Genome-wide identified VvOFP genes family and VvOFP4 functional characterization provide insight into fruit shape in grape.

Ovate Family Proteins (OFPs) are emerging as novel transcriptional regulators of fruit shape. Despite their established role in various species, their involvement in regulating grape fruit shape remains understudied. This study encompassed a comprehensive evaluation of 16 grape OFP genes in total at the whole genome level. Phylogenetic and synteny analyses established a close relationship between grape VvOFP genes and their tomato counterparts. Expression profiling post-treatment with gibberellic acid (GA3) and thidiazuron (TDZ) revealed that certain OFP genes responded to these regulators, with VvOFP4 showing peak expression three days post-anthesis. Functional assays via overexpression of VvOFP4 in tobacco and tomato altered the morphology of both vegetative and reproductive organs, including leaves, stamens, and fruits/pods. Paraffin sections of transgenic tobacco stems and tomato fruits demonstrated that VvOFP4 overexpression modifies cell dimensions, leading to changes in organ morphology. Additionally, treatments with GA3 and TDZ similarly influenced the shape of grape pulp cells and thereby the overall fruit morphology. These findings suggest that the VvOFP4 gene plays a crucial role in fruit shape determination by modulating cell shape and presents a potential target for future grape breeding programs aimed at diversifying fruit shapes.

A chromosome-level genome assembly for the paramylon-producing microalga Euglena gracilis.

Euglena gracilis (E. gracilis), pivotal in the study of photosynthesis, endosymbiosis, and chloroplast development, is also an industrial microalga for paramylon production. Despite its importance, E. gracilis genome exploration faces challenges due to its intricate nature. In this study, we achieved a chromosome-level de novo assembly (2.37 Gb) using Illumina, PacBio, Bionano, and Hi-C data. The assembly exhibited a contig N50 of 619 Kb and scaffold N50 of 1.12 Mb, indicating superior continuity. Approximately 99.83% of the genome was anchored to 46 chromosomes, revealing structural insights. Repetitive elements constituted 58.84% of the sequences. Functional annotations were assigned to 39,362 proteins, enhancing interpretative power. BUSCO analysis confirmed assembly completeness at 80.39%. This first high-quality E. gracilis genome offers insights for genetics and genomics studies, overcoming previous limitations. The impact extends to academic and industrial research, providing a foundational resource.

Co-delivery of Siape1 and Melatonin by 125I-loaded PSMA-targeted Nanoparticles for the Treatment of Prostate Cancer.

BACKGROUND: Both apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) inhibition and melatonin suppress prostate cancer (PCa) growth. OBJECTIVE: This study evaluated the therapeutic efficiency of self-assembled and prostate-specific membrane antigen (PSMA)-targeted nanocarrier loading 125I radioactive particles and encapsulating siRNA targeting APE1 (siAPE1) and melatonin for PCa. METHODS: The linear polyarginine R12 polypeptide was prepared using Fmoc-Arg-Pbf-OH. The PSMA-targeted polymer was synthesized by conjugating azide-modified R12 peptide to PSMA monoclonal antibody (mAb). Before experiments, the PSMA-R12 nanocarrier was installed with melatonin and siAPE1, which were subsequently labeled by 125I radioactive particles. In vitro biocompatibility and cytotoxicity of nanocomposites were examined in LNCaP cells and in vivo biodistribution and pharmacokinetics were determined using PCa tumor-bearing mice. RESULTS: PSMA-R12 nanocarrier was ~120 nm in size and was increased to ~150 nm by melatonin encapsulation. PSMA-R12 nanoparticles had efficient loading capacities of siAPE1, melatonin, and 125I particles. The co-delivery of melatonin and siAPE1 by PSMA-R12-125I showed synergistic effects on suppressing LNCaP cell proliferation and Bcl-2 expression and promoting cell apoptosis and caspase-3 expression. Pharmacokinetics analysis showed that Mel@PSMA-R12-125I particles had high uptake activity in the liver, spleen, kidney, intestine, and tumor, and were accumulated in the tumor sites within the first 8 h p.i., but was rapidly cleared from all the tested organs at 24 h p.i. Administration of nanoparticles to PCa tumors in vivo showed that Mel@PSMA-R12- 125I/siAPE1 had high efficiency in suppressing PCa tumor growth. CONCLUSION: The PSMA-targeted nanocarrier encapsulating siAPE1 and melatonin is a promising therapeutic strategy for PCa and can provide a theoretical basis for patent applications.

Pulsatile gonadotropin-releasing hormone therapy induces spermatogenesis in pituitary stalk interruption syndrome: A case report and review of the literature.

BACKGROUND: Pituitary stalk interruption syndrome (PSIS) is a rare anatomical defect of the pituitary gland falling under the spectrum of holoprosencephaly phenotypes. It is characterized by a deficiency in anterior pituitary hormones, such as growth hormone, gonadotropins, and thyroid hormones. Due to the syndrome's rarity and nonspecific manifestations, there is a lack of standardized treatment strategies. Consequently, early diagnosis through imaging and on-time intervention are crucial for improving patients' outcomes. CASE SUMMARY: A 30-year-old man presented with absent secondary sexual characteristics and azoospermia. Laboratory evaluation revealed a deficiency in gonadotropins, while thyroid function was mostly within normal ranges. Magnetic resonance imaging of the pituitary gland showed pituitary stalk agenesis, hypoplasia of the anterior pituitary, and ectopic posterior pituitary, leading to the diagnosis of PSIS. Initially, the patient underwent 6 mo of gonadotropin therapy without significant changes in hormone levels and secondary sexual characteristics. Pulsatile gonadotropin-releasing hormone therapy was then administered, resulting in the detection of sperm in the semen analysis within 3 mo. After 6 mo, routine semen tests showed normal semen quality. The couple faced challenges in conceiving due to abstinence and underwent three cycles of artificial insemination, which was unsuccessful. They also attempted in vitro fertilization, but unfortunately, the woman experienced a miscarriage 10 wk after the embryo transfer. CONCLUSION: Early detection, accurate diagnosis, and timely treatment are crucial in improving the quality of life and fertility of PSIS patients.

Eco-evolutionary strategies for relieving carbon limitation under salt stress differ across microbial clades.

With the continuous expansion of saline soils under climate change, understanding the eco-evolutionary tradeoff between the microbial mitigation of carbon limitation and the maintenance of functional traits in saline soils represents a significant knowledge gap in predicting future soil health and ecological function. Through shotgun metagenomic sequencing of coastal soils along a salinity gradient, we show contrasting eco-evolutionary directions of soil bacteria and archaea that manifest in changes to genome size and the functional potential of the soil microbiome. In salt environments with high carbon requirements, bacteria exhibit reduced genome sizes associated with a depletion of metabolic genes, while archaea display larger genomes and enrichment of salt-resistance, metabolic, and carbon-acquisition genes. This suggests that bacteria conserve energy through genome streamlining when facing salt stress, while archaea invest in carbon-acquisition pathways to broaden their resource usage. These findings suggest divergent directions in eco-evolutionary adaptations to soil saline stress amongst microbial clades and serve as a foundation for understanding the response of soil microbiomes to escalating climate change.

CircARCN1 aggravates atherosclerosis by regulating HuR-mediated USP31 mRNA in macrophages.

AIMS: Circular RNAs (circRNAs) are considered important regulators of biological processes, but their impact on atherosclerosis development, a key factor in coronary artery disease (CAD), has not been fully elucidated. We aimed to investigate their potential use in patients with CAD and the pathogenesis of atherosclerosis. METHODS AND RESULTS: Patients with stable angina (SA) or acute coronary syndrome (ACS) and controls were selected for transcriptomic screening and quantification of circRNAs in blood cells. We stained carotid plaque samples for circRNAs and performed gain- and loss-of-function studies in vitro. Western blots, protein interaction analysis, and molecular approaches were used to perform the mechanistic study. ApoE-/- mouse models were employed in functional studies with adeno-associated virus-mediated genetic intervention. We demonstrated elevated circARCN1 expression in peripheral blood mononuclear cells from patients with SA or ACS, especially in those with ACS. Furthermore, higher circARCN1 levels were associated with a higher risk of developing SA and ACS. We also observed elevated expression of circARCN1 in carotid artery plaques. Further analysis indicated that circARCN1 was mainly expressed in monocytes and macrophages, which was also confirmed in atherosclerotic plaques. Our in vitro studies provided evidence that circARCN1 affected the interaction between HuR and ubiquitin-specific peptidase 31 (USP31) mRNA, resulting in attenuated USP31-mediated NF-κB activation. Interestingly, macrophage accumulation and inflammation in atherosclerotic plaques were markedly decreased when circARCN1 was knocked down with adeno-associated virus in macrophages of ApoE-/- mice, while circARCN1 overexpression in the model exacerbated atherosclerotic lesions. CONCLUSIONS: Our findings provide solid evidence macrophagic-expressed circARCN1 plays a role in atherosclerosis development by regulating HuR-mediated USP31 mRNA stability and NF-κB activation, suggesting that circARCN1 may serve as a factor for atherosclerotic lesion formation.

Effectiveness and safety of brucea javanica oil assisted TACE versus TACE in the treatment of liver cancer: a systematic review and meta-analysis of randomized controlled trials.

Background: The effectiveness and safety of using Brucea javanica oil (BJO) in combination with Transarterial Chemoembolization (TACE) for liver cancer treatment are subjects of debate. This study aims to assess the comparative effectiveness and safety of BJO-assisted TACE versus TACE alone and quantifies the differences between these two treatment methods. Methods: A systematic search was conducted in multiple databases including PubMed, Cochrane, CNKI, and Wanfang, until 1 July 2023. Meta-analysis was conducted, and the results were presented as mean difference (MD), risk ratio (RR), and 95% confidence intervals (CI). Results: The search yielded 11 RCTs, with a combined sample size of 1054 patients. Meta-analysis revealed that BJO-assisted TACE exhibited superior outcomes compared to standalone TACE. Specific data revealed that BJO-assisted TACE improves clinical benefit rate by 22% [RR = 1.22, 95% CI (1.15, 1.30)], increases the number of people with improved quality of life by 32%, resulting in an average score improvement of 9.53 points [RR = 1.32, 95% CI (1.22, 1.43); MD = 9.53, 95% CI (6.95, 12.10)]. Furthermore, AFP improvement rate improved significantly by approximately 134% [RR = 2.34, 95% CI (1.58, 3.46)], accompanied by notable improvements in liver function indicators, with an average reduction of 27.19 U/L in AST [MD = -27.19, 95% CI (-40.36, -14.02)], 20.77 U/L in ALT [MD = -20.77, 95% CI (-39.46, -2.08)], 12.17 µmol/L in TBIL [MD = -12.17, 95% CI (-19.38, -4.97)], and a decrease of 43.72 pg/mL in VEGF [MD = -43.72, 95% CI (-63.29, -24.15)]. Most importantly, there was a 29% reduction in the occurrence of adverse reactions [RR = 0.71, 95% CI (0.60, 0.84)]. Conclusion: These findings indicate that BJO-assisted TACE may be considered as a potentially beneficial treatment option for liver cancer patients when compared to standalone TACE. It appears to contribute to improved treatment outcomes, enhanced quality of life, and potentially reduced adverse reactions, suggesting it warrants further investigation as a promising approach for liver cancer treatment. Systematic Review Registration: identifier CRD42023428948.

Efficacy and safety assessment of traditional Chinese patent medicine for dyslipidemia: a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis.

Background: The overall prevalence of dyslipidemia continues to increase, which poses a significant risk for coronary artery disease. Some patients with dyslipidemia do not respond to or benefit from conventional lipid-lowering therapy, which warrants the need for alternative and complementary therapies. Chinese patent medicine (CPM) has shown great potential in the treatment of dyslipidemia, but its clinical value needs to be further explored. This study aims to systematically evaluate the efficacy and safety of CPM in treating dyslipidemia. Methods: This study was registered in INPLASY as INPLASY202330090. The randomized controlled trials included in this study were published in January 2013 to March 2023 and retrieved from the Web of Science, PubMed, Embase, Cochrane Library, SinoMed, China National Knowledge Internet, WanFang, and VIP. The bias risk in the study was independently evaluated by two reviewers using the Cochrane Randomized Trial Bias Risk Tool (RoB 2) Review Manager 5.4 software was used for the overall effect analysis and subgroup analysis of four blood lipids, and the trial sequential analysis (TSA) was conducted to check the results. Results: A total of 69 studies were included, involving 6,993 participants. The methodological quality was in the middle level. Meta-analysis showed that CPM markedly improved the levels of total cholesterol (TC) [mean difference (MD) =-0.54 mmol/L; 95% confidence interval (CI): -0.71 to -0.37; P<0.001], triglyceride (TG) (MD =-0.43 mmol/L; 95% CI: -0.53 to -0.33; P<0.001), low-density lipoprotein cholesterol (LDL-C) (MD =-0.40 mmol/L; 95% CI: -0.50 to -0.30; P<0.001) and increased levels of high-density lipoprotein cholesterol (HDL-C) (MD =0.23 mmol/L; 95% CI: 0.18 to 0.27; P<0.001), in patients with dyslipidemia. Though CPM did not differ significantly from statins when used alone, it could improve lipid profile better in all cases when used in combination with statins and with drugs used for comorbidities or co-morbidities. Subgroup analysis found that the efficacy of pill formulations was superior to other formulations, and CPM showed better lipid-lowering response in the context of comorbidity. The TSA confirmed the robustness of the analysis of the LDL-C level. No significant difference was observed in the incidence of adverse events between the treatment group and the control group [risk ratio (RR) =0.89; 95% CI: 0.69-1.16; P=0.40]. Conclusions: CPM can yield superior therapeutic effects in ameliorating dyslipidemia without exacerbating adverse effects as an alternative and complementary therapy. In addition, the therapeutic effect can be improved by emphasizing pill formulation and strengthening the standardization of syndromes.

Collagen in hepatocellular carcinoma: A novel biomarker and therapeutic target.

HCC is globally recognized as a major health threat. Despite significant progress in the development of treatment strategies for liver cancer, recurrence, metastasis, and drug resistance remain key factors leading to a poor prognosis for the majority of liver cancer patients. Thus, there is an urgent need to develop effective biomarkers and therapeutic targets for HCC. Collagen, the most abundant and diverse protein in the tumor microenvironment, is highly expressed in various solid tumors and plays a crucial role in the initiation and progression of tumors. Recent studies have shown that abnormal expression of collagen in the tumor microenvironment is closely related to the occurrence, development, invasion, metastasis, drug resistance, and treatment of liver cancer, making it a potential therapeutic target and a possible diagnostic and prognostic biomarker for HCC. This article provides a comprehensive review of the structure, classification, and origin of collagen, as well as its role in the progression and treatment of HCC and its potential clinical value, offering new insights into the diagnosis, treatment, and prognosis assessment of liver cancer.

α-Ketoglutarate plays an inflammatory inhibitory role by regulating scavenger receptor class a expression through N6-methyladenine methylation during sepsis.

Sepsis arises from an uncontrolled inflammatory response triggered by infection or stress, accompanied by alteration in cellular energy metabolism, and a strong correlation exists between these factors. Alpha-ketoglutarate (α-KG), an intermediate product of the TCA cycle, has the potential to modulate the inflammatory response and is considered a crucial link between energy metabolism and inflammation. The scavenger receptor (SR-A5), a significant pattern recognition receptor, assumes a vital function in anti-inflammatory reactions. In the current investigation, we have successfully illustrated the ability of α-KG to mitigate inflammatory factors in the serum of septic mice and ameliorate tissue damage. Additionally, α-KG has been shown to modulate metabolic reprogramming and macrophage polarization. Moreover, our findings indicate that the regulatory influence of α-KG on sepsis is mediated through SR-A5. We also elucidated the mechanism by which α-KG regulates SR-A5 expression and found that α-KG reduced the N6-methyladenosine level of macrophages by up-regulating the m6A demethylase ALKBH5. α-KG plays a crucial role in inhibiting inflammation by regulating SR-A5 expression through m6A demethylation during sepsis. The outcomes of this research provide valuable insights into the relationship between energy metabolism and inflammation regulation, as well as the underlying molecular regulatory mechanism.

A VMD-BP Model to Predict Laser Welding Keyhole-Induced Pore Defect in Al Butt-Lap Joint.

The detection of keyhole-induced pore positions is a critical procedure for assessing laser welding quality. Considering the detection error due to pore migration and noise interference, this research proposes a regional prediction model based on the time-frequency-domain features of the laser plume. The original plume signal was separated into several signal segments to construct the morphological sequences. To suppress the mode mixing caused by environmental noise, variational modal decomposition (VMD) was utilized to process the signals. The time-frequency features extracted from the decomposed signals were acquired as the input of a backpropagation (BP) neural network to predict the pore locations. To reduce the prediction error caused by pore migration, the effect of the length of the signal segments on the prediction accuracy was investigated. The results show that the optimal signal segment length was 0.4 mm, with an accuracy of 97.77%. The 0.2 mm signal segments failed to eliminate the negative effects of pore migration. The signal segments over 0.4 mm resulted in prediction errors of small and dense pores. This work provides more guidance for optimizing the feature extraction of welding signals to improve the accuracy of welding defect identification.

Haplotype-resolved genome assembly for tetraploid Chinese cherry (Prunus pseudocerasus) offers insights into fruit firmness.

Chinese cherry (Prunus pseudocerasus) holds considerable importance as one of the primary stone fruit crops in China. However, artificially improving its traits and genetic analysis are challenging due to lack of high-quality genomic resources, which mainly result from difficulties associated with resolving its tetraploid and highly heterozygous genome. Herein, we assembled a chromosome-level, haplotype-resolved genome of the cultivar 'Zhuji Duanbing', comprising 993.69 Mb assembled into 32 pseudochromosomes using PacBio HiFi, Oxford Nanopore, and Hi-C. Intra-haplotype comparative analyses revealed extensive intra-genomic sequence and expression consistency. Phylogenetic and comparative genomic analyses demonstrated that P. pseudocerasus was a stable autotetraploid species, closely related to wild P. pusilliflora, with the two diverging ~18.34 million years ago. Similar to other Prunus species, P. pseudocerasus underwent a common whole-genome duplication event that occurred ~139.96 million years ago. Because of its low fruit firmness, P. pseudocerasus is unsuitable for long-distance transportation, thereby restricting its rapid development throughout China. At the ripe fruit stage, P. pseudocerasus cv. 'Zhuji Duanbing' was significantly less firm than P. avium cv. 'Heizhenzhu'. The difference in firmness is attributed to the degree of alteration in pectin, cellulose, and hemicellulose contents. In addition, comparative transcriptomic analyses identified GalAK-like and Stv1, two genes involved in pectin biosynthesis, which potentially caused the difference in firmness between 'Zhuji Duanbing' and 'Heizhenzhu'. Transient transformations of PpsGalAK-like and PpsStv1 increase protopectin content and thereby enhance fruit firmness. Our study lays a solid foundation for functional genomic studies and the enhancement of important horticultural traits in Chinese cherries.

Factors influencing further vertebral height loss following percutaneous vertebroplasty in osteoporotic vertebral compression fractures: A 1-year follow-up study.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCFs) contribute to back pain and functional limitations in older individuals, with percutaneous vertebroplasty (PVP) emerging as a minimally invasive treatment. However, further height loss post-PVP prompts investigation into contributing factors. AIM: To investigate the factors associated with further height loss following PVP with cement augmentation in OVCF patients. METHODS: A total of 200 OVCF patients who underwent successful PVP between January 2021 and December 2022 were included in this study. "Further height loss" during 1 year of follow-up in OVCF patients with bone edema was defined as a vertical height loss of ≥ 4 mm. The study population was divided into two groups for analysis: The "No Further Height Loss group (n = 179)" and the "Further Height Loss group (n = 21)." RESULTS: In comparing two distinct groups of patients, significant differences existed in bone mineral density (BMD), vertebral compression degree, prevalence of intravertebral cleft (IVF), type of bone cement used, and cement distribution patterns. Results from binary univariate regression analysis revealed that lower BMD, the presence of IVF, cleft distribution of bone cement, and higher vertebral compression degree were all significantly associated with further height loss. Notably, the use of mineralized collagen modified-poly(methyl methacrylate) bone cement was associated with a significant reduction in the risk of further height loss. In multivariate regression analysis, lower BMD and the presence of IVF remained significantly associated with further height loss. CONCLUSION: Further height loss following PVP in OVCF patients is influenced by a complex interplay of factors, especially lower BMD and the presence of IVF. These findings underscore the importance of assessing and managing these factors when addressing height loss following PVP in OVCF patients.

Retinal light damage: From mechanisms to protective strategies.

Visible light serves as a crucial medium for vision formation.;however, prolonged or excessive exposure to light is recognized as a significant etiological factor contributing to retinal degenerative diseases. The retina, with its unique structure and adaptability, relies on the homeostasis of cellular functions to maintain visual health. Under normal conditions, the retina can mount adaptive responses to various insults, including light-induced damage. Unfortunately, exposure to intense and excessive light triggers a cascade of pathological alterations in retinal photoreceptor cells, pigment epithelial cells, ganglion cells, and glial cells. These alterations encompass disruption of intracellular REDOX and Ca²âº homeostasis, pyroptosis, endoplasmic reticulum stress, autophagy, and the release of inflammatory cytokines, culminating in irreversible retinal damage. We first delineate the mechanisms of retinal light damage through 4 main avenues: mitochondria function, endoplasmic reticulum stress, cell autophagy, and inflammation. Subsequently, we discuss protective strategies against retinal light damage, aiming to guide research toward the prevention and treatment of light-induced retinal conditions.

Preoperative CT findings predict the development of metachronous contralateral inguinal hernia after unilateral inguinal hernia repair: a single-center retrospective cohort study.

PURPOSE: To identify potential clinical and preoperative CT risk factors that can predict the development of metachronous contralateral inguinal hernia (MCIH) after unilateral inguinal hernia repair (IHR). METHODS: This study included unilateral inguinal hernia patients seen from 2016 to 2019 who underwent CT and subsequent IHR and had at least five years of follow-up. Preoperative CT scans were retrospectively reviewed for the presence of asymmetric spermatic cord fat and weakness of the transversalis fascia. The correlations of each CT feature and other clinical characteristics with the development of MCIH were calculated. The Kaplan-Meier model and multiple logistic regression were used to evaluate the associations among CT features, clinical variables and MCIH. RESULTS: A total of 677 male patients aged > 40 years were included in the study cohort. After more than 5 years of follow-up, 162 patients developed MCIH, representing an incidence of 23.9%. Patients with radical prostatectomy or peritoneal dialysis [P < 0.0001, HR 4.189 (95% CI 2.369 to 7.406)], primary left-sided IHR [P = 0.0032, HR 1.626 (95% CI 1.177 to 2.244)], and direct, femoral or pantaloon hernias were predisposed to MCIH. Asymmetric spermatic cord fat [P = 0.0002, HR 1.203 (95% CI 0.8785 to 1.648)] and weakness of the transversalis fascia [P < 0.0001, HR 7.914 (95% CI 5.666 to 11.05)] on preoperative CT were also identified as risk facts and demonstrated to be independent predictive factors for MCIH development. CONCLUSION: Asymmetric spermatic cord fat and weakness of the transversalis fascia were predictive factors for MCIH development. For decision making regarding prophylactic contralateral IHR at the time of index surgery, preoperative CT findings as well as clinical characteristics should be considered.

The mechanism and therapeutic potential of lncRNA MIR497HG/miR-16-5p axis in breast cancer.

BACKGROUND: Breast cancer has become a major public health problem in the current society, and its incidence rate ranks the first among Chinese female malignant tumors. This paper once again confirmed the efficacy of lncRNA in tumor regulation by introducing the mechanism of the diagnosis of breast cancer by the MIR497HG/miR-16-5p axis. METHODS: The abnormal expression of MIR497HG in breast cancer was determined by RT-qPCR method, and the correlation between MIR497HG expression and clinicopathological characteristics of breast cancer patients was analyzed via Chi-square test. To understand the diagnostic potential of MIR497HG in breast cancer by drawing the receiver operating characteristic curve (ROC). The overexpressed MIR497HG (pcDNA3.1-MIR497HG) was designed and constructed to explore the regulation of elevated MIR497HG on biological function of BT549 and Hs 578T cells through Transwell assays. Additionally, the luciferase gene reporter assay and Pearson analysis evaluated the targeting relationship of MIR497HG to miR-16-5p. RESULTS: MIR497HG was decreased in breast cancer and had high diagnostic function, while elevated MIR497HG inhibited the migration and invasion of BT549 and Hs 578T cells. In terms of functional mechanism, miR-16-5p was the target of MIR497HG, and MIR497HG reversely regulated the miR-16-5p. miR-16-5p mimic reversed the effects of upregulated MIR497HG on cell biological function. CONCLUSIONS: In general, MIR497HG was decreased in breast cancer, and the MIR497HG/miR-16-5p axis regulated breast cancer tumorigenesis, providing effective insights for the diagnosis of patients.

A serial case study of the combined use of intraoperative CT and surgical navigation system for the removal of small foreign bodies in the maxillofacial region.

PURPOSE: The removal of small foreign bodies embedded within the deep soft tissues of the maxillofacial region is a complex and challenging task for maxillofacial surgeons. The purpose of this study was to explore the efficacy of the combination of intraoperative CT and surgical navigation for the removal of small foreign objects in the maxillofacial region. METHODS: A serial case study was conducted involving all consecutive patients who underwent surgical removal of small foreign bodies in the maxillofacial region. The combination of intraoperative CT and a surgical navigation system was used at a single medical institution from January 2018 to December 2022. Comprehensive data, including patient demographics, characteristics of the foreign bodies, previous surgical interventions, duration of the surgical procedure, and removal success rate were collected for this study. Relevant data were recorded into Microsoft Excel sheet and analyzed using SPSS version 22.0. RESULTS: Nine patients (6 males and 3 females) were included in this study, with an average age of 37 years. Each patient had previously undergone an unsuccessful removal attempt utilizing conventional surgical methods based on preoperative CT imaging or C-arm guidance at a local healthcare facility. Four patients also experienced unsuccessful attempts with preoperative CT image-based navigation systems. However, by employing the combined approach of intraoperative CT and surgical navigation, the foreign bodies were successfully removed in all 9 patients. The mean duration of the surgical procedure was 59 min, and the average size of the foreign bodies was approximately 26 mm³. Postoperative follow-up exceeding 6 months revealed no complications. CONCLUSION: The combined use of a surgical navigation system and intraoperative CT represents a potent and effective strategy for the precise localization and subsequent removal of small foreign bodies from the soft tissue structures of the maxillofacial region. This integrative approach appears to increase the success rate of surgical interventions in such cases.

Naringenin enhances the efficacy of ferroptosis inducers by attenuating aerobic glycolysis by activating the AMPK-PGC1α signalling axis in liver cancer.

Liver cancer is a heterogeneous disease characterized by poor responses to standard therapies and therefore unfavourable clinical outcomes. Understanding the characteristics of liver cancer and developing novel therapeutic strategies are imperative. Ferroptosis, a type of programmed cell death induced by lipid peroxidation, has emerged as a potential target for treatment. Naringenin, a natural compound that modulates lipid metabolism by targeting AMPK, shows promise in enhancing the efficacy of ferroptosis inducers. In this study, we utilized liver cancer cell lines and xenograft mice to explore the synergistic effects of naringenin in combination with ferroptosis inducers, examining both phenotypic outcomes and molecular mechanisms. Our study results indicate that the use of naringenin at non-toxic doses to hepatocytes can significantly enhance the anticancer effects of ferroptosis inducers (erastin, RSL3, and sorafenib). The combination index method confirmed a synergistic effect between naringenin and ferroptosis inducers. In comparison to naringenin or ferroptosis inducers alone, the combined therapy caused more robust lipid peroxidation and hence more severe ferroptotic damage to cancer cells. The inhibition of aerobic glycolysis mediated by the AMPK-PGC1α signalling axis is the key to naringenin's effect on reducing ferroptosis resistance in liver cancer, and the synergistic cytotoxic effect of naringenin and ferroptosis inducers on cancer cells was reversed after pretreatment with an AMPK inhibitor or a PGC1α inhibitor. Taken together, these findings suggest that naringenin could boost cancer cell sensitivity to ferroptosis inducers, which has potential clinical translational value.

Developing a dormancy-associated ECM signature in TNBC that is linked to immunosuppressive tumor microenvironment and selective sensitivity to MAPK inhibitors.

Aims: Cellular dormancy is a state of quiescence subpopulation of tumor cells, characterized by low differentiation and lack of mitotic activity. They could evade chemotherapy and targeted therapy, leading to drug resistance and disease recurrence. Recent studies have shown a correlation between dormant cancer cells and unique extracellular matrix (ECM) composition, which is critical in regulating cell behavior. However, their interacting roles in TNBC patients remains to be characterized. Main methods: Dormant cancer cells in MDA-MB-231 cell line with highest PKH26 dye-retaining were FACS-sorted and gene expression was then analyzed. Dormant associated ECM (DA-ECM) signature was characterized by pathway analysis. Unsupervised hierarchical clustering was used to define distinct ECM features for TNBC patients. ECM-specific tumor biology was defined by integration of bulk RNA-seq with single-cell RNA-seq data, analysis of ligand-receptor interactions and enriched biological pathways, and in silico drug screening. We validated the sensitivity of dormant cancer cells to MAPK inhibitors by flow cytometry in vitro. Key findings: We observed that dormant TNBC cells preferentially expressed ∼10 % DA-ECM genes. The DA-ECM High subtype defined by unsupervised hierarchical clustering analysis was associated with immunosuppressive tumor microenvironment. Moreover, ligand-receptor interaction and pathway analysis revealed that the DA-ECM High subtype may likely help maintain tumor cell dormancy through MAPK, Hedgehog and Notch signaling pathways. Finally, in silico drug screening against the DA-ECM signature and in vitro assay showed dormant cancer cells were relatively sensitive to the MAPK pathway inhibitors, which may represent a potential therapeutic strategy for treating TNBC. Significance: Collectively, our research revealed that dormancy-associated ECM characterized tumor cells possess significant ECM remodeling capacity, and treatment strategies towards these cells could improve TNBC patient outcome.