom, anxiety and anger, and product satisfaction would drop significantly. Therefore, by analyzing the uniqueness of mobile Internet products and the characteristics of users, this paper studied the reasons and influencing factors of product interactive waiting, and then used machine learning algorithm to analyze the cost function of interactive waiting experience. Finally, the corresponding interactive waiting experience design strategy was proposed. By comparison, the user experience after product interaction optimization design was 8.4% higher than that before product interaction optimization design, and the user frequency was also 14.7% higher after optimization design. In short, user experience plays an important role in product interaction design. [ABSTRACT FROM AUTHOR]

The treatment and surgical repair of torn Achilles tendons seldom return the wounded tendon to its original elasticity and stiffness. This study explored the in vitro and in vivo simultaneous release of indomethacin and bupivacaine from electrospun polylactide–polyglycolide composite membranes for their capacity to repair torn Achilles tendons. These membranes were fabricated by mixing polylactide–polyglycolide/indomethacin, polylactide–polyglycolide/collagen, and polylactide–polyglycolide/bupivacaine with 1,1,1,3,3,3-hexafluoro-2-propanol into sandwich-structured composites. Subsequently, the in vitro pharmaceutic release rates over 30 days were determined, and the in vivo release behavior and effectiveness of the loaded drugs were assessed using an animal surgical model. High concentrations of indomethacin and bupivacaine were released for over four weeks. The released pharmaceutics resulted in complete recovery of rat tendons, and the nanofibrous composite membranes exhibited exceptional mechanical strength. Additionally, the anti-adhesion capacity of the developed membrane was confirmed. Using the electrospinning technique developed in this study, we plan on manufacturing degradable composite membranes for tendon healing, which can deliver sustained pharmaceutical release and provide a collagenous habitat. [ABSTRACT FROM AUTHOR]

Embedding multiple pharmaceutical drugs into poly(lactic‐co‐glycolic acid) (PLGA) nanofibers is known to improve the regeneration of the Achilles tendon upon implantation after injury and rapidly restore post‐surgery activity. In this study, an implantable material comprising celecoxib, collagen, bupivacaine, and PLGA (CCBP) is prepared by electrospinning. Its in vitro/vivo drug discharge behaviors are evaluated, and its efficacy in tendon regeneration is investigated in a rat model. The regeneration capacity of the wounded tendon is also compared with that of a doxycycline‐collagen‐bupivacaine‐PLGA (DCBP) combination. The results show that, relative to the primary PLGA nanofibers, the pharmaceutical‐embedded nanofibers have thinner fiber diameters and higher hydrophilicity. The drug‐eluting nanofibers also offer a sustained release of celecoxib for at least 30 d in vitro and 28 d in vivo. Achilles tendons regenerated using the CCBP combination nanofibers demonstrate a significantly higher maximum load‐to‐failure than normal tendons and those repaired using the DCBP combination. Additionally, the expression of growth factors and composition of collagen I induced by the CCBP combination are superior to those induced by the DCBP combination. The results suggest that the CCBP combination is a promising scaffold for the repair of ruptured Achilles tendons. [ABSTRACT FROM AUTHOR]

[Display omitted] • Mg-Co-Ni LDH were homogenously grown on the surface of reduced graphene (Mg-Co-Ni LDH/rG- x). • The Mg-Co-Ni LDH/rG- x was fabricated by a novel ball milling combined ion-exchange method. • The present ball milling combined ion-exchange method is versatile and does not needs extra alkali sources or auxiliary assembly reagents. • The Mg-Co-Ni LDH/rG- x based asymmetric supercapacitor achieve high energy density and superlong cycling stability. As an electrode for energy storage, the inherently poor conductivity of metal hydroxides (MHs) can be improved by in situ growth of MHs on conductive carbon based substrates so that their performances on energy storage could be enhanced to a high level. However, the incompatibility of hydrophilic component (metal hydroxides) and hydrophobic counterpart (carbon based materials) makes it difficult to be accomplished. Herein, we presented a scalable and easy-operated strategy by ball-milling combined with ion-exchange technique to grow Mg-Co-Ni LDH (layered double hydroxides) on reduced graphene, in which ball-milling was utilized to disperse the staring material of magnesium acetate on graphene oxide (GO) to obtain the composite of Mg(Ac) 2 /GO. The composite can be in situ transformed to MgO/reduced grapheme (rG) by following heat treatment. While, the ion-exchange reaction could enables the in situ growth of Mg-Co-Ni LDHs on the reduced graphene. The derived products (denoted as Mg-Co-Ni LDH/rG- x) owns nanosheet morphology, surface area of 59–115 m2/g, homogenous elements distribution. As electrode for supercapacitor, the maximum capacitance of 1204F/g@1.0 A/g was achieved and the corresponding asymmetric supercapacitor device shows a large energy density of 44.3 Wh/kg@800 W/kg. Particularly, a superlong cycling stability with 90.5% capacitance retention of the first cycle was attained after continuous charge/discharge for 20 000 cycles at current density of 5.0 A/g, promising great potential for practical energy storage application. The present strategy is simple and scalable that can be widely applied to the synthesis of various hydroxides/oxides or multi-component hydroxides/oxides on carbon substrates forming a composite structure, thus offers a great potential for broad application areas including catalysis, adsorption, energy storage, etc. [ABSTRACT FROM AUTHOR]

In today's rapidly changing economy, efficient lifestyle has become the current situation of most mobile product users. With the development of performance tools and technologies, a fast lifestyle has brought more wealth and opportunities to users. The slow pace and fluctuating time are indirect income losses, which cause user anxiety to some extent. When the waiting time exceeds the user's waiting threshold, users would experience negative emotions, such as boredom, anxiety and anger, and product satisfaction would drop significantly. Therefore, by analyzing the uniqueness of mobile Internet products and the characteristics of users, this paper studied the reasons and influencing factors of product interactive waiting, and then used machine learning algorithm to analyze the cost function of interactive waiting experience. Finally, the corresponding interactive waiting experience design strategy was proposed. By comparison, the user experience after product interaction optimization design was 8.4% higher than that before product interaction optimization design, and the user frequency was also 14.7% higher after optimization design. In short, user experience plays an important role in product interaction design. [ABSTRACT FROM AUTHOR]

Dengue imposes a heavy economic burden on families and society. We used surveillance data reported in 2019 to characterize the dengue epidemic in Zhejiang Province, China, which provided guidance for dengue prevention and control. Dengue epidemics mostly occurred in July to October. People aged 30–44 years, males, and commercial service workers were more likely to suffer from dengue. The epidemic areas were mainly in Hangzhou and Wenzhou. Meanwhile, we assessed the economic cost of dengue in the province from both family and organizational perspectives. The direct economic burden of dengue patients was estimated to be USD 405,038.25, and the indirect economic burden was USD 140,364.90, for a total economic burden of USD 543,213.00. The direct economic burden of dengue patients should be reduced by increasing the coverage and reimbursement of health insurance. Additionally, the total annual cost of dengue prevention and control for the government and organizational sectors was estimated to be USD 7075,654.83. Quantifying the dengue burden is critical for developing disease control strategies, allocating public health resources, and setting health policy priorities. [ABSTRACT FROM AUTHOR]

Salient object detection has made substantial progress due to the exploitation of multi-level convolutional features. The key point is how to combine these convolutional features effectively and efficiently. Due to the step by step down-sampling operations in almost all CNNs, multi-level features usually have different scales. Methods based on fully convolutional networks directly apply bilinear up-sampling to low-resolution deep features and then combine them with high-resolution shallow features by addition or concatenation, which neglects the compatibility of features, resulting in misalignment problems. In this paper, to solve the problem, we propose an alignment integration network (ALNet), which aligns adjacent level features progressively to generate powerful combinations. To capture long-range dependencies for high-level integrated features as well as maintain high computational efficiency, a strip attention module (SAM) is introduced into the alignment integration procedures. Benefiting from SAM, multi-level semantics can be selectively propagated to predict precise salient objects. Furthermore, although integrating multi-level convolutional features can alleviate the blur boundary problem to a certain extent, it is still unsatisfactory for the restoration of a real object boundary. Therefore, we design a simple but effective boundary enhancement module (BEM) to guide the network focus on boundaries and other error-prone parts. Based on BEM, an attention weighted loss is proposed to boost the network to generate sharper object boundaries. Experimental results on five benchmark datasets demonstrate that the proposed method can achieve state-of-the-art performance on salient object detection. Moreover, we extend the experiments on the remote sensing datasets, and the results further prove the universality and scalability of ALNet. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have revolutionized cancer management and have been widely applied; however, they still have some limitations in terms of efficacy and toxicity. There are multiple treatment regimens in Traditional Chinese Medicine (TCM) that play active roles in combination with Western medicine in the field of oncology treatment. TCM with ICIs works by regulating the tumor microenvironment and modulating gut microbiota. Through multiple targets and multiple means, TCM enhances the efficacy of ICIs, reverses resistance, and effectively prevents and treats ICI-related adverse events based on basic and clinical studies. However, there have been few conclusions on this topic. This review summarizes the development of TCM in cancer treatment, the mechanisms underlying the combination of TCM and ICIs, existing studies, ongoing trials, and prospects for future development. [ABSTRACT FROM AUTHOR]

Based on the longitudinal data of 30 Major League Baseball (MLB) teams over seasons from 2017 to 2020, we used random effect (RE) models to conduct regression analyses on the detailed data of pitchers and fielders. Cultural distance (CD) was measured in terms of Hofstede's cultural indicators and Global Preference Survey (GPS) data. The results showed that salary premiums for foreign MLB players existed and CD was significantly positively correlated with salaries. Further, the risk preference (/altruism) difference between foreign pitchers and American pitchers was significantly positively (/negatively) correlated with the salaries of foreign pitchers. Salary estimation data showed that the salary premium was nearly 20% for players from South Korea and Panama, the lowest (only 0.11%) for players from Australia, and only 6.13% for players from Dominican Republic (accounting for the largest proportion of foreign MLB players), indicating that the MLB's foreign player recruitment policy is correct. [ABSTRACT FROM AUTHOR]

In order to improve the rearing of Coccinella septempunctata L. (Coleoptera: Coccinellidae), nutrients such as shrimp, pollen, honey, and lard were added to the basic artificial diet, and the effects of the artificial diet on biological parameters and digestive enzymes were evaluated. The results show that beetles feeding on the supplemented diet exhibited pupation, emergence, fecundity, and hatching rates that were 102.69%, 125.02%, 162.33%, and 119.90% of those supplied with the basic diet, respectively. The addition of shrimp and pollen to the basal diet improved protease, trypsin, chymotrypsin, and aminopeptidase activity in larvae and female adults. The addition of lard improved lipase activity in female adults, and the addition of honey improved invertase activity in adults of both sexes. This study provides guidance for improving the nutritional benefits of ladybug artificial diets. [ABSTRACT FROM AUTHOR]

In this article, we theoretically designed and simulated a silicon core fiber for the simultaneous detection of temperature and refractive index. We first discussed the parameters of the silicon core fiber for near single-mode operation. Second, we designed and simulated a silicon core-based fiber Bragg grating and applied it for simultaneous sensing of temperature and environmental refractive index. The sensitivities for the temperature and refractive index were 80.5 pm/°C and 208.76 dB/RIU, respectively, within a temperature range of 0 to 50 °C and a refractive index range of 1.0 to 1.4. The proposed fiber sensor head can provide a method with simple structure and high sensitivity for various sensing targets. [ABSTRACT FROM AUTHOR]

Motivation: The PAM50 signature/method is widely used for intrinsic subtyping of breast cancer samples. However, depending on the number and composition of the samples included in a cohort, the method may assign different subtypes to the same sample. This lack of robustness is mainly due to the fact that PAM50 subtracts a reference profile, which is computed using all samples in the cohort, from each sample before classification. In this paper we propose modifications to PAM50 to develop a simple and robust single-sample classifier, called MPAM50, for intrinsic subtyping of breast cancer. Like PAM50, the modified method uses a nearest centroid approach for classification, but the centroids are computed differently, and the distances to the centroids are determined using an alternative method. Additionally, MPAM50 uses unnormalized expression values for classification and does not subtract a reference profile from the samples. In other words, MPAM50 classifies each sample independently, and so avoids the previously mentioned robustness issue. Results: A training set was employed to find the new MPAM50 centroids. MPAM50 was then tested on 19 independent datasets (obtained using various expression profiling technologies) containing 9637 samples. Overall good agreement was observed between the PAM50- and MPAM50-assigned subtypes with a median accuracy of 0.792, which (we show) is comparable with the median concordance between various implementations of PAM50. Additionally, MPAM50- and PAM50-assigned intrinsic subtypes were found to agree comparably with the reported clinical subtypes. Also, survival analyses indicated that MPAM50 preserves the prognostic value of the intrinsic subtypes. These observations demonstrate that MPAM50 can replace PAM50 without loss of performance. On the other hand, MPAM50 was compared with 2 previously published single-sample classifiers, and with 3 alternative modified PAM50 approaches. The results indicated a superior performance by MPAM50. Conclusions: MPAM50 is a robust, simple, and accurate single-sample classifier of intrinsic subtypes of breast cancer. [ABSTRACT FROM AUTHOR]

Heart failure is the final destination of most cardiovascular diseases, and its complex molecular mechanisms remain largely uncertain. This study aimed to systematically investigate the underlying molecular mechanisms and diagnostic and therapeutic targets of heart failure using bioinformatics. We obtained 8 healthy samples and 8 heart failure samples from GSE8331 and GSE76701. After removing the batch effect, we performed a differential analysis on it and obtained 185 differentially expressed ID. The results of enrichment analysis showed that the molecular mechanisms of heart failure were mostly related to immune, inflammation, and metabolism-related pathways. Immune cell infiltration analysis showed that the degree of infiltration of Tgd cells and Neurons was significantly enriched in heart failure samples, whereas pDCs and NKTs were in healthy tissue samples. We obtained Hub genes including EGR1, EGR2, FOS and FOSB by PPI network analysis. We established a 4-gene diagnostic model with Hub gene, and validated it in GSE21610 and GSE57338, and evaluated the discriminative ability of Hub gene by ROC curve. The 4-gene diagnostic model has an AUC value of 0.775 in GSE21610 and 0.877 in GSE57338. In conclusion, we explored the underlying molecular mechanisms of heart failure and the immune cell infiltration environment of failing myocardium by performing bioinformatic analysis of the GEO dataset. In addition, we identified EGR1, EGR2, FOS and FOSB as potential diagnostic biomarkers and therapeutic targets for heart failure. More importantly, a diagnostic model of heart failure based on these 4 genes was developed, which leads to a new understanding of the pathogenesis of heart failure and may be an interesting target for future in-depth research. [ABSTRACT FROM AUTHOR]

This study aimed to develop a drug delivery system with hybrid biodegradable antifungal and antibacterial agents incorporated into poly lactic-co-glycolic acid (PLGA) nanofibers, facilitating an extended release of fluconazole, vancomycin, and ceftazidime to treat polymicrobial osteomyelitis. The nanofibers were assessed using scanning electron microscopy, tensile testing, water contact angle analysis, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. The in vitro release of the antimicrobial agents was assessed using an elution method and a high-performance liquid chromatography assay. The in vivo elution pattern of nanofibrous mats was assessed using a rat femoral model. The experimental results demonstrated that the antimicrobial agent-loaded nanofibers released high levels of fluconazole, vancomycin, and ceftazidime for 30 and 56 days in vitro and in vivo, respectively. Histological assays revealed no notable tissue inflammation. Therefore, hybrid biodegradable PLGA nanofibers with a sustainable release of antifungal and antibacterial agents may be employed for the treatment of polymicrobial osteomyelitis. [ABSTRACT FROM AUTHOR]

Background: Blood neutrophil to lymphocyte ratio (NLR) or lymphocyte count may be important markers for immune function. Previous work has shown higher NLR was associated with higher risk of hepatitis B‐related hepatocellular carcinoma (HCC). However, studies in non‐alcoholic fatty liver disease (NAFLD) patients are lacking. Methods: Utilizing the University of Pittsburgh Medical Center (UPMC) electronic health records, we created a retrospective cohort of 27,834 patients diagnosed with NAFLD from 2004 to 2018 with complete NLR data. After an average 5.5 years of follow‐up, 203 patients developed HCC. Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of HCC incidence associated with different levels of NLR and lymphocyte count. Results: Compared with the lowest tertile of NLR (<1.97), the highest tertile of NLR (≥3.09) was statistically significantly associated with a 43% higher risk of HCC incidence (HR = 1.43, 95% CI: 1.01–2.03, ptrend = 0.031) after adjustment for age, sex, race, body mass index, smoking status, history of type 2 diabetes, hyperlipidemia, hypertension, and fibrosis‐4 score category. Conversely the highest tertile of lymphocyte count (≥2.15 K/ul) was significantly associated with a 36% lower risk of HCC (HR = 0.64, 95% CI: 0.43–0.94, ptrend = 0.028) compared to the lowest tertile (<1.55 K/ul). There was no association between neutrophil count and HCC risk. Conclusions: Higher NLR and lower lymphocyte count are associated with significantly higher risk of HCC among NAFLD patients. These findings warrant further investigation of immune response and surveillance in association with HCC development in NAFLD patients. [ABSTRACT FROM AUTHOR]

[Display omitted] • Electrochemically active Oxygen doped carbon (O-PCNs) was fabricated by superbase templated method. • The template basicity on the functionalities and the supercapacitor performances of the derived O-PCNs were disclosed. • The O-PCN-20 is rich in porosity, large in surface area (930 m2/g) and high in active oxygen content (11.4 atom%). • · The O-PCN-20 electrode exhibits large capacitance of 375 F/g@1.0 A/g and energy density of 25.7 Wh/kg@900 W/kg. Templating techniques have been widely adopted for the synthesis of porous carbons, such as oxygen-doped porous carbon nanosheets (O-PCNs), but the effect of the surface characteristics of templates on the surface functionality and performance of a derived carbon has not been well studied. Herein, a series of laboratory-made superbases of K/Mg(OH) 2 with different K/Mg ratios were employed as template to fabricate nanocarbon materials. The aim is to find out how the strength of template basicity could influence the surface functionalities and the supercapacitor performances of the derived O-PCNs. The resulting materials are rich in conjugated hydroxyl and carbonyl groups that are electrochemically active owing to the protection of the conjugated hydroxyl group by KOH and the dehydrogenation step catalyzed by magnesium oxide. Systematic investigations revealed that with the increase of basic strength, the content of the derived electrochemically active oxygen species in the forms of conjugated carbonyl (C O) and hydroxyl (C OH) first increases from 8.4 atom% to 11.4 atom% then decreases to 9.25 atom%. Moreover, the microporosity of the O-PCNs stepwise increases with the rise of KOH loading, ascribable to the effect of KOH etching on the carbon skeleton. The O-PCN-20 templated by 20 % K/Mg(OH) 2 is rich in porosity, large in surface area (930 m2/g) and high in active oxygen content (11.4 atom%). With high active surface area and extra Faradaic capacitance, O-PCN-20 exhibited superior supercapacitor performances including large specific capacitance of 375 F/g@1.0 A/g, high rate capability of 81.1 % (from 1.0 A/g to 20 A/g), energy density of 25.7 Wh/kg@900 W/kg and excellent cycling stability with near 100 % capacitance retentions after 10 000 cycles and more than 86.2 % capacitance retention over 20 000 cycles at large current density of 10 A/g, indicating O-PCN-20 has potential to be used as electrode material for energy storage devices. [ABSTRACT FROM AUTHOR]

Temperature control is needed in the construction process of massive concrete and it can avoid the concrete cracks. Prediction of temperature development based on a hydration kinetics model can reduce the need for adiabatic temperature rise tests for concrete. However, the existing hydration kinetics model cannot accurately describe the hydration process of cement, thereby limiting the ability to further accurately predict the temperature rise of concrete based on the hydration kinetics model. This paper aims to establish a new hydration kinetics model, which is based on nucleation and growth model, and to predict the temperature development of concrete with set-controlling admixture based on this model. In this paper, the nucleation and growth of hydration products and the diffusion of free water by the modified boundary of nucleation and growth (BNG) model and the modified Fuji and Kondo's model are described. The relationship between nucleation rate and apparent activation energy and the relationship between effective diffusion coefficient and apparent activation energy are linear. However, the relationship between growth rate and apparent activation is exponential. Finally, the temperature development of concrete can be calculated by the hydration degree of the cement. [ABSTRACT FROM AUTHOR]

Craniomaxillofacial bone defects are characterized by an irregular shape, bacterial and inflammatory environment, aesthetic requirements, and the need for the functional recovery of oral–maxillofacial areas. Conventional clinical treatments are currently unable to achieve high-quality craniomaxillofacial bone regeneration. Hydrogels are a class of multifunctional platforms made of polymers cross-linked with high water content, good biocompatibility, and adjustable physicochemical properties for the intelligent delivery of goods. These characteristics make hydrogel systems a bright prospect for clinical applications in craniomaxillofacial bone. In this review, we briefly demonstrate the properties of hydrogel systems that can come into effect in the field of bone regeneration. In addition, we summarize the hydrogel systems that have been developed for craniomaxillofacial bone regeneration in recent years. Finally, we also discuss the prospects in the field of craniomaxillofacial bone tissue engineering; these discussions can serve as an inspiration for future hydrogel design. [ABSTRACT FROM AUTHOR]

Networked control systems (NCSs) are widely used in practical applications because of their flexibility in deployment. However, due to the dependence on the communication network, NCSs could be vulnerable to malicious cyberattacks. To address this problem, a novel blockchain technology-assisted networked predictive secure control approach is presented for the first time in this article. First, the introduction of blockchain technology brings a significant boost to the inherent resilience of the NCS in an active manner without relying on any prior knowledge of the system or potential attacks. However, blockchain technology would induce time delays unfavorable to the NCS, which could result in the low real-time performance of the control system. Subsequently, a networked Kalman filter-based predictive control is specially designed to compensate for the low real-time property of blockchain technology. A detailed analysis of the security and stability of the closed-loop NCS with the developed networked predictive secure controller is also presented, while sufficient conditions for the closed-loop system to be simultaneously stable and safe in a probabilistic sense are given. Finally, to verify the performance of the proposed approach in terms of practicality, an experimental prototype of a photovoltaic (PV)-based power generation system subjected to random cyber-attacks is built for voltage regulation. [ABSTRACT FROM AUTHOR]

Objective: Ankle fractures are often combined with syndesmotic instability, requiring reduction and stabilization. However, the optimal level for syndesmotic screw positioning remains unclear. This study aims to evaluate the effect of different syndesmotic screw insertion levels on postoperative clinical outcomes and determine whether an optimal level exists. Methods: This retrospective study included data from 43 adult patients with acute closed ankle fractures combined with intraoperative evidence of unstable syndesmotic injuries who underwent open reduction internal fixation from January 1, 2017 to March 1, 2018 according to the inclusion and exclusion criteria. All 43 patients were divided into three groups based on the syndesmotic screw placement level: trans‐syndesmotic group: screw level of 2–3 cm; inferior‐syndesmotic group: screw level <2 cm; and supra‐syndesmotic group: screw level >3 cm. Clinical outcomes were measured at the final follow‐up, including the American Orthopedic Foot and Ankle Society (AOFAS) ankle‐hindfoot score, Olerud–Molander Ankle Score (OMAS), short‐form 36‐item questionnaire (SF‐36), visual analogue scale (VAS) score and restrictions in ankle range of motion (ROM). The relationships between screw placement level and clinical outcomes were analyzed with the Kruskal–Wallis H‐test and Spearman correlation analysis. Results: The median follow‐up duration was 15 months (range, 10–22 months). No patients developed fracture nonunion or malunion or experienced hardware failure. The outcome scoring systems showed an overall score for the entire group of 94.91 points for the AOFAS ankle‐hindfoot score, 83.14 for the OMAS, 96.65 for the SF‐36, 1.77 for the VAS, 9.14° for the restrictions in dorsiflexion, and 1.30° for the restrictions in plantarflexion. There were no significant differences among three groups in clinical outcomes (P > 0.05). Neither the AOFAS score nor OMAS had significant correlations with screw insertion level (P = 0.825 and P = 0.585, respectively). No postoperative arthritis or widening of the tibiofibular space was observed at the final follow‐up. Conclusion: Different syndesmotic screw placement levels appear not to affect the clinical outcomes of ankle fractures with syndesmotic instability. No optimal level was observed in this study. Our findings suggest other clinically acceptable options apart from syndesmotic screw placement 2–3 cm above the ankle. [ABSTRACT FROM AUTHOR]

We introduce a novel patterning technique based on e-beam lithography using vertically aligned carbon nanotube (VACNT) emitters with self-assembled monolayers (SAMs). A 20 μm line width of silicon wafer patterning was successfully demonstrated using octadecyl trichlorosilane (OTS) as a photoresist. To investigate surface modification by the irradiated electrons from the emitters, both contact angle measurement and energy dispersive X-ray (EDX) analysis were conducted. The patterning mechanism of the electron beam irradiated on OTS-coated substrate by our cold cathode electron beam (C-beam) was demonstrated by the analyzed results. The effect of current density and exposure time on the OTS patterning was studied and optimized for the Si wafer patterning in terms of the electronic properties of the VACNTs. The authors expect the new technique to contribute to the diverse applications to microelectromechanical (MEMS) technologies owing to the advantages of facile operation and precise dose control capability based on field electron emission current from the VACNT emitter arrays. [ABSTRACT FROM AUTHOR]

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) exploit the concept of synthetic lethality and offer great promise in the treatment of tumors with deficiencies in homologous recombination (HR) repair. PARPi exert antitumor activity by blocking Poly(ADP-ribosyl)ation (PARylation) and trapping PARP1 on damaged DNA. To date, the U.S. Food and Drug Administration (FDA) has approved four PARPi for the treatment of several cancer types including ovarian, breast, pancreatic and prostate cancer. Although patients with HR-deficient tumors benefit from PARPi, majority of tumors ultimately develop acquired resistance to PARPi. Furthermore, even though BRCA1/2 mutations are commonly used as markers of PARPi sensitivity in current clinical practice, not all patients with BRCA1/2 mutations have PARPi-sensitive disease. Thus, there is an urgent need to elucidate the molecular mechanisms of PARPi resistance to support the development of rational effective treatment strategies aimed at overcoming resistance to PARPi, as well as reliable biomarkers to accurately identify patients who will most likely benefit from treatment with PARPi, either as monotherapy or in combination with other agents, so called marker-guided effective therapy (Mget). In this review, we summarize the molecular mechanisms driving the efficacy of and resistance to PARPi as well as emerging therapeutic strategies to overcome PARPi resistance. We also highlight the identification of potential markers to predict PARPi resistance and guide promising PARPi-based combination strategies. [ABSTRACT FROM AUTHOR]

The normalized least mean M-estimate (NLMM) algorithm exhibits good robustness in impulsive noises, but it suffers from the trade-off between convergence rate and steady-state misadjustment. In response to this problem, this paper proposes a switching step-sizes NLMM (SSS-NLMM) algorithm, which selects the optimal step-size at each iteration by comparing the mean square deviation (MSD) values of the algorithm with different step-sizes. Furthermore, to improve the convergence of the algorithm in the transition stage, we embed a feedback mechanism on the minimum MSD. Simulations in various environments have verified that the proposed SSS-NLMM algorithm has better performance than its counterparts in terms of convergence rate and steady-state misadjustment. [ABSTRACT FROM AUTHOR]

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) exploit the concept of synthetic lethality and offer great promise in the treatment of tumors with deficiencies in homologous recombination (HR) repair. PARPi exert antitumor activity by blocking Poly(ADP-ribosyl)ation (PARylation) and trapping PARP1 on damaged DNA. To date, the U.S. Food and Drug Administration (FDA) has approved four PARPi for the treatment of several cancer types including ovarian, breast, pancreatic and prostate cancer. Although patients with HR-deficient tumors benefit from PARPi, majority of tumors ultimately develop acquired resistance to PARPi. Furthermore, even though BRCA1/2 mutations are commonly used as markers of PARPi sensitivity in current clinical practice, not all patients with BRCA1/2 mutations have PARPi-sensitive disease. Thus, there is an urgent need to elucidate the molecular mechanisms of PARPi resistance to support the development of rational effective treatment strategies aimed at overcoming resistance to PARPi, as well as reliable biomarkers to accurately identify patients who will most likely benefit from treatment with PARPi, either as monotherapy or in combination with other agents, so called marker-guided effective therapy (Mget). In this review, we summarize the molecular mechanisms driving the efficacy of and resistance to PARPi as well as emerging therapeutic strategies to overcome PARPi resistance. We also highlight the identification of potential markers to predict PARPi resistance and guide promising PARPi-based combination strategies. [ABSTRACT FROM AUTHOR]

Comparison and classification of ball trajectories can provide insight to support coaches and players in analysing their plays or opposition plays. This is challenging due to the innate variability and uncertainty of ball trajectories in space and time. We propose a framework based on Dynamic Time Warping (DTW) to cluster, compare and characterise trajectories in relation to play outcomes. Seventy-two international women's basketball games were analysed, where features such as ball trajectory, possession time and possession outcome were recorded. DTW was used to quantify the alignment-adjusted distance between three dimensional (two spatial, one temporal) trajectories. This distance, along with final location for the play (usually the shot), was then used to cluster trajectories. These clusters supported the conventional wisdom of higher scoring rates for fast breaks, but also identified other contextual factors affecting scoring rate, including bias towards one side of the court. In addition, some high scoring rate clusters were associated with greater mean change in the direction of ball movement, supporting the notion of entropy affecting effectiveness. Coaches and other end users could use such a framework to help make better use of their time by honing in on groups of effective or problematic plays for manual video analysis, for both their team and when scouting opponent teams and suggests new predictors for machine learning to analyse and predict trajectory-based sports. [ABSTRACT FROM AUTHOR]

An automatic colorization algorithm can convert a grayscale image to a colorful image using regression loss functions or classification loss functions. However, the regression loss function leads to brown results, while the classification loss function leads to the problem of color overflow and the computation of the color categories and balance weights of the ground truth required for the weighted classification loss is too large. In this paper, we propose a new method to compute color categories and balance the weights of color images. In this paper, we propose a new method to compute color categories and balance weights of color images. Furthermore, we propose a U-Net-based colorization network. First, we propose a category conversion module and a category balance module to obtain the color categories and to balance weights, which dramatically reduces the training time. Second, we construct a classification subnetwork to constrain the colorization network with category loss, which improves the colorization accuracy and saturation. Finally, we introduce an asymmetric feature fusion (AFF) module to fuse the multiscale features, which effectively prevents color overflow and improves the colorization effect. The experiments show that our colorization network has peak signal-to-noise ratio (PSNR) and structure similarity index measure (SSIM) metrics of 25.8803 and 0.9368, respectively, for the ImageNet dataset. As compared with existing algorithms, our algorithm produces colorful images with vivid colors, no significant color overflow, and higher saturation. [ABSTRACT FROM AUTHOR]

Gout is a common metabolic disease caused by abnormal purine metabolism that promotes the formation and deposition of monosodium urate crystals within joints that causes acute arthritis and can seriously affect the daily life of patients. Pistacia chinensis is one of the traditional medicinal plants of the Anacardiaceae family, and there have been many studies on its biological activity, including anti-inflammatory, antidepressant, antibacterial, antioxidant, and hypoglycemic activities. The aim of this study was to evaluate the antigout effect of P. chinensis leaf essential oil and its constituents through xanthine oxidase inhibition. Leaf essential oil showed good xanthine oxidase inhibitory activity for both substrates, hypoxanthine and xanthine. Six fractions were obtained from open column chromatography, and fraction E1 exhibited the best activity. The constituents of leaf essential oil and fraction E1 were analyzed by GC-MS. The main constituents of both leaf essential oil and fraction E1 were limonene and 3-carene; limonene showed a higher inhibitory effect on xanthine oxidase. Based on the enzyme kinetic investigation, limonene was the mixed-type inhibitor against xanthine oxidase. The results revealed that Pistacia chinensis leaf essential oil and limonene have the potential to act as natural remedies for the treatment of gout. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study investigates the dynamic pattern of learners' evaluation of their learning experiences on the MOOC platform at different stages. Data include 364 evaluative comments from the large MOOC in Consecutive Interpreting for a period of 15 weeks. The results of MANOVA test suggest that MOOC learners left significantly more comments on four areas at the later stage compared with those at the early stage: learning resources, learning community, learning opportunity, and student voice. It suggests that MOOC learners at a later stage are looking for a learning environment which supports self-assessment, peer feedback, and coaching to fulfil their personal needs and expectations. Moreover, qualitative thematic analysis suggests that learning resources addresses three areas: the design of the tasks, helpfulness, and diversity of the resources. Learning community largely refers to peer-feedback, co-instructions of peers, and instructors. Learning opportunities refers to the tasks which improve professional knowledge, self-regulated learning strategies, and language proficiency. Last, student voice indicates three types of tensions: the need for pre-existing knowledge to study MOOCs, learners' diversified personal goals and teaching objectives of MOOCs, preferred learning strategies between MOOC designers and learners. [ABSTRACT FROM AUTHOR]

Gravel packing is one of the main sand control methods for deep‐water high‐temperature and high‐pressure (HT/HP) reservoirs. According to the specific characteristics of deep‐water HT/HP and multichannel, considering the influence of slurry flowing through long‐distance multichannel and the slurry temperature alternation along the flow path, based on α–β wave packing theory, a coupling model of gravel packing in deep‐water HT/HP horizontal wells is established. The packing simulation algorithm and calculation process are designed to realize the gravel packing temperature pressure simulation and multistage refined friction calculation of deep‐water HT/HP horizontal wells. The influence of each packing parameter on the packing process is fully studied. Furthermore, the application simulation of the A10H well of the South China Sea deepwater HP well is carried out. The simulation results show that in the slurry injection stage and α wave packing stage, the packing pressure is low and the residual pressure window is large. In the β wave packing stage, the packing pressure increases rapidly, the residual pressure window shrinks rapidly, and finally, at the end of β wave packing, the residual pressure window becomes narrow. The viscosity of carrier fluid has a significant impact on the pressure window of packing operation. For the design pump rate of 5.6 bpm, the packing cannot be completed with 5.0 cp viscosity carrier fluid. For the carrier fluid with high viscosity, the multi‐β wave packing technique of pump reduction control pressure at the end of the β wave packing stage is used, and this process is simulated in this paper. Considering three constraints: not sand packed in the drilling string, without premature bridging in the α wave packing stage, and α and β wave packing pressure control conditions, the safe range of pump rate is determined under different operation safety margin conditions, which can provide technical support for on‐site operation. [ABSTRACT FROM AUTHOR]

In this paper, the random matrix big data analysis model is thoroughly studied and constructed, the ecological model of college students' innovation and entrepreneurship education is analyzed, and the optimization model of college students' Innovation and entrepreneurship education environmental model based on the random matrix big data analysis model is designed. This paper briefly explains the random matrix and its M-P rate theory deduces the idea of feature extraction by the difference of eigenvalue limit spectrum distribution between different nonrandom matrices and random matrices, gives the data matrix representation method of FEMPL and the specific feature composition basis, and describes the steps of FEMPL feature extraction. A performance model for predicting the running time of Hadoop jobs is constructed using a random matrix. In this paper, innovation and entrepreneurship education has been carried out gradually, and the innovation and entrepreneurship education curriculum, platform, and mechanism have been progressively established. However, there is still a gap between the proper level of innovation and entrepreneurship education development. This study takes education ecology as the research perspective, analyzes the ecosystem of typical schools of innovation and entrepreneurship education, summarizes the dimensions and parameters of the invention and entrepreneurship education ecosystem, constructs an ecological model of innovation and entrepreneurship education for college students, and analyzes the problems and causes of the current innovation and entrepreneurship education ecology for college students based on the model, to propose specific strategies to promote the ecological development of innovation and entrepreneurship education for college students. [ABSTRACT FROM AUTHOR]

Objective. To investigate the ultrasound characteristics and clinical efficacy of coronary arteries before and after immune blocking therapy with gamma globulin in children with Kawasaki disease. Methods. A total of 64 children with Kawasaki disease who were treated in our hospital from January 2018 to October 2021 were selected. All the children were given immune blocking therapy with gamma globulin on the basis of conventional treatment. The disappearance time of related symptoms and signs (fever, mucosal congestion, cervical lymphadenopathy, and swelling of the hands and feet) in children were counted. The white blood cell count (WBC), platelet count (PLT), C-reactive protein (CRP), and procalcitonin (PCT) levels of the children before and after treatment were compared, and the characteristics of coronary echocardiography before and after treatment were observed for analysis and discussion, to carefully observe whether the coronary artery involvement of the children was improved. Results. The inner diameter of the left and right coronary arteries significantly decreased (P < 0.05), and the levels of leukocytes, platelets, CRP, erythrocyte sedimentation rate, vascular endothelial growth factor (VEGF), and endostatin were significantly decreased compared with those before treatment, with a statistical difference (P < 0.05). Conclusion. The effect of gamma globulin in the treatment of Kawasaki disease is remarkable, which can improve the blood indexes, VEGF, and endostatin levels in children, significantly reduce coronary dilatation, and reduce the incidence of coronary artery disease. Echocardiography is of high value in the examination of children with Kawasaki disease, which can accurately detect the size, location, and inner diameter of coronary artery lesions, and can effectively evaluate the treatment effect on children. [ABSTRACT FROM AUTHOR]

Highly accurate measurements of infrared systems cannot be achieved without precise radiometric calibrations. In order to correctly interpret and process infrared images and monitor the performance of infrared cameras, their radiometric calibration is also required periodically. In this paper, an equivalent calibration method is proposed based on an internal blackbody baffle. It is used for the replacement of a large surface-source blackbody covering the aperture for the field calibration of large-aperture equipment. Subsequently, the expressions of the equivalent calibration conversion function (ECCF) are derived based on the grayscale response of the camera and the calibration models of the two methods, and experimental measurements and fits are performed using a cooled mid-wave infrared camera. The results show that the measured functional form is consistent with the physical meaning. Moreover, in the target imaging experiments, the results of the inversion using the equivalent calibration conversion function and the results of the direct calibration of the external blackbody are largely consistent with the average error of 0.198% between the two, and the maximum error is within 1%. The maximum error between the inversion result of radiation brightness and the actual value of the target is 6.29%, and the accuracy fully meets the radiometric measurement requirements. [ABSTRACT FROM AUTHOR]

• Multilayer structure design strategy is proposed to produce electricity/light-heat-hygro multi-responsive luminescent systems. • Residual-free and reversible electricity, light and water stimuli enable rewritable information display. • Programable information display is demonstrated by sequential modulation of different environmental stimuli. Rewritable luminescent materials are attracting widespread attention for information storage and display as they can help to reduce environmental wastes caused by the abuse of single-use and transient systems. Nevertheless, since most reported systems are chemical-stimuli-responsive and single-stimuli-responsive, it remains challenging to achieve the rewritable and programmable display of multiple information in one single system, which is essential to enhance information richness and display intelligence. In this work, an ideal kind of multi-responsive soft luminescent display systems are reported, which consist of heat/humidity-responsive fluorescence-phosphorescence dual-emission film and stacked graphene assembly (SGA) film by using thin poly (dimethyl siloxane) (PDMS) as middle connecting layer. In such multilayer structure, the heat generated by electricity connection or light illumination of bottom SGA film can be instantly transferred across the middle PDMS layer to cause heat-triggered red-to-blue emission color change, or to evaporate water for blue-to-red emission color recovery. Owing to the "residual-free" nature of these electricity, light and water stimuli, multi-responsive rewritability is guaranteed to enable the reversible writing and complete erasure of various letter/pattern information. On this basis, robust electricity/light-heat-hygro multi-responsive soft luminescent display systems are demonstrated, in which diverse letter/pattern information could be facilely programmed to be successively displayed and then completely reset to enable another data writing/erasing cycle by sequential modulation of different environmental stimuli. This study brings programmable merit for rewritable luminescent display systems and is expected to inspire more intelligent ones. [ABSTRACT FROM AUTHOR]

While raw images possess distinct advantages over sRGB images, e.g., linearity and fine-grained quantization levels, they are not widely adopted by general users due to their substantial storage requirements. Very recent studies propose to compress raw images by designing sampling masks within the pixel space of the raw image. However, these approaches often leave space for pursuing more effective image representations and compact metadata. In this work, we propose a novel framework that learns a compact representation in the latent space, serving as metadata, in an end-to-end manner. Compared with lossy image compression, we analyze the intrinsic difference of the raw image reconstruction task caused by rich information from the sRGB image. Based on the analysis, a novel design of the backbone with asymmetric and hybrid spatial feature resolutions is proposed, which significantly improves the rate-distortion performance. Besides, we propose a novel design of the sRGB-guided context model, which can better predict the order masks of encoding/decoding based on both the sRGB image and the the masks of already processed features. Benefited from the better modeling of the correlation between order masks, the already processed information can be better utilized. Moreover, a novel sRGB-guided adaptive quantization precision strategy, which dynamically assigns varying levels of quantization precision to different regions, further enhances the representation ability of the model. Finally, based on the iterative properties of the proposed context model, we propose a novel strategy to achieve variable bit rates using a single model. This strategy allows for the continuous convergence of a wide range of bit rates. We demonstrate how our raw image compression scheme effectively allocates more bits to image regions that hold greater global importance. Extensive experimental results validate the superior performance of the proposed method, achieving high-quality raw image reconstruction with a smaller metadata size, compared with existing SOTA methods. [ABSTRACT FROM AUTHOR]

Achilles tendon rupture is a severe injury, and its optimal therapy remains controversial. Tissue engineering scaffolds play a significant role in tendon healing and tissue regeneration. In this study, we developed tri-layered doxycycline/collagen/bupivacaine (DCB)-composite nanofibrous scaffolds to repair injured Achilles tendons. Doxycycline, collagen, and bupivacaine were integrated into poly(lactic-co-glycolic acid) (PLGA) nanofibrous membranes, layer by layer, using an electrospinning technique as healing promoters, a 3D scaffold, and painkillers, respectively. After spinning, the properties of the nanofibrous scaffolds were characterized. In vitro drug discharge behavior was also evaluated. Furthermore, the effectiveness of the DCB–PLGA-composite nanofibers in repairing ruptured Achilles tendons was investigated in an animal tendon model with histological analyses. The experimental results show that, compared to the pristine PLGA nanofibers, the biomolecule-loaded nanofibers exhibited smaller fiber size distribution and an enhanced hydrophilicity. The DCB-composite nanofibers provided a sustained release of doxycycline and bupivacaine for over 28 days in vivo. Additionally, Achilles tendons repaired using DCB-composite nanofibers exhibited a significantly higher maximum load-to-failure than normal tendons, suggesting that the biomolecule-incorporated nanofibers are promising scaffolds for repairing Achilles tendons. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) degradation by autophagy (ER-phagy) is a recently revealed selective autophagy pathway that plays important roles in organelle turnover and protein degradation, but the biological functions of ER-phagy are largely unknown. Here, we present an ER-targeting Re(I) tricarbonyl complex (Re-ERLAD) that can accumulate in the ER, induce ER-to-lysosome-associated degradation (ERLAD) upon visible light irradiation, and label ER buds and track their morphological alterations during ER-phagy. The emission of Re-ERLAD is sensitive to viscosity, which is a key parameter reflecting the amount of unfolded protein in the ER. Quantitative detection using two-photon fluorescence lifetime imaging microscopy shows that ER viscosity initially increases and then decreases during ERLAD, which reveals that ERLAD is a pathway for alleviating ER stress caused by unfolded proteins. In conclusion, our work presents the first specific photoinducer and tracker of ERLAD, which can be used in studying the regulatory mechanism and function of this process. [ABSTRACT FROM AUTHOR]

Motivation: The precise diagnosis of the major subtypes, lung adenocarcinoma and lung squamous cell carcinoma, of non-small-cell lung cancer is of practical importance as some treatments are subtype-specific. However, in some cases diagnosis via the commonly-used method, that is staining the specimen using immunohistochemical markers, may be challenging. Hence, having a computational method that complements the diagnosis is desirable. In this paper, we propose a gene signature for this purpose. Results: We developed an expression-based method that systematically suggests a huge set of candidate gene signatures and finds the best candidate. By applying this method to a training set, the optimal gene signature was found by considering close to 765 billion candidate signatures. The 8-gene signature found for classifying the 2 aforementioned subtypes comprises TP63, CALML3, KRT5, PKP1, TESC, SPINK1, C9orf152, and KRT7. The signature achieved a high overall prediction accuracy of 0.936 when tested using 34 independent gene expression datasets obtained using different technologies and comprising 2556 adenocarcinoma and 1630 squamous cell carcinoma samples. Additionally, the signature performed well in clinically challenging cases, that is poorly differentiated tumors and specimens obtained from biopsies. In comparison with 2 previously reported signatures, our signature performed better in terms of overall accuracy and especially accuracy of classifying lung squamous cell carcinoma. Conclusions: Our signature is easy to use and accurate regardless of the technology used to obtain the gene expression profiles. It performs well even in clinically challenging cases and thus can assist pathologists in diagnosis of the ambiguous cases. [ABSTRACT FROM AUTHOR]

Background. CYP26A1 has been reported in multiple cancers. However, the role of CYP26A1 in pancreatic cancer (PC) has not been explored. Method. The public data used for this study was obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Cancer Cell Line Encyclopedia (CCLE) cell lines. CCK8, colony formation, and EdU assay were used to assess the proliferation ability of cancer cells. Transwell and wound healing assays were used to evaluate the invasion and migration ability of cancer cells. qRT-PCR and western blot assays were used to analyze the RNA and protein level of genes. Survival package was used for prognosis analysis. Gene Set Enrichment Analysis (GSEA) was used to identify biological pathway differences between two groups. ssGSEA analysis was used to quantify the immune microenvironment in PC tissue. GDSC and TIDE analyses were used for sensitivity analysis of chemotherapy and immunotherapy. Results. Our results showed that CYP26A1 was overexpressed in PC tissue and cell lines. Meanwhile, metastatic PC cell lines tend to have a higher CYP26A1 level compared with the primary PC cell lines based on CCLE data. Moreover, CYP26A1 was associated with worse clinical features. Also, we found that CYP26A1 had a satisfactory efficiency in predicting overall survival, disease-specific survival, and progression-free interval of PC patients, independent of other clinical features. In vitro experiments indicated that CYP26A1 could significantly facilitate the proliferation, invasion, and migration ability of PC cells. GSEA showed that the pathways of angiogenesis, E2F target, MYC target, mTORC signaling, G2M checkpoint, and epithelial-mesenchymal transition were activated in high CYP26A1 patients. Immune infiltration analysis showed that CYP26A1 was positively correlated with macrophages, Th1 cells, and Treg cells, but negatively correlated with Th17 cells. TIDE analysis showed that non_responder patients had a higher CYP26A1 level compared with predicted responder patients of immunotherapy. Drug sensitivity analysis and assay showed that CYP26A1 could increase the chemotherapy sensitivity of gemcitabine. Conclusions. In summary, CYP26A1 promotes PC progression and is a novel biomarker of PC, with potential for clinical application. [ABSTRACT FROM AUTHOR]