Two novel two‐dimensional metal–organic frameworks (2D MOFs), 2D‐M2TCPE (M=Co or Ni, TCPE=1,1,2,2‐tetra(4‐carboxylphenyl)ethylene), which are composed of staggered (4,4)‐grid layers based on ...paddlewheel‐shaped dimers, serve as heterogeneous photocatalysts for efficient reduction of CO2 to CO. During the visible‐light‐driven catalysis, these structures undergo in situ exfoliation to form nanosheets, which exhibit excellent stability and improved catalytic activity. The exfoliated 2D‐M2TCPE nanosheets display a high CO evolution rate of 4174 μmol g−1 h−1 and high selectivity of 97.3 % for M=Co and Ni, and thus are superior to most reported MOFs. The performance differences and photocatalytic mechanisms have been studied with theoretical calculations and photoelectric experiments. This study provides new insight for the controllable synthesis of effective crystalline photocatalysts based on structural and morphological coregulation.
As a result of rational structural design and structure‐directed morphology control, two new 2D MOFs underwent photochemically assisted in situ exfoliation to form nanosheets during visible‐light photocatalytic CO2 reduction (see picture). The exfoliated nanosheets displayed a high CO evolution rate and high selectivity for the formation of CO.
Collagen is a major component in a wide range of drug delivery systems and biomaterial applications. Its basic physical and structural properties, together with its low immunogenicity and natural ...turnover, are keys to its biocompatibility and effectiveness. In addition to its material properties, the collagen triple-helix interacts with a large number of molecules that trigger biological events. Collagen interactions with cell surface receptors regulate many cellular processes, while interactions with other ECM components are critical for matrix structure and remodeling. Collagen also interacts with enzymes involved in its biosynthesis and degradation, including matrix metalloproteinases. Over the past decade, much information has been gained about the nature and specificity of collagen interactions with its partners. These studies have defined collagen sequences responsible for binding and the high-resolution structures of triple-helical peptides bound to its natural binding partners. Strategies to target collagen interactions are already being developed, including the use of monoclonal antibodies to interfere with collagen fibril formation and the use of triple-helical peptides to direct liposomes to melanoma cells. The molecular information about collagen interactions will further serve as a foundation for computational studies to design small molecules that can interfere with specific interactions or target tumor cells. Intelligent control of collagen biological interactions within a material context will expand the effectiveness of collagen-based drug delivery.
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Sepsis is an important cause of neonatal morbidity and mortality; therefore, the early diagnosis of neonatal sepsis is essential.
Our aim was to compare the diagnostic accuracy of procalcitonin ...(PCT), C-reactive protein (CRP), procalcitonin combined with C-reactive protein (PCT + CRP) and presepsin in the diagnosis of neonatal sepsis. We searched seven databases to identify studies that met the inclusion criteria. Two independent reviewers performed data extraction. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under curve (AUC), and corresponding 95% credible interval (95% CI) were calculated by true positive (TP), false positive (FP), false negative (FN), and true negative (TN) classification using a bivariate regression model in STATA 14.0 software. The pooled sensitivity, specificity, PLR, NLR, DOR, AUC, and corresponding 95% CI were the primary outcomes. Secondary outcomes included the sensitivity and specificity in multiple subgroup analyses.
A total of 28 studies enrolling 2661 patients were included in our meta-analysis. The pooled sensitivity of CRP (0.71 (0.63, 0.78)) was weaker than that of PCT (0.85 (0.79, 0.89)), PCT + CRP (0.91 (0.84, 0.95)) and presepsin (0.94 (0.80, 0.99)) and the pooled NLR of presepsin (0.06 (0.02, 0.23)) and PCT + CRP (0.10 (0.05, 0.19)) were less than CRP (0.33 (0.26, 0.42)), and the AUC for presepsin (0.99 (0.98, 1.00)) was greater than PCT + CRP (0.96 (0.93, 0.97)), CRP (0.85 (0.82, 0.88)) and PCT (0.91 (0.89, 0.94)). The results of the subgroup analysis showed that 0.5-2 ng/mL may be the appropriate cutoff interval for PCT. A cut-off value > 10 mg/L for CRP had high sensitivity and specificity.
The combination of PCT and CRP or presepsin alone improves the accuracy of diagnosis of neonatal sepsis. However, further studies are required to confirm these findings.
As the population ages, increasing numbers of older adults are undergoing surgery. Frailty is prevalent in older adults and may be a better predictor of post-operative morbidity and mortality than ...chronological age. The aim of this review was to examine the impact of frailty on adverse outcomes in the 'older old' and 'oldest old' surgical patients.
A systematic review was undertaken. Electronic databases from 2010 to 2015 were searched to identify articles which evaluated the relationship between frailty and post-operative outcomes in surgical populations with a mean age of 75 and older. Articles were excluded if they were in non-English languages or if frailty was measured using a single marker only. Demographic data, type of surgery performed, frailty measure and impact of frailty on adverse outcomes were extracted from the selected studies. Quality of the studies and risk of bias was assessed by the Epidemiological Appraisal Instrument.
Twenty-three studies were selected for the review and they were assessed as medium to high quality. The mean age ranged from 75 to 87 years, and included patients undergoing cardiac, oncological, general, vascular and hip fracture surgeries. There were 21 different instruments used to measure frailty. Regardless of how frailty was measured, the strongest evidence in terms of numbers of studies, consistency of results and study quality was for associations between frailty and increased mortality at 30 days, 90 days and one year follow-up, post-operative complications and length of stay. A small number of studies reported on discharge to institutional care, functional decline and lower quality of life after surgery, and also found a significant association with frailty.
There was strong evidence that frailty in older-old and oldest-old surgical patients predicts post-operative mortality, complications, and prolonged length of stay. Frailty assessment may be a valuable tool in peri-operative assessment. It is possible that different frailty tools are best suited for different acuity and type of surgical patients. The association between frailty and return to pre-morbid function, discharge destination, and quality of life after surgery warrants further research.
Structure-based stabilization of protein–protein interactions (PPIs) is a promising strategy for drug discovery. However, this approach has mainly focused on the stabilization of native PPIs, and ...non-native PPIs have received little consideration. Here, we identified a non-native interaction interface on the three-dimensional dimeric structure of the N-terminal domain of the MERS-CoV nucleocapsid protein (MERS-CoV N-NTD). The interface formed a conserved hydrophobic cavity suitable for targeted drug screening. By considering the hydrophobic complementarity during the virtual screening step, we identified 5-benzyloxygramine as a new N protein PPI orthosteric stabilizer that exhibits both antiviral and N-NTD protein-stabilizing activities. X-ray crystallography and small-angle X-ray scattering showed that 5-benzyloxygramine stabilizes the N-NTD dimers through simultaneous hydrophobic interactions with both partners, resulting in abnormal N protein oligomerization that was further confirmed in the cell. This unique approach based on the identification and stabilization of non-native PPIs of N protein could be applied toward drug discovery against CoV diseases.
Due to the circadian rhythm regulation of almost every biological process in the human body, physiological and biochemical conditions vary considerably over the course of a 24-h period. Thus, optimal ...drug delivery and therapy should be effectively controlled to achieve the desired therapeutic plasma concentrations and therapeutic drug responses at the required time according to chronopharmacological concepts, rather than continuous maintenance of constant drug concentrations for an extended time period. For many drugs, it is not always necessary to constantly deliver a drug into the human body under disease conditions due to rhythmic variations. Pulsatile drug delivery systems (PDDSs) have been receiving more attention in pharmaceutical development by providing a predetermined lag period, followed by a fast or rate-controlled drug release after application. PDDSs are characterized by a programmed drug release, which may release a drug at repeatable pulses to match the biological and clinical needs of a given disease therapy.
This review article focuses on thermoresponsive gating membranes embedded with liquid crystals (LCs) for transdermal drug delivery using PDDS technology. In addition, the principal rationale and the advanced approaches for the use of PDDSs, the marketed products of chronotherapeutic DDSs with pulsatile function designed by various PDDS technologies, pulsatile drug delivery designed with thermoresponsive polymers, challenges and opportunities of transdermal drug delivery, and novel approaches of LC systems for drug delivery are reviewed and discussed. A brief overview of all academic research articles concerning single LC- or binary LC-embedded thermoresponsive membranes with a switchable on-off permeation function through topical application by an external temperature control, which may modulate the dosing interval and administration time according to the therapeutic needs of the human body, is also compiled and presented. In the near future, since thermal-based approaches have become a well-accepted method to enhance transdermal delivery of different water-soluble drugs and macromolecules, a combination of the thermal-assisted approach with thermoresponsive LCs membranes will have the potential to improve PDDS applications but still poses a great challenge.
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Multiple organ damage in severe acute respiratory syndrome (SARS) patients is common; however, the pathogenesis remains controversial. This study was to determine whether the damage was correlated ...with expression of the SARS coronavirus receptor, angiotensin converting enzyme 2 (ACE2), in different organs, especially in the endocrine tissues of the pancreas, and to elucidate the pathogenesis of glucose intolerance in SARS patients. The effect of clinical variables on survival was estimated in 135 SARS patients who died, 385 hospitalized SARS patients who survived, and 19 patients with non-SARS pneumonia. A total of 39 SARS patients who had no previous diabetes and received no steroid treatment were compared to 39 matched healthy siblings during a 3-year follow-up period. The pattern of SARS coronavirus receptor-ACE2 proteins in different human organs was also studied. Significant elevations in oxygen saturation, serum creatinine, lactate dehydrogenase, creatine kinase MB isoenzyme, and fasting plasma glucose (FPG), but not in alanine transaminase were predictors for death. Abundant ACE2 immunostaining was found in lung, kidney, heart, and islets of pancreas, but not in hepatocytes. Twenty of the 39 followed-up patients were diabetic during hospitalization. After 3 years, only two of these patients had diabetes. Compared with their non-SARS siblings, these patients exhibited no significant differences in FPG, postprandial glucose (PPG), and insulin levels. The organ involvements of SARS correlated with organ expression of ACE2. The localization of ACE2 expression in the endocrine part of the pancreas suggests that SARS coronavirus enters islets using ACE2 as its receptor and damages islets causing acute diabetes.
Dynamin, a 100-kDa GTPase, is one of the most-characterized membrane fission machineries catalyzing vesicle release from plasma membrane during endocytosis. The human genome encodes three dynamins: ...DNM1, DNM2 and DNM3, with high amino acid similarity but distinct expression patterns. Ever since the discoveries of dynamin mutations associated with human diseases in 2005, dynamin has become a paradigm for studying pathogenic mechanisms of mutant proteins from the aspects of structural biology, cell biology, model organisms as well as therapeutic strategy development. Here, we review the diseases and pathogenic mechanisms caused by mutations of DNM1 and DNM2, focusing on the activity requirement and regulation of dynamins in different tissues.
The Internet of Underwater Things (IoUT) is a novel class of Internet of Things (IoT), and is defined as the network of smart interconnected underwater objects. IoUT is expected to enable various ...practical applications, such as environmental monitoring, underwater exploration, and disaster prevention. With these applications, IoUT is regarded as one of the potential technologies toward developing smart cities. To support the concept of IoUT, Underwater Wireless Sensor Networks (UWSNs) have emerged as a promising network system. UWSNs are different from the traditional Territorial Wireless Sensor Networks (TWSNs), and have several unique properties, such as long propagation delay, narrow bandwidth, and low reliability. These unique properties would be great challenges for IoUT. In this paper, we provide a comprehensive study of IoUT, and the main contributions of this paper are threefold: (1) we introduce and classify the practical underwater applications that can highlight the importance of IoUT; (2) we point out the differences between UWSNs and traditional TWSNs, and these differences are the main challenges for IoUT; and (3) we investigate and evaluate the channel models, which are the technical core for designing reliable communication protocols on IoUT.
Invadosomes are protrusive and mechanosensitive actin devices critical for cell migration, invasion, and extracellular matrix remodeling. The dynamic, proteolytic, and protrusive natures of ...invadosomes have made these structures fascinating and attracted many scientists to develop new technologies for their analysis. With these exciting methodologies, many biochemical and biophysical properties of invadosomes have been well characterized and appreciated, and those discoveries elegantly explained the biological and pathological effects of invadosomes in human health and diseases. In this review, we focus on these commonly used or newly developed methods for invadosome analysis and effort to reason some discrepancies among those assays. Finally, we explore the opposite regulatory mechanisms among invadosomes and focal adhesions, another actin‐rich adhesive structures, and speculate a potential rule for their switch.
Over the past decades, technologies aiming to probe the properties of subcellular structures have been developed and incorporated into the field of invadosome research. With the help of these technologies, scientists are now able to gain a deeper understanding of invadosomes and raise exciting unanswered questions. In this review, Lin et al. summarize the current knowledge on invadosomes, as well as commonly used and newly developed methods for invadosome analysis.
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