Cell density impacts the susceptibility to ferroptosis by modulating IRP1-mediated iron homeostasis.

Ferroptosis has been implicated in several neurological disorders and may be therapeutically targeted. However, the susceptibility to ferroptosis varies in different cells, and inconsistent results have been reported even using the same cell line. Understanding the effects of key variables of in vitro studies on ferroptosis susceptibility is of critical importance to facilitate drug discoveries targeting ferroptosis. Here, we showed that increased cell seeding density leads to enhanced resistance to ferroptosis by reducing intracellular iron levels. We further identified iron-responsive protein 1 (IRP1) as the key protein affected by cell density, which affects the expression of ferroportin or transferrin receptor and results in altered iron levels. Such observations were consistent across different cell lines, indicating that cell density should be tightly controlled in studies of ferroptosis. Since cell densities vary in different brain regions, these results may also shed light on selective regional vulnerability observed in neurological disorders.

Stiffness Restricts the Stemness of the Intestinal Stem Cells and Skews Their Differentiation Toward Goblet Cells.

BACKGROUND & AIMS: Fibrosis and tissue stiffening are hallmarks of inflammatory bowel disease (IBD). We have hypothesized that the increased stiffness directly contributes to the dysregulation of the epithelial cell homeostasis in IBD. Here, we aim to determine the impact of tissue stiffening on the fate and function of the intestinal stem cells (ISCs). METHODS: We developed a long-term culture system consisting of 2.5-dimensional intestinal organoids grown on a hydrogel matrix with tunable stiffness. Single-cell RNA sequencing provided stiffness-regulated transcriptional signatures of the ISCs and their differentiated progeny. YAP-knockout and YAP-overexpression mice were used to manipulate YAP expression. In addition, we analyzed colon samples from murine colitis models and human IBD samples to assess the impact of stiffness on ISCs in vivo. RESULTS: We demonstrated that increasing the stiffness potently reduced the population of LGR5+ ISCs and KI-67+-proliferating cells. Conversely, cells expressing the stem cell marker, olfactomedin-4, became dominant in the crypt-like compartments and pervaded the villus-like regions. Concomitantly, stiffening prompted the ISCs to preferentially differentiate toward goblet cells. Mechanistically, stiffening increased the expression of cytosolic YAP, driving the extension of olfactomedin-4+ cells into the villus-like regions, while it induced the nuclear translocation of YAP, leading to preferential differentiation of ISCs toward goblet cells. Furthermore, analysis of colon samples from murine colitis models and patients with IBD demonstrated cellular and molecular remodeling reminiscent of those observed in vitro. CONCLUSIONS: Collectively, our findings highlight that matrix stiffness potently regulates the stemness of ISCs and their differentiation trajectory, supporting the hypothesis that fibrosis-induced gut stiffening plays a direct role in epithelial remodeling in IBD.

Nd:YVO4/YVO4 cascaded Raman laser pumped dual-wavelength signal wave MgO:PPLN-OPO with wide range adjustable wavelength interval.

This article presents a dual-wavelength signal wave output system capable of generating a broad range of adjustable wavelength intervals. The setup involved the creation of a dual-wavelength cascaded Raman laser featuring composite cavities operating at 1176 nm and 1313 nm. Experimental investigations were carried out on an external cavity MgO:PPLN-OPO driven by the cascaded Raman laser. By setting the crystal polarization period to 27.6-34.4 µm and the temperature to 50-130°C, adjustable tunable output of dual-wavelength signal wave at 1176 nm-MgO:PPLN-OPO (1550-2294 nm) and 1313 nm-MgO:PPLN-OPO (1768-2189 nm) was achieved with a wavelength interval of 0-218 nm. Under the conditions of a period of 34.4 µm, temperature of 90°C, and an incident Raman power of 2.6 W, the highest conversion efficiency of Raman to dual-wavelength signal wave (2212, 2182 nm) was 34.2%. Furthermore, the maximum output power of dual-wavelength signal wave was recorded at 1.02 W with an incident Raman power of 3.33 W.

Loading-effect-based three-dimensional microfabrication empowers on-chip Brillouin optomechanics.

The acousto-optic interaction known as stimulated Brillouin scattering (SBS) has emerged as a fundamental principle for realizing crucial components and functionalities in integrated photonics. However, the main challenge of integrating Brillouin devices is how to effectively confine both optical and acoustic waves. Apart from that, the manufacturing processes for these devices need to be compatible with standard fabrication platforms and streamlined to facilitate their large-scale integration. Here, we demonstrate a novel, to the best of our knowledge, suspended nanowire structure that can tightly confine photons and phonons. Furthermore, tailored for this structure, we introduce a loading-effect-based three-dimensional microfabrication technique, compatible with complementary metal-oxide-semiconductor (CMOS) technology. This innovative technique allows for the fabrication of the entire structure using a single-step lithography exposure, significantly streamlining the fabrication process. Leveraging this structure and fabrication scheme, we have achieved a Brillouin gain coefficient of 1100 W-1m-1 on the silicon-on-insulator platform within a compact footprint. It can support a Brillouin net gain over 4.1 dB with modest pump powers. We believe that this structure can significantly advance the development of SBS on chip, unlocking new opportunities for a large-scale integration of Brillouin-based photonic devices.

Slow-light-enhanced Brillouin scattering with integrated Bragg grating.

Advancements in photonic integration technology have enabled the effective excitation of simulated Brillouin scattering (SBS) on a single chip, boosting Brillouin-based applications such as microwave photonic signal processing, narrow-linewidth lasers, and optical sensing. However, on-chip circuits still require large pump power and centimeter-scale waveguide length to achieve a considerable Brillouin gain, making them both power-inefficient and challenging for integration. Here, we exploit the slow-light effect to significantly enhance SBS, presenting the first, to the best of our knowledge, demonstration of a slow-light Brillouin-active waveguide on the silicon-on-insulator (SOI) platform. By integrating a Bragg grating with a suspended ridge waveguide, a 2.1-fold enhancement of the forward Brillouin gain coefficient is observed in a 1.25 mm device. Furthermore, this device shows a Brillouin gain coefficient of 1,693 m-1W-1 and a mechanical quality factor of 1,080. The short waveguide length reduces susceptibility to inhomogeneous broadening, enabling the simultaneous achievement of a high Brillouin gain coefficient and a high mechanical quality factor. This approach introduces an additional dimension to enhance acousto-optic interaction efficiency in the SOI platform and holds significant potential for microwave photonic filters and high spatial resolution sensing.

Enhancement of Brillouin nonlinearities with a coupled resonator optical waveguide.

Stimulated Brillouin scattering (SBS) is a nonlinear optical phenomenon mediated from the coupling of photons and phonons. It has found applications in various realms, yet the acousto-optic interaction strength remains relatively weak. Enhancing the SBS with resonant structures could be a promising solution, but this method faces strict constraints in operational bandwidth. Here, we present the first demonstration to our knowledge of the broadband enhancement of Brillouin nonlinearities by a suspended coupled resonator optical waveguide (CROW) on an SOI platform. By comprehensively balancing the Brillouin gain and operational bandwidth, a 3-fold enhancement for the Brillouin gain coefficient (GB) and a broad operational bandwidth of over 80 GHz have been achieved. Furthermore, this 1.1 mm device shows a forward Brillouin gain coefficient of 2422 m-1W-1 and a high mechanical quality factor (Qm) of 1060. This approach marks a pivotal advancement toward wide bandwidth, low energy consumption, and compact integrated nonlinear photonic devices, with potential applications in tunable microwave photonic filters and phonon-based non-reciprocal devices.

Demonstration of a metastable argon laser of 10†W by transverse pumping.

Optically pumped metastable rare gas lasers have been extensively investigated as promising high-energy lasers. These systems employ discharge-excited metastable inert gases as the lasing medium. Following optical pumping, a buffer gas, typically helium, is introduced to facilitate a collisional population transfer to the p2[1/2]1 level, thereby establishing population inversion. To date, laser outputs in the watt level have been demonstrated. However, further power scaling crucially depends on the ability to stably generate high metastable densities at elevated pressures approaching atmospheric conditions. In this Letter, we report a pulsed discharge technique based on a peaking capacitor rapid discharge circuit, which is capable of producing metastable particle densities exceeding 1014 cm-3 at pressures up to 900 mbar. By employing this discharge approach in conjunction with transverse optical pumping, we have realized a maximum output power of 12.5 W from a semiconductor-pumped metastable argon laser system.

Tau suppresses microtubule-regulated pancreatic insulin secretion.

Tau protein is implicated in the pathogenesis of Alzheimer's disease (AD) and other tauopathies, but its physiological function is in debate. Mostly explored in the brain, tau is also expressed in the pancreas. We further explored the mechanism of tau's involvement in the regulation of glucose-stimulated insulin secretion (GSIS) in islet ß-cells, and established a potential relationship between type 2 diabetes mellitus (T2DM) and AD. We demonstrate that pancreatic tau is crucial for insulin secretion regulation and glucose homeostasis. Tau levels were found to be elevated in ß-islet cells of patients with T2DM, and loss of tau enhanced insulin secretion in cell lines, drosophila, and mice. Pharmacological or genetic suppression of tau in the db/db diabetic mouse model normalized glucose levels by promoting insulin secretion and was recapitulated by pharmacological inhibition of microtubule assembly. Clinical studies further showed that serum tau protein was positively correlated with blood glucose levels in healthy controls, which was lost in AD. These findings present tau as a common therapeutic target between AD and T2DM.

Self-Assemblies of Carboxylic Acid Derivatives with Different Symmetry: Adjusting by Solvent and Guest Molecules.

In this research, the self-assembly behaviors of two different symmetry carboxylic acid derivatives (H3BTE and H4BTE) regulated by solvent and guest molecule (coronene, COR) were explored at the liquid/solid interface by scanning tunneling microscopy, and the formation mechanism was investigated by density functional theory. In 1-phenyloctane, only H3BTE molecules dissolved with extremely low concentration and self-assembled into a honeycomb structure and a new strip structure, while H4BTE could not. In 1-heptanoic acid, H3BTE and H4BTE were easily dissolved, in which H3BTE formed a regular row structure and H4BTE formed a tetragonal structure, respectively. The host-guest interaction was investigated by introducing the COR molecules into their self-assembly structures, and due to the different symmetry, H3BTE and H4BTE displayed different accommodation behavior.

Bovine Serum Albumin Template-Mediated Fabrication of Ruthenium Dioxide/Multiwalled Carbon Nanotubes: High-Performance Electrochemical Dopamine Biosensing in Human Serum.

The presence of abnormal dopamine (DA) levels may cause serious neurological disorders, therefore, the quantitative analysis of DA and its related research are of great significance for ensuring health. Herein, the bovine serum albumin (BSA) template method has been proposed for the preparation of catalytically high-performance ruthenium dioxide/multiwalled carbon nanotube (RuO2/MWCNT) nanocomposites. The incorporation of MWCNTs has improved the active surface area and conductivity while effectively preventing the aggregation of RuO2 nanoparticles. The outstanding electrocatalytic performance of RuO2/MWCNTs has promoted the electro-oxidation of DA at neutral pH. The electrochemical sensing platform based on RuO2/MWCNTs has demonstrated a wide linear range (0.5 to 111.1 µM), low detection limit (0.167 µM), excellent selectivity, long-term stability, and good reproducibility for DA detection. The satisfactory recovery range of 94.7% to 103% exhibited by the proposed sensing podium in serum samples signifies its potential for analytical applications. The aforementioned results reveal that RuO2/MWCNT nanostructures hold promising aptitude in the electrochemical sensor to detect DA in real samples, further offering broad prospects in clinical and medical diagnosis.

Natural α-Methylene-γ-Butyrolactone Analogues: Synthesis and Evaluation of Isoaurone Derivatives as Antifungal Agents.

In order to develop novel, efficient and green fungicides, a series of novel isoaurone derivatives were designed and synthesized, which were characterized by 1H and 13C NMR, high-resolution mass spectra and melting points. The target compounds showed different inhibitory activities against seven plant pathogenic fungi. Compounds 1, 12, 17, 20, 22, 24 and intermediate A showed more than 90% inhibition rates against S. s at 50 mg/L. Interestingly, compound 22 and intermediate A showed the great inhibitory effect against S. s with EC50 values of 4.65 and 4.24 mg/L, which were better than the lead compound isoaurone (EC50 = 15.62 mg/L). The EC50 values of compounds 17 and 24 against B. c were 13.94 and 22.13 mg/L. Moreover, compound 19 displayed significant antifungal activity against G. g with the EC50 value of 11.88 mg/L. Theoretical calculations by DFT revealed that the α, ß-unsaturated carbonyl bond and the benzyl ring are very importantly linked to the strength of the fungicidal activity. Therefore, this study identified a valuable antifungal lead compound for further development of green fungicides.

Phytochemical analysis of different Callicarpa species based on integrating metabolomics and chemometrics.

INTRODUCTION: Traditionally, Callicarpa species have been utilized their anti-inflammatory and hemostatic properties. Prominently featured species in the 2020 Edition of the Chinese Pharmacopoeia were Callicarpa nudiflora (CN), Callicarpa macrophylla (CM), Callicarpa formosana (CF), and Callicarpa kwangtungensis (CK), which were formulated into several medicinal preparations. Extensive applications led to the significant depletion of CN's wild resources. The management of germplasm resources was significantly disordered. Adulteration issues were also prevalent. OBJECTIVE: It is imperative that the study aims to identify alternative sources for CN and other pharmacopeial varieties and develop methods to distinguish different Callicarpa species. RESULTS: Data were acquired using three mass spectrometry modes: Data Dependent Analysis (DDA), Data-Independent Analysis (DIA), and full mass spectrometry (MS). The DDA mode identified or inferred information on 54 compounds. The Full MS mode identified or inferred 74 compounds, including 20 that were previously unreported in Callicarpa. These compounds were confirmed using standards. The DIA mode did not facilitate identification due to missing precursor ion data. With metabolomics, 19 differential compounds were identified or inferred. Luteolin, chrysoeriol, and quercetin were selected as potential markers, integrating the 10 active compounds from network pharmacology. CONCLUSION: Based on the relative abundance of these markers, it was proposed that Callicarpa giraldii Hesse ex Rehd. var. (CGHRV) and CM could serve as alternative resource species to CN, while CGHRV and Callicarpa giraldii Hesse ex Rehd. (CGHR) could substitute the pharmacopeial CM. Callicarpa longissimi (CLG) was suggested as an alternative to CK, while Callicarpa cathayana (CC) and Callicarpa rubella (CRL) could replace CF. Furthermore, the absence of certain compounds in CK presented a novel opportunity for the differentiation of various Callicarpa species.

LSTM Short-Term Wind Power Prediction Method Based on Data Preprocessing and Variational Modal Decomposition for Soft Sensors.

Soft sensors have been extensively utilized to approximate real-time power prediction in wind power generation, which is challenging to measure instantaneously. The short-term forecast of wind power aims at providing a reference for the dispatch of the intraday power grid. This study proposes a soft sensor model based on the Long Short-Term Memory (LSTM) network by combining data preprocessing with Variational Modal Decomposition (VMD) to improve wind power prediction accuracy. It does so by adopting the isolation forest algorithm for anomaly detection of the original wind power series and processing the missing data by multiple imputation. Based on the process data samples, VMD technology is used to achieve power data decomposition and noise reduction. The LSTM network is introduced to predict each modal component separately, and further sum reconstructs the prediction results of each component to complete the wind power prediction. From the experimental results, it can be seen that the LSTM network which uses an Adam optimizing algorithm has better convergence accuracy. The VMD method exhibited superior decomposition outcomes due to its inherent Wiener filter capabilities, which effectively mitigate noise and forestall modal aliasing. The Mean Absolute Percentage Error (MAPE) was reduced by 9.3508%, which indicates that the LSTM network combined with the VMD method has better prediction accuracy.

Choriocapillaris reduction accurately discriminates against early-onset Alzheimer's disease.

INTRODUCTION: This study addresses the urgent need for non-invasive early-onset Alzheimer's disease (EOAD) prediction. Using optical coherence tomography angiography (OCTA), we present a choriocapillaris model sensitive to EOAD, correlating with serum biomarkers. METHODS: Eighty-four EOAD patients and 73 controls were assigned to swept-source OCTA (SS-OCTA) or the spectral domain OCTA (SD-OCTA) cohorts. Our hypothesis on choriocapillaris predictive potential in EOAD was tested and validated in these two cohorts. RESULTS: Both cohorts revealed diminished choriocapillaris signals, demonstrating the highest discriminatory capability (area under the receiver operating characteristic curve: SS-OCTA 0.913, SD-OCTA 0.991; P < 0.001). A sparser SS-OCTA choriocapillaris correlated with increased serum amyloid beta (Aß)42, Aß42/40, and phosphorylated tau (p-tau)181 levels (all P < 0.05). Apolipoprotein E status did not affect choriocapillaris measurement. DISCUSSION: The choriocapillaris, observed in both cohorts, proves sensitive to EOAD diagnosis, and correlates with serum Aß and p-tau181 levels, suggesting its potential as a diagnostic tool for identifying and tracking microvascular changes in EOAD. HIGHLIGHTS: Optical coherence tomography angiography may be applied for non-invasive screening of Alzheimer's disease (AD). Choriocapillaris demonstrates high sensitivity and specificity for early-onset AD diagnosis. Microvascular dynamics abnormalities are associated with AD.

Integrated "Two-in-One" Strategy for High-Rate Electrocatalytic CO2 Reduction to Formate.

The electrochemical CO2 reduction reaction (ECR) is a promising pathway to producing valuable chemicals and fuels. Despite extensive studies reported, improving CO2 adsorption for local CO2 enrichment or water dissociation to generate sufficient H* is still not enough to achieve industrial-relevant current densities. Herein, we report a "two-in-one" catalyst, defective Bi nanosheets modified by CrOx (Bi-CrOx), to simultaneously promote CO2 adsorption and water dissociation, thereby enhancing the activity and selectivity of ECR to formate. The Bi-CrOx exhibits an excellent Faradic efficiency (≈ 100 %) in a wide potential range from ‒0.4 to ‒0.9 V. In addition, it achieves a remarkable formate partial current density of 687 mA cm‒2 at a moderate potential of ‒0.9 V without iR compensation, the highest value at ‒0.9 V reported so far. Control experiments and theoretical simulations revealed that the defective Bi facilitates CO2 adsorption/activation while the CrOx accounts for enhancing the protonation process via accelerating H2O dissociation. This work presents a pathway to boosting formate production through tuning CO2 and H2O species at the same time.

Fullerene-like Niobovanadate Cage Built from {(Nb)V5 } Pentagon.

The striking aesthetic appeal of fullerene-like clusters has captured the interest of researchers. Nevertheless, the assembly of fullerene-like polyoxovadanadate (POV) cages remains a significant challenge due to the scarcity of suitable pentagonal motif. Herein, we have successfully synthesized the first fullerene-like all-inorganic POV cage, {(V2 O)V30 Nb12 O102 (H2 O)12 } (V30 Nb12 ), by introducing Nb into the POVs. V30 Nb12 is assembled by 12 heterometallic {(Nb)V5 } pentagons through sharing V centers with Ih symmetry, reminiscent of C60 . To our knowledge, the fullerene-like V30 Nb12 not only represents the highest-nuclearity POV cage but also stands as the first niobovanadate cluster. Notably, V30 Nb12 exhibits excellent solution stability, as confirmed by ESI-MS, FT-IR and UV/Vis spectra. As there is no protection organic ligand on its outer surface, V30 Nb12 can be further modified with Cu-complexes to form a fullerene-like cluster based zigzag chain (Cu-V30 Nb12 ).

Iron, ferroptosis, and ischemic stroke.

Over 30 million people suffer from the consequences of ischemic stroke. The precise molecular mechanism of neuronal damage during ischemic stroke remains unclear; therefore, the effective treatment of post-ischemic stroke remains a critical challenge. Recently, iron has emerged as a crucial factor in post-reperfusion injuries, participating in cell peroxidation, excitotoxicity, and a distinctive cell death pathway, namely, ferroptosis. Since iron is tightly regulated in the brain and important for brain functions, the imbalance of its metabolism, including its overload and deficiency, has been shown to impact ischemic stroke outcomes. This review summarizes the current understanding of pathological events associated with iron in ischemic stroke and discusses relevant drug development.

Phylogenetic distance-decay patterns are not explained by local community assembly processes in freshwater lake microbial communities.

While water and sediment microbial communities exhibit pronounced spatio-temporal patterns in freshwater lakes, the underlying drivers are yet poorly understood. Here, we evaluated the importance of spatial and temporal variation in abiotic environmental factors for bacterial and microeukaryotic community assembly and distance-decay relationships in water and sediment niches in Hongze Lake. By sampling across the whole lake during both Autumn and Spring sampling time points, we show that only bacterial sediment communities were governed by deterministic community assembly processes due to abiotic environmental drivers. Nevertheless, consistent distance-decay relationships were found with both bacterial and microeukaryotic communities, which were relatively stable with both sampling time points. Our results suggest that spatio-temporal variation in environmental factors was important in explaining mainly bacterial community assembly in the sediment, possibly due lesser disturbance. However, clear distance-decay patterns emerged also when the community assembly was stochastic. Together, these results suggest that abiotic environmental factors do not clearly drive the spatial structuring of lake microbial communities, highlighting the need to understand the role of other potential drivers, such as spatial heterogeneity and biotic species interactions.

Production of high-density metastable argon atoms with periodic fast pulsed DC discharge.

Optically pumped metastable rare gas laser (OPRGL), as a potential high-energy laser has attracted much attention. During extensive research on OPRGL, the realization of volume discharge with high-metastable density has always been a priority and is essential to the efficient lasing of OPRGL. A large-volume plasma of He/Ar with high metastable density at atmospheric pressure can be generated by applying peaking capacitors near the electrodes. In this article, 0.8 cm3 of He/Ar plasma at a pressure of 900 mBar, with a peak value of metastable argon density higher than 1014 cm-3 was realized. The metastable density was measured by absorption spectroscopy based on the absorption bandwidths acquired at a pressure range of 400-900 mbar where a probe beam at a weak line with wavelength 772.38 nm was applied. Furthermore, the high metastable density was verified by the laterally-observed laser-induced fluorescence, as well as the laser oscillation of 100 mW under a longitudinal pumping with a short gain length of 8 mm.

Brain regions susceptible to alpha-synuclein spreading.

The spreading of misfolded alpha-synuclein (α-syn) protein has been observed in animal models of Parkinson's disease (PD) and other α-synucleinopathies that mimic human PD pathologies. In animal models, the spreading of α-syn has been associated with motor dysfunction and neuronal death. However, variability in both susceptible brain regions and cellular populations limits our understanding of the consequences of α-syn spreading and the development of associated therapies. Here, we have reviewed the physiological and pathological functions of α-syn and summarized the susceptible brain regions and cell types identified from human postmortem studies and exogenous α-syn injection-based animal models. We have reviewed the methods for inducing α-syn aggregation, the specific hosts, the inoculation sites, the routes of propagation, and other experimental settings that may affect the spreading pattern of α-syn, as reported in current studies. Understanding the spread of α-syn to produce a consistent PD animal model is vital for future drug discovery.