Cyclic stretch promotes vascular homing of endothelial progenitor cells via Acsl1 regulation of mitochondrial fatty acid oxidation.

Endothelial progenitor cells (EPCs) play an important role in vascular repair and re-endothelialization after vessel injury. EPCs in blood vessels are subjected to cyclic stretch (CS) due to the pulsatile pressure, but the role of CS in metabolic reprogramming of EPC, particularly its vascular homing and repair, is largely unknown. In the current study, physiological CS applied to EPCs at a magnitude of 10% and a frequency of 1 Hz significantly promoted their vascular adhesion and endothelial differentiation. CS enhanced mitochondrial elongation and oxidative phosphorylation (OXPHOS), as well as adenosine triphosphate production. Metabolomic study and Ultra-high performance liquid chromatography-mass spectrometry assay revealed that CS significantly decreased the content of long-chain fatty acids (LCFAs) and markedly induced long-chain fatty acyl-CoA synthetase 1 (Acsl1), which in turn facilitated the catabolism of LCFAs in mitochondria via fatty acid ß-oxidation and OXPHOS. In a rat carotid artery injury model, transplantation of EPCs overexpressing Acsl1 enhanced the adhesion and re-endothelialization of EPCs in vivo. MRI and vascular morphology staining showed that Acsl1 overexpression in EPCs improved vascular repair and inhibited vascular stenosis. This study reveals a mechanotransduction mechanism by which physiological CS enhances endothelial repair via EPC patency.

Spatiotemporal dual-periodic soliton pulsation in a multimode fiber laser.

Spatiotemporal mode-locked (STML) fiber lasers have become a new platform for investigating nonlinear phenomena. In this work, spatiotemporal dual-periodic soliton pulsation (SDSP) is firstly observed in an STML fiber laser. It is found that in the SDSP, the long-period pulsations (LPPs) of different transverse modes are synchronous, while the short-period pulsations (SPPs) exhibit asynchronous modulations. The numerical simulation confirms the experimental results and further reveals that the proportion of transverse mode components can manipulate the periods of the LPP and SPP but does not affect the synchronous and asynchronous pulsations of different transverse modes. The obtained results bring the study of spatiotemporal dissipative soliton pulsation into the multi-period modulation stage, which helps to understand the complex spatiotemporal dynamics in STML fiber lasers and discover new dynamics in high-dimensional nonlinear systems.

Remission of organ failure in patients with predicted severe acute pancreatitis treated by somatostation, octreotide and cyclooxygenase-2 inhibitors.

BACKGROUND: /Objectives: Persistent organ failure (OF) in severe acute pancreatitis (SAP) is caused by activation of cytokine cascades, resulting in inflammatory injury. Anti-inflammation may be helpful in OF remission in early SAP. To assess the efficacy of anti-inflammatory regimens for OF prevention and remission in patients with predicted SAP and display clinical doctors' acceptance of these strategies, we conducted this retrospective study in the real world. METHODS: Clinical data of patients with predicted SAP from 2010 to 2017 were retrospectively reviewed. Cases were divided into conventional support (C), C+ somatostatin/octreotide (C + S/O), and C + S/O + Cyclooxygenase-2-inhibitors (C + S/O + COX-2-I). The occurrence of SAP, OF, changes of proportion for three strategies, length of hospital stay, meperidine injection, and cytokine levels were compared. The constituent ratios of the three schemes over eight years were evaluated. RESULTS: A total of 580 cases (C = 124, C + S/O = 290, C + S/O + COX-2-I = 166) were included. The occurrences of SAP in the C + S/O (28.3 %) and C + S/O + COX-2-I (18.1 %) groups were significantly lower than that in C group (60.5 %, P < 0.001), mainly by reducing persistent respiratory failure (P < 0.001) and renal failure (P = 0.002). C + S/O and C + S/O + COX-2-I regimens significantly decreased new onset OF and enhanced OF amelioration within 48 h when compared with C treatment (P < 0.001) in patients with OF score <2 and ≥ 2 on admission, respectively. C + S/O and C + S/O + COX-2-I as compared with C group significantly decrease OF occurrences in a multivariate logistic regression analysis (P < 0.05). CONCLUSIONS: Somatostatin or its analogs and cyclooxygenase-2 inhibitors are promising for OF prevention and remission in patients with predicted SAP. The acceptance of combined strategies in the real world has increased, and the occurrence of SAP has decreased annually.

G4LDB 2.2: a database for discovering and studying G-quadruplex and i-Motif ligands.

Noncanonical nucleic acid structures, such as G-quadruplex (G4) and i-Motif (iM), have attracted increasing research interests because of their unique structural and binding properties, as well as their important biological activities. To date, thousands of small molecules that bind to varying G4/iM structures have been designed, synthesized and tested for diverse chemical and biological uses. Because of the huge potential and increasing research interests on G4-targeting ligands, we launched the first G4 ligand database G4LDB in 2013. Here, we report a new version, termed G4LDB 2.2 (http://www.g4ldb.com), with upgrades in both content and function. Currently, G4LDB2.2 contains >3200 G4/iM ligands, ∼28 500 activity entries and 79 G4-ligand docking models. In addition to G4 ligand library, we have also added a brand new iM ligand library to G4LDB 2.2, providing a comprehensive view of quadruplex nucleic acids. To further enhance user experience, we have also redesigned the user interface and optimized the database structure and retrieval mechanism. With these improvements, we anticipate that G4LDB 2.2 will serve as a comprehensive resource and useful research toolkit for researchers across wide scientific communities and accelerate discovering and validating better binders and drug candidates.

Factors Influencing the Selection of Dentistry as a Career Among Prospective Candidates: A Multicentre Cross-Sectional Study.

OBJECTIVE: This study aimed to analyse the impact of sociodemographic factors on dental school candidates' decision to pursue dentistry as their career of choice. MATERIALS AND METHODS: Candidates shortlisted by three dental schools were invited to participate in a self-administered questionnaire study, featuring a validated instrument containing sociodemographic questions and 16 motivational items grouped into four domains: economic, professional, vocational and personal background reasons. The variations in motivational item scores across sociodemographic factors were assessed using the Mann-Whitney U test (age, sex, ethnicity, having relatives in the dental profession and dentistry as the first choice) and Kruskal-Wallis test (dental school and family income). RESULTS: A total of 295 dental school candidates participated in the study (Universiti Teknologi MARA: 137; Universiti Kebangsaan Malaysia: 99; MAHSA University: 59). Approximately 95% of participants identified dentistry as their primary career choice, with the vocational motivation of 'I like to help people' being the most prominent motivational factor. Dental school emerged as the critical factor significantly influencing three quarters of the motivational items. Sex, ethnicity and having relatives in the dental profession were the remaining factors significantly associated with variations in certain motivational items. Both dental school and ethnicity significantly affected four motivational domains (economic, professional, vocational and personal background). CONCLUSION: This study provides an insightful overview of the sociodemographic factors that impact career decision-making among prospective dental students. The scores for most motivational items varied among shortlisted candidates in three dental schools. The findings hold implications for policy development in dentistry by universities and public policymakers.

Real-World Effectiveness of Primary Series and Booster Doses of Inactivated Coronavirus Disease 2019 Vaccine Against Omicron BA.2 Variant Infection in China: A Retrospective Cohort Study.

BACKGROUND: China has been using inactivated coronavirus disease 2019 (COVID-19) vaccines as primary series and booster doses to protect the population from severe to fatal COVID-19. We evaluated primary and booster vaccine effectiveness (VE) against Omicron BA.2 infection outcomes. METHODS: This was a 13-province retrospective cohort study of quarantined close contacts of BA.2-infected individuals. Outcomes were BA.2 infection, COVID-19 pneumonia or worse, and severe/critical COVID-19. Absolute VE was estimated by comparison with an unvaccinated group. RESULTS: There were 289 427 close contacts ≥3 years old exposed to Omicron BA.2 cases; 31 831 turned nucleic acid amplification test-positive during quarantine, 97.2% with mild or asymptomatic infection, 2.6% with COVID-19 pneumonia, and 0.15% with severe/critical COVID-19. None died. Adjusted VE (aVE) against any infection was 17% for primary series and 22% when boosted. Primary series aVE in adults >18 years was 66% against COVID-19 pneumonia or worse and 91% against severe/critical COVID-19. Booster dose aVE was 74% against pneumonia or worse, and 93% against severe/critical COVID-19. CONCLUSIONS: Inactivated COVID-19 vaccines provided modest protection from infection, very good protection against pneumonia, and excellent protection against severe/critical COVID-19. Booster doses are necessary to provide strongest protection.

Violent Radicalization, Mental Health, and Gender Identity: Considerations for Future Research.

ABSTRACT: This study examines the association between gender identity, mental health, social adversity, and sympathy for violent radicalization (VR). Data were collected through an online survey in Canada. A total of 6003 eligible participants who were residents of Montreal, Toronto, Calgary, or Edmonton and aged from 18 to 35 years were included. We used Fisher exact test to assess gender differences in gender-based discrimination and we used analysis of variance tests to assess differences in scores on bullying, mental health, and sympathy for VR. We used linear regression to assess the relationship between mental health, social adversities, and sympathy for VR. Individuals who self-identified as trans and gender diverse had greater sympathy for VR than females did, experienced online victimization more frequently, and reported higher levels of psychological distress than both male and female participants. Our findings indicate that more research is needed on the association between social adversity and support for VR among this vulnerable population.

Low-power RF signal detection with wideband range based on an optically injected optoelectronic oscillator.

A novel method to detect a low-power radio-frequency (RF) signal with ultra-wide frequency range based on an optically injected optoelectronic oscillator (OEO) is proposed and experimentally demonstrated. The optical injection to a distributed feedback (DFB) laser has the advantages of amplifying one sideband of the modulated optical signal selectively and a wide tunable frequency range. The detection upper range that reaches up to 26 GHz and can be improved theoretically. To the best of the authors' knowledge, this is the widest detection range based on an OEO. At the same time, the detection characteristics are good. The sensitivity of the system is -92 dBm and the maximum gain is 12.18 dB at 15.047 GHz. Considering the real application of the detection system, the properties such as dynamic range and performance for detecting a modulated RF signal are also investigated.

Cyclic Trinuclear Copper(I) Complex Exhibiting Aggregation-Induced Emission: A Novel Fluorescent Probe for the Selective Detection of Gold(III) Ions.

Coordination complexes with aggregation-induced-emission (AIE) behavior has drawn much attention because of their promising applications. Conventionally, the AIE-active metal-organic complexes are prepared from an AIE-active organic ligand, and the construction of such coordination complexes from aggregation-caused-quenching (ACQ) ligands is still challenging. Herein, we have synthesized two new cyclic trinuclear complexes (CTCs), namely, 1 and 2, from copper(I) and silver(I) and a ACQ ligand [4-(3,5-dimethyl-1H-pyrazol-4-yl)benzaldehyde, HL]. (1) exhibited AIE behavior, and the emission intensity is enhanced ∼20 times when it aggregates, which can be attributed to its tight packing and multiple intermolecular hydrogen bonds that restrained the intramolecular rotation, as confirmed by single-crystal X-ray diffraction analysis. On the other hand, (2) displayed ACQ effects, and the emission intensity is decreased ∼5 times when it aggregates. This ACQ behavior of 2 is related to its loose packing and free rotation of the ligand in crystals, resulting in nonradiative decay and fluorescence quenching. Interestingly, the CTCs 1 and 2 both exhibited a good affinity to gold(III) ions, allowing selective detection and sensing of gold ions. More importantly, the 2 shows a good limit of detection (3.28 µmol/L) and an ultrafast responsive time (∼2 s). Our studies pave a new route to designing novel AIE-active coordination complexes and further exploring the functionality of CTCs.

Cumulative and independent effects of experiences of social adversity on support for violent radicalization during the COVID-19 pandemic: the mediating role of depression.

PURPOSE: Social adversity experiences have increased during the pandemic and are potential risk factors for both depression and support for violent radicalization (VR). However, the cumulative and independent effects of various social adversity experiences on support for VR have yet to be explored. This paper examines the cumulative and independent effects of COVID- and non-COVID-related discrimination, exposure to violence, traditional and cyberbullying victimization on support for VR. In addition, we investigate whether depression mediates the relationship between these forms of social adversity and support for VR. METHODS: A total of 6003 young adults (Mage = 27, SDage = 4.40, range 18-35) living in metropolitan areas in Canada responded to an online survey. We used multivariable regression models, controlling for socio-demographic characteristics, to infer covariate adjusted associations between social adversity measures and support for VR. Additionally, we conducted a formal mediation analysis to estimate the proportion mediated by depression. RESULTS: There was a cumulative relationship between experiences of social adversity and support for VR (ß = 1.52; 95% CI: 1.32, 1.72). COVID-related discrimination and cyberbullying victimization were independently associated with stronger support for VR. Depression partially mediated the effect of cumulative social adversity, COVID-related discrimination and cyberbullying on support for VR. CONCLUSION: Prevention programs during the present pandemic should prioritize decreasing discrimination and providing psychosocial support to depressed young adults who experience social adversity. Practitioners should prioritize developing programs that foster digital literacy skills and critical thinking among young adults to address the concerning impact of cyberbullying on support for VR.

A Novel Strategy for Regulating mRNA's Degradation via Interfering the AUF1's Binding to mRNA.

The study on the mechanism and kinetics of mRNA degradation provides a new vision for chemical intervention on protein expression. The AU enrichment element (ARE) in mRNA 3'-UTR can be recognized and bound by the ARE binding protein (AU-rich Element factor (AUF1) to recruit RNase for degradation. In the present study, we proposed a novel strategy for expression regulation that interferes with the AUF1-RNA binding. A small-molecule compound, JNJ-7706621, was found to bind AUF1 protein and inhibit mRNA degradation by screening the commercial compound library. We discovered that JNJ-7706621 could inhibit the expression of AUF1 targeted gene IL8, an essential pro-inflammatory factor, by interfering with the mRNA homeostatic state. These studies provide innovative drug design strategies to regulate mRNA homeostasis.

Protection-Free Strategy for the Synthesis of Boro-Depsipeptides in Aqueous Media under Microwave-Assisted Conditions.

In this report, 19 boron-containing depsipeptides were synthesized via microwave-assisted Passerini three-component reaction (P-3CR) in an aqueous environment. The linker-free DAHMI fluorescent tagging approach was used on selected boron-containing compounds to study the relationship between their structures and their level of cellular uptake of HEK293 cells. The biological data retrieved from the DAHMI experiments indicated that while the structures of tested compounds may be highly similar, their bio-distribution profile could be vastly distinctive. The reported optimized one-pot synthetic strategy along the linker-free in vitro testing protocol could provide an efficient platform to accelerate the development of boron-containing drugs.

The role of the cd99l2 gene on leukocyte interstitial migration in zebrafish.

Leukocytes play an essential role in ontogeny, tissue regeneration, and innate and adaptive immunity. The migration of leukocytes to the infected or traumatized areas is necessary for their immune response function. As an adhesion molecule, CD99L2 is crucial in the extravasation of leukocytes, however, its role in the interstitial migration of leukocytes remains unclear. In this study, the cd99l2 gene was knock-out by TALEN (transcription activator-like effector nuclease) in zebrafish and discovered that the deletion had no effect on zebrafish development. The number of granulocytes and macrophages recruited to the wounded tissue was significantly reduced in the cd99l2 mutants following caudal fin damage. Further research revealed that the expression of mfap4 was drastically decreased in the cd99l2 mutants, which may be one of the reasons that affect the migration of macrophages to the wound site. Moreover,transgenic lines with labeled vasculature, neutrophils and macrophages demonstrated that neutrophils and macrophages migrate throughout the interstitial space to the wound tissue in both wild-type and mutant zebrafish at 60 hours post-fertilization, indicating that the cd99l2 gene is involved in the interstitial migration of leukocytes. Finally, RNA transcription, protein folding, and the P450 pathway were enriched in cd99l2 mutants by RNA-seq analysis. Previous research had demonstrated that the regulation of transcription and signal transduction could be affected by adhesion molecules, which may suggest that the cd99l2 gene is involved in the cascade signaling pathway of leukocyte migration as an adhesion molecule. In conclusion, this study uncovered a novel function of the cd99l2 gene in the process of leukocyte migration in zebrafish, which is expected to provide a theoretical foundation for inflammatory and immune-related diseases.

Socio-cultural correlates of self-reported experiences of discrimination related to COVID-19 in a culturally diverse sample of Canadian adults.

Minorities and marginalized groups have increasingly become the target of discriminatory actions related to the COVID-19 pandemic. Detailed information about the manifestation of COVID-related discrimination is required to develop preventive actions that are not stigmatizing for such groups. The present study investigates experiences of perceived discrimination related to COVID-19 and its socio-cultural correlates in a culturally diverse sample of adults in Quebec (Canada). An online survey was completed by 3273 Quebec residents (49 % 18-39 years old; 57 % female; 49 % White). We used multivariate binomial logistic regression models to assess prevalence of COVID-related discrimination and to investigate socio-cultural correlates of reasons and contexts of discrimination. COVID-related discrimination was reported by 16.58 % of participants. Non-white participants, health-care workers and younger participants were more likely to experience discrimination than White, unemployed and older participants, respectively. Discrimination was reported primarily in association with participants' ethno-cultural group, age, occupation and physical health and in the context of public spaces. Participants of East-Asian descent and essential workers were more likely to report discrimination because of their ethnicity and occupation, respectively. Although young people experienced discrimination across more contexts, older participants were primarily discriminated in the context of grocery stores and because of their age. Our findings indicate that health communication actions informed by a social pedagogy approach should target public beliefs related to the association of COVID-19 with ethnicity, age and occupation, to minimize pandemic-related discrimination. Visible minorities, health-care workers and seniors should be protected and supported, especially in public spaces.

Probes and drugs that interfere with protein translation via targeting to the RNAs or RNA-protein interactions.

Protein synthesis is critical to cell survival and translation regulation is essential to post-transcriptional gene expression regulation. Disorders of this process, particularly through RNA-binding proteins, is associated with the development and progression of a number of diseases, including cancers. However, the molecular mechanisms underlying the initiation of protein synthesis are intricate, making it difficult to find a drug that interferes with this process. Chemical probes are useful in elucidating the structures of RNA-protein complex and molecular mechanism of biological events. Moreover, some of these chemical probes show certain therapeutic benefits and can be further developed as leading compounds. Here, we will briefly review the general process and mechanism of protein synthesis, and emphasis on chemical probes in examples of probing the RNA structural changes and RNA-protein interactions. Moreover, the therapeutic potential of these probes is also discussed to give a comprehensive understanding.

Simple Way of Facilitating Reduction the Fragment for Fractures With Condyle.

To describe a technique that uses a fixation screw with a steel wire ring which is implanted into the mandibular to facilitate the condylar fracture reduction. This technique has been used on 382 patients over the last 8 years from the Department of Oral and Cranio-Maxillofacial Science of Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. No complication has been encountered. Applying this approach, the displaced proximal condylar fragment can be found quickly, and then the fragment can be effectively prevented from being broken again in the reduction process.

Kinetic Studies on Radical Scavenging Activity of Kaempferol Decreased by Sn(II) Binding.

Sn(II) binds to kaempferol (HKaem, 3,4',5,7-tetrahydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) at the 3,4-site forming [Sn(II)(Kaem)2] complex in ethanol. DPPH• scavenging efficiency of HKaem is dramatically decreased by SnCl2 coordination due to formation of acid inhibiting deprotonation of HKaem as ligands and thus reduces the radical scavenging activity of the complex via a sequential proton-loss electron transfer (SPLET) mechanism. Moderate decreases in the radical scavenging of HKaem are observed by Sn(CH3COO)2 coordination and by contact between Sn and HKaem, in agreement with the increase in the oxidation potential of the complex compared to HKaem, leading to a decrease in antioxidant efficiency for fruits and vegetables with Sn as package materials.

Association of klotho gene polymorphism and the regulation of calcium-phosphate metabolism disorders in patients with end-stage renal disease.

BACKGROUND: Klotho G-395-A gene polymorphism is associated with several diseases; however, its association with calcium-phosphate metabolism disorders in end-stage renal disease (ESRD) is unknown. METHODS: A total of 137 patients with ESRD and 80 healthy adults (control) were enrolled in the study. Patients with ESRD were divided into three subgroups: haemodialysis (A1, n = 52), peritoneal dialysis (A2, n = 30), and non-dialysis (A3, n = 55). The klotho G-395-A genotype was detected by TaqMan PCR assay, and ELISA was used to detect the soluble klotho protein (sKL) and fibroblast growth factor (FGF23). Intact parathyroid hormone (iPTH) and other related clinical biochemical parameters were also analyzed for all subjects. RESULTS: (i) Three genotypes (GG, GA and AA) of KL G-395A were detected, and a significant difference between the ESRD and control groups was observed, (ii) sKL was inversely associated with FGF23 in each subgroup and phosphate and positively associated with calcium in A1 and A3. FGF23 was positively associated with phosphate and inversely associated with calcium in each subgroup, (iii) a statistical difference in levels of sKL and FGF23 was observed between GG and AA, as well as between GA and AA. The expression of sKL was lowest and the level of FGF23 was highest in AA and (iv). GA + AA genotypes and FGF23 were risk factors and sKL might be protective factor of calcium-phosphate metabolism disorders. CONCLUSION: Soluble klotho protein and FGF23 were associated with the regulation of calcium and phosphate metabolism, and the A allele of the G-395A klotho gene polymorphism could be a risk factor on calcium-phosphate metabolism disorders in patients with ESRD.

Developing Novel G-Quadruplex Ligands: from Interaction with Nucleic Acids to Interfering with Nucleic Acid⁻Protein Interaction.

G-quadruplex is a special secondary structure of nucleic acids in guanine-rich sequences of genome. G-quadruplexes have been proved to be involved in the regulation of replication, DNA damage repair, and transcription and translation of oncogenes or other cancer-related genes. Therefore, targeting G-quadruplexes has become a novel promising anti-tumor strategy. Different kinds of small molecules targeting the G-quadruplexes have been designed, synthesized, and identified as potential anti-tumor agents, including molecules directly bind to the G-quadruplex and molecules interfering with the binding between the G-quadruplex structures and related binding proteins. This review will explore the feasibility of G-quadruplex ligands acting as anti-tumor drugs, from basis to application. Meanwhile, since helicase is the most well-defined G-quadruplex-related protein, the most extensive research on the relationship between helicase and G-quadruplexes, and its meaning in drug design, is emphasized.