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Background: Sepsis is a life-threatening severe inflammatory reaction caused by the host's dysregulated response to infection. Sepsis-induced myocardial dysfunction (SIMD) has been confirmed to occur in 50 % of patients with septic shock. Currently, the pathophysiological mechanism of SIMD is complex, and there is no targeted treatment. Elabela is another endogenous ligand of Aplnr (APJ). The protective effect of APJ on the heart has been proven. Elabela (Ela) has been shown to have a variety of cardiovascular protective effects. However, there are no studies demonstrating the protective effect of Ela-APJ axis on SIMD., Materials and Methods: In vivo, C57BL/J mice were injected subcutaneously with 1 mg/kg/d Ela for 2 weeks, and in vitro, AC16 cells were treated with 1 μM Ela for 24 h. A 7-0 thread was used to ligate the distal end of the cecum, followed by puncture with a 20-gauge needle. Once a small amount of fluid leaks out, release the cecum back into the abdominal cavity. We measured the survival rates of the mice, performed ultrasound on their hearts, and evaluated the effects of the treatments. The serum and cell supernatant were extracted to detect myocardial injury markers and pyroptosis-related indicators. Western blotting was used to detect autophagy and pyroptosis-related protein. Molecular docking and other experiments were also used to detect changes in related proteins., Results: In vivo, Ela significantly improved the survival rate of septic mice, improved cardiac function, and reduced the production of myocardial injury markers, oxidative stress and pyroptosis. In vitro, Ela unblocked autophagy flow by affecting TFEB transcription. Autophagy reduces inflammation and oxidative stress by selectively degrading inflammatory bodies and ultimately alleviates pyroptosis., Conclusion: We had demonstrated for the first time that in sepsis, Ela promoted the degradation of inflammasomes, reduced oxidative stress, and inhibited the occurrence of pyroptosis by unblocking autophagy flow., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Diabetic cardiomyopathy(DCM) is a chronic complication of diabetes mellitus that leads to cardiac damage in the later stages of the disease, and its pathogenesis is complex, involving metabolic disorders brought about by a variety of aberrant alterations such as endoplasmic reticulum stress, oxidative stress, inflammation, and apoptosis, defects in cardiomyocyte Ca~(2+) transporter, and myocardial fibrosis. Currently, there is a lack of specific diagnosis and treatment in the clinic. Autophagy is a highly conserved scavenging mechanism that removes proteins, damaged organelles or foreign contaminants and converts them into energy and amino acids to maintain the stability of the intracellular environment. Inhibition of autophagy can cause harmful metabolites to accumulate in the cell, while over-activation of autophagy can disrupt normal cellular structures and cause cell death. Prolonged high glucose levels disrupt cardiomyocyte autophagy levels and exacerbate the development of DCM. The protective or detrimental effects of autophagy on cells ring true with the traditional Chinese medicine theory of healthy Qi and pathogenic Qi. Autophagy in the physiological state of the removal of intracellular substances and the generation of substances beneficial to the survival of cells is the inhibition of pathogenic Qi to help the performance of healthy Qi, so the organism is healthy. In the early stages of the disease, when autophagy is impaired and incapable of removing waste substances, pathogenic Qi is prevalent; In the later stages of the disease, excessive activation of autophagy can destroy normal cells, leading to a weakening of healthy Qi. Traditional Chinese medicine has the advantage of targeting multiple sites and pathways. Studies in recent years have confirmed that traditional Chinese medicine monomers or formulas can target autophagy, promote the restoration of autophagy levels, maintain mitochondrial and endoplasmic reticulum homeostasis, and reduce oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis in order to prevent and control DCM. This study provides a review of the relationship between autophagy and DCM and the intervention of traditional Chinese medicine in autophagy for the treatment of DCM, with a view to providing new clinical ideas and methods for the treatment of DCM with traditional Chinese medicine.

Twelve undescribed 2-(2-phenethyl)chromone dimers (1-12) were isolated from EtOAc extract of agarwood originating from Aquilaria filaria in the Philippines, guided by a UHPLC-MS analysis. Their structures were elucidated by 1D NMR, 2D NMR, and HR-ESI-MS spectra. The absolute configuration of 2-(2-phenylethyl)chromone dimers was determined by single-crystal X-ray diffraction analysis and comparison of the experimental and calculated ECD spectra. Compounds 1, 2, 5 and 9-12 exhibited potent to moderate anti-inflammatory activity with IC 50 values in the range of 22.43 ± 0.86 to 53.88 ± 4.06 μM., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aims: Cardiovascular health (CVH) has been proven to reduce cardiovascular disease burden and mortality, but data are lacking regarding cardiac arrhythmias. The aim of this study was to assess the association between CVH metrics and atrial fibrillation/flutter (AF), ventricular arrhythmias, and bradyarrhythmias., Methods and Results: This study analysed data from the Atherosclerosis Risk in Communities (ARIC) cohort, with participants recruited from four different communities across the United States. Cardiovascular health metrics were scored at baseline (1987-89) following the American Heart Association's recommendations and categorized as poor, intermediate, or ideal. Arrhythmia episodes were diagnosed by International Classification of Diseases (ICD)-9 code. Adjusted associations were estimated using Cox models and event rates and population attributable fractions were calculated by CVH metrics category. The study population consisted of 13 078 participants, with 2548 AF, 1363 ventricular arrhythmias, and 706 bradyarrhythmias occurred. The adjusted hazard ratios (HRs) for ideal (vs. poor) CVH metrics were 0.59 [95% confidence interval (CI): 0.50-0.69] for AF, 0.38 (95% CI: 0.28-0.51) for ventricular arrhythmias, and 0.70 (95% CI: 0.51-0.97) for bradyarrhythmia. The risk of incident arrhythmias decreased steadily as the CVH metrics improved from 0 to 14 scores. The adjusted population attributable fractions were calculated to be 29.9% for AF, 54.4% for ventricular arrhythmias, and 21.9% for bradyarrhythmia, respectively. The association between CVH metrics and incident arrhythmias was also seen in people who remained free of coronary heart disease over the follow-up., Conclusion: Achieving ideal CVH metrics recommendations by AHA in midlife was associated with a lower risk of incident arrhythmias later in life., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Elevated blood pressure (BP) is reportedly associated with an increased risk of atrial fibrillation (AF). However, the association between cumulative BP exposure in midlife and incident AF in mid-to-late life remains unclear., Methods and Results: Participants enrolled in the ARIC (Atherosclerosis Risk in Communities) study with 4 consecutive BP measurements and no prevalent AF at baseline were included. Cumulative BP was calculated as the area under the curve from visit 1 to visit 4. Incident AF was identified by study visit ECGs, hospital discharge codes, or death certificates. A total of 9892 participants were included (44.6% men and mean age 62.9±5.7 years at visit 4) with 1550 (15.7%) individuals who developed new-onset AF during an average follow-up of 15.4 years. The incidence rates of AF per 1000 person-years across the 4 quartiles of cumulative systolic BP were 7.9, 9.2, 12.5, and 16.9, respectively. After multivariable adjustment, the hazard ratios for incident AF among participants in the highest quartile of cumulative systolic BP, pulse pressure, and mean arterial pressure were 1.48 (95% CI, 1.27-1.72), 1.81 (95% CI, 1.53-2.13), and 1.22 (95% CI, 1.05-1.41), respectively, compared with those in the lowest quartile. The addition of cumulative systolic BP or pulse pressure slightly improved the ability to predict new-onset AF., Conclusions: Higher exposure to cumulative systolic BP, pulse pressure, and mean arterial pressure was significantly associated with increased risk of incident AF.

Due to the reversible nature of coordination bonds and solvation effect, coordination self-assembly pathways are often difficult to elucidate experimentally in solution, as intermediates and products are in constant equilibration. The present study shows that some of these transient and high-energy self-assembly intermediates can be accessed by means of ball-milling approaches. Among them, highly aqueous-unstable Pd 3 L1 1 and Pd 6 L1 4 open-cage intermediates of the framed Fujita Pd 6 L1 4 cage and Pd 2 L2 2 , Pd 3 L2 1 and Pd 4 L2 2 intermediates of Mukherjee Pd 6 L2 4 capsule are successfully trapped in solid-state, where Pd=tmedaPd 2+ , L1=2,4,6-tris(4-pyridyl)-1,3,5-triazine and L2=1,3,5-tris(1-imidazolyl)benzene). Their structures are assigned by a combination of solution-based characterization tools such as standard NMR spectroscopy, DOSY NMR, ESI-MS and X-ray diffraction. Collectively, these results highlight the opportunity of using mechanochemistry to access unique chemical space with vastly different reactivity compared to conventional solution-based supramolecular self-assembly reactions., (© 2023 Wiley-VCH GmbH.)

Background: Health care resource utilization (HCRU) and costs are important metrics of health care burden, but they have rarely been explored in the setting of cardiac ion channelopathies., Hypothesis: This study tested the hypothesis that attendance-related HCRUs and costs differed between patients with Brugada syndrome (BrS) and congenital long QT syndrome (LQTS)., Methods: This was a retrospective cohort study of consecutive BrS and LQTS patients at public hospitals or clinics in Hong Kong, China. HCRUs and costs (in USD) for Accident and Emergency (A&E), inpatient, general outpatient and specialist outpatient attendances were analyzed between 2001 and 2019 at the cohort level. Comparisons were made using incidence rate ratios (IRRs [95% confidence intervals])., Results: Over the 19-year period, 516 BrS (median age of initial presentation: 51 [interquartile range: 38-61] years, 92% male) and 134 LQTS (median age of initial presentation: 21 [9-44] years, 32% male) patients were included. Compared to LQTS patients, BrS patients had lower total costs (2 008 126 [2 007 622-2 008 629] vs. 2 343 864 [2 342 828-2 344 900]; IRR: 0.857 [0.855-0.858]), higher costs for A&E attendances (83 113 [83 048-83 177] vs. 70 604 [70 487-70 721]; IRR: 1.177 [1.165-1.189]) and general outpatient services (2,176 [2,166-2,187] vs. 921 [908-935]; IRR: 2.363 [2.187-2.552]), but lower costs for inpatient stay (1 391 624 [1 391 359-1 391 889] vs. 1 713 742 [1 713 166-1 714 319]; IRR: 0.812 [0.810-0.814]) and lower costs for specialist outpatient services (531 213 [531 049-531 376] vs. 558 597 [558268-558926]; IRR: 0.951 [0.947-0.9550])., Conclusions: Overall, BrS patients consume 14% less health care resources compared to LQTS patients in terms of attendance costs. BrS patients require more A&E and general outpatient services, but less inpatient and specialist outpatient services than LQTS patients., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Objective: To investigate the protective effect and its possible mechanism of A-kinase anchored protein 1 (AKAP1) on the myocardial injury induced by highland hypobaric hypoxia. Methods: From January 2021 to May 2022, male C57BL/6 SPF grade mice were divided into wild type control (WT) group and highland hypobaric hypoxia (HH) group with 6 mice in each group. HH group simulated 6000 m altitude with low pressure oxygen chamber for 4 weeks to build the model. Primary myocardial cells of SD rats were divided into normoxia control group and hypoxia experimental group ( n =3). Cell models were constructed in a three-gas hypoxia incubator with 1% oxygen concentration for 24 h. AKAP1 protein and mRNA expression in myocardial tissue and cells were detected by western blotting, immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR). After myocardial point injection of the AKAP1 or the control adenovirus, the mice were divided into 3 groups ( n =6) : WT group, highland hypobaric hypoxia overexpression control group (HH+Ad-Ctrl group) and highland hypobaric hypoxia overexpression experimental group (HH+Ad-AKAP1 group). The cardiac function of mice was detected by noninvasive M-type ultrasonic cardiomotive, myocardial fibrosis was detected by Masson and Sirius Red staining, and cardiomyocyte hypertrophy was detected by wheat germ agglutinin. After the expression of AKAP1 in primary cardiomyocytes was downregulated by siRNA and upregulated by adenovirus, the cells were divided into three groups ( n =3) : normoxia control group, hypoxia interference control group (hypoxia+siCtrl group), hypoxia AKAP1 knockdown group (hypoxia+siAKAP1 group) ; normoxia control group, hypoxia overexpression control group (hypoxia+Ad-Ctrl group), hypoxia AKAP1 overexpression group (hypoxia+Ad-AKAP1 group). Apoptosis was detected by flow cytometry, AKAP1, apoptosis-related protein and mRNA expression levels were detected by western blotting and qPCR, mitochondrial membrane potential was detected by JC-1 staining, and mitochondrial reactive oxygen specie (ROS) level was detected by MitoSOX. Results: The expression of AKAP1 in cardiac muscle of HH group was lower than that in the WT group, and the expression of AKAP1 in hypoxia experimental group was lower than that in normoxia control group ( P <0.01). Compared with WT group, the left ventricular ejection fraction and fraction shortening of left ventricle in HH+Ad-Ctrl group were decreased ( P <0.01), myocardial fibrosis and hypertrophy were aggravated ( P <0.01), and the expression of B-cell lymphoma-2 (BCL-2) was decreased, the expressions of BCL-2-associated X protein (BAX), Caspase 3 and Caspase 9 were increased ( P <0.01). After AKAP1 overexpression, compared with HH+Ad-Ctrl group, the left ventricular ejection fraction and left ventricular fraction shortening were increased in HH+Ad-AKAP1 group ( P <0.01), myocardial fibrosis and hypertrophy were reduced ( P <0.01), and the expression of BCL-2 was increased, the expressions of BAX, Caspase 3 and Caspase 9 were decreased ( P <0.01). Compared with normoxia control group, the expression of BCL-2 in hypoxia+siCtrl group was decreased, the expressions of BAX, Caspase 3, Caspase 9 were increased, the apoptosis level was increased ( P <0.01), the mitochondrial membrane potential was decreased and the production of ROS was increased ( P <0.01). After AKAP1 knockdown, compared with hypoxia+siCtrl group, the expression of BCL-2 in hypoxia+siAKAP1 group was decreased, the expressions of BAX, Caspase 3, Caspase 9 were increased, the apoptosis level was increased ( P <0.01), mitochondrial membrane potential was decreased, and the production of ROS was increased ( P <0.01). After AKAP1 overexpression, compared with hypoxia+Ad-Ctrl group, the expression of BCL-2 in hypoxia+Ad-AKAP1 group was increased, the expressions of BAX, Caspase 3 and Caspase 9 were decreased ( P <0.05), the apoptosis level was decreased ( P <0.01), and the mitochondrial membrane potential was enhanced, and the production of ROS was decreased ( P <0.01) . Conclusion: The downregulation of AKAP1 in cardiomyocytes under highland hypobaric hypoxia may lead to the decrease of mitochondrial membrane potential and the increase of ROS generation, leading to the apoptosis of cardiomyocytes, and thus aggravating the myocardial injury at highland hypobaric hypoxia.

Precise control in reaction selectivity is the goal in modern organic synthesis, and it has been widely studied throughout the synthetic community. In comparison, control of divergent reactivity of a given reagent under different reaction conditions is relatively less explored aspect of chemical selectivity. We herein report an unusual reaction between polycyclic aromatic hydrocarbons and periodic acid H 5 IO 6 ( 1 ), where the product outcome is dictated by the choice of reaction conditions. That is, reactions under solution-based condition give preferentially C-H iodination products, while reactions under solvent-free mechanochemical condition provide C-H oxidation quinone products. Control experiments further indicated that the iodination product is not a reaction intermediate toward the oxidation product and vice versa. Mechanistic studies unveiled an in situ crystalline-to-crystalline phase change in 2 during ball-milling treatment, where we assigned it as a polymeric hydrogen-bond network of 1 . We believe that this polymeric crystalline phase shields the more embedded electrophilic I ═O group of 1 from C-H iodination and bias a divergent C-H oxidation pathway (with I═ O ) in the solid state. Collectively, this work demonstrates that mechanochemistry can be employed to completely switch a reaction pathway and unmask hidden reactivity of chemical reagents.

Four new 2-(2-phenethyl)chromone dimers (1-4) were isolated from EtOAc extract of agarwood originating from Aquilaria filaria from Philippines. Their structures were elucidated by spectroscopic analysis (1D and 2D NMR, and HRESIMS) and comparison of the experimental and computed ECD curves. Compounds 1-4 exhibited inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with IC 50 values in the range from 33.94 to 57.53 μM., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective Traditional Chinese medicine (TCM) prescriptions have been used to cure diseases in China for thousands of years, in which many TCM herbs have no definite common quantity. Some key TCM herbs are commonly used and thus deserve in-depth investigations based on a more acceptable classification method. This study analyzes whether TCM prescriptions follow Zipf's law and attempts to obtain the thresholds of key TCM herbs based on the application of Zipf's law. Methods A total of 84,418 TCM prescriptions were collected and standardized. We tested whether Zipf's law and Zipf's distribution fit the Chinese herb distributions. A linear fitting experiment was performed to verify the relationship between the frequency distribution and frequency of TCM herbs. Results The distribution of TCM herbs in TCM prescriptions conformed to Zipf's law. Accordingly, the thresholds were obtained for the key TCM herbs. Conclusion The distribution of TCM herbs in TCM prescriptions follows Zipf's law.

Effects of octenylsuccinate (OS) starch on body composition and intestinal environment in high-fat diet-fed mice were investigated. C57BL/6J mice were treated with a regular-fat (RF) diet, a high-fat (HF) diet, or a high-fat diet supplemented with OS starch (HFOSS). Fecal short-chain fatty acids (SCFAs) were quantified using gas chromatography, and the fecal microbiota profile was analyzed by 16S rDNA sequencing. One-way ANOVA and metastats analysis were performed for statistical analysis. After 22 weeks of feeding, mice in the HFOSS group had significantly lower body weight, body fat, liver weight, and cumulative food intake than those in the HF group but higher than that of the RF group. Fecal total SCFA, acetic, propionic, and butyric acid concentrations were significantly higher in the HFOSS group than that in the HF and RF groups. OS starch intervention increased the relative abundance of Parabacteroides , Alistipes , and Ruminiclostridium&#95;5 and decreased that of Tyzzerella , Oscillibacter , Desulfovibrio , and Anaerotruncus compared with the RF and HF groups. The relative abundance of Lachnospiraceae&#95;UCG-006 in the HFOSS group was lower than that in the HF group but higher than that in the RF group. In conclusion, OS starch prevents fat accumulation in high-fat diet-fed mice and might provide potential health benefits due to its fermentability in the gut and its ability to regulate gut microbial community structure.

Zn-based alloys are considered as new kind of potential biodegradable implanted biomaterials recently. The difficulty of metal implanted biomaterials and bone tissue integration seriously affects the applications of metal implanted scaffolds in bone tissue-related fields. Herein, we self-designed Zn0.8Mn and Zn0.8Mn0.1Li alloys and CaP coated Zn0.8Mn and Zn0.8Mn0.1Li alloys, then evaluated the degradation property and cytocompatibility. The results demonstrated that the Zn0.8Mn0.1Li alloys had profoundly modified the degradation property and cytocompatibility, but Zn0.8Mn0.1Li alloys had particularly adverse effects on the surface morphology of osteoblasts. The results furtherly showed that the CaP-coated Zn0.8Mn and Zn0.8Mn0.1Li alloys scaffold had better biocompatibility, which would further guarantee the biosafety of this new kind of biodegradable Zn-based alloys implants for future clinical applications., 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 © 2022 Qiang, Lv, Hou, Luo, Li, Liu, Meng, Du, Zhang, Chen and Liu.)

Background: The interaction of the pulmonary vein (PV) and putative nonpulmonary triggers of atrial fibrillation (AF) remains unclear and has yet to translate into patient-tailored ablation strategies., Objective: The purpose of this study was to use noncontact mapping to detail the global conduction patterns in paroxysmal and persistent AF and how they are modified during PV ablation., Methods: Forty patients during AF ablation underwent mapping using a noncontact catheter (AcQMap, Acutus Medical, Inc., Carlsbad, CA) before and after PV isolation (PVI). Propagation history maps were analyzed postprocedure for each patient to categorize conduction patterns into focal, organized reentrant, and disorganized patterns (F-Patterns, O-Patterns, and D-Patterns, respectively)., Results: Activation patterns identified by using a noncontact mapping system can be subclassified from 3 main patterns into subtypes (macroreentrant and localized reentrant [MR and LR] subtypes and disorganized 1 and disorganized 2 [D1 and D2] subtypes). Persistent AF demonstrated more D-Patterns and less O-Patterns and F-Patterns than did paroxysmal AF. In addition, patients with PAF inducible after PVI demonstrated a higher region number and higher prevalence of MR subtypes than did those noninducible. PVs remained the critical region and included almost one-third of all patterns across any AF types. PVI was effective to eliminate PV-related functional phenotypes and affected recurrence with other patterns., Conclusion: Activation patterns identified using AcQMap can be classified into 3 main patterns (F-Patterns, O-Patterns, and D-Patterns) as well as subtypes (MR and LR subtypes and D1 and D2 subtypes). PerAF was different from PAF in demonstrating a higher region number and higher prevalence of D-Patterns but a lower region number and lower prevalence of O-Patterns and F-Patterns., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

It is a new hot pot in tissue engineering and regenerative medicine to study the effects of physicochemical properties of implanted biomaterials on regulating macrophage polarization to promote bone regeneration. In this study, we designed and fabricated mineralized collagen (MC) with different microporous structures via in vitro biomimetic mineralization method. The microporous structures, mechanical properties, shore hardness and water contact angle measurements were tested. Live/dead cell staining, CCK-8 assay, phalloidine staining, staining of focal adhesions were used to detect cell behavior. ELISA, qRT-PCR, ALP, and alizarin red staining (ARS) were performed to appraise osteogenic differentiation and investigated macrophage response and their subsequent effects on the osteogenic differentiation. The results showed that RAW264.7 and MC3T3-E1 cells were able to survive on the MC. MC with the microporous structure of approximately 84 μm and 70%-80% porosity could promote M2 macrophage polarization and increase the expression level of TGF-β and VEGF. Moreover, the gene expression of the osteogenic markers ALP, COL-1, and OCN increased. Therefore, MC with different microporous structures mediated osteoimmunomodulation in bone regeneration. These data will provide a new idea of biomaterials inducing bone repair and direct the optimal design of novel immune biomaterials, development, and rational usage., 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 © 2022 Li, Luo, Lv, Qiang, Hou, Liu, Meng, Zhang, Liu and Zhang.)

Previous assessments of the effectiveness of protected areas (PAs) focused primarily on changes in human pressure over time and did not consider the different human-pressure baselines of PAs, thereby potentially over- or underestimating PA effectiveness. We developed a framework that considers both human-pressure baseline and change in human pressure over time and assessed the effectiveness of 338 PAs in China from 2010 to 2020. The initial state of human pressure on PAs was taken as the baseline, and changes in human pressure index (HPI) were further analyzed under different baselines. We used the random forest models to identify the management measures that most improved effectiveness in resisting human pressure for the PAs with different baselines. Finally, the relationships between the changes in the HPI and the changes in natural ecosystems in PAs were analyzed with different baselines. Of PAs with low HPI baselines, medium HPI baselines, and high HPI baselines, 76.92% (n=150), 11.11% (n=12), and 22.86% (n=8) , respectively, showed positive effects in resisting human pressure. Overall, ignoring human-pressure baselines somewhat underestimated the positive effects of PAs, especially for those with low initial human pressure. For PAs with different initial human pressures, different management measures should be taken to improve effectiveness and reduce threats to natural ecosystems. We believe our framework is useful for assessing the effectiveness of PAs globally, and we recommend it be included in the Convention on Biological Diversity Post-2020 Strategy., (© 2022 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Coronoids as polycyclic aromatic macrocycles enclosing a cavity have attracted a lot of attention due to their distinctive molecular and electronic structures. They can be also regarded as nanoporous graphene molecules whose electronic properties are critically dependent on the size and topology of their outer and inner peripheries. However, because of their synthetic challenges, the extended hexagonal coronoids with zigzag outer edges have not been reported yet. Here, we report the on-surface synthesis of C144 hexagonal coronoid with outer zigzag edges on a designed precursor undergoing hierarchical Ullmann coupling and cyclodehydrogenation on the Au(111) surface. The molecular structure is unambiguously characterized by bond-resolved noncontact atomic force microscopy imaging. The electronic properties are further investigated by scanning tunneling spectroscopy measurements, in combination with the density functional theory calculations. Moreover, the values of the harmonic oscillator model of aromaticity are derived from calculations that suggest that the molecular structure is ideally represented by Clar's model. Our results provide approaches toward realizing a hexagonal coronoid with zigzag edges, potentially inspiring fabrication of hexagonal zigzag coronoids with multiple radical characters in the future.

Gap- polymerase chain reaction (PCR), reverse dot-blot assay (RDB), real-time PCR based multicolor melting curve analysis (MMCA assay), multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing are conventional methods to diagnose thalassemia but all of them have limitations. In this study, we applied single-molecule real-time (SMRT) sequencing following multiplex long-range PCR to uncover rare mutations in nine patients and their family members. The patients with different results between Gap-PCR and MMCA assay or with phenotype not matching genotype were included. Using SMRT sequencing, we first identified the carriers with ααα anti3.7 /HKαα, -α 762bp α/αα (chr16:172,648-173,409), αα fusion /α QS α (in a trans configuration), two cases with novel gene rearrangements and another case with a novel 341 bp insertion in α-globin gene cluster, respectively. One carrier with -- SEA /ααα anti4.2 , and two carriers with the coexistence of globin variant and an α-globin gene duplication were also found. Most importantly, we could determine two defects in α-globin gene cluster being a cis or trans configuration in a single test. Our results showed that SMRT has great advantages in detection of α-globin gene triplications, rare deletions and determination of a cis or trans configuration. SMRT is a comprehensive and one-step method for thalassemia screening and diagnosis, especially for detection of rare thalassemia mutations., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Recently, polymer mechanochemistry has attracted much scientific interest due to its potential to develop degradable polymers. When the two ends of a polymer chain experience a linear pulling stress, molecular strain builds up, at sufficiently strong force, a bond scission of the weakest covalent bond results. In contrast, bond-breaking events triggered by conformational stress are much less explored. Here, we discovered that a Zn salen complex would undergo conformational switching upon allosteric complexation with alkanediammonium guests. By controlling the guest chain length, the torsional strain experienced by Zn complex can be modulated to induce bond cleavage with chemical stimulus, and reactivity trend is predicted by conformational analysis derived by DFT calculation. Such strain-release reactivity by a Zn(salen) complex initiated by guest binding is reminiscent of conformation-induced reactivity of enzymes to enable chemical events that are otherwise inhibited., (© 2022 Wiley-VCH GmbH.)

Pd-based molecular square Pd 4 L 4 and triangle Pd 3 L 3 represent the molecular ancestors of metal-coordination polyhedra that have been an integral part of the field for the last 30 years. Conventional solution-based reactions between cis-protected Pd ions and 2,2'-bipyridine exclusively give Pd 4 L 4 and/or Pd 3 L 3 as the sole products. We herein show that, under solvent-free mechanochemical conditions, the self-assembly energy landscape can be thermodynamically manipulated to form an elusive cyclic dimer Pd 2 L 2 for the first time. In the absence of solvent, Pd 2 L 2 is indefinitely stable in the solid-state, but converts rapidly to its thermodynamic products Pd 3 L 3 and Pd 4 L 4 in solution, confirming Pd 2 L 2 as a short-lived kinetic species in the solution-based self-assembly process. Our results highlight how mechanochemistry grants access to a vastly different chemical space than available under conventional solution conditions. This provides a unique opportunity to isolate elusive species in self-assembly processes that are too reactive to both "see" and "capture"., (© 2022 Wiley-VCH GmbH.)

Gangrenous cholecystitis is a kind of acute cholecystitis, whose course of disease progresses rapidly, early diagnosis is difficult and mortality is high, and clinicians are prone to misdiagnosis and missed diagnosis in clinical work.However, gangrenous cholecystitis has been ignored in various guidelines.This paper systematically summarized the pathogenesis, pathological manifestations, epidemiology, clinical diagnosis and treatment of gangrenous cholecystitis, hoping to provide a complete and clear diagnosis and treatment process for clinicians.

Adhesion G-protein-coupled receptors (aGPCRs) are important for organogenesis, neurodevelopment, reproduction and other processes 1-6 . Many aGPCRs are activated by a conserved internal (tethered) agonist sequence known as the Stachel sequence 7-12 . Here, we report the cryogenic electron microscopy (cryo-EM) structures of two aGPCRs in complex with G s : GPR133 and GPR114. The structures indicate that the Stachel sequences of both receptors assume an α-helical-bulge-β-sheet structure and insert into a binding site formed by the transmembrane domain (TMD). A hydrophobic interaction motif (HIM) within the Stachel sequence mediates most of the intramolecular interactions with the TMD. Combined with the cryo-EM structures, biochemical characterization of the HIM motif provides insight into the cross-reactivity and selectivity of the Stachel sequences. Two interconnected mechanisms, the sensing of Stachel sequences by the conserved 'toggle switch' W 6.53 and the constitution of a hydrogen-bond network formed by Q 7.49 /Y 7.49 and the P 6.47 /V 6.47 φφG 6.50 motif (φ indicates a hydrophobic residue), are important in Stachel sequence-mediated receptor activation and G s coupling. Notably, this network stabilizes kink formation in TM helices 6 and 7 (TM6 and TM7, respectively). A common G s -binding interface is observed between the two aGPCRs, and GPR114 has an extended TM7 that forms unique interactions with G s . Our structures reveal the detailed mechanisms of aGPCR activation by Stachel sequences and their G s coupling., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Researches using resting-state functional magnetic resonance imaging (rs-fMRI) have applied different regional measurements to study the intrinsic brain activity (IBA) of patients with Parkinson's disease (PD). Most previous studies have only examined the static characteristics of IBA in patients with PD, neglecting the dynamic features. We sought to explore the concordance between the dynamics of different rs-fMRI regional indices. This study included 31 healthy controls (HCs) and 57 PD patients to calculate the volume-wise (across voxels) and voxel-wise (across periods) concordance using a sliding time window approach. This allowed us to compare the concordance of dynamic alterations in frequently used metrics such as degree centrality (DC), global signal connectivity (GSC), voxel-mirrored heterotopic connectivity (VMHC), the amplitude of low-frequency fluctuations (ALFF), and regional homogeneity (ReHo). We analyzed the changes of concordance indices in the PD patients and investigated the relationship between aberrant concordance values and clinical/neuropsychological assessments in the PD patients. We found that, compared with the HCs, the PD patients had lower volume concordance in the whole brain and lower voxel-wise concordance in the posterior cerebellar lobe, cerebellar tonsils, superior temporal gyrus, and supplementary motor region. We also found negative correlations between these concordance alterations and patients' age. The exploratory results contribute to a better understanding of IBA alterations and pathophysiological mechanisms in PD., 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 © 2022 Tian, Chen, Ma, Li, Li, Wu, Liu, Du, Li and Su.)

Background: Catheter ablation target at the site with large His activation in the left ventricle poses a high risk of atrioventricular (AV) block. We aimed to identify far-field (FF) and near-field (NF) His activation at left upper septum (LUS)., Methods: Three-D mapping of the aortic root and left ventricle was performed in 12 dogs. Two sites located at either the base or apex of the triangle interposed between the hinges of the the noncornary coronary cusp (NCC) - right coronary cusp (RCC) were chosen for a single radiofrequency (RF) application. Bipolar and unipolar pacing with different outputs at both sites was attempted to discern NF and FF His activation., Results: The sites chosen for NF and FF ablation were located at the base and apex of the triangle, which were 8.03 ± 1.18 mm (group 1) and 3.42 ± 0.61 mm (group 2) away from the RCC-NCC junction. Lower A/V ratios were found in group 1. Pacing could not differentiate NF from FF His activation. In group 1, ablation resulted in III degree AV block in all 6 dogs, whereas neither PR prolongation nor AV block occurred in group 2. Pathologic examination of group 1 showed complete/partial necrosis of the His bundle (HB) and left bundle branch in all 6 dogs. In group 2, no necrosis of the HB was seen in the 6/6 dogs., Conclusion: Anatomical localization in the triangle of RCC-NCC junction can help differentiate NF from FF His activation., 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 © 2022 Fu, Liao, Zhang, Zhan, Lin, Liu, Su, Deng, Fang, Liao, Wang, Wu, Xue and Ouyang.)

The effective healing of a bone defect is dependent on the careful coordination of inflammatory and bone-forming cells. In the current work, pro-inflammatory M1 and anti-inflammatory M2 macrophages were co-cultured with primary murine bone mesenchymal stem cells (BMSCs), in vitro , to establish the cross-talk among polarized macrophages and BMSCs, and as well as their effects on osteogenesis. Meanwhile, macrophages influence the osteogenesis of BMSCs through paracrine forms such as exosomes. We focused on whether exosomes of macrophages promote osteogenic differentiation. The results indicated that M1 and M2 polarized macrophage exosomes all can promote osteogenesis of BMSCs. Especially, M1 macrophage-derived exosomes promote osteogenesis of BMSCs through microRNA-21a-5p at the early stage of inflammation. This research helps to develop an understanding of the intricate interactions among BMSCs and macrophages, which can help to improve the process of bone healing as well as additional regenerative processes by local sustained release of exosomes., 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 © 2022 Liu, Luo, Lv, Zhang, Meng, Li, Meng, Qiang, Hou, Hou, Liu and Zhang.)

Background: Diabetes mellitus (DM) is a prognostic marker in elderly patients with cardiovascular diseases, but its predictive value in elderly valvular heart disease (VHD) patients is unclear. This study aimed to investigate the effect of DM on the long-term outcome of elderly VHD patients., Methods: This single-center, observational study enrolled patients aged 65 and older consecutively with confirmed VHD using echocardiography. Patients, divided into the DM group and non-DM group, were followed up for major adverse cardiac and cerebrovascular events (MACCEs), including all-cause death, ischemic stroke, and heart failure rehospitalization., Results: Our study consisted of 532 patients over a median follow-up of 52.9 months. Compared with the non-DM group ( n  = 377), the DM group ( n  = 155) had higher incidences of ischemic stroke (25.2% vs. 13.5%, P =0.001), heart failure rehospitalization (37.4% vs. 20.7%, P < 0.001), and MACCEs (60.0% vs. 35.8%, P < 0.001). After adjustment of confounders by the multivariable cox regression, DM appeared as an independent predictor for MACCEs (adjusted hazard ratio, aHR: 1.88; 95% confidence interval 1.42-2.48; P < 0.001). In the subgroup analysis of VHD etiology and functional style, conversely, DM was a protective factor for MACCEs in the patients with rheumatic VHD compared with those without rheumatic VHD (aHR: 0.43 vs. 2.27, P =0.004)., Conclusions: DM was an independent predictor for ischemic stroke and heart failure rehospitalization in elderly VHD patients undergoing conservative treatment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Yuan-Feng Liang et al.)

Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid-liquid phase separation (LLPS) occurs in a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 (SNHG9) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1)., (© 2021. The Author(s), under exclusive licence to Center for Excellence in Molecular Cell Science, CAS.)

Background: Self-management of ambulatory cancer pain is full of challenges. Motivated by the need for better pain management, we developed a WeChat-supported platform, Medication Housekeeper (MediHK), to enhance communication, optimize outcomes, and promote self-management in the home setting., Objective: We conducted a randomized controlled trial to assess whether the joint physician-pharmacist team through MediHK would provide better self-management of ambulatory patients with cancer pain., Methods: Patients were randomly assigned to either an intervention group or control group. During the 4-week study period, the pharmacist would send 24-hour pain diaries daily, adverse drug reaction (ADR) forms every 3 days, and the Brief Pain Inventory form every 15 days to patients in the intervention group via MediHK. If a patient needed a change in drug/dosage or treatment of an ADR after the comprehensive review, the pharmacist would propose pharmacological interventions to the attending physician, who was then responsible for prescribing or adjusting pain medications. If no adjustments were needed, the pharmacist provided appropriate targeted education based on knowledge deficits. Patients in the control group received conventional care and did not receive reminders to fill out the forms. However, if the control group patients filled out a form via MediHK, the pain management team would review and respond in the same way as for the intervention group. The primary outcomes included pain intensity and pain interference in daily life. Secondary outcomes included patient-reported outcome measures, medication adherence, ADRs, and rehospitalization rates., Results: A total of 100 patients were included, with 51 (51%) in the intervention group and 49 (49%) in the control group. The worst pain scores, least pain scores, and average pain scores in the intervention group and the control group were statistically different, with median values of 4 (IQR 3-7) vs 7 (IQR 6-8; P=.001), 1 (IQR 0-2) vs 2 (IQR 1-3; P=.02), and 2 (IQR 2-4) vs 4 (IQR 3-5; P=.001), respectively, at the end of the study. The pain interference on patients' general activity, mood, relationships with others, and interests was reduced, but the difference was not statistically significant compared with the control group (Ps=.10-.76). The medication adherence rate increased from 43% to 63% in the intervention group, compared with an increase of 33% to 51% in the control group (P<.001). The overall number of ADRs increased at 4 weeks, and more ADRs were monitored in the intervention group (P=.003). Rehospitalization rates were similar between the 2 groups., Conclusions: The joint physician-pharmacist team operating through MediHK improved pain management. This study supports the feasibility of integrating the internet into the self-management of cancer pain., Trial Registration: Chinese Clinical Trial Registry ChiCTR1900023075; https://www.chictr.org.cn/showproj.aspx?proj=36901., (©Lu Zhang, Howard L McLeod, Ke-Ke Liu, Wen-Hui Liu, Hang-Xing Huang, Ya-Min Huang, Shu-Sen Sun, Xiao-Ping Chen, Yao Chen, Fang-Zhou Liu, Xiao Jian. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 16.08.2021.)

The present study aimed to explore the effect of nuclear factor erythroid 2 related factor 2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway in intestinal protection by Sishen Pills against ulcerative colitis(UC). After the UC model was induced by 3% dextran sodium sulfate(DSS), experimental animals were randomly divided into control group, model group, salazosulfapyridine(SASP) group, and low-and high-dose Sishen Pills groups. Drug intervention(ig) was performed for seven consecutive days during modeling. On the 7 th day, the mice were euthanized. The body weight and colon length were recorded, and the histopathological changes of the colon were observed by HE staining. Serum interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and reactive oxygen species(ROS) were detected by ELISA. The protein and mRNA expression of Nrf2, HO-1, and NADPH quinine oxidoreductase-1(NQO-1) was determined by Western blot and reverse transcription-polymerase chain reaction(RT-PCR). Compared with the normal group, the model group exhibited reduced body weight, colon length, and T-AOC, increased IL-6, TNF-α, MDA, and ROS, and diminished protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. Compared with the model group, the SASP group and high-dose Sishen Pills group showed elevated body weight, colon length, and T-AOC, lowered IL-6, TNF-α, MDA, and ROS levels, and increased protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. As assessed by HE staining, Sishen Pills could improve the pathological changes of the colon. The findings suggested that Sishen Pills could protect the colon against UC induced by 3% DSS. The specific mechanism of action may be related to the anti-inflammatory and anti-oxidative stress effects by the activation of the Nrf2/HO-1 signaling pathway.

Objective: To investigate the prevalence and modifiable risk factors of degenerative valvular heart disease (DVHD) among elderly population in southern China., Methods: A stratified multistage sampling method was used to recruit subjects. The contents of the survey included the questionnaire, laboratory examination, echocardiography, and other auxiliary examinations. The possible risk factors of DVHD were analyzed by logistic regression analysis., Results: A total of 3538 subjects ≥ 65 years of age were enrolled. One thousand three hundred and seven subjects (36.9%) were diagnosed with DVHD. Degenerative was the most common etiology of VHD. Prevalence of DVHD increased with advancing age. The prevalence of DVHD differed by living region ( χ 2 = 45.594, P < 0.001), educational level ( χ 2 = 50.557, P < 0.001), and occupation ( χ 2 = 36.961, P < 0.001). Risk factors associated with DVHD included age (two-fold increased risk for each 10-year increase in age), elevated level C-reactive protein (OR = 1.346, 95% CI: 1.100-1.646), elevated level low density lipoprotein (OR = 1.243, 95% CI: 1.064-1.451), coronary artery disease (OR = 1.651, 95% CI: 1.085-2.513), smoking (OR = 1.341, 95% CI: 1.132-1.589), and hypertension (OR = 1.414, 95% CI: 1.221-1.638). Other significant risk factors included reduced or elevated level red blood cell (OR = 1.347, 95% CI: 1.031-1.761; OR = 1.599, 95% CI: 1.097-2.331; respectively), elevated level platelets (OR = 1.891, 95% CI: 1.118-3.198), elevated level uric acid (OR = 1.282, 95% CI: 1.112-1.479), and stroke (OR: 1.738, 95% CI = 1.085-2.513)., Conclusions: The survey characterized the baseline conditions of DVHD cohort of elderly population in Guangzhou city. The established and emerging risk factors for DVHD may represent challenges and opportunities for therapy., (Copyright and License information: Journal of Geriatric Cardiology 2021.)

Perovskite solar cells (PSCs) commonly exhibit significant performance degradation due to ion migration through the top charge transport layer and ultimately metal electrode corrosion. Here, we demonstrate an interfacial management strategy using a boron chloride subphthalocyanine (Cl 6 SubPc)/fullerene electron-transport layer, which not only passivates the interfacial defects in the perovskite, but also suppresses halide diffusion as evidenced by multiple techniques, including visual element mapping by electron energy loss spectroscopy. As a result, we obtain inverted PSCs with an efficiency of 22.0% (21.3% certified), shelf life of 7000 h, T 80 of 816 h under damp heat stress (compared to less than 20 h without Cl 6 SubPc), and initial performance retention of 98% after 2000 h at 80 °C in inert environment, 90% after 2034 h of illumination and maximum power point tracking in ambient for encapsulated devices and 95% after 1272 h outdoor testing ISOS-O-1. Our strategy and results pave a new way to move PSCs forward to their potential commercialization solidly., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Science China Press. All rights reserved.)

Background: Post-operative atrial fibrillation (POAF) is a common yet understudied clinical issue after coronary artery bypass graft (CABG) leading to higher mortality rates and stroke. This systematic review and meta-analysis evaluated the rates of adverse outcomes between patients with and without POAF in patients treated with CABG or combined procedures., Methods: The search period was from the beginning of PubMed and Embase to May 18 th , 2020 with no language restrictions. The inclusion criteria were: (1) studies comparing new onset atrial fibrillation before or after revascularization vs. no new onset AF before or after revascularization. The outcomes assessed included all-cause mortality, cardiac death, cerebral vascular accident (CVA), myocardial infarction (MI), repeated revascularization, major adverse cardiac event (MACE), and major adverse cardiac and cerebrovascular events (MACCEs)., Results: Of the 7,279 entries screened, 11 studies comprising of 57,384 patients were included. Compared to non-POAF, POAF was significantly associated with higher risk of all-cause mortality (Risk Ratio (RR) = 1.58; 95% Confidence Interval (CI): 1.42-1.76, P < 0.00001) with accompanying high level of heterogeneity ( I 2 = 62%)., Conclusions: Patients with POAF after CABG or combined procedures are at an increased risk of all-cause mortality or CVAs. Therefore, POAF after such procedures should be closely monitored and treated judiciously to minimize risk of further complications. While there are studies on POAF versus no POAF on outcomes, the heterogeneity suggests that further studies are needed., (Copyright and License information: Journal of Geriatric Cardiology 2021.)

This study aimed to quantitatively evaluate myocardial work (MW) in advanced stage 3-5 chronic kidney disease (CKD) by a novel non-invasive left ventricular (LV) Pressure-strain loop analysis (PSL). 144 patients with CKD were included (68 with stage 3 CKD group, 76 with stage 4/5 CKD group), and 48 healthy patients were recruited as the control group. All subjects had undergone transthoracic echocardiography. LV myocardial work and efficiency were estimated from LV PSL analysis. There was a significant progressive increase in global work waste (GWW) and reduction in global work efficiency (GWE) in CKD compared to normal controls. No difference in global work index (GWI) and global constructive work (GCW) was observed among the three groups. Subdivided analysis according to systolic blood pressure (SBP) and LV geometry discovered that increased GWW seems to be present frequently in CKD patients with elevated SBP or LV hypertrophy (LVH). Multivariate analysis showed increased peak strain dispersion (PSD), SBP, LV mass index (LVMI), and decreased estimated glomerular filtration rate (eGFR) were significantly associated with increased GWW. The decline of renal function followed by impaired paralleled myocardial energy exploitation. Moreover, increased PSD, SBP, LVMI, and decreased eGFR might be potential drivers of increased GWW.

Oral squamous cell carcinoma (OSCC) is an aggressive tumor whose prognosis has little improvement in the last three decades. Various immune-related genes have been suggested as significant roles in the development and progression of malignant cancers. In this study, we acquired and integrated differentially expressed genes of OSCC patients, including immune-related genes and transcription factors (TFs), from The Cancer Genome Atlas (TCGA) database. TF-mediated network was established to exploring the regulatory mechanisms of prognostic immune-related genes. A 7 immune-related genes prognostic model for OSCC was obtained, including CGB8, CTLA4, TNFRSF19, CCL26, NRG1, TPM2 and PLAU, which was further proved to be an independent prognostic indicator after adjusting for other clinical factors. The immune-related genes prognostic index was significantly negatively correlated to the infiltration abundances of B cells (P < 0.05) and CD8+ T cells (P < 0.05). The novel proposed immune-based prognostic model not only provided a promising biomarker and a way to monitor the long-term treatment of OSCC, but also gave a new insight into a potential immunotherapy strategy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A compact, portable, label-free, and ultra-sensitive sensor is proposed to detect cancerous cells based on Multi-Core Fiber (MCF) comprising of seven cores arranged in a hexagonal shape spliced with Single-Mode Fiber (SMF). Here, cytosensing based on fiber optic Localized Surface Plasmon Resonance (LSPR) is used for the efficient detection of different types of cancer cells. The proposed sensor structure is etched in a controlled manner to increase the evanescent wave (EWs) and coupling of modes between the cores of MCF. The etched MCF based LSPR probe has high refractive index sensitivity (RIS). To further increase the sensitivity, the sensor structure is immobilized with different nanomaterials (NMs) such as optimized size of gold nanoparticles (AuNPs), graphene oxide (GO), and copper oxide nanoflowers (CuO-NFs). AuNPs increase the sensitivity using LSPR, whereas, GO and CuO-NFs helps to increase the biocompatibility of sensor. The developed probe is further coated with 2-deoxy-D-glucose (2-DG) over NMs that are specific for the detection of cancer cells. In this work, various cancerous cell lines i.e. HepG2, Hepa 1-6, MCF-7, A549, and normal cell lines i.e. NCF and LO2 are detected using the developed sensing probe. Various analysis of proposed sensor such as selectivity, reusability, anti-interference ability, and involvement of GLUT receptor in detection has also been performed. The proposed etched sensor is ultra-sensitive for detection of HepG2, Hepa1 6, A549, MCF-7, LO2, and NCF cell lines with a limit of detection (LoD) of 3, 2, 2, 2, 4, 10 cells/mL, respectively in the linear range of 1 × 10 2 -1 × 10 6  cells/mL., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Matrine (MAT), a quinolizidine alkaloid component derived from the root of Sophora flavescens , suppresses experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), by inducing the production of immunomodulatory molecules, e.g., IL-10. In an effort to find the upstream pathway(s) of the mechanism underlying these effects, we have tested certain upregulated immunomodulatory molecules. Among them, we found increased levels of IL-27 and IFN-β, one of the first-line MS therapies. Indeed, while low levels of IFN-β production in sera and type I interferon receptor (IFNAR1) expression in spinal cord of saline-treated control EAE mice were detected, they were significantly increased after MAT treatment. Increased numbers of CD11b + IFN-β + microglia/infiltrating macrophages were observed in the CNS of MAT-treated mice. The key role of IFN-β induction in the suppressive effect of MAT on EAE was further verified by administration of anti-IFN-β neutralizing antibody, which largely reversed the therapeutic effect of MAT. Further, we found that, while MAT treatment induced production of IL-27 and IL-10 by CNS microglia/macrophages, this effect was significantly reduced by IFN-β neutralizing antibody. Finally, the role of IFN-β in MAT-induced IL-27 and IL-10 production was further confirmed in human monocytes in vitro . Together, our study demonstrates that MAT exerts its therapeutic effect in EAE through an IFN-β/IL-27/IL-10 pathway, and is likely a novel, safe, low-cost, and effective therapy as an alternative to exogenous IFN-β for MS., (Copyright © 2020 Chu, Ma, Thome, Ping, Liu, Wang, Zhang, Zhang and Zhu.)

Repairing damage in the craniofacial skeleton is challenging. Craniofacial bones require intramembranous ossification to generate tissue-engineered bone grafts via angiogenesis and osteogenesis. Here, we designed a mineralized collagen delivery system for BMP-2 and vascular endothelial growth factor (VEGF) for implantation into animal models of mandibular defects. BMP-2/VEGF were mixed with mineralized collagen which was implanted into the rabbit mandibular. Animals were divided into (i) controls with no growth factors; (ii) BMP-2 alone; or (iii) BMP-2 and VEGF combined. CT and hisomputed tomography and histological staining were performed to assess bone repair. New bone formation was higher in BMP-2 and BMP-2-VEGF groups in which angiogenesis and osteogenesis were enhanced. This highlights the use of mineralized collagen with BMP-2/VEGF as an effective alternative for bone regeneration., (© The Author(s) 2020. Published by Oxford University Press.)

A highly sensitive and selective optical fiber-based enzymatic biosensor has been proposed in the present study for detection of uric acid (UA) in human serum. The working mechanism of sensor depends on surface plasma property and localized surface plasmon resonance technique. For this purpose, a micro-ball fiber sensor probe of [Formula: see text] diameter was fabricated using advanced fusion-splicer and coated with gold nanoparticles (AuNPs) and graphene oxide (GO) in order to enhance its sensitivity. UV-Visible spectrophotometer and high-resolution transmission electron microscope (HR-TEM) were used to characterize the AuNPs solution and GO aqueous dispersion. The absorbance spectrum of AuNPs and GO are recorded at 519 nm and 230 nm, respectively. The coating of AuNPs and GO over fiber surface were verified by using a scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDX). Thereafter, sensor probe was functionalized with the specific enzyme i.e. uricase for the UA detection. The linearity response of uricase/GO/AuNPs-coated micro-ball optical fiber sensor is reported in the range of [Formula: see text]-1 mM UA concentrations. The reflectance of sensor linearly decreases with the increasing UA concentrations. Sensitivity of the sensor is 2.1 %/mM with a good slope of linearity with detection limit of [Formula: see text]. To test the accuracy of proposed sensor, UA concentration in serum samples have also tested by using proposed sensor and A5800 Automatic Biochemical Analyzer. The results of the developed sensor are consistent with the results of A5800 Automatic Biochemical Analyzer. Thus, proposed sensor can be successfully utilized for UA detection in human serum samples.

Hypertension is an independent risk factor for atrial fibrillation (AF), although its specific mechanisms remain unclear. Previous research has been focused on cyclic stretch, ignoring the role of high hydrostatic pressure. The present study aimed to explore the effect of high hydrostatic pressure stimulation on electrical remodeling in atrial myocytes and its potential signaling pathways. Experiments were performed on left atrial appendages from patients with chronic AF or sinus rhythm, spontaneously hypertensive rats (SHRs) treated with or without valsartan (10 mg/kg/day) and HL-1 cells were exposed to high hydrostatic pressure using a self-developed device. Whole-cell patch-clamp recordings and western blots demonstrated that the amplitudes of I Ca,L , I to , and I Kur were reduced in AF patients with corresponding changes in protein expression. Angiotensin protein levels increased and Ang1-7 decreased, while focal adhesion kinase (FAK) and Src kinase were enhanced in atrial tissue from AF patients and SHRs. After rapid atrial pacing, AF inducibility in SHR was significantly higher, accompanied by a decrease in I Ca,L , upregulation of I to and I Kur , and a shortened action potential duration. Angiotensin upregulation and FAK/Src activation in SHR were inhibited by angiotensin type 1 receptor inhibitor valsartan, thus, preventing electrical remodeling and reducing AF susceptibility. These results were verified in HL-1 cells treated with high hydrostatic pressure, and demonstrated that electrical remodeling regulated by the FAK-Src pathway could be modulated by valsartan. The present study indicated that high hydrostatic pressure stimulation increases AF susceptibility by activating the renin-angiotensin system and FAK-Src pathway in atrial myocytes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Biomaterials regulate macrophages and promote regeneration function, which is a new hot pot in tissue engineering and regenerative medicine. The research based on macrophage materials biology has appeared happy future, but related research on regulating macrophages and promoting tissue regeneration is still in its infancy. The surface roughness of biomaterials is one of the important factors affecting macrophage behavior. Previous study also found that the surface roughness of many biomaterials regulating macrophage polarization, but not including mineralized collagen (MC). In this study, we designed and fabricated MC with different roughness and investigated the influence of MC with different roughness on macrophages. In the study, we found that on the rough surface of MC, macrophages exhibited M1 phenotype-amoeboid morphology and high-level secretory of inflammatory factor (tumor necrosis factor-α and interleukin-6), while smoother surface exhibited M2 phenotype. These data will be beneficial to understand the mechanism deeply and enrich biomaterials tissue regeneration theory, provide a new train of thought biomaterials inducing tissue regeneration and repair and guide the optimum design of new biomaterials, development and reasonable applications., (© The Author(s) 2020. Published by Oxford University Press.)