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• Convenient method to prepare N1 - and N2 -indol-3-yl 1,2,3-triazole. • Trapping in-situ generated α -imino gold carbene with various types of triazoles. • New method to synthesis indol-3-yl pyrazole compounds. A new method was developed to prepare N1 and N2- indol-3-yl 1,2,3-trizole products through gold catalyzed cascade reaction of o -alkynyl arylazides with 1,2,3-triazoles, in which, the in-situ generated α -imino gold carbene intermediate was intercepted by various types of triazole compounds. N1 -selective nucleophilic attack was favored to give moderate to high N1 / N2 selectivity. In addition, indol-3-yl pyrazole compounds were also prepared by using the similar method. [ABSTRACT FROM AUTHOR]

Mangrove‐derived actinobacteria strains are well‐known for producing novel secondary metabolites. The polycyclic tetramate macrolactam (PTM), ikarugamycin (IKA) isolated from Streptomyces xiamenensis 318, exhibits antiproliferative activities against pancreatic ductal adenocarcinoma (PDAC) in vitro. However, the protein target for bioactive IKA is unclear. In this study, whole transcriptome‐based profiling revealed that the glycolysis pathway is significantly affected by IKA. Metabolomic studies demonstrated that IKA treatment induces a significant drop in glucose‐6‐phosphate and a slight increase in intracellular glucose level. Analysis of glucose consumption, lactate production, and the extracellular acidification rate confirmed the inhibitory role of IKA on the glycolytic flux in PDAC cells. Surface plasmon resonance (SPR) experiments and docking studies identified the key enzyme of glycolysis, hexokinase 2 (HK2), as a molecular target of IKA. Moreover, IKA reduced tumor size without overt cytotoxicity in mice with PDAC xenografts and increased chemotherapy response to gemcitabine in PDAC cells in vitro. Taken together, IKA can block glycolysis in pancreatic cancer by targeting HK2, which may be a potential drug candidate for PDAC treatment. [ABSTRACT FROM AUTHOR]

Abstract Temperature dependent relaxation time of 87Rb atoms, namely the longitudinal relaxation lifetime T 1 and the transverse relaxation lifetime T 2 are studied respectively by using the Franzen method and by measuring the optical rotation of a weak, linearly polarized probe light. Although the Franzen measurement in this work is taken with a weak probe light, the absorption of probe light can still destroy the spin polarization of 87Rb atoms to a certain degree. However, a longer relaxation time of T 2 can be well achieved by measuring the optical rotation of linearly polarized light under 6 GHz detuning along the direction of red light. Results show that both T 1 and T 2 obey an exponential decay with temperature, and the temperature dependent decaying rate of relaxation is respectively 27.8 for T 1 and 25.0 for T 2 , indicating that temperature playing a similar role in the reaction to T 1 and T 2. [ABSTRACT FROM AUTHOR]

The reaction of a new pentadentate Schiff base hydrazide ligand, (E)-methyl N′-(2-hydroxy-3-methoxybenzylidene)hydrazinecarboxylate (HL), with lanthanide nitrate, and sodium acetate in the presence of triethylamine, resulted in a novel family of octanuclear neutral compounds, [Ln8(μ3-O)4(L)8(CH3COO)4(CO3)2]·xH2O, where Ln = Gd (1), Tb (2), Dy (3), or Ho (4). Compounds 1–4 contained two unusual Ln4 boat-shaped units, which were held by four L− chelating ligands, two μ3-O2−, and one μ4-CO32−. These structures were interconnected by four CH3COO− ions, forming a novel Ln8 cluster. Magnetic studies revealed antiferromagnetic Gd…Gd interactions in Gd8, which exhibited a significant magnetocaloric effect and a magnetic entropy change as large as 32.49 J K−1 kg−1 at a field of 7 T at 2 K. In addition, Dy8 exhibited a frequency dependent slow relaxation of magnetization at a zero applied direct current magnetic field. [ABSTRACT FROM AUTHOR]

Diabetes is generally accompanied by difficult-to-heal wounds, which often lead to permanent disability and even death of patients. Because of the abundance of a variety of growth factors, platelet rich plasma (PRP) has been proven to have great clinical potential for diabetic wound treatment. However, how to suppress the explosive release of its active components while realizing adaptability to different wounds remains important for PRP therapy. Here, an injectable, self-healing, and non-specific tissue-adhesive hydrogel formed by oxidized chondroitin sulfate and carboxymethyl chitosan was designed as an encapsulation and delivery platform for PRP. With a dynamic cross-linking structural design, the hydrogel can meet the clinical demands of irregular wounds with controllable gelation and viscoelasticity. Inhibition of PRP enzymolysis as well as sustained release of its growth factors is realized with the hydrogel, enhancing cell proliferation and migration in vitro. Notably, greatly accelerated healing of full thickness wounds of diabetic skins is enabled by promoting the formation of granulation tissues, collagen deposition and angiogenesis as well as reducing inflammation in vivo. This self-healing and extracellular matrix-mimicking hydrogel provides powerful assistance to PRP therapy, enabling its promising applications for the repair and regeneration of diabetic wounds. [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights • Hyperthermia induces DNAJA4 expression and P65 phosphorylation in keratinocytes in the presence or absence of HPV infection. • DNAJA4-deficency promotes NF-kappa B (P65) pathway activation in HaCaT cells upon hyperthermia stimulation. • Hyperthermia combined with DNAJA4-deficency causes reduced viability of HaCaT cells. Abstract Background Hyperthermia is an effective treatment against cancer and human papillomavirus (HPV) infection. Previous studies have shown that heat shock proteins are crucial to the action of hyperthermia. Objectives To examine the effects of hyperthermia in combination with DNAJA4-deficiency on human keratinocytes and Condyloma acumunatum (CA) tissues. Methods HaCaT cells were subjected to 44 °C (compared to 37 °C) waterbath for 30 min for stimulation. Foreskin or CA tissues obtained from patients undergoing circumcision or pathological examination were bisected and subjected to similar treatments. DNAJA4-knockout (KO) HaCaT cells were generated with CRISPR/Cas9 technology. mRNA and protein expressions were determined using rt-qPCR and western-blotting. Cell cycle distribution, apoptosis and senescence were analyzed by flow cytometry. Results DNAJA4 was induced in HaCaT cells, foreskin and CA tissues subjected to hyperthermia at both transcriptional and translational levels. NF-kB, 3 3 NF-kB: nuclear factor-kappa B. was activated by hyperthermia in HaCaT cells, and further enhanced by DNAJA4-deficiency. Transcription of TNF-α 4 4 TNF-α: tumor necrosis factor-alpha. ; IL-1B, 5 5 IL-1B: interleukin-1 beta. TNFAIP3 6 6 TNFAIP3: Tumor necrosis factor alpha-induced protein 3. and IL-8 7 7 IL-8: interleukin-8. were induced in HaCaT cells subjected to hyperthermia. DNAJA4-knockout promoted transcriptions of TNF-α and IL-1B, whereas decreased that of TNFAIP3 and IL-8. Reduced cell survival, proliferation and viability were demonstrated using flow cytometry and MTS assays. Furthermore, NF-kB inhibitors reversed most of the phenotypes observed. Conclusions Hyperthermia reduced HaCaT cell proliferation and promoted cytokine expressions responsible for anti-viral activity, mainly through a NF-kB dependent pathway. DNAJA4-deficiency enhanced the activation of NF-kB by hyperthermia in HaCaT cells, indicating that DNAJA4 may be a promising therapeutic target for use in the treatment of cutaneous HPV infections. [ABSTRACT FROM AUTHOR]

Essential thrombocythemia (ET) is an uncommon chronic myeloproliferative disorder with no cure. Patients with ET are at risk of different complications, and currently there are no optimal prognostic standards to predict severe post-diagnosis complications such as thrombosis and hemorrhage. In this study, we retrospectively analyzed the full set of clinical data from 150 Chinese patients with ET enrolled from 2013 to 2016. We discovered that neutrophil-to-lymphocyte ratio (NLR), along with other known clinical parameters such as age, leukocyte count, incidence of thrombotic events is higher in patients with JAK2 V617F mutation. NLR is also higher in patients at high-risk stratification of thrombosis. Multivariate analysis showed that age (P = 0.001, 95% CI 1.023–1.089) and JAK2 V617F mutation (P = 0.003, 95% CI 1.837–21.035) were independent factors for thrombotic events, while age (P = 0.005, 95% CI 1.019–1.111) was the only predictive factor for hemorrhagic events at diagnosis. For future thrombotic events, multivariate analysis revealed NLR as the best predictive parameter (P < 0.001, 95% CI 1.173–1.486) when compared with other clinical parameters such as age (P = 0.037, 95% CI 1.004–1.126), thrombosis at diagnosis (P = 0.036, 95% CI 1.077–9.099) and WBC count (P = 0.047, 95% CI 1.001–1.109). Further ROC curve and Kaplan Meier analysis validated NLR as better prognostic marker for future thrombotic events and thrombosis-free survival. In summary, our data suggest that NLR parameter may possess great prognostic significance for future thrombosis in ET patients. [ABSTRACT FROM AUTHOR]

Pancreatic Ductal Adenocarcinoma (PADC) metastasis is the leading cause of morality of this severe malignant tumor. Proteases are key players in the degradation of extracellular matrix which promotes the cascade of tumor metastasis. As a kind of serine proteases, the kallikrein family performs vital function on the cancer proteolysis scene, which have been proved in diverse malignant tumors. However, the specific member of kallikrein family and its function in PDAC remain unexplored. In this study, by data mining of GEO datasets, we have identified KLK10 is upregulated gene in PDAC. We found that KLK10 was significantly overexpressed in tissues of pancreatic intraepithelial neoplasia (PanIN) and PDAC from Pdx1- C re; LSL- K ras G12D/+ mice (KC) and Pdx1- C re; LSL- K ras G12D/+ ; LSL-Tr p 53 R172H/+ mice (KPC) by immunohistochemical analysis. Moreover, KLK10 is extremely elevated in the PDAC tissues, especially that from the PDAC patients with lymphatic and distant metastasis. Aberrant KLK10 expression is significantly correlated with poor prognosis and shorter survival by univariable and multivariable analysis. Functionally, knockdown of KLK10 observably inhibits invasion and metastatic phenotype of PDAC cells in vitro and metastasis in vivo . In addition, blockade of KLK10 attenuates epithelial-mesenchymal transition and activation of FAK-SRC-ERK signaling, which explains the mechanism of KLK10 in promoting metastasis. Collectively, KLK10 should be considered as a promising biomarker for diagnosis and potential target for therapy in PDAC. [ABSTRACT FROM AUTHOR]

Herein we report a new colorimetric and fluorescent dual-mode sensor for alkaline phosphatase (ALP) activity based on the specific enzyme amplification of ALP and the unique optical properties of graphene quantum dots (GQDs)/silver nanoparticles (AgNPs) hybrid. In this strategy, ALP enabled the removal of phosphate group from ascorbic acid 2-phosphate to yield ascorbic acid. Silver ions could be attached on the surfaces of GQDs via electrostatic interaction and reduced by ascorbic acid to produce AgNPs, which in-situ grew on the surfaces of GQDs, accompanied by a substantial increase in the SPR band of AgNPs and an evident fluorescence quenching of GQDs simultaneously. AgNPs acted as a “nanoquencher” to decrease the fluorescence of GQDs by fluorescence resonance energy transfer from GQDs (donor) to AgNPs (acceptor). The mechanism of ALP sensor was examined by transmission electron microscope (TEM), atomic force microscope (AFM), energy dispersive spectrometer (EDS) and elemental mapping. Under optimal conditions, the detection limits of ALP activity are as low as 0.1 U/L and 0.02 U/L by colorimetric and fluorometric method, respectively. The dual-mode sensor could discriminatively detect ALP in L-02 cell lysates with the recoveries ranging from 93.9% to 106.5%. The probe can be employed to monitor the ALP levels in L-02 cells related to different extents of alcoholic fatty liver injury. The images of confocal laser scanning microscopy reflect that the GQD-based sensor was successfully applied to intracellular imaging of ALP activity in L-02 cells due to its favorable biocompatibility and outstanding fluorescent property. [ABSTRACT FROM AUTHOR]

Four new coordination polymers [Cd 2 (CHDC) 2 (APYZ)(H 2 O) 2 ](H 2 O) ( 1 ), [Cd(HCHDC) 2 (APYZ) (H 2 O)] ( 2 ), [Cd 2 (CHDC) 2 (PYZ)(H 2 O) 2 ](H 2 O) ( 3 ), and [Cd(HCHDC) 2 (PYZ)(H 2 O)] ( 4 ) (H 2 CHDC = 1,4-cyclohexanedicarboxylic acid, APYZ = 2-aminopyrazine, PYZ = pyrazine) have been synthesized under the hydrothermal conditions by changing the pH regulator and the N-containing ligands. The pH regulator impacted on the degree of deprotonation of the 1,4-cyclohexanedicarboxylic acid ligand and resulted in the formation of the two pairs of different networks. Polymers 1 and 3 crystallize in monoclinic, space group P 2 1 / c , exhibit two dimensional 6 3 net, which further formed three-dimensional supramolecular structure by the C H⋯O hydrogen bond interactions. While polymers 2 and 4 possess one dimensional chain structures and further link into two dimensional layered supramolecular structures by intermolecular hydrogen bonding interactions. From all three conformers of H 2 CHDC, e , a - cis is consistently present in the Cd coordination polymers. Furthermore, photoluminescence properties of four polymers are also investigated, the luminescent intensity of polymer 1 (or 2 ) with amino group in pyrazine is dramatically stronger than that of the similar structure of polymer 3 (or 4 ) without amino group in pyrazine, the results shown that the presence of the amino group from 2-aminopyrazine play a key role in increasing the luminescence properties. [ABSTRACT FROM AUTHOR]

Reaction of the nitronyl nitroxide radical NIT-CH 3 and NIT-C 3 H 5 with Tb(hfac) 3 affords two one-dimensional lanthanide–nitronyl nitroxide compounds: [Tb III (hfac) 3 (NIT-CH 3 )] n ( 1 ), and [Tb III (hfac) 3 (NIT-C 3 H 5 )] n ( 2 ) (NIT-CH 3  = 2,4,4,5,5-pentamethylimidazolyl-1-oxyl-3-oxide; NIT-C 3 H 5  = 2-cyclopropyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide). Single crystal X-ray crystallographic analysis reveals that these two compounds are one-dimensional chains built up by Tb(hfac) 3 units bridged by radicals through their NO groups. Magnetic studies show that both Tb complexes exhibit frequency-dependent out-of-phase signals. [ABSTRACT FROM AUTHOR]

Aim To explore the role of tumor necrosis factor-alpha (TNF-α) on Staphylococcus aureus -induced necroptosis in alveolar epithelial cells. Main methods The A549 alveolar epithelial cell line was pretreated with small interfering RNA (siRNA) against receptor interacting protein-3 (RIP3) and then stimulated by S. aureus , where some cells were pretreated with TNF-α or TNF-α with anti-TNF-α antibody simultaneously. A549 cell death was assessed using lactate dehydrogenase (LDH) leakage and flow cytometry analyses. The protein expressions of RIP1, RIP3, cleaved caspase-1, and cleaved caspase-8 were analyzed by western blot. Key findings S. aureus -induced LDH release was increased significantly by TNF-α. In addition, flow cytometry showed that TNF-α increased A549 cell apoptosis and necrosis in S. aureus -infected cell cultures. Levels of RIP3 and cleaved caspase-1 protein in A549 cells infected with S. aureus increased at 12 h post-infection, as shown by western blot. Significant additional increases in RIP3 expression were observed following the addition of TNF-α. Decreasing RIP3 levels by siRNA significantly suppressed the release of LDH induced by TNF-α and S. aureus . RIP3 siRNA also significantly suppressed A549 cell necrosis induced by S. aureus and TNF-α at 6 and 12 h post-infection as shown by flow cytometry analysis. Significance TNF-α enhances the damage of S. aureus on lung epithelial cells, and its mechanism is associated with RIP3 mediated necroptosis. [ABSTRACT FROM AUTHOR]

Three β–diketonate mononuclear Ln-based compounds, formulated as [Tb III (hfac) 3 (dmbpy)]( 1 ), [Dy III (hfac) 3 (dmbpy)]( 2 ) and [Er III (hfac) 3 (dmbpy)]( 3 ) (hfac = hexafluoroacetylacetone, dmbpy = 4,4′-dimethyl-2,2′-dipyridyl) have been synthesized and structurally characterized by single crystal X-ray diffraction. Structure characterization reveals that complexes 1, 2 and 3 are isomorphous. Shape measurement shows the coordination geometry of complex 2 is trigonal dodecahedron (D 2d ). Magnetic property study indicates complex 2 shows SIM behavior with observed frequency-dependent signals at low temperature. [ABSTRACT FROM AUTHOR]

One nitronyl nitroxide radical and its three mononuclear tri-spin compounds [Ln(hfac) 3 (NIT-3py-6OCH 3 ) 2 ] (Ln = Gd 1 , Tb 2 , Dy 3 hfac = hexafluoroacetylacetonate; NIT-3py-6OCH 3 = 2-(3′-pyridine-6′-methoxyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide have been prepared and characterized. Single crystal X-ray analyses show that all these three complexes are isomorphous, which crystallize in P 2 1 / n space group and show similar radical-Ln(III)-radical structures. The center lanthanide(III) ions of them are eight-coordinate in distorted triangular dodecahedral LnO 8 coordination geometry completed by two NIT-3py-6OCH 3 radicals and three hfac − ligands. The magnetic studies reveal that ferromagnetic interactions (between intramolecular Ln and radical) and antiferromagnetic interactions (between the intramolecular radicals) are coexist in these complexes. Tb complex displays frequency-dependent signals at low temperature suggesting that it behaves as SMM. [ABSTRACT FROM AUTHOR]

The polymers [Cd(L)(H2O)] ( 1) and [Zn(L)(4, 4′-bipy)(H2O)3] ( 2) (L = 2, 2-dimethylsuccinated anion) were synthesized under hydrothermal conditions and characterized by IR spectrosopy, elemental analyses, and single-crystal X-ray diffraction analysis. The latter reveals that the polymer 1 exhibits a four-connected dia-topology net based on the novel tetranuclear CdII units, whereas polymer 2 displays a 4-connnected CdSO4 topology net. Moreover, the photoluminescent properties of 1 and 2 were investigated. [ABSTRACT FROM AUTHOR]

Antibiotic-induced immunopathology associated with the release of bacterial cell wall components has been suggested to contribute to poor outcomes in bacterial pneumonia. Adjunctive systemic glucocorticoid steroid (GC) therapy for pneumonia has been a controversial issue. In the present study, we first found that dexamethasone (2.5 mg/kg/day) in combination with oxacillin was beneficial for improving lung injury in mice inoculated intratracheally with live Staphylococcus aureus , and did not interfere with bacterial clearance. Alleviation of lung injury was evidenced by attenuated lung pathology, reduced total protein levels, soluble receptor for advanced glycation end-products (sRAGE), tumor necrosis factor alpha (TNF-α), and keratinocyte chemoattractant (KC) and interleukin (IL)-6 in bronchoalveolar lavage fluid (BALF). It was further confirmed by inhibition of receptor interacting protein-3 (RIP3) expression in pulmonary tissues. As in the live S. aureus experiments, dexamethasone (2.5 mg/kg/day) improved lung injury in mice challenged with heat-killed S. aureus (HKSA). In conclusion, our results demonstrated that an appropriate dose of adjunctive dexamethasone (2.5 mg/kg/day) with oxacillin alleviated experimental S. aureus -induced lung injury via its inhibition of inflammatory cytokine release and RIP3 expression. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate whether the drug nicorandil can improve cardiac remodeling after myocardial infarction (MI) and the underlying mechanisms. Mouse MI was established by the ligation of the left anterior descending coronary artery and H9C2 cells were cultured to investigate the underlying molecular mechanisms. The degree of myocardial collagen (Col) deposition was evaluated by Masson's staining. The expressions of nucleolin, autophagy and myocardial remodeling-associated genes were measured by Western blotting, qPCR, and immunofluorescence. The apoptosis of myocardial tissue cells and H9C2 cells were detected by TUNEL staining and flow cytometry, respectively. Autophagosomes were observed by transmission electron microscopy. Treatment with nicorandil mitigated left ventricular enlargement, improved the capacity of myocardial diastolic-contractility, decreased cardiomyocyte apoptosis, and inhibited myocardial fibrosis development post-MI. Nicorandil up-regulated the expression of nucleolin, promoted autophagic flux, and decreased the expressions of TGF-β1 and phosphorylated Smad2/3, while enhanced the expression of BMP-7 and phosphorylated Smad1 in myocardium. Nicorandil decreased apoptosis and promoted autophagic flux in H 2 O 2 -treated H9C2 cells. Autophagy inhibitors 3-methyladenine (3MA) and chloroquine diphosphate salt (CDS) alleviated the effects of nicorandil on apoptosis. Knockdown of nucleolin decreased the effects of nicorandil on apoptosis and nicorandil-promoted autophagic flux of cardiomyocytes treated with H 2 O 2. Treatment with nicorandil alleviated myocardial remodeling post-MI through up-regulating the expression of nucleolin, and subsequently promoting autophagy, followed by regulating TGF-β/Smad signaling pathway. • Nicorandil alleviated myocardial remodeling post-MI. • Nicorandil up-regulates the expression of C23 in the myocardium of MI. • Nicorandil promoted autophagic flux in the myocardium of MI. • Nicorandil inhibited cardiomyocyte apoptosis via up-regulating C23 expression and subsequently promoting autophagic flux. [ABSTRACT FROM AUTHOR]

Dactylogyrus is one of the most serious parasites in aquaculture, resulting in devastating disease for severe economic impacts. In order to further increase the anthelmintic activity of coumarins, statistically valid three-dimensional quantitative structure-activity relationship (3D-QSAR) models was conducted by comparative molecular field analysis (CoMFA) to obtain better novel and promising anthelmintic coumarins within a total of 52 compounds in this study. By served C24 and C41 as template molecules, the steric and electrostatic fields of comparative molecular field analysis (CoMFA) showed a good correlation and predictive power, which was verified the model reliable. Based on the models, eight newly coumarin derivatives Q1 - Q8 were designed and synthesized, and Q1 , Q2 , Q6 and Q7 showed better antiparasitic activities (the EC 50 values ranged from 0.18 to 0.26 mg/L) than that of coumarin C24 and C41 (the EC 50 values of 0.85 and 0.80 mg/L). By comparing the therapeutic index (TI), the order is the potency of Q4 > Q5 > Q7 > mebendazole > Q2 > Q6 > praziquantel > Q1 > Q3 , which suggests that Q4 should be a viable way for controlling Dactylogyrus infection. Meanwhile, Q4 with a high stability in aquacultural water in immersion suppressed horizontal transmission of Dactylogyrus. These results will be contributed to further improve drug potency on aquacultural parasite control. • 3D-QSAR models was conducted to obtain better novel and promising anthelmintic coumarins. • Four coumarins from the model exhibited excellent antiparasitic activity against Dactylogyrus infection. • Coumarin Q4 suppressed horizontal transmission of Dactylogyrus. [ABSTRACT FROM AUTHOR]

An unreported nitronyl nitroxide radical ligand and corresponding radical-4f and radical-3d-4f complexes were prepared with structure changes from ring-shape to 1D zigzag. Magnetic measurements reveal that two different magnetic interactions coexist in radical-4f complex, while for radical-3d-4f complex, weak ferromagnetic coupling between Cu2+/Ln3+ and radical ligands as well as antiferromagnetic coupling between two adjacent radicals via the Ln3+ are observed. • Radical-4f ring dimer and radical-3d-4f 1D chain complexes have been prepared. • Comparison discussion of structure and magnetic property changes were conducted. • Complexes 2 , 3 and 5 display frequency temperature dependence at low temperature. An unreported nitronyl nitroxide radical ligand and its corresponding radical-4f (complexes 1 – 3) and radical-3d-4f complexes (complexes 4 – 6) were successfully prepared. Structural analyses indicate that the complexes 1 – 3 are cyclic structures consist of two identical units of Ln(hfac) 3 (NIT-5-OCH 3 -3pyridine) (hfac = hexafluoroacetylacetone; Ln = Gd 1 , Tb 2 , Dy 3), while the complexes 4 – 6 show 1D zigzag structures with periodic [Rad–Ln–Rad–Cu] (Ln = Gd 4 , Tb 5 , Dy 6) units. Dc susceptibility measurements reveal that two different magnetic interactions coexist in complex 1: (i) ferromagnetic coupling between Gd3+ and radical through the N O group, (ii) weak antiferromagnetic interaction between Gd3+ and radical through the pyridine ring. While for complex 4 , weak ferromagnetic coupling between Cu2+/Ln3+ and radical ligands as well as antiferromagnetic coupling between two adjacent radicals via the Ln3+ are observed at the same time. Furthermore, AC magnetic studies reveal that complexes 2 , 3 and 5 display slow magnetization relaxation at low-temperature. [ABSTRACT FROM AUTHOR]

Liver fibrosis is involved in the progression of most chronic liver diseases. Even though we have made a huge progress in order to understand the pathogenesis of liver fibrosis, however, there is still a lack of productive treatments. Being a traditional Chinese medicine, Platycodin D (PD), an oleanane kind of triterpenoid saponin has been put to extensive use for treating different kinds of illnesses that include not just anti-nociceptive, but also antiviral, anti-inflammatory, and anti-cancer for thousands of years. Nonetheless, there has been no clarification made for its effects on the progression of liver fibrosis. In this manner, we carried out in vitro studies for the purpose of investigating the anti-fibrosis impact of PD. Activation of hepatic stellate cells was evaluated by means of the detection of the proliferation of HSCs and the expression of specific proteins. We discovered the fact that PD had the potential of activating HSCs. Thereafter, we detected the apoptosis and autophagy of the HSCs; as the results suggested, PD induced apoptosis and autophagy of the HSCs. It augmented the expression level of apoptotic proteins that included Bax, Cytochrome C (cyto-c), cleaved caspase3 and cleaved caspase9, in addition to the autophagy relevant proteins, for instance, LC3II, beclin1, Atg5 and Atg9. Further research was carried out for the investigation of the underlying molecular mechanism, and discovered that PD promoted the phosphorylation of JNK and c-Jun. Treating the JNK inhibitor P600125 inhibited the effect of PD, confirming the impact of PD on the regulation of JNK/c-Jun pathway. Thus, we speculated that PD alleviates liver fibrosis and activation of hepatic stellate via promoting phosphorylation of JNK and c-Jun and further altering the autophagy along with apoptosis of HSCs. [ABSTRACT FROM AUTHOR]

The article presents a study which discusses role of GPAA1 in gastric cancer progression via upregulation of GPI-anchored protein and enhancement of ERBB signalling pathway. It mentions that data mining was performed to determine the pattern of GPAA1 expression and the reason for its overexpression in tumour. It reveals that GPAA1 was an upregulated oncogene in gastric cancer due to chromosomal amplification.

Selective serotonin reuptake inhibitors (SSRIs) have shown promise in cancer therapy, particularly for hepatocellular carcinoma (HCC), but their molecular targets and mechanisms remain unclear. Here, we show that SSRIs exhibit significant anti-HCC effects independent of their classical target, the serotonin reuptake transporter (SERT). Using global inverse gene expression profiling, drug affinity responsive target stability assays, and in silico molecular docking, we demonstrate that citalopram targets glucose transporter 1 (GLUT1), resulting in reduced glycolytic flux. A mutant GLUT1 variant at the citalopram binding site (E380) diminishes the drug's inhibitory effects on the Warburg effect and tumor growth. In preclinical models, citalopram dampens the growth of GLUT1 high liver tumors and displays a synergistic effect with anti-PD-1 therapy. Retrospective analysis reveals that SSRI use correlates with a lower risk of metastasis among patients with HCC. Our study describes a role for SSRIs in cancer metabolism, establishing a rationale for their repurposing as potential anti-cancer drugs for HCC., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Platelet-rich plasma (PRP) has been recognized as an effective therapy in regenerative medicine and surgery, which can reduce the risk of antibiotic abuse and promote the healing of infected wounds. Recent advances in PRP-based treatments have focused on the controlled release of growth factors in PRP with biocompatible hydrogels and antimicrobial promotion by introducing hydrogel components or antibiotics, while the inherent antimicrobial activity of PRP is mostly neglected or sacrificed. Here, we demonstrate the combination of an antimicrobial polysaccharide, carboxymethyl chitosan, and PRP to construct an antimicrobial hydrogel via dynamic bonding with oxidized chondroitin sulfate. Significant inhibitory effects against Staphylococcus aureus and Escherichia coli (95 % of inhibition rate) are achieved through the synergistic contributions of the polysaccharide and PRP. Additionally, the resulting hydrogel promotes the migration of NIH-3T3 fibroblasts and collagen deposition by approximately 1.7 and 1.8 times, respectively, thereby accelerating the healing process of infected wounds. This work may bring new perspectives for potent applications of PRP-based hydrogel dressings for antibiotic-free management of infected wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Hepatic steatosis is a hepatic pathological change closely associated with metabolic disorders, commonly observed in various metabolic diseases such as metabolic syndrome (MetS), with a high global prevalence. Dai-Zong-Fang (DZF), a traditional Chinese herbal formula, is widely used in clinical treatment for MetS, exhibiting multifaceted effects in reducing obesity and regulating blood glucose and lipids. This study aims to explore the mechanism by which DZF modulates the gut microbiota and reduces hepatic steatosis based on the gut-liver axis. Methods: This study utilized db/db mice as a disease model for drug intervention. Body weight and fasting blood glucose were monitored. Serum lipid and transaminase levels were measured. Insulin tolerance test was conducted to assess insulin sensitivity. Hematoxylin and eosin (HE) staining was employed to observe morphological changes in the liver and intestine. The degree of hepatic steatosis was evaluated through Oil Red O staining and hepatic lipid determination. Changes in gut microbiota were assessed using 16S rRNA gene sequencing. Serum lipopolysaccharide (LPS) levels were measured by ELISA. The expression levels of intestinal tight junction proteins, intestinal lipid absorption-related proteins, and key proteins in hepatic lipid metabolism were examined through Western blot and RT-qPCR. Results: After DZF intervention, there was a decrease in body weight, alleviation of glucose and lipid metabolism disorders, reduction in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and mitigation of insulin resistance in mice. DZF significantly modulated the diversity of the gut microbiota, with a notable increase in the abundance of the Bacteroidetes phylum. PICRUSt indicated that DZF influenced various functions in gut microbiota, including carbohydrate and amino acid metabolism. Following DZF intervention, serum LPS levels decreased, intestinal pathological damage was reduced, and the expression of intestinal tight junction protein occludin was increased, while the expression of intestinal lipid absorption-related proteins cluster of differentiation 36 (CD36) and apolipoprotein B48 (ApoB48) were decreased. In the liver, DZF intervention resulted in a reduction in hepatic steatosis and lipid droplets, accompanied by a decrease fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1) and fatty acid transport protein 2 (FATP2). Conversely, there was an increase in the expression of the fatty acid oxidation-related enzyme carnitine palmitoyltransferase-1𝛂 (CPT-1𝛂). Conclusion: DZF can regulate the structure and function of the intestinal microbiota in db/db mice. This ameliorates intestinal barrier damage and the detrimental effects of endotoxemia on hepatic metabolism. DZF not only inhibits intestinal lipid absorption but also improves hepatic lipid metabolism from various aspects, including de novo lipogenesis, fatty acid uptake, and fatty acid oxidation. This suggests that DZF may act on the liver and intestine as target organs, exerting its effects by improving the intestinal microbiota and related barrier and lipid absorption functions, ultimately ameliorating hepatic steatosis and enhancing overall glucose and lipid metabolism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zhu, Zhu, Fu and Liu.)

Aim: To evaluate the clinical application value of the artificial intelligence assisted pathologic myopia (PM-AI) diagnosis model based on deep learning., Methods: A total of 1156 readable color fundus photographs were collected and annotated based on the diagnostic criteria of Meta-pathologic myopia (PM) (2015). The PM-AI system and four eye doctors (retinal specialists 1 and 2, and ophthalmologists 1 and 2) independently evaluated the color fundus photographs to determine whether they were indicative of PM or not and the presence of myopic choroidal neovascularization (mCNV). The performance of identification for PM and mCNV by the PM-AI system and the eye doctors was compared and evaluated via the relevant statistical analysis., Results: For PM identification, the sensitivity of the PM-AI system was 98.17%, which was comparable to specialist 1 ( P =0.307), but was higher than specialist 2 and ophthalmologists 1 and 2 ( P <0.001). The specificity of the PM-AI system was 93.06%, which was lower than specialists 1 and 2, but was higher than ophthalmologists 1 and 2. The PM-AI system showed the Kappa value of 0.904, while the Kappa values of specialists 1, 2 and ophthalmologists 1, 2 were 0.968, 0.916, 0.772 and 0.730, respectively. For mCNV identification, the AI system showed the sensitivity of 84.06%, which was comparable to specialists 1, 2 and ophthalmologist 2 ( P >0.05), and was higher than ophthalmologist 1. The specificity of the PM-AI system was 95.31%, which was lower than specialists 1 and 2, but higher than ophthalmologists 1 and 2. The PM-AI system gave the Kappa value of 0.624, while the Kappa values of specialists 1, 2 and ophthalmologists 1 and 2 were 0.864, 0.732, 0.304 and 0.238, respectively., Conclusion: In comparison to the senior ophthalmologists, the PM-AI system based on deep learning exhibits excellent performance in PM and mCNV identification. The effectiveness of PM-AI system is an auxiliary diagnosis tool for clinical screening of PM and mCNV., (International Journal of Ophthalmology Press.)

Dactylogyrus is one of the most common parasitic diseases in fish and causes huge losses to the aquaculture industry. With the advantages of safety, low toxicity and easy degradation, plant-derived drugs are ideal for the creation of green aquatic ingredients. The use of plant-derived drugs in aquaculture is limited by their low content and high processing costs, which is a challenge that can be solved by the chemical synthesis of plant-derived drugs. Eleven new coumarin derivatives were synthesized and assessed for their anthelmintic activity in this study. Among them, the derivative 7-((1-tosyl-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (N11) has good anthelmintic activity and its mean anthelmintic efficacy against D. intermedius at a concentration of 10 μM reached 99.84%, which is even better than the anthelmintic activity of the positive control mebendazole. Further studies showed that N11 had concentration values of 3.31 and 1.94 μM for 50% maximal effect (EC 50 ) against D. intermedius at 24 and 48 h, respectively. Furthermore, scanning electron microscopy revealed that N11 caused damage to D. intermedius. What is more noteworthy is that a substantial reduction in the ATP content of the parasite was observed following in vitro and in vivo administration of N11. Moreover, it was also found that N11 was able to inhibit the horizontal transmission of D. intermedius. Furthermore, real-time quantitative PCR analysis was utilized to determine the expression profile of genes associated with anti-inflammatory cytokines (IL-10, TGF-β and IL-4) in goldfish. In all examined organs, it was observed that the expression of anti-inflammatory cytokines increased subsequent to treatment with N11, according to the results. Thus, these results all suggest that N11 possesses good anthelmintic activity and is a potentially effective agent for the control of D. intermedius., (© 2023 John Wiley & Sons Ltd.)

Background: Tourniquet pain, described as a dull, tight, poorly localized aching sensation, is common in conscious patients. Although various pain-reduction methods have been implemented, none are completely effective. Femoral periarterial block (FAB) has been shown to attenuate tourniquet-induced hypertension in patients undergoing general anesthesia. We aimed to test the feasibility of FAB in inhibiting thigh tourniquet pain in orthopedic patients under conscious sedation., Methods: Forty-two patients (aged 18-64 years and ASA I-II) scheduled for below-knee orthopedic surgeries with an anticipated tourniquet duration of more than 40 min were recruited and received FAB (Group 1) or not (Group 2). The primary outcome was the occurrence of tourniquet pain. The onset time and severity of the tourniquet pain were recorded. Total doses of sedatives and analgesics administered intraoperatively and hemodynamic changes were documented. The occurrence of local anesthetic systemic toxicity was recorded., Results: Kaplan-Meier time-to-event curves indicated an improved tourniquet tolerance and delayed pain onset. Tourniquet pain occurrence was lower in Group 1 than in Group 2 (30% vs. 95.5%, P=0.02). Tourniquet pain onset was delayed in Group 1 (80[67,84] min vs. 58[51.5,60] min, P<0.01). Fewer patients in Group 1 experienced severe pain (3(15%) vs. 18(81.8%), P<0.01), and less hemodynamic changes (2(10%) vs. 12(54.5%), P<0.01). Local anesthetic systemic toxicity was absent., Conclusions: FAB, applied with regional anesthesia in patients undergoing below-knee orthopedic surgeries, could reduce thigh tourniquet pain, stabilize blood pressure and heart rate, and prolong tourniquet duration.

Objective: Mucosal immunization was an effective defender against pathogens. Nasal vaccines could activate both systemic and mucosal immunity to trigger protective immune responses. However, due to the weak immunogenicity of nasal vaccines and the lack of appropriate antigen carriers, very few nasal vaccines have been clinically approved for human use, which was a major barrier to the development of nasal vaccines. Plant-derived adjuvants are promising candidates for vaccine delivery systems due to their relatively safe immunogenic properties. In particular, the distinctive structure of pollen was beneficial to the stability and retention of antigen in the nasal mucosa., Methods: Herein, a novel wild-type chrysanthemum sporopollenin vaccine delivery system loaded with a w/o/w emulsion containing squalane and protein antigen was fabricated. The unique internal cavities and the rigid external walls within the sporopollenin skeleton construction could preserve and stabilize the inner proteins. The external morphological characteristics were suitable for nasal mucosal administration with high adhesion and retention., Results: Secretory IgA antibodies in the nasal mucosa can be induced by the w/o/w emulsion with the chrysanthemum sporopollenin vaccine delivery system. Moreover, the nasal adjuvants produce a stronger humoral response (IgA and IgG) compared to squalene emulsion adjuvant. Mucosal adjuvant benefited primarily from prolongation of antigens in the nasal cavity, improvement of antigen penetration in the submucosa and promotion of CD8+ T cells in spleen., Disccusion: Based on effective delivering both the adjuvant and the antigen, the increase of protein antigen stability and the realization of mucosal retention, the chrysanthemum sporopollenin vaccine delivery system has the potential to be a promising adjuvant platform. This work provide a novel idea for the fabrication of protein-mucosal delivery vaccine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer YX declared a shared affiliation, with with several of the authors, JL, ZYC, JWC, XZY, to the handling editor at the time of the review., (Copyright © 2023 Liu, Yan, Li, Du, Zhu, Ye, Cao, Dong, Li, Xu, Bai, Li, Zhang, Wang, Li, Sun and Yin.)

Polydopamine (PDA) is a good adhesion agent for lots of gels inspired by the mussel, whereas hybrid organic-inorganic perovskites (HOIPs) usually exhibit extraordinary optoelectronic performance. Herein, mussel-inspired chemistry has been integrated with two-dimensional HOIPs first, leading to the preparation of new crystal (HDA) 2 PbBr 4 ( 1 ) (DA = dopamine). The organic cation dopamine can be introduced into PDA resulting in a thin film of (HPDA) 2 PbBr 4 ( PDA-1 ). The dissolved inorganic components of layered perovskite in DMF solution together with H 2 O 2 addition can facilitate DA polymerization greatly. More importantly, PDA-1 can inherit an excellent semiconductor property of HOIPs and robust adhesion of the PDA hydrogel resulting in a self-adhesive photoelectric coating on various interfaces.

Muscone is the main active compound of Moschus. In this paper, the cardioprotective effect of Muscone on acute myocardial ischemia (AMI) rats and its potential mechanisms were investigated. AMI rat models were established to evaluate the protective effect and antioxidative function of Muscone on the hearts. Moreover, Western blot analysis was conducted to quantify the phosphorylated PI3K and AKT levels in PI3K/Akt pathway for further investigating the mechanism of Muscone. Results showed that Muscone could markedly lessen the infarct size and myocardial injury, improve cardiac function, inhibit cardiomyocyte apoptosis and down-regulate serum reactive oxygen species level as indicated by the decreased MDA, BNP and c-TnI activities and the increased SOD, GSH-px, CAT activities and the expression of Bax protein. In addition, it was revealed that Muscone notably promoted the phosphorylation of PI3K and AKT. These findings denote that Muscone exerts a protective effect in heart via inhibition of oxidative stress and apoptosis, offering new insights into the treatment of CHD and the clinical application of Muscone., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Herein, N 2 -selective β-thioalkylation of benzotriazoles with unactivated alkenes and styrenes is reported. The N 2 -selective β-thioalkylation of benzotriazoles is highly stereospecific and works under simple and mild conditions, exhibiting excellent functional group tolerance. The high N 2 -selectivity is a consequence of the combination of hydrogen bonding and Lewis acid/base activation, which reverses the N 2 -position to be favored for alkylation.

Ambient air quality forecasting evaluation plays an important role in improving forecasting capability. In order to provide better support for refined air quality management, with reference to the UK air quality forecasting evaluation method, this study divided six air quality index (AQI) levels into 12 half-levels and explored AQI, PM 2.5 , and O 3 -8h concentration forecasting evaluation based on the half-level method in "2+26" cities during 2020. Comparison with the AQI range forecasting and AQI level range forecasting evaluation showed that the half-level forecasting evaluation method could combine these two indicators into one, providing feasibility and application value in operational air quality forecasting evaluation. Specific half-level forecasting evaluation showed that the forecasting effect of AQI and O 3 -8h concentration at the low and high levels was significantly worse than that of the middle levels in "2+26" cities. The forecasting effect of the PM 2.5 concentration was relatively stable in different half-levels. The monthly variation curves of AQI, PM 2.5 , and O 3 -8h concentration forecasting accuracy exhibited a bimodal pattern, first rising and then falling and a flat pattern, respectively. The overestimate of PM 2.5 concentration forecasting was significant in each month. The accuracy gaps of AQI and O 3 -8h concentration forecasting in different cities was relatively small; however, the PM 2.5 concentration forecasting accuracy fluctuated greatly. The AQI forecasting accuracies of Beijing and Tianjin were higher than that of neighboring provinces. Additionally, the PM 2.5 and O 3 -8h concentration forecasting effects in Beijing and Henan province were relatively the best.

Background: Early enteral nutrition (EN) after abdominal surgery can improve the prognosis of patients. However, the high feeding intolerance (FI) rate is the primary factor impeding postoperative EN., Methods: Sixty-seven patients who underwent radical subtotal or total gastrectomy for gastric cancer (GC) were randomly allocated to the preoperative oral nutritional supplement group (ONS group) or dietary advice alone (DA group). Both groups were fed via nasojejunal tubes (NJs) from the first day after surgery to the fifth day. The primary endpoint is the FI rate., Results: Of the patients, 66 completed the trial (31 in the ONS group, 35 in the DA group). The FI rate in the ONS group was lower than that in the DA group (25.8% vs. 31.4%, p = 0.249). The postoperative five-day 50% energy compliance rate in the ONS group was higher than that in the DA group (54.8% vs. 48.6%, p = 0.465). The main gastrointestinal intolerance symptoms were distension (ONS vs. DA: 45.2% vs. 62.9, p = 0.150) and abdominal pain (ONS vs. DA: 29.0% vs. 45.7%, p = 0.226). Postoperative nausea/vomiting rate and heartburn/reflux rate were similar between the two groups. We noted no difference in perioperative serum indices, short-term prognosis or postoperative complication rates between the two groups., Conclusions: The study shows that short-term preoperative ONS cannot significantly improve FI and the energy compliance rate in the early stage after radical gastrectomy.

An epidemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. SARS-CoV-2 relies on its spike protein to invade host cells by interacting with the human receptor protein Angiotensin-Converting Enzymes 2 (ACE2). Therefore, designing an antibody or small-molecular entry blockers is of great significance for virus prevention and treatment. This study identified five potential small molecular anti-virus blockers via targeting SARS-CoV-2 spike protein by combining in silico technologies with in vitro experimental methods. The five molecules were natural products that binding to the RBD domain of SARS-CoV-2 was qualitatively and quantitively validated by both native Mass Spectrometry (MS) and Surface Plasmon Resonance (SPR). Anti-viral activity assays showed that the optimal molecule, H69C2, had a strong binding affinity (dissociation constant K D ) of 0.0947 µM and anti-virus IC 50 of 85.75 µM., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

The PM 2.5 forecast models of 95 cities in Beijing-Tianjin-Hebei and its surrounding cities (BTH); the Fenwei Plain (FWP); the border area of Jiangsu, Anhui, Shandong, and Henan (JASH); and the Yangtze River Delta (YRD) regions were established using BP neural network models, and the forecast was carried out for the next seven days in the autumn and winter in 2020. By comparing the forecast results of the BP neural network models, numerical model, and artificial correction, the PM 2.5 forecast effects of the three methods were analyzed and evaluated. The results showed:① The performance of the short-term forecast based on the BP neural network was relatively good but was reduced in the medium and long term and systematically overestimated in four regions. The numerical model effects were lower than those of the BP neural network models. ② The accuracy rates of the PM 2.5 forecast concentration by the three methods were generally low in the four regions, with an average of less than 50%, and the accuracy values in order from high to low were the BP neural network models, artificial correction, and the numerical model. The accuracy rates of IAQI levels of PM 2.5 were significantly improved by the three methods, and the averages were above 65% in the first four days. The effects of the BP neural network models and artificial correction were similar, which were generally higher than those of the numerical model. ③ The numerical model had good effects in the BTH, JASH, and YRD regions, whereas it was the worst when forecasting moderately and above-polluted days in the FWP region. The BP neural network model had a good performance when forecasting short-term PM 2.5 in the BTH, JASH, and FWP regions, whereas it was poor in the YRD region. In general, the performance of artificial correction was relatively good when forecasting moderate-level days and was close to the BP neural network model when forecasting heavily polluted days.

The COVID-19, caused by SARS-CoV-2, is threatening public health, and there is no effective treatment. In this study, we have implemented a multi-targeted anti-viral drug design strategy to discover highly potent SARS-CoV-2 inhibitors, which simultaneously act on the host ribosome, viral RNA as well as RNA-dependent RNA polymerases, and nucleocapsid protein of the virus, to impair viral translation, frameshifting, replication, and assembly. Driven by this strategy, three alkaloids, including lycorine, emetine, and cephaeline, were discovered to inhibit SARS-CoV-2 with EC 50 values of low nanomolar levels potently. The findings in this work demonstrate the feasibility of this multi-targeting drug design strategy and provide a rationale for designing more potent anti-virus drugs., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Reverse prediction and molecular docking techniques were employed to evaluate the feasibility of reniformin A(RA) as an anti-tumor leading compound. Based on the reverse prediction, network pharmacology was used to construct a &quot;disease-compound-target-pathway&quot; network. Thirty-nine tumor-related targets of RA were predicted, which participated in the regulation of multiple cellular activities such as apoptosis, cell cycle, and tumor metastasis, and regulated estrogen signal transduction and inflammatory response. Discovery Studio 2020 was adopted for molecular docking and toxicity prediction(TOPKAT). As revealed by the results, the binding affinity of RA with the tumor-related targets ABL1, ESR1, SRC and BCL-XL was stronger than that of oridonin(OD), while its mutagenicity, rodent carcinogenesis, and oral LD&#95;(50) in rats were all inferior to that of OD. Furthermore, in vitro experiments were performed to confirm the anti-tumor activity of RA, and the mechanism was preliminarily discussed. The results demonstrated that RA was superior to OD in cytotoxicity, inhibition of cell colony formation, and induction of apoptosis. RA, possessing potent anti-tumor activity, is expected to be a new anti-tumor leading compound.

Objective: To evaluate the clinical efficacy and long-term outcomes associated with the treatment of hepatic vein (HV)-type Budd-Chiari syndrome (BCS) via accessory HV (AHV) recanalization., Methods: In total, 26 HV-type BCS patients underwent AHV recanalization between July 2014 and December 2019 at our hospital, while 73 HV-type BCS patients without compensatory AHV underwent main HV (MHV) recanalization and served as controls in the present study. Short- and long-term clinical outcomes were compared., Results: AHV and MHV recanalization approaches were both associated with 100% technical success rates, with one recanalization procedure being performed per patient. Respective clinical success rates for the AHV and MHV recanalization approaches were 96.2% and 94.5% (P = 0.744). Re-obstruction rates were comparable between these two approaches at 20% and 34.8%, respectively (P = 0.17). Primary cumulative 1-, 2-, and 5-year patency rates in the AHV group were 96.0%, 91.6%, and 76.3%, respectively, whereas in the MHV group, these three respective rates were 87.0%, 78.6%, and 58.6% (P = 0.048). Secondary cumulative 1-, 2-, and 5-year patency rates in the AHV group were 96.0%, 96.0%, and 96.0%, respectively, whereas in the MHV group, they were 97.1%, 97.1%, and 81.8%, respectively (P = 0.289). Cumulative 1-, 2-, and 5-year survival rates for AHV group patients were 96.0%, 96.0%, and 96.0%, respectively, while for the MHV group, these respective rates were 98.6%, 95.2%, and 89.7% (P = 0.462)., Conclusion: HV-type BCS can be safely and effectively treated via AHV recanalization, which may achieve longer patency relative to MHV recanalization.

Cytochrome P450 (CYP) gene expression exhibits large interindividual variation attributable to diverse regulatory factors including microRNAs (miRNAs) and hepatic transcription factors (TFs). We used real-time qPCR with 106 human liver samples to measure the expression and interindividual variation of seven miRNAs and four TFs that have been reported to regulate the expression of CYPs; we also identified factors that influence their expression. The results show that expression of the seven miRNAs and the four TFs exhibits a non-normal distribution and the expression variability is high (89- to 618-fold for miRNA and 12- to 85-fold for TFs). Age contributed to the interindividual variation for miR-148a, miR-27b and miR-34a, whereas cigarette smoking and alcohol consumption significantly reduced HNF4α mRNA levels. Association analysis showed significant correlations among the seven miRNAs as well as the four TFs. Furthermore, we systematically evaluated the impact of the seven miRNAs and four TFs on protein content, mRNA levels, translation efficiency and activity of 10 CYPs. The results show that numerous associations (positive and negative) are present between the seven miRNAs or the four TFs and the 10 CYP phenotypes (as indicated by mRNA, protein and activity); specifically, miR-27b, miR-34a and all four TFs played key roles in the interindividual variation of CYPs. Our results extend previous findings and suggest that miR-27b and miR-34a may be potential direct or indirect master regulators of CYP expression and thereby contribute to the interindividual variations in CYP-mediated drug metabolism., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aerobic glycolysis, also known as the Warburg effect, is emerged as a hallmark of most cancer cells. Increased aerobic glycolysis is closely associated with tumor aggressiveness and predicts a poor prognosis. Pancreatic ductal adenocarcinoma (PDAC) is characterized by prominent genomic aberrations and increased glycolytic phenotype. However, the detailed molecular events implicated in aerobic glycolysis of PDAC are not well understood. In this study, we performed a comprehensive molecular characterization using multidimensional ''omic'' data from The Cancer Genome Atlas (TCGA). Detailed analysis of 89 informative PDAC tumors identified substantial copy number variations ( MYC , GATA6 , FGFR1 , IDO1, and SMAD4 ) and mutations ( KRAS , SMAD4 , and RNF43 ) related to aerobic glycolysis. Moreover, integrated analysis of transcriptional profiles revealed many differentially expressed long non-coding RNAs involved in PDAC aerobic glycolysis. Loss-of-function studies showed that LINC01559 and UNC5B-AS1 knockdown significantly inhibited the glycolytic capacity of PDAC cells as revealed by reduced glucose uptake, lactate production, and extracellular acidification rate. Moreover, genetic silencing of LINC01559 and UNC5B-AS1 suppressed tumor growth and resulted in alterations in several signaling pathways, such as TNF signaling pathway, IL-17 signaling pathway, and transcriptional misregulation in cancer. Notably, high expression of LINC01559 and UNC5B-AS1 predicted poor patient prognosis and correlated with the maximum standard uptakevalue (SUVmax) in PDAC patients who received preoperative 18 F-FDG PET/CT. Taken together, our results decipher the glycolysis-associated copy number variations, mutations, and lncRNA landscapes in PDAC. These findings improve our knowledge of the molecular mechanism of PDAC aerobic glycolysis and may have practical implications for precision cancer therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: Cerebral palsy is the most common motor disability of childhood. Spastic cerebral palsy accounts for 60% to 70% of cases. Research has shown that acupuncture can improve the quality of life of children with cerebral palsy, but the mechanism of action remains unclear. This study aims to determine the effectiveness of acupuncture for treatment of children with spastic cerebral palsy and to assess the value of multimodal magnetic resonance imaging (MRI) and ambulatory electroencephalogram (EEG) for evaluation of treatment effect., Methods and Analysis: This randomized controlled trial will enroll a total of 72 children with CP from 2 hospitals-Jiangsu Province Hospital of Chinese Medicine and Nanjing State Hospital of Pediatric-with 36 participants from each hospital. Patients will be randomly assigned (1:1 ratio) to receive "Tonifying Kidney and Invigorating Brain" acupuncture treatment plus standardized physical rehabilitation treatment (treatment group) or only standardized physical rehabilitation (control group). All participants will receive 3 treatment sessions per week for 3 consecutive months; they will then be followed up for another 3 months. The primary outcome measures will include multimodal magnetic resonance imaging (MRI), ambulatory electroencephalogram (EEG), and Gesell Developmental Diagnostic Schedules. The secondary outcome measures will include Gross Motor Function Classification System (GMFCS), Gross Motor Function Measure (GMFM), Functional Independence Measure (WeeFIM), and Modified Ashworth Scale score. Outcome measures (including primary and secondary outcome measures) were collected at the baseline, 3 months and 6 months prior to the intervention.Ethics and dissemination PATIENTS CONSENT:: Obtained., Ethics Approval: The central independent ethics committee of Jiangsu Province Hospital of Traditional Chinese Medicine approved the protocol (2017NL-115-02)., Safety Considerations: Routine blood tests and liver and kidney function tests will be conducted to exclude patients with severe heart, liver, or kidney diseases. The same examinations will be performed again at the end of the study to detect any possible side effects. Possible acupuncture-related adverse events (e.g., fainting, needle stick injury, local infection, subcutaneous hematoma, and low-grade fever) will be documented. Serious adverse events will be reported to the principal investigator immediately. All unexpected and unintended responses, even those not necessarily related to the acupuncture intervention, will be documented as adverse events., Case Dropout Management: Participants have a right to withdraw from the study at any time if they feel uncomfortable upon receiving the treatments or being diagnosed with serious complications or diseases. They will then be referred to the preferred department for further treatment and management. If cases of dropout, the researcher need to contact the participant to reason the problem out, collect and record all the necessary assessments on the last visit as well as the date of last visit. All data available until the date of withdrawal will be stored for further statistical analysis., Discussion: This research is being conducted to assess the value of acupuncture as an intervention for rehabilitation of children with spastic cerebral palsy and also to evaluate the usefulness of multimodal MRI and ambulatory EEG for identifying changes in brain function., Trial Registration: This trial is registered with Chinese Clinical Trials Register, ChiCTR 1900024546 (registered 15 July 2019; retrospective registration, http://www.chictr.org.cn/showproj.aspx?proj=35763).

A literature review was performed to investigate the possible mechanism of scalp acupuncture in stimulating the skin, fascia, muscle, and periosteum and thus affecting cerebral cortex function. The results of literature research show that the effect of scalp acupuncture on cerebral cortex function may be achieved by the stimulation of specific anatomical structures. Stimulation of the skin, fascia, muscle and periosteum can activate the functional areas of the cerebral cortex through the midbrain, thalamus, and brainstem. In addition, different depths of stimulation may affect the deep and shallow sensation of the brain, self-monitoring of the fascia, subcortical central compensation, and cortical discharge. Therefore, exploration of the specific rules and differences in the effect of stimulating different anatomical structures on brain function is the future focus of the clinical and basic research on scalp acupuncture.

A N2-selective β-selenoalkylation of 1,2,3-triazoles with alkenes mediated by diamines has been developed. The reaction proceeds presumably via the interaction of diamines with both the triazole moiety and selenium/alkene complex to construct a U-shaped reaction intermediate. This activation mode will block the N1 position on triazoles and thus favor the N2-selective selenoamination. This stereospecific anti-addition method enables an efficient N2-selective β-selenoalkylation of 1,2,3-triazoles under mild and open-air conditions and might find applications in the synthesis of biologically active molecules.

This paper discusses the concentration characteristics of PM 2.5 , as well as its relationship with meteorological factors in autumn and winter (from September to the following February), from 2013 to 2018 in the Beijing-Tianjin-Hebei (BTH) region. The accuracy and uncertainty of the air quality forecast models NAQPMS(nested air quality prediction modeling system), CMAQ(community multiscale air quality modeling system), and CAMx (comprehensive air quality model with extensions) were analyzed based on the model-predicted and measured PM 2.5 concentration in autumn and winter from 2015 to 2018. The accuracy of NAQPMS, CMAQ, and CAMx during typical heavy air pollution was also tested. Moreover, methods to improve the accuracy of the model forecast were discussed. The results showed that the mean concentrations of PM 2.5 in the BTH region were 122, 98, 82, 99, and 65 μg·m -3 in the five autumn and winter periods, respectively. When the air quality index (AQI) exceeded 150 during each autumn and winter, it reached 229, 198, 210, 204, and 180 μg·m -3 , respectively. There were 64 occurrences of heavy regional PM 2.5 air pollution in autumn and winter from 2013 to 2018. The average duration was longest in the 2013 to 2014 period, and shortest in the 2017 to 2018 period. The peak concentration and average concentration of PM 2.5 decreased year on year, except for the period from 2016 to 2017. In autumn and winter, PM 2.5 concentration had a relatively close relationship with relative humidity, wind and sunshine duration, compared with a weak relationship with temperature and air pressure. Regional heavy air pollution always happened under the condition of low wind speed(less than 2 m·s -1 ),higher relative humidity(greater than 65%),and southwest and northeast wind direction. In addition, the heavy air pollution of PM 2.5 in BTH in autumn and winter can be effectively forecasted by NAQPMS, CMAQ, and CAMx. The predicted and measured PM 2.5 concentration showed a close relationship. The models performed well in forecasting Zhangjiakou, Chengde, and Qinhuangdao, but by contrast overestimated in Tangshan, Shijiazhuang, Baoding, Beijing, and Tianjin. The uncertainty of emission sources, measured and predicted meteorological data, and the atmospheric chemical reaction mechanism may be the main reasons for the overestimate.

Background and Aims: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death worldwide. Neurotransmitter-initiated signalling pathway is profoundly implicated in tumour initiation and progression. Here, we investigated whether dysregulated neurotransmitter receptors play a role during pancreatic tumourigenesis., Methods: The Cancer Genome Atlas and Gene Expression Omnibus datasets were used to identify differentially expressed neurotransmitter receptors. The expression pattern of gamma-aminobutyric acid type A receptor pi subunit (GABRP) in human and mouse PDAC tissues and cells was studied by immunohistochemistry and western blot analysis. The in vivo implications of GABRP in PDAC were tested by subcutaneous xenograft model and lung metastasis model. Bioinformatics analysis, transwell experiment and orthotopic xenograft model were used to identify the in vitro and in vivo effects of GABRP on macrophages in PDAC. ELISA, co-immunoprecipitation, proximity ligation assay, electrophysiology, promoter luciferase activity and quantitative real-time PCR analyses were used to identify molecular mechanism., Results: GABRP expression was remarkably increased in PDAC tissues and associated with poor prognosis, contributed to tumour growth and metastasis. GABRP was correlated with macrophage infiltration in PDAC and pharmacological deletion of macrophages largely abrogated the oncogenic functions of GABRP in PDAC. Mechanistically, GABRP interacted with KCNN4 to induce Ca 2+ entry, which leads to activation of nuclear factor κB signalling and ultimately facilitates macrophage infiltration by inducing CXCL5 and CCL20 expression., Conclusions: Overexpressed GABRP exhibits an immunomodulatory role in PDAC in a neurotransmitter-independent manner. Targeting GABRP or its interaction partner KCNN4 may be an effective therapeutic strategy for PDAC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of this study is to investigate the protective effects of a small molecular fraction (SMF) of Polygoni multiflori Radix Praeparata (PMRP) in a cyclophosphamide (CTX) induced anemia mouse model. Small molecular fraction of PMRP was prepared and identified by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). In pharmacology, we examined the peripheral hemogram and thymus and spleen index. The content of granulocyte-macrophage colony-stimulating factor (GM-CSF) in serum was mensurated by enzyme-linked immunosorbent assay (ELISA); The level of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) in serum and spleen tissue homogenate were detected, and glutathione peroxidase (GSH-PX) was assayed in spleen. The results show that SMF can significantly accelerate the recovery of peripheral hemogram, increase the activity of antioxidant enzymes and GM-CSF in serum and spleen. SMF also increases the number of spleen cells, improves bone marrow pathology. In conclusion, the SMF of PMRP promoted the recovery of hematopoietic function in a CTX-induced anemia mouse, which can support SMF to be used as an adjunct to chemotherapy to counteract its side effects., (Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)