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Noble metal-based materials are the benchmark catalysts for electrocatalysis, but their wide applications are hindered due to their scarcity and high cost. Developing a feasible strategy to achieve higher catalytic activity with low usage of noble metals is vital and urgent. Herein, a simple nitridation route is proposed to design a hybrid material with both ruthenium (Ru) species and mixed metal nitride matrixes (Ru-NiWN

A new family of 6-c MOFs with carboxylic pincers has been finely tuned and NTU-72 shows a high C2H2/C2H4 selectivity and unprecedented recovery of both pure C2H4 and C2H2, because of the recognition of a C2H2 tetramer by carboxylic pincers.

Developing highly active electrocatalysts is a pivotal issue for anion-exchange membrane water electrolyzers (AEMWE). However, realizing the continuous hydrogen generation at a large current density remains challenging. Herein, a novel kind of hybrid electrode is successfully developed by introducing trace iridium (Ir) species onto a hierarchical Ni/Mo

Fat greenling (Hexagrammos otakii) is a kind of economic fish that is widely consumed by human, and its intensive farming technology is making important progress. However, high-density farming may cause the occurrence of diseases in H. otakii. Cinnamaldehyde (CNE) is a new feed additive for aquatic animals and has a positive effect on disease resistance. In the study, dietary CNE was evaluated on the growth performance, digestion, immune response, and lipid metabolism of juvenile H. otakii ( 6.21 ± 0.19 g). Six experimental diets were formulated containing CNE at levels of 0, 200, 400, 600, 800, and 1000 mg/kg for 8 weeks. The percent weight gain (PWG), specific growth rate (SGR), survival (SR), and feeding rate (FR) were significantly increased by including CNE in fish diets regardless of the inclusion level ( P < 0.05 ). The feed conversion ratio (FCR) was significantly decreased among the groups fed CNE supplemented diets ( P < 0.05 ). A significant decrease in hepatosomatic index (HSI) was observed in fish fed 400 mg/kg-1000 mg/kg CNE compared to the control diet ( P < 0.05 ). Fish-fed diets containing 400 mg/kg and 600 mg/kg CNE had a higher level of crude protein in muscles than the control diet ( P < 0.05 ). Moreover, the activities of lipase (LPS) and pepsin (PEP) in the intestinal were markedly increased in juvenile H. otakii-fed dietary CNE ( P < 0.05 ). Apparent digestibility coefficient (ADC) of dry matter, protein, and lipid was significantly increased with CNE supplement ( P < 0.05 ). The activities of catalase (CAT) and acid phosphatase (ACP) in the liver were markedly enhanced by including CNE in juvenile H. otakii diets compared with the control ( P < 0.05 ). The activities of superoxide dismutase (SOD) and alkaline phosphatase (AKP) in the liver were markedly enhanced in juvenile H. otakii treated with CNE supplements 400 mg/kg-1000 mg/kg ( P < 0.05 ). Additionally, the levels of total protein (TP) in the serum were markedly increased by including CNE in juvenile H. otakii diets compared with the control ( P < 0.05 ). In the CNE200, CNE400, and CNE600 groups, albumin (ALB) levels in the serum were markedly higher compared with that in the control ( P < 0.05 ). In the CNE200 and CNE400 groups, the levels of immunoglobulin G (IgG) in the serum were significantly increased compared with that the control group ( P < 0.05 ). The juvenile H. otakii-fed dietary CNE had lower triglycerides (TG) and total cholesterol (TCHO) levels in the serum than fish-fed CNE-free diets ( P < 0.05 ). The gene expression of peroxisome proliferator-activated receptor alpha (PPAR-α), hormone-sensitive lipase (HSL), and carnitine O-palmitoyltransferase 1 (CPT1) in the liver was significantly increased by including CNE in fish diets regardless of the inclusion level ( P < 0.05 ). However, fatty acid synthase (FAS), peroxisome proliferator-activated receptor gamma (PPAR-γ), and acetyl-CoA carboxylase alpha (ACCα) in the liver were markedly decreased with CNE supplements 400 mg/kg-1000 mg/kg ( P < 0.05 ). The glucose-6-phosphate1-dehydrogenase (G6PD) gene expression levels in the liver were markedly decreased compared with the control ( P < 0.05 ). The optimal supplementation level of CNE was shown by curve equation analysis to be 590.90 mg/kg.

Safety issues are one of the main limitations for further application of lithium-ion batteries, and battery degradation is an important causative factor. However, current state-of-health (SOH) estimation methods are mostly developed for a single feature and a single operating condition as well as a single battery material system, which consequently makes it difficult to guarantee robustness and generalization. This paper proposes a data-driven and multi-feature collaborative SOH estimation method based on equal voltage interval discharge time, incremental capacity (IC) and differential thermal voltammetry (DTV) analysis for feature extraction. The deep learning model is constructed based on bi-directional long short-term memory (Bi-LSTM) with the addition of attention mechanism (AM) to focus on the important parts of the features. The proposed method is validated based on a NASA dataset and Oxford University dataset, and the results show that the proposed method has high accuracy and strong robustness. The estimated root mean squared error (RMSE) are below 0.7% and 0.3%, respectively. Compared to single features, the collaboration between multiple features and AM resulted in a 25% error improvement, and the capacity rebound is well captured. The proposed method has the potential to be applied online in an end-cloud collaboration system.

Although the deep learning diagnosis model has been widely used in the fault diagnosis of rotating machinery. However, these methods lack the interpretability of the diagnostic process. In other words, it is still a difficult problem to understand that the structural function and the diagnosis process in the model correspond to each other. Therefore, this paper discusses how to add multi-scale and multi attention mechanism to lightweight network. From different scales, different dimensions, combined with the fault signal characteristics of centrifugal fan, the attention structure of cross layer fusion is designed. How to integrate different functions continuously and effectively to achieve better diagnostic performance is answered. The proposed lightweight multi-scale multi-attention feature fusion network adaptively recalibrates feature weights, which effectively enhances the fault feature learning ability and anti-noise ability. Experimental results show that this network is stronger than other advanced diagnostic models.

The present study was to explore the association between lipoprotein(a) [Lp(a)] and colorectal cancer (CRC) among inpatients. This study included 2822 participants (393 cases vs. 2429 controls) between April 2015 and June 2022. Logistic regression models, smooth curve fitting, and sensitivity analyses were performed to investigate the relationship between Lp(a) and CRC. Compared with the lower Lp(a) quantile 1 (

Purpose Thoracic SMARCA4-deficient undifferentiated tumor (SD-UT) is a highly aggressive disease that is nosologically related to but distinct from SMARCA4-deficient non-small cell lung cancer (SD-NSCLC). No standard treatment guidelines were established for SD-UT. This research explored the efficacy of different treatments in SD-UT, and the prognostic, clinicopathologic and genomic difference between SD-UT and SD-NSCLC. Materials and methods Information of 25 SD-UT and 22 SD-NSCLC patients diagnosed and treated in Fudan University Shanghai Cancer Center from January, 2017 to September, 2022 was analyzed. Results SD-UT was similar to SD-NSCLC in characteristics of onset age, male prevalence, heavy smoking history and metastatic pattern. SD-UT showed a rapid relapse pattern after radical therapy. For Stage IV SD-UT patients, immune checkpoint inhibitor (ICI) plus chemotherapy significantly improved median progression-free survival (PFS) compared to traditional chemotherapy as first-line treatment (26.8 vs. 2.73 months, p = 0.0437), while objective response rates of two arms were comparable (71.4% vs. 66.7%). No significant survival differences were observed between SD-UT and SD-NSCLC under similar treatment settings. SD-UT or SD-NSCLC patients receiving ICI in the first line had significantly prolonged OS than those with ICI in the latter lines or without ICI treatment throughout clinical courses. Genetic study found frequent SMARCA4, TP53 and LRP1B mutations in SD-UT. Conclusion To the best of our knowledge, this is the largest series to date to compare the efficacy of ICI-based treatment to chemotherapy and document frequent mutations of LRP1B in SD-UT. ICI plus chemotherapy is an effective strategy for Stage IV SD-UT.

To address the problem of survival of macroalgal zygote transplants, six adhesives were mixed with Sargassaceae zygotes and incubated to determine their adhesion and germination. The adhesives with the highest zygote survival were selected, and then 4% alginate and 3% CaCl2 were mixed with the zygotes and applied to three adhesion substrates with different levels of roughness. The zygote attachment density was used to determine the combination of adhesives and substrates that was most favorable for zygote adhesion. The results showed that: (1) The zygote attachment density of coated alginate reached 259 ind. cm− 2, with a survival rate of 9.4. Although the attachment density of zygotes encapsulated with hyperbranched polymeric adhesive (HBPA) was low, the material was viscous, adhesive, and slow to dissolve, giving it potential as an outdoor transplant adhesion material. (2) The attachment density of zygotes on brick, cement board, and PVC substrates sprayed with 3% CaCl2 reached 86 ind. cm− 2, 48 ind. cm− 2, and 8 ind. cm− 2, and the survival rate was 52%, 29%, and 5%, respectively. The rougher the substrate, the more zygotes adhered. Therefore, in macroalgae restoration and seaweed farm reconstruction, artificial algal reefs with a rough substrate and granular dents could be used in combination with the application of adhesives. The results of this study will help to address the environmental constraints affecting the artificial transplantation of macroalgae and aid in the development of innovative habitat restoration techniques for macroalgae habitats.

Figure S1. No significant change was observed in LVEF at baseline and after treatment (p=0.669, Kruskal-Wallis rank sum test).

Purpose:This prospective single-arm phase II clinical trial aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) combined with ifosfamide (IFO) as the first-line treatment for patients with advanced or metastatic soft-tissue sarcoma (STS).Patients and Methods:Patients received PLD (30 mg/m2; day 1) in combination with IFO (1.8 g/m2; days 1–5) every 21 days until disease progression, unacceptable toxicities, patient death, or for up to six cycles. The primary endpoint was progression-free survival (PFS; NCT03268772).Results:Overall, 69 patients with chemotherapy-naïve advanced or metastatic STS were enrolled between May 2015 and November 2019. At a median follow-up of 47.2 months, the median PFS and overall survival (OS) were found to be 7.3 [95% confidence interval (CI): 5.7–8.9] and 20.6 (95% CI: 16.3–25.0) months, respectively. The response and disease control rates were 26.1% and 81.2%, respectively. Adverse events were manageable, and no grade 3–4 cardiotoxicities were observed. There was no significant change in left ventricular ejection fraction values between baseline and after treatment (P = 0.669). Exploratory biomarker analysis suggested NF1 single-nucleotide variant was associated with poor OS (P < 0.0001) and PFS (P = 0.044). In addition, 2 patients with BRCA2 loss progressed in the initial 2 months and died within 10 months. Improved OS was observed in homologous recombination deficiency (HRD)-negative patients compared with their HRD-positive counterparts (P = 0.0056).Conclusions:Combination therapy comprising PLD and IFO is an effective and well-tolerated first-line treatment for patients with advanced or metastatic STS.

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ObjectiveThis study was to explore the relationship between fibrinogen and advanced colorectal adenoma among inpatients.MethodsFrom April 2015 to June 2022, 3738 participants (566 case subjects and 3172 control subjects) who underwent colonoscopies enrolled, and smooth curve fitting and logistic regression models were applied to explore the association between fibrinogen and advanced colorectal adenoma. In addition, sensitivity and subgroup analyses were performed to assess the stability of the results.ResultsCompared with lower fibrinogen quantile 1 (< 2.4 g/L), the adjusted OR values for fibrinogen and advanced colorectal adenoma in quantile 2 (2.4–2.75 g/L), quantile 3 (2.76–3.15 g/L), and quantile 4 (≥3.16 g/L) were 1.03 (95% confidence interval [CI]: 0.76–1.41), 1.37 (95% CI: 1.01–1.85), and 1.43 (95% CI: 1.06–1.94), respectively. A linear relationship between fibrinogen and advanced colorectal adenoma was observed. Sensitivity and subgroup analyses showed stable results.ConclusionComplements the evidence that fibrinogen was positively associated with advanced adenomas, suggesting that fibrinogen may play a role in the adenoma-carcinoma sequence.

Background Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the main factor that leads to the deterioration of the disease. Currently, the diagnosis of AECOPD mainly relies on clinical manifestations, good predictors or biomarkers are lacking. We aim to reveal specific biomarkers and potential pathogenesis of AECOPD and provide a research basis for the diagnosis and treatment. Methods Four patients with AECOPD, four patients with stable COPD, and five control subjects were enrolled for RNA sequencing and KEGG analysis. The mRNA level of target genes was verified by quantitative real-time PCR (qPCR) with an expanded sample size (30 patients with AECOPD, 27 patients with stable COPD, and 35 control subjects). ELISA and immunofluorescence were used to identify the target proteins. Furthermore, the expression and function of WNT/β-catenin signaling pathway were assessed in animal models of COPD. Results RNA sequencing showed that 54 genes were up-regulated and 111 genes were down-regulated in the AECOPD. Differentially expressed genes were mainly enriched in WNT signaling pathway, et al. QPCR revealed that multi-genes of the WNT/β-catenin signaling were significantly down-regulated in AECOPD (P P P Conclusion WNT/β-catenin signaling pathway is down-regulated in AECOPD patients and in animal models of COPD. Increased expression of phosphorylated β-catenin in the blood might be a potential biomarker of AECOPD. Activation of WNT/β-catenin pathway may also represent a therapeutic target for AECOPD.

Rotation configuration control of the sp2 bond in the diimidazole–dicarboxylate linker was achieved in a new group of porous coordination isomers, whose structural and topological evaluations from unc to sod were finely understood and validated.

In large low-lift pump stations, the pump assembly comprises an inlet conduit, a pump, and an outlet conduit. A short conical frustum section that connects the elbow section with the impeller inlet directly affects the impeller inflow state, thereby influencing the overall performance. Therefore, investigating the conical frustum section contributes to studying the effect of inflow states on the performances of pump assemblies and similar pumping systems. To improve the pump assembly efficiency, three parameters of the conical frustum section, i.e., the contraction angle, height, and centerline inclination angle, are investigated and optimized via univariate and multivariate analyses. The flow field and external characteristics of the pump assembly are investigated via computational fluid dynamics simulation with a constant head. Furthermore, a comprehensive analysis and discussion of the performance improvement mechanisms are presented. The results indicate that the axial velocity distribution at the impeller inlet conforming to the cascade high-efficiency characteristics will achieve a better pump performance compared with a uniform distribution. The pump efficiency distribution can be predicted and visualized based on the cascade efficiency characteristics and the flow state at the impeller inlet using a machine learning method. In addition, the directions and distribution of the lateral and axial components of the inflow velocities have great impacts on the circulation distribution. A sensible circulation distribution at the guide vane outlet can suppress the entropy production and reduce hydraulic loss of the outlet conduit. In this case, a significant increase in the pump assembly efficiency is obtained.

ObjectiveTo evaluate the performance and validate the diagnostic value of a nucleotide matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS) with the analysis process optimized in identification of mycobacterium species.MethodsThe optimized analysis process was used for mycobacterial identification in the nucleic MALDI-TOF-MS. 108 samples were used for assessing the performance of nucleic MALDI-TOF-MS, including 25 reference standards, 37 clinical isolates, 37 BALF, and 9 plasmids. The BALF of 38 patients suspected of pulmonary mycobacterial infection was collected for validation. Clinical etiological diagnosis was used as the gold standard to evaluate the diagnostic value of nucleotide MALDI-TOF-MS.ResultsThe sensitivity, specificity, and accuracy of the nucleotide MALDI-TOF-MS in mycobacterial identification were 96.91%, 100% and 97.22%, respectively, and the limit of detection for mycobacterium tuberculosis (MTB) was 50 bacteria/mL. Among 38 patients suspected of pulmonary mycobacterial infection, 33 were diagnosed with pulmonary tuberculosis infection, and 5 with non-mycobacterial infection. In clinical validation, the positive rates of MALDI-TOF-MS, Xpert MTB/RIF, culture and AFS in BALF of patients diagnosed with tuberculosis infection were 72.7%, 63.6%, 54.5% and 27.3%, respectively. The sensitivity/specificity of MALDI-TOF-MS, Xpert, culture and AFS in diagnosing MTB were 72.7%/100%, 63.6%/100%, 54.5%/100%, 27.3%/100%, with the areas under the curve of 0.864, 0.818, 0.773, and 0.636, respectively.ConclusionOptimized nucleotide MALDI-TOF-MS has satisfactory sensitivity, specificity and low LOD in the identification of mycobacteria, which may serve as a potential assay for mycobacterial identification.

Persistent heavy rainfall events (PHREs) over the Yangtze–Huaihe River Valley (YHRV) during 1981–2020 are classified into three types (type-A, type-B and type-C) according to pattern correlation. The characteristics of the synoptic systems for the PHREs and their possible development mechanisms are investigated. The anomalous cyclonic disturbance over the southern part of the YHRV during type-A events is primarily maintained and intensified by the propagation of Rossby wave energy originating from the northeast Atlantic in the mid–upper troposphere and the northward propagation of Rossby wave packets from the western Pacific in the mid–lower troposphere. The zonal propagation of Rossby wave packets and the northward propagation of Rossby wave packets during type-B events are more coherent than those for type-A events, which induces eastward propagation of stronger anomaly centers of geopotential height from the northeast Atlantic Ocean to the YHRV and a meridional anomaly in geopotential height over the Asian continent. Type-C events have “two ridges and one trough” in the high latitudes of the Eurasian continent, but the anomalous intensity of the western Pacific subtropical high (WPSH) and the trough of the YHRV region are weaker than those for type-A and type-B events. The composite synoptic circulation of four PHREs in 2020 is basically consistent with that of the corresponding PHRE type. The location of the South Asian high (SAH) in three of the PHREs in 2020 moves eastward as in the composite of the three types, but the position of the WPSH of the four PHREs is clearly westward and northward. Two water vapor conveyor belts and two cold air conveyor belts are tracked during the four PHREs in 2020, but the water vapor path from the western Pacific is not seen, which may be caused by the westward extension of the WPSH.

Introduction Transmembrane protein 16A (TMEM16A) is a Ca2+-activated chloride channel that plays a role in cancer cell proliferation, migration, invasion, and metastasis. However, whether TMEM16A contributes to breast cancer metastasis remains unknown. Objective In this study, we investigated whether TMEM16A channel activation by ROCK1/moesin promotes breast cancer metastasis. Methods Wound healing assays and transwell migration and invasion assays were performed to study the migration and invasion of MCF-7 and T47D breast cancer cells. Western blotting was performed to evaluate the protein expression, and whole-cell patch clamp recordings were used to record TMEM16A Cl− currents. A mouse model of breast cancer lung metastasis was generated by injecting MCF-7 cells via the tail vein. Metastatic nodules in the lung were assessed by hematoxylin and eosin staining. Lymph node metastasis, overall survival, and metastasis-free survival of breast cancer patients were assessed using immunohistochemistry and The Cancer Genome Atlas dataset. Results TMEM16A activation promoted breast cancer cell migration and invasion in vitro as well as breast cancer metastasis in mice. Patients with breast cancer who had higher TMEM16A levels showed greater lymph node metastasis and shorter survival. Mechanistically, TMEM16A promoted migration and invasion by activating EGFR/STAT3/ROCK1 signaling, and the role of the TMEM16A channel activity was important in this respect. ROCK1 activation by RhoA enhanced the TMEM16A channel activity via the phosphorylation of moesin at T558. The cooperative action of TMEM16A and ROCK1 was supported through clinical findings indicating that breast cancer patients with high levels of TMEM16A/ROCK1 expression showed greater lymph node metastasis and poor survival. Conclusion Our findings revealed a novel mechanism underlying TMEM16A-mediated breast cancer metastasis, in which ROCK1 increased TMEM16A channel activity via moesin phosphorylation and the increase in TMEM16A channel activities promoted cell migration and invasion. TMEM16A inhibition may be a novel strategy for treating breast cancer metastasis.

Exploiting highly active and low-cost materials as pH-universal electrocatalysts for the hydrogen evolution reaction (HER) and achieving high-purity hydrogen fuel is highly desirable but remains challenging. Herein, a novel type of coupled heterostructure was designed by simple electrodeposition followed by a sulfurization treatment. This hierarchical structure was composed of nickel sulfides (NiS, NiS

BackgroundThe association between hematologic parameters and anti-programmed death-1 (PD-1) inhibitors was generally examined without considering therapy lines and medicine types. The study was aimed to identify potential hematologic biomarkers associated with clinical outcome in patients with non-small cell lung cancer (NSCLC) treated with first-line pembrolizumab and subsequent-line nivolumab.Materials and methods161 NSCLC patients were categorized into first-line pembrolizumab group (pembrolizumab group) and subsequent-line nivolumab group (nivolumab group). Univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of hematologic parameters for clinical outcomes.ResultsThe median progression-free survival (mPFS) was 9.6 months in the pembrolizumab group and 4.1 months in the nivolumab group (HR =1.61; P = 0.012); the median overall survival (mOS) was not reached in the pembrolizumab group and 17.7 months in the nivolumab group (HR =1.37; P = 0.23). Of the 79 patients in the pembrolizumab group, baseline PD-L1 tumor proportion score (TPS)≥1% was an independent factor of longer PFS and OS. Age≥60 years, absolute platelet count (APC)≥220×109/L and platelet-to-lymphocyte ratio (PLR)≥120 were associated with inferior PFS. Of the 82 patients in the nivolumab group, absolute neutrophil count (ANC)≥3×109/L was associated with longer PFS, while LDH (lactate dehydrogenase)≥160 U/L was associated with inferior PFS and derived neutrophil-to-lymphocyte ratio (dNLR)≥1.2 was associated with longer OS.ConclusionOur study identified multiple clinically accessible prognostic biomarkers in the peripheral blood in both the pembrolizumab and nivolumab subgroups.

The contact characteristics of angular contact ball bearings are closely related to the thermal failure of high-speed spindle systems. This paper establishes a closed-loop iterative model for analyzing the ball–race contact characteristics of machine tool spindle bearings at different combined loads and oil supply temperatures, based on a five-degree-of-freedom quasi-static analysis model and the finite difference method. Additionally, the accuracy of the proposed model is verified by comparing the measured values of temperature rise with the predicted values. Based on the verification of the accuracy of the model, the contact characteristics of machine tool spindle bearings under strong asymmetric loads and high-temperature lubrication oil are discussed in detail. The results show that at elevated temperatures, the internal loads of angular contact ball bearings operating under combined loads become concentrated, which will lead to reduced fatigue life of the bearings and even thermal seizure.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world rapidly, which seriously threatens to human health and safety. The rapid detection of the virus in the early stage is very important to prevent the cross infection and transmission. It is also a key link in the post-treatment examination. This paper has explored the infrared (IR) spectra of spike protein receptor-binding domain (RBD) for SARS-CoV-2 using molecular dynamics simulations, and the absorption bands are assigned. The calculated IR spectra of water and insulin are compared with that measured in the related literatures. The results showed that O-H stretching vibration generated a strong absorption band located around 3591 cm

BACKGROUND AND PURPOSE Ca2+ -activated Cl- channels (Ano1 channels) contribute to the pathogenesis of colorectal cancer. Honokiol is known to inhibit cell proliferation and tumour growth in colorectal cancer. However, the molecular target of honokiol remains unclear. This study aimed to investigate whether honokiol inhibited cell proliferation of colorectal cancer by targeting Ano1 channels. EXPERIMENTAL APPROACH Patch-clamp techniques were performed to study the effect of honokiol on Ca2+ -activated Cl- currents in HEK293 cells overexpressing Ano1- or Ano2-containing plasmids or in human colorectal carcinoma SW620 cells. Site-directed mutagenesis was used to identify the critical residues for honokiol-induced Ano1 inhibition. Proliferation of SW620 cells or human intestinal epithelial NCM460 cells by CCK-8 assays. KEY RESULTS Honokiol blocked Ano1 currents in Ano1-overexpressing HEK293 cells and SW620 cells. Honokiol more potently inhibited Ano1 currents than Ano2 currents. Three amino acids (R429, K430 and N435) were critical for honokiol-induced Ano1 inhibition. The R429A/K430L/N435G mutation reduced the sensitivity of Ano1 to honokiol. Honokiol inhibited SW620 cell proliferation, and this effect was reduced by Ano1-shRNAs. Furthermore, Ano1 overexpression promoted proliferation in NCM460 cells with low Ano1 endogenous expression and resulted in an increased sensitivity to honokiol. Overexpression of the R429A/K430L/N435G mutation reduced WT Ano1-induced increase in the sensitivity of NCM460 cells to honokiol. CONCLUSION AND IMPLICATIONS We identified a new anticancer mechanism of honokiol, through the inhibition of cell proliferation, by targeting Ano1 Ca2+ -activated Cl- channels.

Porous isomers constructed from the same building blocks but different topology break the general preferred coordination rule of organic linkers and metal nodes, representing an invaluable opportunity for enriching their pore chemistry. Herein, a new group of porous isomers (termed as NTU-69 and NTU-70) was prepared from a

Photocatalytic CO

Sphingosine-1-phosphate lyase is encoded by the Sgpl1 gene, degrades S1P, and is crucial for S1P homeostasis in animal models and humans. S1P lyase deficient patients suffer from adrenal insufficiency, severe lymphopenia, and skin disorders. In this study, we used random mutagenesis screening to identify a mouse line carrying a missense mutation of Sgpl1 (M467K). This mutation caused similar pathologies as Sgpl1 knock-out mice in multiple organs, but greatly preserved its lifespan, which M467K mutation mice look normal under SPF conditions for over 40 weeks, in contrast, the knock-out mice live no more than 6 weeks. When treated with Imiquimod, Sgpl1M467K mice experienced exacerbated skin inflammation, as revealed by aggravated acanthosis and orthokeratotic hyperkeratosis. We also demonstrated that the IL17a producing Vγ6+ cell was enriched in Sgpl1M467K skin and caused severe pathology after imiquimod treatment. Interestingly, hyperchromic plaque occurred in the mutant mice one month after Imiquimod treatment but not in the controls, which resembled the skin disorder found in Sgpl1 deficient patients. Therefore, our results demonstrate that Sgpl1M467K point mutation mice successfully modeled a human disease after being treated with Imiquimod. We also revealed a major subset of γδT cells in the skin, IL17 secreting Vγ6 T cells were augmented by Sgpl1 deficiency and led to skin pathology. Therefore, we have, for the first time, linked the IL17a and γδT cells to SPL insufficiency.

This study aimed to detect the expression level of nuclear factor erythroid 2-related factor 2 (Nrf2) in the serum of patients with rheumatoid arthritis (RA) to clarify the correlation between Nrf2 levels and medical parameters, such as disease activity, pro-inflammatory factor, clinical characteristics, as well as changes after treatment.Serum samples were collected from 100 patients with RA and 42 normal controls (NCs). Serum levels of Nrf2 protein, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-17A, and malondialdehyde (MDA) were analyzed. The receiver operating characteristic (ROC) curve was adopted to assess the potential of Nrf2 to predict different levels of disease activity in patients with RA. The relationship between clinical variables and parameters were evaluated.For the first time, it was reported that Nrf2 levels were significantly elevated in the serum of patients with RA compared to those of NCs, as were the MDA levels. The levels of Nrf2 were positively correlated with the disease activity and pro-inflammatory factor levels. The significant cut-off points for Nrf2 to determine RA disease activity were 0.69 ng/mL, 0.69 ng/mL and 1.18 ng/mL. Levels of Nrf2 were higher in RA patients with wrist joint involvement and interstitial lung disease. Moreover, Nrf2 levels decreased after treatment.Serum Nrf2 protein level is potentially a novel indicator to monitor disease activity and prognosis in patients with RA.

By implementing dynamic circulating tumor DNA (ctDNA) analysis, we explored the impact of TP53 mutations on tumor evolution and resistance mechanisms to ensartinib in patients with ALK-positive NSCLC.In a multicenter phase 2 trial, patients with ALK-positive NSCLC who progressed on crizotinib were treated with ensartinib. Blood samples for ctDNA analysis were collected at baseline, cycle 3 day 1, and progression disease (PD) and analyzed with a 212-gene panel.A total of 440 samples were collected from 168 patients. Baseline TP53 mutations (20.2%) significantly correlated with inferior progression-free survival (4.2 mo versus 11.7 mo, p0.0001). Patients with TP53 mutations had higher mutation load than those without TP53 mutations at baseline (13.79 ± 3.72 versus 4.67 ± 0.39, p0.001). Although there was no significant difference in mutation load between these groups at cycle 3 day 1 (5.89 ± 2.25 versus 3.72 ± 0.62, p = 0.425), patients with mutated TP53 developed more mutations at PD (7.07 ± 1.25 versus 3.20 ± 0.33, p = 0.003). Frequency and abundance of secondary ALK mutations G1269A, G1202R, and E1210K increased markedly at PD than baseline. In patients without secondary ALK mutations, we identified ALK-independent resistance mechanisms including bypass signaling activation, downstream effector protein reactivation, epithelial-mesenchymal transformation, and epigenetic dysregulation.Our study highlighted the advantage of ctDNA analysis for monitoring tumor evolution. TP53 mutations promoted genetic evolution and accelerated occurrence of resistance. We also unveiled ALK-dependent resistance mechanisms, mainly by G1269A, G1202R, and E1210K mutations, and ALK-independent resistance mechanisms to ensartinib.

Strengthening regulations on carbon emissions from ships is important for ensuring that China can achieve its dual carbon aims of reaching peak carbon emissions before 2030 and achieving carbon neutrality before 2060. Currently, the primary means of monitoring ship exhaust emissions are the sniffing method and non-imaging optical remote sensing; however, these methods suffer from a low prediction efficiency and high cost. We developed a method for predicting the CO2 content of ship exhaust that uses a convolutional neural network and mid-infrared spectral images. First, a bench experiment was performed to synchronously obtain mid-wave infrared spectral images of the ship exhaust plume and true values for the CO2 concentration from the online monitoring of eight spectral channels. Then, the ResNet50 residual neural network, which is suitable for image prediction tasks, was selected to predict the CO2 content. The preprocessed mid-infrared spectral image of each channel and the corresponding true value for the CO2 content were input to the neural network, and convolution was applied to extract the radiation characteristics. The neural network then mapped the relationship between the true CO2 content and the radiation characteristics for each channel, which it used to predict the CO2 content in the ship exhaust. The results demonstrated that the predicted and true CO2 contents had a root mean square error of

The decadal variability of the summer extreme precipitation over southern China (EPSC) is remarkable, especially for the significant decadal enhancement after the 1990s. The study documented that the summer sea surface temperature (SST) over the North Atlantic and spring sea ice concentration (SIC) over the East Siberian Sea can significantly affect the EPSC. The summer SST over the North Atlantic influences the low-pressure cyclone in the western Pacific by modulating the SST over the tropical Pacific, thus affecting EPSC. A decrease in the SIC of the East Siberian Sea induces a negative Arctic Oscillation, which induces the increased SST over northwest Pacific and the anomalous cyclone over there, in turn, affecting EPSC. Both predictors have a quasi-period of 10–14 years, which provides useful predictive signals for EPSC. The leading 7-year SST and the leading 5-year SIC are chosen to establish the prediction model based on the decadal increment method, which can well predict the EPSC, especially for the shift in the early 1990s. These results provide a clue to the limited predictability of decadal-scale extreme climate events.