Monitoring bloom-forming Aphanizomenon using environmental DNA metabarcoding: Method development, validation, and field application.

Harmful algal blooms (HABs) have emerged as a critical global environmental and ecological concern. Timely and accurate monitoring of the prevalent bloom-forming genera is crucial for HAB management. Conventional microscope-based methods are time-consuming, labor-intensive, and specialized expertise-dependent, often making them impractical for large-scale surveillance. Molecular methods, such as metabarcoding, provide efficient technical solutions; however, the lack of competent PCR primers and further field validation present obstacles to their wide use. Here, we successfully developed Aphanizomenon-specific primers and validated the application of environmental DNA (eDNA) metabarcoding for field-based monitoring of Aphanizomenon in 37 sites across lentic and lotic freshwater ecosystems in Beijing. The sensitivity and specificity tests of newly developed primers demonstrated high performance - comprehensive recovery of biodiversity in Aphanizomenon communities and high ratios (>95%) of Aphanizomenon sequences in datasets. We observed significant correlations between the sequence abundance derived from eDNA metabarcoding and the total cell density determined through microscopic identification across all the sampling sites, both in the spring (r = 0.8086, p < 0.0001) and summer (r = 0.7902, p < 0.0001), thus validating the utility of eDNA metabarcoding based on the newly developed primers for monitoring in the field. Further, we identified key environmental variables that were primary drivers responsible for the spatiotemporal distribution of Aphanizomenon abundance. These variables included temperature, total nitrogen, and dissolved oxygen in lentic ecosystems, and total phosphorus in lotic ecosystems. The method developed and validated here offers an accurate, efficient, and high-throughput tool for the monitoring of Aphanizomenon blooms in freshwater ecosystems.

Minimally invasive thoracoscopic resection of a micronodular thymoma with lymphoid stroma via a subxiphoid single-incision approach: A case report.

RATIONALE: This study aims to present a novel surgical approach for the resection of anterior mediastinal tumors, specifically focusing on micronodular thymoma with lymphoid stroma (MNT), a rare and distinct variant of thymoma. The single subxiphoid incision technique, although reported in limited cases, offers a minimally invasive option with potential benefits. We report the case of a 76-year-old male who underwent this innovative procedure and was diagnosed with MNT, providing insight into the management and outcomes of this rare pathology. PATIENT CONCERNS: The patient presented for the excision of an anterior mediastinal tumor, with the surgery facilitated by sternal hooks to improve visualization. The rarity of MNT and its unclear prognosis underscore the need for enhanced diagnostic accuracy and tailored treatment strategies. DIAGNOSES: Initially diagnosed preoperatively with a thymic cyst, the patient's final diagnosis was revised to MNT following surgery, highlighting the diagnostic challenges associated with this rare tumor. INTERVENTIONS: The tumor was successfully removed using minimally invasive thoracoscopic surgery through a subxiphoid single-incision, demonstrating the feasibility and potential advantages of this approach. OUTCOMES: The patient had a favorable postoperative course, with a swift recovery and no complications, and remained in good health without signs of relapse at the 9-month follow-up. LESSONS: This case underscores the importance of recognizing the unique pathological features of MNT and the need for a cautious diagnostic approach to differentiate it from other cystic lesions. Additionally, the successful use of single-port thoracoscopy under the xiphoid process for the removal of thymic tumors suggests its potential as an effective surgical method for these challenging cases.

Renal cancer: signaling pathways and advances in targeted therapies.

Renal cancer is a highlyheterogeneous malignancy characterized by rising global incidence and mortalityrates. The complex interplay and dysregulation of multiple signaling pathways,including von Hippel-Lindau (VHL)/hypoxia-inducible factor (HIF), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), Hippo-yes-associated protein (YAP), Wnt/ß-catenin, cyclic adenosine monophosphate (cAMP), and hepatocyte growth factor (HGF)/c-Met, contribute to theinitiation and progression of renal cancer. Although surgical resection is thestandard treatment for localized renal cancer, recurrence and metastasiscontinue to pose significant challenges. Advanced renal cancer is associatedwith a poor prognosis, and current therapies, such as targeted agents andimmunotherapies, have limitations. This review presents a comprehensiveoverview of the molecular mechanisms underlying aberrant signaling pathways inrenal cancer, emphasizing their intricate crosstalk and synergisticinteractions. We discuss recent advancements in targeted therapies, includingtyrosine kinase inhibitors, and immunotherapies, such as checkpoint inhibitors.Moreover, we underscore the importance of multiomics approaches and networkanalysis in elucidating the complex regulatory networks governing renal cancerpathogenesis. By integrating cutting-edge research and clinical insights, this review contributesto the development of innovative diagnostic and therapeutic strategies, whichhave the potential to improve risk stratification, precision medicine, andultimately, patient outcomes in renal cancer.

Statins inhibit paclitaxel-induced PD-L1 expression and increase CD8+ T cytotoxicity for better prognosis in breast cancer.

BACKGROUND: In recent years, the widespread use of lipid-lowering drugs, especially statins, has attracted people's attention. Statin use may be potentially associated with a reduced risk of breast cancer. OBJECTIVE: To explore the relationship between statin use and cancer risk. And further explore the potential role of statins in the adjuvant treatment of breast cancer. METHODS: Data for the Mendelian randomization portion of the study were obtained from genome-wide association studies of common cancers in the UK Biobank and FinnGen studies and from the Global Lipid Genetics Consortium's low density lipoprotein (LDL). In addition, the impacts of statins and chemotherapy drugs on breast cancer were examined using both in vitro and in vivo models, with particular attention to the expression levels of the immune checkpoint protein PD-L1 and its potential to suppress tumor growth. RESULTS: Data from about 3.8 million cancer patients and ~1.3 million LDL-measuring individuals were analyzed. Genetically proxied HMGCR inhibition (statins) was associated with breast cancer risk reduction (P=0.0005). In vitro experiments showed that lovastatin significantly inhibited paclitaxel-induced PD-L1 expression and assisted paclitaxel in suppressing tumor cell growth. Furthermore, the combination therapy involving lovastatin and paclitaxel amplified CD8+ T-cell infiltration, bolstering their tumor-killing capacity and enhancing in vivo efficacy. CONCLUSION: The utilization of statins is correlated with improved prognoses for breast cancer patients and may play a role in facilitating the transition from cold to hot tumors. Combination therapy with lovastatin and paclitaxel enhances CD8+ T-cell activity and leads to better prognostic characteristics.

Mechanism of Takifugu bimaculatus Skin Peptides in Alleviating Hyperglycemia in Rats with Type 2 Diabetic Mellitus Based on Microbiome and Metabolome Analyses.

In this study, we aimed to explore the hypoglycemic effects of a hydrolysate on Takifugu bimaculatus skin (TBSH). The effect of the dipeptidyl peptidase-IV (DPP-IV) inhibitory activities from different TBSH fractions was investigated on basic indexes, gut hormones, blood lipid indexes, viscera, and the gut microbiota and its metabolites in rats with type 2 diabetes mellitus (T2DM). The results showed that the <1 kDa peptide fraction from TBSH (TBP) exhibited a more potent DPP-IV inhibitory effect (IC50 = 0.45 ± 0.01 mg/mL). T2DM rats were induced with streptozocin, followed by the administration of TBP. The 200 mg/kg TBP mitigated weight loss, lowered fasting blood glucose levels, and increased insulin secretion by 20.47%, 25.23%, and 34.55%, respectively, rectified irregular hormonal fluctuations, lipid metabolism, and tissue injuries, and effectively remedied gut microbiota imbalance. In conclusion, TBP exerts a hypoglycemic effect in rats with T2DM. This study offers the potential to develop nutritional supplements to treat T2DM and further promote the high-value utilization of processing byproducts from T. bimaculatus. It will provide information for developing nutritional supplements to treat T2DM and further promote the high-value utilization of processing byproducts from T. bimaculatus.

Effective strategies to enhance the diagnosis and treatment of RCC: The application of biocompatible materials.

Renal cell carcinoma (RCC) is recognized as one of the three primary malignant tumors affecting the urinary system, posing a significant risk to human health and life. Despite advancements in understanding RCC, challenges persist in its diagnosis and treatment, particularly in early detection and diagnosis due to issues of low specificity and sensitivity. Consequently, there is an urgent need for the development of effective strategies to enhance diagnostic accuracy and treatment outcomes for RCC. In recent years, with the extensive research on materials for applications in the biomedical field, some materials have been identified as promising for clinical applications, e.g., in the diagnosis and treatment of many tumors, including RCC. Herein, we summarize the latest materials that are being studied and have been applied in the early diagnosis and treatment of RCC. While focusing on their adjuvant effects, we also discuss their technical principles and safety, thus highlighting the value and potential of their application. In addition, we also discuss the limitations of the application of these materials and possible future directions, providing new insights for improving RCC diagnosis and treatment.

Corrigendum to 'Effective strategies to enhance the diagnosis and treatment of RCC: The application of biocompatible materials' [Mater. Today Bio 27 (2024) 101149].

[This corrects the article DOI: 10.1016/j.mtbio.2024.101149.].

Microenvironment modulation of interpenetrating-type hierarchical porous foam carbon by mild-homogeneous activation for H2 storage and CO2 capture under ambient pressure.

Currently, carbon-based porous materials for hydrogen (H2) storage and carbon dioxide (CO2) capture are mostly applied at higher pressures (30-300 bar). However, applications for H2 storage and CO2 capture under ambient pressure conditions are significant for the development of portable, household, and miniaturized H2 energy technologies. This demands a higher standard for the interface microenvironment of adsorbents. Derived from polyurethane foams (PUFs) solid waste, the hierarchical porous foam carbon with interpenetrating-type pore structures exhibits high specific surface area (SBET = 1753 m2/g), abundant oxygen and nitrogen functional groups, and a hierarchical nanopore structure (VUltra = 0.232 cm3/g, VMicro = 0.628 cm3/g and VMeso = 0.186 cm3/g) through the mild-homogeneous sonication-assisted activation process. Under the limited adsorption of pore interface microenvironment composed by hierarchical nanopore structure and dipole-induced interaction (H(Ⅱ)-H(Ⅰ)···N/O and O(Ⅱ) = C(Ⅰ) = O(Ⅱ)···N/O), it exhibits an excellent H2 storage density (2.92 wt% at 77 K, 1 bar) and CO2 capture capacity (5.28 mmol/g at 298 K, 1 bar). This research approach can serve as a reference for the dual-functional design of porous foam carbon, and promote the development of adsorption materials for CO2 capture and energy gas storage under ambient conditions.

miR-29b-triggered epigenetic regulation of cardiotoxicity following exposure to deltamethrin in zebrafish.

Deltamethrin is a classical pyrethroid insecticide that is frequently detected in aquatic environments and organisms. Furthermore, deltamethrin has been detected in samples related to human health and is a potential risk to public health. This study aimed to investigate the mechanism of cardiotoxicity induced by deltamethrin. Zebrafish were exposed to 0.005, 0.05, or 0.5 µg/L deltamethrin for 28 days. The results showed a significant reduction in male reproduction compared to female reproduction. Additionally, the heart rate decreased by 15.75 % in F1 after parental exposure to 0.5 µg/L deltamethrin. To evaluate cardiotoxicity, deltamethrin was administered to the zebrafish embryos. By using miRNA-Seq and bioinformatics analysis, it was discovered that miR-29b functions as a toxic regulator by targeting dnmts. The overexpression of miR-29b and inhibition of dnmts resulted in cardiac abnormalities, such as pericardial edema, bradycardia, and abnormal expression of genes related to the heart. Similar changes in the levels of miR-29b and dnmts were also detected in the gonads of F0 males and F1 embryos, confirming their effects. Overall, the results suggest that deltamethrin may have adverse effects on heart development in early-stage zebrafish and on reproduction in adult zebrafish. Furthermore, epigenetic modifications may threaten the cardiac function of offspring.

Synergistic role of phenylpropanoid biosynthesis and citrate cycle pathways in heavy metal detoxification through secretion of organic acids.

Excessive heavy metal contaminants in soils have serious ecological and environmental impacts, and affect plant growth and crop yields. Phytoremediation is an environmentally friendly means of lowering heavy metal concentrations in soils. In this study, we analyzed phenotypic and physiological traits, and the transcriptome and metabolome, of sheepgrass (Leymus chinensis) exposed to cadmium (Cd), lead (Pb), or zinc (Zn). Phenotypic and physiological analysis indicated that sheepgrass had strong tolerance to Cd/Pb/Zn. Transcriptomic analysis revealed that phenylpropanoid biosynthesis and organic acid metabolism were enriched among differentially expressed genes, and metabolomic analysis indicated that the citrate cycle was enriched in response to Cd/Pb/Zn exposure. Genes encoding enzymes involved in the phenylpropanoid and citrate cycle pathways were up-regulated under the Cd/Pb/Zn treatments. Organic acids significantly reduced heavy metal accumulation and improved sheepgrass tolerance of heavy metals. The results suggest that synergistic interaction of the phenylpropanoid and citrate cycle pathways in sheepgrass roots induced organic acid secretion to alleviate heavy metal toxicity. A cascade of enzymes involved in the interacting pathways could be targeted in molecular design breeding to enhance phytoremediation.

Finite element analysis of meniscus contact mechanical behavior based on kinematic simulation of abnormal gait.

The meniscus plays a crucial role in the proper functioning of the knee joint, and when it becomes damaged, partial removal or replacement is necessary to restore proper function. Understanding the stress and deformation of the meniscus during various movements is essential for developing effective materials for meniscus repair. However, accurately estimating the contact mechanics of the knee joint can be challenging due to its complex shape and the dynamic changes it undergoes during movement. To address this issue, the open-source software SCONE can be used to establish a kinematics model that monitors the different states of the knee joint during human motion and obtains relevant gait kinematics data. To evaluate the stress and deformation of the meniscus during normal human movement, values of different states in the movement gait can be selected for finite element analysis (FEA) of the knee joint. This analysis enables researchers to assess changes in the meniscus. To evaluate meniscus damage, it is necessary to obtain changes in its mechanical behavior during abnormal movements. This information can serve as a reference for designing and optimizing the mechanical performance of materials used in meniscus repair and replacement.

Utilizing Group Model Building to Identify Barriers and Facilitators of Hypertension Management in Primary Health Care, China.

Purpose: Group Model Building (GMB) is a qualitative method that refers to a participatory process. This project aims to identify barriers and facilitators of hypertension management in primary health care in China, through which, the leverage point for intervention may be found. Methods: The GMB was used to identify the factors influencing hypertension management. Graphs over time and causal loop diagram (CLD) were main tools of GMB. To propose the influencing factors, key stakeholders were invited to participate in a workshop. During the workshop, stakeholders were encouraged to plot the graphs over time of the variables about research issues and give a descriptive explanation. And based on this, a CLD was initially developed to establish a model of the interaction of factors. After the workshop, the research group further improved the CLD through repeated mutual discussions, and gave feedback to the participants. The Vensim PLE 9.0 software package was used to build CLD. Results: A total of 14 key stakeholders were invited to participate in the workshop. Finally, 26 influencing factors were identified, which were divided into three dimensions, including the institutional, the community health workers (CHWs), and the patient level. And 5 reinforcing loops and 4 balancing loops were formed in the CLD. Promoting the building of the Medical Community/Regional Medical Association, implementing the family doctor contract service (FDCS), and enhancing the motivation of CHWs may be potential leverage points for hypertension management in China. Conclusion: By using GMB, we have identified key factors in the management of hypertension in primary health care and provided comprehensive suggestions to overcome the obstacles.

Anti-Melanogenic Effects of Takifugu flavidus Muscle Hydrolysate in B16F10 Melanoma Cells and Zebrafish.

Abnormal melanogenesis can lead to hyperpigmentation. Tyrosinase (TYR), a key rate-limiting enzyme in melanin production, is an important therapeutic target for these disorders. We investigated the TYR inhibitory activity of hydrolysates extracted from the muscle tissue of Takifugu flavidus (TFMH). We used computer-aided virtual screening to identify a novel peptide that potently inhibited melanin synthesis, simulated its binding mode to TYR, and evaluated functional efficacy in vitro and in vivo. TFMH inhibited the diphenolase activities of mTYR, reducing TYR substrate binding activity and effectively inhibiting melanin synthesis. TFMH indirectly reduced cAMP response element-binding protein phosphorylation in vitro by downregulating melanocortin 1 receptor expression, thereby inhibiting expression of the microphthalmia-associated transcription factor, further decreasing TYR, tyrosinase related protein 1, and dopachrome tautomerase expression and ultimately impeding melanin synthesis. In zebrafish, TFMH significantly reduced black spot formation. TFMH (200 µg/mL) decreased zebrafish TYR activity by 43% and melanin content by 52%. Molecular dynamics simulations over 100 ns revealed that the FGFRSP (T-6) peptide stably binds mushroom TYR via hydrogen bonds and ionic interactions. T-6 (400 µmol/L) reduced melanin content in B16F10 melanoma cells by 71% and TYR activity by 79%. In zebrafish, T-6 (200 µmol/L) inhibited melanin production by 64%. TFMH and T-6 exhibit good potential for the development of natural skin-whitening cosmetic products.

Injectable and in situ foaming shape-adaptive porous Bio-based polyurethane scaffold used for cartilage regeneration.

Irregular articular cartilage injury is a common type of joint trauma, often resulting from intense impacts and other factors that lead to irregularly shaped wounds, the limited regenerative capacity of cartilage and the mismatched shape of the scaffods have contributed to unsatisfactory therapeutic outcomes. While injectable materials are a traditional solution to adapt to irregular cartilage defects, they have limitations, and injectable materials often lack the porous microstructures favorable for the rapid proliferation of cartilage cells. In this study, an injectable porous polyurethane scaffold named PU-BDO-Gelatin-Foam (PUBGF) was prepared. After injection into cartilage defects, PUBGF forms in situ at the site of the defect and exhibits a dynamic microstructure during the initial two weeks. This dynamic microstructure endows the scaffold with the ability to retain substances within its interior, thereby enhancing its capacity to promote chondrogenesis. Furthermore, the chondral repair efficacy of PUBGF was validated by directly injecting it into rat articular cartilage injury sites. The injectable PUBGF scaffold demonstrates a superior potential for promoting the repair of cartilage defects when compared to traditional porous polyurethane scaffolds. The substance retention ability of this injectable porous scaffold makes it a promising option for clinical applications.

Generalizable transcriptome-based tumor malignant level evaluation and molecular subtyping towards precision oncology.

In cancer treatment, therapeutic strategies that integrate tumor-specific characteristics (i.e., precision oncology) are widely implemented to provide clinical benefits for cancer patients. Here, through in-depth integration of tumor transcriptome and patients' prognoses across cancers, we investigated dysregulated and prognosis-associated genes and catalogued such important genes in a cancer type-dependent manner. Utilizing the expression matrices of these genes, we built models to quantitatively evaluate the malignant levels of tumors across cancers, which could add value to the clinical staging system for improved prediction of patients' survival. Furthermore, we performed a transcriptome-based molecular subtyping on hepatocellular carcinoma, which revealed three subtypes with significantly diversified clinical outcomes, mutation landscapes, immune microenvironment, and dysregulated pathways. As tumor transcriptome was commonly profiled in clinical practice with low experimental complexity and cost, this work proposed easy-to-perform approaches for practical clinical promotion towards better healthcare and precision oncology of cancer patients.

Stimuli-responsive microcarriers and their application in tissue repair: A review of magnetic and electroactive microcarrier.

Microcarrier applications have made great advances in tissue engineering in recent years, which can load cells, drugs, and bioactive factors. These microcarriers can be minimally injected into the defect to help reconstruct a good microenvironment for tissue repair. In order to achieve more ideal performance and face more complex tissue damage, an increasing amount of effort has been focused on microcarriers that can actively respond to external stimuli. These microcarriers have the functions of directional movement, targeted enrichment, material release control, and providing signals conducive to tissue repair. Given the high controllability and designability of magnetic and electroactive microcarriers, the research progress of these microcarriers is highlighted in this review. Their structure, function and applications, potential tissue repair mechanisms, and challenges are discussed. In summary, through the design with clinical translation ability, meaningful and comprehensive experimental characterization, and in-depth study and application of tissue repair mechanisms, stimuli-responsive microcarriers have great potential in tissue repair.

The prediction of pCR and chemosensitivity for breast cancer patients using DLG3, RADL and Pathomics signatures based on machine learning and deep learning.

BACKGROUND: Limited studies have investigated the predictive value of multiomics signatures (radiomics, deep learning features, pathological features and DLG3) in breast cancer patients who underwent neoadjuvant chemotherapy (NAC). However, no study has explored the relationships among radiomic, pathomic signatures and chemosensitivity. This study aimed to predict pathological complete response (pCR) using multiomics signatures, and to evaluate the predictive utility of radiomic and pathomic signatures for guiding chemotherapy selection. METHODS: The oncogenic function of DLG3 was explored in breast cancer cells via DLG3 knockdown. Immunohistochemistry (IHC) was used to evaluate the relationship between DLG3 expression and docetaxel/epirubin sensitivity. Machine learning (ML) and deep learning (DL) algorithms were used to develop multiomics signatures. Survival analysis was conducted by K-M curves and log-rank. Multivariate logistic regression analysis was used to develop nomograms. RESULTS: A total of 311 patients with malignant breast tumours who underwent NAC were retrospectively included in this multicentre study. Multiomics (DLG3, RADL and PATHO) signatures could accurately predict pCR (AUC: training: 0.900; testing: 0.814; external validation: 0.792). Its performance is also superior to that of clinical TNM staging and the single RADL signature in different cohorts. Patients in the low DLG3 group more easily achieved pCR, and those in the high RADL Signature_pCR and PATHO_Signature_pCR (OR = 7.93, 95 % CI: 3.49-18, P < 0.001) groups more easily achieved pCR. In the TEC regimen NAC group, patients who achieved pCR had a lower DLG3 score (4.00 ± 2.33 vs. 6.43 ± 3.01, P < 0.05). Patients in the low RADL_Signature_DLG3 and PATHO_Signature_DLG3 groups had lower DLG3 IHC scores (P < 0.05). Patients in the high RADL signature, PATHO signature and DLG3 signature groups had worse DFS and OS. CONCLUSIONS: Multiomics signatures (RADL, PATHO and DLG3) demonstrated great potential in predicting the pCR of breast cancer patients who underwent NAC. The RADL and PATHO signatures are associated with DLG3 status and could help doctors or patients choose proper neoadjuvant chemotherapy regimens (TEC regimens). This simple, structured, convenient and inexpensive multiomics model could help clinicians and patients make treatment decisions.

The Effects of Four Different Thawing Methods on Quality Indicators of Amphioctopus neglectus.

Amphioctopus neglectus is a species of octopus that is favored by consumers due to its rich nutrient profile. To investigate the influence of different thawing methods on the quality of octopus meat, we employed four distinct thawing methods: air thawing (AT), hydrostatic thawing (HT), flowing water thawing (FWT), and microwave thawing (MT). We then explored the differences in texture, color, water retention, pH, total volatile basic nitrogen (TVB-N), total sulfhydryl content, Ca2+-ATPase activity, and myofibrillar protein, among other quality indicators in response to these methods, and used a low-field nuclear magnetic resonance analyzer to assess the water migration that occurred during the thawing process. The results revealed that AT had the longest thawing time, leading to oxidation-induced protein denaturation, myofibrillar protein damage, and a significant decrease in water retention. Additionally, when this method was utilized, the content of TVB-N was significantly higher than in the other three groups. HT, to a certain extent, isolated the oxygen in the meat and thus alleviated protein oxidation, allowing higher levels of Ca2+-ATPase activity, sulfhydryl content, and springiness to be maintained. However, HT had a longer duration: 2.95 times that of FWT, resulting in a 9.84% higher cooking loss and a 28.21% higher TVB-N content compared to FWT. MT had the shortest thawing time, yielding the lowest content of TVB-N. However, uneven heating and in some cases overcooking occurred, severely damaging the protein structure, with a concurrent increase in thawing loss, W value, hardness, and shear force. Meanwhile, FWT improved the L*, W* and b* values of octopus meat, enhancing its color and water retention. The myofibrillar protein (MP) concentration was also the highest after FWT, with clearer subunit bands in SDS-PAGE electrophoresis, indicating that less degradation occurred and allowing greater springiness, increased Ca2+-ATPase activity, and a higher sulfhydryl content to be maintained. This suggests that FWT has an inhibitory effect on oxidation, alleviating protein oxidation degradation and preserving the quality of the meat. In conclusion, FWT outperformed the other three thawing methods, effectively minimizing adverse changes during thawing and successfully maintaining the quality of octopus meat.

A dual dynamically cross-linked hydrogel promotes rheumatoid arthritis repair through ROS initiative regulation and microenvironment modulation-independent triptolide release.

High oxidative stress and inflammatory cell infiltration are major causes of the persistent bone erosion and difficult tissue regeneration in rheumatoid arthritis (RA). Triptolide (TPL) has become a highly anticipated anti-rheumatic drug due to its excellent immunomodulatory and anti-inflammatory effects. However, the sudden drug accumulation caused by the binding of "stimulus-response" and "drug release" in a general smart delivery system is difficult to meet the shortcoming of extreme toxicity and the demand for long-term administration of TPL. Herein, we developed a dual dynamically cross-linked hydrogel (SPT@TPL), which demonstrated sensitive RA microenvironment regulation and microenvironment modulation-independent TPL release for 30 days. The abundant borate ester/tea polyphenol units in SPT@TPL possessed the capability to respond and regulate high reactive oxygen species (ROS) levels on-demand. Meanwhile, based on its dense dual crosslinked structure as well as the spontaneous healing behavior of numerous intermolecular hydrogen bonds formed after the breakage of borate ester, TPL could remain stable and slowly release under high ROS environments of RA, which dramatically reduced the risk of TPL exerting toxicity while maximized its long-term efficacy. Through the dual effects of ROS regulation and TPL sustained-release, SPT@TPL alleviated oxidative stress and reprogrammed macrophages into M2 phenotype, showing marked inhibition of inflammation and optimal regeneration of articular cartilage in RA rat model. In conclusion, this hydrogel platform with both microenvironment initiative regulation and TPL long-term sustained release provides a potential scheme for rheumatoid arthritis.

In Situ Synthesis of Self-Assembly Supramolecular Crystal Seeds within Continuous Carbon Nanofibers for Improved Fiber Graphitic Structure.

The utilization of carbon-based fibers as a fundamental constituent holds strong appeal for diverse materials and devices. However, the poor fiber graphitic structure resulting from the heat treatment of atactic polyacrylonitrile (PAN) precursors often leads to a modest performance of carbon-based fibers. This paper takes electrospun carbon nanofibers (CNFs) as the research object and provides a seed-assisted graphitization strategy to improve the fiber graphitic structures. The typical melamine/cyanuric acid self-assembly precursor of graphitic carbon nitride is applied as supramolecular seeds in CNFs and demonstrates significant promotion of fiber graphitization, while it decomposes at elevated temperatures. Further studies show that the higher carbon content contributes to the better heat resistance of seeds; thus, nanoscale 2,6-diaminopyridine/cyanuric acid and 2,4,6-triaminopyrimidine/barbituric acid supramolecular seeds are developed. Both systems can be uniformly distributed in PAN precursors through in situ self-assembly and withstand high-temperature carbonization without severe pyrolysis. The dispersed seeds contribute to the formation of fibrillar PAN crystals and promote their conversion to ordered graphitic domains through nucleation and templating roles. The obtained CNFs exhibit increased crystallinity and graphitization degree with improved orientation and refined size of fiber crystals. As a result, the strength, modulus, and elongation at break of CNFs are comprehensively enhanced.