Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis-like disease and inflammation.

A20 is an anti-inflammatory protein that is strongly linked to human disease. Here, we find that mice expressing three distinct targeted mutations of A20's zinc finger 7 (ZF7) ubiquitin-binding motif uniformly developed digit arthritis with features common to psoriatic arthritis, while mice expressing point mutations in A20's OTU or ZF4 motifs did not exhibit this phenotype. Arthritis in A20ZF7 mice required T cells and MyD88, was exquisitely sensitive to tumor necrosis factor and interleukin-17A, and persisted in germ-free conditions. A20ZF7 cells exhibited prolonged IκB kinase activity that drove exaggerated transcription of late-phase nuclear factor-κB response genes in vitro and in prediseased mouse paws in vivo. In addition, mice expressing double-mutant A20 proteins in A20's ZF4 and ZF7 motifs died perinatally with multi-organ inflammation. Therefore, A20's ZF4 and ZF7 motifs synergistically prevent inflammatory disease in a non-catalytic manner.

An unanticipated discourse of HB-EGF with VANGL2 signaling during embryo implantation.

Implantation is the first direct encounter between the embryo and uterus during pregnancy, and Hbegf is the earliest known molecular signaling for embryo-uterine crosstalk during implantation. The downstream effectors of heparin-binding EGF (HB-EGF) in implantation remain elusive due to the complexity of EGF receptor family. This study shows that the formation of implantation chamber (crypt) triggered by HB-EGF is disrupted by uterine deletion of Vangl2, a key planar cell polarity component (PCP). We found that HB-EGF binds to ERBB2 and ERBB3 to recruit VANGL2 for tyrosine phosphorylation. Using in vivo models, we show that uterine VAGL2 tyrosine phosphorylation is suppressed in Erbb2/Erbb3 double conditional knockout mice. In this context, severe implantation defects in these mice lend support to the critical role of HB-EGF-ERBB2/3-VANGL2 in establishing a two-way dialogue between the blastocyst and uterus. In addition, the result addresses an outstanding question how VANGL2 is activated during implantation. Taken together, these observations reveal that HB-EGF regulates the implantation process by influencing uterine epithelial cell polarity comprising VANGL2.

Aliphatic Hyperbranched Polycarbonates Solid Polymer Electrolytes with High Li-Ion Transference Number for Lithium Metal Batteries.

In this work, hyperbranched polycarbonate-poly(ethylene oxide) (PEO)-based solid polymer electrolytes (HBPC-SEs) are successfully synthesized via a straightforward organo-catalyzed "A1"+"B2"-ring-opening polymerization approach. The temperature-dependent ionic conductivity of HBPC-SEs, composed of different polycarbonate linkages and various LiTFSI concentrations, is investigated. The results demonstrate that HBPC-SE with an ether-carbonate alternating structure exhibits superior ionic conductivity, attributed to the solubility of Li salts in the polymer matrix and the mobility of the polymer segments. The HBPC1-SE with 30 wt% LiTFSI presents the highest ionic conductivities of 2.15  × 10-5, 1.78 × 10-4, and 6.07 × 10-4 Scm-1 at 30, 60, and 80 °C, respectively. Compared to traditional PEO-based electrolytes, the incorporation of polycarbonate segments significantly enhances the electrochemical stability window (5 V) and Li+ transference number (0.53) of HBPC-SEs. Furthermore, the LiFePO4/HBPC1-SE-3/Li cell exhibits exceptional rate capability and long-cycling performance, maintaining a discharge capacity of 130 mAh g-1 at 0.5C with a capacity retention of 95% after 300 cycles.

Clinical Effects of Tibial Posterior Tendon Reconstruction in the Treatment of Young Athletes With Accessory Navicular Bone Syndrome.

OBJECTIVE: To compare the effects of anchor reconstruction of posterior tibial tendon with the traditional Kidner's procedure for accessory navicular bone syndrome. METHODS: A retrospective analysis was conducted on 40 young athletes diagnosed with accessory navicular bone syndrome who were admitted to our hospital from 2018 to 2021. Among them, 20 patients underwent the modified Kidner procedure for the anchor reconstruction of the posterior tibial tendon (Experimental group), while the remaining 20 patients were treated with the traditional Kidner's procedure (Control group). Regular follow-ups were conducted to evaluate the degree of relief of foot symptoms and functional recovery. RESULTS: All patients were followed up for 12 to 24 months (mean duration: 18.6±3.7) after the operation. At the last follow-up, significant differences were observed in the function and symptom relief of the affected foot compared to the preoperative state. The experimental group had a mean operation time of 52.10 ± 3.41 minutes, significantly shorter than the control group's 61.25 ± 2.75 minutes. The mean time to return to normal activity was 12.65 ± 1.23 weeks for the experimental group, compared to 15.25 ± 1.16 weeks for the control group. CONCLUSION: The modified Kidner procedure demonstrates a higher patient satisfaction rate compared to the traditional Kidner procedure. This is attributed to its shorter duration, reduced trauma, and quicker recovery of normal activity.

Cannabinoid and planar cell polarity signaling converges to direct placentation.

Directed trophoblast migration toward the maternal mesometrial pole is critical for placentation and pregnancy success. Trophoblasts replace maternal arterial endothelial cells to increase blood supply to the placenta. Inferior trophoblast invasion results in pregnancy complications including preeclampsia, intrauterine growth restriction, miscarriage, and preterm delivery. The maternal chemotactic factors that direct trophoblast migration and the mechanism by which trophoblasts respond to these factors are not clearly understood. Here, we show that invasive trophoblasts deficient in Vangl2, a core planar cell polarity (PCP) component, fail to invade in maternal decidua, and this deficiency results in middle-gestational fetal demise. Previously, we have shown that tightly regulated endocannabinoids via G protein-coupled cannabinoid receptor CB1 are critical to the invasion of trophoblasts called spiral artery trophoblast giant cells (SpA-TGCs). We find that CB1 directly interacts with VANGL2. Trophoblast stem cells devoid of Cnr1 and/or Vangl2 show compromised cell migration. To study roles of VANGL2 and CB1 in trophoblast invasion in vivo, we conditionally deleted Cnr1 (coding CB1) and Vangl2 in progenitors of SpA-TGCs using trophoblast-specific protein alpha (Tpbpa)-Cre. We observed that signaling mediated by VANGL2 and CB1 restrains trophoblasts from random migration by keeping small GTPases quiescent. Our results show that organized PCP in trophoblasts is indispensable for their directed movement and that CB1 exerts its function by direct interaction with membrane proteins other than its canonical G protein-coupled receptor role.

Impacts of mining on vegetation phenology and sensitivity assessment of spectral vegetation indices to mining activities in arid/semi-arid areas.

Measuring the impact of mining activities on vegetation phenology and assessing the sensitivity of vegetation indices (VIs) to it are crucial for understanding land degradation in mining areas and enhancing the carbon sink capacity following the ecological restoration of mines. To this end, we have developed a novel technical framework to quantify the impact of mining activities on vegetation, and applied it to the Bainaimiao copper mining area in Inner Mongolia. Phenological indices are extracted based on the VI time series data of Sentinel-2, and changes in phenological differences in various directions are used to quantify the impact of mining activities on vegetation. Finally, indicators such as mean difference, standard deviation, index value distribution interval, and concentration of index value distribution were selected to assess the sensitivity of the Enhanced Vegetation Index (EVI), Green Chlorophyll Index (GCI), Global Environmental Monitoring Index (GEMI), Green Normalized Difference Vegetation Index (GNDVI), Normalized Difference Vegetation Index (NDVI), Renormalized Difference Vegetation Index (RDVI), Red-Edge Chlorophyll Index (RECI), and Soil-Adjusted Vegetation Index (SAVI) to mining activities. The results of the study show that the impact of mining activities on surrounding vegetation extends to an area three times larger than the actual mining activity area. When compared with the reference and unaffected areas, the affected area experienced a delay of approximately 10 days in seasonal vegetation development. Environmental pollution caused by the tailings pond was identified as the primary factor influencing this delay. Significant variations in the sensitivity of each VI to assess mining activities in arid/semi-arid areas were observed. Notably, GCI, GNDVI and RDVI displayed relatively high sensitivity to discrepancies in the spectral attributes of vegetation within the affected area, while SAVI reflected the overall spectral stability of the vegetation in the affected area. The research findings have the potential to provide valuable technical guidance for holistic environmental management in mining areas and hold great significance in preventing further land degradation and supporting ecological restoration in mining areas.

Reduction of endocytic activity accelerates cell elimination during tissue remodeling of the Drosophila epidermal epithelium.

Epithelial tissues undergo cell turnover both during development and for homeostatic maintenance. Cells that are no longer needed are quickly removed without compromising the barrier function of the tissue. During metamorphosis, insects undergo developmentally programmed tissue remodeling. However, the mechanisms that regulate this rapid tissue remodeling are not precisely understood. Here, we show that the temporal dynamics of endocytosis modulate physiological cell properties to prime larval epidermal cells for cell elimination. Endocytic activity gradually reduces as tissue remodeling progresses. This reduced endocytic activity accelerates cell elimination through the regulation of Myosin II subcellular reorganization, junctional E-cadherin levels, and caspase activation. Whereas the increased Myosin II dynamics accelerates cell elimination, E-cadherin plays a protective role against cell elimination. Reduced E-cadherin is involved in the amplification of caspase activation by forming a positive-feedback loop with caspase. These findings reveal the role of endocytosis in preventing cell elimination and in the cell-property switching initiated by the temporal dynamics of endocytic activity to achieve rapid cell elimination during tissue remodeling.

Electrode Surface-Modified Strategy for Improving the Voltage of Aqueous Supercapacitors.

Endowing aqueous supercapacitors (SCs) with high voltage is of great practical significance, but it is restricted by the water decomposition reaction occurring in the electrodes. Here, a novel surface treatment strategy is proposed to inhibit the hydrogen evolution reaction/oxygen evolution reaction at the cathode and anode by forming a passivation layer at the whole electrode surface, which widens the electrochemical stability window of the electrode and working voltage of the aqueous SCs. In addition, the cathode overpotential is increased from -1.3 to -1.48 V, and the anode is expanded from 1.42 to 1.59 V. Importantly, the aqueous SCs can work stably at 3 V operating voltage, enabling the coulombic efficiency and capacitance retention of the optimized SCs is 97% and 96% after 5000 cycles, respectively. This strategy of surface modification provides effective guidance to achieve high-voltage aqueous energy storage devices.

Diverse Reactions of Formazanate/Formazan with Tetrylenes: Reduction, C-H Bond Activation, Substitution and Addition.

The reactivity of the formazanate potassium salt [LtBu K(thf)] (LtBu= PhNNC(4-t BuPh)NNPh) with the group 14 chlorotetrylenes [{PhC(t BuN)2 }ECl] (E=Si, Ge, Sn) was investigated. Three corresponding compounds with unique configurations were formed, demonstrating the diverse reactivity of the system. In addition to the anticipated salt metathesis reactions of the potassium salt with the chlorine function of tetrylenes, unexpected reduction/insertion steps into the N=N bond of the formazanate (Si, Ge) and subsequent C-H activation (Ge) were also observed. Furthermore, when the neutral formazan ligand [LtBu H] was exposed to silylenes [{PhC(t BuN)2 }SiCl] and [LPh SiNMePy], substitution and addition reactions occurred. These discoveries significantly enrich the diversity of formazanate/formazan redox chemistry, opening up new avenues for exploration in this field.

Synthesis of Functional Isosorbide-Based Polyesters and Polyamides by Passerini Three-Component Polymerization.

Environmental issues are becoming more and more prominent, and bio-based polymers are essential to alleviate environmental degradation by replacing traditional polymers. With this context, a new family of functional isosorbide-based polyesters and polyamides with high glass transition temperature are prepared via Passerini-Three component polymerization (P-3CP). To optimize the P-3CP conditions, the influence of the polymerization solvent, temperature, feed ratio on the molar mass of final polymers are investigated. The higher molar mass (up to 10100 g/mol) and yield (>70 %) are achieved under very mild conditions (30 °C, standard atmosphere). Functional side groups, such as alkenyl, alkynyl and methyl ester, were introduced into polymer structure via P-3CP by using functional isocyanides. The obtained polyesters and polyamides are characterized by nuclear magnetic resonance (NMR) and infrared (IR) spectroscopies, differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). All polymers are thermal stable and amorphous with variable glass transition temperatures (Tg ). The obtained polyester has Tg up to 87.5 °C, while the Tg of polyamides (ISPA-2) is detected to be 97.5 °C depending on the amide bonds in the polymer backbone and the benzene ring side groups. The cytotoxicity is investigated by the CCK-8 assay against mBMSC cells to confirm the biological safety. Overall, this novel strategy provides an efficient approach to produce functional isosorbide-based polyesters and polyamides, which are promising prospect for being applied to biodegradable materials.

Fully Tin-Coated Coinage Metal Ions: A Pincer-Type Bis-stannylene Ligand for Exclusive Tetrahedral Complexation.

The synthesis of a novel bis-stannylene pincer ligand and its complexation with coinage metals (CuI , AgI and AuI ) are described. All coinage metal centres are in tetrahedral coordination environments in the solid state and are exclusively coordinated by four neutral SnII donors. 119 Sn NMR provided information about the behaviour in solution. All of the isolated compounds have photoluminescent properties, and these were investigated at low and elevated temperatures. Compared to the free bis-stannylene ligand, coordination to coinage metals led to an increase in the luminescence intensity. The new compounds were investigated in detail through all-electron relativistic density functional theory (DFT) calculations.

Fully Tin-Coated Coinage Metal Ions: A Pincer-Type Bis-stannylene Ligand for Exclusive Tetrahedral Complexation.

Invited for the cover of this issue are the groups of P. W. Roesky (Karlsruhe) and F. Weigend (Marburg). The image depicts coinage metal cores with tetrahedrally coordinating tin atoms. Read the full text of the article at 10.1002/chem.202203583.

Treatment outcomes for response-based radiotherapy in children and adolescents with central nervous system germinoma: a prospective study.

PURPOSE: The optimal dose and range of radiotherapy for central nervous system (CNS) germinoma have not yet been established. This study aimed to investigate the effects of individualized radiotherapy on the prognosis of patients with germinoma. METHODS: Based on imaging examination, tumor markers, and pathologic results, patients with germinoma received different radiotherapy strategies, including R1 (24 Gy whole ventricular irradiation + tumor-bed boost to 40 Gy), R2 (24-30 Gy craniospinal irradiation + tumor-bed boost to 54 Gy), R3 (24 Gy craniospinal irradiation + tumor-bed boost to 40 Gy), and R4 (30 Gy craniospinal irradiation + tumor-bed boost to 54 Gy with 45 Gy to spinal metastasis). RESULTS: A total of 77 patients were enrolled in this study between January 2015 and March 2021. The 3-year event-free survival (EFS) and overall survival (OS) of the whole cohort were 94.7% ± 2.6% and 96.0% ± 2.3%, respectively. The 3-year EFS for patients with localized and metastatic disease were 96.6% ± 2.4% and 89.2% ± 7.2%, respectively. The 3-year EFS of patients receiving R1, R2, R3, and R4 radiotherapy were 100%, 94.1% ± 5.7%, 100%, and 86.2% ± 9.1%, respectively. CONCLUSION: Good prognosis was still achieved after reducing dose and extent of radiation for the patients who achieved complete response (CR) after induction chemotherapy or pathological CR after second-look surgery.

A Barium Complex of the Silanide SiH3-: Hydride Surrogate and Source of Silicon.

The silanide SiH3- is an archetypical anion. Its metathesis chemistry is, however, still underdeveloped. We have conveniently prepared the barium silanide complex [(dtbpCbz)BaSiH3]8 with a bulky carbazolide ligand by reaction of the corresponding barium amide with phenyl silane in a good yield. The silanide complex was then used in various metathesis reactions, displaying distinct reactivity toward different substrates. Toward organic substrates such as carbodiimide or benzophenone, the silanide acted as a hydride surrogate, and formamidinate or diphenylmethoxide ligands were formed. Toward the monocoordinated cation [(dtbpCbz)Ge]+, transfer of SiH3- was observed, and the decomposition of the silylgermylene [(dtbpCbz)GeSiH3] was studied. For the heavier, more easily reducible congeners [(dtbpCbz)Sn]+ and [(dtbpCbz)Pb]+ as substrates, [(dtbpCbz)SiH3] was obtained under elimination of elemental Sn and Pb, so that formally SiH3+ was transferred to the dtbpCbz- ligand.

Diet modulates brain network stability, a biomarker for brain aging, in young adults.

Epidemiological studies suggest that insulin resistance accelerates progression of age-based cognitive impairment, which neuroimaging has linked to brain glucose hypometabolism. As cellular inputs, ketones increase Gibbs free energy change for ATP by 27% compared to glucose. Here we test whether dietary changes are capable of modulating sustained functional communication between brain regions (network stability) by changing their predominant dietary fuel from glucose to ketones. We first established network stability as a biomarker for brain aging using two large-scale (n = 292, ages 20 to 85 y; n = 636, ages 18 to 88 y) 3 T functional MRI (fMRI) datasets. To determine whether diet can influence brain network stability, we additionally scanned 42 adults, age < 50 y, using ultrahigh-field (7 T) ultrafast (802 ms) fMRI optimized for single-participant-level detection sensitivity. One cohort was scanned under standard diet, overnight fasting, and ketogenic diet conditions. To isolate the impact of fuel type, an independent overnight fasted cohort was scanned before and after administration of a calorie-matched glucose and exogenous ketone ester (d-ß-hydroxybutyrate) bolus. Across the life span, brain network destabilization correlated with decreased brain activity and cognitive acuity. Effects emerged at 47 y, with the most rapid degeneration occurring at 60 y. Networks were destabilized by glucose and stabilized by ketones, irrespective of whether ketosis was achieved with a ketogenic diet or exogenous ketone ester. Together, our results suggest that brain network destabilization may reflect early signs of hypometabolism, associated with dementia. Dietary interventions resulting in ketone utilization increase available energy and thus may show potential in protecting the aging brain.

High-Throughput Nano-DESI Mass Spectrometry Imaging of Biological Tissues Using an Integrated Microfluidic Probe.

Nanospray desorption electrospray mass spectrometry imaging (nano-DESI MSI) enables quantitative mapping of hundreds of molecules in biological samples with minimal sample pretreatment. We have recently developed an integrated microfluidic probe (iMFP) for nano-DESI MSI. Herein, we describe an improved design of the iMFP for the high-throughput imaging of tissue sections. We increased the dimensions of the primary and spray channels and optimized the spray voltage and solvent flow rate to obtain a stable operation of the iMFP at both low and high scan rates. We observe that the sensitivity, molecular coverage, and spatial resolution obtained using the iMFP do not change to a significant extent as the scan rate increases. Using a scan rate of 0.4 mm/s, we obtained high-quality images of mouse uterine tissue sections (scan area: 3.2 mm × 2.3 mm) in only 9.5 min and of mouse brain tissue (scan area: 7.0 mm × 5.4 mm) in 21.7 min, which corresponds to a 10-15-fold improvement in the experimental throughput. We have also developed a quantitative metric for evaluating the quality of ion images obtained at different scan rates. Using this metric, we demonstrate that the quality of nano-DESI MSI data does not degrade substantially with an increase in the scan rate. The ability to image biological tissues with high throughput using iMFP-based nano-DESI MSI will substantially speed up tissue mapping efforts.

Stereoselective Activation of Small Molecules by a Stable Chiral Silene.

The reaction of the dilithium salt of the enantiopure (S)-BINOL (1,1'-bi-2-naphthol) with two equivalents of the amidinate-stabilized chlorosilylene [LPh SiCl] (LPh =PhC(NtBu)2 ) led to the formation of the first example of a chiral cyclic silene species comprising an (S)-BINOL ligand. The reactivity of the Si=C bond was investigated by reaction with elemental sulfur, CO2 and HCl. The reaction with S8 led to a Si=C bond cleavage and concomitantly to a ring-opened product with imine and silanethione functional groups. The reaction with CO2 resulted in the cleavage of the CO2 molecule into a carbonyl group and an isolated O atom, while a new stereocenter is formed in a highly selective manner. According to DFT calculations, the [2+2] cycloaddition product is the key intermediate. Further reactivity studies of the chiral cyclic silene with HCl resulted in a stereoselective addition to the Si=C bond, while the fully selective formation of two stereocenters was achieved. The quantitative stereoselective addition of CO2 and HCl to a Si=C bond is unprecedented.

Electrochemical Exfoliation of Two-Dimensional Phosphorene Sheets and its Energy Application.

Recently, single or few-layer phosphorene has attracted intense attention due to its exceptional physicochemical properties. To this end, mass production of high-quality phosphorene nanosheets with specific functionalities represents a pivotal factor for the basic academic studies and practical applications. Among the current synthetic methods, electrochemical exfoliation of black phosphorous is one of the most hopeful ways for mass-production of phosphorene sheets owing to the uncomplicated apparatus, low cost as well as significant efficiency. Especially, regulating the electrochemical parameters not only induces adjustable phosphorene characteristics but also enables them a promising candidate in energy applications. In this Review, a concise and crucial studies of the recent and most representative developments in this domain was introduced, including the relationship between exfoliation philosophy, internal mechanisms, processing techniques, and multiple applications of phosphorene. At the end, a summary discussion and future perspectives is also provided.

Efficacy and safety comparison between R-CHOP and modified NHL-BFM-90 regimens in children and adolescents with diffuse large B-cell lymphoma.

Studies comparing the efficacy and safety of R-CHOP and modified non-Hodgkin lymphoma Berlin-Frankfurt-Münster-90 (NHL-BFM-90) regimens in children and adolescents with diffuse large B-cell lymphoma (DLBCL) are lacking. Thus, we retrospectively analyzed 85 DLBCL patients aged ≤18 years from 2000 to 2020; 74 patients received the modified NHL-BFM-90 regimen, and 11 received the R-CHOP regimen. The 5-year OS and event-free survival (EFS) rates between the modified NHL-BFM-90 and R-CHOP regimens were 91.0% vs. 90.9% (P = 0.466) and 89.8% vs. 68.6% (P = 0.055), respectively. In the stratified analysis, the survival outcome of pediatric patients treated with the modified NHL-BFM-90 regimen was not significantly different from that of adolescent patients. The OS and EFS rates of patients with early-stage disease were both 100%. Patients in the advanced-stage group who were treated with the modified NHL-BFM-90 regimen had superior EFS rates (P < 0.05). The frequency of severe adverse events from the two regimens was similar. There were no treatment-related deaths. We concluded that the modified NHL-BFM-90 regimen has better efficacy than R-CHOP in DLBCL patients with advanced-stage disease. However, the R-CHOP regimen might be an option for early-stage DLBCL. Further prospective studies are needed to guide clinical decisions about treatment.

Development and Validation of a Novel Nomogram to Predict the Risk of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) has been a complex disorder resulted from genetic and environmental risk factors. The aim of this study was to identify the risk factors associated with IVDD in orthopaedic patients and develop a prediction model for predicting the risk of IVDD. A total of 309 patients were retrospectively included in the study and randomly divided into the training group and the validation group. The least absolute shrinkage and selection operator regression (LASSO) and the univariate logistic regression analysis were used to optimize factors selection for the IVDD risk model. Multivariable logistic regression analysis was used to establish a predicting nomogram model incorporating the factors. In addition, discrimination, calibration, and clinical usefulness of the nomogram model were evaluated via the C-index, receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA). Then, based on the results above, the relationship between IVDD and angiotensin II (AngII) level in peripheral blood was examined prospectively. The predictors of the nomogram include age, sex, hypertension, diabetes, gout, working posture, and exercising hours per week. The C-index values of the training and validation groups were 0.916 (95% CI, 0.876-0.956) and 0.949 (95% CI, 0.909-0.989), respectively, which indicated that the model displayed good discrimination. In addition, the area under the curve (AUC) values of the ROC curve of the training and the validation group were 0.815 (95% CI, 0.759-0.870) and 0.805 (95% CI, 0.718-0.892), respectively, revealing the satisfactory discrimination performance of the model. The prospective investigation showed that the average AngII level in the degenerated group (97.62 ± 44.02 pg/mL) was significantly higher than that in the nondegenerated group (52.91 ± 9.01 pg/mL) (p < 0.001). This present study explored the risk factors for IVDD and established a prediction model, which would effectively predict the risk of IVDD. In addition, based on the prediction model, AngII was revealed to be a potentially auxiliary clinical diagnostic marker for IVDD.