Search

Doping and blending strategies are crucial means to precisely control the excited states and energy level in conjugated molecular systems. However, effective models and platforms are rarely proposed to systematically explore the effects of the formation of trapped doped centers on heterogeneous structures, energy level and ultrafast photophysical process. Herein, for deeply understanding the impact of molecular doping in film energy levels and photoexcitation dynamics, we set a supramolecular N-B coordination composed by the conjugated molecules of pyridine functionalized diarylfluorene (host material), named as ODPF-Phpy and ODPF-(Phpy)2, and the molecule of tris(perfluorophenyl)borane (BCF) (guest material). The generation of the molecular-level coordination bond increased the binding energy of N atoms and tuned the band-gap, leading to a new fluorescent emission center with longer excitation wavelength and emission wavelength. The intermolecular Förster resonance energy transfer (FRET) in blending films make it present inconsistent fluorescent behaviors compared to that in solution. The charge transfer (CT) state of N-B coordinated compounds and the changed dielectric constant of blending films resulted in a large PL spectra red-shift with the increased dopant ratio, causing a wide-tunable fluorescent color. The excited state behaviors of two compounds in blending system was further investigated by the transient absorption (TA) spectroscopy. Finally, we found supramolecular coordination blending can effectively improve the films’ photoluminescence quantum yield (PLQY) and conductivity. We believe this exploration in the internal coordination mechanisms would deepen the insights about doped semiconductors and is helpful in developing novel high-efficient fluorescent systems.

Grassland degradation caused by increases in livestock grazing threatens a variety of ecosystem services. Understanding changes in plant community assembly during the process of grassland degradation in the presence of grazing is important to help restore degraded grasslands worldwide but has received little attention thus far. The grassland degradation process is typified by heterogeneous degradation, i.e., gradual formation of degraded patches (hereafter "patchy degradation"). Here, we experimentally examined the effects of herbivore grazing and patchy degradation on plant community assembly using nine pairs of non-degraded (intact) and patch-degraded (fragmented) grasslands subject to grazing by different-sized herbivores (i.e., NG, no grazing; SG, sheep grazing; CG, cattle grazing) over four years. Using a null-model approach, we estimated the relative magnitude of deterministic processes of community assembly by comparing the observed and expected β-diversity. We found that in the absence of herbivore grazing, deterministic processes played a greater role in community assembly, regardless of whether patchy degradation had occurred. However, the deterministic processes resulted in plant communities being more spatially similar in non-degraded grasslands while being more dissimilar in patchy degraded grasslands. Compared with non-degraded grasslands, species with strong competitive abilities (i.e., Leymus chinensis) were less dominant in patchy degraded grasslands, indicating relaxed competition and a reduced role of species interactions over plant communities. Instead, patchy degradation added the role of environmental variables over plant communities. Sheep grazing consistently promoted more stochastic plant community assembly in both non-degraded and patch-degraded grasslands, while cattle grazing promoted more stochastic plant community assembly only in the non-degraded state, having no effect in the patch-degraded state. Our study offers important insights into changes in plant community assembly during ongoing patch-degradation of grasslands, indicating the role of increased environmental filtering of soil and reduced species interactions in driving plant community dynamics with increasing grassland patchy degradation. We also uncovered an herbivore species-specific effect on plant community assembly during the process of grassland degradation, which will better inform and improve future grassland restoration planning efforts. This article is protected by copyright. All rights reserved.

Racial differences in effort at work, if they exist, can potentially explain race-based wage/earnings disparities in the labor market. The authors estimate specifications of time spent on non-work activities at work by Black and White males and females with data from the American Time Use Survey. Estimates reveal that trivially small differences occur between non-Hispanic Black and non-Hispanic White males in time spent not working while on the job that disappear entirely when correcting for non-response errors. The findings imply that Black–White male differences in the fraction of the workday spent not working are either not large enough to partially explain the Black–White wage gap, or simply do not exist at all.

Inflammation and apoptosis are main pathological processes that lead to the development of cardiac hypertrophy. Lupeol, a natural triterpenoid, has shown anti-inflammatory and anti-apoptotic activities as well as potential protective effects on cardiovascular diseases. In this study we investigated whether lupeol attenuated cardiac hypertrophy and fibrosis induced by pressure overload in vivo and in vitro, and explored the underlying mechanisms. Cardiac hypertrophy was induced in mice by transverse aortic constriction (TAC) surgery, and in neonatal rat cardiomyocytes (NRCMs) by stimulation with phenylephrine (PE) in vitro. We showed that administration of lupeol (50 mg ·kg

Mutations in genes encoding mitochondrial aminoacyl-tRNA synthetases are linked to diverse diseases. However, the precise mechanisms by which these mutations affect mitochondrial function and disease development are not fully understood. Here, we develop a Drosophila model to study the function of dFARS2, the Drosophila homologue of the mitochondrial phenylalanyl–tRNA synthetase, and further characterize human disease-associated FARS2 variants. Inactivation of dFARS2 in Drosophila leads to developmental delay and seizure. Biochemical studies reveal that dFARS2 is required for mitochondrial tRNA aminoacylation, mitochondrial protein stability, and assembly and enzyme activities of OXPHOS complexes. Interestingly, by modeling FARS2 mutations associated with human disease in Drosophila, we provide evidence that expression of two human FARS2 variants, p.G309S and p.D142Y, induces seizure behaviors and locomotion defects, respectively. Together, our results not only show the relationship between dysfunction of mitochondrial aminoacylation system and pathologies, but also illustrate the application of Drosophila model for functional analysis of human disease-causing variants.

In The Growth of Incarceration in the United States, the National Research Council documents the large and persistent racial disparities in imprisonment that accompanied the more than quadrupling of the U.S. incarceration rate since the 1980s. Largely unnoticed by policy makers and opinion leaders in recent years is an unprecedented decrease in the number of African American women incarcerated at the same time that the number of white women in prison has grown to new heights. The result of these recent changes is a near convergence in black-white female incarceration rates from 2000 to 2016. In some states, the changes occurred abruptly and almost instantaneously. In other states, the convergence has been gradual. We find that changes in the population composition—the fraction of the population that is black—was the major contributor to the decline in the disparity among women. We also find that race-specific differences in drug overdose deaths stemming from the recent increases in opioid use lowered the disparity by increasing the white female imprisonment rate and lowering it for black women.

Many species of lizards are capable of tail regeneration. There has been increased interest in the study of lizard tail regeneration in recent years as it is an amenable regeneration model for amniotes. In this study, Gekko japonicus was used as a model to investigate the initiation of vascularization, innervation and myogenesis during tail regeneration. We found that angiogenesis and axon regeneration occurred almost simultaneously within 4 days post amputation. The results showed that the endothelial cells of the original vasculature proliferated and extended into the blastema as capillary vessels, which inter-connected to form a capillary network. The nerve fibers innervated the regenerated tissue from the original spinal cord and dorsal root ganglia, and the fiber bundles increased during 14 days. Regenerating muscle tissues emerged 2 weeks after amputation. PAX3 and PAX7 expression were detected during myogenesis, with PAX7 showing a continuous increase in expression from day 3 until the day 14, whereas PAX3 reached a peak level on day 10 day post amputation, and then declined quickly to level as normal control on day 14. PCNA and PAX3 double-positive satellite cells were observed in the original rostral tissues, indicating the involvement of satellite cell proliferation during tail regeneration. Taken together, these data suggest that tail regeneration in Gekko japonicus involved rapid angiogenesis from the beginning to the day 10 and followed by capillary remodeling. The innervation of regenerated tail was significant on day 4 and increased gradually during regeneration, while the regenerated muscle tissues was obvious on day 14 after amputation.

Noradrenergic neuroblastoma is characterized by a core transcriptional regulatory circuitry (CRC) comprised of transcription factors (TF) such as PHOX2B, HAND2, and GATA3, which form a network with MYCN. At normal physiologic levels, MYCN mainly binds to promoters but when aberrantly upregulated as in neuroblastoma, MYCN also binds to enhancers. Here, we investigated how MYCN invades enhancers and whether CRC TFs play a role in this process. HAND2 was found to regulate chromatin accessibility and to assist MYCN binding to enhancers. Moreover, HAND2 cooperated with MYCN to compete with nucleosomes to regulate global gene transcription. The cooperative interaction between MYCN and HAND2 could be targeted with an Aurora A kinase inhibitor plus a histone deacetylase inhibitor, resulting in potent downregulation of both MYCN and the CRC TFs and suppression of MYCN-amplified neuroblastoma tumor growth. This study identifies cooperation between MYCN and HAND2 in neuroblastoma and demonstrates that simultaneously targeting MYCN and CRC TFs is an effective way to treat this aggressive pediatric tumor.Significance:HAND2 and MYCN compete with nucleosomes to regulate global gene transcription and to drive a malignant neuroblastoma phenotype.

This study derives radiatively-active hydrometeors frequencies (HFs) from CloudSat-CALIPSO satellite data to evaluate cloud fraction in present-day simulations by CMIP5 models. Most CMIP5 models do not consider precipitating and/or convective hydrometeors but CESM1-CAM5 in CMIP5 has diagnostic snow and CESM2-CAM6 in CMIP6 has prognostic precipitating ice (snow) included. However, the models do not have snow fraction available for evaluation. Since the satellite-retrieved hydrometeors include the mixtures of floating, precipitating and convective ice and liquid particles, a filtering method is applied to produce estimates of cloud-only HF (or NPCHF) from the total radiatively-active HF (THF), which is the sum of NPCHF, precipitating ice HF and convective HF. The reference HF data for model evaluation include estimates of liquid-phase NPCHF from CloudSat radar-only data (2B-CWC) and ice-phase THF from CloudSat-CALIPSO 2C-ICE combined radar/lidar data. The model evaluation results show that cloud fraction from CMIP5 multi-model mean (MMM) is significantly underestimated (up to 30 %) against the total HF estimates, mainly below the mid-troposphere over the extratropics and in the upper-troposphere over the midlatitude lands and a few tropical convective regions. The CMIP5 cloud fraction biases are reduced dramatically when compared to the cloud-only HF estimates, but the area of overestimates expands from the tropical convective regions to mid-latitudes in the lower and upper troposphere. There is no CMIP5 standard output snow fraction available for comparison against CloudSat-CALIPSO estimate. The implications of these results show that hydrometeors frequency estimates from CloudSat-CALIPSO provide a reference for GCM’s cloud fraction from stratiform and convective form.

A rhabditid entomopathogenic nematode (EPN), Oscheius chongmingensis, has a stable symbiotic relationship with the bacterial strain Serratia nematodiphila S1 harbored in its intestines and drastically reduced viability when associated with a non-native strain (186) of the same bacterial species. This nematode is thus a good model for understanding the molecular mechanisms and interactions involved between a nematode host and a member of its intestinal microbiome. Transcriptome analysis and RNA-seq data indicated that expression levels of the majority (8797, 87.59%) of mRNAs in the non-native combination of O. chongmingensis and S. nematodiphila 186 were downregulated compared with the native combination, including strain S1. Accordingly, 88.84% of the total uniq-sRNAs mapped in the O. chongmingensis transcriptome were specific between the two combinations. Six DEGs, including two transcription factors (oc-daf-16 and oc-goa-1) and four kinases (oc-pdk-1, oc-akt-1, oc-rtk, and oc-fak), as well as an up-regulated micro-RNA, oc-miR-71, were found to demonstrate the regulatory mechanisms underlying diminished host viability induced by a non-native bacterial strain. Oc-rtk and oc-fak play key roles in the viability regulation of O. chongmingensis by positively mediating the expression of oc-daf-16 to indirectly impact its longevity and stress tolerances and by negatively regulating the expression of oc-goa-1 to affect the olfactory chemotaxis and fecundity. In response to the stress of invasion by the non-native strain, the expression of oc-miR-71 in the non-native combination was upregulated to downregulate the expression of its targeting oc-pdk-1, which might improve the localization and activation of the transcription factor DAF-16 in the nucleus to induce longevity extension and stress resistance enhancement to some extent. Our findings provide novel insight into comprehension of how nematodes deal with the stress of encountering novel potential bacterial symbionts at the physiological and molecular genetic levels and contribute to improved understanding of host–symbiont relationships generally.

BackgroundSimulated oral processing can be used to evaluate the palatability of cooked rice. Previously, we established a simulated oral processing method using a texture analyzer equipped with a multiple extrusion cell probe (TA/MEC). However, the relationship between oral processing and starch fine structure remains unknown.MethodsIn this study, we analyzed the oral processing properties using TA/MEC and characterized the starch fine structure of japonica rice by size-exclusion chromatography (SEC) and fluorophore-assisted capillary electrophoresis (FACE). The relationship between starch fine structure and oral processing of cooked japonica rice was further investigated.ResultsCooked rice structure contains fast-breakdown (Type I structure), slow-breakdown (Type II structure) and unbreakable structures (Type III structure). Fast-breakdown and slow-breakdown structure were positively correlated with the content of amylose and shorter amylopectin branches. The content of longer amylopectin branches was positively correlated with the contribution of unbreakable structure.ConclusionThe results indicated that cooked japonica rice varieties with more amylose and shorter amylopectin branches tend to form a harder texture and need more work to break down the fast and slow breakdown structures related to rice kernel fragmentation. Meanwhile, cooked japonica rice varieties possess stronger molecular entanglements due to their longer amylopectin branches and contribute more to the breakdown of unbreakable structures. These results can guide breeders to select rice varieties with desirable eating qualities for cultivation.

Objective: To explore the effect of Philadelphia chromosome karyotype (Ph) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the treatment of acute lymphoblastic leukemia (ALL).The data of 429 patients with all from January 2012 to December 2020 were retrospectively analyzed. According to the results of cytogenetic karyotype analysis, they were divided into PhAmong the 429 patients, 6 (1.40%) died during induction therapy, 60 (13.99%) had no response, 363 (84.62%) achieved complete remission (CR) and 287 (66.90%) achieved minimal residual disease negative (MRD-). There was no significant difference in short-term efficacy (CR%, CR1%, MRD-%) among PhKaryotype (Ph费城染色体核型和异基因造血干细胞移植对急性淋巴细胞白血病患者疗效的影响.探究费城染色体核型（Ph）和异基因造血干细胞移植（allo-HSCT）对急性淋巴细胞白血病（ALL）患者疗效的影响.回顾性分析2012年1月－2020年12月血液科429例ALL患者的资料，根据细胞遗传学核型分析结果将患者分为Ph在429例ALL患者中，6例（1.40%）在诱导治疗期间死亡，60例（13.99%）无反应，最终达到完全缓解（CR）共363例（84.62%），达到微小残留病灶阴性（MRD-）共有287例（66.90%）。Ph核型（Ph

Supplemental figures and tables for a manuscript submitted to the journal "International Journal of Molecular Sciences".

Predicting postoperative survival of lung cancer patients (LCPs) is an important problem of medical decision-making. However, the imbalanced distribution of patient survival in the dataset increases the difficulty of prediction. Although the synthetic minority oversampling technique (SMOTE) can be used to deal with imbalanced data, it cannot identify data noise. On the other hand, many studies use a support vector machine (SVM) combined with resampling technology to deal with imbalanced data. However, most studies require manual setting of SVM parameters, which makes it difficult to obtain the best performance. In this paper, a hybrid improved SMOTE and adaptive SVM method is proposed for imbalance data to predict the postoperative survival of LCPs. The proposed method is divided into two stages: in the first stage, the cross-validated committees filter (CVCF) is used to remove noise samples to improve the performance of SMOTE. In the second stage, we propose an adaptive SVM, which uses fuzzy self-tuning particle swarm optimization (FPSO) to optimize the parameters of SVM. Compared with other advanced algorithms, our proposed method obtains the best performance with 95.11% accuracy, 95.10% G -mean, 95.02% F1, and 95.10% area under the curve (AUC) for predicting postoperative survival of LCPs.

Ectomycorrhiza-associated bacteria, especially endofungal bacterial microbiota (EBM) in the fruiting body, play important roles in driving the establishment and function of ectomycorrhizae. However, the influence of ectomycorrhizal fungus bolete identity on their EBM is still unclear. We analysed the EBM of three different bolete fruiting body species on Thousand Island Lake, including Tylopilus felleus, Tylopilus areolatus and Boletus queletii, and compared them with their corresponding mycosphere soil bacterial microbiota by high-throughput sequencing. The EBM was classified into Bacillus, Pseudomonas, Burkholderia and Stenotrophomonas genera. Proteobacteria, Bacteroidetes and Acidobacteria were predominant in the EBM of bolete fruiting bodies as well as their mycosphere soil, while Firmicutes was significantly higher in the EBM. Moreover, the core microbiome (342 operational taxonomic units) of the EBM was shared among the three bolete fungal species. The relative abundances of gene families related to cell cycle control and nucleotide, coenzyme and lipid metabolism were significantly higher in the EBM than in the corresponding mycosphere soil bacterial microbiota, but there was no difference among the three different boletes. The results suggested that the host identity of ectomycorrhizal fungus boletes could affect the EBM, which might be mainly due to the selection of host fungi for the different functional EBM needed.

PurposeQualitative methods are not suitable to process high volumes of policy texts for exploring policy evolution. Therefore, it is hard to use qualitative methods to systematically analyze the characteristics of complex policy networks. So the authors propose a bibliometric research study for exploring policy evolution from time–agency–theme perspectives to excavate the rules and existing problems of China's medical informatization policy and to provide suggestions for formulating and improving the future medical informatization policies.Design/methodology/approachInitially, 615 valid samples are obtained by retrieving related China's medical informatization policy documents, and the joint policy-making agency network and the co-occurrence network models of medical informatization policies are defined, and then the authors research China's medical informatization policies from single-dimension and multi-dimension view.FindingsThe analysis results reveal that China's medical informatization policy process can be divided into four stages; the policy-making agencies are divided into four subgroups by community detection analysis according to the fast unfolding algorithm; the core policy theme keywords are identified based on the eigenvector centrality of the nodes in those networks; the focuses of theme terms are varied in different stages and the correlations between agencies and themes are gradually decentralized.Practical implicationsThese findings provide experience and evidence on leveraging informatics in the medical and healthcare field of China. Also, they can help scholars and practitioners better understand the current status and future directions of medical and healthcare informatics development in China and provide a reference to formulate and improve China's future medical informatization policies.Originality/valueThis study proposes a quantitative bibliometric-based research framework to describe transitions and trends of China's medical informatization policy.

Cement-based stabilization by deep mixing or grouting is a popular method used to enhance soft clay ground because clay gradation has a significant effect on its unconfined compression strength. However, the functional relationship between the gradation and the strength is currently unclear, which limits the assessment and cognition for the strength formation of cement-based stabilized soft clay. Strength experiments controlling the sand ratio were conducted, in addition to the literature review, to clarify the sand incorporation effect on the strength. An effective cement ratio (the mass ratio of cement to involved clay) was proposed to evaluate the strength of stabilized clay with sand incorporation. In order to combat data dispersion and the labour-intensive nature of these experiments, meso-mechanical numerical simulations were carried out by the finite element method. This served to enrich the data and clarify the mesoscopic mechanism. The numerical result indicates that the strength of stabilized clay at low sand incorporation ratio is mainly controlled by the strength of the cement-clay-water matrix, thus verifying the rationality of studying the effective cement ratio. Subsequently, the threshold sand ratio in the cement-clay-water matrix was discussed to optimize the stabilization of soft clay.

Gastric cancer (GC) is common in East Asia, yet its molecular and pathogenic mechanisms remain unclear. Circular RNAs (circRNAs) are differentially expressed in GC and may be promising biomarkers. Here, we investigated the role and regulatory mechanism of circTMC5 in GC. CircTMC5 expression was detected in human GC and adjacent tissues using microarray assays and qRT-PCR, while the clinicopathological characteristics of patients with GC were used to assess its diagnostic and prognostic value. The circTMC5/miR-361-3p/RABL6 axis was examined in vitro and vivo, and the immune roles of RABL6 were evaluated using bioinformatics analyses and immunohistochemistry (IHC). CircTMC5 was highly expressed in GC tissues, plasma, and cell lines, and was closely related to histological grade, pathological stage, and T classification in patients with GC. CircTMC5 expression was also an independent prognostic factor for GC and its combined detection with carcinoembryonic antigen may improve GC diagnosis. Low circTMC5 expression correlated with good prognosis, inhibited GC cell proliferation, and promoted apoptosis. Mechanistically, circTMC5 overexpression promoted GC cell proliferation, invasion, and metastasis but inhibited apoptosis by sponging miR-361-3p and up-regulating RABL6 in vitro and vivo, whereas miR-361-3p up-regulation had the opposite effects. RABL6 was highly expressed in GC and was involved in immune regulation and infiltration in GC. CircTMC5 promotes GC and sponges miR-361-3p to up-regulate RABL6 expression, thus may have diagnostic and prognostic value in GC. RABL6 also displays therapeutic promise due to its role in the immune regulation of GC.

The MYCN gene encodes the transcription factor N-Myc, a driver of neuroblastoma (NB). Targeting G-quadruplexes (G4s) with small molecules is attractive strategy to control the expression of undruggable proteins such as N-Myc. However, selective binders to G4s are challenging to identify due to the structural similarity of many G4s. Here, we report the discovery of a small molecule ligand (4) that targets the noncanonical, hairpin containing G4 structure found in the MYCN gene using small molecule microarrays (SMMs). Unlike many G4 binders, the compound was found to bind to a pocket at the base of the hairpin region of the MYCN G4. This compound stabilizes the G4 and has affinity of 3.5 ± 1.6 μM. Moreover, an improved analog, MY-8, suppressed levels of both MYCN and MYCNOS (a lncRNA embedded within the MYCN gene) in NBEB neuroblastoma cells. This work indicates that the approach of targeting complex, hybrid G4 structures that exist throughout the human genome may be an applicable strategy to achieve selectivity for targeting disease-relevant genes including protein coding (MYCN) as well as non-coding (MYCNOS) gene products.

BACKGROUND Approximately 90% of new cases of noncardiac gastric cancer (GC) are related to Helicobacter pylori (H. pylori), and cytotoxin-associated gene A (CagA) is one of the main pathogenic factors. Recent studies have shown that the pharmacological effects of cryptotanshinone (CTS) can be used to treat a variety of tumors. However, the effects of CTS on H. pylori, especially CagA+ strain-induced gastric mucosal lesions, on the development of GC is unknown. AIM To assess the role of CTS in CagA-induced proliferation and metastasis of GC cells, and determine if CagA+ H. pylori strains causes pathological changes in the gastric mucosa of mice. METHODS The effects of CTS on the proliferation of GC cells were assessed using the Cell Counting Kit-8 (CCK-8) assay, and the abnormal growth, migration and invasion caused by CagA were detected by CCK-8 and transwell assays. After transfection with pSR-HA-CagA and treatment with CTS, proliferation and metastasis were evaluated by CCK-8 and transwell assays, respectively, and the expression of Src homology 2 (SH2) domain–containing phosphatase 2 (SHP2) and phosphorylated SHP2 (p-SHP2) was detected using western blotting in AGS cells. The enzyme-linked immunosorbent assay was used to determine the immunoglobulin G (IgG) level against CagA in patient serum. Mice were divided into four groups and administered H. pylori strains (CagA+ or CagA-) and CTS (or PBS) intragastrically, and establishment of the chronic infection model was verified using polymerase chain reaction and sequencing of isolated strains. Hematoxylin and eosin staining was used to assess mucosal erosion in the stomach and toxicity to the liver and kidney. RESULTS CTS inhibited the growth of GC cells in dose- and time-dependent manners. Overexpression of CagA promoted the growth, migration, and invasion of GC cells. Importantly, we demonstrated that CTS significantly inhibited the CagA-induced abnormal proliferation, migration, and invasion of GC cells. Moreover, the expression of p-SHP2 protein in tumor tissue was related to the expression of IgG against CagA in the serum of GC patients. Additionally, CTS suppressed the protein expression levels of both SHP2 and p-SHP2 in GC cells. CTS suppressed CagA+ H. pylori strain-induced mucosal erosion in the stomach of mice but had no obvious effects on the CagA- H. pylori strain group. CONCLUSION CTS inhibited CagA-induced proliferation and the epithelial-mesenchymal transition of GC cells in vitro, and CagA+ H. pylori strains caused mucosal erosions of the stomach in vivo by decreasing the protein expression of SHP2.

Lily Kai Man Xu,1 Toby Yiu Bong Chan2,3 1Faculty of Medicine, McMaster University, Hamilton, Ontario, Canada; 2Division of Ophthalmology, Department of Surgery, McMaster University, Waterloo Regional Campus, Kitchener-Waterloo, Ontario, Canada; 3Ocular Health Centre, Kitchener, Ontario, CanadaCorrespondence: Toby Yiu Bong Chan, McMaster University, Waterloo Regional Campus, Kitchener-Waterloo, Ontario, Canada, Tel +1 519 208 8104, Fax +1 519 208 8101, Email toby.yb.chan@gmail.comPurpose: After tube shunt surgery, many factors may contribute to insufficient filtration over time, prompting further intervention to achieve optimal intraocular pressure (IOP) control. This study explores whether ab interno XEN gel stent implantation could be a viable approach in eyes that need further IOP reduction after tube shunt surgery.Methods: This is a retrospective, single-surgeon case series on ab interno XEN45 gel stent implantation in eyes that had previous tube shunt surgery. Main outcome measures were IOP and number of glaucoma medications at the pre-operative visit, post-operative week (POW) 1, and post-operative month (POM) 1, 3, 6, and 12. Adverse events and further interventions were noted. Surgery outcome was qualified as absolute success (IOP ≤ 18mmHg or ≥ 20% IOP reduction without glaucoma medications), qualified success (IOP ≤ 18mmHg or ≥ 20% IOP reduction with glaucoma medications), or failure (IOP > 18mmHg and < 20% IOP reduction with maximum tolerated glaucoma medications).Results: 7 eyes from 6 patients were included in this study. IOP was reduced from 23.9 ± 5.3 mmHg (mean ± standard deviation) pre-operatively to 14.0 ± 5.3 mmHg at POM12 (p < 0.05). Number of glaucoma medications was reduced from 4.3 ± 1.3 pre-operatively to 1.6 ± 1.6 at POM12 (p < 0.05). Hypotony and choroidal effusion were noted in one case which resolved before POM1. Bleb needling was required in 3 of the 7 eyes (43%), with one eye requiring needling twice. By POM12, 2 of 7 eyes (29%) achieved absolute success, 4 eyes (57%) qualified success, and 1 eye (14%) was qualified as failure.Conclusion: Ab interno XEN gel stent can effectively reduce IOP and number of glaucoma medications after failed tube shunt surgery. Nonetheless, further interventions such as bleb needling may still be required to optimize IOP control.Keywords: glaucoma, MIGS, tube shunt, Ahmed glaucoma valve, Baerveldt glaucoma device, ab interno XEN implant

We address the issue of multi-aircraft cooperative strategic trajectory planning in free-route airspace (FRA) in this study, taking into consideration the impact of time-varying and altitude-varying wind forecast uncertainty. A bi-level planning model was established in response to the properties of the wind. The upper level focused on minimizing the flight time, while the lower level aimed to reduce potential conflicts. Meanwhile, a heuristic approach based on conflict severity (CS) within the framework of a cooperative co-evolution evolutionary algorithm (CCEA) was proposed to accelerate the convergence speed in view of the complexity of this optimization issue. In order to conduct the experiments, historical data of 1479 flights over western Chinese airspace were retrieved. The number of conflicts, total flight time, total flight time variance, and deviation were used as indicators to evaluate the safety, efficiency, and predictability of the trajectory. When compared to a trajectory in the structured airspace, the optimal solution was conflict-free and reduced the total flight time by about 17.7%, the variance by 11.7%, and the deviation by 37.5%. Additionally, the contrast with the two-stage model demonstrated that the proposed method was entirely meaningful. The outcome of this survey can provide an effective trajectory-planning method, which is crucial for the sustainable development of future air traffic management (ATM).

Arachidonate 5-lipoxygenase (Alox5) belongs to a class of nonheme iron-containing dioxygenases involved in the catalysis of leukotriene biosynthesis. However, the effects of Alox5 itself on pathological cardiac remodeling and heart failure remain elusive.The role of Alox5 in pathological cardiac remodeling was investigated by Alox5 genetic depletion, AAV9-mediated overexpression in cardiomyocytes, and a bone marrow (BM) transplantation approach. Neonatal rat cardiomyocytes were used to explore the effects of Alox5 in vitro. Molecular and signaling pathways were revealed by CUTTag, IP-MS, RNA sequencing and bioinformatic analyses.Untargeted metabolomics showed that serum 5-HETE (a primary product of Alox5) levels were little changed in patients with cardiac hypertrophy, while Alox5 expression was significantly upregulated in murine hypertensive cardiac samples and human cardiac samples of hypertrophy, which prompted us to test whether high Alox5 levels under hypertensive stimuli were directly associated with pathologic myocardium in an enzymatic activity-independent manner. Herein, we revealed that Alox5 deficiency significantly ameliorated transverse aortic constriction (TAC)-induced hypertrophy. Cardiomyocyte-specific Alox5 depletion attenuated hypertensive ventricular remodeling. Conversely, cardiac-specifical Alox5 overexpression showed a pro-hypertrophic cardiac phenotype. Ablation of Alox5 in bone marrow-derived cells did not affect pathological cardiac remodeling and heart failure. Mechanically, Runx2 was identified as a target of Alox5. In this regard, Alox5 PEST domain could directly bind to Runx2 PTS domain, promoting nuclear localization of Runx2 in an enzymatic activity-independent manner, simultaneously contributed to liquid-liquid phase separation (LLPS) of Runx2 at specific domain in the nucleus and increased transcription of EGFR in cardiomyocytes. Runx2 depletion alleviated hypertrophy in Ang II-pretreated Alox5-overexpressing cardiomyocytes.Overall, our study demonstrated that targeting Alox5 exerted a protective effect against cardiac remodeling and heart failure under hypertensive stimuli by disturbing LLPS of Runx2 and substantial reduction of EGFR transcription activation in cardiomyocytes. Our findings suggest that negative modulation of Alox5-Runx2 may provide a therapeutic approach against pathological cardiac remodeling and heart failure.National Natural Science Foundation of China.

A new [4+2] cycloaddition of allenyne-alkyne is developed. The reaction is believed to proceed with forming an α,3-dehydrotoluene intermediate. This species behaves as a σπ-diradical to react with a hydrogen atom donor, whereas it displays a zwitterionic reactivity toward weak nucleophiles. The efficiency of trapping α,3-dehydrotoluene depends not only on its substituents but also the trapping agents. Notable features of the reaction are the activating role of the extra alkyne of the 1,3-diyne that reacts with the allenyne moiety and the opposite mode of trapping with oxygen and nitrogen nucleophiles. Oxygen nucleophiles result in the oxygen-end incorporation at the benzylic position of the α,3-dehydrotoluene, whereas with amine nucleophiles the nitrogen-end is incorporated into the aromatic core. Relying on the allenyne-alkyne cycloaddition as an enabling strategy, a concise total synthesis of phosphodiesterase-4 inhibitory selaginpulvilin A is realized.

The neural crest lineage regulatory transcription factors (TFs) form a core regulatory circuitry (CRC) in neuroblastoma (NB) to specify a noradrenergic tumor phenotype. Oncogenic subversion of CRC TFs is well documented, but the role of loss of tumor suppressors plays remains unclear. Zinc-finger TF CASZ1 is a chromosome 1p36 (chr1p36) tumor suppressor. Single-cell RNA sequencing data analyses indicate that CASZ1 is highly expressed in developing chromaffin cells coincident with an expression of NB CRC TFs. In NB tumor cells, the CASZ1 tumor suppressor is silenced while CRC components are highly expressed. We find the NB CRC component HAND2 directly represses CASZ1 expression. ChIP-seq and transcriptomic analyses reveal that restoration of CASZ1 upregulates noradrenergic neuronal genes and represses expression of CRC components by remodeling enhancer activity. Our study identifies that the restored CASZ1 forms a negative feedback regulatory circuit with the established NB CRC to induce noradrenergic neuronal differentiation of NB.

In this study, ferric chloride and sulfuric acid were used to increase the Fe-containing minerals on the biochar surface before a pyrolysis at 600 °C. The pristine and Fe-modified biochars prepared at different concentrations of sulfuric acid (50FBC and 72FBC) were characterized and analyzed, and their capacity of As(V) adsorption under various pH and ionic strength were evaluated. The results showed that the maximum adsorption capacities of As(V) calculated by the Langmuir model for 50FBC and 72FBC are 10.33 and 15.61 mg g