A multicenter analysis of genomic profiles and PD-L1 expression of primary lymphoepithelioma-like carcinoma of the lung.

To understand the molecular mechanism of tumorigenesis of pulmonary lymphoepithelioma-like carcinoma and explore potential therapeutic strategies, we investigated the genomic profiles and PD-L1 expression of 29 Chinese pulmonary lymphoepithelioma-like carcinoma patients at various stages. We performed capture-based targeted sequencing on tissue samples collected from 27 patients with sufficient samples using a panel consisting of 520 cancer-related genes, spanning 1.64 Mb of the human genome. We identified 184 somatic mutations in 109 genes from 26 patients. One patient had no mutations detected by this panel. Copy number variations were detected in 52% (14/27) of the patients, with a majority having advanced-stage disease (10/14). Except for the detection of ERBB2 amplification and KRAS mutation in two patients, no other classic lung cancer driver mutations were detected. Interestingly, 78% (21/27) of the patients had mutations in epigenetic regulators. Of the 184 mutations identified, 51 occurred in 29 epigenetics-related genes. Furthermore, we performed PD-L1 immunohistochemistry staining using the Dako 22C3 assay and demonstrated that 69% (20/29) of the cohort had positive PD-L1 expression, of which three patients received and benefited from a PD-1 inhibitor. In conclusion, we elucidated a distinct genomic landscape associated with pulmonary lymphoepithelioma-like carcinoma with no classic lung cancer driver mutation but an enrichment of mutations in epigenetic regulators. The detection of high PD-L1 expression and lack of any canonical druggable driver mutations raises the potential of checkpoint immunotherapy for pulmonary lymphoepithelioma-like carcinoma.

Molecular characterization and function analysis of Epinephelus coioides Hsp22 response to SGIV and Vribro alginolyticus infection.

Heat shock protein 22 (Hsp22) is an important regulatory factor response to various stresses in mammals. In this study, the full length cDNA of Epinephelus coioides Hsp22, which was 1680bp in length, with a 289 bp 5' UTR, a 725 bp 3'UTR, and a 666 bp open reading frame encoding 221 amino acids, was obtained. E. coioides Hsp22 contains a highly conserved α-crystallin domain. E. coioides Hsp22 mRNA was detected in all tissues examined by quantitative real-time PCR, with the highest expression in blood, followed by the spleen, skin, gill, head kidney, muscle, heart, liver, trunk kidney, stomach, pyloric caeca, intestine, brain and thymus. The expression patterns of E. coioides Hsp22 response to infection with Singapore grouper iridovirus (SGIV) and Vribro alginolyticus, the important pathogens of E. coioides, were studied. The expression levels of the gene were up-regulated in the tissues examined. Subcellular localization analysis demonstrated that E. coioides Hsp22 was distributed in both the cytoplasm and nucleus. In addition, E. coioides Hsp22 significantly inhibited the SGIV-induced cell apoptosis. In summary, the E. coioides Hsp22 might play a critical role in pathogenic stimulation.

A comparative transcriptomic study on developmental gonads provides novel insights into sex change in the protandrous black porgy (Acanthopagrus schlegelii).

Protandrous black porgy (Acanthopagrus schlegelii) is a popular and valuable commercial marine fish in China and East Asian countries. Controlling and managing its breeding has been an imperative step towards obtaining a sustainable supply of this fish in aquaculture production systems. Therefore, study on the molecular mechanisms of sex change in black porgy has both scientific and commercial importance. Previously, we identified some candidate genes related to sex determination and differentiation from a high-quality genome assembly of the black porgy. In the present study, transcriptome sequencing of developmental gonads (including testis, ovotestis and ovary) of black porgy was performed to further investigate the sex-change mechanisms. Our results showed that the highly expressed male-related genes (dmrt1, piwi1, piwi2, sox9, sox30 and amh) at the male phase were significantly down-regulated to a substantial degree at the intersexual stage, and the female-related genes (jnk1, vasa, wnt4, figla and foxl2) were distinctly up-regulated when the fish grows into a female adult, suggesting the potential roles of these genes in sex change of the black porgy. These data also support a previous hypothesis that the femaleness will be switched on when the testis is entering the degenerated stage through the diminished dmrt1 expression. Our transcriptome data provide a very useful genomic resource for future studies on sex change and practical aquaculture in the black porgy.

Molecular cloning and expression pattern of IGFBP-2a in black porgy (Acanthopagrus schlegelii) and evolutionary analysis of IGFBP-2s in the species of Perciformes.

Insulin-like growth factor-binding protein-2 (IGFBP-2) plays a key role in regulating growth and development by its affinity with insulin-like growth factors (IGFs). In this study, we cloned the coding sequence (CDS) of IGFBP-2a from the black porgy (Acanthopagrus schlegelii) muscle and identified that the full-length CDS of IGFBP-2a was 882 bp. Real-time quantitative PCR revealed that IGFBP-2a was most abundant in the liver of the black porgy and backcross breed (F1♀×black porgy♂) but remained lower in each tested tissue in self-cross breed (F1♀×F1♂). In addition, the IGFBP-2a expression in the liver of three breeds showed a negative correlation with their growth rates, indicating that the IGFBP-2a played a growth-inhibiting role in the three breeds. We further identified 810 bp IGFBP-2b gene from the draft genome of black porgy. Finally, we examined the IGFBP-2a and IGFBP-2b genes by scanning the genomes of the species of Perciformes and found the IGFBP-2 gene duplication took place earlier than the divergence of perciform species. Interestingly, six positively selected sites were detected in both Perciformes IGFBP-2 genes, although both genes were identified to be under purifying selection. Specially, these positively selected sites were located in the functional domains, suggesting these sites played key roles in the growth of Perciformes. Our study partially explains the molecular basis for the prepotency in black porgy hybrids, which will provide guidance for their cultivation in the future.

Smartphone access, digital economy, and pesticide use intensity: Evidence from China.

Pesticide overuse has been an increasing concern in China. Digital technology, such as smartphone access, is considered an effective way to promote proper use of pesticides. Using the Chinese Extended Family Database (2015, 2017, and 2019), this study empirically examines the impact of smartphone access on pesticide use intensity among Chinese farmers. The results show a "double-edged sword" effect of smartphone access on pesticide use intensity. In rural areas with a low level of digital economy, greater smartphone access led to higher pesticide use intensity. In rural areas with a high digital economy level, smartphone access reduced pesticide use intensity. The study results show that reducing pesticide use intensity through digital technology is not a linear process but a complicated one that involves social and engineering integration, including an increase in access to smartphones, development of a regional digital economy, reconstruction of agricultural extension systems, and enhancement of the capacity of digital technology.

Structure and gene expression changes of the gill and liver in juvenile black porgy (Acanthopagrus schlegelii) under different salinities.

Black porgy (Acanthopagrus schlegelii) is an important marine aquaculture species in China. It is an ideal object for the cultivation of low-salinity aquaculture strains in marine fish and the study of salinity tolerance mechanisms in fish because of its strong low-salinity tolerance ability. Gill is the main osmoregulatory organ in fish, and the liver plays an important role in the adaptation of the organism to stressful environments. In order to understand the coping mechanisms of the gills and livers of black porgy in different salinity environments, this study explored these organs after 30 days of culture in hypoosmotic (0.5 ppt), isosmotic (12 ppt), and normal seawater (28 ppt) at histologic, physiologic, and transcriptomic levels. The findings indicated that gill exhibited a higher number of differentially expressed genes than the liver, emphasizing the gill's heightened sensitivity to salinity changes. Protein interaction networks and enrichment analyses highlighted energy metabolism as a key regulatory focus at both 0.5 ppt and 12 ppt salinity in gills. Additionally, gills showed enrichment in ions, substance transport, and other metabolic pathways, suggesting a more direct regulatory response to salinity stress. The liver's regulatory patterns at different salinities exhibited significant distinctions, with pathways and genes related to metabolism, immunity, and antioxidants predominantly activated at 0.5 ppt, and molecular processes linked to cell proliferation taking precedence at 12 ppt salinity. Furthermore, the study revealed a reduction in the volume of the interlamellar cell mass (ILCM) of the gills, enhancing the contact area of the gill lamellae with water. At 0.5 ppt salinity, hepatic antioxidant enzyme activity increased, accompanied by oxidative stress damage. Conversely, at 12 ppt salinity, gill NKA activity significantly decreased without notable changes in liver structure. These results underscore the profound impact of salinity on gill structure and function, highlighting the crucial role of the liver in adapting to salinity environments.

Iron­calcium dual crosslinked graphene oxide/alginate aerogel microspheres for extraordinary elimination of tetracycline in complex wastewater: Performance, mechanism, and applications.

Antibiotics have been considered as a group of emerging contaminants for their stable chemical structure, significant pseudo-persistence, and biological toxicity. Tetracycline (TC), as one of the typical antibiotics frequently detected in environmental media, can cause the dissemination and accumulation of antibiotic resistance gene (ARG), ultimately threatening human health and environmental safety. Herein, a novel iron­calcium di-crosslinked graphene oxide/alginate (GO/SA-Fe3+-Ca2+) aerogel was facilely synthesized for TC uptake. It was found that the introduction of GO nanosheets and Fe3+ sites into composite enormously enhanced TC removal. Specifically, TC can be stably and efficiently eliminated over the wide pH range of 5-8. The fitted maximum qe with Liu isotherm model at 308 K reached 1664.05 mg/g, surpassing almost all reported sorbents. The pseudo-second-order kinetic model with chemical sorption characteristics better fitted TC adsorption process, which was endothermic and spontaneous in nature. Multifarious adsorptive sites of GO/SA-Fe3+-Ca2+ synergically participated in TC uptake through multi-mechanisms (e.g., π-π EDA, cation-π bonding, H-bonding, Fe3+-coordination, and electrostatic attraction, etc.). The as-prepared composite showed satisfactory TC removal in several runs of adsorption-desorption operations, high salinity, and model aquaculture wastewater. Moreover, the packed-column could continuously run for >200 h until adsorption saturation was achieved with a dynamic adsorption capacity of 216.69 mg/g, manifesting its scale-up engineering applications. All above merits make as-constructed composite an alternative sorbent for eliminating TC from complex wastewater.

Neoadjuvant toripalimab combined with axitinib in patients with locally advanced clear cell renal cell carcinoma: a single-arm, phase II trial.

BACKGROUND: A combination of axitinib and immune checkpoint inhibitors (ICIs) demonstrated promising efficacy in the treatment of advanced renal cell carcinoma (RCC). This study aims to prospectively evaluate the safety, efficacy, and biomarkers of neoadjuvant toripalimab plus axitinib in non-metastatic clear cell RCC. METHODS: This is a single-institution, single-arm phase II clinical trial. Patients with non-metastatic biopsy-proven clear cell RCC (T2-T3N0-1M0) are enrolled. Patients will receive axitinib 5 mg twice daily combined with toripalimab 240 mg every 3 weeks (three cycles) for up to 12 weeks. Patients then will receive partial (PN) or radical nephrectomy (RN) after neoadjuvant therapy. The primary endpoint is objective response rate (ORR). Secondary endpoints include disease-free survival, safety, and perioperative complication rate. Predictive biomarkers are involved in exploratory analysis. RESULTS: A total of 20 patients were enrolled in the study, with 19 of them undergoing surgery. One patient declined surgery. The primary endpoint ORR was 45%. The posterior distribution of πORR had a mean of 0.44 (95% credible intervals: 0.24-0.64), meeting the predefined primary endpoint with an ORR of 32%. Tumor shrinkage was observed in 95% of patients prior to nephrectomy. Furthermore, four patients achieved a pathological complete response. Grade ≥3 adverse events occurred in 25% of patients, including hypertension, hyperglycemia, glutamic pyruvic transaminase/glutamic oxaloacetic transaminase (ALT/AST) increase, and proteinuria. Postoperatively, one grade 4a and eight grade 1-2 complications were noted. In comparison to patients with stable disease, responders exhibited significant differences in immune factors such as Arginase 1(ARG1), Melanoma antigen (MAGEs), Dendritic Cell (DC), TNF Superfamily Member 13 (TNFSF13), Apelin Receptor (APLNR), and C-C Motif Chemokine Ligand 3 Like 1 (CCL3-L1). The limitation of this trial was the small sample size. CONCLUSION: Neoadjuvant toripalimab combined with axitinib shows encouraging activity and acceptable toxicity in locally advanced clear cell RCC and warrants further study. TRIAL REGISTRATION NUMBER: clinicaltrials.gov, NCT04118855.

Percutaneous endoscopic gastrostomy placement: caregiver decision making in Taiwan.

BACKGROUND/PURPOSE: To explore Taiwanese caregivers' decision making experiences of accepting a percutaneous endoscopic gastrostomy tube for their family member. METHODS: A phenomenological approach was used for the interview and analysis. Semi-structured, in-depth interviews were conducted with a purposive sample of 26 caregivers of patients who had percutaneous endoscopic gastrostomy tube in southern Taiwan. RESULTS: Five themes were recognized to reflect caregivers' decision making experiences with a percutaneous endoscopic gastrostomy: awareness of suffering, awareness of options, uncertainty, opportunity, and contentment with the decision. CONCLUSION: Caregivers' decisions to proceed with a percutaneous endoscopic gastrostomy procedure were mediated by desires to relieve patients' suffering. To empower caregivers to make enteral feeding decisions, nurses must provide sufficient information about percutaneous gastrostomy tubes and their care, support decision making and help to identify an opportunity for gastrostomy tube placement.

Exploring the Nexus between Moderate-to-Vigorous Physical Activity, Self-Disclosure, Social Anxiety, and Adolescent Social Avoidance: Insights from a Cross-Sectional Study in Central China.

Objectives: Psychological issues among adolescents represent a prevalent challenge in today's society. The purpose of this study is to explore the associations among moderate-to-vigorous physical activity, self-disclosure, social anxiety, and social avoidance in adolescents. Methods: This study collected cross-sectional data from 427 students in eight provincial key junior and senior high schools in the central China region of three provinces using snowball sampling and convenience sampling from July to August 2023. A structural equation model was employed to investigate the relationship between moderate-to-vigorous physical activity and social avoidance among adolescents. Results: The findings indicate that moderate-to-vigorous physical activity is negatively correlated with social anxiety (standardized coefficient = -0.219, p < 0.001) and positively correlated with self-disclosure (standardized coefficient = 0.454, p < 0.001). Social anxiety is negatively correlated with self-disclosure (standardized coefficient = -0.220, p < 0.001). Social avoidance is positively correlated with social anxiety (standardized coefficient = 0.461, p < 0.001) and negatively correlated with self-disclosure (standardized coefficient = -0.331, p < 0.001). Conclusions: The chain-mediated dual-path model between moderate-to-vigorous physical activity and social avoidance is facilitated by social anxiety and self-disclosure. In other words, adolescents who engage in more moderate to high-intensity physical activities exhibit lower levels of social anxiety, and those who have a stronger inclination for self-disclosure tend to demonstrate lower levels of social avoidance. In light of these findings, it is recommended that the government, society, schools, and families collaborate synergistically to promote the holistic well-being of adolescents and advance the development of a healthier China.

HPLC-MS-based untargeted metabolomic analysis of differential plasma metabolites and their associated metabolic pathways in reproductively anosmic black porgy, Acanthopagrus schlegelii.

Olfaction, a universal form of chemical communication, is a powerful channel for animals to obtain social and environmental cues. The mechanisms by which fish olfaction affects reproduction, breeding and disease control are not yet clear. To evaluate metabolites profiles, plasma from anosmic and control black porgy during reproduction was analyzed by non-targeted metabolomics using ultra high-performance liquid chromatography-mass spectrometry and multivariate statistical analysis techniques, including principal component analysis and orthogonal partial least squares discriminant analysis. The metabolite profiles of anosmia and control groups were found to be significantly separated. Ten different differential metabolites, mainly including amino acids, such as isoleucine and methionine, and lipids, such as phosphatidylserine, were screened based on the combined analysis of variable importance in the projection and p values. In addition, six key differential metabolic pathways were analyzed using the Kyoto Encyclopedia of Genes and Genomes and enriched for four metabolic pathways including the citrate acid (TCA) cycle, tyrosine metabolism, arginine and proline metabolism, and arginine synthesis. The TCA cycle enhances fertility through the reduction of pyruvate kinase, and intermediate derivatives (acetyl CoA, malonyl CoA) act as signaling factors that regulate immune cell function. The tyrosine cycle can indirectly participate and promote reproduction in black porgy through melanin-concentrating hormone. Arginine and proline metabolism can promote reproduction by promoting growth hormone and enhance immunity in anosmic black porgy by stimulating T lymphocytes. Our metabolomic study revealed that anosmia in black porgy played an active role in immunity and reproduction and provided theoretical support for breeding and disease control.

Liver Transcriptome Analysis of the Black Porgy (Acanthopagrus schlegelii) under Acute Low-Temperature Stress.

High nutritional value and the development of efficient biotechnological methods of controlled production have made black porgy (Acanthopagrus schlegelii) an economically important fish in Chinese aquaculture in recent years. However, aquaculture production of the species faces multiple issues associated with reduced growth rate, low reproduction ability, and high mortality during production, which are associated with the species' limited tolerance to low temperatures. To date, comprehensive information on the genetic-based mechanisms of cold tolerance and adaptation to low temperature in the species are still unavailable. In this study, the HiSeq™2500 (Illumina) sequencing platform was used to analyze the transcriptomic profile of the liver tissue in the black porgy subjected to different extents of cold shock, including a control temperature group (AS, T = 15 °C), an intermediate temperature group (AL1, T = 10 °C), and an acute low-temperature stress group (AL2, T = 5 °C). For this purpose, three standardized cDNA libraries of AS, AL1, and AL2 were established. We obtained 43,258,908, 48,239,072, and 38,983,833 clean reads from the AS group, AL1 group, and AL2 group, respectively. After pairwise comparison, 70 differentially expressed genes (DEGs) were identified in the examined fish groups. Among them, 60 genes were found to be significantly differentially expressed after trend analysis. GO annotation and enrichment results showed that they were mainly enriched into three categories: biological processes (12 subcategories), molecular functions (7 subcategories), and cellular components (7 subcategories). KEGG analysis results indicated that all significantly differentially expressed genes were annotated to 102 signaling pathways, including biological rhythm, cholesterol metabolism, glycerolipid metabolism, animal autophagy, FoxO signaling pathway, steroid biosynthesis, and regulation of adipocyte lipolysis and apoptosis. Four of them, namely: G6PC, GPX1, GCK, and HSPE1 were randomly selected for further qRT-PCR verification of data reliability obtained by RNA-Seq technology. In this study, we found that environmental acute cold stress mainly affected the black porgy's biological processes related to metabolism, apoptosis, and signal transduction. The data that we have reported provides baseline information for further studies concerning the genetic responses of the black porgy under cold stress conditions, the improvement of its aquaculture production, and other economically important matters regarding their limited tolerance to cold shock.

Comparative Proteomics of the Acanthopagrus schlegelii Gonad in Different Sex Reversal.

A substantial proportion of Acanthopagrus schlegelii individuals change sex from male to female during their lifetime. However, the mechanisms underlying sex change are unknown. In this research, iTRAQ analyses of proteins obtained from A.schlegelii gonads in four different stages of development were compared. In total, 4692 proteins were identified, including common sex-specific proteins, such as sperm-associated antigen 6 and cilia- and flagella-associated proteins in males, and zona pellucida sperm-binding proteins in females. Furthermore, proteins involved in the integrin signaling pathway, inflammation mediated by the chemokine and cytokine signaling pathways, pyruvate metabolism, CCKR signaling map, de novo purine biosynthesis and the ubiquitin proteasome pathway were upregulated in female gonads, whereas proteins implicated in DNA replication, the heterotrimeric G-protein signaling pathway, Gi alpha- and Gs alpha-mediated pathways, wnt signaling pathway, and hedgehog signaling pathway were upregulated in male gonads. Interestingly, cathepsins were only identified in ovaries, indicating their potential involvement in rapid ovarian development. Apoptosis-related proteins expressed in ovaries (such as MAPK and Cdc42) may protect them from cancer. This is the first report on the gonad proteome from A.schlegelii in different stages of sex reversal, and the results provide important fundamental data for studying the molecular mechanisms of sex reversal.

Effects of lüfukang capsules on coronary artery ligation-induced arrhythmia in dogs.

OBJECTIVE: To observe the effects of Lüfukang Capsules on arrhythmia induced by ligation of coronary artery in dogs. METHODS: Thirty dogs were randomly divided into 5 groups, the model group administrated with equal volume of distilled water, the positive control group administrated with Wenxin Granules, and the small, medium and large dosage LFKC groups, 6 dogs in each group. Thirty minutes after medication, electrocardiogram was conducted and the time of arrhythmia occurrence, times of ventricular premature beat (VP), and incidence rates of ventricular tachycardia (VT) and ventricular fibrillation (VF) were recorded in the model dogs with arrhythmia induced by ligation of coronary artery. RESULTS: Compared with the model group, the occurrence time of arrhythmia induced by the coronary artery ligation in the medium and large LFKC groups was significantly delayed (20.45 +/- 9.10 and 19.92 +/- 3.78, respectively, both P < 0.05). The frequency of VP in the medium and large LFKC groups was also significantly decreased (8.17 +/- 6.62 and 3.83 +/- 2.79, respectively, both P < 0.01). CONCLUSION: LFKC has anti-arrhythmic effects for the experimental arrhythmia induced by the ligation of coronary artery in dogs.

Combination therapy of first and third generation EGFR-TKIs for an advanced lung adenocarcinoma patient harboring EGFR mutations and amplification: a case report.

The paradigm for the pharmacological management of advanced non-small cell lung cancer (NSCLC) has been revolutionized by the development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Developing resistance to target therapy is unavoidable. Mostly, treatments for single molecular alteration after acquiring EGFR-TKI treatment resistance are well studied. However, there is limited evidence of treatment strategies for complex resistance mechanisms. Presented here is a case of an EGFR-mutated NSCLC patient who developed a complex resistance profile: T790M point mutation and EGFR amplification after first-line EGFR-TKI. This patient was safely treated with a combination of osimertinib and icotinib and achieved a significant clinical response and clear molecular response. Here we present the clinical evidence of the efficacy of osimertinib combined with icotinib in the treatment of EGFR classical mutation along with resistant mutation of T790M point mutation and EGFR amplification.

A first case report of clinical response to targeted therapy in a patient with primary myoepithelial carcinoma of the lung harboring EGFR exon 19 deletion.

BACKGROUND: Primary myoepithelial carcinoma of the lung is a rare subtype in lung cancer. Comprehensive molecular profiling of myoepithelial carcinoma of the lung is absent, neither was clinical evidence of targeted therapy available for this disease. Therefore, the optimal treatment regimen of this tumor needs to be established. CASE PRESENTATION: Here we present a case of a 68-year-old patient with stage IVB primary myoepithelial carcinoma of the lung who harbored EGFR exon 19 deletion and KRAS mutation and underwent icotinib targeted therapy, achieving partial response (PR) with progression free survival (PFS) of 3 months. CONCLUSION: To our knowledge, this study describes the first documented case of primary myoepithelial carcinoma lung cancer patient harboring EGFR exon 19 deletion and KRAS mutation, and showed clinical efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) treatment in this patient.

Integrated histological and molecular analyses of rebiopsy samples at osimertinib progression improve post-progression survivals: A single-center retrospective study.

BACKGROUND: This single-center retrospective cohort study sought to investigate the impact of rebiopsy analysis after osimertinib progression in improving the survival outcomes. METHODS: Eighty-nine patients with EGFR T790M-positive advanced NSCLC who received second- or further-line osimertinib between January 2017 and July 2019 were included in this study. The co-primary study endpoints were post-progression progression-free survival (pPFS), defined as the time from osimertinib progression until progression from further-line treatment, and post-progression overall survival (pOS), defined as the time from osimertinib progression until death or the last follow-up date. RESULTS: Pairwise analysis revealed that receiving targeted therapy as further-line treatment after osimertinib progression did not statistically improve the pPFS (P = 0.285) or the pOS (P = 0.903) compared to chemotherapy. However, patients who submitted rebiopsy samples at osimertinib progression for histological and molecular analyses, particularly those who had actionable markers and received highly matched therapy, had significantly longer pPFS and pOS as compared to those who received low-level matched therapy (pPFS = 10.0 m vs. 4.1 m, P = 0.005; pOS = 19.4 m vs. 10.0 m, P = 0.023), unmatched therapy (pPFS = 10.0 m vs. 4.7 m, P = 0.009; pOS = 19.4 m vs. 7.0 m, P = 0.001), and those without rebiopsy data (Rebiopsy vs Non-rebiopsy; pPFS = 6.1 m vs. 3.3 m, P = 0.014; pOS = 11.7 m vs. 6.8 m, P = 0.011). CONCLUSION: Our real-world cohort study demonstrates that integrated histological and molecular analyses of rebiopsy specimens after osimertinib progression could provide more opportunities for individualized treatments to improve the post-progression survival of patients with advanced NSCLC. Our findings provide clinical evidence that supports the inclusion of NGS-based analysis of rebiopsy specimens as standard-of-care after osimertinib progression and warrants further prospective evaluation.

The complete mitochondrial genome of the hybrid of Acanthopagrus schlegelii (♀) × Pagrus major (♂) with phylogenetic analysis.

In this study, we firstly determined the complete mitochondrial DNA sequence of the hybrid of Acanthopagrus schlegelii (♀)×Pagrus major (♂) using the next-generation sequencing and Polymerase Chain Reaction-based method (PCR). The total length of the hybrid mitochondrial genome was identical to the female parent as 16,649 bp in length, which contained 13 protein-coding genes (PCGs), two ribosomal RNA genes, 22 transfer RNA genes, and one displacement loop locus (a control region). The overall nucleotide composition is: 28.0%A, 27.9%T, 27.9%C, and 16.2%G, with a total A + T content of 45.9%. This study discovered the 99.8% sequence identity between the hybrid and its female parent, which confirmed the maternal inheritance pattern followed by the mitochondrial genome of the hybrid. The complete mitochondrial genome sequence of this hybrid sea bream may provide a valuable and useful resource for population genetic study and monitoring, and as well as for further conservation effort on this species.

Draft genome of the protandrous Chinese black porgy, Acanthopagrus schlegelii.

Background: As one of the most popular and valuable commercial marine fishes in China and East Asian countries, the Chinese black porgy (Acanthopagrus schlegelii), also known as the blackhead seabream, has some attractive characteristics such as fast growth rate, good meat quality, resistance to diseases, and excellent adaptability to various environments. Furthermore, the black porgy is a good model for investigating sex changes in fish due to its protandrous hermaphroditism. Here, we obtained a high-quality genome assembly of this interesting teleost species and performed a genomic survey on potential genes associated with the sex-change phenomenon. Findings: We generated 175.4 gigabases (Gb) of clean sequence reads using a whole-genome shotgun sequencing strategy. The final genome assembly is approximately 688.1 megabases (Mb), accounting for 93% of the estimated genome size (739.6 Mb). The achieved scaffold N50 is 7.6 Mb, reaching a relatively high level among sequenced fish species. We identified 19 465 protein-coding genes, which had an average transcript length of 17.3 kb. By performing a comparative genomic analysis, we found 3 types of genes potentially associated with sex change, which are useful for studying the genetic basis of the protandrous hermaphroditism. Conclusions: We provide a draft genome assembly of the Chinese black porgy and discuss the potential genetic mechanisms of sex change. These data are also an important resource for studying the biology and for facilitating breeding of this economically important fish.