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Light chain cardiac amyloidosis (AL-CA) is a severe and progressively infiltrative disease caused by the deposition of misfolded monoclonal immunoglobulin light chains in the myocardial extracellular space. It is associated with poor prognosis and typically presents as diastolic heart failure, arrhythmias, and atrial appendage thrombosis. We report a case of light chain cardiac amyloidosis with bilateral atrial appendage thrombosis. The patient died from refractory heart failure four months after diagnosis.
This study reports the precise molecular design of maleimide-styrene alternating copolymers, poly-(MI-alt-S), as host polymers for supramolecular guest-host electro-optic (EO) materials, combining a benchmark push-pull tetraene chromophore to achieve performance optimization. Leveraging the inherent sequence control, high glass transition temperature, and synthetic versatility of poly-(MI-alt-S), four fluorophenyl-substituted copolymers were synthesized to incorporate three to five fluorine atoms onto the phenyl side chains, tuning the weak hydrogen bonding interactions. Guided by theoretical calculations, this work encompasses monomer synthesis, copolymerization, and spectroscopic characterization of fluorobenzyl ether-functionalized poly-(MI-alt-S) polymers to reveal how subtle variations in fluorine substitution govern nanoscale morphology, critical cracking thickness, electric field poling, and EO performance of guest-host polymers. EO activity, polar order, and thermal stability of poled films were evaluated using high-accuracy attenuated total reflection (ATR) measurement. Notably, two of the polymers demonstrated large and thermally stable EO coefficients of ∼170 pm/V at 1306 nm and ∼100 pm/V at 1541 nm, among the best ATR-validated performances for guest-host polymers. These findings highlight that tailored nonclassical hydrogen bonds from fluorophenyl side chains effectively balance intermolecular interactions, mechanical properties, orientational polarization, and thermal stability, illustrating how molecular-level precision in the design of guest-host EO polymers translates into optimized photonic functionality.
The relationship between migraine and lipid metabolism, as well as its underlying mechanisms, remains poorly defined. In lipid metabolism, long-chain fatty acids (LCFAs) play a role in regulating cellular energy homeostasis and inflammation. Emerging evidence suggests a link between LCFAs and migraine pathophysiology. We investigated the association between altered plasma LCFAs and migraine-related disability. In this cross-sectional study, plasma samples and clinical data were collected from 118 individuals with migraine, comprising 79 with episodic migraine (EM) and 39 with chronic migraine (CM), and 118 matched healthy controls. Concentrations of 13 plasma LCFAs were quantified using targeted gas chromatography-mass spectrometry. Associations with migraine phenotype and clinical burden were assessed using regression and correlation analyses. Plasma levels of palmitic acid (C16:0), stearic acid (C18:0), and arachidonic acid (C20:4 n-6) were significantly higher in migraine patients than in controls, whereas docosahexaenoic acid (C22:6 n-3) levels were significantly lower. Multivariate logistic regression identified C16:0, C18:0, and C20:4 n-6 as independent correlates of migraine (AUC = 0.912). Notably, higher levels of C16:0 and C20:4 n-6 were independently associated with with CM relative to EM (AUC = 0.762), and positively correlated with monthly headache days, acute medication use, and disability scores. Our study showed that increased concentrations of plasma LCFAs, specifically C16:0, C18:0, and C20:4 n-6, were independently associated with migraine. C16:0 and C20:4 n-6 were associated with the burden of migraine-related disability. These findings suggest a potential role for the regulation of lipid metabolism in the management and prevention of migraine.
3-indolepropionic acid (IPA) is an important gut microbiota-derived metabolite and has anti-inflammatory properties. We have observed the potential antidepressant effects of IPA, and therefore conducted this study to further detect its potential antidepressant effects and search for the possible action mechanisms. Chronic restraint stress (CRS) was used to induce depression-like behaviors (DLBs) in mice, and then IPA was administered to mice with DLBs (double-blind manner, 20 mg/kg, once daily for 10 consecutive days, intraperitoneal injection, ten days). The feces and hippocampus samples were collected to detect gut microbiota compositions, short-chain fatty acids (SCFAs), G protein-coupled receptor 43 (GPR43), and inflammation-related factors. Disordered gut microbiota, decreased SCFA levels, decreased GPR43 (SCFA receptors), and increased inflammation levels were observed in CRS-induced depressed mice. After IPA treatment, DLBs in CRS mice were significantly improved, along with the improved gut microbiota and increased SCFA levels, especially acetic acid, propanoic acid, and valeric acid. Meanwhile, we found that IPA could increase the level of GPR43 and decrease the levels of inflammation-related factors in the hippocampus of CRS mice. In addition, close relationships among SCFAs, GPR43, and inflammation-related factors were observed. These results suggested that IPA might exert antidepressant effects through gut microbiota modulation, which elevated SCFA levels and subsequently alleviated brain inflammation.
Recognition-encoded melamine oligomers (REMO) are synthetic polymers based on an alternating triazine-piperazine backbone equipped with side chains that promote sequence-selective formation of duplexes and provide a basis for molecular replication via template-directed synthesis. Here we report the development of a method for determining the sequence of a REMO using a backbone fragmentation strategy. Methyl iodide was used to selectively methylate nitrogen atoms on the backbone without alkylating sites on the side chains. Nitrogen quaternisation generated electrophilic sites on the backbone that underwent aminolysis in methylamine solution. Each chain cleavage reaction generated three different fragments that were detectable by LCMS. This two-step fragmentation procedure was verified as a viable sequencing method for REMO of different length equipped with a variety of different side chains. The sequencing method was also used to investigate the fidelity of a replication process using base-filling with a mixed sequence REMO template.
Structural indicators extracted from concept maps, such as node counts, connection density, and cycle counts, are often used as proxies for systems thinking. However, it remains unclear whether a structurally complex concept map actually reflects deeper semantic understanding of a sustainability system. This study developed the Structural-Semantic Dual Assessment (SSDA) framework as an exploratory tool to examine whether and how structural indicators correspond to semantic understanding. Forty-seven preservice STEM teachers with a geography background completed a concept-mapping task on the evolution of the Lop Nur human-land system. The SSDA framework assessed three dimensions of systems thinking: Network Structuring, Nonlinear Mechanism Deconstruction, and Spatiotemporal Reasoning. For each dimension, graph-theoretic structural indicators were extracted from the maps and compared with expert semantic ratings. We further used correlation analysis, principal component analysis-based structural-semantic profiling, representative case analysis, and a supplementary causal-chain completeness analysis. Most participants identified system elements and annotated spatiotemporal information with reasonable consistency, but feedback mechanisms showed a different pattern. Some participants described feedback loops coherently in writing yet drew few or no closed cycles in their maps. The correspondence between structural indicators and semantic scores varied by dimension: structural indicators showed moderate correspondence with spatiotemporal reasoning but almost no correspondence with mechanistic understanding. Cross-classifying structural and semantic scores produced four learner profiles, revealing structural-semantic mismatches in both directions. The supplementary causal-chain completeness analysis further showed that valid mechanism chains depended on both structural support and link validity, especially for development-restoration tensions, feedback relations, and cross-spatiotemporal governance. These findings indicate that structural indicators alone provide only a partial picture of systems thinking in concept maps. Structural, semantic, and causal-chain evidence are best interpreted side by side and dimension by dimension. As an exploratory framework, SSDA may support preservice STEM teacher education by helping participants develop professional judgment in evaluating systems thinking.
Liquid crystals (LCs) are a class of materials that combine molecular order and fluidity, making them crucial for technologies from displays to sensors. However, polymeric LC materials typically lack molecular precision, limiting systematic control over their phase behavior. Here, we report a modular synthetic strategy to prepare amphiphilic columnar liquid crystals based on hydrophobic di- and trialkylated galloyl cores attached to a sequence-defined polar oligomer grown by a thiolactone-based iterative protocol. This approach enables independent variation of (i) polar monomer type (e.g., hydroxyethyl acrylate and N,N-dimethylacrylamide), (ii) oligomer length (from 1-mer to tetramer), and (iii) core topology (two or three C18 chains). Differential scanning calorimetry, polarized optical microscopy, and X-ray scattering show that the number of hydrophobic C18 chains on the aromatic core is the dominant parameter governing mesophase stability. Derivatives with three C18 chains exhibit higher melting and isotropization temperatures and more pronounced transitions from lamellar crystals to hexagonally packed columnar mesophases than their two C18 analogues. The chemistry and length of the sequence-defined polar block further tune crystallization and mesophase behavior, i.e. hydrogen-bonding heads increase thermal stability, whereas bulkier PEG-like heads reduce crystallinity and can destabilize mesophases. Increasing oligomer length reduces crystallization enthalpies and can introduce competing liquid-crystalline states. These results demonstrate that the liquid crystalline behavior can be encoded at the molecular level, providing a basis for designing responsive and sequence-programmed LC materials.
The proliferation of unregistered, substandard, and falsified (SF) veterinary pharmaceuticals represents a critical global threat to animal health, food security, and environmental conservation. In sub-Saharan Africa, these products exacerbate the emergence of antimicrobial resistance (AMR), potentially accelerating the transition toward a "post-antibiotic" era. Despite Ethiopia's relatively developed regulatory framework compared to neighboring states, vulnerabilities such as inadequate diagnostic facilities, porous supply chains, and limited postmarketing surveillance results in enforcement persist. This descriptive study was conducted to determine the prevalence and quality profile of selected veterinary antimicrobials, including antibacterials, anthelmintics, and antiprotozoals, circulating in the Ethiopian market. Postmarket quality surveillance (PMS) study was conducted across five administrative regions. A total of 142 samples were collected and evaluated through three distinct regulatory tiers: verification of Ethiopian Agricultural Authority (EAA) registration status, standardized visual/physical screening, and official pharmacopeial (compendial) laboratory testing. The majority of sampled products (95.7%) were imported, predominantly from China (75.7%) and India (15.0%). Primary sampling sites included veterinary retail outlets (50.7%) and clinics (22.9%). Regulatory analysis revealed that 17.9% (n = 25) of samples were unregistered. Visual screening identified an administrative substandard prevalence of 24.3% among registered products. Of the 44 samples subjected to compendial laboratory analysis, 22.7% (n = 10) failed to meet established pharmacopeial specifications. While suspected falsified products were identified through labeling discrepancies, laboratory confirmation of falsification is ongoing. Unregistered and substandard veterinary medicines are circulating in the Ethiopian supply chain, posing severe risks to animal health and contributing to the regional AMR crisis. These findings necessitate urgent, concerted efforts from stakeholders to strengthen the national regulatory system, enhance EAA laboratory capacity, and secure the pharmaceutical supply chain through targeted postmarketing enforcement.
The diversity of molecular weight distribution (MWD) is a cornerstone in materials property control within the polymer community. Modulating the shape of the MWD profile through an established polymerization process is challenging, as it requires overcoming inherent kinetic limitations. In this work, we report a dual-catalysis strategy to construct a tunable bimodal distribution via one-pot ring-opening metathesis polymerization (ROMP) of norbornene. A composite catalytic system, comprising two metathesis catalysts with distinct reactivities, is designed, and the catalysts interact cooperatively to mediate chain growth rather than proceeding in an isolated manner. Three-fold regulation of peak spacing (23.8-170.0 kg/mol), relative peak height (0.2-1.0), and molecular weight span is readily achieved by adjusting the catalyst composition ratio, polymerization time, and total catalyst loading. The rheological measurements of representative unimodal and bimodal samples show that the bimodal polymer has reduced storage modulus G' and complex viscosity (η*) compared with its unimodal counterpart. Additionally, an equation is derived to predict the contributions of the two catalytic populations to the resulting distribution by quantifying the effect of catalyst composition linked to the kinetic differences, which serves as a predictive framework integrated into the developed strategy. Kinetic experiments and theoretical computations reveal a fusion-catalysis mechanism behind bimodal distribution formation, in which propagating chains dynamically shuttle between two kinetic behaviors through the switching of ligand association states. This work establishes a robust strategy enabling previously inaccessible control over distribution shape via one-pot ROMP, advancing MWD engineering toward broader polymerization platforms.
Heat shock proteins (HSPs) maintain cellular homeostasis and regulate immune responses across species. HSP90 stabilises and activates regulatory proteins, while HSP70 facilitates protein folding and prevents aggregation. In this study, the complete cDNA sequences of Dastarcus helophoroides - HSP70, HSP90, and β-actin (used as a reference for real-time quantitative polymerase chain reaction) - were obtained using rapid amplification of cDNA ends-polymerase chain reaction, and the expression of HSP70 and HSP90 under cold stress was analysed. The full-length cDNA of HSP90 contains a 2346-bp open reading frame (ORF) encoding 781 amino acids with a molecular weight (MW) of 89.6 kDa. The HSP70 cDNA contains a 1911-bp ORF encoding 636 amino acids (MW: 69.7 kDa), and the β-actin cDNA contains a 1131-bp ORF encoding 376 amino acids (MW: 41.7 kDa). Cold stress significantly affected HSP expression: HSP90 expression peaked at -15 °C, with a 9.45-fold increase compared to the control (P < 0.05), whereas HSP70 expression increased markedly at -10 °C, with a 60.42-fold increase compared to the control (P < 0.05). These findings have important biological implications for predicting insect performance under fluctuating thermal environments and for optimising low-temperature storage and release strategies of D. helophoroides in biological control programmes.
Diabetic retinopathy (DR) is a leading cause of preventable blindness, with complex molecular pathophysiology spanning multiple biological compartments. This systematic review and meta-analysis aimed to synthesize proteomic findings from human DR studies to identify consistent cross-compartment molecular signatures and evaluate their clinical translation potential. Following a prespecified PRISMA protocol, we searched databases and registries to September 2025. Two reviewers independently screened, extracted, and assessed risk of bias using validated tools. Proteomic results were standardized to log2 fold-change (Log2FC) with reconstructed SEs where necessary. Random-effects multilevel models (REML) incorporated protein- and study-level variance. Prespecified subgroup analyses (aqueous, vitreous, plasma), meta-regression (compartment, protein family, interactions), and diagnostics (Egger's test, trim-and-fill, leave-one-out) probed robustness. Qualitative synthesis integrated 28 eligible studies across vitreous, aqueous, plasma/serum, tears, and urine. Twenty-eight studies contributed data. Quantitative synthesis showed overall protein upregulation in DR (Log2FC = 1.49; 95% CI: 0.72-2.27). Subgroup analyses demonstrated strong and consistent effects in vitreous (Log2FC = 2.41) and aqueous (1.28 humors, with plasma estimates weaker and more heterogeneous. Fibrinogen chains (FGA, FGB, FGG) were robustly upregulated across compartments and exceeded complement proteins (β = +1.41; p < 0.001). Publication-bias adjustment (trim-and-fill, k0 = 5) yielded a reduced but still significant effect (Log2FC = 1.10). Qualitative evidence highlighted vitronectin, RBP4, prothrombin, and afamin as additional stage-specific candidates, while tear- and urine-based markers showed potential for noninvasive screening. This first integrated systematic review and meta-analysis of multicompartment proteomic studies in diabetic retinopathy shows consistent upregulation of fibrinogen chains across ocular compartments, highlights vitronectin and stage-specific proteins as additional candidates, and establishes a rigorous evidence base to guide biomarker validation and clinical translation.
Large language models (LLMs) have the potential to provide individualized preventive care guidance at scale. Research, however, has found mixed performance among a small set of LLMs queried about select preventive care activities. These findings call for testing a larger set of LLMs on a wider range of preventive care topics. This study aims to assess whether various popular LLMs generate outputs about preventive care consistent with a comprehensive set of recommendations from the US Preventive Services Task Force (USPSTF). We investigated whether 35 popular LLMs produced outputs consistent with all publicly available USPSTF recommendations (n=142) published as of May 2025. The study occurred in 2 waves (wave 1, 2025: 28 LLMs; wave 2, 2026: 10 LLMs; 3 LLMs overlapping across waves). LLMs received queries from simulated users who, in baseline prompts, sought nonbinding, hypothetical advice about whether to participate in particular preventive care activities given their inclusion in a relevant population. LLM raters assessed LLM-USPSTF concordance (interrater reliability, wave 1: κ=0.8893; wave 2: κ=0.9366). Wave 2 tested chain-of-thought, few-shot, and role-based prompts (3 variants each for 426 tests per prompting approach per model). Wave 2 also tested an iterative prompt that sought clarification about previous LLM responses and a prompt that eliminated the user's reference to nonbinding, hypothetical advice. Automated methods classified responses to detect sources of LLM-USPSTF discrepancy. Further tests prompted LLMs to rate preventive care activities for relevant populations using the USPSTF grading scale. Focusing on cases where LLM raters agreed, the study found in its baseline prompts that the LLM with the highest concordance rate generated responses consistent with USPSTF recommendations in 66.92% (89/133) of tests in wave 1 and 87.77% (122/139) of tests in wave 2; the LLM with the lowest rate accorded with USPSTF recommendations in 45.19% (61/135) of tests in wave 1 and in 50.36% (69/137) of tests in wave 2. Eliminating reference to nonbinding, hypothetical advice did not alter the highest-performing model's rate of concordance (122/139, 87.77%). The highest concordance rate increased with chain-of-thought (404/421, 95.96%), role-based (371/416, 89%), and iterative prompting (127/140, 90.71%); however, it moderately decreased with few-shot prompting (361/419, 86.15%). Automated content analysis found high rates of LLMs avoiding definitive recommendations. When prompted to grade preventive care activities, the highest-performing LLM matched USPSTF grades in 85.92% (122/142) of tests in wave 1 and in 94.37% (134/142) of tests in wave 2. LLMs' consistency with USPSTF recommendations varies. Deviations result mainly from LLMs' avoidance of definitive statements. LLM-USPSTF concordance has improved markedly in newer models, and this concordance increases with particular prompting approaches.
Mixed polyethylene (PE) and polypropylene (PP) generate roughly 250 million tons of plastic waste annually, yet their mechanical recycling still relies on additive- and reactive chemistry-based compatibilization, raising costs and complicating waste streams that can obstruct circularity at scale. Here, we report an additive-free, thermal solvent immersion annealing strategy that compatibilizes PP/PE blends post-manufacturing. Elevated temperatures partially melt crystalline regions while the solvent selectively swells amorphous domains, broadening PP/PE interfaces and promoting local chain mixing. Upon solvent removal, chain recrystallization generates entangled intercrystallite loops that bridge PP and PE domains, enabling efficient stress transfer and transforming brittle blends into tough, strain-hardening materials. We demonstrate broad applicability across PP/PE compositions and molecular identities, supported by experiments and molecular dynamics simulations that directly track loop formation and its role in stress transfer during sample deformation. This work establishes a new compatibilization pathway based on entangled intercrystallite loop formation, enabled by partial melting and recrystallization, and offers a scalable route to mechanical recycling of plastic waste via phase-specific engineering.
Simultaneously achieving mechanical robustness and autonomous self-healing in ionogels remains a fundamental challenge for durable, skin-like electronics. Conventional approaches often improve mechanical strength by introducing rigid or densely cross-linked polymer networks, but such strategies inevitably restrict polymer chain mobility and hinder dynamic bond reconfiguration required for healing. Here, a zwitterionic side-chain engineered tough ionogel (ZESTI) is developed to overcome this trade-off through molecular-level design. Hydrophilic zwitterions are covalently grafted onto a hydrophobic polyurethane backbone to preferentially interact with the ionic liquid through ion-dipole interactions and thereby regulate its distribution. This architecture simultaneously facilitates dipole-dipole interactions for mechanical reinforcement and ion-dipole coordination for efficient self-healing under ambient conditions. As a result, ZESTI exhibits an exceptional combination of tensile strength (10.40 MPa), stretchability (1606%), toughness (56.03 MJ m-3), and ambient self-healing efficiency exceeding 83%, while maintaining high ionic conductivity via enhanced ion hopping. When constructed as a self-reporting packaging interface, ZESTI provides stable protection and state perception under sharp contact and restores signal output after mechanical damage through self-healing. This work offers a generalizable design strategy that reconciles mechanical toughness with dynamic functionality in ionogels, establishing a general design paradigm for next-generation self-sustaining iontronic devices.
Mycobacteriosis in avian species is generally caused by Mycobacterium avium subsp. avium and M. genavense, although sporadic reports also exist of other nontuberculous mycobacterium species in birds. Here, we describe disseminated mycobacteriosis caused by M. shimoidei (a rare and infrequently reported pathogen in humans and animals) in a bird species. A captive, adult white-cheeked turaco (Tauraco leucotis) was presented because of persistent dyspnea unresponsive to treatment. The animal was treated unsuccessfully with antimicrobials and later euthanized on welfare grounds. At autopsy, granulomas were identified in the lungs and spleen. Histologically, the coalescing granulomas with central necrosis contained numerous chains of slender, slightly curved, 2-µm acid-fast bacilli, suggesting mycobacterial infection. Bacterial isolation confirmed Mycobacterium spp., which was identified as M. shimoidei by partial sequencing of the 16S rRNA and rpoB genes. Our report expands the known host range of M. shimoidei and highlights the importance of molecular testing methods in identifying atypical nontuberculous mycobacteria (NTM) in zoologic collections. Our case also underscores the need for enhanced epidemiologic surveillance of NTM infections in avian species, given their potential implications for both animal and public health.
Herpes simplex keratitis (HSK) is a leading cause of infectious corneal blindness. Host antiviral responses, particularly type I interferon (IFN) signaling, are impaired during corneal herpes simplex virus type 1 (HSV-1) infection, partly due to viral immune evasion and metabolic reprogramming. This study investigated if topical glycolysis inhibition restores mitochondrial antiviral signaling (MAVS)-associated innate antiviral signaling and improves HSK outcomes. In vitro and in vivo infection models were established using the HSV-1 McKrae strain. A stable hexokinase 2 (HK2)-knockdown human corneal epithelial cell (HCEC) line was generated using lentivirus. Protein/mRNA levels were analyzed via western blot (WB), immunofluorescence (IF), enzyme linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR). Protein interactions were confirmed by co-immunoprecipitation (Co-IP). Murine corneal pathology and viral proteins were assessed by slit-lamp imaging, IF, and WB. Elevated HK2 expression was detected in HSK models. HK2 knockdown or 2-deoxy-d-glucose (2-DG)-mediated inhibition reduced HSV-1 replication (lower infected cell protein 0 [ICP0], higher interferon-stimulated gene 56 [ISG56]). Co-IP confirmed the interaction between HK2 and MAVS protein, and HK2 inhibition activated the TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3) pathway. Topical application of 2-DG improved murine corneal epithelial integrity, reduced viral proteins (glycoprotein D, ICP0), and showed efficacy comparable to acyclovir. Topical glycolysis inhibition enhances corneal antiviral defenses via MAVS-mediated type I IFN signaling, controlling HSV-1 and alleviating disease. It reveals a novel corneal metabolism-antiviral immunity link, highlights HK2 as a therapeutic target for HSK, and supports metabolic therapies for HSK and ocular herpes virus infections.
The steady increase in atmospheric CO2 levels is a key driver of anthropogenic climate change, prompting widespread global concern. In this context, the sustainable conversion of CO2 into value-added chemicals represents an attractive route toward carbon-neutral manufacturing and green chemistry. Here, we developed a proof-of-concept hybrid microbial-enzymatic electrosynthesis system that combines microbial electrosynthesis (MES) and enzymatic electrosynthesis (EES) to convert CO2 into decanoic acid under ambient conditions, using electrical energy. In the MES module, CO2 was converted to acetate via the Wood-Ljungdahl pathway of Clostridium ljungdahlii, using H2 produced by electrochemical water splitting as the electron donor. In the downstream EES module, acetate was transformed into acetyl-CoA, which was then elongated to decanoic acid through an in vitro reversed β-oxidation (rBOX) pathway driven by bioelectrocatalytic NADH regeneration. To verify the functional coupling between the two modules, 13C isotopic labeling was employed to trace carbon flow from CO2 to acetate and further to decanoic acid, confirming that MES-derived carbon served directly as the precursor for downstream chain elongation in the EES module. Under optimized conditions, the hybrid MES-EES system produced 0.80 mM decanoic acid with 81.3% specificity. These results demonstrate the successful hybrid of MES and EES, enabling the de novo bioelectrosynthesis of decanoic acid from CO2 and presenting a promising approach for coupling CO2 resource utilization with renewable electrical energy.
The NOD-like receptor Family, pyrin domain-containing 3 protein (NLRP3) inflammasome is a macromolecular complex critical for inflammatory responses. Its excessive activation or improper regulation is intimately associated with the development of various inflammatory diseases. However, currently available drugs directly targeting the NLRP3 inflammasome are limited. In preliminary analyses, detecting the level of secreted interleukin-1 beta (IL-1β) revealed that betamethasone-17,21-dipropionate (also known as betamethasone dipropionate, BD), a clinically used glucocorticoid, potentially inhibits NLRP3 inflammasome activation. In vitro, the role and preliminary mechanism of BD in inhibiting the activation of NLRP3 inflammasome were investigated in THP-1-differentiated macrophages and bone marrow-derived macrophages (BMDMs) using enzyme-linked immunosorbent assay (ELISA), Cell Counting Kit-8 (CCK-8), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blotting (WB). The preliminary effects of BD on the assembly of NLRP3 inflammasome were assessed in HEK293T cells overexpressing NLRP3/ASC/caspase-1/NEK7 through drug affinity responsive target stability (DARTS) and co-immunoprecipitation (Co-IP) approaches. In vivo, the effect of BD on LPS-induced systemic inflammation was assessed by measuring serum concentrations of IL-1β and TNF-α via ELISA, and by recording mouse survival rates and body weights. BD significantly inhibited NLRP3 inflammasome activation by suppressing pro-IL-1β expression in vitro. Mechanistic studies showed that it decreased pro-IL-1β expression by suppressing NF-κB signaling. In vivo, BD downregulated the serum concentrations of IL-1β and TNF-α, and increase the survival rate of mice using the LPS-induced systemic inflammation model. Collectively, our data verify that BD inhibits NLRP3 inflammasome activation by suppressing pro-IL-1β expression. These findings suggest that BD may be a potential therapeutic approach for inflammatory diseases. However, further studies are needed to elucidate its precise role and specific mechanism in clinical practice.
Self-assembled molecular cages and capsules attracted considerable attention, owing to their unique structures and ability to function as nano-reactors and catalysts. In recent years, porous liquids have emerged into an intriguing class of functional materials. Herein, we prepared a series of per-ethylene-glycol (EG)-functionalized resorcin[4]arene hosts, bearing side chains with three, four, or five EG units (compounds 1d, 1e, and 1f, respectively). We studied their melting points, solubility, self-assembly, and encapsulation abilities. Interestingly, 1e and 1f were found to be viscous liquids at RT and compound 1d melts at 104°C-105°C, while alkyl-substituted resorcin[4]arenes (1a and 1c) melt at ∼300°C. We found in contrast to expectations, that the number of EG groups on the side chains affects the self-assembly, the stability of the formed aggregates, and the encapsulation power of those systems in organic solvents. System 1d behaved, in CDCl3, much like alkyl-substituted resorcin[4]arenes, forming self-assembled hexameric capsules of comparable stability and size capable of encapsulating even tetra-hexyl ammonium salts. Compounds 1e and 1f, however, form, in CDCl3, hexameric capsules, which are more dynamic than the capsules of 1c or even 1d that encapsulate smaller ammonium salts and appear to be promising candidates for the preparation of liquid capsules and capsular liquids.
Osteoporosis (OP) is a metabolic bone disease with limited treatment options. Schisandrin B (Sch B) has shown potential in bone regulation, but its mechanisms, particularly regarding the gut-bone axis, remain unclear. An ovariectomized (OVX) mouse model of OP was established and treated with Sch B. Bone microarchitecture was assessed by micro-CT; bone metabolism markers were measured by western blotting; Gut microbiota composition was analyzed via 16 S rRNA sequencing, and fecal short-chain fatty acids (SCFAs) were quantified. Intestinal barrier function was evaluated by histology and tight junction protein expression. In vitro, MC3T3-E1 cells were used to assess osteogenic differentiation and transcriptomic changes. Treatment with Sch B improves bone mineral density and trabecular microarchitecture in OVX mice, promotes bone formation, and inhibits bone resorption. It maintains intestinal integrity, restores mucosal structure, goblet cell function, and the expression of tight junction proteins. Furthermore, it increases microbial a-diversity, restores β-diversity, inhibits the proliferation of pathogenic Proteobacteria and Shigella, and enriches beneficial bacterial groups. Concurrently, it elevates the levels of SCFAs. Critically, ablation of the gut microbiota with antibiotics abolished the osteoprotective effects of Sch B, confirming that its action is dependent on the microbial composition. In vitro, Sch B ameliorates the impairment of osteogenic differentiation and mineralization in MC3T3-E1 cells. Sch B improves bone metabolism and alleviates OP by remodeling the gut microbiota structure and increasing SCFAs, while also enhancing intestinal barrier function to maintain gut microecological homeostasis.