Exploring resveratrol against Alzheimer's disease and Parkinson's disease through integrating network pharmacology, bioinformatics, and experimental validation strategy in vitro.

Background: The study aims to investigate the pharmacological basis and molecular mechanisms of resveratrol in the treatment of Alzheimer's disease (AD) and Parkinson's disease (PD) through the approach of treating different diseases with the same method, guided by traditional Chinese medicine theory. Utilizing network pharmacology and bioinformatics methods, this research aims to provide modern medical evidence for the theory of treating different diseases with the same method in traditional Chinese medicine. Methods: Omnibus from Swiss Target Prediction, TCMSP, SuperPred, SEA, HIT, CTD, TCMIP and Gene Expression Disease datasets for resveratrol related genes, Alzheimer's disease, and Parkinson's disease were obtained from the GEO database. Core targets were identified by weighted gene coexpression network analysis (WGCNA) and minimum absolute contraction and selection operator (LASSO). The expression of core targets was verified in AD and PD cell models. The immune characteristics of AD and PD were analyzed by CIBERSORT algorithm. Finally, the potential mechanism of resveratrol intervention on the core target was studied by molecular docking technique. Results: The results of network pharmacological analysis showed that resveratrol acted on 85 common targets such as STAT3 and CASP3, affected AGE-RAGE signaling pathway and PI3K-Akt signaling pathway, and showed the effect of "same disease and different treatment" for AD and PD. Three core targets associated with AD and PD (PLK4, FCGRT, and PRKAR2A) were finally identified through comprehensive transcriptome analysis, and experimentally verified in cell models of AD and PD. At the same time, the analysis of immune cell infiltration suggested that AD and PD had dysregulation of inflammation, and the core target was significantly related to M2 macrophages. Conclusion: Resveratrol may play a potential mechanism of "treating the same disease with different diseases" and target three core targets (PLK4, FCGRT and PRKAR2A) to improve the disease process of AD and PD by participating in the regulation of immune and inflammatory pathways. These findings have potential implications for clinical practice and future research.

Phosphorus dynamics in volcanic soils of Weizhou Island, China: implications for environmental and agricultural applications.

The dynamics of phosphorus are intricately governed by geological and ecological processes. Examining phosphorus dynamics in volcanic islands can enhance our comprehension of its behavior within such unique geological systems. However, research on phosphorus dynamics in volcanic islands remains limited. We investigated the phosphorus content of volcaniclastic rocks and basalt soils from Weizhou Island, China, to understand the influencing factors on phosphorus dynamics. The results indicate that in the volcaniclastic profile, phosphorus concentrates at 20-40 cm (17 mg/kg), decreases at 40-60 cm (11.9 mg/kg), and increases at 80-200 cm up to 46.4 mg/kg proximate to the bedrock, for the basalt profile, phosphorus content increases from the surface (80.2 mg/kg) towards the bedrock (83.9 mg/kg). The differences in phosphorus distribution between volcaniclastic rocks and basalts reflect the influence of parent material, rock weathering degree, carbonate content, topographic elevation, sea level changes, and geological activities. A strong positive correlation (R = 0.96907) between total and available phosphorus has been observed, suggesting that total phosphorus content effectively predicts available phosphorus content. Volcaniclastic rocks in wharves and high-elevation areas show low total phosphorus, while forest land with dense vegetation and neutral to alkaline soil supports higher total phosphorus due to enhanced bioavailability for plant absorption and utilization. Overall, the basalt soil of the volcanic island Weizhou Island demonstrates superior long-term fertility compared to the volcaniclastic soil. Despite its low total phosphorus content, it mainly exists in a highly bioavailable form, facilitating plant absorption, which is crucial for enhancing agricultural yields and ecosystem restoration on volcanic islands.

Optimizing entropy weight model to accurately predict variation of pharmaceuticals and personal care products in the estuaries and coasts of the South China.

Pharmaceuticals and personal care products (PPCPs) have raised increasing concern worldwide due to their continuous release and potential hazards to the ecosystem and human health. This study optimized the entropy weight model (EW-WRSR) that combines entropy weight with multi-criteria decision analysis to investigate pollution patterns of PPCPs in the coasts and estuaries. The results revealed that occurrences of PPCPs from the 1940s to the present were consistent with using PPCPs, different types of human activities, and local urban development. This helped better understand the history of PPCP contamination and evaluate the uncertainty of EW-WRSR. The model predicted hotspots of PPCPs that were consistent with the actual situation, indicating that PPCPs mainly enter the nearshore ecosystem by the form of sewage discharge and residual aquaculture. This study can provide method that identifying highly contaminated regions on a global scale.

Microplastics and arsenic speciation in edible bivalves from the coast of China: Distribution, bioavailability, and human health risk.

Bivalves, such as oysters and mussels, are exposed to environmental pollutants, like microplastics (MPs) and arsenic (As). This study investigated co-existence and interaction of MPs and As (total As and As species) in two bivalve species from the Chinese coastline. Smaller MPs (20-100 µm) averaged 30.98 items/g, while larger MPs (100-500 µm) averaged 2.98 items/g. Oysters contained more MPs (57.97 items/g) in comparison to mussels (11.10 items/g). In Contrast, mussels had a higher As concentrations (8.36-23.65 mg/kg) than oysters (4.97-11.02 mg/kg). The size and composition of MPs influenced As uptake and speciation in bivalves, with inorganic arsenic (iAs) and methylated arsenic (MMA and DMA) correlating with larger-sized MPs. Polyethylene (PE) may interact with the formation of arsenobetaine (AsB) in oyster. This study provides valuable insights into the interaction of MPs and As in marine ecosystems and highlights their implications for food safety.

Betulin Enables Multifunctional Cellulose-Based Insulative Foams with Low Environmental Impacts.

The significance of synthetic foams as insulative materials stems from their mechanical and water resistance as well as their cost-effectiveness. Broadly, the design of building envelopes should also consider fire and mold resistance and the impacts on the environment (end of life and compostability). This study addresses these issues considering the ever-increasing demand for sustainable sources to develop highly porous insulative materials. We introduce a versatile strategy based on wet-foam laying of cellulosic fibers that leads to hierarchical structures whose performance is tailored by the surface incorporation of betulin (BT), a bioactive molecule extracted from tree bark, combined with poly(dimethylsiloxane) (PDMS) after installation of urethane linkages. As such, we introduce an eco-friendly alternative to traditional polyurethane foams with competitive mechanical and thermal insulation performance. The modification of the fiber foams at low BT loading simultaneously endows superhydrophobicity (water contact angle >150°), fire retardancy (self-extinguish within 10 s), microbial resistance, and durability (no degradation in soil conditions after 3 months). BT plays a critical role as an antimicrobial and hydrophobic agent that synergizes with PDMS to achieve fire resistance. The life cycle assessment of the BT-modified foams reveals a significant reduction in greenhouse gas emission and human toxicity compared with rigid polyurethane foams by 96 and 92%, respectively. Overall, the valorization of the bark-derived BT is demonstrated by considering the scalability and cost-effectiveness of solid foams designed to substitute petroleum-derived counterparts.

Billed advance care planning visits may be occurring among older adults with high risk of mortality.

CONTEXT: Advance care planning (ACP) is a process that helps people prepare to make decisions about their future medical care. OBJECTIVES: We sought to understand who was received billed ACP visits and measure the association with health care utilization, cost, and mortality. METHODS: We used a randomly sampled 20 % cohort of Medicare fee-for-service (FFS) beneficiaries' files to conduct a retrospective cohort study. Beneficiaries with a billed ACP visit were matched to controls using a 2-stage propensity score matching process that included assigning a pseudo-ACP visit date for controls. Outcomes included healthcare utilization, mortality, and total medical cost per month. We used descriptive statistics for univariate analysis and fit multilevel logistic regression, multilevel linear regression, or Cox regression models. RESULTS: We identified 183,513 beneficiaries who received any billed ACP visit and 550,539 matched controls. Of those who had a ACP visit, the mean age was 76.5 years and high-risk comorbidities were common: 16 % dementia, 10 % congestive heart failure, 10 % cancer. Beneficiaries who had an ACP visit had slightly more health care utilization than controls. Beneficiaries who had an ACP visit were more likely to die (3.1% vs. 1.0 %, p < 0.01, OR=3.0, 95 %CI 2.9-3.2) in the unadjusted and adjusted analyses compared to matched controls. Total monthly medical costs were 33 % higher among beneficiaries who had an ACP visit. CONCLUSION: Our results suggest that ACP visits may be preferentially utilized amongst individuals with higher risk of mortality. There may be an opportunity to increase ACP visits among older adults at lower risk for mortality. KEY MESSAGE: This article suggests that ACP visits are likely targeted to older adults with a higher risk of mortality than those at lower risk of mortality suggesting an opportunity to reach people before they are facing end-of-life decisions.

Synergistic Electrocatalysis and Spatial Nanoconfinement to Accelerate Sulfur Conversion Kinetics in Aqueous Zn-S Battery.

Aqueous zinc batteries based on the conversion-type sulfur cathodes are promising in energy storage system due to the high theoretical energy density, low cost, and good safety. However, the multi-electron solid-state intermediate conversion reaction of sulfur cathodes generally possess sluggish kinetics, which leads to lower discharge voltage and inefficient sulfur utilization, thus suppressing the practical energy density. Herein, sulfur nanoparticles derived from metal-organic frameworks confined in situ within electrospun fibers derived sulfur and nitrogen co-doped carbon nanofibers (S@S,N-CNF) composite, which possesses yolk-shell S@C nanostructure, is fabricated through successive sulfidation, pyrolysis, and sulfide oxidation processes, and served as a high-performance cathode material for Zn-S battery. The S and N dopants on carbon can collectively catalyse sulfur reduction reaction (SRR) by lowering energy barrier and accelerating kinetics to increase discharge voltage and specific capacity. Meanwhile, the yolk-shell S@C structure with spatially confined S nanoparticle yolks is beneficial to improve charge transfer and lower activation energy, thus further expediting SRR kinetics. Furthermore, extensive density functional theory (DFT) calculations reveal that S and N dual-doping can thermodynamically and dynamically reduce the energy barrier of rate-determining step (i.e., the transformation of *ZnS4 into *ZnS2) for the overall SRR, thereby significantly accelerating SRR kinetics.

Engagement in mHealth-Prompted Self-Measured Blood Pressure Monitoring Among Participants Recruited From a Safety-Net Emergency Department: Secondary Analysis of the Reach Out Trial.

Background: Hypertension, a key modifiable risk factor for cardiovascular disease, is more prevalent among Black and low-income individuals. To address this health disparity, leveraging safety-net emergency departments for scalable mobile health (mHealth) interventions, specifically using text messaging for self-measured blood pressure (SMBP) monitoring, presents a promising strategy. This study investigates patterns of engagement, associated factors, and the impact of engagement on lowering blood pressure (BP) in an underserved population. Objective: We aimed to identify patterns of engagement with prompted SMBP monitoring with feedback, factors associated with engagement, and the association of engagement with lowered BP. Methods: This is a secondary analysis of data from Reach Out, an mHealth, factorial trial among 488 hypertensive patients recruited from a safety-net emergency department in Flint, Michigan. Reach Out participants were randomized to weekly or daily text message prompts to measure their BP and text in their responses. Engagement was defined as a BP response to the prompt. The k-means clustering algorithm and visualization were used to determine the pattern of SMBP engagement by SMBP prompt frequency-weekly or daily. BP was remotely measured at 12 months. For each prompt frequency group, logistic regression models were used to assess the univariate association of demographics, access to care, and comorbidities with high engagement. We then used linear mixed-effects models to explore the association between engagement and systolic BP at 12 months, estimated using average marginal effects. Results: For both SMBP prompt groups, the optimal number of engagement clusters was 2, which we defined as high and low engagement. Of the 241 weekly participants, 189 (78.4%) were low (response rate: mean 20%, SD 23.4) engagers, and 52 (21.6%) were high (response rate: mean 86%, SD 14.7) engagers. Of the 247 daily participants, 221 (89.5%) were low engagers (response rate: mean 9%, SD 12.2), and 26 (10.5%) were high (response rate: mean 67%, SD 8.7) engagers. Among weekly participants, those who were older (>65 years of age), attended some college (vs no college), married or lived with someone, had Medicare (vs Medicaid), were under the care of a primary care doctor, and took antihypertensive medication in the last 6 months had higher odds of high engagement. Participants who lacked transportation to appointments had lower odds of high engagement. In both prompt frequency groups, participants who were high engagers had a greater decline in BP compared to low engagers. Conclusions: Participants randomized to weekly SMBP monitoring prompts responded more frequently overall and were more likely to be classed as high engagers compared to participants who received daily prompts. High engagement was associated with a larger decrease in BP. New strategies to encourage engagement are needed for participants with lower access to care.

Edible bird's nest alleviates pneumonia caused by tobacco smoke inhalation through the TNFR1/NF-κB/NLRP3 pathway.

Exposure to cigarette smoke directly damages the lungs and causes lung inflammation. The anti-inflammatory properties of edible bird's nest (EBN) have been reported. We aimed to determine the effect of EBN on pneumonia in a mouse model exposed to cigarette smoke. Fifty BALB/c mice were randomly divided into control, model, positive drug, low-dose EBN, and high-dose EBN groups (n = 10 each). Except for the control group, the mice in each group were exposed to four cigarettes once a day for 8 days. In addition, we validated the effects of EBN on A549 cells and investigated the mechanism by which EBN alleviates lung inflammation. Edible bird's nest (EBN) could alleviate the structural damage of lung tissue and the smoke-induced inflammatory response in mice. The best effect was observed at the high dose of EBN (0.019 g). The mice treated with EBN had a stronger ability than those in the model group to resist cigarette smoke stimulation, as indicated by a decrease in serum and lung inflammatory markers (interleukin 6 [IL-6], tumor necrosis factor-α [TNF-α], and interleukin 8 [IL-8]), an increase in serum interleukin 10 (IL-10) levels, and a decrease in the expression of inflammasome NOD-like receptor pyrin 3 (NLRP3). In addition, our cell experiments showed that EBN attenuated cigarette smoke-induced pulmonary inflammation mainly by inhibiting the tumor necrosis factor receptor 1 (TNFR1)/nuclear factor-kappa B (NF-κB)/NLRP3 pathway. These findings provide theoretical evidence for the positive nutritional qualities of EBN for the lung by demonstrating that it inhibits the TNFR1/NF-κB/NLRP3 signaling pathway, which prevents the development of cigarette smoke-induced pulmonary inflammation.

Ultrastructural insights into cellular organization, energy storage and ribosomal dynamics of an ammonia-oxidizing archaeon from oligotrophic oceans.

Introduction: Nitrososphaeria, formerly known as Thaumarchaeota, constitute a diverse and widespread group of ammonia-oxidizing archaea (AOA) inhabiting ubiquitously in marine and terrestrial environments, playing a pivotal role in global nitrogen cycling. Despite their importance in Earth's ecosystems, the cellular organization of AOA remains largely unexplored, leading to a significant unanswered question of how the machinery of these organisms underpins metabolic functions. Methods: In this study, we combined spherical-chromatic-aberration-corrected cryo-electron tomography (cryo-ET), scanning transmission electron microscopy (STEM), and energy dispersive X-ray spectroscopy (EDS) to unveil the cellular organization and elemental composition of Nitrosopumilus maritimus SCM1, a representative member of marine Nitrososphaeria. Results and Discussion: Our tomograms show the native ultrastructural morphology of SCM1 and one to several dense storage granules in the cytoplasm. STEM-EDS analysis identifies two types of storage granules: one type is possibly composed of polyphosphate and the other polyhydroxyalkanoate. With precise measurements using cryo-ET, we observed low quantity and density of ribosomes in SCM1 cells, which are in alignment with the documented slow growth of AOA in laboratory cultures. Collectively, these findings provide visual evidence supporting the resilience of AOA in the vast oligotrophic marine environment.

Pulse Feature-Enhanced Classification of Microalgae and Cyanobacteria Using Polarized Light Scattering and Fluorescence Signals.

Harmful algal blooms (HABs) pose a global threat to the biodiversity and stability of local aquatic ecosystems. Rapid and accurate classification of microalgae and cyanobacteria in water is increasingly desired for monitoring complex water environments. In this paper, we propose a pulse feature-enhanced classification (PFEC) method as a potential solution. Equipped with a rapid measurement prototype that simultaneously detects polarized light scattering and fluorescence signals of individual particles, PFEC allows for the extraction of 38 pulse features to improve the classification accuracy of microalgae, cyanobacteria, and other suspended particulate matter (SPM) to 89.03%. Compared with microscopic observation, PFEC reveals three phyla proportions in aquaculture samples with an average error of less than 14%. In this paper, PFEC is found to be more accurate than the pulse-average classification method, which is interpreted as pulse features carrying more detailed information about particles. The high consistency of the dominant and common species between PFEC and microscopy in all field samples also demonstrates the flexibility and robustness of the former. Moreover, the high Pearson correlation coefficient accounting for 0.958 between the cyanobacterial proportion obtained by PFEC and the cyanobacterial density given by microscopy implies that PFEC serves as a promising early warning tool for cyanobacterial blooms. The results of this work suggest that PFEC holds great potential for the rapid and accurate classification of microalgae and cyanobacteria in aquatic environment monitoring.

Research on the phase error of a Sagnac interferometer induced by modulation of a multifunctional integrated optical modulator.

High-precision IFOG requires an optical sensitivity of up to 10-8 rads-1 for interferometers; noise and error are two of the main reasons limiting its accuracy improvement. Any potential source of the signal error is worth being studied. This article introduces work on the modulation signal error caused by the mechanical vibration energy loss of MIOC crystals. This article theoretically derives and simulates the frequency spectrum of an energy loss from the perspective of electromechanical coupling and verifies it through experiments. This article also verifies the influence of MIOC mechanical loss on the output of a Sagnac interferometer through experiments. This study is an indispensable part of the bottleneck for improving the accuracy of ultrahigh-precision closed-loop IFOG and has potential engineering application value.

The gut microbiome promotes locomotion of Drosophila larvae via octopamine signaling.

The gut microbiome is a key partner of animals, influencing various aspects of their physiology and behaviors. Among the diverse behaviors regulated by the gut microbiome, locomotion is vital for survival and reproduction, although the underlying mechanisms remain unclear. Here, we reveal that the gut microbiome modulates the locomotor behavior of Drosophila larvae via a specific neuronal type in the brain. The crawling speed of germ-free (GF) larvae was significantly reduced compared to the conventionally reared larvae, while feeding and excretion behaviors were unaffected. Recolonization with Acetobacter and Lactobacillus can fully and partially rescue the locomotor defects in GF larvae, respectively, probably due to the highest abundance of Acetobacter as a symbiotic bacterium in the larval gut, followed by Lactobacillus. Moreover, the gut microbiome promoted larval locomotion, not by nutrition, but rather by enhancing the brain levels of tyrosine decarboxylase 2 (Tdc2), which is an enzyme that synthesizes octopamine (OA). Overexpression of Tdc2 rescued locomotion ability in GF larvae. These findings together demonstrate that the gut microbiome specifically modulates larval locomotor behavior through the OA signaling pathway, revealing a new mechanism underlying larval locomotion regulated by the gut microbiome.

Solid Wood Modification toward Anisotropic Elastic and Insulative Foam-Like Materials.

The methods used to date to produce compressible wood foam by top-down approaches generally involve the removal of lignin and hemicelluloses. Herein, we introduce a route to convert solid wood into a super elastic and insulative foam-like material. The process uses sequential oxidation and reduction with partial removal of lignin but high hemicellulose retention (process yield of 72.8%), revealing fibril nanostructures from the wood's cell walls. The elasticity of the material is shown to result from a lamellar structure, which provides reversible shape recovery along the transverse direction at compression strains of up to 60% with no significant axial deformation. The compressibility is readily modulated by the oxidation degree, which changes the crystallinity and mobility of the solid phase around the lumina. The performance of the highly resilient foam-like material is also ascribed to the amorphization of cellulosic fibrils, confirmed by experimental and computational (molecular dynamics) methods that highlight the role of secondary interactions. The foam-like wood is optionally hydrophobized by chemical vapor deposition of short-chained organosilanes, which also provides flame retardancy. Overall, we introduce a foam-like material derived from wood based on multifunctional nanostructures (anisotropically compressible, thermally insulative, hydrophobic, and flame retardant) that are relevant to cushioning, protection, and packaging.

Effects of Dietary Colostrum Basic Protein on Bone Growth and Calcium Absorption in Mice.

Colostrum basic protein (CBP) is a trace protein extracted from bovine colostrum. Previous studies have shown that CBP can promote bone cell differentiation and increase bone density. However, the mechanism by which CBP promotes bone activity remains unclear. This study investigated the mechanism of the effect of CBP on bone growth in mice following dietary supplementation of CBP at doses that included 0.015%, 0.15%, 1.5%, and 5%. Compared with mice fed a normal diet, feeding 5% CBP significantly enhanced bone rigidity and improved the microstructure of bone trabeculae. Five-percent CBP intake triggered significant positive regulation of calcium metabolism in the direction of bone calcium accumulation. The expression levels of paracellular calcium transport proteins CLDN2 and CLDN12 were upregulated nearly 1.5-fold by 5% CBP. We conclude that CBP promotes calcium absorption in mice by upregulating the expression of the calcium-transporting paracellular proteins CLND2 and CLND12, thereby increasing bone density and promoting bone growth. Overall, CBP contributes to bone growth by affecting calcium metabolism.

Ultrasoft and High-Adhesion Block Copolymers for Neuromorphic Computing.

The "von Neumann bottleneck" is a formidable challenge in conventional computing, driving exploration into artificial synapses. Organic semiconductor materials show promise but are hindered by issues such as poor adhesion and a high elastic modulus. Here, we combine polyisoindigo-bithiophene (PIID-2T) with grafted poly(dimethylsiloxane) (PDMS) to synthesize the triblock-conjugated polymer (PIID-2T-PDMS). The polymer exhibited substantial enhancements in adhesion (4.8-68.8 nN) and reductions in elastic modulus (1.6-0.58 GPa) while maintaining the electrical characteristics of PIID-2T. The three-terminal organic synaptic transistor (three-terminal p-type organic artificial synapse (TPOAS)), constructed using PIID-2T-PDMS, exhibits an unprecedented analog switching range of 276×, surpassing previous records, and a remarkable memory on-off ratio of 106. Moreover, the device displays outstanding operational stability, retaining 99.6% of its original current after 1600 write-read events in the air. Notably, TPOAS replicates key biological synaptic behaviors, including paired-pulse facilitation (PPF), short-term plasticity (STP), and long-term plasticity (LTP). Simulations using handwritten digital data sets reveal an impressive recognition accuracy of 91.7%. This study presents a polyisoindigo-bithiophene-based block copolymer that offers enhanced adhesion, reduced elastic modulus, and high-performance artificial synapses, paving the way for the next generation of neuromorphic computing systems.

Immunoregulation of bovine lactoferrin together with osteopontin promotes immune system development and maturation.

The immune system of infants is partly weak and immature, and supplementation of infant formula can be of vital importance to boost the development of the immune system. Lactoferrin (LF) and osteopontin (OPN) are essential proteins in human milk with immunoregulation function. An increasing number of studies indicate that proteins have interactions with each other in milk, and our previous study found that a ratio of LF : OPN at 1 : 5 (w/w, denoted as LOP) had a synergistic effect on intestinal barrier protection. It remains unknown whether LOP can also exert a stronger effect on immunoregulation. Hence, we used an in vitro model of LPS-induced macrophage inflammation and in vivo models of LPS-induced intestinal inflammation and early life development. We showed that LOP increased the secretion of the granulocyte-macrophage colony-stimulating factor (132%), stem cell factor (167%) and interleukin-3 (176%) in bone marrow cells, as well as thymosin (155%) and interleukin-10 (161%) in the thymus, more than LF or OPN alone during development, and inhibited changes in immune cells and cytokines during the LPS challenge. In addition, analysis of the components of digested proteins in vitro revealed that differentially expressed peptides may provide immunoregulation. Lastly, LOP increased the abundance of Rikenellaceae, Muribaculum, Faecalibaculum, and Elisenbergiella in the cecum content. These results imply that LOP is a potential immunomodifier for infants and offers a new theoretical basis for infant formula innovation.

3D-Printed Biomimetic Structural Colors.

Resolution control and expansibility have always been challenges to the fabrication of structural color materials. Here, a facile strategy to print cholesteric liquid crystal elastomers (CLCEs) into complex structural color patterns with variable resolution and enhanced expansibility is reported. A volatile solvent is introduced into the synthesized CLC oligomers, modifying its rheological properties and allowing direct-ink-writing (DIW) under mild conditions. The combination of printing shear flow and anisotropic deswelling of ink drives the CLC molecules into an ordered cholesteric arrangement. The authors meticulously investigate the influence of printing parameters to achieve resolution control over a wide range, allowing for the printing of multi-sized 1D or 2D patterns with constant quality. Furthermore, such solvent-cast direct-ink-writing (DIW) strategy is highly expandable and can be integrated easily into the DIW of bionic robots. Multi-responsive bionic butterfly and flower are printed with biomimetic in both locomotion and coloration. Such designs dramatically reduced the processing difficulty of precise full-color printing and expanded the capability of structural color materials to collaborate with other systems.

Efficacy, Safety, and Tolerability of Inclisiran in Patients With Homozygous Familial Hypercholesterolemia: Results From the ORION-5 Randomized Clinical Trial.

BACKGROUND: Homozygous familial hypercholesterolemia is a genetic disease characterized by extremely high levels of low-density lipoprotein cholesterol (LDL-C) and a high risk of premature cardiovascular events. The proof-of-concept study ORION-2 (A Study of Inclisiran in Participants With Homozygous Familial Hypercholesterolemia) showed that inclisiran, a small interfering RNA that prevents production of the hepatic PCSK9 protein (proprotein convertase subtilisin/kexin type 9), could lead to durable reductions in LDL-C levels when added to statins and ezetimibe in patients with homozygous familial hypercholesterolemia. METHODS: ORION-5 was a phase 3, 2-part, multicenter study in 56 patients with homozygous familial hypercholesterolemia and elevated LDL-C levels despite maximum tolerated doses of LDL-C-lowering therapies with or without lipoprotein apheresis. Patients eligible for part 1 (double-blind, 6 months) were randomized 2:1 to receive either 300 mg of inclisiran sodium (equivalent to 284 mg of inclisiran) or placebo. Placebo-treated patients from part 1 were transitioned to inclisiran in part 2 (open-label, 18 months). The primary end point was the percentage change in LDL-C levels from baseline to day 150. RESULTS: The mean age of the patients was 42.7 years, and 60.7% were women. The mean baseline LDL-C levels were 294.0 mg/dL and 356.7 mg/dL in the inclisiran and placebo groups, respectively. The placebo-corrected percentage change in LDL-C level from baseline to day 150 was -1.68% (95% CI, -29.19% to 25.83%; P=0.90), and the difference was not statistically significant between the inclisiran and placebo groups. The placebo-corrected percentage change in PCSK9 levels from baseline to day 150 was -60.6% with inclisiran treatment (P<0.0001); this was sustained throughout the study, confirming the effect of inclisiran on its biological target of PCSK9. No statistically significant differences between the inclisiran and placebo groups were observed in the levels of other lipids and lipoproteins (apolipoprotein B, total cholesterol, and non-high-density lipoprotein cholesterol). Adverse events and serious adverse events did not differ between the inclisiran and placebo groups throughout the study. CONCLUSIONS: Inclisiran treatment did not reduce LDL-C levels in patients with homozygous familial hypercholesterolemia despite substantial lowering of PCSK9 levels. Inclisiran was well-tolerated, and the safety findings were consistent with previously reported studies and the overall safety profile. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03851705.

A Choline-Based Antifreezing Complexing Agent with Selective Compatibility for Zn-Br2 Flow Batteries.

The high freezing point of polybromides, charging products, is a significant obstacle to the rapid development of zinc-bromine flow batteries (Zn-Br2 FBs). Here, a choline-based complexing agent (CCA) is constructed to liquefy the polybromides at low temperatures. Depending on quaternary ammonium group, choline can effectively complex with polybromide anions and form dense oil-phase that has excellent antifreezing property. Benefiting from indispensable strong ion-ion interaction, the highly selectively compatible CCA, consisting of choline and N-methyl-N-ethyl-morpholinium salts (CCA-M), can be achieved to further enhance bromine fixing ability. Interestingly, the formed polybromides with CCA-M are able to keep liquid even at -40 °C. The CCA-M endows Zn-Br2 FBs at 40 mA cm-2 with unprecedented long cycle life (over 150 cycles) and high Coulombic efficiency (CE, average ≈98.8%) at -20 °C, but also at room temperature (over 1200 cycles, average CE: ≈94.7%). The CCA shows a promising prospect of application and should be extended to other antifreezing bromine-based energy storage systems.