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.

Development of predictive models for pathological response status in breast cancer after neoadjuvant therapy based on peripheral blood inflammatory indexes.

BACKGROUND: Achieving a pathological complete response (pCR) after neoadjuvant therapy (NAT) is considered to be a critical factor for a favourable prognosis in breast cancer. However, discordant pathological complete response (DpCR), characterised by isolated responses in the breast or axillary, represents an intermediate pathological response category between no response and complete response. This study aims to investigate predictive factors and develop models based on peripheral blood inflammatory indexes to more accurately predict NAT outcomes. METHOD: A total of 789 eligible patients were enrolled in this retrospective study. The patients were randomized into training and validation cohort according to a 7:3 ratio. Lasso and uni/multivariable logistic regression analysis were applied to identify the predictor variables. Two Nomograms combining clinico-pathologic features and peripheral blood inflammatory indexes were developed. RESULT: Molecular Subtype, HALP, P53, and FAR were used to construct the predictive models for traditional non pCR (T-NpCR) and total-pCR (TpCR). The T-NpCR group was divided into DpCR and non pCR (NpCR) subgroups to construct a new model to more accurately predict NAT outcomes. cN, HALP, FAR, Molecular Subtype, and RMC were used to construct the predictive models for NpCR and DpCR. The receiver operating characteristic (ROC) curves indicate that the model exhibits robust predictive capacity. Clinical Impact Curves (CIC) and Decision Curve Analysis (DCA) indicate that the models present a superior clinical utility. CONCLUSION: HALP and FAR were identified as peripheral blood inflammatory index predictors for accurately predicting NAT outcomes.

Cold Exposure Therapy Sensitizes Nanodrug-Mediated Radioimmunotherapy of Breast Cancer.

Cold exposure (CE) therapy can quickly induce tumor starvation by brown adipose tissue (BAT) thermogenesis. Exploring the combined antitumor mechanism of CE and traditional therapies (such as radiotherapy (RT)) is exciting and promising. In this study, we investigated the effect of CE in combination with nitric oxide (NO) gas therapy on sensitizing tumors to RT and promoting tumor radio-immunotherapy. We first constructed a liposome (SL) loaded with the NO prodrug S-nitroso-N-acetylpenicillamine (SNAP). When SL is injected, the glutathione (GSH) within the tumor region promotes the release of NO from SNAP. Subsequently, the superoxide anion produced by RT reacts with NO to generate peroxynitrite (ONOO-), which has strong oxidative properties and induces cell death. Meanwhile, the mice were exposed to a CE environment of 4 °C. CE-mediated BAT thermogenesis induced tumor starvation, which led to a decrease in ATP and GSH content within the tumor as well as an improvement in the hypoxic microenvironment and a decrease in myeloid-derived suppressor cells. All of the above have promoted the effectiveness of RT and activated the systemic antitumor immunity. In the bilateral tumor experiment, treatment of the primary tumor inhibited the growth of the distant tumor and promoted the infiltration of CD8+ T cells into the tumor. These findings reveal that the synergy of CE, NO gas therapy, and RT could confer high effective anticancer effects, providing possibilities in personalized cancer treatment.

Cadmium-induced protein AS8: A protein to improve Cd accumulation and transport via Cd uptake in poplar.

The pollution of soil with heavy metals (HMs) has become an environmental problem of global concern. Phytoremediation, whereby plants extract HMs from soil, can efficiently and substantially reduce HM pollution in soil in an environmentally friendly manner. Cadmium-induced protein AS8 (CIPAS8) is present in many plants and its expression is induced by HMs. In this study, PeCIPAS8 and SlCIPAS8 were transformed into 84K poplar to study their effects on tolerance to, and translocation of, cadmium (Cd) in woody plants. Localization analyses showed that two CIPAS8 proteins were localized at the plasma membrane when transiently expressed in tobacco leaf epidermal cells. Compared with wild-type 84K poplar seedlings, transgenic poplar lines overexpressing PeCIPAS8 or SlCIPAS8 showed increased Cd contents and decreased Cd tolerance. Transgenic poplar lines overexpressing PeCIPAS8 or SlCIPAS8 accumulated more Cd in the roots, stems, and leaves, but the plant height did not differ significantly, compared with wild-type 84K poplar under Cd stress during the vegetative stage. CIPAS8 increased the Cd influx rate of transgenic poplar roots compared with that of the wild type, and affected the transcription levels of other metal transporters. These findings show that CIPAS8 increases Cd flux into plant tissues and demonstrate moderate Cd sensitivity of the plant. Therefore, CIPAS8 is an influx transporter with the potential to increase the uptake of toxic HMs by woody plants growing in HM-contaminated soils.

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.

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.].

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.

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.

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.

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.

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.

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.

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.

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.