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We describe "universal" DNA primers for polymerase chain reaction (PCR) amplification of a 710-bp fragment of the mitochondrial cytochrome c oxidase subunit I gene (COI) from 11 invertebrate phyla: Echinodermata, Mollusca, Annelida, Pogonophora, Arthropoda, Nemertinea, Echiura, Sipuncula, Platyhelminthes, Tardigrada, and Coelenterata, as well as the putative phylum Vestimentifera. Preliminary comparisons revealed that these COI primers generate informative sequences for phylogenetic analyses at the species and higher taxonomic levels.
This study employs bibliometric methods to systematically analyze research hotspots and evolving trends in the field of single-port robot-assisted radical prostatectomy (SP-RARP). By searching the Web of Science Core Collection (WoSCC) for relevant literature from 2008 to 2025, a total of 271 records were ultimately included. Co-occurrence networks for countries, institutions, scholars, journals, and keywords were then visualized and subjected to cluster analysis. The results indicate that the number of publications in this field has experienced a notable increase since 2019, with 187 papers produced between 2020 and 2025, and the total citation count peaking in 2025 (reaching 1,107 citations). In terms of national contributions and collaboration networks, the United States accounts for the highest publication volume (164 articles) and, alongside Italy, forms the central nodes of the global collaboration network. China ranks third in publication volume, while countries such as the UK, South Korea, and France demonstrate notable activity in transnational collaboration. The Cleveland Clinic Foundation records the highest institutional output, with scholars such as Simone Crivellaro identified among the most active contributors in this field; relevant findings are predominantly published in specialized journals such as the Journal of Endourology. Keyword evolution indicates that the research focus has shifted from early explorations of minimally invasive approaches and surgical feasibility to in-depth studies on complication control, optimization of functional outcomes, and advanced perioperative care practices using dedicated single-port platforms. In summary, SP-RARP has expanded the strategies for minimally invasive treatment of prostate cancer and demonstrates potential for optimizing perioperative outcomes. However, given the evolution of new technologies, there remains a clear need to design rigorous, high-quality clinical trials to further solidify the evidence base for its long-term oncological and functional benefits.
Two novel actinobacterium strains ZYX-F-536T and ZYX-F-553 were isolated from marine sediment in Yongxing Island, Hainan Province, China. Based on 16S rRNA gene sequence analysis, the strain ZYX-F-536T belongs to the genus Micromonospora, with high similarities to strain ZYX-F-553 (99.9%), Micromonospora alfalfae MED01T (99.0%), Micromonospora auratinigra DSM 44815T (99.0%), Micromonospora saelicesensis Lupac 09T ZYX (99.0%), Micromonospora arida LB32T (99.0%) and Micromonospora foliorum PSH25T (98.9%). The novel isolate ZYX-F-536T contained meso-diaminopimelic acid, glycine and d-alanine in the cell wall. The whole-cell sugars were rhamnose, ribose, glucose and xylose. The predominant menaquinones were MK-10(H4) (38.6%), MK-10(H6) (31.2%) and MK-10(H8) (20.1%). The characteristic phospholipids were phosphatidylethanolamine, phosphatidylinositol, diphosphatidylglycerol and two unknown phospholipids. The major fatty acids (>10%) were C15:0, C16:0, C17:0 and anteiso-C17:0. Genome sequencing showed a DNA G+C content of 71.9 mol%. The low ANI and dDDH values demonstrated that strain ZYX-F-536T could be readily distinguished from the closely related species. Based on phylogenetic, chemotaxonomic and physiological characteristics, strain ZYX-F-536T represents a novel species of the genus Micromonospora, for which the name Micromonospora yongxingensis sp. nov. is proposed. The type strain is ZYX-F-536T (=CCTCC AA 2025094T=JCM 38260T).
To evaluate the efficacy and safety of Lianxia Xiaopi Granules (LXXP) in treating functional dyspepsia (FD) with combined cold and heat pattern in Chinese medicine (CM). A multicenter, randomized, double-blind, and placebo-controlled trial was conducted at 11 centers between April 1, 2021, and October 24, 2022 in China. Using stratified block randomization at a 2:1 ratio, patients diagnosed with FD were randomly assigned to receive either LXXP (3.5 g/bag, equivalent to 8.337 g of raw herbs) or a placebo (3.5 g/bag) 3 times daily for 8 weeks. The primary outcome was dyspepsia symptom response rate. Secondary outcomes included individual dyspepsia symptom response rate, Chinese medicine syndrome efficacy evaluation scale including reduction rate of CM symptom total score, cure and effective rates, and safety analysis. Subgroup analyses were performed according to postprandial distress syndrome (PDS) or epigastric pain syndrome (EPS) subtypes and Helicobacter pylori (Hp) infection status. A total of 240 participants completed the trial, 160 in the LXXP group and 80 in the placebo group. At week 8, the dyspepsia symptom response rate was significantly higher in the LXXP group than in the placebo group [54.38% (87/160) vs. 32.50% (26/80), P=0.0013]. LXXP significantly improved postprandial fullness, early satiety, and bloating compared with the placebo group (P<0.05). Subgroup analysis showed greater efficacy in PDS and Hp-negative patients (P<0.05). Safety analysis revealed no significant differences in adverse events between the 2 groups. LXXP effectively improves FD symptoms, particularly in PDS and Hp-negative patients, supporting its application in CM-based treatment. (Trial registration No. ChiCTR2100041993).
Diabetic nephropathy (DN) is the most prevalent microvascular complication of diabetes, where a hyperglycemic environment can induce chronic damage to renal vessels and parenchyma, severely endangering patients' health. TangShenKang decoction (TSK) is a traditional Chinese medicine formula developed based on the clinical and pathological characteristics of DN. In this study, through transcriptomic data analysis of a rat DN model and a TSK intervention group, the key regulatory gene AT2R was identified. Molecular mechanisms underlying TSK's effects on inflammation and fibrosis in DN were investigated using Western blot, quantitative polymerase chain reaction (qPCR), and immunofluorescence staining experiments, with further in vivo validation of TSK's therapeutic effects on DN. The results showed that TSK can activate AT2R in the DN model and promote SHP1 phosphorylation, thereby inhibiting the phosphorylation of IκBα, an important protein in the NFκB signaling pathway, reducing the secretion of inflammatory cytokines such as TNF-α, IL-1β, and IL-6, and suppressing the progression of inflammation. Meanwhile, after activating AT2R, TSK can effectively inhibit the epithelial-mesenchymal transition (EMT) process in DN, downregulate the expression of p-Smad2/3 in the TGF-β signaling axis, and decrease the expression levels of fibrosis phenotype molecules such as connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), and fibronectin 1 (FN1), thereby alleviating renal fibrosis in DN. In conclusion, the therapeutic effect of TSK on DN may be mediated through the activation of the AT2R/ATIP1/SHP1 axis, which subsequently inhibits inflammation- and fibrosis-related signaling pathways.
Alzheimer's disease and related dementias (ADRD) are progressive neurodegenerative conditions where early detection is critical for timely intervention and care planning. However, current diagnostic methods are often inaccessible, costly, and delayed, especially for underserved populations. There is a growing need for scalable, noninvasive tools that can support timely diagnosis. Spontaneous speech contains rich acoustic and linguistic markers that can serve as noninvasive behavioral markers for cognitive decline. Foundation models, pretrained on large-scale audio or text data, generate high-dimensional embeddings that encode rich contextual and acoustic information. This study benchmarks open-source foundation language and speech models to evaluate their effectiveness in detecting ADRD from spontaneous speech as a potential solution for early, noninvasive, and scalable ADRD detection. In this study, we used the Pioneering Research for Early Prediction of Alzheimer's and Related Dementias EUREKA (PREPARE) Challenge dataset, which consists of audio recordings from over 1600 participants with 3 distinct categories of cognitive decline: healthy control (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). We further excluded samples that are non-English, nonspontaneous speech, or of poor quality. Our final samples included 703 (59.13%) HC, 81 (6.81%) MCI, and 405 (34.06%) AD cases. We systematically benchmarked 18 open-source foundation speech and language models to classify cognitive status into 3 categories (HC, MCI, or AD). Post hoc interpretability analysis was performed for the best-performing model using Shapley additive explanations linking high-dimensional embeddings with explainable acoustic and linguistic markers. Whisper-medium model achieved the highest performance among speech models at 0.731 accuracy and 0.802 area under the curve, while Bidirectional Encoder Representations from Transformers with pause annotation achieved the top accuracy of 0.662 and 0.744 area under the curve among language models. Overall, ADRD detection based on state-of-the-art automatic speech recognition model-generated audio-embeddings outperformed other models, and the inclusion of nonsemantic information, such as pause patterns, consistently improved the classification performance of text-embedding-based models. Our work presents a comprehensive comparative evaluation of state-of-the-art speech and language models for AD and MCI detection on a large, clinically relevant dataset. Embeddings derived from acoustic models, which capture both semantic and acoustic information, show promising performance and highlight the potential for developing a more scalable, noninvasive, and cost-effective early detection tool for ADRD.
The long-term risks of specific cardiovascular diseases (CVDs) among offspring exposed to various types of maternal diabetes in utero and the mechanisms underlying these risks remain unclear. To investigate the association between maternal diabetes during pregnancy and risks of overall CVD and specific CVD subtypes in offspring and whether adverse perinatal and early-life outcomes mediate associations. This nationwide population-based cohort study using linked national registers included individuals born in Sweden between January 1, 1973, and December 31, 2014, with follow-up through December 31, 2023. Maternal diabetes during pregnancy, including gestational diabetes and pregestational diabetes (type 1 and type 2). The main outcomes were incident overall CVD and specific CVD subtypes in offspring, identified from national inpatient and outpatient registers. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. Sibling analyses were conducted to account for shared familial factors. Mediation analyses assessed the contribution of congenital heart disease (CHD), preterm birth, and large for gestational age (LGA). The study included 4 274 414 individuals (51.39% male; mean [SD] age, 27.4 [15.0] years at the end of follow-up), of whom 61 336 (1.46%) were exposed to maternal diabetes and 4 213 078 (98.56%) were not exposed. During a median 27.6 years (IQR, 17.2-37.4 years) of follow-up, 7.36% of total participants had a diagnosis of CVD. Any maternal diabetes was associated with an increased risk of overall CVD in offspring (HR, 1.16; 95% CI, 1.12-1.20); risk of CVD was higher for pregestational diabetes (HR, 1.29; 95% CI, 1.21-1.38) than for gestational diabetes (HR, 1.11; 95% CI, 1.05-1.17). These associations were also found in sibling analyses. Increased risks in offspring prenatally exposed to maternal diabetes were found for some CVD subtypes, including venous thromboembolism (HR, 1.20; 95% CI, 1.07-1.34), cerebrovascular diseases (HR, 1.31; 95% CI, 1.12-1.52), atrial fibrillation (HR, 1.27; 95% CI, 1.05-1.54), and heart failure (HR, 1.65; 95% CI, 1.37-2.00). In mediation analyses, CHD, preterm birth, and LGA directly and/or indirectly mediated 31.87%, 16.06%, and 14.18% of the association between any diabetes and offspring CVD risk, respectively. This cohort study found that maternal diabetes during pregnancy was associated with increased long-term risks of overall CVD and some CVD subtypes in offspring, particularly following pregestational diabetes. These findings highlight the importance of associations of perinatal and early-life factors and offspring CVD risk later in life, especially in mothers with diabetes.
Hepatocellular carcinoma (HCC), a malignancy driven by multifaceted genetic and epigenetic mechanisms, is the leading cause of cancer deaths worldwide. Long non-coding RNAs (lncRNAs), particularly super-enhancer-associated lncRNAs (SE-lncRNAs), have emerged as critical regulators of tumorigenesis. In our study, we explored the expression of super-enhancer (SE)-associated lncRNA (seRNA) in HCC and investigated the role of a SE-lncRNA, HDAC11-AS1, in the progression of HCC. HCC-specific SE-lncRNAs were identified by H3K27ac ChIP-seq data (from ENCODE database) of Huh7, HepG2, and normal liver tissues using the ROSE algorithm. HDAC11-AS1 overexpression was validated in 36 pairs of HCC patient samples and adjacent tissues. The effects of HDAC11-AS1 on HCC proliferation and migration was analyzed in vitro and in vivo by overexpression or knockdown of HDAC11-AS1. Co-expression genes analysis of HDAC11-AS1, qPCR, western blot analysis and immunohistochemistry (IHC) were used to detect the regulation of Histone Deacetylase 11(HDAC11) and Nucleoporin 210 (NUP210).ChIA-PET data analysis, RNA pulldown and RNA immunoprecipitation (RIP) were used to explore the interaction between HDAC11-AS1 and tanscription factor (YY1)/cofactors (EP300 and SMC3). In this study, we identified HDAC11-AS1, a SE-lncRNA significantly overexpressed in HCC tissues and associated with poor prognosis. Downregulation of HDAC1-AS1 suppressed proliferation and migration of HCC in vitro and in vivo. Mechanistically, HDAC11-AS1 as a pivotal SE-lncRNA driving HCC progression through transcriptional regulation of HDAC11 and NUP210 by interacting with transcription factor YY1 and cofactor (EP300 and SMC3) in stabilizing enhancer-promoter looping. Our findings reveal that HDAC11-AS1 functions as a molecular scaffold that stabilizes enhancer-promoter (E-P) looping, thereby promoting super-enhancer activity and the subsequent transcription of oncogenic drivers.
In recent years, the modification of gem-dinitro and trinitromethyl-based energetic materials has attracted considerable attention. This study summarizes recent strategies for improving material performance by introducing fluorine atoms into asymmetric gem-polynitro structures. It was found that the introduction of fluorine atoms effectively increases the thermal stability and density of these materials while maintaining their detonation performance. Frontier molecular orbital (FMO) analysis reveals that the incorporation of fluorine atoms enlarges the HOMO-LUMO gap, thereby enhancing molecular stability. Furthermore, atomic dipole moment corrected Hirshfeld (ADCH) atomic charge and electrostatic potential (ESP) analyses indicate that introducing fluorine into the parent asymmetric gem-dinitro/trinitromethyl energetic materials effectively enhances thermal stability by promoting a more uniform charge distribution across the system. Finally, based on the known experimental structure 5, a novel compound (5-F) was designed. Computational results demonstrate that both the detonation velocity and density of compound 5-F are significantly improved. This research strategy provides valuable guidance for the design and synthesis of next-generation gem-polynitro energetic materials. All calculations were performed using Gaussian 16 software and the Multiwfn program package, and the Grimme dispersion correction was employed in the present work. Specifically, the M06-2X functional combined with the def2-TZVP basis set was used for molecular structure (1-4) optimization and frequency calculation; the B3PW91 functional and 6-31G** basis set were adopted for density calculation (5-F); the B3LYP functional and 6-31G** basis set were utilized for structural optimization in enthalpy of formation calculation, while the single-point energy was calculated at the M06-2X/def2-TZVP level (5-F).
This study seeks to investigate the underlying mechanism of glycolytic key gene bisphosphoglycerate mutase (BPGM) in nonalcoholic fatty liver disease (NAFLD). qRT-PCR and immunohistochemistry were utilized to detect BPGM levels in clinical NAFLD samples. HepG2 cells and liver organoids were treated with free fatty acid. (FFA). The role of BPGM in NAFLD was explored at cellular, organoid, and animal levels. Metabolomics was performed to analyze differential metabolites and metabolic pathways. Furthermore, we examined the regulatory mechanisms of BPGM by HIF-1α in NAFLD. Results indicated that high expression of BPGM in NAFLD samples was correlated with NAFLD progression. Moreover, Severe group had higher BPGM expression than Mild group. FFA treatment induced time-dependent steatosis and BPGM upregulation in HepG2 cells and liver organoids, whereas BPGM knockdown attenuated lipid accumulation, cellular injury, and oxidative stress. At the animal level, knockdown of BPGM reversed high-fat diet (HFD) induced lipid accumulation and liver tissue injury. Metabolomics studies showed significant changes of metabolic pathways including glycolysis/gluconeogenesis and pyruvate metabolism. Verification experiment showed FFA increased pyruvic acid levels, and knockdown of BPGM decreased pyruvic acid levels. Pyruvic acid further reversed the changes in NAFLD progression caused by BPGM knockdown at the cellular and organoid levels. Finally, HIF-1α regulated the expression of BPGM in NAFLD. Together, our findings suggest that BPGM contributes to abnormal glucose metabolism and promotes hepatic steatosis, thereby driving NAFLD progression.
Precise tumor imaging is essential for accurate intraoperative decision-making, thereby directly influencing patient prognosis. Optical molecular probes enabling non-invasive, dynamic assessment of cancerous lesions are clinically crucial. However, current optical molecular probes face challenges in dodging false-positive and false-negative signals at once during imaging, limiting their clinical diagnostic use. Here, we introduce a class of lysosome-targeted, activatable optical probes (Dx-NH2), leveraging the increased lysosomal abundance during tumor metabolic reprogramming. Lysosomal protonation retains probes for better single-cell resolution and fewer false-negative signals. To enable more high-precision tumor imaging, we synthesized probe CN-D-GGT from CN-D-NH2 by introducing a γ-glutamyltransferase substrate, following our group's prior offensive and defensive integration strategy. Due to its smart design, CN-D-GGT, upon activation, shows marked changes in fluorescence and photoacoustic signals, enabling its application for multi-modal imaging. It also has high specificity, distinguishing cancer cells in co-culture (∼6-fold) and clearly differentiating tumors from normal and inflamed tissues (T/N or T/I signal ratios > 3.5). Importantly, it can also differentiate cancerous from adjacent tissues in clinical samples. This work has developed a probe that can accurately light tumors in complex pathological environments, with the potential to assist in intraoperative resection decision-making, avoid excessive or missed resection.
The development of dual-functional electrocatalysts with outstanding properties in oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is of great significance in the field of hydroelectrolysis hydrogen production. Herein, we propose to simultaneously optimize the HER and OER properties of NiFe-LDH-based composite electrocatalysts through cerium doping and RuO2 modification. Benefiting from the synergistic effect of flower-like surface morphology with a large number of fine structures, formation of highly active species as well as RuO2 containing Ru3+ species, RuO2-Ce-NiFe-LDH-0.01/NF only needs low overpotential of 48 and 214 mV for HER and OER to achieve 10 mA cm-2, respectively. More significant, the electrolyzer of RuO2-Ce-NiFe-LDH-0.01/NF//RuO2-Ce-NiFe-LDH-0.01/NF only demands 1.48 V to deliver 10 mA cm-2 and demonstrates robust stability for 100 h. This work opens up a pathway to develop remarkable bifunctional electrocatalysts, demonstrating their enormous potential for industrial applications in water electrolysis.
Early neurological deterioration (END) is a frequent and serious complication after intravenous thrombolysis in acute ischemic stroke (AIS), yet the clinical relevance of thrombotic molecular markers related to coagulation, fibrinolysis, and endothelial dysfunction remains incompletely understood. In this retrospective cohort study, 91 patients with AIS treated with intravenous thrombolysis were included between November 2022 and February 2025. Plasma levels of thrombin-antithrombin complex (TAT), plasmin inhibitor-plasmin complex (PIC), thrombomodulin (TM), and tissue-type plasminogen activator-plasminogen activator inhibitor-1 complex (t-PAIC) were measured before thrombolysis and at 1, 6, and 24 h thereafter. Stroke etiology was classified according to the Trial of Org 10,172 in Acute Stroke Treatment criteria into large artery atherosclerosis (LAA) and small vessel disease (SVD) subtypes, and patients were further categorized into END and non-END groups. Patients with LAA exhibited significantly higher plasma TAT levels at all time points and a higher incidence of END than those with SVD. Plasma TM levels were higher in the non-END group, with statistically significant differences observed at 24 h after thrombolysis. Multivariable analysis identified higher TM levels at 24 h as an independent protective factor against END, whereas elevated t-PAIC levels were independently associated with increased END risk. Given that END may occur early after thrombolysis, these associations should be interpreted cautiously in terms of temporal sequence. A combined model incorporating TM and t-PAIC demonstrated good discriminative performance for END, with an area under the curve of 0.849. These findings indicate distinct coagulation-endothelial response patterns between AIS subtypes and suggest that TM and t-PAIC may serve as complementary biomarkers associated with END risk following intravenous thrombolysis, although further validation is required.
Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins constitute the core molecular machinery that drives intracellular vesicular trafficking and membrane fusion in eukaryotic cells. Beyond their canonical roles in neurotransmitter release, autophagic flux, and exosome secretion, accumulating evidence indicates that dysregulated SNARE expression and function contribute to tumor progression. In central nervous system tumors (CNSTs), aberrant SNARE activity has been increasingly implicated in invasive growth, chemotherapy resistance, and tumor microenvironment remodeling. Guided by the 2021 World Health Organization classification of tumors of the central nervous system (WHO CNS5), this review summarizes current advances on the pathogenic roles of SNARE proteins in glioblastoma, medulloblastoma, meningioma, and pituitary neuroendocrine tumors, and discusses their translational potential as molecular biomarkers and therapeutic targets for precision neuro-oncology.
Massive abdominal wall defects resulting from radical abdominal wall endometriosis (AWE) resection present a major reconstructive challenge. This study aims to assess feasibility and short-term safety of a standardized retromuscular-onlay dual-mesh repair technique in this setting. In this single-center retrospective study, 9 patients with massive abdominal wall endometriosis underwent radical excision and standardized retromuscular-onlay dual-mesh reconstruction between January 2024 and June 2025. A series of postoperative complications was analyzed, including surgical site infection, symptomatic seroma, hematoma, wound pain and numbness, mesh infection, incisional hernia, and recurrence of abdominal wall endometriosis. All nine patients, with a history of cesarean delivery, were diagnosed with type III AWE. Clinical presentation uniformly featured a palpable abdominal wall mass and pain accompanying the menstrual cycle. Previous surgical intervention for AWE had been undertaken in 22.2% (2/9) of patients. All reconstructive procedures were successfully performed. We recorded a mean specimen diameter of 9.61 ± 2.56 cm, an operative time of 114.00 ± 41.81 min, and an estimated blood loss of 15.70 ± 11.61 mL. The mean postoperative hospital stay was 8.50 ± 2.72 days, and drains were maintained for a mean of 5.00 ± 1.05 days. In this small cohort study, no surgical site infections, mesh infections, hematomas, or symptomatic seromas requiring intervention occurred. At a mean follow-up of 6 months, no clinical recurrence of AWE or incisional hernia was observed. Only one patient (11.1%) reported a slight numbness in the skin of the surgical area. This standardized dual-mesh reconstruction technique appears feasibility and short-term safety for massive AWE-related abdominal wall defects, with encouraging short-term outcomes and low early complication rates in this initial experience. Longer-term follow-up and prospective multi-center studies are needed to confirm durability.
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Post-transplant relapse remains a major clinical challenge in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Real-time quantitative PCR (RQ-PCR) for BCR::ABL1 is the current standard for measurable residual disease (MRD) monitoring, whereas digital PCR (dPCR) offers substantially higher analytical sensitivity. Whether this increased sensitivity translates into additional prognostic value after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. In this prospective study (NCT06211166), 270 patients with Ph + ALL were longitudinally monitored after allo-HSCT. MRD was assessed in parallel using dPCR, RQ-PCR, and MFC. Based on the first post-transplant MRD detection pattern, patients were categorized into four groups: double-negative (n = 80), dPCR-single-positive (n = 158), RQ-PCR-single-positive (n = 3), and double-positive (n = 29). The dPCR-single-positive pattern was the most prevalent MRD status, accounting for 58.5% of patients. dPCR positivity independently predicted subsequent MFC-MRD conversion (HR 9.56, P = 0.029), with a median lead time of 77 days. In addition, dPCR detected BCR::ABL1 positivity earlier than RQ-PCR, preceding subsequent hematologic relapse by a median of 64.5 and 91.5 days, respectively. However, the cumulative incidence of hematologic relapse (CIR), the primary endpoint of this study, did not differ significantly among the four MRD-defined groups (P = 0.60). Consistently, isolated dPCR positivity was not associated with inferior 2-year leukemia-free survival (LFS; P = 0.30) or overall survival (OS; P = 0.60). Although dPCR detects molecular disease earlier and anticipates MFC-MRD by 2 months after allo-HSCT in Ph + ALL, isolated ultra-low-level BCR::ABL1 positivity does not impact relapse risk, LFS, or OS. Routine MRD monitoring with RQ-PCR plus MFC remains sufficient for prognostic stratification, while dPCR primarily provides an ultra-early signal to guide timely intervention rather than improving survival prediction.
Postmenopausal osteoporosis (PMOP) is a skeletal disorder marked by progressive bone mineral density decline and increased susceptibility to fractures. Accumulating evidence indicates that coupled osteogenesis and angiogenesis are indispensable for bone remodeling and repair. This study investigated the therapeutic potential of dendrobine in concurrently modulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and angiogenic activity in the context of PMOP. BMSCs were isolated from Sprague-Dawley rats and rigorously characterized prior to experimentation. Cell viability was quantified using CCK-8 assays, and apoptosis was assessed via flow cytometry. To evaluate angiogenesis, tube formation capacity was measured following coculture of BMSCs and human umbilical vein endothelial cells (HUVECs), and protein levels of angiogenic factors (VEGF, MMP2, and MMP9) were quantified by western blotting. Osteogenic differentiation was assessed by Alizarin red staining for mineralized nodule formation, ALP staining, and western blotting of osteogenic markers (Runx2, OCN, and OPN). Following PMOP modeling via bilateral ovariectomy (OVX), H&E staining and micro-computed tomography were conducted. Western blotting was performed to measure protein levels of core Hippo pathway components (Mst1, Lats1, Yap1, and Taz) in femoral bone tissue. Results showed that dendrobine significantly promoted BMSC viability and suppressed apoptosis in a dose-dependent manner. In BMSC-HUVEC cocultures, dendrobine markedly augmented tube formation and upregulated VEGF, MMP2, and MMP9. Concurrently, dendrobine enhanced osteogenic differentiation, as evidenced by increased ALP activity, enhanced mineralization, and elevated protein levels of Runx2, OCN, and OPN. In OVX rats, dendrobine treatment ameliorated trabecular bone loss and restored bone parameters toward sham levels. Consistently, dendrobine elevated the expression of osteogenic and angiogenic proteins in vivo. Moreover, dendrobine suppressed Mst1 and Lats1 expression while promoting Yap1 and Taz expression in OVX rats. In conclusion, dendrobine alleviates PMOP by coordinately enhancing osteogenesis and angiogenesis through inhibition of the Hippo pathway and subsequent activation of the Yap1/Taz signaling.
Doxorubicin (DOX) is a cytotoxic chemotherapeutic drug, the clinical value of which is limited by its cardiotoxicity. Krüppel-like factor 9 (KLF9) is known to modulate cell proliferation, differentiation, and apoptosis and plays critical roles in cardiovascular diseases. Here, we aimed to explore the potential effect of KLF9 on DOX-induced cardiotoxicity. C57BL/6J mice with cardiac-specific overexpression or silencing of KLF9 received single intraperitoneal injections of DOX to establish a DOX-induced cardiotoxicity model. The cardiac function of the mice was monitored by echocardiography, cardiac morphology was evaluated by histopathological staining, biomarkers of myocardial injury were detected using ELISA, and TUNEL staining and Western blotting were performed to evaluate apoptosis. In addition, H9c2 cells were used to validate the function of KLF9 in vitro. To test the involvement of thioredoxin reductase 2 (Txnrd2), ROS and p53 in the observed effects, siRNAs directed against p53 and Txnrd2 and the ROS inhibitor N-acetyl cysteine (NAC) were used. KLF9 expression was upregulated in the hearts of DOX-treated mice and H9c2 cells. Cardiac-specific KLF9 overexpression exacerbated, while cardiac-specific KLF9 silencing alleviated, DOX-induced apoptosis, acute myocardial injury and dysfunction. Mechanistically, KLF9 deficiency resulted in upregulation of Txnrd2 expression and subsequent suppression of apoptosis through modulation by ROS/p53 signalling. KLF9 exerts a pro-apoptotic effect on DOX-induced cardiotoxicity by inhibiting Txnrd2 and regulating the ROS/p53 signalling pathway. KLF9 deficiency may be a promising target for mitigating DOX-induced cardiotoxicity.
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