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CDK8 is a transcriptional cyclin-dependent kinase and considered as a potential target in colon cancer therapeutics. Here, a novel selective CDK8 inhibitor was identified against colon cancer

Jing Wang,1– 3,* Yue Jiang,1,2,* Cai-Yue Mei,1,2 Zhen-Yu Wang,1,2 Fa-Gang Zhong,4 Xing-Xing Zhang,4 Lu-Chao Lv,5 Meng-Jun Lu,1,2 Han Wu,1,2 Xinan Jiao1– 3 1Jiangsu Key Laboratory of Zoonosis/Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu Province, People’s Republic of China; 2Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu Province, People’s Republic of China; 3Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou, Jiangsu Province, People’s Republic of China; 4State Key Laboratory for Sheep Genetic Improvement and Healthy Production, Institute of Animal Husbandry and Veterinary, Xinjiang Academy of Agricultural and Reclamation Science, Shihezi, Xinjiang Province, People’s Republic of China; 5College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinan Jiao, Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, No. 48 Wenhui East Road, Yangzhou, Jiangsu 225009, People’s Republic of China, Tel +86-514-87971136, Fax +86-514-87991747, Email jiao@yzu.edu.cn

Rhodamine dyes have been widely employed in biological imaging and sensing. However, it is always a challenge to design rhodamine derivatives with huge Stokes shift to address the draconian requirements of single-excitation multicolor imaging. In this work, we described a generally strategy to enhance the Stokes shift of rhodamine dyes by completely breaking their electronic symmetry. As a result, the Stokes shift of novel rhodamine dye DQF-RB-Cl is up to 205 nm in PBS, which is the largest in all the reported rhodamine derivatives. In addition, we successfully realized the single excitation trichromatic imaging of mitochondria, lysosomes and cell membranes by combining DQF-RB-Cl with commercial lysosomal targeting probe Lyso-Tracker Green and membrane targeting dye Dil. This is the organic synthetic dyes for SLE-trichromatic imaging in cells for the first time. These results demonstrate the potential of our design as a useful strategy to develop huge Stokes shift fluorophore for bioimaging.

The second near-infrared (NIR-II) fluorescent imaging shows great potential for deep tissue analysis at high resolution in living body owing to low background autofluorescence and photon scattering. However, reversible monitoring of redox homeostasis using NIR-II fluorescent imaging remains a challenge due to the lack of appropriate probes. In this study, a series of stable and multifunctional NIR-II dyes (NIR-II Cy3s) were constructed based on trimethine skeleton. Significantly, introducing the 1,4-diethyl-decahydroquinoxaline group to the NIR-II Cy3s not only effectively increased the wavelength, but also served as an effective response site for HClO, which can be restored by reactive sulfur species (RSS). Based on this, NIR-II Cy3s were used for reversible monitoring of HClO/RSS-mediated redox processes in the pathophysiology environment. Finally, NIR-II Cy3-988 was successfully utilized for assessment of the redox environments and drug treatment effects in acute inflammation model.

Diabetes mellitus, as the most common metabolic disease, is common worldwide and represents a crucial global health concern. The purpose of this research was to investigate the related risk factors and to develop a re-amputation risk nomogram in diabetic patients who have undergone an amputation.A observational analysis was performed on 459 patients who have underwent amputation for diabetic foot from January 2014 through December 2019 at the First Affiliated Hospital of Wenzhou Medical University. The least absolute shrinkage and selection operator regression and stepwise regression methods were implemented to determine risk selection for the re-amputation risk model, and the predictive nomogram was established with these features. Calibration curve, receiver operating characteristic curve, and decision curve analysis of this re-amputation nomogram were assessed.Predictors contained in this predictive model included smoking, glycated hemoglobin A1c (HbA1c), ankle-brachial index (ABI) and C-reactive protein (CRP). Good discrimination with a C-index of 0.725 (95% CI, 0.6624-0.7876) and good calibration were displayed with this predictive model. The decision curve analysis showed that this re-amputation nomogram predicting risk adds more benefit than none strategy if the threshold probability of a patient was6% and59%.This novel re-amputation nomogram incorporating smoking, glycated hemoglobin A1c (HbA1c), ankle-brachial index (ABI), C-reactive protein (CRP), and smoking could be easily used to predict individual re-amputation risk prediction in diabetic foot patients who have undergone an amputation. In the future, further analysis and external testing will be needed as much as possible to reconfirm that this new Nomogram can accurately predict the risk of toe re-amputation.

Gut microbiota is a complex microecosystem, which is called the second genome of the human body. Herbal medicine can balance tumor-suppressing bacteria and tumor-promoting bacteria and exert its anti-cancer effect by regulating gut microbiota. Traditional Chinese medicine (TCM) has a history of thousands of years in prevention and treatment of diseases in China. In recent decades, TCM has been shown to have an obvious advantage in prolonging the survival time and improving the living quality of patients with cancer. Notably, gut microbiota has become a new pathway to understanding TCM. In this review, we will focus on gut microbiota and tumor progression, especially the diversity, functionality and metabolites of gut microbiota affected by TCM in various cancer. We will also discuss the potential mechanism of gut microbiota for exploring TCM in anti-cancer effect. This article aims to comprehensively review the anti-cancer research of TCM by regulating gut microbiota, and address future perspectives and challenges of gut microbiota in TCM intervention for cancer.

Tumor-specific, hypoxia-activated prodrugs have been developed to alleviate the side effects of chemotherapy drugs. However, the release efficiency of hypoxia-activated prodrugs is restricted by the degree of tumor hypoxia, which further leads to poor cancer treatment effects. On the other hand, oxygen is consumed gradually in photodynamic therapy (PDT), which aggravates hypoxia at the tumor site. In this study, we combined hypoxia-activated prodrugs with PDT agents to promote the prodrugs release, thereby improving their bioavailability and therapeutic effects. As a proof of concept, a mitochondria-targeted molecular prodrug, CS-P, was designed and synthesized. It can be selectively activated by tumor hypoxia to release chemotherapeutic drugs and photosensitizers, and then further discharge drugs after light irradiation. The design strategy proposed in this paper provides a new idea for enhancing hypoxia-activated prodrug release and real-time monitoring prodrug release.

Tumor-specific imaging is a major challenge in clinical tumor resection. To overcome this problem, several activatable probes have been developed for use in tumor imaging. However, most of these probes are activated based on a single-factor stimulation and are irreversible. Therefore, false signals that make tumor-specific imaging difficult are easily generated. We have developed a new dual-stimulus responsive near-infrared (NIR) reversible adenosine 5'-triphosphate (ATP)-pH probe for fluorescence and photoacoustic ratiometric imaging of tumors. Since the H+ and ATP content is significantly higher in the tumor microenvironment than that in normal tissues, the Forster resonance energy transfer-based probe ATP-pH was constructed with silicon rhodamine as the donor, CS dye as the acceptor, and ATP/H+ recognition units that could only be activated when both H+ and ATP were connected to the acceptor. The ATP-pH probe is reversibly activated by both the H+ and ATP, which effectively reduces the cumulative response of the probe in circulation after intravenous injection. Further, the NIR ratiometric property of the probe makes it suitable for in vivo imaging. Finally, our probe was successfully utilized in ratiometric photoacoustic and fluorescence tumor imaging and ratiometric fluorescence imaging-guided tumor resection.

A simple and efficient methodology for the synthesis of large sterically hindered triarylamines in a single step was developed. A direct N,N-diarylation of 8-aminoquinoline with sterically hindered...

Mitochondria-targeted fluorescent probes are highly important to obtain mitochondrial function information. However, the accuracy of the current mitochondria-targeted fluorescent probes is unsatisfactory owing to the following two reasons. In the first case, some probes that always have a mitochondria-targeting group, thus, would react with the analytes outside of mitochondria and enter mitochondria with the generated fluorophore signal, which leads to a false-positive result. In the other case, after response to the analytes in mitochondria, some probes could diffuse from mitochondria to other organelles, thus triggering a false-negative result. To avoid the two problems, herein, we develop a precipitated fluorophore-based probe, which precipitates in situ after reacting with analytes, for the accurate detection of mitochondrial analytes. The probe was modified with HQPQ, a novel solid-state fluorophore that is insoluble in water. As a proof of concept, we designed and synthesized a probe (HQPQ-B) for H2O2 detection. Based on the different mitochondria-targeting capacities of quinoline salts and quinolone, HQPQ loses the mitochondria-targeting ability after reacting with analytes outside of mitochondria, thus avoiding a false-positive result. On the contrary, when the probe first localized in mitochondria and then reacted with analytes, HQPQ would precipitate and remain in mitochondria without diffusing to other sites, thus avoiding a false-negative result. Therefore, HQPQ enables the accurate detection of mitochondrial analytes. We believe that the novel strategy based on HQPQ will be a general strategy for accurate detection of mitochondrial analytes without interference from other sites, which enables an accurate study on mitochondrial function.

Lithium ion batteries (LIBs) have been widely used in new energy vehicles, large-scale energy storage, and intelligent electronic equipment due to their excellent electrochemical performance. Facing the increasing demands on good safety and high energy density, solid-state batteries as important candidates have become a hot spot in the research of LIBs. Developing high-performance solid-state electrolytes is the key to realizing the application of solid-state LIBs. Metal organic frameworks (MOFs) or covalent organic frameworks (COFs) are a kind of crystal material with regular channels and an ultra-high specific surface area, providing a promising structural platform for designing fast ionic conducting materials. Recently, researchers have designed and synthesized multiple types of MOF- and COF-based solid-state electrolytes (SSEs) with excellent performance. The recent progress, prospects and challenges of MOF-/COF-based SSEs will be systematically introduced, and some unique materials with specific characteristics or high conducting properties of other metal (sodium, zinc or magnesium) ions will also be highlighted in this review.

During a 2018 antimicrobial resistance surveillance of Escherichia coli isolates from diarrheal calves in Xinjiang Province, China, an unexpectedly high prevalence (48.5%) of fosfomycin resistance was observed. This study aimed to reveal the determinants of fosfomycin resistance and the underlying transmission mechanism. Polymerase chain reaction (PCR) screening showed that all fosfomycin-resistant E. coli carried the fosA3 gene. Pulsed-field gel electrophoresis (PFGE) and southern blot hybridization revealed that the 16 fosA3-positive isolates belonged to four different PFGE patterns (i.e., A, B, C, D). The fosA3 genes of 11 clonally related strains (pattern D) were located on the chromosome, while others were carried by plasmids. Whole-genome and long-read sequencing indicated that the pattern D strains were E. coli O101:H9-ST10, and the pattern C, B, and A strains were O101:H9-ST167, O8:H30-ST1431, and O101:H9 with unknown ST, respectively. Among the pattern C strains, the blaCTX-M-14 gene was co-localized with the fosA3 gene on the F18:A-:B1 plasmids. Interestingly, phylogenetic analysis based on core genome single nucleotide polymorphisms (cgSNPs) showed that the O101:H9-ST10 strains were closely related to a Australian-isolated Chroicocephalus-origin E. coli O101:H9-ST10 strain producing CTX-M-14 and FosA3, with a difference of only 11 SNPs. These results indicate possible international dissemination of the high-risk E. coli clone O101:H9-ST10 by migratory birds.

During a 2018 antimicrobial resistance surveillance of Escherichia coli isolates from diarrheal calves in Xinjiang Province, China, an unexpectedly high prevalence (48.5%) of fosfomycin resistance was observed. This study aimed to reveal the determinants of fosfomycin resistance and the underlying transmission mechanism. Polymerase chain reaction (PCR) screening showed that all fosfomycin-resistant E. coli carried the fosA3 gene. Pulsed-field gel electrophoresis (PFGE) and southern blot hybridization revealed that the 16 fosA3-positive isolates belonged to four different PFGE patterns (i.e., A, B, C, D). The fosA3 genes of 11 clonally related strains (pattern D) were located on the chromosome, while others were carried by plasmids. Whole-genome and long-read sequencing indicated that the pattern D strains were E. coli O101:H9-ST10, and the pattern C, B, and A strains were O101:H9-ST167, O8:H30-ST1431, and O101:H9 with unknown ST, respectively. Among the pattern C strains, the blaCTX-M-14 gene was co-localized with the fosA3 gene on the F18:A-:B1 plasmids. Interestingly, phylogenetic analysis based on core genome single nucleotide polymorphisms (cgSNPs) showed that the O101:H9-ST10 strains were closely related to a Australian-isolated Chroicocephalus-origin E. coli O101:H9-ST10 strain producing CTX-M-14 and FosA3, with a difference of only 11 SNPs. These results indicate possible international dissemination of the high-risk E. coli clone O101:H9-ST10 by migratory birds.

Photodynamic therapy (PDT) has emerged as one of the most up-and-coming non-invasive therapeutic modalities for cancer therapy in rencent years. However, its therapeutic effect was still hampered by the short life span, limited diffusion distance and ineluctable depletion of singlet oxygen (1O2), as well as the hypoxic microenvironment in the tumor tissue. Such problems have limited the application of PDT and appropriate solutions are highly demand. Methods: Herein, a programmatic treatment strategy is proposed for the development of a smart molecular prodrug (D-bpy), which comprise a two-photon photosensitizer and a hypoxia-activated chemotherapeutic prodrug. A rhodamine dye was designed to connect them and track the drug release by the fluorescent signal generated through azo bond cleavage. Results: The prodrug (D-bpy) can stay on the cell membrane and enrich at the tumor site. Upon light irradiation, the therapeutic effect was enhanced by a stepwise treatment: (i) direct generation of 1O2 on the cell membrane induced membrane destruction and promoted the D-bpy uptake; (ii) deep tumor hypoxia caused by two-photon PDT process further triggered the activation of the chemotherapy prodrug. Both in vitro and in vivo experiments, D-bpy have exhabited excellent tumor treatment effect. Conclusion: The innovative programmatic treatment strategy provides new strategy for the design of follow-up anticancer drugs.

Fluorescent probes have been widely employed in biological imaging and sensing. However, it is always a challenge to design probes with high sensitivity. In this work, based on rhodamine skeleton, we developed a general strategy to construct sensitivity-enhanced fluorescent probe with the help of theoretical calculation for the first time. As a proof of concept, we synthesized a series of HOCl probes. Experiment results showed that with the C-9 of pyronin moiety of rhodamine stabilized by an electron donor group, probe DQF-S exhibited an importantly enhanced sensitivity (LOD: 0.2 nmol/L) towards HOCl together with fast response time ( 650 nm) and large Stokes shift. Bioimaging studies indicated that DQF-S can not only effectively detect basal HOCl in various types of cells, but also be successfully applied to image tumor tissue in vivo. These results demonstrate the potential of our design as a useful strategy to develop excellent fluorescent probes for bioimaging.

Carbon materials with multi-components and hollow structures can be used as promising candidates in microwave absorption materials, however, rational design and construction of the special structures is still hard to achieve. In this work, a hollow structural bimetallic carbon polyhedron (CoMo@HNCP) is synthesized by the pyrolysis of core-shell ZIF-8@HZIF-CoMo polyhedrons. Owing to the uniform distribution of Mo2C and metallic Co nanoparticles in the hollow N-doped carbon shell, the generated multi-heterogeneous interfaces are in favor of dipolar and interfacial polarization, resulting in enhanced conduction loss, matched impedance as well as multiple scatterings. Typically, with a filler loading of 30 wt%, the minimum RL of CoMo@HNCP reaches −44.8 dB and the effective absorption bandwidth is as wide as 6.56 GHz with the absorber thickness of 2.5 mm, which is better than that of ZIF-8 derived N-doped carbon polyhedron and HZIF-CoMo derived bimetallic carbon polyhedron. The usage of bimetallic HZIF to assemble core-shell nanomaterials is proven to be an novel and excellent way to assembly microwave absorbers with multi-heterogeneous interfaces and hollow structures.

We disclose a novel method for the synthesis of fluorescent N,N'-chelate organoboron compounds in high efficiency by treatment of aminoquinolates with NaBAr4/R'COOH in the presence of an iodine cat...

NLRP3 inflammasome activation plays a key role in a variety of inflammatory diseases as IBD. Here a series of pterostilbene derivatives were designed and synthesized based on previous SAR, leading to discovery of new effective NLRP3 inflammasome inhibitors with metabolic stability. Among them, the most effective compound 27 showed high inhibitory efficacy (against IL-1 β: IC

Two-photon (TP) imaging with a donor-acceptor (D-A) type fluorophore is an emerging tool for bioimaging and sensing. However, current TP probes suffer from serious solvatochromic quenching in aqueous solution due to their strong intramolecular charge transfer (ICT) in excited states. In this work, based on solvatochromism reversal, we report a novel strategy to develop TP probes for bioimaging. Specifically, compared with the normal two-photon probes that showed a fluorescence off with ICT suppressed, the novel probes exhibited strong fluorescence in the aqueous solution when their ICT was inhibited. This strategy not only provides a new way for the design of high-performance TP probes, but also expands the biological analysis toolbox for use in living systems.

Haematopoietic lineage commitments are presented by a canonical roadmap in which haematopoietic stem cells or multipotent progenitors (MPPs) bifurcate into progenitors of more restricted lineages and ultimately mature to terminally differentiated cells. Although transcription factors playing significant roles in cell-fate commitments have been extensively studied, integrating such knowledge into the dynamic models to understand the underlying biological mechanism remains challenging. The hypothesis and modelling approach of the endogenous network has been developed previously and tested in various biological processes and is used in the present study of haematopoietic lineage commitments. The endogenous network is constructed based on the key transcription factors and their interactions that determine haematopoietic cell-fate decisions at each lineage branchpoint. We demonstrate that the process of haematopoietic lineage commitments can be reproduced from the landscape which orchestrates robust states of network dynamics and their transitions. Furthermore, some non-trivial characteristics are unveiled in the dynamical model. Our model also predicted previously under-represented regulatory interactions and heterogeneous MPP states by which distinct differentiation routes are intermediated. Moreover, network perturbations resulting in state transitions indicate the effects of ectopic gene expression on cellular reprogrammes. This study provides a predictive model to integrate experimental data and uncover the possible regulatory mechanism of haematopoietic lineage commitments.

Studies have shown that the abnormal activation of the NLRP3 inflammasome is involved in a variety of inflammatory-based diseases. In this study, a high content screening model targeting the activation of inflammasome was first established and pterostilbene was discovered as the active scaffold. Based on this finding, total of 50 pterostilbene derivatives were then designed and synthesized. Among them, compound 47 was found to be the best one for inhibiting cell pyroptosis [inhibitory rate (IR) = 73.09% at 10 μM], showing low toxicity and high efficiency [against interleukin-1β (IL-1β): half-maximal inhibitory concentration (IC50) = 0.56 μM]. Further studies showed that compound 47 affected the assembly of the NLRP3 inflammasomes by targeting NLRP3. The in vivo biological activity showed that this compound significantly alleviated dextran sodium sulfate (DSS)-induced colitis in mice. In general, our study provided a novel lead compound directly targeting the NLRP3 protein, which is worthy of further research and structural optimization.

Ethnopharmacological relevance Jianpi Yangzheng Xiaozheng Decoction (JPYZXZ) is an empirical compound prescription based on the theory of traditional Chinese medicine. JPYZXZ, which is “Qi-invigorating, spleen-strengthening and stasis-removing,” can improve the quality of life of gastric cancer patients and prolong their survival; however, the exact mechanism underlying the antitumor effects of this compound is still not clear. Aim of the study The aim of this study is to clearly define the effect of JPYZXZ and its components, Jianpi Yangzheng Decoction (JPYZ) and Xiao Zheng San Jie Decoction (XZSJ), on inhibiting the progression of gastric cancer. Materials and methods The effect of JPYZXZ and its components on the motility of gastric cancer MGC-803 cells was measured by MTT, adhesion, transwell assays and wound-healing assays. JPYZXZ, JPYZ and XZSJ were administered to 615 mice with gastric cancer xenografts, and their effect on the inhibition of subcutaneous transplantation was analyzed. THP-1 monocyte cells were used to establish tumor-associated macrophage (TAM) models. The polarized state of the TAMs was detected by Flow Cytometry, ELISA and Immunohistochemistry. The mRNA and protein expression of tumor epithelial-mesenchymal transition (EMT) and TAM-related genes was determined by Real-time PCR and Western Blot, respectively. Results We determined that both JPYZXZ and its components inhibited the progress of gastric cancer in vitro, and JPYZXZ was clearly more effective than JPYZ or XZSJ. The in vivo results demonstrated that the JPYZXZ and XZSJ group exhibited a significant decrease in the tumor weight compared to the control group. Further analysis indicated that JPYZXZ was more active than JPYZ or XZSJ in inhibiting the gastric cancer EMT transformation both in vivo and in vitro. However, JPYZ was more effective compared with JPYZXZ for inducing the phenotypic change in macrophages from M2 to M1. Conclusions Our results demonstrate that both JPYZXZ and its components prevent the progress of gastric cancer. JPYZXZ inhibits the gastric cancer EMT more effectively than JPYZ and XZSJ, but JPYZ primarily works to regulate the phenotypic change in macrophages from M2 to M1.

The competitive growth of form II and form I in isotactic polybutene-1(PB-1) was investigated with fast scanning chip calorimetry. By systematically varying the isothermal time, the pre-crystallized PB-1 samples with different crystallinity of form II are obtained and then used to study the competition between the growth of form II and the transformation of form II into form I. All the samples were annealed at 258 K for 60s to help nucleation of form I so that fast transformation could be performed. Crystal transformation kinetics results indicated that the competitive growth of form II and form I can be classified into three regimes. When the crystallinity of form II is small enough, fast transformation from form II to form I does not take place, attributed to lacking of the nuclei of form I as the degree of internal stress is extremely low. This suggests that only certain strength of internal stress and certain crystallinity of form II enable the nucleation of form I and then promote the transformation from form II to form I. With increasing crystallinity of form II, both fast transformation and slow transformation are observed. When crystallinity of form II further increases, only fast transformation is observed. However, the transition rate decreases and then reaches a plateau, resulting from the rearrangement of polymer chains and the increasing regularity of form II, indicating that the increasing regularity of form II inhibits the transformation from form II to form I.

Background Aromatase excess syndrome (AEXS) is a rare autosomal dominant disorder caused by CYP19A1 overexpression. Clinical manifestations of AEXS include pre- or peri-pubertal gynecomastia, advanced bone age and compromised adult height. Case presentation Here we report an 8-year-old boy diagnosed with AEXS by chromosomal array that revealed a 1.1 Mb novel de novo duplication at 15q21.2, with a predicted final height of 157.4 cm. We prescribed letrozole and growth hormone (GH) to maximize his linear growth. Without further bone age advancement, his height increased from 137.7 cm to 144 cm after an 8-month treatment period. Conclusions We identified a novel duplication at 15q21.2 in AEXS, and found that aromatase inhibitor (AI) plus GH might provide a better growth-promoting approach for AEXS patients.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver disorders that is featured by the extensive deposition of fat in the hepatocytes. Current treatments are very limited due to its unclear pathogenesis. Here, we investigated the function of circ_0057558 and miR-206 in NAFLD. High-fat diet (HFD) feeding mouse was used as an in vivo NAFLD model and long-chain-free fatty acid (FFA)-treated liver cells were used as an in vitro NAFLD model. qRT-PCR was used to measure levels of miR-206, ROCK1 mRNA, and circ_0057558, while Western blotting was employed to determine protein levels of ROCK1, p-AMPK, AMPK, and lipogenesis-related proteins. Immunohistochemistry were performed to examine ROCK1 level. Oil-Red O staining was used to assess the lipid deposition in cells. ELISA was performed to examine secreted triglyceride (TG) level. Dual-luciferase assay was used to validate interactions of miR-206/ROCK1 and circ_0057558/miR-206. RNA immunoprecipitation was employed to confirm the binding of circ_0057558 with miR-206. Circ_0057558 was elevated while miR-206 was reduced in both in vivo and in vitro NAFLD models. miR-206 directly bound with ROCK1 3’-UTR and suppressed lipogenesis and TG secretion through targeting ROCK1/AMPK signaling. Circ_0057558 directly interacted with miR-206 to disinhibit ROCK1/AMPK signaling. Knockdown of circ_0057558 or overexpression of miR-206 inhibited lipogenesis, TG secretion and expression of lipogenesis-related proteins. ROCK1 knockdown reversed the effects of circ_0057558 overexpression. Injection of miR-206 mimics significantly ameliorated NAFLD progression in vivo. Circ_0057558 acts as a miR-206 sponge to de-repress the ROCK1/AMPK signaling and facilitates lipogenesis and TG secretion, which greatly contributes to NAFLD development and progression.

Background Leigh syndrome, the most common mitochondrial syndrome in pediatrics, has diverse clinical manifestations and is genetically heterogeneous. Pathogenic mutations in more than 75 genes of two genomes (mitochondrial and nuclear) have been identified. PDHA1 encoding the E1 alpha subunit is an X‐chromosome gene whose mutations cause pyruvate dehydrogenase complex deficiency. Methods Here, we have described a 12‐year‐old boy with lethal neuropathy who almost died of a sudden loss of breathing and successive cardiac arrest. Extracorporeal membrane oxygenation rescued his life. His diagnosis was corrected from Guillain–Barré syndrome to Leigh syndrome 1 month later by clinical exome sequencing. Furthermore, we used software to predict the protein structure caused by frameshift mutations. We treated the boy with vitamin B1, coenzyme Q10, and a ketogenic diet. Results A PDHA1 mutation (NM_000284.4:c.1167_1170del) was identified as the underlying cause. The amino acid mutation was p.Ser390LysfsTer33. Moreover, the protein structure prediction results suggested that the protein structure has changed. The parents of the child were negative, so the mutation was de novo. The comprehensive assessment of the mutation was pathogenic. His condition gradually improved after receiving treatment. Conclusion This case suggests that gene detection should be popularized to improve diagnosis accuracy, especially in developing countries such as China., Here, we describe a 12‐year‐old boy with a lethal neuropathy who almost died of a sudden loss of breathing and successive cardiac arrest. One month later, we found that the child had a de novo mutation (NM_000284.4: c.1167_1170del) in the PDHA1 gene through clinical exome sequencing, and corrected his diagnosis from Guillain‐Barré syndrome to Leigh syndrome. This case shows that genetic detection should be popularized to improve diagnostic accuracy, especially in developing countries such as China.

As a typical group of coordination polymers, metal-organic zeolite (MOZs) frameworks inherit the topological and structural advantages of inorganic zeolites and display great application potential in many areas, including gas adsorption/separation, catalysis, luminescence and chemical sensing. In this review, we outline the recent progress in the synthesis, functionalization and application of metal-organic zeolite frameworks, mainly focusing on the basic structural design principle and synthesis strategy on 4-connect inorganic nodes and 2-connect organic linkers. Employing different valent metals, small inorganic TO42- units and high-nuclear clusters as 4-connect nodes, we derived multi-types of MOZs with a modified framework charge, improved stability and enhanced photo-/eletrocatalytic activity. Besides, the selection, functionalization and defect-engineering on the 2-connect ligands generated different topological and functional MOZs. Finally, the future trends and some perspectives in this area are outlined.

Recent studies have reported that the expression levels of far upstream element‑binding protein 1 (FUBP1) were upregulated and served a crucial role in several types of cancer. However, the underlying molecular mechanisms and clinical significance of FUBP1 in pancreatic adenocarcinoma (PAAD) remain unclear. The present study aimed to determine the expression levels of FUBP1 in patients with PAAD and subsequently investigated the biological functions and mechanisms of FUBP1 using in vitro assays. FUBP1 expression levels and survival outcomes in patients with PAAD were analyzed using The Cancer Genome Atlas and starBase databases. Reverse transcription‑quantitative PCR was used to analyze the mRNA expression levels of FUBP1 in PAAD and adjacent normal tissues. In addition, the expression of FUBP1 was knocked down with small interfering RNA and overexpressed using FUBP1‑overexpressed plasmids, and the effects on biological functions, including cell proliferation, migration and invasion, were investigated. Western blotting and immunofluorescence assays were used to determine the role of FUBP1 in epithelial‑mesenchymal transition (EMT). The results of the present study revealed that the expression levels of FUBP1 were upregulated in PAAD tissues compared with adjacent normal tissues and the upregulated expression was significantly associated with poor survival. The knockdown of FUBP1 expression significantly inhibited the proliferative, migratory and invasive abilities of the PAAD PaTu8988 cell line, while the overexpression of FUBP1 promoted cell proliferation, migration and invasion in the PAAD SW1990 cell line. Furthermore, the knockdown of FUBP1 downregulated the expression levels of EMT‑related markers, including N‑cadherin, β‑catenin and vimentin, while the expression levels of E‑cadherin were upregulated. The knockdown of FUBP1 was also revealed to regulate the TGFβ/Smad signaling cascade by downregulating phosphorylated‑Smad2/3 and TGFβ1 expression levels. Conversely, the overexpression of FUBP1 reversed these effects. In conclusion, the findings of the present study indicated that FUBP1 may be a potential oncogene that mediates the EMT of PAAD via TGFβ/Smad signaling. These data suggested that FUBP1 may represent a potential biomarker for the diagnosis of PAAD or a target for the treatment of patients with PAAD.

To explore the feasibility of the rapid start-up of partial denitrification and the stable accumulation of NO

We disclose a novel method for the synthesis of fluorescent

In the past decade, the number of frozen-thawed embryo transfer (FET) has increased dramatically with the expansion of surgical indications and the improvement of freezing related technologies. How to improve the success rate and reduce the adverse effects of FET is our research priorities. This study aimed to investigate the safety and effectiveness of Gushen'antai pills (GSATP) by measuring the ongoing pregnancy rate (OPR) in patients from FET and hormone therapy (HT) cycle. From November 2019 to May 2020, 5 Chinese hospitals conducted a multi-center, randomized, double-blind, placebo-controlled study. In total, 271 HT FET cycles in patients were randomly divided (1:1 ratio) to receive GSATP (6 g, tid) or placebo (6g, tid) for 12 weeks of pregnancy. Patients, clinicians, and researchers were blinded to treatment allocation. The primary endpoint was the OPR at week 12 of pregnancy. The secondary endpoints were vaginal bleeding or brown discharge rate, implantation rate (IR), clinical pregnancy rate (CPR) and abortion rate (AR). Adverse events were recorded during the treatment period. The results showed that the OPR remained higher in the GSATP group when compared to placebo group (56.62% vs. 44.44%, p = 0.045). Vaginal bleeding or brown discharge rate was lower in the GSATP group than the placebo group (10% vs. 23.08%, p = 0.032), while the IR (35.16% vs. 27.64%, p = 0.070), CPR (58.82% vs. 48.15%, p = 0.078), incidence of total adverse events (8.09% vs. 3.22%, p = 0.051) and AR (3.75% vs. 7.69%, p = 0.504) were similar between GSATP and placebo groups. Subgroup analysis showed that there were significant differences in CPR (74.19% vs. 54.17%, p = 0.004) and OPR (72.04% vs. 51.04%, p = 0.003) between GSATP group and Placebo group when the patient was younger than 35 years old. This multi-center, randomized, double-blinded, placebo-controlled clinical study showed for the first evidence that GSATP may have potential to improve the OPR and decrease vaginal bleeding or brown discharge rate in HT FET cycle patients.

This study aimed to investigate the relationship between the severity of albuminuria and wound healing in type 2 diabetic foot ulcers. A total of 121 patients with diabetic foot ulcers were recruited from January 2015 to June 2017 and divided into nonproliferation and proliferation groups according to their healing status. Univariate and multivariate logistic regression were performed to assess the risk factors of wound proliferation. Skin biopsies were also taken from normal tissue near the wound in 54 participants. The microvessel density as well as the relationships among the microvessel density, albuminuria and wound proliferation were evaluated. Results showed that in a multiple linear regression model, factors including body-mass index, microalbuminuria, and macroalbuminuria showed independently significant association with wound healing in patients. The receiver operating characteristic curve analysis indicated albuminuria as a predicator for wound healing with a cutoff value of 32 mg/g. Meanwhile, normoalbuminuric patients showed significantly higher level of skin microvessels density than microalbuminuria and macroalbuminuria patients, while microalbuminuria patients also had statistically more microvessels that macroalbuminuria patients. The microvessel density were statistically significantly higher in the proliferation group than that in the nonproliferation group. In summary, this study suggested that albuminuria can be used as an independent indicator for the healing of type 2 diabetic foot ulcers.

OBJECTIVE: To study the clinical features of children with adenovirus pneumonia and hemophagocytic lymphohistiocytosis (HLH). METHODS: A retrospective analysis was performed on the mediacal data of 7 children with adenovirus pneumonia and HLH from March to September, 2019. RESULTS: The age of these children ranged from 11 months to 5 years, and among these children, 5 were aged < 2 years and 5 were boys. None of these children had underlying diseases. All children were hospitalized due to persistent high fever and cough, and the peak temperature of fever was 39℃ to 41℃. With disease progression, 7 children developed hepatomegaly and 6 developed splenomegaly. Routine blood test results showed reductions in two or three lineages of blood cells, with increases in serum ferritin (SF), C-reactive protein (CRP), procalcitonin (PCT), and lactate dehydrogenase (LDH). Phagocytosis of blood cells was observed in 6 children. Radiological examination of lungs showed pneumonia changes. All 7 children were diagnosed with human adenovirus type 7 infection based on pathogenic metagenome detection. No abnormality was found by HLH gene detection and the children were diagnosed with secondary HLH. All children received intravenous immunoglobulin. Among these children, 4 received dexamethasone and etoposide chemotherapy, 3 received dexamethasone alone, and 4 received plasma exchange. Of the 7 children, 2 died and 5 were recovered. Compared with those who survived, the children who died had significantly greater reductions in the three lineages of blood cells and significantly greater increases in serum levels of CRP, PCT, SF, and LDH. CONCLUSIONS: The children with adenovirus pneumonia and HLH have main clinical features of persistent high fever, progressive reductions in two or three lineages of peripheral blood cells, and involvement of other organ systems, including hepatosplenomegaly. Significant increases in serum levels of CRP, PCT, SF, and LDH may suggest a poor prognosis.