The safety and short-term effect of mixed approach in laparoscopic right hemicolectomy for right colon cancer compared with middle approach: a retrospective study.

PURPOSE: To investigate whether the mixed approach is a safe and advantageous way to operate laparoscopic right hemicolectomy. METHODS: A retrospective study was performed on 316 patients who underwent laparoscopic right hemicolectomy in our center. They were assigned to the middle approach group (n = 158) and the mixed approach group (n = 158) according to the surgical approaches. The baseline data like gender、age and body mass index as well as the intraoperative and postoperative conditions including operation time, blood loss, postoperative hospital stay and complications were analyzed. RESULTS: There were no significant differences in age, sex, BMI, ASA grade and tumor characteristics between the two groups. Compared with the middle approach group, the mixed approach group was significantly lower in terms of operation time (217.61 min vs 154.31 min, p < 0.001), intraoperative blood loss (73.8 ml vs 37.97 ml, p < 0.001) and postoperative drainage volume. There was no significant difference in the postoperative complications like postoperative anastomotic leakage, postoperative infection and postoperative intestinal obstruction. CONCLUSIONS: Compared with the middle approach, the mixed approach is a safe and advantageous way that can significantly shorten the operation time, reduce intraoperative bleeding and postoperative drainage volume, and does not prolong the length of hospital stay or increase the morbidity postoperative complications.

Genome-wide detections for runs of homozygosity and selective signatures reveal novel candidate genes under domestication in chickens.

BACKGROUND: Indigenous chickens were developed through a combination of natural and artificial selection; essentially, changes in genomes led to the formation of these modern breeds via admixture events. However, their confusing genetic backgrounds include a genomic footprint regulating complex traits, which is not conducive to modern animal breeding. RESULTS: To better evaluate the candidate regions under domestication in indigenous chickens, we considered both runs of homozygosity (ROHs) and selective signatures in 13 indigenous chickens. The genomes of Silkie feather chickens presented the highest heterozygosity, whereas the highest inbreeding status and ROH number were found in Luhua chickens. Short ROH (< 1 Mb), were the principal type in all chickens. A total of 291 ROH islands were detected, and QTLdb mapping results indicated that body weight and carcass traits were the most important traits. An ROH on chromosome 2 covering VSTM2A gene was detected in 12 populations. Combined analysis with the Tajima's D index revealed that 18 genes (e.g., VSTM2A, BBOX1, and RYR2) were under selection and covered by ROH islands. Transcriptional analysis results showed that RYR2 and BBOX1 were specifically expressed in the heart and muscle tissue, respectively. CONCLUSION: Based on genome-wide scanning for ROH and selective signatures, we evaluated the genomic characteristics and detected significant candidate genes covered by ROH islands and selective signatures. The findings in this study facilitated the understanding of genetic diversity and provided valuable insights for chicken breeding and conservation strategies.

Risk factors and clinical significance of lower perigastric lymph node metastases in Siewert type II and III esophagogastric junction adenocarcinoma: a retrospective cohort study.

BACKGROUND: No consensus has been concluded with regarding to the scope of lymph node (LN) dissection for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). This study aimed to explore risk factors for lower perigastric LN (LPLN) metastases (including no. 4d, 5, 6, and 12a LN stations) and analyze the indications for LPLN dissection. METHODS: In total, 302 consecutive patients with Siewert type II and III AEG who underwent total gastrectomy (TG) were enrolled. The logistic regression model was used to perform uni- and multivariate analyses of risk factors for LPLN metastases. Kaplan-Meier curves were used for survival analysis, and log-rank tests were used for group comparisons. Basing on the guidelines of Japanese Gastric Cancer Association, the LN metastases (LNM) as well as the efficiency index (EI) of each LN station was further evaluated. RESULTS: The independent risk factors for LPLN metastases in patients with Siewert type II and III AEG were distance from the esophagogastric junction (EGJ) to the distal end of the tumor (> 4.0 cm), preoperative carcinoembryonic antigen (CEA) ( +), pT4 stage, and HER-2 ( +). LPLN metastases was an independent risk factor for overall survival following TG. The LNM and EI of LPLN were 8.6% and 2.31%, respectively. The LNM of LPLN > 10% under the stratification of the distance from the EGJ to the distal end of the tumor (> 4.0 cm), pT4, preoperative CEA ( +), and HER-2 ( +) exhibited EI values of 3.55%, 2.09%, 2.51%, and 3.64%, respectively. CONCLUSIONS: LPLN metastases was a malignant factor for the prognosis of patients with Siewert type II and III AEG. For patients with preoperative CEA ( +), pT4 stage, HER-2 ( +), and the distance from the EGJ to the distal end of the tumor (> 4.0 cm), TG with LPLN dissection is prioritized for clinical recommendation.

[Health Risk Assessment of Heavy Metals in Soils of a City in Guangdong Province Based on Source Oriented and Monte Carlo Models].

Taking a city in Guangdong Province as the research area, the concentration and spatial distribution characteristics of heavy metals in the surface soil were studied to clarify the situation of soil heavy metal pollution and priority control factors, providing basic data for the prevention and control of soil heavy metal pollution in the city. The content characteristics of heavy metals in 221 soil samples in the city were analyzed, and the potential health risk assessment and source analysis were carried out through the Monte Carlo model, the potential health risk assessment (HRA) model, and the PMF receptor model. It was found that heavy metals ω(As), ω(Hg), ω(Cd), ω(Pb), ω(Cr), ω(Cu), ω(Ni), and ω(Zn) in the soil of the city were 18.16, 0.43, 1.46, 68.57, 98.34, 64.19, 26.53, and 257.32 mg·kg-1, respectively, with a moderate to high degree of variation. Except for Ni concentration, the soil concentrations of other heavy metal elements exceeded the background values of soil in Guangdong Province to a certain extent, and the concentrations of Cd and Zn exceeded the national secondary standards, resulting in severe heavy metal pollution; the main sources of heavy metals were industrial sources, and natural parent materials, lead battery manufacturing, transportation, artificial cultivation, and pesticide and fertilizer inputs also had an undeniable impact on the accumulation of heavy metals in the soil. Heavy metals in the soil had a certain degree of tolerable carcinogenic health risk for both children and adults, whereas non-carcinogenic risks could be ignored. The potential health risk of children was greater than that of adults, and the main exposure route was through oral intake. The input sources of pesticides and fertilizers and As should be the main controlling factors for the health risks of heavy metals in the city's soil, followed by mixed sources and Cr. There were differences in the spatial distribution characteristics and relative pollution levels of heavy metals, and it is necessary to deepen zoning monitoring and control, strengthen soil pollution prevention and control, and reduce human input of heavy metals in soil.

Association between elevated blood-brain barrier permeability and the risk of progressive cognitive decline: A longitudinal study.

BACKGROUND: The breakdown of the blood-brain barrier (BBB) is intricately linked to the onset and advancement of cognitive impairment and dementia. This investigation explores the correlation between blood-brain barrier permeability, assessed through the cerebrospinal fluid/serum albumin ratio (QAlb), in a clinical cohort and the evolution of cognitive decline. METHODS: This prospective observational cohort study included 295 participants. Cognitive decline progression was characterized by an escalation in the overall deterioration scale and/or clinical dementia rating scores. The investigation delves into the correlation between blood-brain barrier permeability and the advancement of cognitive impairment among patients. RESULTS: The APOE 4 allele and diabetes mellitus among individuals exhibited increased BBB permeability (P < 0.05). Moreover, AD patients exhibited the highest QAlb levels, signifying elevated BBB permeability compared to individuals with MCI and SCD (P < 0.05). After mean 17 months following up, 117 patients (51.31 %) were identified as experiencing cognitive decline progression, and we found that only AD diagnosis, CDR, and QAlb (All P < 0.05) were significant predictors of cognitive decline progression. CONCLUSION: Our study emphasizes the clinical relevance of QAlb in detecting individuals with an elevated risk of cognitive decline. It suggests that heightened BBB permeability could contribute to clinical deterioration and serves as a plausible therapeutic target.

Discrepancies in Perceived Indulgent Parenting, Relationship Satisfaction, and Psychological Well-Being of Adolescents and Parents.

Indulgent parenting has been associated with adolescents' psychological well-being problems; however, prior research has primarily relied on adolescents' report of such parenting behavior and its association with their own well-being, often overlooking parents' perceptions of indulgence and their own well-being. In this study, we address this gap in the literature by examining the agreement and disagreement between parents' and adolescents' perceptions of indulgent parenting and the implications for the psychological well-being of both adolescents and their parents. Further, we explore the role of adolescent-parent relationship satisfaction as a potential factor affecting these associations. Our investigation was based on data from 128 parent-adolescent dyads. Utilizing structural equation modeling with double-entry intraclass correlations (ICC_DE), our analyses revealed several main findings: (1) adolescents perceived higher levels of indulgent parenting than their parents did; (2) disagreement in perceived indulgent parenting between parents and adolescents was linked to psychological well-being problems for both adolescents and their parents; and (3) disagreement in perceptions in indulgent parenting had a stronger association with adolescents' well-being problems when adolescents reported greater relationship satisfaction with their parents. These findings provide insights into perceptions of indulgent parenting within parent-adolescent relationships and bring psychological implications for both adolescents and their parents.

Metabolites assay offers potential solution to improve the rooster semen cryopreservation.

Semen cryopreservation represents a promising technology utilized for preserving high-quality chicken varieties in husbandry practices. However, the efficacy of this methodology is significantly impeded by the diminished quality of sperm. Metabolites, as the end products of metabolic reactions, serve as indicators of biological processes and offer insights into physiological conditions. In this study, we investigaged the sperm quality and alteration in metabolic profiles during the cryopreservation of Longyou Partridge Chicken semen. Following artificial semen collection, four groups of semen samples were established based on four points of the cryopreservation process (Ⅰ, fresh semen; Ⅱ, semen added extender and chilled at 4 °C for 30 min; Ⅲ, semen added cryoprotectants; Ⅳ, semen gradient freezed and stored in liquid nitrogen). Semen cryopreservation has a negative effect on the percentage of sperm in a straight-line trajectory (LIN), has no significant effect on total motile sperms (TM) or the proportion of sperm with typical morphology (NM). Metabolites were identified using LC-MS technique and analyses including Principal Component Analysis (PCA), Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), Univariate statistical analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were employed to identify metabolites. A total of 2471 metabolites had been identified, with the majority of the list being made up of amino acids and their metabolites as well as benzene and substituted derivatives. Group II exhibits 882 metabolites with significantly elevated abundance relative to Group I, alongside 37 metabolites displaying decreased abundance. In Group III, 836 metabolites demonstrate notably augmented abundance compared to Group II, while 87 metabolites exhibit reduced abundance. Furthermore, Group IV showcases 513 metabolites with markedly heightened abundance in comparison to Group III, and 396 metabolites with decreased abundance. Specific metabolites such as 5-Hydroxylysine, Phosphocholine, and alpha-d-glucose-6-phosphate exhibited a progressive decline during the cryopreservation process, correlating with either dilution and chilling, cryoprotectant addition, or freezing. In conclusion, our investigation systematically examined the changes of seminal metabolome and sperm quality throughout the cryopreservation process of rooster semen.

[Pollution Characteristics and Risk Assessment of Polycyclic Aromatic Hydrocarbons in Soils of Guangzhou].

In order to comprehensively study the pollution characteristics of polycyclic aromatic hydrocarbons （PAHs） in soils of Guangzhou， 222 topsoil samples were collected and analyzed. The ecological risk of soil PAHs pollution was evaluated using the effect interval low/median method （ERL/ERM） and the （BaP） toxicity equivalent method， and the health risk of soil PAHs pollution was evaluated using the lifelong cancer risk increment model. The source of PAHs was analyzed using the characteristic compound ratio method and PMF model. The results indicated that： the content of surface soil （∑16PAHs） in Guangzhou was 38-11 115 µg·kg-1， with an average of 526 µg·kg-1， and 16 types of polycyclic aromatic hydrocarbon monomers showed strong variation. There was a certain degree of ecological risk of PAHs in Guangzhou， and there was already a significant ecological risk of PAHs pollution in individual sampling points， which were generally in a state of mild pollution. Based on the results of the health risk assessment， the contribution rates of total cancer risk in both adults and children were presented as follows： skin contact > ingestion of soil > respiratory intake. The health risk of children was greater than that of adults， and the overall health risk was within an acceptable range. Source analysis showed that the main sources of soil PAHs in Guangzhou were coal （37.1%）； diesel （32%）； coking （17.3%）； and mixed sources of traffic emissions， biomass combustion， and petrochemical product volatilization （13.6%）. The overall source of soil PAHs belonged to mixed sources. The research results have enriched our understanding of the pollution status of PAHs in the surface soil of Guangzhou and are helpful in promoting soil pollution prevention and control actions.

Long noncoding RNA LRG modulates Drosophila locomotion by sequestering Synaptotagmin 1 protein.

Apparently, the genomes of many organisms are pervasively transcribed, and long noncoding RNAs (lncRNAs) make up the majority of cellular transcripts. LncRNAs have been reported to play important roles in many biological processes; however, their effects on locomotion are poorly understood. Here, we presented a novel lncRNA, Locomotion Regulatory Gene (LRG), which participates in locomotion by sequestering Synaptotagmin 1 (SYT1). LRG deficiency resulted in higher locomotion speed which could be rescued by pan-neuronal overexpression but not by limited ellipsoid body, motoneuron or muscle-expression of LRG. At the molecular level, the synaptic vesicles (SVs) release and movement-related SYT1 protein was recognized as LRG-interacting protein candidate. Furthermore, LRG had no effects on SYT1 expression. Genetically, the behavioral defects in LRG mutant could be rescued by pan-neuronal knock-down of Syt1. Taken together, all the results suggested LRG exerts regulatory effects on locomotion via sequestering SYT1 thereby blocking its function without affecting its expression. Our work displays a new function of lncRNA and provides insights for revealing the pathogenesis of neurological diseases with motor disorders.

Crosstalk between metabolic remodeling and epigenetic reprogramming: A new perspective on pancreatic cancer.

Pancreatic cancer is a highly malignant solid tumor with a poor prognosis and a high mortality rate. Thus, exploring the mechanisms underlying the development and progression of pancreatic cancer is critical for identifying targets for diagnosis and treatment. Two important hallmarks of cancer-metabolic remodeling and epigenetic reprogramming-are interconnected and closely linked to regulate one another, creating a complex interaction landscape that is implicated in tumorigenesis, invasive metastasis, and immune escape. For example, metabolites can be involved in the regulation of epigenetic enzymes as substrates or cofactors, and alterations in epigenetic modifications can in turn regulate the expression of metabolic enzymes. The crosstalk between metabolic remodeling and epigenetic reprogramming in pancreatic cancer has gained considerable attention. Here, we review the emerging data with a focus on the reciprocal regulation of metabolic remodeling and epigenetic reprogramming. We aim to highlight how these mechanisms could be applied to develop better therapeutic strategies.

Exploring the novel antioxidant peptides in low-salt dry-cured ham: Preparation, purification, identification and molecular docking.

Dry-cured ham is important source of bioactive peptides. In this study, the antioxidant activities of peptides and components from low and fully salted dry-cured hams were compared by peptidomics. And novel antioxidant peptides were identified and characterized. The results showed that the peptides (<3 KDa) extracted from low-salt dry-cured ham had higher antioxidant activity. Therefore, the antioxidant peptides in low-salt dry-cured ham were further characterized and the mechanism of their antioxidant activity was investigated. From the five candidate peptides selected, we found DWPDARGIWHND (DD12) to be highly stable, non-sensitizing, and non-toxic with the highest free radical scavenging activity. Molecular docking predicted that DD12 interacted with Keap1 through hydrogen-bond formation and hydrophobic interactions, suggesting that DD12 had good cellular antioxidant activity. DD12 peptide can bind to DPPH• and ABTS•+, resulting in strong free radical scavenging activity. Our findings support the development and application of natural antioxidant peptides in dry-cured ham.

Roseburia intestinalis sensitizes colorectal cancer to radiotherapy through the butyrate/OR51E1/RALB axis.

The radioresistant signature of colorectal cancer (CRC) hampers the clinical utility of radiotherapy. Here, we find that fecal microbiota transplantation (FMT) potentiates the tumoricidal effects of radiation and degrades the intertwined adverse events in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC mice. FMT cumulates Roseburia intestinalis (R. intestinalis) in the gastrointestinal tract. Oral gavage of R. intestinalis assembles at the CRC site and synthetizes butyrate, sensitizing CRC to radiation and alleviating intestinal toxicity in primary and CRC hepatic metastasis mouse models. R. intestinalis-derived butyrate activates OR51E1, a G-protein-coupled receptor overexpressing in patients with rectal cancer, facilitating radiogenic autophagy in CRC cells. OR51E1 shows a positive correlation with RALB in clinical rectal cancer tissues and CRC mouse model. Blockage of OR51E1/RALB signaling restrains butyrate-elicited autophagy in irradiated CRC cells. Our findings highlight that the gut commensal bacteria R. intestinalis motivates radiation-induced autophagy to accelerate CRC cell death through the butyrate/OR51E1/RALB axis and provide a promising radiosensitizer for CRC in a pre-clinical setting.

The association between the AIP and undiagnosed diabetes in ACS patients with different body mass indexes and LDL-C levels: findings from the CCC-ACS project.

BACKGROUND: The atherogenic index of plasma (AIP) has been demonstrated to be significantly associated with the incidence of prediabetes and diabetes. This study aimed to investigate the association between the AIP and undiagnosed diabetes in acute coronary syndrome (ACS) patients. METHODS: Among 113,650 ACS patients treated with coronary angiography at 240 hospitals in the Improving Care for Cardiovascular Disease in China-ACS Project from 2014 to 2019, 11,221 patients with available clinical and surgical information were included. We analyzed these patients' clinical characteristics after stratification according to AIP tertiles, body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C) levels. RESULTS: The AIP was independently associated with a greater incidence of undiagnosed diabetes. The undiagnosed diabetes was significantly greater in the T3 group than in the T1 group after adjustment for confounders [T3 OR 1.533 (1.199-1.959) p < 0.001]. This relationship was consistent within normal weight patients and patients with an LDL-C level ≥ 1.8 mmol/L. In overweight and obese patients, the AIP was significantly associated with the incidence of undiagnosed diabetes as a continuous variable after adjustment for age, sex, and BMI but not as a categorical variable. The area under the receiver operating characteristic curve (AUC) of the AIP score, triglyceride (TG) concentration, and HDL-C concentration was 0.601 (0.581-0.622; p < 0.001), 0.624 (0.603-0.645; p < 0.001), and 0.493 (0.472-0.514; p = 0.524), respectively. A nonlinear association was found between the AIP and the incidence of undiagnosed diabetes in ACS patients (p for nonlinearity < 0.001), and this trend remained consistent between males and females. The AIP may be a negative biomarker associated with undiagnosed diabetes ranging from 0.176 to 0.738. CONCLUSION: The AIP was significantly associated with the incidence of undiagnosed diabetes in ACS patients, especially in those with normal weight or an LDL-C level ≥ 1.8 mmol/L. A nonlinear relationship was found between the AIP and the incidence of undiagnosed diabetes, and this trend was consistent between male and female patients. The AIP may be a negative biomarker associated with undiagnosed diabetes and ranges from 0.176 to 0.738.

The significance of an immunohistochemical marker-based panel in assisting the diagnosis of parathyroid carcinoma.

PURPOSE: Parathyroid carcinoma (PC) is an endocrine malignancy with a poor prognosis. However, the diagnosis of PC is still a difficult problem. A model with immunohistochemical (IHC) staining of 5 biomarkers has been reported from limited samples for the differential diagnosis of PC. In the present study, a series of IHC markers was applied in relatively large samples to optimize the diagnostic model for PC. METHODS: In this study, 44 patients with PC, 6 patients with atypical parathyroid tumors and 57 patients with parathyroid adenomas were included. IHC staining for parafibromin, Ki-67, galectin-3, protein-encoding gene product 9.5 (PGP9.5), E-cadherin, and enhancer of zeste homolog 2 (EZH2) was performed on formalin-fixed, paraffin-embedded tissue samples. The effects of clinical characteristics, surgical procedure, and IHC staining results of tumor tissues on the diagnosis and prognosis of PC were evaluated retrospectively. RESULTS: A logistic regression model with IHC results of parafibromin, Ki-67, and E-cadherin was created to differentiate PC with an area under the curve of 0.843. Cox proportional hazards analysis showed that negative parafibromin staining (hazard ratio: 3.26, 95% confidence interval: 1.28-8.34, P = 0.013) was related to the recurrence of PC. CONCLUSION: An IHC panel of parafibromin, Ki-67 and E-cadherin may help to distinguish PC from parathyroid neoplasms. Among the 6 IHC markers and clinical features examined, the risk factor related to PC recurrence was parafibromin staining loss.

Whole-genome variants dataset of 209 local chickens from China.

Compared to commercial chickens, local breeds exhibit better in meat quality and flavour, but the productivity (e.g., growth rate, body weight) of local chicken breeds is rather low. Genetic analysis based on whole-genome sequencing contributes to elucidating the genetic markers or putative candidate genes related to some economic traits, facilitating the improvement of production performance, the acceleration of breeding progress, and the conservation of genetic resources. Here, a total of 209 local chickens from 13 breeds were investigated, and the observation of approximately 91.4% high-quality sequences (Q30 > 90%) and a mapping rate over 99% for each individual indicated good results of this study, as confirmed by a genome coverage of 97.6%. Over 19 million single nucleotide polymorphisms (SNPs) and 1.98 million insertion-deletions (InDels) were identified using the reference genome (GRCg7b), further contributing to the public database. This dataset provides valuable resources for studying genetic diversity and adaptation and for the cultivation of new chicken breeds/lines.

Changes in Intestinal Flora and Serum Metabolites Pre- and Post-Antitumor Drug Therapy in Patients with Non-Small Cell Lung Cancer.

OBJECTIVE: this study aimed to identify the relationships between gut microbiota, metabolism, and non-small cell lung cancer (NSCLC) treatment outcomes, which are presently unclear. METHODS: in this single-center prospective cohort study, we investigated changes in the gut microbiota and serum metabolite profile in 60 patients with NSCLC after four cycles of anticancer therapy. RESULTS: The microbial landscape of the gut exhibited a surge in Proteobacteria and Verrucomicrobiota populations, alongside a decline in Firmicutes, Actinobacteriota, and Bacteroidota. Furthermore, a significant shift in the prevalence of certain bacterial genera was noted, with an increase in Escherichia/Shigella and Klebsiella, contrasted by a reduction in Bifidobacterium. Metabolomic analysis uncovered significant changes in lipid abundances, with certain metabolic pathways markedly altered post-treatment. Correlation assessments identified strong links between certain gut microbial genera and serum metabolite concentrations. Despite these findings, a subgroup analysis delineating patient responses to therapy revealed no significant shifts in the gut microbiome's composition after four cycles of treatment. CONCLUSIONS: This study emphasizes the critical role of gut microbiota changes in NSCLC patients during anticancer treatment. These insights pave the way for managing treatment complications and inform future research to improve patient care by understanding and addressing these microbiota changes.

Red blood cell distribution width is associated with sarcopenia risk in early-stage non-small cell lung cancer.

BACKGROUND: Sarcopenia has received increasing attention in non-small cell lung cancer (NSCLC). Red blood cell distribution width (RDW) is a significant component of the complete blood count and indicates the heterogeneity of erythrocyte volume. Little information is known about RDW in relation to sarcopenia in early-stage (IA-IIIA) NSCLC. The purpose of the present study was to investigate the association between RDW and sarcopenia risk in early-stage NSCLC patients. METHODS: This study included 378 patients with pathologically confirmed stage IA-IIIA NSCLC. Sarcopenia was defined by measuring the skeletal muscle index (SMI) at the eleventh thoracic vertebra level. The maximum Youden index on the receiver operating characteristic (ROC) curve was used to estimate the cutoff value for RDW to predict sarcopenia. Logistic regression analyses were carried out to assess the independent risk factors for sarcopenia in NSCLC. RESULTS: The ROC curve indicated that the best cutoff point for RDW to predict sarcopenia was 12.9 (sensitivity of 43.80% and specificity of 76.76%, respectively). Moreover, there were significant differences in hemoglobin (p < 0.001), comorbidities (p = 0.001), histological type (p = 0.002), and cancer stage (p = 0.032) between the high RDW and low RDW groups. Logistic regression analyses revealed that high RDW is an independent risk factor for sarcopenia in early-stage NSCLC. CONCLUSION: RDW is associated with sarcopenia risk in early-stage NSCLC.

Advanced insights on tumor-associated macrophages revealed by single-cell RNA sequencing: The intratumor heterogeneity, functional phenotypes, and cellular interactions.

Single-cell RNA sequencing (scRNA-seq) is an emerging technology used for cellular transcriptome analysis. The application of scRNA-seq has led to profoundly advanced oncology research, continuously optimizing novel therapeutic strategies. Intratumor heterogeneity extensively consists of all tumor components, contributing to different tumor behaviors and treatment responses. Tumor-associated macrophages (TAMs), the core immune cells linking innate and adaptive immunity, play significant roles in tumor progression and resistance to therapies. Moreover, dynamic changes occur in TAM phenotypes and functions subject to the regulation of the tumor microenvironment. The heterogeneity of TAMs corresponding to the state of the tumor microenvironment has been comprehensively recognized using scRNA-seq. Herein, we reviewed recent research and summarized variations in TAM phenotypes and functions from a developmental perspective to better understand the significance of TAMs in the tumor microenvironment.

COX6A2 deficiency leads to cardiac remodeling in human pluripotent stem cell-derived cardiomyocytes.

BACKGROUND: Cardiac remodeling is the initiating factor for the development of heart failure, which can result from various cardiomyopathies. Cytochrome c oxidase subunit 6A2 (COX6A2) is one of the components of cytochrome c oxidase that drives oxidative phosphorylation. The pathogenesis of myocardial remodeling caused by COX6A2 deficiency in humans remains unclear because there are no suitable research models. In this study, we established a COX6A2-deficient human cardiac myocyte (CM) model that mimics the human COX6A2 homozygous mutation and determined the effects of COX6A2 dysfunction and its underlying mechanism. METHODS: A human COX6A2 homozygous knockout cardiomyocyte model was established by combining CRISPR/Cas9 gene editing technology and hiPSC-directed differentiation technology. Cell model phenotypic assays were done to characterize the pathological features of the resulting COX6A2-deficient cardiomyocytes. RESULTS: COX6A2 gene knockout did not affect the pluripotency and differentiation efficiency of hiPSCs. Myocardial cells with a COX6A2 gene knockout showed abnormal energy metabolism, increased oxidative stress levels, abnormal calcium transport activity, and decreased contractility. In addition, L-carnitine and trimetazidine significantly improved energy metabolism in the COX6A2-deficient human myocardial model. CONCLUSIONS: We have established a COX6A2-deficient human cardiomyocyte model that exhibits abnormal energy metabolism, elevated oxidative stress levels, abnormal calcium transport, and reduced contractility. This model represents an important tool to gain insight into the mechanism of action of energy metabolism disorders resulting in myocardial remodeling, elucidate the gene-phenotype relationship of COX6A2 deficiency, and facilitate drug screening.

Cascaded-TOARNet: A cascaded framework based on mixed attention and multiscale information for thoracic OARs segmentation.

BACKGROUND: Accurate and automated segmentation of thoracic organs-at-risk (OARs) is critical for radiotherapy treatment planning of thoracic cancers. However, this has remained a challenging task for four major reasons: (1) thoracic OARs have diverse morphologies; (2) thoracic OARs have low contrast with the background; (3) boundaries of thoracic OARs are blurry; (4) class imbalance issue caused by small organs. PURPOSE: To overcome the above challenges and achieve accurate and automated segmentation of thoracic OARs on thoracic CT. METHODS: A novel cascaded framework based on mixed attention and multiscale information for thoracic OARs segmentation, called Cascaded-TOARNet. This cascaded framework comprises two stages: localization and segmentation. During the localization stage, TOARNet locates each organ to crop the regions of interest (ROIs). During the segmentation stage, TOARNet accurately segments the ROIs, and the segmentation results are merged into a complete result. RESULTS: We evaluated our proposed method and other common segmentation methods on two public datasets: the AAPM Thoracic Auto-Segmentation Challenge dataset and the Segmentation of Thoracic Organs at Risk (SegTHOR) dataset. Our method demonstrated superior performance, achieving a mean Dice score of 92.6% on the SegTHOR dataset and 90.8% on the AAPM dataset. CONCLUSIONS: This segmentation method holds great promise as an essential tool for enhancing the efficiency of thoracic radiotherapy planning.