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A novel theranostic probe called CX-B-DF is constructed for precise chemotherapy guided by near-infrared (NIR) fluorescence imaging. Moreover, the theranostic probe shows high cytotoxicity to cancer cells under dual activation (H 2 O 2 and TP), which causes the accuracy of drug release to be improved and the toxic side effects to be reduced.

Findings of multi-session transcranial direct current stimulation (tDCS) as an adjunctive treatment of neurocognitive dysfunction in schizophrenia have been inconsistent. This meta-analysis of randomized controlled trials (RCTs) investigated the neurocognitive effects of adjunctive multi-session tDCS for schizophrenia. Twelve RCTs covering 418 schizophrenia patients were included and analyzed in this meta-analysis. The RevMan software (Version 5.3) was used to calculate risk ratios (RRs) and standardized mean differences (SMDs) with their 95% confidence intervals (CIs). Adjunctive tDCS outperformed the comparator in improving working memory deficits (SMD = 0.34, 95% CI: 0.03, 0.65; I 2 = 52%; p = 0.03), but no significant effects were found in other cognitive domains. No group differences were found with regard to total psychopathology measured by the Brief Psychiatric Rating Scale and the Positive and Negative Symptom Scale (SMD =-0.29, 95%CI: -0.61, 0.03; I 2 = 50%, p = 0.07) and discontinuation due to any reason (RR=0.80, 95%CI: 0.39, 1.66; I 2 = 9%, p = 0.56). Adjunctive tDCS appears to have a significant therapeutic effect improving the working memory deficits in schizophrenia., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Metal-organic frameworks (MOFs) consisting of organic radicals are of great interest because they have exhibited unique and intriguing optical, electronic, magnetic, and chemo-catalytic properties, and thus have demonstrated great potential applications in optical, electronic, and magnetic devices, and as catalysts. However, the preparation of MOFs bearing stable organic radicals is very challenging because most organic radicals are highly reactive and difficult to incorporate into the framework of MOFs. Herein we reported a post-synthetic modification strategy to prepare a novel MOF containing phenazine radical cations, which was used as heterogeneous catalyst for aza-Diels-Alder reaction. The zinc-based metal-organic framework Zn 2 (PHZ) 2 (dabco) (N) was successfully synthesized from 5,10-di(4-benzoic acid)-5,10-dihydrophenazine (PHZ), triethylene diamine (dabco) with Zn(NO 3 ) 2  ⋅ 6H 2 O by solvothermal method. The as-synthesized MOF N was partially oxidized by AgSbF 6 to form MOF R containing ∼10% phenazine radical cation species. The resultant MOF R was found to keep the original crystal type of N and very persistent under ambient conditions. Consequently, MOF R was successfully employed in radical cation-catalyzed aza-Diels-Alder reactions with various imine substrates at room temperature with high reaction conversion. Moreover, heterogeneous catalyst MOF R was reusable up to five times without much loss of catalytic activity, demonstrating its excellent stability and recyclability. Therefore, the post-synthetic modification developed in this work is expected to become a versatile strategy to prepare radical-based MOFs for the application of heterogeneous catalysts in organic synthesis., (© 2021 Wiley-VCH GmbH.)

In the assistive research area, human-computer interface (HCI) technology is used to help people with disabilities by conveying their intentions and thoughts to the outside world. Many HCI systems based on eye movement have been proposed to assist people with disabilities. However, due to the complexity of the necessary algorithms and the difficulty of hardware implementation, there are few general-purpose designs that consider practicality and stability in real life. Therefore, to solve these limitations and problems, an HCI system based on electrooculography (EOG) is proposed in this study. The proposed classification algorithm provides eye-state detection, including the fixation, saccade, and blinking states. Moreover, this algorithm can distinguish among ten kinds of saccade movements (i.e., up, down, left, right, farther left, farther right, up-left, down-left, up-right, and down-right). In addition, we developed an HCI system based on an eye-movement classification algorithm. This system provides an eye-dialing interface that can be used to improve the lives of people with disabilities. The results illustrate the good performance of the proposed classification algorithm. Moreover, the EOG-based system, which can detect ten different eye-movement features, can be utilized in real-life applications.

Cancer ranks as a leading cause of death in every country of the world. However, if they are discovered early, a lot of cancers can be prevented or cured. Discovering and monitoring cancer markers are the main methods for early diagnosis of cancer. To date, many fluorescent probes designed and used for early cancer diagnosis can only react with a single marker, which always causes insufficient accuracy in complex systems. Herein, a novel near-infrared (NIR) fluorescent probe (CyO-DNP) for the sequential detection of H 2 S and H + is synthesized. In this probe, a heptamethine dye is selected as the fluorophore and a 2,4-dinitrophenyl (DNP) ether is chosen as recognition group. In the presence of H 2 S, CyO-DNP is transformed into CyO, which exhibits an intense fluorescence at 663 nm. Then, H + induces the protonation of CyO to obtain CyOH, and the final fluorescence emission at 793 nm significantly enhances. Owing to the low cytotoxicity and the NIR fluorescence emission, CyO-DNP can sequentially monitor endogenous H 2 S and H + in cancer cells and image exogenous and endogenous H 2 S and H + in mice. It is worth mentioning that CyO-DNP can effectively avoid the false positive signal caused by the liver and kidney and discriminate normal mice and tumor mice accurately. For all we know, CyO-DNP is the first fluorescent probe for early accurate diagnosis of cancer by sequentially detecting H 2 S and H + .

This paper is to illustrate the infestation and related ecological characteristics of chigger mites on the Asian house rat (Rattus tanezumi). A total of 17,221 chigger mites were collected from 2,761 R. tanezumi rats, and then identified as 131 species and 19 genera in 2 families. Leptotrombidium deliense, the most powerful vector of scrub typhus in China, was the first major dominant species on R. tanezumi. All the dominant mite species were of an aggregated distribution among different individuals of R. tanezumi. The species composition and infestations of chiggers on R. tanezumi varied along different geographical regions, habitats and altitudes. The species-abundance distribution of the chigger mite community was successfully fitted and the theoretical curve equation was Ŝ (R)=37e-(0.28R)2. The total chigger species on R. tanezumi were estimated to be 199 species or 234 species, and this further suggested that R. tanezumi has a great potential to harbor abundant species of chigger mites. The results of the species-plot relationship indicated that the chigger mite community on R. tanezumi in Yunnan was an uneven community with very high heterogeneity. Wide geographical regions with large host samples are recommended in the investigations of chigger mites.

Cysteine (Cys), a kind of small molecule biological thiol, not only involves in the regulation of physiological processes, but also is considered a marker of tumor. However, it is challenging to develop suitable probe for detecting Cys in tumors. In this paper, a near-infrared (NIR) fluorescent probe named IX for Cys has been designed and synthesized. The probe shows a NIR emission peak at 770 nm with large Stokes shift (180 nm) upon adding Cys. It displays high sensitivity to Cys with 6-fold increase of fluorescence intensity. Meanwhile, IX has the high selectivity to Cys over other potential interference such as Hcy and GSH, which have similar structure with Cys. In addition, a possible mechanism of fluorescence enhancement is the reaction of IX with Cys to release IX-OH, which is verified by fluorescence spectra, MS and HPLC. Next, IX can selectively image Cys in HCT-116 cells thanks to the low cytotoxicity. Most important of all, the fluorescent probe IX has visualized Cys in HCT116-xenograft tumor mice due to the near-infrared properties with large Stokes shift., 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 © 2021 Elsevier B.V. All rights reserved.)

Toll-like receptor (TLR) signaling pathways need to be tightly controlled to avoid excessive inflammation and unwanted damage to the host. Myeloid differentiation primary response gene 88 (MyD88) is a critical adaptor of TLR signaling. Here, we identified the speckle-type POZ protein (SPOP) as a MyD88-associated protein. SPOP was recruited to MyD88 following TLR4 activation. TLR4 activation also caused the translocation of SPOP from the nucleus to the cytoplasm. SPOP depletion promoted the aggregation of MyD88 and recruitment of the downstream signaling kinases IRAK4, IRAK1 and IRAK2. Consistently, overexpression of SPOP inhibited the TLR4-mediated activation of NF-κB and production of inflammatory cytokines, whereas SPOP depletion had the opposite effects. Furthermore, knockdown of SPOP increased MyD88 aggregation and inflammatory cytokine production upon TLR2, TLR7 and TLR9 activation. Our findings reveal a mechanism by which MyD88 is regulated and highlight a role for SPOP in limiting inflammatory responses.

Background: The coronavirus disease 2019 (COVID-19) epidemic has been largely controlled in China, to the point where case fatality rate (CFR) data can be comprehensively evaluated., Methods: Data on confirmed patients, with a final outcome reported as of 29 March 2020, were obtained from official websites and other internet sources. The hospitalized CFR (HCFR) was estimated, epidemiological features described, and risk factors for a fatal outcome identified., Results: The overall HCFR in China was estimated to be 4.6% (95% CI 4.5-4.8%, P < 0.001). It increased with age and was higher in males than females. Although the highest HCFR observed was in male patients ≥70 years old, the relative risks for death outcome by sex varied across age groups, and the greatest HCFR risk ratio for males vs. females was shown in the age group of 50-60 years, higher than age groups of 60-70 and ≥ 70 years. Differential age/sex HCFR patterns across geographical regions were found: the age effect on HCFR was greater in other provinces outside Hubei than in Wuhan. An effect of longer interval from symptom onset to admission was only observed outside Hubei, not in Wuhan. By performing multivariate analysis and survival analysis, the higher HCFR was associated with older age (both P < 0.001), and male sex (both P < 0.001). Only in regions outside Hubei, longer interval from symptom onset to admission, were associated with higher HCFR., Conclusions: This up-to-date and comprehensive picture of COVID-19 HCFR and its drivers will help healthcare givers target limited medical resources to patients with high risk of fatality.

A near-infrared fluorescent probe, CyAc, is synthesized for accurately diagnosing cancer in vivo by sequential detection of Cys and H + . CyAc can not only achieve a good distinction between normal cells and cancer cells, but also distinguish normal mice from tumor mice.

The reduced coenzymes (NADH and NADPH) are an important product in energy metabolism and closely related to the occurrence and development of cancer. So it is necessary to use a powerful detection tool to visualize NAD(P)H in energy metabolism of tumor cells and find a new strategy to improve cancer treatment based on NAD(P)H. Herein, a novel multifunctional probe (Cy-N) is synthesized with good near-infrared fluorescence (NIRF) response to NAD(P)H and the photoacoustic (PA) and photothermal properties are successfully activated by NAD(P)H. The probe is successfully applied in visualizing NAD(P)H in energy metabolism of tumor cells and imaging NAD(P)H in bacteria. Moreover, the probe can be used to image NAD(P)H in energy metabolism of tumor-bearing mice by dual-modal imaging (NIRF and PA). More importantly, in terms of the role of NAD(P)H in energy metabolism, the photothermal therapy (PTT) is activated by NAD(P)H and a novel strategy of enhanced PTT is proposed by injecting glucose. As far as we know, this is the first probe to detect NAD(P)H in energy metabolism through dual-modal imaging, and also the first probe to activate PTT based on NAD(P)H, which will provide important information of the diagnosis and treatment of cancer., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Diabetes is one of the metabolic diseases marked by hyperglycemia and is often accompanied by the occurrence of some complications. As a biomarker of oxidative stress, hydrogen peroxide (H 2 O 2 ) has close association with the occurrence and development of diabetes and its complications. Unfortunately, there is no fluorescent probe reported for imaging H 2 O 2 in diabetic mice. Here, a novel near-infrared (NIR) fluorescent probe named QX-B was designed and synthesized to detect H 2 O 2 . For the probe, the quinolinium-xanthene dye is used as the fluorophore and borate ester is chosen as the response group. After the addition of H 2 O 2 , a strong NIR fluorescence signal at 772 nm is observed. The probe not only shows high sensitivity with 10-fold enhancement but also displays excellent selectivity to H 2 O 2 over other possible interfering species. In the meantime, the possible response mechanism of QX-B toward H 2 O 2 was proposed and verified by the high-performance liquid chromatography (HPLC) experiment, mass spectra (MS) experiment, and density functional theory (DFT) calculation. Furthermore, based on the low cell cytotoxicity of QX-B, it has been applied in imaging exogenous and endogenous H 2 O 2 in HeLa cells, HCT116 cells, 4T1 cells, and zebrafish successfully. More importantly, inspired by the performance of NIR fluorescence, QX-B has been used in monitoring H 2 O 2 in diabetic mice for the first time. This provides very important information for the diagnosis and treatment of diabetes and its complications.

Carbon monoxide (CO), as a crucial gasotransmitter, is endogenously produced by the degradation of heme and plays a critical role in regulating various physiological and pathophysiological processes such as oxidative stress. Thus, an effective fluorescent probe for investigating the relationships between CO and oxidative stress in vivo is necessary. In this paper, a ratiometric near-infrared (NIR) fluorescent probe (CP-CO) based on a coumarin-benzopyran fluorophore for imaging CO is developed. CP-CO itself displays strong coumarin emission due to its spironolactone structure. After the probe is reacted with CO and PdCl 2 , a notable enhancement of emission intensity at 690 nm can be found, which results in an obvious red shift of emission (200 nm). Moreover, CP-CO exhibits high sensitivity toward CO and produces a high enhancement ratio (203-fold). In addition, the probe is applied for ratiometric monitoring of exogenous and endogenous CO levels in HepG2 cells. Furthermore, the fluorescence imaging of CP-CO in zebrafish is performed by two-photon excitation along with excellent penetration ability. Most importantly, CP-CO can visualize the upregulation of CO under lipopolysaccharide (LPS)-induced oxidative stress in a zebrafish model, which vividly reveals its excellent ability in the elucidation of CO function in related biological events.

Toxic hepatitis which is induced by chemical substance is a serious threat to human health. More and more studies have shown that peroxynitrite (ONOO - ) is related with the development of toxic hepatitis. So it is important to find a tool to study ONOO - change during the diagnosis and therapy of toxic hepatitis. Herein, a series of novel near-infrared (NIR) fluorescence dyes (DDM-R) with long emission wavelength (740-770 nm) and large Stokes shift (~200 nm) are developed. Among the dyes, DDM-OH with great spectral performance and facilely modified feature is used to construct probe DDM-ONOO - . The probe have the preference of high sensitivity and excellent selectivity for ONOO - . In addition, DDM-ONOO - was applied in detecting exogenous and endogenous ONOO - in cells and further used in detecting ONOO - of CCl 4 -induced toxic hepatitis in cells by fluorescence imaging, 3D quantification analysis, flow cytometry. More importantly, by visualizing ONOO - , the probe was used to monitor the diagnosis of CCl 4 -induced toxic hepatitis in mice and evaluate the therapeutic efficacy of hepatoprotective medicines (NAC, SM, DDB). The results show that the probe will provide a powerful tool for the diagnosis and treatment of toxic hepatitis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A novel water-soluble near-infrared fluorescent probe named QX-P with simple synthesis is developed. QX-P has high sensitivity and selectivity to ALP. Moreover, the probe can not only visualize ALP activity in four cell lines, but also real-time image ALP activity during the diagnosis and treatment of diabetes in mice.

The topic of noncovalent spin-spin interactions is of increasing general interest in supramolecular radical chemistry. In this report, a series of exo - and endo -TEMPO radical-functionalized metallacycles 1 - 4 and metallacages 5 and 6 were constructed via coordination-driven self-assembly, wherein the number, location, and distance of the spins were precisely controlled. Their intriguing spin-spin interactions were systematically investigated by electron paramagnetic resonance (EPR) and were well interpreted at the molecular level assisted by X-ray crystallography analysis. The results revealed their distinct spin-spin interactions in the solution state, wherein the spin-spin interaction of metallacycle 3 was much stronger than that of the other five assemblies mainly due to its shorter intramolecular spin-spin distance. In the solid state, 1 - 6 exhibited obvious spin-spin (dipole-dipole) interactions because of the close arrangement of TEMPO units as indicated in their single crystals. Specifically, a large zero-field splitting (ZFS; D = 17.5 mT) was observed in the crystalline form of metallacycle 4 , which arose from the strong intermolecular spin-spin coupling. Interestingly, when the counterion of PF 6 - in 4 was changed to BF 4 - , the BF 4 - counterion analog 4a also exhibited a large ZFS, but the ZFS originated from the intramolecular spin-spin interaction due to a small variation in its crystal conformation. Moreover, the reversible on-off switching of the ZFS in 4 and 4a via the crystal-to-amorphous transformation induced by mechanical grinding and solvent vapor stimuli was also successfully realized. The unique and controllable inter- and intramolecular spin-spin interactions in this work reveal new insights for the understanding and manipulation of spin-spin interactions and may open up a new way to develop organic spin materials in the future.

As a kind of toxic gas, carbon monoxide (CO) can hinder uptake of oxygen in humans. However, more and more studies have shown that CO is an important gaseous messenger in the body and playing an indispensable role in intracellular signaling pathways. So, it is necessary to develop an analytical method to study CO in living organisms. Although there are many CO-responsive probes, most of them have the disadvantages of a small Stokes shift or short emission wavelength. In order to address the above issue, a novel probe (FDX-CO) with a large Stokes shift (190 nm) and long emission wavelength (770 nm) was firstly synthesized to detect CO. The probe shows high sensitivity and superior selectivity toward CO. Moreover, the probe was successfully used for visualizing exogenous and endogenous CO in cells by fluorescence imaging, 3D quantification analysis and flow cytometric analysis. More importantly, FDX-CO could excellently detect CO in mice, which suggests that this probe has the potential ability to image CO in vivo. This probe can be viewed as a useful tool in the research of CO.

Objective: To analyze the role of endoplasmic reticulum stress response in the development of osteoblast apoptosis and osteolysis in osteolytic bone tissue, and to explore the causes of artificial joint loosening, so as to provide new ideas and theoretical basis for the prevention and treatment of artificial joint loosening., Methods: The animal model of osteolysis induced by wear particles was established by mouse skull, and randomly divided into 4 groups, 7 rats in each group:group 1, blank control group;group 2, wear particles tial6v4 nano alloy powder (TiNPs) group;group 3, endoplasmic reticulum stress response positive control (TiNPs+Tg) group; group 4, endoplasmic reticulum stress response inhibitor (TiNPs+4-PBA) group. The pathological changes of osteolysis were observed by toluidine blue staining, HE staining and ALP staining;the expression of endoplasmic reticulum stress response marker protein was detected by Western Blotting;the apoptosis of osteoblasts in osteolytic skull tissue was detected by TUNEL and Caspase-3 immunohistochemistry., Results: Wear particles TiNPs can induce osteolysis in vitro, aggravate the infiltration of inflammatory cells and inhibit the differentiation and maturation of osteoblasts. At the same time, wear particles can also up regulate the markers of endoplasmic reticulum stress response and promote the apoptosis of osteoblasts in osteolytic bone tissue. After adding 4-PBA, an inhibitor of endoplasmic reticulum stress (4-PBA), on the basis of wear particles TiNPs, the symptoms of osteolysis were significantly relieved, bone erosion and inflammatory infiltration were significantly reduced, the differentiation and maturation of osteoblasts were improved, the number of apoptotic osteoblasts decreased sharply, and the expression of endoplasmic reticulum stress marker protein gradually decreased., Conclusion: Endoplasmic reticulum stress is involved in the formation of osteolysis and plays an important role in the occurrence and development of osteolysis. At the same time, endoplasmic reticulum stress can be used as a new therapeutic target to provide new ideas and methods for clinical reversal or treatment of osteolysis and aseptic loosening.

Objective: Unilateral vocal fold paralysis (UVFP) can be caused by iatrogenic injury or tumor-induced damage to the recurrent laryngeal nerve. Studies of comprehensive rehabilitation therapies for patients suffering from severe UVFP are limited. The purpose of this case report is to describe an improvement in complete aphonia after comprehensive rehabilitation therapies in a patient with severe UVFP due to a lung tumor., Methods: An 81-year-old woman with a history of bronchial adenoma had complete aphonia due to compression of the left recurrent laryngeal nerve by the tumor. Dynamic fibrolaryngoscope revealed paralysis of the left vocal fold. The patient was treated with interferential current therapy, vocal training, and kinesiology taping. Indicators of voice recovery were scored according to the grade, roughness, breathiness, asthenia, strain scale, and the voice handicap index., Results: After 10 days of comprehensive rehabilitation treatment, the patient recovered from complete aphonia to normal communication. The hoarseness and breathiness of patient were significantly improved. In addition, the grade, roughness, breathiness, asthenia, strain, and the voice handicap index scores changed from severe to mild or absent., Conclusion: This case provided a novel comprehensive treatment for a patient with UVFP, which was safe, cost-effective, and easy to implement in clinic., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

It has been a challenging topic and perpetual task to design and synthesize covalent macrocycles with characteristic self-assembling behaviors and excellent host-guest properties in supramolecular chemistry. Herein, we present a family of macrocyclic diphenylamine[n]arenes (DPA[n]s, n = 3-7) consisting of methyldiphenylamine units through a facile one-pot synthesis strategy. Unlike many other reported macrocyclic arenes, the resultant non-planar DPA[n]s feature intrinsic π-π stacking interactions, interesting self-assembling behaviors and ethene/ethyne capture properties. Specifically, strong multiple intermolecular edge-to-face aromatic interactions in DPA[3] have been systematically investigated both in solid and solution states. The intriguing findings on the intermolecular edge-to-face stacking interaction mode in the macrocycle would further highlight the importance of noncovalent π-π interaction in supramolecular self-assembly. This study will also shed light on the macrocyclic and supramolecular chemistry and, we expect, will provide a direction for design and synthesis of covalent macrocycles in this area.

Aims: An ongoing outbreak of 2019 novel coronavirus (CoV) disease (COVID-19), caused by severe acute respiratory syndrome (SARS) CoV-2, has been spreading in multiple countries. One of the reasons for the rapid spread is that the virus can be transmitted from infected individuals without symptoms. Revealing the pathological features of early-phase COVID-19 pneumonia is important for understanding of its pathogenesis. The aim of this study was to explore the pulmonary pathology of early-phase COVID-19 pneumonia in a patient with a benign lung lesion., Methods and Results: We analysed the pathological changes in lung tissue from a 55-year-old female patient with early-phase SARS-CoV-2 infection. In this case, right lower lobectomy was performed for a benign pulmonary nodule. Detailed clinical, laboratory and radiological data were also examined. This patient was confirmed to have preoperative SARS-CoV-2 infection by the use of real-time reverse transcription polymerase chain reaction and RNA in-situ hybridisation on surgically removed lung tissues. Histologically, COVID-19 pneumonia was characterised by exudative inflammation. The closer to the visceral pleura, the more severe the exudation of monocytes and lymphocytes. Perivascular inflammatory infiltration, intra-alveolar multinucleated giant cells, pneumocyte hyperplasia and intracytoplasmic viral-like inclusion bodies were seen. However, fibrinous exudate and hyaline membrane formation, which were typical pulmonary features of SARS pneumonia, were not evident in this case. Immunohistochemical staining results showed an abnormal accumulation of CD4+ helper T lymphocytes and CD163+ M2 macrophages in the lung tissue., Conclusion: The results highlighted the pulmonary pathological changes of early-phase SARS-CoV-2 infection, and suggested a role of immune dysfunction in the pathogenesis of COVID-19 pneumonia., (© 2020 John Wiley & Sons Ltd.)

Adenosine triphosphate (ATP) is mainly produced in mitochondria and plays an important role in lots of pathological processes such as colitis. Unfortunately, to date, few suitable fluorescence probes have been developed for monitoring the ATP level in colitis. Herein, a fluorescence nanoprobe named NIR@ZIF-90 is proposed and prepared by encapsulating a rhodamine-based near-infrared (NIR) dye into zeolitic imidazolate frameworks (ZIF-90). The nanoprobe is nonfluorescent because the emission of NIR is suppressed by the encapsulation, while in the presence of ATP, the framework of ZIF-90 is dissembled to release NIR and thus NIR fluorescence at 750 nm is observed. The nanoprobe shows high sensitivity to ATP with a 72-fold increase and excellent selectivity to ATP over other nucleotides. Moreover, with low cytotoxicity and good mitochondria-targeted ability, NIR@ZIF-90 is used to image ATP in colorectal cancer cells (HCT116). In addition, due to the NIR emission, the nanoprobe is further employed to successfully monitor the ATP level in a colitis mouse model. To the best of our knowledge, the nanoprobe is the first example to study colitis in vivo with the guidance of ATP, which will provide an efficient tool for understanding colitis.

Acute lung injury (ALI) and the subsequent acute respiratory distress syndrome remain devastating diseases with high mortality rates and poor prognoses among patients in intensive care units. The present study is aimed at investigating the role and underlying mechanisms of microRNA-31-5p ( miR-31-5p ) on lipopolysaccharide- (LPS-) induced ALI. Mice were pretreated with miR-31-5p agomir, antagomir, and their negative controls at indicated doses for 3 consecutive days, and then they received a single intratracheal injection of LPS (5 mg/kg) for 12 h to induce ALI. MH-S murine alveolar macrophage cell lines were cultured to further verify the role of miR-31-5p in vitro. For AMP-activated protein kinase α (AMPK α ) and calcium-binding protein 39 (Cab39) inhibition, compound C or lentiviral vectors were used in vivo and in vitro. We observed an upregulation of miR-31-5p in lung tissue upon LPS injection. miR-31-5p antagomir alleviated, while miR-31-5p agomir exacerbated LPS-induced inflammation, oxidative damage, and pulmonary dysfunction in vivo and in vitro. Mechanistically, miR-31-5p antagomir activated AMPK α to exert the protective effects that were abrogated by AMPK α inhibition. Further studies revealed that Cab39 was required for AMPK α activation and pulmonary protection by miR-31-5p antagomir. We provide the evidence that endogenous miR-31-5p is a key pathogenic factor for inflammation and oxidative damage during LPS-induced ALI, which is related to Cab39-dependent inhibition of AMPK α ., Competing Interests: The authors declare that there are no conflicts of interests., (Copyright © 2020 Wan-li Jiang et al.)

Chemical investigation on a marine sponge, Dactylospongia elegans , yielded five new γ-oxygenated butenolide sesterterpene derivatives, dactylospenes A-E ( 1 - 5 ), as well as two known biosynthetically related compounds, luffariellolide ( 6 ) and furospinosulin B ( 7 ). The structures of these compounds were elucidated on the basis of their spectroscopic data, experimental and calculated electronic circular dichroism (ECD) analysis, as well as comparison of the NMR data with those of known analogs. These metabolites are the first γ-oxygenated butenolide sesterterpenes to be reported from this genus. These compounds were evaluated in antimicrobial, anti-inflammatory, and cytotoxic assays. Only compounds 1 , 3 , and 6 exhibited moderate cytotoxicity against DU145, SW1990, Huh7, and PANC-1 cancer cell lines with IC 50 values in the range of 2.11-13.35 μM. Furthermore, compound 2 , without cytotoxicity, exhibited significant inhibitory effects (inhibitory rate 77.5%) on nitric oxide production induced by lipopolysaccharide at 10 μM.

Acute lung injury (ALI) is a severe lung syndrome with high morbidity and mortality, due to its complex mechanism and lack of effective therapy. The use of placenta‑derived mesenchymal stem cells (pMSCs) has provided novel insight into treatment options of ALI. The effects of pMSCs on lipopolysaccharide (LPS)‑induced inflammation were studied using a co‑culture protocol with LPS‑stimulated RAW264.7 cells. An LPS‑induced ALI Sprague‑Dawley rat model was developed by intravenously injecting 7.5 mg/kg LPS, and intratracheal instillation of 1x105 pMSCs was performed after administration of LPS to investigate the therapeutic potential of these cells. pMSCs ameliorated LPS‑induced ALI, as suggested by downregulated pro‑inflammatory cytokine tumor necrosis factor‑α and increased anti‑inflammatory cytokine interleukin‑10 in both cell and animal models. Moreover, the protein and leukocyte cells in bronchoalveolar lavage fluid decreased at a rapid rate after treatment with pMSCs. Histopathology demonstrated that pMSCs alleviated the infiltration of inflammatory cells, pulmonary hyperemia and hemorrhage, and interstitial edema. In addition, pMSC reduced the LPS‑induced expression of C‑X‑C motif chemokine ligand 12 in RAW264.7 macrophages and in lung tissue of ALI rats. This demonstrated that pMSCs are therapeutically effective in LPS‑induced ALI.

Objective: To evaluate accuracy and safety of individualized 3D printing guided template for thoracolumbar pedicle screw placement in patients with ankylosing spondylitis., Methods: From January 2016 to September 2019, thoracolumbar spine three-dimensional CT data of 8 patients with ankylosing spondylitis were included, Mimics 17.0 and ideaMaker computer software were applied to design thoracolumbar pedicle screw guided template of patients with AS, physical model of all patients (T 10 -L 2 )were printed by 3D printer, 2 parts in each patient, and divided into guide-plate-assisted screw group (experimental group) and free-hand nail group (control group). Thoracolumbar pedicle screws of both groups were placed by the same spinal surgeon. The accuracy of pedicle screw placement between two groups were evaluated according to results of postoperative CT, the accuracy of the fixation of thoracolumbar pedicle screw was divided into 4 grades, grade 0 and 1 screws were acceptable nails, grade 2 and 3 screws were unacceptable nails. The diameter and length of pedicle screws, the distance between entry point and posterior median line designed by preoperative 3D printing were compared with actual use in operation., Results: Twenty three blocks of thoracolumbar 3D printing screw of ankylosing spondylitis guided templates were designed and printed in guide-plate-assisted screw group, 46 screws were inserted and 44 screws were accepted. The time of implanting a screw into thoracolumbar pedicle was (4.20±1.15) min, the frequency of X-ray was (5.00±1.25) times and the average adjustment times of screw and Kirschner needle during screw placement was (1.76±1.32) times. In the control group, 46 nails were placed by traditional surgical method and 30 screws were accepted. The time of implanting a screw into thoracolumbar pedicle was (14.67±2.23) min, the frequency of X-ray fluoroscopy was (14.46±2.21) times and the average times of Kirschner needle adjustment was (4.76±3.39) times. The success rates between experimental group and control group were 95.65%(44 / 46) and 56.22%(30 / 46) respectively, and had statistical difference (χ 2 =13.538, P <0.05). There was no significant difference in diameter, length of pedicle screws and the distance of posterior median line between virtual designed by 3D printing before operation and actual situation in opertaion ( P >0.05). The operation time of inserting a single screw, the times of X-ray fluoroscopy, and the average times of adjustment screw and Kirschner needle in experimental group were significant less than those in control group( P <0.01)., Conclusion: The personalized guide template assisted the thoracolumbar fixation designed by 3D printing could significantly improve safety, accuracy and efficiency of surgery, especially suitable for thoracolumbar vertebral bodies requiring posterior pedicle screw fixation for fracture or dislocation with AS.

Background: China incurs an extremely low treatment coverage of multidrug-resistant tuberculosis (MDR-TB). This study aimed to understand the experience of MDR-TB patients on quality of health care, and the clinical impact through an up to six-year follow-up., Methods: Cohorts of MDR-TB patients were built in TB/MDR-TB designated hospitals in four regions of China from 2014 to 2015. Patients were followed up during treatment course, and yearly confirmation afterward until 2019. Delay in MDR-TB diagnosis and treatment was calculated upon bacteriological confirmation and treatment initiation. Risk factors for unfavourable outcomes were identified by multivariate logistic regression., Results: Among 1168 bacteriological-positive TB patients identified from a 12-million population, 58 (5.0%) MDR-TB cases were detected. The median delay for MDR-TB diagnosis was 90.0 days, with 13.8% having a delay above 180.0 days. MDR-TB treatment was only recommended to 19 (32.8%) participants, while the rest continued with regimen for drug-susceptible TB. In MDR-TB treatment group, 36.8% achieved treatment success, while the others had incomplete treatment (21.1%), loss to follow-up (36.8%) and TB relapse (5.3%). For non-MDR-TB treatment group, 33.3% succeeded, 25.6% relapsed, 2.6% failed, 23.1% died, and 15.4% were lost to follow-up. Overall, only 35.7% (20/56) of detected MDR-TB patients had favourable outcomes and higher education level was positively associated with it (adjusted odds ratio [aOR]: 3.60, 95% confidence interval [CI]: 1.04-12.5)., Conclusions: A large proportion of patients did not receive MDR-TB treatment and had unfavourable outcomes. Delayed MDR-TB diagnosis resulted in poor quality of MDR-TB care. Rapid diagnosis, regulated patient management and high-quality MDR-TB treatment should be enhanced in China.

Alteration of visual scanpaths under emotional facial expression in schizophrenia patients has been described in recent years; however, it is not clear whether such results are different when they transfer to faces in natural social scenes. The present study was designed to investigate the effects of emotional faces in natural social scenes on the gaze patterns of patients with schizophrenia, compared to gaze at isolated faces. A novel theme identification task was used where participants selected a positive, neutral or negative word to describe an emotional picture. Participants were 29 patients with schizophrenia and 31 healthy controls. The Positive and Negative Syndrome Scale (PANSS) and the Scale of Social Function in Psychosis Inpatients (SSPI) were used to assess symptoms and social functioning. In total, patients with schizophrenia showed significantly fewer fixations, saccades numbers and decreased fixations in areas of interest. As expected, patients showed shorter scanpath length, but only in the pictures with social settings. Furthermore, the effect size of scanpaths parameters under social scene was all greater than isolated face. In addition, patients compared to controls showed more abnormal scanpath parameters processing negative and neutral faces than positive faces, especially in social scene. The present study suggests that scanpath length for social scene faces may be more sensitive than for isolated face pictures. Our findings further support restricted scanpath whilst recognizing emotional facial expressions in natural social scenes as a favorable topic for further investigation as a trait marker., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest with regard to this manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To investigate the effects of aerobic exercise and resveratrol on janus kinase 2(JAK2) and transforming growth factor-β1(TGF-β1) in renal tissue of type 2 diabetes rats and its mechanism. Methods: The model of type 2 diabetic rats was established through SD rats fed high-fat diet for 5 weeks together with intraperitoneal infecting after a low dose of STZ. The rats were randomly divided into diabetic control group(DC), diabetic exercise group(DE), diabetic resveratrol group(DR), diabetic exercise and resveratrol group(DER), normal control group(NC), 12 rats in each group. Exercise-related groups performed 8 weeks treadmill exercise (20 m/min, 60 min/day). Resveratrol was administered to drug-related groups for 8 weeks (45 mg/kg, 7 day/week). Eight weeks later, we examined blood glucose concentrations, 24 h microalbuminuria(UA), serum creatinine(Scr), blood urea nitrogen(BUN), and the expressions of TGF-β1, janus kinase 2(JAK2) and JAK2 mRNA in renal tissue. Results: After eight weeks of intervention, compared with NC group, the concentrations blood glucose, 24 h UA, Scr, BUN, the expressions of TGF-β1, JAK2 and JAK2 mRNA were increased significantly in DC group(P＜0.05). Compared with DC group, the concentrations of blood glucose, 24 h UA, Scr, BUN, the expressions of TGF-β1, JAK2 and JAK2 mRNA were decreased significantly in DE group, DR group and DER group(P＜0.05). Conclusion: Exercise, resveratrol and combined intervention may decrease the expressions of JAK2 mRNA, JAK2 and TGF-β1, which further attenuate renal injury for type 2 diabetes. The renal protective effect produced by exercise and resveratrol combined intervention is better than that produced by exercise or resveratrol intervention alone.

Antipsychotic-induced dyslipidemia could increase the risk of cardiovascular diseases. This is a meta-analysis of randomized double-blind placebo-controlled trials to examine the efficacy and safety of adjunctive metformin for dyslipidemia induced by antipsychotics in schizophrenia. The standardized mean differences (SMDs) and risk ratios (RRs) with their 95% confidence intervals (CIs) were calculated using the random-effects model with the RevMan 5.3 version software. The primary outcome was the change of serum lipid level. Twelve studies with 1215 schizophrenia patients (592 in metformin group and 623 in placebo group) were included and analyzed. Adjunctive metformin was significantly superior to placebo with regards to low density lipoprotein cholesterol (LDL-C) [SMD: -0.37 (95%CI:-0.69, -0.05), P = 0.02; I 2  = 78%], total cholesterol [SMD: -0.47 (95%CI:-0.66, -0.29), P < 0.00001; I 2  = 49%], triglyceride [SMD: -0.33 (95%CI:-0.45, -0.20), P < 0.00001; I 2  = 0%], and high density lipoprotein cholesterol [SMD: 0.29 (95%CI:0.02, 0.57), P = 0.03; I 2  = 69%]. The superiority of metformin in improving LDL-C level disappeared in a sensitivity analysis and 80% (8/10) of subgroup analyses. Metformin was significantly superior to placebo with regards to decrease in body weight, body mass index, glycated hemoglobin A1c, fasting insulin, and homeostasis model assessment-insulin resistance (P = 0.002-0.01), but not regarding changes in waist circumference, waist-to-hip rate, leptin, fasting glucose, and blood pressure (P = 0.07-0.33). The rates of discontinuation due to any reason [RR: 0.97 (95%CI: 0.66, 1.43), P = 0.89; I 2  = 0%] was similar between the two groups. Adjunctive metformin could be useful to improve total cholesterol and triglyceride levels, but it was not effective in improving LDL-C level in schizophrenia.

Liver fibrosis is a major stage in the development of liver disease, and it is important to investigate its pathogenesis for early intervention or even reversal. Recent studies have found that intestinal disease can aggravate liver fibrosis through the role of the "gut-liver axis". Hypoxia is considered to be a typical characteristic of many diseases including ulcerative colitis and liver fibrosis. However, there is no fluorescent probe for hypoxia detection to investigate the "gut-liver axis". Herein we design and synthesize a turn-on fluorescent probe termed Cy-AP, which displays high sensitivity and selectivity to hypoxia given by sodium dithionite (Na 2 S 2 O 4 ) in vitro with near-infrared (NIR) emission (725 nm). The possible response mechanism of Cy-AP toward hypoxia is given and proved though HPLC, MS, and theory calculation. Moreover, on the basis of low cell cytotoxicity, the probe is used in visualizing hypoxia in four cell lines (HepG2, HCT116, HeLa, and MCF-7 cells) by fluorescence imaging, flow cytometry, and 3D imaging. Furthermore, due to its NIR emission, Cy-AP can monitor the hypoxia condition in vivo such as in liver fibrosis mice and ulcerative colitis mice models. In particular, the probe can validate the existence and mechanism of the "gut-liver axis" in vivo by monitoring hypoxia. To the best of our knowledge, this is the first work to give a strategy for studying the "gut-liver axis" by a NIR hypoxia-sensitive fluorescent probe, which will provide some powerful support for delaying the progression of liver fibrosis and thus promoting the treatment of liver disease.

Objectives: This is a meta-analysis of randomized double-blind controlled-placebo trials (RCTs) examining the effectiveness, tolerability, and safety of intranasal esketamine in treating major depressive disorder (MDD)., Methods: Standardized mean difference (SMD), risk ratio (RR) and their 95% confidence intervals (CIs) were calculated using RevMan version 5.3., Results: Four RCTs with 7 active arms covering 708 patients with MDD on intranasal esketamine (n = 419) and placebo (n = 289) were included. Compared with placebo, adjunctive intranasal esketamine was associated with significantly greater study-defined response (RR=1.39, 95%CI: 1.18 to 1.64, P<0.0001) and remission (RR=1.42, 95%CI: 1.17 to 1.72, P = 0.0004) at endpoint assessment. Intranasal esketamine had greater study-defined response starting at 2 h (RR= 2.77, 95%CI: 1.62 to 4.76, P = 0.0002), peaking at 24 h (RR=5.42, 95%CI: 1.38 to 21.20, P = 0.02), and at least lasting for 28 days (RR=1.36, 95%CI: 1.16 to 1.58, P = 0.0001). Similarly, intranasal esketamine had significantly greater study-defined remission starting at 2 h (RR=7.71, 95%CI: 2.16 to 27.55, P = 0.002), peaking at 24 h (RR=6.87, 95%CI: 1.55 to 30.35, P = 0.01), and lasting for 28 days (RR=1.38, 95%CI: 1.11 to 1.72, P = 0.004). Intranasal esketamine had a significantly higher rate of discontinuation due to intolerability (RR=3.50, 95%CI: 1.38 to 8.86, P = 0.008). Discontinuation due to any reasons and inefficacy were similar between the two groups., Conclusion: Intranasal esketamine appears to have an ultra-rapid antidepressant effect for MDD, at least lasting for 28 days. The long-term therapeutic effect and safety of intranasal esketamine need to be further examined in large-scale RCTs., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020. Published by Elsevier B.V.)

Objective: To assess the health status and health service utilization of children born to syphilis infected mothers during pregnancy, in order to prevent mother-to-child transmission of syphilis to the newborns. Methods: Women with maternal syphilis were studied by trained researchers via phone calls, in Shanghai during 2014-2015. Data related to demographics, status of infection and health care, utilization by both mothers and their children were collected through specifically designed questionnaires. Non-parametric tests including chi-square were used to assess the health status and health service utilization of children born to mothers with different demographic and socioeconomic characteristics. Results: A total of 495 children born to mothers with maternal syphilis were recruited from 1 000 syphilis infected parturient women. A total of 61 out of the 495 children were diagnosed as having congenital syphilis (57 children were diagnosed at birth and another 4 were diagnosed during the follow-up period). Children born to women who received syphilis treatment during pregnancy were at lower risk on congenital syphilis ( χ (2)=7.214, P =0.027). 37.8 % of the children were reported to have had different illnesses in the past three months, mainly involving upper respiratory infections (32.3 % ) or diarrhea (3.6 % ). Children diagnosed with congenital syphilis showed a higher prevalence of different kinds of diseases, compared to those without congenital syphilis (47.5 % vs. 36.6 % ). 81.6 % of the children had received regular child health care services. Subjects with the following factors as: being immigrant, with lower education, unemployed, unmarried and multipara, were related to the less use of regular child healthcare services. Only 39.7 % of the parents would inform the care-takers about the risk of congenital syphilis infection of their own children at the child health care centers. Mothers with residency of Shanghai, having higher education level and employed, were less willing to inform doctors about the risk of congenital syphilis infection of their children. Conclusions: Loss to follow-up among children born to syphilis infected pregnant women remained a serious problem. Few parents would be willing to inform the healthcare takers that their children are at risk of syphilis, when receiving child health care services at the centers. It was necessary to integrate the congenital syphilis follow-up programs into the routine child care services so as to timely diagnose and treat the patients with congenital syphilis.

Objective: To explore the application value of 3D printing technology in preoperative surgery plan and intraoperative auxiliary operation for adult kyphoscoliosis deformity., Methods: The clinical data of 12 adult patients with kyphoscoliosis deformity treated from September 2017 to January 2019 were retrospectively analyzed. There were 3 males and 9 females, aged from 21 to 63 years old with an average of (47.67±13.32) years old. Among them, 4 cases were congenital kyphoscoliosis, 2 cases were old tuberculosis thoracolumbar kyphosis ; 2 cases were idiopathic kyphoscoliosis, 4 cases were degenerative kyphoscoliosis. The CT scan data of the patient's spine was imported into Mimics17.0 software to establish the three dimensional model of the spine, and the spine model was produced by 3D printer. Using the spine model simulated operation, preoperative surgery program planning and formulated a precise surgery, and further analysed postoperative imaging parameters improvement. All the patients were followed up for more than 1 year. Before and after operation and at the last follow-up, the scoliosis Cobb angle, maximum kyphosis Cobb angle, and coronal plane balance (distance between C 7 plumbline and center sacral vertical line, C 7 PL-CSVL), sagittal plane balance (sagittal vertical axis, SVA), pelvic parameters and other related imaging parameters were measured to further evaluate its orthopedic effect., Results: Twelve patients with spine deformity were treated with different osteotomy and internal fixation fusion methods under the guidance of a 1∶1 spine model (pedicle screw placement of 4 patients with severe deformity were assisted by pedicle screw guide plates), nail placement and osteotomy have good effects, no major tissue damage such as blood vessels, nerves and spinal cord during and after surgery, no complications such as cerebrospinal fluid leakage and infection. Preoperative Cobb angle of scoliosis was (56.5±22.5) °, Cobb angle of kyphosis was (65.2±19.5) °, C 7 PL-CSVL was (45.8±16.9) mm, SVA was (48.7±25.4) mm. Postoperative at 4 weeks, Cobb angle of scoliosis was (20.8±11.5) °, and Cobb angle of kyphosis was (22.0±6.6) °, with correction rates of (65.1±9.7)% and (64.6± 10.6)%, respectively ; C 7 PL-CSVL was (22.3±8.9) mm, and SVA was (23.3±13.1) mm, all of which were significantly improved compared with preoperative results. The mean follow-up time was (18.5±7.9) months in 12 patients. At the last follow-up, the Cobb angles of scoliosis and kyphosis were (22.2±10.8) ° and (23.6±7.7) °, respectively, C 7 PL-CSVL was (23.5±10.8) mm, and SVA was (24.7±12.5) mm. The results were statistically significant compared preoperative ( P <0.05). There was no significant difference at the postoperative at 4 weeks and the last follow-up ( P >0.05)., Conclusion: The 3D print model can visually and clearly show the vertebral morphology and structure of adult kyphoscolisis and its spatial relationship with the adjacent vertebrae, blood vessels, and nerves, which provides a good and intuitive stereoscopic anatomical structure observation for the individualization of the surgical plan. Pre-simulation of operations to determine the internal fixation, fusion segment and osteotomy orthopedic way, may to provide a reference for actual clinical surgery, and can improve the accuracy and safety of surgery.

We herein present a new family of crown ether-based covalent organic frameworks (CE-COFs) for the first time. The CE-COFs show excellent phase-transfer catalytic performance in various nucleophilic substitution reactions.

A novel hepatocyte-targeting near-infrared fluorescent probe named Gal-NIR is developed. Gal-NIR shows ratiometric response to ONOO- with high sensitivity and selectivity. Moreover, the probe can accurately target the hepatocyte, and thus is used for assessing drug-induced hepatotoxicity and its remediation by using hepatoprotective medicines in living cells and mice.

A total of six treatments, including continuous conventional tillage (CT), rotary tillage (RT), subsoiling (ST), no-tillage (NT), conventional-no tillage (CT-NT) and subsoiling-no tillage (ST-NT), were conducted to examine the effects of different tillage types on soil aggregates distribution and stability of irrigated sierozem on continuous 8-year-tillage maize fields in the Gansu Yellow River irrigated area in 2014-2017. The results showed that the aggregation and stability of large aggregates in 0-40 cm soil layer were increased by NT and ST-NT treatments, while the size distribution and stability in plough layer were significantly decreased by CT and RT treatments due to strong soil disturbance. Compared with RT, the mechanical stability of aggregates under dry sieving NT was the best. The contents of >0.25 mm aggregate (R 0.25 ), mean weight diameter (MWD) and geometric mean diameter (GMD) increased by 5.8%, 8.0%, and 13.0%, respectively, and fractal dimension (D) decreased by 3.6%. The water-stable aggregates in ST-NT was the best, with R 0.25 , MWD and GMD increased by 55.3%, 15.1% and 8.7%, respectively, and D value decreased by 0.8%. The percentage of aggregate destruction (PAD) and unstable aggregate index (E LT ) of NT and ST-NT treatments were the lowest. PAD was reduced by 5.9% and 7.7% compared with RT, E LT was reduced by 5.8% and 7.2%, respectively. All the results indicated that the subsoiling-notillage (ST-NT) rotation mode was more conducive to the enhancement of soil aggregate content and stability and consistent with the local farmers operating habits, which would be an ideal tillage method and had certain application value for the sustainable agricultural development in this area.

A new heterometallic macrocycle with photochromic properties was succesfully constructed through coordination-driven self-assembly, which features interesting photoswitchable Förster resonance energy transfer (FRET) behaviour.

Azoreductase (AzoR) is an essential reductive enzyme which is closely associated with the intestinal disease such as ulcerative colitis (UC). To date, only a few fluorescent probes for detecting AzoR activity in bacteria or cells have been constructed successfully. It is still challenging to design fluorescent probes for in situ monitoring AzoR in vivo. In this paper, a near-infrared (NIR) fluorescent probe (Cy-Azo) based on hemicyanine is designed and synthesized. The emission of the probe is located at 735 nm in the NIR region, which is favorable for its application in vivo. In addition, Cy-Azo shows high sensitivity to AzoR activity with 17-fold fluorescence enhancement and is particularly selective to AzoR over other enzymes, ions, and amino acids. Meanwhile, a possible response mechanism (the azo group in Cy-Azo is reduced by AzoR and cleaved resulting in the production of Cy-NH 2 ) was proposed and verified by HPLC, MS, and theory calculation. In addition, based on low cell cytotoxicity, Cy-Azo is successfully applied in visualizing the activity of AzoR in two cell lines (HCT116 and HepG2 cells) and three types of bacteria ( E. coli , S. aureus , and P. aeruginosa ). In particular, due to its NIR emission, the probe can monitor AzoR activity in acute and chronic UC mice models. To our knowledge this is the first fluorescent probe for detecting AzoR activity in vivo, which can provide much important information for the diagnosis and treatment of UC.

Background: Novel therapeutic strategies are urgently needed for patients with a delayed diagnosis of pancreatic ductal adenocarcinoma (PDAC) in order to improve their chances of survival. Recent studies have shown potent anti-neoplastic effects of curcumin and its analogues. In addition, the role of histone methyltransferases on cancer therapeutics has also been elucidated. However, the relationship between these two factors in the treatment of pancreatic cancer remains unknown. Our working hypothesis was that L48H37, a novel curcumin analog, has better efficacy in pancreatic cancer cell growth inhibition in the absence of histone-lysine N-methyltransferase 2D (KMT2D)., Aim: To determine the anti-cancer effects of L48H37 in PDAC, and the role of KMT2D on its therapeutic efficacy., Methods: The viability and proliferation of primary (PANC-1 and MIA PaCa-2) and metastatic (SW1990 and ASPC-1) PDAC cell lines treated with L48H37 was determined by CCK8 and colony formation assay. Apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) levels, and cell cycle profile were determined by staining the cells with Annexin-V/7-AAD, JC-1, DCFH-DA, and PI respectively, as well as flow cytometric acquisition. In vitro migration was assessed by the wound healing assay. The protein and mRNA levels of relevant factors were analyzed using Western blotting, immunofluorescence and real time-quantitative PCR. The in situ expression of KMT2D in both human PDAC and paired adjacent normal tissues was determined by immunohistochemistry. In vivo tumor xenografts were established by injecting nude mice with PDAC cells. Bioinformatics analyses were also conducted using gene expression databases and TCGA., Results: L48H37 inhibited the proliferation and induced apoptosis in SW1990 and ASPC-1 cells in a dose- and time-dependent manner, while also reducing MMP, increasing ROS levels, arresting cell cycle at the G2/M stages and activating the endoplasmic reticulum (ER) stress-associated protein kinase RNA-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/activating transcription factor 4 (ATF4)/CHOP signaling pathway. Knocking down ATF4 significantly upregulated KMT2D in PDAC cells, and also decreased L48H37-induced apoptosis. Furthermore, silencing KMT2D in L48H37-treated cells significantly augmented apoptosis and the ER stress pathway, indicating that KMT2D depletion is essential for the anti-neoplastic effects of L48H37. Administering L48H37 to mice bearing tumors derived from control or KMT2D-knockdown PDAC cells significantly decreased the tumor burden. We also identified several differentially expressed genes in PDAC cell lines expressing very low levels of KMT2D that were functionally categorized into the extrinsic apoptotic signaling pathway. The KMT2D high- and low-expressing PDAC patients from the TCGA database showed similar survival rates,but higher KMT2D expression was associated with poor tumor grade in clinical and pathological analyses., Conclusion: L48H37 exerts a potent anti-cancer effect in PDAC, which is augmented by KMT2D deficiency., Competing Interests: Conflict-of-interest statement: There is no conflict of interest.

Aberrant microRNAs are widely identified in multiple cancers, including lung cancer. miR-135a-5p can function as a significant tumor regulator in diverse cancers via impacting multiple genes in oncogenic pathways. Nevertheless, the biological role of miR-135a-5p in lung cancer is poorly known. Here, we investigated its function in lung cancer. As exhibited, miR-135a-5p was elevated in lung cancer cells in contrast to BEAS-2B cells. Then, we inhibited miR-135a-5p expression by transfecting LV-anti-miR-135a-5p into lung cancer cells. As displayed, miR-135a-5p was obviously reduced in A549 and H1299 cells. Knockdown of miR-135a-5p repressed lung cancer cell growth and cell proliferation. Meanwhile, cell colony formation capacity was depressed, cell apoptosis was enhanced and cell cycle progression was blocked in G1 phase by inhibition of miR-135a-5p in vitro. Additionally, the migration and invasion of A549 and H1299 cells was strongly depressed by LV-anti-miR-135a-5p. For another, by using informatics analysis, lysyl oxidase-like 4 (LOXL4) was speculated as the downstream target of miR-135a-5p. We validated their direct correlation and moreover, overexpression of miR-135a-5p restrained LOXL4 levels in lung cancer cells. Subsequently, we proved that miR-135a-5p promoted lung cancer development via targeting LOXL4 by carrying out the in vivo assays. Taken these together, our study revealed miR-135a-5p might be indicated as a perspective for lung cancer via targeting LOXL4., (© 2019 Wiley Periodicals, Inc.)

In this work, we report a facile, sensitive, selective, and reproducible DNA impedimetric sensor device. We demonstrate that, combined with exonuclease III, the easily prepared electrochemically reduced graphene oxide (rGO) could be a desirable platform to amplify signals in electrochemical impedance spectroscopy for ultrasensitive DNA detection. Guided by enzyme assisted target recycling, efficient interfacial tuning can be obtained, from the situation with high impedance caused by single-stranded DNA probes directly adsorbed onto rGO to the one with low impedance due to the continuous desorption of target-probe DNA hybrids and the consequent digestion of DNA probes. Just a few DNA targets can specifically trigger the enzymatic digestion of a large number of DNA probes. It is the excellent electrical conductivity of rGO that further enlarges the changes of electron transfer resistance after the removal of DNA probes. As a result of synergistically combining both enzymatic and electrical amplification, the enlarged changes of impedimetric signals can be measured to sensitively report DNA targets. The specificity has been guaranteed by the intrinsic recognition of hybrids through both rGO and exonuclease III. A limit of detection as low as 10 aM target DNA in the matrix of cell culture medium, as well as a wide linear range and good discrimination of mismatched sequences even at the one-base level, suggests its great application prospect in biosensing and biomedical analysis. It also has other advantages including easy operation, low cost, and convenient regeneration, with more competitive performance in developing impedimetric biosensors.

The colon is an alternative graft organ for esophageal reconstruction. The present study reviewed our experience with the colon interposition for esophageal replacement following corrosive ingestion, to evaluate the outcomes of colon interposition based on our surgical experience. The clinical data of 119 patients who underwent colon interposition for esophageal replacement from January 2005 to March 2017 were retrospectively analyzed. The routes of the colon interposition were retrosternal in 119 (100%). The median operative time was 390 min (range: 290-610 min) and the median blood loss was 615 mL (range: 270-2500 mL). Of these 119 patients, the cervical anastomosis was performed at the hypopharynx (n=20, 16.8%), the larynx (n=3, 2.5%), and the cervical esophagus (n=96, 80.7%). Five patients experienced cervical anastomotic leakage (4 cases for esophagus-colon, and one for hypopharynx-colon). One patient experienced wound infection of the abdominal wall. Three patients had injury of recurrent laryngeal nerve and hoarseness. Three patients had stress ulcer with bleeding and treated with octreotide. Two patients suffered from incomplete intestinal obstruction. The postoperative follow-up was made for 12 months in all patients and all of them were alive. In conclusion, The colon is well-suited for esophageal reconstruction. The selection of the colon graft should be flexible and be based on the inspection of blood supply and the length needed. We must therefore make every effort to reduce the number of postoperative complications, and improve the quality of life for patients.

Nitric oxide (NO) plays vital roles in many physiological process and is closely related to many diseases. So far, a number of fluorescent probes have been constructed for the detection of NO successfully. However, the probes still suffer from long-time reaction and limited selectivity. Herein, a fluorescent probe named dRB-OPD is synthesized and used to recognize NO. The probe contains a deoxy-rhodamine B as fluorophore and o-phenylenediamino as reaction site. dRB-OPD shows fast response to NO within 40 s with 170-fold fluorescence enhancement. Moreover, the probe shows high selectivity towards NO over dehydroascorbic acid (DHA), ascorbic acid (AA), and methylglyoxal (MGO). Particularly, the probe can avoid the serious interference from cysteine (Cys) found in the rhodamine lactam-based fluorescent NO probes (RB-OPD). In addition, the probe is applied for the detection of exogenous and endogenous NO in the HepG2 and RAW 264.7 cells with satisfactory results., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study aimed to investigate the effect of food to microorganisms rate (F/M) on organic removal, extracellular polymeric substances (EPS) and soluble microbial products (SMP) of the pure oxygen aerated activated sludge running in batch mode. The F/M rates were controlled by adjusting the MLSS concentrations (2000, 5000, 8000 mg/L) and/or the initial TOC concentrations (100, 500 mg/L). Results showed that at high F/M rate (0.25 kg TOC/kg MLSS), the substrate degradation rate in the oxygen aerated reactor could reach 1.347 mg TOC/(L·min)), much higher than that in the air aerated reactor (0.640 mg TOC/(L·min)). The SMP concentrations with oxygen aeration were also higher than those with air aeration under high F/M conditions. The total EPS contents in the pure oxygen aerated sludge were significantly lower regardless of the different F/M rates. High F/M condition would lead to more amount of polysaccharides synthesis rather than proteins synthesis in EPS., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

With the strength of liquid nuclear magnetic resonance (NMR) to noninvasively and specifically realize the structural elucidation and quantitative analysis of small organic molecules, in principle, liquid in situ electrochemical-NMR (EC-NMR) possesses great advantages for detecting dissolved species during the electrochemical process. However, the intrinsic incompatibilities between the coupling techniques as well as the sophisticated setups modification still limit the applications toward a wide range. To overcome these bottlenecks, herein we propose an easy-to-construct design with good compatibility and presenting improved electrochemical and NMR performances. As proof of concept, model experiments of alcohol electrooxidation were performed to confirm the capacity of this device for liquid in situ EC-NMR study. The temporal evolution of both the product and the current distributions can be reliably recorded to aid mechanistic and kinetic understanding of electrocatalysis. The depiction of the selective electrooxidation reveals the surface structure-catalytic functionality. This work demonstrates the universality and effectivity of the proposed platform to develop the liquid in situ EC-NMR technique as a useful tool for the dynamic analysis of electrochemical processes at a molecular level.

Graphene oxide (GO) membranes have the potential to be next-generation membranes. However, the GO layer easily swells in water and risks shedding during the long-term filtration. Organic GO interlayer organic cross-linking agent was not resistant to oxidation, which limits the application scope of GO membrane. In this study, an inorganic cross-linked GO membrane was prepared via the reaction of sodium tetraborate and GO hydroxyl groups, and a -B-O-C- cross-linking bond was detected by X-ray photoelectron spectroscopy (XPS). Additionally, a new atomic force microscope scratch method to evaluate the cross-linking force of a nanoscale GO layer was proposed. It showed that the critical destructive load of the inorganic cross-linked GO membrane increased from 8 to 80 nN, which was a 10-fold increase from that of the nonlinked sample. During the NaOH/sodium dodecyl sulfate (SDS) destructive wash tests, morphology, flux and retention rate of inorganic cross-linked GO remained stable while the comparative membranes showed significant destruction. At the same time, based on the better oxidation resistance, organic membrane fouling was effectively controlled by the introduction of trace ·OH radicals. This study provides a new perspective for GO membrane preparation, interlayer cross-linking force testing and membrane fouling control.

A field experiment was conducted to examine the effects of subsoiling 35 cm with maize straw returning, subsoiling 35 cm without maize straw returning, and rotary tillage without maize straw returning on soil compaction, soil bulk density, soil infiltration, soil water content in 0-100 cm depth, nutrients uptake and production of maize on sierozem in the Gansu Yellow River irrigated area in 2015-2017. Compared with subsoiling 35 cm without maize straw returning and rotary tillage without maize straw returning, subsoiling 35 cm with maize straw returning significantly decreased the soil compaction and soil density in 0-40 cm depth. Compared with that in 2015 (before experiment), soil compaction and soil bulk density in subsoiling 35 cm with straw returning was decreased by 42.6% and 7.0%, respectively, after harvest in 2017. Compared with other treatments, subsoiling 35 cm with straw returning had the lowest variation of soil compaction (6.1%) and soil bulk density (3.2%) in 0-40 cm depth before sowing and after harvest in 2016 and 2017. The soil infiltration rate in subsoiling 35 cm with straw returning was significantly improved by 33.6% compared with rotary tillage without maize straw returning. Subsoiling 35 cm with straw retention could significantly increase soil water content and decrease water variation in 0-100 cm soil depth in spring (before maize sowing) and autumn (after maize harvest). Compared with rotary tillage without maize straw returning, water storage in subsoiling 35 cm with straw retention was increased by 15.5% and 5.6% in spring and autumn, respectively. The water use efficiency was enhanced by 32.4%. Furthermore, subsoiling 35 cm with straw retention could increase maize economic yield and biomass yield by 25.6% and 33.3%, compared with rotary tillage without straw retention. Subsoilng and straw retention could promote nutrient absorption, with N, P 2 O 5 and K 2 O uptake increased by 49.6%, 51.5% and 37.6%, compared with rotary tillage. Overall, our results suggested that subsoiling 35 cm straw retention could improve soil characteristics, stabilize the phy-sical properties of the plough layer, increase soil water content in the 0-100 cm soil layer, and reduce water variation in spring and autumn. Consequently, it was the best management to promote the water and nutrient utilization of maize and achieve high yield. Our findings could provide theoretical basis for further research on the construction technology of the plough layer in Gansu irrigation area.