Metabolomics analysis reveals the effect of fermentation on the chemical composition and antioxidant activity of Paeonia lactiflora Root.

Fermentation is an effective means of enhancing the nutritional value of natural medicines, however, it is unclear how the metabolites changed during the fermentation of Paeonia lactiflora root (PLR). This study intends to elucidate how the active constituents and antioxidant activity of PLR change during fermentation. The study examined the levels of total glucosides of paeony (TGP), total flavonoids content (TFC), total phenols content (TPC), and antioxidant capability by high performance liquid chromatography (HPLC) and spectrophotometry. The chemical compositions before and after PLR fermentation were compared utilizing ultra-high performance liquid chromatography-mass spectrometry (UHPLC - MS). The findings from this study indicate that TGP, TFC and TPC peaked at Day 2 of fermentation, and the antioxidant capacity increased after fermentation. Of the 109 detected compounds, 18 were discrepant compounds. In summary, fermentation is an essential strategy for enhancing the functional activity of PLR. The current study could establish a scientific basis for future research on the fermentation of PLR, and provides new insights into the influence of fermentation on chemical composition as well as the antioxidant activity of drugs.

Iron deficiency: prevalence, mortality risk, and dietary relationships in general and heart failure populations.

Background: Iron deficiency (ID) is the most common nutritional deficiency, with little research on its prevalence and long-term outcomes in the general population and those with heart failure (HF). Both the relationships between dietary iron and ID, as well as dietary folate and ID, are understudied. Methods: We used data from the National Health and Nutrition Examination Survey from 1999 to 2002 to investigate the prevalence, prognosis, and relationship between dietary and ID defined by different criteria in the general population (n = 6,660) and those with HF (n = 182). Results: There was no significant difference in the prevalence of ID between HF patients and the general population after propensity score matching. Transferrin saturation (TSAT) <20% was associated with higher 5-year all-cause mortality (HR: 3.49, CI: 1.40-8.72, P = 0.007), while ferritin <30 ng/ml was associated with higher 10-year (HR: 2.70, CI: 1.10-6.67, P = 0.031) and 15-year all-cause mortality (HR: 2.64, CI: 1.40-5.00, P = 0.003) in HF patients. Higher dietary total folate but dietary iron reduced the risk of ID (defined as ferritin <100 ng/ml) in HF patients (OR: 0.80; 95% CI: 0.65-1.00; P = 0.047). Conclusions: The prevalence of ID was identical in HF and non-HF individuals. Ferritin <30 ng/ml was associated with long-term outcomes whereas TSAT <20% was associated with short-term prognosis in both the general population and HF patients. A diet rich in folate might have the potential for prevention and treatment of ID in HF patients.

A Double Perovskite Single Crystal CsCuAgI3.

Eco-friendly halide double perovskites are attracting significant attention as potential substitutes for traditional lead-based halide perovskites. However, their typically wide or indirect band gap limits further technological advancement. This study presents a new, eco-friendly, all-inorganic millimeter-scale CsCuAgI3 single crystal (SC). The crystal exhibits a direct band gap of 2.02 eV at the G-point, markedly superior to that of traditional double perovskites. The absorption and photoluminescence spectra further corroborate its band gap attributes. Owing to the B-site Cu-Ag disorder, the crystal possesses a higher Urbach energy (119 meV), indicative of structural disorder. CsCuAgI3 exhibits a wide Stokes shift of 230 nm, a wide full width at half-maximum (fwhm) of 152 nm, a long fluorescence lifetime of 7.29 µs, and excellent stability. In addition, a photoelectric detection prototype was prepared using a CsCuAgI3 single crystal. Using a 375 nm laser as the excitation source, the device showed a very sensitive photoelectric response, clocking in at (0.37/0.21) seconds. This work offers new insights into developing novel lead-free double perovskite single crystals and exploring their potential applications.

Toll-interacting protein is activated by the transcription factor GATA1 and Sp1 to negatively regulate NF-κB and MAPK pathways in the Japanese eel (Anguilla japonica).

Toll-interacting protein (Tollip) serves as a crucial inhibitory factor in the modulation of Toll-like receptor (TLR)-mediated innate immunological responses. The structure and function of Tollip have been well documented in mammals, yet the information in teleost remained limited. This work employed in vitro overexpression and RNA interference in vivo and in vitro to comprehensively examine the regulatory effects of AjTollip on NF-κB and MAPK signaling pathways. The levels of p65, c-Fos, c-Jun, IL-1, IL-6, and TNF-α were dramatically reduced following overexpression of AjTollip, whereas knocking down AjTollip in vivo and in vitro enhanced those genes' expression. Protein molecular docking simulations showed AjTollip interacts with AjTLR2, AjIRAK4a, and AjIRAK4b. A better understanding of the transcriptional regulation of AjTollip is crucial to elucidating the role of Tollip in fish antibacterial response. Herein, we cloned and characterized a 2.2 kb AjTollip gene promoter sequence. The transcription factors GATA1 and Sp1 were determined to be associated with the activation of AjTollip expression by using promoter truncation and targeted mutagenesis techniques. Collectively, our results indicate that AjTollip suppresses the NF-κB and MAPK signaling pathways, leading to the decreased expression of the downstream inflammatory factors, and GATA1 and Sp1 play a vital role in regulating AjTollip expression.

System-level time computation and representation in the suprachiasmatic nucleus revealed by large-scale calcium imaging and machine learning.

The suprachiasmatic nucleus (SCN) is the mammalian central circadian pacemaker with heterogeneous neurons acting in concert while each neuron harbors a self-sustained molecular clockwork. Nevertheless, how system-level SCN signals encode time of the day remains enigmatic. Here we show that population-level Ca2+ signals predict hourly time, via a group decision-making mechanism coupled with a spatially modular time feature representation in the SCN. Specifically, we developed a high-speed dual-view two-photon microscope for volumetric Ca2+ imaging of up to 9000 GABAergic neurons in adult SCN slices, and leveraged machine learning methods to capture emergent properties from multiscale Ca2+ signals as a whole. We achieved hourly time prediction by polling random cohorts of SCN neurons, reaching 99.0% accuracy at a cohort size of 900. Further, we revealed that functional neuron subtypes identified by contrastive learning tend to aggregate separately in the SCN space, giving rise to bilaterally symmetrical ripple-like modular patterns. Individual modules represent distinctive time features, such that a module-specifically learned time predictor can also accurately decode hourly time from random polling of the same module. These findings open a new paradigm in deciphering the design principle of the biological clock at the system level.

Robust Nanoparticles Growth in the Interior of Porous Sponges for Efficient Dye Adsorption and Emulsion Separation.

Emulsified oils and dye contaminants already pose a huge threat to global ecosystems and human health. It is a significant research topic to develop efficient, rapid, versatile methods for emulsion separation and dye adsorption. The membrane material modified with common methods only modified the outer surface of the membrane, while the interior is hardly fully decorated. In this investigation, a solvent exchange method was used to in situ grow nanoparticles in the interior of a porous sponge. These nanoparticles were obtained with polyethyleneimine, gallic acid, and tannic acid via Michael addition and Schiff base reaction. The prepared nanoparticle-coated sponges provided efficient separation of dyes, emulsions, and complex contaminants. The separation efficiency of the dye reached 99.49%, and the separation efficiency of the emulsion was as high as 99.87% with a flux of 11140.3 L m-2 h-1. Furthermore, the maximum adsorption capacity reached 486.8 mg g-1 for cationic dyes and 182.1 mg g-1 for anionic dyes. More importantly, the nanoparticles were highly robust on the surface of the porous sponge, and the modified sponge could have long-term applications in hazardous environments. Overall, it is envisioned that the nanoparticles-modified porous sponge exhibited considerable potential for emulsion and dye wastewater treatment.

Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny.

Human hematopoiesis starts at early yolk sac and undergoes site- and stage-specific changes over development. The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood. Here, we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells (HSPCs) at different developmental stages, including yolk-sac (YS), AGM, fetal liver (FL), umbilical cord blood (UCB) and adult peripheral blood (PB) mobilized HSPCs. These stage-specific HSPCs display differential intrinsic properties, such as metabolism, self-renewal, differentiating potentialities etc. We then generated highly co-related gene regulatory network (GRNs) modules underlying the differential HSC key properties. Particularly, we identified GRNs and key regulators controlling lymphoid potentiality, self-renewal as well as aerobic respiration in human HSCs. Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells. Therefore, GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.

Origami metamaterials for ultra-wideband and large-depth reflection modulation.

The dynamic control of electromagnetic waves is a persistent pursuit in modern industrial development. The state-of-the-art dynamic devices suffer from limitations such as narrow bandwidth, limited modulation range, and expensive features. To address these issues, we fuse origami techniques with metamaterial design to achieve ultra-wideband and large-depth reflection modulation. Through a folding process, our proposed metamaterial achieves over 10-dB modulation depth over 4.96 - 38.8 GHz, with a fractional bandwidth of 155% and tolerance to incident angles and polarizations. Its ultra-wideband and large-depth reflection modulation performance is verified through experiments and analyzed through multipole decomposition theory. To enhance its practical applicability, transparent conductive films are introduced to the metamaterial, achieving high optical transparency (>87%) from visible to near-infrared light while maintaining cost-effectiveness. Benefiting from lightweight, foldability, and low-cost properties, our design shows promise for extensive satellite communication and optical window mobile communication management.

The effect of distal locking mode on postoperative mechanical complications in intertrochanteric fractures: a retrospective cohort study of five hundred and seven patients.

PURPOSE: The optimal choice of distal locking modes remains a subject due to limited available data, and therefore, this study aims to investigate the relationship between distal locking mode and postoperative mechanical complications in an intertrochanteric fracture (ITF) population who underwent closed reduction and intramedullary fixation with a PFNA-II. METHODS: Patients aged 65 years or older who underwent surgery with PFNA-II fixation in a university teaching hospital between January 2020 and December 2021 were potentially eligible. Based on the distal locking mode, patients were classified into static, dynamic, and limited dynamic groups, among which the differences were tested using univariate analysis. Multivariate logistic regression was used to examine whether the distal locking mode was independently associated with the risk of postoperative one year mechanical complications, adjusting for covariates and potential confounders. Subgroup analyses were performed to evaluate the robustness of the findings. RESULT: Among 507 eligible patients, 33 (6.5%) developed postoperative mechanical complications. In the univariate analysis, sex (P = 0.007), fracture type (P = 0.020), LAT Parker ratio (P = 0.023), and lateral femoral (P = 0.003) wall showed that the differences were significant. Compared to the static group, the limited dynamic group and the dynamic group showed higher odds of postoperative mechanical complications (OR = 3.314, 95% CI: 1.215-9.041; and OR = 3.652, 95% CI: 1.451-9.191, respectively). These associations were robust across a series of analyses, including adjusting for confounders and subgroup analyses. CONCLUSION: Using a distal non-static locking mode significantly increases the risk of postoperative mechanical complications, and static locking could be a preferable option when treating an intertrochanteric fracture.

Prediction of blood-brain barrier penetrating peptides based on data augmentation with Augur.

BACKGROUND: The blood-brain barrier serves as a critical interface between the bloodstream and brain tissue, mainly composed of pericytes, neurons, endothelial cells, and tightly connected basal membranes. It plays a pivotal role in safeguarding brain from harmful substances, thus protecting the integrity of the nervous system and preserving overall brain homeostasis. However, this remarkable selective transmission also poses a formidable challenge in the realm of central nervous system diseases treatment, hindering the delivery of large-molecule drugs into the brain. In response to this challenge, many researchers have devoted themselves to developing drug delivery systems capable of breaching the blood-brain barrier. Among these, blood-brain barrier penetrating peptides have emerged as promising candidates. These peptides had the advantages of high biosafety, ease of synthesis, and exceptional penetration efficiency, making them an effective drug delivery solution. While previous studies have developed a few prediction models for blood-brain barrier penetrating peptides, their performance has often been hampered by issue of limited positive data. RESULTS: In this study, we present Augur, a novel prediction model using borderline-SMOTE-based data augmentation and machine learning. we extract highly interpretable physicochemical properties of blood-brain barrier penetrating peptides while solving the issues of small sample size and imbalance of positive and negative samples. Experimental results demonstrate the superior prediction performance of Augur with an AUC value of 0.932 on the training set and 0.931 on the independent test set. CONCLUSIONS: This newly developed Augur model demonstrates superior performance in predicting blood-brain barrier penetrating peptides, offering valuable insights for drug development targeting neurological disorders. This breakthrough may enhance the efficiency of peptide-based drug discovery and pave the way for innovative treatment strategies for central nervous system diseases.

Efficient Atomically Dispersed Co/N-C Catalysts for Formic Acid Dehydrogenation and Transfer Hydrodeoxygenation of Vanillin.

Atomically dispersed catalysts have gained considerable attention due to their unique properties and high efficiency in various catalytic reactions. Herein, a series of Co/N-doped carbon (N-C) catalysts was prepared using a metal-lignin coordination strategy and employed in formic acid dehydrogenation (FAD) and hydrodeoxygenation (HDO) of vanillin. The atomically dispersed Co/N-C catalysts showed outstanding activity, acid resistance, and long-term stability in FAD. The improved activity and stability may be attributed to the high dispersion of Co species, increased surface area, and strong Co-N interactions. XPS and XAS characterization revealed the formation of Co-N3 centers, which are assumed to be the active sites. In addition, DFT calculations demonstrated that the adsorption of formic acid on single-atom Co was stronger than that on Co13 clusters, which may explain the high catalytic activity. The Co/N-C catalyst also showed promising performance in the transfer HDO of vanillin with formic acid, without any external additional molecular H2.

Investigation of formaldehyde sources and its relative emission intensity in shipping channel environment.

Formaldehyde (HCHO) is considered one of the most abundant gas-phase carbonyl compounds in the atmosphere, which can be directly emitted through transportation sources. Long-Path Differential Optical Absorption Spectroscopy (LP-DOAS) was used to observe HCHO in the river channel of Wusong Wharf in Shanghai, China for the whole year of 2019. Due to the impact of ship activity, the annual average HCHO level in the channel is about 2.5 times higher than that in the nearby campus environment. To explain the sources of HCHO under different meteorological conditions, the tracer-pair of CO and Ox (NO2+O3) was used on the clustered air masses. The results of the source appointment show that primary, secondary and background account for 24.14% (3.34 ± 1.19 ppbv), 44.78% (6.20 ± 2.04 ppbv) and 31.09% (4.31 ± 2.33 ppbv) of the HCHO in the channel when the air masses were from the mixed direction of the city and channel, respectively. By performing background station subtraction at times of high primary HCHO values and resolving the plume peaks, directly emitted HCHO/NO2 in the channel environment and plume were determined to be mainly distributed between 0.2 and 0.3. General cargo ships with higher sailing speeds or main engine powers tend to have higher HCHO/NO2 levels. With the knowledge of NO2 (or NOx) emission levels from ships, this study may provide data support for the establishment of HCHO emission factors.

Comparison of outcomes after total hip arthroplasty between patients with osteonecrosis of the femoral head in Association Research Circulation Osseous stage III and stage IV: a five-year follow-up study.

BACKGROUND: No large cohort study has evaluated the surgical outcomes of THA between different stages of ONFH patients. This study aimed to compare the surgical outcomes of ONFH patients who underwent THA in ARCO stage III versus IV, in terms of operative parameters, one-year hip function assessments and postoperative at least five-year complications, to inform optimized management of ONFH. METHOD: From our prospectively collected database, 876 patients undergoing THA between October 2014 and April 2017 were analyzed and divided into ARCO stage III group (n = 383) and ARCO stage IV group(n = 493). Details of demographics, medical record information, adverse events and clinical scores of both groups were collected and compared. Proper univariate analysis was used for the analysis. RESULT: There were no statistically significant differences in baseline characteristics between the two groups. Compared to ARCO stage IV patients, ARCO stage III patients showed a shorter operative time (p < 0.01), less bleeding (p < 0.01), fewer one-year readmissions (p = 0.026) and complications (p = 0.040), and significantly higher HHS (p < 0.01) one year after THA. In addition, ARCO stage IV patients seem more likely to suffer prosthesis dislocation (p = 0.031). CONCLUSION: Although ARCO stage IV patients in the study cohorts appeared to suffer more one-year complications, no significant difference was observed at long-term follow-up. Enhanced clinical guidance on preventing early prosthesis dislocation may help improve the prognosis of final-stage ONFH patients.

High-performance ferroelectric field-effect transistors with ultra-thin indium tin oxide channels for flexible and transparent electronics.

With the development of wearable devices and hafnium-based ferroelectrics (FE), there is an increasing demand for high-performance flexible ferroelectric memories. However, developing ferroelectric memories that simultaneously exhibit good flexibility and significant performance has proven challenging. Here, we developed a high-performance flexible field-effect transistor (FeFET) device with a thermal budget of less than 400 °C by integrating Zr-doped HfO2 (HZO) and ultra-thin indium tin oxide (ITO). The proposed FeFET has a large memory window (MW) of 2.78 V, a high current on/off ratio (ION/IOFF) of over 108, and high endurance up to 2×107 cycles. In addition, the FeFETs under different bending conditions exhibit excellent neuromorphic properties. The device exhibits excellent bending reliability over 5×105 pulse cycles at a bending radius of 5 mm. The efficient integration of hafnium-based ferroelectric materials with promising ultrathin channel materials (ITO) offers unique opportunities to enable high-performance back-end-of-line (BEOL) compatible wearable FeFETs for edge intelligence applications.

EDI-OCT as an auxiliary examination for the differential diagnosis of bullous CSC and Vogt-Koyanagi-Harada: A case report.

A 46-year-old male patient visited our clinic with a complaint of blurred vision in the right eye accompanied by headache and insomnia. The fundus examination showed three bullous retinal detachments in the right eye. Considering the prodromal symptoms and other fundus characteristics such as vitreous cells in the posterior pole and multifocal fluorescence leakages on fundus fluorescein angiography (FFA), initial diagnosis was considered as Vogt-Koyanagi-Harada (VKH). However, oral glucocorticoids didn't improve patient's vision. Further enhanced depth imaging (EDI)-optical coherence tomography (OCT) scan displayed hyper-reflective lesions at the choroidal layer. We proposed that hyper-reflective lesions at the choroidal layer on EDI-OCT may characterize the bullous variant of central serous chorioretinopathy (CSC). After fundus photocoagulation treatment, the patient's vision improved.

Modulating Polarization in Second Harmonic Generation through Symmetry Evolution in Plasmonic Lattices.

We report a strategy for preparing cost-effective plasmonic square lattices with tunable unit structures of circles, crosses, and circle-cross pairs on a centimeter scale. The asymmetrical electromagnetic (EM) field distribution of the lattice enhances second harmonic generation (SHG) under oblique incidence. The SHG signals are progressively strengthened as the unit symmetry decreases from C∞v (circle) to C4v (cross) to C2v (circle-cross pair). The peak SHG signal is observed from the plasmonic lattice with a circle-cross pair, showcasing a conversion efficiency of 1.0 × 10-2, which is a 7.3-fold enhancement relative to the dielectric lattice comprised of circle units. This notably high conversion efficiency of SHG is on par with that of phase-matched bulk nanostructures under normal incidence, benefiting from the Bloch-surface plasmon polariton (Bloch-SPP) modes associated with the distribution of the photonic local density of states (LDOS). Furthermore, the SHG emission exhibits distinctive directional and polarization characteristics as the unit symmetry is reduced. This work offers valuable insights into a structural symmetry-dependent SHG in plasmonic lattices and the way forward for the design of functional nonlinear plasmonic devices.

CircHIVEP2 alleviates Parkinson's nerve damage and inflammatory response by targeting miR-485-3p.

OBJECTIVE: Dysregulation of covalently closed circular RNAs (circRNAs) has been associated with neurological disorders, the role of circHIVP2 in Parkinson's disease (PD) and its molecular mechanism is not well understood. METHODS: 127 patients with PD and 85 healthy people were enrolled. RT-qPCR was employed to examine the levels of circHIVEP2. ROC curve to explore the diagnostic. Mpp+ induced the SH-SY5Y to construct an in vitro PD cell model. Cell viability, apoptosis, and secretion levels of inflammatory factors were analyzed by CCK-8, flow cytometry, and ELISA assay. CircHIVEP2 targets miRNA predicted by bioinformatics database and validated by the dual luciferase reporter and RIP assays. RESULTS: CircHIVEP2 was typically lower in PD patients than in controls. CircHIVEP2 has certain specificity and sensitivity to recognize PD patients from healthy individuals. miR-485-3p, a target miRNA of circHIVEP2, was significantly elevated in PD patients. Additionally, MPP+ induction reduced cell viability and promoted apoptosis and inflammatory factor overproduction. However, overexpression of circHIVEP2 significantly inhibited the effects of MPP+, but this inhibition was significantly attenuated by elevated miR-485-3p. CONCLUSION: circHIVEP2 is a potential diagnostic biomarker for PD, and its upregulation mitigated MPP+-induced nerve damage and inflammation and this may be through targeted by the miR-485-3p.

Ionic Diffusive Nanomemristors with Dendritic Competition and Cooperation Functions for Ultralow Voltage Neuromorphic Computing.

Realization of dendric signal processing in the human brain is of great significance for spatiotemporal neuromorphic engineering. Here, we proposed an ionic dendrite device with multichannel communication, which could realize synaptic behaviors even under an ultralow action potential of 80 mV. The device not only could simulate one-to-one information transfer of axons but also achieve a many-to-one modulation mode of dendrites. By the adjustment of two presynapses, Pavlov's dog conditioning experiment was learned successfully. Furthermore, the device also could emulate the biological synaptic competition and synaptic cooperation phenomenon through the comodulation of three presynapses, which are crucial for artificial neural network (ANN) implementation. Finally, an ANN was further constructed to realize highly efficient and anti-interference recognition of fashion patterns. By introducing the cooperative device, synaptic weight updates could be improved for higher linearity and larger dynamic regulation range in neuromorphic computing, resulting in higher recognition accuracy and efficiency. Such an artificial dendric device has great application prospects in the processing of more complex information and the construction of an ANN system with more functions.

Low-Density and High-Performance Fiber-Reinforced PP/POE Composite Foam via Irradiation Crosslinking.

This study addresses the challenge of achieving foam with a high expansion ratio and poor mechanical properties, caused by the low melt viscosity of semi-crystalline polypropylene (PP). We systematically employ a modification approach involving blending PP with polyolefin elastomers (POE), irradiation crosslinking, and fiber reinforcement to prepare fiber-reinforced crosslinked PP/POE composite foam. Through optimization and characterization of material composition and processing conditions, the obtained fiber-reinforced crosslinked PP/POE composite foam exhibits both low density and high performance. Specifically, at a crosslinking degree of 12%, the expansion ratio reaches 16 times its original value, and a foam density of 0.057 g/cm3 is reduced by 36% compared to the non-crosslinked PP/POE system with a density of 0.089 g/cm3. The density of the short-carbon-fiber-reinforced crosslinked sCF/PP/POE composite foam is comparable to that of the crosslinked PP/POE system, but the tensile strength reaches 0.69 MPa, representing a 200% increase over the crosslinked PP/POE system and a 41% increase over the non-crosslinked PP/POE system. Simultaneously, it exhibits excellent impact strength, tear resistance, and low heat shrinkage. Irradiation crosslinking is beneficial for enhancing the melt strength and resistance to high temperature thermal shrinkage of PP/POE foam, while fiber reinforcement contributes significantly to improving mechanical properties. These achieve a good complementary effect in low-density and high-performance PP foam modification.