Herein, the electrodeposited-film electrode CFeCoNiP was fabricated to serve as a bifunctional electrocatalyst for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Kinetic ...Tafel slope analysis suggests that the HER follows the Volmer-Tafel mechanism (29 mV dec
−1
), indicating that the recombination of the two adsorbed hydrogen atoms is the rate-determining step. The FeCoNi-based thick film (thickness: 168.3 μm) shows a metallic state favorable for electron transfer; on the other hand, in the case of the FeCoNi-based thin film (thickness: 389.2 nm), the in
operando
XAS investigation reveals that Fe
3+
-assisted water dissociation promotes the formation of Co
2+
-μ-H-Ni
3+
(catalyst-H
ad
) species, which subsequently undergoes reductive elimination to furnish H
2
gas
via
the HER process. During the OER, the CoNi-oxide matrix acts as a chemical and electroconductive host to build/stabilize the key intermediate Fe
4+
&z.dbd;O/Fe
3+
-O&z.rad; motifs; this subsequently triggers the catalytic O-O bond formation (30 mV dec
−1
) through the radical-radical coupling of the adjacent Fe
4+
&z.dbd;O/Fe
3+
-O&z.rad; motifs or/and OH
−
attack on the Fe
4+
-induced electrophilic oxygen center, leading to the release of O
2
. The mechanistic experiments provide advanced insights into the catalytic kinetics/intermediates and demonstrate that the electronically cooperative interplay among Fe/Co/Ni leads to enhanced alkaline water electrolysis. The CFeCoNiP catalyst exhibits an excellent HER activity (specific activity
j
s
= 0.227 mA cm
−2
) with a low charge transfer resistance (3.9 Ω) and an overpotential of 37 mV, achieving the current density of 10 mA cm
2
; moreover, it shows good OER activity (
j
s
= 1.798 mA cm
−2
) with low charge transfer resistance (2.1 Ω) and an overpotential of 250 mV, approaching a current density of 10 mA cm
−2
in a 1 M NaOH aqueous solution. The CFeCoNiP/NF (electrodeposited on Ni foam) electrode-pair device achieved the current densities of 100 and 500 mA cm
−2
at the voltages of 1.65 and 1.86 V, respectively, under alkaline conditions.
In operando XAS investigation on FeCoNi-based thin film unravels that Fe
3+
-assisted water dissociation promotes the formation of Co
2+
-μ-H-Ni
3+
species, and the conductive character of Co
2+
Ni
3+
-oxide matrix facilitates the coupling of adjacent Fe
4+
&z.dbd;O/Fe
3+
-O&z.rad; motifs.
Positive fluid balance is a prognostic factor for mortality in patients with sepsis; however, the association between cumulated fluid balance (CFB) and sepsis-induced multi-organ dysfunction syndrome ...(MODS) has yet to be elucidated. In this study, we sought to determine whether CFB is correlated with MODS and mortality in cases of septic shock.
The study retrospectively recruited patients with septic shock from the intensive care unit of a tertiary care hospital. Multiple organ dysfunction syndrome (MODS) was identified as sequential organ failure assessment (SOFA) score ≥ 2 in more than one organ system. The CFB is the sum of all daily intake and output. An independent t-test, single and multivariate logistic regression, the receiver operating characteristic (ROC) curves, and the Pearson correlation coefficient were used to determine whether a relationship exists between CFB and the development of MODS and mortality.
Among the 104 patients enrolled in the study, 58 (55.8%) survived more than 28 days, and 73 (70.2%) developed MODS on day 3. The values of CFB in the first 24 hours and 72 hours after diagnosis of septic shock in patients with MODS were higher than these in patients without MODS (1086.6 ± 176.3 vs. 325.5 ± 205.7 ml, p = 0.013 and 2408 ± 361 vs. 873.1 ± 489 ml, p < 0.0001). In a multivariate logistic regression, the independent factors associated with the development of MODS on day 3 were APACHE II score at ICU admission (27.6 ± 7.6 in patients with MODS vs. 20.5 ± 6.4 in those without; O.R. 1.18; 95% C.1 I. 1.08-1.30; p < 0.001), disseminated intravascular coagulopathy (DIC) (n = 28; 38.4% vs. n = 2; 6.5%; O.R. 23.67; 95% C.I. 3.58-156.5; p = 0.001), and CFB in the first 72 hours (72-hr CFB) > median (1767.50ml) (n = 41; 56.2% vs. n = 11; 35.5%; O.R. 3.67; 95% C.I., 1.18-11.40; p = 0.024). Moreover, a multivariate logistic regression also identified neoplasm (n = 25; 54.3% vs. n = 17; 29.3%; O.R. 3.45; 95% C.I. 1.23-10.0; p = 0.019) and 72-hr CFB > median (n = 30; 65.2% vs. n = 21; 36.2%; O.R. 4.13; 95% C.I. 1.34-12.66; p = 0.013) as independent factors associated with 28-day mortality. 72-hr CFB values were strongly correlated with the SOFA score (r = 0.445, p < 0.0001). The area under the ROC curve revealed that 72-hr CFB has good discriminative power in associating the development of MODS (0.644, p = 0.002) and predicting subsequent 28-day mortality (0.704, p < 0.0001).
72-hr CFB appears to be correlated with the likelihood of developing MODS and mortality in patients with septic shock. Thus, it appears that 72-hr CFB could perhaps be used as an indicator for MODS and a predictor for mortality in those patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The coronavirus disease 2019 (COVID‑19) outbreak, which has caused >46 millions confirmed infections and >1.2 million coronavirus related deaths, is one of the most devastating worldwide crises in ...recent years. Infection with COVID‑19 results in a fever, dry cough, general fatigue, respiratory symptoms, diarrhoea and a sore throat, similar to those of acute respiratory distress syndrome. The causative agent of COVID‑19, SARS‑CoV‑2, is a novel coronavirus strain. To date, remdesivir has been granted emergency use authorization for use in the management of infection. Additionally, several efficient diagnostic tools are being actively developed, and novel drugs and vaccines are being evaluated for their efficacy as therapeutic agents against COVID‑19, or in the prevention of infection. The present review highlights the prevalent clinical manifestations of COVID‑19, characterizes the SARS‑CoV‑2 viral genome sequence and life cycle, highlights the optimal methods for preventing viral transmission, and discusses possible molecular pharmacological mechanisms and approaches in the development of anti‑SARS‑CoV‑2 therapeutic agents. In addition, the use of traditional Chinese medicines for management of COVID‑19 is discussed. It is expected that novel anti‑viral agents, vaccines or an effective combination therapy for treatment/management of SARS‑CoV‑2 infection and spread therapy will be developed and implemented in 2021, and we would like to extend our best regards to the frontline health workers across the world in their fight against COVID‑19.
We propose all‐dielectric metasurfaces that can be actively re‐configured using the phase‐change material Ge2Sb2Te5 (GST) alloy. With selectively controlled phase transitions on the composing GST ...elements, metasurfaces can be tailored to exhibit varied functionalities. Using phase‐change GST rod as the basic building block, we have modelled metamolecules with tunable optical response when phase change occurs on select constituent GST rods. Tunable gradient metasurfaces can be realized with variable supercell period consisting of different patterns of the GST rods in their amorphous and crystalline states. Simulation results indicate a range of functions can be delivered, including multilevel signal modulating, near‐field coupling of GST rods, and anomalous reflection angle controlling. This work opens up a new space in exploring active meta‐devices with broader applications that cannot be achieved in their passive counterparts with permanent properties once fabricated.
The all‐dielectric reconfigurable metasurfaces based on switchable phase‐change material Ge2Sb2Te5 with functional diversity for light modulation are shown. The tunability of EIT resonance on phase‐change metamolecule and the steering of gradient metasurface are demonstrated by selectively modifying the phase of selected constituent Ge2Sb2Te5 rods.
Electronic device versions of the neural functions of the human retina have high potential for use in artificial vision. This study demonstrates halide perovskite artificial human photoreceptors with ...specific photoresponses to red, green, and blue colors, which are consistent with human retinal photoreceiving cones and rods. In contrast to the current programmable spectral‐response technologies, a novel microcavity structure is combined in this study with a perovskite absorber to achieve a targeted spectrum without using external optical filters. The fabricated artificial photoreceptors exhibit excellent performance including a high detectivity of more than 1013 Jones, a large linear dynamic range of 154 dB, and a short response time of 580 ns. These values are equal to or better than those of the natural human retina. These devices can easily be monolithically integrated on a single flexible substrate by using vacuum deposition, and a true proof‐of‐concept full‐color image reconstruction is demonstrated.
Microcavity‐integrated monolithic flexible perovskite artificial human photoreceptors are demonstrated. The artificial cones and rods exhibit a true similarity with the natural human retina and exhibit excellent specific detectivity, large linear dynamic range, short response time, and low noise current. The potential of these versatile structures is manifested by reproducing a realistic full‐color image.
Antipsychotics have been linked to prolongation of the QT interval. However, little is known about the risk of ventricular arrhythmia (VA) and/or sudden cardiac death (SCD) associated with individual ...antipsychotic drug use. This study was designed to investigate the association between specific antipsychotic drugs and the risk of VA and/or SCD.
We conducted a case-crossover study using a nation-wide population-based sample obtained from Taiwan's National Health Insurance Research Database. A total of 17 718 patients with incident VA and/or SCD were enrolled. Conditional logistic regression models were applied to examine the effects of antipsychotic drug use on the risk of VA/SCD during various case and control time windows of 7, 14, and 28 days. The effect of the potency of a human ether-à-go-go-related gene (hERG) potassium channel blockade was also assessed. Antipsychotic drug use was associated with a 1.53-fold increased risk of VA and/or SCD. Antipsychotic drugs with increased risk included clothiapine, haloperidol, prochlorperazine, thioridazine, olanzapine, quetiapine, risperidone, and sulpiride. The association was significantly higher among those with short-term use. Antipsychotics with a high potency of the hERG potassium channel blockade had the highest risk of VA and/or SCD.
Use of antipsychotic drugs is associated with an increased risk of VA and/or SCD. Careful evaluations of the risks and benefits of antipsychotic treatment are highly recommended.
Golgi apparatus (GA) is assembled as a crescent-like ribbon in mammalian cells under immunofluorescence microscope without knowing the shaping mechanisms. It is estimated that roughly 1/5 of the ...genes encoding kinases or phosphatases in human genome participate in the assembly of Golgi ribbon, reflecting protein modifications play major roles in building Golgi ribbon.
To explore how Golgi ribbon is shaped as a crescent-like structure under the guidance of protein modifications, we identified a protein complex containing the scaffold proteins Ajuba, two known GA regulators including the protein kinase Aurora-A and the protein arginine methyltransferase PRMT5, and the common substrate of Aurora-A and PRMT5, HURP. Mutual modifications and activation of PRMT5 and Aurora-A in the complex leads to methylation and in turn phosphorylation of HURP, thereby producing HURP p725. The HURP p725 localizes to GA vicinity and its distribution pattern looks like GA morphology. Correlation study of the HURP p725 statuses and GA structure, site-directed mutagenesis and knockdown-rescue experiments were employed to identify the modified HURP as a key regulator assembling GA as a crescent ribbon.
The cells containing no or extended distribution of HURP p725 have dispersed GA membranes or longer GA. Knockdown of HURP fragmentized GA and HURP wild type could, while its phosphorylation deficiency mutant 725A could not, restore crescent Golgi ribbon in HURP depleted cells, collectively indicating a crescent GA-constructing activity of HURP p725. HURP p725 is transported, by GA membrane-associated ARF1, Dynein and its cargo adaptor Golgin-160, to cell center where HURP p725 forms crescent fibers, binds and stabilizes Golgi assembly factors (GAFs) including TRIP11, GRASP65 and GM130, thereby dictating the formation of crescent Golgi ribbon at nuclear periphery.
The Ajuba/PRMT5/Aurora-A complex integrates the signals of protein methylation and phosphorylation to HURP, and the HURP p725 organizes GA by stabilizing and recruiting GAFs to its crescent-like structure, therefore shaping GA as a crescent ribbon. Therefore, the HURP p725 fiber serves a template to construct GA according to its shape. Video Abstract.
HLA‐G is considered as an immune checkpoint protein and a tumor‐associated antigen. In the previous work, it is reported that CAR‐NK targeting of HLA‐G can be used to treat certain solid tumors. ...However, the frequent co‐expression of PD‐L1 and HLA‐G) and up‐regulation of PD‐L1 after adoptive immunotherapy may decrease the effectiveness of HLA‐G‐CAR. Therefore, simultaneous targeting of HLA‐G and PD‐L1 by multi‐specific CAR could represent an appropriate solution. Furthermore, gamma‐delta T (γδT) cells exhibit MHC‐independent cytotoxicity against tumor cells and possess allogeneic potential. The utilization of nanobodies offers flexibility for CAR engineering and the ability to recognize novel epitopes. In this study, Vδ2 γδT cells are used as effector cells and electroporated with an mRNA‐driven, nanobody‐based HLA‐G‐CAR with a secreted PD‐L1/CD3ε Bispecific T‐cell engager (BiTE) construct (Nb‐CAR.BiTE). Both in vivo and in vitro experiments reveal that the Nb‐CAR.BiTE‐γδT cells could effectively eliminate PD‐L1 and/or HLA‐G‐positive solid tumors. The secreted PD‐L1/CD3ε Nb‐BiTE can not only redirect Nb‐CAR‐γδT but also recruit un‐transduced bystander T cells against tumor cells expressing PD‐L1, thereby enhancing the activity of Nb‐CAR‐γδT therapy. Furthermore, evidence is provided that Nb‐CAR.BiTE redirectes γδT into tumor‐implanted tissues and that the secreted Nb‐BiTE is restricted to the tumor site without apparent toxicity.
Elevated PD‐L1 in solid tumors increases the risk of immune escape from HLA‐G‐CAR cell therapy. The bicistronic mRNA construct that drives PD‐L1 Nb‐BiTE and HLA‐G Nb‐CAR in γδT cells via electroporation is designed to address this issue. This Nb‐CAR.BiTE‐γδT therapy can overcome HLA‐G and PD‐L1 dilemma and even kill tumor cells with inadequate antigen expression, resulting in potent anti‐tumor activity without apparent toxicity.
Amiodarone is a commonly used antiarrhythmic agent but exhibits potential pulmonary toxicity. In this case series, we describe the clinical, radiographic, and histologic manifestations of three ...patients who developed interstitial lung disease (ILD) following amiodarone treatment for variable lengths of time with different dosages. The presentations on computed tomographic images and in pulmonary pathology differed among the three patients. All three had immediate discontinuation of amiodarone and received treatment with systemic corticosteroids. One patient eventually died from ventilator‐associated pneumonia after an initial improvement. The other two patients recovered well but later experienced ILD recurrence following brief re‐exposure to amiodarone. Through this case series, we aim to demonstrate the variable features of amiodarone‐related ILD, and highlight the importance of timely amiodarone cessation and avoiding re‐exposure to prevent the progression and recurrence of ILD.
Amiodarone‐related interstitial lung disease may exhibit variable clinical, radiographic, and histologic presentations. Prompt discontinuation and avoiding re‐exposure of the agent is important to prevent the progression and recurrence of the interstitial lung disease.
Key points
Endocrine gland‐derived vascular endothelial growth factor (EG‐VEGF) is a critical factor that facilitates trophoblast invasion in placenta.
Plasma miR‐141 and miR‐200a levels were ...elevated, while EG‐VEGF was decreased in peripheral blood and placenta of preeclamptic patients. Furthermore, numbers of cilia in the placenta from preeclamptic women were significantly decreased.
Elevated miR‐141 and miR‐200a inhibited the expression of EG‐VEGF, downstream extracellular signal‐regulated kinase (ERK)/matrix metalloproteinase 9 signalling and cilia formation, thus leading to defective trophoblast invasion.
The growth of the primary cilium, which transduced ERK signalling upon EG‐VEGF induction for proper trophoblast invasion, was also inhibited by miR‐141 and miR‐200a upregulation.
Preeclampsia is a severe gestational complication, and inadequate trophoblast invasion during placental development is an important pathoaetiology. Endocrine gland‐derived vascular endothelial growth factor (EG‐VEGF) is a critical factor that facilitates trophoblast invasion in placenta. By binding to the primary cilium, EG‐VEGF initiates the signalling cascade for proper embryo implantation and placental development. The miR‐200 family was predicted to target the EG‐VEGF 5′‐untranslated region, and its specific binding site was confirmed using a dual luciferase and a co‐transfection assay. In the peripheral blood and placenta of preeclamptic patients, EG‐VEGF showed significantly lower expression, whereas plasma miR‐141 and miR‐200a had higher expression compared with the controls. The biological significance of miR‐141 and miR‐200a was verified using an overexpression method in a trophoblast cell line (HTR‐8/SVneo). Elevated miR‐141 and miR‐200a inhibited the expression of EG‐VEGF, matrix metalloproteinase 9 (MMP9) and downstream extracellular signal‐regulated kinase (ERK) signalling, thus leading to defective trophoblast invasion. Additionally, the growth of the primary cilium, which transduces ERK/MMP9 signalling upon EG‐VEGF induction, was inhibited by miR‐141 and miR‐200a upregulation. Furthermore, the number of cilia in the human placenta of preeclamptic women was significantly decreased compared to normal placenta. In conclusion, the study uncovers the clinical correlations among the miR‐200 family, EG‐VEGF and the primary cilium in preeclampsia and the underlying molecular mechanisms. The results indicate that miR‐141 and miR‐200a directly targeted EG‐VEGF, suppressed primary cilia formation and inhibited trophoblast invasion. Thus, miR‐141 and miR‐200a could be explored as promising miRNA biomarkers and therapeutic targets in preeclampsia.
Key points
Endocrine gland‐derived vascular endothelial growth factor (EG‐VEGF) is a critical factor that facilitates trophoblast invasion in placenta.
Plasma miR‐141 and miR‐200a levels were elevated, while EG‐VEGF was decreased in peripheral blood and placenta of preeclamptic patients. Furthermore, numbers of cilia in the placenta from preeclamptic women were significantly decreased.
Elevated miR‐141 and miR‐200a inhibited the expression of EG‐VEGF, downstream extracellular signal‐regulated kinase (ERK)/matrix metalloproteinase 9 signalling and cilia formation, thus leading to defective trophoblast invasion.
The growth of the primary cilium, which transduced ERK signalling upon EG‐VEGF induction for proper trophoblast invasion, was also inhibited by miR‐141 and miR‐200a upregulation.