Therapeutic effect of Nepenthes kampotiana Lecomte ethanol extract (Nk-EE) on androgenic alopecia through the inhibition of apoptosis and 5α-reductase activity.

There is increasing interest in hair loss treatment because a growing number of people affected. Nepenthes kampotiana Lecomte is known for its anticancer effects, but its potential for preventing hair loss has not been researched. Therefore, this study focused on the hair loss prevention effects of N. kampotiana Lecomte ethanol extract (Nk-EE). The results showed that Nk-EE had a proliferative effect on human follicle dermal papilla cells and inhibited cell death. In vivo experiments using androgenic areata models showed that Nk-EE had a positive effect on a variety of biomarkers such as hair-to-skin ratio, hair type frequency, and hair thickness. The results of this study suggest that Nk-EE has potential as an effective treatment for androgenic alopecia.

Rational Design of Liquid-Liquid Microdispersion Droplet Microreactors for the Controllable Synthesis of Highly Uniform and Monodispersed Dextran Microspheres.

Hydrogel microspheres are biocompatible materials widely used in biological and medical fields. Emulsification and stirring are the commonly used methods to prepare hydrogels. However, the size distribution is considerably wide, the monodispersity and the mechanical intensity are poor, and the stable operation conditions are comparatively narrow to meet some sophisticated applications. In this paper, a T-shaped stepwise microchannel combined with a simple side microchannel structure is developed to explore the liquid-liquid dispersion mechanism, interfacial evolution behavior, satellite droplet formation mechanism and separation, and the eventual successful synthesis of dextran hydrogel microspheres. The effect of the operation parameters on droplet and microsphere size is comprehensively studied. The flow pattern and the stable operation condition range are given, and mathematical prediction models are developed under three different flow regimes for droplet size prediction. Based on the stable operating conditions, a microdroplet-based method combined with UV light curing is developed to synthesize the dextran hydrogel microsphere. The highly uniform and monodispersed dextran microspheres with good mechanical intensity are synthesized in the developed microfluidic platform. The size of the microsphere could be tuned from 50 to 300 µm with a capillary number in the range of 0.006-0.742. This work not only provides a facile method for functional polymeric microsphere preparation but also offers important design guidelines for the development of a robust microreactor.

Synthesis and antiproliferative activity of CBD aromatic ester derivatives.

This study involved the synthesis of a series of novel cannabidiol (CBD) aromatic ester derivatives, including CBD-8,12-diaromaticester derivatives (compounds 2a-2t) and CBD-8,12-diacetyl-21-aromaticester derivatives (compound 5a-5c). The antiproliferative activities of these compounds against human liver cancer cell lines HePG2 and HeP3B as well as human pancreatic cancer cell lines ASPC-1 and BXPC-3 were evaluated in vitro using the CCK-8 assay. The results indicated that compound 2f exhibited an IC50 value of 2.75 µM against HePG2, which is 5.32-fold higher than that of CBD. Additionally, compounds 2b and 5b demonstrated varying degrees of improved anticancer activity (IC50 5.95-9.21 µM) against HePG2.

Glutamine maintains the stability of alveolar structure and function after lung transplantation by inhibiting autophagy.

Excessive autophagy may lead to degradation and damage of alveolar epithelial cells after lung transplantation, eventually leading to alveolar epithelial cell loss, affecting the structural integrity and function of alveoli. Glutamine (Gln), a nutritional supplement, regulates autophagy through multiple signaling pathways. In this study, we explored the protective role of Gln on alveolar epithelial cells by inhibiting autophagy. In vivo, a rat orthotopic lung transplant model was carried out to evaluate the therapeutic effect of glutamine. Ischemia/reperfusion (I/R) induced alveolar collapse, edema, epithelial cell apoptosis, and inflammation, which led to a reduction of alveolar physiological function, such as an increase in peak airway pressure, and a decrease in lung compliance and oxygenation index. In comparison, Gln preserved alveolar structure and function by reducing alveolar apoptosis, inflammation, and edema. In vitro, a hypoxia/reoxygenation (H/R) cell model was performed to simulate IR injury on mouse lung epithelial (MLE) cells and human lung bronchus epithelial (Beas-2B) cells. H/R impaired the proliferation of epithelial cells and triggered cell apoptosis. In contrast, Gln normalized cell proliferation and suppressed I/R-induced cell apoptosis. The activation of mTOR and the downregulation of autophagy-related proteins (LC3, Atg5, Beclin1) were observed in Gln-treated lung tissues and alveolar epithelial cells. Both in vivo and in vitro, rapamycin, a classical mTOR inhibitor, reversed the beneficial effects of Gln on alveolar structure and function. Taken together, Glnpreserved alveolar structure and function after lung transplantation by inhibiting autophagy.

The association between systemic inflammation markers and paroxysmal atrial fibrillation.

BACKGROUND: Systemic inflammation markers have recently been identified as being associated with cardiac disorders. However, limited research has been conducted to estimate the pre-diagnostic associations between these markers and paroxysmal atrial fibrillation (PAF). Our aim is to identify potential biomarkers for early detection of PAF. METHODS: 91 participants in the PAF group and 97 participants in the non-PAF group were included in this study. We investigated the correlations between three systemic inflammation markers, namely the systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), and PAF. RESULTS: The proportion of patients with PAF gradually increased with increasing logSII, logSIRI, and logAISI tertiles. Compared to those in the lowest tertiles, the PAF risks in the highest logSII and logSIRI tertiles were 3.2-fold and 2.9-fold, respectively. Conversely, there was no significant correlation observed between logAISI and PAF risk within the highest tertile of logAISI. The restricted cubic splines (RCS) analysis revealed a non-linear relationship between the elevation of systemic inflammation markers and PAF risk. Specifically, the incidence of PAF is respectively increased by 56%, 95%, and 150% for each standard deviation increase in these variables. The ROC curve analysis of logSII, logSIRI and logAISI showed that they had AUC of 0.6, 0.7 and 0.6, respectively. It also demonstrated favorable sensitivity and specificity of these systemic inflammation markers in detecting the presence of PAF. CONCLUSIONS: In conclusion, our study reveals significant positive correlations between SII, SIRI, and AISI with the incidence of PAF.

Investigation molecular structure of anticancer drug with topological indices.

A crucial consideration in examining the physicochemical characteristics of chemical compound structures is topological indices. In addition, topological indices will serve as a description of a molecule under test by translating each molecule's structure into a real number. In this paper, we calculate topological indices [Formula: see text] and [Formula: see text] for anticancer drugs, where da is the degree of vertex a in graph G and 0≠α,ß∈R. By choosing of parameters α and ß, some of new/old results for topological indices are obtained. The results of this study may assist to chemists in identifying the chemical, physical and biological activity associated with them.

AutoCancer as an automated multimodal framework for early cancer detection.

Current studies in early cancer detection based on liquid biopsy data often rely on off-the-shelf models and face challenges with heterogeneous data, as well as manually designed data preprocessing pipelines with different parameter settings. To address those challenges, we present AutoCancer, an automated, multimodal, and interpretable transformer-based framework. This framework integrates feature selection, neural architecture search, and hyperparameter optimization into a unified optimization problem with Bayesian optimization. Comprehensive experiments demonstrate that AutoCancer achieves accurate performance in specific cancer types and pan-cancer analysis, outperforming existing methods across three cohorts. We further demonstrated the interpretability of AutoCancer by identifying key gene mutations associated with non-small cell lung cancer to pinpoint crucial factors at different stages and subtypes. The robustness of AutoCancer, coupled with its strong interpretability, underscores its potential for clinical applications in early cancer detection.

Transcriptome analysis of Pennisetum americanum × Pennisetum purpureum and Pennisetum americanum leaves in response to high-phosphorus stress.

Excessive phosphorus (P) levels can disrupt nutrient balance in plants, adversely affecting growth. The molecular responses of Pennisetum species to high phosphorus stress remain poorly understood. This study examined two Pennisetum species, Pennisetum americanum × Pennisetum purpureum and Pennisetum americanum, under varying P concentrations (200, 600 and 1000 µmol·L- 1 KH2PO4) to elucidate transcriptomic alterations under high-P conditions. Our findings revealed that P. americanum exhibited stronger adaption to high-P stress compared to P. americanum× P. purpureum. Both species showed an increase in plant height and leaf P content under elevated P levels, with P. americanum demonstrating greater height and higher P content than P. americanum× P. purpureum. Transcriptomic analysis identified significant up- and down-regulation of key genes (e.g. SAUR, GH3, AHP, PIF4, PYL, GST, GPX, GSR, CAT, SOD1, CHS, ANR, P5CS and PsbO) involved in plant hormone signal transduction, glutathione metabolism, peroxisomes, flavonoid biosynthesis, amino acid biosynthesis and photosynthesis pathways. Compared with P. americanum× P. purpureum, P. americanum has more key genes in the KEGG pathway, and some genes have higher expression levels. These results contribute valuable insights into the molecular mechanisms governing high-P stress in Pennisetum species and offer implications for broader plant stress research.

Transportation engineering for enhanced production of plant natural products in microbial cell factories.

Plant natural products (PNPs) exhibit a wide range of biological activities and have essential applications in various fields such as medicine, agriculture, and flavors. Given their natural limitations, the production of high-value PNPs using microbial cell factories has become an effective alternative in recent years. However, host metabolic burden caused by its massive accumulation has become one of the main challenges for efficient PNP production. Therefore, it is necessary to strengthen the transmembrane transport process of PNPs. This review introduces the discovery and mining of PNP transporters to directly mediate PNP transmembrane transportation both intracellularly and extracellularly. In addition to transporter engineering, this review also summarizes several auxiliary strategies (such as small molecules, environmental changes, and vesicles assisted transport) for strengthening PNP transportation. Finally, this review is concluded with the applications and future perspectives of transportation engineering in the construction and optimization of PNP microbial cell factories.

Novel L-(CaP-ZnP)/SA Nanocomposite Hydrogel with Dual Anti-Inflammatory and Mineralization Effects for Efficient Vital Pulp Therapy.

Background: Vital pulp therapy (VPT) is considered a conservative treatment for preserving pulp viability in caries and trauma-induced pulpitis. However, Mineral trioxide aggregate (MTA) as the most frequently used repair material, exhibits limited efficacy under inflammatory conditions. This study introduces an innovative nanocomposite hydrogel, tailored to simultaneously target anti-inflammation and dentin mineralization, aiming to efficiently preserve vital pulp tissue. Methods: The L-(CaP-ZnP)/SA nanocomposite hydrogel was designed by combining L-Arginine modified calcium phosphate/zinc phosphate nanoparticles (L-(CaP-ZnP) NPs) with sodium alginate (SA), and was characterized with TEM, SEM, FTIR, EDX, ICP-AES, and Zeta potential. In vitro, we evaluated the cytotoxicity and anti-inflammatory properties. Human dental pulp stem cells (hDPSCs) were cultured with lipopolysaccharide (LPS) to induce an inflammatory response, and the cell odontogenic differentiation was measured and possible signaling pathways were explored by alkaline phosphatase (ALP)/alizarin red S (ARS) staining, qRT-PCR, immunofluorescence staining, and Western blotting, respectively. In vivo, a pulpitis model was utilized to explore the potential of the L-(CaP-ZnP)/SA nanocomposite hydrogel in controlling pulp inflammation and enhancing dentin mineralization by Hematoxylin and eosin (HE) staining and immunohistochemistry staining. Results: In vitro experiments revealed that the nanocomposite hydrogel was synthesized successfully and presented desirable biocompatibility. Under inflammatory conditions, compared to MTA, the L-(CaP-ZnP)/SA nanocomposite hydrogel demonstrated superior anti-inflammatory and pro-odontogenesis effects. Furthermore, the nanocomposite hydrogel significantly augmented p38 phosphorylation, implicating the involvement of the p38 signaling pathway in pulp repair. Significantly, in a rat pulpitis model, the L-(CaP-ZnP)/SA nanocomposite hydrogel downregulated inflammatory markers while upregulating mineralization-related markers, thereby stimulating the formation of robust reparative dentin. Conclusion: The L-(CaP-ZnP)/SA nanocomposite hydrogel with good biocompatibility efficiently promoted inflammation resolution and enhanced dentin mineralization by activating p38 signal pathway, as a pulp-capping material, offering a promising and advanced solution for treatment of pulpitis.

Evaluation of best management practices for mitigating harmful algal blooms risk in an agricultural lake basin using a watershed model integrated with Bayesian Network approach.

Lake eutrophication caused by nitrogen and phosphorus has led to frequent harmful algal blooms (HABs), especially under the unknown challenges of climate change, which have seriously damaged human life and property. In this study, a coupled SWAT-Bayesian Network (SWAT-BN) model framework was constructed to elucidate the mechanisms between non-point source nitrogen pollution in agricultural lake watersheds and algal activities. A typical agricultural shallow lake basin, the Taihu Basin (TB), China, was chosen in this study, aiming to investigate the effectiveness of best management practices (BMPs) in controlling HABs risks in TB. By modeling total nitrogen concentration of Taihu Lake from 2007 to 2022 with four BMPs (filter strips, grassed waterway, fertilizer application reduction and no-till agriculture), the results indicated that fertilizer application reduction proved to be the most effective BMP with 0.130 of Harmful Algal Blooms Probability Reduction (HABs-PR) when reducing 40% of fertilizer, followed by filter strips with 0.01 of HABs-PR when 4815ha of filter strips were conducted, while grassed waterway and no-till agriculture showed no significant effect on preventing HABs. Furthermore, the combined practice between 40% fertilizer application reduction and 4815ha filter strips construction showed synergistic effects with HABs-PR increasing to 0.171. Precipitation and temperature data were distorted to model scenarios of extreme events. As a result, the combined approach outperformed any single BMP in terms of robustness under extreme climates. This research provides a watershed-level perspective on HABs risks mitigation and highlights the strategies to address HABs under the influence of climate change.

Bronze age Northern Eurasian genetics in the context of development of metallurgy and Siberian ancestry.

The Eurasian Bronze Age (BA) has been described as a period of substantial human migrations, the emergence of pastoralism, horse domestication, and development of metallurgy. This study focuses on two north Eurasian sites sharing Siberian genetic ancestry. One of the sites, Rostovka, is associated with the Seima-Turbino (ST) phenomenon (~2200-1900 BCE) that is characterized by elaborate metallurgical objects found throughout Northern Eurasia. The genetic profiles of Rostovka individuals vary widely along the forest-tundra Siberian genetic cline represented by many modern Uralic-speaking populations, and the genetic heterogeneity observed is consistent with the current understanding of the ST being a transcultural phenomenon. Individuals from the second site, Bolshoy Oleni Ostrov in Kola, in comparison form a tighter cluster on the Siberian ancestry cline. We further explore this Siberian ancestry profile and assess the role of the ST phenomenon and other contemporaneous BA cultures in the spread of Uralic languages and Siberian ancestry.

E-PVT: enhanced position-velocity-time scheduler for computer-controlled optical finishing with comprehensive considerations of dynamics constraints, continuity and efficiency.

Deterministic computer-controlled optical finishing is an essential approach for achieving high-quality optical surfaces. Its determinism and convergence rely heavily on precise and smooth motion control to guide the machine tool over an optical surface to correct residual errors. One widely supported and smooth motion control model is position-velocity-time (PVT), which employs piecewise cubic polynomials to describe positions. Our prior research introduced a PVT-based velocity scheduling method, demonstrating sub-nanometer level convergence in ion beam figuring (IBF) processes. However, three challenges remained. Firstly, this method relies on quadratic programming, resulting in computational intensiveness for dense tool paths. Secondly, the dynamics constraints and velocity and acceleration continuities are not comprehensively considered, limiting the full potential of PVT-based control. Thirdly, no compensation mechanism existed when dynamics constraints are exceeded. In this study, in response to these challenges, we proposed the Enhanced PVT (E-PVT) method, reducing the time complexity from O(n3) to O(n) while fully addressing dynamics constraints and continuities. A novel compensation method utilizing particle swarm optimization was proposed to address situations where dynamics constraints might be exceeded while maintaining the overall processing efficiency. Validation through simulation and experimentation confirmed the improved performance of E-PVT.

High-resolution and highly-multiplexed option for fiber-fed spectrograph of the wide field MUltiplexed Survey Telescope (MUST).

In recent decades, rapid advances in astronomical imaging campaigns have generated an urgent need for detailed spectroscopic surveys with increased speed and efficiency. The 6.5 m MUltiplexed Survey Telescope (MUST) aims to address these current demands. The performance of the multi-object fiber-fed spectrograph (MOFS) plays a critical role for spectroscopic survey telescopes, directly influencing the realization of scientific aims. In this paper, we demonstrate a high-resolution and highly-multiplexed option for MOFS of MUST. The system is believed to be first to apply a 92 mm × 92 mm large-size detector in a Schmidt-like camera and reduces the average central obscuration to 14%. Thanks to the F/1.25 camera design with excellent image quality, the spectrograph achieves up to 800 150µm-large-core optical fibers integration. It can obtain the broadband spectral information (395 nm-435 nm, 520 nm-570 nm, 610 nm-680 nm) of 800 objects with a high resolution of >16,000 within one exposure. The spectrograph theory, design method, and final system scheme of the MOFS can offer good reference and guidance for the spectrograph design in the spectroscopic survey.

Generation of a switchable and tunable rectangular pulse and multi-pulse with different peak powers at the L-band.

A novel, to our knowledge, L-band erbium-doped fiber laser, utilizing a nonlinear optical loop mirror (NOLM) as a mode-locker, is presented in this study. Through precise adjustments of the polarization controllers (PCs), the laser achieves the generation of rectangular pulses with distinct single wavelengths, λ 1=1593n m and λ 2=1571n m, as well as dual-wavelength operation. The laser's operational mode can extend further to include harmonic mode-locking (HML). Furthermore, the investigation reveals the emergence of trapezoidal pulses and low-peak-power rectangular pulses within proximity of the conventional rectangular pulses. Notably, the evolutions of these low-peak-power pulses with the pump power also adhere to the peak power clamping (PPC) effect. Remarkably, the relative positioning of these pulses remains consistent across varying pump power levels or harmonic orders. Intriguingly, the evolution of the trapezoidal pulse with respect to pump power stands in stark contrast to that of the h-shaped pulse.

Optimized optical system with a 1.65 m wide-field corrector for the 6.5 m high-performance MUltiplexed Survey Telescope.

The development of modern large-scale spectroscopic survey telescopes responds to the urgent demand for spectral information in astronomical research. Tsinghua University has previously proposed a 6.5 m MUltiplexed Survey Telescope consisting of a Ritchey-Chretien configuration and a 1.8 m multi-element wide-field corrector, achieving excellent performance and world-leading survey efficiency. However, an optimized 1.65 m multi-element corrector with five lenses is proposed to overcome the constraints on glass uniformity and verification in fabrication of the previous corrector design. It maintains outstanding image quality, with the 80% enclosed energy diameter not more than 0.559 arcsec within 3° FoV over up to a 55° zenith angle. The optimized optical system does not revise the working mode of the ADC or the curvature of the primary mirror while ensuring the reasonability and accuracy of manufacturing of large corrector elements. It provides a more feasible reference optical design for the MUltiplexed Survey Telescope in subsequent iterations and communications with manufacturers.

Integrated ATAC-seq and RNA-seq Analysis of In Vitro Cultured Skeletal Muscle Satellite Cells to Understand Changes in Cell Proliferation.

Skeletal muscle satellite cells, the resident stem cells in pig skeletal muscle, undergo proliferation and differentiation to enable muscle tissue repair. The proliferative and differentiative abilities of these cells gradually decrease during in vitro cultivation as the cell passage number increases. Despite extensive research, the precise molecular mechanisms that regulate this process are not fully understood. To bridge this knowledge gap, we conducted transcriptomic analysis of skeletal muscle satellite cells during in vitro cultivation to quantify passage number-dependent changes in the expression of genes associated with proliferation. Additionally, we explored the relationships between gene transcriptional activity and chromatin accessibility using transposase-accessible chromatin sequencing. This revealed the closure of numerous open chromatin regions, which were primarily located in intergenic regions, as the cell passage number increased. Integrated analysis of the transcriptomic and epigenomic data demonstrated a weak correlation between gene transcriptional activity and chromatin openness in expressed genic regions; although some genes (e.g., GNB4 and FGD5) showed consistent relationships between gene expression and chromatin openness, a substantial number of differentially expressed genes had no clear association with chromatin openness in expressed genic regions. The p53-p21-RB signaling pathway may play a critical regulatory role in cell proliferation processes. The combined transcriptomic and epigenomic approach taken here provided key insights into changes in gene expression and chromatin openness during in vitro cultivation of skeletal muscle satellite cells. These findings enhance our understanding of the intricate mechanisms underlying the decline in cellular proliferation capacity in cultured cells.

Intein-mediated temperature control for complete biosynthesis of sanguinarine and its halogenated derivatives in yeast.

While sanguinarine has gained recognition for antimicrobial and antineoplastic activities, its complex conjugated structure and low abundance in plants impede broad applications. Here, we demonstrate the complete biosynthesis of sanguinarine and halogenated derivatives using highly engineered yeast strains. To overcome sanguinarine cytotoxicity, we establish a splicing intein-mediated temperature-responsive gene expression system (SIMTeGES), a simple strategy that decouples cell growth from product synthesis without sacrificing protein activity. To debottleneck sanguinarine biosynthesis, we identify two reticuline oxidases and facilitated functional expression of flavoproteins and cytochrome P450 enzymes via protein molecular engineering. After comprehensive metabolic engineering, we report the production of sanguinarine at a titer of 448.64 mg L-1. Additionally, our engineered strain enables the biosynthesis of fluorinated sanguinarine, showcasing the biotransformation of halogenated derivatives through more than 15 biocatalytic steps. This work serves as a blueprint for utilizing yeast as a scalable platform for biomanufacturing diverse benzylisoquinoline alkaloids and derivatives.

Detailed Complementary Consistency: Wave Function Tells Particle How to Hop, Particle Tells Wave Function How to Collapse.

In mixed quantum-classical dynamics, the quantum subsystem can have both wave function and particle-like descriptions. However, they may yield inconsistent results for the expectation value of the same physical quantity. We here propose a novel detailed complementary consistency (DCC) method based on the principle of detailed internal consistency. Namely, the wave function along each trajectory tells the particle how to hop, while the particle tells the wave function how to collapse based on active states in the trajectory ensemble. As benchmarked in a diverse array of representative models with localized nonadiabatic couplings, DCC not only achieves fully consistent results (i.e., identical populations calculated based on wave functions and active states) but also closely reproduces the exact quantum results. Due to the high performance, our new DCC method has great potential to give a consistent and accurate mixed quantum-classical description of general nonadiabatic dynamics after further development.

Salvianolic acid B inhibits the growth and metastasis of A549 lung cancer cells through the NDRG2/PTEN pathway by inducing oxidative stress.

Salvianolic acid B (Sal B) has demonstrated anticancer activity against various types of cancer. However, the underlying mechanism of Sal B-mediated anticancer effects remains incompletely understood. This study aims to investigate the impact of Sal B on the growth and metastasis of human A549 lung cells, as well as elucidate its potential mechanisms. In this study, different concentrations of Sal B were administered to A549 cells. The effects on migration and invasion abilities were assessed using MTT, wound healing, and transwell assays. Flow cytometry analysis was employed to evaluate Sal B-induced apoptosis in A549 cells. Western blotting and immunohistochemistry were conducted to measure the expression levels of cleaved caspase-3, cleaved PARP, and E-cadherin. Commercial kits were utilized for detecting intracellular reactive oxygen species (ROS) and NAD+. Additionally, a xenograft model with transplanted A549 tumors was employed to assess the anti-tumor effect of Sal B in vivo. The expression levels of NDRG2, p-PTEN, and p-AKT were determined through western blotting. Our findings demonstrate that Sal B effectively inhibits proliferation, migration, and invasion in A549 cells while inducing dose-dependent apoptosis. These apoptotic responses and inhibition of tumor cell metastasis are accompanied by alterations in intracellular ROS levels and NAD+/NADH ratio. Furthermore, our in vivo experiment reveals that Sal B significantly suppresses A549 tumor growth compared to an untreated control group while promoting increased cleavage of caspase-3 and PARP. Importantly, we observe that Sal B upregulates NDRG2 expression while downregulating p-PTEN and p-AKT expressions. Collectively, our results provide compelling evidence supporting the ability of Sal B to inhibit both growth and metastasis in A549 lung cancer cells through oxidative stress modulation as well as involvement of the NDRG2/PTEN/AKT pathway.