Making 2D Materials Sparkle in Energy Storage via Assembly.

ConspectusTwo-dimensional (2D) materials such as graphene and MXenes offer appealing opportunities in electrochemical energy storage due to their large surface area, tunable surface chemistry, and unique electronic properties. One of the primary challenges in utilizing these materials for practical electrodes, especially those with industrial-level thickness, is developing a highly interconnected and porous conductive network. This network is crucial for supporting continuous electron transport, rapid ion diffusion, and effective participation of all active materials in electrochemical reactions. Moreover, the demand for efficient energy storage in advanced electronic devices and electric vehicles has led to the need for not only thicker but also denser electrodes to achieve compact energy storage. Traditional densification methods often compromise between volumetric capacitance and ion-accessible surface area, which can diminish rate performance. As versatile building blocks, 2D materials can overcome these limitations through the assembly into complex superstructures such as 1D fibers, 2D thin films, and 3D porous networks, a capability less attainable by other nanomaterials.This Account explores the pathways from exfoliated 2D nanosheets to densely packed, yet porous assemblies tailored for compact energy storage. Focusing on graphene and MXenes, we delve into the intricate relationships between surface structure, assembly behaviors, and electrochemical performance. We emphasize the crucial role of surface chemistry and interfacial interactions in forming stable colloidal dispersions and subsequent macroscopic structures. Furthermore, we highlight how solvents, acting as spacers, are instrumental in microstructure formation and how capillary force-driven densification is essential for creating compact assemblies. With precise control over shrinkage, the customized dense assemblies can strike a balance between high packing density and sufficient porosity, ensuring efficient ion transport, mechanical stability, and high volumetric performance across various electrochemical energy storage technologies.Furthermore, we highlight the importance of understanding and manipulating the surface chemistry of 2D materials at the atomic level to optimize their assembly and enhance electrochemical behaviors. Advanced in situ characterizations with high temporal and spatial resolution are necessary to gain deeper insights into the complex assembly process. Moreover, the integration of machine learning and computational chemistry emerges as a promising method to predict and design new materials and assembly strategies, potentially accelerating the development of next-generation energy storage systems. Our insights into the assembly and densification of 2D materials provide a comprehensive foundation for future research and practical applications in compact, high-performance energy storage devices. This exploration sets the stage for a transformative approach to overcoming the challenges of current energy storage technologies, promising significant advancements in 2D materials in the field.

Proton is Essential or Not: A Fresh Look on Pseudocapacitive Energy Storage of PANI Composites.

Protonation has been considered essential for the pseudocapacitive energy storage of polyaniline (PANI) for years, as proton doping in PANI chains not only activates electron transport pathways, but also promotes the proceeding of redox reactions. Rarely has the ability for PANI of storing energy without protonation been investigated, and it remains uncertain whether PANI has pseudocapacitive charge storage properties in an alkaline electrolyte. Here, this work first demonstrates the pseudocapacitive energy storage for PANI without protonation using a PANI/graphene composite as a model material in an alkaline electrolyte. Using in situ Raman spectroscopy coupled with electrochemical quartz crystal microbalance (EQCM) measurements, this work determines the formation of -N= group over potential on a PANI chain and demonstrates the direct contribution of OH- in the nonprotonation type of oxidation reactions. This work finds that the PANI/graphene composite in an alkaline electrolyte has excellent cycling stability with a wider operation voltage of 1 V as well as a slightly higher specific capacitance than that in an acidic electrolyte. The findings provide a new perspective on pseudocapacitive energy storage of PANI-based composites, which will influence the selection of electrolytes for PANI materials and expand their application in energy storage fields.

Dual Defect Passivation at the Buried Interface for Printable Mesoscopic Perovskite Solar Cells with Reduced Open-Circuit Voltage Loss.

Numerous defects exist at the buried interface between the perovskite and adjacent electron transport layers in perovskite solar cells, resulting in severe non-radiative recombination and excessive open-circuit voltage (VOC) loss. Herein, a dual defect passivation strategy utilizing guanidine sulfate (GUA2SO4) as an interface modifier is first reported. On the one hand, the SO4 2- preferentially interacts with Pb-related defects, generating water-insoluble lead oxysalts complexes. Additionally, GUA+ diffuses into the perovskite and induces the formation of low-dimensional perovskite. These reactions effectively suppress trap states at the buried interface and perovskite boundaries in printable mesoscopic perovskite solar cells (p-MPSCs), thus increasing the carrier lifetime. Meanwhile, GUA2SO4 optimizes the interface energy band alignment, thus accelerating the charge extraction and transfer at the buried interface. This synergistic effect of trap passivation and interface energy band alignment modulation is strongly demonstrated by an increase in average VOC of 70 mV and the power conversion efficiency improvement from 17.51% to 18.70%. This work provides a novel approach to efficiently improve the performance of p-MPSCs through dual-targeted defect passivation at the buried interface.

Short-term antiplatelet versus anticoagulant therapy after left atrial appendage closure: a systematic review and meta-analysis.

This meta-analysis compared the efficacy and safety of different antithrombotic regimens after left atrial appendage closure (LAAC). PubMed, Embase, Medline, Cochrane Library databases were systematically searched from their inception to March 2023. Patients were divided into short-term oral anticoagulation (OAC) group and antiplatelet therapy (APT) group. The incidence of events were performed using RevMan 5.4. The events including device-related thrombus (DRT), ischemic stroke/systemic embolization (SE), major bleeding, any bleeding, any major adverse event and all-cause mortality. Subgroup analysis were based on OAC alone or OAC plus single antiplatelet therapy (SAPT) in OAC group. Oral anticoagulants include warfarin and direct oral anticoagulant (DOAC). Fourteen studies with 35,166 patients were included. We found that the incidence of DRT (OR = 0.49, 95% CI 0.36-0.66, P＜0.0001) and all-cause mortality (OR = 0.71, 95% CI 0.57-0.89, P = 0.002) were significantly lower in OAC group than APT group. However, there was no statistical differences in the incidence rates of ischemic stroke/SE (OR = 0.77, 95% CI 0.49-1.20, P = 0.25), major bleeding (OR = 0.84, 95% CI 0.55-1.27, P = 0.84), any bleeding (OR = 0.83, 95% CI 0.56-1.22, P = 0.34) and any major adverse event (OR = 0.56, 95% CI 0.30-1.03, P = 0.06) in the two groups. Subgroup analysis found that the incidence of DRT, all-cause mortality and any major adverse event in OAC monotherapy were lower than that in APT group (P＜0.05), but not statistically different from other outcome. The incidence of DRT, all-cause mortality, any major adverse event and any bleeding in DOAC were significantly better than APT group (P＜0.05). While warfarin only has better incidence of DRT than APT (P＜0.05), there was no statistical difference between the two groups in other outcome (P＞0.05). The incidence of DRT was significantly lower than APT group (P＜0.05), major bleeding were higher, and the rest of the outcome did not show any statistically significant differences(P＞0.05) when OAC plus SAPT. Based on the existing data, short-term OAC may be favored over APT for patients who undergo LAAC. DOAC monotherapy may be favored over warfarin monotherapy or OAC plus APT, when selecting anticoagulant therapies.

[Tanshinone â ¡A Ameliorates Cartilage Degeneration in Ovariectomized Rats by Regulating TGF-ß1/Smad2/MMPs Signaling Pathway]. / ä¸¹å‚é ®â ¡A通过调节TGF-ß1/Smad2/MMPsä¿¡å·é€šè·¯æ”¹å–„åµå·¢æ‘˜é™¤å¤§é¼ å ³èŠ‚è½¯éª¨é€€è¡Œæ€§æ”¹å˜.

Objective: To investigate the ameliorative effect of tanshinone ⅡA (Tan) on osteoarticular degeneration in ovariectomized rats (a postmenopausal estrogen deficiency model) and the mechanisms involved. Methods: Eight-week-old female Sprague Dawley (SD) rats were randomly allocated to 5 groups (n=10 each), including a Sham operation group (Sham), an ovariectomy group (OVX), and low, medium, and high-dose Tan groups. Eight weeks after bilateral ovariectomy, the rats in the low, medium, and high-dose Tan groups were treated with Tan at the doses of 5, 10, and 20 mg/kg for a duration of 28 days. Evaluation of the rat articular cartilage was performed using X-ray imaging, anatomical observation, hematoxylin and eosin (H&E) staining, and toluidine blue staining. Immunohistochemistry was performed to assess the expression levels of transforming growth factor ß1 (TGF-ß1), phosphorylated-smad2 (p-Smad2), type Ⅱ collagen (CⅡ), matrix metalloproteinase 9 (MMP-9), and MMP-13 in the cartilage tissue. Results: The knee joints of the OVX rats exhibited narrowed joint spaces, osteophyte formation, cartilage erosion or even localized cartilage cracks, faded methylene blue staining on the cartilage surface, disordered arrangement of chondrocytes, unclear or interrupted tidal line, and increased Kellgren-Lawrence grading, Pelletier grading, Mankin grading, and OARSI scores compared to those of the Sham group (P<0.01), as revealed by X-ray imaging, anatomical observation, and histological examination results. Tan ameliorated the degenerative changes in the knee joint caused by OVX in a dose-dependent manner while improving Kellgren-Lawrence grading, Pelletier grading, Mankin grading, and OARSI scores. Immunohistochemistry findings showed that TGF-ß1, p-Smad2, and CⅡ expression levels were significantly increased (P<0.01), while MMP-9 and MMP-13 expression levels were significantly decreased (P<0.01) in the articular cartilage of the Tan group compared to those of the OVX group, with all these effects being dose-dependent. Conclusion: Tan mitigates articular cartilage degeneration in ovariectomized rats, which may be related to the regulation of TGF-ß1/Smad2/MMPs signaling pathway.

Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can spread rapidly within skilled nursing facilities. After identification of a case of Covid-19 in a skilled nursing facility, we assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents. METHODS: We conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms that had been present during the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with SARS-CoV-2 infection were categorized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic. RESULTS: Twenty-three days after the first positive test result in a resident at this skilled nursing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2. Among 76 residents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 subsequently developed symptoms (median time to onset, 4 days). Samples from these 24 presymptomatic residents had a median rRT-PCR cycle threshold value of 23.1, and viable virus was recovered from 17 residents. As of April 3, of the 57 residents with SARS-CoV-2 infection, 11 had been hospitalized (3 in the intensive care unit) and 15 had died (mortality, 26%). Of the 34 residents whose specimens were sequenced, 27 (79%) had sequences that fit into two clusters with a difference of one nucleotide. CONCLUSIONS: Rapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.

Application of long non-coding RNA RBAT1 in improving diagnosis and prognosis of ovarian carcinoma.

Tumorigenesis of bladder cancer and retinoblastoma is correlated with long non-coding RNA (lncRNA) RBAT1. However, the role of RBAT1 in ovarian carcinoma (OC) is unclear. Thus, the study explored the role of RBAT1 in OC. This research enrolled patients with OC ( n = 68), irritable bowel disease (IBD, n = 68, females), digestive tract inflammation (DTI, n = 68, females), urinary tract infection (UTI, n = 68, females), endometriosis (EM, n = 68, females), and healthy controls (HCs, n = 68) to collect plasma sampled. OC and paired non-tumor tissues were collected from patients with OC. RBAT1 accumulation in all samples was analyzed using RT-qPCR. The role of plasma RBAT1 in OC diagnosis was examined using the ROC curves with OC patients as the true positive cases and other patients and HCs as the true negative cases. The role of RBAT1 in predicting the survival of OC patients was analyzed using the survival curve study. RBAT1 was overexpressed in both OC plasma and tissues. Plasma RBAT1 levels were correlated with RBAT1 levels in OC tissues but not in non-tumor tissues. Plasma RBAT1 could distinguish OC patients from other patients and HCs. Patients with high plasma RBAT1 levels had a shorter survival. RBAT1 is overexpressed in OC and might be applied to improve the diagnosis and prognosis of OC.

Negative life events and aggression among Chinese rural left-behind adolescents: do self-esteem and resilience mediate the relationship?

BACKGROUND: Left-behind adolescents (LBAs) are adolescents aged 11-18 years who are separated from their parents and left behind in local cities by one or both parents for a period of more than 6 months. LBAs in rural areas are likely to engage in aggressive behavior, which can affect interpersonal relationships, reduce academic performance, and even lead to anxiety and depression. To our knowledge, no studies have examined the mediating effect of resilience and self-esteem on the relationship between negative life events and aggression among Chinese rural LBAs. Therefore, this study aimed to explore the relationship between negative life events and aggression among Chinese rural LBAs and how self-esteem and resilience mediate the association. METHODS: Using a stratified random sampling method, 1344 LBAs in Hunan Province of China were investigated. Information was collected by a self-designed sociodemographic questionnaire, Adolescent Self-Rating Life Events Checklist, Resilience Scale Chinese Adolescent, Rosenberg Self-Esteem Scale and Aggression Scales to assess the psychology of LBAs. Data analysis was conducted using descriptive statistics, Pearson correlation, and regression analysis to estimate direct and indirect effects using bootstrap analysis. RESULTS: Negative life events were significantly related to self-esteem (r = - 0.338), resilience (r = - 0.359), and aggression (r = 0.441). Aggression was directly affected by self-esteem (ß = - 0.44) and resilience (ß = - 0.34). Negative life events were not only directly related to aggression (ß = 0.34, 95% CI: 0.275 ~ 0.398) but also showed an indirect effect on aggression through self-esteem and resilience. The direct effect, total effect and indirect effect of negative life events on aggression through self-esteem and resilience were 0.3364, 0.4344 and 0.0980, respectively. The mediating effect of self-esteem and resilience accounted for 22.56% of the relationship between negative life events and aggression. CONCLUSIONS: We found that self-esteem and resilience mediated most negative life events on aggression. It is imperative for educators and families to improve LBAs' self-esteem and resilience to reduce the occurrence of aggression. Future intervention studies should be designed to strengthen self-esteem and resilience.

Hydroxyl Radical-Mediated Efficient Photoelectrocatalytic NO Oxidation with Simultaneous Nitrate Storage Using A Flow Photoanode Reactor.

The selective conversion of dilute NO pollutant into low-toxic product and simultaneous storage of metabolic nitrogen for crop plants remains a great challenge from the perspective of waste management and sustainable chemistry. This study demonstrates that this bottleneck can be well tackled by refining the reactive oxygen species (ROS) on Ni-modified NH2 -UiO-66(Zr) (Ni@NU) using nickel foam (NF) as a three-dimensional (3D) substrate through a flow photoanode reactor via the gas-phase photoelectrocatalysis. By rationally refining the ROS to ⋅OH, Ni@NU/NF can rapidly eliminate 82 % of NO without releasing remarkable NO2 under a low bias voltage (0.3 V) and visible light irradiation. The abundant mesoporous pores on Ni@NU/NF are conducive to the diffusion and storage of the formed nitrate, which enables the progressive conversion NO into nitrate with selectivity over 99 % for long-term use. Through calculation, 90 % of NO could be recovered as the nitrate species, indicating that this state-of-the-art strategy can capture, enrich and recycle the pollutant N source from the atmosphere. This study offers a new perspective of NO pollutant treatment and sustainable nitrogen exploitation, which may possess great potential to the development of highly efficient air purification systems for industrial and indoor NOx control.

SARS-CoV-2 Outbreak among Malayan Tigers and Humans, Tennessee, USA, 2020.

We report an outbreak of severe acute respiratory syndrome coronavirus 2 involving 3 Malayan tigers (Panthera tigris jacksoni) at a zoo in Tennessee, USA. Investigation identified naturally occurring tiger-to-tiger transmission; genetic sequence change occurred with viral passage. We provide epidemiologic, environmental, and genomic sequencing data for animal and human infections.

Sulphur ylide-mediated cyclopropanation and subsequent spirocyclopropane rearrangement reactions.

The efficient construction of cyclopropyl spiroindoline skeletons and the exploration of related follow-up synthetic transformations have elicited considerable interest amongst members of the chemistry community. Here, we describe a formal (2 + 1) annulation and three-component (1 + 1 + 1) cascade cyclisation via sulphur ylide cyclopropanation under mild conditions. The spiro-cyclopropyl iminoindoline moiety can be readily transformed into another medicinally interesting pyrrolo[3,4-c]quinoline framework through a novel rearrangement process.

Correlations of High-frequency Ultrasound Evaluation of Brachial Artery Endothelial Dilatation and Carotid Atherosclerosis with Glucose and Lipid Metabolism, Inflammatory Cytokines, Severity of Coronary Artery Disease and Vascular Endothelial Function in Elderly Patients.

The study aimed to explore the correlations of the results of the high-frequency ultrasound evaluation of the brachial artery endothelial dilatation and carotid atherosclerosis with glucose and lipid metabolism, inflammatory cytokines, the severity of coronary artery disease (CAD) and vascular endothelial function in elderly patients. 78 elderly patients with CAD in Beijing Anzhen Hospital were selected. The high-frequency ultrasonography was carried out to observe the flow-mediated dilatation (FMD) and intima-media thickness (IMT) and to analyze their correlations with inflammatory cytokines [C-reactive protein (CRP) and plasminogen activator inhibitor (PAI-1)], endothelial function [nitric oxide (NO) and endothelin-1 (ET-1)], glycolipid metabolism [high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG) and fasting blood glucose (FBG)] and the severity of CAD. FMD, NO and HDL-C: patients with single-vesselCAD> those with double-vessel CAD>those with multi-vessel CAD. IMT, CRP, PAI-1, FBG, ET-1, TC and TG: patients with single-vesselCAD< those with double-vessel CAD

Bioimaging guided pharmaceutical evaluations of nanomedicines for clinical translations.

Nanomedicines (NMs) have emerged as an efficient approach for developing novel treatment strategies against a variety of diseases. Over the past few decades, NM formulations have received great attention, and a large number of studies have been performed in this field. Despite this, only about 60 nano-formulations have received industrial acceptance and are currently available for clinical use. Their in vivo pharmaceutical behavior is considered one of the main challenges and hurdles for the effective clinical translation of NMs, because it is difficult to monitor the pharmaceutic fate of NMs in the biological environment using conventional pharmaceutical evaluations. In this context, non-invasive imaging modalities offer attractive solutions, providing the direct monitoring and quantification of the pharmacokinetic and pharmacodynamic behavior of labeled NMs in a real-time manner. Imaging evaluations have great potential for revealing the relationship between the physicochemical properties of NMs and their pharmaceutical profiles in living subjects. In this review, we introduced imaging techniques that can be used for in vivo NM evaluations. We also provided an overview of various studies on the influence of key parameters on the in vivo pharmaceutical behavior of NMs that had been visualized in a non-invasive and real-time manner.

Dynamic routing, modulation, and spectrum assignment based on fuzzy logic control in elastic optical networks.

Considering the constantly changing network resources and randomly generated spectrum fragmentation problem, a dynamic routing, modulation, and spectrum assignment based on the fuzzy logic control (RMSA-FLC) algorithm is proposed in this paper. A fuzzy logic control (FLC) system based on the degree of fragmentation optimization and the degree of link selection is constructed. The path-control weight (PW) is achieved as the output of the FLC system, and the path and spectrum allocation scheme with the maximum PW is selected for the immediate reservation requests. The simulation results show that the proposed RMSA-FLC algorithm can effectively reduce the blocking probability and improve the spectrum resource utilization in a dynamic elastic optical network.

MALT1 positively relates to Th17 cells, inflammation/activity degree, and its decrement along with treatment reflects TNF inhibitor response in ankylosing spondylitis patients.

BACKGROUND: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) facilitates CD4+ T-cell differentiation, immune response, inflammation, and osteoclastogenesis. This study aimed to explore the relation between MALT1 and treatment efficacy to tumor necrosis factor inhibitor (TNFi) in ankylosing spondylitis (AS) patients. METHODS: This study recruited 73 AS patients underwent adalimumab treatment. Peripheral blood mononuclear cell (PBMC) was obtained at Week (W) 0, W4, W8, and W12 after treatment initiation; then, MALT1 was measured using RT-qPCR. Furthermore, PBMC and serum at W0 were proposed to flow cytometry and ELISA for Th1 cells, Th17 cells, IFN-γ, and IL-17A levels measurement. Besides, 20 osteoarthritis patients and 20 healthy controls (HCs) were enrolled to detect MALT1. RESULTS: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 expression was higher in AS patients compared with HCs (p < 0.001) and osteoarthritis patients (p < 0.001). Besides, MALT1 expression was positively linked with CRP (p = 0.002), BASDAI (p = 0.026), PGADA (p = 0.040), ASDASCRP (p = 0.028), Th17 cells (p = 0.020), and IL-17A (p = 0.017) in AS patients, but did not relate to other clinical features, Th1 cells or IFN-γ (all p>0.050). MALT1 was decreased along with treatment only in AS patients with ASAS40 response (p < 0.001), but not in those without ASAS40 response (p = 0.064). Notably, MALT1 expression was of no difference at W0 (p = 0.328), W4 (p = 0.280), and W8 (p = 0.080), but lower at W12 (p = 0.028) in AS patients with ASAS40 response compared with those without ASAS40 response. CONCLUSION: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 positively correlates with Th17 cells, inflammatory, and activity degree; meanwhile, its decrement along with treatment reflects the response to TNF inhibitor in AS patients.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 in rheumatoid arthritis: Longitudinal change after treatment and correlation with treatment efficacy of tumor necrosis factor inhibitors.

BACKGROUND: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) correlates with treatment outcomes in inflammatory bowel disease and rheumatoid arthritis (RA). This study aimed to further evaluate the MALT1 longitudinal change and its relationship with tumor necrosis factor inhibitors (TNFi) response in RA patients. METHODS: Seventy-one RA patients receiving TNFi [etanercept (n = 42) or adalimumab (n = 29)] were enrolled. MALT1 was detected by RT-qPCR in peripheral blood samples of RA patients before treatment (W0), at week (W)4, W12, and W24 after treatment. RA patients were divided into response/non-response, remission/non-remission patients according to their treatment outcome at W24. Meanwhile, MALT1 was also detected by RT-qPCR in 30 osteoarthritis patients and 30 healthy controls (HCs). RESULTS: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 was elevated in RA patients compared with HCs (Z=-6.392, p < 0.001) and osteoarthritis patients (Z = -5.020, p < 0.001). In RA patients, MALT1 was positively correlated with C-reactive protein (rs  = 0.347, p = 0.003), but not other clinical characteristics, treatment history, or current TNFi category. Meanwhile, MALT1 decreased from W0 to W12 in total RA patients (x2  = 86.455, p < 0.001), etanercept subgroup (x2  = 46.636, p < 0.001), and adalimumab subgroup (x2  = 41.291, p < 0.001). Moreover, MALT1 at W24 (p = 0.012) was decreased in response patients compared with non-response patients; MALT1 at W12 (p = 0.027) and W24 (p = 0.010) were reduced in remission patients than non-remission patients. In etanercept subgroup, MALT1 at W24 (p = 0.013) was decreased in response patients compared with non-response patients. In adalimumab subgroup, MALT1 at W24 (p = 0.015) was lower in remission patients than non-remission patients. CONCLUSION: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 reduction after treatment is associated with response and remission to TNFi in RA patients.

ED50 and ED95 of propofol combined with different doses of esketamine for children undergoing upper gastrointestinal endoscopy: A prospective dose-finding study using up-and-down sequential allocation method.

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, ED50 ). 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 ED50 (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.

Rapid Optical Biosensing of SARS-CoV-2 Spike Proteins in Artificial Samples.

Tests for SARS-CoV-2 are crucial for the mass surveillance of the incidence of infection. The long waiting time for classic nucleic acid test results highlights the importance of developing alternative rapid biosensing methods. Herein, we propose a fiber-optic biolayer interferometry-based biosensor (FO-BLI) to detect SARS-CoV-2 spike proteins, extracellular domain (ECD), and receptor-binding domain (RBD) in artificial samples in 13 min. The FO-BLI biosensor utilized an antibody pair to capture and detect the spike proteins. The secondary antibody conjugated with horseradish peroxidase (HRP) reacted with the enzyme substrate for signal amplification. Two types of substrates, 3,3'-diaminobenzidine (DAB) and an advanced 3-Amino-9-ethylcarbazole (i.e., AMEC), were applied to evaluate their capabilities in enhancing signals and reaching high sensitivity. After careful comparison, the AMEC-based FO-BLI biosensor showed better assay performance, which detected ECD at a concentration of 32-720 pM and RBD of 12.5-400 pM in artificial saliva and serum, respectively. The limit of detection (LoD) for SARS-CoV-2 ECD and RBD was defined to be 36 pM and 12.5 pM, respectively. Morphology of the metal precipitates generated by the AMEC-HRP reaction in the fiber tips was observed using field emission scanning electron microscopy (SEM). Collectively, the developed FO-BLI biosensor has the potential to rapidly detect SARS-CoV-2 antigens and provide guidance for "sample-collect and result-out on-site" mode.

Modulating p-AMPK/mTOR Pathway of Mitochondrial Dysfunction Caused by MTERF1 Abnormal Expression in Colorectal Cancer Cells.

Human mitochondrial transcription termination factor 1 (MTERF1) has been demonstrated to play an important role in mitochondrial gene expression regulation. However, the molecular mechanism of MTERF1 in colorectal cancer (CRC) remains largely unknown. Here, we found that MTERF1 expression was significantly increased in colon cancer tissues compared with normal colorectal tissue by Western blotting, immunohistochemistry, and tissue microarrays (TMA). Overexpression of MTERF1 in the HT29 cell promoted cell proliferation, migration, invasion, and xenograft tumor formation, whereas knockdown of MTERF1 in HCT116 cells appeared to be the opposite phenotype to HT29 cells. Furthermore, MTERF1 can increase mitochondrial DNA (mtDNA) replication, transcription, and protein synthesis in colorectal cancer cells; increase ATP levels, the mitochondrial crista density, mitochondrial membrane potential, and oxygen consumption rate (OCR); and reduce the ROS production in colorectal cancer cells, thereby enhancing mitochondrial oxidative phosphorylation (OXPHOS) activity. Mechanistically, we revealed that MTERF1 regulates the AMPK/mTOR signaling pathway in cancerous cell lines, and we also confirmed the involvement of the AMPK/mTOR signaling pathway in both xenograft tumor tissues and colorectal cancer tissues. In summary, our data reveal an oncogenic role of MTERF1 in CRC progression, indicating that MTERF1 may represent a new therapeutic target in the future.

Introduction, Transmission Dynamics, and Fate of Early Severe Acute Respiratory Syndrome Coronavirus 2 Lineages in Santa Clara County, California.

We combined viral genome sequencing with contact tracing to investigate introduction and evolution of severe acute respiratory syndrome coronavirus 2 lineages in Santa Clara County, California, from 27 January to 21 March 2020. From 558 persons with coronavirus disease 2019, 101 genomes from 143 available clinical samples comprised 17 lineages, including SCC1 (n = 41), WA1 (n = 9; including the first 2 reported deaths in the United States, with postmortem diagnosis), D614G (n = 4), ancestral Wuhan Hu-1 (n = 21), and 13 others (n = 26). Public health intervention may have curtailed the persistence of lineages that appeared transiently during February and March. By August, only D614G lineages introduced after 21 March were circulating in Santa Clara County.