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In this work, the conformational behaviors of ring polyelectrolyte in tetravalent salt solutions are discussed in detail through molecular dynamics simulation. For simplification, here we have neglected the effect of the twisting interaction, although it has been well known that both bending and twisting interactions play a deterministic in the steric conformation of a semiflexible ring polymer. The salt concentration CS and the bending energy b take a decisive role in the conformation of the ring polyelectrolyte (PE). Throughout our calculations, the b varies from b = 0 (freely joint chain) to b = 120. The salt concentration CS changes in the range of 3.56 × 10−4 M ≤ CS ≤ 2.49 × 10−1 M. Upon the addition of salt, ring PE contracts at first, subsequently re-expands. More abundant conformations are observed for a semiflexible ring PE. For b = 10, the conformation of semiflexible ring PE shifts from the loop to two-racquet-head spindle, then it condenses into toroid, finally arranges into coil with the increase of CS. As b increases further, four phase transitions are observed. The latter two phase transitions are different. The semiflexible ring PE experiences transformation from toroid to two racquet head spindle, finally to loop in the latter two phase transitions. Its conformation is determined by the competition among the bending energy, cation-bridge, and entropy. Combined, our findings indicate that the conformations of semiflexible ring PE can be controlled by changing the salt concentration and chain stiffness. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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]

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]

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]

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]

Background: Understanding the risk of chikungunya virus (CHIKV) infection and rheumatic sequelae across populations, including travelers and the military, is critical. We leveraged healthcare delivery data of over 9 million U.S. Military Health System (MHS) beneficiaries to identify cases, and sampled controls, to estimate the risk of post-CHIKV rheumatic sequelae. Methodology/principal findings: MHS beneficiary CHIKV infections diagnosed 2014–2018 were identified from the Disease Reporting System internet, TRICARE Encounter Data Non-Institutional, and Comprehensive Ambulatory/Professional Encounter Record systems. Non-CHIKV controls were matched (1:4) by age, gender, beneficiary status, and encounter date. The frequency of comorbidities and incident rheumatic diagnoses through December 2018 were derived from International Classification of Diseases codes and compared between cases and controls. Poisson regression models estimated the association of CHIKV infection with rheumatic sequelae. We further performed a nested case-control study to estimate risk factors for post-CHIKV sequelae in those with prior CHIKV. 195 CHIKV cases were diagnosed between July 2014 and December 2018. The median age was 42 years, and 43.6% were active duty. 63/195 (32.3%) of CHIKV cases had an incident rheumatic diagnosis, including arthralgia, polyarthritis, polymyalgia rheumatica, and/or rheumatoid arthritis, compared to 156/780 (20.0%) of controls (p < 0.001). CHIKV infection remained associated with rheumatic sequelae (aRR = 1.579, p = 0.008) after adjusting for prior rheumatic disease and demography. Those with rheumatic CHIKV sequelae had a median 7 healthcare encounters (IQR 3–15). Among CHIKV infections, we found no association between post-CHIKV rheumatic sequelae and demography, service characteristics, or comorbidities. Conclusions/significance: CHIKV infection is uncommon but associated with rheumatic sequelae among MHS beneficiaries, with substantial healthcare requirements in a proportion of cases with such sequelae. No demographic, clinical, or occupational variables were associated with post-CHIKV rheumatic sequelae, suggesting that prediction of these complications is challenging in MHS beneficiaries. These findings are important context for future CHIKV vaccine decision making in this and other populations. Author summary: We examined U.S. Military Health System (MHS) healthcare delivery data to identify the likelihood of rheumatic complications after chikungunya virus (CHIKV) infection. Overall, CHIKV infections were rare in the MHS, with 195 cases found in the records between 2014 and 2018 (a period which encompassed the peak of the CHIKV epidemic in the Americas). Of these, about 32% received a rheumatic diagnosis after infection, including arthralgia, polyarthritis, polymyalgia rheumatica, and rheumatoid arthritis. Patients who had a rheumatic diagnosis had on average 7 healthcare encounters for their post-CHIKV rheumatic complication, and a quarter had more than 15 healthcare encounters. We did not find any demographic, clinical, or occupational characteristics associated with developing rheumatic complications after CHIKV, suggesting that predicting rheumatic complications from CHIKV may be challenging in MHS beneficiaries. These findings may provide important context for decisions about implementing an approved chikungunya vaccine to military servicemembers and other MHS beneficiaries. [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]

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]

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]

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]

Motivation Post-translational modifications (PTMs) on proteins regulate protein structures and functions. A single protein molecule can possess multiple modification sites that can accommodate various PTM types, leading to a variety of different patterns, or combinations of PTMs, on that protein. Different PTM patterns can give rise to distinct biological functions. To facilitate the study of multiple PTMs on the same protein molecule, top-down mass spectrometry (MS) has proven to be a useful tool to measure the mass of intact proteins, thereby enabling even PTMs at distant sites to be assigned to the same protein molecule and allowing determination of how many PTMs are attached to a single protein. Results We developed a Python module called MSModDetector that studies PTM patterns from individual ion mass spectrometry (I2MS) data. I2MS is an intact protein mass spectrometry approach that generates true mass spectra without the need to infer charge states. The algorithm first detects and quantifies mass shifts for a protein of interest and subsequently infers potential PTM patterns using linear programming. The algorithm is evaluated on simulated I2MS data and experimental I2MS data for the tumor suppressor protein p53. We show that MSModDetector is a useful tool for comparing a protein's PTM pattern landscape across different conditions. An improved analysis of PTM patterns will enable a deeper understanding of PTM-regulated cellular processes. Availability and implementation The source code is available at https://github.com/marjanfaizi/MSModDetector. [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]

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]

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]

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]

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]

• CNT worsened ammonia inhibition when TAN was above 2500 mg N/L. • Potassium transport was interrupted by the interactive effects of CNT and ammonia. • CNT formed potassium channel and dispatched proton motivate force. • CNT affected intercellular ATP level and reduced microbial detoxification activity. • Enhanced secretion of bound EPS was related to the presence of ammonia and CNT. Carbon-based materials are promising in improving the performance and stability of anaerobic digestion (AD). However, it is not clear if carbon-based materials would have any interaction with ammonia on AD performance, especially when ammonia is above inhibition level. This study aims to explore the effects of ammonia on carbon nanotube assisted AD reactors. Methanogenic performance, intracellular energy production, potassium transport activity as well as extracellular polymeric substance (EPS) changes were investigated. The results show that the presence of CNT may mitigate or worsen the ammonia inhibition depending on the total ammonia nitrogen (TAN) concentration. Further investigation found that potassium transportation process of the culture was disturbed with the presence of CNT, which dispatched the proton motive force. As a result, the intracellular energy level reduced, and the microbial detoxification capability decreased. TAN exhibited a strong positive correlation with microbes' detoxification activity, and CNT concentration was positively correlated with polysaccharide which created a physical structure to protect cell membrane. [ABSTRACT FROM AUTHOR]

Bats harbor many zoonotic viruses, including highly pathogenic viruses of humans and other mammals, but they are typically asymptomatic in bats. To further understand the antiviral immunity of bats, we screened and identified a series of bat major histocompatibility complex (MHC) I Ptal-N*01:01–binding peptides derived from four different bat-borne viruses, i.e., Hendra virus (HeV), Ebola virus (EBOV), Middle East respiratory syndrome coronavirus (MERS-CoV), and H17N10 influenza-like virus. The structures of Ptal-N*01:01 display unusual peptide presentation features in that the bat-specific 3–amino acid (aa) insertion enables the tight “surface anchoring” of the P1-Asp in pocket A of bat MHC I. As the classical primary anchoring positions, the B and F pockets of Ptal-N*01:01 also show unconventional conformations, which contribute to unusual peptide motifs and distinct peptide presentation. Notably, the features of bat MHC I may be shared by MHC I from various marsupials. Our study sheds light on bat adaptive immunity and may benefit future vaccine development against bat-borne viruses of high impact on humans. [ABSTRACT FROM AUTHOR]

Improving predictive understanding of Earth system variability and change requires data–model integration. Efficient data–model integration for complex models requires surrogate modeling to reduce model evaluation time. However, building a surrogate of a large-scale Earth system model (ESM) with many output variables is computationally intensive because it involves a large number of expensive ESM simulations. In this effort, we propose an efficient surrogate method capable of using a few ESM runs to build an accurate and fast-to-evaluate surrogate system of model outputs over large spatial and temporal domains. We first use singular value decomposition to reduce the output dimensions and then use Bayesian optimization techniques to generate an accurate neural network surrogate model based on limited ESM simulation samples. Our machine-learning-based surrogate methods can build and evaluate a large surrogate system of many variables quickly. Thus, whenever the quantities of interest change, such as a different objective function, a new site, and a longer simulation time, we can simply extract the information of interest from the surrogate system without rebuilding new surrogates, which significantly reduces computational efforts. We apply the proposed method to a regional ecosystem model to approximate the relationship between eight model parameters and 42 660 carbon flux outputs. Results indicate that using only 20 model simulations, we can build an accurate surrogate system of the 42 660 variables, wherein the consistency between the surrogate prediction and actual model simulation is 0.93 and the mean squared error is 0.02. This highly accurate and fast-to-evaluate surrogate system will greatly enhance the computational efficiency of data–model integration to improve predictions and advance our understanding of the Earth system. [ABSTRACT FROM AUTHOR]

Ischemic stroke is usually followed by inflammatory responses mediated by microglia. However, the effect of statins on directly preventing posthypoxia microglia inflammatory factors to prevent injury to surrounding healthy neurons is unclear. Atorvastatin and rosuvastatin, which have different physical properties regarding their lipid and water solubility, are the most common HMG-CoA reductase inhibitors (statins) and might directly block posthypoxia microglia inflammatory factors to prevent injury to surrounding neurons. Neuronal damage and microglial activation of the peri-infarct areas were investigated by Western blotting and immunofluorescence after 24 hours in a middle cerebral artery occlusion (MCAO) rat model. The decrease in neurons was in accordance with the increase in microglia, which could be reversed by both atorvastatin and rosuvastatin. The effects of statins on blocking secretions from posthypoxia microglia and reducing the secondary damage to surrounding normal neurons were studied in a coculture system in vitro. BV2 microglia were cultured under oxygen glucose deprivation (OGD) for 3 hours and then cocultured following reperfusion for 24 hours in the upper wells of transwell plates with primary neurons being cultured in the bottom wells. Inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and cyclooxygenase-2 (COX2), which are activated by the nuclear factor-kappa B (NF-κB) signaling pathway in OGD-induced BV2 microglia, promoted decreased release of the anti-inflammatory cytokine IL-10 and apoptosis of neurons in the coculture systems according to ELISA and Western blotting. However, pretreatment with atorvastatin or rosuvastatin significantly reduced neuronal death, synaptic injury, and amyloid-beta (Aβ) accumulation, which might lead to increased low-density lipoprotein receptors (LDLRs) in BV2 microglia. We concluded that the proinflammatory mediators released from postischemia damage could cause damage to surrounding normal neurons, while HMG-CoA reductase inhibitors prevented neuronal apoptosis and synaptic injury by inactivating microglia through blocking the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Improving predictive understanding of Earth system variability and change requires data-model integration. Efficient data-model integration for complex models requires surrogate modeling to reduce model evaluation time. However, building a surrogate of a large-scale Earth system model (ESM) with many output variables is computationally intensive because it involves a large number of expensive ESM simulations. In this effort, we propose an efficient surrogate method capable of using a few ESM runs to build an accurate and fast-to-evaluate surrogate system of model outputs over large spatial and temporal domains. We first use singular value decomposition to reduce the output dimensions, and then use Bayesian optimization techniques to generate an accurate neural network surrogate model based on limited ESM simulation samples. Our machine learning based surrogate methods can build and evaluate a large surrogate system of many variables quickly. Thus, whenever the quantities of interest change such as a different objective function, a new site, and a longer simulation time, we can simply extract the information of interest from the surrogate system without rebuilding new surrogates, which significantly saves computational efforts. We apply the proposed method to a regional ecosystem model to approximate the relationship between 8 model parameters and 42 660 carbon flux outputs. Results indicate that using only 20 model simulations, we can build an accurate surrogate system of the 42 660 variables, where the consistency between the surrogate prediction and actual model simulation is 0.93 and the mean squared error is 0.02. This highly-accurate and fast-to-evaluate surrogate system will greatly enhance the computational efficiency in data-model integration to improve predictions and advance our understanding of the Earth system. [ABSTRACT FROM AUTHOR]

[Display omitted] • Wood was reengineered as a structural material with excellent stability and strength. • Wood compression deformation was fixed through DES-assisted densification. • In-situ lignin modification aiming to boost reactivity occurs during pretreatment. • Cross-linking occurs during densification between autologous molecules and matrix. Densified wood is preferable for structural applications because of its excellent mechanical properties and sustainability, but the fixation of its compression deformation and the prevention of water-induced mechanical deterioration remain challenging. Herein, an eco-friendly and highly efficient method was designed for producing dimensionally-stable densified wood, including deep eutectic solvent (DES) pretreatment and subsequent temperature-assisted compression. Hemicellulose, amorphous cellulose, and lignin were in-situ depolymerized or modified by DES pretreatment, and then they were repolymerized or recondensed by temperature-assisted compression to form a crosslinking network to achieve deformation fixation. This DES-assisted densified wood showed a lower set recovery rate (4.7% vs. 69.8%) and higher bending strength (173.7 MPa vs. 69.2 MPa) than densified natural wood. Moreover, its surface hardness could be maintained at a higher level even after a water-soaking/boiling test due to its excellent dimensional stability. DES pretreatment could be considered as a suitable and green strategy for producing high-strength structural wood with excellent dimensional stability. [ABSTRACT FROM AUTHOR]

Vehicles generally move smoothly and with high speeds on elevated roads, thereby producing specific traffic-related carbon emissions in contrast to ground roads. Hence, a portable emission measurement system was adopted to determine traffic-related carbon emissions. The on-road measurement results revealed that the instantaneous emissions of CO 2 and CO from elevated vehicles were 17.8% and 21.9% higher than those from ground vehicles, respectively. Based on it, the vehicle specific power was confirmed to exhibit a positive exponential relationship with instantaneous CO 2 and CO emissions. In addition to carbon emissions, carbon concentrations on roads were simultaneously measured. The average CO 2 and CO emissions on elevated roads in urban areas were 1.2% and 6.9% higher than those on ground roads, individually. Finally, a numerical simulation was performed, and the results verified that elevated roads could deteriorate the air quality on ground roads but improve the air quality above them. What ought to be paid attention to is that the elevated roads present varied traffic behaviour and cause particular carbon emissions, indicating that comprehensive consideration and further balance among the traffic-related carbon emissions are necessary when building elevated roads to alleviate the traffic congestion in urban areas. • Vehicles exhaust CO 2 and CO on elevated roads were 17.8% and 21.9% higher than those on ground roads. • The instantaneous CO 2 and CO emissions increase exponentially as VSP enhance. • CO 2 and CO concentrations on elevated road are 1.2% and 6.9% higher than that on ground road. [ABSTRACT FROM AUTHOR]

The electrolysis of seawater into clean hydrogen energy requires the development of effective electrocatalysts. Yet, most current research focuses on the activity of electrocatalysts while disregarding their corrosion resistance. We developed a unique porous stake-like composite catalyst on a nickel foam substrate (designated by CoMoCH–Cu 2 SeS/NF) using a new monometallic cation release method, demonstrating an outstanding catalytic activity and a high resistance to seawater corrosion. CoMoCH–Cu 2 SeS/NF porous stake-like structure provides a large reaction zone and lots of catalytic active centers. Moreover, the synergistic effect of Cu 2 SeS and CoMoCH facilitates the electron transfer. Doping high-valence Mo element into CoCH generates a strong electronic structural interactions between metals. Hence, the CoMoCH–Cu 2 SeS/NF composite catalyst demonstrates an outstanding OER/HER performance in different alkaline solutions, with a low overpotential and good continuous electrolysis durability. The electrode pair assembled by such a composite catalyst delivers a current density of 100 mA cm−2 at 1.72 V in alkaline simulated seawater. In natural seawater, CoMoCH/NF has a lower electrochemical corrosion rate of 0.85 mm/a than Cu 2 SeS/NF (9.97 mm/a) and CoCH/NF (5.72 mm/a). The carbonate anions in the CoCH intercalation structure and the doping of Mo element with strong corrosion resistance enhanced the chlorine corrosion resistance of CoMoCH–Cu 2 SeS/NF in natural seawater and protected the Cu 2 SeS active components. This research may guide the design and development of high-activity and corrosion-resistant composite electrocatalysts with novel architectures for hydrogen production by seawater electrolysis. [Display omitted] • Construction of stake-like CoMoCH–Cu 2 SeS/NF composite electrocatalyst by a new monometallic cation release method. • Proposing an anti-corrosion strategy with CoMoCH protective layer for seawater electrolysis. • Revealing the negatively charged anions can inhibit the chloride corrosion by electrostatic repulsion. • Achieving the comprehensive improvement of catalytic activity and corrosion resistance. [ABSTRACT FROM AUTHOR]

Introduction: The objective of the study was to identify trends in incidence of adult diffuse gliomas in the United States and evaluate the contribution of age, period, and cohort effects to the trends. Methods: Using the Surveillance, Epidemiology, and End Results 9 database, primary diffuse glioma patients (≥20 years old) diagnosed from 1973 to 2014 were identified. Incidence trends were analyzed using joinpoint regression and age‐period‐cohort modeling. Results: Overall, the incidence for adult glioma decreased slowly from 1985 to 2014 (annual percent change [APC] = 0.5%, 95% confidence intervals [CI], 0.3%‐0.6%). In histology subtype‐stratified analysis, glioblastoma and nonglioblastoma exhibited opposite trends. The incidence for glioblastoma increased from 1978 to 2014 (APC for year 1978‐1992 = 2.7%, 95% CI, 1.8%‐3.6%; APC for 1992‐2014 = 0.3%, 95% CI, 0%‐0.6%), while the incidence for nonglioblastoma decreased significantly from 1982 to 2014 (APC = 2.2%, 95% CI, 2.0%‐2.5%). Age‐period‐cohort modeling revealed significant period and cohort effects, with the patterns for glioblastoma and nonglioblastoma distinctive from each other. Compared with adults born 1890s, those born 1920s had approximately 4‐fold the risk of glioblastoma after adjustment of age and period effects, while the risk of nonglioblastoma was reduced by half in individuals in the 1939 cohort as compared with those in the 1909 cohort. Conclusions: The results support the hypothesis of etiological heterogeneity of diffuse gliomas by histology subtypes. The established risk factors cannot fully explain the distinct patterns by histology subtypes, which necessitate further epidemiological studies. While the incidence for adult glioma decreased slowly from 1985 to 2014, glioblastoma and nonglioblastoma displayed distinctive patterns of age, period, and birth cohort effects. [ABSTRACT FROM AUTHOR]

Abstract: Calibration of the Energy Exascale Earth System Model (E3SM), land model (ELMv0) is challenging because of its model complexity, strong model nonlinearity, and significant computational requirements. Therefore, only a limited number of simulations can be allowed in any attempt to find a near‐optimal solution within an affordable time. The goal of this study is to calibrate some of the ELMv0 parameters to improve model projection of carbon fluxes. We propose a computationally efficient global optimization procedure using sparse‐grid based surrogates. We first use advanced sparse grid (SG) interpolation to construct a surrogate system of the ELMv0, and then calibrate the surrogate model in the optimization process. As the surrogate model is a polynomial whose evaluation is fast, it can be efficiently evaluated a sufficiently large number of times in the optimization, which facilitates the global search. We calibrate eight parameters against five years of net ecosystem exchange, total leaf area index, and latent heat flux data from the U.S. Missouri Ozark flux tower. The calibrated model is then used for predicting the three variables in the following 4 years. The results indicate that an accurate surrogate model can be created for the ELMv0 with a relatively small number of SG points, i.e., a few ELMv0 simulations that can be fully parallel. And, the application of the optimized parameters leads to a better model performance and a higher predictive capability than the default parameter values in the ELMv0. [ABSTRACT FROM AUTHOR]

• A QSP model quantified the PD-enhanced TMDD of an engineered cytokine in cynos. • The model simultaneously described PK and PD of several lymphocyte subsets. • The model can simulate PK/PD at alternative dosing regimen. • The model will be useful for interpreting clinical data and support regimen optimization. • The model can be adapted for other lymphoproliferative cytokine agonists. XmAb24306 is a lymphoproliferative interleukin (IL)-15/IL-15 receptor α (IL-15Rα) Fc-fusion protein currently under clinical investigation as an immunotherapeutic agent for cancer treatment. XmAb24306 contains mutations in IL-15 that attenuate its affinity to the heterodimeric IL-15 receptor βγ (IL-15R). We observe substantially prolonged pharmacokinetics (PK) (half-life ∼ 2.5 to 4.5 days) in single- and repeat-dose cynomolgus monkey (cyno) studies compared to wild-type IL-15 (half-life ∼ 1 hour), leading to increased exposure and enhanced and durable expansion of NK cells, CD8+ T cells and CD4–CD8– (double negative [DN]) T cells. Drug clearance varied with dose level and time post-dose, and PK exposure decreased upon repeated dosing, which we attribute to increased target-mediated drug disposition (TMDD) resulting from drug-induced lymphocyte expansion (i.e., pharmacodynamic (PD)-enhanced TMDD). We developed a quantitative systems pharmacology (QSP) model to quantify the complex PKPD behaviors due to the interactions of XmAb24306 with multiple cell types (CD8+, CD4+, DN T cells, and NK cells) in the peripheral blood (PB) and lymphoid tissues. The model, which includes nonspecific drug clearance, binding to and TMDD by IL15R differentially expressed on lymphocyte subsets, and resultant lymphocyte margination/migration out of PB, expansion in lymphoid tissues, and redistribution to the blood, successfully describes the systemic PK and lymphocyte kinetics observed in the cyno studies. Results suggest that after 3 doses of every-two-week (Q2W) doses up to 70 days, the relative contributions of each elimination pathway to XmAb24306 clearance are: DN T cells > NK cells > CD8+ T cells > nonspecific clearance > CD4+ T cells. Modeling suggests that observed cellular expansion in blood results from the influx of cells expanded by the drug in lymphoid tissues. The model is used to predict lymphoid tissue expansion and to simulate PK-PD for different dose regimens. Thus, the model provides insight into the mechanisms underlying the observed PK-PD behavior of an engineered cytokine and can serve as a framework for the rapid integration and analysis of data that emerges from ongoing clinical studies in cancer patients as single-agent or given in combination. [Display omitted] [ABSTRACT FROM AUTHOR]

Chinese chestnut (Castanea mollissima Blume) is native to China and distributes widely in arid and semi-arid mountain area with barren soil. As a perennial crop, chestnut is an alternative food source and acts as an important commercial nut tree in China. Starch is the major metabolite in nuts, accounting for 46 ~ 64% of the chestnut dry weight. The accumulation of total starch and amylopectin showed a similar increasing trend during the development of nut. Amylopectin contributed up to 76% of the total starch content at 80 days after pollination (DAP). The increase of total starch mainly results from amylopectin synthesis. Among genes associated with starch biosynthesis, CmSBEs (starch branching enzyme) showed significant increase during nut development. Two starch branching enzyme isoforms, CmSBE I and CmSBE II, were identified from chestnut cotyledon using zymogram analysis. CmSBE I and CmSBE II showed similar patterns of expression during nut development. The accumulations of CmSBE transcripts and proteins in developing cotyledons were characterized. The expressions of two CmSBE genes increased from 64 DAP and reached the highest levels at 77 DAP, and SBE activity reached its peak at 74 DAP. These results suggested that the CmSBE enzymes mainly contributed to amylopectin synthesis and influenced the amylopectin content in the developing cotyledon, which would be beneficial to chestnut germplasm selection and breeding. [ABSTRACT FROM AUTHOR]

An optical fiber optofluidic biosensor for the detection of DNA hybridization and methylation has been proposed and experimentally demonstrated. An in-line fiber Michelson interferometer was formed in the photonic crystal fiber. A micrhole in the collapsed region, which combined the tunable mode coupler and optofluidic channel, was fabricated by using femtosecond laser micromachining. The mode field diameter of the guided light is changed with the refractive index in the optofluidic channel, which results in the tunable coupling ratio. Label-free detections of the DNA hybridization and methylation have been experimentally demonstrated. The probe single stranded DNA (ssDNA) was bound with the surface of the optofluidic channel through the Poly- l -lysine layer, and the hybridization between a short 22-mer probe ssDNA and a complementary target ssDNA was carried out and detected by interrogating the fringe visibility of the reflection spectrum. Then, the DNA methylation was also detected through the binding between the methylated DNA and the 5-methylcytosine (5-mC) monoclonal antibody. The experiments results demonstrate that the limit of detection of 5 nM is achieved, establishing the tunable mode coupler as a sensitive and versatile biosensor. The sensitive optical fiber optofluidic biosensor possesses high specificity and low temperature cross-sensitivity. [ABSTRACT FROM AUTHOR]

Introduction: The viral etiological characteristics and prevalence of hospitalized children with acute respiratory tract infection were preliminary studied in Wuhan City during the COVID-19 pandemic, to provide a reliable scientific basis for better understanding of the role of various pathogens in cases and for the prevention and clinical treatment of acute respiratory tract infection. Methods: A total of 69,086 children with acute respiratory infections hospitalized and treated in our department from January 2018 to December 2022 were enrolled as our research subjects. Sociodemographic and clinical data as well as nasopharyngeal samples were collected from patients. Respiratory syncytial virus (RSV), adenovirus (ADV), infuenza virus A (FluA), infuenza virus B (FluB), and parainfluenza virus (PIV) were detected by direct immunofluorescence (DFA) to understand and analyze the epidemic characteristics of respiratory pathogens in children during the COVID-19 pandemic. Results: The total detection rate of respiratory pathogens was 24.52% of the 69,086 hospitalized children. The frequency of respiratory viruses in those ADV, RSV, FluA, FluB, and PIV was 14.67%, 46.40%, 7.76%, 5.23%, and 25.95%. There were significant differences between the various pathogens (P < 0.001). There were the fewest pathogen-positive patients and positive detection rate in 2020 during the COVID-19 pandemic. There were significant differences in the pathogen detection rate among different years (P < 0.001). In addition, the results showed that the total detection rate of respiratory virus tested in different age groups was significantly different (P < 0.001). The positive detection rate was highest in the 1–3-year-old age group, which is prone to acute respiratory infections. We also found that different pathogens showed obvious seasonal fluctuation and epidemic. RSV reached its peak in winter. ADV is mainly prevalent in spring and summer. FluA has a high detection rate in winter. Winter and spring are the peak seasons for FluB infection, whereas PIV is detected in all seasons, with a higher incidence rate in the spring and summer. Conclusion: The epidemiological distribution of pathogens of acute respiratory tract infection in hospitalized children in Wuhan from 2018 to 2022 varies with gender, age, and season. Nonpharmaceutical interventions (NPIs) were implemented as control measures worldwide and reduced the transmission of respiratory pathogens. NPIs are likely to be the primary driver of the dramatic reduction in respiratory virus infection activity in the early stages of the COVID-19 pandemic, to dissolving NPIs can lead to a recurrence of viral infection pathogens, especially in children. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a toxic heavy metal affecting the normal growth of plants. Nitrate (NO 3 −) and ammonium (NH 4 +) are the primary forms of inorganic nitrogen (N) absorbed by plants. However, the mechanism of N absorption and regulation under Cd stress remains unclear. This study found that: (1) Cd treatment affected the biomass, root length, and Cd2+ flux in Solanum nigrum seedling roots. Specifically, 50 μM Cd significantly inhibited NO 3 − influx while increased NH 4 + influx compared with 0 and 5 μM Cd treatments measured by non-invasive micro-test technology. (2) qRT-PCR analysis showed that 50 μM Cd inhibited the expressions of nitrate transporter genes, SnNRT2;4 and SnNRT2;4-like , increased the expressions of ammonium transporter genes, SnAMT1;2 and SnAMT1;3 , in the roots. (3) Under NH 4 + supply, 50 μM Cd significantly induced the expressions of the aquaporin genes, SnPIP1;5 , SnPIP2;7 , and SnTIP2;1. Our results showed that 50 μM Cd stress promoted NH 4 + absorption by up-regulating the gene expressions of NH 4 + transporter and aquaporins, suggesting that high Cd stress can affect the preference of N nutrition in S. nigrum. [Display omitted] • 50 μM Cd increased Cd2+ influx of S. nigrum seedlings compared with 5 μM Cd. • 50 μM Cd inhibited NO 3 − influx and NH 4 + efflux in root meristem zone. • NH 4 + influx was promoted by 50 μM Cd in root elongation zone compared with 5 μM Cd. • Cd treatment promoted NH 4 + transporter SnAMT1;3 expression in roots. • 50 μM Cd promoted aquaporin SnTIP2;1 expression in roots. [ABSTRACT FROM AUTHOR]

A novel porous and hydrophobic Brønsted acidic solid catalyst (POSS-[VMPS][H 2 SO 4 ]) was successfully synthesized by copolymerization of polyhedral oligomeric vinylsilsesquioxanes (POSSs) and sulfonic acid-functionalized imidazole ionic liquids. Catalytic tests for the esterification of oleic acid with methanol have shown that this newly obtained polymeric hybrid exhibits very high catalytic activity and selectivity, which was more active or comparable to those of the common solid acid Amberlite-732 and liquid acid H 2 SO 4 . Moreover, the catalyst has a good recyclability without significant loss in the activity. [ABSTRACT FROM AUTHOR]

In this study, a new type of highly cross-linked cationic polymer microspheres was synthesized by a simple procedure of combining 1,2,4,5-tetrakis(bromomethyl)benzene and 4,4′-bipyridine. The influence of solvent used on the material structure and morphology was investigated and the obtained cationic polymers were fully characterized by FT-IR, BET, SEM, EDS, and TGA. Catalytic tests in the synthesis of cyclic carbonate from carbon dioxide (CO 2 ) and epoxides under mild conditions, along with comparisons to various counterparts, well demonstrate that the newly designed cross-linked cationic polymer with regular spherical structure exhibits high activity and selectivity, coupled with easy recovery and steadily reuse. [ABSTRACT FROM AUTHOR]

Background: During cell-cycle progression, substrates of a single master regulatory enzyme can be modified in a specific order. Here, we used experimental and computational approaches to dissect the quantitative mechanisms underlying the ordered degradation of the substrates of the ubiquitin ligase APC/CCdc20, a key regulator of chromosome segregation in mitosis. Results: We show experimentally that the rate of catalysis varies with different substrates of APC/CCdc20. Using a computational model based on multi-step ubiquitination, we then show how changes in the interaction between a single substrate and APC/CCdc20 can alter the timing of degradation onset relative to APC/CCdc20 activation, while ensuring a fast degradation rate. Degradation timing and dynamics depend on substrate affinity for the enzyme as well as the catalytic rate at which the substrate is modified. When two substrates share the same pool of APC/CCdc20, their relative enzyme affinities and rates of catalysis influence the partitioning of APC/CCdc20 among substrates, resulting in substrate competition. Depending on how APC/CCdc20 is partitioned among its substrates, competition can have minor or major effects on the degradation of certain substrates. We show experimentally that increased expression of the early APC/CCdc20 substrate Clb5 does not delay the degradation of the later substrate securin, arguing against a role for competition with Clb5 in establishing securin degradation timing. Conclusions: The degradation timing of APC/CCdc20 substrates depends on the multi-step nature of ubiquitination, differences in substrate-APC/CCdc20 interactions, and competition among substrates. Our studies provide a conceptual framework for understanding how ordered modification can be established among substrates of the same regulatory enzyme, and facilitate our understanding of how precise temporal control is achieved by a small number of master regulators to ensure a successful cell division cycle. [ABSTRACT FROM AUTHOR]

We investigate the lateral current spreading effect and its influences on the transmission characteristics of ridge waveguide electroabsorption modulators. An RF equivalent circuit based on a transmission line model explicitly accounting for this effect is proposed. The equivalent circuit parameters in our model extracted from S11 curve fitting are used to simulate the S21 response (electro-optical response (E/O) response), which matches well with the measured direct S21 small-signal modulation response. The physical significance of our model parameters can be well explained based on the secondary ion mass spectroscopy doping profiling and the simulation of the current spreading effect in our device structure. [ABSTRACT FROM AUTHOR]

Furanocoumarin compound psoralen (PRN) is a major active ingredient found in herbaceous plants. PRN has been used for the treatment of various dermal diseases in China. We evaluated the inhibitory effect of PRN on cytochrome P450 2B6 (CYP2B6) and found that PRN induced a time-, concentration-, and NADPH-dependent inactivation of CYP2B6 with the values of K I and k inact being 110.2 μM and 0.200 min −1 , respectively. Ticlopidine, a CYP2B6 substrate, prevented the enzyme from the inactivation induced by PRN. Exogenous nucleophile glutathione (GSH) and catalase/superoxide dismutase showed limited protection of CYP2B6 from the inactivation. The estimated partition ratio of the inactivation was approximately 400. GSH trapping experiments indicates that an epoxide or/and γ -ketoenal intermediate was formed in microsomal incubations with PRN. In summary, PRN was characterized as a mechanism-based inactivator of CYP2B6. [ABSTRACT FROM AUTHOR]

Human lysozyme is a natural non-specific immune factor in human milk that plays an important role in the defense of breastfed infants against pathogen infection. Although lysozyme is abundant in human milk, there is only trace quantities in pig milk. Here, we successfully generated transgenic cloned pigs with the expression vector pBAC-hLF-hLZ-Neo and their first generation hybrids (F1). The highest concentration of recombinant human lysozyme (rhLZ) with in vitro bioactivity was 2759.6 ± 265.0 mg/L in the milk of F0 sows. Compared with wild-type milk, rhLZ milk inhibited growth of Escherichia coli K88 during the exponential growth phase. Moreover, rhLZ in milk from transgenic sows was directly absorbed by the intestine of piglets with no observable anaphylactic reaction. Our strategy may provide a powerful tool for large-scale production of this important human protein in pigs to improve resistance to pathogen infection. [ABSTRACT FROM AUTHOR]

[Display omitted] • Human activities played a dominant role in the vegetation restoration. • Population emigration made the greatest contribution to vegetation change (62.47%). • The effect of population migration on vegetation varied with elevation. • The Grain-for-Green program had a positive effect on vegetation. With the continuous increase in urbanization and non-farm wages, many rural labor forces have transferred to urban areas, significantly changing the population distribution and affecting vegetation restoration and ecological environment improvement. This study analyzed the spatiotemporal patterns of vegetation in Chongqing from 2000 to 2018 based on the MODIS EVI dataset, and 862 samples were randomly selected to quantitatively analyze the contribution degree of population emigration to vegetation greenness by using the multivariate linear regression model under the conditions of controlling climate, topography, and policy factors. The results showed that the vegetation in Chongqing presented a significant improvement trend. Human activities played a dominant role in the vegetation restoration in Chongqing from 2000 to 2018. The contribution of population spatial redistribution to vegetation changes was 62.47%, and the contributions gradually decreased with increasing elevation, which were 73.90%, 45.02%, and 17.87% in the low, medium, and high altitude areas, respectively. Furthermore, the Grain-for-Green program significantly affected vegetation variation, and the project had the greatest ecological benefits in medium-altitude areas. [ABSTRACT FROM AUTHOR]

The ubiquitin protein ligase anaphase-promoting complex or cyclosome (APC/C) controls mitosis by promoting ordered degradation of securin, cyclins, and other proteins. The mechanisms underlying the timing of APC/C substrate degradation are poorly understood. We explored these mechanisms using quantitative fluorescence microscopy of GFP-tagged APC/C Cdc20 substrates in living budding yeast cells. Degradation of the S cyclin, CIb5, begins early in mitosis, followed 6 min later by the degradation of securin and DbF4. Anaphase begins when less than half of securin is degraded. The spindle assembly checkpoint delays the onset of CIb5 degradation but does not influence securin degradation. Early CIb5 degradation depends on its interaction with the Cdkl-Cksl complex and the presence of a Cdc20-binding "ABBA motif" in its N-terminal region. The degradation of securin and Dbf4 is delayed by Cdk1-dependent phosphorylation near their Cdc20-binding sites. Thus, a remarkably diverse array of mechanisms generates robust ordering of APC/CCdc20 substrate destruction. [ABSTRACT FROM AUTHOR]

This work develops a new functionality in UCODE_2014 to evaluate Bayesian credible intervals using the Markov Chain Monte Carlo (MCMC) method. The MCMC capability in UCODE_2014 is based on the FORTRAN version of the differential evolution adaptive Metropolis (DREAM) algorithm of Vrugt et al. (2009), which estimates the posterior probability density function of model parameters in high-dimensional and multimodal sampling problems. The UCODE MCMC capability provides eleven prior probability distributions and three ways to initialize the sampling process. It evaluates parametric and predictive uncertainties and it has parallel computing capability based on multiple chains to accelerate the sampling process. This paper tests and demonstrates the MCMC capability using a 10-dimensional multimodal mathematical function, a 100-dimensional Gaussian function, and a groundwater reactive transport model. The use of the MCMC capability is made straightforward and flexible by adopting the JUPITER API protocol. With the new MCMC capability, UCODE_2014 can be used to calculate three types of uncertainty intervals, which all can account for prior information: (1) linear confidence intervals which require linearity and Gaussian error assumptions and typically 10s-100s of highly parallelizable model runs after optimization, (2) nonlinear confidence intervals which require a smooth objective function surface and Gaussian observation error assumptions and typically 100s-1,000s of partially parallelizable model runs after optimization, and (3) MCMC Bayesian credible intervals which require few assumptions and commonly 10,000s-100,000s or more partially parallelizable model runs. Ready access allows users to select methods best suited to their work, and to compare methods in many circumstances. [ABSTRACT FROM AUTHOR]