Identification of STAT3 as a biomarker for cellular senescence in liver fibrosis: A bioinformatics and experimental validation study.

BACKGROUND: Cellular senescence is associated with a dysregulated inflammatory response, which is an important driver of the development of liver fibrosis (LF). This study aimed to investigate the effect of cellular senescence on LF and identify potential key biomarkers through bioinformatics analysis combined with validation experiments in vivo and in vitro. METHODS: The Gene Expression Omnibus (GEO) database and GeneCards database were used to download the LF dataset and the aging-related gene set, respectively. Functional enrichment analysis of differential genes was then performed using GO and KEGG. Hub genes were further screened using Cytoscape's cytoHubba. Diagnostic values for hub genes were evaluated with a receiver operating characteristic (ROC) curve. Next, CIBERSORTx was used to estimate immune cell types and ratios. Finally, in vivo and in vitro experiments validated the results of the bioinformatics analysis. Moreover, molecular docking was used to simulate drug-gene interactions. RESULTS: A total of 44 aging-related differentially expressed genes (AgDEGs) were identified, and enrichment analysis showed that these genes were mainly enriched in inflammatory and immune responses. PPI network analysis identified 6 hub AgDEGs (STAT3, TNF, MMP9, CD44, TGFB1, and TIMP1), and ROC analysis showed that they all have good diagnostic value. Immune infiltration suggested that hub AgDEGs were significantly associated with M1 macrophages or other immune cells. Notably, STAT3 was positively correlated with α-SMA, COL1A1, IL-6 and IL-1ß, and was mainly expressed in hepatocytes (HCs). Validation experiments showed that STAT3 expression was upregulated and cellular senescence was increased in LF mice. A co-culture system of HCs and hepatic stellate cells (HSCs) further revealed that inhibiting STAT3 reduced HCs senescence and suppressed HSCs activation. In addition, molecular docking revealed that STAT3 was a potential drug therapy target. CONCLUSIONS: STAT3 may be involved in HCs senescence and promote HSCs activation, which in turn leads to the development of LF. Our findings suggest that STAT3 could be a potential biomarker for LF.

Rational Design of 2D Metal Halide Perovskites with Low Congruent Melting Temperature and Large Melt-Processable Window.

Metal halide perovskites (MHPs) have garnered significant attention due to their distinctive optical and electronic properties, coupled with excellent processability. However, the thermal characteristics of these materials are often overlooked, which can be harnessed to cater to diverse application scenarios. We showcase the efficacy of lowering the congruent melting temperature (Tm) of layered 2D MHPs by employing a strategy that involves the modification of flexible alkylammonium through N-methylation and I-substitution. Structural-property analysis reveals that the N-methylation and I-substitution play pivotal roles in reducing hydrogen bond interactions between the organic components and inorganic parts, lowering the rotational symmetry number of the cation and restricting the residual motion of the cations. Additional I···I interactions enhance intermolecular interactions and lead to improved molten stability, as evidenced by a higher viscosity. The 2D MHPs discussed in this study exhibit low Tm and wide melt-processable windows, e.g., (DMIPA)2PbI4 showcasing a low Tm of 98 °C and large melt-processable window of 145 °C. The efficacy of the strategy was further validated when applied to bromine-substituted 2D MHPs. Lowering the Tm and enhancing the molten stability of the MHPs hold great promise for various applications, including glass formation, preparation of high-quality films for photodetection, and fabrication of flexible devices.

Room-Temperature Anisotropic Actuation Driven by a Synergistic Order-Disorder and Displacive Phase Transition in a Ferroelectric Crystal.

Actuating materials convert different forms of energy into mechanical responses. To satisfy various application scenarios, they are desired to have rich categories, novel functionalities, clear structure-property relationships, fast responses, and, in particular, giant and reversible shape changes. Herein, we report a phase transition-driven ferroelectric crystal, (rac-3-HOPD)PbI3 (3-HOPD = 3-hydroxypiperidine cation), showing intriguingly large and anisotropic room-temperature actuating behaviors. The crystal consists of rigid one-dimensional [PbI3] anionic chains running along the a-axis and discrete disk-like cations loosely wrapping around the chains, leaving room for anisotropic shape changes in both the b- and c-axes. The shape change is switched by a ferroelectric phase transition occurring at around room temperature (294 K), driven by the exceptionally synergistic order-disorder and displacive phase transition. The rotation of the cations exerts internal pressure on the stacking structure to trigger an exceptionally large displacement of the inorganic chains, corresponding to a crystal lattice transformation with length changes of +24.6% and -17.5% along the b- and c-axis, respectively. Single crystal-based prototype devices of circuit switches and elevators have been fabricated by exploiting the unconventional negative temperature-dependent actuating behaviors. This work provides a new model for the development of multifunctional mechanically responsive materials.

Halogen Substitution Regulates High Temperature Dielectric Switch in Lead-Free Chiral Hybrid Perovskites.

Hybrid metal halides (HMHs) based phase transition materials have received widespread attention due to their excellent performance and potential applications in energy harvesting, optoelectronics, ferroics, and actuators. Nevertheless, effectively regulating the properties of phase transitions is still a thorny problem. In this work, two chiral lead-free HMHs (R-3FP)2 SbCl5 (1; 3FP=3-fluoropyrrolidinium) and (R-3FP)2 SbBr5 (2) were synthesized. By replacing the halide ions in the inorganic skeleton, the phase transition temperature of 2 changes with an increase of about 20 K, compared with 1. Meanwhile, both compounds display reversible dielectric switching properties. Through crystal structure analysis and Hirshfeld surface analysis, their phase transitions are ascribed to the disorder of the cations and deformation of the inorganic chains.

Transcriptomic evaluation of N6-methyladenosine modification can be used to identify differentially gene and immune-related biological processes in TX mice with liver fibrosis.

BACKGROUND: N6-methyladenosine (m6A) modification controls the stability, splicing, and translation of mRNA, which is important in the development of illnesses. Wilson's disease (WD) is an autosomal recessive liver copper metabolic disorder that causes liver fibrosis. The role of m6A methylation in WD-induced liver fibrosis development is still unclear. Thus, the goal of this study was to examine the scope of m6A methylation and further explore the potential targets related to WD-induced liver fibrosis. RESULTS: A total of 1930 significantly different m6A peaks were found on 1737 mRNAs, of which 993 were hypermethylated and 744 were hypomethylated when comparing normal and WD-induced liver fibrosis mice (n = 3). In parallel, 1261 differentially expressed mRNAs, comprising 557 upregulated and 704 downregulated mRNAs, were found. Overall, 114 mRNAs with significant changes in m6A levels and RNA expression were identified via joint analysis. Then, through PPI network construction and functional enrichment analysis, 12 hub genes were identified, these genes were mainly enriched in the inflammatory response and immunomodulation, and they are associated with immune cell infiltration. CONCLUSIONS: The significant difference in the amount of mRNA m6A modifications indicates that m6A modification is involved in the progression of WD-induced liver fibrosis, and theidentified hub genes are involved in inflammation and immune infiltration. These results may provide insights for subsequent studies on potential regulatory mechanisms.

Liver transcriptomic and proteomic analyses provide new insight into the pathogenesis of liver fibrosis in mice.

BACKGROUND: Liver fibrosis (LF) is a kind of progressive liver injury reaction. The goal of this study was to achieve a more detailed understanding of the molecular changes in response to CCl4-induced LF through the identification of a differentially expressed liver transcriptomic and proteomic. RESULTS: A total of 1224 differentially expressed genes (DEGs) and 302 differentially expressed proteins (DEPs) were significantly identified at the transcriptomic and proteomic level, respectively, and 69 genes (hereafter "cor-DEGs-DEPs" genes) were detected at both levels. Pathway enrichment analysis showed that these cor-DEGs-DEPs genes were significantly enriched in 133 pathways. Importantly, among the cor-DEGs-DEPs genes, Gstm1, Gstm3, Ephx1 and Gstp1 were shown to be associated with metabolic pathways, and confirmed by RT-qPCR and parallel reaction monitoring (PRM) verification. CONCLUSIONS: Through the combined analysis of transcriptomic and proteomic data, this study provides valuable insights into the potential mechanism of the pathogenesis of LF, and lays a theoretical foundation for the further development of targeted therapy for LF.

Comprehensive analysis of mRNAs in the cerebral cortex in APP/PS1 double-transgenic mice with Alzheimer's disease based on high-throughput sequencing of N4-acetylcytidine.

N4-acetylcytidine (ac4C), a significant modified nucleoside, participates in the development of many diseases. Messenger RNAs (mRNAs) contain most of the information of the genome and are the molecules that transmit information from genes to proteins. Alzheimer's disease (AD) is a progressive neurodegenerative disease in which fibrillar amyloid plaques are present. However, it remains unknown how mRNA ac4C modification affects the development of AD. In the current study, ac4C-modified mRNAs were comprehensively analyzed in AD mice by ac4C-RIP-seq and RNA-seq. Next, a protein-protein interaction (PPI) network was constructed to examine the relationships between the genes with differential ac4C modification levels and their RNA expression levels. The differentially expressed genes (DEGs) acquired above were subjected to Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to further analyze the molecular mechanisms in AD. In total, 3312 significant ac4C peaks were found on 2512 mRNAs, 1241 of which were hyperacetylated and 1271 of which were hypoacetylated. In addition, 956 mRNAs with differential expression were found, including 520 upregulated mRNAs and 436 downregulated mRNAs. Overall, 134 mRNAs with simultaneous changes at the ac4C levels as well as RNA expression levels were identified via joint analysis. Then, through PPI network construction and functional enrichment analysis, 37 key mRNAs were screened, which were predominantly enriched in GABAergic synapses and the PI3K/AKT signaling pathway. The significant difference in the abundance of mRNA ac4C modification indicates that this modification is associated with AD progression, which may provide insight for more investigations of the potential mechanisms.

A Two-Dimensional Hybrid Lead Bromide Ferroelectric Semiconductor with an Out-of-Plane Polarization.

A two-dimensional (2D) organic-inorganic hybrid perovskite (OIHP) material with out-of-plane ferroelectricity is the key to the miniaturization of vertical-sandwich-type ferroelectric optoelectronic devices. However, 2D OIHP ferroelectrics with out-of-plane polarization are still scarce, and effective design strategies are lacking. Herein, we report a novel 2D Dion-Jacobson perovskite ferroelectric semiconductor synthesized by a rigid-to-flexible cationic tailoring strategy, achieving an out-of-plane polarization of 1.7 µC/cm2 and high photoresponse. Integrating out-of-plane ferroelectricity with excellent photoelectric properties affords a promising platform to investigate ferroelectricity-related effects in vertical optoelectronic devices.

LncRNA ENST00000440246.1 Promotes Alzheimer's Disease Progression by Targeting PP2A.

Alzheimer's disease (AD) is an extremely prevalent neurodegenerative disease. Long noncoding RNAs (lncRNAs) play pivotal roles in the regulation of AD. However, the function of most lncRNAs in AD remains to be elucidated. In this study, the effects of lncRNA ENST00000440246.1 on the biological characteristics of AD were explored. Differentially expressed lncRNAs in AD were identified through bioinformatics analysis and peripheral blood from thirty AD patients was collected to verify the expression of these lncRNAs by quantitative real-time polymerase chain reaction (RT-qPCR). The correlations between lncRNAs and the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA) were assessed by Pearson's correlation analysis. Immunofluorescence (IF), Cell Counting Kit-8 (CCK-8) and flow cytometry assays were conducted to evaluate the biological effect of ENST00000440246.1 and protein phosphatase 2 A (PP2A) in SK-N-SH cells. Gene expression at the protein and mRNA levels was analyzed by Western blotting and RT-qPCR. The interaction between PP2A and ENST00000440246.1 was confirmed by IntaRNA and RNA pulldown assays. ENST00000440246.1 was upregulated and significantly negatively correlated with the MMSE and MoCA scores and the overexpression of ENST00000440246.1 inhibited cell proliferation and facilitated apoptosis and Aß expression in SK-N-SH cells. Mechanistically, ENST00000440246.1 targeted PP2A and regulated AD-related gene expression. The silencing of ENST00000440246.1 had the opposite effect. Furthermore, PP2A overexpression reversed the influence of ENST00000440246.1 overexpression in SK-N-SH cells. In conclusion, ENST00000440246.1 could promote AD progression by targeting PP2A, which indicates that ENST00000440246.1 has the potential to be a diagnostic target in AD.

[(4AMTP)PbBr2]2PbBr4: a Nontypical Cation-Coordinated Perovskite Showing Deep-Blue Emissions and Blue-Light Photoelectric Response.

Metal-halide perovskites have been extensively investigated due to their fascinating structural diversity and outstanding optoelectronic properties. We report the photoluminescence and photoelectric response behavior of a nontypical Dion-Jacobson perovskite [(4AMTP)PbBr2]2PbBr4 (4AMTP = 4-aminomethyltetrahydropyran cation), featuring neutral PbBr2 layers incorporated into the cationic layers between the anionic [PbBr4]2- layers. A 4AMTP-coordinated PbBr2 unit constitutes the unique nontypical dication layer. The seven-coordinated PbBr6O unit forms a largely distorted decahedron with a short distance from the inorganic [PbBr4]2- layer. The photoluminescence behavior of [(4AMTP)PbBr2]2PbBr4 shows crystal size dependence. Larger crystals show purplish-blue emission with two peaks at 414 and 431 nm, whereas smaller grain size (<50 µm) crystals demonstrate a single emission peak at 425 nm. Meanwhile, it shows a blue-light photoelectric response under the illumination of 405 nm with an on/off ratio of 175 for single-crystal devices and 97 for thin-film devices. The photoresponse performance is proportional to the molar extinction coefficient of the absorption band edge.

Bursaphelenchus xylophilus: An Important Pathogenic Factor of Pine Wilt Disease and Its Relationship with Bursaphelenchus mucronatus.

Pine wilt disease is the most devastating pine disease caused by Bursaphelenchus xylophilus. Bursaphelenchus mucronatus is morphologically similar to B. xylophilus and geographically overlaps in its distribution. Although interspecific hybridization of the two nematodes has been performed in vitro, the dynamic regularity of hybrid formation and its risk in forests has not been well evaluated. In this study, a hybrid of B. xylophilus and Bursaphelenchus mucronatus mucronatus was identified in the laboratory and fields by molecular markers. The heterozygosity of ITS-5.8S loci for identification was unstable in the hybrid population, and the allele inherited from B. m. mucronatus was lost over several generations. We also provided evidence that hybrids existed in some new epidemic areas, while old epidemic areas were usually dominated by B. xylophilus. Hybrids could be generated when B. m. mucronatus was invaded by B. xylophilus, and the pathogenicity of the hybrids was similar to that of B. xylophilus. These findings may improve the understanding of the natural hybridization between B. xylophilus and B. m. mucronatus and pathogenic variation in pine wilt disease, providing new insights for future studies on disease detection, transmission, and quarantine.

[Evaluation of implementation effect of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for acute tonsillitis].

The purpose of this article is to evaluate the clinical effect of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for acute tonsillitis. The applicability and application of the Guideline were evaluated based on the clinicians by using the electronic questionnaire. Questionnaires about 538 on application evaluation and 502 questionnaires on applicability evaluation were completed from April 28 to July 9, 2018. The subjects in the questionnaires include the clinicians with junior title, intermediate title, and senior title that have used this Guideline. The descriptive statistical analysis of the collected questionnaire was carried out. In the applicability evaluation, according to the classification of professional titles, the application rate was highest in intermediate title clinicians (26.77%), followed by junior (23.98%) and deputy senior (19.33%) professional title clinicians. In the quality evaluation, the rationality of application scope (98.61%) and the terminology accuracy (98.81%) scores were higher, and the rationality of differentiation and classification (96.05%) was the lowest. The applicability evaluation suggested that clinicians believed this Guideline had high safety (98.42%), reasonable content (98.03%), significant effect (99.6%), reduced use of antibiotics in Western medicine (93.89%), and a high applicability ratio (96.44%). In the application evaluation, Department of lung disease showed the highest application rate (44.24%); rationality of the Guideline was more than 97% in treatment rules and prophylaxis except the syndrome differentiation (92.75%); a high ratio of clinicians believed the recommended scheme was good: curative effect 97.4%, safety 97.59%, and economy 93.87%. The study shows that the clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for acute tonsillitis is of good quality, high clinical use and good effect. It can be used as a standardized treatment scheme for acute tonsillitis in traditional Chinese medicine. But there are some unsuitable contents and need to be further improved. The Guideline should strengthen the revision on differentiation of symptoms and signs as well as prophylaxis.

Study on Tandem Polymer Light Emitting Devices.

We report tandem polymer light emitting devices by using the PEDOT∶PSS/ZnO/PEIE charge generation layer (CGL) and investigate the influences of the conductance and thickness of PEDOT∶PSS layer on the properties of the devices. The results indicate that the conductance and thickness of PEDOT∶PSS layer have marginal impact on the J-V characteristics of the devices, while significant influences of device efficiency upon utilization of different PEDOT∶PSS specimens mainly come from their different strengths on exciton quenching. Luminance efficiency of TOLEDs with the PEDOT∶PSS thickness of 60 nm in CGL is better than TOLEDs with the PEDOT∶PSS thickness of 30 nm in CGL, the reason is that PEDOT∶PSS thickness of 60 nm the surface topography is more even . Luminance efficiency and driving voltage of the tandem devices match the sum of the luminance efficiency and driving voltage of the component light-emitting units, respectively, indicating that charges generated in the CGL can be injected efficiently into the adjacent light-emitting units. Incorporation of a V2O5 layer into the CGL structure only slightly affects the J-V and LE-I characteristics of the tandem devices, suggesting that the utilization of the PEDOT∶PSS/ZnO/PEIE CGL enables the simplification of the CGL structure without compromising device performance. The luminescence spectra of TOLEDs obviously involves two light emitting unit of spectrum, which shows that two light emitting unit in TOLEDs is normal work. Measurements on the capacitance-voltage characteristics of the CGL-based devices confirm that under negative bias (ITO anode) charges are accumulated and displaced in the CGL, which is totally in line with the full operation of light emitting units in the tandem devices. PEDOT∶PSS/ZnO/PEIE layer is evidenced the effective CGL. On this basis, for the first time we report tandem polymer light emitting devices containing three SY-PPV light-emitting units，which show the mixture of luminance efficiency and external quantum efficiency of 21.7 cd·A-1 and 6.95%, similar to the total luminance efficiency and external quantum efficiency of constituent LEUs. At 5 000 cd·m-2, the luminance efficiency and external quantum efficiency of the tandem devices are 20.5 cd·A-1 and 6.6%. Thus, the increase in the number of light emitting units leads to almost no performance losses, implying the robustness of the PEDOT∶PSS/ZnO/PEIE CGL. Tandem polymer light emitting devices containing three SY-PPV light-emitting units of the luminescent spectra is close to the light emitting unit. Further efforts on the optimization of hole injection layer in the CGL to minimize exciton quenching are underlying to promote the luminance efficiency of tandem polymer light emitting devices.

[Advantages and evidence of Chinese medicine in prevention and treatment of adult acute tonsillitis].

Though evaluation and analysis on the relevant literatures at home and abroad in recent years, the total number of retrieved literature was 2 664. According to the inclusion criteria and exclusion criteria,the literatures were screened out, and the results were as follows：374 literatures. To analyse the advantages and evidence of Chinese medicine in the prevention and treatment of adult acute tonsillitis. It is found to be effective, convenient and practical for the treatment of acute tonsillitis by traditional Chinese medicine (TCM) like treatment according to syndrome differentiation, Chinese patent drug, self Chinese medicine prescription and external treatment. TCM has obvious advantages in the prevention and treatment of acute tonsillitis, has the function of supplementing or substituting antibiotics, and has the function of regulating the defense function of organism.

[How to draft editorial explanation for transparent and concise guideline on clinical practice--Case analysis].

Clinical practice guideline (CPG) should be concise and readability, which can be possible to implement CPG into practice smoothly. A formal published CPG can't load its developing process and details. An editorial explanation of CPG is much useful to show details and logic process of developing CPG. Although there are many different standards for developing CPG, being nothing to do with process management of CPG. By referring to editorial explanation on international standards, a request for CPG was investigated in this study. An editorial explanation for clinical practice guideline should be transparency, logic and traceable. A good editorial explanation could make users or readers to learn what goes on behind the scenes. A standardized editorial explanation could supervise the GCP developing and improve the quality of GCP.

Encapsulating Naphthalene in an Electron-Deficient MOF to Enhance Fluorescence for Organic Amines Sensing.

Host-guest encapsulation of electron-rich naphthalene molecules into a weakly emissive porous metal-organic framework based on π-electron-deficient (π-acidic) naphthalene diimide tectons leads to orange-emissive crystals, which can be used to sense strongly basic organic amines in a fast response, high photostability, and tunable sensitivity. Moreover, such host-guest inclusion crystals are also a good photochromic probe for the detection of weakly basic N-methyl-2-pyrrolidone and N,N-dimethylformamide molecules.

Persistently high prevalence of primary resistance and multidrug resistance of tuberculosis in Heilongjiang Province, China.

BACKGROUND: The spread of multidrug-resistant tuberculosis (MDR-TB) Mycobacterium tuberculosis (M. tuberculosis) strains has been a big challenge to the TB control and prevention in China. Knowledge about patterns of drug resistance in TB high-burden areas of China is crucial to develop appropriate control strategies. We conducted a comprehensive investigation of the resistance pattern of M. tuberculosis in Heilongjiang Province. METHODS: 1427 M. tuberculosis clinical strains were isolated from pulmonary TB patients hospitalized between 2007 and 2012. The susceptibility of the isolates to the first-line anti-TB drugs and the resistance of MDR M. tuberculosis to fluoroquinolones were examined. We also performed a statistical analysis to identify the correlated risk factors for high burden of MDR-TB. RESULTS: The global resistance rates of 2007-2012 to the first-line drugs and MDR were 57.0 and 22.8 %, respectively. Notably, the primary MDR-TB and pan-resistance rates were as high as 13.6 and 5.0 %, respectively. Of MDR M. tuberculosis isolates (2009), approximately 13 % were not susceptible to any of the fluoroquinolones tested. Being age of 35 to 54, high re-treatment proportion, the presence of cavity lesion, and high proportion of shorter hospitalization are correlated with the development of MDR-TB. CONCLUSIONS: The high prevalence of drug resistant, MDR-TB, and fluoroquinolone-resistant MDR-TB is a big concern for TB control. More importantly, in order to control the development of MDR-TB effectively, we need to pay more attention to the primary resistance. Targeting reducing the prevalence of the risk factors may lead to better TB control in China.

The CYP1B1 Leu432Val polymorphism and risk of urinary system cancers.

The cytochrome P450 1B1 (CYP1B1) gene plays a key role in the metabolism of various carcinogens. The CYP1B1 Leu432Val polymorphism leads to leucine to valine substitution at codon 432. A lot of studies have shown that the CYP1B1 Leu432Val polymorphism was associated with urinary system cancers, especially prostate cancer. However, the results were still inconclusive. In this meta-analysis, by searching online databases and references of related reviews, we identified 17 eligible studies to assess the relationship between CYP1B1 Leu432Val polymorphism and urinary system cancers, including 7,783 cancer cases and 7,238 controls. By pooling all eligible studies, we found that the CYP1B1 Leu432Val polymorphism was not associated with overall urinary system cancers. However, in subgroup analyses, we found that the variant 432Val allele significantly increased the risk of prostate cancer (Val vs. Leu, odds ratio (OR) = 1.064, 95% confidence interval (CI) 0.981-1.154; Pheterogeneity = 0.002), while no association was found for bladder cancer (Val vs. Leu, OR = 0.942, 95% CI 0.853-1.041; Pheterogeneity = 0.504). No evidence of publication bias was found (Begg's test, P = 0.053; Egger's test, P = 0.073). In conclusion, based on 17 eligible studies, we found that the CYP1B1 Leu432Val polymorphism was associated with an increased risk of prostate cancer, while no association of bladder cancer was observed.