Covalent organic frameworks (COF) possess a robust and porous crystalline structure, making them an appealing candidate for energy storage. Herein, we report an exfoliated polyimide COF composite ...(P‐COF@SWCNT) prepared by an in situ condensation of anhydride and amine on the single‐walled carbon nanotubes as advanced anode for potassium‐ion batteries (PIBs). Numerous active sites exposed on the exfoliated frameworks and the various open pathways promote the highly efficient ion diffusion in the P‐COF@SWCNT while preventing irreversible dissolution in the electrolyte. During the charging/discharging process, K+ is engaged in the carbonyls of imide group and naphthalene rings through the enolization and π‐K+ effect, which is demonstrated by the DFT calculation and XPS, ex‐situ FTIR, Raman. As a result, the prepared P‐COF@SWCNT anode enables an incredibly high reversible specific capacity of 438 mA h g−1 at 0.05 A g−1 and extended stability. The structural advantage of P‐COF@SWCNT enables more insights into the design and versatility of COF as an electrode.
We prepare a polyimide covalent organic framework composite anode by effective in‐situ condensation of anhydride and amine on the surface of single‐walled carbon nanotubes. The construction of the conductive network accelerates the transport of electron. Dual electroactive sites in the framework, carbonyls and aromatic naphthalene rings, could store more potassium ions by the enolization and π‐K+ effect.
Summary
The low temperature and elevated hydrostatic pressure in hadal trenches at water depths below 6000 m render sample collection difficult. Here, in situ hadal water microbial samples were ...collected from the Mariana Trench and analysed. The hadal microbial communities at different depths were revealed to be consistent and were dominated by heterotrophic Marinimicrobia. Thirty high‐quality metagenome‐assembled genomes (MAGs) were retrieved to represent the major hadal microbes affiliated with 12 prokaryotic phyla. Most of the MAGs were newly reported and probably derived from novel hadal inhabitants as exemplified by a potentially new candidate archaeal phylum in the DPANN superphylum. Metabolic reconstruction indicated that a great number of the MAGs participated in nitrogen and sulfur cycling, in which the nitrification process was driven sequentially by Thaumarchaeota and Nitrospirae and sulfur oxidization by Rhodospirillales in the Alphaproteobacteria class. Moreover, several groups of hadal microbes were revealed to be potential carbon monoxide oxidizers. Metatranscriptomic result highlighted the contribution of Chloroflexi in degrading recalcitrant dissolved organic matter and Marinimicrobia in extracellular protein decomposition. The present work provides an in‐depth view on the hadal microbial communities regarding their endemism and element cycles.
MicroRNAs (MiRNAs, MiRs) represent a class of conserved small non‐coding RNAs that affect post‐transcriptional gene regulation and play a vital role in angiogenesis, proliferation, apoptosis, ...migration and invasion. They are essential for a wide range of physiological and pathological processes, especially for vascular diseases. However, data concerning miRNAs in endothelial progenitor cells (EPCs) and deep vein thrombosis (DVT) remain incomplete. We explored miRNAs that modulate angiogenesis in EPCs and thrombolysis, and analysed their underlying mechanisms using a DVT model, dual‐luciferase reporter assay, qRT‐PCR, Western blot, immunofluorescence staining, flow cytometry analysis, CCK‐8 assay, angiogenesis assay, wound healing and Transwell assay. We found that miR‐205 enhanced the homing ability of EPCs to DVT sites and promoted thrombosis resolution and recanalization, which significantly reduced venous thrombus. Additionally, we demonstrated that miR‐205 overexpression significantly enhanced angiogenesis in vivo and in vitro, migration, invasion, F‐actin filaments and proliferation in EPCs, and inhibited cell apoptosis. Conversely, down‐regulation of miR‐205 played the opposite role in EPCs. Importantly, this study demonstrated that miR‐205 directly targeted PTEN to modulate the Akt/autophagy pathway and MMP2 expression, subsequently playing a key role in EPC function and DVT recanalization and resolution. These results elucidated the pro‐angiogenesis effects of miR‐205 in EPCs and established it as a potential target for DVT treatment.
To provide a complete toxicity profile, toxicity spectrum, and a safety ranking of immune checkpoint inhibitor (ICI) drugs for treatment of cancer.
Systematic review and network meta-analysis.
...Electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) were systematically searched to include relevant studies published in English between January 2007 and February 2018.
Only head-to-head phase II and III randomised controlled trials comparing any two or three of the following treatments or different doses of the same ICI drug were included: nivolumab, pembrolizumab, ipilimumab, tremelimumab, atezolizumab, conventional therapy (chemotherapy, targeted therapy, and their combinations), two ICI drugs, or one ICI drug with conventional therapy. Eligible studies must have reported site, organ, or system level data on treatment related adverse events. High quality, single arm trials and placebo controlled trials on ICI drugs were selected to establish a validation group.
36 head-to-head phase II and III randomised trials (n=15 370) were included. The general safety of ICI drugs ranked from high to low for all adverse events was as follows: atezolizumab (probability 76%, pooled incidence 66.4%), nivolumab (56%, 71.8%), pembrolizumab (55%, 75.1%), ipilimumab (55%, 86.8%), and tremelimumab (54%, not applicable). The general safety of ICI drugs ranked from high to low for severe or life threatening adverse events was as follows: atezolizumab (49%, 15.1%), nivolumab (46%, 14.1%), pembrolizumab (72%, 19.8%), ipilimumab (51%, 28.6%), and tremelimumab (28%, not applicable). Compared with conventional therapy, treatment-related adverse events for ICI drugs occurred mainly in the skin, endocrine, hepatic, and pulmonary systems. Taking one ICI drug was generally safer than taking two ICI drugs or one ICI drug with conventional therapy. Among the five ICI drugs, atezolizumab had the highest risk of hypothyroidism, nausea, and vomiting. The predominant treatment-related adverse events for pembrolizumab were arthralgia, pneumonitis, and hepatic toxicities. The main treatment-related adverse events for ipilimumab were skin, gastrointestinal, and renal toxicities. Nivolumab had a narrow and mild toxicity spectrum, mainly causing endocrine toxicities. Integrated evidence from the pooled incidences, subgroup, and sensitivity analyses implied that nivolumab is the best option in terms of safety, especially for the treatment of lung cancer.
Compared with other ICI drugs used to treat cancer, atezolizumab had the best safety profile in general, and nivolumab had the best safety profile in lung cancer when taking an integrated approach. The safety ranking of treatments based on ICI drugs is modulated by specific treatment-related adverse events.
PROSPERO CRD42017082553.
Recent studies on nitrate transporters (NRTs) have greatly increased our knowledge of the mechanisms regulating nitrogen (N) homeostasis in plants. However, an understanding of how these NRTs are ...regulated is still lacking.
The nitrogen limitation adaptation (nla) mutant is hypersensitive to N limitation. In the nla mutant, 15N-nitrate spotted on old leaves preferentially accumulated in the youngest leaves. Analysis of leaf cross-sections indicated that NLA expression was expressed in the sieve element and companion cell system. The results of bimolecular fluorescence complementation (BiFC), split-ubiquitin yeast two-hybrid and co-immunoprecipitation (CoIP) assays demonstrated that NLA interacts with NRT1.7 in the plasma membrane.
The following findings suggest that NLA directs the ubiquitination of NRT1.7: the down-regulation of NRT1.7 protein abundance in 35S::NLA/35S::Myc-NRT1.7 double transgenic plants compared with 35S::Myc-NRT1.7 transgenic plants; the up-regulation of NRT1.7 protein abundance in the nla mutant compared with wild-type plants; and the direct degradation of truncated NRT1.7 recombinant protein by NLA. Furthermore, analysis of NLA and NRT1.7 protein abundance in mirna827 knock-out plants showed that N deficiency-guided translational repression of NLA depends on miRNA827.
Our findings reveal that plants regulate source-to-sink remobilization of nitrate by the ubiquitin-mediated post-translational regulatory pathway.
Backgrounds
We intended to identify the incidence and risk factors (RFs) for Postoperative urinary retention (POUR) after applying a risk‐stratified catheterization optimization method in enhanced ...recovery after surgery (ERAS)‐total joint arthroplasty (TJA).
Methods
A total of 381 patients were prospectively monitored for POUR. POUR diagnosis was done by a perioperative specialist. Data on potential risk factors (RFs) for POUR were accumulated. Univariate analysis (UA) was conducted to identify possible indicators of POUR, followed by multivariate analysis (MA) of identified indicators.
Results
POUR occurred in 5.5% of cases, including 8 (3.4%) patients underwent total knee arthroplasty and 13 (10.4%) patients underwent total hip arthroplasty. In UA, age, sex, American Society of Anesthesiologists (ASA) score, and the type of operation were significantly different on UA (P = 0.046, P = 0.022, P = 0.000 and P = 0.049, respectively). Other additional predictors, including body mass index (BMI), international prostate symptom score (IPSS) score, preoperative haemoglobin (Hb), duration of operation, estimated intraoperative blood loss, intraoperative fluid volume, fluid infusion volume within 24 h postoperatively were not associated with POUR (P > 0.05). MA results demonstrated that age, ASA score, type of operation and standard intraoperative placement of an indwelling bladder catheter (SIP‐IBC) were strongly associated with POUR development risk (P < 0.05).
Conclusion
Overall, we had a low POUR incidence in our study cohort. However, with the shift from non‐ERAS TJA to ERAS TJA protocol, it is crucial to closely monitor the male gender, advanced age, THA and SIP‐IBC, as these variables can markedly enhance POUR risk.
Reducing in‐hospital complications post TJA is both crucial and urgent in enhancing treatment efficacy and patient experience. Herein, under ERAS protocol, the number of POUR cases that required bladder catheterization was 3.4% for TKA and 10.1% for THA, which is in accordance with other reports. We also found that male gender, advanced age, THA, and SIP‐IBC all significantly elevated POUR development risk.
The regulation of adaptive responses to phosphorus (P) deficiency by the microRNA399 (miR399)/PHOSPHATE2 (PHO2) pathway has been well studied in Arabidopsis (Arabidopsis thaliana) but not in maize ...(Zea mays). Here, we show that miR399 transcripts are strongly induced in maize by phosphate (Pi) deficiency. Transgenic maize plants that overexpressed MIR399b accumulated excessive amounts of P in their shoots and displayed typical Pi-toxicity phenotypes. We reannotated ZmPHO2 with an additional 1,165 bp of the 5′ untranslated region. miR399-guided posttranscriptional repression of ZmPHO2 was mainly observed in the P-efficient lines. We identified Pi-deficiency-induced long-noncoding RNA1 (PILNCR1) from our strand-specific RNA libraries. Transient expression assays in Nicotiana benthamiana and maize leaf protoplasts demonstrated that PILNCR1 inhibits ZmmiR399-guided cleavage of ZmPHO2. The abundance of PILNCR1 was significantly higher in P-inefficient lines than in P-efficient lines, which is consistent with the abundance of ZmmiR399 transcripts. These results indicate that the interaction between PILNCR1 and miR399 is important for tolerance to low Pi in maize.
•Cisplatin induced persistent activation of microglia in the spinal cord.•Both i.t. and i.p. injections of microglial inhibitor minocycline attenuated cisplatin-induced CIPN.•I.t. injection of ...anti-TREM2 antibody alleviated cisplatin-induced CIPN.•Functional blockade of TREM2 suppressed the pro-inflammatory response of microglia.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse side effect of many antineoplastic agents. Patients treated with chemotherapy often report pain and paresthesias in a “glove-and-stocking” distribution. Diverse mechanisms contribute to the development and maintenance of CIPN. However, the role of spinal microglia in CIPN is not completely understood. In this study, cisplatin-treated mice displayed persistent mechanical allodynia, sensory deficits and decreased density of intraepidermal nerve fibers (IENFs). In the spinal cord, activation of microglia, but not astrocyte, was persistently observed until week five after the first cisplatin injection. Additionally, mRNA levels of inflammation related molecules including IL-1β, IL-6, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) and CD16, were increased after cisplatin treatment. Intraperitoneal (i.p.) or intrathecal (i.t.) injection with minocycline both alleviated cisplatin-induced mechanical allodynia and sensory deficits, and prevented IENFs loss. Furthermore, cisplatin enhanced triggering receptor expressed on myeloid cells 2 (TREM2) /DNAX-activating protein of 12 kDa (DAP12) signaling in the spinal cord microglia. The blockage of TREM2 by i.t. injecting anti-TREM2 neutralizing antibody significantly attenuated cisplatin-induced mechanical allodynia, sensory deficits and IENFs loss. Meanwhile, anti-TREM2 neutralizing antibody prominently suppressed the spinal IL-6, TNF-α, iNOS and CD16 mRNA level, but it dramatically up-regulated the anti-inflammatory cytokines IL-4 and IL-10. The data demonstrated that cisplatin triggered persistent activation of spinal cord microglia through strengthening TREM2/DAP12 signaling, which further resulted in CIPN. Functional blockage of TREM2 or inhibition of microglia both benefited for cisplatin-induced peripheral neuropathy. Microglial TREM2/DAP12 may serve as a potential target for CIPN intervention.
Small-size (<5 nm) gold nanostructures supported on reducible metal oxides have been widely investigated because of the unique catalytic properties they exhibit in diverse redox reactions. However, ...arguments about the nature of the gold active site have continued for two decades, due to the lack of comparable catalyst systems with specific gold species, as well as the scarcity of direct experimental evidence for the reaction mechanism under realistic working conditions. Here we report the determination of the contribution of single atoms, clusters and particles to the oxidation of carbon monoxide at room temperature, by the aid of in situ X-ray absorption fine structure analysis and in situ diffuse reflectance infrared Fourier transform spectroscopy. We find that the metallic gold component in clusters or particles plays a much more critical role as the active site than the cationic single-atom gold species for the room-temperature carbon monoxide oxidation reaction.
PDF
