Search

The blood-brain-barrier prevents many imaging agents and therapeutics from being delivered to the brain that could fight central nervous system diseases such as Alzheimer's disease and strokes. However, techniques such as the use of stapled peptides or peptide shuttles may allow payloads through, with bioconjugation achieved via bio-orthogonal tetrazine/norbornene click chemistry. A series of lanthanide-tetrazine probes have been synthesised herein which could be utilised in bio-orthogonal click chemistry with peptide-based delivery systems to deliver MRI agents through the blood-brain-barrier. The Gd complexes show higher relaxivities than the clinical standard of Gd(DOTA) at 1.4 T and phosphorescence is observed from the Eu and Tb complexes via tetrazine sensitization, with supporting in vitro cytotoxicity and cell imaging. A bio-orthogonal click reaction between a Gd-tetrazine complex and a cyclic-RGD-norbornene conjugate was successful and the resulting clicked probe demonstrated enhanced relaxivity and could potentially act as a peptide shuttle for the Gd MRI agent., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Blonanserin (BNS) is a well-tolerated and effective drug for treating schizophrenia., Aim: To investigate which types of patients would obtain the most benefit from BNS treatment., Methods: A total of 3306 participants were evaluated in a 12-week, prospective, multicenter, open-label post-marketing surveillance study of BNS. Brief psychiatric rating scale (BPRS) scores were calculated to evaluate the effectiveness of BNS, and its safety was assessed with the incidence of adverse drug reactions. Linear regression was used to screen the influencing factors for the reduction of BPRS total score, and logistic regression was used to identify patients with a better response to BNS., Results: The baseline BPRS total score (48.8 ± 15.03) decreased to 27.7 ± 10.08 at 12 weeks ( P < 0.001). Extrapyramidal symptoms (14.6%) were found to be the most frequent adverse drug reactions. The acute phase, baseline BPRS total score, current episode duration, number of previous episodes, dose of concomitant antipsychotics, and number of types of sedative-hypnotic agents were found to be independent factors affecting the reduction of BPRS total score after treatment initiation. Specifically, patients in the acute phase with baseline BPRS total score ≥ 45, current episode duration < 3 months, and ≤ 3 previous episodes derived greater benefit from 12-week treatment with BNS., Conclusion: Patients in the acute phase with more severe symptoms, shorter current episode duration, fewer previous episodes, and a lower psychotropic drug load derived the greatest benefit from treatment with BNS., Competing Interests: Conflict-of-interest statement: Hai-Yun Li is an employee of Sumitomo Pharma (Suzhou) Co., Ltd. The other authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

In this paper, the problem of highly performance motion control of tank bidirectional stabilizer with dead zone nonlinearity and uncertain nonlinearity is addressed. First, the electromechanical coupling dynamics model of bidirectional stabilizer is developed finely. Second, the dead zone nonlinearity in bidirectional stabilizer is characterized as the combination of an uncertain time-varying gain and a bounded disturbance term. Meanwhile, an adaptive robust controller with dead zone compensation is proposed by organically combining adaptive technique and extended state observer (ESO) through backstepping method. The adaptive technique is employed to reduce the impact of unknown system parameter and dead zone parameter. Furthermore, the ESO is constructed to compensate the lumped uncertainties including unmodeled dynamics and dead zone residual, and integrated together via a feedforward cancellation technique. Moreover, the adaptive robust control law is derived to ensure final global stability. In stability analysis, the asymptotic tracking performance of the proposed controller can be guaranteed as the uncertainty nonlinearities in tank bidirectional stabilizer are constant. It is also guaranteed to achieve bounded tracking performance when time-varying uncertainties exist. Extensive co-simulation and experimental results verify the superiority of the proposed strategy., Competing Interests: Declaration of Competing Interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication., (Copyright © 2024 ISA. Published by Elsevier Ltd. All rights reserved.)

Although platinum-based chemotherapy is the frontline regimen for colorectal cancer (CRC), drug resistance remains a major challenge affecting its therapeutic efficiency. However, there is limited research on the correlation between chemotherapy resistance and lipid metabolism, including PIK3CA mutant tumors. In this present study, we found that PIK3CA-E545K mutation attenuated cell apoptosis and increased the cell viability of CRC with L-OHP treatment in vitro and in vivo . Mechanistically, PIK3CA-E545K mutation promoted the nuclear accumulation of SREBP1, which promoted the transcription of Apolipoprotein A5 (APOA5). APOA5 activated the PPARγ signaling pathway to alleviate reactive oxygen species (ROS) production following L-OHP treatment, which contributed to cell survival of CRC cells. Moreover, APOA5 overexpression enhanced the stemness-related traits of CRC cells. Increased APOA5 expression was associated with PIK3CA mutation in tumor specimens and poor response to first-line chemotherapy, which was an independent detrimental factor for chemotherapy sensitivity in CRC patients. Taken together, this study indicated that PIK3CA-E545K mutation promoted L-OHP resistance by upregulating APOA5 transcription in CRC, which could be a potent target for improving L-OHP chemotherapeutic efficiency. Our study shed light to improve chemotherapy sensitivity through nutrient management in CRC.

Background: An early diagnosis and treatment of invasive fungal disease (IFD) is associated with improved outcome, but the moderate sensitivity of noninvasive diagnostic tests makes this challenging. Invasive diagnostic procedures such as bronchoalveolar lavage (BAL) have a higher yield but are not without risk. The detection and sequencing of microbial cell-free DNA (mcfDNA) may facilitate a noninvasive diagnosis., Materials: In a prospective observational study, we collected plasma in the 120 hours preceding or following a BAL in patients with hematological malignancies suspected for a pulmonary IFD. The EORTC/MSGERC2020 criteria were used for IFD classification. Sequencing was performed by Karius (Redwood City, CA) using their Karius Test (KT) on plasma and a "research use only test" on BAL fluid if available. Cases with a probable/proven IFD were identified based on standard diagnostic tests on serum and BAL (microscopy, polymerase chain reaction, galactomannan, culture) and used to calculate the sensitivity, specificity, and additional diagnostic value of the KT., Results: Of 106 patients enrolled, 39 (37%) had a proven/probable invasive aspergillosis, 7 (7%) a non- Aspergillus IFD, and 4 (4%) a mixed IFD. The KT detected fungal mcfDNA in 29 (28%) patients. Compared with usual diagnostic tests, the sensitivity and specificity were 44.0% (95% confidence interval [CI], 31.2-57.7) and 96.6% (95% CI, 88.5%-99.1%). Sensitivity of the KT was higher in non- Aspergillus IFD ( Mucorales :2/3, Pneumocystis jirovecii : 3/5). On BAL, the sensitivity was 72.2% (95% CI, 62.1-96.3), and specificity 83.3% (95% CI, 49.1-87.5)., Conclusions: Sequencing of mcfDNA may facilitate a noninvasive diagnosis of IFD in particular non- Aspergillus IFD. However, on plasma and similar to currently available diagnostics, it cannot be used as a "rule-out" test., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: To analyze recurrent factors in patients with clinical early-stage cervical cancer (ESCC) following hysterectomy and adjuvant radiotherapy., Methods: We collected data from patients with ESCC, staged according to the 2009 Federation International of Gynecology and Obstetrics (FIGO) staging criteria, who underwent hysterectomy followed by adjuvant radiotherapy between 2012 and 2019. These patients were subsequently restaged using the 2018 FIGO criteria. Univariable and multivariable analyses, along with nomogram analyses, were conducted to explore factors associated with recurrence-free survival (RFS)., Results: A total of 310 patients met the inclusion criteria, with a median follow-up time of 46 months. Among them, 126 patients with ESCC were restaged to stage III C1 or III C2 after surgery due to lymph node metastasis (LNM) based on the 2018 FIGO staging criteria. Of these, 60 (19.3%) experienced relapse. The 1-, 3-, and 5-year RFS rates were 93.9%, 82.7%, and 79.3%, respectively. Multivariate analysis revealed that the number of positive lymph nodes (LNs), tumor diameter (TD) > 4 cm, and parametrial invasion (PI) were associated with recurrence. The nomogram indicated their predictive value for 3-year and 5-year RFS. Notably, the 5-year recurrence rate (RR) increased by 30.2% in patients with LNM, particularly those with ≥ 3 positive LNs (45.5%). Patients with stage III C2 exhibited a significantly higher RR than those with IIIC1 (56.5% vs. 24.3%, p < 0.001). The 5-year RFS for patients with TD > 4 cm was 65.8%, significantly lower than for those with TD ≤ 4 cm (88.2%). Subgroup analysis revealed higher 5-year RRs in patients with stage III C2 than that in patients with III-C1 (56.5% vs. 24.3%, p < 0.001), demonstrating a significant difference in the RFS survival curve., Conclusion: RR in patients with clinical ESCC after hysterectomy followed by adjuvant radiotherapy is correlated with the number of positive LNs, TD > 4 cm, and PI. Emphasis should be placed on the common high-risk factor of LNM association with recurrence after radical hysterectomy in ESCC., (© 2024. The Author(s).)

Due to the adverse effects of de-metallation in past concerning FDA-approved gadolinium-based contrast agents (GBCAs), researchers have been focusing on developing safer and more efficient alternatives that could avoid toxicity caused by free gadolinium ions. Herein, two chiral GBCAs, Gd-LS with sulfonate groups and Gd-T with hydroxyl groups, are reported as potential candidates for magnetic reasonance imaging (MRI). The r 1 relaxivities of TSAP, SAP isomers of Gd-LS and SAP isomer of Gd-T at 1.4 T, 37 °C in water are 7.4 mM -1 s -1 , 14.5 mM -1 s -1 and 5.2 mM -1 s -1 , respectively. Results show that the hydrophilic functional groups introduced to the chiral macrocyclic scaffold of Gd-T and Gd-LS both give constructive influences on the second-sphere relaxivity and enhance the overall r 1 value. Both cases indicate that the design of GBCAs should also focus on the optimal window in Solomon-Bloembergen-Morgan (SBM) theory and the effects caused by the second-sphere and outer-sphere relaxivity., (© 2023. The Author(s).)

The pseudorabies virus (PRV) TJ strain, a variant of PRV, induces more severe neurological symptoms and higher mortality in piglets and mice than the PRV SC strain isolated in 1980. However, the mechanism underlying responsible for the discrepancy in virulence between these strains remains unclear. Our study investigated the differences in neurotropism between PRV TJ and PRV SC using both in vitro and in vivo models. We discovered that PRV TJ enters neural cells more efficiently than PRV SC. Furthermore, we found that PRV TJ has indistinguishable genomic DNA replication capability and axonal retrograde transport dynamics compared to the PRV SC. To gain deeper insights into the mechanisms underlying these differences, we constructed gene-interchanged chimeric virus constructs and assessed the affinity between envelope glycoprotein B, C, and D (gD) and corresponding receptors. Our findings confirmed that mutations in these envelope proteins, particularly gD, significantly contributed to the heightened attachment and penetration capabilities of PRV TJ. Our study revealed the critical importance of the gD ΔR278/P279 and gD V338A in facilitating viral invasion. Furthermore, our observations indicated that mutations in envelope proteins have a more significant impact on viral invasion than on virulence in the mouse model. Our findings provide valuable insights into the roles of natural mutations on the PRV envelope glycoproteins in cell tropism, which sheds light on the relationship between cell tropism and clinical symptoms and offers clues about viral evolution., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze the important effect of 3D printing personalized lumbar support on lumbar pain and lumbar function in patients with lumbar disc herniation., Methods: From October 2018 to May 2021, 60 patients initially diagnosed with lumbar disc herniation were selected and divided into an observation group and a control group, with 30 patients in each group. Among them, there were 18 males and 12 females in the observation group;the age ranged from 24 to 56 years old, with an average of (45.23±6.07) years old. The course of disease ranged from 1 to 24 months, with an average of(6.25±0.82) months, and rehabilitation treatment was carried out by wearing 3D printed personalized lumbar support. There were 19 males and 11 females in the control group;the age ranged from 25 to 57 years old, with an average of (42.78±7.58) years old. The course of disease ranged from 1 to 24 months, with an average of (6.72±1.36) months, and rehabilitation treatment is carried out by wearing traditional lumbar protective equipment. The Japanese Orthopaedic Association (JOA) scores, lumbar Oswestry dysfunction index (ODI) and visual analogue scale (VAS) were evaluated and compared between the two groups before and 1 course after treatment (3 weeks)., Results: There was no statistically significant difference in JOA, ODI, and VAS between two groups before treatment ( P >0.05). After one course of treatment (3 weeks), JOA scores of both groups was increased compared to before treatment ( P <0.05), while ODI and VAS decreased compared to before treatment ( P <0.05). After treatment, JOA score of observation group was higher than that of control group ( P <0.05), while ODI and VAS scores were lower than those of control group. No adverse events occurred in both groups., Conclusion: The application of 3D printing personalized lumbar support can effectively alleviate the pain of patients with lumbar disc herniation and improve their lumbar function of patients.

Chemical structures bearing a combination of aggregation-induced emission enhancement (AIEE) and intramolecular charge transfer (ICT) properties attracted the attention of many researchers. Recently, there is an increasing demand to pose tunable AIEE and ICT fluorophores that could present their conformation changes-related emission colors by adjusting the medium polarity. In this study, we designed and synthesized a series of 4-alkoxyphenyl-substituted 1,8-naphthalic anhydride derivatives NAxC using the Suzuki coupling reaction to construct donor-acceptor (D-A)-type fluorophores with alkoxyl substituents of varying carbon chain lengths (x = 1, 2, 4, 6, 12 in NAxC). To explain the observation that molecules with longer carbon chains revealed unusual fluorescence enhancement in water, we study the optical properties and evaluate their locally excited (LE) and ICT states by solvent effects combined with Lippert-Mataga plots. Then, we explored the self-assembly abilities of these molecules in water-organic (W/O) mixed solutions and observed the morphology of its nanostructure using a fluorescence microscope and SEM. The results show that NAxC, x = 4, 6, 12 show different degrees of self-assembly behaviors and corresponding aggregation-induced emission enhancement (AIEE) progresses. At the same time, different nanostructures and corresponding spectral changes can be obtained by adjusting the water ratio in the mixed solution. That is, NAxC compounds present different transitions between LE, ICT and AIEE based on the polarity, water ratio and time changes. We designed NAxC as the structure-activity relationship (SAR) of the surfactant to demonstrate that AIEE comes from the formation of micelle-like nanoaggregates, which causes a restriction of the transfer from the LE state to the ICT state, and micelle formation results in a blue-shift in emission and enhances the intensity in the aggregate state. Among them, NA12C is most likely to form micelles and the most obvious fluorescence enhancement, which will switch over time due to the nano-aggregation transition.

Breast cancer is the leading cancer in women. Around 20-30% breast cancer patients undergo invasion or metastasis after radical surgical resection and eventually die. Number of breast cancer patients show poor sensitivity toward treatments despite the advances in chemotherapy, endocrine therapy, and molecular targeted treatments. Therapeutic resistance and tumor recurrence or metastasis develop with the ongoing treatments. Conducive treatment strategies are thus required. Chimeric antigen receptor (CAR)-modified T-cell therapy has progressed as a part of tumor immunotherapy. However, CAR-T treatment has not been effective in solid tumors because of tumor microenvironment complexity, inhibitory effects of extracellular matrix, and lacking ideal tumor antigens. Herein, the prospects of CAR-T cell therapy for metastatic breast cancer are discussed, and the targets for CAR-T therapy in breast cancer (HER-2, C-MET, MSLN, CEA, MUC1, ROR1, EGFR) at clinical level are reviewed. Moreover, solutions are proposed for the challenges of breast cancer CAR-T therapy regarding off-target effects, heterogeneous antigen expression by tumor cells and immunosuppressive tumor microenvironment. Ideas for improving the therapeutics of CAR-T cell therapy in metastatic breast cancer are suggested., Competing Interests: Declaration of Conflict Interest The author claims that there is no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The petrochemical industry is relatively strict regarding safety rules in the workplace. The workplace involves high-risk categories that are intolerant of human error. Especially in the current situation with COVID-19, concerns regarding prevention and safety in the workplace have increased. In light of this pandemic, the company must know whether all employees recognize the implementation of COVID-19 prevention. In addition, employee awareness of safety grounded in the affective domain of human thought is lacking. This study investigates the safety attitudes and COVID-19 prevention in the workplace based on the affective domain of employees. A survey questionnaire based on the Likert scale was utilized to collect data from 618 employees in the petrochemical industry. Descriptive analysis and analysis of variance were used to examine the data. The results reveal that employees in the petrochemical industry have a positive degree of responses to COVID-19 prevention, safety attitudes, and the affective domain, regardless of employment characteristics such as gender, age, position, and work experience. This study concludes that a positive affective domain of employees is followed by a positive safety attitude; thus, effective COVID-19 prevention was established in the workplace based on the perspectives and attitudes of the employees.

Construction of lanthanide heterometallic complex is important for engineering multifunction molecular containers. However, it remains a challenge because of the similar ionic radii of lanthanides. Herein we attempt to prepare chiral lanthanide heterometallic tetrahedra. Upon crystallization with a mixture of [Eu 2 L 3 ] and [Ln 2 L 3 ] (Ln=Gd, Tb and Dy) helicates, a mixture of heterometallic Eu n Ln' 4-n (L 6 ) (n=0-4) tetrahedra was prepared. Selective formation of heterometallic tetrahedron was observed as MS deconvolution results deviated from statistical results. The formation of heterometallic tetrahedron was found to be sensitive to ionic radii as well as the ratio of the two helicates used in the crystallization., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Image-guided tumor ablation eliminates tumor cells by physical or chemical stimulation, which shows less invasive and more precise in local tumor treatment. Tumor ablation provides a treatment option for medically inoperable patients. Currently, clinical ablation techniques are widely used in clinical practice, including cryoablation, radiofrequency ablation (RFA), and microwave ablation (MWA). Previous clinical studies indicated that ablation treatment activated immune responses besides killing tumor cells directly, such as short-term anti-tumor response, immunosuppression reduction, specific and non-specific immune enhancement, and the reduction or disappearance of distant tumor foci. However, tumor ablation transiently induced immune response. The combination of ablation and immunotherapy is expected to achieve better therapeutic results in clinical application. In this paper, we provided a summary of the principle, clinical application status, and immune effects of tumor ablation technologies for tumor treatment. Moreover, we discussed the clinical application of different combination of ablation techniques with immunotherapy and proposed possible solutions for the challenges encountered by combined therapy. It is hoped to provide a new idea and reference for the clinical application of combinate treatment of tumor ablation and immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer XY declared a shared parent affiliation with the authors LY, LZ, GC, ZX, QW, JB to the handling editor at the time of review., (Copyright © 2022 Yin, Li, Zhu, Chen, Xiang, Wang, Bi and Wang.)

The conformal coating or surface modification in high aspect ratio nanostructures is a tough challenge using traditional physical/chemical vapor deposition, especially for metal deposition. In this work, the growth behavior of iridium (Ir) metal formed by atomic layer deposition (ALD) in anodic aluminum oxide (AAO) templates was explored deeply. It is found that the surface hydrophilicity is crucial for the nucleation of ALD Ir. An in situ ALD Al 2 O 3 layer with an ultra-hydrophilic surface can greatly promote the nucleation of ALD Ir in AAO nanopores. The effect of the Ir precursor pulse time, diameter, and length of AAO nanopores on the infiltration depth of ALD Ir was investigated systematically. The results show that the infiltration depth of ALD Ir in AAO nanopores is in proportion to the pore diameter and the square root of the Ir precursor pulse time, which follows a diffusion-limited model. Furthermore, the Ir precursor pulse time to obtain conformal Ir coating throughout all the AAO channels is in proportion to the square of the aspect ratio of AAO templates. In addition, the conformal Ir deposition in AAO nanopores is also related to the Ir precursor purge time and the O 2 partial pressure. Insufficient Ir purge time could cause a CVD-like reaction, leading to the reduction of the infiltration depth in AAO. Higher O 2 partial pressure can facilitate Ir nucleation with more Ir precursor consumption at the entrance of nanopores, decreasing the infiltration depth in AAO nanopores, so appropriate O 2 partial pressure should be chosen for ALD Ir in high aspect ratio materials. Above all, our research is valuable for surface modification or coating of metal by ALD in high aspect ratio nanostructures for 3D microelectronics, nano-fabrication, catalysis and energy fields.

Glioma is the most common malignant primary brain tumor, and the accurate diagnosis of glioma has always been a challenge. Moreover, cerebellar glioma, which is difficult to be detected by magnetic resonance imaging, is not usually diagnosed until after the appearance of clinical symptoms. In this study, TRZD, a near-infrared (NIR) persistent luminescence (PL) nanoparticle with a dual function of imaging and therapy, was synthesized based on ZnGa 2 O 4 :Cr 3+ ,Sn 4+ . TRZD showed excellent rechargeable NIR PL for more than 30 hours in vivo with good tissue penetration for long-term autofluorescence-free imaging. The tumor growth of both the subcutaneous and orthotropic glioma models was significantly inhibited by TRZD. This is the first-time approach using NIR PL nanoprobes for both diagnosis and therapy of glioma. This is also the first-time report of nanotechnology-based diagnosis and therapy of cerebellar gliomas. This study offers a highly promising multifunctional nanoparticle for theranostics of a wide range of brain diseases.

To improve the safety of orthotropic steel bridge decks and the construction efficiency of bridge deck pavement by enhancing the performance of pavement materials, a new-generation, high-performance cold-mix resin was prepared by carrying out the combination of micro-characteristic analysis and performance test. Meanwhile, the pavement performance and fatigue performance of high-performance cold-mix resin mixtures and hot-mix epoxy saphalt mixtures as a control group were studied experimentally. The results show that different kinds of epoxy resins show bisphenol structure in essence. The curing exothermic peak temperature of the cold-mix resin increases with the heating rate. Both the specific heat capacity (△ C P ) of cold-mix resin and cold-mix resin asphalts exhibit a sudden change between -20 °C and 40 °C. In resin asphalt mixtures, cold-mix resin forms the network structure skeleton whereas the asphalt distributed in the form of tiny particles. The dosage of respective component has a significant effect on the tensile strength and elongation at break of cold-mix resin. Compared with hot-mix epoxy asphalt mixtures, cold-mix resin mixtures exhibit comparable water stability and high and low-temperature performance, as well as greater fatigue life.

Controlled formation of desired lanthanide supramolecular complexes is challenging because of the difficulties in predicting coordination geometry, as well as a labile coordination number. Herein, we explore the effect of ionic radii and linker length on supramolecular species formation. A helicate-to-tetrahedron transformation occurred between [Ln 2 L1 3 ] and [Ln 4 L1 6 ] (Ln = La, Sm, Eu, Gd, Tb and Lu). For six lanthanide ions, the unfavored tetrahedron [La 4 L1 6 ] can only be observed in a concentrated mixture with the helicate [La 2 L1 3 ] where no pure [La 4 L1 6 ] species was isolated via crystallization. For Sm, Eu, Gd, Tb, the [Ln 4 L1 6 ] supramolecular tetrahedron can be isolated via crystallization from diisopropyl ether. A similar result was also observed for Lu, but the tetrahedral structure was found to be relatively stable and transformed back to [Lu 2 L1 3 ] much slower upon dissolution.  No tetrahedron formation was observed with L3 giving rise to only [Ln 2 L3 3 ] species, in which L3 contains a longer and more flexible linker compared with that of L1. Results show that the supramolecular transformation in these systems is governed by both the ionic radii as well as the ligand design. Special focus is on both [Eu 2 L1 3 ] and [Eu 4 L1 6 ] which form chiral entities and exhibit interesting circular polarized luminescence., (© 2021. The Author(s).)

A series of water-soluble chiral cyclen-based chelators with chemical handles for selective targeting have been synthesized (cyclen = 1,4,7,10-Tetraazacyclododecane). Optical studies, relaxivity measurements, and competitive titrations were performed to show the versatility of these chiral chelators. The complexations of L3, L4, and L5 with Lu 3+ , Y 3+ , Sc 3+, and Cu 2+ were successfully demonstrated in around 90% to 100% yields. Efficient and rapid radiolabeling of L5 with 177 Lu was achieved under mild conditions with 96% yield. The chelators exhibit near quantitative labeling efficiencies with a wide range of radiometal ions, which are promising for the development of targeting specific radiopharmaceutical and molecular magnetic resonance imaging contrast agents.

Pronation external rotation (PER) fractures are unstable ankle fractures that require anatomically stable fixation. However, due to the long distance between the fibula and the posterior malleolus in PER IV, existing approaches may make it difficult for the fixation of the associated posterior joint and the lateral malleolus. We describe an S-type posterolateral approach for the open reduction and internal fixation of posterior malleolar fractures with an associated lateral malleolar fracture in PER IV., (Copyright © 2020 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Chirality is ubiquitous within biological systems where many of the roles and functions are still undetermined. Given this, there is a clear need to design and develop sensitive chiral optical probes that can function within a biological setting. Here we report the design and synthesis of magnetically responsive Circularly Polarized Luminescence (CPL) complexes displaying exceptional photophysical properties (quantum yield up to 31 % and |g lum | up to 0.240) by introducing chiral substituents onto the macrocyclic scaffolds. Magnetic CPL responses are observed in these chiral Eu III complexes, promoting an exciting development to the field of magneto-optics. The |g lum | of the 5 D 0 → 7 F 1 transition increases by 20 % from 0.222 (0 T) to 0.266 (1.4 T) displaying a linear relationship between the Δg lum and the magnetic field strength. These Eu III complexes with magnetic CPL responses, provides potential development to be used in CPL imaging applications due to improved sensitivity and resolution., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

Using Epstein-Barr virus (EBV)-induced cancer cells and HeLa cells as a comparative study model, a novel and safe dual-EBV-oncoproteins-targeting pH-responsive peptide engineering, coating, and guiding approach to achieve precision targeting and treatment strategy against EBV-associated cancers is introduced. Individual functional peptide sequences that specifically bind to two overexpressed EBV-specific oncoproteins, EBNA1 (a latent cellular protein) and LMP1 (a transmembrane protein), are engineered in three different ways and incorporated with a pH-sensitive tumor microenvironment (TME)-cleavable linker onto the upconversion nanoparticles (UCNP) NaGdF 4 :Yb 3+ , Er 3+ @NaGdF 4 (UCNP-P n , n = 5, 6, and 7). A synergistic combination of the transmembrane LMP1 targeting ability and the pH responsiveness of UCNP-P n is found to give specific cancer differentiation with higher cellular uptake and accumulation in EBV-infected cells, thus a lower dose is needed and the side effects and health risks from treatment would be greatly reduced. It also gives responsive UC signal enhancement upon targeted dual-protein binding and shows efficacious EBV cancer inhibition in vitro and in vivo. This is the first example of simultaneous imaging and inhibition of two EBV latent proteins, and serves as a blueprint for next-generation peptide-guided precision delivery nanosystem for the safe monitoring and treatment against one specific cancer., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Objective: To investigate the clinical prognostic factors of initially-treated AML children with t(8;21)/RUNX1-RUNX1T1 + ., Methods: Clinical data of 41 initially-treated AML children with t(8;21)/RUNX1-RUNX1T1 + in our hospital in period from January 2009 to January 2017 were retrospectively analyzed. The baseline clinical characteristics, cumulative recurrence, event-free survival (EFS) and overall survival (OS) were recorded, and the influencing factors of prognosis were evaluated by χ2 test and Cox regression model., Results: The complete remission (CR) rates in the first course and the second course of induction chemotherapy were respectively 82.93% (34/41) and 97.56% (40/41). The median EFS time and OS time were 30 months and 31 months respectively. The EFS rate and OS rate of children with CR after the first treatment course were significantly higher than those of children without CR (P＜0.05). The EFS rate of male children was significantly higher than that of female children (P＜0.05). The OS rate of children < 10 years old was significantly higher than that of children≥10 years old (P＜0.05). The expression level of RUNX1-RUNX1T1 gene after the second induction remission was the influencing factor of cumulative recurrence rate, EFS rate and OS rate in children (P＜0.05). Multivariate analysis by Cox regression model showed that the decreased levels of RUNX1-RUNX1T1 gene expression < 3 log after the second induction remission was the independent risk factor for EFS rate and OS rate in children (P＜0.05). The cumulative recurrence rate of children with RUNX1-RUNX1T1 gene expression increase for＞1 log after decreased 3 log was significantly higher than that of children with≤1 log (P＜0.05)., Conclusion: Iuithally-treated AML children with t(8;21)/RUNX1-RUNX1T1 + show the fine clinical prognosis after standard chemotherapy. The expression level of RUNX1-RUNX1T1 gene should be closely relates with the recurrence and long-term survival of AML children.

Shining examples: ChemPlusChem is pleased to present its Special Collection on Fluorescent Biomolecules and their Building Blocks, organized in collaboration with Guest Editors Ka-Leung Wong, Chi-Sing Lee, and Ga-Lai Law. This collection features a top range of contributions related to the development and use of new fluorescent reporters, including lanthanide- and transition-metal-based probes, fluorescent nucleoside analogues, and fluorescent nanocelluloses., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

To study the association between urinary phthalate metabolite levels, endometriosis, and their effects on human granulosa cells, we recruited patients who underwent laparoscopy to confirm endometriosis (n = 123) and control patients (n = 78). Liquid chromatography-tandem mass spectrometry was used to measure the following five urinary phthalate metabolites: mono-n-butyl phthalate (MnBP), mono(2-ethylhexyl) phthalate, monobenzyl phthalate, mono(2-ethyl-5-oxo-hexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate. Urinary MnBP levels were higher in patients with endometriosis than in controls after multivariable logistic regression including the number of deliveries, body mass index, and use of medicine as covariables. MnBP correlates with other phthalate metabolites. Previous studies found that endometriosis was a detrimental condition for granulosa cells. In our study, we observed whether MnBP affected granulosa cells. MnBP treatment altered the gene expression of BIRC5, BUB1B, CDC20, cyclin B1, IL-1β, TNF-α, inhibin-B, StAR, and P450ssc and attenuated the ratio of the mitochondrial membrane potential in human granulosa cells. Moreover, MnBP decreased the expression of the anti-Mullerian hormone. These findings suggest that MnBP concentration is associated with endometriosis and may affect the health and steroidogenesis of human granulosa cells., Competing Interests: The authors declare no competing financial interests.

Epstein-Barr nuclear antigen 1 (EBNA1) plays a vital role in the maintenance of the viral genome and is the only viral protein expressed in nearly all forms of Epstein-Barr virus (EBV) latency and EBV-associated diseases, including numerous cancer types. To our knowledge, no specific agent against EBV genes or proteins has been established to target EBV lytic reactivation. Here we report an EBNA1- and Zn 2+ -responsive probe (ZRL 5 P 4 ) which alone could reactivate the EBV lytic cycle through specific disruption of EBNA1. We have utilized the Zn 2+ chelator to further interfere with the higher order of EBNA1 self-association. The bioprobe ZRL 5 P 4 can respond independently to its interactions with Zn 2+ and EBNA1 with different fluorescence changes. It can selectively enter the nuclei of EBV-positive cells and disrupt the oligomerization and oriP -enhanced transactivation of EBNA1. ZRL 5 P 4 can also specifically enhance Dicer1 and PML expression, molecular events which had been reported to occur after the depletion of EBNA1 expression. Importantly, we found that treatment with ZRL 5 P 4 alone could reactivate EBV lytic induction by expressing the early and late EBV lytic genes/proteins. Lytic induction is likely mediated by disruption of EBNA1 oligomerization and the subsequent change of Dicer1 expression. Our probe ZRL 5 P 4 is an EBV protein-specific agent that potently reactivates EBV from latency, leading to the shrinkage of EBV-positive tumors, and our study also suggests the association of EBNA1 oligomerization with the maintenance of EBV latency.

In the host, many RING domain E3 ligases have been reported to inhibit viral replication through various mechanisms. In a previous screen, we found that porcine RING finger protein 114 (pRNF114), a RING domain E3 ubiquitin ligase, inhibits classical swine fever virus (CSFV) replication. This study aimed to clarify the underlying antiviral mechanism of pRNF114 against CSFV. Upon CSFV infection, pRNF114 mRNA was upregulated both in vitro and in vivo CSFV replication was significantly suppressed in PK-pRNF114 cells stably expressing pRNF114 by the lentivirus-delivered system, whereas CSFV growth was enhanced in PK-15 cells with RNF114 knockout by the CRISPR/Cas9 system. The RING domain of pRNF114, which has E3 ubiquitin ligase activity, is crucial for its antiviral activity. Mechanistically, pRNF114 interacted with the CSFV NS4B protein through their C-terminal domains, which led to the K27-linked polyubiquitination and degradation of NS4B through a proteasome-dependent pathway. Collectively, these findings indicate that pRNF114 as a critical regulator of CSFV replication and uncover a mechanism by which pRNF114 employs its E3 ubiquitin ligase activity to inhibit CSFV replication. IMPORTANCE Porcine RING finger protein 114 (pRNF114) is a member of the RING domain E3 ligases. In this study, it was shown that pRNF114 is a potential anti-CSFV factor and the anti-CSFV effect of pRNF114 depends on its E3 ligase activity. Notably, pRNF114 targets and catalyzes the K27-linked polyubiquitination of the NS4B protein and then promotes proteasome-dependent degradation of NS4B, inhibiting the replication of CSFV. To our knowledge, pRNF114 is the first E3 ligase to be identified as being involved in anti-CSFV activity, and targeting NS4B could be a crucial route for antiviral development., (Copyright © 2019 Zhang et al.)

One-step cyclization of a tetraazamacrocycle 5 with 70% yield in a 25-g scale was performed. Its chiral DOTA derivatives, L4 , has ∼93% of TSAP coordination isomer in its Eu(III) and Yb(III) complexes in aqueous solution. [GdL4] 5- exhibits a high relaxivity, making it a promising and efficient MRI contrast agent. High luminescence dissymmetry factor ( g lum ) values of 0.285 (Δ J = 1) for [TbL3] - and 0.241 (Δ J = 1) for [TbL4] 5- in buffer solutions were recorded.

Background: HCV (Hepatitis C virus) is a prevalent chronic disease with potentially deadly consequences, especially for drug users. However, there are no special HCV or HIV (human immunodeficiency virus)-related intervention programs that are tailored for drug users in China; to fill this gap, the purpose of this study was to explore HCV and HIV-related knowledge among drug users in MMT (methadone maintenance treatment) sites of China and to investigate the effectiveness of HCV and HIV-related education for improving the knowledge of IDUs (injection drug users) and their awareness of infection., Methods: The study was a randomized cluster controlled trial that compared a usual care group to a usual care plus HCV/HIV-REP (HCV/HIV-Reduction Education Program) group with a 24-week follow-up. The self-designed questionnaires, the HCV- and HIV-related knowledge questionnaire and the HIV/HCV infection awareness questionnaire, were used to collect the data. Four MMT clinics were selected for this project; two MMT clinics were randomly assigned to the research group, with subjects receiving their usual care plus HCV/HIV-REP, and the remaining two MMT clinics were the control group, with subjects receiving their usual care over 12 weeks. Sixty patients were recruited from each MMT clinic. A total of 240 patients were recruited. Follow-up studies were conducted at the end of the 12th week and the 24th week after the intervention., Results: At baseline, the mean score (out of 20 possible correct answers) for HCV knowledge among the patients in the group receiving the intervention was 6.51 (SD = 3.5), and it was 20.57 (SD = 6.54) for HIV knowledge (out of 45 correct answers) and 8.35 (SD = 2.8) for HIV/HCV infection awareness (out of 20 correct answers). At the 12-week and 24-week follow-up assessments, the research group showed a greater increase in HCV-/HIV-related knowledge (group × time effect, F = 37.444/11.281, P < 0.05) but no difference in their HIV/HCV infection awareness (group × time effect, F = 2.056, P > 0.05)., Conclusion: An MMT-based HCV/HIV intervention program could be used to improve patient knowledge of HCV and HIV prevention, but more effort should be devoted to HIV/HCV infection awareness., Trial Registration: Protocols for this study were approved by institution review board (IRB) of Shanghai Mental Health Center (IRB:2009036), and registered in U.S national institutes of health (http://www.clinicaltrials.gov, NCT01647191 ). Registered 23 July 2012.

New chiral atropisomeric biphenyl diols 3 , 4 and 6 containing additional peripheral chiral centers with different steric bulkiness and/or electronic properties were synthesized. The X-ray crystal structure of 3 shows the formation of a supramolecular structure whereas that of 6 , containing additional CF 3 substituents, shows the formation of a monomeric structure. Diols 1 - 6 were found to be active organocatalysts in oxo-Diels-Alder reactions in which 2 recorded a 72% ee with trimethylacetaldehyde as a substrate.

A cyclen backbone was utilized to study the effect of backbone rigidity on Eu(iii) luminescence sensitization using a 1,2-HOPO derivative and 2-thenoyltrifluoroacetonate (TTA) as chromophores. The restriction of molecular movement of Eu-Cy-HOPO brought about by the increased rigidity provided a tightly packed coordination environment for the octadentate Eu(iii) center which resulted in the highest overall quantum yield (30.2%) and sensitization efficiency (64.6%) among 1,2-HOPO sensitized Eu(iii) complexes. Eu-Cy-HOPO is also the first 1,2-HOPO-based lanthanide complex to emit Eu(iii) luminescence under two-photon excitation.

Triboluminescence (TL) is a form of light emission induced upon mechanical forces on the material. However, our understanding of this phenomenon is still unclear and more examples are therefore needed in order to elucidate its mechanism. In this work, two types of TL complexes, [Eu( pp -dbm-Cl₂)₃phen] and [Eu( mm -dbm-Cl₂)₃phen], which also displays aggregation-induced emission (AIE) were synthesized and investigated for its photo-physical and crystal structural properties. These complexes were crystallized in a centro-symmetric space group P 2₁/ n , and remarkably, displayed TL upon grinding that may be due to the presence of extensive π···π, C-H···π and C-H···Cl-C interactions in the close molecular packing of its structure. This rare example deviates from the widely accepted mechanism of TL, hence widening the scope of our understanding in the area.

The synthesis of a new CF₃-containing stereogenic atropisomeric pair of ortho-disubstituted biphenyl scaffold is presented. The atropisomers are surprisingly conformationally stable for isolation. X-ray structures show that their stability comes from an intramolecular hydrogen bond formation from their two hydroxyl groups and renders the spatial arrangement of their peripheral CF₃ and CH₃ groups very different. The synthesized stereogenic scaffold proved to be effective in catalyzing the asymmetric N -nitroso aldol reaction of enamine and nitrosobenzene. Compared to similar scaffolds without CF₃ groups, one of our atropisomer exhibits an increase in enantioselectivity in this reaction.

Classical swine fever virus (CSFV), the etiological agent of classical swine fever in pigs, is a member of the Pestivirus genus within the Flaviviridae family. It has been proposed that CSFV infection is significantly inhibited by methyl-β-cyclodextrin (MβCD) treatment. However, the exact engagement of cellular cholesterol in the life cycle of CSFV remains unclear. Here, we demonstrated that pretreatment of PK-15 cells with MβCD significantly decreased the cellular cholesterol level and resulted in the inhibition of CSFV infection, while replenishment of exogenous cholesterol in MβCD-treated cells recovered the cellular cholesterol level and restored the viral infection. Moreover, we found that depletion of cholesterol acted on the early stage of CSFV infection and blocked its internalization into the host cells. Furthermore, we showed that 25-hydroxycholesterol, a regulator of cellular cholesterol biosynthesis, exhibited a potent anti-CSFV activity by reducing cellular cholesterol level. Taken together, our findings highlight the engagement of cholesterol in the life cycle of CSFV and its potential use as an antiviral target.

Epstein-Barr virus (EBV) infects more than 90% of humans worldwide and establishes lifelong latent infection in the hosts. It is closely associated with endemic forms of a wide range of human cancers and directly contributes to the formation of some. Despite its critical role in cancer development, no EBV- or EBV latent protein-targeted therapy is available. The EBV-encoded latent protein, Epstein-Barr nuclear antigen 1 (EBNA1), is expressed in all EBV-associated tumors and acts as the only latent protein in some of these tumors. This versatile protein functions in the maintenance, replication, and segregation of the EBV genome and can therefore serve as an attractive therapeutic target to treat EBV-associated cancers. In the last decades, efforts have been made for designing specific EBNA1 inhibitors to decrease EBNA1 expression or interfere with EBNA1-dependent functions. In this review, we will briefly introduce the salient features of EBNA1, summarize its functional domains, and focus on the recent developments in the identification and design of EBNA1 inhibitors related to various EBNA1 domains as well as discuss their comparative merits., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Discrete lanthanide(III) tetranuclear cubane-like clusters seldom occur throughout the Ln III series and behave as single-molecule magnets (SMMs). Herein, a series of cubanes, [Ln 4 (μ 3 -OH) 4 (μ-tfa) 4 (hfa) 4 (phen) 4 ] (1-9, Ln = La-Dy (except Pm), tfa = trifluoroacetate, hfa = hexafluoroacetylacetonate, phen = 1,10-phenanthroline), and dinuclear clusters, [Ln 2 (μ-OH) 2 (hfa) 4 (phen) 2 ] (10-16, Ln = Tb-Lu), were synthesized and characterized. Two types of clusters were formed due to the change of preferred coordination geometry for lighter and heavier Ln III ions which favor nine-coordinated cubanes and eight-coordinated dimers, respectively. A magnetic study shows that 8-Tb 4 and 9-Dy 4 are ferromagnetically coupled and SMM in nature because of the larger Ln···Ln distance compared to other discrete cubanes. The anisotropic barriers, U eff , of 9-Dy 4 are determined to be 67.0 K. In addition, the photophysical properties of 6-Eu 4 , 8-Tb 4 , and 10-Tb 2 owing to tfa, hfa, and phen sensitization and O-H quenching are discussed.

Despite established clinical utilisation, there is an increasing need for safer, more inert gadolinium-based contrast agents, and for chelators that react rapidly with radiometals. Here we report the syntheses of a series of chiral DOTA chelators and their corresponding metal complexes and reveal properties that transcend the parent DOTA compound. We incorporated symmetrical chiral substituents around the tetraaza ring, imparting enhanced rigidity to the DOTA cavity, enabling control over the range of stereoisomers of the lanthanide complexes. The Gd chiral DOTA complexes are shown to be orders of magnitude more inert to Gd release than [GdDOTA] - . These compounds also exhibit very-fast water exchange rates in an optimal range for high field imaging. Radiolabeling studies with (Cu-64/Lu-177) also demonstrate faster labelling properties. These chiral DOTA chelators are alternative general platforms for the development of stable, high relaxivity contrast agents, and for radiometal complexes used for imaging and/or therapy.

In this study, the removal of nutrients and chlorpyrifos as well as shifts of planktonic bacterial communities in constructed microcosms were investigated to evaluate the influence of Phragmites australis, Nymphaea alba, and Myriophyllum verticillatum, and their combination, on the restoration of eutrophic water containing chlorpyrifos. Plant-treated groups showed a higher pollutant removal rate than did no-remediation controls, indicating that treatment with plants is effective at remediation of eutrophic water containing chlorpyrifos. Different plants showed different performance on the remediation of eutrophic water, e.g., P. australis manifested stronger capacity for removal of sediment chlorpyrifos. This finding indicated that an appropriate plant combination is needed to deal with complex wastewater. During the treatments, the planktonic bacterial communities were influenced by the concentrations of nutrients and pollutants. The changes of composition of bacterial communities indicated a strong correlation between the bacterial communities and the concentrations of pollutants. The plants also influenced the planktonic bacterial communities, especially at the early phase of treatments. For example, P. australis increased the abundance of Limnohabitans and Nevskia significantly and decreased the abundance of Devosia, Luteolibacter, Methylibium, and Caulobacter significantly. The abundance of Hydrocarboniphaga significantly increased in N. alba-treated microcosms, whereas in M. verticillatum-treated microcosms, the abundance of Limnohabitans and Bdellovibrio significantly increased. Our results suggest that the planktonic bacterial communities may be altered during phytoremediation, and the functions of the affected bacteria should be concerned., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Depression is one of the most frequent psychiatric symptoms observed in people during the development of Alzheimer's disease (AD). We hypothesized that genetic factors conferring risk of depression might affect AD development. In this study, we screened 31 genes, which were located in 19 risk loci for major depressive disorder (MDD) identified by two recent large genome-wide association studies (GWAS), in AD patients at the genomic and transcriptomic levels. Association analysis of common variants was performed by using summary statistics of the International Genomics of Alzheimer's Project (IGAP), and association analysis of rare variants was conducted by sequencing the entire coding region of the 31 MDD risk genes in 107 Han Chinese patients with early-onset and/or familial AD. We also quantified the mRNA expression alterations of these MDD risk genes in brain tissues of AD patients and AD mouse models, followed by protein-protein interaction network prediction to show their potential effects in AD pathways. We found that common and rare variants of L3MBTL2 were significantly associated with AD. mRNA expression levels of 18 MDD risk genes, in particular SORCS3 and OAT, were differentially expressed in AD brain tissues. 13 MDD risk genes were predicted to physically interact with core AD genes. The involvement of HACE1, NEGR1, and SLC6A15 in AD was supported by convergent lines of evidence. Taken together, our results showed that MDD risk genes might play an active role in AD pathology and supported the notion that depression might be the "common cold" of psychiatry.

Endometriosis is an inflammatory disease associated with multiple pathogenic factors and studies regarding roles of trace metals in endometriosis have been inconsistent and limited. The aim of this cross-sectional study was to compare the blood levels of miscellaneous trace metals measured by inductively coupled plasma mass spectrometry in infertile women with and without endometriosis. Zinc level is associated with declining odds (adjusted OR=0.39, 95% CI=0.18-0.88) of endometriosis. By contrast, lead level is associated with increasing odds (adjusted OR=2.59, 95% CI=1.11-6.06) of endometriosis. The cadmium levels were higher in women with endometriosis, but the aOR was not significant. Zinc has anti-inflammatory characteristics and regulates homeostasis of zinc-containing superoxide dismutase. High lead levels might induce reactive oxygen species and deplete antioxidant defense mechanisms. Further prospective study is needed to test for their causal associations., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A unique, dual-function, photoactivatable anticancer prodrug, RuEuL, has been tailored that features a ruthenium(II) complex linked to a cyclen-europium chelate via a π-conjugated bridge. Under irradiation at 488 nm, the dark-inactive prodrug undergoes photodissociation, releasing the DNA-damaging ruthenium species. Under evaluation-window irradiation (λ irr = one-photon 350 nm or two-photon 700 nm), the drug delivery process can be quantitatively monitored in real-time because of the long-lived red europium emission. Linear relationships between released drug concentration and ESI-MS or luminescence responses are established. Finally, the efficiency of the new prodrug is demonstrated both in vitro RuEuL anticancer prodrug over some existing ones and open the way for decisive improvements in multipurpose prodrugs.

Predictable stereoselective formation of supramolecular assembly is generally believed to be an important but complicated process. Here, we show that point chirality of a ligand decisively influences its supramolecular assembly behavior. We designed three closely related chiral ligands with different point chiralities, and observe their self-assembly into europium (Eu) tetrametallic tetrahedral cages. One ligand exhibits a highly diastereoselective assembly into homochiral (either ΔΔΔΔ or ΛΛΛΛ) Eu tetrahedral cages whereas the two other ligands, with two different approaches of loosened point chirality, lead to a significant breakdown of the diastereoselectivity to generate a mixture of (ΔΔΔΔ and ΛΛΛΛ) isomers. The cages are highly emissive (luminescence quantum yields of 16(1) to 18(1)%) and exhibit impressive circularly polarized luminescence properties (|g lum |: up to 0.16). With in-depth studies, we present an example that correlates the nonlinear enhancement of the chiroptical response to the nonlinearity dependence on point chirality.

In order to understand the effect of mechanical stretch on corneal extracellular matrix remodeling, human keratoconus fibroblasts (HKCFBs) were subjected to cyclic stretch in vitro and the expression of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and inflammatory cytokines were evaluated. HKCFBs were seeded into a flexible membrane base and subjected to a cyclic stretch regimen of 10% equibiaxial stretch at a stretching frequency of 1 Hz for 6 h using a Flexcell tension unit. An antibody directed against interleukin‑6 (IL‑6 Ab) was used to investigate the roles of IL‑6 on mechanical stretch mediated regulation of MMP in HKCFBs. Culture supernatants were assayed using an enzyme‑linked immunosorbent assay for MMP‑1 and ‑3, TIMP‑1 and ‑2, and IL‑6. Total RNA from the cells was extracted, and quantitative polymerase chain reaction was used to determine mRNA for MMP‑1 and ‑3, TIMP‑1 and ‑2, and IL‑6. In stretched cells, levels of MMP‑1 and ‑3 demonstrated an increase compared with unstretched cells, but levels of TIMP‑1, and ‑2 revealed a decrease. Mechanical stretch significantly increased the mRNA expression and protein synthesis of IL‑6 compared with unstretched cells. IL‑6 induced MMP‑1 and ‑3 expression, whereas no significant effects were observed in levels of TIMP‑1 and ‑2 compared with the untreated control groups. Additionally, the IL‑6 Ab markedly inhibited the stretch‑induced increase in MMP‑1 and ‑3 in culture supernatants in a dose‑dependent manner. No significant differences in TIMP‑1 and ‑2 protein levels were detected between stretched cells treated with IL‑6 Ab and stretched cells without IL‑6 Ab treatment. These results indicate that cyclical mechanical stretch augments IL‑6 production and MMP expression, and reduces levels of TIMP in HKCFBs. Thus, it is suggested that IL‑6 mediates the stretch‑induced MMP expression.

A novel dual-imaging cisplatin-carrying molecular cargo capable of performing simultaneous optical and MR imaging is reported herein. This long-lasting MRI contrast agent (r 1 relaxivity of 23.4 mM -1 s -1 at 3T, 25 o C) is a photo-activated cisplatin prodrug ( PtGdL ) which enables real-time monitoring of anti-cancer efficacy. PtGdL is a model for monitoring the drug delivery and anti-cancer efficacy by MRI with a much longer retention time (24 hours) in several organs such as renal cortex and spleen than GdDOTA and its motif control GdL . Upon complete release of cisplatin, all PtGdL is converted to GdL enabling subsequent MRI analyses of therapy efficacy within its reasonably short clearance time of 4 hours. There is also responsive fluorescence enhancement for monitoring by photon-excitation., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

In this work, we synthesized a series of lanthanide(III) β-diketonate complexes to investigate the induction of triboluminescence. Triboluminescence (TL) spectra, solid-state emission spectra, and luminescence lifetimes of the complexes were obtained to prove consistent emitting species for steady-state and triboluminescence measurements. Detailed analyses of the crystal lattice packing were conducted in an attempt to correlate crystal symmetry, gas discharge, and structural arrangements with "triboexcitation", and it is found that either noncentrosymmetric or centrosymmetic compounds can be TL-active. Furthermore, an intensely TL compound, Eu(dbm) 4 TMP, was achieved, and its light emission can be seen under daylight upon mechanical stress.

Detailed understanding of the interaction between a chiral molecule and a noble metal surface is essential to rationalize and advance interfacial self-assembly of amino acids and metal-mediated anchoring of proteins. Here we demonstrate that individual Au@Ag core-shell nanocuboids can serve as a plasmonic reporter of an extended helical network formed among chemisorbed cysteine molecules, through generating an interband absorption enhanced, Ag-surface-exclusive circular dichroism (CD) band in the UV region. The observed unusual, strong CD response in the hybrid Au@Ag-cysteine system can be used to probe in real time conformational evolution and structural rearrangement of biomolecules in general and also monitor the interfacial interaction between a metal surface and an adsorbed molecule, opening up the possibility of using Ag nanostructures as promising stereochemically attuned nanosensors., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)