Multivalence-State Tungsten Species Facilitated Iridium Loading for Robust Acidic Water Oxidation.

The development of the proton exchange membrane water electrolyzer (PEMWE) is still limited by the prohibitive cost and scarcity of iridium (Ir)-based oxygen evolution reaction (OER) catalyst. This work presents a novel catalyst synthesized by precursor-atomization and rapid joule-heating method, successfully doping iridium atoms into polyvalent tungsten blends (W0 , W5+ , W6+ ) based on titanium substrate. The vacancy engineering of unsaturated tungsten oxide (W5+ , W6+ ) reconstructs the electronic structure of the catalyst surface, which resulting in the low-valence state iridium species, avoiding excessive oxidation of iridium and accelerating the catalytic kinetics. Meanwhile, metallic tungsten (W0 ) improves the conductivity of catalyst and guarantees the stable existence of oxygen vacancy. The TiIrWOx possesses excellent performance in acidic OER catalysis, requiring overpotential of only 181 mV to drive 10.0 mA cm-2 , and exhibiting a high mass activity of 753 A gIr -1 at an overpotential of 300 mV. The membrane electrode assembly (MEA) with TiIrWOx as anode electrocatalyst can reduce the Ir consumption amount by >60% compared to commercial IrO2 , and it can operated over 120 h at a current density of 1.0 A cm-2 .

Phase II study of SOXIRI (S-1/oxaliplatin/irinotecan) chemotherapy in patients with unresectable pancreatic ductal adenocarcinoma.

BACKGROUND: To provide data on the safety and efficacy of a combination chemotherapy regimen consisting of S-1, oxaliplatin, and irinotecan (SOXIRI) as a first-line therapy in unresectable pancreatic ductal adenocarcinoma (UPDA) patients. METHODS: Patients with UPDA and no prior treatment chemotherapy in the UPDA setting were enrolled. The primary endpoint was the objective response rate (ORR). Secondary endpoints were overall survival (OS), progression-free survival (PFS) and adverse events. Patients received 80 mg/m2 S-1 twice a day for 2 weeks in an alternate-day administration cycle, 85 mg/m2 oxaliplatin on Day 1, and 150 mg/m2 irinotecan on Day 1 of a 2-week cycle. RESULTS: In these 62 enrolled patients, the ORR was 27.4 %, median OS was 12.1 months, and median PFS was 6.5 months. Major grade 3 or 4 toxicity included neutropenia (22.3 %), leucopenia (16.1 %), nausea (9.7 %), vomiting (9.7 %), thrombocytopenia (6.5 %), anorexia (8.5 %), anemia (4.8 %), and diarrhea (1.6 %). No treatment-related deaths occurred. In addition, the analysis of 32 patients suffering pain revealed that the rate of pain relief was 34.4 %. CONCLUSION: SOXIRI might be a standard regimen with an acceptable toxicity profile and favorable efficacy for use as chemotherapy in patients with UPDA.

Crystallizing Self-Standing Covalent Organic Framework Membranes for Ultrafast Proton Transport in Flow Batteries.

Covalent organic frameworks (COFs) display great potential to be assembled into proton conductive membranes for their uniform and controllable pore structure, yet constructing self-standing COF membrane with high crystallinity to fully exploit their ordered crystalline channels for efficient ionic conduction remains a great challenge. Here, a macromolecular-mediated crystallization strategy is designed to manipulate the crystallization of self-standing COF membrane, where the -SO3 H groups in introduced sulfonated macromolecule chains function as the sites to interact with the precursors of COF and thus offer long-range ordered template for membrane crystallization. The optimized self-standing COF membrane composed of highly-ordered nanopores exhibits high proton conductivity (75 mS cm-1 at 100 % relative humidity and 20 °C) and excellent flow battery performance, outperforming Nafion 212 and reported membranes. Meanwhile, the long-term run of membrane is achieved with the help of the anchoring effect of flexible macromolecule chains. Our work provides inspiration to design self-standing COF membranes with ordered channels for permselective application.

Tumor response assessment by measuring the single largest lesion per organ in advanced non-small cell lung cancer patients treated with PD-1/PD-L1 inhibitor.

Background: For Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST1.1), measuring up to two target lesions per organ is an arbitrary criterion. Objectives: We sought to compare response assessment using RECIST1.1 and modified RECIST1.1 (mRECIST1.1, measuring the single largest lesion per organ) in advanced non-small cell lung cancer (aNSCLC) patients undergoing anti-PD-1/PD-L1 monotherapy. Methods: Concordance of radiologic response categorization between RECIST1.1 and mRECIST1.1 was compared using the Kappa statistics. C-index was calculated to evaluate prognostic accuracy of radiologic response by the two criteria. The Kaplan-Meier method and Cox regression analysis were conducted for progression-free survival (PFS) and overall survival (OS). Results: Eighty-seven patients who had at least two target lesions in any organ per the RECIST1.1 were eligible for comparison analysis. Tumor response showed excellent concordance when measured using the RECIST1.1 and mRECIST1.1 (Kappa = 0.961). C-index by these two criteria was similar for PFS (0.784 versus 0.785) and OS (0.649 versus 0.652). Responders had significantly longer PFS and OS versus non-responders (p < 0.05), whichever criterion adopted. Radiologic response remained a significant predictor of PFS and OS in multivariate analysis (p < 0.05). Conclusion: The mRECIST1.1 was comparable to RECIST1.1 in response assessment among aNSCLC patients who received single-agent PD-1/PD-L1 inhibitor. The mRECIST1.1, with reduced number of lesions to be measured, may be sufficient and more convenient to assess antitumor activity in clinical practice.

Enhancement of recombinant human interleukin-22 production by fusing with human serum albumin and supplementing N-acetylcysteine in Pichia Pastoris.

Interleukin-22 (IL-22) plays an important role in the treatment of organ failure, which can induce anti-apoptotic and proliferative signaling pathways; Nevertheless, the practical utilization of IL-22 is hindered by the restricted efficacy of its production. Pichia pastoris presents a viable platform for both industrial and pharmaceutical applications. In this study, we successfully generated a fusion protein consisting of truncated human serum albumin and human IL-22 (HSA-hIL-22) using P. pastoris, and examined the impact of antioxidants on HSA-hIL-22 production. We have achieved the production of HSA-hIL-22 in the culture medium at a yield of approximately 2.25 mg/ml. Moreover, 0-40 mM ascorbic acid supplementation did not significantly affect HSA-hIL-22 production or the growth rate of the recombinant strain. However, 80 mM ascorbic acid treatment had a detrimental effect on the expression of HSA-hIL-22. In addition, 5-10 mM N-acetyl-l-cysteine (NAC) resulted in an increase of HSA-hIL-22 production, accompanied by a reduction in the growth rate of the recombinant strain. Conversely, 20-80 mM NAC supplementation inhibited the growth of the recombinant strains and reduced intact HSA-hIL-22 production. However, neither NAC nor ascorbic acid exhibited any effect on superoxide dismutase (SOD) and malondialdehyde (MDA) levels, except that NAC increased GSH content. Furthermore, our findings indicate that recombinant HSA-hIL-22, which demonstrated the ability to stimulate the proliferation of HepG2 cells, possesses bioactivity. In addition, NAC did not affect HSA-hIL-22 bioactivity. In conclusion, our study demonstrates that NAC supplementation can enhance the secretion of functional HSA-hIL-22 proteins produced in P. pastoris without compromising their activity.

Impact of interstitial cells of Cajal on slow wave and gallbladder contractility in a guinea pig model of acute cholecystitis.

BACKGROUND: Impaired interstitial cells of Cajal (ICCs) are central to the pathophysiology of acute cholecystitis (AC). Common bile duct ligation is a common model of AC, producing acute inflammatory changes and decrease in gallbladder contractility. AIM: To investigate the origin of slow wave (SW) in the gallbladder and the effect of ICCs on gallbladder contractions during the process of AC. METHODS: Methylene blue (MB) with light was used to establish selective impaired ICCs gallbladder tissue. Gallbladder motility was assessed using the frequency of SW and gallbladder muscle contractility in vitro in normal control (NC), AC12h, AC24h, and AC48h groups of guinea pigs. Hematoxylin and eosin and Masson-stained gallbladder tissues were scored for inflammatory changes. ICCs pathological changes alterations were estimated using immunohistochemistry and transmission electron microscopy. The alterations of c-Kit, α-SMA, cholecystokinin A receptor (CCKAR), and connexin 43 (CX43) were assessed using Western blot. RESULTS: Impaired ICCs muscle strips resulted in the decrease in gallbladder SW frequency and contractility. The frequency of SW and gallbladder contractility were significantly lower in the AC12h group. Compared with the NC group, the density and ultrastructure of ICCs were remarkably impaired in the AC groups, especially in the AC12h group. The protein expression levels of c-Kit were significantly decreased in the AC12h group, while CCKAR and CX43 protein expression levels were significantly decreased in the AC48h group. CONCLUSION: Loss ICCs could lead to a decrease in gallbladder SW frequency and contractility. The density and ultrastructure of ICCs were clearly impaired in the early stage of AC, while CCKAR and CX43 were significantly reduced at end stage.

Machine learning-based risk model incorporating tumor immune and stromal contexture predicts cancer prognosis and immunotherapy efficacy.

The immune and stromal contexture within the tumor microenvironment (TME) interact with cancer cells and jointly determine disease process and therapeutic response. We aimed at developing a risk scoring model based on TME-related genes of squamous cell lung cancer to predict patient prognosis and immunotherapeutic response. TME-related genes were identified through exploring genes that correlated with immune scores and stromal scores. LASSO-Cox regression model was used to establish the TME-related risk scoring (TMErisk) model. A TMErisk model containing six genes was established. High TMErisk correlated with unfavorable OS in LUSC patients and this association was validated in multiple NSCLC datasets. Genes involved in pathways associated with immunosuppressive microenvironment were enriched in the high TMErisk group. Tumors with high TMErisk showed elevated infiltration of immunosuppressive cells. High TMErisk predicted worse immunotherapeutic response and prognosis across multiple carcinomas. TMErisk model could serve as a robust biomarker for predicting OS and immunotherapeutic response.

Continuation of anti-PD-1 therapy plus physician-choice treatment beyond first progression is not associated with clinical benefit in patients with advanced non-small cell lung cancer.

Objective: Few data are available on the optimal treatment options after disease progression from first-line treatment of immune checkpoint inhibitors (ICIs) plus chemotherapy. This study aimed to describe the safety and efficacy of continuing ICIs beyond first progress disease (PD) in non-small cell lung cancer (NSCLC). Methods: Patients with NSCLC previously treated with first-line anti-PD-1 antibody plus platinum-doublet chemotherapy and hence had PD as per Response Evaluation Criteria in Solid Tumors v1.1 were enrolled. For the subsequent line, patients received physician's choice (PsC) with or without an anti-PD-1 antibody. The primary outcome was progression-free survival after second-line treatment (PFS2). Secondary outcomes included overall survival (OS) from the initiation of first-line treatment, post-second-progression survival (P2PS), overall response rate (ORR), disease control rate (DCR), and safety during second-line treatment. Results: Between July 2018 and January 2021, 59 patients were included. A total of 33 patients received a physician-decided second-line regimen plus ICIs (PsC plus ICIs group), and 26 patients did not continue ICIs (PsC group). There was no significant difference in PFS2 between the PsC plus ICIs group and the PsC group (median, 6.5 vs. 5.7 months, p = 0.46). median OS (28.8 vs. 29.2 months), P2PS (13.4 vs. 18.7 months), ORR (18.2% vs. 19.2%), and DCR (78.8% vs, 84.6%) were also similar between the two groups. No new safety signals were observed. Conclusion: In this real-world setting, patients treated with continued ICIs beyond their first disease progression did not experience clinical benefit but without compromising safety.

An automated detection of epileptic seizures EEG using CNN classifier based on feature fusion with high accuracy.

BACKGROUND: Epilepsy is a neurological disorder that is usually detected by electroencephalogram (EEG) signals. Since manual examination of epilepsy seizures is a laborious and time-consuming process, lots of automatic epilepsy detection algorithms have been proposed. However, most of the available classification algorithms for epilepsy EEG signals adopted a single feature extraction, in turn to result in low classification accuracy. Although a small account of studies have carried out feature fusion, the computational efficiency is reduced due to too many features, because there are also some poor features that interfere with the classification results. METHODS: In order to solve the above problems, an automatic recognition method of epilepsy EEG signals based on feature fusion and selection is proposed in this paper. Firstly, the Approximate Entropy (ApEn), Fuzzy Entropy (FuzzyEn), Sample Entropy (SampEn), and Standard Deviation (STD) mixed features of the subband obtained by the Discrete Wavelet Transform (DWT) decomposition of EEG signals are extracted. Secondly, the random forest algorithm is used for feature selection. Finally, the Convolutional Neural Network (CNN) is used to classify epilepsy EEG signals. RESULTS: The empirical evaluation of the presented algorithm is performed on the benchmark Bonn EEG datasets and New Delhi datasets. In the interictal and ictal classification tasks of Bonn datasets, the proposed model achieves an accuracy of 99.9%, a sensitivity of 100%, a precision of 99.81%, and a specificity of 99.8%. For the interictal-ictal case of New Delhi datasets, the proposed model achieves a classification accuracy of 100%, a sensitivity of 100%, a specificity of 100%, and a precision of 100%. CONCLUSION: The proposed model can effectively realize the high-precision automatic detection and classification of epilepsy EEG signals. This model can provide high-precision automatic detection capability for clinical epilepsy EEG detection. We hope to provide positive implications for the prediction of seizure EEG.

Effect of N-acetyl-l-cysteine on Cell Phenotype and Autophagy in Pichia pastoris Expressing Human Serum Albumin and Porcine Follicle-Stimulating Hormone Fusion Protein.

Pichia pastoris is widely used for the production of recombinant proteins, but the low secretion efficiency hinders its wide application in biopharmaceuticals. Our previous study had shown that N-acetyl-l-cysteine (NAC) promotes human serum albumin and porcine follicle-stimulating hormone fusion protein (HSA-pFSHß) secretion by increasing intracellular GSH levels, but the downstream impact mechanism is not clear. In this study, we investigated the roles of autophagy as well as cell phenotype in NAC promoting HSA-pFSHß secretion. Our results showed that NAC slowed down the cell growth rate, and its effects were unaffected by Congo Red and Calcofluor White. Moreover, NAC affected cell wall composition by increasing chitin content and decreasing ß-1,3-glucan content. In addition, the expressions of vesicular pathway and autophagy-related genes were significantly decreased after NAC treatment. Further studies revealed that autophagy, especially the cytoplasm-to-vacuole targeting (Cvt) pathway, mitophagy and pexophagy, was significantly increased with time, and NAC has a promoting effect on autophagy, especially at 48 h and 72 h of NAC treatment. However, the disruption of mitophagy receptor Atg32, but not pexophagy receptor Atg30, inhibited HSA-pFSHß production, and neither of them inhibited the NAC-promoted effect of HSA-pFSHß. In conclusion, vesicular transport, autophagy and cell wall are all involved in the NAC-promoted HSA-pFSHß secretion and that disruption of the autophagy receptor alone does not inhibit the effect of NAC.

Smooth muscle cells, interstitial cells and neurons in the gallbladder (GB): Functional syncytium of electrical rhythmicity and GB motility (Review).

The motility of the gallbladder (GB) involves the storage, concentration and delivery of bile. GB motor functions are controlled by multiple complex factors, such as extrinsic and intrinsic innervation, humoral factors and neuropeptides. GB emptying results from coordinated contractions of the muscular layers of the GB wall. Depolarization of GB smooth muscle (GBSM) depends on the activation of the regular depolarization­repolarization potential, referred to as slow waves (SWs). These rhythmic SWs of GBSM contraction are mediated by several cell types, including smooth muscle cells (SMCs), GB neurons, telocytes (TC) and specialized pacemaker cells called interstitial cells of Cajal (ICC). The present article introduced a new GB motor unit, the SMC­TC­ICC­neuron (STIN) syncytium. In GB, STIN cells provide pacemaker activity, propagation pathways for SWs, transduction of inputs from motor and sensory neurons and mechanosensitivity. The present review provided an overview of STIN cells, mechanisms generating GBSM contractile behavior and GB motility, and discussed alterations of STIN cell function under different disease conditions.

LRRC3B and its promoter hypomethylation status predicts response to anti-PD-1 based immunotherapy.

Background: The leucine rich repeat containing 3B (LRRC3B) gene is a tumor suppressor gene involved in the anti-tumor immune microenvironment. Expression of LRRC3B and DNA methylation at the LRRC3B promoter region may serve as a useful marker to predict response to anti-PD-1 therapy. However, no studies have yet systematically explored the protective role of LRRC3B methylation in tumor progression and immunity. Methods: Expression of LRRC3B of 33 cancer types in The Cancer Genome Atlas (TCGA) was downloaded from UCSC Xena (http://xena.ucsc.edu/). And, we evaluated the differential expression of LRRC3B according to tumor stage, overall survival, and characteristics of the tumor microenvironment. The immunotherapeutic cohorts included IMvigor21, GSE119144, and GSE72308 which were obtained from the Gene Expression Omnibus database. We conducted pearson correlation analysis of LRRC3B and tumor microenvironment (TME) in pan-cancer. Also, six immune cell types (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells) and tumor purity were analyzed using the Tumor IMmune Estimation Resource (TIMER1.0) (Tumor IMmune Estimation Resource (TIMER2.0). And, a "silencing score" model base on LRRC3B promoter methylation to predict overall survival (OS) by multivariate Cox regression analysis was constructed. Finally, the model was applied to predict anti-PD-1 therapy in non-small cell lung cancer (NSCLC) and breast cancer (BRCA). Results: LRRC3B expression associated with less tumor invasion, less severe tumor stage, and decreased metastasis. The inactivation of LRRC3B promoted the enrichment of immuneosuppressive cells, including myeloid-derived suppressor cells (MDSCs), cancer-associated fibroblasts (CAFs), M2 subtype of tumor-associated macrophages (M2-TAMs), M1 subtype of tumor-associated macrophages (M1-TAMs), and regulatory T (Treg) cells. A high silencing score was significantly associated with immune inhibition, low expression of LRRC3B, poor patient survival, and activation of cancer-related pathways. Conclusion: Our comprehensive analysis demonstrated the potential role of LRRC3B in the anti-tumor microenvironment, clinicopathological features of cancer, and disease prognosis. It suggested that LRRC3B methylation could be used as a powerful biomarker to predict immunotherapy responses in NSCLC and BRCA.

Application of attenuation coefficient in the assessment of hepatic involvement in children and adolescents with Wilson's disease.

BACKGROUND: To investigate whether the attenuation coefficient (ATT) can be used as a noninvasive index to assess liver involvement in children and adolescents with Wilson's disease (WD). METHODS: Children and adolescents diagnosed with WD were retrospectively collected from the First Affiliated Hospital of the Anhui University of Traditional Chinese Medicine between May 2022 and August 2022. The findings on ATT, Shear Wave Measurement (SWM), AST to platelet ratio index (APRI), and fibrosis 4 (FIB-4) score were obtained. The liver involvement of WD was classified into 3 groups based on serum levels of collagen type IV (CIV), hyaluronic acid (HA), laminin (LN) and precollagen type III N-terminal peptide (PIIINP): (1) Group1 (n = 25), no abnormalities in CIV, HA, LN and PIIINP; (2) Group2 (n = 19), elevation of 1 or 2 indexes in CIV, HA, LN, and PIIINP; Group3 (n = 18), elevation of 3 or 4 indicators in CIV, HA, LN, and PIIINP. The levels of ATT, SWM, APRI and FIB-4 were compared between the 3 groups; and correlation of ATT with SWM and triglyceride (TG) was performed using Spearman's correlation analysis. The Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of ATT alone and its combination with SWM, APRI, and FIB-4 in children and adolescents with WD. RESULTS: A total of 62 children and adolescents with WD were retrospectively retrieved. ATT levels were significantly different in intergroup comparisons (P < 0.001). The ROC curve showed that the area under the curve (AUC) for the diagnosis of hepatic steatosis using ATT was 0.714, 0.712 and 0.867 in Group 1 versus Group 2, Group 2 versus Group 3, and Group 1 versus Group 3, respectively; the sensitivity for the diagnosis of hepatic steatosis in Group 1 versus Group 2 was 89.47% with the cutoff value of ATT of 0.73 dB/cm/MHz. No significant correlation found between ATT and TG (ρ = 0.154, P = 0.231). Compared to ATT alone, the combination of ATT with APRI and FIB-4 or the combination of ATT with SWM, APRI, and FIB-4 showed a better diagnostic efficacy in Group 1 versus Group 2 (both P = 0.038). CONCLUSION: ATT could be used as a non-invasive index for the evaluation of liver steatosis in children and adolescents with WD, with a good clinical applicative value. Furthermore, ATT in combination with APRI, FIB-4, and SWM might have better diagnostic efficacy than ATT alone.

High-Valence-Manganese Driven Strong Anchoring of Iridium Species for Robust Acidic Water Oxidation.

Designing an efficient and durable electrocatalyst for the sluggish anodic oxygen evolution reaction (OER) has been the primary goal of using proton exchange membrane electrolyzer owing to the highly acidic and oxidative environment at the anode. In this work, it is reported that high-valence manganese drives the strong anchoring of the Ir species on the manganese dioxide (MnO2 ) matrix via the formation of an Mn-O-Ir coordination structure through a hydrothermal-redox reaction. The iridium (Ir)-atom-array array is firmly anchored on the Mn-O-Ir coordination structure, endowing the catalyst with excellent OER activity and stability in an acidic environment. Ir-MnO2 (160)-CC shows an ultralow overpotential of 181 mV at j = 10 mA cm-2 and maintains long-term stability of 180 h in acidic media with negligible decay, superior to most reported electrocatalysts. In contrast, when reacting with low-valence MnO2 , Ir species tend to aggregate into IrOx nanoparticles, leading to poor OER stability. Density functional theory (DFT) calculations further reveal that the formation of the Mn-O-Ir coordination structure can optimize the adsorption strength of *OOH intermediates, thus boosting the acidic OER activity and stability.

[Cuproptosis-related immune gene signature predicts clinical benefits from anti-PD-1/PD-L1 therapy in non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) remains the major cause of cancer-related death. Immune checkpoint inhibition has become the cornerstone treatment for NSCLC. Cuproptosis is a newly identified form of cell death relying on mitochondrial respiration that might play a role in shaping tumor immune microenvironment (TIME). The clinical significance of cuproptosis-related genes (CRGs) remains unclear and warrant investigation. The current study extracted RNA sequencing profiles and corresponding clinical information from six aggregated datasets from the Gene Expression Omnibus (GEO) repository as the training set, and from The Cancer Genome Atlas (TCGA) database as the testing set. Cuproptosis-related immune genes (CRIMGs) were obtained through coexpression analysis, univariate Cox regression analysis, and LASSO analysis for overall survival (OS) association analysis. Consensus clustering was employed to divide the subjects into clusters. Stepwise multivariate Cox regression was used to establish the prognostic CRIMG_score from the CRIMGs. A 17-gene prediction signature was established that informed patients' OS both in the training and testing datasets (p < 0.001). The predictive value of the signature in terms of immunotherapeutic responses was assessed in two publicly available NSCLC immunotherapy datasets (POPLAR and OAK studies) and an internal dataset from Sun Yat-sen University Cancer Center (ORIENT-11 study). Patients in the high-risk group displayed worse survival, a characteristic suppressive tumor immune microenvironment, and low immunotherapeutic benefits compared to those in the low-risk group. Collectively, the CRIMG_score established herein could serve as a promising indicator of prognosis and immunotherapeutic response in patients with NSCLC.

Optimizing the tumor shrinkage threshold for evaluating immunotherapy efficacy for advanced non-small-cell lung cancer.

PURPOSE: The rise of immune checkpoint inhibitors (ICIs) in recent years has coincided with unusual clinical response patterns. Modification of the sum of longest diameters (SLD)-based threshold that reflecting dynamic change of the tumor burden and predicting response to ICIs, may markedly improve current treatment regimens. METHODS: The baseline and post-treatment SLD of target lesion was recorded and the maximum percent change of the SLD from baseline was designated as SLD-change score. The optimal cut-off value was obtained using the X-tile program. The relationship between SLD-change score and survival outcome (PFS, OS) was evaluated. RESULTS: 10% cut-off value of SLD-change score was found to be most distinctive for PFS. Responders defined according to this cut-off value showed a significant improvement for PFS and OS. Bone metastasis and brain metastasis were also two independent prognostic factors of PFS and OS, respectively. CONCLUSIONS: 10% SLD change score could discriminate for ICIs treatment response, which holds great promise in promoting the development of precise immunotherapeutic strategy.

The Biomimetics of Mg2+-Concentration-Resolved Microenvironment for Bone and Cartilage Repairing Materials Design.

With the increase in population aging, the tendency of osteochondral injury will be accelerated, and repairing materials are increasingly needed for the optimization of the regenerative processes in bone and cartilage recovery. The local environment of the injury sites and the deficiency of Mg2+ retards the repairing period via inhibiting the progenitor osteogenesis and chondrogenesis cells' recruitment, proliferation, and differentiation, which results in the sluggish progress in the osteochondral repairing materials design. In this article, we elucidate the Mg2+-concentration specified effect on the cell proliferation, osteochondral gene expression, and differentiation of modeling chondrocytes (extracted from New Zealand white rabbit) and osteoblasts (MC3T3-E1). The concentration of Mg2+ in the culture medium affects the proliferation, chondrogenesis, and osteogenesis: (i) Appropriate concentrations of Mg2+ promote the proliferation of chondrocytes (1.25−10.0 mM) and MC3T3-E1 cells (2.5−30.0 mM); (ii) the optimal concentration of Mg2+ that promotes the gene expression of noncalcified cartilage is 15 mM, calcified cartilage 10 mM, and subchondral bone 5 mM, respectively; (iii) overdosed Mg2+ leads to the inhibition of cell activity for either chondrocytes (>20 mM) or osteoblasts (>30 mM). The biomimetic elucidation for orchestrating the allocation of gradient concentration of Mg2+ in accordance of the physiological condition is crucial for designing the accurate microenvironment in osteochondral injury defects for optimization of bone and cartilage repairing materials in the future.

High-Efficiency CO2 /N2 Separation Enabled by Rotation of Electrostatically Anchored Flexible Ligands in Metal-Organic Framework.

Metal organic frameworks (MOF) are of great potential for molecular separation, but the ligand rotation flexibility makes them remain challenging in the construction of fixed nanochannels for precise sieving. Here we report an electrostatic-anchoring strategy to fix the rotation of 2-methylimidazole (2-MIM) ligand in ZIF-8. Electrostatic inducer trifluoroacetate anchored at and blocked the six-membered windows of ZIF-8, and meanwhile induced the positive 2-MIM rotated from initial 49° to 68°, thus opening neighbored four-membered windows with a constant size of 3.4 Å. The obtained ZIF-8 significantly enhanced the CO2 /N2 adsorption selectivity from 14.02 to 332.86. Further membrane-based separation exhibited an outstanding CO2 /N2 selectivity of up to 137 with a desired permeability of 286 Barrer, which exceeded the 2019 upper bound. This strategy provides a new inspiration for fixing the ligand rotation in soft MOF for desired precise molecular sieving.

Gravity-driven electrospun membranes for effective removal of perfluoro-organics from synthetic groundwater.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are emerging contaminants in water and soil. Electrospun membranes with open structure could treat PFAS in a gravity-driven mode with ultralow pressure needs. The electrospun ultrathin fibers (67 ± 27 nm) was prepared for the enhanced specific surface area; where polyvinylidene fluoride (PVDF) backbones and the grafted quaternary ammonium moieties (QA; PVDF-g-QA membranes) provided both hydrophobicity and anion-exchange ability (electrostatic interaction). High affinity towards the perfluorooctanoic acid (PFOA)/perfluorooctanesulfonic acid (PFOS) molecules (denoted as PFOX collectively) was observed, and >95% PFOX was removed from synthetic groundwater with a flux of 32.3 Lm-2h-1 at ΔPo = 313 Pa. With a higher octanol/water partitioning coefficient (Log Kow = 6.3) and close dispersion interaction parameter to the membrane backbones (16.6% difference in δd), the effective PFOS removal remained under alkaline and high conductivity conditions due to the intensive hydrophobic interaction compared to that of PFOA. Long-term studies exhibited >90% PFOX removal in an 8 h test with a capacity of 258 L/m2. Under mild regeneration conditions, PFOA and PFOS were concentrated by 35-fold and 39-fold, respectively. Overall, the gravity-driven electrospun PVDF-g-QA membranes, with adsorptive effectiveness and ease of regeneration, showed great potential in PFAS remediation.

Negative regulation of seed germination by maternal AFB1 and AFB5 in Arabidopsis.

The plant hormone auxin suppresses seed germination, but how auxin does it remains poorly understood. While studying the functions of the AUXIN SIGNALING F-BOX (AFB) auxin co-receptors in Arabidopsis, we consistently isolated AFB1 and AFB5 in reproductive tissues in co-immunoprecipitation experiments using their interacting protein ASK1 as the bait. However, T2 seeds of the AFB1 or AFB5 transgenic lines generated for the co-immunoprecipitation experiments frequently failed to germinate, which led to the studies of seed germination in these plants and afb1 and afb5 mutants, and AFB1 and AFB5 expression in nearly mature fruit and imbibed seeds using AFB1:GUS and AFB5:GUS lines. We found that AFB1 and AFB5 acted in maternal tissues to suppress seed germination and their effects were positively correlated with the plants' sensitivity to indole acetic acid. Conversely, afb1 and afb5 single mutants exhibited faster seed germination than the wild type and the seeds of the afb1-5afb5-5 double mutant germinated even faster than those of the afb1-5 and afb5-5 single mutants. Seed germination of the afb1-5afb5-5 double mutant also exhibited higher sensitivity to gibberellic acid than that of the wild-type and the afb1-3, afb1-5 and afb5-5 single mutants. Both AFB1 and AFB5 were expressed in the funiculus during seed maturation, and AFB1 was also transiently expressed in a small chalazal region surrounding the hilum in the seed coat during seed imbibition. Therefore, AFB1 and AFB5 likely suppress seed germination in the funiculus and AFB1 also briefly suppresses seed germination in the chalaza during seed imbibition.