Prediction model for hepatitis B e antigen seroconversion in chronic hepatitis B with peginterferon-alfa treated based on a response-guided therapy strategy.

BACKGROUND: Models for predicting hepatitis B e antigen (HBeAg) seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) after nucleos(t)ide analog treatment are rare. AIM: To establish a simple scoring model based on a response-guided therapy (RGT) strategy for predicting HBeAg seroconversion and hepatitis B surface antigen (HBsAg) clearance. METHODS: In this study, 75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa (PEG-IFNα) treatment and a 24-wk follow-up. Logistic regression analysis was used to assess parameters at baseline, week 12, and week 24 to predict HBeAg seroconversion at 24 wk post-treatment. The two best predictors at each time point were used to establish a prediction model for PEG-IFNα therapy efficacy. Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0. RESULTS: The two most meaningful predictors were HBsAg ≤ 1000 IU/mL and HBeAg ≤ 3 S/CO at baseline, HBsAg ≤ 600 IU/mL and HBeAg ≤ 3 S/CO at week 12, and HBsAg ≤ 300 IU/mL and HBeAg ≤ 2 S/CO at week 24. With a total score of 0 vs 2 at baseline, week 12, and week 24, the response rates were 23.8%, 15.2%, and 11.1% vs 81.8%, 80.0%, and 82.4%, respectively, and the HBsAg clearance rates were 2.4%, 3.0%, and 0.0%, vs 54.5%, 40.0%, and 41.2%, respectively. CONCLUSION: We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNα therapy.

Changes in the etiology of liver cirrhosis and the corresponding management strategies.

We read with interest the article by Xing Wang, which was published in the recent issue of the World Journal of Hepatology 2023; 15: 1294-1306. This article focuses particularly on the prevalence and trends in the etiology of liver cirrhosis (LC), prognosis for patients suffering from cirrhosis-related complications and hepatocellular carcinoma (HCC), and management strategies. The etiology of cirrhosis varies according to geographical, economic, and population factors. Viral hepatitis is the dominant cause in China. Vaccination and effective treatment have reduced the number of people with viral hepatitis, but the overall number is still large. Patients with viral hepatitis who progress over time to LC and HCC remain an important population to manage. The increased incidence of metabolic syndrome and alcohol consumption is likely to lead to a potential exponential increase in metabolic dysfunction-associated steatotic liver disease (MASLD)-associated LC and alcoholic liver disease in the future. Investigating the evolution of the etiology of LC is important for guiding the direction of future research and policy development. These changing trends indicate a need for greater emphasis on tackling obesity and diabetes, and implementing more effective measures to regulate alcohol consumption in order to reduce the occurrence of MASLD. In an effort to help cope with these changing trends, the authors further proposed countermeasures for healthcare authorities doctors, and patients.

Ultrasound-guided percutaneous high-frequency irreversible electroporation in porcine livers using four electrode needles: A feasibility and safety study.

BACKGROUND: Malignant liver tumors seriously endanger human health. Among different therapeutic approaches, high-frequency irreversible electroporation (H-FIRE) is a recently emerging tumor ablation technique. The objective of this study was to evaluate the feasibility and safety of ultrasound-guided percutaneous H-FIRE using four electrode needles in porcine livers. METHODS: Twelve experimental pigs underwent percutaneous H-FIRE ablation using a compound steep-pulse therapeutic device. Liver tissues adjacent to the gallbladder, blood vessels, and bile ducts were selected as the ablation targets. Pigs were randomly divided into three groups: (1) immediately after ablation (N = 4), (2) 2 days after ablation (N = 4), and (3) 7 days after ablation (N = 4). Blood routine, liver and kidney function, and myocardial enzyme levels were measured before and after ablation. Ultrasound, contrast-enhanced ultrasound (CEUS), contrast-enhanced magnetic resonance imaging (MRI), and hematoxylin-eosin staining were performed to evaluate the ablation performance. RESULTS: Ultrasound-guided percutaneous H-FIRE ablations using four electrode needles were successfully performed in all 12 experimental pigs. The general conditions of the pigs, including postoperative activities and feeding behaviors, were normal, with no significant changes compared with the preoperative conditions. The imaging features of ultrasound, CEUS, and MRI demonstrated no significant changes in the gallbladder walls, bile ducts, or blood vessels close to the ablation areas. Laboratory tests showed that liver function indices and myocardial enzymes increased temporarily after H-FIRE ablation, but decreased to normal levels at 7 days after ablation. Histopathological examinations of porcine liver specimens showed that this technique could effectively ablate the target areas without damaging the surrounding or internal vascular systems and gallbladder. CONCLUSIONS: This study demonstrated the feasibility and safety of ultrasound-guided percutaneous H-FIRE ablation in porcine livers in vivo, and proposed a four-needle method to optimize its clinical application.

Global trends and hotspots of treatment for nonalcoholic fatty liver disease: A bibliometric and visualization analysis (2010-2023).

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is chronic, with its progression leading to liver fibrosis and end-stage cirrhosis. Although NAFLD is increasingly common, no treatment guideline has been established. Many mechanistic studies and drug trials have been conducted for new drug development to treat NAFLD. An up-to-date overview on the knowledge structure of NAFLD through bibliometrics, focusing on research hotspots, is necessary to reveal the rational and timely directions of development in this field. AIM: To research the latest literature and determine the current trends in treatment for NAFLD. METHODS: Publications related to treatment for NAFLD were searched on the Web of Science Core Collection database, from 2010 to 2023. VOSviewers, CiteSpace, and R package "bibliometrix" were used to conduct this bibliometric analysis. The key information was extracted, and the results of the cluster analysis were based on network data for generating and investigating maps for country, institution, journal, and author. Historiography analysis, bursts and cluster analysis, co-occurrence analysis, and trend topic revealed the knowledge structure and research hotspots in this field. GraphPad Prism 9.5.1.733 and Microsoft Office Excel 2019 were used for data analysis and visualization. RESULTS: In total, 10829 articles from 120 countries (led by China and the United States) and 8785 institutions were included. The number of publications related to treatment for NAFLD increased annually. While China produced the most publications, the United States was the most cited country, and the United Kingdom collaborated the most from an international standpoint. The University of California-San Diego, Shanghai Jiao Tong University, and Shanghai University of Traditional Chinese Medicine produced the most publications of all the research institutions. The International Journal of Molecular Sciences was the most frequent journal out of the 1523 total journals, and Hepatology was the most cited and co-cited journal. Sanyal AJ was the most cited author, the most co-cited author was Younossi ZM, and the most influential author was Loomba R. The most studied topics included the epidemiology and mechanism of NAFLD, the development of accurate diagnosis, the precise management of patients with NAFLD, and the associated metabolic comorbidities. The major cluster topics were "emerging drug," "glucagon-like peptide-1 receptor agonist," "metabolic dysfunction-associated fatty liver disease," "gut microbiota," and "glucose metabolism." CONCLUSION: The bibliometric study identified recent research frontiers and hot directions, which can provide a valuable reference for scholars researching treatments for NAFLD.

Identification of GnRH-like peptide and its potential signaling pathway involved in the oocyte meiotic maturation in the Chinese mitten crab, Eriocheir sinensis.

Gonadotropin-releasing hormone (GnRH) plays a pivotal role in reproductive regulation in vertebrates. However, GnRH was rarely isolated and its function remains poorly characterized in invertebrates. The existence of GnRH in ecdysozoa has been controversial for a long. Here, we isolated and identified two GnRH-like peptides from brain tissues in Eriocheir sinensis. Immunolocalization showed that the presence of EsGnRH-like peptide in brain, ovary and hepatopancreas. Synthetic EsGnRH-like peptides can induce germinal vesicle breakdown (GVBD) of oocyte. Similar to vertebrates, ovarian transcriptomic analysis revealed a GnRH signaling pathway in the crab, in which most genes exhibited dramatically high expression at GVBD. RNAi knockdown of EsGnRHR suppressed the expression of most genes in the pathway. Co-transfection of the expression plasmid for EsGnRHR with reporter plasmid bearing CRE-luc or SRE-luc response element into 293T cells showed that EsGnRHR transduces its signal via cAMP and Ca2+ signaling transduction pathways. In vitro incubation of the crab oocyte with EsGnRH-like peptide confirmed the cAMP-PKA cascade and Ca2+ mobilization signaling cascade but lack of a PKC cascade. Our data present the first direct evidence of the existence of GnRH-like peptides in the crab and demonstrated its conserved role in the oocyte meiotic maturation as a primitive neurohormone.

Dose prediction of organs at risk in patients with cervical cancer receiving brachytherapy using needle insertion based on a neural network method.

OBJECTIVE: A neural network method was employed to establish a dose prediction model for organs at risk (OAR) in patients with cervical cancer receiving brachytherapy using needle insertion. METHODS: A total of 218 CT-based needle-insertion brachytherapy fraction plans for loco-regionally advanced cervical cancer treatment were analyzed in 59 patients. The sub-organ of OAR was automatically generated by self-written MATLAB, and the volume of the sub-organ was read. Correlations between D2cm3 of each OAR and volume of each sub-organ-as well as high-risk clinical target volume for bladder, rectum, and sigmoid colon-were analyzed. We then established a neural network predictive model of D2cm3 of OAR using the matrix laboratory neural net. Of these plans, 70% were selected as the training set, 15% as the validation set, and 15% as the test set. The regression R value and mean squared error were subsequently used to evaluate the predictive model. RESULTS: The D2cm3/D90 of each OAR was related to volume of each respective sub-organ. The R values for bladder, rectum, and sigmoid colon in the training set for the predictive model were 0.80513, 0.93421, and 0.95978, respectively. The ∆D2cm3/D90 for bladder, rectum, and sigmoid colon in all sets was 0.052 ± 0.044, 0.040 ± 0.032, and 0.041 ± 0.037, respectively. The MSE for bladder, rectum, and sigmoid colon in the training set for the predictive model was 4.779 × 10-3, 1.967 × 10-3 and 1.574 × 10-3, respectively. CONCLUSION: The neural network method based on a dose-prediction model of OAR in brachytherapy using needle insertion was simple and reliable. In addition, it only addressed volumes of sub-organs to predict the dose of OAR, which we believe is worthy of further promotion and application.

Expression profile of circular RNAs in patients with unstable angina.

BACKGROUND: Circular RNAs (circRNAs) are a new class of noncoding RNAs, which interfere with gene transcription by absorbing microRNAs (miRNAs). OBJECTIVE: The expression profile and roles of circRNAs in unstable angina (UA) patients remains unclear. METHODS: An initial screening of circRNA expression by microarray analysis was performed using blood samples from three pairs of UA patients and matched healthy individuals. The differential expression of the chosen six circRNAs from the results of the microarray analysis was validated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The microarray results demonstrated that some circRNAs were markedly different in UA patients, when compared with matched healthy individuals. In these UA patients, 22 circRNAs were upregulated and six circRNAs were downregulated when a P-value of < 0.05 was considered as a cut-off level and the fold change was > 1.5. Among the six circRNAs chosen for further analysis, qRT-PCR identified that five of these were upregulated, and the remaining circRNA was downregulated. By comparing the outcome of the six candidate circRNAs between the circRNAs microarray assay and RT-PCR validation, it was found that four circRNAs (hsa_circ_0002229, hsa_circ_0005580, hsa_circ_0046667, and hsa_circ_0001451) had the same variation trend. CONCLUSION: The present study provided the expression profile of circRNAs in UA patients. Moreover, some circRNAs have the potential to be biomarkers for the detection of UA patients. Further studies with a larger population will focus on hsa_circ_0002229, hsa_circ_0005580, hsa_circ_0046667 and hsa_circ_0001451.

Control of Grain Weight and Size in Rice (Oryza sativa L.) by OsPUB3 Encoding a U-Box E3 Ubiquitin Ligase.

Grain weight and size, mostly determined by grain length, width and thickness, are crucial traits affecting grain quality and yield in rice. A quantitative trait locus controlling grain length and width in rice, qGS1-35.2, was previously fine-mapped in a 57.7-kb region on the long arm of chromosome 1. In this study, OsPUB3, a gene encoding a U-box E3 ubiquitin ligase, was validated as the causal gene for qGS1-35.2. The effects were confirmed firstly by using CRISPR/Cas9-based mutagenesis and then through transgenic complementation of a Cas9-free knock-out (KO) mutant. Two homozygous KO lines were produced, each having a 1-bp insertion in OsPUB3 which caused frameshift mutation and premature termination. Compared with the recipient and a transgenic-negative control, both mutants showed significant decreases in grain weight and size. In transgenic complementation populations derived from four independent T0 plants, grain weight of transgenic-positive plants was significantly higher than transgenic-negative plants, coming with increased grain length and a less significant decrease in grain width. Based on data documented in RiceVarMap V2.0, eight haplotypes were classified according to six single-nucleotide polymorphisms (SNPs) found in the OsPUB3 coding region of 4695 rice accessions. Significant differences on grain size traits were detected between the three major haplotypes, Hap1, Hap2 and Hap3 that jointly occupy 98.6% of the accessions. Hap3 having the largest grain weight and grain length but intermediate grain width exhibits a potential for simultaneously improving grain yield and quality. In another set of 257 indica rice cultivars tested in our study, Hap1 and Hap2 remained to be the two largest groups. Their differences on grain weight and size were significant in the background of non-functional gse5, but non-significant in the background of functional GSE5, indicating a genetic interaction between OsPUB3 and GSE5. Cloning of OsPUB3 provides a new gene resource for investigating the regulation of grain weight and size.

Effect of Rabeprazole and Rebamipide in the Treatment of Upper Gastrointestinal Hemorrhage Associated with Dual Antiplatelet Therapy in Elderly Patients with Coronary Heart Disease.

To investigate the therapeutic effect of rabeprazole and rebamipide on patient age over 60 with dual antiplatelet therapy (DAPT)-related upper gastrointestinal hemorrhage following percutaneous coronary intervention (PCI). A total of 360 patients age over 60 undergoing PCI were recruited for antiplatelet therapy involving a combined treatment of aspirin (100 mg/d) and clopidogrel (75 mg/d). The enrolled patients were divided into 4 groups: the control group, the rabeprazole group, the rebamipide group, and the rabeprazole + rebamipide group. The incidence and severity of any upper gastrointestinal hemorrhage and the incidence of major adverse cardiac events (MACEs) were observed 6 months after the operation. The incidence of upper gastrointestinal hemorrhage in the 4 groups was 11.1%, 3.3%, 8.9%, and 1.1%, respectively, and the differences were statistically significant (P < 0.05). On comparing the groups, the differences between the control group and the rabeprazole group, those between the control group and the rabeprazole + rebamipide group, and those between the rebamipide group and the rabeprazole + rebamipide group were found to be statistically significant (P < 0.05). The severity of the upper gastrointestinal hemorrhage in the rabeprazole group and the rabeprazole + rebamipide group was significantly lower than that in the control group. The 4 groups exhibited no significant differences in the incidence of MACEs (P > 0.05). For patients age over 60 receiving DAPT following PCI in our study population, treatment with rabeprazole or a combination of rabeprazole and rebamipide could reduce the risk of upper gastrointestinal hemorrhage, as well as reduce its severity.

Control of Grain Shape and Size in Rice by Two Functional Alleles of OsPUB3 in Varied Genetic Background.

Grain shape and size are key determinants of grain appearance quality and yield in rice. In our previous study, a grain shape QTL, qGS1-35.2, was fine-mapped using near-isogenic lines (NILs) derived from a cross between Zhenshan 97 (ZS97) and Milyang 46 (MY46). One annotated gene, OsPUB3, was found to be the most likely candidate gene. Here, knockout and overexpression experiments were performed to investigate the effects of OsPUB3 on grain shape and size. Four traits were tested, including grain length, grain width, grain weight, and the ratio of grain length to width. Knockout of OsPUB3 in NILZS97, NILMY46, and another rice cultivar carrying the OsPUB3MY46 allele all caused decreases in grain width and weight and increases in the ratio of grain length to width. Results also showed that the magnitude of the mutational effects varied depending on the target allele and the genetic background. Moreover, it was found that NILZS97 and NILMY46 carried different functional alleles of OsPUB3, causing differences in grain shape rather than grain weight. In the overexpression experiment, significant differences between transgenic-positive and transgenic-negative plants were detected in all four traits. These results indicate that OsPUB3 regulates grain shape and size through a complex mechanism and is a good target for deciphering the regulatory network of grain shape. This gene could be used to improve grain appearance quality through molecular breeding as well.

The effects of changes in flowering plant composition caused by nitrogen and phosphorus enrichment on plant-pollinator interactions in a Tibetan alpine grassland.

Soil eutrophication from atmospheric deposition and fertilization threatens biodiversity and the functioning of terrestrial ecosystems worldwide. Increases in soil nitrogen (N) and phosphorus (P) content can alter the biomass and structure of plant communities in grassland ecosystems; however, the impact of these changes on plant-pollinator interactions is not yet clear. In this study, we tested how changes in flowering plant diversity and composition due to N and P enrichment affected pollinator communities and pollination interactions. Our experiments, conducted in a Tibetan alpine grassland, included four fertilization treatments: N (10 g N m-2 year-1), P (5 g P m-2 year-1), a combination of N and P (N + P), and control. We found that changes in flowering plant composition and diversity under the N and P treatments did not alter the pollinator richness or abundance. The N and P treatments also had limited effects on the plant-pollinator interactions, including the interaction numbers, visit numbers, plant and pollinator species dissimilarity, plant-pollinator interaction dissimilarity, average number of pollinator species attracted by each plant species (vulnerability), and average number of plant species visited by each pollinator species (generality). However, the N + P treatment increased the species and interaction dissimilarity in flowering plant and pollinator communities and decreased the generality in plant-pollinator interactions. These data highlight that changes in flowering plants caused by N + P enrichment alter pollination interactions between flowering plants and pollinators. Owing to changes in flowering plant communities, the plant-pollinator interactions could be sensitive to the changing environment in alpine regions.

High nerve density in breast cancer is associated with poor patient outcome.

Active crosstalk between the nervous system and breast cancer cells has been experimentally demonstrated in vitro and in animal models. However, low frequencies of peripheral nerve presence in human breast cancers reported in previous studies (~30% of cases) potentially negate a major role of the nervous system in breast cancer development and progression. This study aimed to clarify the incidence of nerves within human breast cancers and to delineate associations with clinicopathological features. Immunohistochemical staining was conducted in formalin-fixed paraffin-embedded breast cancer tissue sections using antibodies against the pan-neuronal markers protein gene product 9.5 and growth-associated protein 43, and the sympathetic nerve-specific marker tyrosine hydroxylase. Nerve trunks and isolated nerve fibers were quantitated. The chi-squared test was used to determine the associations between nerve counts and clinicopathological parameters. The log-rank test was used to compare differences in patient progression-free survival (PFS) and overall survival (OS). The overall frequency of peripheral nerves in breast cancers was 85%, a markedly higher proportion than reported previously. Of note, most nerves present in breast cancers were of the sympathetic origin. While high density of nerve trunks or isolated nerve fibers was associated with poor PFS and OS of patients, high nerve trunk density appeared also to predict poor patient PFS independently of lymph node metastasis. Innervation of breast cancers is a common event correlated with poor patient outcomes. These findings support the notion that the nervous system plays an active role in breast cancer pathogenesis.

Effect of Acupuncture on the Cognitive Control Network of Patients with Knee Osteoarthritis: Study Protocol for a Randomized Controlled Trial.

Purpose: Abnormal central nervous system function is the key central pathological factor leading to chronic pain in patients with knee osteoarthritis (KOA). Acupuncture can effectively relieve the pain of KOA patients. However, the central nervous mechanism of acupuncture treating KOA is not fully understood. This trial will use functional magnetic resonance imaging (fMRI) analysis techniques to investigate the potential central nervous mechanism of acupuncture treatment of KOA. Materials and Methods: A total of 108 patients will be randomized (in a 1:1:1 ratio) into three groups, this trial will include 4-week treatment, patients in groups A and B will receive 20 acupuncture and sham acupuncture sessions, respectively, patients in group C will not receive any intervention, and all patients will receive fMRI scans before and after the intervention. The Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) will be the primary clinical outcome. Then, we will explore the functional changes of the cognitive control network (CCN) in the brains of KOA patients through whole brain functional connectivity (FC) analysis and seed-based functional connectivity (sFC) analysis. Pearson correlation coefficient will be used to analyze the relationship between the improved value of the clinical correlation scale and the change of fMRI data. Discussion: This trial will analyze the efficacy of verum acupuncture, sham acupuncture and the waiting-list for KOA and explore the activity of the CCN in three groups of patients by fMRI, so as to reveal the central nervous mechanisms of acupuncture in the treatment of KOA. Study Registration: This study is approved by the Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine (No: 2019HL-133-01) and registered in the Chinese Clinical Trial Registry, ChiCTR2000038554.

Combined System of Organic Substrate and Straw-Degrading Microbial Agents Improved Soil Organic Matter Levels and Microbial Abundance in a Rice-Wheat Rotation.

Rice-wheat rotation is one of the most intensive agricultural planting modes in China and is pivotal to develop optimized straw-returning management in situ to improve soil fertility and productivity in agricultural ecosystems. Previous studies have mainly focused on the effects of straw return with a single application of organic fertilizers. The integrated management of different fertilizers in improving the management of straw return in situ is not well known. In this study, a field experiment was conducted from 2017 to 2019 to explore the effects of a combined system of modified organic substrate (MOS) and straw-degrading compound microbial agent (CMA) on soil physiochemical properties, labile organic carbon, microbial activities, and soil microbial community composition under the background of direct crop straw return and chemical fertilizer utilization. Four treatments were designed: (1) control check; (2) CMA; (3) MOS; and (4) MOS + CMA. The results showed that the MOS + CMA treatment had the combined advantages of soil organic matter (SOM) accumulation, soil nutrient increase and soil microbial community alteration, which may be more suitable for improving the quality and fertility of sandy loam soil. This study provides novel insights for further understanding the effects of organic substrates and composite microbial agents on SOM changes and microbial community composition and function in the field, which has important implications for sustainable crop production and agricultural development.

Effects of tank-mix adjuvants on physicochemical properties and dosage delivery at low dilution ratios for unmanned aerial vehicle application in paddy fields.

BACKGROUND: Unmanned aerial vehicles (UAVs) have been developed to improve the efficiency of pesticide applications, and they are now widely utilized in Asia. The deposition and retention periods of pesticides on plant surfaces present serious challenges for modern precision agriculture, as these factors directly affect pesticide bioavailability, efficacy, and loss. Tank-mix adjuvants have been utilized to improve pesticide performance, but their effects on physicochemical properties and dosage delivery at low dilutions are not well understood. RESULTS: We found that different tank-mix adjuvants affected droplet impact behavior, the wetting and spreading of spray dilutions, and pesticide deposition on rice leaves by changing the physicochemical properties of spray dilutions. The adjuvant methyl oxirane polymer with oxirane, mono (3,5,5-trimethylhexyl) ether (adjuvant c) significantly reduced the dynamic surface tension of the spray dilution and inhibited the rebound of large droplets (D0  = 2 ± 0.2 mm) and spray droplets (0.2 MPa with a LU-01 nozzle) on rice leaves, and improved the wetting and spreading performance of the spray dilution on rice leaves. Field tests showed that adjuvant c could significantly increase the deposition of chlorantraniliprole on rice leaves. CONCLUSION: Overall, the use of appropriate tank-mix adjuvants at low dilution ratios for UAV application in paddy fields can improve the performance of spray dilutions, increase the effective deposition and wetting spread of pesticides on rice leaves, further reduce the dosage of pesticide products and improve pesticide utilization. © 2022 Society of Chemical Industry.

Identification of the Fosl1/AMPK/autophagy axis involved in apoptotic and inflammatory effects following spinal cord injury.

Strategies for reducing spinal cord injury (SCI) have become a research focus because an effective treatment of SCI is unavailable. The objective of this study was to explore the underlying mechanisms of Fosl1 following SCI. Based on the analysis of the Gene Expression Omnibus (GEO) database, Fosl1 was found to be highly enhanced in SCI. This result was confirmed in our animal model, and Fosl1 was found to be obviously expressed in neurons. Next, we treated PC-12 cells with H2O2 to mimic injured neurons and further verified that Fosl1 silencing upregulated AMPK expression, promoted autophagy and inhibited inflammation and apoptosis. Subsequently, a special inhibitor of AMPK was used to examine the role of AMPK, and we learned that the inhibition of AMPK suppressed autophagy and promoted inflammation and apoptosis following Fosl1 silencing. These changes completely reversed the beneficial effects of Fosl1 silencing on injured PC-12 cells. Moreover, treatment with an AMPK activator resulted in effects that were opposite those of the inhibitor. Finally, rats were injected intrathecally with si-Fosl1 to detect its role in vivo. The results showed that si-Fosl1 improved neurological function and decreased apoptosis and inflammation at 14 d postoperation, and the activator further benefited the rats of si-Fosl1 treatment. In conclusion, Fosl1 inhibits autophagy and promotes inflammation and apoptosis through the AMPK signaling pathway following SCI in vivo and in vitro.

Zinc-Mediated Allylation-Lactonization One-Pot Reaction to Methylene Butyrolactones: Renewable Monomers for Sustainable Acrylic Polymers with Closed-Loop Recyclability.

Despite biomass-derived methylene butyrolactone monomers having great potential in substituting the petroleum-based methacrylates for synthesizing the sustainable acrylic polymers, the possible industrial production of these cyclic monomers is unfortunately not practical due to moderate overall yields and harsh reaction conditions or a time-consuming multistep process. Here we report a convenient and effective synthetic approach to a series of biomass-derived methylene butyrolactone monomers via a zinc-mediated allylation-lactonization one-pot reaction of biorenewable aldehydes with ethyl 2-(bromomethyl)acrylate. Under simple room-temperature sonication conditions, near-quantitative conversions (>90%) can be accomplished within 5-30 min, providing pure products with high isolated yields of 70-80%. Their efficient polymerizations with a high degree of control and complete chemoselectivity were enabled by the judiciously chosen Lewis pair catalyst based on methylaluminum bis(2,6-di-tert-butyl-4-methylphenoxide) [MeAl(BHT)2] Lewis acid and 3-diisopropyl-4,5-dimethylimidazol-2-ylidene (I i Pr) Lewis base, affording new poly(methylene butyrolactone)s with high thermal stability and thermal properties tuned in a wide range as well as pendant vinyl groups for postfunctionalization. Through the development of an effective depolymerization setup (370-390 °C, ca. 100 mTorr, 1 h, a muffle furnace), thermal depolymerizations of these polymers have been achieved with monomer recovery up to 99.8%, thus successfully constructing sustainable acrylic polymers with closed-loop recyclability.

D

The X(3872), whose mass coincides with the D^{0}D[over ¯]^{*0} threshold, is the most extended hadron object. Since its discovery in 2003, debates have never stopped regarding its internal structure. We propose a new object, the X atom, which is the D^{±}D^{*∓} composite system with positive charge parity and a mass of (3879.89±0.07) MeV, formed mainly due to the Coulomb force. We show that a null signal of the X atom can be used to put a lower limit on the binding energy of the X(3872). From the current knowledge of the X(3872) properties, the production rate for the X atom relative to the X(3872) in B decays and at hadron colliders should be at least 1×10^{-3}. New insights into the X(3872) will be obtained through studying the X atom.