Search

Background: Early initiation of biologics in moderate-to-severe Crohn's disease (CD) may significantly alter disease progression, resulting in better patient outcomes. Limited real-world data exist on the impact of early biologic use in patients with CD in the United States., Aims: We aimed to characterize biologic initiation and subsequent healthcare resource utilization (HCRU) in adults with recently diagnosed CD., Methods: Patients with CD who initiated biologic treatment within 2 years of diagnosis (index date) were identified from medical and pharmacy claims (Merative L.P. MarketScan Database from 2010 to 2016) and classified as early (≤ 12 months post-index) or late (> 12-24 months post-index) biologic initiators. Propensity score matching balanced patient characteristics up to 1 year post-index. Differences in HCRU frequency and costs 1-2 years post-index were compared between the matched groups., Results: After propensity score matching, 672 pairs of early and late biologic initiators were identified. Patients who initiated biologics early had fewer outpatient visits (15.5 vs 19.8, 95% confidence interval [CI] for difference: 2.7, 6.1) and lower total medical costs ($13,646.20 vs $22,180.70, 95% CI for difference: 4748.9, 12,320.1) 1-2 years post-index than late biologic initiators. Early biologic initiators had higher medication costs 1-2 years post-index ($33,766.30 vs $30,580.70, 95% CI: 546.1, 5825.1) but lower combined medical and medication costs ($47,412.50 vs $52,761.50, 95% CI: 801.5, 9896.40)., Conclusions: While biologic treatments are costly, patients initiating biologics sooner after diagnosis appear to have better HCRU outcomes and require fewer healthcare resources at 1-2 years post-index, potentially leading to overall cost savings., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Zoonotic coronaviruses (CoVs) caused major human outbreaks in the last two decades. One of the biggest challenges during future CoV disease is ensuring rapid detection and diagnosis at the early phase of a zoonotic event, and active surveillance to the zoonotic high-risk CoVs appears the best way at the present time to provide early warnings. However, there is neither an evaluation of spillover potential nor diagnosis tools for the majority of CoVs. Here, we analyzed the viral traits, including population, genetic diversity, receptor and host species for all 40 alpha- and beta-CoV species, where the human-infecting CoVs are from. Our analysis proposed 20 high-risk CoV species, including 6 of which jumped to human, 3 with evidence of spillover but not to human and 11 without evidence of spillover yet, which prediction were further supported by an analysis of the history of CoV zoonosis. We also found three major zoonotic sources: multiple bat-origin CoV species, the rodent-origin sub-genus Embecovirus and the CoV species AlphaCoV1. Moreover, the Rhinolophidae and Hipposideridae bats harbour a significantly higher proportion of human-threatening CoV species, whereas camel, civet, swine and pangolin could be important intermediate hosts during CoV zoonotic transmission. Finally, we established quick and sensitive serologic tools for a list of proposed high-risk CoVs and validated the methods in serum cross-reaction assays using hyper-immune rabbit sera or clinical samples. By comprehensive risk assessment of the potential human-infecting CoVs, our work provides a theoretical or practical basis for future CoV disease preparedness.

Methane activation by photocatalysis is one of the promising sustainable technologies for chemical synthesis. However, the current efficiency and stability of the process are moderate. Herein, a PdCu nanoalloy (~2.3 nm) was decorated on TiO 2 , which works for the efficient, stable, and selective photocatalytic oxidative coupling of methane at room temperature. A high methane conversion rate of 2480 μmol g -1 h -1 to C 2 with an apparent quantum efficiency of ~8.4% has been achieved. More importantly, the photocatalyst exhibits the turnover frequency and turnover number of 116 h -1 and 12,642 with respect to PdCu, representing a record among all the photocatalytic processes (λ > 300 nm) operated at room temperature, together with a long stability of over 112 hours. The nanoalloy works as a hole acceptor, in which Pd softens and weakens C-H bond in methane and Cu decreases the adsorption energy of C 2 products, leading to the high efficiency and long-time stability., (© 2023. Springer Nature Limited.)

Finding highly efficient hydrogen evolution reaction (HER) catalysts is pertinent to the ultimate goal of transformation into a net-zero carbon emission society. The design principles for such HER catalysts lie in the well-known structure-property relationship, which guides the synthesis procedure that creates catalyst with target properties such as catalytic activity. Here we report a general strategy to synthesize 10 kinds of single-atom-doped CoSe 2 -DETA (DETA = diethylenetriamine) nanobelts. By systematically analyzing these products, we demonstrate a volcano-shape correlation between HER activity and Co atomic configuration (ratio of Co-N bonds to Co-Se bonds). Specifically, Pb-CoSe 2 -DETA catalyst reaches current density of 10 mA cm -2 at 74 mV in acidic electrolyte (0.5 M H 2 SO 4 , pH ~0.35). This striking catalytic performance can be attributed to its optimized Co atomic configuration induced by single-atom doping., (© 2023. The Author(s).)

Alkaline fuel cells can permit the adoption of platinum group metal-free (PGM-free) catalysts and cheap bipolar plates, thus further lowering the cost. With the exploration of PGM-free hydrogen oxidation reaction (HOR) catalysts, nickel-based compounds have been considered as the most promising HOR catalysts in alkali. Here we report an interfacial engineering through the formation of nickel-vanadium oxide (Ni/V 2 O 3 ) heterostructures to activate Ni for efficient HOR catalysis in alkali. The strong electron transfer from Ni to V 2 O 3 could modulate the electronic structure of Ni sites. The optimal Ni/V 2 O 3 catalyst exhibits a high intrinsic activity of 0.038 mA cm -2 and outstanding stability. Experimental and theoretical studies reveal that Ni/V 2 O 3 interface as the active sites can enable to optimize the hydrogen and hydroxyl bindings, as well as protect metallic Ni from extensive oxidation, thus achieving the notable activity and durability., (© 2023 Wiley-VCH GmbH.)

H 2 O 2 is widely used as an oxidant for photocatalytic methane conversion to value-added chemicals over oxide-based photocatalysts under mild conditions, but suffers from low utilization efficiencies. Herein, we report that O 2 is an efficient molecular additive to enhance the utilization efficiency of H 2 O 2 by suppressing H 2 O 2 adsorption on oxides and consequent photogenerated holes-mediated H 2 O 2 dissociation into O 2 . In photocatalytic methane conversion over an anatase TiO 2 nanocrystals predominantly enclosed by the {001} facets (denoted as TiO 2 {001})-C 3 N 4 composite photocatalyst at room temperature and ambient pressure, O 2 additive significantly enhances the utilization efficiency of H 2 O 2 up to 93.3%, giving formic acid and liquid-phase oxygenates selectivities respectively of 69.8% and 97% and a formic acid yield of 486 μmol HCOOH ·g catalyst -1 ·h -1 . Efficient charge separation within TiO 2 {001}-C 3 N 4 heterojunctions, photogenerated holes-mediated activation of CH 4 into ·CH 3 radicals on TiO 2 {001} and photogenerated electrons-mediated activation of H 2 O 2 into ·OOH radicals on C 3 N 4 , and preferential dissociative adsorption of methanol on TiO 2 {001} are responsible for the active and selective photocatalytic conversion of methane to formic acid over TiO 2 {001}-C 3 N 4 composite photocatalyst., (© 2022. The Author(s).)

Over the past few decades, much progress has been made in the clinical use of electrical stimulation of the central nervous system (CNS) to treat an ever-growing number of conditions from Parkinson's disease (PD) to epilepsy as well as for sensory restoration and many other applications. However, little is known about the effects of microstimulation at the cellular level. Most of the existing research focuses on the effects of electrical stimulation on neurons. Other cells of the CNS such as microglia, astrocytes, oligodendrocytes, and vascular endothelial cells have been understudied in terms of their response to stimulation. The varied and critical functions of these cell types are now beginning to be better understood, and their vital roles in brain function in both health and disease are becoming better appreciated. To shed light on the importance of the way electrical stimulation as distinct from device implantation impacts non-neuronal cell types, this review will first summarize common stimulation modalities from the perspective of device design and stimulation parameters and how these different parameters have an impact on the physiological response. Following this, what is known about the responses of different cell types to different stimulation modalities will be summarized, drawing on findings from both clinical studies as well as clinically relevant animal models and in vitro systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Williams, Kushwah, Dhawan, Zheng and Cui.)

What Is Known and Objective: Propofol and esketamine are routine anaesthetics used in sedation or general anaesthesia for paediatric procedures. Coadministration could reduce the dose of either propofol or esketamine required and lower the incidence of drug-related adverse events. We designed a four-arm randomized controlled trial in children undergoing diagnostic upper gastrointestinal endoscopy to investigate the dose of propofol with different doses of esketamine inducing appropriate depth of anaesthesia in 50% patients (median effective dose, ED 50 )., Methods: After getting the approval of the research ethics committee and informed consent, 92 paediatric patients planning for upper gastrointestinal endoscopy were divided into four groups randomly: esketamine 0, 0.25, 0.5 and 1 mg/kg groups (n = 23/group). Propofol doses followed the Dixon and Massey up-and-down method with different starting and interval doses between groups. During the first attempt of endoscope insertion, if patients' reactions prevented the insertion, it would be considered as a failure. The awakening time, total propofol doses, as well as the perioperative and post-procedure adverse events were evaluated and recorded for each patient., Results and Discussion: The ED 50 (median, 95% confidence interval) of propofol was significantly greater in esketamine 0 and 0.25 mg/kg groups in comparison with the esketamine 0.5 and 1 mg/kg groups (4.1 [3.3-4.9]; 3.1 [2.5-3.8] mg/kg vs. 1.8 [1.1-2.4]; 0.8 [0.2-1.3] mg/kg, respectively, p < .05). The total doses of propofol in esketamine 0.5 and 1 mg/kg groups were statistically lower than these in esketamine 0 and 0.25 mg/kg group (p < .01). The mean blood pressure was lower in the esketamine 0 mg/kg group than that in 1 mg/kg group after administration and during the procedure (p < .01). The esketamine 1 mg/kg group showed a higher incidence of vomiting and visual disturbances than the other three groups (p < .001)., What Is New and Conclusion: In children who accomplished diagnostic paediatric upper gastrointestinal endoscopy under deep sedation/anaesthesia, the total dosage of propofol needed was reduced significantly in esketamine 0.5 and 1 mg/kg groups with a corresponding reduce in propofol-related hemodynamic changes. However, a higher incidence of esketamine-related adverse effects was found in esketamine 1 mg/kg group., (© 2022 John Wiley & Sons Ltd.)

Chronic microstimulation is faced with challenges that require an additional understanding of stability and safety. We implanted silicon arrays coated with poly(3,4-ethylenedioxythiophene) (PEDOT)/Carbon Nanotubes (CNT), or PCand IrOx into the cortex of GCaMP6s mice and electrically stimulated them for up to 12 weeks. We quantified neuronal responses to stimulation using two-photon imaging and mesoscale fluorescence microscopy and characterized electrode performance over time. We observed dynamic changes in stimulation stability over time and a significant advantage in energy efficiency using PC coated electrodes over IrOx coated electrodes. In a subset of mice, we observed abnormal ictal cortical responses or cortical spreading depression using stimulation parameters commonly used in intracortical stimulation applications, suggesting the need to investigate the potential neuronal damage and redefine the stimulation safety limit. This study not only revealed the dynamic changes in stimulation efficiency after implantation but also reiterates the potential for PC as a high-efficiency material in chronic neuromodulation., Competing Interests: The authors report no conflict of interest., (© 2022 The Author(s).)

Due to the limitation of human studies with respect to individual difference or the accessibility of fresh tissue samples, how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in pathological complications in lung, the main site of infection, is still incompletely understood. Therefore, physiologically relevant animal models under realistic SARS-CoV-2 infection conditions would be helpful to our understanding of dysregulated inflammation response in lung in the context of targeted therapeutics. Here, we characterized the single-cell landscape in lung and spleen upon SARS-CoV-2 infection in an acute severe disease mouse model that replicates human symptoms, including severe lung pathology and lymphopenia. We showed a reduction of lymphocyte populations and an increase of neutrophils in lung and then demonstrated the key role of neutrophil-mediated lung immunopathology in both mice and humans. Under severe conditions, neutrophils recruited by a chemokine-driven positive feedback produced elevated "fatal signature" proinflammatory genes and pathways related to neutrophil activation or releasing of granular content. In addition, we identified a new Cd177 high cluster that is undergoing respiratory burst and Stfa high cluster cells that may dampen antigen presentation upon infection. We also revealed the devastating effect of overactivated neutrophil by showing the highly enriched neutrophil extracellular traps in lung and a dampened B-cell function in either lung or spleen that may be attributed to arginine consumption by neutrophil. The current study helped our understanding of SARS-CoV-2-induced pneumonia and warranted the concept of neutrophil-targeting therapeutics in COVID-19 treatment. IMPORTANCE We demonstrated the single-cell landscape in lung and spleen upon SARS-CoV-2 infection in an acute severe disease mouse model that replicated human symptoms, including severe lung pathology and lymphopenia. Our comprehensive study revealed the key role of neutrophil-mediated lung immunopathology in SARS-CoV-2-induced severe pneumonia, which not only helped our understanding of COVID-19 but also warranted the concept of neutrophil targeting therapeutics in COVID-19 treatment.

Background: ITPR1 is a key gene for autophagy, but its biological function is still unclear, and there are few studies on the correlation between ITPR1 gene expression and the occurrence and development of breast cancer., Methods: Analyze the expression of ITPR1 through online databases such as Oncomine and TIMER. Kaplan-Meier plotter and other databases were used to evaluate the impact of ITPR1 on clinical prognosis. The expression of ITPR1 in analysis of 145 cases of breast cancer and 30 cases of adjacent normal tissue was detected by Immunohistochemistry. Statistical analysis was used to evaluate the clinical relevance and prognostic significance of abnormally expressed proteins. And the Western Blot was used to detect the expression of ITPR1 between breast cancer tissues and cells. The TIMER database studied the relationship between ITPR1 and cancer immune infiltration. And used the ROC plotter database to predict the response of ITPR1 to chemotherapy, endocrine therapy and anti-HER2 therapy in patients with breast cancer., Results: Compared with normal breast samples, ITPR1 was significantly lower in patients with breast cancer. And the increased expression of ITPR1 mRNA was closely related to longer overall survival (OS), distant metastasis free survival (DMFS), disease specific survival (DSS) and relapse free survival (RFS) in breast cancer. And the expression level of ITPR1 was higher in patients treated with chemotherapy than untreated patients. In addition, the expression of ITPR1 was positively correlated with related gene markers of immune cells in different types of breast cancer, especially with BRCA basal tissue breast cancer., Conclusion: ITPR1 was lower expressed in breast cancer. The higher expression of ITPR1 suggested favorable prognosis for patients. ITPR1 was related to the level of immune infiltration, especially in BRCA-Basal patients. All research results indicated that ITPR1 might affect breast cancer prognosis and participate in immune regulation. In short, ITPR1 might be a potential target for breast cancer therapy., (© 2022. The Author(s).)

SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19. However, whether lymphocytes are targets of viral infection is yet to be determined, although SARS-CoV-2 RNA or antigen has been identified in T cells from patients. Here, we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells (PBCs) or postmortem lung T cells, and the infectious virus could also be detected from viral antigen-positive PBCs. We next prove that SARS-CoV-2 infects T lymphocytes, preferably activated CD4 + T cells in vitro. Upon infection, viral RNA, subgenomic RNA, viral protein or viral particle can be detected in the T cells. Furthermore, we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments. Next, we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis. In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways. Finally, we demonstrated that LFA-1, the protein exclusively expresses in multiple leukocytes, is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells, compared to a list of other known receptors. Collectively, this work confirmed a SARS-CoV-2 infection of T cells, in a spike-ACE2-independent manner, which shed novel insights into the underlying mechanisms of SARS-CoV-2-induced lymphopenia in COVID-19 patients., (© 2022. The Author(s).)

Electrosynthesis of hydrogen peroxide (H 2 O 2 ) in the acidic environment could largely prevent its decomposition to water, but efficient catalysts that constitute entirely earth-abundant elements are lacking. Here we report the experimental demonstration of narrowing the interlayer gap of metallic cobalt diselenide (CoSe 2 ), which creates high-performance catalyst to selectively drive two-electron oxygen reduction toward H 2 O 2 in an acidic electrolyte. The enhancement of the interlayer coupling between CoSe 2 atomic layers offers a favorable surface electronic structure that weakens the critical *OOH adsorption, promoting the energetics for H 2 O 2 production. Consequently, on the strongly coupled CoSe 2 catalyst, we achieved Faradaic efficiency of 96.7 %, current density of 50.04 milliamperes per square centimeter, and product rate of 30.60 mg cm -2  h -1 . Moreover, this catalyst shows no sign of degradation when operating at -63 milliamperes per square centimeter over 100 hours., (© 2021 Wiley-VCH GmbH.)

Patients with COVID-19 generally raise antibodies against SARS-CoV-2 following infection, and the antibody level is positively correlated to the severity of disease. Whether the viral antibodies exacerbate COVID-19 through antibody-dependent enhancement (ADE) is still not fully understood. Here, we conducted in vitro assessment of whether convalescent serum enhanced SARS-CoV-2 infection or induced excessive immune responses in immune cells. Our data revealed that SARS-CoV-2 infection of primary B cells, macrophages and monocytes, which express variable levels of FcγR, could be enhanced by convalescent serum from COVID-19 patients. We also determined the factors associated with ADE, and found which showed a time-dependent but not viral-dose dependent manner. Furthermore, the ADE effect is not associated with the neutralizing titer or RBD antibody level when testing serum samples collected from different patients. However, it is higher in a medium level than low or high dilutions in a given sample that showed ADE effect, which is similar to dengue. Finally, we demonstrated more viral genes or dysregulated host immune gene expression under ADE conditions compared to the no-serum infection group. Collectively, our study provides insight into the understanding of an association of high viral antibody titer and severe lung pathology in severe patients with COVID-19.

Electrical microstimulation has shown promise in restoring neural deficits in humans. Electrodes coated with materials like the conducting polymer poly(3,4-ethylenedioxythiophene) doped with acid-functionalized carbon nanotubes (PEDOT/CNTs, or PC) exhibit superior charge injection than traditional metals like platinum. However, the stimulation performance of PC remains to be fully characterized. Advanced imaging techniques and transgenic tools allow for real-time observations of neural activity in vivo. Herein, microelectrodes coated with PC and iridium oxide (IrOx) (a commonly used high-charge-injection material) are implanted in GCaMP6s mice and electrical stimulation is applied while imaging neuronal calcium responses. Results show that PC-coated electrodes stimulate more intense and broader GCaMP responses than IrOx. Two-photon microscopy reveals that PC-coated electrodes activate significantly more neuronal soma and neuropil than IrOx-coated electrodes in constant-voltage stimulation and significantly more neuronal soma in constant-current stimulation. Furthermore, with the same injected charge, both materials activate more spatially confined neural elements with shorter pulses than longer pulses, providing a means to tune stimulation selectivity. Finite element analyses reveal that the PC coating creates a denser and nonuniform electric field, increasing the likelihood of activating nearby neural elements. PC coating can significantly improve energy efficiency for electrical stimulation applications., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced NanoBiomed Research published by Wiley‐VCH GmbH.)

Electrical microstimulation has enabled partial restoration of vision, hearing, movement, somatosensation, as well as improving organ functions by electrically modulating neural activities. However, chronic microstimulation is faced with numerous challenges. The implantation of an electrode array into the neural tissue triggers an inflammatory response, which can be exacerbated by the delivery of electrical currents. Meanwhile, prolonged stimulation may lead to electrode material degradation., which can be accelerated by the hostile inflammatory environment. Both material degradation and adverse tissue reactions can compromise stimulation performance over time. For stable chronic electrical stimulation, an ideal microelectrode must present 1) high charge injection limit, to efficiently deliver charge without exceeding safety limits for both tissue and electrodes, 2) small size, to gain high spatial selectivity, 3) excellent biocompatibility that ensures tissue health immediately next to the device, and 4) stable in vivo electrochemical properties over the application period. In this review, the challenges in chronic microstimulation are described in detail. To aid material scientists interested in neural stimulation research, the in vitro and in vivo testing methods are introduced for assessing stimulation functionality and longevity and a detailed overview of recent advances in electrode material research and device fabrication for improving chronic microstimulation performance is provided., (© 2021 Wiley-VCH GmbH.)

Operating fuel cells in alkaline environments permits the use of platinum-group-metal-free (PGM-free) catalysts and inexpensive bipolar plates, leading to significant cost reduction. Of the PGM-free catalysts explored, however, only a few nickel-based materials are active for catalyzing the hydrogen oxidation reaction (HOR) in alkali; moreover, these catalysts deactivate rapidly at high anode potentials owing to nickel hydroxide formation. Here we describe that a nickel-tungsten-copper (Ni 5.2 WCu 2.2 ) ternary alloy showing HOR activity rivals Pt/C benchmark in alkaline electrolyte. Importantly, we achieved a high anode potential up to 0.3 V versus reversible hydrogen electrode on this catalyst with good operational stability over 20 h. The catalyst also displays excellent CO-tolerant ability that Pt/C catalyst lacks. Experimental and theoretical studies uncover that nickel, tungsten, and copper play in synergy to create a favorable alloying surface for optimized hydrogen and hydroxyl bindings, as well as for the improved oxidation resistance, which result in the HOR enhancement.

Neuraminidase (NA) is a promising target for development of anti-influenza drugs. In this study a dihydrofurocoumarin derivative ZINC05577497 was discovered as a lead NA inhibitor based on docking-based virtual screening technique. The optimization of lead ZINC05577497 led to the discovery of a series of novel NA inhibitors 5a-5j. Compound 5b has the most potent activity against NA with IC 50  = 0.02 µM, which is lower than those of the reference oseltamivir carboxylate (OSC) (IC 50  = 0.04 µM) and ZINC05577497 (IC 50  = 0.11 µM). Other target compounds also show potential inhibition of NA activity. Molecular docking results indicate that the good potency of 5b may be attributed to the elongation of the dihydrofurocoumarin ring to the 150-cavity. The results of this paper will be useful to discover more potent NA inhibitors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aim: To study the effect of zymosan, a ligand found on the surface of fungi, on gap junctional intercellular communication (GJIC) in cultured human corneal fibroblasts (HCFs)., Methods: Zymosan was added to the medium of cultured HCFs with or without the administration of mitogen-activated protein kinase (MAPK) inhibitors or the inhibitor kappa B kinase 2 (IKK2) inhibitor IV. The protein and mRNA levels of connexin 43 (Cx43) in HCFs were measured by Western blot, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses. The GJIC activity was tested using a dye-coupling assay., Results: The reduction of Cx43 protein and mRNA levels as well as a significant decrease in GJIC activity were observed in cultured HCFs when zymosan was added into the culture medium. Compared with controls (no zymosan), the protein level of Cx43 was reduced by 45% and 54% in the presence of zymosan at 200 and 600 µg/mL, respectively ( P <0.05); and it was reduced by 45%, 48%, and 75% in the presence of zymosan (600 µg/mL) for 24, 36, and 48h, respectively ( P <0.05). The mRNA expression of Cx43 was reduced by 98% in the presence of zymosan ( P <0.05). The effects of zymosan on Cx43 expression and GJIC activity were attenuated by the administration of PD98059 [an extracellular signal-regulated kinase (ERK) signaling inhibitor] ( P <0.05), c-Jun NH2-terminal kinase (JNK) inhibitor II ( P <0.05), and IKK2 inhibitor IV ( P <0.05)., Conclusion: Zymosan inhibits the activity of GJIC in cultured HCFs. This effect is likely regulated via the nuclear factor-κB (NF-κB), MAPK/ERK, and JNK signaling pathways. The inhibitory effects of zymosan on Cx43 expression and GJIC activity in HCFs may induce damage of corneal stroma during corneal fungal infection., (International Journal of Ophthalmology Press.)

Although the Turing structures, or stationary reaction-diffusion patterns, have received increasing attention in biology and chemistry, making such unusual patterns on inorganic solids is fundamentally challenging. We report a simple cation exchange approach to produce Turing-type Ag 2 Se on CoSe 2 nanobelts relied on diffusion-driven instability. The resultant Turing-type Ag 2 Se-CoSe 2 material is highly effective to catalyze the oxygen evolution reaction (OER) in alkaline electrolytes with an 84.5 % anodic energy efficiency. Electrochemical measurements show that the intrinsic OER activity correlates linearly with the length of Ag 2 Se-CoSe 2 interfaces, determining that such Turing-type interfaces are more active sites for OER. Combing X-ray absorption and computational simulations, we ascribe the excellent OER performance to the optimized adsorption energies for critical oxygen-containing intermediates at the unconventional interfaces., (© 2021 Wiley-VCH GmbH.)

Following acute infection, individuals COVID-19 may still shed SARS-CoV-2 RNA. However, limited information is available regarding the active shedding period or whether infectious virus is also shed. Here, we monitored the clinical characteristics and virological features of 38 patients with COVID-19 (long-term carriers) who recovered from the acute disease, but still shed viral RNA for over 3 months. The median carrying history of the long-term carriers was 92 days after the first admission, and the longest carrying history was 118 days. Negative-positive viral RNA-shedding fluctuations were observed. Long-term carriers were mostly elderly people with a history of mild infection. Infectious SARS-CoV-2 was isolated from the sputum, where high level viral RNA was found. All nine full-length genomes of samples obtained in March-April 2020 matched early viral clades circulating in January-February 2020, suggesting that these patients persistently carried SARS-CoV-2 and were not re-infected. IgM and IgG antibodies and neutralizing-antibody profiles were similar between long-term carriers and recovered patients with similar disease courses. In summary, although patients with COVID-19 generated neutralizing antibodies, they may still shed infectious SARS-CoV-2 for over 3 months. These data imply that patients should be monitored after discharge to control future outbreaks.

Hepatocellular carcinoma (HCC) is one of the common malignant tumors with poor overall prognosis. As a tumor suppressor, the function of miR-559 in HCC is not clear. In this study, quantitative real-time PCR was carried out to measure the expression of miR-559 in HCC cell lines. The effects of miR-559 on HCC cell proliferation, migration, and invasion were evaluated through a series of functional assays. The mechanism through which miR-559 regulates HCC cells was investigated by dual-luciferase reporter assay and functional experiments. The results revealed that miR-559 expression was low in HCC cell lines. Upregulation of miR-559 suppressed HCC cell proliferation, migration, and invasion. Dual-luciferase reporter assay confirmed Golgi membrane protein 73 (GP73) as a target gene of miR-559. Moreover, miR-559 could negatively regulate GP73 expression in HCC cells. These results demonstrated that low-level expression of miR-559 was associated with HCC, and overexpression of miR-559 could inhibit HCC cell growth and invasion via targeting GP73., (© 2020 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Hydroxide exchange membrane fuel cells offer possibility of adopting platinum-group-metal-free catalysts to negotiate sluggish oxygen reduction reaction. Unfortunately, the ultrafast hydrogen oxidation reaction (HOR) on platinum decreases at least two orders of magnitude by switching the electrolytes from acid to base, causing high platinum-group-metal loadings. Here we show that a nickel-molybdenum nanoalloy with tetragonal MoNi 4 phase can catalyze the HOR efficiently in alkaline electrolytes. The catalyst exhibits a high apparent exchange current density of 3.41 milliamperes per square centimeter and operates very stable, which is 1.4 times higher than that of state-of-the-art Pt/C catalyst. With this catalyst, we further demonstrate the capability to tolerate carbon monoxide poisoning. Marked HOR activity was also observed on similarly designed WNi 4 catalyst. We attribute this remarkable HOR reactivity to an alloy effect that enables optimum adsorption of hydrogen on nickel and hydroxyl on molybdenum (tungsten), which synergistically promotes the Volmer reaction.

The metabolic gene isocitrate dehydrogenase 1 ( IDH1 ) is commonly mutated in lower grade glioma (LGG) and secondary glioblastoma (GBM). Regulatory T cells (Tregs) play a significant role in the suppression of antitumor immunity in human glioma. Given the importance of Tregs in the overall framework of designing immune-based therapies, a better understanding on their association with IDH mutational status remains of critical clinical importance. Using multispectral imaging analysis, we compared the incidence of Tregs in IDH-mutant and IDH wild-type glioma from patient tumor samples of LGG. An orthotopic IDH-mutant murine model was generated to evaluate the role of mutant IDH on Treg infiltration by immunohistochemistry. When compared to IDH wild-type controls, Tregs are disproportionally underrepresented in mutant disease, even when taken as a proportion of all infiltrating T cells. Our findings suggest that therapeutic agents targeting Tregs may be more appropriate in modulating the immune response to wild-type disease., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)

In this study, we highlight that surface nitrogen-injection engineering brings a high formation rate for CO 2 reduction to formate, which is high level among the reported electrocatalysts. Surface nitrogen-injection engineering can increase the amounts of active sites and optimize the electronic structure simultaneously. Taking an example of SnS 2 precursors, the final-obtained surface N-enriched Sn(S) nanosheets (denoted as N-Sn(S) nanosheets) exhibit a 5-fold of current density and 2.45-fold of Faradaic efficiency than pristine SnS 2 derived Sn(S) nanosheets (denoted as Sn(S) nanosheets). On account of high activity and selectivity, the formation rate of formate is 14 times than that of pristine samples and reaches up to 1358 μmol h -1 cm -2 . Moreover, this strategy is proven to be general to other metal sulfides, such as CuS and In 2 S 3 . We anticipate that surface nitrogen-injection engineering offers new avenues to rational design of advanced electrocatalysts for CO 2 reduction reaction.

Apart from active metals, supports also contribute significantly to the catalytic performance of supported metal catalysts. On account of the formed strain and defects, the heterostructured surface of the support may play a crucial role to activate the reactant molecules, while it is usually neglected. In this work, the Pt/γ-Mo 2 N catalyst was prepared via a facile solution method. This Pt/γ-Mo 2 N catalyst showed excellent activity and stability for catalyzing the water-gas shift (WGS) reaction. The reaction rates at 240 °C were 16.5 mol CO mol Pt -1 s -1 in product-free gas and 5.36 mol CO mol Pt -1 s -1 in full reformate gas, which were almost 20 times that of the catalysts reported. It is found that the molybdenum species in the surface of the Pt/γ-Mo 2 N catalyst is molybdenum oxide as MoO 3 . This surface MoO 3 is very easily reduced even at room temperature, and it transformed into highly distorted MoO x (2 < x < 3) in the WGS reaction. The MoO x on the catalyst surface greatly enhanced the capability of generating active oxygen vacancies to dissociate H 2 O molecules, which induced unexpectedly superior catalytic performance. Therefore, the intrinsically active surface in the Pt/γ-Mo 2 N catalyst for the WGS reaction was molybdenum oxide as MoO x (2 < x < 3).

Aim: To explore the effects of alarmins produced by necrotic human conjunctival fibroblasts on the release of matrix metalloproteinases (MMPs) by human corneal fibroblasts (HCFs)., Methods: A necrotic cell supernatant (NHCS) was prepared by subjecting human conjunctival fibroblasts to three cycles of freezing and thawing. The amounts of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in NHCS were determined by enzyme-linked immunosorbent assays. HCFs exposed to NHCS or other agents in culture were assayed for the release of MMPs as well as for intracellular signaling by immunoblot analysis. The abundance of MMP mRNAs in HCFs was examined by reverse transcription and real-time polymerase chain reaction analysis., Results: NHCS increased the release of MMP-1 and MMP-3 by HCFs as well as the amounts of the corresponding mRNAs in the cells. NHCS also induced activation of mitogen-activated protein kinase (MAPK) signaling pathways mediated by extracellular signal-regulated kinase (ERK), p38, and c-Jun NH 2 -terminal kinase (JNK) as well as elicited that of the nuclear factor (NF)-κB signaling pathway by promoting phosphorylation of the endogenous NF-κB inhibitor IκB-α. Inhibitors of MAPK and NF-κB signaling as well as IL-1 and TNF-α receptor antagonists attenuated the NHCS-induced release of MMP-1 and MMP-3 by HCFs. Furthermore, IL-1β and TNF-α were both detected in NHCS, and treatment of HCFs with these cytokines induced the release of MMP-1 and MMP-3 in a concentration-dependent manner., Conclusion: Alarmins, including IL-1β and TNF-α, produced by necrotic human conjunctival fibroblasts triggered MMP release in HCFs through activation of MAPK and NF-κB signaling. IL-1β and TNF-α are therefore potential therapeutic targets for the amelioration of corneal stromal degradation in severe ocular burns., (International Journal of Ophthalmology Press.)

A considerable challenge in the conversion of carbon dioxide into useful fuels comes from the activation of CO 2 to CO 2 .- or other intermediates, which often requires precious-metal catalysts, high overpotentials, and/or electrolyte additives (e.g., ionic liquids). We report a microwave heating strategy for synthesizing a transition-metal chalcogenide nanostructure that efficiently catalyzes CO 2 electroreduction to carbon monoxide (CO). We found that the cadmium sulfide (CdS) nanoneedle arrays exhibit an unprecedented current density of 212 mA cm -2 with 95.5±4.0 % CO Faraday efficiency at -1.2 V versus a reversible hydrogen electrode (RHE; without iR correction). Experimental and computational studies show that the high-curvature CdS nanostructured catalyst has a pronounced proximity effect which gives rise to large electric field enhancement, which can concentrate alkali-metal cations resulting in the enhanced CO 2 electroreduction efficiency., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Selective and efficient catalytic conversion of carbon dioxide (CO 2 ) into value-added fuels and feedstocks provides an ideal avenue to high-density renewable energy storage. An impediment to enabling deep CO 2 reduction to oxygenates and hydrocarbons (e.g., C 2+ compounds) is the difficulty of coupling carbon-carbon bonds efficiently. Copper in the +1 oxidation state has been thought to be active for catalyzing C 2+ formation, whereas it is prone to being reduced to Cu 0 at cathodic potentials. Here we report that catalysts with nanocavities can confine carbon intermediates formed in situ , which in turn covers the local catalyst surface and thereby stabilizes Cu + species. Experimental measurements on multihollow cuprous oxide catalyst exhibit a C 2+ Faradaic efficiency of 75.2 ± 2.7% at a C 2+ partial current density of 267 ± 13 mA cm -2 and a large C 2+ -to-C 1 ratio of ∼7.2. Operando Raman spectra, in conjunction with X-ray absorption studies, confirm that Cu + species in the as-designed catalyst are well retained during CO 2 reduction, which leads to the marked C 2+ selectivity at a large conversion rate.

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1-4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5-7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.

In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.

Electrical stimulation of the muscle has been proven efficacious in preventing atrophy and/or reanimating paralyzed muscles. Intramuscular electrodes made from metals have significantly higher Young's Moduli than the muscle tissues, which has the potential to cause chronic inflammation and decrease device performance. Here, we present an intramuscular electrode made from an elastomeric conducting polymer composite consisting of PEDOT-PEG copolymer, silicone and carbon nanotubes (CNT) with fluorosilicone insulation. The electrode wire has a Young's modulus of 804 (±99) kPa, which better mimics the muscle tissue modulus than conventional stainless steel (SS) electrodes. Additionally, the non-metallic composition enables metal-artifact free CT and MR imaging. These soft wire (SW) electrodes present comparable electrical impedance to SS electrodes of similar geometric surface area, activate muscle at a lower threshold, and maintain stable electrical properties in vivo up to 4 weeks. Histologically, the SW electrodes elicited significantly less fibrotic encapsulation and less IBA-1 positive macrophage accumulation than the SS electrodes at one and three months. Further phenotyping the macrophages with the iNOS (pro-inflammatory) and ARG-1 (pro-healing) markers revealed significantly less presence of pro-inflammatory macrophage around SW implants at one month. By three months, there was a significant increase in pro-healing macrophages (ARG-1) around the SW implants but not around the SS implants. Furthermore, a larger number of AchR clusters closer to SW implants were found at both time points compared to SS implants. These results suggest that a softer implant encourages a more intimate and healthier electrode-tissue interface. STATEMENT OF SIGNIFICANCE: Intramuscular electrodes made from metals have significantly higher Young's Moduli than the muscle tissues, which has the potential to cause chronic inflammation and decrease device performance. Here, we present an intramuscular electrode made from an elastomeric conducting polymer composite consisting of PEDOT-PEG copolymer, silicone and carbon nanotubes with fluorosilicone insulation. This elastomeric composite results in an electrode wire with a Young's modulus mimicking that of the muscle tissue, which elicits significantly less foreign body response compared to stainless steel wires. The lack of metal in this composite also enables metal-artifact free MRI and CT imaging., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: To understand the prevalence, diagnosis and treatment of chronic critical illness (CCI) in China. Methods: The clinical data of 472 adult patients admitted to ICU in 53 hospitals, including basic information, disease-related data, nutrition program, etc., were collected on May 10, 2019, by means of multi-center cross-sectional study. If surgical intervention was needed or the occurrence of the disease was directly related to the surgery, ICU patients were regarded as surgical ICU cases ( n =211). In this study, the diagnostic criteria for CCI were: (1) admission to ICU >14 days;(2) combined with persistent organ dysfunction. The prevalence,distribution and treatment of CCI and surgery-related CCI were recorded and analyzed. The Mann-Whitney U test, chi-square test or Fisher exact test were used for comparative analysis. Results: Among the 472 ICU patients from 53 hospitals, 326 were male (69.1%) and 146 were female (30.9%). The prevalence of CCI was 30.7% (145/472). Among 211 surgery-related ICU patients, 57 developed CCI with a prevalence of 27.0%. As compared to non-CCI patients, higher APACHE II score [median (IQR) 13.5 (10.0, 18.3) vs. 11.0 (7.0, 16.0), U =2970.000, P =0.007], higher Charlson comorbidity index [median (IQR) 4.0 (2.0, 7.0) vs. 3.0 (1.0, 5.0), U = 3570.000, P =0.036] and higher ratio of breath dysfunction [68.4% (39/57) vs. 48.1% (74/154), χ(2)=6.939, P =0.008] and renal dysfunction [42.1% (24/57) vs. 18.2% (28/154), χ(2)=12.821, P <0.001] were found in surgery-related CCI patients. While SOFA score, Glasgow coma score and other visceral function were not significantly different between surgery-related CCI and non-CCI patients (all P >0.05). NUTRIC score showed that surgery-related CCI patients had higher nutritional risk [43.9% (25/57) vs. 26.6%(41/154), U =5.750, P =0.016] and higher ratio of mechanical ventilation [66.7% (38/57) vs. 52.3% (79/154), χ(2)=3.977, P =0.046] than non-CCI patients. On the survey day, the daily caloric requirements of 50.2% (106/211) of surgery-related ICU patients were calculated according to the standard adult caloric intake index (104.6 to 125.5 kJ·kg(-1)·d(-1), 1 kJ=0.239 kcal), and the daily caloric requirements of 46.4% (98/211) of patients were calculated by physicians according to the severity of the patient's condition. 60.2% (127/211) of nutritional support therapy was enteral nutrition (including a combination of enteral and parenteral nutrition), while the remaining patients received parenteral nutrition (24.6%, 52/211), simple glucose infusion (9.0%, 19/211), or oral diet (6.2%, 13/211). The target calorie of CCI group was 104.6 (87.9, 125.5) kJ·kg(-1)·d(-1), and the actual calorie intake accounted for 0.98 (0.80, 1.00) of the target calory. In the non-CCI group, the target calorie was 104.6 (87.9, 125.5) kJ·kg(-1)·d(-1), and the actual calorie consumed accounted for 0.91 (0.66, 1.00) of the target calorie. There was no statistically significant difference between two groups ( P =0.248, P =0.150). Conclusion: The prevalence of CCI and surgery-related CCI in ICU is high, along with severe complications, respiratory and renal dysfunction and mechanical ventilation. Surgical patients admitted to ICU are at high nutritional risk, and active and correct nutritional support is essential for such patients.

Many platinum group metal-free inorganic catalysts have demonstrated high intrinsic activity for diverse important electrode reactions, but their practical use often suffers from undesirable structural degradation and hence poor stability, especially in acidic media. We report here an alkali-heating synthesis to achieve phase-mixed cobalt diselenide material with nearly homogeneous distribution of cubic and orthorhombic phases. Using water electroreduction as a model reaction, we observe that the phase-mixed cobalt diselenide reaches the current density of 10 milliamperes per square centimeter at overpotential of mere 124 millivolts in acidic electrolyte. The catalyst shows no sign of deactivation after more than 400 h of continuous operation and the polarization curve is well retained after 50,000 potential cycles. Experimental and computational investigations uncover a boosted covalency between Co and Se atoms resulting from the phase mixture, which substantially enhances the lattice robustness and thereby the material stability. The findings provide promising design strategy for long-lived catalysts in acid through crystal phase engineering.

The majority of emerging and reemerging zoonotic viral pathogens are RNA viruses. Pathogen discovery programs of emerging infectious diseases (EIDs) in wildlife have implicated rodents and shrews as hosts of diverse human pathogens, such as hantaviruses, arenaviruses, paramyxoviruses, etc. Despite these threats, little is known about the diversity of viruses circulating among rodents and shrews in Kenya, meaning the risk of infectious disease outbreak from these small mammals could be oblivious. This study reports the first surveillance toward understanding the diversity of RNA viruses carried by rodents and shrews in areas of high-potential contact with humans in Kenya through molecular detection. A total of 617 samples comprising fecal, urine, and tissues from 138 rodents and 5 shrews were screened for eight different families of viruses using RT-PCR assays. The results highlight the presence of diverse astroviruses, paramyxoviruses, hepeviruses, and arenavirus, circulating in both wild and synanthropic Kenyan rodents and shrews. Most of the viruses detected in this study are novel strains and some belong to the families that contain important human viral pathogens. Notably, a novel arenavirus was detected in Grammomys macmillani , a rodent species newly identified to harbor arenavirus, and it potentially represent a novel arenavirus species. Our findings demonstrate the need for continued pathogen surveillance among these small mammals as well as among the vulnerable and exposed livestock and humans. This would help in development and implementation of effective preventive and control strategies on EIDs in countries with rich wildlife biodiversity like Kenya., (Copyright © 2019 Onyuok, Hu, Li, Fan, Kering, Ochola, Zheng, Obanda, Ommeh, Yang, Agwanda and Shi.)

The advancement of neural prostheses requires implantable neural electrodes capable of electrically stimulating or recording signals from neurons chronically. Unfortunately, the implantation injury and presence of foreign bodies lead to chronic inflammation, resulting in neuronal death in the vicinity of electrodes. A key mediator of inflammation and neuronal loss are reactive oxygen and nitrogen species (RONS). To mitigate the effect of RONS, a superoxide dismutase mimic compound, manganese(III) meso-tetrakis-(N-(2-aminoethyl)pyridinium-2-yl) porphyrin (iSODm), was synthesized to covalently attach to the neural probe surfaces. This new compound showed high catalytic superoxide scavenging activity. In microglia cell line cultures, the iSODm coating effectively reduced superoxide production and altered expression of iNOS, NADPH oxidase, and arginase. After 1 week of implantation, iSODm coated electrodes showed significantly lower expression of markers for oxidative stress immediately adjacent to the electrode surface, as well as significantly less neurons undergoing apoptosis. STATEMENT OF SIGNIFICANCE: One critical challenge in the translation of neural electrode technology to clinically viable devices for brain computer interface or deep brain stimulation applications is the chronic degradation of the device performance due to neuronal degeneration around the implants. One of the key mediators of inflammation and neuronal degeneration is reactive oxygen and nitrogen species released by injured neurons and inflammatory microglia. This research takes a biomimetic approach to synthesize a compound having similar reactivity as superoxide dismutase, which can catalytically scavenge reactive oxygen and nitrogen species, thereby reducing oxidative stress and decreasing neuronal degeneration. By immobilizing the compound covalently on the surface of neural implants, we show that the neuronal degeneration and oxidative stress around the implants is significantly reduced., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In order to address material limitations of biologically interfacing electrodes, modified silica nanoparticles are utilized as dopants for conducting polymers. Silica precursors are selected to form a thiol modified particle (TNP), following which the particles are oxidized to sulfonate modified nanoparticles (SNPs). The selective inclusion of hexadecyl trimethylammonium bromide allows for synthesis of both porous and nonporous SNPs. Nonporous nanoparticle doped polyethylenedioxythiophene (PEDOT) films possess low interfacial impedance, high charge injection (4.8 mC cm -2 ), and improved stability under stimulation compared to PEDOT/poly(styrenesulfonate). Porous SNP dopants can serve as drug reservoirs and greatly enhance the capability of conducting polymer-based, electrically controlled drug release technology. Using the SNP dopants, drug loading and release is increased up to 16.8 times, in addition to greatly expanding the range of drug candidates to include both cationic and electroactive compounds, all while maintaining their bioactivity. Finally, the PEDOT/SNP composite is capable of precisely modulating neural activity in vivo by timed release of a glutamate receptor antagonist from coated microelectrode sites. Together, this work demonstrates the feasibility and potential of doping conducting polymers with engineered nanoparticles, creating countless options to produce composite materials for enhanced electrical stimulation, neural recording, chemical sensing, and on demand drug delivery., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The anode oxygen evolution reaction (OER) is known to largely limit the efficiency of electrolyzers owing to its sluggish kinetics. While crystalline metal oxides are promising as OER catalysts, their amorphous phases also show high activities. Efforts to produce amorphous metal oxides have progressed slowly, and how an amorphous structure benefits the catalytic performances remains elusive. Now the first scalable synthesis of amorphous NiFeMo oxide (up to 515 g in one batch) is presented with homogeneous elemental distribution via a facile supersaturated co-precipitation method. In contrast to its crystalline counterpart, amorphous NiFeMo oxide undergoes a faster surface self-reconstruction process during OER, forming a metal oxy(hydroxide) active layer with rich oxygen vacancies, leading to superior OER activity (280 mV overpotential at 10 mA cm -2 in 0.1 m KOH). This opens up the potential of fast, facile, and scale-up production of amorphous metal oxides for high-performance OER catalysts., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a new promising target for the treatment of ovarian cancer. Our previous study showed that cross-reacting material 197 (CRM197), a specific HB-EGF inhibitor, significantly reverses resistance against paclitaxel in paclitaxel-resistant ovarian cancer cells. However, the mechanism of the effect of CRM197 on the reversion of paclitaxel resistance was unclear. In this study, in vitro and in vivo data suggested that CRM197 treatment sensitized paclitaxel-resistant ovarian cancer cells to paclitaxel, at least in part, via nucleus accumbens-1 (NAC-1) and its downstream pathway, DNA damage-inducible 45-γ interacting protein (Gadd45gip1)/growth arrest and DNA damage-inducible 45 (Gadd45), in A2780/Taxol and SKOV3/Taxol cells. The results also showed that CRM197 activated the proapoptotic JNK/p38MAPK pathway to enhance caspase-3 activity and apoptosis by downregulation of the NAC-1/Gadd45gip1/Gadd45 pathway, leading to reversion of paclitaxel resistance in A2780/Taxol and SKOV3/Taxol cells. This study provides the first mechanism through which CRM197 significantly reverses resistance against paclitaxel by modulating the NAC-1/Gadd45gip1/Gadd45 pathway in paclitaxel-resistant ovarian cancer cells, and the mechanism of HB-EGF inhibition as a novel therapeutic strategy for patients with paclitaxel-resistant ovarian cancer., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Most adult parasitoids depend on carbohydrate-rich food as an energy source for longevity, fecundity, and mobility. Thus, providing sugars has been proposed as a technique to maximize the biological control efficacy of parasitoids. However, the sugars provided for parasitoids need to be carefully selected because herbivore hosts might also benefit. Here we explore the effects of 12 naturally occurring sugars on the longevity and fecundity of the rice pest, Chilo suppressalis, and the longevity of its parasitoid, Cotesia chilonis, as well as the effect of sugars on sugar consumption of C. chilonis. Results showed that none of the tested sugars significantly impacted the longevity of C. suppressalis, but fructose, glucose, maltose, and sucrose significantly increased its fecundity. The longevity of C. chilonis was significantly increased when fed fructose, glucose, sucrose, maltose, trehalose, and melezitose. Our data suggest that C. chilonis consumed larger quantities of glucose, fructose, and sucrose followed by maltose, melezitose, and trehalose and the longevity of C. chilonis was positively correlated to sugar consumption. Our data also suggest that the herbivore C. suppressalis and its parasitoid C. chilonis responded differently to trehalose and melezitose. Although additional studies are needed, our data suggest that these sugars could be considered as candidate components for sugar sprays to enhance the activity and efficacy of C. chilonis, but without benefiting its pest host., (© The Author(s) 2019. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Material interfaces permit electron transfer that modulates the electronic structure and surface properties of catalysts, leading to radically enhanced rates for many important reactions. Unlike conventional thoughts, the nanoscale interfacial interactions have been recently envisioned to be able to affect the reactivity of catalysts far from the interface. However, demonstration of such unlocalized alterations in existing interfacial materials is rare, impeding the development of new catalysts. We report the observation of unprecedented long-range activation of polydymite Ni 3 S 4 nanorods through the interfacial interaction created by PdS x nanodots (dot-on-rod structure) for high-performance water catalytic electroreduction. Experimental results show that this local interaction can activate Ni 3 S 4 rods with length even up to 25 nanometers due to the tailored surface electronic structure. We anticipate that the long-range effect described here may be also applicable to other interfacial material systems, which will aid the development of newly advanced catalysts for modern energy devices., Competing Interests: The authors declare no competing financial interest.

Intracellular pH is an important modulator of cell functions, and its subtle change may dramatically affect the cellular activities and cause diseases. A reliable imaging of the intracellular pH is still a great challenge. We imaged the intracellular pH during the cell cycle at the single living cell level using newly designed cell-penetrating peptide conjugated pH nanosensors on a home-built in situ microscopic cell culture platform. The conjugated cell-penetrating peptide greatly enhanced the uptake of nanosensors without sacrificing the pH response. We observed a gradual alkalization from interphase to prophase and rapid acidification from prometaphase to telophase, reflecting variation and consumption of the species related to the energy storage during cell cycle. We realized SERS-based pH and fluorescence dual-mode imaging when the pH sensor was further modified with fluorescence dye. The integration of SERS imaging with in situ microscopic cell culture system offers great opportunity for revealing the intracellular pH-related biological and pathological processes.

The incorporation of defects, such as vacancies, into functional materials could substantially tailor their intrinsic properties. Progress in vacancy chemistry has enabled advances in many technological applications, but creating new type of vacancies in existing material system remains a big challenge. We show here that ionized nitrogen plasma can break bonds of iron-carbon-nitrogen-nickel units in nickel-iron Prussian blue analogues, forming unconventional carbon-nitrogen vacancies. We study oxygen evolution reaction on the carbon-nitrogen vacancy-mediated Prussian blue analogues, which exhibit a low overpotential of 283 millivolts at 10 milliamperes per square centimeter in alkali, far exceeding that of original Prussian blue analogues and previously reported oxygen evolution catalysts with vacancies. We ascribe this enhancement to the in-situ generated nickel-iron oxy(hydroxide) active layer during oxygen evolution reaction, where the Fe leaching was significantly suppressed by the unconventional carbon-nitrogen vacancies. This work opens up opportunities for producing vacancy defects in nanomaterials for broad applications.

Dromedary camels are important reservoir hosts of various coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV) that cause human infections. CoV genomes regularly undergo recombination during infection as observed in bat SARS-related CoVs. Here we report for the first time that only a small proportion of MERS-CoV receptor-binding domain positive (RBD) of spike protein positive camel sera in Kenya were also seropositive to MERS-CoV nucleocapsid (NP). In contrast, many of them contain antibodies against bat HKU8-related (HKU8r)-CoVs. Among 584 camel samples that were positive against MERS-CoV RBD, we found only 0.48 (8.22%) samples were also positive for NP. Furthermore, we found bat HKU8r-CoV NP antibody in 73 (12.5%) of the MERS-CoV RBD positive and NP negative samples, yet found only 3 (0.43%) of the HKU8r-CoV S1 antibody in the same samples. These findings may indicate co-infection with MERS-CoV and a HKU8r-CoV in camels. It may also raise the possibility of the circulation of a recombinant coronavirus virus with the spike of MERS-CoV and the NP of a HKU8r-CoV in Kenya. We failed to find molecular evidence of an HKU8r-CoV or a putative recombinant virus. Our findings should alert other investigators to look for molecular evidence of HKU8r-CoV or recombinants.