The impact of Sangju Qingjie Decoction on the pulmonary microbiota in the prevention and treatment of chronic obstructive pulmonary disease.

Objective: Exploring the effect of SJQJD on the pulmonary microbiota of chronic obstructive pulmonary disease (COPD) rats through 16S ribosomal RNA (rRNA) sequencing. Methods: A COPD rat model was constructed through smoking and lipopolysaccharide (LPS) stimulation, and the efficacy of SJQJD was evaluated by hematoxylin and eosin (H&E) staining and Enzyme-Linked Immunosorbnent Assay (ELISA). The alveolar lavage fluid of rats was subjected to 16S rRNA sequencing. The diversity of lung microbiota composition and community structure was analyzed and differential microbiota were screened. Additionally, machine learning algorithms were used for screening biomarkers of each group of the microbiota. Results: SJQJD could improve lung structure and inflammatory response in COPD rats. 16s rRNA sequencing analysis showed that SJQJD could significantly improve the abundance and diversity of bacterial communities in COPD rats. Through differential analysis and machine learning methods, potential microbial biomarkers were identified as Mycoplasmataceae, Bacillaceae, and Lachnospiraceae. Conclusion: SJQJD could improve tissue morphology and local inflammatory response in COPD rats, and its effect may be related to improve pulmonary microbiota.

Microcystin-LR Induces Estrogenic Effects at Environmentally Relevant Concentration in Black-Spotted Pond Frogs (Pelophylax nigromaculatus): In Situ, In Vivo, In Vitro, and In Silico Investigations.

Harmful cyanobacterial blooms are frequent and intense worldwide, creating hazards for aquatic biodiversity. The potential estrogen-like effect of Microcystin-LR (MC-LR) is a growing concern. In this study, we assessed the estrogenic potency of MC-LR in black-spotted frogs through combined field and laboratory approaches. In 13 bloom areas of Zhejiang province, China, the MC-LR concentrations in water ranged from 0.87 to 8.77 µg/L and were correlated with sex hormone profiles in frogs, suggesting possible estrogenic activity of MC-LR. Tadpoles exposed to 1 µg/L, an environmentally relevant concentration, displayed a female-biased sex ratio relative to controls. Transcriptomic results revealed that MC-LR induces numerous and complex effects on gene expression across multiple endocrine axes. In addition, exposure of male adults significantly increased the estradiol (E2)/testosterone (T) ratio by 3.5-fold relative to controls. Downregulation of genes related to male reproductive endocrine function was also identified. We also showed how MC-LR enhances the expression of specific estrogen receptor (ER) proteins, which induce estrogenic effects by activating the ER pathway and hypothalamic-pituitary-gonadal (HPG) axis. In aggregate, our results reveal multiple lines of evidence demonstrating that, for amphibians, MC-LR is an estrogenic endocrine disruptor at environmentally relevant concentrations. The data presented here support the need for a shift in the MC-LR risk assessment. While hepatoxicity has historically been the focus of MC-LR risk assessments, our data clearly demonstrate that estrogenicity is a major mode of toxicity at environmental levels and that estrogenic effects should be considered for risk assessments on MC-LR going forward.

Chelatococcus albus sp. nov., a bacterium isolated from hot spring microbial mat.

A Gram-stain-negative, non-endospore-forming, motile, short rod-shaped strain, designated SYSU G07232T, was isolated from a hot spring microbial mat, sampled from Rehai National Park, Tengchong, Yunnan Province, south-western China. Strain SYSU G07232T grew at 25-50 °C (optimum, 37 °C), at pH 5.5-9.0 (optimum, pH 6.0) and tolerated NaCl concentrations up to 1.0 % (w/v). Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain SYSU G07232T showed closest genetic affinity with Chelatococcus daeguensis K106T. The genomic features and taxonomic status of this strain were determined through whole-genome sequencing and a polyphasic approach. The predominant quinone of this strain was Q-10. Major cellular fatty acids comprised C19 : 0 cyclo ω8c and summed feature 8. The whole-genome length of strain SYSU G07232T was 4.02 Mbp, and the DNA G+C content was 69.26 mol%. The average nucleotide identity (ANIm ≤84.85 % and ANIb ≤76.08  %) and digital DNA-DNA hybridization (≤ 21.9 %) values between strain SYSU G07232T and the reference species were lower than the threshold values recommended for distinguishing novel prokaryotic species. Thus, based on the provided phenotypic, phylogenetic, and genetic data, it is proposed that strain SYSU G07232T (=KCTC 8141T=GDMCC 1.4178T) be designated as representing a novel species within the genus Chelatococcus, named Chelatococcus albus sp. nov.

Haglund resection versus Haglund non-resection for calcific insertional Achilles tendinopathy with Haglund deformity: A retrospective study.

BACKGROUND: Calcific insertional Achilles tendinopathy(CIAT) with Haglund deformity is a type of recalcitrant tendinopathy. The necessity of concomitant removal of Haglund deformity during CIAT treatment is controversial. The present study aimed to evaluate the functional outcomes between Haglund resection and Haglund non-resection in the treatment of CIAT with Haglund deformity. METHODS: A retrospective study included 29 patients who were underwent Achilles tendon debridement, bursal excision, and subsequent tendon reattachment.for CIAT with Haglund deformity. All patients were divided into 2 groups according to Haglund resection (resection group, n = 16) and Haglund non-resection (non-resection group, n = 13) using the parallel line method on lateral calcaneal X ray after surgery. Patients were evaluated in terms of the American Orthopedic Foot and Ankle Society (AOFAS), Visual Analog Scale (VAS) and Victorian Institute of Sports Assessment-Achilles (VISA-A) scores and the mean time of activities of daily living (ADL). Anatomy changes included the Fowler-Philip angle, calcaneal pitch angle and Achilles tendon force arm were measured with radiography preoperatively and postoperatively. RESULTS: Both groups exhibited a significant increase in AOFAS, VAS and VISA-A scores after surgery. There were no significant differences between the resection group and the non-resection group for the AOFAS (92.38 ± 5.7 vs. 93.15 ± 12.17; P = 0.82), VAS (0.5 ± 0.52 vs. 0.61 ± 0.87; P = 0.66) and VISA-A questionnaire (82.56 ± 13.46 vs. 74.92 ± 16.4; P = 0.18) at the latest follow-up. The mean time of ADL in the non-resection group was significantly faster compared to that of the resection group (8.15 ± 2.51 weeks vs. 11.31 ± 4.06 weeks, P = 0.02). The Fowler-Philip angle of the resection group decreased from 55.55° ± 12.34° preoperatively to 44.52° ± 10.24° at the latest follow-up (P = 0.001). The Fowler-Philip angle of the non-resection group decreased from 54.38° ± 8.41° preoperatively to 46.52° ± 8.02° at the latest follow-up (P = 0.016). The calcaneal pitch angle of the resection group increased from 22.76° ± 5.37° preoperatively to 25.98° ± 6. 4° at the latest follow-up (P = 0.018). The Achilles tendon force arm of the resection group decreased from 178.50 mm ± 5.37 mm preoperatively to 173.90 mm ± 8.07 mm at the latest follow-up (P = 0.018). CONCLUSION: Resection or non-resection of the posterosuperior calcaneal tuberosity for CIAT with Haglund deformity would both provide satisfactory functional outcomes. Haglund non-resection may expedite patients' return to their daily activities, suggesting a Haglund deformity resection may be unnecessary in the surgical treatment for CIAT with Haglund deformity.

AIM2 regulates autophagy to mitigate oxidative stress in aged mice with acute liver injury.

The cytoplasmic pattern recognition receptor, absent in melanoma 2 (AIM2), detects cytosolic DNA, activating the inflammasome and resulting in pro-inflammatory cytokine production and pyroptotic cell death. Recent research has illuminated AIM2's contributions to PANoptosis and host defense. However, the role of AIM2 in acetaminophen (APAP)-induced hepatoxicity remains enigmatic. In this study, we unveil AIM2's novel function as a negative regulator in the pathogenesis of APAP-induced liver damage in aged mice, independently of inflammasome activation. AIM2-deficient aged mice exhibited heightened lipid accumulation and hepatic triglycerides in comparison to their wild-type counterparts. Strikingly, AIM2 knockout mice subjected to APAP overdose demonstrated intensified liver injury, compromised mitochondrial stability, exacerbated glutathione depletion, diminished autophagy, and elevated levels of phosphorylated c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). Furthermore, our investigation revealed AIM2's mitochondrial localization; its overexpression in mouse hepatocytes amplified autophagy while dampening JNK phosphorylation. Notably, induction of autophagy through rapamycin administration mitigated serum alanine aminotransferase levels and reduced the necrotic liver area in AIM2-deficient aged mice following APAP overdose. Mechanistically, AIM2 deficiency exacerbated APAP-induced acute liver damage and inflammation in aged mice by intensifying oxidative stress and augmenting the phosphorylation of JNK and ERK. Given its regulatory role in autophagy and lipid peroxidation, AIM2 emerges as a promising therapeutic target for age-related acute liver damage treatment.

Integrative analysis identifies oxidative stress biomarkers in non-alcoholic fatty liver disease via machine learning and weighted gene co-expression network analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally, with the potential to progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. Given the absence of effective treatments to halt its progression, novel molecular approaches to the NAFLD diagnosis and treatment are of paramount importance. Methods: Firstly, we downloaded oxidative stress-related genes from the GeneCards database and retrieved NAFLD-related datasets from the GEO database. Using the Limma R package and WGCNA, we identified differentially expressed genes closely associated with NAFLD. In our study, we identified 31 intersection genes by analyzing the intersection among oxidative stress-related genes, NAFLD-related genes, and genes closely associated with NAFLD as identified through Weighted Gene Co-expression Network Analysis (WGCNA). In a study of 31 intersection genes between NAFLD and Oxidative Stress (OS), we identified three hub genes using three machine learning algorithms: Least Absolute Shrinkage and Selection Operator (LASSO) regression, Support Vector Machine - Recursive Feature Elimination (SVM-RFE), and RandomForest. Subsequently, a nomogram was utilized to predict the incidence of NAFLD. The CIBERSORT algorithm was employed for immune infiltration analysis, single sample Gene Set Enrichment Analysis (ssGSEA) for functional enrichment analysis, and Protein-Protein Interaction (PPI) networks to explore the relationships between the three hub genes and other intersecting genes of NAFLD and OS. The distribution of these three hub genes across six cell clusters was determined using single-cell RNA sequencing. Finally, utilizing relevant data from the Attie Lab Diabetes Database, and liver tissues from NASH mouse model, Western Blot (WB) and Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) assays were conducted, this further validated the significant roles of CDKN1B and TFAM in NAFLD. Results: In the course of this research, we identified 31 genes with a strong association with oxidative stress in NAFLD. Subsequent machine learning analysis and external validation pinpointed two genes: CDKN1B and TFAM, as demonstrating the closest correlation to oxidative stress in NAFLD. Conclusion: This investigation found two hub genes that hold potential as novel targets for the diagnosis and treatment of NAFLD, thereby offering innovative perspectives for its clinical management.

Integrated analysis of single-cell and bulk RNA sequencing data reveals the association between hypoxic tumor cells and exhausted T cells in predicting immune therapy response.

Continuous stimulation of tumor neoantigens and various cytokines in the tumor microenvironment leads to T cell dysfunction, but the specific mechanisms by which these key factors are distributed among different cell subpopulations and how they affect patient outcomes and treatment response are incompletely characterized. By integrating single-cell and bulk sequencing data of non-small cell lung cancer patients, we constructed a clinical outcome-associated T cell exhaustion signature. We discovered a significant association between the T cell exhaustion state and tumor cell hypoxia. Hypoxic malignant cells were significantly correlated with the proportion of exhausted T cells, and they co-occurred in patients at advanced stage. By analyzing the ligand-receptor interactions between these two cell states, we observed that T cells were recruited towards tumor cells through production of chemokines such as CXCL16-CXCR6 axis and CCL3/CCL4/CCL5-CCR5 axis. Based on 15 immune checkpoint blockade (ICB)-treatment cohorts, we constructed an interaction signature that can be used to predict the response to immune checkpoint blockade therapy. Among genes composed of the signature, CXCR6 alone has similarly high prediction efficacy (Area Under Curve (AUC) = 1, 0.89 and 0.73 for GSE126044, GSE135222 and GSE93157, respectively) with the signature and thus could serve as a potential biomarker for predicting immunotherapy response. Together, we have discovered and validated a significant association between exhausted T cells and hypoxic malignant cells, elucidating key interaction factors that significantly associated with response to immunotherapy.

Prognostic value of lymph node-to-primary tumor ratio of PET standardized uptake value for nasopharyngeal carcinoma: a recursive partitioning risk stratification analysis.

Background: Induction chemotherapy (IC) combined with concurrent chemoradiotherapy has become the standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Data on the prognostic value of the lymph node-to-primary tumor ratio (NTR) of positron emission tomography (PET) standardized uptake value (SUV) for patients treated with IC were limited. Objectives: To evaluate the prognostic value of the SUV NTR for patients with LA-NPC treated with IC. Design: In all, 467 patients with pretreatment 18F-fluorodeoxyglucose PET/computed tomography (CT) scans between September 2017 and November 2020 were retrospectively reviewed. Methods: The receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off value of SUV NTR. Kaplan-Meier method was used to evaluate survival rates. The recursive partitioning analysis (RPA) was performed to construct a risk stratification model. Results: The optimal cutoff value of SUV NTR was 0.74. Multivariate analyses showed that SUV NTR and overall stage were independent predictors for distant metastasis-free survival (DMFS) and regional recurrent-free survival (RRFS). Therefore, an RPA model based on the endpoint of DMFS was generated and categorized the patients into three distinct risk groups: RPA I (low risk: SUV NTR < 0.74 and stage III), RPA II (medium risk: SUV NTR < 0.74 and stage IVa, or SUV NTR ⩾ 0.74 and stage III), and RPA III (high risk: SUV NTR ⩾ 0.74 and stage IVa), with a 3-year DMFS of 98.9%, 93.4%, and 84.2%, respectively. ROC analysis showed that the RPA model had superior predictive efficacy than the SUV NTR or overall stage alone. Conclusion: SUV NTR was an independent prognosticator for distant metastasis and regional recurrence in locoregionally advanced NPC. The RPA risk stratification model based on SUV NTR provides improved DMFS and RRFS prediction over the eighth edition of the TNM (Tumor Node Metastasis) staging system.

Etoposide combined with cytarabine and pegfilgrastim for poorly mobilizing patients with multiple myeloma and lymphoma: A prospective multicentre study.

A chemotherapy-based mobilization regimen in patients who mobilize poorly, based on etoposide, cytarabine and pegfilgrastim (EAP), has recently been introduced. The aim of this prospective study was to investigate the efficacy and safety of the EAP regimen in patients with poorly mobilizing multiple myeloma (MM) or lymphoma. This single-arm clinical trial was performed at eight public hospitals in China and was registered as a clinical trial (NCT05510089). The inclusion criteria were; (1) diagnosis of MM or lymphoma, (2) defined as a 'poor mobilizer' and (3) aged 18-75 years. The EAP regimen consisted of etoposide 75 mg/m2 /day on days 1-2, cytarabine 300 mg/m2 every 12 h on days 1-2 and pegfilgrastim 6 mg on day 6. The primary endpoint of the study was the ratio of patients achieving adequate mobilization (≥2.0 × 106 CD34+ cells/kg). From 1 September 2022 to 15 August 2023, a total of 58 patients were enrolled, 53 (91.4%) achieved adequate mobilization, while 41 (70.7%) achieved optimal mobilization with a median number of cumulative collected CD34+ cells was 9.2 (range 2.1-92.7) × 106 /kg and the median number of apheresis per patient of 1.2. The median time from administration of the EAP regimen to the first apheresis was 12 days. Approximately 8.6% of patients required plerixa for rescue, which was successful. Twelve (20.7%) of the 58 patients suffered grade 2-3 infections, while 25 (43.1%) required platelet transfusions. The duration of neutrophil and platelet engraftment was 11 days. In conclusion, these results suggest that the EAP mobilization regimen might be a promising option for poorly mobilizing patients with MM or lymphoma.

Comprehensive pan-cancer analysis unveils the significant prognostic value and potential role in immune microenvironment modulation of TRIB3.

TRIB3, a pseudokinase, was previously studied within only some specific cancer types, leaving its comprehensive functions in pan-cancer contexts largely unexplored. Here, we performed an integrated analysis of TRIB3 expression, prognosis, genetic alterations, functional enrichment and tumor immune-related characteristics in 33 cancer types. Our results showed that TRIB3 exhibits high expression levels across 24 different cancer types and correlates closely with unfavorable prognoses. Meanwhile, TRIB3 shows mutations in a wide spectrum of 22 distinct cancer types, with the predominant mutation types being missense mutations and gene amplifications, and significant changes in DNA methylation levels in 14 types of cancer. We further discovered that TRIB3 expression is significantly associated with cancer immune-related genome mutations, such as tumor mutational burden (TMB), microsatellite instability (MSI) and DNA mismatch repair (MMR), and infiltration of immunosuppressive cells, such as CD4+ Th2 cells and myeloid-derived suppressor cells (MDSCs), into the tumor microenvironment. These results indicated that the expression of TRIB3 might reshape the tumor immune microenvironment (TIME) and lead to immunosuppressive "cold" tumors. In addition, our results confirmed that the loss of function of TRIB3 inhibits cell proliferation, promotes apoptosis, and leads to significant enrichment of "hot" tumor-related immune pathways, at least in breast cancer cells, which further supports the important role of TRIB3 in cancer prognosis and TIME regulation. Together, this pan-cancer investigation provided a comprehensive understanding of the critical role of TRIB3 in human cancers, and suggested that TRIB3 might be a promising prognostic biomarker and a potential target for cancer immunotherapy.

The der(1;7)(q10;p10) defining a distinct profile from -7/del(7q) in myelodysplastic syndromes: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Myelodysplastic syndromes (MDS) are myeloid neoplasms characterized by ineffective hematopoiesis due to stem cell abnormalities. Monosomy 7q aberrations are a common cytogenetic abnormality in MDS. Specifically, an unbalanced translocation der(1;7)(q10;p10) [der(1;7)] has been identified in MDS patients, which is a monosomy 7q aberration variant like -7/del(7q). However, knowledge of der(1;7)'s features remains limited. Existing studies have compared the clinical and genetic characteristics of der(1;7) to those of -7/del(7q) but yielded inconsistent findings. Accordingly, we conducted meta-analyses comparing der(1;7) to -7/del(7q). METHODS: Publications were searched from the following databases up to January 10, 2023: Pubmed, Web of Science, Embase, Cochrane, and ClinicalTrials.gov. Eligible studies were assessed for risks of bias. Relevant data were extracted from included studies and analyzed using random-effects models. Publication bias was evaluated and sensitivity analyses were performed. RESULTS: The comparative meta-analyses included 405 MDS patients with der(1;7) from nine studies. The analysis revealed that der(1;7) was associated with a greater male preponderance (86.1% vs. 68.3%, Odds Ratios (ORs) 2.007, p < 0.01) than -7/del(7q), lower platelets counts compared to del(7q), higher hemoglobin levels than -7, lower absolute neutrophil counts, and higher percentage of patients with non-excess blasts (66.9% vs. 41.3%, ORs 2.374, p = 0.01) in comparison with -7/del(7q). The der(1;7) existed more as a sole karyotype aberration (55.6% vs. 37.0%, ORs 2.902, p = 0.02), co-occurred more often with +8 (22.7% vs. 4.2%, ORs 5.714, p = 0.04) whereas less -5/del(5q) (1.5% vs. 41.3%, ORs 0.040, p < 0.01) and complex karyotype (7.3% vs. 54.8%, OR 0.085, p < 0.01). The der(1;7) was associated with higher frequencies of RUNX1 (40.8% vs. 12.3%, ORs 4.764, p < 0.01), ETNK1 (28.1% vs. 2.5%, ORs 42.106, p < 0.01) and EZH2 (24.8% vs. 6.9%, ORs 3.767, p = 0.02) mutations, but less TP53 mutation (2.4% vs. 45.3%, ORs 0.043, p < 0.01). Moreover, der(1;7) patients had longer time to progression (Hazard Ratios (HRs) 0.331, p = 0.02), better overall survival (OS) than -7 patients (HRs 0.557, p < 0.01), but similar OS with del(7q) patients (HRs 0.837, p = 0.37). CONCLUSION: The findings revealed distinct clinical, cytogenetic, and molecular characteristics distinguishing der(1;7) from -7/del(7q), indicating der(1;7) defines a unique subtype within MDS with monosomy 7q. These findings support classifying der(1;7) as a separate MDS entity in future.

Individuals with higher suicide risk showed more anger and disgust during rest.

Previous research showed that suicide risk was associated with the anger trait and the facial expression of anger when advising on life dilemmas. We investigated if suicide risk was associated with the facial expression of anger during rest, a state when individuals often reflect upon their lives. Participants took a 1-min rest before being assessed for suicide risk. We measured 147 participants' frontal-view facial expressions during their rest 1475-3694 times using automated facial expression analysis technology. Participants' suicide risk was significantly positively correlated with their anger and disgust during the rest, which may be related to psychological pain and death-related thoughts among individuals with suicide risk. Therefore, rest for clinical patients should not be seen simply as a "rest" for the mind. Rather, for counselors, rest may open a window to look into patients' inner thoughts that may be important to their lives.

Radiation-induced nasopharyngeal ulcers after re-irradiation with intensity-modulated radiotherapy in locoregional recurrent nasopharyngeal carcinoma patients: a dose-volume-outcome analysis.

OBJECTIVE: To analyze the interrelation between radiation dose and radiation-induced nasopharyngeal ulcer (RINU) in locoregional recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). METHODS: Clinical data were collected from 363 patients with locoregional recurrent NPC who received re-irradiated with definitive IMRT from 2009 to 2017. Twenty-nine patients were diagnosed with RINU. Univariate and multivariate analyses were used to re-evaluate the first and second radiotherapy plans and to identify predictive dosimetric factors. RESULTS: All dosimetric parameters were notably associated with the progression to RINU (p < 0.01) using paired samples Wilcoxon signed rank tests. Multivariate analysis showed that EQD2_ [Formula: see text]D80 (dose for 80 percent volume of the unilateral nasopharynx lesion) was an independent prognostic factor for RINU (p = 0.001). The area under the ROC curve for EQD2_ [Formula: see text]D80 was 0.846 (p < 0.001), and the cutoff point of 137.035 Gy could potentially be the dose tolerance of the nasopharyngeal mucosa. CONCLUSIONS: The sum of equivalent dose in 2 Gy fractions (EQD2) in the overlapping volumes between initial and re-irradiated nasopharyngeal mucosal tissue can be effective in predicting the hazard of developing RINU in NPC patients undergoing radical re­irradiation with IMRT and we propose a EQD2_ [Formula: see text]D80 threshold of 137.035 Gy for the nasopharynx.

Large-scale loss-of-function perturbations reveal a comprehensive epigenetic regulatory network in breast cancer.

OBJECTIVE: Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression; however, the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive. It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets. METHODS: We employed high-throughput sequencing-based high-throughput screening (HTS2) to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators. Then, bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer. RESULTS: Utilizing these gene expression signatures, we classified the epigenetic regulators into five distinct clusters, each characterized by specific functions. We discovered functional similarities between BAZ2B and SETMAR, as well as CLOCK and CBX3. Moreover, we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation. Notably, we constructed an epigenetic regulatory network based on the gene expression signatures, which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer. CONCLUSIONS: Our work deciphered the extensive regulation among hundreds of epigenetic regulators. The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.

Bioinspired synthesis and biological evaluation of ent-protulactones A and B.

The bioinspired and stereoselective synthesis of the furo[3,2-b] furan lactone (-)-protulactone A and the dioxabicyclo[3.3.1]nonane lactone (+)-protulactone B has been achieved based on the chiron approach. The synthesis features the utilization of a number of one-pot, sequential transformations, including a cascade reaction of reductive elimination and nucleophilic addition in a one-pot process and a one-pot sequence via cross-metathesis/acetonide deprotection/O-Michael addition/lactonization to streamline the synthesis route and avoid the tedious work of product purification. Synthetic protulactones and their analogues were evaluated for their in vitro antiproliferative activity against selected tumor cell lines (MCF-7 and Capan 2) and showed minor cytotoxicity.

Prognostic Factors for Patients with Proliferative Hepatocellular Carcinoma After Liver Resection.

Purpose: There is a scarcity of predictive models currently accessible for prognosticating proliferative hepatocellular carcinoma (HCC), an integrated class of subtype, characterized by a dismal prognosis. Consequently, this study aimed to develop and validate a novel prognostic model capable of accurately predicting the prognosis of proliferative HCC after curative resection. Patients and Methods: This retrospective multicenter study included patients with solitary HCC who underwent curative liver resection from August 2014 to December 2020 (n = 816). Patients were stratified into either the proliferative HCC cohort (n = 259) or the nonproliferative HCC cohort (n = 557) based on histological criteria. Disease-free survival (DFS) was compared between the two groups before and after one-to-one propensity score matching (PSM). Of all the proliferative HCC patients, 203 patients were assigned to training cohort, and 56 patients were assigned to validation cohort. Univariate and multivariate analyses were performed in training cohort to identify risk factors associated with worse DFS. Thereafter, a predictive model was constructed, subsequently validated in the validation cohort. Results: The DFS of proliferative HCC was significantly worse than nonproliferative HCC before and after PSM. Meanwhile, multivariate regression analysis revealed that liver cirrhosis (P = 0.032) and larger tumor size (P = 0.000) were independent risk factors of worse DFS. Lastly, the discriminative abilities of the predictive model for 1, 3, 5-year DFS rates, as determined by receiver operating characteristic (ROC) curves, were 0.702, 0.720, and 0.809 in the training cohort and 0.752, 0.776, and 0.851 in the validation cohort, respectively. Conclusion: This study developed a predictive model with satisfactory accuracy to predict the worse DFS in proliferative HCCs after liver resection. Moreover, this predictive model may serve as a valuable tool for clinicians to predict postoperative HCC recurrence, thereby enabling them to implement early preventative strategies.

The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients.

This meta-analysis aimed to evaluate the diagnostic accuracy of touch imprint cytology (TIC) for sentinel lymph node (SLN) metastases of patients with clinical node-negative early breast cancer. The PubMed, Web of Science, Embase, and the Cochrane Library databases were meticulously searched to retrieve literature published from January 2005 to September 2022 by two independent reviewers. The meta-analysis was performed using STATA16.0, Meta-Disc 1.4, and RevMan 5.4.9. According to the inclusion criteria, 4,073 patients from 13 studies were included in this meta-analysis. The pooled sensitivity and specificity of TIC for detecting SLN metastases were 0.77 (95% CI 0.66-0.85) and 0.99 (95% CI 0.97-1.00), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 76.15 (95% CI 29.16-198.84) and 0.23 (95% CI 0.15-0.36), respectively. The pooled diagnostic odds ratio was 326.82 (95% CI 132.76-804.56) and the area under the sROC curve was 0.97 (95% CI 0.95-0.98), respectively. This meta-analysis revealed that TIC with high sensitivity and specificity is a feasibility and accuracy diagnosis technique for intraoperative detection of SLN metastases in breast cancer.

The ferroptosis landscape in acute myeloid leukemia.

Ferroptosis induction through the suppression of glutathione peroxidase 4 (GPX4) and apoptosis-inducing factor mitochondria-associated 2 (AIFM2) has proven to be an effective approach in eliminating chemotherapy-resistant cells of various types. However, a comprehensive understanding of the roles of GPX4 and AIFM2 in acute myeloid leukemia (AML) has not yet been achieved. Using cBioPortal, DepMap, GEPIA, Metascape, and ONCOMINE, we compared the transcriptional expression, survival data, gene mutation, methylation, and network analyses of GPX4- and AIFM2-associated signaling pathways in AML. The results revealed that high expression levels of GPX4 and AIFM2 are associated with an adverse prognosis for AML patients. Overexpression of AIFM2 correlated with elevated mutation frequencies in NPM1 and DNMT3A. GPX4 upregulation modulated the following pathways: GO:0045333, cellular respiration; R-HSA-5389840, mitochondrial translation elongation; GO:0009060, aerobic respiration; R-HSA-9609507, protein localization; and R-HSA-8953854, metabolism of RNA. On the other hand, the overexpression of AIFM2 influenced the following processes: GO:0048704, embryonic skeletal system morphogenesis; GO:0021546, rhombomere development; GO:0009954, proximal/distal pattern formation; and GO:0048732, gland development. This study identifies the high expression of GPX4 and AIFM2 as novel biomarkers predicting a poor prognosis for AML patients. Furthermore, ferroptosis induction may improve the stratified treatment of AML.

Radiomic signatures reveal multiscale intratumor heterogeneity associated with tissue tolerance and survival in re-irradiated nasopharyngeal carcinoma: a multicenter study.

BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.