Kopsileuconines A-D: bisindole alkaloids with cytotoxic activity from Kopsia hainanensis.

Kopsileuconines A-D (1-4), four monoterpenoid bisindole alkaloids with unprecedented skeletons, along with their biosynthetically related precursors (5-8) were isolated from the roots of Kopsia hainanensis. Compound 1 possessed an undescribed C-6-C-5' dimerization pattern of aspidofractinine-type alkaloids. Compounds 2-4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids with undescribed skeletons, respectively. Their structures with absolute configurations were fully accomplished by extensive spectroscopic analysis, quantum-chemical calculations, and X-ray crystallography. A plausible biosynthetic pathway for 1-4 was proposed. Compound 2 exhibited a significant inhibitory effect against human lung cancer cell lines PC9 (EGFR mutant), with an IC50 value of 15.07 ± 1.19 µM.

Primary hepatic lymphoma presenting as pyogenic liver abscess: A case report.

BACKGROUND: Primary hepatic lymphoma (PHL) is a lymphoproliferative disorder confined to the liver without peripheral lymph node involvement and bone marrow invasion. PHL is extremely rare in clinical practice. The etiology and pathogenesis of PHL are largely unknown. There are no common standard protocols or guidelines for the treatment of PHL. CASE SUMMARY: We report the case of a 66-year-old man who presented with fever and abdominal pain for three weeks. Computed tomography and magnetic resonance imaging scans showed a pyogenic liver abscess. The patient underwent a right posterior hepatectomy. The surgical pathology revealed aggressive B-cell lymphoma, with a primary consideration of diffuse large B-cell lymphoma of non-germinal center origin. CONCLUSION: This article reviews the characteristics, mechanism and treatment of PHL and provides insight into the diagnosis of PHL.

Alstomaphylines A-K, monoterpenoid bisindole alkaloids from Alstonia macrophylla with AChE inhibitory activity and cytotoxicity.

Eleven undescribed monoterpenoid bisindole alkaloids, alstomaphyines A-K (1-11), along with three known analogues were isolated from the leaves and stem bark of the Alstonia macrophylla. Compounds 1-3 were unprecedented dimerization alkaloids incorporating a macroline-type motif with an ajmaline-type motif via a C-C linkage. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculation, and CD exciton chirality method. Compounds 1-3 displayed potential inhibitory bioactivity against AChE with IC50 values of 4.44 ± 0.35, 3.59 ± 0.18, and 3.71 ± 0.23 µM, respectively. Enzyme kinetic study revealed compounds 1-3 as mixed competitive AChE inhibitors. Besides, compounds 8 and 12-14 exhibited better cytotoxicity against human cancer cell line HT-29 than cisplatin. Flow cytometry data revealed that compounds 8, 13, and 14 significantly induced the HT-29 cells arrest in G0/G1 phase in a concentration-dependent manner.

Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA.

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.

Nomograms incorporating hsa_circ_0029325 highly expressed in exosomes of hepatocellular carcinoma predict the postoperative outcomes.

BACKGROUND: Liquid biopsies, for example, exosomal circular RNA (circRNA) can be used to assess potential predictive markers for hepatocellular carcinoma (HCC) in patients after curative resection. This study aimed to search for effective prognostic biomarkers for HCC in patients after surgical resection based on exosomal circRNA expression profiles. We developed two nomograms incorporating circRNAs to predict the postoperative recurrence-free survival (RFS) and overall survival (OS) of HCC patients. METHOD: Plasma exosomes isolated from HCC patients and healthy individuals were used for circRNA microarray analysis to explore differentially expressed circRNAs. Pearson correlation analysis was used to evaluate the correlation between circRNAs and clinicopathological features. Cox regression analysis was used to explore the correlation between circRNA and postoperative survival time as well as recurrence time. A nomogram based on circRNA and clinicopathological characteristics was established and further evaluated to predict prognosis and recurrence. RESULT: Among 60 significantly upregulated circRNAs and 25 downregulated circRNAs, hsa_circ_0029325 was selected to verify its power for predicting HCC outcomes. The high expression level of exosomal hsa_circ_0029325 was significantly correlated with OS (P = 0.001, HR = 2.04, 95% CI 1.41-3.32) and RFS (P = 0.009, HR = 1.62, 95% CI 1.14-2.30). Among 273 HCC patients, multivariate regression analysis showed that hsa_circ_0029325 (HR = 1.96, 95% CI 1.21-3.18), tumor size (HR = 2.11, 95% CI 1.33-3.32), clinical staging (HR = 2.31, 95% CI 1.54-3.48), and tumor thrombus (HR = 1.74, 95% CI 1.12-2.7) were independent risk factors for poor prognosis in HCC patients after radical resection. These independent predictors of prognosis were incorporated into the two nomograms. The AUCs under the 1-year, 3-year, and 5-year survival and recurrence curves of the OS and RFS nomograms were 0.755, 0.749, and 0.742 and 0.702, 0.685, and 0.642, respectively. The C-index, calibration curves, and clinical decision curves showed that the two prediction models had good predictive performance. These results were verified in the validation cohort with 90 HCC patients. CONCLUSION: Our study established two reliable nomograms for predicting recurrence and prognosis in HCC patients. We also show that it is feasible to screen potential predictive markers for HCC after curative resection through exosomal circRNA expression profile analysis.

Correction: Chen et al. HP3D-V2V: High-Precision 3D Object Detection Vehicle-to-Vehicle Cooperative Perception Algorithm. Sensors 2024, 24, 2170.

In the original publication [...].

Mesenchymal Stem Cell-Based Therapies for Temporomandibular Joint Repair: A Systematic Review of Preclinical Studies.

Temporomandibular disorders (TMDs) are a heterogeneous group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory muscles, and associated structures. Mesenchymal stromal/stem cells (MSCs) have emerged as a promising therapy for TMJ repair. This systematic review aims to consolidate findings from the preclinical animal studies evaluating MSC-based therapies, including MSCs, their secretome, and extracellular vesicles (EVs), for the treatment of TMJ cartilage/osteochondral defects and osteoarthritis (OA). Following the PRISMA guidelines, PubMed, Embase, Scopus, and Cochrane Library databases were searched for relevant studies. A total of 23 studies involving 125 mice, 149 rats, 470 rabbits, and 74 goats were identified. Compliance with the ARRIVE guidelines was evaluated for quality assessment, while the SYRCLE risk of bias tool was used to assess the risk of bias for the studies. Generally, MSC-based therapies demonstrated efficacy in TMJ repair across animal models of TMJ defects and OA. In most studies, animals treated with MSCs, their derived secretome, or EVs displayed improved morphological, histological, molecular, and behavioral pain outcomes, coupled with positive effects on cellular proliferation, migration, and matrix synthesis, as well as immunomodulation. However, unclear risk in bias and incomplete reporting highlight the need for standardized outcome measurements and reporting in future investigations.

Associations Between Stroke Type, Ischemic Stroke Subtypes, and Post-Stroke Cognitive Trajectories.

Background: It is unclear how post-stroke cognitive trajectories differ by stroke type and ischemic stroke subtype. We studied associations between stroke types (ischemic, hemorrhagic), ischemic stroke subtypes (cardioembolic, large artery atherosclerotic, lacunar/small vessel, cryptogenic/other determined etiology), and post-stroke cognitive decline. Methods: This pooled cohort analysis from four US cohort studies (1971-2019) identified 1,143 dementia-free individuals with acute stroke during follow-up: 1,061 (92.8%) ischemic, 82 (7.2%) hemorrhagic, 49.9% female, 30.8% Black. Median age at stroke was 74.1 (IQR, 68.6, 79.3) years. Outcomes were change in global cognition (primary) and changes in executive function and memory (secondary). Outcomes were standardized as T-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Median follow-up for the primary outcome was 6.0 (IQR, 3.2, 9.2) years. Linear mixed-effects models estimated changes in cognition after stroke. Results: On average, the initial post-stroke global cognition score was 50.78 points (95% CI, 49.52, 52.03) in ischemic stroke survivors and did not differ in hemorrhagic stroke survivors (difference, -0.17 points [95% CI, -1.64, 1.30]; P=0.82) after adjusting for demographics and pre-stroke cognition. On average, ischemic stroke survivors showed declines in global cognition, executive function, and memory. Post-stroke declines in global cognition, executive function, and memory did not differ between hemorrhagic and ischemic stroke survivors. 955 ischemic strokes had subtypes: 200 (20.9%) cardioembolic, 77 (8.1%) large artery atherosclerotic, 207 (21.7%) lacunar/small vessel, 471 (49.3%) cryptogenic/other determined etiology. On average, small vessel stroke survivors showed declines in global cognition and memory, but not executive function. Initial post-stroke cognitive scores and cognitive declines did not differ between small vessel survivors and survivors of other ischemic stroke subtypes. Post-stroke vascular risk factor levels did not attenuate associations. Conclusion: Stroke survivors had cognitive decline in multiple domains. Declines did not differ by stroke type or ischemic stroke subtype.

Dorsal raphe nucleus to basolateral amygdala 5-HTergic neural circuit modulates restoration of consciousness during sevoflurane anesthesia.

The advent of general anesthesia (GA) has significant implications for clinical practice. However, the exact mechanisms underlying GA-induced transitions in consciousness remain elusive. Given some similarities between GA and sleep, the sleep-arousal neural nuclei and circuits involved in sleep-arousal, including the 5-HTergic system, could be implicated in GA. Herein, we utilized pharmacology, optogenetics, chemogenetics, fiber photometry, and retrograde tracing to demonstrate that both endogenous and exogenous activation of the 5-HTergic neural circuit between the dorsal raphe nucleus (DR) and basolateral amygdala (BLA) promotes arousal and facilitates recovery of consciousness from sevoflurane anesthesia. Notably, the 5-HT1A receptor within this pathway holds a pivotal role. Our findings will be conducive to substantially expanding our comprehension of the neural circuit mechanisms underlying sevoflurane anesthesia and provide a potential target for modulating consciousness, ultimately leading to a reduction in anesthetic dose requirements and side effects.

Antiviral C-geranylated flavonoids from Artocarpus communis.

Ten C-geranylated flavonoids, along with three known analogues, were isolated from the leaves of Artocarpus communis. The chemical structures of these compounds were unambiguously determined via comprehensive spectroscopic analysis, single-crystal X-ray diffraction experiments, and quantum chemical electronic circular dichroism calculations. Structurally, artocarones A-I (1-9) represent a group of unusual, highly modified C-geranylated flavonoids, in which the geranyl chain is cyclised with the ortho-hydroxy group of flavonoids to form various heterocyclic scaffolds. Notably, artocarones E and G-I (5 and 7-9) feature a 6H-benzo[c]chromene core that is hitherto undescribed in C-geranylated flavonoids. Artocarone J (10) is the first example of C-9-C-16 connected C-geranylated aurone. Meanwhile, the plausible biosynthetic pathways for these rare C-geranylated flavonoids were also proposed. Notably, compounds 1, 2, 4, 8, 11, and 12 exhibited promising in vitro inhibitory activities against respiratory syncytial virus and herpes simplex virus type 1.

Polymorphisms of CYP7A1 and HADHB Genes and Their Effects on Milk Production Traits in Chinese Holstein Cows.

Our preliminary research proposed the cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and hydroxyacyl-coenzyme A dehydrogenase trifunctional multienzyme complex beta subunit (HADHB) genes as candidates for association with milk-production traits in dairy cattle because of their differential expression across different lactation stages in the liver tissues of Chinese Holstein cows and their potential roles in lipid metabolism. Hence, we identified single-nucleotide polymorphisms (SNPs) of the CYP7A1 and HADHB genes and validated their genetic effects on milk-production traits in a Chinese Holstein population with the goal of providing valuable genetic markers for genomic selection (GS) in dairy cattle, This study identified five SNPs, 14:g.24676921A>G, 14:g.24676224G>A, 14:g.24675708G>T, 14:g.24665961C>T, and 14:g.24664026A>G, in the CYP7A1 gene and three SNPs, 11:g.73256269T>C, 11:g.73256227A>C, and 11:g.73242290C>T, in HADHB. The single-SNP association analysis revealed significant associations (p value ≤ 0.0461) between the eight SNPs of CYP7A1 and HADHB genes and 305-day milk, fat and protein yields. Additionally, using Haploview 4.2, we found that the five SNPs of CYP7A1 formed two haplotype blocks and that the two SNPs of HADHB formed one haplotype block; notably, all three haplotype blocks were also significantly associated with milk, fat and protein yields (p value ≤ 0.0315). Further prediction of transcription factor binding sites (TFBSs) based on Jaspar software (version 2023) showed that the 14:g.24676921A>G, 14:g.24675708G>T, 11:g.73256269T>C, and 11:g.73256227A>C SNPs could alter the 5' terminal TFBS of the CYP7A1 and HADHB genes. The 14:g.24665961C>T SNP caused changes in the structural stability of the mRNA for the CYP7A1 gene. These alterations have the potential to influence gene expression and, consequently, the phenotype associated with milk-production traits. In summary, we have confirmed the genetic effects of CYP7A1 and HADHB genes on milk-production traits in dairy cattle and identified potential functional mutations that we suggest could be used for GS of dairy cattle and in-depth mechanistic studies of animals.

Exploiting Waste towards More Sustainable Flame-Retardant Solutions for Polymers: A Review.

The development of sustainable flame retardants is gaining momentum due to their enhanced safety attributes and environmental compatibility. One effective strategy is to use waste materials as a primary source of chemical components, which can help mitigate environmental issues associated with traditional flame retardants. This paper reviews recent research in flame retardancy for waste flame retardants, categorizing them based on waste types like industrial, food, and plant waste. The paper focuses on recent advancements in this area, focusing on their impact on the thermal stability, flame retardancy, smoke suppression, and mechanical properties of polymeric materials. The study also provides a summary of functionalization methodologies used and key factors involved in modifying polymer systems. Finally, their major challenges and prospects for the future are identified.

SLC34A2 promotes cell proliferation by activating STX17-mediated autophagy in esophageal squamous cell carcinoma.

BACKGROUND: Solute carrier family 34 member 2 (SLC34A2) has been implicated in the development of various malignancies. However, the clinical significance and underlying molecular mechanisms of SLC34A2 in esophageal squamous cell carcinoma (ESCC) remain elusive. METHODS: Western blotting, quantitative real-time PCR and immunohistochemistry were utilized to evaluate the expression levels of SLC34A2 mRNA/protein in ESCC cell lines or tissues. Kaplan-Meier curves were employed for survival analysis. CCK-8, colony formation, EdU and xenograft tumor model assays were conducted to determine the impact of SLC34A2 on ESCC cell proliferation. Cell cycle was examined using flow cytometry. RNA-sequencing and enrichment analysis were carried out to explore the potential signaling pathways. The autophagic flux was evaluated by western blotting, mRFP-GFP-LC3 reporter system and transmission electron microscopy. Immunoprecipitation and mass spectrometry were utilized for identification of potential SLC34A2-interacting proteins. Cycloheximide (CHX) chase and ubiquitination assays were conducted to test the protein stability. RESULTS: The expression of SLC34A2 was significantly upregulated in ESCC and correlated with unfavorable clinicopathologic characteristics particularly the Ki-67 labeling index and poor prognosis of ESCC patients. Overexpression of SLC34A2 promoted ESCC cell proliferation, while silencing SLC34A2 had the opposite effect. Moreover, SLC34A2 induced autophagy to promote ESCC cell proliferation, whereas inhibition of autophagy suppressed the proliferation of ESCC cells. Further studies showed that SLC34A2 interacted with an autophagy-related protein STX17 to promote autophagy and proliferation of ESCC cells by inhibiting the ubiquitination and degradation of STX17. CONCLUSIONS: These findings indicate that SLC34A2 may serve as a prognostic biomarker for ESCC.

Clinical and biochemical characteristics, and outcome in 33 patients with ceftriaxone-induced liver injury.

PURPOSE: To summarize the clinical and biochemical characteristics of patients with ceftriaxone-induced liver injury and guide the selection of safe medication. METHODS: Retrieved domestic and foreign databases from inception to October 2023, collected case data conforming to ceftriaxone-induced liver injury, and statistically analyzed the data. RESULTS: A total of 617 articles were retrieved, and 16 articles with 33 cases (10 children, 23 adults) were included. Males represented 60% (18/30), with a male-to-female ratio of 1.5:1. The age of onset ranged from 2 days to 96 years, with 15 of 23 adults (65%) over 55 years old. The time from ceftriaxone use to liver injury fluctuated between 0.5 and 47 days. Only 9 patients (27.3%, 9/33) had clinical symptoms, and the clinical classification was dominated by cholestatic injury (46.2%, 12/26). There was a significant difference in the clinical classification of ceftriaxone-induced liver injury between children and adults (P = 0.0126), with hepatocellular injury predominating in children and cholestatic injury predominating in adults. The severity of liver injury was mainly mild (66.7%, 12/18). Peak values of alanine aminotransferase ranging from 228.5 to 8098 U/L, aspartate aminotransferase ranging from 86.7 to 21575 U/L, alkaline phosphatase ranging from 143 to 2434 U/L, and total bilirubin ranging from 3.35 to 66.1 mg/dL. There was a significant difference in peak values of alkaline phosphatase between children and adults (P = 0.027), with a higher peak value of alkaline phosphatase in adults (1039 ± 716.4 U/L vs. 257 ± 134.9 U/L). Patients with normal imaging examinations accounted for the majority (61.5%, 7/13). The prognosis of 32 patients (97%, 32/33) was good, and one child with sickle cell anemia who developed immune hemolysis, progressive renal failure, and acute liver injury after using ceftriaxone died in the end. CONCLUSION: Ceftriaxone-induced liver injury can occur at any age, with a higher risk in the elderly, and age may be related to the clinical classification. Although the clinical manifestations are not specific, close monitoring of liver biochemical indicators during the use can detect liver injury early. Most cases have a good prognosis, but for people with concomitant sickle cell anemia, it is necessary to be vigilant about the occurrence of severe hemolytic anemia.

HP3D-V2V: High-Precision 3D Object Detection Vehicle-to-Vehicle Cooperative Perception Algorithm.

Cooperative perception in the field of connected autonomous vehicles (CAVs) aims to overcome the inherent limitations of single-vehicle perception systems, including long-range occlusion, low resolution, and susceptibility to weather interference. In this regard, we propose a high-precision 3D object detection V2V cooperative perception algorithm. The algorithm utilizes a voxel grid-based statistical filter to effectively denoise point cloud data to obtain clean and reliable data. In addition, we design a feature extraction network based on the fusion of voxels and PointPillars and encode it to generate BEV features, which solves the spatial feature interaction problem lacking in the PointPillars approach and enhances the semantic information of the extracted features. A maximum pooling technique is used to reduce the dimensionality and generate pseudoimages, thereby skipping complex 3D convolutional computation. To facilitate effective feature fusion, we design a feature level-based crossvehicle feature fusion module. Experimental validation is conducted using the OPV2V dataset to assess vehicle coperception performance and compare it with existing mainstream coperception algorithms. Ablation experiments are also carried out to confirm the contributions of this approach. Experimental results show that our architecture achieves lightweighting with a higher average precision (AP) than other existing models.

Anti-inflammatory naphthoquinone-monoterpene adducts and neolignans from Eugenia caryophyllata.

A phytochemical investigation on the buds of edible medicinal plant, Eugenia carvophyllata, led to the discovery of seven new compounds, caryophones A-G (1-7), along with two biogenetically-related known ones, 2-methoxy-7-methyl-1,4-naphthalenedione (8) and eugenol (9). Compounds 1-3 represent the first examples of C-5-C-1' connected naphthoquinone-monoterpene adducts with a new carbon skeleton. Compounds 4-7 are a class of novel neolignans with unusual linkage patterns, in which the C-9 position of one phenylpropene unit coupled with the aromatic core of another phenylpropene unit. The chemical structures of the new compounds were determined based on extensive spectroscopic analysis, X-ray diffraction crystallography, and quantum-chemical calculation. Among the isolates, compounds (-)-2, 3, 6, and 9 showed significant in vitro inhibitory activities against respiratory syncytial virus (RSV)-induced nitric oxide (NO) production in RAW264.7 cells.

Enhanced reduction of graphene oxide via laser-dispersion coupling: Towards large-scale, low-defect graphene for crease-free heat-dissipating membranes in advanced flexible electronics.

The advancement of flexible electronics demands improved components, necessitating heat dissipation membranes (HDMs) to exhibit high thermal conductivity while maintaining structural integrity and performance stability even after extensive deformation. Herein, we have devised a laser-modulated reduction technique for graphene oxide (GO), enabling the fabrication of high-quality, large-scale, low-defect graphene, which yields high-performance HDMs after orderly deposition. The work underscores the crucial role of the laser wavelength and dispersion liquid's coupling intensity in influencing the morphology and properties of graphene. Optimal coupling effect and energy conversion are realized when a laser of 1064 nm wavelength irradiates a triethylene glycol (TEG)/N,N-Dimethylformamide (DMF) dispersion. This unique synergy generates high transient energy, which facilitates the deprotonation process and ensures a swift, comprehensive GO reduction. In contrast to conventional water-based laser reduction methods, the accelerated reaction magnifies the size of the graphene sheets by mitigating the ablation effect. After membrane construction with an ordered structure, the corresponding membrane exhibits a high thermal conductivity of 1632 W m-1 K-1, requiring only ∼1/10 of the total preparation time required by other reported methods. Remarkably, the resulting HDM demonstrates superior resilience against creasing and folding, maintaining excellent smoothness and negligible reduction in thermal conductivity after violent rubbing. The combination of exceptional flexibility and thermal conductivity in HDMs paves the way for long-term practical use in the flexible electronics industry.

The safety, feasibility, and oncological outcomes of laparoscopic completion total gastrectomy for remnant gastric cancer: a prospective study with 3-year follow-up (FUGES-004 study).

BACKGROUND: The efficacy of laparoscopic completion total gastrectomy (LCTG) for remnant gastric cancer (RGC) remains controversial. METHODS: The primary outcome was postoperative morbidity within 30 days after surgery. Secondary outcomes included 3-year disease-free survival (DFS), 3-year overall survival (OS), and recurrence. Inverse probability treatment weighted (IPTW) was used to balance the baseline between LCTG and OCTG. RESULTS: Final analysis included 46 patients with RGC who underwent LCTG at the FJMUUH between June 2016 and June 2020. The historical control group comprised of 160 patients who underwent open completion total gastrectomy (OCTG) in the six tertiary teaching hospitals from CRGC-01 study. After IPTW, no significant difference was observed between the LCTG and OCTG groups in terms of incidence (LCTG vs. OCTG: 28.0 vs. 35.0%, P =0.379) or severity of complications within 30 days after surgery. Compared with OCTG, LCTG resulted in better short-term outcomes and faster postoperative recovery. However, the textbook outcome rate was comparable between the two groups (45.9 vs. 32.8%, P =0.107). Additionally, the 3-year DFS and 3-year OS of LCTG were comparable to those of OCTG (DFS: log-rank P =0.173; OS: log-rank P =0.319). No significant differences in recurrence type, mean recurrence time, or 3-year cumulative hazard of recurrence were observed between the two groups (all P >0.05). Subgroup analyses and concurrent comparisons demonstrated similar trends. CONCLUSIONS: This prospective study suggested that LCTG was noninferior to OCTG in both short-term and long-term outcomes. In experienced centers, LCTG may be considered as a viable treatment option for RGC.

A facile and smart strategy to enhance bone regeneration with efficient vitamin D3 delivery through sterosome technology.

The spontaneous healing of critical-sized bone defects is often limited, posing an increased risk of complications and suboptimal outcomes. Osteogenesis, a complex process central to bone formation, relies significantly on the pivotal role of osteoblasts. Despite the well-established osteogenic properties of vitamin D3 (VD3), its lipophilic nature confines administration to oral or muscle injection routes. Therefore, a strategic therapeutic approach involves designing a multifunctional carrier to enhance efficacy, potentially incorporating it into the delivery system. Here, we introduce an innovative sterosome-based delivery system, utilizing palmitic acid (PA) and VD3, aimed at promoting osteogenic differentiation and facilitating post-defect bone regeneration. The delivery system exhibited robust physical characteristics, including excellent stability, loading efficiency, sustained drug release and high cellular uptake efficiency. Furthermore, comprehensive investigations demonstrated outstanding biocompatibility and osteogenic potential in both 2D and 3D in vitro settings. A critical-sized calvarial defect model in mice recapitulated the notable osteogenic effects of the sterosomes in vivo. Collectively, our research proposes a clinically applicable strategy for bone healing, leveraging PA/VD3 sterosomes as an efficient carrier to deliver VD3 and enhance bone regenerative effects.

Shape-memory microfluidic chips for fluid and droplet manipulation.

Fluid manipulation is an important foundation of microfluidic technology. Various methods and devices have been developed for fluid control, such as electrowetting-on-dielectric-based digital microfluidic platforms, microfluidic pumps, and pneumatic valves. These devices enable precise manipulation of small volumes of fluids. However, their complexity and high cost limit the commercialization and widespread adoption of microfluidic technology. Shape memory polymers as smart materials can adjust their shape in response to external stimuli. By integrating shape memory polymers into microfluidic chips, new possibilities for expanding the application areas of microfluidic technology emerge. These shape memory polymers can serve as actuators or regulators to drive or control fluid flow in microfluidic systems, offering innovative approaches for fluid manipulation. Due to their unique properties, shape memory polymers provide a new solution for the construction of intelligent and automated microfluidic systems. Shape memory microfluidic chips are expected to be one of the future directions in the development of microfluidic technology. This article offers a summary of recent research achievements in the field of shape memory microfluidic chips for fluid and droplet manipulation and provides insights into the future development direction of shape memory microfluidic devices.