Mesoporous Vinylene-Linked Covalent Organic Frameworks with Heteroatom-Tuned Crystallinity and Photocatalytic Behaviors.

Owing to its prominent π-delocalization and stability, vinylene linkage holds great merits in the construction of covalent organic frameworks (COFs) with promising semiconducting properties. However, carbon-carbon double bond formation reaction always exhibits relatively low reversibility, unfavorable for the formation of high crystalline frameworks through self-error correction and assembling processes. In this work, we report a heteroatom-tuned strategy to build up a series of two-dimensional (2D) vinylene-linked COFs by Knoevenagel condensation of an electron-deficient methylthiazolyl-based monomer with different triformyl substituted (hetero-)aromatic derivatives. The resulting COFs show high-quality periodic mesoporous structures with high surface areas. Embedding heteroatoms into the backbones enables significantly improving their crystallinity, and finely tailoring their semiconducting structures. Upon visible light stimulation, one of the as-prepared COFs with donor-π-acceptor structure could deliver a nearly seven-fold increase in the catalytic activity of hydrogen generation as compared with the other two. Meanwhile, in combination with high crystallinity and the matched conduction band energy level, such kind of COFs can be able to selectively generate singlet oxygen and superoxide radicals in a high ratio of up to 30:1, allowing for catalyzing aerobic thioanisole oxidation in distinctly tunable activities through the substituent electronic effect of the substrates.

GINv2.0: a comprehensive topological network integrating molecular interactions from multiple knowledge bases.

Knowledge bases have been instrumental in advancing biological research, facilitating pathway analysis and data visualization, which are now widely employed in the scientific community. Despite the establishment of several prominent knowledge bases focusing on signaling, metabolic networks, or both, integrating these networks into a unified topological network has proven to be challenging. The intricacy of molecular interactions and the diverse formats employed to store and display them contribute to the complexity of this task. In a prior study, we addressed this challenge by introducing a "meta-pathway" structure that integrated the advantages of the Simple Interaction Format (SIF) while accommodating reaction information. Nevertheless, the earlier Global Integrative Network (GIN) was limited to reliance on KEGG alone. Here, we present GIN version 2.0, which incorporates human molecular interaction data from ten distinct knowledge bases, including KEGG, Reactome, and HumanCyc, among others. We standardized the data structure, gene IDs, and chemical IDs, and conducted a comprehensive analysis of the consistency among the ten knowledge bases before combining all unified interactions into GINv2.0. Utilizing GINv2.0, we investigated the glycolysis process and its regulatory proteins, revealing coordinated regulations on glycolysis and autophagy, particularly under glucose starvation. The expanded scope and enhanced capabilities of GINv2.0 provide a valuable resource for comprehensive systems-level analyses in the field of biological research. GINv2.0 can be accessed at: https://github.com/BIGchix/GINv2.0 .

Vocational training for pediatric clinical research coordinators: current status and demand analysis / 中华医学教育探索杂志

Objective:To investigate the current status of vocational training for pediatric clinical research coordinators (CRC), and discuss the construction of base-based pediatric CRC training, and to promote the ability of pediatric CRCs.Methods:From July 25 to October 16, 2023, an anonymous self-designed questionnaire survey was conducted through the Wenjuanxing platform to investigate the current situation of pediatric CRC vocational training and base training needs. The data were collated using Excel. Categorical data were described as numbers and percentages.Results:A total of 328 usable questionnaires were returned. Only 7.62% (25 people) believed that existing CRC training was sufficient and could meet actual work needs; 4.88% (16 people) responded that there was no training; 46.34% (152 people) believed that the training was insufficient to support actual work needs; 87.50% (287 people) believed that continuous CRC training was needed; 46.95% (154 people) preferred experienced CRCs for teaching, who should have at least 3 years of CRC work experience; and 46.95% (154 people) preferred a duration of 3 months for CRC training. The preferred training methods were: practice under the direction of experienced CRCs (90.85%, 298 people), step-by-step teaching of practical skills (88.41%, 290 people), case analysis and discussion (87.20%, 286 people), process simulation (83.23%, 273 people), and lecture-based teaching (76.52%, 251 people). The preferred post-training assessment methods were: case analysis (76.52%, 251 people), operation simulation (74.09%, 243 people), process simulation (73.17%, 240 people), written examination (66.16%, 217 people), and interview (63.72%, 209 people).Conclusions:The current pediatric CRC training is not enough to meet actual work needs. It is urgent to develop and promote a CRC training system that can meet work needs, laying the foundation for the construction of pediatric clinical research ecology in China.

Decoding Aging Hallmarks at the Single-Cell Level.

Organismal aging exhibits wide-ranging hallmarks in divergent cell types across tissues, organs, and systems. The advancement of single-cell technologies and generation of rich datasets have afforded the scientific community the opportunity to decode these hallmarks of aging at an unprecedented scope and resolution. In this review, we describe the technological advancements and bioinformatic methodologies enabling data interpretation at the cellular level. Then, we outline the application of such technologies for decoding aging hallmarks and potential intervention targets and summarize common themes and context-specific molecular features in representative organ systems across the body. Finally, we provide a brief summary of available databases relevant for aging research and present an outlook on the opportunities in this emerging field.

Electronic Transmission Channels Promoting Charge Separation of Conjugated Polymers for Photocatalytic CO2 Reduction with Controllable Selectivity.

Conjugated polymers (CPs) represent a promising platform for photocatalytic CO2 fixation owing to their suitable band structures that meet the requirements of the reduction potential of CO2 to value-added fuels. However, the photocatalytic performance of CPs is rather restrained by the low charge transfer efficiency. Herein, we rationally designed three CPs with a more delocalized electronic transmission channel and planar molecular structure, which are regarded to evidently reduce the exciton binding energy (Eb ) and accelerate the internal charge transfer process. Besides, the assembly of suitable electron-output "tentacles" and cocatalysts on the surface of CPs could effectively facilitate interfacial electron delivery. Accordingly, the optimal P-2CN exhibits an apparent quantum yield of 4.6 % at 420 nm for photocatalytic CO2 to CO. Further adjusting the amounts of cyano groups and cocatalysts, the CO selectivity could be obtained in the range of 0-80.5 %.

Structure-Property Relationship of Cyano-Functionalized Conjugated Polymers for Photocatalytic Hydrogen Production.

Conjugated polymers (CPs) have garnered increasing attention in the field of photocatalysis due to their stability and molecular tunability. Understanding the structure-property relationship in CPs and addressing appropriate molecular design strategies are pivotal to improving the photocatalytic performance of CPs. Herein, a new efficient cyano (CN) engineering approach was proposed to promote the photocatalytic performance of CPs, and three representative CP-based photocatalysts with different CN contents were tailor-made to investigate the relationship between CN functionalization and photocatalytic activity. A series of systematically experimental and theoretical studies reveal that CN functionalization contributes to strengthening the donor-acceptor (D-A) interaction, enhancing the light absorption ability, charge separation/transfer efficiency, and hydrophilicity of CPs, and also facilitating the output of separated photoinduced electrons from CPs to Pt cocatalyst. Thus, the dicyano-functionalized polymer (P-2CN) manifests an attractive photocatalytic performance in hydrogen production. This study provides a facile strategy to develop excellent CP-based photocatalysts for solar fuel production.

Dorsal root ganglion receptor subtype P2X3R mediates postoperative-hyperalgesic priming in mice / 中国药理学通报

Aim To investigate the differences in the role of different purinergic receptor subtypes at different sites in postoperative-hyperalgesic priming in mice. Methods A postoperative-hyperalgesic priming model was constructed by injecting PGE

The global integrative network: integration of signaling and metabolic pathways.

The crosstalk between signaling and metabolic pathways has been known to play key roles in human diseases and plant biological processes. The integration of signaling and metabolic pathways can provide an essential reference framework for crosstalk analysis. However, current databases use distinct structures to present signaling and metabolic pathways, which leads to the chaos in the integrated networks. Moreover, for the metabolic pathways, the metabolic enzymes and the reactions are disconnected by the current widely accepted layout of edges and nodes, which hinders the topological analysis of the integrated networks. Here, we propose a novel "meta-pathway" structure, which uses the uniformed structure to display the signaling and metabolic pathways, and resolves the difficulty in linking the metabolic enzymes to the reactions topologically. We compiled a comprehensive collection of global integrative networks (GINs) by merging the meta-pathways of 7077 species. We demonstrated the assembly of the signaling and metabolic pathways using the GINs of four species-human, mouse, Arabidopsis, and rice. Almost all of the nodes were assembled into one major network for each of the four species, which provided opportunities for robust crosstalk and topological analysis, and knowledge graph construction. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-022-00078-1.

Dynamic DNA 5-hydroxylmethylcytosine and RNA 5-methycytosine Reprogramming During Early Human Development.

After implantation, complex and highly specialized molecular events render functionally distinct organ formation, whereas how the epigenome shapes organ-specific development remains to be fully elucidated. Here, nano-hmC-Seal, RNA bisulfite sequencing (RNA-BisSeq), and RNA sequencing (RNA-Seq) were performed, and the first multilayer landscapes of DNA 5-hydroxymethylcytosine (5hmC) and RNA 5-methylcytosine (m5C) epigenomes were obtained in the heart, kidney, liver, and lung of the human foetuses at 13-28 weeks with 123 samples in total. We identified 70,091 and 503 organ- and stage-specific differentially hydroxymethylated regions (DhMRs) and m5C-modified mRNAs, respectively. The key transcription factors (TFs), T-box transcription factor 20 (TBX20), paired box 8 (PAX8), krueppel-like factor 1 (KLF1), transcription factor 21 (TCF21), and CCAAT enhancer binding protein beta (CEBPB), specifically contribute to the formation of distinct organs at different stages. Additionally, 5hmC-enriched Alu elements may participate in the regulation of expression of TF-targeted genes. Our integrated studies reveal a putative essential link between DNA modification and RNA methylation, and illustrate the epigenetic maps during human foetal organogenesis, which provide a foundation for understanding the in-depth epigenetic mechanisms for early development and birth defects.

Does the Presence of Type 2 Diabetes or Metabolic Syndrome Impact Reduction in Waist Circumference During Weight Loss?

OBJECTIVES: Our aim in this study was to compare the change in waist circumference given the same degree of weight loss in patients who meet the criteria for metabolic syndrome or type 2 diabetes and those who do not meet these criteria. Because visceral adiposity is a key feature of both conditions and intra-abdominal adipocytes show higher lipolytic activity, we sought to determine whether changes in waist circumference differed in individuals with and without these conditions. METHODS: The Ottawa Hospital Weight Management Clinic offers a course in lifestyle modification and uses 12 weeks of total meal replacement. We compared the decrease in waist circumference between patients with metabolic syndrome or diabetes and those without these conditions who had lost a similar amount of weight using measurements from the first 6 weeks of meal replacement. RESULTS: We evaluated 3,559 patients who attended the program between September 1992 and April 2015. The patient population was largely Caucasian and of European descent and all meetings were face to face. The mean weight loss for men was 15.1±20.2 kg, and the mean weight loss for women was 9.7±2.4 kg. There were no significant differences in decrease in waist circumference between those with and without metabolic syndrome in both men (11.7±3.9 cm vs 11.4±3.8 cm, p=0.48) and women (9.0±3.6 cm vs 9.1±3.7 cm, p=0.26). CONCLUSIONS: Our results show that, given the same degree of weight loss, patients with and without diabetes or metabolic syndrome experience a similar change in waist circumference.

Molecular Design of Covalent Triazine Frameworks with Anisotropic Charge Migration for Photocatalytic Hydrogen Production.

Covalent triazine frameworks (CTFs) represent promising polymeric photocatalysts for photocatalytic hydrogen production with visible light. However, the separation and transfer of charges in CTFs are isotropic because of the uniform distribution of donor-acceptor motifs in the skeleton. Herein, to achieve the anisotropic charge carrier separation and migration, thiophene (Th) or benzothiadiazole (BT) unit is selected as the dopant to modify the molecular structure of CTF-based photocatalysts. Both theoretical and experimental studies reveal that the incorporation of Th or BT units induces the anisotropic charge carrier separation and migration at the interface of CTFs. The optimized polymer manifests a much enhanced photocatalytic activity for photocatalytic hydrogen production with visible light, and thus this study provides a useful tool to design conjugated polymer photocatalysts at the molecular level for solar energy conversion.

Insulin-like growth factor-binding protein-7 (IGFBP7) links senescence to heart failure.

Heart failure (HF) is a rising global cardiovascular epidemic driven by aging and chronic inflammation. As elderly populations continue to increase, precision treatments for age-related cardiac decline are urgently needed. Here we report that cardiac and blood expression of IGFBP7 is robustly increased in patients with chronic HF and in an HF mouse model. In a pressure overload mouse HF model, Igfbp7 deficiency attenuated cardiac dysfunction by reducing cardiac inflammatory injury, tissue fibrosis and cellular senescence. IGFBP7 promoted cardiac senescence by stimulating IGF-1R/IRS/AKT-dependent suppression of FOXO3a, preventing DNA repair and reactive oxygen species (ROS) detoxification, thereby accelerating the progression of HF. In vivo, AAV9-shRNA-mediated cardiac myocyte Igfbp7 knockdown indicated that myocardial IGFBP7 directly regulates pathological cardiac remodeling. Moreover, antibody-mediated IGFBP7 neutralization in vivo reversed IGFBP7-induced suppression of FOXO3a, restored DNA repair and ROS detoxification signals and attenuated pressure-overload-induced HF in mice. Consequently, selectively targeting IGFBP7-regulated senescence pathways may have broad therapeutic potential for HF.

A Fully Coplanar Donor-Acceptor Polymeric Semiconductor with Promoted Charge Separation Kinetics for Photochemistry.

Charge generation and separation are regarded as the major constraints limiting the photocatalytic activity of polymeric photocatalysts. Herein, two new linear polyarylether-based polymers (PAE-CPs) with distinct linking patterns between their donor and acceptor motifs were tailor-made to investigate the influence of different linking patterns on the charge generation and separation process. Theoretical and experimental results revealed that compared to the traditional single-stranded linker, the double-stranded linking pattern strengthens donor-acceptor interactions in PAE-CPs and generates a coplanar structure, facilitating charge generation and separation, and enabling red-shifted light absorption. With these prominent advantages, the PAE-CP interlinked with a double-stranded linker exhibits markedly enhanced photocatalytic activity compared to that of its single-strand-linked analogue. Such findings can facilitate the rational design and modification of organic semiconductors for charge-induced reactions.

Applications of Oxford Nanopore Sequencing in Schizosaccharomyces pombe.

Recent years have seen great progresses in third-generation sequencing. New commercial platforms from Oxford Nanopore Technologies (ONT) can generate ultra-long reads from single-molecule nucleic acid fragments of kilobases up to megabases, exceeding the limitation of short reads and dependency on template amplification suffered by the previous generation of sequencing technologies. Moreover, it can detect epigenetic modifications directly, as well as providing all-around field usage, being pocket-sized and low cost. It has already been applied to yeast research in many aspects, such as complete de novo genome assemblies, the phylogeny of large-brewing yeasts, gene isoform identification, and base modification detection. These applications have delivered novel insights into yeast genomic and transcriptomic analysis.

Effects of S-oxiracetam on learning and memory impairment in mice / 中国药科大学学报

@#To investigate the effects and possible molecular mechanism of S-oxiracetam(S-ORC) on learning and memory impairment in mice, mice were divided into 5 groups, control group, model group, high-dose of S-ORC (0.96 g/kg), medium-dose of S-ORC (0.48 g/kg) and low-dose of S-ORC (0.24 g/kg) treatment groups.Step-down test and Y-maze test were used to investigate the effects of S-ORC on the brain.The results of step-down test revealed that the mice in high and medium-dose groups could significantly decrease the reaction time, fault times and prolong the incubation periods of memory compared with the model group.Compared with the model group, the fault times of mice in high and medium-dose groups decreased significantly and the right times to find the safety increased significantly in Y-maze test.Furthermore, through treatment with S-ORC (high and medium-dose groups), the content of Ach in mice brain was significantly higher than that in model group, and the level of AChE decreased significantly.The above results suggest that the underlying mechanism of S-ORC on learning and memory impairment in mice may include the amelioration of the central cholinergic nervous system.

Research progress of α7 nicotinic acetylcholine receptors in central nervous system diseases / 中国临床药理学与治疗学

Alpha-7 nicotinic acetylcholine receptors (α7 nAChRs) are expressed in the central nervous system (CNS) and are thought to play a role in a wide variety of psychiatric and neurological disorders. Activation of α7 nAChR leads to an anti-inflammatory effect, which may show beneficial effects in those central nervous system disorders. In the present article, we summarize information on receptor distribution and expression, and review the effects of α7 nAChR on the CN disorders (e.g., Alzheimer's disease, Parkinson's disease, and stroke), which may provide a new idea for the development of the treatment of CNS diseases.

Long-term results of total hip arthroplasty with 4th ceramic-on-ceramic bearing for patients with history of hip injury / 中华骨科杂志

Objective:To evaluate the long-term clinical outcomes of total hip arthroplasty with the 4th ceramic-on-ceramic bearing in patients with history of hip injury.Methods:During December 2008 to December 2011, a total of 153 patients (157 hips) with history of hip injury were treated with 4th ceramic-on-ceramic bearing total hip arthroplasty. There were 25 cases (25 hips) were not followed up (16.3%). Ultimately, a total of 128 cases (132 hips) aged 49.26±14.18 (range 17-76) years including 87 males and 41 females were included in the study. In these patients, there were 15 cases (11.4%) with acetabular fracture, 90 cases (68.2%) with femoral fracture, 5 cases (3.8%) with hip dislocation and 22 cases (16.7%) with unknown history. Clinical outcomes, including operation duration, Harris score, range of motion, complications and noises, were evaluated. The survivorship was investigated by using Kaplan-Meier method.Results:The operation duration was 135.61±41.65 (range 64-320) min. The average follow-up duration was 9.62±0.82 (range 8.2-11.3) years. The Harris score increased from preoperative 44.07±19.71 to 94.03±4.10 at the last follow-up ( t=24.155, P<0.001). The range of hip motion increased from 75.90±28.05 degrees to 117.14±12.36 degrees ( t=13.176, P<0.001). There was no significant difference in Harris scores and ranges of motion among the groups with different history of fracture and dislocation. There were periprosthetic fracture in 1 case and hip dislocation in 2 cases. There was no periprosthetic hip infection or fracture of ceramic liner during the follow up. Thirteen cases (13 hips, 9.8%), including squeaking in 9 cases (6.8%) and clicking in 4 cases (3.0%), reported hip noise without pain and impairment on the quality of life. The survivorship was 100% at 10 years when regarded revision as an end point. However, the survivorship was 99.24% (95% CI: 97.8%, 100%) at 10 years when reoperation revision as an end point. Conclusion:Total hip arthroplasty with 4th ceramic-on-ceramic bearing could have excellent results for patients with a history of hip fracture or dislocation in the long-term follow-up. Although the prevalence of hip noise was about 10% in this cohort study, there was no impairment on the quality of life.

Bioinformatics analysis of key toxicity pathways in the mode of action of oral exposure to hexavalent chromium / 环境与职业医学

Background Oral exposure to hexavalent chromium [Cr(VI)] can lead to gastrointestinal tumorigenesis in mice, and the mechanism is not yet clear. To predict health risk due to chemical exposure, data mining and computational toxicology analysis has become an important tool in toxicology research, which can help to elucidate mode of action (MOA) and identify key toxicity pathways. Objective This study aims to identify and evaluate key events in the MOA of oral Cr(VI) exposure. Methods Gene sets established from Comparative Toxicogenomics Database (CTD) and Gene Expression Omnibus (GEO) respectively were imported into Ingenuity® Pathway Analysis (IPA) software for pathway enrichment analysis and biological function analysis to identify potential key toxicity pathways of target organs/tissues toxicity of oral exposure to Cr(Ⅵ). Next, the weight of evidence (WOE) of the identified key toxicity pathways in the MOA of oral exposure to Cr(VI) was evaluated based on the modified Bradford Hill principle. Results A total of 54 pieces of literature related to oral Cr(VI) exposure were screened in CTD, among which 18 and 9 were related to liver and intestine with 125 and 272 corresponding genes, respectively. The pathway enrichment and biological function analysis results showed that liver and intestinal perturbation pathways were mainly related to cell stress and injury, cell cycle regulation, and apoptosis, indicating that Nrf2 pathway and AHR pathway might be the key toxicity pathways involved in the cytotoxic-mediated MOA. Meanwhile, the dose (≥170 mg·L−1 sodium dichromate) and the time point (90 d) of the activation of Nrf2 pathway was similar to the emergence of crypt cell proliferation. It was proposed that Nrf2 pathway activation might be a key event for cytotoxic-mediated MOA of small intestinal tumors. The WOE results showed moderate validity of evidence in this hypothesis, with high validity of evidence for biological plausibility and dose-response manner. Conclusion Nrf2 pathway activation might be the key event in the cytotoxic-mediated MOA of small intestinal tumors induced by oral exposure to Cr(VI) via initiating or maintaining crypt cell proliferation.

Analysing the meta-interaction between pathways by gene set topological impact analysis.

BACKGROUND: Pathway analysis is widely applied in transcriptome analysis. Given certain transcriptomic changes, current pathway analysis tools tend to search for the most impacted pathways, which provides insight into underlying biological mechanisms. Further refining of the enriched pathways and extracting functional modules by "crosstalk" analysis have been proposed. However, the upstream/downstream relationships between the modules, which may provide extra biological insights such as the coordination of different functional modules and the signal transduction flow have been ignored. RESULTS: To quantitatively analyse the upstream/downstream relationships between functional modules, we developed a novel GEne Set Topological Impact Analysis (GESTIA), which could be used to assemble the enriched pathways and functional modules into a super-module with a topological structure. We showed the advantages of this analysis in the exploration of extra biological insight in addition to the individual enriched pathways and functional modules. CONCLUSIONS: GESTIA can be applied to a broad range of pathway/module analysis result. We hope that GESTIA may help researchers to get one additional step closer to understanding the molecular mechanism from the pathway/module analysis results.

Universal concept signature analysis: genome-wide quantification of new biological and pathological functions of genes and pathways.

Identifying new gene functions and pathways underlying diseases and biological processes are major challenges in genomics research. Particularly, most methods for interpreting the pathways characteristic of an experimental gene list defined by genomic data are limited by their dependence on assessing the overlapping genes or their interactome topology, which cannot account for the variety of functional relations. This is particularly problematic for pathway discovery from single-cell genomics with low gene coverage or interpreting complex pathway changes such as during change of cell states. Here, we exploited the comprehensive sets of molecular concepts that combine ontologies, pathways, interactions and domains to help inform the functional relations. We first developed a universal concept signature (uniConSig) analysis for genome-wide quantification of new gene functions underlying biological or pathological processes based on the signature molecular concepts computed from known functional gene lists. We then further developed a novel concept signature enrichment analysis (CSEA) for deep functional assessment of the pathways enriched in an experimental gene list. This method is grounded on the framework of shared concept signatures between gene sets at multiple functional levels, thus overcoming the limitations of the current methods. Through meta-analysis of transcriptomic data sets of cancer cell line models and single hematopoietic stem cells, we demonstrate the broad applications of CSEA on pathway discovery from gene expression and single-cell transcriptomic data sets for genetic perturbations and change of cell states, which complements the current modalities. The R modules for uniConSig analysis and CSEA are available through https://github.com/wangxlab/uniConSig.