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Purpose: This study aimed to analyse the correlation between blood glucose control and the severity of COVID-19 infection in patients with diabetes. Methods: Clinical and imaging data of a total of 146 patients with diabetes combined with COVID-19 who visited our hospital between December 2022 and January 2023 were retrospectively collected. The patients were divided into the 'good blood glucose control' group and the 'poor blood glucose control' group based on an assessment of their blood glucose control. The clinical data, computed tomography (CT) appearance and score and the severity of COVID-19 infection of the two groups were compared, with the severity of COVID-19 infection being the dependent variable to analyse other influencing factors. Results: The group with poor blood glucose control showed a higher lobar involvement degree and total CT severity score (CTSS) than the group with good blood glucose control (13.30 ± 5.25 vs. 10.38 ± 4.84, p < 0.05). The two groups exhibited no statistically significant differences in blood lymphocyte, leukocyte, C-reaction protein, pleural effusion, consolidation, ground glass opacity or crazy-paving signs. Logistic regression analysis showed that the total CTSS significantly influences the clinical severity of patients (odds ratio 1.585, p < 0.05), whereas fasting plasma glucose and blood glucose control are not independent factors influencing clinical severity (both p > 0.05). The area under the curve (AUC) of CTSS prediction of critical COVID-19 was 0.895 with sensitivity of 79.3% and specificity of 88.1% when the threshold value is 12. Conclusion: Blood glucose control is significantly correlated with the CTSS; the higher the blood glucose is, the more severe the lung manifestation. The CTSS can also be used to evaluate and predict the clinical severity of COVID-19. [ABSTRACT FROM AUTHOR]

The cultivation of critical thinking with the assistance of Information Communication Technology (ICT) tools has drawn much attention from researchers and practitioners in the field of Teaching English to Speakers of Other Languages (TESOL). With the purpose of exploring whether the application could help improve students' critical thinking and ESOL (English for Speakers of Other Languages) skills and how ICT tools are applied in TESOL to cultivate critical thinking, a systematic review was conducted and a total of 22 eligible studies were analyzed. The results show that: (1) students' critical thinking and ESOL skills have demonstrated improvement in the studies applying ICT tools to TESOL; (2) the ICT application is unbalanced across different ESOL skills and various types of ICT tools have been used in different ways to promote students' critical thinking. [ABSTRACT FROM AUTHOR]

Understanding selectivity-dependent molecular mechanism of inhibitors towards CDK2 over CDK6 is prominent for improving drug design towards the CDK family. Multiple short molecular dynamics (MD) simulations combined with MM-GBSA approach are adopted to investigate molecular mechanism on binding selectivity of inhibitors X64, X3A, and 4 AU to CDK2 and CDK6. The RMSF analysis and calculations of molecular surface areas indicate that local structural and global flexibility of CDK6 are stronger than that of CDK2. Based on dynamics cross-correlation maps (DCCMs), motion modes of CDK2 and CDK6 produce difference due to associations of X64, X3A, and 4 AU. The calculated binding free energies (BFEs) demonstrate that the compensation between binding enthalpy and entropy of X64, X34, and 4 AU is a key force driving selectivity of inhibitors towards CDK2 over CDK6. This work provides valuable information for designing highly selective inhibitors towards CDK2 and CDK6 and further promotes identification of efficient anticancer drugs in the future. [ABSTRACT FROM AUTHOR]

This study aimed to overcome the difficulty of conducting the horizontal-well cavity leaching test in the field and to investigate the long-term stability of the horizontal-well salt-cavity natural gas storage. The simulation test design is combined with the similarity theory to study the cavity expansion characteristics and the influence law of cavity leaching parameters. Through the design of a rubber hose connection, an integrated closed test system for multi-stage horizontal-well cavity leaching and brine drainage was built. The test system also realises the repeatable backward movement of the injection well during the test. A similarity simulation of the test design was carried out, and the test platform was constructed to carry out multi-stage horizontal-well leaching tests with a nitrogen cushion. In the horizontal-well leaching tests with a nitrogen cushion, the influence laws of the well spacing, flow rate and liquid level position on cavity expansion were investigated. Based on the morphological characteristics of the horizontal-well cavity, a numerical model of the horizontal-well salt cavity was developed, which reflects the real cavity morphology leached in the test. The long-term stability of the horizontal-well salt-cavity natural gas storage under different internal pressures was investigated through numerical simulation. [ABSTRACT FROM AUTHOR]

Background: With the continuous discovery of new borderline thyroid lesions and benign and malignant "gray areas", coupled with the limitations of traditional immune indicators, the differential diagnosis of papillary thyroid carcinoma (PTC) has become more difficult. Cyclin D1 and P21 are cell cycle regulators involved in the occurrence and metastasis of multiple tumors, including PTC, but their specific functions are unclear. Methods: In our study, immunohistochemical staining was used to explore the expression of Cyclin D1 and P21 in PTC, paracancerous tissue, follicular adenoma (FA) and papillary thyroid hyperplasia. In addition, their relationship with the clinicopathological features of PTC and their differential diagnostic value in distinguishing between intralymph node PTC metastases and intralymph node ectopic thyroid tissue were studied. Results: Among 200 primary PTC lesions, Cyclin D1 and P21 were found to be expressed in 186 (93.00%) and 177 (88.50%), respectively, and their expression levels were significantly higher in PTC tissue than in adjacent tissue, FA tissue and papillary thyroid hyperplasia tissue (P < 0.05). The expression levels of Cyclin D1 and P21 were positively correlated with tumor size and lymph node metastasis (P < 0.05) but not with sex, age, number of tumor lesions, histological subtype, chronic lymphocytic thyroiditis or TNM stage (P < 0.05). The expression levels of Cyclin D1 and P21 were significantly correlated (P < 0.05). The positivity rates of Cyclin D1 and P21 in intralymph node PTC metastases were 97.96% (48/49) and 89.80% (44/49), respectively, which were significantly higher than those in intralymph node ectopic thyroid tissue (P < 0.05). The sensitivity (Se) and negative predictive value (NPV) of Cyclin D1 and P21 detection alone or in combination were higher than those of the combined detection of the classical antibody markers CK19, HBME-1 and Galectin-3. Besides, the Se, Sp, PPV and NPV of Cyclin D1 and P21 in differentiating intralymph node PTC metastases and intralymph node ectopic thyroid tissue were higher. Conclusions: The results of our study show that Cyclin D1 and P21 are highly sensitive and specific markers for the diagnosis of PTC that are superior to traditional classical antibodies. And, these two markers are of great value in the differential diagnosis of intralymph node PTC metastases and intralymph node ectopic thyroid tissue. [ABSTRACT FROM AUTHOR]

This study explores strategies for long‐term reservoir simulations by combining generic rule‐based reservoir management model (RMM) and machine learning (ML) models for two major multipurpose reservoirs — Allatoona Lake and Lake Sidney Lanier in the southeastern United States. First, a standalone RMM is developed to simulate daily release and storage during Water Year 1981–2015. Next, using Long‐Short Term Memory (LSTM) as the ML technique, a standalone LSTM model is trained based on reservoir inflow and meteorological observations to simulate reservoir release and estimate reservoir storage through water balance calculation. Three hybrid modeling strategies are developed, one using RMM output as an additional LSTM input (H1), another using LSTM as the initial release estimate in RMM (H2), and the third combining the first two strategies (H3). The Nash–Sutcliffe efficiency (NSE) for release (NSE‐r), storage (NSE‐s), and their mean (NSE‐avg) are used for model evaluation. Overall, H1 improves NSE‐r to 0.65 and 0.54 for Allatoona and Lanier, respectively, compared to standalone RMM (0.44 and 0.21); however, its storage trajectory did not produce a physically feasible solution, similar to LSTM. H2 and especially H3 show that they can retain the best features from RMM and LSTM, with H3 NSE‐avg being 0.695 and 0.55 for Allatoona and Lanier outperforming RMM (0.615 and 0.29). The findings suggest a robust simulation capacity for large‐scale water management in future studies. [ABSTRACT FROM AUTHOR]

A Cox proportional hazard (CoxPH) model is conventionally used to assess exposure–response (E–R), but its performance to uncover the ground truth when only one dose level of data is available has not been systematically evaluated. We established a simulation workflow to generate realistic E–R datasets to assess the performance of the CoxPH model in recovering the E–R ground truth in various scenarios, considering two potential reasons for the confounded E–R relationship. We found that at high doses, when the pharmacological effects are largely saturated, missing important confounders is the major reason for inferring false‐positive E–R relationships. At low doses, when a positive E–R slope is the ground truth, either missing important confounders or mis‐specifying the interactions can lead to inaccurate estimates of the E–R slope. This work constructed a simulation workflow generally applicable to clinical datasets to generate clinically relevant simulations and provide an in‐depth interpretation on the E–R relationships with confounders inferred by the conventional CoxPH model. [ABSTRACT FROM AUTHOR]

A novel composite was fabricated by hybridizing terbium 1,3,5-benzenetricarboxylic MOF (TB-MOF) with Cx[6]. The obtained composite TB-Cx[6] possessed long-term stability and dispersion stability and was used for on-site analysis of the anti-COVID-19 disinfection product Prednis via a combing remote sampling technique. [ABSTRACT FROM AUTHOR]

The reason why music can affect people's emotional experience is that the stimulation can be transmitted to the brain through hearing, such as the thalamus and lenticular nucleus. Music therapy has a positive auxiliary treatment effect on mental health. Therefore, an evaluation model of the auxiliary effect of music therapy on mental health based on artificial intelligence technology is proposed. We construct the constraint index parameters for the evaluation of music therapy's auxiliary effect on mental health, take parent pressure, self-pressure, teacher pressure, and social pressure as the questionnaire object parameters, take class type as the independent variable, carry out an independent sample t-test, and construct an adaptive information extraction model for the evaluation of music therapy's auxiliary effect on mental health. Paired sample t-test is used to analyze whether there is a difference between the experimental group and the control group on the learning stress scale. According to the analysis of the difference between the experimental group and the control group, combined with the difference test analysis of the data of the stress release of music therapy on mental health, the quantitative evaluation of the auxiliary effect of music therapy on mental health is realized through artificial intelligence optimization control. The experimental results show that the accuracy and reliability of this method to analyze the auxiliary effect of music therapy on mental health are high. There are obvious changes in the data of students' self-pressure, and the difference between the average value and standard deviation of the data before and after the course is obvious. From the perspective of the effectiveness of the course, the students in the class who implement the four relaxation experience courses in the course are under the pressure of parents, self-pressure, teacher pressure, and social pressure. There are obvious changes in the five aspects of learning pressure compared with that before the implementation of the course. After the course experience, the pressure value of most students decreases, and the course intervention effect is obvious. [ABSTRACT FROM AUTHOR]

Tumor targeting and effective immunomodulation are of critical significance during tumor treatment by sonodynamic therapy (SDT). Herein, the probiotic engineering of the clinically approved sonosensitizer (hematoporphyrin monomethyl ether (HMME)) is reported onto the probiotic bacterium Bifidobacteria Longum (BiL) for sonosensitive bifidobacterium construction (HMME@BiL cells). Based on the hypoxic tropism feature of the strain, effective tumor‐targeted sonodynamic therapeutics can be achieved both in vitro and in vivo. To improve the immunological responses against tumor during sonodynamics, a recently‐developed stimulator of interferon genes immune agonist SR717 has been employed to improve the anti‐tumor immunity with prominent activities, eradicating both primary and metastatic tumors with high efficiency and satisfied biocompatibility. The present work provides a promising paradigm of microbiotic nanomedicine in a sophisticated sonoimmunotherapeutic strategy against malignant tumors. [ABSTRACT FROM AUTHOR]

Tumor targeting and effective immunomodulation are of critical significance during tumor treatment by sonodynamic therapy (SDT). Herein, the probiotic engineering of the clinically approved sonosensitizer (hematoporphyrin monomethyl ether (HMME)) is reported onto the probiotic bacterium Bifidobacteria Longum (BiL) for sonosensitive bifidobacterium construction (HMME@BiL cells). Based on the hypoxic tropism feature of the strain, effective tumor‐targeted sonodynamic therapeutics can be achieved both in vitro and in vivo. To improve the immunological responses against tumor during sonodynamics, a recently‐developed stimulator of interferon genes immune agonist SR717 has been employed to improve the anti‐tumor immunity with prominent activities, eradicating both primary and metastatic tumors with high efficiency and satisfied biocompatibility. The present work provides a promising paradigm of microbiotic nanomedicine in a sophisticated sonoimmunotherapeutic strategy against malignant tumors. [ABSTRACT FROM AUTHOR]

Anion exchange membranes (AEMs) with excellent antifouling property are essential for treating highly saline organic wastewater through electrodialysis (ED). In this study, we proposed a strategy of surface charge inversion to construct a blocked- nanolayer based on in-suit dopamine (DA) deposition followed by grafting negative-charged 2-acrylamide-2-methylpropanesulfonic acid (AMPS) for promoting the antifouling performance of AEM. It's indicated that the surface hydrophilicity and negative charge density was gradually enhanced with the increase of AMPS grafting density without sacrifices of ion exchange capability, swelling ratio and desalination performance. In the simulated fouling experiments, the optimal AEM-AMPS-105 membrane exhibited excellent antifouling property due to the improved surface hydrophilicity and high electrostatic repulsion against organic matter. It's highlighted that the transmembrane voltage of modified membrane after operating 200 min was reduced from 7.12 V to 4.85 V with a significant decrease of energy consumption by 55.1 % while maintaining a high current efficiency level of 85.5 %. Moreover, the modified membrane performed significantly enhanced salt/contaminant selectivity and high stability in dye wastewater treatment. We anticipated that the construction of charge-blocked nanolayer by surface charge inversion offered a practical method for improving the organic fouling-resistance of AEMs. [Display omitted] • An anion exchange membrane with a negative-charged blocking nanolayer was developed by surface charge inversion. • Surface hydrophilicity and negative charge density was gradually improved with the increase of AMPS grafting density. • The constructed AMPS nanolayer contributed to formationing the hydration layer and enhancing the electrostatic exclusion effect. • Modified AEM exhibited excellent antifouling ability and stability. [ABSTRACT FROM AUTHOR]

The impact of various exercise modalities on the improvement of sleep quality in adults remains controversial. This study aimed to perform a network meta-analysis to analyze the effects of different exercise interventions on sleep quality in adults. The PubMed, Cochrane, Embase, Web of Science, and EBSCO databases were searched for studies published from March 18, 1993, to March 18, 2023. The Cochrane risk of bias tool was used to assess the quality of the included studies. Then, a random-effects network meta-analysis was conducted within a frequentist framework. A total of 2142 participants from 27 randomized controlled trials were included in the analysis. Exercise modalities such as Pilates, yoga, and traditional Chinese exercises were found to significantly improve sleep quality when compared to a no-exercise control group, with Pilates exhibiting the most potent effect at a 95.3% improvement level. This study demonstrates that exercise interventions are effective in enhancing sleep quality in adults. Adapting exercise to individual preferences and needs may maximize the sleep-related benefits of the activity. The review was registered with PROSPERO, registration number CRD42023434565. • Exercise interventions have significant effects on sleep quality in adults: network meta-analysis. • Pilates, yoga, and traditional Chinese sports outperform the no-exercise group: 27 randomized controlled trials. • Pilates resulted in the largest improvements in sleep quality scores. • The benefits of exercise interventions can be maximized by adapting them to individual preferences and needs. [ABSTRACT FROM AUTHOR]

Polytetrafluoroethylene (PTFE) hollow fiber membrane holds tremendous potential for the treatment of complex wastewater due to its outstanding chemical and thermal stability. However, its treatment efficiency is often hindered by the low water permeate flux arising from the inherent hydrophobicity of PTFE. Here, we present a gentle and convenient hydrophilic modification method that involves immersion in a nonionic surfactant aqueous solution, followed by dopamine self-polymerization. The nonionic surfactant facilitated the penetration of the dopamine solution into the membrane, where dopamine self-polymerized to form a hydrophilic layer on the surface and inner pores of the membrane. The hydrophilicity-modified PTFE hollow fiber membranes demonstrated an impressive increase in water permeate flux, reaching 10231.4 L m−2 h−1, nearly ten times that of the original membrane. Even after prolonged exposure to a strong acid solution (pH = 1) or an oxidant solution (1000 mg L−1 NaClO) for two weeks, this membrane still maintained its favorable water permeability. Furthermore, the modified PTFE membranes also exhibited remarkable resistance to fouling by humic acid. These results showcased a straightforward method for designing a hydrophilic layer on PTFE hollow fiber membranes, underscoring their significant potential for real wastewater treatment applications. [Display omitted] • Mild and convenient method for hydrophilic modification of PTFE membranes. • Overall hydrophilic modification on the surface and within pores. • Maintaining excellent water permeability under acidic and oxidizing conditions. • Improved resistance to humic acid (HA) and high flux for tap water. [ABSTRACT FROM AUTHOR]

[Display omitted] The favorable benefit–risk profile of polatuzumab vedotin, as demonstrated in a pivotal Phase Ib/II randomized study (GO29365; NCT02257567), coupled with the need for effective therapies in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), prompted the need to accelerate polatuzumab vedotin development. An integrated, fit-for-purpose clinical pharmacology package was designed to support regulatory approval. To address key clinical pharmacology questions without dedicated clinical pharmacology studies, we leveraged non-clinical and clinical data for polatuzumab vedotin, published clinical data for brentuximab vedotin, a similar antibody–drug conjugate, and physiologically based pharmacokinetic and population pharmacokinetic modeling approaches. We review strategies and model-informed outcomes that contributed to regulatory approval of polatuzumab vedotin plus bendamustine and rituximab in R/R DLBCL. These strategies made polatuzumab vedotin available to patients earlier than previously possible; depending on the strength of available data and the regulatory/competitive environment, they may also prove useful in accelerating the development of other agents. [ABSTRACT FROM AUTHOR]

Background. Hepatocellular carcinoma (HCC) is highly aggressive with a poor prognosis and survival rate. Certain ANGPTL members have been implicated in tumor progression. However, the relevance of the ANGPTL gene family to HCC remains poorly understood. In this study, we explored the role of ANGPTLs in the prognosis of HCC. Methods. From the CCLE database, we studied the expression of ANGPTLs in a range of cancer cell lines. The UCSC, HCCDB, and Human Protein Atlas databases were used to analyze the differences in mRNA and protein expression of ANGPTLs in HCC tissues. Additionally, the correlation between ANGPTL mRNA and methylation levels and clinicopathological features were assessed in the TCGA database. The correlation between ANGPTL mRNA and overall survival was determined by the Kaplan-Meier plotter. cBioPortal database was used to analyze ANGPTL genomic alterations. Genes associated with ANGPTLs were determined by enrichment with KEGG. Moreover, the differentially expressed genes of ANGPTLs were analyzed by the LinkedOmics database, and the KEGG pathway and miRNA targets of ANGPTLs were also enriched. Results. There was a significant correlation between the ANGPTL members (excluding ANGPTL2) and the prognosis of HCC patients according to the Kaplan-Meier plotter analysis (p < 0.05). ANGPTL1 was the gene with the highest mutation frequency. ANGPTLs are involved in certain pathways that may influence the development of HCC. Conclusion. In summary, the expression of some members of ANGPTLs was significantly correlated with HCC prognosis, suggesting that the ANGPTL gene family members may be promising molecular markers for HCC treatment and prognosis. [ABSTRACT FROM AUTHOR]

In this study, pumpkin seeds peptide was purified, characterized, and evaluated for their zinc‐chelating capability, as well as in vitro bioaccessibility and transportation. Raw pumpkin seeds protein hydrolysate (PSPH) was produced by papain hydrolysis. The peptide fractions with the highest zinc‐chelating abilities were purified using immobilized metal affinity chromatography (IMAC) followed by gel filtration chromatography (GF). Eight peptides were identified, two of which with the lowest molecular weights were synthesized (RPKHPLK and RPKHPLSHDL) for determining potential bioaccessibility and bioavailability. Our results showed that the gastrointestinal stability of RPKHPLK‐Zn and RPKHPLSHDL‐Zn was higher than that of inorganic zinc salts in the simulated gastrointestinal tract model. Furthermore, the influence of the peptide zinc chelates on zinc transport was explored in vitro using Caco‐2 cell monolayer model. It was also shown that both RPKHPLK‐Zn and RPKHPLSHDL‐Zn could increase zinc transport rate and may be used to facilitate effective zinc absorption. The result of this study may provide important implications for developing plant protein foods with higher nutritional value. Practical Application: As a potential alternative protein source, pumpkin seeds may find promising applications in plant‐based foods and drinks to meet the growing market for nonanimal foods. In this study, pumpkin seed protein peptides were prepared and purified, and the zinc‐chelating peptides were identified and evaluated for the abilities to promote the uptake of zinc. This type of mineral peptide chelates could be incorporated into plant‐based foods to increase mineral contents, which is significantly higher in foods originated from animals. The result of our study may provide important information for food industry to increase the nutritional value of plant‐based foods. [ABSTRACT FROM AUTHOR]

The cell stress‐responsive transcription factor p53 influences the expression of its target genes and subsequent cellular responses based in part on its dynamics (changes in level over time). The mechanisms decoding p53 dynamics into subsequent target mRNA and protein dynamics remain unclear. We systematically quantified p53 target mRNA and protein expression over time under two p53 dynamical regimes, oscillatory and rising, using RNA‐sequencing and TMT mass spectrometry. Oscillatory dynamics allowed for a greater variety of dynamical patterns for both mRNAs and proteins. Mathematical modeling of empirical data revealed three distinct mechanisms that decode p53 dynamics. Specific combinations of these mechanisms at the transcriptional and post‐transcriptional levels enabled exclusive induction of proteins under particular dynamics. In addition, rising induction of p53 led to higher induction of proteins regardless of their functional class, including proteins promoting arrest of proliferation, the primary cellular outcome under rising p53. Our results highlight the diverse mechanisms cells employ to distinguish complex transcription factor dynamics to regulate gene expression. SYNOPSIS: Time‐series transcriptomics and proteomics reveal that different dynamics of the transcription factor p53 generate diverse p53 target mRNA and protein expression patterns. Mathematical modeling uncovers distinct mechanisms that decode p53 dynamics. Complementary RNA‐Seq and proteomics experiments were performed at high temporal resolution under oscillating or rising p53 dynamical regime following DNA damage.Oscillatory p53 dynamics enabled greater diversity of target RNA and protein induction profiles than rising p53 dynamics, largely due to the degradation properties of its targets.Gene regulatory network motifs, such as feed forward loops, can explain exclusive induction under a given p53 dynamical regime.Cells with rising p53 dynamics exhibited a higher induction of proteins, which likely contributes to the loss of proliferative potential in these cells. [ABSTRACT FROM AUTHOR]

Induction of mitochondrial‐targeted therapies is demonstrated to be predominantly effective in malignant melanoma therapeutics mediated by programmed cell death (PCD). The pivotal control to switch cell apoptosis to pyroptosis is exhibited to overcome the apoptosis‐resisting characters and induce immune responses against the melanoma. Yet approaches to trigger this switch are limited by far. In the present work, it is found that oligomycin A (OA), a mitochondrial respiratory inhibitor, can effectively suppress mitochondrial functionalities and induce the intracellular oxidative stresses in situ, ultimately inducing apoptosis‐to‐pyroptosis switch against melanoma. The authors have encapsulated OA into the designed cyclic argine‐glycine‐aspartic (c(RGDyC)) decorated iron constructed metal‐organic framework (MIL101‐NH2‐Fe) to develop tumorous glutathione responsive nanocatalytic therapeutics, aiming to trigger intensive apoptosis‐to‐pyroptosis PCD against melanoma, accompanied with the sensitized immunotherapy via the immune checkpoint blockade. The present work offers a prominent PCD switch to destruct melanoma with promising clinical perspectives. [ABSTRACT FROM AUTHOR]

aimed to retrospectively analyze Willis covered stent (WCS)'s therapeutic efficacy in intracranial pseudoaneurysms (PSAs) of the internal carotid artery (ICA). Methods: Between June 2018 and July 2021, 56 individuals with intracranial PSAs of the ICA treated with WCS in three centers were included to analyze information regarding medical records, operative parameters, imaging findings and follow-up data. Results: All WCSs were successfully targeted to the ICA lesions. Total exclusion of PSA was found in 53 cases (94.6%) right upon surgery, and mild endoleak into the aneurysm remained in 3 cases (5.4%). Intraoperative thrombosis occurred in 1 case (1.8%), and tirofiban was utilized for recanalization. Follow-up by angiography showed total aneurysm occlusion in the total number of individuals, including in the 3 above cases with residual endoleak. In-stent stenosis occurred in 7 (12.5%) patients. No stent-related ischemic event was encountered. Predictive factors of late in-stent stenosis following WCS implantation in this patient group were irregular post-operative antiplatelet treatment (p = 0.015) and C4-C5 segment of the ICA (p = 0.043). Conclusion: WCSs are effective in treating intracranial PSAs of the ICA. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV)-induced discoloration and cracking pose formidable challenges for thermally modified wood (TMW) when used in outdoor applications. Herein, we propose a novel pretreatment strategy using deep eutectic solvent (DES) to enhance the weathering resistance of TMW. DES-assisted TMW (DES-TMW) was prepared by coating wood with choline chloride/citric acid (CA) DES, followed by thermal modification. During the DES-assisted thermal modification process, the cross-linking of the lignin network in DES-TMW was increased as a result of lignin self-polymerization, cross-linking with autologous molecules and furfural, as well as esterified connections caused by CA. This in-situ modification reduces the quantity of photosensitive phenolic hydroxyl groups within lignin by forming cross-linked structures, reducing phenoxy free radical generation during the weathering and obstructing chromophores production pathways, thus enhancing the photostability of lignin. Consequently, the DES-TMW exhibited remarkable resistance to discoloration and cracking compared to TMW. These findings provide evidence that our strategy can effectively enhance the photostability of wood, thereby contributing to the development and production of sustainable outdoor wood products capable of withstanding changing weather conditions. [Display omitted] • Eco-friendly DES-assisted method for photostable thermally modified wood (TMW). • In-situ lignin modification during treatment created stable cross-linked structures. • DES-assisted method inhibited chromophore formation and photodegradation of lignin. • DES-assisted TMW (DES-TMW) showed excellent resistance to color change and cracking. [ABSTRACT FROM AUTHOR]

Complemented croplands are a crucial component of cropland resources and play a significant role in ensuring national food security. In recent decades, to counter the loss of prime farmland caused by urban construction, the Chinese government introduced a requisition–compensation balance policy, leading to the substantial expansion of new croplands. Therefore, there is an urgent need to determine whether these complemented croplands can be effectively used. Taking Southwest China as a case study, we used high-precision long-term land-use data from 1990 to 2020 to reveal the dynamics of complemented cropland utilization, evaluate the efficiency of complemented cropland utilization from the perspective of abandoned farmland, and identify the factors driving complemented cropland use efficiency based on more than 13 million land parcels. The results showed that: (1) From 1990 to 2020, complemented cropland amounted to approximately 1170.07 × 104 hm2, accounting for 32.67% of the total arable land area in 1990. The potential grain production capacity of these complemented croplands was significantly lower than that of base croplands. (2) The abandonment of complemented croplands was more serious than that of base croplands, and 47.03% of the complemented croplands experienced abandonment at least once during the study period, and the average efficiency of the complemented croplands was 75.61%. (3) The labor population ratio, elevation, and land parcel size played pivotal roles in influencing the complemented cropland utilization efficiency; however, there was substantial variation among the different provinces. Labor replacement, overcoming farming difficulties brought by mountainous terrain, and improving farmers' income are the keys to alleviating cropland abandonment in mountainous areas and improving cropland utilization efficiency. This study provides novel insights into the efficiency assessment and exploration of the mechanisms driving complemented croplands and can provide references for cropland management. [Display omitted] • A novel perspective for the evaluation of cropland use efficiency was developed. • Complemented cropland abandonment was more serious than that of base cropland. • Average use efficiency of complemented cropland was 75.61% in Southwest China. • Labor force ratio, elevation, and land parcel size were the primary driving factors. [ABSTRACT FROM AUTHOR]

Cultivated land plays a pivotal role in ensuring national food security. The challenges of non-agriculture, non-grain production and the marginalization of cultivated land have become increasingly pronounced in the context of urbanization and industrialization in China, posing potential threats to long-term food security. This study employs a combination of remote sensing and statistical data to reveal the effects of non-agriculturalization, non-grainization, and the marginalization of cultivated land on grain production potential (GPP) at the grid scale. From 1992 to 2020, the total farmland area initially exhibited an ascending trend followed by a subsequent decline, resulting in a net decrease of approximately 0.84% in China. the northward shift in the center of gravity of cultivated land has accentuated the spatial disparity between grain production and consumption. Non-agriculturalization, non-grainization, and marginalization of cultivated land contributed 35.22%, 22.58%, and 42.20% to the GPP loss, respectively. GPP loss exhibited significant differences across the agroclimatic zones, with the combined loss in the Middle-lower Yangtze Plain and Huang-Huai-Hai Plain exceeding 60% of the national total. Cultivated land marginalization has emerged as the most impactful land-use change affecting GPP, leading to a substantial loss of approximately 11471.30 × 104 t. The affected area is predominantly concentrated in the southern region. The marginalization of cultivated land has not been effectively alleviated, and the expansion trend continues. Conservation endeavors targeting cultivated land should prioritize enhancing farmers' willingness to cultivate, curbing the extensive utilization of farmland, and mitigating the escalating trend of farmland marginalization. [ABSTRACT FROM AUTHOR]

[Display omitted] Electronic toll collection (ETC) has been designed and implemented to improve traffic efficiency and reduce traffic-related air pollution. However, the real-world impact of ETC on these factors is currently under-qualified. With this consideration, we attempted to reveal the effect of ETC on traffic efficiency and traffic pollution using portable emission measurement systems. Firstly, in contrast to the manual toll collection (MTC), ETC offer lower emissions and time savings, and there exist a quadratic relationship between emission rates and vehicle specific power. Secondly, vehicles in acceleration state emit more pollutants than other situations such as deceleration, steady cruising and idling in both ETC and MTC lanes. Thirdly, ETC lanes show 34.25% and 13.63% lower CO 2 and NO x emissions, respectively, along with a 46.55% timesaving compared to MTC lanes. Finally, the study identifies engine load percent as the primary factor impacting emissions, accounting for 60–88% of the variance. [ABSTRACT FROM AUTHOR]

This paper introduces an advanced Short‐term Nodal Load Forecasting (STNLF) method that forecasts nodal load profiles for the next day in power systems, based on the combined use of three machine learning techniques. Least Absolute Shrinkage and Selection Operator (LASSO) is employed to reduce the number of features for a single nodal load forecasting. Principal Component Analysis (PCA) is used to capture the features of historical loads in low‐dimensional space compared to the original high‐dimensional load space where features are barely possible to depict. Bayesian Ridge Regression (BRR) is utilized to decide the parameters of the prediction model from a statistics perspective. Tests based on modified PJM load data demonstrate the effectiveness of the proposed STNLF method compared to the state‐of‐the‐art General Regression Neural Network (GRNN) method. Moreover, the reliability of the day‐ahead Unit Commitment (UC) solution is shown to have been improved, based on the forecasted load data using the proposed STNLF method. [ABSTRACT FROM AUTHOR]

Models are an important tool to predict Earth system dynamics. An accurate prediction of future states of ecosystems depends on not only model structures but also parameterizations. Model parameters can be constrained by data assimilation. However, applications of data assimilation to ecology are restricted by highly technical requirements such as model-dependent coding. To alleviate this technical burden, we developed a model-independent data assimilation (MIDA) module. MIDA works in three steps including data preparation, execution of data assimilation, and visualization. The first step prepares prior ranges of parameter values, a defined number of iterations, and directory paths to access files of observations and models. The execution step calibrates parameter values to best fit the observations and estimates the parameter posterior distributions. The final step automatically visualizes the calibration performance and posterior distributions. MIDA is model independent, and modelers can use MIDA for an accurate and efficient data assimilation in a simple and interactive way without modification of their original models. We applied MIDA to four types of ecological models: the data assimilation linked ecosystem carbon (DALEC) model, a surrogate-based energy exascale earth system model: the land component (ELM), nine phenological models and a stand-alone biome ecological strategy simulator (BiomeE). The applications indicate that MIDA can effectively solve data assimilation problems for different ecological models. Additionally, the easy implementation and model-independent feature of MIDA breaks the technical barrier of applications of data–model fusion in ecology. MIDA facilitates the assimilation of various observations into models for uncertainty reduction in ecological modeling and forecasting. [ABSTRACT FROM AUTHOR]

The dire wolf was one of the successful top predators in North America during the Pleistocene. It is best known from the southern part of North America, and it even immigrated to South America. Fossils of dire wolves are very rare north of 42° North latitude in North America. That distribution supported the belief that the low temperatures and ice sheets in the higher latitudes of North American formed an insurmountable barrier for the dispersal of dire wolves. Here we report the first record of the dire wolf fossil in Eurasia. The fossil is a partial mandibular fragment with a tooth recovered from a Late Pleistocene underwater sand mine site near the city of Harbin in Northeastern China. Other mammalian fossils from the same site suggest that this dire wolf coexisted with the typical Mammuthus - Coelodonta fauna of Eurasia. The newly discovered specimen has a huge m1; much larger than gray wolves and other large canids from the same region. The massive m1 trigonid accounts for a high percentage of its overall length. The m1 talonid is reduced, but retains a small entoconid. The m2-3 alveoli suggest that the two teeth were smaller than those of the gray wolf. The combination of these morphologies is present only in the dire wolf. When the body mass spectra of medium and large-bodied carnivores from Asia and North America were compared, the Asian dire wolf occupies a position nearly overlapping the spotted hyena (Crocuta crocuta ultima). During the Late Pleistocene, C. crocuta u ltima was one of the most widely distributed and dominant carnivores in Asia. Competition from hyenas may have kept dire wolf Asian populations at very low levels leading to their rarity as fossils rare in Asia. [ABSTRACT FROM AUTHOR]

Hydrologic predictions at rural watersheds are important but also challenging due to data shortage. Long short-term memory (LSTM) networks are a promising machine learning approach and have demonstrated good performance in streamflow predictions. However, due to its data-hungry nature, most LSTM applications focus on well-monitored catchments with abundant and high-quality observations. In this work, we investigate predictive capabilities of LSTM in poorly monitored watersheds with short observation records. To address three main challenges of LSTM applications in data-scarce locations, i.e., overfitting, uncertainty quantification (UQ), and out-of-distribution prediction, we evaluate different regularization techniques to prevent overfitting, apply a Bayesian LSTM for UQ, and introduce a physics-informed hybrid LSTM to enhance out-of-distribution prediction. Through case studies in two diverse sets of catchments with and without snow influence, we demonstrate that 1) when hydrologic variability in the prediction period is similar to the calibration period, LSTM models can reasonably predict daily streamflow with Nash–Sutcliffe efficiency above 0.8, even with only 2 years of calibration data; 2) when the hydrologic variability in the prediction and calibration periods is dramatically different, LSTM alone does not predict well, but the hybrid model can improve the out-of-distribution prediction with acceptable generalization accuracy; 3) L2 norm penalty and dropout can mitigate overfitting, and Bayesian and hybrid LSTM have no overfitting; and 4) Bayesian LSTM provides useful uncertainty information to improve prediction understanding and credibility. These insights have vital implications for streamflow simulation in watersheds where data quality and availability are a critical issue. [ABSTRACT FROM AUTHOR]

Although there is increased interest in utilizing machine learning (ML) to support drug development, technical hurdles associated with complex algorithms have limited widespread adoption. In response, we have developed Pharm‐AutoML, an open‐source Python package that enables users to automate the construction of ML models and predict clinical outcomes, especially in the context of pharmacological interventions. In particular, our approach streamlines tedious steps within the ML workflow, including data preprocessing, model tuning, model selection, results analysis, and model interpretation. Moreover, our open‐source package helps to identify the most predictive ML pipeline among defined search spaces by selecting the best data preprocessing strategy and tuning the ML model hyperparameters. The package currently supports multiclass classification tasks, and additional functions are being developed. Using a set of five publicly available biomedical datasets, we show that our Pharm‐AutoML outperforms other ML frameworks, including H2O with default settings, by demonstrating improved predictive accuracy of classification. We further illustrate how model interpretation methods can be utilized to help explain the fine‐tuned ML pipeline to end users. Pharm‐AutoML provides both novice and expert users improved clinical predictions and scientific insights. [ABSTRACT FROM AUTHOR]

[Display omitted] • SAR investigation of lodoxamide derivatives. • Compound 4b exhibits high and equivalent potency on human, mouse and rat GPR35. • Compound 4b has an appropriate cLogP value compared to lodoxamide. • Compound 4b alleviates clinical symptoms of DSS-induced IBD in mice by oral administration. The G protein-coupled receptor 35 (GPR35) has been identified as a potential target in the treatment of inflammatory bowel disease (IBD). However, the lack of high and equipotent agonists on both human and mouse GPR35 has limited the in vivo study of GPR35 agonists in mouse models of IBD. In this study, structural modifications to lodoxamide provides a series of high and equivalent agonists on human, mouse, and rat GPR35. These molecules eliminate the species selectivity of human to mouse and rat orthologs that have been prevalent with GPR35 agonists including lodoxamide. The cLogP properties are also optimized to make the compounds more obedient to drug-like rules, yielding compound 4b (cLogP = 2.41), which activates human, mouse or rat GPR35 with EC 50 values of 76.0, 63.7 and 77.8 nM, respectively. Oral administration of compound 4b at 20 mg/kg alleviates clinical symptoms of DSS-induced IBD in mice, and is slightly more effective than 5-ASA at 200 mg/kg. In summary, it can serve as a new start point for exploiting more potent GPR35 agonists without species differences for the treatment of IBD, and warrants further study. [ABSTRACT FROM AUTHOR]

This article presents a quint-band passive negative group delay circuit (Q-NGDC) by using Taguchi's optimization method for the first time. This Q-NGDC mainly consists of a semi-circle and a multi-stub resonator, and it is evolved from a simple NGDC (Type I) to a well-designed one (Type VI) through three optimization stages. It is found that, with the application of Taguchi's method (TM) in conjunction with full-wave simulations, the efficiency of the designed passive multi-band NGDC has been improved significantly. The proposed Q-NGDC was fabricated and tested, and the experimental results show that the five operation bands have been achieved at the center frequencies of 1.76, 2.80, 3.84, 4.42, and 5.28 GHz, with the corresponding group delay values of −1.85, −2.15, −1.45, −1.6, and −1.1 ns. The measured transmission coefficients are −4.4, −7.8, −9.7, −9.3, and − 8.9 dB. Furthermore, the proposed NGDC shows the best figure of merit (FOM) at each resonant frequency with a relatively small size. The proposed NGDC can be potentially applied to WCDMA, 5G communication, Zigbee (IEEE802.15.4), and Wi-Fi (IEEE802.11n) systems. [ABSTRACT FROM AUTHOR]

Diversified ion-selective separation applications have dramatically incentivized the exploitation and performance modulation of highly ion-selective nanofiltration (NF) membranes. However, the ion selectivity of NF membranes is synergistically governed by multi-scale factors of membrane structural parameters and operational parameters, with the intrinsic ion-selective mechanism still ambiguous. Herein, we proposed an ensemble machine learning (ML) method to decouple key factors affecting the ionic selectivity of polyamide NF membranes. Membrane structural parameters and operational parameters were typically extracted as input variables and linked to mono−/divalent ion selectivity by model training based on Random Forest and XGBoost algorithms. The feature importance assessment indicated the critical role of membrane structure parameters on ion selectivity, wherein pore radius dominated the mono−/divalent anionic selectivity while zeta potential for mono−/divalent cationic selectivity. Partial dependence analyses further depicted intensive insights regarding the influence of membrane structural parameters on ion selectivity. Moreover, stochastic dataset splitting measurements demonstrated the accurate predictive capability of the model simultaneously possessing excellent stability and reliability. We anticipated that the implementation of ensemble ML in explicating the intricate ion-selective mechanism created platforms for understanding the structure-membrane performance correlation and orientally manufacturing highly ion-selective NF membranes. [Display omitted] • Ensemble machine learning was implemented to decouple the key features affecting ion selectivities of polyamide membranes. • RF and XGBoost algorithms were adopted to learn from relevant variables and evaluate permutation features importance. • Mono-/divalent anionic selectivity was dominated by pore size while zeta potential for mono-/divalent cationic selectivity. [ABSTRACT FROM AUTHOR]

Mangrove Avicennia marina has the importantly potential for cadmium (Cd) pollution remediation in coastal wetlands. Unfortunately, the molecular mechanisms and transporter members for Cd uptake by the roots of A. marina are not well documented. In this study, photosynthetic and phenotypic analysis indicated that A. marina is particularly tolerant to Cd. The content and flux analysis indicated that Cd is mainly retained in the roots, with greater Cd influx in fine roots than that in coarse roots, and higher Cd influx in the root meristem zone as well. Using transcriptomic analysis, a total of 5238 differentially expressed genes were identified between the Cd treatment and control group. Moreover, we found that 54 genes were responsible for inorganic ion transport. Among these genes, AmHMA2, AmIRT1, and AmPCR2 were localized in the plasma membrane and AmZIP1 was localized in both plasma membrane and cytoplasm. All above gene encoding transporters showed significant Cd transport activities using function assay in yeast cells. In addition, the overexpression of AmZIP1 or AmPCR2 in Arabidopsis improved the Cd tolerance of transgenic plants. This is particularly significant as it provides insight into the molecular mechanism for Cd uptake by the roots of mangrove plants and a theoretical basis for coastal wetland phytoremediation. [Display omitted] • ETR and qP are sensitive biological indicators for Cd stress in A. marina. • Cd influx is most effective in the meristem and elongation zones of the root. • Cd affects the expression of genes related to inorganic ion transport. • AmHMA2, AmIRT1, AmZIP1, and AmPCR2 are the most important Cd transporters. • Overexpression of AmZIP1 improved the Cd tolerance of Arabidopsis. [ABSTRACT FROM AUTHOR]

Background: Infratentorial craniotomy patients have a high incidence of postoperative nausea and vomiting (PONV). Enhanced Recovery After Surgery (ERAS) protocols have been shown in multiple surgical disciplines to improve outcomes, including reduced PONV. However, very few studies have described the application of ERAS to infratentorial craniotomy. The aim of this study was to examine whether our ERAS protocol for infratentorial craniotomy could improve PONV. Methods: We implemented an evidence-based, multimodal ERAS protocol for patients undergoing infratentorial craniotomy. A total of 105 patients who underwent infratentorial craniotomy were randomized into either the ERAS group (n = 50) or the control group (n = 55). Primary outcomes were the incidence of vomiting, nausea score, and use of rescue antiemetic during the first 72 h after surgery. Secondary outcomes included postoperative anxiety level, sleep quality, and complications. Results: Over the entire 72 h post-craniotomy observation period, the cumulative incidence of vomiting was significantly lower in the ERAS group than in the control group. Meanwhile, the incidence of vomiting was significantly lower in the ERAS group on postoperative days (PODs) 2 and 3. Notably, the proportion of patients with mild nausea (VAS 0–4) was higher in the ERAS group as compared to the control group on PODs 2 or 3. Additionally, the postoperative anxiety level and quality of sleep were significantly better in the ERAS group. Conclusion: Successful implementation of our ERAS protocol in infratentorial craniotomy patients could attenuate postoperative anxiety, improve sleep quality, and reduce the incidence of PONV, without increasing the rate of postoperative complications. Trial registration: ChiCTR-INR-16009662, 27 Oct 2016, Clinical study on the development and efficacy evaluation of Enhanced Recovery After Surgery (ERAS) in Neurosurgery. [ABSTRACT FROM AUTHOR]

Purpose: Data from in vitro and animal studies support the preventive effect of tea (Camellia sinensis) against colorectal cancer. Further, many epidemiologic studies evaluated the association between tea consumption and colorectal cancer risk, but the results were inconsistent. We conducted a meta-analysis of prospective cohort studies to systematically assess the association between tea consumption and colorectal cancer risk. Methods: A comprehensive literature review was conducted to identify the related articles by searching PubMed and Embase up to June, 2019. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a fixed effect model. Results: Twenty cohort articles were included in the present meta-analysis involving 2,068,137 participants and 21,437 cases. The combined RR of colorectal cancer for the highest vs. lowest tea consumption was determined to 0.97 (95% CI 0.94–1.01) with marginal heterogeneity (I2 = 24.0%, P = 0.093) among all studies. This indicated that tea consumption had no significant association with colorectal cancer risk. Stratified analysis showed that no significant differences were found in all subgroups. We further conducted the gender-specific meta-analysis for deriving a more precise estimation. No significant association was observed between tea consumption and colorectal cancer risk in male (combined RR = 0.97; 95% CI 0.90–1.04). However, tea consumption had a marginal significant inverse impact on colorectal cancer risk in female (combined RR = 0.93; 95% CI 0.86–1.00). Further, we found a stronger inverse association between tea consumption and risk of colorectal cancer among the female studies with no adjustment of coffee intake (RR: 0.90; 95% CI 0.82–1.00, P < 0.05) compared to the female studies that adjusted for coffee intake (RR = 0.97; 95% CI 0.87–1.09, P > 0.05). Conclusions: Our finding indicates that tea consumption has no significant impact on the colorectal cancer risk in both genders combined, but gender-specific meta-analysis shows that tea consumption has a marginal significant inverse impact on colorectal cancer risk in female. [ABSTRACT FROM AUTHOR]

Purpose: The established two-analyte integrated population pharmacokinetic model was applied to assess the impact of intrinsic/extrinsic factors on the pharmacokinetics (PK) of polatuzumab vedotin (pola) in patients with non-Hodgkin lymphoma (NHL) following bodyweight-based dosing. Methods: Model simulations based on individual empirical Bayes estimates were used to evaluate the impact of intrinsic/extrinsic factors as patient subgroups on Cycle 6 exposures. Intrinsic factors included bodyweight, age, sex, hepatic and renal functions. Extrinsic factors included rituximab/obinutuzumab or bendamustine combination with pola and manufacturing process. The predicted impact on exposures along with the established exposure-response relationships were used to assess clinical relevance. Results: No clinically meaningful differences in Cycle 6 pola exposures were found for the following subgroups: bodyweight 100–146 kg versus 38–<100 kg, age ≥ 65 years versus <65 years, female versus male, mild hepatic impairment versus normal, mild-to-moderate renal impairment versus normal. Co-administration of rituximab/obinutuzumab or bendamustine, and change in the pola manufacturing process, also had no meaningful impact on PK. Conclusions: In patients with NHL, bodyweight-based dosing is adequate, and no further dose adjustment is recommended for the heavier subgroup (100–146 kg). In addition, no dose adjustments are recommended for other subgroups based on intrinsic/extrinsic factors evaluated. [ABSTRACT FROM AUTHOR]

The high incidence of premature rupture of membranes (PROM) is closely related to the lack of screening methods. Herein, a rapid and sensitive detection model for procalcitonin (PCT) and interleukin-6 (IL-6) was established utilizing the principle of antigen antibody binding and combined with surface enhanced Raman spectroscopy (SERS) and immunochromatographic assay (ICA), which could be used for the detection of specific biomarkers at a low concentration of peripheral blood and early detection of PROM patients. 5,5′-Dithiobis-2-nitrobenzoic acid labeled monoclonal anti-IL-6 on gold nanocages (GNCs) and 4-methylthiobenzoic acid labeled monoclonal anti-PCT on GNCs were employed as SERS tags. In the presence of IL-6 and PCT, the antigen-SERS tag complexes were trapped and concentrated on the two test lines. The unique characteristics of GNCs with hollow and multi-branch angle allowed high SERS performance in the system by increasing the biological binding sites and hot spots. Through finite difference time domain simulation, it could be concluded that the electromagnetic field between the gaps of GNC dimers was stronger than that of the single GNC, which proved the feasibility of ICA based on surface enhanced Raman scattering (SERS-ICA) in theory. The detection limits of IL-6 and PCT in phosphate buffer were 7.897 pg mL−1 and 7.725 pg mL−1, meanwhile the detection limits of peripheral blood were 8.414 pg mL−1 and 8.017 pg mL−1, respectively. In addition, the detection of real-world samples showed that SERS-ICA was available to evaluate the concentrations of IL-6 and PCT. The experimental data of SERS-ICA were in accordance with that of enzyme-linked immunosorbent assay. These results indicated that SERS-ICA had great potential in the early screening of PROM. [ABSTRACT FROM AUTHOR]

Ultrasensitive detection of specific biomarkers in clinical serum is helpful for early diagnosis of cervical cancer. In this paper, a surface-enhanced Raman scattering (SERS)-based immunoassay was developed for the simultaneous determination of squamous cell carcinoma antigen (SCCA) and osteopontin (OPN) in cervical cancer serum. Au-Ag nanoshuttles (Au-AgNSs) as SERS tags and hydrophobic filter paper-based Au nanoflowers (AuNFs) as capture substrate were constructed into a sandwich structure which served as an ultrasensitive SERS-based immunoassay platform. Finite difference time domain simulation confirmed that the electromagnetic field coupled between the AuNFs had a prominent SERS signal enhancement effect, which improved the detection sensitivity. SERS mapping showed that hexadecenyl succinic anhydride hydrophobic treatment could prevent the analyte from being quickly absorbed by the filter paper and increase the retention time to be more evenly distributed on the filter paper substrate. The immunoassay platform was verified to have good selectivity and reproducibility. With this method, the detection limits of SCCA and OPN in human serum were as low as 8.628 pg/mL and 4.388 pg/mL, respectively. Finally, in order to verify the feasibility of its clinical application, the serum samples of healthy subjects; cervical intraepithelial neoplasia I (CINI), CINII, and CINIII; and cervical cancer patients were analyzed, and the reliability of the results was confirmed by enzyme-linked immunosorbent assay experiments. The constructed SERS-based immunoassay platform could be used as a clinical tool for early screening of cancers in the future. [ABSTRACT FROM AUTHOR]

Background: Genetic factors, diet and inflammation are associated with the development of dementia. In this study, we aimed at evaluating the impact of the dietary inflammatory index (DII) scores and genetic susceptibility on the development of dementia. Methods: This prospective study involved 207,301 participants aged between 39 and 72 years from UK biobank. A web-based 24-h dietary questionnaire was collected at least once from participants between 2006 and 2012. The DII was calculated based on inflammatory effect score of nutrients. Individual AD-GRS (Alzheimer's disease genetic risk score) was calculated. Incident dementia was ascertained through hospital or death records. Results: Of all 207,301 participants, 468 incident cases of all-cause dementia (165 AD, 91 VD and 26 FTD) were reported during a follow-up period of 11.4 years. The participants in the highest quintile (Q) of DII scores reported a higher risk for all-cause dementia (Q5 vs. Q3, hazard ratio (HR) = 1.702; 95% CI: 1.285–2.255) and VD (Q5 vs. Q3, HR = 2.266, 95% CI: 1.133–4.531) compared to participants in the Q3. Besides, when compared with the Q1, there was a higher risk for AD in the subjects of Q5 (Q5 vs. Q1, HR = 1.590; 95% CI: 1.004–2.519). There was a non-linear relationship between DII score and all-cause incidence (P for non-linear = 0.038) by restricted cubic splines. Subgroup analysis found that the increased risk for all-cause dementia and AD was more pronounced in the elderly, women, and higher educated population. Cox regression models indicated that compared with the participants who had a low AD-GRS risk and in the lowest tertile of DII, participants had a high AD-GRS and the highest tertile of DII were associated with a higher risk of AD (HR = 1.757, 95% CI: 1.082–2.855, P = 0.023). Conclusions: The DII scores were independently associated with an augmented risk for all-cause dementia, AD and VD. Additionally, high AD-GRS with higher DII scores was significantly associated with a higher risk of AD. [ABSTRACT FROM AUTHOR]

Linear frequency conversion enabled by a temporal boundary of a resonant cavity provides a promising alternative to generating new frequency components, where the temporal boundary can be introduced by rapidly modifying the refractive index of the cavity. However, the perturbed photon dynamics during the ultrafast linear process is still vague. Here, the photon dynamics based on temporal coupled‐mode theory are explored and the phenomena are demonstrated with a silicon metasurface via simulations and experiments in the terahertz regime. With the time‐varying real and imaginary parts of the refractive index, a periodic modulation (Td) of the amplification coefficient of the newly generated photons is observed where the optimized coefficient occurs in the first period at td = Td /2. It further establishes a dynamic critical coupling condition to improve the amplification coefficient in the dynamic process. The scheme of linear frequency conversion via temporal boundary can revolutionize the paradigm of parametric amplification from nonlinear to linear processes, and conversion efficiency will be improved in a high‐quality factor cavity. The ultrafast modulation will find applications in optical signal processing, modulators, and reconfigurable intelligent surfaces for development of the next‐generation communications. [ABSTRACT FROM AUTHOR]

Two sulfoxide-containing Schiff bases, (E)-(((2-(methylsulfinyl phenyl) imino)methyl)-4-nitrophenol (HL1) and (E)-3,5-dibromo-2-(((2-(methylsulfinyl phenyl)imino)methyl)phenol (HL2), were prepared by condensation and subsequent oxidation reactions. In the presence of triethylamine, reactions of HL1 with 0.5 equivalent of copper acetate, cobalt acetate, nickel acetate and zinc acetate in ethanol afforded four metal complexes: (η2-N,O-L1)Cu(η3-O,N,O-L1) (1) and (η3-O,N,O-L1)2M (M = Co, 2; Ni, 3; Zn, 4), respectively. Similarly, treatment of HL2 with 0.5 equivalent of cobalt acetate and nickel acetate obtained two cobalt/nickel complexes: (η3-O,N,O-L2)2M (M = Co, 5; Ni, 6). Reactions of HL1 and one equivalent of Ru(PPh3)3Cl2 in tetrahydrofuran in the presence of triethylamine afforded a ruthenium(II) complex, (η3-O,N,S-L1)Ru(PPh3)2Cl (7). The molecular structures of HL1 and 1-7 have been confirmed by single-crystal X-ray diffraction. In addition, the UV–Vis, infrared, and fluorescence spectroscopies of 1–7 along with their electrochemical properties were also investigated. [ABSTRACT FROM AUTHOR]

Natural killer cells (NK cells) play an important role in innate immunity. NK cells recognize self and nonself depending on the balance of activating receptors and inhibitory receptors. After binding to their ligands, NK cell receptors trigger subsequent signaling conduction and then determine whether NK is activated or inhibited. Furthermore, NK cell response includes cytotoxicity and cytokine release, which is tightly related to the activation of NK cell-activating receptors and the inhibition of inhibitory receptors on the surfaces of NK cells. The expression and function of NK cell surface receptors also alter in virus infection, tumor, and autoimmune diseases and influence the occurrence and development of diseases. So, it is important to understand the mechanism of recognition between NK receptors and their ligands in pathological conditions and the signaling pathways of NK cell receptors. This review mainly summarizes the research progress on NK cell surface receptors and their signal pathways. [ABSTRACT FROM AUTHOR]

Myelosuppression is one of the most common and severe adverse events associated with anti-cancer therapies and can be a source of drug attrition. Current mathematical modeling methods for assessing cytopenia risk rely on indirect measurements of drug effects and primarily focus on single lineage responses to drugs. However, anti-cancer therapies have diverse mechanisms with varying degrees of effect across hematopoietic lineages. To improve predictive understanding of drug-induced myelosuppression, we developed a quantitative systems pharmacology (QSP) model of hematopoiesis in vitro for quantifying the effects of anti-cancer agents on multiple hematopoietic cell lineages. We calibrated the system parameters of the model to cell kinetics data without treatment and then validated the model by showing that the inferred mechanisms of anti-proliferation and/or cell-killing are consistent with the published mechanisms for three classes of drugs with different mechanisms of action. Using a set of compounds as a sample set, we then analyzed novel compounds to predict their mechanisms and magnitude of myelosuppression. Further, these quantitative mechanisms are valuable for the development of translational in vivo models to predict clinical cytopenia effects. Author summary: Reduced bone marrow activity and levels of mature blood cells is an undesirable side effect of many anti-cancer therapies. Selecting promising lead compounds for further development requires understanding of potential myelosuppressive effects. However, existing preclinical experiments and modeling formulations fail to consider drug effects on multiple blood cell types or the mechanistic differences between how drugs induced myelosuppression. Here we developed a quantitative systems pharmacology (QSP) model that estimates a drug candidate's effect on multiple precursor and mature blood cell lineages and further distinguishes how the drug affects these populations—through cell-killing or anti-proliferation mechanisms. This modeling formalism is valuable for vetting compounds for therapeutic development and for further translational modeling to anticipate the clinical effects of compounds. [ABSTRACT FROM AUTHOR]

A 3,5-didocosyloxybenzyl alcohol tag that was introduced at the anomeric position of the carbohydrate acceptor was applied in the assembly of a pentasaccharide. The intrinsic high solubility in nonpolar solvent and precipitation properties in polar solvent are crucial features of this tag. Thus, rapid and simple precipitation-centrifugation can be conducted throughout the synthetic route at each step to ease work-up and purification processes, and reduce the amount of solvent required. This method provides an efficient, environmental-friendly, and economical approach to synthesize complex oligosaccharides. [ABSTRACT FROM AUTHOR]

Real-time detection of heavy metal ions in water was implemented by using a composite optical waveguide (COWG) based polarimetric interferometer. The COWG was made by local deposition of a tapered nanometric layer of high-index materials onto a single-mode slab glass waveguide, and it is a low-cost robust waveguide with a locally large modal birefringence. The COWG-based polarimetric interferometer operates with a single incident laser beam and uses the transverse electric and transverse magnetic modes as the sensing and reference beams, respectively, and it can easily detect 0.1 ppm lead(II) ions in water via nonspecific adsorption on the tapered layer of TiO2. The excellent linearity was obtained between the lead(II) concentration and the ratio of concentration to the phase-difference change (Δ[lowercase_phi_synonym]), suggesting that adsorption of lead(II) ions on the TiO2 film follows the Langmuir isotherm model. The saturation adsorption leads to Δ[lowercase_phi_synonym]max = 7.485π. By use of the eigenvalue equations for a homogeneous waveguide to fit the measured refractive-index (RI) sensitivity of the interferometer, the equivalent thickness of Teq = 26.05 nm for the tapered TiO2 layer used was achieved. With Teq = 26.05 nm and Δ[lowercase_phi_synonym]max = 7.485π and the thickness of 0.264 nm for the lead(II) adlayer, the adlayer RI was derived to be nad ≈ 1.945 at the maximum coverage. [ABSTRACT FROM AUTHOR]

Background: Infratentorial craniotomy patients have a high incidence of postoperative nausea and vomiting (PONV). Enhanced Recovery After Surgery (ERAS) protocols have been shown in multiple surgical disciplines to improve outcomes, including reduced PONV. However, very few studies have described the application of ERAS to infratentorial craniotomy. The aim of this study was to examine whether our ERAS protocol for infratentorial craniotomy could improve PONV.Methods: We implemented an evidence-based, multimodal ERAS protocol for patients undergoing infratentorial craniotomy. A total of 105 patients who underwent infratentorial craniotomy were randomized into either the ERAS group (n = 50) or the control group (n = 55). Primary outcomes were the incidence of vomiting, nausea score, and use of rescue antiemetic during the first 72 h after surgery. Secondary outcomes included postoperative anxiety level, sleep quality, and complications.Results: Over the entire 72 h post-craniotomy observation period, the cumulative incidence of vomiting was significantly lower in the ERAS group than in the control group. Meanwhile, the incidence of vomiting was significantly lower in the ERAS group on postoperative days (PODs) 2 and 3. Notably, the proportion of patients with mild nausea (VAS 0-4) was higher in the ERAS group as compared to the control group on PODs 2 or 3. Additionally, the postoperative anxiety level and quality of sleep were significantly better in the ERAS group.Conclusion: Successful implementation of our ERAS protocol in infratentorial craniotomy patients could attenuate postoperative anxiety, improve sleep quality, and reduce the incidence of PONV, without increasing the rate of postoperative complications.Trial Registration: ChiCTR-INR-16009662, 27 Oct 2016, Clinical study on the development and efficacy evaluation of Enhanced Recovery After Surgery (ERAS) in Neurosurgery. [ABSTRACT FROM AUTHOR]

A two‐analyte integrated population pharmacokinetic (PK) model that simultaneously describes concentrations of antibody‐conjugated monomethyl auristatin E (acMMAE) and unconjugated MMAE following repeated administrations of polatuzumab vedotin (pola) was developed based on data from four clinical studies of pola in patients with non‐Hodgkin lymphoma. A two‐compartment model with a nonspecific, time‐dependent linear clearance, a linear time‐dependent exponentially declining clearance, and a Michaelis–Menten clearance provided a good fit of the acMMAE plasma PK profiles. All three acMMAE elimination pathways contributed to the input to the central compartment of unconjugated MMAE, which was also described by a two‐compartment model. Population PK parameters, covariate effects, and interindividual variability of model parameters were estimated. The impact of clinically relevant covariates on PK exposures of each analyte were quantified and reported to support key label claims. [ABSTRACT FROM AUTHOR]

Most of the current exemplar-based face sketch synthesis approaches directly synthesize face sketches from face photos. However, due to the great difference between face photos and sketches, as well as the cluttered backgrounds in photo images, there tends to be some noise, deformation and missing parts on the synthesized face sketches by most of the exemplar-based methods. Besides, most exemplar-based methods exist a common problem: they only produce satisfactory results when training and test samples originate from the same dataset. To address these issues, in this paper we propose a simple but effective method which consists of two stages: the preprocessing stage and the sketch synthesis stage. In the preprocessing stage, we first design a fully convolutional neural network for preprocessing (pFCN). To fit the preprocessing task, the pFCN is trained by an L1 based total loss function, which is simple yet could enhance the facial features. Then the full-size photo is fed to the well-trained pFCN to generate the feature map, which we call a semi-sketch since it bridges the discrepancy between photo and sketch. At the sketch synthesis stage, the semi-sketches and an existing exemplar-based method are employed to synthesize the final sketches. Extensive experiments on public face sketch datasets verify that the proposed two-stage method improves the sketch synthesis quality of the state-of-the-art exemplar-based methods in terms of both recognition accuracy and perceptual quality. In addition, the experiments on cross-dataset indicate that the proposed method provides a new means for strengthening the generalization ability of the exemplar-based method. [ABSTRACT FROM AUTHOR]

During endovascular treatment of complex intracranial dural arteriovenous fistulas (DAVFs) of the transverse sigmoid sinus, it can be difficult to preserve the patency of the dural sinus. We have described the details of the transvenous balloon-assisted technique using Copernic RC balloon as a treatment option for patients with complex DAVFs of the transverse sigmoid sinus. In these 2 cases, the Copernic RC balloon was navigated into the internal jugular vein and placed at the distal end of the DAVFs in the transverse sinus. After the balloon was fully inflated, a transarterial glue embolization or transvenous Onyx tunnel technique was performed, with complete exclusion of the fistula and patency of the transverse sigmoid sinus. No immediate or delayed postoperative complications occurred. Transvenous Copernic RC balloon-assisted embolization of DAVFs in the transverse and sigmoid sinuses is safe and can offer complete occlusion of DAVFs and remission of clinical symptoms. [ABSTRACT FROM AUTHOR]