Response surface methodology optimization of extraction and enrichment conditions of total triterpenoid saponins from Celosiae Semen and evaluation of its lipid-lowering activity.

The saponin-enriched extract from Celosiae Semen is a promising resource owing to its lipid-lowering activity. However, triterpenoid saponins are difficult to extract owing to their high molecular weight and strong water solubility. The aim of this paper was to explore an eco-friendly and effective technology of extraction and enrichment of total triterpenoid saponins to obtain high lipid-lowering fractions. Initially, Box-Behnken design experiments were employed to optimize the heat reflux extraction process on the basic of mono-factor experiments. Afterwards, the crude extract was further purified using D-101 resin, and the purification parameters were investigated based on adsorption/desorption experiments and biological activity assay. Under optimal conditions, the purity of the finally obtained total triterpenoid saponins was increased by 7.28-fold. The lipid-lowering activities of the six main triterpenoid saponins were evaluated in HepG2 cells induced by palmitic acid. The results of Oil Red O staining showed that the compounds all exhibited potential lipid-lowering activity. The structure-activity relationship analysis suggested that the oligosaccharide chain at C-28 played an essential role in their lipid-lowering activity and the substituent group at C-23 site also showed important effects. The optimal extraction and purification methods may facilitate the utilization of Celosiae Semen for the industrial production as a functional food and drug.

OTUB1 alleviates NASH through inhibition of the TRAF6-ASK1 signaling pathways.

BACKGROUND AND AIMS: NAFLD is considered as the hepatic manifestation of the metabolic syndrome, which includes insulin resistance, obesity and hyperlipidemia. NASH is a progressive stage of NAFLD with severe hepatic steatosis, hepatocyte death, inflammation, and fibrosis. Currently, no pharmacological interventions specifically tailored for NASH are approved. Ovarian tumor domain, ubiquitin aldehyde binding 1 (OTUB1), the founding member of deubiquitinases, regulates many metabolism-associated signaling pathways. However, the role of OTUB1 in NASH is unclarified. METHODS AND RESULTS: We demonstrated that mice with Otub1 deficiency exhibited aggravated high-fat diet-induced and high-fat high-cholesterol (HFHC) diet-induced hyperinsulinemia and liver steatosis. Notably, hepatocyte-specific overexpression of Otub1 markedly alleviated HFHC diet-induced hepatic steatosis, inflammatory responses, and liver fibrosis. Mechanistically, we identified apoptosis signal-regulating kinase 1 (ASK1) as a key candidate target of OTUB1 through RNA-sequencing analysis and immunoblot analysis. Through immunoprecipitation-mass spectrometry analysis, we further found that OTUB1 directly bound to tumor necrosis factor receptor-associated factor 6 (TRAF6) and suppressed its lysine 63-linked polyubiquitination, thus inhibiting the activation of ASK1 and its downstream pathway. CONCLUSIONS: OTUB1 is a key suppressor of NASH that inhibits polyubiquitinations of TRAF6 and attenuated TRAF6-mediated ASK1 activation. Targeting the OTUB1-TRAF6-ASK1 axis may be a promising therapeutic strategy for NASH.

Baohuoside I inhibits FXR signaling pathway to interfere with bile acid homeostasis via targeting ER α degradation.

Epimedii folium (EF) is an effective herbal medicine in osteoporosis treatment, but the clinical utilization of EF has been limited due to potential hepatotoxicity. The previous studies identified that baohuoside I (BI), the main active component of EF, was relevant to EF-induced liver injury. However, the mechanisms of BI causing direct injury to hepatocytes remain unclear. Here, we reveal that BI inhibits FXR-mediated signaling pathway via targeting estrogen receptor α (ER α), leading to the accumulation of bile acids (BAs). Targeted bile acid analyses show BI alters the BA composition and distribution, resulting in impaired BA homeostasis. Mechanistically, BI induces FXR-dependent hepatotoxicity at transcriptional level. Additionally, ER α is predicted to bind to the FXR promoter region based on transcription factor binding sites databases and we further demonstrate that ER α positively regulates FXR promoter activity and affects the expression of target genes involved in BA metabolism. Importantly, we discover that ER α and its mediated FXR transcription regulation might be involved in BI-induced liver injury via ligand-dependent ER α degradation. Collectively, our findings indicate that FXR is a newly discovered target gene of ER α mediated BI-induced liver injury, and suggest BI may be responsible for EF-induced liver injury.

Ultrasonography in the evaluation of various factors of developmental dysplasia of the hip in infants: Results from a retrospective study in a large hospital of northwest China.

BACKGROUND: The occurrence and development of developmental dysplasia of the hip (DDH) are related to a variety of factors, which have been reported in the literature, but the literature does not mention factors related to the severity of DDH. The purpose of this study is to analyze the related factors of the occurrence and severity of DDH in combination with the Graf ultrasonic diagnostic classification. METHODS: This study was a monocentric retrospective study describing the factors associated with DDH in a large hospital of northwest China. A total of 3046 infants (6092 hips) within 6 months after birth using the Graf method were admitted to our department between 2014 and 2018. We analyzed data of DDH. After reviewing medical charts and diagnostic examination results, we assessed whether factors such as ethnicity, gender, gestational age, birth weight, diagnosis age, maternal age, mode of delivery, fetal presentation, amniotic fluid volume and birth order, had any effect on development of hip. RESULT: ① Analysis showed that DDH mostly occurs in female and left hip joint, related to intrauterine fetal presentation, amniotic fluid volume, gestational age, mode of delivery, prenatal weight, and diagnosis age after birth, and the occurrence of DDH is also related to maternal age (All P＜0.05). Ethnicity and first born showed have no obvious correlation with DDH incidence (p = 0.718, 0.147, respectively). ② The strongest correlation was found with amniotic fluid, followed by birth weight. ③ The severity of DDH was correlated with ethnicity, births, prenatal weight, gestational age, diagnosis age and maternal age (All P＜0.05, respectively). ④ There were significant differences in treatment methods, duration and prognosis among different types of DDH. CONCLUSIONS: The occurrence and development of DDH are related to a variety of factors. Ultrasound examination can provide an early assessment of the hip development status of infants and may play an important role in establishing an early clinical diagnosis treatment and monitoring and prognosis.

[Current situation and prospect of resource evaluation and sustainable utilization on Bletilla].

The plants of Bletilla are one of the groups in Orchidaceae with the highest economic value. As the traditional Chinese medicinal material, Bletillae Rhizoma exhibits excellent efficacy in hemostatic, antibiosis, detumescent, anticancer activities and regenerating tissue to heal wound, which has great development potential. However, Bletillae Rhizoma is mainly collected from wild resources. At present, the quantity of wild resources of Bletilla plants has sharply decreased and is far from meeting the needs. Resource appraisal and breeding and cultivation of excellent germplasms of Bletilla plants are important for scientific utilization of the resources of the genus. This paper reviewed the following researches of Chinese Bletilla resources: species and distribution, genetic diversity, active ingredient evaluation, breeding, as well as seeding production and cultivation techniques. Suggestions were also provided in further researches on the resources evaluation, sustainable development and efficient utilization of Chinese Bletilla plants.

A multicenter survey of first-line treatment patterns and gene aberration test status of patients with unresectable Stage IIIB/IV nonsquamous non-small cell lung cancer in China (CTONG 1506).

BACKGROUND: In recent years, systemic chemotherapy and molecular targeted therapy have become standard first-line treatments for locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). The objective of this survey was to investigate first-line anticancer treatment patterns and gene aberration test status of patients with advanced nonsquamous NSCLC in China. METHODS: Patients included in this study had unresectable Stage IIIB/IV nonsquamous NSCLC and were admitted during August 2015 to March 2016 into one of 12 tertiary hospitals throughout China for first-line anticancer treatment. Patient data (demographics, NSCLC histologic type, Eastern Cooperative Oncology Group [ECOG] Performance Status [PS], gene aberration test and results [if performed], and first-line anticancer treatment regimen) were extracted from medical charts and entered into Medical Record Abstraction Forms (MERAFs), which were collated for analysis. RESULTS: Overall, 1041 MERAFs were collected and data from 932 MERAFs were included for analysis. Patients with unresectable Stage IIIB/IV nonsquamous NSCLC had a median age of 59 years, 56.4% were male, 58.2% were never smokers, 95.0% had adenocarcinoma, and 92.9% had an ECOG PS ≤1. A total of 665 (71.4%) patients had gene aberration tests; 46.5% (309/665) had epidermal growth factor receptor (EGFR) gene mutations, 11.5% (48/416) had anaplastic lymphoma kinase (ALK) gene fusions, and 0.8% (1/128) had a c-ros oncogene 1 gene fusion. The most common first-line treatment regimen for unresectable Stage IIIB/IV nonsquamous NSCLC was chemotherapy (72.5%, 676/932), followed by tyrosine kinase inhibitors (TKIs; 26.1%, 243/932), and TKIs plus chemotherapy (1.4%, 13/932). Most chemotherapy regimens were platinum-doublet regimens (93.5%, 631/676) and pemetrexed was the most common nonplatinum chemotherapy-backbone agent (70.2%, 443/631) in platinum-doublet regimens. Most EGFR mutation-positive patients (66.3%, 205/309) were treated with EGFR-TKIs. CONCLUSIONS: Findings from our survey of 12 tertiary hospitals throughout China showed an increased rate of gene aberration testing, compared with those rates reported in previous surveys, for patients with advanced nonsquamous NSCLC. In addition, pemetrexed/platinum-doublet chemotherapy was the predominant first-line chemotherapy regimen for this population. Most patients were treated based on their gene aberration test status and results.

[Ultrasonographic Features of Hepatic Epithelioid Hemangioendothelioma on B-mode and Contrast-enhanced Ultrasound].

OBJECTIVE: To investigate the ultrasonographic features of hepatic epithelioid hemangioendothelioma (HEHE) on B-mode and contrast-enhanced ultrasound (CEUS). METHODS: From January 2012 to September 2016, 17 patients with surgery or biopsy confirmed HEHE were retrospectively analyzed for their clinical history, ultrasonographic data of B-mode ultrasound and CEUS characteristics. RESULTS: The mean age of the 17 patients was (42.88±13.95) yr. (range 23-69 yr.). On B-mode ultrasound, 6 case (6/17, 35.3%) were single lesion, while 11 case (11/17, 64.7%) had multiple lesions, of which 10 cases involved the global liver. There were 88.2% of lesions (15/17) located underneath the liver capsule, and 94.1% of lesions (16/17) with regular shape. The mean diameter of the lesions was (3.93±2.23) cm. The lesions appeared as hypoechoic (13/17, 76.5%), hyperechoic (1/17, 5.9%) and mixed-echoic (3/17, 17.6%). 7 patients underwent CEUS, 5 of them (5/7, 71.4%) showed a rim-like hyperenhancement in arterial phase while the other 2 presented overall hyperenhancement of the lesions with uneven perfusion inside. All cases demonstrated hypoenhancement in portal and delay phases. CONCLUSION: Multiple subcapsular hypoechoic focal liver lesions with regular shape remind of the possibility of HEHE. CEUS could provide considerable value in its diagnosis.

[A Preliminary Study on Portal Vein Hemodynamic Changes and Liver Regeneration in Rats after 70% Partial Hepatectomy].

OBJECTIVE: To explore portal vein hemodynamic changes and liver regeneration in rats after 70% partial hepatectomy (PH). METHODS: Rats were randomly subjected into sham operation group and 70% PH group. A 5-12 MHz high-frequency linear transducer was applied to measure the portal vein diameter (PVD) and the maximum portal vein velocity (PVV) before and after operation on day 1, 3, 7, 14. On the corresponding time, liver tissue morphological changes were observed, and the expression level of PCNA was measured, and the liver regeneration rate (LRR) was calculated. RESULTS: On day 1 after PH, PCNA began to increase, and hepatocyte vacuolated obviously which squeezed and narrowed the hepatic sinusoid. Meanwhile, PVD started to dilate and PVV decelerated. On day 3 after operation, PCNA peaked and active mitosis resulted in the disorders of hepatic structure. PVD peaked and PVV decelerated to the lowest. Until the 14 d after operation, the cell morphology, lobular structure and PCNA recovered gradually accompany by LRR above 90%. PVD and PVV also almost recovered to levels closed to sham group (P < 0.05). CONCLUSION: The hemodynamic parameters PVD, PVV correlated with hepatic pathology changes, mitosis status and regenerated liver volume after PH, which state the potential possibility for ultrasound image study in liver regeneration surveillance.

Lung cancer treatment disparities in China: a question in need of an answer.

BACKGROUND: Substantial progress has been made in the treatment of malignancies in the People's Republic of China in recent years. The goal of this study was to identify the extent to which national treatment guidelines are being used to customize patient care in lung cancer and to analyze the reasons for treatment disparities. METHODS: Patient characteristics and treatments were investigated retrospectively for the period from October 2004 to January 2013 using the outpatient database of the Guangdong Lung Cancer Institute (GLCI) in China. RESULTS: A total of 2,535 outpatients with lung cancer were studied in this retrospective analysis. The treatment disparity was 45.3%. Overall, 20.6% of patients with stage I non-small cell lung cancer (NSCLC) were overtreated, and 20.1% of stage II patients were undertreated. Only 19.6% of stage IIIA patients and 30.7% of stage IIIB patients underwent the recommended combination of chemotherapy and radiotherapy, respectively. For advanced NSCLC, the greatest treatment disparity appeared in the second-line setting and beyond. Patients who were positive for epidermal growth factor receptor (EGFR) and receiving EGFR tyrosine kinase inhibitors experienced significant prolongation of survival compared with patients who were EGFR negative or whose EGFR mutation status was unknown (hazard ratio: 0.79; p = .037). The treatment disparities were significantly larger among patients aged younger than 65 years and in patients from developing regions compared with patients aged 65 years and older and from developed regions, respectively (p < .001, p = .046). The difference in treatment disparity was statistically significant between GLCI and other hospitals (p < .001). CONCLUSION: This retrospective study of a large number of patients from an outpatient oncology database demonstrated large disparities in the treatment of lung cancer in China. It is important to develop a new guideline for recommendations that are based on resource classification.

New finding based on Comparative Toxicogenomics Database: Hepatic YY1 mediates drug-induced liver injury.

BACKGROUND: YY1 plays a crucial part in the onset and progression of numerous liver diseases, yet the significant contribution of YY1 to drug-induced liver injury (DILI) appears to have been underestimated by researchers. PURPOSE: To reveal the underlying role of YY1 in DILI. METHOD: The compounds that interact with YY1 were queried in the Comparative Toxicogenomics Database (CTD), with the majority found to be hepatotoxic, which includes certain widely used drugs. Molecular docking and SPR characterized the robust binding of hepatotoxic compounds to YY1. The duty of YY1 in DILI was investigated in Diosbulbin B (DIOB), a recently identified hepatotoxic compound that tightly associates with YY1, and further validated on ANIT, LCA, APAP, and CDDP. Transcriptomic analysis disclosed the underlying mechanisms involved in DIOB-induced liver injury. RT-qPCR, immunohistochemistry, immunofluorescence, western blotting, and cellular transfection techniques were employed to validate the specific mechanism. RESULTS: Among the 94 compounds affecting YY1 expression in the CTD, 59 compounds exhibited hepatotoxicity, showing close interactions with YY1 and almost consistent binding sites by molecular docking. The SPR validated the tough binding of several hepatotoxic compounds to YY1, including five FDA-approved hepatotoxic drugs. Mechanistically, the involvement of YY1 in DILI was uncovered through the cholestasis lens, mice hepatic YY1 was up-regulated by hepatotoxic DIOB and transcriptionally inhibited FXR and its downstream BSEP and MRP2 expression, initiating early in cholestatic liver injury and persisting to drive the progression of cholestasis. ANIT and LCA-induced model of cholestasis provided evidence for the hypothesis that YY1 frequently mediates drug induced cholestasis (DIC). APAP and CDDP indicated that YY1 may also be involved in hepatocellular and mixed type DILI. CONCLUSION: YY1 widely mediated the development of DIC and also might be engaged in other types of DILI. YY1 presented a common target for hepatotoxic medications and the targeting of liver YY1 for drug development may offer a novel approach for managing DILI.

Integration of untargeted and pseudotargeted metabolomics reveals specific markers for authentication and adulteration detection of Fritillariae Bulbus using tandem mass spectrometry and chemometrics.

Authentication and adulteration detection of closely related herbal medicines is a thorny issue in the quality control and market standardization of traditional Chinese medicine. Taking Fritillariae Bulbus (FB) as a case study, we herein proposed a three-step strategy that integrates mass spectrometry-based metabolomics and multivariate statistical analysis to identify specific markers, thereby accurately identifying FBs and determining the adulteration level. First, an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based untargeted metabolomics method was employed to profile steroid alkaloids in five sorts of FB and screen potential differential markers. Then, the reliability of the screened markers was further verified by the distribution in different FB groups acquired from ultra-high performance liquid chromatography triple quadrupole mass spectrometry-based pseudotargeted metabolomics analysis. As a result, a total of 16 compounds were screened out to be the specific markers, which were successfully applied to distinguish five FBs by using discriminant analysis model. Besides, partial least squares regression models based on specific markers allowed accurate prediction of three sets of adulterated FBs. All the models afforded good linearity and good predictive ability with regression coefficient of prediction (R2p) > 0.9 and root mean square error of prediction (RMSEP) < 0.1. The reliable results of discriminant and quantitative analysis revealed that this proposed strategy could be potentially used to identify specific markers, which contributes to rapid chemical discrimination and adulteration detection of herbal medicines with close genetic relationship.

Melanoma differentiation-associated protein 5 prevents cardiac hypertrophy via apoptosis signal-regulating kinase 1-c-Jun N-terminal kinase/p38 signaling.

Pathological cardiac hypertrophy (CH) is driven by maladaptive changes in myocardial cells in response to pressure overload or other stimuli. CH has been identified as a significant risk factor for the development of various cardiovascular diseases, ultimately resulting in heart failure. Melanoma differentiation-associated protein 5 (MDA5), encoded by interferon-induced with helicase C domain 1 (IFIH1), is a cytoplasmic sensor that primarily functions as a detector of double-stranded ribonucleic acid (dsRNA) viruses in innate immune responses; however, its role in CH pathogenesis remains unclear. Thus, the aim of this study was to examine the relationship between MDA5 and CH using cellular and animal models generated by stimulating neonatal rat cardiomyocytes with phenylephrine and by performing transverse aortic constriction on mice, respectively. MDA5 expression was upregulated in all models. MDA5 deficiency exacerbated myocardial pachynsis, fibrosis, and inflammation in vivo, whereas its overexpression hindered CH development in vitro. In terms of the underlying molecular mechanism, MDA5 inhibited CH development by promoting apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, thereby suppressing c-Jun N-terminal kinase/p38 signaling pathway activation. Rescue experiments using an ASK1 activation inhibitor confirmed that ASK1 phosphorylation was essential for MDA5-mediated cell death. Thus, MDA5 protects against CH and is a potential therapeutic target.

Predicting the severity of mycoplasma pneumoniae pneumonia in pediatric and adult patients: a multicenter study.

The purpose of this study is to develop a nomogram model for early prediction of the severe mycoplasma pneumoniae pneumonia (SMPP) in Pediatric and Adult Patients. A retrospective analysis was conducted on patients with MPP, classifying them into SMPP and non-severe MPP (NSMPP) groups. A total of 550 patients (NSMPP 374 and SMPP 176) were enrolled in the study and allocated to training, validation cohorts. 278 patients (NSMPP 224 and SMPP 54) were retrospectively collected from two institutions and allocated to testing cohort. The risk factors for SMPP were identified using univariate analysis. For radiomic feature selection, Spearman's correlation and the least absolute shrinkage and selection operator (LASSO) were utilized. Logistic regression was used to build different models, including clinical, imaging, radiomics, and integrated models (combining clinical, imaging, and radiomics features selected). The model's discrimination was evaluated using a receiver operating characteristic curve, its calibration with a calibration curve, and the results were visualized using the Hosmer-Lemeshow goodness-of-fit test. Thirteen clinical features and fourteen imaging features were selected for constructing the clinical and imaging models. Simultaneously, a set of twenty-five radiomics features were utilized to build the radiomics model. The integrated model demonstrated good calibration and discrimination in the training cohorts (AUC, 0.922; 95% CI: 0.900, 0.942), validation cohorts (AUC, 0.879; 95% CI: 0.806, 0.920), and testing cohorts (AUC, 0.877; 95% CI: 0.836, 0.916). The discriminatory and predictive efficacy of the clinical model in testing cohorts increased further after clinical and radiological features were incorporated (AUC, 0.849 vs. 0.922, P = 0.002). The model demonstrated exemplary predictive efficacy for SMPP by leveraging a comprehensive set of inputs, encompassing clinical data, quantitative and qualitative radiological features, along with radiomics features. The integration of these three aspects in the predictive model further enhanced the performance of the clinical model, indicating the potential for extensive clinical applications.

To nap or not? Evidence from a meta-analysis of cohort studies of habitual daytime napping and health outcomes.

Habitual daytime napping is a common behavioral and lifestyle practice in particular countries and is often considered part of a normal daily routine. However, recent evidence suggests that the health effects of habitual daytime napping are controversial. We systematically searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to March 9, 2024, to synthesize cohort studies of napping and health outcome risk. A total of 44 cohort studies with 1,864,274 subjects aged 20-86 years (mean age 56.4 years) were included. Overall, habitual napping increased the risk of several adverse health outcomes, including all-cause mortality, cardiovascular disease, metabolic disease, and cancer, and decreased the risk of cognitive impairment and sarcopenia. Individuals with a napping duration of 30 min or longer exhibited a higher risk of all-cause mortality, cardiovascular disease, and metabolic disease, whereas those with napping durations less than 30 min had no significant risks. No significant differences in napping and health risks were observed for napping frequency, percentage of nappers, sample size, sex, age, body mass index, follow-up years, or comorbidity status. These findings indicate that individuals with a long napping duration should consider shortening their daily nap duration to 30 min or less.

[The methodology and influential factors of real-time elastography in liver examination].

OBJECTIVE: To investigate the methodology and influential factors of real-time elastography (RTE) in liver examination. METHODS: Forty normal volunteers received the examination of liver with RTE. All strain images were analyzed by the Strain Histogram Measurement and the liver fibrosis index (LFI) values were recorded. Two-tailed t-test was used to evaluate the significance of the potential influence factors of RTE, including inter-lobar variations, respiratory phase, different sections and gender. A paired two-tailed t-test and Bland-Altman test were used in the analysis of the inter- and intra-observer consistency. RESULTS: There were significant differences between the LFI values in the left lobe and those in the right lobe (2.52 +/- 0.47 vs. 1.58 +/- 0.41), also between right intercostal and right sub-costal approach (1.58 +/- 0.41 vs. 1. 59 +/- 0.45). There were no significant differences either between the LFI values of end-expiration and those of end-inspiration (2.61 +/- 0.54 vs. 1.58 +/- 0.41) or between male and female (1.57 +/- 0.37 vs. 1.60 +/- 0.46). RTE showed goodness of fit between the inter- and intra-observer consistency. CONCLUSION: Liver stiffness measurement performed by RTE at end-inspiration in the right lobe with inter-costal approach may reveal liver elasticity more accurately.

Experience of IVIG Treatment in an Overweight 14-year-old Child With Kawasaki Disease: A Case Report.

Kawasaki disease, or mucocutaneous lymph node syndrome, is an acute systemic vasculitis involving small and medium-sized vessels. It can be complicated by varying degrees of cardiac damage, especially coronary artery disease. The disease mainly occurs in children aged < 5 years, with rarer cases in older children and adults. Intravenous immunoglobulin combined with aspirin is the widely accepted treatment regimen in the acute phase, but the dosage recommended by the American Heart Association guidelines is not suitable for heavier children. This article reports the successful management of an overweight 14-year-old child with Kawasaki disease.

Comparative morphology and plant volatile responses of antennal sensilla in Cinara cedri (Hemiptera: Lachninae), Eriosoma lanigerum (Hemiptera: Eriosomatinae), and Therioaphis trifolii (Hemiptera: Calaphidinae).

Olfaction is important for mediating aphid behaviors and is involved in host location and mating. Antennal primary rhinaria play a key role in the chemoreception of aphids. The function of the peripheral olfactory system in the subfamily Aphidinae has been intensively studied, but little is known about other subfamilies of Aphididae. Therefore, three aphid species were selected to study the olfactory reception of plant volatiles: Cinara cedri (Lachninae), Eriosoma lanigerum (Eriosomatinae), and Therioaphis trifolii (Calaphidinae). In this study, the morphology and distribution of the antennal sensilla of apterous adults were observed by scanning electron microscopy. Three morphological types were identified (placoid sensilla, coeloconic sensilla, and trichoid sensilla); the first two were distributed on the antennal primary rhinaria. A pattern of primary rhinaria in C. cedri was found that differed from that of E. lanigerum and T. trifolii and consists of 1 large placoid sensillum (LP) on the 4th segment, 2 LPs on the 5th segment, and a group of sensilla on the 6th antennal segments. Later, we recorded and compared neuronal responses of the distinct placoid sensilla in the primary rhinaria of the three aphid species to 18 plant volatiles using a single sensillum recording (SSR) technique. The results indicated that the functional profiles based on the tested odorants of the primary rhinaria of the three investigated aphid species were clustered into three classes, and exhibited excitatory responses to certain types of odorants, especially terpenes. In C. cedri, the ORNs in LP6 exhibited the highest responses to (±)-citronellal across all tested chemicals, and showed greater sensitivity to (±)-citronellal than to (+)-limonene. ORNs in LP5 were partially responsive to α-pinene and (-)-ß-pinene in a dose-dependent manner. Across different species, E. lanigerum showed significantly stronger neuronal responses of LP5 to several terpenes, such as (-)-linalool and α-terpineol, compared to other species. In T. trifolii, the neuronal activities in LP6 showed a greater response to methyl salicylate as compared to LP5. Overall, our results preliminarily illustrate the functional divergence of ORNs in the primary rhinaria of aphids from three subfamilies of Aphididae and provide a basis for better understanding the mechanism of olfactory recognition in aphids.

Identification of Key Novel lncRNAs RP11-400N13.3 and RP11-197K6.1 that Construct ceRNA Networks Associated with Recurrence and Metastasis in Colon Cancer.

BACKGROUND: Colon adenocarcinoma (COAD) is a major cause of cancer mortality worldwide. The occurrence and development of colon cancer is regulated by complex mechanisms that require further exploration. Recently, long non-coding RNAs (lncRNAs) were found to be related to the mortality of colon cancer patients through their participation in competing endogenous RNA (ceRNA) networks. Therefore, screening the lncRNAs involved in colon cancer may contribute to clarifying the complex mechanisms. METHODS: In this study, we explored the potential lncRNAs associated with colon cancer by establishing a ceRNA network using bioinformatics, followed by biological verification. RESULTS: RP11-197K6.1 and RP11-400N13.3 were screened out owing to their involvement in the expression of CDK2NA, a gene that potentially prevents colon cancer cells from high oxygen levels. CONCLUSIONS: Our work explored the mechanisms of recurrence and metastasis in colon cancer and provided potential targets for drug development.

Visible-Light-Induced Desaturative ß-Alkoxyoxalylation of N-Aryl Cyclic Amines with Difluoromethyl Bromides and H2O Via a Triple Cleavage Process.

A visible-light-driven desaturative ß-alkoxyoxalyation of N-aryl cyclic amines with difluoromethyl bromides and H2O has been reported. This tandem reaction is triggered by homolysis of the C-Br bond to produce the difuoroalkyl radical, which undergoes the subsequent defluorinated ß-alkoxyoxalylation cascades to afford a wide range of ß-ketoester/ketoamides substituted enamines. The prominent feature of this reaction contains photocatalyst-free, transition-metal free, and mild conditions. The 18O labeling experiment disclosed that H2O is the oxygen source of the carbonyl unit.

A case of West syndrome and global developmental delay in a child with a heterozygous mutation in the TBL1XR1 gene: A case report.

BACKGROUND: TBL1XR1, also known as IRA1 or TBLR1, encodes a protein that is localized in the nucleus and is expressed in most tissues. TBL1XR1 binds to histones H2B and H4 in vitro and functions in nuclear receptor-mediated transcription. TBL1XR1 is also involved in the regulation of the Wnt-ß-catenin signaling pathway. Mutations in the TBL1XR1 gene impair the Wnt-ß-catenin signaling pathway's ability to recruit Wnt-responsive element chromatin, affecting brain development. Mutations in this gene cause various clinical phenotypes, including Pierpont syndrome, autism spectrum disorder, speech and motor delays, mental retardation, facial dysmorphism, hypotonia, microcephaly, and hearing impairment. CASE SUMMARY: A 5-month-old female child was admitted with "episodic limb tremors for more than 1 month." At the time of admission, the child had recurrent episodes of limb tremors with motor retardation and a partially atypical and hypsarrhythmic video electroencephalogram. It was determined that a heterozygous mutation in the TBL1XR1 gene caused West syndrome and global developmental delay. Recurrent episodes persisted for 6 months following oral treatment with topiramate; the addition of oral treatment with vigabatrin did not show any significant improvement, and the disease continued to recur. The child continued to have recurrent episodes of limb tremors at follow-up until 1 year and 3 months of age. Additionally, she developed poor eye contact and a poor response to name-calling. CONCLUSION: We report the case of a child with West syndrome and a global developmental delay caused by a heterozygous mutation in the TBL1XR1 gene. This study adds to our understanding of the clinical phenotype of TBL1XR1 mutations and provides a realistic and reliable basis for clinicians.