Genomic adaptations for arboreal locomotion in Asian flying treefrogs.

SignificanceTo adapt to arboreal lifestyles, treefrogs have evolved a suite of complex traits that support vertical movement and gliding, thus presenting a unique case for studying the genetic basis for traits causally linked to vertical niche expansion. Here, based on two de novo-assembled Asian treefrog genomes, we determined that genes involved in limb development and keratin cytoskeleton likely played a role in the evolution of their climbing systems. Behavioral and morphological evaluation and time-ordered gene coexpression network analysis revealed the developmental patterns and regulatory pathways of the webbed feet used for gliding in Rhacophorus kio.

Molecular characterization of PSEUDO RESPONSE REGULATOR family in Rosaceae and function of PbPRR59a and PbPRR59b in flowering regulation.

BACKGROUND: PSEUDO RESPONSE REGULATOR (PRR) genes are essential components of circadian clock, playing vital roles in multiple processes including plant growth, flowering and stress response. Nonetheless, little is known about the evolution and function of PRR family in Rosaceae species. RESULTS: In this study, a total of 43 PRR genes in seven Rosaceae species were identified through comprehensive analysis. The evolutionary relationships were analyzed with phylogenetic tree, duplication events and synteny. PRR genes were classified into three groups (PRR1, PRR5/9, PRR3/7). The expansion of PRR family was mainly derived from dispersed and whole-genome duplication events. Purifying selection was the major force for PRR family evolution. Synteny analysis indicated the existence of multiple orthologous PRR gene pairs between pear and other Rosaceae species. Moreover, the conserved motifs of eight PbPRR proteins supported the phylogenetic relationship. PRR genes showed diverse expression pattern in various tissues of pear (Pyrus bretschneideri). Transcript analysis under 12-h light/ dark cycle and constant light conditions revealed that PRR genes exhibited distinct rhythmic oscillations in pear. PbPRR59a and PbPRR59b highly homologous to AtPRR5 and AtPRR9 were cloned for further functional verification. PbPRR59a and PbPRR59b proteins were localized in the nucleus. The ectopic overexpression of PbPRR59a and PbPRR59b significantly delayed flowering in Arabidopsis transgenic plants by repress the expression of AtGI, AtCO and AtFT under long-day conditions. CONCLUSIONS: These results provide information for exploring the evolution of PRR genes in plants, and contribute to the subsequent functional studies of PRR genes in pear and other Rosaceae species.

Serum electrolyte concentrations and risk of atrial fibrillation: an observational and mendelian randomization study.

BACKGROUND: Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the relationship between AF and serum electrolytes remains unclear. METHODS: A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association. RESULTS: In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively. CONCLUSIONS: Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.

MT1G induces lipid droplet accumulation through modulation of H3K14 trimethylation accelerating clear cell renal cell carcinoma progression.

BACKGROUND: Lipid droplet formation is a prominent histological feature in clear cell renal cell carcinoma (ccRCC), but the significance and mechanisms underlying lipid droplet accumulation remain unclear. METHODS: Expression and clinical significance of MT1G in ccRCC were analyzed by using TCGA data, GEO data and scRNASeq data. MT1G overexpression or knockdown ccRCC cell lines were constructed and in situ ccRCC model, lung metastasis assay, metabolomics and lipid droplets staining were performed to explore the role of MT1G on lipid droplet accumulation in ccRCC. RESULTS: Initially, we observed low MT1G expression in ccRCC tissues, whereas high MT1G expression correlated with advanced disease stage and poorer prognosis. Elevated MT1G expression promoted ccRCC growth and metastasis both in vitro and in vivo. Mechanistically, MT1G significantly suppressed acylcarnitine levels and downstream tricarboxylic acid (TCA) cycle activity, resulting in increased fatty acid and lipid accumulation without affecting cholesterol metabolism. Notably, MT1G inhibited H3K14 trimethylation (H3K14me3) modification. Under these conditions, MT1G-mediated H3K14me3 was recruited to the CPT1B promoter through direct interaction with specific promoter regions, leading to reduced CPT1B transcription and translation. CONCLUSIONS: Our study unveils a novel mechanism of lipid droplet accumulation in ccRCC, where MT1G inhibits CPT1B expression through modulation of H3K14 trimethylation, consequently enhancing lipid droplet accumulation and promoting ccRCC progression. Graphical abstract figure Schematic diagram illustrating MT1G/H3K14me3/CPT1B-mediated lipid droplet accumulation promoted ccRCC progression via FAO inhibition.

Exercise-induced α-ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1-dependent adrenal activation.

Beneficial effects of resistance exercise on metabolic health and particularly muscle hypertrophy and fat loss are well established, but the underlying chemical and physiological mechanisms are not fully understood. Here, we identified a myometabolite-mediated metabolic pathway that is essential for the beneficial metabolic effects of resistance exercise in mice. We showed that substantial accumulation of the tricarboxylic acid cycle intermediate α-ketoglutaric acid (AKG) is a metabolic signature of resistance exercise performance. Interestingly, human plasma AKG level is also negatively correlated with BMI. Pharmacological elevation of circulating AKG induces muscle hypertrophy, brown adipose tissue (BAT) thermogenesis, and white adipose tissue (WAT) lipolysis in vivo. We further found that AKG stimulates the adrenal release of adrenaline through 2-oxoglutarate receptor 1 (OXGR1) expressed in adrenal glands. Finally, by using both loss-of-function and gain-of-function mouse models, we showed that OXGR1 is essential for AKG-mediated exercise-induced beneficial metabolic effects. These findings reveal an unappreciated mechanism for the salutary effects of resistance exercise, using AKG as a systemically derived molecule for adrenal stimulation of muscle hypertrophy and fat loss.

Root-to-shoot signaling positively mediates source-sink relation in late growth stages in diploid and tetraploid wheat.

Non-hydraulic root source signaling (nHRS) is a unique positive response to soil drying in the regulation of plant growth and development. However, it is unclear how the nHRS mediates the tradeoff between source and sink at the late growth stages and its adaptive mechanisms in primitive wheat. To address this issue, a root-splitting design was made by inserting solid partition in the middle of the pot culture to induce the occurrence of nHRS using four wheat cultivars (MO1 and MO4, diploid; DM22 and DM31, tetraploid) as materials. Three water treatments were designed as 1) both halves watered (CK), 2) holistic root system watered then droughted (FS), 3) one-half of the root system watered and half droughted (PS). FS and PS were designed to compare the role of the full root system and split root system to induce nHRS. Leaves samples were collected during booting and anthesis to compare the role of nHRS at both growth stages. The data indicated that under PS treatment, ABA concentration was significantly higher than FS and CK, demonstrating the induction of nHRS in split root design and nHRS decreased cytokinin (ZR) levels, particularly in the PS treatment. Soluble sugar and proline accumulation were higher in the anthesis stage as compared to the booting stage. POD activity was higher at anthesis, while CAT was higher at the booting stage. Increased ABA (nHRS) correlated with source-sink relationships and metabolic rate (i.e., leaf) connecting other stress signals. Biomass density showed superior resource acquisition and utilization capabilities in both FS and PS treatment as compared to CK in all plants. Our findings indicate that nHRS-induced alterations in phytohormones and their effect on source-sink relations were allied with the growth stages in primitive wheat.

tsRFun: a comprehensive platform for decoding human tsRNA expression, functions and prognostic value by high-throughput small RNA-Seq and CLIP-Seq data.

tRNA-derived small RNA (tsRNA), a novel type of regulatory small noncoding RNA, plays an important role in physiological and pathological processes. However, the understanding of the functional mechanism of tsRNAs in cells and their role in the occurrence and development of diseases is limited. Here, we integrated multiomics data such as transcriptome, epitranscriptome, and targetome data, and developed novel computer tools to establish tsRFun, a comprehensive platform to facilitate tsRNA research (http://rna.sysu.edu.cn/tsRFun/ or http://biomed.nscc-gz.cn/DB/tsRFun/). tsRFun evaluated tsRNA expression profiles and the prognostic value of tsRNAs across 32 types of cancers, identified tsRNA target molecules utilizing high-throughput CLASH/CLEAR or CLIP sequencing data, and constructed the interaction networks among tsRNAs, microRNAs, and mRNAs. In addition to its data presentation capabilities, tsRFun offers multiple real-time online tools for tsRNA identification, target prediction, and functional enrichment analysis. In summary, tsRFun provides a valuable data resource and multiple analysis tools for tsRNA investigation.

PET/CT Recognition of Costal Cartilage Infection After Breast Implant Surgery.

BACKGROUND: Postoperative infection of breast implants can lead to implant removal and other complications. This study aimed to investigate the presence of costal cartilage infection following breast implant surgery and the diagnostic role of PET/CT in identifying this rare complication. PATIENTS AND METHODS: A retrospective study included 16 patients with persistent infections after breast implant removal surgery. Patients underwent PET/CT scans before surgery, and surgical plans were made based on PET/CT findings. Surgical procedures were guided by PET/CT, and specimens were collected for pathological examination and microbiological culture. Follow-up assessments were performed at 1, 3, and 12 months postoperatively. RESULTS: Among the 16 patients, 11 were diagnosed with costal cartilage infection, whereas 5 had subcutaneous soft tissue infections. PET/CT accurately identified costal cartilage infection in all cases and localized the infected costal cartilage in the majority of cases. Microbiological culture results showed various pathogens. All patients were cured with one or staged surgery. CONCLUSION: Costal cartilage infection following breast implant surgery is a significant concern. PET/CT plays a crucial role in the accurate diagnosis and localization of infected costal cartilage, aiding in appropriate surgical management. Patients should be closely monitored for the possibility of costal cartilage infection when experiencing persistent symptoms after breast implant surgery.

Characterization and application of Bacillus velezensis D6 co-producing α-amylase and protease.

BACKGROUND: Research on the co-production of multiple enzymes by Bacillus velezensis as a novel species is still a topic that needs to be studied. This study aimed to investigate the fermentation characteristics of B. velezensis D6 co-producing α-amylase and protease and to explore their enzymatic properties and applications in fermentation. RESULTS: The maximum co-production of α-amylase and protease reached 13.13 ± 0.72 and 2106.63 ± 64.42 U mL-1, respectively, under the optimal fermented conditions (nutrients: 20.0 g L-1 urea, 20.0 g L-1 glucose, 0.7 g L-1 MnCl2; incubation conditions: initial pH 7.0, temperature 41 °C, 8% inoculation size and 30% working volume). Moreover, the genetic co-expression of α-amylase and protease increased from 0 to 24 h and then decreased after 36 h at the transcriptional level, which coincided with the growth trend of B. velezensis D6. The optimal reaction temperature of α-amylase was 55-60 °C, while that of protease was 35-40 °C. The activities of α-amylase and protease were retained by over 80% after thermal treatment (90 °C, 1 h), which indicated that two enzymes co-produced by B. velezensis D6 demonstrated excellent thermal stability. Moreover, the two enzymes were stable over a wide pH range (pH 4.0-8.0 for α-amylase; pH 4.0-9.0 for protease). Finally, the degrees of hydrolysis of corn, rice, sorghum and soybeans by α-amylase from B. velezensis D6 reached 44.95 ± 2.95%, 57.16 ± 2.75%, 52.53 ± 4.01% and 20.53 ± 2.42%, respectively, suggesting an excellent hydrolysis effect on starchy raw materials. The hydrolysis degrees of mackerel heads and soybeans by protease were 43.93 ± 2.19% and 26.38 ± 1.72%, respectively, which suggested that the protease from B. velezensis D6 preferentially hydrolyzed animal-based protein. CONCLUSION: This is a systematic study on the co-production of α-amylase and protease by B. velezensis D6, which is crucial in widening the understanding of this species co-producing multi-enzymes and in exploring its potential application. © 2024 Society of Chemical Industry.

Machine learning on MRI radiomic features: identification of molecular subtype alteration in breast cancer after neoadjuvant therapy.

OBJECTIVES: Recent studies have revealed the change of molecular subtypes in breast cancer (BC) after neoadjuvant therapy (NAT). This study aims to construct a non-invasive model for predicting molecular subtype alteration in breast cancer after NAT. METHODS: Eighty-two estrogen receptor (ER)-negative/ human epidermal growth factor receptor 2 (HER2)-negative or ER-low-positive/HER2-negative breast cancer patients who underwent NAT and completed baseline MRI were retrospectively recruited between July 2010 and November 2020. Subtype alteration was observed in 21 cases after NAT. A 2D-DenseUNet machine-learning model was built to perform automatic segmentation of breast cancer. 851 radiomic features were extracted from each MRI sequence (T2-weighted imaging, ADC, DCE, and contrast-enhanced T1-weighted imaging), both in the manual and auto-segmentation masks. All samples were divided into a training set (n = 66) and a test set (n = 16). XGBoost model with 5-fold cross-validation was performed to predict molecular subtype alterations in breast cancer patients after NAT. The predictive ability of these models was subsequently evaluated by the AUC of the ROC curve, sensitivity, and specificity. RESULTS: A model consisting of three radiomics features from the manual segmentation of multi-sequence MRI achieved favorable predictive efficacy in identifying molecular subtype alteration in BC after NAT (cross-validation set: AUC = 0.908, independent test set: AUC = 0.864); whereas an automatic segmentation approach of BC lesions on the DCE sequence produced good segmentation results (Dice similarity coefficient = 0.720). CONCLUSIONS: A machine learning model based on baseline MRI is proven useful for predicting molecular subtype alterations in breast cancer after NAT. KEY POINTS: • Machine learning models using MRI-based radiomics signature have the ability to predict molecular subtype alterations in breast cancer after neoadjuvant therapy, which subsequently affect treatment protocols. • The application of deep learning in the automatic segmentation of breast cancer lesions from MRI images shows the potential to replace manual segmentation..

CT features of calcified micro-gastric gastrointestinal stromal tumors: a case series.

BACKGROUND: Due to the lack of corresponding clinical symptoms, small calcified gastric gastrointestinal stromal tumors (GISTs) are often overlooked in clinical practice. Therefore, there is an unmet need to define the imaging features of calcified micro-gastric GISTs to facilitate diagnosis. This study retrospectively analyzed the computed tomography (CT) features of pathologically confirmed calcified micro-gastric GISTs. METHODS: The medical records (gastroscopy, pre-treatment gastric CT imaging [pre- and post-contrast scans], pathology) of patients with calcified gastric GISTs < 1 cm in diameter confirmed pathologically after endoscopic submucosal dissection, endoscopic submucosal excavation, or endoscopic full-thickness resection were retrospectively reviewed. RESULTS: Seven patients had 8 calcified gastric GISTs < 1 cm in diameter. Six patients hadsingle lesions, and 1patients had multiple lesions. Six patients had lesions in the gastric fundus, 1 patient had a lesion in the body of the stomach. Lesions had a mean diameter of 5.2 mm (range, 1.3 mm ~ 7 mm). Unenhanced CT scans showed spots and high-density nodular calcifications in 3 submucosal lesions, 2 lesions in the muscularis propria, and 3 subserosal lesions that protruded outside the stomach. Among the 8 lesions, only two had solid soft tissue components surrounding the calcification, with one of these two showing post contrast enhancement of the solid soft tissue component. CONCLUSIONS: Novel CT features of gastric GISTs included: commonly found in the gastric antrum, small size (< 1 cm in diameter), calcification, few solid soft tissue components, and no abnormal enhancement in most cases.

Self-reported critical gaps in the essential knowledge and capacity of spatial epidemiology between the current university education and competency-oriented professional demands in preparing for a future pandemic among public health postgraduates in China: a nationwide cross-sectional survey.

BACKGROUND: Spatial epidemiology plays an important role in public health. Yet, it is unclear whether the current university education in spatial epidemiology in China could meet the competency-oriented professional demands. This study aimed to understand the current situation of education and training, practical application, and potential demands in spatial epidemiology among public health postgraduates in China, and to assess the critical gaps in a future emerging infectious diseases (EID) pandemic preparedness and response. METHODS: This study was divided into three parts. The first part was a comparative study on spatial epidemiology education in international public health postgraduate training. The second part was a cross-sectional survey conducted among public health professionals. The third part was a nationwide cross-sectional survey conducted among public health postgraduates at Chinese universities from October 2020 to February 2021. Data was collected by the WeChat-based questionnaire star survey system and analyzed using the SPSS software. RESULTS: International education institutions had required public health postgraduates to master the essential knowledge and capacity of spatial epidemiology. A total of 198 public health professionals were surveyed, and they had a median of 4.00 (IQR 3.13-4.53) in demand degree of spatial epidemiology. A total of 1354 public health postgraduates were surveyed from 51 universities. Only 29.41% (15/51) of universities offered spatial epidemiology course. Around 8.05% (109/1354) of postgraduates had learned spatial epidemiology, and had a median of 1.05 (IQR 1.00-1.29) in learning degree and a median of 1.91 (IQR 1.05-2.78) in practical application degree of spatial epidemiology. To enhance professional capacity, 65.95% (893/1354) of postgraduates hoped that universities would deliver a credit-course of spatial epidemiology. CONCLUSIONS: A huge unmet education and training demand in spatial epidemiology existed in the current education system of public health postgraduates in China. To enhance the competency-oriented professional capacity in preparedness and response to a future pandemic, it is urgent to incorporate the teaching and training of spatial epidemiology into the compulsory curriculum system of public health postgraduates in China.

Application of Multiple-Optimization Filtering Algorithm in Remote Sensing Image Denoising.

Denoising remote sensing images is crucial in the application and research of remote sensing imagery. Noise in remote sensing images originates from sensor characteristics, signal transmission, and environmental conditions, among which Gaussian noise is the most common type. In this paper, we proposed a multiple-optimization bilateral filtering (MOBF) algorithm based on edge detection and differential evolution (DE) methods. The proposed algorithm optimizes the spatial domain filtering kernel and the spatial domain Gaussian kernel by using the standard deviation and width of the edge response. By employing the DE algorithm, the individuals in the population based on the standard deviation of the gray value domain are subjected to iterative mutation, crossover, and selection operations to refine the latent solution vectors and determine the optimal color space for optimizing the standard deviation of the pixel range domain kernel. As a result, the MOBF algorithm, which does not require any parameter input, is realized. To verify the feasibility and effectiveness of the proposed algorithm, denoising experiments were conducted on remote sensing images by using evaluation metrics such as the mean squared error, peak signal-to-noise ratio, and structural similarity index. The experimental results revealed that the MOBF algorithm outperforms traditional algorithms for all three evaluation metrics.

Urinary malate dehydrogenase 2 is a new biomarker for early detection of non-small-cell lung cancer.

Reliable and noninvasive biomarkers for the early diagnosis of non-small-cell lung cancer (NSCLC) are an unmet need. This study aimed to screen and validate potential urinary biomarkers for the early diagnosis of NSCLC. Using protein mass spectrometry, urinary MDH2 was found to be abundant both in patients with lung cancer and lung cancer model mice compared with controls. Urine samples obtained as retrospective and prospective cohorts including 1091 NSCLC patients and 736 healthy controls were measured using ELISA. Patients with stage I NSCLC had higher urinary MDH2 compared with healthy controls. The area under the receiver-operating characteristic curve (AUC) for the urinary MDH2 was 0.7679 and 0.7234 in retrospective and prospective cohorts to distinguish stage I cases from controls. Urinary MDH2 levels correlated with gender and smoking history. MDH2 expression levels were elevated in lung cancer tissues. MDH2 knockdown using shRNA inhibited the proliferation of lung cancer cells. Our study demonstrated that urinary MDH2 concentration was higher in early-stage NSCLC patients compared with that in controls and that MDH2 could serve as a potential biomarker for early detection of NSCLC.

Succinate induces skeletal muscle fiber remodeling via SUNCR1 signaling.

The conversion of skeletal muscle fiber from fast twitch to slow-twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid (TCA) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber-type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain IIb expression. Further, by using pharmacological or genetic loss-of-function models generated by phospholipase Cß antagonists, SUNCR1 global knockout, or SUNCR1 gastrocnemius-specific knockdown, we found that the effects of succinate on skeletal muscle fiber-type remodeling are mediated by SUNCR1 and its downstream calcium/NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR1 signaling pathway. These findings suggest the potential beneficial use of succinate-based compounds in both athletic and sedentary populations.

Comparative genomic investigation of high-elevation adaptation in ectothermic snakes.

Several previous genomic studies have focused on adaptation to high elevations, but these investigations have been largely limited to endotherms. Snakes of the genus Thermophis are endemic to the Tibetan plateau and therefore present an opportunity to study high-elevation adaptations in ectotherms. Here, we report the de novo assembly of the genome of a Tibetan hot-spring snake (Thermophis baileyi) and then compare its genome to the genomes of the other two species of Thermophis, as well as to the genomes of two related species of snakes that occur at lower elevations. We identify 308 putative genes that appear to be under positive selection in Thermophis We also identified genes with shared amino acid replacements in the high-elevation hot-spring snakes compared with snakes and lizards that live at low elevations, including the genes for proteins involved in DNA damage repair (FEN1) and response to hypoxia (EPAS1). Functional assays of the FEN1 alleles reveal that the Thermophis allele is more stable under UV radiation than is the ancestral allele found in low-elevation lizards and snakes. Functional assays of EPAS1 alleles suggest that the Thermophis protein has lower transactivation activity than the low-elevation forms. Our analysis identifies some convergent genetic mechanisms in high-elevation adaptation between endotherms (based on studies of mammals) and ectotherms (based on our studies of Thermophis).

[Laparoscopic management of persistent Müllerian duct syndrome: A case report and pedigree investigation].

OBJECTIVE: To investigate the clinical characteristics, diagnosis, treatment and etiology of persistent Müllerian duct syndrome (PMDS). METHODS: A 3-year-old boy was diagnosed with PMDS according to the clinical manifestations and the results of ultrasonography, laboratory examinations and earlier surgical examination. We performed genetic tests for the patient and his family members, removed the infantile uterus by laparoscopic wedge hysterectomy, biopsied and descended the bilateral testes, and ligated the bilateral internal rings, followed by a retrospective analysis and review of relevant literature. RESULTS: The operation was successful. Gonad biopsy revealed testis tissue, and PMDS was confirmed by intraoperative findings and related examinations. Good bilateral testicular blood supply was found during the 6-month follow-up after surgery. Medical exome sequencing showed the AMHR2 gene c.1499G > A (p.Cys500Tyr) mutant homozygote (A/A) in the patient and his sister and mutant heterozygote (G/A) in his parents. CONCLUSIONS: Laparoscopy is definitely effective for the treatment of PMDS. In surgery, the infantile uterus should be removed in case of good blood supply to the testis, and so were the bilateral testes if they cannot be descended. The homozygous mutation in the AMHR2 gene c. 1499G > A (p. Cys500Tyr) can lead to male PMDS. Pedigree investigation may provide some evidence for possible fertility in PMDS patients.

[A review on the effect of Claudin-18 on bronchopulmonary dysplasia in preterm infants].

Bronchopulmonary dysplasia (BPD) has the main manifestations of pulmonary edema in the early stage and characteristic alveolar obstruction and microvascular dysplasia in the late stage, which may be caused by structural and functional destruction of the lung epithelial barrier. The Claudin family is the main component of tight junction and plays an important role in regulating the permeability of paracellular ions and solutes. Claudin-18 is the only known tight junction protein solely expressed in the lung. The lack of Claudin-18 can lead to barrier dysfunction and impaired alveolar development, and the knockout of Claudin-18 can cause characteristic histopathological changes of BPD. This article elaborates on the important role of Claudin-18 in the development and progression of BPD from the aspects of lung epithelial permeability, alveolar development, and progenitor cell homeostasis, so as to provide new ideas for the pathogenesis and clinical treatment of BPD.

Circular RNA circ_0020710 drives tumor progression and immune evasion by regulating the miR-370-3p/CXCL12 axis in melanoma.

BACKGROUND: Circular RNAs (circRNAs) have been reported to have critical regulatory roles in tumor biology. However, their contribution to melanoma remains largely unknown. METHODS: CircRNAs derived from oncogene CD151 were detected and verified by analyzing a large number of melanoma samples through quantitative real-time polymerase chain reaction (qRT-PCR). Melanoma cells were stably transfected with lentiviruses using circ_0020710 interference or overexpression plasmid, and then CCK-8, colony formation, wound healing, transwell invasion assays, and mouse xenograft models were employed to assess the potential role of circ_0020710. RNA immunoprecipitation, luciferase reporter assay and fluorescence in situ hybridization were used to evaluate the underlying mechanism of circ_0020710. RESULTS: Our findings indicated that circ_0020710 was generally overexpressed in melanoma tissues, and high level of circ_0020710 was positively correlated with malignant phenotype and poor prognosis of melanoma patients. Elevated circ_0020710 promoted melanoma cell proliferation, migration and invasion in vitro as well as tumor growth in vivo. Mechanistically, we found that high level of circ_0020710 could upregulate the CXCL12 expression via sponging miR-370-3p. CXCL12 downregulation could reverse the malignant behavior of melanoma cells conferred by circ_0020710 over expression. Moreover, we also found that elevated circ_0020710 was correlated with cytotoxic lymphocyte exhaustion, and a combination of AMD3100 (the CXCL12/CXCR4 axis inhibitor) and anti-PD-1 significantly attenuated tumor growth. CONCLUSIONS: Elevated circ_0020710 drives tumor progression via the miR-370-3p/CXCL12 axis, and circ_0020710 is a potential target for melanoma treatment.