Anti-inflammatory discovery of sesquiterpenoids and a jasmonic acid derivative from Artemisia stolonifera.

Eleven previously undescribed sesquiterpenoids (8-18), one undescribed jasmonic acid derivative (35) and 28 known compounds were isolated from the leaves of Artemisia stolonifera. Undescribed compounds with their absolute configurations were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction and ECD calculation. Compound 8 was identified as a rare sesquiterpenoid featuring a rearranged 5/8 bicyclic ring system, whereas compound 17 was found to be an unprecedented monocyclic sesquiterpenoid with methyl rearrangement. Evaluation of biological activity showed that compounds 1-5 and 7 displayed cytotoxicity against six tumor cells. In the meantime, compounds 11, 12, 18 and 35 exhibited inhibitory effects against LPS-stimulated NO production in RAW 264.7 macrophage cells and reduced the transcription of IL-6 and IL-1ß in a dose-dependent manner at 25, 50 and 100 µM. Moreover, the anti-inflammatory-based network pharmacology and molecular docking analyses revealed potential target proteins of 11, 12, 18 and 35.

Hepatic kynurenic acid mediates phosphorylation of Nogo-A in the medial prefrontal cortex to regulate chronic stress-induced anxiety-like behaviors in mice.

Exercise training effectively relieves anxiety disorders via modulating specific brain networks. The role of post-translational modification of proteins in this process, however, has been underappreciated. Here we performed a mouse study in which chronic restraint stress-induced anxiety-like behaviors can be attenuated by 14-day persistent treadmill exercise, in association with dramatic changes of protein phosphorylation patterns in the medial prefrontal cortex (mPFC). In particular, exercise was proposed to modulate the phosphorylation of Nogo-A protein, which drives the ras homolog family member A (RhoA)/ Rho-associated coiled-coil-containing protein kinases 1(ROCK1) signaling cascade. Further mechanistic studies found that liver-derived kynurenic acid (KYNA) can affect the kynurenine metabolism within the mPFC, to modulate this RhoA/ROCK1 pathway for conferring stress resilience. In sum, we proposed that circulating KYNA might mediate stress-induced anxiety-like behaviors via protein phosphorylation modification within the mPFC, and these findings shed more insights for the liver-brain communications in responding to both stress and physical exercise.

Three coordination polymers based on 4,4'-bis(2-methylimidazol-1-yl)diphenyl ether: Synthesis, structure and selective fluorescent sensing properties.

Three CPs [Zn2(PDA)2(BMIOPE)2·3H2O]n (1), [Co(Br-BDC)(BMIOPE)]n (2) and [Co(MIP)(BMIOPE)]n (3) were synthesized by solvothermal method based on dual-ligand strategy (H2PDA, Br-H2BDC, BMIOPE and H2MIP are 1,3-phenylenediacetic acid, 5-bromo-isophthalic acid, 4,4'-bis(2-methylimidazol-1-yl)diphenyl ether and 5-methylisophthalic acid, respectively). Complexes 1 and 3 exhibit twofold parallel interwoven sql nets. Complex 2 is 2D layer structure. The luminescence property investigations showed that complexes 1-3 could act as multi-responsive fluorescent sensors to detect UO22+, Cr2O72- and CrO42- and nitrofurantoin (NFT) through fluorescence turn-off process, presenting excellent sensitivity and selectivity. Finally, the possible fluorescent quenching mechanisms of complexes 1-3 toward the above pollutants are also further investigated by employing spectroscopic methods and quantum chemical calculations. The fluorescence lifetime measurements manifest the mechanism of fluorescence quenching is static quenching process.

Comorbidity increases the risk of pulmonary tuberculosis: a nested case-control study using multi-source big data.

BACKGROUND: Some medical conditions may increase the risk of developing pulmonary tuberculosis (PTB); however, no systematic study on PTB-associated comorbidities and comorbidity clusters has been undertaken. METHODS: A nested case-control study was conducted from 2013 to 2017 using multi-source big data. We defined cases as patients with incident PTB, and we matched each case with four event-free controls using propensity score matching (PSM). Comorbidities diagnosed prior to PTB were defined with the International Classification of Diseases-10 (ICD-10). The longitudinal relationships between multimorbidity burden and PTB were analyzed using a generalized estimating equation. The associations between PTB and 30 comorbidities were examined using conditional logistic regression, and the comorbidity clusters were identified using network analysis. RESULTS: A total of 4265 cases and 17,060 controls were enrolled during the study period. A total of 849 (19.91%) cases and 1141 (6.69%) controls were multimorbid before the index date. Having 1, 2, and ≥ 3 comorbidities was associated with an increased risk of PTB (aOR 2.85-5.16). Fourteen out of thirty comorbidities were significantly associated with PTB (aOR 1.28-7.27), and the associations differed by sex and age. Network analysis identified three major clusters, mainly in the respiratory, circulatory, and endocrine/metabolic systems, in PTB cases. CONCLUSIONS: Certain comorbidities involving multiple systems may significantly increase the risk of PTB. Enhanced awareness and surveillance of comorbidity are warranted to ensure early prevention and timely control of PTB.

Two new quinazoline alkaloids produced by Aspergillus versicolor and their antimicrobial activities.

Two new quinazoline alkaloids versicomides G-H (1 and 2), together with seven known compounds, were isolated from Aspergillus versicolor HYQZ-215 obtained from the sediment of Qarhan Salt Lake. Their structures were elucidated by NMR, HRESIMS, and quantum chemical ECD calculations data. The antimicrobial activities of these compounds were evaluated against seven agricultural pathogenic fungi and eight clinically drug-resistant bacteria.

A Chinese patient with Rothmund-Thomson syndrome.

INTRODUCTION: Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder that has been reported in all ethnicities, with several identifiable pathogenic variants. There have been reported cases indicating that RTS may lead to low birth weight in fetuses, but specific data on the fetal period are lacking. Genetic testing for RTS II is currently carried out by identifying pathogenic variants in RECQL4. METHODS: In order to determine the cause, we performed whole-genome sequencing (WGS) analysis on the patient and his parents. Variants detected by WGS were confirmed by Sanger sequencing and examined in family members. RESULTS: After analyzing the WGS data, we found a heterozygous nonsense mutation c.2752G>T (p.Glu918Ter) and a novel frameshift insertion mutation c.1547dupC (p.Leu517AlafsTer23) of RECQL4, which is a known pathogenic/disease-causing variant of RTS. Further validation indicated these were compound heterozygous mutations from parents. CONCLUSION: Our study expands the mutational spectrum of the RECQL4 gene and enriches the phenotype spectrum of Chinese RTS patients. Our information can assist the patient's parents in making informed decisions regarding their future pregnancies. This case offers a new perspective for clinicians to consider whether to perform prenatal diagnosis.

Erratum: MicroRNA-449a Inhibits Tumor Metastasis through AKT/ERK1/2 Inactivation by Targeting Steroid Receptor Coactivator (SRC) in Endometrial Cancer: Erratum.

[This corrects the article DOI: 10.7150/jca.27748.].

Variation of carbon source and sink along the environmental gradient from lakeside to highlands in Yuanchi swamp wetlands, Changbai Mountains, China.

Lacustrine wetlands have long-term carbon storage capacity and contribute significantly to regional carbon cycle, but it is unclear how its carbon sinks respond to climate change. We measured soil heterotrophic respiration carbon emissions (CO2 and CH4), vegetation carbon sequestration, and related environmental factors (temperature, water level, etc.) of five kinds of natural swamps (Phragmites marsh-L, Carex schmidtii marsh-C, Rhododendron capitatum swamp-D, Betula fruticose swamp-H, Larix olgensis swamp-LT)by using static chamber gas chromatography and relative growth equation methods, along the water environmental gradients from lakeside to highlands in Yuanchi of Changbai Mountains. We quantified the carbon source/sink function (CSS) and global warming potential (GWP) of various swamp types by estimating ecosystem net carbon balance, and revealed the variation patterns and formation mechanisms of CSS and GWP along the environmental gradients, aiming to explore the response of carbon source/sink of lakeside wetland in high altitude area to climate change. The results showed that marshes (L and C) were weak sources (-1.018 and -0.090 t C·hm-1·a-1) at the lower habitats of the water environment gradient, shrub swamps (D and H) were strong or weak sinks (1.956 and 0.239 t C·hm-1·a-1) at the middle habitats, forest swamp (LT) was strong source (-3.214 t C·hm-1·a-1) at the upper habitat. The spatial changes were promoted by water level and suppressed by soil temperature. For GWP, strong thermal radiation for marshes (from 44.682 to 59.282 t CO2·hm-1·a-1), cold radiation for shrub swamps (from -0.920 to -7.008 t CO2·hm-1·a-1), and weak thermal radiation for forest swamp (11.668 t CO2·hm-1·a-1), and their GWP was only promoted by soil temperature. Under current climate change background, marshes and forest swamp at both ends of the water environment gradient from lakeside to highlands played a positive feedback effect due to the increases of CH4 or CO2 emissions, while the middle shrub swamp still maintained a negative feedback effect in Yuanchi located the high-altitude area of the temperate Changbai Mountains.

Discovery of pyranonaphthoquinones and an eighteen-membered ring macrolide from the rhizospheric soil-derived fungus Phialocephala sp. YUD18001 by OSMAC strategy.

Two new pyranonaphthoquinones, phialoyxinones A (1) and B (2), a new eighteen-membered ring lactone, phialoyxtone (3), and five known pyranonaphthoquinone derivatives were identified from the fungus Phialocephala sp. YUD18001, which was isolated from the rhizospheric soil associated with Gastrodia elata. Their structures were unequivocally established by a comprehensive interpretation of the spectroscopic data, with the stereochemistry for 1-3 was defined by a combination of TDDFT calculations, and the DP4+ probability analysis based on NMR chemical shift calculations. All of the new compounds 1-3 were evaluated for cytotoxicity and acetylcholinesterase inhibitory, compound 2 exhibited in vitro cytotoxic activities against five human cancer cell lines (HL-60, SMMC-7721, A549, MCF-7 and SW480) with IC50 values ranging from 11.80 to 19.32 µM. Compounds 2 and 3 exhibited moderate AChE inhibitory activities. A putative biosynthetic pathway for the pyranonaphthoquinones was proposed.

Nitro-oleic acid ameliorates erectile dysfunction in a streptozotocin-induced rat model of diabetes by inhibiting oxidative stress and apoptosis and activating the NO/cGMP pathway.

The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction (DMED) a challenging endeavor. Notable factors contributing to DMED include oxidative stress, nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway activation, and apoptosis, while nitro-oleic acid (NO2-OA) has been shown to be beneficial in treating these aspects of this condition. We, herein, investigated the effects and possible mechanisms of NO2-OA on erectile function as assessed in a streptozotocin-induced rat model of diabetes. Our results revealed that the erectile function of DMED rats was significantly impaired compared with that of the control group. However, in response to 4 weeks of NO2-OA treatment, there was an improvement in erectile function. The expression of oxidative stress-related indicators was significantly increased and the NO/cGMP pathway was impaired in the DMED group. The expression of proapoptotic factors was increased, while that of antiapoptotic factors was decreased in the DMED group. Moreover, the cell morphology in the cavernous tissue of the DMED group also changed adversely. NO2-OA treatment significantly reversed all these changes observed in the DMED group. In conclusion, NO2-OA treatment partially improved erectile function in DMED rats through mechanisms that included inhibition of oxidative stress, activation of the NO/cGMP pathway, and a reduction in apoptosis.

Corrigendum: Serum CYR61 is associated with airway inflammation and is a potential biomarker for severity in chronic obstructive pulmonary disease.

[This corrects the article DOI: 10.3389/fmed.2021.781596.].

Influence of the Surface State on the Interfacial Bonding Strength of the Cold-Rolled Brass/Carbon Steel Composite.

To improve the interfacial bonding of dissimilar composites, the interaction mechanism between the surface state and severe plastic deformation to strengthen the interfacial bonding strength was revealed. In this study, the different surface states of the steel strip were designed by louver blade grinding (LBG) and diamond bowl grinding (DBG), and the cold-rolled composite method was developed to prepare the brass/carbon steel composite strips. The results show that the steel surface after DBG has a large roughness of 9.79 µm, a hard hardening layer of 6.2 GPa, and high cleanliness of 1.34 atomic % oxygen content, while that after LBG has a roughness of 1.31 µm, a hardening layer of 4.2 GPa, and an oxygen content of 2.37 atomic %. The large roughness promotes the breaking of the hardening layer; the hardening layer is beneficial to obtain sufficient interfacial stress to expose the fresh metal; and the high cleanliness reduces the barrier to the fresh metal and contributes to the bonding of the fresh metal. The interface of the cold-rolled brass/carbon steel composite strip after LBG and DBG is mechanical bonding and metallurgical bonding, respectively. In the process of the cold-rolling composite, large shear deformation occurs at the interface of brass and steel, resulting in a high concentration of vacancy and dislocation defects, which provides a channel for interdiffusion of atoms at the interface. Under the diffusion driving force provided by the cold-rolling shear deformation heat, a nanodiffusion layer with a thickness of 60 nm and high interfacial bond strength was formed.

[LC-MS analysis of 2-(2-phenylethyl) chromones in sodium chloride-treated suspension cells of Aquilaria sinensis].

Qualitative and quantitative analysis of 2-(2-phenylethyl) chromones in sodium chloride(NaCl)-treated suspension cells of Aquilaria sinensis was conducted by UPLC-Q-Exactive-MS and UPLC-QQQ-MS/MS. Both analyses were performed on a Waters T3 column(2.1 mm×50 mm, 1.8 µm) with 0.1% formic acid aqueous solution(A)-acetonitrile(B) as mobile phases at gradient elution. MS data were collected by electrospray ionization in positive ion mode. Forty-seven phenylethylchromones was identified from NaCl-treated suspension cell samples of A. sinensis using UPLC-Q-Exactive-MS, including 22 flindersia-type 2-(2-phenylethyl) chromones and their glycosides, 10 5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones and 15 mono-epoxy or diepoxy-5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones. Additionally, 25 phenylethylchromones were quantitated by UPLC-QQQ-MS/MS. Overall, the rapid and efficient qualitative and quantitative analysis of phenylethylchromones in NaCl-treated suspension cells of A. sinensis by two LC-MS techniques, provides an important reference for the yield of phenylethylchromones in Aquilariae Lignum Resinatum using in vitro culture and other biotechnologies.

Qualitative analysis on the transdermal absorption from the dichloromethane extract of the Sambucus adnata wall. based on UPLC-Q-Exactive Orbitrap/MS.

Sambucus adnata Wall.(SAW) has been used to treat osteoarthritis by the Yi nationality in China. The present study established an overall identification strategy based on ultra-high performance liquid chromatography-tandem Q-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap/MS) method to characterize the multiple chemical constituents of SAW before and after percutaneous penetration. Nineteen compounds, including triterpenoids, fatty acids, lignans, flavonoid, and amide, were tentatively identified in the dichloromethane extract of SAW, while fourteen ingredients penetrated the skin. Among them, eleven components were reported for the first time in SAW.

A Ni(II) Coordination Polymer as a Multifunctional Luminescent Sensor for Detection of UO22+, Cr2O72-, CrO42- and Nitrofurantoin.

A new Ni coordination polymer [Ni(MIP)(BMIOPE)]n (1) was constructed (BMIOPE = 4,4'-bis(2-methylimidazol-1-yl)diphenyl ether, and H2MIP = 5-methylisophthalic acid), possessing two-dimensional (2D) twofold parallel interwoven net structure with a 44∙62 point symbol. Complex 1 has been successfully obtained based on mixed-ligand strategy. The fluorescence titration experiments revealed that complex 1 could act as multifunctional luminescent sensor to simultaneously detect UO22+, Cr2O72- and CrO42-, and NFT (nitrofurantoin). The limit of detection (LOD) values for complex 1 are 2.86 × 10-5, 4.09 × 10-5, 3.79 × 10-5 and 9.32 × 10-5 M for UO22+, Cr2O72-, CrO42- and NFT. The Ksv values are 6.18 × 103, 1.44 × 104, 1.27 × 104 and 1.51 × 104 M-1 for NFT, CrO42-, Cr2O72- and UO22+. Finally, the mechanism of its luminescence sensing is studied in detail. These results manifest that complex 1 is a multifunctional sensor for sensitive fluorescent UO22+, Cr2O72-, CrO42- and NFT detection.

Geographical distribution of Ixodes persulcatus and associated pathogens: Analysis of integrated data from a China field survey and global published data.

The increasing incidence and range expansion of tick-borne diseases have caused global threats to human and animal health under the background of climate and socioeconomic changes. As an efficient vector in transmission of tick-borne diseases, a growing burden caused by Ixodes persulcatus and associated pathogens could not be underestimated. This study summarized the distribution, hosts, and pathogens of I. persulcatus, and predicted the suitable habitats of this tick species worldwide. An integrated database involving a field survey, reference book, literature review, and related website was constructed. Location records of I. persulcatus and associated pathogens were incorporated into distribution maps using ArcGIS software. Positive rates for I. persulcatus-associated agents were estimated by meta-analysis. The global distribution of the tick species was predicted using Maxent model. I. persulcatus was distributed in 14 countries across the Eurasian continent, involving Russia, China, Japan, and several Baltic Sea states, which ranged between 21°N to 66°N. The tick species fed on 46 species of hosts, and 51 tick-borne agents could be harbored by I. persulcatus. The predictive model showed that I. persulcatus could be predominantly distributed in northern Europe, western Russia, and northern China. Our study fully clarified the potential public health risks posed by I. persulcatus and I. persulcatus-borne pathogens. Surveillance and control measures of tick-borne diseases should be enhanced to promote the health of humans, animals, and ecosystems.

Clinical outcomes of pulmonary hypertension in pregnancy among women with congenital heart disease in China.

OBJECTIVE: Pulmonary arterial hypertension (PAH) increases the risk for perinatal women and newborns, especially in women with congenital heart disease (CHD). We explored the maternal, perinatal, and postneonatal outcomes of PAH in pregnant women with CHD in China. METHODS: A total of 95 pregnant women with CHD-PAH in Beijing Anzhen Hospital from 2009 to 2013 were included retrospectively. We described their characteristics and examined the associations between the grade of PAH and maternal, perinatal, and postneonatal outcomes. RESULTS: The New York Heart Association (NYHA) classification grade, delivery mode, and infant outcomes in CHD-PAH patients were analyzed. Overall 95 patients with CHD-PAH, there were 17 patients in mild group(17.7%), 27 patients in moderate group (28.1%), and 51 patients in severe group (53.1%)。The CHD patients with mild PAH, were mostly NYHA class I-II and CHD patients with severe PAH were NYHA class II-IVs. Cesarean section (67.7%) was the most common method of delivery. The rate of therapeutic abortion in the severe group (76.9%) was obviously higher than that in other groups (11.5% in mild group and moderate group respectively), whereas there was no term delivery in severe group, with 2 cases in mild group and moderated group respectively . The rates of heart failure and therapeutic abortion in pregnant women were positively associated with the severity of PAH. The rate of term delivery was higher in patients whose CHD had been corrected by cardiac surgery (83.3%) before pregnancy. CONCLUSION: Patients with severe PAH have poor cardiac adaptability, poor maternal and fetal outcomes, and are contraindicated during pregnancy. Patients with mild PAH are not absolutely contraindicated during pregnancy, but their heart burden increases significantly in the third trimester. Patients in mid-gestation should preferentially be delivered by cesarean section. When pregnant patients prefer to continue pregnancy, their close monitoring is essential. We provide useful data for guiding management of pregnancy and delivery in patients with CHD in China.