miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells.

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

Electrostatic microfiltration (EM) enriches and recovers viable microorganisms at low-abundance in large-volume samples and enhances downstream detection.

Rapid and sensitive detection of pathogens in various samples is crucial for disease diagnosis, environmental surveillance, as well as food and water safety monitoring. However, the low abundance of pathogens (<10 CFU) in large volume (1 mL-1 L) samples containing vast backgrounds critically limits the sensitivity of even the most advanced techniques, such as digital PCR. Therefore, there is a critical need for sample preparation that can enrich low-abundance pathogens from complex and large-volume samples. This study develops an efficient electrostatic microfiltration (EM)-based sample preparation technique capable of processing ultra-large-volume (≥500 mL) samples at high throughput (≥10 mL min-1). This approach achieves a significant enrichment (>8000×) of extremely-low-abundance pathogens (down to level of 0.02 CFU mL-1, i.e., 10 CFU in 500 mL). Furthermore, EM-enabled sample preparation facilitates digital amplification techniques sensitively detecting broad pathogens, including bacteria, fungi, and viruses from various samples, in a rapid (≤3 h) sample-to-result workflow. Notably, the operational ease, portability, and compatibility/integrability with various downstream detection platforms highlight its great potential for widespread applications across diverse settings.

Exploring the role of interleukin-6 receptor blockade in epilepsy and associated neuropsychiatric conditions through a mendelian randomization study.

BACKGROUND: The interplay between inflammation, immune dysregulation, and the onset of neurological disorders, including epilepsy, has become increasingly recognized. Interleukin (IL)-6, a pro-inflammatory cytokine, is suspected to not only mediate traditional inflammatory pathways but also contribute to neuroinflammatory responses that could underpin neuropsychiatric symptoms and broader psychiatric disorders in epilepsy patients. The role of IL-6 receptor (IL6R) blockade presents an intriguing target for therapeutic intervention due to its potential to attenuate these processes. AIM: To explore the potential of IL6R blockade in reducing the risk of epilepsy and investigate whether this pathway might also influence associated psychiatric and neuropsychiatric conditions due to neuroinflammation. METHODS: Mendelian randomization (MR) analysis employing single nucleotide polymorphisms (SNPs) in the vicinity of the IL6R gene (total individuals = 408225) was used to evaluate the putative causal relationship between IL6R blockade and epilepsy (total cases/controls = 12891/312803), focal epilepsy (cases/controls = 7526/399290), and generalized epilepsy (cases/controls = 1413/399287). SNP weights were determined by their effect on C-reactive protein (CRP) levels and integrated using inverse variance-weighted meta-analysis as surrogates for IL6R effects. To address potential outlier and pleiotropic influences, sensitivity analyses were conducted employing a variety of MR methods under different modeling assumptions. RESULTS: The genetic simulation targeting IL6R blockade revealed a modest but significant reduction in overall epilepsy risk [inverse variance weighting: Odds ratio (OR): 0.827; 95% confidence interval (CI): 0.685-1.000; P = 0.05]. Subtype analysis showed variability, with no significant effect observed in generalized, focal, or specific childhood and juvenile epilepsy forms. Beyond the primary inflammatory marker CRP, the findings also suggested potential non-inflammatory pathways mediated by IL-6 signaling contributing to the neurobiological landscape of epilepsy, hinting at possible links to neuroinflammation, psychiatric symptoms, and associated mental disorders. CONCLUSION: The investigation underscored a tentative causal relationship between IL6R blockade and decreased epilepsy incidence, likely mediated via complex neuroinflammatory pathways. These results encouraged further in-depth studies involving larger cohorts and multifaceted psychiatric assessments to corroborate these findings and more thoroughly delineate the neuro-psychiatric implications of IL-6 signaling in epilepsy. The exploration of IL6R blockade could herald a novel therapeutic avenue not just for seizure management but also for addressing the broader psychiatric and cognitive disturbances often associated with epilepsy.

Chemical Recycling of Poly(cyclohexene carbonate)s via Synergistic Catalysis.

Chemical recycling of polymers to the corresponding monomers offers a valuable solution to address the current plastics crisis for creating an ideal and circular polymer economy. Here, we present a bimetallic synergistic depolymerization of the widely studied CO2-based polycarbonates, poly(cyclohexene carbonate)s, to epoxide monomers efficiently. The bimetallic CrIII-complex-mediated highly selective depolymerization and repolymerization was achieved via the regulation of reaction temperature, thus closing the circular loop of poly(cyclohexene carbonate)s in situ. Mechanistic investigation has revealed that the formation of epoxides undergoes a direct chain-end unzipping process. A bimetallic catalysis involving a nucleophilic attack of the metal-alkoxide species toward the methine carbon atom bound with an adjacent carbonyl that is activated by the other metal center features a lower energy barrier in DFT calculations, which promotes the epoxide extrusion.

The causal relationship between androgenetic alopecia and serum uric acid: A bidirectional Mendelian randomization analysis.

BACKGROUND: Despite numerous studies investigating the association between androgenetic alopecia (AGA) and serum uric acid (SUA), the causal relationship between AGA and SUA remains unknown. METHODS: We utilized bidirectional Mendelian randomization (MR) to explore the causality between AGA and SUA. Our study chose single nucleotide polymorphisms associated with genome-wide significance (p < 5×10-8) for the exposure and showing low linkage disequilibrium (R2 < 0.001) as IVs. Various MR methods were employed to evaluate causality, including inverse-variance weighted (IVW), Weighted Median, MR-Egger, Weighted Mode and Simple Mode. Sensitivity analyses were performed to test the robustness of the results. RESULTS: Using the IVW method, we did not find a significant causal relationship between AGA and SUA (OR = 1.00, 95% CI 0.99-1.01; p = 0.451). Similarly, the IVW method did not reveal evidence of causality between SUA and AGA (OR = 0.97, 95% CI = 0.91-1.03; p = 0.301). The results from other methods were consistent with those of the IVW approach. CONCLUSION: The study did not identify a causal relationship between AGA and SUA. Future research should involve larger cohorts and advanced methods to validate the findings and explore the complex interactions between AGA and SUA levels in different populations.

Effect of information-motivation-behavioral skills model based perioperative nursing on pain in patients with gallstones.

BACKGROUND: The incidence of cholecystolithiasis is on the rise. Use of information, motivation, and behavioral skills can play a positive role in promoting changes in individual health behaviors. However, reports on the effects of information-motivation-behavioral (IMB) skills model based high-quality nursing as a perioperative nursing intervention for patients with gallstones are nonexistent. AIM: To explore the application of IMB skills model based high-quality nursing in patients with gallstones. METHODS: Two hundred and sixteen patients with cholecystolithiasis treated at our hospital from January 2022 to January 2023 were enrolled and divided into a control, high-quality, and combined nursing groups, with 72 patients in each group. The control, high-quality, and combination groups received conventional, high-quality, and IMB skills model based perioperative nursing services, respectively. Differences in clinical indicators, stress levels, degree of pain, emotional state, and quality of life were observed, and complications and nursing satisfaction among the three groups were evaluated. RESULTS: After nursing, the time to recovery of gastrointestinal function in the high-quality and combined nursing groups was significantly shorter than that of the control group, with the recovery of gastrointestinal function being the fastest in the combined nursing group (P < 0.05). After nursing intervention, cortisol and norepinephrine levels in the high-quality and combined nursing groups were closer to normal than those of the control group 24 h after surgery, with the combined nursing group having the closest to normal levels (P < 0.05). After 3 and 7 d of intervention, the patients' pain significantly improved, which was more prominent in the high-quality and combination groups. Meanwhile, the pain score in the combination group was significantly lower than those of the control and high-quality nursing groups (P < 0.05). After nursing intervention, the emotional states of all patients improved, and the scores of patients in the combination group were significantly lower than those of the control and high-quality nursing groups. The quality of life of patients in the high-quality and combined nursing groups significantly improved after nursing intervention compared to that of the control group, with the combined nursing group having the highest quality of life score. After intervention, the incidence of complications in the high-quality and combination groups was significantly lower than that of the control group (P < 0.05), but the difference between the combination and high-quality nursing groups was not significant. Nursing satisfaction of patients in the high-quality and combination groups was significantly higher than that of the control group, with the nursing satisfaction being the highest in the combination group (P < 0.05). CONCLUSION: IMB skills model based nursing can improve surgical stress levels, degrees of pain, emotional state, quality of life, and nursing satisfaction of patients with gallstones and reduce the incidence of complications.

Effect of vascular senescence on the efficacy and safety of warfarin: insights from rat models and a prospective cohort study.

Warfarin, with its narrow therapeutic range, requires the understanding of various influencing factors for personalized medication. Vascular senescence, marked by vascular stiffening and endothelial dysfunction, has an unclear effect on the efficacy and safety of warfarin. Based on previous studies, we hypothesized that vascular senescence increases the risk of bleeding during warfarin therapy. This study aimed to explore these effects using animal models and clinical cohorts. We established rat models of vascular senescence and calcification using d-galactose (D-Gal), vitamin D and nicotine (VDN). After validating the models, we examined changes in the International Normalized Ratio (INR) at fixed warfarin doses (0.20 and 0.35 mg/kg). We found that vascular senescence caused significantly elevated INR values and increasd bleeding risk. In the prospective clinical cohort study(NCT06428110), hospitalized warfarin patients with standard dose adjustments were divided into vascular senescence and control groups based on ultrasound and Computed Tomography (CT) diagnosis. Using propensity score matching (PSM) to exclude the influence of confounding factors, we found that the vascular senescence group had lower steady-state warfarin doses and larger dose adjustments, with a higher probability of INR exceeding the therapeutic range. The vascular senescence group tended to experience more bleeding or thromboembolic/ischemic events during one year of follow-up, while there was no statistical difference. In conclusion, vascular senescence leads to unstable INR values and increases higher bleeding risk during warfarin therapy, highlighting the importance of considering vascular senescence in future precision warfarin therapies. Significance Statement Many factors influence warfarin efficacy, however, the effect of vascular senescence remains unclear. This study aimed to investigate the effects of vascular senescence on the efficacy and safety of warfarin. Through both rat models and clinical cohort studies, our findings indicated that vascular senescence may compromise the stability of warfarin, presenting challenges in maintaining its efficacy and safety.

Astragalus polysaccharides sensitize ovarian cancer stem cells to PARPi by inhibiting mitophagy via PINK1/Parkin signaling.

Ovarian cancer (OC) remains the most lethal gynecological malignant tumor. PARP inhibitors (PARPi) have significantly improved survival, particularly in patients with OC with BRCA1/2 mutations. However, the majority of patients eventually develop resistance to PARPi. Cancer stem cells (CSCs) are considered the source of drug resistance in cancer. Our study found that the synergistic effect of astragalus polysaccharides (APSs) and PARPi was observed in ovarian cancer stem cells (OCSCs) by decreasing cell viability and self-renewal potential while inducing apoptosis. The present study also demonstrated that OCSCs had increased mitophagy. Furthermore, it was observed that APS in combination with PARPi inhibits mitophagy and downregulates the PINK1 protein level in OCSCs. The overexpression of PINK1 via the pEGFP(+)-PINK1 plasmid resulted in a partial reversal of the increased susceptibility of OCSCs when PARPi were administrated concurrently with APS. In conclusion, APS increases OCSC sensitivity to PARPi by inhibiting mitophagy via the PINK1/Parkin pathway regulation.

Multi-Stimuli-Responsive Fluorescent Molecule with AIE and TICT Properties Based on 1,8-Naphthalimide.

A multi-stimuli responsive fluorophore, named NBDNI, was developed by constructing a 1,8-naphthalimide derivative in which a rotatable electron-donating N,N-dimethylaniline group attached to its 4-position. This molecular structure endowed NBDNI with aggregate-induced emission (AIE) and twisted intramolecular charge transfer (TICT) properties, enabling remarkable fluorescence changes in response to multiple external stimuli: (i) sensitivity to polarity in various solvent systems and polymer matrix; (ii) significant fluorescence response and excellent linearity towards temperature changes in solution; (iii) distinct switch of fluorescence color upon acid and base treatments; (iv) reversible mechanochromism behavior in the solid state. Moreover, the mechanisms underlying the aforementioned stimuli-responsive phenomena have been proposed based on comprehensive systematic measurements. Furthermore, preliminary applications such as fluorescence thermometry and acid/base test paper have been demonstrated. This research will bring about new opportunities for the development of novel stimuli-responsive luminescent materials.

Efficacy and safety of KRAS G12C inhibitor IBI351 monotherapy in patients with advanced non-small cell lung cancer: results from a phase 2 pivotal study.

INTRODUCTION: KRAS G12C mutation is a well-recognized and increasingly promising therapeutic target with significant unmet clinical needs in NSCLC patients. IBI351 is a potent covalent and irreversible inhibitor of KRAS G12C. Here, we present the efficacy and safety of IBI351 from an open-label, single-arm, phase 2 pivotal study. METHODS: Eligible NSCLC patients with KRAS G12C who failed standard therapy were enrolled. IBI351 was orally administered at a dose of 600 mg twice daily. Primary endpoint was confirmed objective response rate (ORR) assessed by independent radiological review committee (IRRC) as per RECIST v1.1. Other endpoints were safety, IRRC-confirmed disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS). RESULTS: As of December 13, 2023, 116 pts were enrolled (ECOG PS 1: 91.4%; brain metastasis: 30.2%; prior treatments with both anti-PD-1/PD-L1 inhibitors and platinum-based chemotherapy: 84.5%). As per IRRC assessment, confirmed ORR was 49.1% (95% CI: 39.7-58.6), and DCR was 90.5% (95% CI: 83.7-95.2). The median DoR was not reached while disease progression or death events occurred in 22 (38.6%) pts, and the median PFS was 9.7 months (95% CI: 5.6-11.0). OS data was immature. Treatment-related adverse events (TRAEs) occurred in 107 (92.2%) pts while 48 (41.4%) pts had grade≥3 TRAEs. Common TRAEs were anemia (44.8%), alanine aminotransferase increased (28.4%), aspartate aminotransferase increased (27.6%), asthenia (26.7%) and protein urine present (25.0%). TRAEs leading to treatment discontinuation occurred in 9 (7.8%) pts. In biomarker evaluable pts (n=95), all pts had positive KRAS G12C in tissue while 72 pts were blood positive and 23 pts were blood negative for KRAS G12C. Pts with KRAS G12C in both blood and tissue had higher tumor burden at baseline (p <0.05) and worse PFS (p <0.05). Tumor mutation profiling identified TP53 (45.3%), STK11 (30.5%) and KEAP1 (21.1%) as the most common genes co-mutated with KRAS G12C. Among 13 genes with mutation frequency ≥5%, mutations of 6 genes (STK11, KEAP1, PIK3CG, POLE, SMAD4, and BRINP3) were significantly associated with worse PFS (p <0.05). Mutation in STK11 also showed significant association with higher tumor burden at baseline and lower response rate (p <0.05). CONCLUSIONS: IBI351 monotherapy demonstrated promising and sustained efficacy with manageable safety, supporting its potential as a new treatment option for KRAS G12C-mutant NSCLC.

Diagnostic value of procalcitonin in infections in patients with malignant hematologic diseases. / é™é’™ç´ åŽŸåœ¨æ¶æ€§è¡€æ¶²ç— æ‚£è€ æ„ŸæŸ“ä¸­çš„è¯Šæ–­ä»·å€¼.

OBJECTIVES: The incidence of infections in patients with malignant hematologic diseases is extremely high and significantly affects their prognosis. Identifying early and precise biomarkers for infection is crucial for guiding the treatment of infections in these patients. Previous studies have shown that procalcitonin (PCT) can serve as an early diagnostic marker for bloodstream infections in patients with malignant hematologic diseases. This study aims to compare serum PCT levels in these patients with different pathogens, disease types, infection sites, and severity levels. METHODS: Clinical data and laboratory results of infected patients with malignant hematologic diseases treated at the Department of Hematology, the Third Xiangya Hospital of Central South University from January 2018 to August 2023 were collected. General patient information was retrospectively analyzed. Serum PCT levels were compared among patients with different pathogens, types of malignant hematologic diseases, infection sites, and infection severity; Receiver operator characteristic (ROC) curves were used to determine the cut-off values and diagnostic value of serum PCT levels in diagnosing bloodstream infections versus local infections and severe infections versus non-severe infections. Mortality rates after 4-7 days of anti-infective treatment were compared among groups with rising, falling, and unchanged PCT levels. RESULTS: A total of 526 patients with malignant hematologic diseases were included. The main pathogens were Gram-negative bacteria (272 cases, 51.7%), followed by Gram-positive bacteria (120 cases, 22.8%), fungi (65 cases, 12.4%), viruses (23 cases, 4.4%), and mixed pathogens (46 cases, 8.7%). The main types of malignant hematologic diseases were acute myeloid leukemia (216 cases, 41.1%), acute lymphoblastic leukemia (107 cases, 20.3%), and lymphoma (93 cases, 17.7%). Granulocyte deficiency was present in 68.3% (359 cases) of the patients during infection, with severe infection in 24.1% (127 cases). Significant differences in serum PCT levels were found among patients with different types of pathogens (P<0.001), with the highest levels in Gram-negative bacterial infections. Significant differences in serum PCT levels were also found among patients with different types of malignant hematologic diseases (P<0.05), with the highest levels in lymphoma patients. Serum PCT levels were significantly higher in systemic infections and severe infections compared to local infections and non-severe infections (both P<0.001). ROC curve analysis showed that the cut-off values for diagnosing bloodstream infections and severe infections were 0.22 and 0.28 ng/mL, with areas under the curve of 0.670 and 0.673, respectively. After 4-7 days of anti-infective treatment, the mortality rates of the PCT declining, PCT unchanged, and PCT rising groups were 11.9%, 21.2%, and 35.7%, respectively, and pairwise comparisons were statistically significant (all P<0.05). CONCLUSIONS: PCT can be used as an auxiliary indicator for early identification of different pathogens, infection sites, and severity levels in patients with malignant hematologic diseases combined with infections. Dynamic monitoring of PCT levels after empirical antibiotic treatment provides important guidance for assessing patient's prognosis.

Regional citrate anticoagulation versus LMWH anticoagulation for CRRT in liver failure patients without increased bleeding risk.

BACKGROUND: The optimal anticoagulation regimen for continuous renal replacement therapy (CRRT) in liver failure (LF) patients without increased bleeding risk remains controversial. Therefore, we conducted a monocentric retrospective study to evaluate the efficacy and safety of the regional citrate anticoagulation (RCA) versus low molecular weight heparin (LMWH) anticoagulation for CRRT in LF without increased bleeding risk. METHOD: According to the anticoagulation strategy for CRRT, patients were divided into the RCA and LMWH-anticoagulation groups. The evaluated endpoints were patient survival, filter lifespan, bleeding, citrate accumulation, and totCa/ionCa ratio. RESULT: Totally 167 and 164 filters were used in the RCA and LMWH group, respectively. The median filter lifespan was significantly longer in the RCA group (34 h (IQR = 24-54) versus 24 h (IQR = 18-45.5) [95%CI, 24.5-33]; p < 0.001). The 4-week mortality rate was significantly higher in the LMWH-anticoagulation group (71 (57.72%) vs 53 (40.46%); p = 0.006). After adjusted the important parameters in the multivariate COX regression model, the mortality risk was significantly reduced in the RCA group (HR = 0.668 [95%CI, 0.468-0.955]; p = 0.027). In the LMWH group, 30 bleeding episodes (24,19%) were observed, whereas only 7 (5.34%) occurred in the RCA group (p < 0.001). Two patients (1.5%) in the RCA group occurred citrate accumulation. CONCLUSIONS: In LF patients without increased bleeding risk who underwent CRRT, RCA significantly extended the filter lifespan and improved patient survival rate. There was no significant difference in the rate of adverse events between the two groups.

Computational identification of novel potential genetic pathogenesis and otherwise biomarkers in acute liver allograft rejection.

Acute cellular rejection (ACR) is a prevalent postoperative complication following liver transplantation (LT), exhibiting an increasing incidence of morbidity and mortality. However, the molecular mechanisms of ACR following LT remain unclear. To explore the genetic pathogenesis and identify biomarkers of ACR following LT, three relevant Gene Expression Omnibus (GEO) datasets consisting of data on ACR or non-ACR patients after LT were comprehensively investigated by computational analysis. A total of 349 upregulated and 260 downregulated differentially expressed genes (DEGs) and eight hub genes (ISG15, HELZ2, HNRNPK, TIAL1, SKIV2L2, PABPC1, SIRT1, and PPARA) were identified. Notably, HNRNPK, TIAL1, and PABPC1 exhibited the highest predictive potential for ACR with AUCs of 0.706, 0.798, and 0.801, respectively. KEGG analysis of hub genes revealed that ACR following LT was predominately associated with ferroptosis, protein processing in the endoplasmic reticulum, complement and coagulation pathways, and RIG-I/NOD/Toll-like receptor signaling pathway. According to the immune cell infiltration analysis, γδT cells, NK cells, Tregs, and M1/M2-like macrophages had the highest levels of infiltration. Compared to SIRT1, ISG15 was positively correlated with γδT cells and M1-like macrophages but negatively correlated with NK cells, CD4+ memory T cells, and Tregs. In conclusion, this study identified eight hub genes and their potential pathways, as well as the immune cells involved in ACR following LT with the greatest levels of infiltration. These findings provide a new direction for future research on the underlying mechanism of ACR following LT.

RT-RPA-PfAgo detection platform for one-tube simultaneous typing diagnosis of human respiratory syncytial virus.

Human respiratory syncytial virus (HRSV) is the most prevalent pathogen contributing to acute respiratory tract infections (ARTI) in infants and young children and can lead to significant financial and medical costs. Here, we developed a simultaneous, dual-gene and ultrasensitive detection system for typing HRSV within 60 minutes that needs only minimum laboratory support. Briefly, multiplex integrating reverse transcription-recombinase polymerase amplification (RT-RPA) was performed with viral RNA extracted from nasopharyngeal swabs as a template for the amplification of the specific regions of subtypes A (HRSVA) and B (HRSVB) of HRSV. Next, the Pyrococcus furiosus Argonaute (PfAgo) protein utilizes small 5'-phosphorylated DNA guides to cleave target sequences and produce fluorophore signals (FAM and ROX). Compared with the traditional gold standard (RT-qPCR) and direct immunofluorescence assay (DFA), this method has the additional advantages of easy operation, efficiency and sensitivity, with a limit of detection (LOD) of 1 copy/µL. In terms of clinical sample validation, the diagnostic accuracy of the method for determining the HRSVA and HRSVB infection was greater than 95%. This technique provides a reliable point-of-care (POC) testing for the diagnosis of HRSV-induced ARTI in children and for outbreak management, especially in resource-limited settings.

Design, semi-synthesis and bioevaluation of koumine-like derivatives as potential antitumor agents in vitro and in vivo.

Aims: Five series of novel koumine-like compounds were designed, semi-synthesized and systematically evaluated for antitumor activities.Methods: All compounds were evaluated for antiproliferative activity against four human cancer cell lines, including HT-29, HCT-116, HCT-15 and Caco-2.Results: Most compounds exhibited much higher antiproliferation activities (IC50 <10 µM) than koumine. Two selected compounds A4 and C5 showed comparable antitumor effects to 5-FU in vivo, as well as better safety profiles. Further studies suggested that A4 and C5 could arrest HT-29 cell cycle in G2 phase and raise reactive oxygen species level, thus inducing cell apoptosis related to Erk MAPK and NF-κB signaling pathways inhibition.Conclusion: These results will greatly promote the druggability study of these koumine-like compounds.

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Treatment with autophagic inhibitors enhances oligonol­induced apoptotic effects in nasopharyngeal carcinoma cells.

Although the combination of chemotherapy and radiotherapy has increased the survival rate of patients with nasopharyngeal carcinoma (NPC), certain patients do not respond well to the treatment and have a poor prognosis. Therefore, novel therapeutic drugs and strategies to improve prognosis of patients with NPC are required. As certain plant extracts can suppress the viability of cancer cells, the present study investigated whether oligonol, a polyphenolic compound primarily found in lychee fruit, exerts anticancer activities in NPC cells. MTT, ELISA and immunoblotting were performed to investigate cell survival, cytokeratin-18 fragment release, and the expression of apoptosis and autophagy markers, respectively. Oligonol decreased the viability of NPC-TW01 and NPC/HK1NPC cell lines. Oligonol increased the protein expression of several apoptosis markers, including cleaved caspase-8 and -3, cleaved PARP and cytokeratin 18 fragment. Moreover, it also increased expression of autophagy markers Beclin 1 and LC3-II, as well as LC3-II/LC3-I ratio in both NPC cell lines. Furthermore, treatment with autophagy inhibitors 3-methyladenine or LY294002 significantly increased oligonol-induced viability inhibition in NPC-TW01 cells. Combined treatment of oligonol + LY294002 reduced LC3-II expression and the LC3II/LC3I ratio while increasing cleaved caspase-8 and -3, cleaved PARP and cytokeratin 18 fragment expression in NPC-TW01 cells. These findings indicated autophagy inhibitors could enhance viability inhibition and apoptotic effects induced by oligonol in NPC cells.

Conversion of Bamboo into Strong, Waterproof, and Biodegradable Thermosetting Plastic through Cell Wall Structure Directed Manipulation.

Reckoning with the global environmental challenge of plastic pollution, particularly in terms of recycling and biodegradation of thermosetting plastics, sustainable alternatives are imperative. The rapidly growing and eco-friendly material bamboo has great potential as a sustainable resource; however, it lacks the inherent self-bonding and plasticity characteristics found in plastics. This study presents a feasible approach to enhance the plasticity of bamboo by selectively removing part of its lignin and disrupting the crystalline structure of cellulose. Concurrently, this process selectively transforms hydroxyl groups into highly reactive dialdehyde groups to increase the reactivity of bamboo. The resulting activated bamboo units undergo a hot-pressing process to transform them into a type of thermosetting plastic (ABTP). The ABTP is highly moldable, and its color can be precisely regulated by adjusting the lignin content. Additionally, it exhibits exceptional solvent and water resistance, along with notable mechanical properties, including a tensile strength of 50 MPa, flexural strength of 80 MPa, flexural modulus of 5 GPa, and Shore D hardness approaching 90. Furthermore, the bamboo-derived plastic exhibits exceptional reusability and biodegradability, presenting feasible and environmentally friendly alternatives to conventional plastics while harnessing the sustainable development potential of bamboo.

Bibliometric study of the application of the chicken embryo chorioallantoic membrane model in cancer research: the top 100 most cited articles.

The chicken embryo chorioallantoic membrane (CAM) model has played a crucial role in various aspects of cancer research. The purpose of this study is to help researchers clarify the research direction and prospects of the CAM model. A bibliometric analysis was conducted on the top 100 most cited articles on use of the CAM model in tumour research, retrieved from the Web of Science Core Collection database. Tools such as Bibliometrix, VOSviewer, CiteSpace and Excel were utilized for the visualization network analysis. The 100 articles analysed were mainly from the USA, China and European countries such as Germany and France. Tumour research involving CAM model experiments demonstrated reliability and scientific rigor (average citation count = 156.2). The analysis of keywords, topics and subject areas revealed that the applications of this model ranged from the biological characteristics of tumours to molecular mechanisms and signaling pathways, to recent developments in nanotechnology and clinical applications. Additionally, nude mouse experiments have been more frequently performed in recent years. We conclude that the CAM model is efficient, simple and cost-effective, and has irreplaceable value in various aspects of cancer research. In the future, the CAM model can further contribute to nanotechnology research.

Down regulation of RBM10 promotes proliferation and metastasis via miR-224-5p/RBM10/p53 feedback loop in lung adenocarcinoma.

RNA-binding motif protein 10 (RBM10) has a tumor suppressor role in multiple cancers. Combining Oncomine database results with tissue samples, Western blot analysis showed that RBM10 was significantly lower in lung adenocarcinoma (LUAD) than in adjacent normal tissues. Moreover, KM analysis revealed that the group with higher RBM10 expression in LUAD correlated with better overall survival (OS). Luciferase reporter assay revealed that an important tumor-promotive miRNA, miR-224-5p, was directly bound to the 3'UTR of RBM10, resulting in inhibition of RBM10 expression, and promoted LUAD progression both in vitro and in vivo. Mechanistically, we found that miR-224-5p directly targeted RBM10 to inhibit p53 expression during LUAD progression. Meanwhile, p53 affected RBM10 expression through p53/miR-224-5p axis. Our study identified RBM10 as a key tumor suppressor in the proliferation and metastasis of LUAD. The findings provide a novel mechanism involving a feedback loop of miR-224-5p/RBM10/p53 regulated tumor progression in LUAD, which may help with the design of more effective LUAD treatments.