Ultrahigh bandwidth measuring approach of an I-FOG based on axial magnetic sensitivity.

The bandwidth is one of the key indicators of the interferometric fiber optic gyroscope (I-FOG) in the application with high frequency jitter. The traditional bandwidth measurement equipment, such as the angular vibration table, can only provide angular vibrations of hundreds of hertz and cannot meet the measurement needs of a high bandwidth gyro. We propose an approach, with which a signal of several thousand hertz can be provided and can measure a high bandwidth of I-FOGs. The bandwidth measurement approach is based on the axial magnetic sensitivity. We present the measurement principle, derive the axial magnetic sensitivity expression of the fiber coil in I-FOGs, and demonstrate the bandwidth measuring system. With this system, the bandwidth of an I-FOG is measured and the experimental result shows that the bandwidth is ∼10 kHz. It is proved that this new, to the best of our knowledge, approach is capable of testing the bandwidth of the I-FOG at ultrahigh frequencies.

Comparative mitogenome analyses uncover mitogenome features and phylogenetic implications of the subfamily Cobitinae.

BACKGROUND: Loaches of Cobitinae, widely distributed in Eurasian continent, have high economic, ornamental and scientific value. However, the phylogeny of Cobitinae fishes within genera or family level remains complex and controversial. Up to now, about 60 Cobitinae mitogenomes had been deposited in GenBank, but their integrated characteristics were not elaborated. RESULTS: In this study, we sequenced and analyzed the complete mitogenomes of a female Cobits macrostigma. Then we conducted a comparative mitogenome analysis and revealed the conserved and unique characteristics of 58 Cobitinae mitogenomes, including C. macrostigma. Cobitinae mitogenomes display highly conserved tRNA secondary structure, overlaps and non-coding intergenic spacers. In addition, distinct base compositions were observed among different genus and significantly negative linear correlation between AT% and AT-skew were found among Cobitinae, genus Cobitis and Pangio mitogenomes, respectively. A specific 3 bp insertion (GCA) in the atp8-atp6 overlap was identified as a unique feature of loaches, compared to other Cypriniformes fish. Additionally, all protein coding genes underwent a strong purifying selection. Phylogenetic analysis strongly supported the paraphyly of Cobitis and polyphyly of Misgurnus. The strict molecular clock predicted that Cobitinae might have split into northern and southern lineages in the late Eocene (42.11 Ma), furthermore, mtDNA introgression might occur (14.40 Ma) between ancestral species of Cobitis and ancestral species of Misgurnus. CONCLUSIONS: The current study represents the first comparative mitogenomic and phylogenetic analyses within Cobitinae and provides new insights into the mitogenome features and evolution of fishes belonging to the cobitinae family.

Glochidiol, a natural triterpenoid, exerts its anti-cancer effects by targeting the colchicine binding site of tubulin.

Glochidiol has been shown to have potentially antiproliferative activity in vitro, however its anticancer mechanisms specifically against lung cancer remain unknown. This study aimed to investigate the anti-lung cancer effects of glochidiol in HCC-44 cells in vitro and in vivo. In the present study, glochidiol was found to have potent antiproliferative activity against lung cancer cell lines NCI-H2087, HOP-62, NCI-H520, HCC-44, HARA, EPLC-272H, NCI-H3122, COR-L105 and Calu-6 with IC50 values of 4.12 µM, 2.01 µM, 7.53 µM, 1.62 µM, 4.79 µM, 7.69 µM, 2.36 µM, 6.07 µM and 2.10 µM, respectively. In vivo, glochidiol was found to effectively inhibit lung cancer HCC-44 xenograft tumor growth in nude mice. Docking analysis found that glochidiol forms hydrogen bonds with residues of tubulin. Glochidiol was also found to inhibit tubulin polymerization in vitro with an IC50 value of 2.76 µM. Immunofluorescence staining and EBI competition assay suggest that glochidiol may interact with tubulin by targeting the colchicine binding site. Thus, glochidiol might be a novel colchicine binding site inhibitor with the potential to treat lung cancer.

In situ detection of plasma exosomal microRNA for lung cancer diagnosis using duplex-specific nuclease and MoS2 nanosheets.

MicroRNAs (miRNAs) encapsulated in tumor-derived exosomes are becoming ideal biomarkers for the early diagnosis and prognosis of lung cancer. However, the accuracy and sensitivity are often hampered by the extraction process of exosomal miRNA using traditional methods. Herein, this study developed a fluorogenic quantitative detection method for exosomal miRNA using the fluorescence quenching properties of molybdenum disulfide (MoS2) nanosheets and the enzyme-assisted signal amplification properties of duplex-specific nuclease (DSN). First, a fluorescently-labeled nucleic acid probe was used to hybridize the target miRNA to form a DNA/RNA hybrid structure. Under the action of the DSN, the DNA single strand in the DNA/RNA hybrid strand was selectively digested into smaller oligonucleotide fragments. At the same time, the released miRNA target triggers the next reaction cycle, so as to achieve signal amplification. Then, MoS2 was used to selectively quench the fluorescence of the undigested probe leaving the fluorescent signal of the fluorescently-labeled probe fragments. The fluorometric signals for miRNA-21 had a maximum excitation/emission wavelength of 488/518 nm. Most importantly, the biosensor was then applied for the accurate quantitative detection of miRNA-21 in exosome lysates extracted from human plasma and this method was able to successfully distinguish lung cancer patients from healthy people. This biosensor provides a simple, rapid, and a highly specific quantitative method for exosomal miRNA and has promising potential to be used in the early diagnosis of lung cancer.

Modified homodyne laser interferometer based on phase modulation for simultaneously measuring displacement and angle.

Many researchers from scientific and industrial fields have devoted their efforts to the laser interferometer, aiming to improve the measurement accuracy and extend the practical applications. Here, we present a modified homodyne laser interferometer based on phase modulation for simultaneously measuring displacement and angle. The active sawtooth wave phase modulation enhances immunity of this interferometer to the environmental fluctuations and laser power drift. Based on polarized optic theory and the sinusoidal measurement retro-reflector, a modified Michelson-type interferometer configuration is designed to simultaneously measure displacement and angle. Phase difference between the reference and measurement interference signals can be obtained using the sawtooth wave phase modulation and zero crossing detection technique, where the real-time displacement and angle values can be derived directly. Experimental results demonstrate our proposed interferometer has good static and dynamic performance.

Sinusoidal Phase-Modulated Angle Interferometer for Angular Vibration Measurement.

Primary angular vibration calibration devices based on laser interferometers play a crucial role in evaluating the dynamic performance of inertial sensing devices. Here, we propose a sinusoidal phase-modulated angle interferometer (SPMAI) to realize angular vibration measurements over a frequency range of 1-1000 Hz, in which the sinusoidal measurement retro-reflector (SMR) and the phase generation carrier (PGC) demodulation algorithm are adopted to track the dynamic angle variation. A comprehensive theoretical analysis is presented to reveal the relationship between demodulation performance of the SPMAI and several factors, such as phase modulation depth, carrier phase delay and sampling frequency. Both the simulated and experimental results demonstrate that the proposed SPMAI can achieve an angular vibration measurement with amplitude of sub-arcsecond under given parameters. Using the proposed SPMAI, the frequency bandwidth of an interferometric fiber-optic gyroscope (IFOG) is successfully determined to be 848 Hz.

Molecular characterization and functional analysis of the vitellogenin receptor in the rice stem borer, Chilo suppressalis.

As a member of the low-density lipoprotein receptor (LDLR) superfamily, vitellogenin (Vg) receptor (VgR) is responsible for the uptake of Vg into developing oocytes and is a potential target for pest control. Here, a full-length VgR complementary DNA (named as CsVgR) was isolated and characterized in the rice stem borer, Chilo suppressalis. The composite CsVgR gene contained an open reading frame of 5,484 bp encoding a protein of 1,827 amino acid residues. Structural analysis revealed that CsVgR contained two ligand-binding domains (LBDs) with four Class A (LDLRA ) repeats in LBD1 and seven in LBD2, which was structurally different from most non-Lepidopteran insect VgRs having five repeats in LBD1 and eight in LBD2. The developmental expression analysis showed that CsVgR messenger RNA expression was first detectable in 3-day-old pupae, sharply increased in newly emerged female adults, and reached a peak in 2-day-old female adults. Consistent with most other insects VgRs, CsVgR was exclusively expressed in the ovary. Notably, injection of dsCsVgR into late pupae resulted in fewer follicles in the ovarioles as well as reduced fecundity, suggesting a critical role of CsVgR in female reproduction. These results may contribute to the development of RNA interference-mediated disruption of reproduction as a control strategy of C. suppressalis.

Light depolarization based on dispersion degree of polarization.

The dispersion degree of polarization, a new definition of the depolarization degree of partially polarized beams, is first proposed, to the best of our knowledge, to measure the performance of fiber depolarizers. First, the description of the polarization based on the Poincaré sphere is introduced. Then, the modified Delaunay triangulation algorithm is introduced, and the calculation formula of the dispersion degree of polarization is given based on this algorithm. The experimental device was set up, and the dispersion degree of polarization of the depolarized light after the fiber depolarizer was measured to be 47.3%. The components and proportions of polarization in the depolarized light were also obtained. Compared with the degree of polarization, the dispersion degree of polarization can quantitatively analyze the light polarization evaluation in the time dimension and provide a numerical reference for improving the depolarizer, thus increasing the fiber sensor's accuracy.

Expression of UBE2C in lung adenocarcinoma based on database analysis and its clinical significance. / 基于数据库挖掘UBE2Cåœ¨è‚ºè ºç™Œä¸­çš„è¡¨è¾¾åŠå ¶ä¸´åºŠæ„ä¹‰.

OBJECTIVES: To analyze the expression level of ubiquitin conjugating enzyme E2C (UBE2C) in lung adenocarcinoma and its clinical significance. METHODS: The differences in mRNA and protein expression levels of UBE2C in normal lung tissues and lung adenocarcinoma (LUAD) tissues were determined with the Cancer Genome Atlas (TCGA), Oncomine, and human protein atlas (HPA) databases. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of UBE2C in LUAD. The correlation between UBE2C and LUAD clinicopathological parameters, as well as its relationship with LUAD prognosis was analyzed based on TCGA, International Cancer Genome Consortium (ICGC), and cbioPortal databases. Gene set enrichment analysis (GSEA) was used to analyze the possible pathways of UBE2C in the progression of LUAD. RESULTS: The mRNA expression level of UBE2C was higher in LUAD tissues than in the normal lung tissues (P<0.01) and it was positively correlated with TNM and N stages (both P<0.05). The UBE2C protein expression level was also increased in LUAD tissues than in the normal lung tissues (P<0.01). ROC curve analysis indicated that UBE2C could be used as an auxiliary diagnostic index for LUAD (AUC=0.969, 95% CI 0.953 to 0.984, P<0.01). Survival analysis showed that the overall survival (OS) of UBE2C high expression group was significantly lower than that of low expression group (P<0.05). The OS of LUAD patients with UBE2C change was lower than that of patients without change (P<0.01). UBE2C was highly expressed in the gene set relevant to cell cycle, p53 signaling pathway, DNA mismatch repair, and DNA replication (all P<0.01). CONCLUSIONS: The expression level of UBE2C is significantly up-regulated in LUAD tissues. The high expression or genetic alteration of UBE2C indicates poor prognosis in LUAD patients. UBE2C can be used as a potential molecular diagnostic marker for LUAD and a potential target for LUAD treatment.

Molecular characterization of glutamate-gated chloride channel and its possible roles in development and abamectin susceptibility in the rice stem borer, Chilo suppressalis.

Glutamate-gated chloride channels (GluCls) mediate fast inhibitory neurotransmission in invertebrate nervous systems, and are of considerable interest in insecticide discovery. The full length cDNA encoding CsGluCl was cloned from the rice stem borer Chilo suppressalis (Walker). Multiple cDNA sequence alignment revealed three variants of CsGluCl generated by alternative splicing of exon 3 and exon 9. While all the transcripts were predominantly expressed in both nerve cord and brain, the expression patterns of these three variants differed among other tissues and developmental stages. Specifically, the expression level of CsGluCl C in cuticle was similar to that in nerve cord and brain, and was the predominant variant in late pupae and early adult stages. Both injection and oral delivery of dsGluCl significantly reduced the mRNA level of CsGluCl. Increased susceptibility to abamectin and reduced larvae growth and pupation rate were observed in dsGluCl-treated larvae. Thus, our results provide the evidence that in addition to act as the target of abamectin, GluCls also play important physiological roles in the development of insects.

Research on the Frequency-Dependent Halfwave Voltage of a Multifunction Integrated Optical Chip in an Interferometric Fiber Optic Gyroscope.

The multifunction integrated optical chip (MIOC) is one of the most critical parts of the interferometric fiber optic gyroscope (IFOG), and research on the halfwave voltage of the MIOC is meaningful for a high-precision IFOG. In this paper, the correlation between the frequency and halfwave voltage, which affects the interference light intensity of IFOG, is presented theoretically. A widespread measurement method for frequency dependence of the halfwave voltage, based on lock-in amplification and sinusoidal modulation, is proposed. Further, the measurement result and the oscillation of interference light intensity in the Sagnac interferometer are presented, which are in great agreement with the theory. This paper proposes the frequency dependence of the halfwave voltage and provides a new error research direction for the improvement of the MIOC in a high-precision IFOG.

Effects of mechanical ventilation with different tidal volume on oxidative stress and antioxidant in lung.

PURPOSE: The aim of this study was to investigate the changes in oxidative stress and antioxidants in lung tissue under different tidal volume ventilation conditions. METHODS: Forty-eight male Wistar rats were randomized into four groups, namely, group C, the control group, which was not ventilated, and groups C1, C2 and C3, the treatment groups, which were ventilated for 2 h with tidal volumes of 8, 30 and 42 ml/kg, respectively. The right middle lobe was assayed for malondialdehyde (MDA), the right posterior lobe was assayed using Western blotting for Nrf2, GCLm and SrX1 and the left lobe was assayed for Nrf2, GCLm and SrX1 mRNA. RESULTS: The MDA levels were increased in the three treatment groups, with MDA levels highest in group C3 and lowest in group C1 (C3 > C2 > C1) (all P < 0.05). The mRNA expression of Nrf2, GCLm and SrX1 was highest in group C3 and lowest in group 1 (C3 > C2 > C1) (all P < 0.05). No significant difference was observed between group C1 and group C (P > 0.05). A Western blot analysis showed that Nrf2, GCLm and SrX1 expression was highest in group C3 and lowest in group C1 (C3 > C2 > C1) (all P < 0.05). No significant difference was observed between group C1 and group C (P > 0.05). CONCLUSIONS: Oxidative stress and antioxidant enzyme levels in the lungs of rats were positively associated with the tidal volumes of mechanical ventilation, suggesting that higher tidal volumes cause more severe oxidative stress and increased antioxidant responses.

Stat3 inhibits Beclin 1 expression through recruitment of HDAC3 in nonsmall cell lung cancer cells.

Recent studies have shown that Beclin 1, a key regulator of autophagic process, is frequently downregulated and may serve as an independent prognostic biomarker for nonsmall cell lung cancer. However, the molecular mechanisms underlying its downregulation remain poorly understood. The signal transducer and activator of transcription 3 (Stat3) is a transcription factor which plays a crucial role for multiple tumor growth and progression. Here, we demonstrate that Beclin 1 is a direct transcriptional target of Stat3 in lung cancer cells. Interleukin-6 (IL-6) treatment or transfection of a constitutively activated Stat3 in AGS and NCI-H1650 cells inhibited Beclin 1 expression. At the molecular level, we further revealed that Stat3 could directly bind to the promoter region of Beclin 1 and repressed its transcription through recruiting histone deacetylase 3 (HDAC3). Collectively, our results suggest that the activated Stat3 may represent an important mechanism for Beclin 1 downregulation in nonsmall cell lung cancer development.

Diagnostic accuracy and microbial profiles of tuberculous pleurisy: a comparative study of metagenomic next generation sequencing and GeneXpert Mycobacterium tuberculosis.

Introduction: There is a clinical challenge in diagnosing tuberculous pleurisy accurately and promptly, highlighting the urgent need for a rapid and sensitive diagnostic method. This study aimed to evaluate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) and GeneXpert Mycobacterium tuberculosis (MTB) for identifying tuberculous pleurisy and analyzing the microbial profiles of both tuberculous and non-tuberculous pleural effusions. Methods: The study enrolled 31 patients with suspected tuberculous pleurisy, of which 15 were confirmed to have tuberculous pleurisy and subsequently allocated to the tuberculous pleurisy group (TP group), while the remaining 16 individuals were assigned to the non-tuberculous pleurisy group (NTP group). mNGS and GeneXpert MTB were performed on pleural effusion samples, and the diagnostic accuracy of both tests was compared. We employed established formulas to compute crucial indicators, including sensitivity, specificity, missed diagnosis rate, misdiagnosed rate, positive predictive value (PPV), and negative predictive value (NPV). Results: The results showed that both tests had high specificity (100%) and positive predictive value (100%) for detecting tuberculous pleurisy, along with comparable sensitivity (46.67% for mNGS and 40.0% for GeneXpert MTB). Further analysis of the combined efficacy of mNGS and GeneXpert MTB showed that the combined test had a sensitivity of 66.67% and a specificity of 100%. mNGS analysis revealed that MTB was detected in 7 out of 15 patients with tuberculous pleural effusions, while non-tuberculous pleural effusions were associated with a diverse range of microbial genera and species. The most frequently detected genera at the microbial genus level in the NTP group were Microbacterium spp. (6/16), Prevotella spp. (5/16), and Campylobacter spp. (5/16). Discussion: These findings suggest that mNGS and GeneXpert MTB are useful diagnostic tools for identifying patients with tuberculous pleurisy, and mNGS can provide valuable insights into the microbial profiles of both tuberculous and non-tuberculous pleural effusions.

Pathogenesis of sarcopenia in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common pulmonary disease characterized by persistent respiratory symptoms and airflow obstruction. In addition to lung diseases, chronic obstructive pulmonary disease (COPD) is often associated with other organ diseases, and sarcopenia is one of the common diseases. In recent years, multiple factors have been proposed to influence muscle dysfunction in COPD patients, including systemic and local inflammation, oxidative stress, hypoxia, hypercapnia, protein synthesis, catabolic imbalance, nutritional changes, disuse, ageing, and the use of medications such as steroids. These factors alone or in combination can lead to a reduction in muscle mass and cross-sectional area, deterioration of muscle bioenergy metabolism, defects in muscle repair and regeneration mechanisms, apoptosis and other anatomical and/or functional pathological changes, resulting in a decrease in the muscle's ability to work. This article reviews the research progress of possible pathogenesis of sarcopenia in COPD.

Investigating the evolution process of lung adenocarcinoma via random walk and dynamic network analysis.

Lung adenocarcinoma (LUAD) is a typical disease regarded as having multi-stage progression. However, many existing methods often ignore the critical differences among these stages, thereby limiting their effectiveness for discovering key biological molecules and biological functions as signals at each stage. In this study, we propose a method to discover the evolution between biological molecules and biological functions by investigating the multi-stage biological molecules of LUAD. The method is based on the random walk algorithm and the Monte Carlo method to generate clusters as the modules, which were used as subgraphs of the differentiated biological molecules network in each stage. The connection between modules of adjacent stages is based on the measurement of the Jaccard coefficient. The online gene set enrichment analysis tool (DAVID) was used to obtain biological functions corresponding to the individual important modules. The core evolution network was constructed by combining the aforementioned two networks. Since the networks here are all dynamic, we also propose a strategy to visualize the dynamic information together in one network. Eventually, 12 core modules and 11 core biological functions were found through such evolutionary analyses. Among the core biological functions that we obtained, six functions are related to the disease, the biological function of neutrophil chemotaxis is not directly associated with LUAD but can serve as a predictor, two functions may serve as a predictive signal, and two functions need to be verified through more biological evidence. Compared with two alternative design methods, the method proposed in this study performed more efficiently.

Machine learning-assisted prediction of pneumonia based on non-invasive measures.

Background: Pneumonia is an infection of the lungs that is characterized by high morbidity and mortality. The use of machine learning systems to detect respiratory diseases via non-invasive measures such as physical and laboratory parameters is gaining momentum and has been proposed to decrease diagnostic uncertainty associated with bacterial pneumonia. Herein, this study conducted several experiments using eight machine learning models to predict pneumonia based on biomarkers, laboratory parameters, and physical features. Methods: We perform machine-learning analysis on 535 different patients, each with 45 features. Data normalization to rescale all real-valued features was performed. Since it is a binary problem, we categorized each patient into one class at a time. We designed three experiments to evaluate the models: (1) feature selection techniques to select appropriate features for the models, (2) experiments on the imbalanced original dataset, and (3) experiments on the SMOTE data. We then compared eight machine learning models to evaluate their effectiveness in predicting pneumonia. Results: Biomarkers such as C-reactive protein and procalcitonin demonstrated the most significant discriminating power. Ensemble machine learning models such as RF (accuracy = 92.0%, precision = 91.3%, recall = 96.0%, f1-Score = 93.6%) and XGBoost (accuracy = 90.8%, precision = 92.6%, recall = 92.3%, f1-score = 92.4%) achieved the highest performance accuracy on the original dataset with AUCs of 0.96 and 0.97, respectively. On the SMOTE dataset, RF and XGBoost achieved the highest prediction results with f1-scores of 92.0 and 91.2%, respectively. Also, AUC of 0.97 was achieved for both RF and XGBoost models. Conclusions: Our models showed that in the diagnosis of pneumonia, individual clinical history, laboratory indicators, and symptoms do not have adequate discriminatory power. We can also conclude that the ensemble ML models performed better in this study.

Relationship between tumor mutational burden, gene mutation status, and clinical characteristics in 340 cases of lung adenocarcinoma.

Tumor mutational burden (TMB) is an emerging predictive marker of response to immune checkpoint inhibitor therapies. We evaluated the correlation between clinical indicators and high-throughput sequencing results and TMB in lung adenocarcinoma patients, with the aim of finding simpler and more economical factors as surrogate markers for TMB. The medical records, next-generation sequencing data, and immunohistochemistry results of 340 lung adenocarcinoma patients who were admitted to the First Affiliated Hospital of Zhengzhou University between 2019 and 2020 were collected. The mutated genes were screened for, and the obtained mutated genes were subjected to functional enrichment analysis using R software. A protein-protein interaction (PPI) network was also constructed, and significant modules in the network were identified. Gene Ontology (GO) analyses were performed for the core genes. Univariate and multivariate correlation analyses were performed to judge the correlation between gene mutations and TMB. Genes with a junction mutation rate >1 were selected to construct PPI network and 13 high-connection core genes were screened. The results of GO enrichment analysis showed that the biological processes related to mutant core genes mainly included mitotic cell cycle and cell aging. Subsequently, ATM (p = 0.006) and PIK3CA (p = 0.008) mutation positivity were identified by univariate and multivariate correlation analysis, while TP53 (p = 0.003) and EGFR (p = 0.008) mutation negativity were significantly associated with elevated TMB. The results of this study demonstrate that ATM- and PIK3CA-positive and EGFR-negative mutation status are strongly associated with high levels of TMB and have the potential to be predictive biomarkers of response to immune checkpoint inhibitors in lung adenocarcinoma patients.

Intracranial complete response to toripalimab and anlotinib in a patient with recurrent brain metastases of small cell lung cancer after failure of second-line maintenance therapy: a case report.

Background: Approximately 10-25% of patients with small cell lung cancer (SCLC) have brain metastases at the time of diagnosis. Radiotherapy is a common treatment for brain metastases, but the relapse rates are high. Accumulating evidence suggests that immunotherapy may have a better therapeutic effect for brain metastases. Here, we reported a patient with limited-stage SCLC and relapsed brain metastases who achieved sustained intracranial complete response (CR) to programmed cell death-1 (PD-1) inhibitor toripalimab and multikinase inhibitor anlotinib. Case Description: A 59-year-old female patient developed brain metastases after initial treatment for limited stage SCLC. CR of brain lesions was achieved after intensity-modulated radiation therapy followed by chemotherapy with irinotecan plus lobaplatin and concurrent anlotinib. PD-1 inhibitor sintilimab combined with anlotinib were given as maintenance therapy. Small and asymptomatic brain lesions relapsed 2.5 months after achieving CR. Another three cycles of sintilimab combined with anlotinib failed to control the relapsed brain lesions. Following two cycles of another PD-1 inhibitor toripalimab combined with anlotinib, the relapsed brain metastases disappeared. Then the patient received another seven cycles of this regimen with sustained CR, and no serious adverse reactions occurred. Interestingly, the primary lung tumor achieved sustained CR from the end of initial treatment to the last follow-up. Conclusions: This case suggests that toripalimab in combination with anlotinib may be a promising treatment option for patients with brain metastases from SCLC.

Comparative genome anatomy reveals evolutionary insights into a unique amphitriploid fish.

Triploids are rare in nature because of difficulties in meiotic and gametogenic processes, especially in vertebrates. The Carassius complex of cyprinid teleosts contains sexual tetraploid crucian carp/goldfish (C. auratus) and unisexual hexaploid gibel carp/Prussian carp (C. gibelio) lineages, providing a valuable model for studying the evolution and maintenance mechanism of unisexual polyploids in vertebrates. Here we sequence the genomes of the two species and assemble their haplotypes, which contain two subgenomes (A and B), to the chromosome level. Sequencing coverage analysis reveals that C. gibelio is an amphitriploid (AAABBB) with two triploid sets of chromosomes; each set is derived from a different ancestor. Resequencing data from different strains of C. gibelio show that unisexual reproduction has been maintained for over 0.82 million years. Comparative genomics show intensive expansion and alterations of meiotic cell cycle-related genes and an oocyte-specific histone variant. Cytological assays indicate that C. gibelio produces unreduced oocytes by an alternative ameiotic pathway; however, sporadic homologous recombination and a high rate of gene conversion also exist in C. gibelio. These genomic changes might have facilitated purging deleterious mutations and maintaining genome stability in this unisexual amphitriploid fish. Overall, the current results provide novel insights into the evolutionary mechanisms of the reproductive success in unisexual polyploid vertebrates.