Metaplastic thymoma in the middle mediastinum: a rare case report and surgical treatment analysis of a 32-year-old female patient.

Background: Metaplastic thymoma (MT), an exceedingly rare variant of primary thymic epithelial neoplasms, is distinguished by its indolent progression and unique histopathological profile. It presents a biphasic pattern characterized by solid epithelial and spindle cell components, potentially leading to diagnostic confusion with type A thymomas or the type A component of type AB thymomas. Accurate diagnosis is pivotal for optimal therapeutic strategies and prognostication. Case Description: We document an exceptional case of a 32-year-old woman, incidentally discovered to have a mediastinal nodule in the middle compartment on chest computed tomography (CT). The lesion was excised via video-assisted thoracoscopic surgery. Histological evaluation revealed a biphasic cellular architecture comprising epithelioid and spindle cells. Immunohistochemical analysis demonstrated significant positivity for CK5/6 and P40 in epithelial cells, and vimentin and epithelial membrane antigen in spindle cells, with a low proliferation index marked by Ki-67. Noteworthy, fluorescence in situ hybridization (FISH) analysis identified a YAP1::MAML2 gene fusion, with a predominant pattern suggestive of fusion gene presence, thus corroborating the diagnosis of MT. Conclusions: This report underscores the critical role of a multifaceted diagnostic approach, including histopathological, immunohistochemical, and genetic analyses, in the identification of MT. The detection of the YAP1::MAML2 gene fusion through FISH analysis provides a robust diagnostic marker, highlighting the necessity for clinical and pathological vigilance for this rare tumor.

Sustained amphiregulin expression in intermediate alveolar stem cells drives progressive fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrotic disease. Recent studies have highlighted the persistence of an intermediate state of alveolar stem cells in IPF lungs. In this study, we discovered a close correlation between the distribution pattern of intermediate alveolar stem cells and the progression of fibrotic changes. We showed that amphiregulin (AREG) expression is significantly elevated in intermediate alveolar stem cells of mouse fibrotic lungs and IPF patients. High levels of serum AREG correlate significantly with profound deteriorations in lung function in IPF patients. We demonstrated that AREG in alveolar stem cells is both required and sufficient for activating EGFR in fibroblasts, thereby driving lung fibrosis. Moreover, pharmacological inhibition of AREG using a neutralizing antibody effectively blocked the initiation and progression of lung fibrosis in mice. Our study underscores the therapeutic potential of anti-AREG antibodies in attenuating IPF progression, offering a promising strategy for treating fibrotic diseases.

Successful percutaneous coronary intervention in a congenital single right coronary artery with acute myocardial infarction: A case report and literature review.

RATIONALE: Single coronary artery (SCA) is a rare coronary artery malformation. SCA combined with atherosclerotic plaques can cause severe and widespread myocardial ischemia and infarction, leading to hemodynamic instability and even sudden death. PATIENT CONCERNS: A 48-year-old Chinese man was admitted for treatment of persistent chest tightness and panic for 5 hours. The patient was a lorry driver with high work intensity and mental stress, with body mass index of 33.78, history of smoking and alcohol consumption, but no history of hypertension and diabetes. DIAGNOSES: Admission examination showed Troponin was 183.083 µg/L and CK-MB value was >300 µg/L. The patient was diagnosed with a congenital single right coronary artery (RCA) with acute myocardial infarction (AMI) by coronary angiography (CAG). Due to atherosclerotic plaques rupture, a complete occlusion of the proximal RCA with thrombolysis in myocardial infarction grade 0 of distal blood flow were found. INTERVENTIONS AND OUTCOMES: The patient was treated with thrombus aspiration and thrombolytic therapy by percutaneous coronary intervention under the support of intra-aortic balloon pump. Postoperative the chest tightness and panic were relieved, and CAG revealed that the proximal thrombus of the RCA was reduced, and distal blood flow was restored to thrombolysis in myocardial infarction grade 3. After 2 weeks of intensive antithrombotic and lipid-regulating drug therapy, the patient was successfully discharged. Follow-up for 6 months, the patient was able to live and work normally without experiencing chest tightness and chest pain. Computed tomography angiography (CTA) confirmed a congenital single RCA with patent lumen and no severe stenosis. LESSONS: The congenital single RCA is very rare, and it is fatal in conjunction with acute coronary syndrome. Early detection and appropriate treatment is critical for AMI patient with single RCA. CAG is the gold standard for diagnosis of single RCA, and CTA is a necessary to describe the anatomical course of abnormal coronary arteries.

Inhibitory effects of Eplerenone on angiogenesis via modulating SGK1/TGF-ß pathway in contralateral kidney of CKD pregnancy rats.

BACKGROUND: Eplerenone is a selective aldosterone receptor blocker that is effective in preventing the progression of chroinic kidney disease (CKD). However, its mechanism and role in CKD pregnancy still remain uncertain. The aim of this study was to evaluate whether eplerenone could attenuated the fibrosis of unilateral ureteral obstruction (UUO) pregnant rats' contralateral kidney, improved pregnancy outcome and explore its therapeutic mechanisms. METHODS: A pregnancy rat model of UUO established, female Wistar rats were randomly assigned into sham-operated group (Sham group),sham-operated combined pregnancy group (SP group), unilateral ureteral obstruction combined pregnancy group (UUO + Pregnancy group), unilateral ureteral obstruction combined pregnancy, administered eplerenone (UUO + Pregnancy+Eplerenone group). On the 18th day of pregnancy, the rats were placed in a metabolic cage, 24 h urine was collected and stored at -80 °C. Next day, all animals were euthanized, and serum was collected by centrifugation and stored at -20 °C. Then the right kidney was extracted, a part of the kidney was placed in 4% paraformaldehyde for morphology, immunohistochemical staining, and immunofluorescence staining, and the other part was placed in a - 80 °C refrigerator for RNA and protein extraction. In vitro, HUVECs was treated with aldosterone, progesterone and estradiol, VEGFA and its receptor blocker bevacizumab. The ability of proliferation, migration and tubularization of HUVECs was detected by CCK-8, scratch wound assay and endothelial tube formation assay. And the co-expression of CD34 and α-SMA of HUVECs was detected by Flow cytometry. RESULTS: Immunofluorescence results showed that the co-expression of CD34 and α-SMA increased in the UUO + Pregnancy group was significantly increased. The expression of SGK-1, TGFß-1, Smad2, Smad3, VEGF-A, VEGFR2, CD34, α-SMA and Collagen I was significantly higher in the kidneys of the UUO + Pregnancy group compared to the Sham group and SP group. Eplerenone inhibited the expression of those results. In vitro, the ability of proliferation, migration and tubularization was increased after treated with aldosterone, aldosterone with progesterone and estradiol or VEGFA. Similarly, the expression of α-SMA on the surface of HUVECs treated with aldosterone, aldosterone with progesterone and estradiol were increased, while eplerenone supressed its expression. CONCLUSION: Eplerenone inhibits renal angiogenesis by blocking the SGK-1/TGFß signal transduction pathway, thereby inhibiting the phenotypic transformation of endothelial cells, slowing down renal fibrosis, and reducing kidney damage caused by pregnancy.

Two-Year Outcomes and Biomarker Analysis of Locally Advanced Gastric and Gastroesophageal Junction Adenocarcinoma After Neoadjuvant Chemotherapy and Immunotherapy from the Phase II WuhanUHGI001 Trial.

BACKGROUND: This study reports the 2-year outcomes and biomarker analysis results of patients with locally advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinoma who received neoadjuvant chemotherapy and immunotherapy in a phase II WuhanUHGI001 trial. METHODS: Eligible patients with cT3/4aN+M0 locally advanced G/GEJ adenocarcinoma were screened, enrolled, and treated with 3 cycles of neoadjuvant tislelizumab and SOX followed by D2 gastrectomy and another 5 cycles of postoperative adjuvant SOX. The primary endpoint was major pathological response. RESULTS: Of the 49 included patients, 24 (49.0%) achieved major pathological response and 13 (26.5%) achieved pathological complete response. During a median follow-up of 26.8 months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 69.4% and 81.2%, respectively. Grade 3-4 adverse events occurred in six patients (12.2%) during the neoadjuvant period, eight patients (17.0%) during the postoperative period, and seven patients (15.2%) during the adjuvant period. Biomarker analysis revealed that the pathological complete response showed no association with 2-year PFS and OS. Major pathological response showed a potentially strong association with improved 2-year PFS and OS rates. In addition, preoperative circulating tumor cells combined with pathological responses are helpful in prognosis assessment. In addition, our results showed that T downstaging, lymphocyte-to-monocyte ratio, and CD3+ T cells were independent factors that affect PFS. The signet ring cell component (SRCC), T downstaging, and neutrophil-to-lymphocyte ratio were independent factors affecting OS. Prognostic nomograms of PFS and OS constructed based on the multivariate Cox regression results demonstrated suitable calibration and discrimination ability. CONCLUSIONS: Neoadjuvant tislelizumab plus SOX exhibits promising efficacy and acceptable toxicity in patients with locally advanced G/GEJ adenocarcinoma. In addition, our study established a prognostic risk signature and nomograms based on clinicopathological characteristics, which can accurately predict patient outcomes and aid in personalized treatment planning.

Fluctuation theorem in the quantum Otto engine with long-range interaction.

The fluctuation of the quantum Otto engine has recently received a lot of attention, while applying the many body with a long-range interaction to a quantum heat engine may enhance our ability of controlling it. Using the two-point measurement and its generalization, we explore the fluctuation theorem of work and heat in a single stroke as well as in a cycle. We discover that the fluctuations of work in a cycle as well as fluctuations of heat in a single stroke or cycle can be connected to the fluctuation of work in a single stroke. Then we numerically investigate the effect of a long-range interaction on these fluctuation theorems, and our result shows that the fluctuation can be improved by manipulating the long-range interaction.

Research progress on interferon and cellular senescence.

Since the 12 major signs of aging were revealed in 2023, people's interpretation of aging will go further, which is of great significance for understanding the occurrence, development, and intervention in the aging process. As one of the 12 major signs of aging, cellular senescence refers to the process in which the proliferation and differentiation ability of cells decrease under stress stimulation or over time, often manifested as changes in cell morphology, cell cycle arrest, and decreased metabolic function. Interferon (IFN), as a secreted ligand for specific cell surface receptors, can trigger the transcription of interferon-stimulated genes (ISGs) and play an important role in cellular senescence. In addition, IFN serves as an important component of SASP, and the activation of the IFN signaling pathway has been shown to contribute to cell apoptosis and senescence. It is expected to delay cellular senescence by linking IFN with cellular senescence and studying the effects of IFN on cellular senescence and its mechanism. This article provides a review of the research on the relationship between IFN and cellular senescence by consulting relevant literature.

Ganoderic Acid A prevents bone loss in lipopolysaccharide-treated male rats by reducing oxidative stress and inflammatory.

Ganoderic Acid A (GAA) has demonstrated beneficial effects in anti-inflammatory and anti-oxidative stress studies. However, it remains unknown whether GAA exerts positive impacts on bone loss induced by lipopolysaccharide (LPS). This study aims to investigate the influence of GAA on bone loss in LPS-treated rats. The study assesses changes in the viability and osteogenic potential of MC3T3-E1 cells, as well as osteoclast differentiation in RAW264.7 cells in the presence of LPS using CCK-8, ALP staining, AR staining, and Tartrate-resistant acid phosphatase (TRAP) staining. In vitro experiments indicate that LPS-induced inhibition of osteoclasts (OC) and Superoxide Dismutase 2 (SOD2) correlates with heightened levels of inflammation and oxidative stress. Furthermore, GAA has displayed the ability to alleviate oxidative stress and inflammation, enhance osteogenic differentiation, and suppress osteoclast differentiation. Animal experiment also proves that GAA notably upregulates SOD2 expression and downregulates TNF-α expression, leading to the restoration of impaired bone metabolism, improved bone strength, and increased bone mineral density. The collective experimental findings strongly suggest that GAA can enhance osteogenic activity in the presence of LPS by reducing inflammation and oxidative stress, hindering osteoclast differentiation, and mitigating bone loss in LPS-treated rat models.

GREMI: an Explainable Multi-omics Integration Framework for Enhanced Disease Prediction and Module Identification.

Multi-omics integration has demonstrated promising performance in complex disease prediction. However, existing research typically focuses on maximizing prediction accuracy, while often neglecting the essential task of discovering meaningful biomarkers. This issue is particularly important in biomedicine, as molecules often interact rather than function individually to influence disease outcomes. To this end, we propose a two-phase framework named GREMI to assist multi-omics classification and explanation. In the prediction phase, we propose to improve prediction performance by employing a graph attention architecture on sample-wise co-functional networks to incorporate biomolecular interaction information for enhanced feature representation, followed by the integration of a joint-late mixed strategy and the true-class-probability block to adaptively evaluate classification confidence at both feature and omics levels. In the interpretation phase, we propose a multi-view approach to explain disease outcomes from the interaction module perspective, providing a more intuitive understanding and biomedical rationale. We incorporate Monte Carlo tree search (MCTS) to explore local-view subgraphs and pinpoint modules that highly contribute to disease characterization from the global-view. Extensive experiments demonstrate that the proposed framework outperforms state-of-the-art methods in seven different classification tasks, and our model effectively addresses data mutual interference when the number of omics types increases. We further illustrate the functional- and disease-relevance of the identified modules, as well as validate the classification performance of discovered modules using an independent cohort. Code and data are available at https://github.com/Yaolab-fantastic/GREMI.

Papillary adenoma of the lung: A case report and literature review.

Papillary adenoma of the lung, a rare and benign tumor, is easily confused with other primary benign or malignant lung tumors and especially with lung adenocarcinoma that has a papillary growth pattern. Enhanced understanding and an accurate diagnosis of papillary adenomas of the lung are crucial for clinical treatment and prognostic assessment. A 61-year-old man who presented with an opportunistic finding in relation to a left lower lobe lung nodule during an examination was admitted to The First Hospital of China Medical University (Shenyang, China) for further treatment. Computed tomography (CT) revealed a well-circumscribed left lower lobe nodule (diameter, ~1 cm), comprising branched papillae with a fibrovascular core and no other structural components. The tumor cells appeared relatively uniform in shape and well arranged with round or oval nuclei. No nucleoli or mitotic figures were observed. Immunohistochemically, the papillary structures of the tumor cells were strongly and diffusely positive for cytokeratin (CK), CK7, Napsin-A and thyroid transcription factor 1. The Ki-67 index was ~1%. A pathological diagnosis of primary papillary adenoma of the lung was made based on these findings. A left lower-lobe wedge resection was performed and the patient's postoperative course was uneventful. Surgical resection is the preferred treatment. Papillary adenoma of the lung is very rare, and its clinical manifestations and CT images are non-specific. It is important to avoid misdiagnosing of papillary adenoma of the lung as another type of lung tumor, especially adenocarcinoma. A clear understanding of the morphological and immunohistochemical features of papillary adenomas is important for the diagnosis of this rare lung tumor.

Robot-assisted Single-port Radical Prostatectomy with the SHURUI SP and da Vinci SP Platforms: Comparison of the Technology, Intraoperative Performance, and Outcomes.

Background and objective: The purpose-built SHURUI single-port (SP) robotic platform has recently been introduced for several procedures in urology, general surgery, and gynecology. However, comparative evidence on its performance in relation to earlier models such as the da Vinci SP is lacking. Our aim was to compare the step-by-step techniques and 1-yr outcomes for radical prostatectomy (RP) between the SHURUI SP and da Vinci SP robots. Methods: Data were retrieved from two prospectively maintained databases. The SHURUI SP robot was used to perform RP in 34 patients in China (September 2021 to August 2022); the da Vinci SP robot was used to perform 100 consecutive RP cases in the USA (June 2019 to October 2020). A comparative analysis was conducted before and after 1:1 propensity score matching for age, body mass index, American Urological Association symptom score, prostate size, prostate-specific antigen (PSA) levels, biopsy grade group, and D'Amico risk group. Intraoperative performance and short-term oncological and continence outcomes were compared between the groups. Biochemical recurrence was defined as two consecutive postoperative PSA levels >0.2 ng/ml. Continence was defined as full recovery of urinary control without the use of pads. The Kaplan-Meier method was used to estimate continence recovery curves, and a log-rank test for trend was used to detect ordered differences in continence recovery between the SHURUI SP and da Vinci SP groups after surgery. Key findings and limitations: For the matched SHURUI and da Vinci groups, median age (69 vs 69 yr), median PSA (8.4 vs 7.1 ng/ml), and the proportion of patients with low-risk (33.3% vs 29.6%), intermediate-risk (66.7% vs 63%), and high-risk disease (0% vs 7.4%) were comparable (all p > 0.05). All surgeries were successfully accomplished without conversion. A higher percentage of cases in the SHURUI group involved extraperitoneal access (81.5% vs 0%; p < 0.001) and a pure SP approach (25.9% vs 0%; p = 0.01), while a higher percentage of cases in the da Vinci group had nerve-sparing surgery. The median total operative (215 vs 110 min; p < 0.001) and median console time (162 vs 75 min; p < 0.001) were significantly longer in the SHURUI group. No intraoperative or major postoperative complications were observed in either group. Rates of positive surgical margins (18.5% vs 14.8%; p = 1.0) and extraprostatic extension (14.8% vs 29.6%; p = 0.19) were similar. At median follow-up of 13.5 versus 15.9 mo, none of the patients had experienced biochemical recurrence. At 1 yr after surgery, the continence rate was 96.3% in both groups. Conclusions: Despite differences in driving mechanisms between the two SP robotic systems, RP can be performed safely and effectively with the SHURUI RP robot during the initial learning phase, with similar short-term oncological and continence outcomes to those with the da Vinci SP robot. Patient summary: We compared two surgical robots (SHURUI SP and da Vinci SP) used to perform robotic surgery to remove the prostate through a single keyhole incision instead of multiple incisions. Our results show comparable technology and similar surgical and short-term cancer control outcomes for the two robots.

Induction of antiherbivore defense responses in poplars using a methyl jasmonate and mesoporous silica nanoparticle complex.

BACKGROUND: Poplar in China has long been plagued by the fall webworm Hyphantria cunea. Enhancing plant immunity using chemical elicitors is an environmentally friendly approach to pest control. The phytohormone methyl jasmonate (MeJA) can stimulate the chemical defenses of poplars against herbivores but has been shown to have limited efficacy in practice. Here, we studied the effects of a MeJA and mesoporous silica nanoparticle (MSN) complex (MeJA@MSN) regarding the induction of poplar resistance to H. cunea, which may provide strategies for the effective use of MeJA. RESULTS: The silicon-based phytohormone complex (MeJA@MSNs) exhibited excellent biological and physiochemical properties, such as excellent biocompatibility and plant tissue transportability. The changes in metabolites in poplar leaves induced by MeJA, MSNs, and MeJA@MSNs were investigated by metabolic analysis. MeJA@MSNs led to highly potent induced resistance along with elevated salicylaldehyde content, which increased with the dose administered. The salicylaldehyde metabolite showed a strong antifeedant effect on H. cunea larvae at a dosage of 1 µg, with the 50% lethal dose being 20.4 µg/mg. Furthermore, transcriptional analysis showed that MeJA@MSNs upregulated key genes in biosynthetic pathways more than MeJA and MSNs. CONCLUSION: Our results show that MeJA and MSNs interact positively in poplar, leading to salicylaldehyde accumulation and increased induced resistance to H. cunea, providing new insights into the underlying resistance mechanisms induced by MeJA@MSNs. © 2024 Society of Chemical Industry.

Nuclear receptor 4A1 ameliorates renal fibrosis by inhibiting vascular endothelial growth factor A induced angiogenesis in UUO rats.

INTRODUCTION: Angiogenesis is closely related to renal fibrosis; however, its basic mechanism remains unclear. In our study, we found that nuclear receptor 4A1 (NR4A1) inhibits vascular endothelial growth factor A (VEGFA)-induced angiogenesis, ameliorating renal fibrosis. METHODS: We prepared a renal fibrosis animal model with unilateral ureteral obstruction (UUO) and NR4A1 knockdown UUO mice model, Using Human umbilical vein endothelial cells (HUVECs) to conduct all in vitro experiments. We then detected and analyzed the expression levels of NR4A1 and other genes related to angiogenesis and fibrosis. RESULTS: The angiogenesis related genes, such as VEGFA, vascular endothelial growth factor receptor-2 (VEGFR-2), endoglin (CD105), as well as the expression of fibrosis related genes that included, α-smooth muscle actin (α-SMA), Vimentin, and Collagen I are all significantly increased in the UUO rat model. In addition, the expression of NR4A1 of the kidney tissue of UUO rats was significantly reduced. Therefore, according to the above results, we speculated that angiogenesis may exacerbate renal fibrosis and NR4A1 may repress renal fibrosis by inhibiting angiogenesis. To further verify the above results, we used VEGFA to stimulate HUVECs with (or without) overexpression or knockdown of NR4A1. The results showed that with prolonged stimulation using VEGFA, the expression of NR4A1 decreases. Overexpression of NR4A1 significantly inhibits the expression of related indicators of angiogenesis and renal fibrosis. Furthermore, knockdown of NR4A1 induces endothelial cell proliferation and migration; therefore, exacerbating angiogenesis and fibrosis. Finally, the results of NR4A1 knockdown UUO mice showed that knockdown of NR4A1 can aggravating kidney damage and induce the expression of angiogenesis and renal fibrosis related indicators, while UUO can significantly induce kidney damage, angiogenesis and renal fibrosis. When knockdown of NR4A1, renal kidney damage, angiogenesis and fibrosis becomes more severe than UUO. Thus, all of these results indicate that NR4A1 can ameliorate renal fibrosis by inhibiting angiogenesis. CONCLUSIONS: NR4A1 can inhibit angiogenesis to ameliorate renal fibrosis.

The association between body mass index and bone mineral density in older adults: a cross-sectional study of community population in Beijing.

BACKGROUND: Older subjects have a higher risk for vertebral compression fracture. Maintaining a higher bone mineral density (BMD) at this age can protect individuals from osteoporosis-related events. Body mass index (BMI) has been found to have a robust association with BMD. However, excessive BMI is detrimental to bone health and may cause systemic disorders. Therefore, the present study aimed to determine the association between BMI and BMD, and identify a reasonable BMI range. METHODS: A total of 961 participants were recruited from community-dwelling residents between August 2021 and May 2022. A weighted multivariate linear regression model was applied to identify the relationship between BMI and BMD. Meanwhile, subgroup stratified analysis by BMI quartile and gender was also performed. A non-linear relationship and threshold value were determined based on the smooth curve fittings and threshold effects analysis model. RESULTS: A robust relationship was found between BMI and BMD, which remained significant in subgroups stratified by gender and BMI quartile. The BMI inflection point values in lumbar BMD and femoral neck BMD were 25.2 kg/m2 and 27.3 kg/m2, respectively. For individuals with BMI < 25.2 kg/m2, an increase in BMI was related to an increase in lumbar BMD. For BMI > 25.2 kg/m2, an increase in BMI was associated with a decrease in lumbar BMD. For subjects with BMI < 27.3 kg/m2, the femoral neck BMD rose by 0.008 kg/m2 for each unit rise in BMI. However, when BMI exceeded 27.3 kg/m2, the femoral neck BMD increased only by 0.005 kg/m2. Fracture risk assessment based on the spinal deformity index (SDI) failed to determine the optimal BMI range. CONCLUSIONS: This study found an inflection point between BMI and lumbar/ femoral neck BMD in older community-dwelling subjects. An appropriate BMI but not an excessive BMI may allow older adults to have a better BMD.

Engineering hypoxia-responsive 6-aminonicotinamide prodrugs for on-demand NADPH depletion and redox manipulation.

Glucose-6-phosphate dehydrogenase (G6PD) is a promising target in cancer therapy. However, poor cellular uptake and off-target toxicity have impeded the clinical translation of a canonical G6PD inhibitor (6-aminonicotinamide/6AN). Here, we report a prodrug strategy to address this issue. The tailored 6AN prodrug contains an azo-bearing protection moiety. The hydrophobic prodrug showed increased cellular uptake than 6AN and was vulnerable to hypoxia, resulting in NAD(P)H quinone dehydrogenase 1 (NQO1)-triggered cleavage of azo bonds. Intriguingly, the prodrug showed configuration-dependent anti-cancer potency. Despite the lower thermodynamic stability, the cis isomer showed enhanced cellular uptake compared to the trans counterpart due to the increased aqueous solubility. Moreover, the boosted potency of the cis isomer compared to the trans isomer arose from the enhancement of NOQ1-catalyzed 6AN release under hypoxia, a hallmark of solid tumors. The discovery of hypoxia-responsive 6AN prodrugs in the current work opens up new avenues for G6PD-targeting cancer medicines.

BCAA-producing Clostridium symbiosum promotes colorectal tumorigenesis through the modulation of host cholesterol metabolism.

Identification of potential bacterial players in colorectal tumorigenesis has been a focus of intense research. Herein, we find that Clostridium symbiosum (C. symbiosum) is selectively enriched in tumor tissues of patients with colorectal cancer (CRC) and associated with higher colorectal adenoma recurrence after endoscopic polypectomy. The tumorigenic effect of C. symbiosum is observed in multiple murine models. Single-cell transcriptome profiling along with functional assays demonstrates that C. symbiosum promotes the proliferation of colonic stem cells and enhances cancer stemness. Mechanistically, C. symbiosum intensifies cellular cholesterol synthesis by producing branched-chain amino acids (BCAAs), which sequentially activates Sonic hedgehog signaling. Low dietary BCAA intake or blockade of cholesterol synthesis by statins could partially abrogate the C. symbiosum-induced cell proliferation in vivo and in vitro. Collectively, we reveal C. symbiosum as a bacterial driver of colorectal tumorigenesis, thus identifying a potential target in CRC prediction, prevention, and treatment.

Timing, initiation and function: An in-depth exploration of the interaction network among neutrophil extracellular traps related genes in acute pancreatitis.

BACKGROUND: Exogenous inhibition of neutrophil extracellular traps (NETs) was believed to alleviate acute pancreatitis (AP). This study aimed to comprehensively explore the key biological behavior of NETs including timing and pathogenesis in AP by integrating of single cell RNA sequencing(scRNA-seq) and bulk RNA-seq. METHODS: Differentially expressed NETs-related genes and the hub genes of NETs were screened by bulk RNA-seq. ScRNA-seq was used to identify the cell types in pancreas of AP mice and to depict the transcriptomic maps in neutrophils. The mouse AP models were build to verify the timing of initiation of NETs and underlying pathogenesis of damage on pancreas acinar cells. RESULTS: Tlr4 and Ccl3 were screened for hub genes by bulk RNA-seq. The trajectory analysis of neutrophils showed that high expression of Ccl3, Cybb and Padi4 can be observed in the middle stage during AP. Macrophages might be essential in the biological behavior of neutrophils and NETs. Through animal models, we presented that extensive NETs structures were formed at mid-stage of inflammation, accompanied by more serious pancreas and lung damage. NETs might promote necroptosis and macrophage infiltration in AP, and the damage on pancreatic injury could be regulated by Tlr4 pathway. Ccl3 was considered to recruit neutrophils and promote NETs formation. CONCLUSION: The findings explored the underlying timing and pathogenesis of NETs in AP for the first time, which provided gene targets for further studies.

Innovative application of CRISPR for eliminating Ustiloxin in Cordyceps militaris: Enhancing food safety and quality.

Cordyceps militaris (L.) Fr. Has long been recognized as a valuable functional food consumed in numerous countries. However, biosynthetic gene clusters of this species and safety regarding mycotoxin production remain largely unexplored. In this study, a ribosomally synthesized and post-translationally modified peptide (RiPP) cluster responsible for the production of cyclopeptide mycotoxins in Cordyceps was unveiled via genome mining. Ustiloxin B and a novel, predominant and Cordyceps specific ustiloxin I were confirmed by extraction and structural analysis. The difference between Ustiloxins I and B lied in the side chain at C19, where an additional methyl substituent in Ustiloxin I resulted in an alanine moiety substitution for glycine of Ustiloxin B. The simultaneous deletion of the two adjacent core genes, CmustYb and CmustYa, using a single guide RNA designed in the intergenic region, and subsequent in-situ complementation via AMA-mediated CRISPR/Cas9 system confirmed the RiPP cluster's responsibility for ustiloxin production. The cultivation of the edited strain yielded ustiloxin-free fruiting bodies without affecting agronomic characters. PCR and genome resequencing confirmed the absence of any off-target events or foreign sequence remnants. This study marks a significant advancement in utilizing CRISPR technology to control ustiloxins in food, underscoring its broader implications for food safety and quality improvement.

Novel self-powered sandwich type Aptamer sensor for estrogen detection assisted with peroxidase mimic Cu-MOF.

A novel self-powered and flexible enzymatic biofuel cell (EBFC)-based aptasensor was developed for the sensitive and selective detection of 17 ß-estradiol (E2). A flexible polyvinyl alcohol (PVA)-tannic acid­carbon nanotube/reduced graphene oxide (PTCR) substrate was modified with gold nanoparticles (AuNPs) and thiolated aptamer 1 (Apt1) to yield Apt1@AuNPs/PTCR. A copper-based metal-organic framework (Cu-MOF) with peroxidase mimicking activity was employed to anchor glucose oxidase (GOD) and Apt2, forming the Cu-MOF@GOD/Apt2 tag. When E2 was recognized by Apt1, the anchored E2 quantitatively recognized Cu-MOF@GOD/Apt2 to create a Cu-MOF@GOD/Apt2-E2-Apt1 sandwich structure for glucose oxidation to generate electrical power. Increased E2 concentrations enhanced Cu-MOF@GOD/Apt2 capture and amplified the electrical signal. The electrical power increased linearly as the E2 concentration increased from 1.0 pM to 1.0 nM. The sensor was successfully applied to various food samples and blood serum detection. This work promoted the application of novel self-powered biosensors for food safety analysis.