Safety and Pharmacokinetic Assessment of the FIC CLDN18.2/4-1BB Bispecific Antibody in Rhesus Monkeys.

Gastric cancer is one of the most common cancers worldwide, particularly in China, with over half a million new cases and over 400 thousand deaths in 2022. Zolbetuximab, a first-in-class investigational monoclonal antibody (mAb) targeting tumor-associated antigen CLDN18.2 which is highly expressed on gastric cancer cells, was recently reported to meet the primary endpoint in Phase III trial as first-line treatment in CLDN18.2 positive and HER2-negative gastric cancers. In the present study, we developed a humanized bispecific antibody (bsAb) CLDN18.2/4-1BB named PM1032. PM1032 activates immune cells via CLDN18.2 mediated crosslinking of 4-1BB, a potent stimulator of T/NK cells. It induced strong immunological memory in multiple tumor-bearing animal models, indicating significant potential as an effective treatment for CLDN18.2 positive cancers such as gastric cancer. Since liver and gastrointestinal (GI) related toxicities were reported in 4-1BB and CLDN18.2 targeting programs during the clinical development, respectively, extensive pharmacokinetics (PK) and safety profile characterization of PM1032 was performed in rhesus monkeys. PM1032 had a half-life comparable to a conventional IgG1 mAb, and serum drug concentration increased in a dose-dependent pattern. Furthermore, PM1032 was generally well tolerated, with no significant abnormalities observed in toxicity studies, including the liver and stomach. In summary, PM1032 demonstrated good PK and an exceptional safety profile in rhesus monkeys supporting further investigation in clinical studies.

Stable Electron-Transport-Layer-Free Perovskite Solar Cells with over 22% Power Conversion Efficiency.

Due to their low cost and simplified production process, electron-transport-layer-free (ETL-free) perovskite solar cells (PSCs) have attracted great attention recently. However, the performance of ETL-free PSCs is still at a disadvantage compared to cells with a conventional n-i-p structure due to the severe recombination of charge carriers at the perovskite/anode interface. Here, we report a strategy to fabricate stable ETL-free FAPbI3 PSCs by in situ formation of a low dimensional perovskite layer between the FTO and the perovskite. This interlayer gives rise to the energy band bending and reduced defect density in the perovskite film and indirect contact and improved energy level alignment between the anode and perovskite, which facilitates charge carrier transport and collection and suppresses charge carrier recombination. As a result, ETL-free PSCs with a power conversion efficiency (PCE) exceeding 22% are achieved under ambient conditions.

Regional Functionalization Molecular Design Strategy: A Key to Enhancing the Efficiency of Multi-Resonance OLEDs.

Herein, we propose a regional functionalization molecular design strategy that enables independent control of distinct pivotal parameters through distinct segments of the molecule. Three novel blue emitters A-BN, DA-BN, and A-DBN, have been successfully synthesized by integrating highly rigid and three-dimensional adamantane-containing spirofluorene units into the MR framework. These molecules form two distinctive functional parts: part 1 comprises a boron-nitrogen (BN)-MR framework with adjacent benzene and fluorene units forming a central luminescent core characterized by an exceptionally rigid planar geometry, allowing for narrow FWHM values; part 2 includes peripheral mesitylene, benzene, and adamantyl groups, creating a unique three-dimensional "umbrella-like" conformation to mitigate intermolecular interactions and suppress exciton annihilation. The resulting A-BN, DA-BN, and A-DBN exhibit remarkably narrow FWHM values ranging from 18 to 14 nm and near-unity photoluminescence quantum yields. Particularly, OLEDs based on DA-BN and A-DBN demonstrate outstanding efficiencies of 35.0% and 34.3%, with FWHM values as low as 22 nm and 25 nm, respectively, effectively accomplishing the integration of high color purity and high device performance.

Functional Proteomics Analysis of Norfloxacin-Resistant Edwardsiella tarda.

Multidrug-resistant Edwardsiella tarda threatens both sustainable aquaculture and human health, but the control measure is still lacking. In this study, we adopted functional proteomics to investigate the molecular mechanism underlying norfloxacin (NOR) resistance in E. tarda. We found that E. tarda had a global proteomic shift upon acquisition of NOR resistance, featured with increased expression of siderophore biosynthesis and Fe3+-hydroxamate transport. Thus, either inhibition of siderophore biosynthesis with salicyl-AMS or treatment with another antibiotic, kitasamycin (Kit), which was uptake through Fe3+-hydroxamate transport, enhanced NOR killing of NOR-resistant E. tarda both in vivo and in vitro. Moreover, the combination of NOR, salicyl-AMS, and Kit had the highest efficacy in promoting the killing effects of NOR than any drug alone. Such synergistic effect not only confirmed in vitro and in vivo bacterial killing assays but also applicable to other clinic E. tarda isolates. Thus, our data suggest a proteomic-based approach to identify potential targets to enhance antibiotic killing and propose an alternative way to control infection of multidrug-resistant E. tarda.

Inhibition of ERK downregulates autophagy via mitigating mitochondrial fragmentation to protect SH-SY5Y cells from OGD/R injury.

BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) is the main cause leading to high mortality and neurological disability in patients with cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Our previous study found that extracellular signal-regulated kinase (ERK) activation, dynamin-related protein1 (Drp1)/Mitofusin2 (Mfn2)-dependent mitochondrial dynamics imbalance, and excessive autophagy were involved in the mechanism of nerve injury after CA/CPR. However, the specific pathological signaling pathway is still unknown. This study aimed to explore the molecular function changes of ERK-Drp1/Mfn2-autophagy signaling pathway in SH-SY5Y cell oxygen-glucose deprivation/reoxygenation (OGD/R) model, to further clarify the pathophysiological mechanism of CIRI, and to provide a new strategy for cerebral protection after CIRI. METHODS: SH-SY5Y cells were pretreated with drugs 24 h before OGD/R. The Drp1 and Mfn2 knockdown were adopted small interfering RNAs. The overexpression of p-Drp1S616 and Mfn2 were used recombinant plasmids. The expression levels of mitochondrial dynamics proteins (p-Drp1, Drp1, Mfn2, Mfn1 and Opa1) and autophagy markers (LC3, Beclin1 and p62) were measured with the Western blotting. The mRNA levels after transfection were determined by PCR. Cell injury and viability were evaluated with released LDH activity and CCK8 assay kits. Mitochondria morphology and autophagosome were observed under transmission electron microscopy. Mitochondrial function was detected by the mitochondrial permeability transition pore assay kit. The co-expression of p-ERK, p-Drp1 and LC3 was assessed with multiple immunofluorescences. One-way analysis of variance followed by least significance difference post hoc analysis (for equal homogeneity) or Dunnett's T3 test (for unequal homogeneity) were used for statistical tests. RESULTS: ERK inhibitor-PD98059 (PD) protects SH-SY5Y cells from OGD/R-induced injury; while ERK activator-TPA had the opposite effect. Similar to autophagy inhibitor 3-MA, PD downregulated autophagy to improve cell viability; while autophagy activator-rapamycin further aggravated cell death. PD and Drp1-knockdown synergistically attenuated OGD/R-induced Drp1 activation, mPTP opening and cell injury; overexpression of Drp1S616E or ablating Mfn2 partly abolished the protective effects of PD. Multiple immunofluorescences showed that p-ERK, p-Drp1 and LC3 were co-expressed. CONCLUSION: Inhibition of ERK downregulates autophagy via reducing Drp1/Mfn2-dependent mitochondrial fragmentation to antagonize mitochondrial dysfunction and promotes cell survival in the SH-SY5Y cells OGD/R model. Video Abstract.

Digital measurement method for comparing the absolute marginal discrepancy of three-unit ceramic fixed dental prostheses fabricated using conventional and digital technologies.

BACKGROUND: In clinical practice, control of the marginal fit of fixed dental prostheses is hindered by evaluation method, which needs to be further improved to increase its clinical applicability. This study aimed to quantitatively analyze the absolute marginal discrepancy of three-unit ceramic fixed dental prostheses fabricated by conventional and digital technologies using a digital measurement method based on the digital impression technology and open source software. METHODS: A digital workflow and the conventional impression combined with the lost-wax heat-pressed technique were adopted to separately fabricate 10 glass ceramic fixed dental prostheses. Three-dimensional data for the abutments, fixed dental prostheses, and fixed dental prostheses seated on the abutments, were obtained using a dental scanner. The two datasets were aligned using registration technology, specifically "multi-points registration" and "best fit alignment," by reverse engineering software. Subsequently, the three-dimensional seated fit between the fixed dental prostheses and abutments were reconstructed. The margin of the abutment and crown was extracted using edge-sharpening and other functional modules, and the absolute marginal discrepancy was measured by the distance between the margin of the abutment and crown. One-way analysis of variance was used to statistically analyze the measurement results. RESULTS: Using the digital measurement method, the mean value of absolute marginal discrepancy for fixed dental prostheses fabricated by the conventional method was 106.69 ± 6.46 µm, and that fabricated by the digital workflow was 102.55 ± 6.96 µm. The difference in the absolute marginal discrepancy of three-unit all-ceramic fixed dental prostheses fabricated using the two methods was not statistically significant (p > 0.05). CONCLUSIONS: The digital measurement method for absolute marginal discrepancy was preliminarily established based on open source software and applied in three-unit ceramic fixed dental prostheses. The absolute marginal discrepancy of three-unit ceramic fixed dental prostheses fabricated using digital technology was comparable to that of conventional technique.

Three-point sectional-cast digital method for transferring the interocclusal relationship for full-mouth rehabilitation of worn dentition.

For full-mouth rehabilitation of worn dentition, "diagnostic" interim restorations are required to reestablish the interocclusal relationship. It is important but challenging to transfer the interocclusal relationship and to map the basic form and contour of interim restorations to the final restorations. Alignment of interim restorations and working casts is difficult when using digital workflows because of a lack of consistent hard tissue reference points. The digital workflow presented in this study used a "3-point sectional-cast digital cross-mounting method" to transfer the interocclusal relationship during full-mouth rehabilitation. An intermediate cast was made with three interim restorations: one on an incisor and two on molars. The interocclusal relationship and occlusal morphologies of the diagnostic interim prostheses were transferred and aligned to working casts using the 3-point sectional casts.

Sulfone-Embedded Heterocyclic Narrowband Emitters with Strengthened Molecular Rigidity and Suppressed High-Frequency Vibronic Coupling.

Sulfone-embedded heterocyclics are of great interest in organic light-emitting diodes (OLEDs), however, exploring highly efficient narrowband emitters based on sulfone-embedded heterocyclics remains challenging. Herein, five emitters with different sulfur valence state and molecular rigidity, namely tP, tCPD, 2tCPD, tPD and tPT, are thoroughly analysed. With restricted twisting of flexible peripheral phenyl by strengthening molecular rigidity, molecular emission spectra can be enormously narrowed. Further, introducing the sulfone group with bending vibration in low-frequency region that suppresses high-frequency vibration, sharp narrow full-widths at half-maximum of 28 and 25 nm are achieved for 2tCPD and tPD, respectively. Maximum external quantum efficiencies of 22.0 % and 27.1 % are successfully realized for 2tCPD- and tPD-based OLED devices. These results offer a novel design strategy for constructing narrowband emitters by introducing sulfone group into a rigid molecular framework.

Taurine promotes Oreochromis niloticus survival against Edwardsiella tarda infection.

Edwardsiella tarda represents one of the most important pathogens that infects a variety of hosts including aquatic animals and humans. The outbreak of E. tarda infection is frequently reported in aquaculture that causes huge economic loss. Due to the widespread of antibiotic resistance, available antibiotics to treat bacterial infection are limited. Therefore, enhancing aquatic animals to survive upon E. tarda infection become an urgent issue. In this study, we profiled the metabolomic change of tilapia in-between the dying and survival fish upon E. tarda infection. The dying and survival fish mounts differential metabolic response, from which we identify a key metabolite, taurine, whose abundance is increased in both the survival group and the dying group but is more significant in the survival group. Exogenous taurine increases tilapia survival rate by 37.5% upon E. tarda infection. Further quantitative PCR analysis demonstrate taurine increases the expression of immune genes in liver, spleen and head kidney. Therefore, our study shows a new strategy to enhance fish immune response against bacterial infection.

Novel Polycyclic Fused Amide Derivatives: Properties and Applications for Sky-blue Electroluminescent Devices.

Aromatic imide derivatives play a critical role in boosting the electroluminescent (EL) performance of organic light-emitting diodes (OLEDs). However, the majority of aromatic imide-based materials are limited to long wavelength emission OLEDs rather than blue emissions due to their strong electron-withdrawing characteristics. Herein, two novel polycyclic fused amide units were reported as electron acceptor to be combined with either a tetramethylcarbazole or acridine donor via a phenyl linker to generate four conventional fluorescence blue emitters of BBI-4MeCz, BBI-DMAC, BSQ-4MeCz and BSQ-DMAC for the first time. BSQ-4MeCz and BSQ-DMAC based on a BSQ unit exhibited higher thermal stability and photoluminescence quantum yields than BBI-4MeCz and BBI-DMAC based on a BBI unit due to their more planar acceptor structure. The intermolecular interactions that exist in the BSQ series materials effectively inhibit the molecular rotation and configuration relaxation, and thus allow for blue-shifted emissions. Blue OLED devices were constructed with the developed materials as emitters, and the effects of both the structure of the polycyclic fused amide acceptor and the electron donor on the EL performance were clarified. Consequently, a sky-blue OLED device based on BSQ-DMAC was created, with a high maximum external quantum efficiency of 4.94% and a maximum luminance of 7761 cd m-2.

Novel compound heterozygous mutations of DNAH5 identified in a pediatric patient with Kartagener syndrome: case report and literature review.

BACKGROUND: Kartagener syndrome is a subtype of primary ciliary dyskinesia that may exhibit various symptoms including neonatal respiratory distress and frequent infections of the lung, sinus and middle ear because of the impaired function of motile cilia. In addition to typical symptoms of primary ciliary dyskinesia, patients with Kartagener syndrome also show situs inversus. It is an autosomal recessive disorder which is mostly caused by mutations in DNAH5. Kartagener syndrome is often underdiagnosed due to challenges in the diagnosis process. As next-generation sequencing becomes widely used in clinical laboratories, genetic testing provides an accurate approach to the diagnosis of Kartagener syndrome. CASE PRESENTATION: A 7-year-old female patient presented with runny nose of 6 years duration and recurrent cough with phlegm of 2 years duration. Kartagener syndrome was diagnosed through diagnostic tests such as nasal nitric oxide (NO) concentration and transmission electron microscopy, and after performing other exams that corroborated the diagnosis, such as computed tomography, bronchoscopy and hearing test. Whole-exome sequencing was performed for the patient and both parents. The pediatric patient was diagnosed as Kartagener syndrome with the typical symptoms of ciliary dyskinesia including bronchiectasis, sinusitis, conductive hearing loss and situs inversus along with a reduced nasal NO concentration and ciliary abnormalities. The patient carried two novel compound heterozygous mutations in DNAH5, NM_001369:c.12813G > A (p. Trp4271Term) and NM_001369:c.9365delT (p. Leu3122Term). Both mutations lead to premature stop codons and thus are pathogenic. The p. Trp4271Term and p. Leu3122Term mutations were inherited from the father and the mother of the patient individually. A literature review was also conducted to summarize DNAH5 mutations in pediatric patients with Kartagener syndrome across different ethnic groups. CONCLUSIONS: Our study provides a good example of the diagnosis of Kartagener syndrome in pediatric patients using a series of diagnostic tests combined with genetic testing. Two novel loss-of-function mutations in DNAH5 were identified and validated in a pediatric patient with Kartagener syndrome.

In Situ Interface Engineering for Highly Efficient Electron-Transport-Layer-Free Perovskite Solar Cells.

Electron-transport-layer free perovskite solar cells (ETL-free PSCs) have attracted great attention due to their low cost and simple manufacturing process. However, an additional interface layer has to be introduced, and the currently achieved efficiency remains far from full-structure PSCs. Here, we report an in situ interface engineering strategy by the methylammonium acetate (MAAc) ionic liquid perovskite precursor. We found that a dipole layer was in situ constructed through the physical adsorption of the residual MAAc polar molecules on the indium tin oxide electrode, which is significantly different from the treatment by the interface layer in previous reports. This allows a decrease of the effective work function and enables in situ band bending in the perovskite semiconductor. The in situ band bending facilitates charge collection and hinders interfacial charge recombination, leading to ETL-free PSCs with a maximum power conversion efficiency of 21.08%, which is the highest report to date.

Learner behaviors in synchronous online prosthodontic education during the 2020 COVID-19 pandemic.

STATEMENT OF PROBLEM: Synchronous online prosthodontic courses became a popular learning mode during the 2020 COVID-19 pandemic crisis. Nonetheless, the extent of learner participation and completion of these courses remains unknown. PURPOSE: The purpose of this study was to assess learner behaviors in synchronous online prosthodontic continuing education lectures in China during the 2020 COVID-19 pandemic. MATERIAL AND METHODS: All live online prosthodontic courses held by an online dental school in China from February to May 2020 were retrieved. The no-cost lectures could be accessed anonymously and viewed repeatedly on the day of broadcast. Learning behavior data (teacher speaking time, audience total, timing of first visit to the online classroom, viewing time, and completion rate) were obtained. Learning progress was calculated by dividing viewing time by teacher speaking time. When a learner progressed through 95% of a lecture, the lecture was considered completed. RESULTS: A total of 41 781 learners participated in 18 online prosthodontic courses, which had a mean duration of 77.2 ±15.8 minutes. For each lecture, 2321 ±1454 participants attended, with 510 ±404 participants completing each session. There were 13 098 participants (31.35%) who viewed the lectures for less than 1 minute. Approximately half of the participants viewed the lectures for less than 10 minutes, with their learning progress failing to pass 10%. The average completion rate was 21.97%, with variation in completion rate dependent on when a learner first visited the online classroom. Significant differences were found among the lecture completion rates and the timing of the first visit to the online classroom (P<.001). CONCLUSIONS: Synchronous online prosthodontic education courses in China had a high number of participants but low learning progress and completion rates during the 2020 COVID-19 pandemic.

Characteristics of correct diagnosis versus misdiagnosis of paediatric tracheobronchial foreign body.

PURPOSE: To characterize and compare children with correct diagnosis (CD) and misdiagnosis (MD) of tracheobronchial foreign body (TBFB). METHODS: A retrospective study was performed to review the medical records of children with CD group and MD group of TBFB. CD was defined when TBFB was identified during the first hospital visit. Otherwise, MD was considered. Demographic information, including gender, age, and clinical information, including clinical presentations and characteristics of foreign bodies, were retrieved. These characteristics were compared between two groups by Student's t-test or Wilcoxon two-sample test, or Chi-square analysis or Fisher's exact test, when appropriate. RESULTS: A total of 462 children with final diagnosis of TBFB were identified, with 276 children having CD and 186 children having MD. The most common location to identify the TBFB was right main bronchus in both CD and MD groups. Children with the previous history of respiratory tract foreign body were more likely to receive the CD. Children in MD group were more likely to have fever, as well as wheezing and crackles during physical examination. They were more likely to have pneumonia. Most common TBFB were peanuts. The majority of the TBFB were removed by the flexible bronchoscope coupled with forceps. CONCLUSION: Careful history taking and physical examination, especially for those children with unclear causes for their pneumonia or asthma, or children with no improvement on the treatments, should be performed to rule out the possibility of TBFB. Bronchoscopy should be performed if necessary.

The antiviral mechanism of the crude extract from the flowers of Trollius chinensis based on TLR 3 signaling pathway.

The effects of crude extract from the flowers of Trollius chinensis on expressions of mRNA and proteins related to vital genes (TLR 3, TBK 1, IRF 3 and IFN ß) in TLR 3 signaling pathway were investigated in the presence/absence of Polyinosinic acid-polycytidylic acid (PolyI: C) to ascertain the antiviral mechanism of these flowers. Real-time PCR and western blot were applied to determine the expressions of mRNA and proteins, respectively, and immunofluorescence assay was employed to study the effect on IRF 3 distribution between nuclei and cytoplasma. In the absence of PolyI:C, the crude extract reduced the mRNA expression of TLR 3, IRF 3 and IFN ß and the protein expression of TLR 3, and increased the protein expression of IRF 3 and the distribution of IRF 3 in nuclei. In the presence of PolyI:C, the extract reduced the mRNA and protein expressions of TLR 3 and the mRNA expression of IFN ß, meanwhile inhibited the translocation of IRF 3 into nuclei. The antiviral mechanism of the crude extract from the flowers of T. chinensis is to protect the host from inflammatory damage through intervening the TLR 3 signaling pathway and reducing the secretion of inflammatory factors.

Decreased long non-coding RNA lincFOXF1 indicates poor progression and promotes cell migration and metastasis in osteosarcoma.

Long non-coding RNAs have been demonstrated to be important regulators of various cancers, though the precise mechanisms remain unclear. Although lincFOXF1 has been reported to act as a tumour suppressor, its function and underlying mechanisms in osteosarcoma have not yet been explored. We employed quantitative real-time polymerase chain reaction (qRT-PCR) to evaluate the expression of lincFOXF1 and GAPDH in osteosarcoma tissues and cell lines, and colony-formation, CCK8, wound-healing, and transwell assays were conducted to analyse the proliferation, migration, and invasion capacity of osteosarcoma cells. Subcellular localization analysis by fractionation and RNA immunoprecipitation assays were performed to elucidate the mechanism responsible for lincFOXF1-mediated phenotypes of osteosarcoma cells. The results revealed that lincFOXF1 expression is significantly decreased and strongly related to Enneking stage as well as metastasis in osteosarcoma patients. Further experiments showed that lincFOXF1 inhibits the migration, invasion and metastasis of cells in vitro and vivo. Mechanistic investigation demonstrated that lincFOXF1 physically binds to EZH2, a polycomb repressive complex 2 (PRC2) component, and a search for downstream targets suggested that G-protein-coupled receptor kinase-interacting protein 1 (GIT1) is involved in the lincFOXF1-mediated repression of osteosarcoma cells migration and invasion. Moreover, GIT1 expression is inversely correlated with lincFOXF1 in osteosarcoma. The present findings indicate that lincFOXF1 is involved in the progression of osteosarcoma through binding with EZH2, further regulating GIT1 expression. Our results suggest that lincFOXF1 may serve as a biomarker and therapeutic target for osteosarcoma patients.

Effects of Electron Affinity and Steric Hindrance of the Trifluoromethyl Group on the π-Bridge in Designing Blue Thermally Activated Delayed Fluorescence Emitters.

To explore the correlation of the acceptor electron affinity and the molecular conformation to the thermally activated delayed fluorescence (TADF) feature, a series of d-π-A molecules were designed and synthesized with triazine (Trz) as the acceptor (A) and carbazole (Cz) or tert-butylcarbazole (BuCz) as the donor (D). On the phenylene bridge between D and A, methyl or trifluoromethyl was incorporated close either to D or to A to tune the molecular conformation and the electron-withdrawing ability of acceptor. Both the twist angles and the singlet and triplet energy difference (ΔEST ) were observed strongly dependent on the type and position of the substituent on the π-bridge. Only those molecules with trifluoromethyl locating close to the D side, namely TrzCz-CF3 and TrzBuCz-CF3 , exhibit TADF feature, verifying that both sufficient electron affinity of the A unit and large dihedral angle between D and the π-bridge are necessary to ensure the occurrence of TADF. The blue organic light-emitting diodes fabricated with TrzCz-CF3 and TrzBuCz-CF3 achieved external quantum efficiencies of 9.40 % and 14.22 % with CIE coordinates of (0.19, 0.23) and (0.18, 0.29) respectively. This study provides practical design strategy for blue TADF materials particularly when planar and less crowded group is used as donor.

X-box-binding protein 1 is required for pancreatic development in Xenopus laevis.

X-box-binding protein 1 (XBP1) is a protein containing the basic leucine zipper structure. It belongs to the cAMP-response element binding protein (CREB)/activating transcription factor transcription factor family. As the main transcription factor, spliced XBP1 (XBP1s) participates in many physiological and pathological processes and plays an important role in embryonic development. Previous studies showed that XBP1-knockout mice died because of pancreatic exocrine function deficiency, indicating that XBP1 plays an important role in pancreatic development. However, the exact role of XBP1 in pancreatic development remains unclear. This study aimed to investigate the role of XBP1 in the pancreatic development of Xenopus laevis embryos. Whole-mount in situ hybridization and quantitative real-time PCR results revealed that the expression levels of pancreatic progenitor marker genes pdx1, p48, ngn3, and sox9 were downregulated in XBP1s morpholino oligonucleotide (MO)-injected embryos. The expression levels of pancreatic exocrine and endocrine marker genes insulin and amylase were also downregulated. Through the overexpression of XBP1s, the phenotype and gene expressions were opposite to those in XBP1s MO-injected embryos. Luciferase and chromatin immunoprecipitation assays showed that XBP1s could bind to the XBP1-binding site in the foxa2 promoter. These results revealed that XBP1 is required in the pancreatic development of Xenopus laevis and might function by regulating foxa2.

Comprehensive evaluation of effects and safety of statin on the progression of liver cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Statin has been more and more widely used in chronic liver disease, however, existed studies have attained contradictory results. According to the present study, we aimed to test the efficacy and safety of statin via a meta-analysis. METHODS: Different databases were searched for full-text publication based on inclusion and exclusion criteria. For data-pooling, fixed-effect model was applied if heterogeneity wasn't detected. Otherwise, random-effect model was adopted. Heterogeneity was detected by I squire (I2) test. All results of analysis were illustrated as forest plots. Publication bias was assessed using the Begg's adjusted rank correlation test. Standard mean difference (SMD) was calculated in continuous variables. Pooled hazard ratio or odds ratio was calculated in catergorical variables. RESULTS: Seventeen clinical studies were finally included. Hepatic portal hemodynamic parameters were improved in statin users for a short-term response. For a long-term follow-up, statin treatment surprisingly decreased mortality rate (HR = 0.782, 95% CI: 0.718-0.846, I2 > 50%) and lower the occurrence of hepatocellular carcinoma (HR = 0.75, 95% CI: 0.64-0.86, I2 > 50%) in liver cirrhosis. Statin seemed not to decrease the risk of esophageal variceal bleeding and spontaneous bacterial peritonitis. However, statin was proved to decrease the risk of hepatic encephalopathy and ascites. Incidence of drug related adverse events didn't increase in statin users. Dose-dependent effects of statin on hepatocellular carcinoma development, decompensated cirrhosis events occurrence, and liver cirrhosis progression. CONCLUSION: Statin influenced parameters of hepatic portal vessel pressure in short-term treatment. Prognosis of liver cirrhosis benefited from statin treatment in long term follow-up. The efficacy and safety of statin in liver cirrhosis treatment is confirmed. To date, similar study is hardly seen before.

Transcriptome analysis of bronchoalveolar lavage fluid from children with severe Mycoplasma pneumoniae pneumonia reveals novel gene expression and immunodeficiency.

BACKGROUND: A growing number of severe Mycoplasma pneumoniae pneumonia (MPP) cases have been reported recently. However, the pathogenesis of severe MPP is not clear. In the current study, transcriptome sequencing was used to identify gene expression and alternative splicing profiles to provide insights into the pathogenesis of severe MPP. METHODS: RNAs of bronchoalveolar lavage fluid (BALF) samples from three severe MPP children and three mild MPP children were analyzed respectively by deep sequencing followed by computational annotation and quantification. RESULTS: The gene expression analysis revealed 14 up-regulated and 34 down-regulated genes in severe MPP children comparing to mild MPP children. The top 10 most up-regulated genes were IGHV1-69, CH17-472G23.1, ATP1B2, FCER2, MUC21, IL13, FCRLB, CLEC5A, FAM124A, and INHBA. The top 10 most down-regulated genes were OSTN-AS1, IL22RA2, COL3A1, C1orf141, IGKV2-29, RP11-731F5.2, IGHV4-4, KIRREL, DNASE1L3, and COL6A2. Clustering analysis revealed similar expression pattern of CLEC5A, IL13, FCER2, and FLT1. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed changes related to primary immunodeficiency in severe MPP children comparing to mild MPP children; the pathway involves CD19, TNFRSF13C, CD79A, and AICDA genes. Among the differentially expressed genes, significant alternative splicing events were found in FCER2 and FCRLA. CONCLUSIONS: The current study on RNA sequencing provides novel insights into the pathogenesis of severe MPP in terms of gene expression and alternative splicing. The up-regulation of IL13, FCER2, FLT1, and CLEC5A and the down-regulation of CD79A, AICDA, CD19, and TNFRSF13C may contribute to the pathogenesis of severe MPP. The differential expressions of FCER2 and FCRLA could be due to their alternative splicing.