Negative regulation of immunoreceptor signaling is required for preventing hyperimmune activation and maintaining immune homeostasis. The roles of p38IP in immunoreceptor signaling remain unclear. ...Here, we show that p38IP suppresses T‐cell receptor (TCR)/LPS‐activated NF‐κB and p38 by targeting TAK1 kinase and that p38IP protein levels are downregulated in human PBMCs from rheumatoid arthritis (RA) patients, inversely correlating with the enhanced activity of NF‐κB and p38. Mechanistically, p38IP interacts with TAK1 to disassemble the TAK1‐TAB (TAK1‐binding protein) complex. p38IP overexpression decreases TCR‐induced binding of K63‐linked polyubiquitin (polyUb) chains to TAK1 but increases that to TAB2, and p38IP knockdown shows the opposite effects, indicating unanchored K63‐linked polyUb chain transfer from TAB2 to TAK1. p38IP dynamically interacts with TAK1 upon stimulation, because of the polyUb chain transfer and the higher binding affinity of TAK1 and p38IP for polyUb‐bound TAB2 and TAK1, respectively. Moreover, p38IP scaffolds the deubiquitinase USP4 to deubiquitinate TAK1 once TAK1 is activated. These findings reveal a novel role and the mechanisms of p38IP in controlling TCR/LPS signaling and suggest that p38IP might participate in RA pathogenesis.
Synopsis
The p38‐interacting protein p38IP is a negative regulator of immunoreceptor signaling. p38IP inhibits TAK1 activation by disassembling the TAK1‐TAB complex, thereby scaffolding the deubiquitinase USP4 to deubiquitinate TAK1.
p38IP suppresses TCR/LPS‐induced NF‐κB and p38 MAPK activation and cytokine production.
p38IP competes with TAK1‐binding proteins and promotes USP4‐dependent deubiquitination of TAK1.
Changes in affinity upon polyUb‐binding determine the association between p38IP and TAK1.
The p38‐interacting protein p38IP is a negative regulator of immunoreceptor signaling. p38IP inhibits TAK1 activation by disassembling the TAK1‐TAB complex, thereby scaffolding the deubiquitinase USP4 to deubiquitinate TAK1.
Phase matchability is a prerequisite for infrared nonlinear optical (IR‐NLO) crystals. Hitherto, it is relatively infrequent to design and synthesize phase‐matching (PM) materials from known ...non‐phase‐matching (NPM) materials. This work reports a series of PM chalcogenides AMII3Ga5S11 (A = K, Rb, Cs; MII = Cd, Mn) with diamond‐like frameworks (DLFs), which are derived from the known NPM AMII4Ga5S12 in the A2S−MIIS−Ga2S3 pseudoternary diagram. Notably, ACd3Ga5S11 and AMn3Ga5S11 are isomeric and exhibit different DLFs and remarkable overall properties. Especially, KCd3Ga5S11 achieves the coexistence of wide band gap (Eg = 3.25 eV), strong second‐harmonic‐generation (SHG) response (1.7 × benchmark AgGaS2) and ultrahigh laser‐induced damage threshold (36.5 × benchmark AgGaS2), which is the best IR‐NLO chalcogenides with DLF known to date. Theoretical calculations reveal that their superior performance and PM behavior are benefited from the anisotropic structural characteristics, i.e., DLFs. This work demonstrates the feasibility of designing PM IR‐NLO materials via the partial removal of asymmetric building blocks in DLF structures of NPM materials that is accessible and controllable by chemistry means.
A series of novel infrared nonlinear optical (IR‐NLO) materials with excellent performances are designed and the change from a non‐phase‐matching (NPM) parent compound AMII4Ga5S12 to the phase‐matching (PM) AMII3Ga5S11 is observed. This interesting phase matchability transformation in diamond‐like frameworks is ascribed to the partial removal of asymmetric building blocks.
Neoadjuvant chemoradiotherapy (nCRT) and surgery have been recommended as the standard treatments for locally advanced esophageal squamous cell carcinoma (ESCC). In addition, nodal metastases ...decreased in frequency and changed in distribution after neoadjuvant therapy. This study aimed to examine the optimal strategy for lymph node dissection (LND) in patients with ESCC who underwent nCRT.
The hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were calculated using the Cox proportional hazard model. To determine the minimal number of LNDs (n-LNS) or least station of LNDs (e-LNS), the Chow test was used.
In total, 333 patients were included. The estimated cut-off values for e-LNS and n-LNS were 9 and 15, respectively. A higher number of e-LNS was significantly associated with improved OS (HR: 0.90; 95% CI 0.84-0.97, P = 0.0075) and DFS (HR: 0.012; 95% CI: 0.84-0.98, P = 0.0074). The e-LNS was a significant prognostic factor in multivariate analyses. The local recurrence rate of 23.1% in high e-LNS is much lower than the results of low e-LNS (13.3%). Comparable morbidity was found in both the e-LNS and n-LND subgroups.
This cohort study revealed an association between the extent of LND and overall survival, suggesting the therapeutic value of extended lymphadenectomy during esophagectomy. Therefore, more lymph node stations being sampled leads to higher survival rates among patients who receive nCRT, and standard lymphadenectomy of at least 9 stations is strongly recommended.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Oxidative degradation of chitin, initiated by lytic polysaccharide monooxygenases (LPMOs), contributes to microbial bioconversion of crystalline chitin, the second most abundant biopolymer ...in nature. However, our knowledge of oxidative chitin utilization pathways, beyond LPMOs, is very limited. Here, we describe a complete pathway for oxidative chitin degradation and its regulation in a marine bacterium,
Pseudoalteromonas prydzensis
. The pathway starts with LPMO-mediated extracellular breakdown of chitin into C1-oxidized chitooligosaccharides, which carry a terminal 2-(acetylamino)−2-deoxy-D-gluconic acid (GlcNAc1A). Transmembrane transport of oxidized chitooligosaccharides is followed by their hydrolysis in the periplasm, releasing GlcNAc1A, which is catabolized in the cytoplasm. This pathway differs from the known hydrolytic chitin utilization pathway in enzymes, transporters and regulators. In particular, GlcNAc1A is converted to 2-keto-3-deoxygluconate 6-phosphate, acetate and NH
3
via a series of reactions resembling the degradation of D-amino acids rather than other monosaccharides. Furthermore, genomic and metagenomic analyses suggest that the chitin oxidative utilization pathway may be prevalent in marine Gammaproteobacteria.
Electrochemical CO
2
conversion into highly value-added dialkyl carbonate by coupling cathodic CO
2
reduction reactions with anodic oxidation reactions is prospective. However, the structures of ...electrocatalysts should be well conquered for achieving high faradaic efficiency (FE) of dialkyl carbonate. In this work, a dual-channel superstructured Ni single-atom catalyst (SAC) with a unique site coordination configuration bonded
via
one axial oxygen atom and four planar nitrogen atoms was controllably constructed and is capable of providing a preeminent performance for CO
2
-to-CO conversion, achieving an exclusively high FE and a partial current density of CO (99% of FE, 325 mA cm
−2
@−0.6 V
vs.
RHE) with excellent stability. By virtue of the atomic to nano- to micro-scopic manipulation of the pentacoordinated Ni SAC for CO production, the convergent paired electrosynthesis of dimethyl carbonate (DMC) from CO
2
was pioneeringly performed, achieving a high FE of DMC up to 80%. The mechanism study unveiled that such axial oxygen coordination configuration is helpful to decrease the energy barriers for the generation of a key *COOH intermediate and the dissociation of H
2
O and CH
3
OH, accelerating the convergent paired electrosynthesis. The proof of concept in the innovative convergent paired electrosynthesis could open up a new horizon in the fields of CO
2
utilization.
A dual-channel superstructured Ni single-atom catalyst with a unique axial oxygen coordination configuration was controllably constructed and affords a preeminent performance for convergent paired electrosynthesis of dimethyl carbonate from CO
2
.
Objective
Inconclusive results are available as to whether chemo/radiotherapy should be administered to resectable esophageal cancer patients before surgery (neoadjuvant therapy) or after surgery ...(adjuvant therapy). The paper, via a meta-analysis of effects of treatment modalities when administering chemo/radiotherapy, aims to systematically evaluate the effect of timing of chemo/radiotherapy and surgery.
Methods
We performed a systematic literature search for clinical trials of neoadjuvant and adjuvant therapy for patients with esophageal cancer. Using meta-analysis, we conducted direct and adjusted indirect comparisons of overall survival, complete resection rate (R0 resection), perioperative mortality, leakage rate and local recurrence in patients with resectable esophageal cancer.
Results
A total of 32 studies involving 7985 patients with esophageal cancer were included in the meta-analysis. Twenty-five randomized controlled studies indirectly compared neoadjuvant/adjuvant therapy with surgery alone, while five non-randomized controlled studies and two randomized controlled studies directly compared neoadjuvant with adjuvant therapy. Neoadjuvant therapy followed by surgery, compared with surgery along with adjuvant therapy, showed a significant overall survival advantage in our pooled analysis (HR 0.88; 95% CI 0.79–0.98). Directly compared with adjuvant therapy, neoadjuvant therapy demonstrated a lower local recurrence rate (OR 0.56; 95% CI 0.43–0.74) with low heterogeneity (
I
2
= 1%). Neoadjuvant therapy, comparing to surgery with or without adjuvant therapy, showed a significantly higher R0 resection rate (OR 2.86; 95% CI 2.02–4.04) with moderate heterogeneity (
I
2
= 38%) and no significant differences in postoperative anastomotic leakage (
P
= 0.50). However, neoadjuvant therapy, compared with surgery adjuvant therapy, significantly increased perioperative mortality in both direct and indirect comparisons (
P
< 0.01).
Conclusions
We found that neoadjuvant therapy was associated with higher overall survival and R0 resection rate without increasing postoperative anastomotic leakage for patients with resectable esophageal cancer, whereas neoadjuvant therapy was associated with higher perioperative mortality after esophagectomy.
Several transition metal complexes of triaminoguanidine (TAG) nitrate, TAG-Ni, TAG-Co, graphene oxide (GO)/TAG-Ni (GT-Ni), GO/TAG-Co (GT-Co), and GO/ TAG-Cu (GT-Cu) were prepared using GO as a ...stabilizer. It has been shown that these complexes are promising energetic catalysts for decomposition of ammonium perchlorate (AP), which was uniformly coated with the mentioned catalysts. The decomposition kinetic parameters and mechanisms of the complexes have been studied by means of differential scanning calorimetry/thermogravimetric techniques. Results show that the presence of GO in such hybrid catalysts is able to stabilize AP before its decomposition, but the strong catalytic effects occur on HClO4 as the intermediate of the initial decomposition of AP. In the cases of TAG-Co, GT-Co, and GT-Cu, they would make the two-step decomposition of AP into a single step. The heat releases have been greatly increased as well because of a more complete decomposition. More importantly, the thermolysis mechanism of AP could be changed by simply modifying the type of metal ions. Under the effect of these catalysts, the decomposition more or less shifts to two-dimensional growth of the nuclei model, which indicates that the metal ions played key roles as active centers. The decomposition usually starts from the surface of AP, where the contact of the catalysts further enhanced the surface reactions. The inclusion of GO on the surface of the AP crystal may hinder the evaporation of NH3, and therefore the mechanism has been changed to the phase boundary-controlled reaction.
•Various modified CL-20 crystalline composites with graphene/polydopamine as the dopants have been prepared;•These CL-20 based composites have improved thermal stability, and lower mechanical ...sensitivity;•Some of the abovementioned CL-20 based composites have even higher density with exclusion of polymorphic transition;
Hexanitrohexaazaisowurtzitane (CL-20) is a well-known high energy density nitramine, but it is of high sensitivity and has the problem of polymorphic transition. In order to reduce the sensitivity of ε-CL-20 and improve the stability of its crystal structure, the polydopamine (PDA)-coated graphene oxide (GO) was used to dope ε-CL-20 crystals by strategy of in-situ coating followed with a solvent-non-solvent crystallization process. It has been shown that modified CL-20 crystals with the best performances are of polygon shape with a smooth surface and with the average diameter of 16 μm, much smaller than that of raw ε-CL-20 (140 μm). In addition, the doping can either improve the polymorphic transition temperature up to 19.0 °C or exclude such a transition due to formation of completely new crystal phase with better stability, depending on the type and content of the dopants. The density of a certain GO@PDA modified CL-20 is even slightly higher than that of pristine ε-CL-20 due to better assembling of the molecules under the nucleation of the dopants. CL-20/PDAG-2 does not show any polymorphic transition peak. Moreover, the XRD spectrum of CL-20/PDAG-2 also demonstrates that it is a completely new crystal phase better than the other four reported ones in terms of thermal stability.
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