Risk factors for distant metastasis and prognosis of the penile cancer with distant metastasis.

Background: Penile cancer (PC) is a rare malignant tumor, whose distant metastasis (DM) is associated with the poorest outcomes. The risk factors associated with DM and prognosis of the PC with DM remain elusive. This study was aimed at investigating risk factors associated with DM and constructing prediction models of PC with DM. Methods: This study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database over a period of 2000-2020, including clinical characteristics such as age, marital status, tumor size, Tumor Node Metastasis (TNM) staging, and treatment information. Utilizing univariate and multivariate logistic regression, alongside cox regression analysis, we identified independent risk factors for DM and prognosis in the total cases and the cases with DM. Nomograms were developed for predicting DM and prognosis in PC patients. Results: Enrolling 1,488 cases, our study identified tumor size and N stage as independent predictors of DM. The predictive nomogram for DM achieved an area under the curve (AUC) of 0.904. Notably, the 1-, 3-, and 5-year cumulative survival rates for PC with DM were 35%, 17%, and 13%, respectively, with larger tumor size associated with prognosis of PC cases with DM. This study verified a correlation between advanced age and TNM stage, as well as chemotherapy with the poor PC prognosis. The nomogram yielded 0.72, 0.69 and 0.69, in predicting 1-, 3-, and 5-year overall survivals (OS), while 0.73, 0.70 and 0.69 in predicting 1-, 3-, 5-year cancer specific survivals (CSS), respectively. Conclusions: This study investigated risk factors of PC with DM. Also, nomograms for predicting DM, OS and CSS of PC patients were developed.

Access to New Clinic Appointments for Patients With Cancer.

Importance: Racial and ethnic disparities have been observed in the outpatient visit rates for specialist care, including cancer care; however, little is known about patients' experience at the critical step of attempting to access new clinic appointments for cancer care. Objective: To determine simulated English-speaking, Spanish-speaking, and Mandarin-speaking patient callers' ability to access new clinic appointments for 3 cancer types (colon, lung, and thyroid cancer) that disproportionately impact Hispanic and Asian populations. Design, Setting, and Participants: This cross-sectional audit study was conducted between November 2021 and March 2023 using 479 clinic telephone numbers that were provided by the hospital general information personnel at 143 hospitals located across 12 US states. Using standardized scripts, trained research personnel assigned to the roles of English-speaking, Spanish-speaking, and Mandarin-speaking patients called the telephone number for a clinic that treats colon, lung, or thyroid cancer to inquire about a new clinic appointment. Data analysis was conducted from June to September 2023. Main Outcomes and Measures: The primary outcome was whether the simulated patient caller was able to access cancer care (binary variable, yes or no), which was defined to include being provided with a clinic appointment date or scheduling information. Multivariable logistic regression analysis was performed to determine factors independently associated with simulated patient callers being able to access cancer care. Results: Of 985 total calls (399 English calls; 302 Spanish calls; 284 Mandarin calls), simulated patient callers accessed cancer care in 409 calls (41.5%). Differences were observed based on language type, with simulated English-speaking patient callers significantly more likely to access cancer care compared with simulated Spanish-speaking and Mandarin-speaking patient callers (English, 245 calls [61.4%]; Spanish, 110 calls [36.4%]; Mandarin, 54 calls [19.0%]; P < .001). A substantial number of calls ended due to linguistic barriers (291 of 586 Spanish or Mandarin calls [49.7%]) and workflow barriers (239 of 985 calls [24.3%]). Compared with English-speaking simulated patient callers, the odds of accessing cancer care were lower for Spanish-speaking simulated patient callers (adjusted odds ratio [aOR], 0.34; 95% CI, 0.25-0.46) and Mandarin-speaking simulated patient callers (aOR, 0.13; 95% CI, 0.09-0.19). Compared with contacting clinics affiliated with teaching hospitals, callers had lower odds of accessing cancer care when contacting clinics that were affiliated with nonteaching hospitals (aOR, 0.53; 95% CI, 0.40-0.70). Conclusions and Relevance: In this cross-sectional audit study, simulated patient callers encountered substantial barriers when attempting to access clinic appointments for cancer care. These findings suggest that interventions focused on mitigating these barriers are necessary to increase access to cancer care for all patients.

Deep profiling of plasmalogens by coupling the Paternò-Büchi derivatization with tandem mass spectrometry.

Plasmalogens are a special class of glycerophospholipids characterized by a vinyl ether bond (-C = C-O-) at the sn-1 position of the glycerol backbone. Altered plasmalogen profiles have been observed in neurodegenerative diseases and cancers. Profiling of plasmalogens requires specifying the vinyl ether bond and differentiating them from various types of isobars and isomers. Herein, by coupling C = C derivatization via offline Paternò-Büchi reaction with liquid chromatography-tandem mass spectrometry, we have developed a sensitive workflow for analysis of plasmalogens from biological samples. Using bovine heart lipid extract as a model system, we profiled more than 100 distinct structures of plasmenylethanolamines (PE-Ps) and plasmenylcholines (PC-Ps) at the C = C location level, far exceeding previous reports. Analysis of human glioma and normal brain tissue samples revealed elevated n-10 C = C isomers of PE-Ps in the glioma tissue samples. These findings suggest that the developed workflow holds potential in aiding the study of altered metabolism of plasmalogens in clinical samples.

Diagnosis of benign and malignant peripheral lung lesions based on a feature model constructed by the random forest algorithm for grayscale and contrast-enhanced ultrasound.

Rationale and objectives: To construct a predictive model for benign and malignant peripheral pulmonary lesions (PPLs) using a random forest algorithm based on grayscale ultrasound and ultrasound contrast, and to evaluate its diagnostic value. Materials and methods: We selected 254 patients with PPLs detected using chest lung computed tomography between October 2021 and July 2023, including 161 malignant and 93 benign lesions. Relevant variables for judging benign and malignant PPLs were screened using logistic regression analysis. A model was constructed using the random forest algorithm, and the test set was verified. Correlations between these relevant variables and the diagnosis of benign and malignant PPLs were evaluated. Results: Age, lesion shape, size, angle between the lesion border and chest wall, boundary clarity, edge regularity, air bronchogram, vascular signs, enhancement patterns, enhancement intensity, homogeneity of enhancement, number of non-enhancing regions, non-enhancing region type, arrival time (AT) of the lesion, lesion-lung AT difference, AT difference ratio, and time to peak were the relevant variables for judging benign and malignant PPLs. Consequently, a model and receiver operating characteristic curve were constructed with an AUC of 0.92 and an accuracy of 88.2%. The test set results showed that the model had good predictive ability. The index with the highest correlation for judging benign and malignant PPLs was the AT difference ratio. Other important factors were lesion size, patient age, and lesion morphology. Conclusion: The random forest algorithm model constructed based on clinical data and ultrasound imaging features has clinical application value for predicting benign and malignant PPLs.

The potential of 18F-FDG PET/CT metabolic parameter-based nomogram in predicting the microvascular invasion of hepatocellular carcinoma before liver transplantation.

PURPOSE: Microvascular invasion (MVI) is a critical factor in predicting the recurrence and prognosis of hepatocellular carcinoma (HCC) after liver transplantation (LT). However, there is a lack of reliable preoperative predictors for MVI. The purpose of this study is to evaluate the potential of an 18F-FDG PET/CT-based nomogram in predicting MVI before LT for HCC. METHODS: 83 HCC patients who obtained 18F-FDG PET/CT before LT were included in this retrospective research. To determine the parameters connected to MVI and to create a nomogram for MVI prediction, respectively, Logistic and Cox regression models were applied. Analyses of the calibration curve and receiver operating characteristic (ROC) curves were used to assess the model's capability to differentiate between clinical factors and metabolic data from PET/CT images. RESULTS: Among the 83 patients analyzed, 41% were diagnosed with histologic MVI. Multivariate logistic regression analysis revealed that Child-Pugh stage, alpha-fetoprotein, number of tumors, CT Dmax, and Tumor-to-normal liver uptake ratio (TLR) were significant predictors of MVI. A nomogram was constructed using these predictors, which demonstrated strong calibration with a close agreement between predicted and actual MVI probabilities. The nomogram also showed excellent differentiation with an AUC of 0.965 (95% CI 0.925-1.000). CONCLUSION: The nomogram based on 18F-FDG PET/CT metabolic characteristics is a reliable preoperative imaging biomarker for predicting MVI in HCC patients before undergoing LT. It has demonstrated excellent efficacy and high clinical applicability.

A Model Combining Conventional Ultrasound Characteristics, Strain Elastography and Clinicopathological Features to Predict Ki-67 Expression in Small Breast Cancer.

To establish a predictive model incorporating conventional ultrasound, strain elastography and clinicopathological features for Ki-67 expression in small breast cancer (SBC) which defined as maximum diameter less than2 cm. In this retrospective study, 165 SBC patients from our hospital were allocated to a high Ki-67 group (n = 104) and a low Ki-67 group (n = 61). Multivariate regression analysis was performed to identify independent indicators for developing predictive models. The area under the receiver operating characteristic (AUC) curve was also determined to establish the diagnostic performance of different predictive models. The corresponding sensitivities and specificities of different models at the cutoff value were compared. Conventional ultrasound parameters (spiculated margin, absence of posterior shadowing and Adler grade 2-3), strain elastic scores and clinicopathological information (HER2 positive) were significantly correlated with high expression of Ki-67 in SBC (all p < .05). Model 2, which incorporated conventional ultrasound features and strain elastic scores, yielded good diagnostic performance (AUC = 0.774) with better sensitivity than model 1, which only incorporated ultrasound characteristics (78.85%vs. 55.77%, p = .000), with specificities of 77.05% and 62.30% (p = .035), respectively. Model 3, which incorporated conventional ultrasound, strain elastography and clinicopathological features, yielded better performance (AUC = 0.853) than model 1 (AUC = 0.694) and model 2 (AUC = 0.774), and the specificity was higher than model 1 (86.89% vs. 77.05%, p = .001). The predictive model combining conventional ultrasound, strain elastic scores and clinicopathological features could improve the predictive performance of Ki-67 expression in SBC.

Ultrasound-based radiomics nomogram for predicting axillary lymph node metastasis in early-stage breast cancer.

PURPOSE: We aimed at assessing the predictive ability of ultrasound-based radiomics combined with clinical characteristics for axillary lymph node (ALN) status in early-stage breast cancer patients and to compare performance in different peritumoral regions. MATERIALS AND METHODS: A total of 755 patients (527 in the primary cohort and 228 in the external validation cohort) were enrolled in this study. Ultrasound images for all patients were acquired and radiomics analysis performed for intratumoral and different peritumoral regions. The MRMR and LASSO regression analyses were performed on extracted features from the primary cohort to construct a radiomics signature formula combined with clinical characteristics. Pearson's coefficient and the variance inflation factor (VIF) were performed to check the correlation and the multicollinearity among the final predictors. The best performing model was selected to develop a nomogram, which was established by performing binary logistic regression and acquiring cut-off values based on the corresponding nomogram scores of the masses. RESULTS: Among all the radiomics models, the "Mass + Margin3mm" model exhibited the best performance. The areas under the curves (AUC) of the nomogram in the primary and external validation cohorts were 0.906 (95% confidence intervals [CI] 0.882-0.930) and 0.922 (95% CI 0.894-0.960), respectively. They both showed good calibrations. The nomogram exhibited a good ability to discriminate between positive and negative lymph nodes (AUC: 0.853 (95% CI 0.816-0.889) in primary cohort, 0.870 (95% CI 0.818-0.922) in validation cohort), and between low-volume and high-volume lymph nodes (AUC: 0.832 (95% CI 0.781-0.884) in primary cohort, 0.911 (95% CI 0.858-0.964) in validation cohort). CONCLUSIONS: The established nomogram is a prospective clinical prediction tool for non-invasive assessment of ALN status. It has the ability to enhance the accuracy of early-stage breast cancer treatment.

Knowledge mapping and research trends of distraction osteogenesis in oral and maxillofacial surgery.

BACKGROUND: Distraction osteogenesis (DO) has found extensive use in oral and maxillofacial surgery for correcting maxillofacial deformities due to its numerous advantages. However, comprehensive scientific and visual analyses of this field on a global scale are rare. Therefore, this study aims to provide a summary of the global trends and current status of DO in oral and maxillofacial surgery. METHOD: Publications concerning DO in oral and maxillofacial surgery were comprehensively searched and selected from the Web of Science Core Collection(WOSCC) database. We evaluated the annual contributions from institutions, journals, countries, and authors using bibliometric analysis software. RESULTS: A total of 541 publications were included in this study. The USA played a predominant role in this field, leading in both publication volume and international collaboration. Harvard University and the University of Hong Kong secured the top position in total publications, while the University of Texas System topped the list in total citations within this field. The Journal of Oral and Maxillofacial Surgery emerged as the primary contributing journal, and Cheung LX emerged as the primary contributing author in the field of distraction osteogenesis (DO) in oral and maxillofacial surgery. Keywords such as 'orthognathic surgery,' 'reconstruction,' and 'osteogenesis' are anticipated to be prominent topics in future research. CONCLUSION: Between 1995 and 2023, there has been rapid growth in the total number of publications within the field of distraction osteogenesis (DO) in oral and maxillofacial surgery. The USA stands out as the predominant country in this field. Surgeries, orthognathic surgery, and osteogenesis have emerged as prominent topics. The findings of our study offer valuable insights for scholars seeking to identify research hotspots and chart the developmental direction of DO in oral and maxillofacial surgery.

TXNDC12 inhibits lipid peroxidation and ferroptosis.

Ferroptosis is a type of regulated cell death characterized by lipid peroxidation and subsequent damage to the plasma membrane. Here, we report a ferroptosis resistance mechanism involving the upregulation of TXNDC12, a thioredoxin domain-containing protein located in the endoplasmic reticulum. The inducible expression of TXNDC12 during ferroptosis in leukemia cells is inhibited by the knockdown of the transcription factor ATF4, rather than NFE2L2. Mechanistically, TXNDC12 acts to inhibit lipid peroxidation without affecting iron accumulation during ferroptosis. When TXNDC12 is overexpressed, it restores the sensitivity of ATF4-knockdown cells to ferroptosis. Moreover, TXNDC12 plays a GPX4-independent role in inhibiting lipid peroxidation. The absence of TXNDC12 enhances the tumor-suppressive effects of ferroptosis induction in both cell culture and animal models. Collectively, these findings demonstrate an endoplasmic reticulum-based anti-ferroptosis pathway in cancer cells with potential translational applications.

OGT/HIF-2α axis promotes the progression of clear cell renal cell carcinoma and regulates its sensitivity to ferroptosis.

O-GlcNAc transferase (OGT) acts in the development of various cancers, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, we found that OGT was upregulated in ccRCC and this upregulation was associated with a worse survival. Moreover, OGT promoted the proliferation, clone formation, and invasion of VHL-mutated ccRCC cells. Mechanistically, OGT increased the protein level of hypoxia-inducible factor-2α (HIF-2α) (the main driver of the clear cell phenotype) by repressing ubiquitin‒proteasome system-mediated degradation. Interestingly, the OGT/HIF-2α axis conferred ccRCC a high sensitivity to ferroptosis. In conclusion, OGT promotes the progression of VHL-mutated ccRCC by inhibiting the degradation of HIF-2α, and agents that can modulate the OGT/HIF-2α axis may exert therapeutic effects on mutated VHL ccRCC.

Rare presentation of esophageal squamous cell carcinoma with rectal metastasis: A case report.

Esophageal cancer is usually diagnosed at an advanced stage, resulting in poor survival. The common sites of distant metastasis include lung, liver and bones. The present study reports a rare case of esophageal squamous cell carcinoma (SCC) with rectal metastasis. A 65-year-old man was diagnosed with middle thoracic esophageal SCC with multiple lymph node metastasis. The patient achieved good response after chemoradiotherapy and adjuvant chemotherapy. During following up, the computed tomography and magnetic resonance scans showed a mass in front of the rectum with intact mucosa. Biopsies were performed and histopathological findings showed SCC, consistent with metastasis from primary esophageal SCC. The patient subsequently received palliative chemoradiotherapy to the rectal tumour and survived for 5 months. To the best of our knowledge, the present case is the first report of metastatic rectal SCC from the esophagus. It is important to take a biopsy of this unexpected lesion for histological analysis, which can help to discriminate metastatic from primary cancer. The goal of treatment is palliative therapy to improve quality of life and survival for this metastatic disease.

NEDD4L in human tumors: regulatory mechanisms and dual effects on anti-tumor and pro-tumor.

Tumorigenesis and tumor development are closely related to the abnormal regulation of ubiquitination. Neural precursor cell expressed developmentally downregulated 4-like (NEDD4L), an E3 ubiquitin ligase critical to the ubiquitination process, plays key roles in the regulation of cancer stem cells, as well as tumor cell functions, including cell proliferation, apoptosis, cell cycle regulation, migration, invasion, epithelial-mesenchymal transition (EMT), and tumor drug resistance, by controlling subsequent protein degradation through ubiquitination. NEDD4L primarily functions as a tumor suppressor in several tumors but also plays an oncogenic role in certain tumors. In this review, we comprehensively summarize the relevant signaling pathways of NEDD4L in tumors, the regulatory mechanisms of its upstream regulatory molecules and downstream substrates, and the resulting functional alterations. Overall, therapeutic strategies targeting NEDD4L to treat cancer may be feasible.

Camrelizumab combined with apatinib in the treatment of patients with hepatocellular carcinoma: a real-world assessment.

Although a phase II clinical trial confirmed that camrelizumab combined with apatinib is effective in patients with hepatocellular carcinoma (HCC), we generally lack data on the results of this regimen in real-world clinical practice. In this study, the efficacy and safety of camrelizumab combined with apatinib in the treatment of patients with HCC were re-evaluated. Data from 86 patients with HCC were collected and combinatorically treated with camrelizumab and apatinib at the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China. The objective remission rate and disease control rate were 25.6% and 72.1%, respectively. The median progression-free survival was 5 months (95% CI 3.7-6.3 months), and the median overall survival time was 19.0 months (95% CI 16.9-21.1 months). The 12- and 18-month survival rates were 70.9% and 54.2%, respectively. The most common grade 3-4 adverse events were hypertension (24.4%), thrombocytopenia (16.3%), and hyperbilirubinemia (9.3%). Multivariate regression analysis showed that operation history was an independent risk factor for overall survival.

Assessing the effectiveness of camrelizumab plus apatinib versus sorafenib for the treatment of primary liver cancer: a single-center retrospective study.

Although the effectiveness of camrelizumab plus apatinib has been confirmed in a phase II clinical study, the efficacy of camrelizumab plus apatinib versus sorafenib for primary liver cancer (PLC) remains unverified. We retrospectively collected the data of 143 patients with PLC who received camrelizumab plus apatinib or sorafenib as the first-line treatment at The First Affiliated Hospital of Anhui Medical University from April 2018 to November 2021. Of these, 71 patients received an intravenous injection of camrelizumab 200 mg (body weight ≥ 50 kg) or 3 mg/kg (body weight < 50 kg) followed by an oral dosage of apatinib 250 mg/day every 3 weeks and 72 patients received sorafenib 400 mg orally, twice a day in 28-day cycles. The primary outcomes were overall survival and progression-free survival. The secondary outcomes were objective response rate, disease control rate, and safety. The median median progression-free survival and median overall survival with camrelizumab plus apatinib and sorafenib were 6.0 (95% confidence interval (CI) 4.2-7.8) and 3.0 months (95% CI 2.3-3.7) and 19.0 (95% CI 16.4-21.6) and 12.0 months (95% CI 8.9-15.1), respectively (death hazard ratio: 0.61, P = 0.023). Grade 3/4 treatment-related adverse events were noted in 50 (70.4%) patients in the camrelizumab plus apatinib group and 19 (26.4%) patients in the sorafenib group. Two treatment-related deaths were recorded. Clinically significant improvements were observed in overall survival and progression-free survival with camrelizumab plus apatinib versus sorafenib. Although the side effects of camrelizumab plus apatinib are relatively high, they can be controlled.

Chirality-enhanced transport and drug delivery of graphene nanocarriers to tumor-like cellular spheroid.

Chirality, defined as "a mirror image," is a universal geometry of biological and nonbiological forms of matter. This geometry of molecules determines how they interact during their assembly and transport. With the development of nanotechnology, many nanoparticles with chiral geometry or chiroptical activity have emerged for biomedical research. The mechanisms by which chirality originates and the corresponding synthesis methods have been discussed and developed in the past decade. Inspired by the chiral selectivity in life, a comprehensive and in-depth study of interactions between chiral nanomaterials and biological systems has far-reaching significance in biomedicine. Here, we investigated the effect of the chirality of nanoscale drug carriers, graphene quantum dots (GQDs), on their transport in tumor-like cellular spheroids. Chirality of GQDs (L/D-GQDs) was achieved by the surface modification of GQDs with L/D-cysteines. As an in-vitro tissue model for drug testing, cellular spheroids were derived from a human hepatoma cell line (i.e., HepG2 cells) using the Hanging-drop method. Our results reveal that the L-GQDs had a 1.7-fold higher apparent diffusion coefficient than the D-GQDs, indicating that the L-GQDs can enhance their transport into tumor-like cellular spheroids. Moreover, when loaded with a common chemotherapy drug, Doxorubicin (DOX), via π-π stacking, L-GQDs are more effective as nanocarriers for drug delivery into solid tumor-like tissue, resulting in 25% higher efficacy for cancerous cellular spheroids than free DOX. Overall, our studies indicated that the chirality of nanocarriers is essential for the design of drug delivery vehicles to enhance the transport of drugs in a cancerous tumor.

Allelic expression of AhNSP2-B07 due to parent of origin affects peanut nodulation.

Legumes are well-known for establishing a symbiotic relationship with rhizobia in root nodules to fix nitrogen from the atmosphere. The nodulation signaling pathway 2 (NSP2) gene plays a critical role in the symbiotic signaling pathway. In cultivated peanut, an allotetraploid (2n = 4x = 40, AABB) legume crop, natural polymorphisms in a pair of NSP2 homoeologs (Na and Nb) located on chromosomes A08 and B07, respectively, can cause loss of nodulation. Interestingly, some heterozygous (NBnb) progeny produced nodules, while some others do not, suggesting non-Mendelian inheritance in the segregating population at the Nb locus. In this study, we investigated the non-Mendelian inheritance at the NB locus. Selfing populations were developed to validate the genotypical and phenotypical segregating ratios. Allelic expression was detected in roots, ovaries, and pollens of heterozygous plants. Bisulfite PCR and sequencing of the Nb gene in gametic tissue were performed to detect the DNA methylation variations of this gene in different gametic tissues. The results showed that only one allele at the Nb locus expressed in peanut roots during symbiosis. In the heterozygous (Nbnb) plants, if dominant allele expressed, the plants produced nodules, if recessive allele expressed, then no nodules were produced. qRT-PCR experiments revealed that the expression of Nb gene in the ovary was extremely low, about seven times lower than that in pollen, regardless of genotypes or phenotypes of the plants at this locus. The results indicated that Nb gene expression in peanut depends on the parent of origin and is imprinted in female gametes. However, no significant differences of DNA methylation level were detected between these two gametic tissues by bisulfite PCR and sequencing. The results suggested that the remarkable low expression of Nb in female gametes may not be caused by DNA methylation. This study provided a unique genetic basis of a key gene involved in peanut symbiosis, which could facilitate understanding the regulation of gene expression in symbiosis in polyploid legumes.

Metabolic genes, a potential predictor of prognosis and immunogenicity of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC). Many ccRCCs are diagnosed at an advanced stage due to the lack of early symptoms, with a high mortality rate and a poor prognosis. The occurrence and development of ccRCC are closely related to metabolic disorders. This study aims to explore the relationship between metabolic genes and prognosis, immune microenvironment, and tumor development of ccRCC. Using data from TCGA, GEO, and ArrayExpress, we successfully established a risk model (riskScore) based on 4 metabolic genes (MGs) that can accurately predict the prognosis and immune microenvironment of ccRCCs. In addition, we determined the role of PAFAH2 in suppressing tumor cell proliferation and migration in ccRCC in vitro. Our research may shed new light on ccRCC patients' prognosis and treatment management.

Protein-Targeted Glycan Editing on Living Cells Disrupts KRAS Signaling.

The frequent mutation of KRAS oncogene in some of the most lethal human cancers has spurred incredible efforts to develop KRAS inhibitors, yet only one covalent inhibitor for the KRASG12C mutant has been approved to date. New venues to interfere with KRAS signaling are desperately needed. Here, we report a "localized oxidation-coupling" strategy to achieve protein-specific glycan editing on living cells for disrupting KRAS signaling. This glycan remodeling method exhibits excellent protein and sugar specificity and is applicable to different donor sugars and cell types. Attachment of mannotriose to the terminal galactose/N-acetyl-D-galactosamine epitopes of integrin αv ß3 , a membrane receptor upstream of KRAS, blocks its binding to galectin-3, suppresses the activation of KRAS and downstream effectors, and mitigates KRAS-driven malignant phenotypes. Our work represents the first successful attempt to interfere with KRAS activity by manipulating membrane receptor glycosylation.

Prognostic nomogram and risk factors for predicting survival in patients with pT2N0M0 esophageal squamous carcinoma.

This study analyzed the impact of factors affecting overall survival in patients with pT2N0M0 esophageal squamous carcinoma (ESCC) and developed a nomogram to predict overall survival (OS). We reviewed the clinical data of 413 patients with pathological T2N0M0 ESCC after radical esophagectomy in two hospitals. Data from one institution was used as the training cohort. A nomogram was established using Cox proportional hazard regression for identifying the prognostic factors affecting for OS in ESCC patients. The area under the curve (AUC), calibration curves and decision curve analysis (DCA) were used to evaluate prognostic efficacy, which was validated in an independent validation cohort. In the training cohort (N = 304), the median OS was 69.33 months, and the 3-, 5- and 10-year OS rates were 76.80%, 67.00% and 56.90%, respectively. The median OS of the validation cohort (N = 109) was 73.50 months, and the 3-, 5- and 10-year OS rates were 77.00%, 67.80% and 55.60%, respectively. According to Cox univariate and multivariate analyses, sex, age, tumor length and the number of resected lymph nodes were identified as predictors of OS. We developed nomograms and performed internal and external validation. The time-dependent receiver operating characteristic (ROC) curve and area under the curve (AUC) value, calibration curve and decision curve analysis (DCA) showed good prediction ability of the nomogram. The developed nomogram can effectively predict OS after esophagectomy in patients with pT2N0M0 ESCC.

LncRNA GAS5 suppresses TGF-ß1-induced transformation of pulmonary pericytes into myofibroblasts by recruiting KDM5B and promoting H3K4me2/3 demethylation of the PDGFRα/ß promoter.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a condition that may cause persistent pulmonary damage. The transformation of pericytes into myofibroblasts has been recognized as a key player during IPF progression. This study aimed to investigate the functions of lncRNA growth arrest-specific transcript 5 (GAS5) in myofibroblast transformation during IPF progression. METHODS: We created a mouse model of pulmonary fibrosis (PF) via intratracheal administration of bleomycin. Pericytes were challenged with exogenous transforming growth factor-ß1 (TGF-ß1). To determine the expression of target molecules, we employed quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemical and immunofluorescence staining. The pathological changes in the lungs were evaluated via H&E and Masson staining. Furthermore, the subcellular distribution of GAS5 was examined using FISH. Dual-luciferase reporter assay, ChIP, RNA pull-down, and RIP experiments were conducted to determine the molecular interaction. RESULTS: GAS5 expression decreased whereas PDGFRα/ß expression increased in the lungs of IPF patients and mice with bleomycin-induced PF. The in vitro overexpression of GAS5 or silencing of PDGFRα/ß inhibited the TGF-ß1-induced differentiation of pericytes to myofibroblasts, as evidenced by the upregulation of pericyte markers NG2 and desmin as well as downregulation of myofibroblast markers α-SMA and collagen I. Further mechanistic analysis revealed that GAS5 recruited KDM5B to promote H3K4me2/3 demethylation, thereby suppressing PDGFRα/ß expression. In addition, KDM5B overexpression inhibited pericyte-myofibroblast transformation and counteracted the promotional effect of GAS5 knockdown on pericyte-myofibroblast transformation. Lung fibrosis in mice was attenuated by GAS5 overexpression but promoted by GAS5 deficiency. CONCLUSION: GAS5 represses pericyte-myofibroblast transformation by inhibiting PDGFRα/ß expression via KDM5B-mediated H3K4me2/3 demethylation in IPF, identifying GAS5 as an intervention target for IPF.