Background: Takayasu arteritis (TAK) is a heterogeneous large-vessel vasculitis, and existing anatomical classifications provide limited prognostic information. Methods: In this multicenter cohort study, 338 patients with TAK from three tertiary centers were included. Arterial involvement across 18 vascular territories was assessed, and unsupervised hierarchical clustering identified imaging-defined vascular phenotypes. Clinical associations were analysed using multivariable logistic regression, and long-term outcomes were evaluated in 305 patients with follow-up data. Findings: Five vascular phenotypes were identified: Iliac–Cardio–Cerebral (n=39), Abdominal (n=78), Thoracic–Pulmonary (n=89), Vertebral (n=41), and Brachiocephalic (n=91). Outcomes differed significantly across phenotypes, including all-cause mortality (log-rank p=0.003) and cumulative adverse events (log-rank p<0.001). The Iliac–Cardio–Cerebral phenotype had the highest risks of mortality (HR=6.9, p<0.0001), total adverse events (HR=2.22, 95% CI 1.24–3.97), and cardiovascular events (HR=4.51, 95% CI 1.83–11.12). The Abdominal, Thoracic–Pulmonary, and Vertebral phenotypes were associated with increased renal, pulmonary, and cerebrovascular events, respectively, whereas the Brachiocephalic phenotype showed the most favourable prognosis. Interpretation: Imaging-defined vascular phenotypes identify distinct risks of organ-specific complications and mortality in TAK. This phenotype-based framework may improve prognostic stratification and support individualized management.

Background: Cleft palate (CP) is a prevalent craniofacial malformation, with the TGFβ pathway playing a critical role. Recent evidence links autophagy to regulating mouse embryonic palatal mesenchyme (MEPM) cells, but its interaction with TGFβ-activated phosphorylation cascades remains largely unknown. Here, we investigated the interplay between these pathways during palatogenesis. Methods: H&E and IHC analyses revealed increased expression of Beclin 1 and LC3 during the critical period of palatal shelf elevation and fusion (E13.5–E15.5). Bulk RNA sequencing (Bulk RNA-seq) further revealed enrichment of autophagy-related pathways and their interaction with TGFβ signaling. TMT-based phosphoproteomics was performed on TGFβ2-treated MEPM cells. Results: We identified 23,471 peptides and 3952 proteins, including 6339 phosphopeptides corresponding to 2195 phosphoproteins. Differential analysis found 477 phosphopeptides with increased abundance and 53 with decreased abundance, revealing the enrichment of seven serine (p-Ser) motifs (RxxS, SDxD, SDxE, SP, SxDE, SxEE, SxxxxD) and one threonine (p-Thr) motif (TP). Notably, kinase-substrate enrichment analysis identified CSNK2A as a previously unrecognized phosphorylation regulator, together with MAPKs and CDKs. Functional enrichment showed significant involvement of mTOR, MAPK, and autophagy/mitophagy pathways. Conclusions: Our findings revealed that TGFβ2 reshapes the MEPM phosphoproteome through Smad-independent pathway, expanding the palate-specific phospho-signaling atlas beyond the canonical Smad cascade.

Turner syndrome (TS) girls experience accelerated ovarian reserve depletion, exhibiting a strong demand for ovarian tissue cryopreservation (OTC) to preserve fertility and ovarian function. However, the current knowledge of OTC in TS is limited, and predicting follicular presence is insufficient. This study aims to investigate ovarian follicular reserve based on karyotypes, thereby contributing empirical data to informed decision-making in TS populations. The retrospective case-control study comprised 26 TS patients and 52 age-matched non-TS (NTS) controls who underwent OTC between January 2022 and March 2025. The TS cohort included 45,X (n = 2), 45,X/46,XX (n = 6), and ‘other’ (n = 18), the latter encompassing 7 cases with 47,XXX mosaicism and 11 with structural X-chromosome abnormalities (SCA). Ovarian volume, estimated total follicle count (TFC), anti-Müllerian hormone (AMH), and follicle-stimulating hormone (FSH) were compared between the TS and NTS across age cohorts (0–5, 6–10, and > 10 years), and further analyzed across TS karyotype categories. Follicles were found in 91.7

Background and aimsInflammatory stimuli drive metabolic reprogramming in macrophages, supplying energy, reducing equivalents, and methyl donors required for the production of inflammatory mediators such as IL-1β; however, metabolic strategies to regulate this pathway remain unclear. Here, we aimed to define the mechanism by which D-mannose suppresses one-carbon metabolism in inflammatory macrophages and thereby epigenetically restrains inflammatory responses.MethodsUntargeted metabolomics was used to define the global metabolic effects of D-mannose in inflammatory macrophages. 6-phosphogluconate dehydrogenase activity and real-time ATP rate assays were performed to assess nicotinamide adenine dinucleotide phosphate (NADPH) and adenosine triphosphate (ATP) generation. S-adenosylmethionine (SAM) and cytokine levels were measured by enzyme-linked immunosorbent assay, and epigenetic regulation at the Il1b promoter was examined by chromatin immunoprecipitation-qPCR and immunoblotting. A murine full-thickness skin wound model with macrophage depletion was used for in vivo validation.ResultsD-mannose suppressed metabolic flux through glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway, resulting in reduced ATP and NADPH production. This metabolic restriction impaired one-carbon metabolism, decreased SAM abundance, and reduced histone H3 lysine 36 trimethylation enrichment at the Il1b promoter, thereby repressing Il1b transcription. These effects were reversed by exogenous SAM supplementation. Macrophages exhibited a metabolic bottleneck associated with low mannose phosphate isomerase (Mpi) expression. Consistently, Mpi overexpression reversed the D-mannose-induced reductions in ATP and SAM levels, as well as Il1b expression. Topical D-mannose also lowered SAM and IL-1β levels in wound tissues and accelerated wound healing in vivo.ConclusionsD-mannose suppresses macrophage pro-inflammatory transcription through a one-carbon metabolism-epigenetic axis, supporting its potential as a metabolism-targeted strategy for inflammatory wound repair.

Bone morphogenetic protein (BMP) signaling has multiple functions in immune cells, especially in the differentiation of T cells. Previously, we found that BMP6 can dramatically promote the IFN-γ production in Th1. However, the interactions between BMP6 and Th17 cells remain poorly characterized. The evidence implicates dysregulated Th17 cell differentiation as a pivotal mechanism in psoriatic pathogenesis, yet the therapeutic potential of BMP6 in this autoimmune disease needs to be further explored. This study aimed to evaluate the potentially beneficial role of BMP6 in the Th17-induced psoriatic models and investigate its possible mechanisms. Th17 cells were intervened with BMP6 in vitro. The differentiation of Th17 was observed through multi-platform assessment combining flow cytometry, qRT-PCR, and ELISA. Signaling pathway activation was evaluated by Western blotting. RNAseq was used to further discover the impact of BMP6 on Th17. For in vivo experiments, the psoriatic model of C57BL/6 mice was established and treated with BMP6 i.d., and the Th17 cells were evaluated by flow cytometry. BMP6 treatment suppressed Th17 differentiation via the Smad1/5/9 pathway and impaired mitochondrial metabolism of Th17. In the imiquimod-induced psoriatic murine model, pharmacological BMP6 administration significantly attenuated disease progression and downregulated pathogenic Th17 cell frequency in lesional skin. Our finding elucidates the potential mechanism underlying the inhibitory effects of BMP6 in Th17-induced autoimmune diseases and furnish a theoretical foundation for its clinical application.

Dihydromyricetin (DHM), a flavonoid extracted from rattan tea, possesses notable anti-inflammatory and antioxidant properties. This study aims to evaluate the protective effects and underlying mechanisms of DHM on cyclophosphamide (CTX)-induced spermatogenic dysfunction in mice and in vitro. Mice were divided into six groups: a control group receiving a vehicle via gavage; a CTX-treated group administered CTX (120 mg/kg/ week) dissolved in normal saline by intraperitoneal injection; CTX plus Levocarnitine (LC) groups receiving 10 mL/kg/day LC via gavage; and CTX plus DHM groups receiving 37.5 mg/kg, 75 mg/kg, and 150 mg/kg of DHM dissolved in saline solution via gavage. Male mice treated with CTX were given DHM for two weeks. DHM significantly improved the morphology of reproductive organs, increased sperm count, motility, and viability, and restored blood-testis barrier (BTB) integrity. Mechanistically, DHM reduced the expression of proteins in the TGF-beta 3/p38 MAPK pathway, thereby preserving BTB tight junctions. In vitro, DHM increased the viability and reduced apoptosis in acrolein (ACR)-damaged TM4 Sertoli cells, improved cytoskeletal integrity, and upregulated Claudin-11 expression. These findings suggest that DHM ameliorates CTX-induced spermatogenic dysfunction, which is associated with the modulation of the TGF-beta 3/p38 MAPK signaling pathway, indicating its potential as a promising candidate for the treatment of male infertility.

Natural killer (NK) cell immunosuppression represents a critical factor in patients with progressive hepatocellular carcinoma (HCC), yet its underlying characteristics at the single-cell level remain poorly defined. This study investigates the functional and metabolic alterations in NK cells associated with progressive HCC. We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood samples from six treatment-naïve HCC patients, categorised into progressive and stable disease groups based on a 3-year follow-up. This was complemented by multicolor flow cytometry of peripheral blood, alongside multicolor fluorescence analyses of paired tumour and adjacent tissues. Our analyses revealed a significant reduction in NK cell proportion and a marked downregulation of immune-related genes in patients with progressive HCC. scRNA-seq further identified a distinct NK cell characterised by high expression of HAVCR2 (TIM3). Compared to TIM3-NK cells, TIM3+NK cells exhibited an exhausted phenotype, evidenced by upregulated CD39 and TIGIT, impaired functional capacity (reduced CD107a and IFN-γ) and downregulated key glycolytic enzymes (HK2, ATP5a). Clinically, high TIM3 expression correlated with shorter progression-free survival and an increased risk of tumour progression. Collectively, our findings delineate a state of NK cell immunosuppression and metabolic impairment in progressive HCC, potentially driven by glycolytic reprogramming and establish TIM3 as a critical marker and potential therapeutic target.

We evaluated whether ovarian tissue cryopreservation (OTC) is a viable option for girls and young women who have already undergone hematopoietic stem cell transplantation (HSCT). We enrolled 142 patients who underwent OTC either before or after HSCT. Participants were categorized into three groups: "after HSCT group" (n = 16), "no-chemo group" before OTC (n = 75), and "chemo group" before OTC (n = 51). The after HSCT cohort had a mean age of 12.06 years at OTC, with half being pre-pubertal. Comparative analysis across age (0-12 and 13-24 years) revealed that the after-HSCT group consistently presented with significantly elevated FSH and diminished AMH levels relative to the no-chemo group. Ovarian volume per ovary was also markedly reduced in the after-HSCT group compared to the no-chemo group across all ages. Crucially, the estimated total follicle count per ovary was significantly lower in the after-HSCT group than in both pre-HSCT groups among 0-12 years, and versus the "no-chemo group" in 13-24 years. This confirms pre-HSCT fertility preservation as the paramount strategy. However, OTC post-HSCT emerges as a viable salvage option for carefully selected patients, underscoring the need for long-term follow-up to identify candidates and expand fertility possibilities in survivorship care.

Elevated serum ferritin levels predict adverse outcomes in many autoimmune diseases. However, its clinical significance in Takayasu arteritis (TAK) is not clear. This study aimed to evaluate the predictive value of serum ferritin for major adverse cardiovascular events (MACEs) in TAK. A two-center retrospective cohort study was conducted. A total of 189 treatment-naïve TAK patients who underwent serum ferritin testing at baseline were consecutively enrolled and followed longitudinally. The association between serum ferritin levels and adverse events was assessed using survival analyses. Thirty-seven patients (19.6

OBJECTIVE:To develop a safer strategy for preserving ovarian function in patients facing gonadotoxic therapies, this study evaluated the natural osmolytes l-proline and betaine as dimethyl sulfoxide (DMSO)-free alternatives for human ovarian tissue cryopreservation (OTC). METHOD:The study first characterized the physicochemical properties of the cryoprotectants (CPAs). Ovarian cortical tissues from 10 patients were then processed into biopsies, which were randomized and cryopreserved using slow freezing with 1.5 M l-proline, betaine or DMSO (control). After thawing and a 4-day in vitro culture, assessment included estradiol secretion, glucose uptake, follicular viability (Calcein-AM), apoptosis (TUNEL), and markers of angiogenesis (CD31) and proliferation (Ki-67). RESULTS:l-Proline demonstrated cryoprotective efficacy comparable to DMSO in key follicular metrics: estradiol secretion and follicular viability were not significantly different between the l-proline and DMSO groups, and both were superior to betaine. Apoptosis was equally low in the l-proline and DMSO groups, and considerably lower than in the betaine group. In contrast, DMSO showed higher glucose uptake and expression of CD31 and Ki-67. CONCLUSION:l-Proline is an effective natural alternative to DMSO for OTC, achieving equivalent preservation of the follicular reserve and function with a favorable biosafety profile. These findings highlight its significant translational potential for enhancing the safety profile of clinical fertility preservation.

AIM:To investigate the role and epigenetic mechanism of methyltransferase 14 (METTL14)-mediated N6-adenylate methylation (m6A) modification of long non-coding RNAs (lncRNAs) in the pathogenesis of periodontitis. MATERIALS AND METHODS:A periodontal ligament-targeted Mettl14-cKO mouse model (Gli1-CreERT2;Mettl14fl/fl) was established using silk ligatures. Human periodontal ligament cells (PDLCs) were used for in vitro assays. MeRIP-seq, RNA-seq, RNA pull-down, mass spectrometry, RIP Co-IP and CUT&Tag were performed to elucidate the METTL14-NEAT1_2-YBX1 axis. RESULTS:METTL14 expression was significantly up-regulated in inflamed periodontal tissue. METTL14 deficiency alleviated alveolar bone destruction and suppressed IL-6 expression in vivo and in vitro. Mechanistically, METTL14 catalysed m6A modification of nuclear paraspeckle assembly transcript 1_2 (NEAT1_2), facilitating NEAT1_2 degradation. NEAT1_2-organised paraspeckles (PSPs) sequestered the transcription factor Y-box binding protein 1 (YBX1) under normal conditions. In periodontitis, METTL14-induced NEAT1_2 down-regulation triggered PSP disassembly, resulting in the translocation of YBX1 to the nucleus and increased IL-6 transcription. Neat1_2 knockdown exacerbated bone loss and neutralised the protective effect of METTL14 deficiency. CONCLUSION:METTL14-mediated m6A modification exacerbates periodontitis by disrupting NEAT1_2-dependent PSP sequestration of YBX1. This study identifies the METTL14-NEAT1_2 axis as a critical regulator of periodontal inflammation, suggesting that METTL14 is a potential therapeutic target for periodontitis.

OBJECTIVE:This study aimed to evaluate and validate the utility of a conventional ultrasound-based carotid grading system in assessing disease activity in Takayasu arteritis (TA) with carotid artery involvement, distinguishing between active and inactive patients, and monitoring therapeutic response. METHODS:The 108 patients were classified into the clinically-active group (CAG) and the clinically-inactive group (CIG), and were further classified into Grades I-V according to carotid ultrasound imaging characteristics, with Grades I, II, and V categorized as the ultrasound-active group (UAG), and Grades III and IV as the ultrasound-inactive group (UIG). Intergroup differences were compared, and the diagnostic performance of the ultrasound grading system for disease activity was evaluated by the ROC curve analysis. Treatment response assessed in 68 follow-up patients based on ultrasound grading. RESULTS:The CAG exhibited higher inflammatory markers and greater carotid wall thickness (p < 0.05). Grades I, II, and V predominated in the CAG, whereas Grades III and IV were more frequent in the CIG. Compared to the UIG, the UAG showed significantly elevated ESR, CRP, C3, and IgM, and thicker carotid walls (p < 0.05). The ultrasound grading system achieved an AUC of 0.710 for identifying clinical activity in TA. Combined with carotid wall thickness, diagnostic performance surpassed either parameter alone. Among 68 follow-up patients, the UAG had higher inflammatory markers and greater wall thickness at baseline but demonstrated more pronounced improvement in disease activity after treatment. CONCLUSIONS:Conventional ultrasound is a reliable tool for characterizing vascular wall inflammation and monitoring therapeutic response in TA patients with carotid artery involvement.

Megalobrama amblycephala is an economically important fish species in Chinese aquaculture, but its high sensitivity to hypoxia poses a major challenge for farming. This study aims to investigate the role of the E3 ubiquitin ligase parkin in regulating hypoxia signaling in fish. Under hypoxic stress, parkin expression was significantly upregulated in oxygen-sensitive tissues (brain and gills) and embryos of M. amblycephala, consistent with the expression of hypoxia-responsive genes. Ma-parkin was found to exhibit high conservation in its key functional domains. Mechanistically, it directly interacts with Ma-hif-α, promoting their ubiquitination and proteasomal degradation via E3 ligase activity, thereby suppressing hif-mediated transcriptional activation. Critical residues T74 and C333 were identified as essential for this activity; mutations at these sites impaired Ma-hif-α degradation and ubiquitination, as well as HRE transactivation. Furthermore, we found that Ma-hif-α can regulate the transcription of parkin, forming a negative feedback loop to fine-tune the hypoxic response. Our study demonstrates that parkin serves as a key negative regulator of the hypoxia signaling pathway in M. amblycephala, operating through a finely tuned feedback mechanism. The E3 ubiquitin ligase activity of parkin, dependent on critical residues T74 and C333, directly mediates hif-α ubiquitination and degradation. The reciprocal regulation between hif-α and parkin forms a regulatory circuit that modulates the hypoxic response. These findings not only reveal a conserved adaptive mechanism to hypoxia in fish but also identify specific molecular targets for genetic improvement of hypoxia tolerance in aquaculture species.

BACKGROUND:Coronary artery vasculitis (CAV) is a relatively rare etiology of coronary artery disease (CAD), which could lead to recurrent complications once treated with coronary stents. However, differentiating between CAV and atherosclerotic CAD is challenging. CASE SUMMARY:Included in this case series were 10 symptomatic patients who were initially considered as having atherosclerotic CAD but were eventually diagnosed with CAV at our center from August 2021 to October 2024. We describe the clinical and imaging characteristics of these patients. DISCUSSION:This case series shows several classic CAV characteristics on coronary computed tomography angiography, raising the awareness of CAV misdiagnosis and highlighting the importance of timely order and dedicated imaging analysis for the diagnosis of CAV. TAKE-HOME MESSAGE:Coronary computed tomography angiography can provide comprehensive information on plaque characteristics, coronary artery wall abnormalities, and pericoronary inflammation, which can help cardiologists and radiologists differentiate between CAV and atherosclerotic CAD.

Cancer patients often suffer from depression, the presence of which promotes the deterioration of the cancer patient's condition and thus affects the patient's survival. However, the exact mechanisms underlying the relationship between depression and tumour progression remain unclear, and this complexity involves multi-system and multi-level interactions, with several key challenges remaining in current research. First, the extreme complexity of biological systems. Depression and tumors involve multiple pathways such as neuroendocrine, immune system, and metabolism, respectively, and there are nonlinear interactions between these pathways (e.g., HPA axis activation affects both immunosuppression and tumor angiogenesis), so it is difficult to isolate the predominant role of a single mechanism, and there are feedback loops (e.g., inflammatory factors (e.g., IL-6) can both induce depressive symptoms and promote tumor growth) form a "feedback loop between depression and tumors" that makes it difficult to determine the direction of causality. Second, the potential blind spot of mechanism research. There is insufficient direct evidence for the brain-tumor axis, and it is known that the vagus nerve or sympathetic nerves can directly modulate the tumor microenvironment (TME) (e.g., via β-adrenergic receptors), but there is a lack of technical support for in vivo imaging on how the CNS remotely affects tumors through the neural circuits; whereas depression-associated disturbances of the intestinal flora or in certain stages of tumor development (e.g., metastatic) or specific microenvironments (e.g., areas of hyper-infiltrating T-cells) may have long-term effects on the tumors, but such changes are difficult to capture in short-term experiments and cannot be precisely temporally resolved by existing technologies. However, there are limitations in current research methods. Existing studies have relied on mouse models of chronic stress (e.g., chronic unpredictable stress), but the "depression-like behaviour" of mice is fundamentally different from the clinical manifestations of depression in humans, and the TME (e.g., immune composition) is different from that of humans. Finally, for patients with cancer-associated depression, clinical treatment is usually a two-pronged strategy, but the combination of anticancer and antidepressant drugs has limitations, such as drug-drug interactions, safety issues, and the challenge of individualised treatment in clinical practice. Therefore, by elucidating the relationship between depression and tumour bidirectional effects, this review relatively clarifies how depression affects TME to promote tumour progression by influencing changes in immunosuppression, hormonal changes, glutamate/glutamate receptors, and intestinal flora. Further, some potential therapeutic strategies are proposed for the clinical treatment of this group of patients through the above pathological mechanism; at the same time, it was found that antidepressant drugs have potential antitumor activity, and their dual pharmacological effects may provide synergistic therapeutic benefits for patients with cancer-associated depressive disorders. This finding not only expands the choice of drugs for tumour therapy but also provides a new theoretical basis for comprehensive treatment strategies in the field of psycho-oncology.

Periodontal disease is a risk factor for many systemic diseases such as Alzheimer’s disease and adverse pregnancy outcomes. Cleft palate (CP), the most common congenital craniofacial defect, has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection. A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring. However, the precise relationship remains unclear. In this study, the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P. gingivalis injected intravenously and orally into pregnant mice. We investigated an obvious increasing CP (12.5%) in sonicated P. gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium. Then glycolysis and H4K12 lactylation (H4K12la) were detected to elevate in both mouse embryonic palatal mesenchyme (MEPM) cells and macrophages under P. gingivalis exposure which further promoted the transcription of metallopeptidase domain17 (ADAM17), subsequently mediated the shedding of transforming growth factor-beta receptor 1 (TGFBR1) in MEPM cells and mer tyrosine kinase (MerTK) in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate, eventually caused abnormalities in palate fusion and ossification. The abnormal efferocytosis also led to a predominance of M1 macrophages, which indirectly inhibited palatal osteogenesis via extracellular vesicles. Furthermore, pharmacological ADAM17 inhibition could ameliorate the abnormality of P. gingivalis-induced abnormal palate development. Therefore, our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.

OBJECTIVE:This article reports the second live birth in China after frozen-thawed ovarian tissue transplantation to prevent iatrogenic premature ovarian insufficiency (POI). METHOD:A patient with aplastic anemia received ovarian tissue cryopreservation before hematopoietic stem cell transplantation, and four ovarian cortex strips were thawed and transplanted into her peritoneal pocket 18 months later. RESULTS:Pregnancy occurred spontaneously 5 years after grafting, and a healthy girl was born at 39 weeks of gestation. Until now, the child has developed normally without any major diseases. CONCLUSION:Ovarian tissue cryopreservation and transplantation (OTCT) can be assessed as a successful method especially to prevent iatrogenic POI. In our cryobank for OTCT, which is the first official one in China, intensive research to improve this method has been performed, and we propose after our success for the second pregnancy in China to include this method in the official guidelines for prevention and treatment of (especially iatrogenic) POI.

Adequate blood supply around bone grafts is crucial in periodontal regenerative surgery. Research suggests that cortical perforation during surgery can stimulate angiogenesis and cell migration, increase blood supply to the surgical site, and promote local tissue regeneration. However, the effects of perforation on the local tissue microenvironment and the molecular mechanisms by which corticotomy promotes bone regeneration remain unclear. In this study, a rat model was established to investigate the effect of cortical perforation on osteogenesis around bone grafts. Different groups of alveolar bone were ground to prepare conditioned medium, and the effect on osteogenic differentiation of periodontal ligament stem cells (PDLSCs) was observed in vitro. Finally, we focused on the nerve growth factor (NGF) with the most obvious difference and verified the role of NGF and its potential molecular mechanism in vivo and in vitro. The results showed that osteogenesis around the local bone graft was more pronounced after corticotomy. Additionally, using a tissue-conditioned medium promoted the osteogenic differentiation of PDLSCs, while the expression of NGF increased locally after corticotomy. Further investigation using exogenous NGF or NGF inhibitors confirmed that NGF plays a crucial role in promoting osteogenesis around the bone graft, specifically through activating the JNK/c-Jun pathway. These findings suggest that targeting the mechanism by which cortical perforation promotes bone regeneration could lead to new therapeutic strategies for enhancing bone augmentation in regenerative surgery.

Abnormal embryonic development leads to the formation of cleft palate (CP) which is difficult to be detected by genetic screening and needs sequent treatment from infants to adults. There are no interceptive treatment about CP until now. Germline deletion of phosphatase and tensin homolog (Pten) was related to embryonic malformation and regulated tumor cell proliferation through glycolysis. However, the role of Pten in CP and the relationship between CP, Pten, and glycolysis are unknown. In our research, we constructed Pten knockdown models in vitro and in vivo. Our results provided preliminary evidence that blocking Pten by its inhibitor such as VO-OHpic might be an effective interceptive treatment in early period of palate development when pregnant mother expose in harmful environment during the early period of palate development to reducing CP occurring which was related with the crosstalk between Pten, and glycolysis in the process.