KLF10/CBS increases the sensitivity of gastric carcinoma cells to methionine restriction by promoting sulfur transfer pathway.

Gastric cancer metastasis is a major cause of poor prognosis. Our previous research showed that methionine restriction (MR) lowers the invasiveness and motility of gastric carcinoma. In this study, we investigated the particular mechanisms of MR on gastric carcinoma metastasis. In vitro, gastric carcinoma cells (AGS, SNU-5, MKN7, KATO III, SNU-1, and MKN45) were grown in an MR medium for 24 h. In vivo, BALB/c mice were given a methionine-free (Met-) diet. Transwell assays were used to investigate cell invasion and migration. The amounts of Krüppel like factor 10 (KLF10) and cystathionine ß-synthase (CBS) were determined using quantitative real-time PCR and Western blot. To determine the relationship between KLF10 and CBS, chromatin immunoprecipitation and a dual-luciferase reporter experiment were used. Hematoxylin-eosin staining was used to detect lung metastasis. Liquid chromatography-mass spectrometry was used to determine cystathionine content. MR therapy had varying effects on the invasion and migration of gastric carcinoma cells AGS, SNU-5, MKN7, KATO III, SNU-1, and MKN45. KLF10 was highly expressed in AGS cells but poorly expressed in KATO III cells. KLF10 improved MR's ability to prevent gastric carcinoma cell invasion and migration. In addition, KLF10 may interact with CBS, facilitating transcription. Further detection revealed that inhibiting the KLF10/CBS-mediated trans-sulfur pathway lowered Met-'s inhibitory effect on lung metastasis development. KLF10 transcription activated CBS, accelerated the trans-sulfur pathway, and increased gastric carcinoma cells' susceptibility to MR.

[Risk factors for hip osteoarthritis after arthroscopy in patients with femoroacetabular impingement].

OBJECTIVE: To investigate the risk factors of hip osteoarthritis（HOA） after hip arthroscopy in patients with femoro-acetabular impingement（FAI） syndrome, and to reduce and prevent HOA. METHODS: From September 2018 to September 2020, 106 patients with FAI underwent hip arthroscopy, including 40 males and 66 females, aged from 20 to 55 years old with an average age of （33.05±10.19） years old. The mechanism of injury included 51 cases for sports injury, 36 for traffic accidents, and 19 for blunt object injury. The duration of the disease ranged from 5 to 19 days with an average of （12.02±3.69） days. All patients were followed up for 18 months. Patients were divided into HOA group （23 cases） and non-HOA group （83 cases） according to the occurrence of HOA. Multivariate Logistic regression was used to analyze the risk factors of HOA after hip arthroscopy in FAI patients. RESULTS: By univariate analysis, aged from 50 to 70 years old, female, body mass index（BMI）> 30 kg·m-2, physical labor, cam type, postoperative infection, last follow-up hip degree of motion （range of motion, ROM） （flexion, abduction, adduction, internal rotation） and Tönnis grade 1 and above of the HOA group were higher than those of the non-HOA group （P<0.05）, and the relative appendicular skeletal muscle index （RASM） was lower than that of non-HOA group（P<0.05）. By multiple Logistic regression analysis, cam type, BMI>30 kg·m-2, last follow-up hip internal rotation ROM and Tönnis grade 1 were risk factors for HOA after hip arthroscopy in FAI patients （P<0.05）. CONCLUSION: FAI classification, body mass index, hip ROM and Tönnis grade are all related to HOA after hip arthroscopy in FAI patients. Follow-up and intervention should be strengthened in high-risk FAI patients to reduce the occurrence of HOA.

Intelligent carboxymethyl cellulose composite films containing Garcinia mangostana shell anthocyanin with improved antioxidant and antibacterial properties.

In this study, anthocyanin from Garcinia mangostana shell extract (Mse) was used as pH indicator to prepare intelligent carboxymethyl cellulose (CMC) based composite films. The structure and properties of the CMC-based composite films were characterized and discussed in detail. Results showed that the CMC-based composite films with Mse had excellent mechanical, antibacterial and antioxidant abilities. Especially, the carboxymethyl cellulose/corn starch/Garcinia mangostana shell extract (CMC/Cst/Mse) composite film had best mechanical properties (20.62 MPa, 4.06 % EB), lowest water vapor permeability (1.80 × 10-12 g·cm/(cm2·s·Pa)), excellent ultraviolet (UV) blocking performance, and the best antibacterial and antioxidant abilities. The pH sensitivity of composite films which had Mse obviously changed with time when the fish freshness was monitored at 25 °C. Given the good pH sensitivity of the composite films, it had significant potential for application of intelligent packaging film as a food packaging material to indicate the freshness of fish.

Beyond the Stereotype of Tolerance: Diversified Milieu and Contextual Difference.

We explore whether there are value preferences of creative workers in addition to tolerance and how these value preferences vary among different occupation categories and countries. We use a dataset of 1968 and 1076 observations in China and the U.S., respectively, from the World Values Survey dataset (2017-2020, wave 7) (WVS 7), with a Structure Equation Modelling (SEM) and Multinomial Logit Model (MLM) at the micro level. The findings reveal that (1) the Chinese sample is more likely to have a balanced preference of tolerance towards migrants, religions, and homosexuality, while the American sample's preference of tolerance is much more likely to be interpreted as accepting homosexuality only; (2) the American sample also shows preferences towards responsibility, technology, work style, and political actions, while a preference for happiness and political actions is identified in the Chinese sample; and (3) with a higher level of creativity, the difference regarding understanding of tolerance is more likely to be highlighted between China and the U.S. This study provides a quite unconventional perspective for understanding the composition of preferences and, to a certain extent, reconciles the inconsistency between the theoretical advocacy of building up a selected milieu and the reality of creative workers' blended value mix.

An ultrafast and self-powered MoSxSe2-x/Si photodetector with high light-trapping structures and a SiOx interface layer.

MoSxSe2-x nanofilms, as a typical metal dichalcogenide, have attracted great interest, due to their adjustable bandgap and distinctive electronic and optical properties. However, the inherent bandgap of MoSxSe2-x and the strong interface recombination impede the actualization of a high-sensitivity photodetector (PD). Few-layer MoSxSe2-x nanofilms were prepared with vertically orientation at 450 °C, which would be a less restrictive choice of substrates. Herein, a self-powered MoSxSe2-x/SiOx/Si photodetector was fabricated which exhibits unprecedented performance with excellent reproducibility and stability from 405 nm to 980 nm, a high responsivity (0.450 A W-1), normalized detectivity (4.968 × 1012 Jones) and ultrafast photoresponse (τr = 1.20 µs, τf = 4.92 µs) at zero bias under 980 nm incident laser illumination with a density of 200 µW cm-2. Significantly, the self-powered PD is capable of detecting ultraweak IR signals below 200 µW cm-2 with high on-off ratios. More importantly, an oxidized atomic layer is generated through the wet oxidation in the Piranha solution. The PD can work well at high frequencies even at 100 kHz, which shows its potential application in high-frequency photoelectric devices and health monitors. Summing up, this work not only suggests that an ultrathin SiOx interface layer can reduce carrier recombination via simple interface engineering, but also proposes a novel strategy for the preparation of high-performance and low-cost optoelectronic devices.

Hepatic venous pressure gradient: Inaccurately estimates portal venous pressure gradient in alcoholic cirrhosis and portal hypertension.

BACKGROUND: Portal hypertension (PHT) in patients with alcoholic cirrhosis causes a range of clinical symptoms, including gastroesophageal varices and ascites. The hepatic venous pressure gradient (HVPG), which is easier to measure, has replaced the portal venous pressure gradient (PPG) as the gold standard for diagnosing PHT in clinical practice. Therefore, attention should be paid to the correlation between HVPG and PPG. AIM: To explore the correlation between HVPG and PPG in patients with alcoholic cirrhosis and PHT. METHODS: Between January 2017 and June 2020, 134 patients with alcoholic cirrhosis and PHT who met the inclusion criteria underwent various pressure measurements during transjugular intrahepatic portosystemic shunt procedures. Correlations were assessed using Pearson's correlation coefficient to estimate the correlation coefficient (r) and determination coefficient (R2). Bland-Altman plots were constructed to further analyze the agreement between the measurements. Disagreements were analyzed using paired t tests, and P values < 0.05 were considered statistically significant. RESULTS: In this study, the correlation coefficient (r) and determination coefficient (R2) between HVPG and PPG were 0.201 and 0.040, respectively (P = 0.020). In the 108 patients with no collateral branch, the average wedged hepatic venous pressure was lower than the average portal venous pressure (30.65 ± 8.17 vs. 33.25 ± 6.60 mmHg, P = 0.002). Hepatic collaterals were identified in 26 cases with balloon occlusion hepatic venography (19.4%), while the average PPG was significantly higher than the average HVPG (25.94 ± 7.42 mmHg vs 9.86 ± 7.44 mmHg; P < 0.001). The differences between HVPG and PPG < 5 mmHg in the collateral vs no collateral branch groups were three cases (11.54%) and 44 cases (40.74%), respectively. CONCLUSION: In most patients, HVPG cannot accurately represent PPG. The formation of hepatic collaterals is a vital reason for the strong underestimation of HVPG.

Reversible data hiding in encrypted images with multi-prediction and adaptive huffman encoding.

With the rapid development of multimedia technology and the massive accumulation of user data, a huge amount of data is rapidly generated and shared over the network, while the problems of inappropriate data access and abuse persist. Reversible data hiding in encrypted images (RDHEI) is a privacy-preserving method that embeds protected data in an encrypted domain and accurately extracts the embedded data without affecting the original content. However, the amount of embedded data has been one of the major limitations in the performance and application of RDHEI. Currently, the main approaches to improve the capacity of RDHEI are either to increase the overall capacity or to reduce the length of the auxiliary information. In this paper, we propose a novel RDHEI scheme based on multi-prediction and adaptive Huffman encoding. To increase the overall capacity, we propose a multi-prediction, called MED+GAP predictor, to generate the label map data of non-reference pixels prior to image encryption. Then, an adaptive Huffman coding is designed to compress the generated labels in order to reduce the embedding length of the auxiliary information used for the extraction and recovery. Experiments show that the proposed method with MED+GAP predictor and adaptive Huffman coding improves 0.052 bpp, 0.023 bpp, and 0.047 bpp on average over the other state-of-the-art methods on the BOSSBase, BOWS-2, and UCID datasets, respectively, while maintaining security and reversibility.

Impact Fracture Simulation of Laminated Glass Based on Thick Shell Elements and a Cohesive Zone Model.

Laminated glass is extensively used in automotive windshields, making it crucial to have a comprehensive understanding of its fracture mechanism to ensure driver and pedestrian safety in various windshield impact scenarios. Current research on the cohesive zone model of glass impact failure has encountered challenges related to accuracy and computational efficiency. This paper addresses these issues by utilizing the finite element software LS-DYNA, which integrates a cohesive zone model and thick shell (Tshell) elements to simulate and analyze the impact failure process of laminated glass. The combination of Tshell and cohesive elements was validated using a DCB example. Subsequently, the proposed method was applied to simulate the impact damage on an automobile's front windshield, providing valuable insights from the obtained results. Finally, the influence of curvature, the number of layers, and the thickness ratio of each layer were investigated, leading to some valuable conclusions. Firstly, an increase in the thickness of the upper glass layer correlates with a decrease in the peak acceleration of the dummy-head model due to the ductility of PVB material. Secondly, when a curvature exists, the arched configuration of the windshield promotes higher resistance against impact, consequently leading to increased peak acceleration.

Methionine restriction attenuates the migration and invasion of gastric cancer cells by inhibiting nuclear p65 translocation through TRIM47.

The prevention and treatment of gastric cancer has been the focus and difficulty of medical research. We aimed to explore the mechanism of inhibiting migration and invasion of gastric cancer cells by methionine restriction (MR). The human gastric cancer cell lines AGS and MKN45 cultured with complete medium (CM) or medium without methionine were used for in vitro experiments. MKN45 cells were injected tail vein into BALB/c nude mice and then fed with normal diet or methionine diet for in vivo experiments. MR treatment decreased cell migration and invasion, increased E-cadherin expression, decreased N-cadherin and p-p65 expressions, and inhibited nuclear p65 translocation of AGS and MKN45 cells when compared with CM group. MR treatment increased IκBα protein expression and protein stability, and decreased IκBα protein ubiquitination level and TRIM47 expression. TRIM47 interacted with IκBα protein, and overexpression of TRIM47 reversed the regulatory effects of MR. TRIM47 promoted lung metastasis formation and partially attenuated the effect of MR on metastasis formation in vivo compared to normal diet group mice. MR reduces TRIM47 expression, leads to the degradation of IκBα, and then inhibits the translocation of nuclear p65 and the migration and invasion of gastric cancer cells.

Chiral metasurface zone plate for transmission-reflection focusing of circularly polarized terahertz waves.

The properties of traditional Fresnel zone plates have been greatly enhanced by metasurfaces, which allow the control of polarization, orbital angular momentum, or other parameters on the basis of focusing. In this Letter, a new, to the best of our knowledge, method for circularly polarized wave manipulation based on a zone plate is proposed. Chiral meta-atoms and binary geometric phase are used for the simultaneous focusing of reflected and transmitted terahertz waves. The silicon-based dielectric chiral units, which show great performance of spin-selective transmission near 0.54 THz, separate the orthogonal circularly polarized components. A binary Pancharatnam-Berry (P-B) phase gradient is obtained by rotating the unit 90 degrees, then the phase zone plate can be easily designed. The simulation results show that the proposed chiral metasurface zone plate has the function of reflection-transmission separation and focusing for the circularly polarized terahertz waves. In addition, we also demonstrate the possibility of using a 1064-nm continuous infrared laser to adjust the intensity of our devices, based on photo-generated carriers in silicon. The design principle of the chiral metasurface zone plates can be extended to other wavelengths, providing new ideas for the regulation of circularly polarized light.

A novel nomogram predicting overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in portal hypertension patients.

We aim to develop a nomogram to predict overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosystemic shunt (TIPS) in patients with portal hypertension, according to demographic/clinical indicators such as age, creatinine, blood ammonia, indocyanine green retention rate at 15 min (ICG-R15) and percentage of Portal pressure gradient (PPG) decline. In this retrospective study, 296 patients with portal hypertension who received elective TIPS in Beijing Shijitan Hospital from June 2018 to June 2020 were included. These patients were randomly divided into a training cohort (n = 207) and a validation cohort (n = 89). According to the occurrence of OHE, patients were assigned to OHE group and non-OHE group. Both univariate and multivariate analyses were performed to determine independent variables for predicting OHE after TIPS. Accordingly, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to compare the accuracy and superiority of a novel model with conventional Child-Pugh and MELD scoring model. Age (OR 1.036, 95% CI 1.002-1.070, p = 0.037), Creatinine (OR 1.011, 95% CI 1.003-1.019, p = 0.009), Blood ammonia (OR 1.025, 95% CI 1.006-1.044, p = 0.011), ICG-R15 (OR 1.030, 95% CI 1.009-1.052, p = 0.004) and Percentage decline in PPG (OR 1.068, 95% CI 1.029-1.109, p = 0.001) were independent risk factors for OHE after TIPS using multifactorial analysis. A nomogram was constructed using a well-fit calibration curve for each of these five covariates. When compared to Child-Pugh and MELD score, this new nomogram has a better predictive value (C-index = 0.828, 95% CI 0.761-0.896). Consistently, this finding was reproduceable in validation cohort and confirmed with DCA. A unique nomogram was developed to predict OHE after TIPS in patients with PHT, with a high prediction sensitivity and specificity performance than commonly applied scoring systems.

Treatment and prognostic risk factors for intracranial infection after craniocerebral surgery.

The objective of this study was to determine risk factors of pejorative evolution course in patients suffering from postoperative cranial infection. The data of patients who developed an intracranial infection after craniocerebral surgery in the neurosurgical intensive care unit of the First Affiliated Hospital of Nanjing Medical University in Nanjing, Jiangsu, China, from February 2018 to August 2019 were retrospectively analyzed. Logistic regression was used to analyze the factors influencing the prognosis of intracranial infection treatment. Sixty-four patients developed an infection after craniocerebral surgery, and 48 of them with negative CSF cultures received experimental anti-infectives. In 16 patients, cerebrospinal fluid culture showed pandrug-resistant pathogens, including 11 Acinetobacter baumannii (11), Klebsiella pneumoniae (3), Escherichia coli (1), and Candida glabrata (1). Nine patients received intraventricular or intrathecal injections of polymyxin B. The mean duration of infection treatment was 22.2 ± 9.9 days, and the clinical cure rate was 85.9% (55/64). Logistic multivariate regression analysis showed that inadequate CSF drainage (OR, 6.839; 95% CI, 1.130-41.383; P = 0.036) and infection with drug-resistant bacteria (OR, 24.241; 95% CI, 2.032-289.150; P = 0.012) were independent risk factors for postoperative intracranial infection. Intracranial infection with positive CSF culture and inadequate CSF drainage are factors contributing to the poor prognosis of intracranial infection. Moreover, early anti-infection treatment and adequate CSF drainage may improve patient outcomes. In particular, intraventricular or intrathecal injection of polymyxin B may be a safe and effective treatment strategy for MDR/XDR gram-negative bacilli infection.

Marine Dehalogenator and Its Chaperones: Microbial Duties and Responses in 2,4,6-Trichlorophenol Dechlorination.

Marine environments contain diverse halogenated organic compounds (HOCs), both anthropogenic and natural, nourishing a group of versatile organohalide-respiring bacteria (OHRB). Here, we identified a novel OHRB (Peptococcaceae DCH) with conserved motifs but phylogenetically diverse reductive dehalogenase catalytic subunit (RdhAs) from marine enrichment culture. Further analyses clearly demonstrate the horizontal gene transfer of rdhAs among marine OHRB. Moreover, 2,4,6-trichlorophenol (TCP) was dechlorinated to 2,4-dichlorophenol and terminated at 4-chlorophenol in culture. Dendrosporobacter and Methanosarcina were the two dominant genera, and the constructed and verified metabolic pathways clearly demonstrated that the former provided various substrates for other microbes, while the latter drew nutrients, but might provide little benefit to microbial dehalogenation. Furthermore, Dendrosporobacter could readily adapt to TCP, and sporulation-related proteins of Dendrosporobacter were significantly upregulated in TCP-free controls, whereas other microbes (e.g., Methanosarcina and Aminivibrio) became more active, providing insights into how HOCs shape microbial communities. Additionally, sulfate could affect the dechlorination of Peptococcaceae DCH, but not debromination. Considering their electron accessibility and energy generation, the results clearly demonstrate that bromophenols are more suitable than chlorophenols for the enrichment of OHRB in marine environments. This study will greatly enhance our understanding of marine OHRB (rdhAs), auxiliary microbes, and microbial HOC adaptive mechanisms.

Solvothermal synthesis of bifunctional carbon dots for tartrazine and Fe(III) detection from chamomile residue by ternary DES pretreatment.

A ternary deep eutectic solvent (DES) consisting of choline chloride, lactic acid, and urea in a molar ratio of 1:2:2 was used to pretreat chamomile residue, followed by carbon dots (CDs) preparation using a one-pot solvothermal method. The CDs prepared under the suitable conditions had a high quantum yield of 47.34% and could be used as a bifunctional fluorescent probe for the detection of tartrazine and Fe(III). The concentration of tartrazine or Fe(III) had a good linear relationship with the fluorescence intensity of CDs that the determination coefficient (R2) was 0.9957 and 0.9943, and the limit of detection (LOD) was 40 nM and 119 nM, respectively. After verifying the different fluorescence quenching mechanisms of CDs by these two substances, a quantitative analysis was performed on real samples with recoveries of 90.70%∼104.29%. Overall, this study provided a promising technology for chemical conversion from low-cost chamomile residue to attractive bifunctional fluorescent probe.

Comparison of mNGS and conventional culture in non-organ transplant critically ill patients supported by ECMO: a single-center study.

Objectives: Infection is one of the important causes of death in intensive care unit (ICU) patients. At present, there are few articles focused on the detailed analysis of pathogenic microorganisms detected in different therapy periods of critically ill patients supported by extracorporeal membrane oxygenation (ECMO). Methods: From October 2020 to October 2022, ECMO-assisted patients who underwent multiple times of both metagenomic next-generation sequencing (mNGS) test and conventional culture were enrolled continuously in the First Affiliated Hospital of Zhengzhou University. The baseline data, laboratory test results, and pathogenic microorganisms detected by mNGS and traditional culture in different time periods were recorded and analyzed. Results: In the present study, 62 patients were included finally. According to whether the patients survived at discharge, they were divided into the survivor group (n = 24) and the non-survivor group (n = 38). Then, according to the different types of ECMO support, they were divided into the veno-venous ECMO (VV ECMO) group (n = 43) and the veno-arterial ECMO (VA ECMO) group (n = 19). The summit period of specimens of traditional culture and mNGS detection of ECMO patients was 7 days after admission, and the largest number of specimens of surviving patients appeared after ECMO withdrawal. The total number of traditional culture specimens was 1,249, the positive rate was 30.4% (380/1,249), and the positive rate of mNGS was 79.6% (82/103). A total of 28 kinds of pathogenic microorganisms were cultured from conventional culture, and 58 kinds of pathogenic microorganisms were detected by mNGS, including Mycobacterium, Rickettsia, and Chlamydia psittaci. In conventional culture, the most frequent Gram-negative bacteria, Gram-positive bacteria, and fungi were Klebsiella pneumoniae, Corynebacterium striatum, and Candida glabrata, and those with the highest frequency of occurrence in mNGS detection were Acinetobacter baumannii, Enterococcus faecium, and Aspergillus flavus. Conclusions: Throughout the whole treatment process, different kinds of suspicious biological specimens of high-infection-risk ICU patients supported by ECMO should undergo both mNGS detection and traditional culture early and repeatedly.

Assembly and analytical validation of a metagenomic reference catalog of human gut microbiota based on co-barcoding sequencing.

Human gut microbiota is associated with human health and disease, and is known to have the second-largest genome in the human body. The microbiota genome is important for their functions and metabolites; however, accurate genomic access to the microbiota of the human gut is hindered due to the difficulty of cultivating and the shortcomings of sequencing technology. Therefore, we applied the stLFR library construction method to assemble the microbiota genomes and demonstrated that assembly property outperformed standard metagenome sequencing. Using the assembled genomes as references, SNP, INDEL, and HGT gene analyses were performed. The results demonstrated significant differences in the number of SNPs and INDELs among different individuals. The individual displayed a unique species variation spectrum, and the similarity of strains within individuals decreased over time. In addition, the coverage depth analysis of the stLFR method shows that a sequencing depth of 60X is sufficient for SNP calling. HGT analysis revealed that the genes involved in replication, recombination and repair, mobilome prophages, and transposons were the most transferred genes among different bacterial species in individuals. A preliminary framework for human gut microbiome studies was established using the stLFR library construction method.

Computed tomography perfusion in differentiating portal hypertension: A correlation study with hepatic venous pressure gradient.

BACKGROUND: Hepatic venous pressure gradient (HVPG) is the gold standard for diagnosis of portal hypertension (PH), invasiveness and potential risks in the process of measurement limited its widespread use. AIM: To investigate the correlation of computed tomography (CT) perfusion parameters with HVPG in PH, and quantitatively assess the blood supply changes in liver and spleen parenchyma before and after transjugular intrahepatic portosystemic shunt (TIPS). METHODS: Twenty-four PH related gastrointestinal bleeding patients were recruited in this study, and all patients were performed perfusion CT before and after TIPS surgery within 2 wk. Quantitative parameters of CT perfusion, including liver blood volume (LBV), liver blood flow (LBF), hepatic arterial fraction (HAF), spleen blood volume (SBV) and spleen blood flow (SBF), were measured and compared before and after TIPS, and the quantitative parameters between clinically significant PH (CSPH) and non-CSPH (NCSPH) group were also compared. Then the correlation of CT perfusion parameters with HVPG were analyzed, with statistical significance as P < 0.05. RESULTS: For all 24 PH patients after TIPS, CT perfusion parameters demonstrated decreased LBV, increased HAF, SBV and SBF, with no statistical difference in LBF. Compared with NCSPH, CSPH showed higher HAF, with no difference in other CT perfusion parameters. HAF before TIPS showed positive correlation with HVPG (r = 0.530, P = 0.008), while no correlation was found in other CT perfusion parameters with HVPG and Child-Pugh scores. CONCLUSION: HAF, an index of CT perfusion, was positive correlation with HVPG, and higher in CSPH than NCSPH before TIPS. While increased HAF, SBF and SBV, and decreased LBV, were found after TIPS, which accommodates a potential non-invasive imaging tool for evaluation of PH.

The first high-quality chromosome-level genome of the Sipuncula Sipunculus nudus using HiFi and Hi-C data.

Sipuncula is a class of exocoelomic unsegmented animals whose evolutionary relationships are unresolved. The peanut worm Sipunculus nudus is a globally distributed, economically important species belonging to the class Sipuncula. Herein, we present the first high-quality chromosome-level assembly of S. nudus based on HiFi reads and high-resolution chromosome conformation capture (Hi-C) data. The assembled genome was 1,427 Mb, with a contig N50 length of 29.46 Mb and scaffold N50 length of 80.87 Mb. Approximately 97.91% of the genome sequence was anchored to 17 chromosomes. A BUSCO assessment showed that 97.7% of the expectedly conserved genes were present in the genome assembly. The genome was composed of 47.91% repetitive sequences, and 28,749 protein-coding genes were predicted. A phylogenetic tree demonstrated that Sipuncula belongs to Annelida and diverged from the common ancestor of Polychaeta. The high-quality chromosome-level genome of S. nudus will serve as a valuable reference for studies of the genetic diversity and evolution of Lophotrochozoa.

Myeloid-specific blockade of Notch signaling ameliorates nonalcoholic fatty liver disease in mice.

Rationale: Macrophages play a central role in the development and progression of nonalcoholic fatty liver disease (NAFLD). Studies have shown that Notch signaling mediated by transcription factor recombination signal binding protein for immunoglobulin kappa J region (RBP-J), is implicated in macrophage activation and plasticity. Naturally, we asked whether Notch signaling in macrophages plays a role in NAFLD, whether regulating Notch signaling in macrophages could serve as a therapeutic strategy to treat NAFLD. Methods: Immunofluorescence staining was used to detect the changes of macrophage Notch signaling in the livers of human patients with NAFLD and choline deficient amino acid-defined (CDAA) diet-fed mice. Lyz2-Cre RBP-Jflox or wild-type C57BL/6 male mice were fed with CDAA or high fat diet (HFD) to induce experimental steatohepatitis or steatosis, respectively. Liver histology examinations were performed using hematoxylin-eosin (H&E), Oil Red O staining, Sirius red staining and immunohistochemistry staining for F4/80, Col1α1 and αSMA. The expression of inflammatory factors, fibrosis or lipid metabolism associated genes were evaluated by quantitative reverse transcription (qRT)-PCR, Western blot or enzyme-linked immunosorbent assay (ELISA). The mRNA expression of liver samples was profiled by using RNA-seq. A hairpin-type decoy oligodeoxynucleotides (ODNs) for transcription factor RBP-J was loaded into bEnd.3-derived exosomes by electroporating. Mice with experimental NAFLD were treated with exosomes loading RBP-J decoy ODNs via tail vein injection. In vivo distribution of exosomes was analyzed by fluorescence labeling and imaging. Results: The results showed that Notch signaling was activated in hepatic macrophages in human with NAFLD or in CDAA-fed mice. Myeloid-specific RBP-J deficiency decreased the expression of inflammatory factors interleukin-1 beta (IL1ß) and tumor necrosis factor alpha (TNFα), attenuated experimental steatohepatitis in mice. Furthermore, we found that Notch blockade attenuated lipid accumulation in hepatocytes by inhibiting the expression of IL1ß and TNFα in macrophages in vitro. Meanwhile, we observed that tail vein-injected exosomes were mainly taken up by hepatic macrophages in mice with steatohepatitis. RBP-J decoy ODNs delivered by exosomes could efficiently inhibit Notch signaling in hepatic macrophages in vivo and ameliorate steatohepatitis or steatosis in CDAA or HFD mice, respectively. Conclusions: Combined, macrophage RBP-J promotes the progression of NAFLD at least partially through regulating the expression of pro-inflammatory cytokines IL1ß and TNFα. Infusion of exosomes loaded with RBP-J decoy ODNs might be a promising therapy to treat NAFLD.

Whole-transcriptome analyses identify key differentially expressed mRNAs, lncRNAs, and miRNAs associated with male sterility in watermelon.

Male sterility is a valuable trait for watermelon breeding, as watermelon hybrids exhibit obvious heterosis. However, the underlying regulatory mechanism is still largely unknown, especially regarding the related non-coding genes. In the present study, approximately 1035 differentially expressed genes (DEGs), as well as 80 DE-lncRNAs and 10 DE-miRNAs, were identified, with the overwhelming majority down-regulated in male-sterile floral buds. Enrichment analyses revealed that the general phenylpropanoid pathway as well as its related metabolisms was predicted to be altered in a mutant compared to its fertile progenitor. Meanwhile, the conserved genetic pathway DYT1-TDF1-AMS-MS188-MS1, as well as the causal gene ClAMT1 for the male-sterile mutant Se18, was substantially disrupted during male reproductive development. In addition, some targets of the key regulators AMS and MS188 in tapetum development were also down-regulated at a transcriptional level, such as ABCG26 (Cla004479), ACOS5 (Cla022956), CYP703A2 (Cla021151), PKSA (Cla021099), and TKPR1 (Cla002563). Considering lncRNAs may act as functional endogenous target mimics of miRNAs, competitive endogenous RNA networks were subsequently constructed, with the most complex one containing three DE-miRNAs, two DE-lncRNAs, and 21 DEGs. Collectively, these findings not only contribute to a better understanding of genetic regulatory networks underlying male sterility in watermelon, but also provide valuable candidates for future research.