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Abstract Background Recent research has indicated that parental use of central nervous system-targeting medications during periconceptional periods may affect offspring across various developmental and behavioral domains. The present study sought to investigate the potential influence of paternal use of donepezil, a specific reversible central acetylcholinesterase inhibitor that activates the cholinergic system to promote cognition, on offspring. Results In this study, male rats were bred after 21 days of oral donepezil administration at a dose of 4 mg/kg to generate F1 offspring. Both male and female F₁ offspring displayed enhanced performance in learning and short-term memory tests, including novel object recognition, Y maze, and operant learning. Transcriptomic analysis revealed notable alterations in genes associated with the extracellular matrix in the hippocampal tissue of the F1 generation. Integration with genes related to intelligence identified potential core genes that may be involved in the observed behavioral enhancements. Conclusions These findings indicate that prolonged paternal exposure to donepezil may enhance the learning and memory abilities of offspring, possibly by targeting nonneural, extracellular regions. Further research is required to fully elucidate any potential transgenerational effects.

Abstract Background Acute necrotizing encephalopathy (ANE) and myocarditis are both acute, life-threatening conditions that can be triggered by COVID-19. We report a case of sequential ANE and myocarditis following a COVID-19 infection. Case presentation A 27-year-old female patient was brought to the emergency department due to episodes of fever for two days and a 9-h altered state of consciousness. Her condition rapidly developed into stuporous and hemodynamic instability within serval hours. Veno-arterial extracorporeal membrane oxygenation (ECMO) was rapidly initiated with other supportive treatments. The following-up MRI showed bilateral, symmetrically distributed lesions in the brainstem, bilateral hippocampal regions, and bilateral basal ganglia, consistent with ANE. The diagnosis was confirmed through the detection of SARS-CoV-2 and the exclusion of other potential causes. After weeks of medical treatment, her condition stabilized, and she was transferred for further rehabilitation treatment. Conclusions This case study indicates that COVID-19 may simultaneously and rapidly affect the central nervous system and cardiovascular system, leading to poor outcomes. Accurate diagnosis and timely invasive bridging therapy, when necessary, can be lifesaving. Further exploration of potential mechanisms underlying COVID-19 central nervous system (CNS) and cardiovascular system manifestations will be important.

Purpose: This study aims to compare the effectiveness of pencil push-up training and binocular vision training in treating post-operative mild under-correction in patients with intermittent exotropia. Methods: A prospective cohort study was conducted, including patients who underwent surgery for intermittent exotropia at Children’s Hospital of Nanjing Medical University between June 2022 and January 2023 and experienced post-operative mild under-correction (-8∆ to -15∆). Patients were divided into two groups: pencil push-up training group and binocular vision training group. All patients underwent measurements of exodeviation and stereoacuity at distance and near, sensory fusion, and fusion convergence amplitude. The data were analyzed using independent sample t-tests, repeated measures analysis of variance, and Chi-square tests. Results: There were no statistically significant differences in exodeviation at distance and near between the two training groups before the training. After 6 months of training, the exodeviation at distance and near achieved a significant decrease in both groups (P < 0.05), and the pencil push-up training group showed a similar distance and near exodeviation compared to the binocular vision training group (t = 1.58, P ＞ 0.05; t = 0.43, P ＞ 0.05). After 6 months of training, the binocular vision training group exhibited significantly superior stereoacuity and fusion convergence amplitude compared to the pencil push-up training group (P < 0.001). Conclusion: Both pencil push-up training and binocular vision training are effective in reducing exodeviation in patients with post-operative mild under-correction of intermittent exotropia. However, binocular vision training demonstrates superior efficacy in restoring stereopsis and fusion convergence amplitude compared to pencil push-up training.

BackgroundIn recent years, there has been significant research interest in immunotherapy for colorectal cancer (CRC). Specifically, immunotherapy has emerged as the primary treatment for patients with mismatch repair gene defects (dMMR) or microsatellite highly unstable (MSI-H) who have colorectal cancer. Yet, there is currently no data to support the practicality and safety of neoadjuvant immunotherapy for colorectal cancer with dMMR or MSI-H. Therefore, a study was conducted to identify the postoperative pathology, safety profile, and imaging features of patients with dMMR or MSI-H CRC following neoadjuvant immunotherapy.MethodsThe retrospective study was carried out on patients with locally advanced or metastatic CRC who received immunotherapy at Sichuan Cancer Hospital, with approval from the hospital’s ethics committee. The study aimed to assess the short-term effectiveness of immunotherapy by focusing on pathological complete response (pCR) as the primary outcome, while also considering secondary endpoints such as objective response rate, disease-free survival, and safety profile.ResultsTwenty patients with dMMR/MSI-H CRC who underwent neoadjuvant immunotherapy as part of the treatment were enrolled between May 2019 and February 2024 at Sichuan Cancer Hospital. Out of these patients, eight patients received PD-1 blockade monotherapy as neoadjuvant treatment, while 12 were administered a combined therapy of anti-CTLA-4 and anti-PD-1. 12 patients received Nivolumab plus Ipilimumab regimen and 8 patients received PD-1 blockades (2 patients were Pembrolizumab, 2 patients were Sintilimab, 4 patients were Tislelizumab) monotherapy. Additionally, 19 patients underwent surgery after immunotherapy and of these, 15 (75.0%) achieved complete pathological response (pCR), 8 (66.7%) achieved the same on Nivolumab plus Ipilimumab immunotherapy while 7 (87.5%) achieved on PD-1 antibody monotherapy. The overall response rate (ORR) was 75%, with 45.0% of patients experiencing grade I/II immunotherapy-related adverse events. The most frequent adverse event observed was increased ALT i.e. 20%. Notably, no postoperative complications were observed.ConclusionBased on the findings, neoadjuvant immunotherapy for colorectal cancer may be both safe and effective in clinical practice. Furthermore, the study suggested that dual immunotherapy could potentially increase the immunotherapy cycle and contribute to a superior pCR rate. However, the conclusion emphasized the need for further prospective clinical trials to validate these results.

Abstract Organic electrochemical transistors (OECTs) are of great interest in low‐power bioelectronics and neuromorphic computing, as they utilize organic mixed ionic‐electronic conductors (OMIECs) to transduce ionic signals into electrical signals. However, the poor environmental stability of OMIEC materials significantly restricts the practical application of OECTs. Therefore, the non‐fused planar naphthalenediimide (NDI)‐dialkoxybithiazole (2Tz) copolymers are fine‐tuned through varying ethylene glycol (EG) side chain lengths from tri(ethylene glycol) to hexa(ethylene glycol) (namely P‐XO, X = 3–6) to achieve OECTs with high‐stability and low threshold voltage. As a result, the NDI‐2Tz copolymers exhibit ambipolarity, rapid response (

Abstract Background Ultrasound-guided percutaneous axillary vein cannulation can reduce cannulation failure and mechanical complications, is as safe and effective as internal jugular vein cannulation, and is superior to subclavian vein cannulation using landmark technique. As far, reports of venovenous extracorporeal membrane oxygenation (VV-ECMO) with percutaneous axillary vein cannulation are rare. Case presentation A 64-year-old man presenting with dyspnea and chest tightness after aspirating sewage was admitted to the emergency department. Computed tomography (CT) showed diffuse exudation of both lungs and arterial blood gas analysis showed an oxygenation index of 86. He was diagnosed with aspiration pneumonia-induced acute respiratory distress syndrome (ARDS) and intubated for deteriorated oxygenation. Despite the combination therapy of protective mechanical ventilation and prone position, the patient’s oxygenation deteriorated further, accompanied with multiple organ dysfunction syndrome, which indicated the requirement of support with VV-ECMO. However, vascular ultrasound detected multiple thrombus within bilateral internal jugular veins. As an alternative, right axillary vein was chosen as the access site of return cannula. Subsequently, femoral-axillary VV-ECMO was successfully implemented under the ultrasound guidance, and the patient’s oxygenation was significantly improved. Unfortunately, the patient died of hyperkalemia-induced ventricular fibrillation after 36 h of VV-ECMO running. Despite the poor prognosis, the blood flow during ECMO run was stable, and we observed no bleeding complication, vascular injury, or venous return disorder. Conclusions Axillary vein is a feasible alternative access site of return cannula for VV-ECMO if internal jugular vein access were unavailable.

Abstract Epidemiological investigations indicate that parental drug abuse experiences significantly influenced the addiction vulnerability of offspring. Studies using animal models have shown that paternal cocaine use and highly motivated drug-seeking behavior are important determinants of offspring addiction susceptibility. However, the key molecules contributing to offspring addiction susceptibility are currently unclear. The motivation for cocaine-seeking behavior in offspring of male rats was compared between those whose fathers self-administered cocaine (SA) and those who were yoked with them and received non-contingent cocaine administrations (Yoke). We found that paternal experience with cocaine-seeking behavior, but not direct cocaine exposure, could lead to increased lever-pressing behavior in male F1 offspring. This effect was observed without significant changes to the dose-response relationship. The transcriptomes of ventral tegmental area (VTA) in offspring were analyzed under both naive state and after self-administration training. Specific transcriptomic changes in response to paternal cocaine-seeking experiences were found, which mainly affected biological processes such as synaptic connections and receptor signaling pathways. Through joint analysis of these candidate genes and parental drug-seeking motivation scores, we found that gamma-aminobutyric acid receptor subunit gamma-3 (Gabrg3) was in the hub position of the drug-seeking motivation-related module network and highly correlated with parental drug-seeking motivation scores. The downregulation of Gabrg3 expression, caused by paternal motivational cocaine-seeking, mainly occurred in GABAergic neurons in the VTA. Furthermore, down-regulating GABAergic Gabrg3 in VTA resulted in an increase in cocaine-seeking behavior in the Yoke F1 group. This down-regulation also reduced transcriptome differences between the Yoke and SA groups, affecting processes related to synaptic formation and neurotransmitter transmission. Taken together, we propose that paternal cocaine-seeking behavior, rather than direct drug exposure, significantly influences offspring addiction susceptibility through the downregulation of Gabrg3 in GABAergic neurons of the VTA, highlighting the importance of understanding specific molecular pathways in the intergenerational inheritance of addiction vulnerability.

Abstract It has been previously established that paternal development of a strong incentive motivation for cocaine can predispose offspring to develop high cocaine-seeking behavior, as opposed to sole exposure to the drug that results in drug resistance in offspring. However, the adaptive changes of the reward circuitry have not been fully elucidated. To infer the key nuclei and possible hub genes that determine susceptibility to addiction in offspring, rats were randomly assigned to three groups, cocaine self-administration (CSA), yoked administration (Yoke), and saline self-administration (SSA), and used to generate F1. We conducted a comprehensive transcriptomic analysis of the male F1 offspring across seven relevant brain regions, both under drug-naïve conditions and after cocaine self-administration. Pairwise differentially expressed gene analysis revealed that the orbitofrontal cortex (OFC) exhibited more pronounced transcriptomic changes in response to cocaine exposure, while the dorsal hippocampus (dHip), dorsal striatum (dStr), and ventral tegmental area (VTA) exhibited changes that were more closely associated with the paternal voluntary cocaine-seeking behavior. Consistently, these nuclei showed decreased dopamine levels, elevated neuronal activation, and elevated between-nuclei correlations, indicating dopamine-centered rewiring of the midbrain circuit in the CSA offspring. To determine if possible regulatory cascades exist that drive the expression changes, we constructed co-expression networks induced by paternal drug addiction and identified three key clusters, primarily driven by transcriptional factors such as MYT1L, POU3F4, and NEUROD6, leading to changes of genes regulating axonogenesis, synapse organization, and membrane potential, respectively. Collectively, our data highlight vulnerable neurocircuitry and novel regulatory candidates with therapeutic potential for disrupting the transgenerational inheritance of vulnerability to cocaine addiction.

Abstract Gut microbiota can influence host gene expression and physiology through metabolites. Besides, the presence or absence of gut microbiome can reprogram host transcriptome and epitranscriptome as represented by N6‐methyladenosine (m6A), the most abundant mammalian mRNA modification. However, which and how gut microbiota‐derived metabolites reprogram host transcriptome and m6A epitranscriptome remain poorly understood. Here, investigation is conducted into how gut microbiota‐derived metabolites impact host transcriptome and m6A epitranscriptome using multiple mouse models and multi‐omics approaches. Various antibiotics‐induced dysbiotic mice are established, followed by fecal microbiota transplantation (FMT) into germ‐free mice, and the results show that bile acid metabolism is significantly altered along with the abundance change in bile acid‐producing microbiota. Unbalanced gut microbiota and bile acids drastically change the host transcriptome and the m6A epitranscriptome in multiple tissues. Mechanistically, the expression of m6A writer proteins is regulated in animals treated with antibiotics and in cultured cells treated with bile acids, indicating a direct link between bile acid metabolism and m6A biology. Collectively, these results demonstrate that antibiotic‐induced gut dysbiosis regulates the landscape of host transcriptome and m6A epitranscriptome via bile acid metabolism pathway. This work provides novel insights into the interplay between microbial metabolites and host gene expression.

Abstract Amphibians and reptiles, especially the critically endangered Chinese alligators, are vulnerable to climate change. Historically, the decline in suitable habitats and fragmentation has restricted the distribution of Chinese alligators to a small area in southeast Anhui Province in China. However, the effects of climate change on range‐restricted Chinese alligator habitats are largely unknown. We aimed to predict current and future (2050s and 2070s) Chinese alligator distribution and identify priority conservation areas under climate change. We employed species distribution models, barycenter migration analyses, and the Marxian model to assess current and future Chinese alligator distribution and identify priority conservation areas under climate change. The results showed that the lowest temperature and rainfall seasonality in the coldest month were the two most important factors affecting the distribution of Chinese alligators. Future predictions indicate a reduction (3.39%–98.41%) in suitable habitats and a westward shift in their distribution. Further, the study emphasizes that suitable habitats for Chinese alligators are threatened by climate change. Despite the impact of the Anhui Chinese Alligator National Nature Reserve, protection gaps persist, with 78.27% of the area lacking priority protected area. Our study provides crucial data for Chinese alligator adaptation to climate change and underscores the need for improved conservation strategies. Future research should refine conservation efforts, consider individual plasticity, and address identified limitations to enhance the resilience of Chinese alligator populations in the face of ongoing climate change.

IntroductionDuring the de-escalation phase of circulatory shock, norepinephrine weaning may induce diverse arterial pressure responses in patients with different vasomotor tones. Dynamic arterial elastance (Eadyn) has been extensively studied to predict the arterial pressure response to interventions. We conducted this meta-analysis to systematically assess the predictive performance of Eadyn for the mean arterial pressure (MAP) response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome.Materials and methodsA systematic literature search was conducted on May 29, 2023 (updated on January 21, 2024), to identify relevant studies from electronic databases. The area under the hierarchical summary receiver operating characteristic curve (AUHSROC) was estimated as the primary measure of diagnostic accuracy because of the varied thresholds reported. Additionally, we observed the distribution of the cutoff values of Eadyn, while computing the optimal value and its corresponding 95% confidential interval (CI).ResultsA total of 5 prospective studies met eligibility, comprising 183 participants, of whom 67 (37%) were MAP responders. Eadyn possessed an excellent ability to predict the MAP response to norepinephrine weaning in patients with vasoplegic syndrome, with an AUHSROC of 0.93 (95% CI: 0.91–0.95), a pooled sensitivity of 0.94 (95% CI: 0.85–0.98), a pooled specificity of 0.73 (95% CI: 0.65–0.81), and a pooled diagnostic odds ratio of 32.4 (95% CI: 11.7–89.9). The cutoff values of Eadyn presented a nearly conically symmetrical distribution; the mean and median cutoff values were 0.89 (95% CI: 0.80–0.98) and 0.90 (95% CI: not estimable), respectively.ConclusionsThis meta-analysis with limited evidences demonstrates that Eadyn may be a reliable predictor of the MAP response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome.Systematic Review RegistrationPROSPERO CRD42023430362.

Currently, impacts of rapid cropland reclamation and its intense structural changes in internal paddy-upland on ecosystem service are insufficient in Sanjiang Plain, China. Further, land management systems of Sanjiang Plain consist of state-owned and private farms; however, exploring the impact of different land management systems on “land use–landscape–ecosystem service” is still lacking. To reveal this issue, the integrated methodology of “land dynamic tracking–landscape index–improved ecosystem service assessment” was established. Results are displayed below: From 1990 to 2020, land use was featured by decreases in forest (−3308.62 km2), grassland (−6030.86 km2), waters (−475.81 km2), and unused land (−3037.27 km2), with a slight increase in constructed land (+403.25 km2) and a rapid increase in cropland (+12,447.56 km2). Although nearly equal increments of cropland on state-owned and private farms (i.e., 6156.70 km2 vs. 6290.86 km2) were monitored, different cropland structure changes were still revealed, namely a drastic expansion of paddy fields (13,788.32 km2) and an acute decrease in upland crops (−7631.62 km2) on state-owned farms, but both a slight increments in paddy fields (5920.08 km2) and upland crops (370.78 km2) on private farms. For landscape, private farms were more fragmented (SHDI = +0.63%), causing a decrease in aggregation (AI = −0.56%) and a more complex shape (LSI = +23.3%), by contrast, state-owned farms displayed an increased integrity (SHDI = −9.88%), along with an increase in aggregation (AI = +0.43%) and simplified shape (LSI = −13.30%). Evaluated ecosystem service value changed from 338.62 to 296.25 billion yuan from 1990 to 2020, a loss rate of 12.58% in Sanjiang Plain. Then, a new finding showed a higher loss rate on state-owned than private farms (i.e., 30.15% vs. only 6.18%). This study revealed differentiated processes of “land use–landscape–ecosystem service” in different land management system regions in China, providing new findings in the fields of land management system, ecological landscape, and environment.

Toll/interleukin-1 receptor (TIR) domain-containing proteins play a critical role in immune responses in diverse organisms, but their function in bacterial systems remains to be fully elucidated. This study, focusing on Escherichia coli, addresses how TIR domain-containing proteins contribute to bacterial immunity against phage attack. Through an exhaustive survey of all E. coli genomes available in the NCBI database and testing of 32 representatives of the 90% of the identified TIR domain-containing proteins, we found that a significant proportion (37.5%) exhibit antiphage activities. These defense systems recognize a variety of phage components, thus providing a sophisticated mechanism for pathogen detection and defense. This study not only highlights the robustness of TIR systems in bacterial immunity, but also draws an intriguing parallel to the diversity seen in mammalian Toll-like receptors (TLRs), enriching our understanding of innate immune mechanisms across life forms and underscoring the evolutionary significance of these defense strategies in prokaryotes.Here, Wang et al survey Escherichia coli genomes to show that TIR domain-containing proteins in E. coli serve as robust anti-phage systems. [ABSTRACT FROM AUTHOR]

In order to develop a rapid measuring method for canopy density of Chinese alligator (Alligator sinensis) habitat, the images of the habitat are captured from 1 meter off the ground. Then, a canopy density calculating method is established based on an adaptive bimodal threshold segmentation algorithm. The accuracy of the proposed method is evaluated and compared with two methods based on Otsu’s algorithm and iterative algorithm, respectively. The results show that the accuracy of the method based on the adaptive bimodal threshold segmentation algorithm is the highest (absolute error: 0.018±0.016) among these three methods. Please note that the accuracy is higher for images captured on cloudy days as compared to the images captured on sunny days. Moreover, the accuracy is highest for the images with low canopy density (absolute error: 0.006±0.004), and is relatively low for the images with high canopy density (absolute error: 0.020±0.016). The adaptive bimodal threshold segmentation method satisfies the accuracy requirements of canopy density of Chinese alligator (Alligator sinensis) habitat. [ABSTRACT FROM AUTHOR]

Almost all elongator tRNAs (Transfer RNAs) harbor 5-methyluridine 54 and pseudouridine 55 in the T arm, generated by the enzymes TrmA and TruB, respectively, in Escherichia coli. TrmA and TruB both act as tRNA chaperones, and strains lacking trmA or truB are outcompeted by wild type. Here, we investigate how TrmA and TruB contribute to cellular fitness. Deletion of trmA and truB in E. coli causes a global decrease in aminoacylation and alters other tRNA modifications such as acp³U47. While overall protein synthesis is not affected in ΔtrmA and ΔtruB strains, the translation of a subset of codons is significantly impaired. As a consequence, we observe translationally reduced expression of many specific proteins, that are either encoded with a high frequency of these codons or that are large proteins. The resulting proteome changes are not related to a specific growth phenotype, but overall cellular fitness is impaired upon deleting trmA and truB in accordance with a general protein synthesis impact. In conclusion, we demonstrate that universal modifications of the tRNA T arm are critical for global tRNA function by enhancing tRNA maturation, tRNA aminoacylation, and translation, thereby improving cellular fitness irrespective of the growth conditions which explains the conservation of trmA and truB. [ABSTRACT FROM AUTHOR]

[Objectives] To prepare 20 (S)-protopanaxadiol PLGA nanoparticles (20(S)-PPD-PLGA-NPs). [Methods] 20 (S)-PPD-PLGA-NPs were prepared by emulsion solvent evaporation method, and the optimal formulation was screened by Box-Behnken experiment with particle size and drug loading as the indicators through single factor experiment, and the drug release in vitro was carried out. [Results] The average diameter of the nanoparticles was (119.60±2.29) nm and the polydispersity index was (0.12±0.02), the size was uniform. The encapsulation efficiency and drug loading of protopanaxadiol were (87.99±1.29)% and (14.86±0.25)%, respectively. [Conclusions] The 20 (S)-PPD-PLGA-NPs were successfully prepared by emulsion solvent evaporation method, and the 20 (S)-PPD-PLGA-NPs had good stability, to lay a foundation for the study of 20 (S)-PPD-PLGA-NPs in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Abstract Background Integrating quantitative trait loci (QTL) data related to molecular phenotypes with genome-wide association study (GWAS) data is an important post-GWAS strategic approach employed to identify disease-associated molecular features. Various types of molecular phenotypes have been investigated in neuropsychiatric disorders. However, these findings pertaining to distinct molecular features are often independent of each other, posing challenges for having an overview of the mapped genes. Methods In this study, we comprehensively summarized published analyses focusing on four types of risk-related molecular features (gene expression, splicing transcriptome, protein abundance, and DNA methylation) across five common neuropsychiatric disorders. Subsequently, we conducted supplementary analyses with the latest GWAS dataset and corresponding deficient molecular phenotypes using Functional Summary-based Imputation (FUSION) and summary data-based Mendelian randomization (SMR). Based on the curated and supplemented results, novel reliable genes and their functions were explored. Results Our findings revealed that eQTL exhibited superior ability in prioritizing risk genes compared to the other QTL, followed by sQTL. Approximately half of the genes associated with splicing transcriptome, protein abundance, and DNA methylation were successfully replicated by eQTL-associated genes across all five disorders. Furthermore, we identified 436 novel reliable genes, which enriched in pathways related with neurotransmitter transportation such as synaptic, dendrite, vesicles, axon along with correlations with other neuropsychiatric disorders. Finally, we identified ten multiple molecular involved regulation patterns (MMRP), which may provide valuable insights into understanding the contribution of molecular regulation network targeting these disease-associated genes. Conclusions The analyses prioritized novel and reliable gene sets related with five molecular features based on published and supplementary results for five common neuropsychiatric disorders, which were missed in the original GWAS analysis. Besides, the involved MMRP behind these genes could be given priority for further investigation to elucidate the pathogenic molecular mechanisms underlying neuropsychiatric disorders in future studies.

Near-infrared (NIR) phosphor-converted light-emitting diodes/laser diodes (LEDs/LDs) are prospective lighting sources for NIR spectroscopy. However, developing NIR phosphor materials with desired thermal robustness and high photoelectric efficiency is a crucial challenge for their applications. In this work, based on the cationic radius matching effect, a series of (Lu,Y)3(Al,Sc,Cr)2Al3O12 NIR phosphor ceramics (LuYScCr NIR-PCs) were fabricated by vacuum sintering. Excellent thermal stability (95%@150 ℃) was obtained in the prepared NIR-PCs, owing to their weak electron–phonon coupling effect (small Huang–Rhys factor). Being excited at 460 nm, NIR-PCs realized a broadband emission (650–850 nm) with internal quantum efficiency (IQE) of 60.68%. Combining NIR-PCs with LED/LD chips, the maximum output power of the encapsulated LED prototype was 447 mW@300 mA with photoelectric efficiency of as high as 18.6 %@180 mA, and the maximum output power of the LD prototype was 814 mW@2.5 A. The working temperatures of NIR-PCs were 70.8 ℃@300 mA (LED) and 102.8 ℃@3 A (LD). Finally, the prepared NIR-PCs applied in food detection were verified in this study, demonstrating their anticipated application prospects in the future.

Introduction: The Shengxian decoction (SXT), a Chinese herbal medication used to treat heart failure, is composed of Astragali Radix, Anemarrhenae Rhizoma, Bupleuri Radix, Cimicifuage Rhizoma, and Platycodonis Radix. Knowledge of the excretion of the active compounds in this herbal medication is vital for investigating the underlying mechanisms behind its compatibility. However, this remains unclear. Methods: Liquid chromatography coupled with mass spectrometry was performed in both positive and negative modes to assay 18 constituents of SXT from rat urinary, fecal, and biliary samples. Results: The methodology was validated and showed good linearity (r ≥ 0.9), precision, stability, repeatability, and recovery. The relative standard deviations and relative errors for the precision and accuracy did not exceed 15%. The recoveries of all the compounds ranged from 77.37% to 114.82%, and the matrix effect was between 82.53% and 105.71%. The results suggested that, when combined with Platycodonis Radix, the levels of 14 constituents from the four herbs were reduced in the urine, while the levels of six constituents were reduced in the feces. Conclusions: The comparative excretion results indicated that Platycodonis Radix reduced the excretion of compounds in SXT, demonstrating the compatibility mechanism and holistic properties of these compounds, favoring the pharmacological effects of SXT.

To integrate large-scale variable renewable energy resources (RESs) in modern power grids, the coordinating control area (CA) operation is the most cost-effective method. This article reviews the technical aspects of CA cooperation. Firstly, a brief overview of the active balancing control within each CA is discussed. Secondly, three general control structures for CA cooperation are innovatively proposed, the corresponding implementation details are analyzed, and some representative technologies are also provided in the systematic analysis. Then, some future research directions such as large-scale power sharing by DC, active power control of RES bases, and the new structure for distributed energy resources in local power grids are prospected. Finally, the changes in power systems brought about by their evolution and importance for further promoting cooperation between CAs are summarized.

Sugar content is an essential indicator for evaluating crisp pear quality and categorization, being used for fruit quality identification and market sales prediction. In this study, we paired a support vector machine (SVM) algorithm with genetic algorithm optimization to reliably estimate the sugar content in crisp pears. We evaluated the spectral data and actual sugar content in crisp pears, then applied three preprocessing methods to the spectral data: standard normal variable transformation (SNV), multivariate scattering correction (MSC), and convolution smoothing (SG). Support vector regression (SVR) models were built using processing approaches. According to the findings, the SVM model preprocessed with convolution smoothing (SG) was the most accurate, with a correlation coefficient 0.0742 higher than that of the raw spectral data. Based on this finding, we used competitive adaptive reweighting (CARS) and the continuous projection algorithm (SPA) to select key representative wavelengths from the spectral data. Finally, we used the retrieved characteristic wavelength data to create a support vector machine model (GASVR) that was genetically tuned. The correlation coefficient of the SG–GASVR model in the prediction set was higher by 0.0321 and the root mean square prediction error (RMSEP) was lower by 0.0267 compared with those of the SG–SVR model. The SG–CARS–GASVR model had the highest correlation coefficient, at 0.8992. In conclusion, the developed SG–CARS–GASVR model provides a reliable method for detecting the sugar content in crisp pear using hyperspectral technology, thereby increasing the accuracy and efficiency of the quality assessment of crisp pear.

The demand for precise indoor localization services is steadily increasing. Among various methods, fingerprint-based indoor localization has become a popular choice due to its exceptional accuracy, cost-effectiveness, and ease of implementation. However, its performance degrades significantly as a result of multipath signal attenuation and environmental changes. In this paper, we propose an indoor localization method based on fingerprints using self-attention and long short-term memory (LSTM). By integrating a self-attention mechanism and LSTM network, the proposed method exhibits outstanding positioning accuracy and robustness in diverse experimental environments. The performance of the proposed method is evaluated under two different experimental scenarios, which involve 2D and 3D moving trajectories, respectively. The experimental results demonstrate that our approach achieves an average localization error of 1.76 m and 2.83 m in the respective scenarios, outperforming the existing state-of-the-art methods by 42.67% and 31.64%.

Abstract The primary triggers that stimulate the body to generate platelet antibodies via immune mechanisms encompass events such as pregnancy, transplantation, and blood transfusion. Interestingly, our findings revealed that a subset of male patients with hepatocellular carcinoma (HCC), despite having no history of transplantation or blood transfusion, has shown positive results in platelet antibody screenings. This hints at the possibility that certain factors, potentially related to the tumor itself or its treatment, may affect antibody production. To delve the causes we initiated this study. We employed a case–control study approach to analyze potential influential factors leading to the positive results via univariate and multivariate regression analysis. We utilized Kendall’s tau-b correlation to examine the relationship between the strength of platelet antibodies and peripheral blood cytopenia. Antitumor medication emerged as an independent risk factor for positive results in HCC patients, and the strength of platelet antibodies positively correlated with the severity of anemia and thrombocytopenia. Without history of blood transfusion, transplantation, pregnancy, those HCC patients underwent recent tumor medication therapy are experiencing peripheral erythrocytopenia or thrombocytopenia, for them platelet antibody screenings holds potential clinical value for prevention and treatment of complications like drug-immune-related anemia and/or bleeding.

Abstract Background Glycerol, as a by-product, mainly derives from the conversion of many crops to biodiesel, ethanol, and fatty ester. Its bioconversion to 1,3-propanediol (1,3-PDO) is an environmentally friendly method. Continuous fermentation has many striking merits over fed-batch and batch fermentation, such as high product concentration with easy feeding operation, long-term high productivity without frequent seed culture, and energy-intensive sterilization. However, it is usually difficult to harvest high product concentrations. Results In this study, a three-stage continuous fermentation was firstly designed to produce 1,3-PDO from crude glycerol by Clostridium butyricum, in which the first stage fermentation was responsible for providing the excellent cells in a robust growth state, the second stage focused on promoting 1,3-PDO production, and the third stage aimed to further boost the 1,3-PDO concentration and reduce the residual glycerol concentration as much as possible. Through the three-stage continuous fermentation, 80.05 g/L 1,3-PDO as the maximum concentration was produced while maintaining residual glycerol of 5.87 g/L, achieving a yield of 0.48 g/g and a productivity of 3.67 g/(L·h). Based on the 14 sets of experimental data from the first stage, a kinetic model was developed to describe the intricate relationships among the concentrations of 1,3-PDO, substrate, biomass, and butyrate. Subsequently, this kinetic model was used to optimize and predict the highest 1,3-PDO productivity of 11.26 g/(L·h) in the first stage fermentation, while the glycerol feeding concentration and dilution rate were determined to be 92 g/L and 0.341 h−1, separately. Additionally, to achieve a target 1,3-PDO production of 80 g/L without the third stage fermentation, the predicted minimum volume ratio of the second fermenter to the first one was 11.9. The kinetics-based two-stage continuous fermentation was experimentally verified well with the predicted results. Conclusion A novel three-stage continuous fermentation and a kinetic model were reported. Then a simpler two-stage continuous fermentation was developed based on the optimization of the kinetic model. This kinetics-based development of two-stage continuous fermentation could achieve high-level production of 1,3-PDO. Meanwhile, it provides a reference for other bio-chemicals production by applying kinetics to optimize multi-stage continuous fermentation. Graphical Abstract

The COVID-19 pandemic has transformed vaccinology. Rapid deployment of mRNA vaccines has saved countless lives. However, these platforms have inherent limitations including lack of durability of immune responses and mucosal immunity, high cost, and thermal instability. These and uncertainties about the nature of future pandemics underscore the need for exploring next-generation vaccine platforms. Here, we present a novel protein-based, bacteriophage T4 platform for rapid design of efficacious vaccines against bacterial and viral pathogens. Full-length antigens can be displayed at high density on a 120 × 86 nm phage capsid through nonessential capsid binding proteins Soc and Hoc. Such nanoparticles, without any adjuvant, induce robust humoral, cellular, and mucosal responses when administered intranasally and confer sterilizing immunity. Combined with structural stability and ease of manufacture, T4 phage provides an excellent needle-free, mucosal pandemic vaccine platform and allows equitable vaccine access to low- and middle-income communities across the globe.