Cell firing between ON alpha retinal ganglion cells and coupled amacrine cells in the mouse retina.

Gap junctions are channels that allow for direct transmission of electrical signals between cells. However, the ability of one cell to be impacted or controlled by other cells through gap junctions remains unclear. In this study, heterocellular coupling between ON α retinal ganglion cells (RGCs) and displaced amacrine cells (ACs) in the mouse retina was utilized as a model. The impact of the extent of coupling of interconnected ACs on the synchronized firing between coupled ON α RGC-ACs pairs was investigated. It was observed that the synchronized firing between the ON α RGC-ACs pairs was increased by the dopamine 1 receptor antagonist SCH23390, while it was eradicated by the agonist SKF38393. Subsequently, coupled ON α RGC-AC pairs were infected with the channelrhodopsin-2(ChR2) mutation L132C. The spikes of ON α RGCs (without ChR2) could be triggered by ACs (with ChR2) through the gap junction, and vice versa. Furthermore, it was observed that ON α RGCs stimulated with 3-10 Hz currents by whole-cell patch could elicit synchronous spikes in the coupled ACs, and vice versa. The study implies that the synchronized firing between ON α RGC-AC pairs could potentially be affected by the coupling of interconnected ACs, and another cell type could selectively control the firing of one cell type, and information could be forcefully transmitted. The key role of gap junctions in synchronizing firing and driving cells between α RGCs and coupled ACs in the mouse retina is highlighted.

Gap junctions fine-tune ganglion cell signals to equalize response kinetics within a given electrically coupled array.

Retinal ganglion cells (RGCs) summate inputs and forward a spike train code to the brain in the form of either maintained spiking (sustained) or a quickly decaying brief spike burst (transient). We report diverse response transience values across the RGC population and, contrary to the conventional transient/sustained scheme, responses with intermediary characteristics are the most abundant. Pharmacological tests showed that besides GABAergic inhibition, gap junction (GJ)-mediated excitation also plays a pivotal role in shaping response transience and thus visual coding. More precisely GJs connecting RGCs to nearby amacrine and RGCs play a defining role in the process. These GJs equalize kinetic features, including the response transience of transient OFF alpha (tOFFα) RGCs across a coupled array. We propose that GJs in other coupled neuron ensembles in the brain are also critical in the harmonization of response kinetics to enhance the population code and suit a corresponding task.

Hypolipidemic effect of polysaccharide from Sargassum fusiforme and its ultrasonic degraded polysaccharide on zebrafish fed high-fat diet.

Sargassum fusiforme is a brown seaweed that grows abundantly along the rocky coastlines of Asian countries. The polysaccharides derived from Sargassum fusiforme (SFPS) have received much interest due to their various bioactivities, such as hypolipidemic, hypoglycemic, and antioxidant activities. In this study, we extracted and purified SFPS, and obtained the ultrasonic degradation product (SFPSUD). The lipid regulatory effects of SFPS and SFPSUD were investigated in a zebrafish model fed a high-fat diet. The results showed that SFPS significantly decreased the levels of total cholesterol (TC) and triglycerides (TG), and increased the activities of lipoprotein lipase (LPL) and hepatic lipase (HL). SFPSUD was more effective than the SFPS in reducing the TC and TG levels in zebrafish, as well as increasing the LPL and HL activities. Histopathological observations of zebrafish livers showed that SFPSUD significantly improved lipid metabolism disorder in the hepatocytes. The possible lipid-lowering mechanism in zebrafish associated with SFPS and SFPSUD may involve acceleration of the lipid metabolism rate by increasing the activities of LPL and HL. Thus, SFPSUD could be tested as a highly effective hypolipidemic drug. Our results suggest that SFPS and SFPSUD have potential uses as functional foods for the prevention and treatment of hyperlipidemia. Ultrasound can be effectively applied to degrade SFPS to improve its physicochemical properties and bioactivities.

Spectroscopy in Nanoscopic Cavities: Models and Recent Experiments.

The ability of nanophotonic cavities to confine and store light to nanoscale dimensions has important implications for enhancing molecular, excitonic, phononic, and plasmonic optical responses. Spectroscopic signatures of processes that are ordinarily exceedingly weak such as pure absorption and Raman scattering have been brought to the single-particle limit of detection, while new emergent polaritonic states of optical matter have been realized through coupling material and photonic cavity degrees of freedom across a wide range of experimentally accessible interaction strengths. In this review, we discuss both optical and electron beam spectroscopies of cavity-coupled material systems in weak, strong, and ultrastrong coupling regimes, providing a theoretical basis for understanding the physics inherent to each while highlighting recent experimental advances and exciting future directions.

Rapid Mining of Fast Ion Conductors via Subgraph Isomorphism Matching.

The rapidly evolving field of inorganic solid-state electrolytes (ISSEs) has been driven in recent years by advances in data-mining techniques, which facilitates the high-throughput computational screening for candidate materials in the databases. The key to the mining process is the selection of critical features that underline the similarity of a material to an existing ISSE. Unfortunately, this selection is generally subjective and frequently under debate. Here we propose a subgraph isomorphism matching method that allows an objective evaluation of the similarity between two compounds according to the topology of the local atomic environment. The matching algorithm has been applied to discover four structure types that are highly analogous to the LiTi2(PO4)3 NASICON prototype. We demonstrate that the local atomic environments similar to LiTi2(PO4)3 endow these four structures with favorable Li diffusion tunnels and ionic conductivity on par with those of the prototype. By further taking into account the electronic structure and electrochemical stability window, 13 compounds are identified to be potential ISSEs. Our findings not only offer a promising approach toward rapid mining of fast ion conductors without limitation in the compositional range but also reveal insights into the design of ISSEs according to the topology of their framework structures.

Achieving optimal trade-off for student dropout prediction with multi-objective reinforcement learning.

Student dropout prediction (SDP) in educational research has gained prominence for its role in analyzing student learning behaviors through time series models. Traditional methods often focus singularly on either prediction accuracy or earliness, leading to sub-optimal interventions for at-risk students. This issue underlines the necessity for methods that effectively manage the trade-off between accuracy and earliness. Recognizing the limitations of existing methods, this study introduces a novel approach leveraging multi-objective reinforcement learning (MORL) to optimize the trade-off between prediction accuracy and earliness in SDP tasks. By framing SDP as a partial sequence classification problem, we model it through a multiple-objective Markov decision process (MOMDP), incorporating a vectorized reward function that maintains the distinctiveness of each objective, thereby preventing information loss and enabling more nuanced optimization strategies. Furthermore, we introduce an advanced envelope Q-learning technique to foster a comprehensive exploration of the solution space, aiming to identify Pareto-optimal strategies that accommodate a broader spectrum of preferences. The efficacy of our model has been rigorously validated through comprehensive evaluations on real-world MOOC datasets. These evaluations have demonstrated our model's superiority, outperforming existing methods in achieving optimal trade-off between accuracy and earliness, thus marking a significant advancement in the field of SDP.

Dynamic tracking of onion-like carbon nanoparticles in cancer cells using limited-angle holographic tomography with self-supervised learning.

This research presents a novel approach for the dynamic monitoring of onion-like carbon nanoparticles inside colorectal cancer cells. Onion-like carbon nanoparticles are widely used in photothermal cancer therapy, and precise 3D tracking of their distribution is crucial. We proposed a limited-angle digital holographic tomography technique with unsupervised learning to achieve rapid and accurate monitoring. A key innovation is our internal learning neural network. This network addresses the information limitations of limited-angle measurements by directly mapping coordinates to measured data and reconstructing phase information at unmeasured angles without external training data. We validated the network using standard SiO2 microspheres. Subsequently, we reconstructed the 3D refractive index of onion-like carbon nanoparticles within cancer cells at various time points. Morphological parameters of the nanoparticles were quantitatively analyzed to understand their temporal evolution, offering initial insights into the underlying mechanisms. This methodology provides a new perspective for efficiently tracking nanoparticles within cancer cells.

Insight into the Contact Mechanism of Ag/Al-Si Interface for the Front-Side Metallization of TOPCon Silicon Solar Cells.

For N-type tunnel-oxide-passivated-contact silicon solar cells, optimal Ag/Al-Si contact interface is crucial to improve the efficiency. However, the specific roles of Ag and Al at the interface have not been clearly elucidated. Hence, this work delves into the sintering process of Ag/Al paste and examines the impact of the Ag/Al-Si interface structure on contact quality. By incorporating TeO2 into PbO-based Ag/Al paste, the Ag/Al-Si interface structure can be modulated. It can be found that TeO2 accelerates the sintering of Ag powder and increases Ag colloids within glass layer, while it simultaneously impedes the diffusion of molten Al. It leads to a reduced Al content near the Ag/Al-Si interface and a shorter diffusion distance of Al into Si. Notably, it can be demonstrated that the diffusion of Al in Si layer is more effective to reduce the contact resistance than the precipitation of Ag colloids. Therefore, the PbO-based Ag/Al paste, which favors Al diffusion, leads to solar cells with lower contact resistance and series resistance, higher fill factor, and superior photoelectric conversion efficiency. In brief, this work is significant for optimizing metallization of silicon solar cells and other semiconductor devices.

Photoreceptor-Mimetic Microflowers for Restoring Light Responses in Degenerative Retina through a 2D Nanopetal/Cell Biointerface.

Retinitis pigmentosa is the main cause of inherited human blindness and is associated with dysfunctional photoreceptors (PRs). Compared with traditional methods, optoelectronic stimulation can better preserve the structural integrity and genetic content of the retina. However, enhancing the spatiotemporal accuracy of stimulation is challenging. Quantum dot-doped ZnIn2S4 microflowers (MF) are utilized to construct a biomimetic photoelectric interface with a 0D/3D heterostructure, aiming to restore the light response in PR-degenerative mice. The MF bio interface has dimensions similar to those of natural PRs and can be distributed within the curved spatial region of the retina, mimicking cellular dispersion. The soft 2D nano petals of the MF provide a large specific surface area for photoelectric activation and simulate the flexibility interfacing between cells. This bio interface can selectively restore the light responses of seven types of retina ganglion cells that encode brightness. The distribution of responsive cells forms a pattern similar to that of normal mice, which may reflect the generation of the initial "neural code" in the degenerative retina. Patch-clamp recordings indicate that the bio interface can induce spiking and postsynaptic currents at the single-neuron level. The results will shed light on the development of a potential bionic subretinal prosthetic toolkit for visual function restoration.

Enzyme activity test paper with high wet strength and anion adsorption properties fabricated from whole cationized softwood chemical fiber.

Paper-based test film material is widely used in a variety of test instruments for different applications. The enzyme activity test paper sheet is one of the most popularly used test papers. Here we present a novel fabrication of paper-based enzyme activity test paper without cationic resin added in. The chemical pulping fibers were first beaten to different degrees (from 14.6 to 41.5°SR) with a PFI beater. After that, the fibers were modified with a cationic agent (3-chloro-2-hydroxypropyl trimethyl ammonium chloride) under the system of alkali and water solution. Finally, the test papers were made with the modified fiber by a regular paper former in lab. The results showed that beating is beneficial for the improvement of the cationization reaction which is indicated by the Zeta potential, FTIR and EDS. The main mechanisms involved are the destruction of crystalline zone, increase of free hydroxyl group and defibrillation. This hypothesis was supported by the SEM, XRD and fiber analyzer. Beating under the optimized condition, the wet strength and liquid absorbability of test paper can meet the application requirement, and the test results of enzyme activity are quite close to those of commercial test papers.

Adaptive Signal Modulation Evolved by the Inherent Nonlinearity of Phase-Change Quantum-Dot String.

To simulate a topological neural network handling weak signals via stochastic resonance (SR), it is necessary to introduce an inherent nonlinearity into nanoscale devices. We use the self-assembly method to successfully fabricate a phase-change quantum-dot string (PCQDS) crossing Pd/Nb:AlNO/AlNO/Nb:AlNO/Pd multilayer. The inherent nonlinearity of phase change couples with electron tunneling so that PCQDS responds to a long signal sequence in a modulated output style, in which the pulse pattern evolves to that enveloped by two sets of periodic wave characterized by neural action potential. We establish an SR mode consisting of several two-state systems in which dissipative tunneling is coupled to environment. Size oscillations owing to NbO QDs adaptively adjust barriers and wells, such that tunneling can be periodically modulated by either asymmetric energy or local temperature. When the external periodic signals are applied, the system first follows the forcing frequency. Subsequently, certain PCQDs oscillate independently and consecutively to produce complicated frequency and amplitude modulations.

MATN4 as a target gene of HIF-1α promotes the proliferation and metastasis of osteosarcoma.

BACKGROUND: Osteosarcoma is a highly malignant bone tumor that exhibits rapid growth and early metastasis. Hypoxia plays a pivotal role in promoting the proliferation and metastasis of osteosarcoma through a series of molecular events, which are partially mediated and regulated by HIF-1α. However, the regulatory network associated with HIF-1α in osteosarcoma remains limited. Therefore, the objective of this study was to identify critical hypoxia-associated genes and investigate their effects and molecular mechanisms in osteosarcoma cells. METHODS: Through bioinformatics analysis, matrilin-4 (MATN4) was identified as a crucial gene associated with hypoxia. The expression of MATN4 and HIF-1α was assessed using immunohistochemistry, RT-qPCR, and western blotting. The proliferative capacity of osteosarcoma cells was assessed through the utilization of CCK-8, EDU staining, and colony formation assays. The effects of MATN4 on the mobility of OS cells were evaluated using wound-healing assays and transwell assays. The interaction between MATN4 and HIF-1α was detected through chromatin immunoprecipitation. RESULTS: MATN4 is overexpressed in osteosarcoma tissue and cells, particularly in osteosarcoma cells with high metastatic potential. Knockdown of MATN4 inhibits the proliferation, migration, and invasion abilities of osteosarcoma cells and reverses the promoting effects of hypoxia on these functions. Additionally, HIF-1α binds to MATN4 and upregulates its expression. Interestingly, knockdown of HIF-1α reduces the stimulatory effects of MATN4 overexpression on the proliferation, migration, and invasion of osteosarcoma cells under hypoxic conditions. CONCLUSIONS: Taken together, our results suggest that MATN4 is regulated by HIF-1α and confers a more aggressive phenotype on OS cells. This evidence suggests that MATN4 may act as a potential target for OS diagnosis and treatment.

Effects of drug-induced liver injury on the in vivo fate of liposomes.

Liposomes represent one of the most extensively studied nano-carriers due to their potential in targeted drug delivery. However, the complex in vivo fate, particularly under pathological conditions, presents challenges for clinical translation of liposomal therapeutics. Liver serves as the most important organ for liposome accumulation and metabolism. Unfortunately, the fate of liposomes under pathological liver conditions has been significantly overlooked. This study aimed to investigate the in vivo pharmacokinetic profile and biodistribution profile of liposomes under drug-induced liver injury (DILI) conditions. Two classic DILI animal models, i.e. acetaminophen-induced acute liver injury (AILI) and triptolide-induced subacute liver injury (TILI), were established to observe the effect of pathological liver conditions on the in vivo performance of liposomes. The study revealed significant changes in the in vivo fate of liposomes following DILI, including prolonged blood circulation and enhanced hepatic accumulation of liposomes. Changes in the composition of plasma proteins and mononuclear phagocyte system (MPS)-related cell subpopulations collectively led to the altered in vivo fate of liposomes under liver injury conditions. Despite liver injury, macrophages remained the primary cells responsible for liposomes uptake in liver, with the recruited monocyte-derived macrophages exhibiting enhanced ability to phagocytose liposomes under pathological conditions. These findings indicated that high capture of liposomes by the recruited hepatic macrophages not only offered potential solutions for targeted delivery, but also warned the clinical application of patients under pathological liver conditions.

Effects of Surface IR783 Density on the In Vivo Behavior and Imaging Performance of Liposomes.

Background: Nanoparticles conjugated with fluorescent probes have versatile applications, serving not only for targeted fluorescent imaging but also for evaluating the in vivo profiles of designed nanoparticles. However, the relationship between fluorophore density and nanoparticle behavior remains unexplored. Methods: The IR783-modified liposomes (IR783-sLip) were prepared through a modified ethanol injection and extrusion method. The cellular uptake efficiency of IR783-sLip was characterized by flow cytometry and fluorescence microscope imaging. The effects of IR783 density on liposomal in vivo behavior were investigated by pharmacokinetic studies, biodistribution studies, and in vivo imaging. The constitution of protein corona was analyzed by the Western blot assay. Results: Dense IR783 modification improved cellular uptake of liposomes in vitro but hindered their blood retention and tumor imaging performance in vivo. We found a correlation between IR783 density and protein corona absorption, particularly IgM, which significantly impacted the liposome performance. Meanwhile, we observed that increasing IR783 density did not consistently improve the effectiveness of tumor imaging. Conclusions: Increasing the density of modified IR783 on liposomes is not always beneficial for tumor near-infrared (NIR) imaging yield. It is not advisable to prematurely evaluate novel nanomaterials through fluorescence dye conjugation without carefully optimizing the density of the modifications.

Effect of acupuncture on tic disorder: a randomized controlled clinical trial based on energy metabolomics and infrared thermography.

BACKGROUND: Acupuncture is a method for treating tic disorder. However, there is a lack of sufficient clinical objective basis in regards of its treatment efficacy. Indeed, there are structural abnormalities present in energy metabolism and infrared thermography in children with tic disorder. Therefore, this study proposes a clinical trial scheme to explore the possible mechanism of acupuncture in treating tic disorder. METHODS: This randomized controlled trial will recruit a total of 90 children, in which they will be divided into non-intervention group and intervention group. The non-intervention group consists of 30 healthy children while the intervention group consists of 60 children with tic disorder. The intervention group will be randomly allocated into either the treatment group or the control group, with 30 children randomly assigned in each group. Children either received acupuncture treatment and behavioral therapy (treatment group) or sham acupuncture treatment and behavioral therapy (control group), 3 treatment sessions per week for a period of 12 weeks, with a total of 36 treatment sessions. Outcome measures include YGTSS, urinary and fecal metabolomics, infrared thermography of body surface including governor vessel. For the intervention group, these outcome measures will be collected at the baseline and 90th day prior to intervention. Whereas for the non-intervention group, outcome measures (excluding YGTSS) will be collected at the baseline. DISCUSSION: The main outcome will be to observe the changes of the severity of tic condition, the secondary outcome will be to observe the changes of structural characteristic of infrared thermography of body surface/acupoints along the governor vessel and to evaluate the changes of urinary and fecal metabolomics at the end of the treatment, so as to analyze the relationship between them and to provide further knowledge in understanding the possible mechanism of acupuncture in improving the clinical symptoms via regulating and restoring the body metabolomics network, which in future it can develop as a set of clinical guideline (diagnosis, treatment, assessment, prognosis) in treating tic disorder. ChiCTR2300075188(Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 29 August 2023).

Advances and prospects in deuterium metabolic imaging (DMI): a systematic review of in vivo studies.

BACKGROUND: Deuterium metabolic imaging (DMI) has emerged as a promising non-invasive technique for studying metabolism in vivo. This review aims to summarize the current developments and discuss the futures in DMI technique in vivo. METHODS: A systematic literature review was conducted based on the PRISMA 2020 statement by two authors. Specific technical details and potential applications of DMI in vivo were summarized, including strategies of deuterated metabolites detection, deuterium-labeled tracers and corresponding metabolic pathways in vivo, potential clinical applications, routes of tracer administration, quantitative evaluations of metabolisms, and spatial resolution. RESULTS: Of the 2,248 articles initially retrieved, 34 were finally included, highlighting 2 strategies for detecting deuterated metabolites: direct and indirect DMI. Various deuterated tracers (e.g., [6,6'-2H2]glucose, [2,2,2'-2H3]acetate) were utilized in DMI to detect and quantify different metabolic pathways such as glycolysis, tricarboxylic acid cycle, and fatty acid oxidation. The quantifications (e.g., lactate level, lactate/glutamine and glutamate ratio) hold promise for diagnosing malignancies and assessing early anti-tumor treatment responses. Tracers can be administered orally, intravenously, or intraperitoneally, either through bolus administration or continuous infusion. For metabolic quantification, both serial time point methods (including kinetic analysis and calculation of area under the curves) and single time point quantifications are viable. However, insufficient spatial resolution remains a major challenge in DMI (e.g., 3.3-mL spatial resolution with 10-min acquisition at 3 T). CONCLUSIONS: Enhancing spatial resolution can facilitate the clinical translation of DMI. Furthermore, optimizing tracer synthesis, administration protocols, and quantification methodologies will further enhance their clinical applicability. RELEVANCE STATEMENT: Deuterium metabolic imaging, a promising non-invasive technique, is systematically discussed in this review for its current progression, limitations, and future directions in studying in vivo energetic metabolism, displaying a relevant clinical potential. KEY POINTS: • Deuterium metabolic imaging (DMI) shows promise for studying in vivo energetic metabolism. • This review explores DMI's current state, limits, and future research directions comprehensively. • The clinical translation of DMI is mainly impeded by limitations in spatial resolution.

Alleviating Structure Collapse of Polycrystalline LiNixCoyMn1-x-yO2 via Surface Co Enrichment.

The structure collapse issues have long restricted the application of polycrystalline LiNixCoyMn1-x-yO2 (NCM) at high voltages beyond 4.4 V vs Li/Li+. Herein, for LiNi0.55Co0.12Mn0.33O2 (P-NCM), rapid surface degradation is observed upon the first charge, along with serious particle fragmentation upon repeated cycles. To alleviate these issues, a surface Co enrichment strategy is proposed [i.e., Co-enriched NCM (C-NCM)], which promotes the in situ formation of a robust surface rock-salt (RS) layer upon charge, serving as a highly stable interface for effective Li+ migration. Benefiting from this stabilized surface RS layer, Li+ extraction occurs mainly through this surface RS layer, rather than along the grain boundaries (GBs), thus reducing the risk of GBs' cracking and even particle fragmentation upon cycles. Besides, O loss and TM (TM = Ni, Co, and Mn) dissolution are also effectively reduced with fewer side reactions. The C-NCM/graphite cell presents a highly reversible capacity of 205.1 mA h g-1 at 0.2 C and a high capacity retention of 86% after 500 cycles at 1 C (1 C = 200 mA g-1), which is among the best reported cell performances. This work provides a different path for alleviating particle fragmentation of NCM cathodes.

Association of fetal fraction and cell-free fetal DNA with adverse pregnancy outcomes: A systematic review.

BACKGROUND: Adverse pregnancy outcomes, which can be caused by multiple factors, present a significant threat to the health of mothers and their babies. Cell-free fetal DNA (cffDNA) from placental trophoblast cells might be able to reflect placental and fetal status. Previous studies have yielded controversial results regarding the association of FF or cffDNA with various adverse pregnancy outcomes. A previous study has attempted to systematically assess the association between low fetal fraction (FF) and adverse pregnancy outcomes, but it failed to perform quantitative analyses due to the few studies included. In the present study, we attempted to quantitatively assess the association of FF (or cffDNA) with adverse pregnancy outcomes and further analyze the causes of heterogeneity. OBJECTIVES: To investigate the association of high/low FF or cffDNA with adverse pregnancy outcomes. SEARCH STRATEGY: We searched the databases of PubMed, Embase, Cochrane, and Web of Science from January 1, 1990, to June 15, 2022 in this meta-analysis. SELECTION CRITERIA: Studies on the relationships of adverse pregnancy outcomes in women with FF or cell free DNA were included. Non-English literature was excluded. DATA COLLECTION AND ANALYSIS: Data about pregnancy outcomes and cell free DNA were extracted and meta-analyzed. Subgroup analysis was performed by different outcomes. MAIN RESULTS: There were 11 studies included involving 8280 participants. No significant heterogeneity was observed among the studies (I2 = 27%, 25%), and a fixed-effect model was used for weighted quantitative analysis. The results revealed that the FF or cffDNA during pregnancy was significantly associated with adverse pregnancy outcomes in pregnant women (OR = 1.57, 95% CI [1.24, 1.99], P = 0.233). The overall incidence of the maternal adverse outcomes was 8% (95% CI: 5-13). Subgroup analysis of different outcomes showed an evident association between low FF or cffDNA and hypertensive disorders of pregnancy (HDP) (OR = 1.76, 95% CI [1.36, 2.27], P = 0.581). There was no evidence that the occurrence of spontaneous preterm birth (sPTB) and placental abnormality was associated with FF or cffDNA. No association was observed between low FF or cffDNA during pregnancy and adverse outcomes in fetuses (OR = 1.39, 95% CI [0.99, 1.94], P = 0.242). The overall incidence of adverse outcomes in fetuses was 8% (95% CI: 6-11). There were controversies over the association between high FF or cffDNA and HDP, and sPTB and small for gestational age infant, among different studies. CONCLUSIONS: Pregnant women with low FF or cffDNA during the first or second trimester of pregnancy have an overall increased risk of adverse pregnancy outcomes, especially HDP. However, the association between FF and various pregnancy outcomes needs to be further explored by more prospective studies.

Mechanochemically Robust LiCoO2 with Ultrahigh Capacity and Prolonged Cyclability.

Pushing intercalation-type cathode materials to their theoretical capacity often suffers from fragile Li-deficient frameworks and severe lattice strain, leading to mechanical failure issues within the crystal structure and fast capacity fading. This is particularly pronounced in layered oxide cathodes because the intrinsic nature of their structures is susceptible to structural degradation with excessive Li extraction, which remains unsolved yet despite attempts involving elemental doping and surface coating strategies. Herein, a mechanochemical strengthening strategy is developed through a gradient disordering structure to address these challenges and push the LiCoO2 (LCO) layered cathode approaching the capacity limit (256 mAh g-1, up to 93% of Li utilization). This innovative approach also demonstrates exceptional cyclability and rate capability, as validated in practical Ah-level pouch full cells, surpassing the current performance benchmarks. Comprehensive characterizations with multiscale X-ray, electron diffraction, and imaging techniques unveil that the gradient disordering structure notably diminishes the anisotropic lattice strain and exhibits high fatigue resistance, even under extreme delithiation states and harsh operating voltages. Consequently, this designed LCO cathode impedes the growth and propagation of particle cracks, and mitigates irreversible phase transitions. This work sheds light on promising directions toward next-generation high-energy-density battery materials through structural chemistry design.

Analysis of the effects of M2 macrophage-derived PDE4C on the prognosis, metastasis and immunotherapy benefit of osteosarcoma.

Tumour-associated macrophages (TAMs), encompassing M1 and M2 subtypes, exert significant effects on osteosarcoma (OS) progression and immunosuppression. However, the impacts of TAM-derived biomarkers on the progression of OS remains limited. The GSE162454 profile was subjected to single-cell RNA (scRNA) sequencing analysis to identify crucial mediators between TAMs and OS cells. The clinical features, effects and mechanisms of these mediators on OS cells and tumour microenvironment were evaluated via biological function experiments and molecular biology experiments. Phosphodiesterase 4C (PDE4C) was identified as a pivotal mediator in the communication between M2 macrophages and OS cells. Elevated levels of PDE4C were detected in OS tissues, concomitant with M2 macrophage level, unfavourable prognosis and metastasis. The expression of PDE4C was observed to increase during the conversion process of THP-1 cells to M2 macrophages, which transferred the PDE4C mRNA to OS cells through exosome approach. PDE4C increased OS cell proliferation and mobility via upregulating the expression of collagens. Furthermore, a positive correlation was observed between elevated levels of PDE4C and increased TIDE score, decreased response rate following immune checkpoint therapy, reduced TMB and diminished PDL1 expression. Collectively, PDE4C derived from M2 macrophages has the potential to enhance the proliferation and mobility of OS cells by augmenting collagen expression. PDE4C may serve as a valuable biomarker for prognosticating patient outcomes and response rates following immunotherapy.