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With the rapid development of microgrid in the electric power industry, the microgrid electric energy transaction has begun to be marketized, and the research on the microgrid electric energy trusted transaction has important theoretical research value and social value. The existing blockchain-based microgrid electric energy trusted transaction models mostly focus on energy management and scheduling control between microgrids when conducting electric energy transactions, and do not fully consider the bidding problems in the market-based transaction of microgrid electric energy, resulting in trading strategies are difficult to adapt to new market changes. In response to this problem, this paper proposes a reliable transaction approach for microgrid electric energy based on a continuous two-way auction mechanism. The proposed strategy accounts for the volatility of electricity prices in the microgrid trading market and employs the continuous two-way auction mechanism to evaluate the microgrid electricity trading tactics. In the microgrid electric energy transaction, the self-adaptive learning theory is applied to adjust the quotations of both parties, so that both parties can make reasonable quotations according to the market environment. By simulating experimental data, the findings indicate that the continuous two-way auction mechanism transaction strategy enables both parties to modify their quotations based on market transaction information, thereby displaying a high degree of flexibility in microgrid electricity's market-oriented trading. [ABSTRACT FROM AUTHOR]

Background: Patients with non‐small‐cell lung cancer (NSCLC) and uncommon EGFR alterations typically have worse treatment outcomes than patients with classically EGFR‐mutated NSCLC. This study aimed to investigate the efficacy and safety of PD‐1 blockade with sintilimab plus anti‐angiogenic treatment with anlotinib in patients with NSCLC harboring uncommon EGFR mutations. Methods: Patients with metastatic NSCLC harboring uncommon EGFR mutations after two previous treatments, including a platinum‐based chemotherapy regimen and a targeted treatment (or chemotherapy only for patients harboring EGFR ex20ins), received sintilimab combined with anlotinib. The primary endpoint was objective response rate (ORR). Results: At data cutoff (September 27, 2022), median follow‐up was 22.3 months (range, 1.2–37.6). Among 21 enrolled patients, 12 had EGFR ex20ins and nine had other uncommon EGFR mutations such as L861Q, G719A, and G709X. Overall, eight patients (38.1%) achieved an objective response, and 18 (85.7%) achieved disease control. Median (95% CI) progression‐free survival (PFS) was 7.0 (5.4–8.6) months, and median overall survival (OS) was 20.0 (15.6–24.4) months. The 12‐month PFS rate (95% CI) was 22.2% (7.4–42.0), and the 12‐month OS rate was 66.7% (42.5–82.5). Patients harboring EGFR ex20ins had similar ORR and PFS to those with other mutations. Six patients (28.6%) experienced grade 3 treatment‐related adverse events (TRAEs); hand‐foot syndrome was the most common grade 3 TRAE (2 patients; 9.5%). No grade ≥4 TRAEs were observed. Conclusions: The combination of sintilimab and anlotinib demonstrated durable efficacy and was generally well tolerated in patients with NSCLC and uncommon EGFR mutations who had received prior standard‐of‐care treatments. (ClinicalTrials.gov identifier: NCT04790409). [ABSTRACT FROM AUTHOR]

Charge–spin interconversion provides an effective way to generate spin current, spin–orbit torque, and unconventional magnetoresistance that is different from the magnetoresistance originated from spin-polarized current. A widely studied system that leads to all these phenomena is the ferromagnet/heavy metal bilayer, in which spin accumulation/current is generated through either the spin Hall effect in the heavy metal layer or Rashba–Edelstein effect at the ferromagnet/heavy metal interface. The subsequent interaction of the current-induced spins with the ferromagnet generates spin–orbit torque, and the inverse conversion of the backflow spin current to charge current in the heavy metal layer leads to different types of magnetoresistances. Many proof-of-concept devices and applications have been demonstrated based on the spin–orbit torque and magnetoresistance in the bilayer system, including non-volatile memory, logic, nano-oscillator, magnetic sensor, neuromorphic and scholastic computing, etc. In addition to the bilayer systems, recently there is also a growing interest in charge–spin interconversion in single-layer ferromagnets. In this Perspective, we first introduce the charge–spin interconversion in different systems based on phenomenological models, after which we show how the spin–orbit torque and spin Hall magnetoresistance in ferromagnet/heavy metal bilayers can be exploited for magnetic sensing applications. We also discuss charge–spin interconversion in single-layer ferromagnets via the anomalous Hall effect. [ABSTRACT FROM AUTHOR]

In order to improve the dispersibility and uneven distribution of carbon nanotubes (CNTs) in the copper matrix, the surface of CNTs were modified to enhance their dispersibility in the copper matrix. In this paper, different concentrations (7.5%, 15%, 30%) of HNO3 were used to functionalize the surface of CNTs to improve the chemical inertness of CNTs, and surface modification was performed on the purified and de-hybridized CNTs to make the CNTs better dispersed in the metal matrix. At the same time, the mechanical properties and electrical conductivity of the carbon nanotube-reinforced copper-based composites were analyzed. According to research result, 15% HNO3 combined with subsequent surface treatment have the best effect on surface modification of CNTs, significantly improving the dispersibility of CNTs and better exerting the excellent coordination effect of CNTs in copper-based composite. In addition, it is confirmed that the obtained Cu-CNTs/Cu composites have excellent comprehensive properties, which provide a new idea to improve the characteristics of copper-based composites doped with CNTs. [ABSTRACT FROM AUTHOR]

The incidence of laryngeal carcinoma accounts for 1 to 5% of systemic malignancies and ranks second among head and neck malignancies. Screening more effective targets are meaningful for the treatment of laryngeal carcinoma. The purpose was to research the action of miR-21-5p in the occurrence of laryngeal carcinoma. Genecards combined with g:profiler was used for cluster analysis to predict gene-related miRNAs. Q-PCR assay was performed for measuring the level of miR-21-5p and Kruppel-like factor 6 (KLF6). miR-21-5p-mimic, miR-21-5p-inhibitor and sh-KLF6 were transfected using LipofectamineTM 2000. Both CCK-8 and EdU experiments were undertaken to detect cell proliferation ability. Western blot was used to detect apoptosis and epithelial–mesenchymal transition (EMT) related proteins. Wound healing assay and transwell assay were undertaken for migration and invasion, respectively. Three online software (ENCORI, miRWalk, and miRDB) were applied to screen the downstream of miR-21-5p. At the same time, a dual-luciferase reporter experiment was processed to verify the binding. Finally, a rescue experiment was applied to reveal the mediating role of miR-21-5p and KLF6. MiR-21-5p expressed highly in laryngeal carcinoma tissues and cell lines. Knockdown of miR-21-5p reduced the EMT, while enhancing apoptosis of laryngeal carcinoma cell lines. MiR-21-5p targeted KLF6 with negative relationships. The rescue assay results confirmed that sh-KLF6 rescued the action of miR-21-5p knockdown in developing laryngeal carcinoma cells. MiR-21-5p promotes the occurrence and development of laryngeal cancer by targeting KLF6. This finding may provide new insights into miRNA as a biomarker for diagnosing and treating laryngeal carcinoma in the future. [ABSTRACT FROM AUTHOR]

Significance: Autophagy and apoptosis are two important cellular mechanisms behind brain injuries, which are severe clinical situations with increasing incidences worldwide. To search for more and better treatments for brain injuries, it is essential to deepen the understanding of autophagy, apoptosis, and their interactions in brain injuries. This article first analyzes how autophagy and apoptosis participate in the pathogenetic processes of brain injuries respectively and mutually, then summarizes some promising treatments targeting autophagy and apoptosis to show the potential clinical applications in personalized medicine and precision medicine in the future. Recent Advances: Most current studies suggest that apoptosis is detrimental to brain recovery. Several studies indicate that autophagy can cause unnecessary death of neurons after brain injuries, while others show that autophagy is beneficial for acute brain injuries (ABIs) by facilitating the removal of damaged proteins and organelles. Whether autophagy is beneficial or detrimental in ABIs depends on many factors, and the results from different research groups are diverse or even controversial, making this topic more appealing to be explored further. Critical Issues: Neuronal autophagy and apoptosis are two primary pathological processes in ABIs. How they interact with each other and how their regulations affect the outcome and prognosis of brain injuries remain uncertain, making these answers more critical. Future Directions: Insights into the interplay between autophagy and apoptosis and the accurate regulations of their balance in ABIs may promote personalized and precise treatments in the field of brain injuries. Antioxid. Redox Signal. 38, 234–257. [ABSTRACT FROM AUTHOR]

Herein, the surface of multi‐walled carbon nanotubes (MWCNTs) is treated with HNO3 oxidation to carry on oxygen‐containing functional groups. Then, the pretreatment surface of MWCNTs are plated with copper to improve the low wettability of carbon nanotubes (CNTs). Finally, metal matrix composite blocks with excellent properties are prepared by spark plasma sintering (SPS). When the content of the reinforcing phase is 0.25 wt%, the tensile strength and hardness of Cu‐MWCNTs/Cu composite compared with pure copper are increased by 34.6% and 136.1%, respectively. [ABSTRACT FROM AUTHOR]

Tribolium castaneum is one of the most harmful storage pests in the world. The aim of this study was to determine the chemical composition, repellent, and contact activities of Moutan cortex essential oil against this insect pest. In addition, the effects of Moutan cortex were examined on the expressions of three major detoxifying enzyme genes in T. castaneum. Four components were identified in this essential oil by gas chromatography-mass spectrometry (GC-MS), which was predominantly paeonol (99.13%). Paeonol exerted significant repellent activity against T. castaneum, which was more potent than the positive control N.N-diethyl-meta-toluamide (DEET). The most significant contact toxicity was observed at 24 h after exposure to paeonol. Further, quantitative real-time PCR (qRT-PCR) was used to assess expression changes in three detoxification enzyme genes in T. castaneum, including carboxylesterase (CarE), glutathione S-transferase (Gst) and cytochrome P4506BQ8 (Cyp6bq8). Among these, Gst was most highly up-regulated after treatment with paeonol with the highest expression level of 4.9-fold (Rps18 as internal reference gene) greater than control at 24 h following treatment. Data indicated that Gst might play a critical role in metabolic detoxification of toxic xenobiotics. Taken together, our findings might lay a foundation for development of paeonol as a potential natural repellent or pesticide to control storage pests. [ABSTRACT FROM AUTHOR]

Background: Brain metastasis is a common and lethal complication of non-small cell lung cancer (NSCLC). It is mostly diagnosed only after symptoms develop, at which point very few treatment options are available. Therefore, patients who have an increased risk of developing brain metastasis need to be identified early. Our study aimed to identify genomic and epigenomic biomarkers for predicting brain metastasis risk in NSCLC patients. Methods: Paired primary lung tumor tissues and either brain metastatic tissues or cerebrospinal fluid (CSF) samples were collected from 29 patients with treatment-naïve advanced NSCLC with central nervous system (CNS) metastases. A control group comprising 31 patients with advanced NSCLC who died without ever developing CNS metastasis was also included. Somatic mutations and DNA methylation levels were examined through capture-based targeted sequencing with a 520-gene panel and targeted bisulfite sequencing with an 80,672 CpG panel. Results: Compared to primary lung lesions, brain metastatic tissues harbored numerous unique copy number variations. The tumor mutational burden was comparable between brain metastatic tissue (P = 0.168)/CSF (P = 0.445) and their paired primary lung tumor samples. Kelch-like ECH-associated protein (KEAP1) mutations were detected in primary lung tumor and brain metastatic tissue samples of patients with brain metastasis. KEAP1 mutation rate was significantly higher in patients with brain metastasis than those without (P = 0.031). DNA methylation analysis revealed 15 differentially methylated blocks between primary lung tumors of patients with and without CNS metastasis. A brain metastasis risk prediction model based on these 15 differentially methylated blocks had an area under the curve of 0.94, with 87.1% sensitivity and 82.8% specificity. Conclusions: Our analyses revealed 15 differentially methylated blocks in primary lung tumor tissues, which can differentiate patients with and without CNS metastasis. These differentially methylated blocks may serve as predictive biomarkers for the risk of developing CNS metastasis in NSCLC. Additional larger studies are needed to validate the predictive value of these markers. [ABSTRACT FROM AUTHOR]

[Display omitted] • A-site fluorinated D-A polymer PxF-T hybridized CdS photocatalyst are prepared. • Photocatalytic activity of the hybrid catalyst has been enhanced by ca. 30 times. • Carrier lifetimes in hybrid catalyst has been prolonged over 200 ps. • D-A polarity shows direct impact on photocatalytic performance. • Trade-off effect of fluorination on D-A polarity is discovered. Conventional inorganic semiconducting photocatalysts are facing insufficient light harvesting as well as severe charge recombination problems. Constructing heterostructures is a well-known strategy for accelerating charge separation, especially when hybridizing with donor–acceptor (D-A) conjugated polymers, which features tunable bandgap and high absorption coefficient, these problems can be simultaneously eased. However, the singlet exciton binding energy of D-A polymers is too high for efficient exciton dissociation. In this work, we designed fluorine substituted D-A polymer PxF-T (x = 1, 2, 4) and studied polarity effect on the interfacial charge transfer in CdS/PxF-T. By adjusting the numbers of F substitutions in the acceptor unit, the electron-withdrawing ability of A site can be improved while the polarity of the whole organic molecules is tuned. Among 1, 2, 4 substitutions, the photocatalytic hydrogen production results show that the single F substitution induces the most efficient hydrogen production activity of 6327.7 μmol·g−1·h−1, which is 30.1 times higher than that of pristine CdS. In addition, electrochemical test and time-resolved transient absorption study further confirmed the improved charge transfer activity. Density functional theory calculations reveal that the F introduction induced polarity change is responsible for the improved interfacial charge transfer efficiency, however the increased number of substitutions is not necessarily favorable for improved polarity. This work uncovers the effect of fluorine substitution on the intramolecular polarity of D-A semiconductor for the fabrication of efficient hybrid photocatalysts. [ABSTRACT FROM AUTHOR]

Numerous studies have shown that copy number variation (CNV) in lncRNA regions play critical roles in the initiation and progression of cancer. However, our knowledge about their functionalities is still limited. Here, we firstly provided a computational method to identify lncRNAs with copy number variation (lncRNAs-CNV) and their driving transcriptional perturbed subpathways by integrating multidimensional omics data of cancer. The high reliability and accuracy of our method have been demonstrated. Then, the method was applied to 14 cancer types, and a comprehensive characterization and analysis was performed. LncRNAs-CNV had high specificity in cancers, and those with high CNV level may perturb broad biological functions. Some core subpathways and cancer hallmarks widely perturbed by lncRNAs-CNV were revealed. Moreover, subpathways highlighted the functional diversity of lncRNAs-CNV in various cancers. Survival analysis indicated that functional lncRNAs-CNV could be candidate prognostic biomarkers for clinical applications, such as ST7-AS1, CDKN2B-AS1 and EGFR-AS1. In addition, cascade responses and a functional crosstalk model among lncRNAs-CNV, impacted genes, driving subpathways and cancer hallmarks were proposed for understanding the driving mechanism of lncRNAs-CNV. Finally, we developed a user-friendly web interface-LncCASE (http://bio-bigdata.hrbmu.edu.cn/LncCASE/) for exploring lncRNAs-CNV and their driving subpathways in various cancer types. Our study identified and systematically characterized lncRNAs-CNV and their driving subpathways and presented valuable resources for investigating the functionalities of non-coding variations and the mechanisms of tumorigenesis. [ABSTRACT FROM AUTHOR]

Background: Hyperthyroidism-induced hypercalcemia has been reported previously, but hypercalcemia accompanied by severe osteoporosis and significant thymic enlargement in patients with hyperthyroidism is quite rare. We report the coexistence of hypercalcemia, osteoporosis and thymic enlargement in a patient with Graves' disease. Case presentation: A 22-year-old female was diagnosed as Graves' disease with obviously elevated serum calcium and reduced parathyroid hormone levels. Dual-energy x-ray absorptiometry and chest enhanced computer tomography (CT) revealed severe osteoporosis and a significant enlargement of thymus. After the successful control of hyperthyroidism with methimazole, hypercalcemia was corrected, bone mineral density was improved and thymus also shrank obviously. Conclusion: This is a very rare case of hypercalcemia accompanied by severe osteoporosis and significant thymic enlargement induced by Graves' disease. In clinical practice, examination of thymus and bone density should be considered when a patient with Graves' disease was present with hypercalcemia. [ABSTRACT FROM AUTHOR]

The memristive effect become a bio-electronics research focus with the development of sustainable systems and the application of multifunctional electronic devices. In this paper, the natural Lophatherum gracile Brongn (LGB) was employed as active layer to prepare Ag/LGB/fluorine-doped tin oxide (FTO) bio-memristor. Further, different doping ratios nano silver powders (Ag nanoparticle) were doped into LGB functional layers at 0 wt%, 0.2 wt%, 0.33 wt%, 1.0 wt%, 2.0 wt%, 10.0 wt% and 20.0 wt%. It is found that the capacitive-coupled memristive performance of the Ag/Ag-doped-LGB/FTO devices was markedly changed. Finally, it is confirmed that Ag ions transferring and Ag filament formation under the applied voltage are responsible for capacitive-coupled memristive behavior. This research has revealed the realization of capacitive-coupled memristive effect of bio-memristor, which opens a new way to achieve multifunctional performance for electronic device. Image 1 • Natural LGB can be used as a functional layer for preparation of bio-memristor. • The Ag/Ag-doped-LGB/FTO devices were prepared by spin-coating method. • A capacitive-coupled memristive effect is observed in Ag/Ag-doped-LGB/FTO device. • The Ag/Ag-2.0 wt% doped-LGB/FTO device display largest HRS/LRS resistance ratio. • This work reveals that the natural LGB is a useful functional layer in bio-memristor. [ABSTRACT FROM AUTHOR]

We report on investigation of a spin Hall magnetoresistance sensor based on NiFe/AuxPt1−x bilayers. Compared to NiFe/Pt, the NiFe/AuxPt1−x sensor exhibits a much lower power consumption (reduced by about 57%) due to 80% enhancement of spin-orbit torque efficiency of AuxPt1−x at an optimum composition of x = 0.19 as compared to pure Pt. The enhanced spin-orbit torque efficiency allows us to increase the thickness of NiFe from 1.8 nm to 2.5 nm without significantly increasing the power consumption. We show that, by increasing the NiFe thickness, we were able to improve the working field range (±0.86 Oe), operation temperature range (150 °C), and detectivity (0.71 nT/ Hz at 1 Hz) of the sensor, which is important for practical applications. [ABSTRACT FROM AUTHOR]

Background: Small-cell lung cancer (SCLC) remains an aggressive cancer with short-term survival due to limited therapeutic options. Apatinib is a small-molecule tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor-2. This study aimed to investigate the efficacy and safety of apatinib in patients with extensive-stage (EC) SCLC who had progressed after two or three previous therapies.Methods: Eligible patients were histologically confirmed ES-SCLC after two or three previous treatments, including a platinum-based regimen. Patients received apatinib at an initial dose of 500 mg once daily. The primary endpoint was the objective response rate.Results: Forty patients were enrolled. At the data cut-off time (November 15, 2018), the median follow-up was 7.4 months; no patients remained on treatment, and five were still in follow-up. An objective response was achieved in 7 of 40 patients (17.5%) in the intention-to-treat population, and 7 of 38 patients (18.4%) in the per-protocol population. The median progression-free survival and overall survival were 3.0 months and 5·8 months, respectively. The most commonly observed grade 3 or greater treatment-related adverse events were hypertension, hand-foot syndrome, increased L-gamma-glutamyltransferase.Conclusions: Apatinib exhibited efficacy and an acceptable safety profile in previously heavily-treated ES-SCLC patients. Further exploration of apatinib in phase III trials is warranted.Trial Registration: NCT02945852. [ABSTRACT FROM AUTHOR]

Polylactic acid (PLA) has attracted increasing interest as a sustainable plastic because it can be degraded into CO2 and H2O in nature. However, this process is sluggish, and even worse, it is a CO2‐emitting and carbon resource waste process. Therefore, it is highly urgent to develop a novel strategy for recycling post‐consumer PLA to achieve a circular plastic economy. Herein, we report a one‐pot photoreforming route for the efficient and selective amination of PLA waste into value‐added alanine using CoP/CdS catalysts under mild conditions. Results show the alanine production rate can reach up to 2.4 mmol gcat−1 h−1, with a high selectivity (>75 %) and excellent stability. Time‐resolved transient absorption spectra (TAS) reveal that CoP can rapidly extract photogenerated electrons from CdS to accelerate proton reduction, favoring hole‐dominated PLA oxidation to coproduce alanine. This study offers an appealing way for upcycling PLA waste and creates new opportunities for green synthesis of amino acids. [ABSTRACT FROM AUTHOR]

Polylactic acid (PLA) has attracted increasing interest as a sustainable plastic because it can be degraded into CO2 and H2O in nature. However, this process is sluggish, and even worse, it is a CO2‐emitting and carbon resource waste process. Therefore, it is highly urgent to develop a novel strategy for recycling post‐consumer PLA to achieve a circular plastic economy. Herein, we report a one‐pot photoreforming route for the efficient and selective amination of PLA waste into value‐added alanine using CoP/CdS catalysts under mild conditions. Results show the alanine production rate can reach up to 2.4 mmol gcat−1 h−1, with a high selectivity (>75 %) and excellent stability. Time‐resolved transient absorption spectra (TAS) reveal that CoP can rapidly extract photogenerated electrons from CdS to accelerate proton reduction, favoring hole‐dominated PLA oxidation to coproduce alanine. This study offers an appealing way for upcycling PLA waste and creates new opportunities for green synthesis of amino acids. [ABSTRACT FROM AUTHOR]

Compared with a disordered network, the ordered framework is more beneficial to improving the multifunctional properties (including thermal, electrical, and mechanical properties) of epoxy-based composites. However, current methods for building aligned structures are both energy and time-consuming on account of the tedious and lengthy lyophilization process. Herein, a new strategy is proposed to obtain low-density graphene aerogels (GAs) with long-range oriented structures through a lyophilization-free processes. Due to the minimum thermal boundary resistance, the prepared aligned graphene/epoxy composite exhibits an ultrahigh thermal conductivity of ∼11.6 W/(m·K) at a graphene content of 1.84 vol%, i.e., an enhancement efficiency of 3640% per 1 vol%. In addition, the compressive strength of the composite is increased by 2.6 times compared to epoxy (from 0.29 MPa to 0.76 MPa). Because the composite shows a modulus as low as 0.5–1.0 MPa, it has excellent deformability and compression performance. Moreover, the obtained 3-mm-thick composite achieves an electromagnetic interference shielding effectiveness (EMI SE) of 40 dB due to the interconnected graphene network structure, which meets the requirements of commercial EMI shielding applications. Hence, this strategy can be used to synthesize aligned graphene/epoxy composites with excellent multifunctional performances, which can be simultaneously used as elastic thermal interface materials (TIMs) and EMI shielding materials in the fields of advanced electronic packaging. [Display omitted] • Aligned graphene aerogel (GA) was fabricated by a lyophilization-free approach. • The compressive strength of the composite is increased by 2.6 times compared to epoxy (0.29 MPa to 0.76 MPa) and the composite shows a modulus as low as 0.48–1.0 MPa, exhibiting excellent deformability and compression performance. • The vertical pathways and high-quality give composite an ultrahigh thermal conductivity (∼11.6 W/m·K) with ultralow graphene loading (1.84 vol%), i.e., an enhancement efficiency of 3640% per 1 vol%. • The obtained 3-mm-thick composite achieves an electromagnetic interference shielding effectiveness of 40 dB due to the interconnected network structure. [ABSTRACT FROM AUTHOR]

• This study evaluated the long-term benefits of atezolizumab in NSCLC in China. • Clinically meaningful benefits and no new safety concerns were observed. • Gene mutations that were enriched in atezolizumab responders were identified. • Patient subgroups with higher rates of atezolizumab-related SAEs were identified. To evaluate the long-term safety and efficacy of atezolizumab monotherapy in Chinese patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC). In this open-label, single-arm, multicenter study, patients received atezolizumab 1200 mg intravenously on Day 1 of each 21-day cycle. The primary endpoint was incidence of atezolizumab-related serious adverse events (SAEs). Secondary endpoints included other safety and efficacy measures. Patients with available tumor tissue and blood samples underwent biomarker analyses. Patients with available tumor biopsies underwent exome sequencing. The safety and evaluable populations included 101 and 97 patients, respectively. Exome sequencing data were available for 31 patients. Median follow-up time was 27.43 months. Atezolizumab-related SAEs and immune-related adverse events occurred in 25.7% and 47.5% of the safety population, respectively, and in the following subgroups: central nervous system metastases (n = 14), 35.7% and 35.7%; squamous NSCLC (n = 39), 33.3% and 53.8%. The 24-month overall survival rate was 37.4%. Median overall survival and progression-free survival by RECIST v1.1 were 15.31 and 2.86 months, respectively; objective response rate was 16.5% in the evaluable population. PRRC2C (odds ratio: 12.780, P = 0.014) and ZMYND8 (odds ratio: 19.963, P = 0.016) gene mutations were significantly enriched in atezolizumab responders vs non-responders. Patients with CD8+ TILs > 10% vs ≤ 10% were significantly more likely to be atezolizumab responders. No new safety concerns were raised, and clinically meaningful benefits of atezolizumab monotherapy were shown. The results of the biomarker analyses may guide future therapeutic strategies. [ABSTRACT FROM AUTHOR]

The peak shear strength of discontinuities between two different rock types is essential to evaluate the stability of a rock slope with interlayered rocks. However, current research has paid little attention to shear strength parameters of discontinuities with different joint wall compressive strength (DDJCS). In this paper, a neural network methodology was used to predict the peak shear strength of DDJCS considering the effect of joint wall strength combination, normal stress and joint roughness. The database was developed by laboratory direct shear tests on artificial joint specimens with seven different joint wall strength combinations, four designed joint surface topographies and six types of normal stresses. A part of the experimental data was used to train a back-propagation neural network model with a single-hidden layer. The remaining experimental data was used to validate the trained neural network model. The best geometry of the neural network model was determined by the trial-and-error method. For the same data, multivariate regression analysis was also conducted to predict the peak shear strength of DDJCS. Prediction precision of the neural network model and multivariate regression model was evaluated by comparing the predicted peak shear strength of DDJCS with experimental data. The results showed that the capability of the developed neural network model was strong and better than the multivariate regression model. Finally, the established neural network model was applied in the stability evaluation of a typical rock slope with DDJCS as the critical surface in the Badong formation of China. [ABSTRACT FROM AUTHOR]

Evidence suggests that activation of the MET signaling pathway might be associated with EGFR-TKI resistance. EGFR TKI-resistant lung cancers often remain sensitive to inhibition of the EGFR pathway; thus, c-MET inhibitors are likely to be effective when combined with continued EGFR-TKI treatment. Here, we described a 56-year-old male who became refractory after first-line gefitinib therapy and was confirmed to have c-MET overexpression without a T790M mutation, c-MET amplification or MET exon 14 alterations. A complete response to crizotinib occurred in this patient. Our case report uncovered the underlying mechanism of c-MET overexpression in affecting EGFR-TKI sensitivity, and crizotinib may assist in overcoming this problem. [ABSTRACT FROM AUTHOR]

Abstract Background Infection is one of the main reasons for hospitalization worldwide, and is associated with an increased risk of cardiovascular mortality. It is unclear whether this association is modified by the presence of reduced renal function. The aim of this study was to analyze the relationship between estimated glomerular filtration rate (eGFR) and cardiovascular mortality in patients hospitalized with infection. Methods This cohort study included all adult, incident patients who were hospitalized at one of four hospitals in China between 2012 and 2015, had a discharge diagnosis of infection, and had a serum creatinine measurement at admission. Patients receiving renal replacement therapy were excluded. Hospital data were linked to death registry data. All-cause and cardiovascular mortality were evaluated according to admission eGFR [≥60 (reference), 30–59 and < 30 mL/min/1.73m2] using multivariable Cox regression and competing risk analyses. Results During a median follow-up period of 2.39 years, 40,524 patients were hospitalized with infection (mean age 61 years, 54.3% female 18.4% diabetic). Of these, 4781 died. Lower admission eGFR was associated with progressively increased risks of cardiovascular mortality (≥60 mL/min/1.73m2 reference; 30–59 mL/min/1.73m2 subdistribution hazard ratio [SHR] 2.15, 95% CI 1.85–2.50, P<.01; <30 mL/min/1.73m2 SHR 3.19, 95% CI 2.68–3.80, P <.01). The proportion of deaths due to cardiovascular disease increased as the eGFR decreased, predominantly due to ischemic heart disease. Conclusions Patients hospitalized with infections and reduced renal function have significantly increased risks of cardiovascular mortality. Heart status should be carefully monitored following infections, especially for those with reduced renal function. Highlights • Infections increase cardiovascular mortality in patients with reduced eGFR. • Cardiovascular death after infections are predominantly due to ischemic heart disease. • Heart status should be monitored following infections, especially for those with reduced eGFR. [ABSTRACT FROM AUTHOR]

Abstract Recent research has paid little attention to the difference in shear strength between discontinuities with different joint wall material (DDJM) and discontinuities with identical joint wall material (DIJM) and what are the controlling factors of shear properties of DDJM. Bedding planes between argillaceous limestone and mudstone in the Badong formation in the Three Gorges area of China were investigated using physical model tests. The effect of joint wall material combination on the shear properties of DDJM was first revealed by conducting tests on a series of artificial joint specimens that were made of different joint wall materials and with varying joint surface topographies under different normal stresses. The results indicate that: the peak shear strength of DDJM is not equal to the lower peak shear strength of DIJM for two joint wall materials of the DDJM, even so it is closer to the lower peak shear strength than to the higher one; effect of joint roughness and normal stress on peak shear strength of DDJM is similar with DIJM; effect of joint wall material combination on peak shear strength of DDJM is greater with larger roughness and higher normal stresses. Based on the data acquired from the physical model tests, a new empirical equation to estimate the peak shear strength of DDJM was developed. The capability of the equation was validated by comparing estimates with data from direct shear tests on natural DDJM samples gained from the Badong formation. Finally, the proposed empirical equation was applied to the stability analysis of a rock slope in the Badong formation. Highlights • Discontinuities with different joint wall material (DDJM) were studied. • Physical model tests were performed to investigate shear properties of DDJM. • Effect of joint material combination was first revealed. • A new equation to estimate shear strength of DDJM was proposed and validated. • The proposed equation was applied in the stability analysis of a rock slope. [ABSTRACT FROM AUTHOR]

By exploiting the amorphous–crystalline transition of CuS, which results in greatly increased absorption throughout the entire near-infrared region, a novel smart off–on CuS photoacoustic imaging agent with good photostability and low cost is developed. More importantly, the photoacoustic imaging ability of CuS can be effectively activated by body temperature for in vivo cancer imaging. [ABSTRACT FROM AUTHOR]

Abstract: Magnetoresistance (MR) sensors provide cost‐effective solutions for diverse industrial and consumer applications, including emerging fields such as internet‐of‐things (IoT), artificial intelligence, and smart living. Commercially available MR sensors such as anisotropic magnetoresistance (AMR) sensors, giant magnetoresistance (GMR) sensors, and tunnel magnetoresistance (TMR) sensors typically require an appropriate magnetic bias for both output linearization and noise suppression, resulting in increased structural complexity and manufacturing cost. Here, an all‐in‐one spin Hall magnetoresistance (SMR) sensor with built‐in AC excitation and rectification detection is demonstrated, which effectively eliminates the requirements of any linearization and domain stabilization mechanisms separated from the active sensing layer. This is made possible by the coexistence of SMR and spin–orbit torque (SOT) in ultrathin NiFe/Pt bilayers. Despite the simplest possible structure, the fabricated Wheatstone bridge sensor exhibits essentially zero DC offset, negligible hysteresis, and a detectivity of around 1 nT Hz−1/2 at 1 Hz. In addition, it also shows an angle dependence to external field similar to those of GMR and TMR, though it does not have any reference layer (unlike GMR and TMR). The superior performances of SMR sensors are evidently demonstrated in the proof‐of‐concept experiments on rotation angle measurement, and vibration and finger motion detection. [ABSTRACT FROM AUTHOR]

We propose a simple scheme for magnetic angular position sensor based on current-induced spin-orbit torque effect. A full range detection of 360° is realized with a pair of Hall crosses made of heavy metal/ferromagnet heterostructures. The current axes of the two Hall crosses are aligned orthogonal to each other, such that when both devices are subject to a rotational in-plane magnetic field, the differential Hall voltage due to current pulses of opposite polarity exhibits a sine and cosine angular dependence on the field direction, respectively. The field rotational angle is then calculated from the sine and cosine output signals via the arctan2 function. A linear correspondence between the calculated and actual field angle is obtained in the field range of 500–2000 Oe, with an average angle error of 0.38°–0.65°. [ABSTRACT FROM AUTHOR]

B Carbon Nanotubes b Metal matrix nanocomposites are widely studied recently due to their extensive functions and expansive application prospects. In article number 2200368, Ting Zhou, Yanjun Xu, Ming Lei, and colleagues treated the surface of multi-walled carbon nanotubes (MWCNTs) with HNO SB 3 sb oxidation to carry on oxygen-containing functional groups; then the pretreatment surface of MWCNT were plated with copper to improve the low wettability of CNTs. [Extracted from the article]

MOF-derived materials are known as effective electrocatalysts for hydrogen evolution reaction (HER). Herein, a new 2D structured Ni-MOF (CUST-516) was synthesized, and physically post-decorated with glucose, urea and Ni(NO 3) 2 ·6H 2 O simultaneously, used as precursors to obtain Ni/Ni 3 S 2 @CN electrocatalyst by high temperature calcination. Ni/Ni 3 S 2 @CN shows excellent HER activity with low overpotentials of 141 ​mV and 187 ​mV at 10 ​mA ​cm−2 as well as long-term stability up to 24 ​h in 1.0 ​M KOH and 0.5 ​M ​H 2 SO 4 solutions, respectively. The excellent electrocatalytic performance of Ni/Ni 2 S 3 @CN can be attributed to the synergistic effect of multi-components, the unique pore structure derived from precursor MOF, which enables the nanoparticles to be evenly distributed. Moreover, the post-decorated sources help to generate the doping of N elements and carbon layers, which increases the conductivity, prevents the aggregation of nanoparticles and corrosion, resulting in the enhanced complementary properties. This work provides a general post-decorated MOFs derivatization strategy to synthesize low-cost and efficient HER electrocatalysts. In this study, Ni/Ni 3 S 2 @CN electrocatalyst was synthesized using the post-decorated MOF powders as precursors by high temperature calcination. Ni/Ni 3 S 2 @CN exhibits excellent hydrogen generation activity and durability for 24 ​h in alkaline and acidic media. The excellent HER catalytic activity of Ni/Ni 3 S 2 @CN can be attributed the synergy effect of multicomponent, uniformly distribution, N doped carbon layers protecting. [Display omitted] • A new 2D structured Ni-MOF (CUST-516) was used to obtain Ni/Ni 3 S 2 @CN electrocatalyst. • Ni/Ni 3 S 2 @CN exhibits satisfactory hydrogen production performance. • This work provides a simple MOFs derivatization strategy to synthesize low-cost and efficient HER electrocatalysts. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have been reported to play a critical role in cancer invasion and metastasis. Our previous study showed that miR-375 frequently downregulated in gastric cancer suppresses cell proliferation by targeting Janus kinase 2 (JAK2). Here, we further found that the expression level of miR-375 is significantly decreased in metastatic gastric cancer tissues compared with the non-metastasis controls. Ectopic expression of miR-375 inhibits the migration and invasion of gastric cancer cells partially by targeting JAK2. Furthermore, miR-375 expression is negatively regulated by the metastasis associated transcription factor Snail, which directly binds to the putative promoter of miR-375. Moreover, overexpression of Snail can partially reverse the inhibition of gastric cancer cell migration caused by miR-375. Taken together, these data suggest that miR-375 may be negatively regulated by Snail and involved in gastric cancer cell migration and invasion potentially by targeting JAK2. [ABSTRACT FROM AUTHOR]

The widespread use of insecticides in Chinese herbal medicines has created a compelling need for the development of a multiresidue analytical method to help assure herbs safety. The operating variables affecting the performance of the multiresidue analysis of 34 organochlorine and 12 pyrethroid pesticides in chrysanthemum, a widely used kind of Chinese herbal medicines, were evaluated. Three different extraction solvents including n-hexane and its mixtures with acetone and petroleum ether were compared, and n-hexane was found to be an appropriate option. A combination of gel permeation chromatography and SPE was selected as the optimum cleanup, in comparison with dispersive SPE, or the two former methods alone. The determination of the 46 pesticide residues in the spiked chrysanthemum samples was performed by GC with electron capture detection. The average recoveries ranged from 71.3 to 102.6% with RSDs of 1.4-15.7% for all of the pesticides. The LOQs were in the range of 0.0015-0.2 mg/kg, while the LODs were between 0.0005 and 0.1 mg/kg. The satisfactory accuracy, and precision, in combination with a good separation and few interferences, have demonstrated the strong potential of this technique for its application in chrysanthemum analysis. [ABSTRACT FROM AUTHOR]

The aim of this study is to describe the characteristics of fatal drowning in Guangdong Province during the period 2004-2005. Twelve areas were randomly chosen by stratified cluster sampling, and a retrospective cross-sectional survey was conducted in 2006 to collect death cases during the 2004-2005 period. Causes of death relating to drowning were coded according to International Classification of Diseases, the tenth version. During 2004-2005, 849 unintentional drowning deaths occurred, representing a drowning rate of 5.6/100,000 per year. The rate was higher in rural areas (6.4/100,000) than in city (3.7/100,000), and the rate ratio of male to female was 1.5. The elderly aged 80 years and over and children aged 5-9 years had higher mortalities among all age groups, representing rates of 28.8 and 11.0 per 100,000 person years. For children aged 5-9 years, deaths from drowning accounted for the highest proportion (62.5%) of all injury deaths. The most common site of drowning was natural bodies of water (60.8%), and summer was the highest risk season for drowning. The results suggest drowning is an important public health problem, and it primarily threatens children in Guangdong province. Drowning intervention programs should be a health priority in Guangdong province. [ABSTRACT FROM AUTHOR]

Abstract: The creep behavior of bagasse-based composites with virgin and recycled polyvinyl chloride (B/PVC) and high density polyethylene (B/HDPE) as well as a commercial wood and HDPE composite decking material was investigated. The instantaneous deformation and creep rate of all composites at the same loading level increased at higher temperatures. At a constant load level, B/PVC composites had better creep resistance than B/HDPE systems at low temperatures. However, B/PVC composites showed greater temperature-dependence. Several creep models (i.e., Burgers model, Findley’s power law model, and a simpler two-parameter power law model) were used to fit the measured creep data. Time–temperature superposition (TTS) was attempted for long-term creep prediction. The four-element Burgers model and the two-parameter power law model fitted creep curves of the composites well. The TTS principle more accurately predicted the creep response of the PVC composites compared to the HDPE composites. [Copyright &y& Elsevier]

An enzyme-linked immunosorbent assay (ELISA) was used for the determination of residues of imidacloprid and thiamethoxam insecticides in honey after simple dilution of the samples without either extraction or cleanup. The ELISA enabled accurate determination of imidacloprid and thiamethoxam down to limits of 20 and 5 ng g-1 in honey, respectively. Average recoveries of imidacloprid and thiamethoxam from the fortified honey samples were 90-120 and 96-122%, and coefficients of variation ranged 5-12 and 3-15%, respectively. The results from the ELISA agreed well with those by liquid chromatography-mass spectrometry (LC-MS) for the insecticide-spiked samples, with a correlation coefficient (r2) of 0.96 and a regression coefficient (slope) of 1.03. The results indicate that ELISA is a suitable tool for the quantification of imidacloprid and thiamethoxam in honey. [ABSTRACT FROM AUTHOR]

The working models of LCoS (Liquid Crystal on Silicon) were optimized in parameter space by simulation. Two modes were selected, which were suitable for phase modulation. One was the RTN-52° mode, the other was parallel alignment ECB mode. Phase changes were measured when various voltages are applied to LCoS. In addition, we showed some results when the LCoS was used as a Fresnel lens. [Copyright &y& Elsevier]

Phenoxypyridine, the bioisostere of diaryl ethers, has been widely introduced into bioactive molecules as an active scaffold, which has different properties from diaryl ethers. In this paper, the bioactivities, structure-activity relationships, and mechanism of compounds containing phenoxypyridine were summarized, which may help to explore the lead compounds and discover novel pesticides with potential bioactivities. [ABSTRACT FROM AUTHOR]

Photocatalytic ozonation offers a potential approach for highly efficient organic degradation by in-situ generation of reactive •OH via electron reduction of ozone. Herein, we synthesized a Mn single atom photocatalyst for promoting the •OH generation from O 3 activation under visible light irradiation. Theoretical calculation and experimental studies reveal that Mn single atoms on carbon nitride significantly promote the excitation and transfer of photo-generated electrons, making charge carriers enriched around MnN 4 sites and shortening their migration path to participate in surface reactions. Meanwhile, Mn single atoms serve as adsorption and catalytic sites for O 3 , favoring a fast one-electron-reduction reaction kinetics. More importantly, the trade-off between the number of available electrons and active sites in photocatalytic performance was observed from regulating the density of Mn single atoms. This work offers an intriguing regulation strategy for enriching surface charges on single atom catalyst interface toward efficient •OH production and removal of aqueous organics. [Display omitted] • Mn single atom catalysts demonstrate high performance in photocatalytic ozonation. • The anchored Mn single atoms enrich photo charge carriers for promoting O 3 adsorption. • One-electron reduction path ensures efficient O 3 activation to hydroxyl radicals. • A higher Mn single atom density favors higher photocatalytic performance. [ABSTRACT FROM AUTHOR]

In order to discover new pesticides with novel modes of action and further study the sulfoximine scaffolds, 30 novel sulfoximine derivatives were designed, synthesized, and evaluated for their insecticidal and antifungal activities. The preliminary bioassay results showed that the insecticidal activity of target compounds was weak, only I‐12 displayed 80.39% larvicidal activity against Nilaparvata lugen, slightly lower than sulfoxaflor (97.87%) at 100 μg/ml. However, most of the compounds also displayed fair to good fungicidal activities against eight representative phytopathogenic fungi, and I‐5 showed slightly lower fungicidal activity against Sclerotinia scleotiorum than the control drug difenoconazole (2.26 μg/ml) with an EC50 of 8.75 μg/ml. The structure–activity relationship showed that the compound exhibited better antifungal activity when the R was 2.4‐disubstituted phenyl. Our studies suggested that sulfoximine scaffolds may also have potential plant‐fungal activity. This is the first report on the use of sulfoximide scaffolds as fungicides. [ABSTRACT FROM AUTHOR]

• Magnetic nanoplatform was developed to overcome tumor hypoxia. • The enhanced SDT plays a great role in the alleviation of thermotolerance. • The synergistic effect between SDT/MHT was revealed via modulating ROS and HSPs. As a promising treatment modality with spatial and temporal control, alternating magnetic field (AMF) triggered magnetic hyperthermal therapy (MHT) shows broad and promising applications to overcome the drawbacks of traditional focal therapies in combating cancer. However, the MHT efficacy is still not satisfactory with the presence of heat shock proteins (HSPs). In addition, sustained tumor hypoxia haunts practical implications for the treatment of solid tumors. Herein, a novel magnetic nanosystem composed of hollow iron oxide nanoparticles (HIONs), Fe 3 O 4 , and sonosensitizers, hematoporphyrin (HP) was rationally designed and successfully synthesized. The hollow HIONs show a large inner cavity for loading sonosensitizer molecules and possess nanozyme activity for catalyzing decomposition of endogenous overexpressed hydrogen peroxide (H 2 O 2) to produce molecular oxygen (O 2) that can overcome tumor hypoxia, thus augmenting the sonodynamic therapy (SDT)-induced highly toxic reactive oxygen species (ROS) production for efficient cancer cell apoptosis. Importantly, the generated ROS can also activates the cleavage of HSPs that further eliminate themotolerance and facilitates MHT efficacy. The synergistic catalysis-enhanced SDT efficiency and MHT effect realized most potent tumor suppression efficacy. This work develops a versatile nanoplatform for a multifunctional strategy and broadens the biological applications by rationally designing their structure. [ABSTRACT FROM AUTHOR]

Insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) can provide safe and effective control of some major pests, but evolution of resistance by pests diminishes these benefits. Better understanding of the genetics and mechanisms of resistance is urgently needed to improve methods for monitoring, managing, and countering pest resistance to Bt toxins. Here we used CRISPR-mediated knockouts to evaluate the role of five genes encoding candidate Bt toxin receptors in Spodoptera exigua (beet armyworm), a devastating pest of vegetable, field and flower crops. We compared susceptibility to Bt toxins Cry1Ac, Cry1Fa, and Cry1Ca between the parent susceptible strain and each of five strains homozygous for the knockout of one of the candidate genes (SeAPN1, SeCad1, SeABCC1, SeABCC2 or SeABCC3). The results from the 15 pairwise comparisons reveal that SeABCC2 has a major role and SeCad1 a minor role in mediating toxicity of Cry1Ac and Cry1Fa. SeABCC2 also has a minor role in toxicity of Cry1Ca. In addition, the results imply little or no role for the other three candidate receptors in toxicity of Cry1Ac or Cry1Fa; or for the four candidate receptors other than SeABCC2 in toxicity of Cry1Ca. Image 1 • CRISPR-mediated knockouts used to evaluate the role of five genes encoding candidate Bt receptors in Spodoptera exigua. • SeABCC2 has a major role and SeCad1 a minor role in mediating toxicity of Cry1Ac and Cry1Fa. • SeABCC2 also has a minor role in toxicity of Cry1Ca. [ABSTRACT FROM AUTHOR]

The adoption of transgenic crops expressing Bacillus thuringiensis (Bt) insecticidal crystalline (Cry) proteins has reduced insecticide application, increased yields, and contributed to food safety worldwide. However, the efficacy of transgenic Bt crops is put at risk by the adaptive resistance evolution of target pests. Previous studies indicate that resistance to Bacillus thuringiensis Cry1A and Cry1F toxins was genetically linked with mutations of ATP-binding cassette (ABC) transporter subfamily C gene ABCC2 in at least seven lepidopteran insects. Several strains selected in the laboratory of the Asian corn borer, Ostrinia furnacalis, a destructive pest of corn in Asian Western Pacific countries, developed high levels of resistance to Cry1A and Cry1F toxins. The causality between the O. furnacalisABCC2 (OfABCC2) gene and resistance to Cry1A and Cry1F toxins remains unknown. Here, we successfully generated a homozygous strain (OfC2-KO) of O. furnacalis with an 8-bp deletion mutation of ABCC2 by the CRISPR/Cas9 approach. The 8-bp deletion mutation results in a frame shift in the open reading frame of transcripts, which produced a predicted protein truncated in the TM4-TM5 loop region. The knockout strain OfC2-KO showed much more than a 300-fold resistance to Cry1Fa, and low levels of resistance to Cry1Ab and Cry1Ac (<10-fold), but no significant effects on the toxicities of Cry1Aa and two chemical insecticides (abamectin and chlorantraniliprole), compared to the background NJ-S strain. Furthermore, we found that the Cry1Fa resistance was autosomal, recessive, and significantly linked with the 8-bp deletion mutation of OfABCC2 in the OfC2-KO strain. In conclusion, in vivo functional investigation demonstrates the causality of the OfABCC2 truncating mutation with high-level resistance to the Cry1Fa toxin in O. furnacalis. Our results suggest that the OfABCC2 protein might be a functional receptor for Cry1Fa and reinforces the association of this gene to the mode of action of the Cry1Fa toxin. [ABSTRACT FROM AUTHOR]

The small naphthoquinone molecules modified reduced-graphene oxide with chemical absorption of polysulfides based on the abundant keto functional groups, leads to the significantly improved cycling performance for Li-S batteries. • Organic NQ molecule-decorated rGO was applied as host for Li-S batteries. • Chemical absorption of polysulfides/sulfur can be achieved. • The S/NQ-rGO electrode delivers outstanding electrochemical performance. Graphene-based materials are explored to be promising candidates for lithium-sulfur batteries based on their unique two-dimensional geometry structure and excellent electric conductivity. However, the inferior ability to confine polysulfides results in quick capacity fading and poor cycling stability of graphene-related electrode materials. Herein, small organic naphthoquinone (NQ) molecules with redox active properties are introduced to the reduced graphene oxide (rGO) as an advanced sulfur host to significantly prolong cycle life for Li-S batteries. The effective combination between small NQ organic molecules and rGO successfully leads to the conductive composite network, where the keto groups from NQ play the key role in promoting the chemical absorption of polysulfides/sulfur by forming the S O interaction. Notably, the NQ-rGO composite shows superior lithium polysulfides absorptivity with a sulfur loading of 65.3%. The S/NQ-rGO displays outstanding electrochemical performances for lithium-sulfur batteries, in terms of large reversible capacities with excellent cycling stability (936 mAh g−1 after 200 cycles at 0.1C and 670 mAh g−1 after 500 cycles at 1C) and superior rate ability (525 mAh g−1 at 5C). [ABSTRACT FROM AUTHOR]

Boron/oxygen co‐doped carbons (BOC) have great potentials as sulfur host materials for lithium–sulfur batteries, because they can increase electronic conductivity and anchor polysulfides. However, the doping interface as a key chemically active site still lacks in‐depth understanding owing to the difficulty in design at the molecular scale. Herein, the BOC network derived from covalent organic framework (COF) is prepared on the surface of CNTs via rational design of the organic condensation reaction. This strategy enables boron and oxygen heteroatoms to be uniformly doped throughout porous carbon because of the uniformly‐distributed two elements in the COF precursor. Thereby, the BOC matrix is demonstrated to play a pivotal role in promoting the chemical absorption of polysulfides and enhancing cycling stability. The BOC@CNT with 68.5% sulfur shows superior lithium polysulfides absorptivity and displays superior electrochemical performances as a cathode for Li–S batteries, including a large reversible capacity (1077 mA h g−1 after 200 cycles at 0.2 C), and outstanding cycling stability (794 mA h g−1 after 500 cycles at 1 C). The demonstrated strategy for fabricating BOC network by COF precursor for Li–S batteries provides a new approach to rationally design uniform heteroatom interfaces for good electrochemical performances. [ABSTRACT FROM AUTHOR]

Background: Individualized drug response prediction is vital for achieving personalized treatment of cancer and moving precision medicine forward. Large-scale multi-omics profiles provide unprecedented opportunities for precision cancer therapy.Methods: In this study, we propose a pipeline to identify subpathway signatures for anticancer drug response of individuals by integrating the comprehensive contributions of multiple genetic and epigenetic (gene expression, copy number variation and DNA methylation) alterations.Results: Totally, 46 subpathway signatures associated with individual responses to different anticancer drugs were identified based on five cancer-drug response datasets. We have validated the reliability of subpathway signatures in two independent datasets. Furthermore, we also demonstrated these multi-omics subpathway signatures could significantly improve the performance of anticancer drug response prediction. In-depth analysis of these 46 subpathway signatures uncovered the essential roles of three omics types and the functional associations underlying different anticancer drug responses. Patient stratification based on subpathway signatures involved in anticancer drug response identified subtypes with different clinical outcomes, implying their potential roles as prognostic biomarkers. In addition, a landscape of subpathways associated with cellular responses to 191 anticancer drugs from CellMiner was provided and the mechanism similarity of drug action was accurately unclosed based on these subpathways. Finally, we constructed a user-friendly web interface-CancerDAP ( http://bio-bigdata.hrbmu.edu.cn/CancerDAP/ ) available to explore 2751 subpathways relevant with 191 anticancer drugs response.Conclusions: Taken together, our study identified and systematically characterized subpathway signatures for individualized anticancer drug response prediction, which may promote the precise treatment of cancer and the study for molecular mechanisms of drug actions. [ABSTRACT FROM AUTHOR]

Anaprazole, a newly developed oral proton pump inhibitor, was evaluated for safety, tolerability, and pharmacokinetics in healthy Chinese subjects. This study involved administering either anaprazole sodium enteric‐coated tablet or placebo, followed by monitoring the incidence and severity of any adverse events (AEs). The pharmacokinetic parameters of anaprazole, its isomer, and main metabolisms were determined. The results showed that both single‐dose (2.5‐120 mg) and multiple‐dose (20 mg once daily, 40 mg once daily, or 20 mg twice daily) oral administration of anaprazole sodium enteric‐coated tablet were safe and well tolerated. Following single‐dose administration, the median time to reach maximum plasma concentration of anaprazole was between 3.50 and 5.25 hours, with mean elimination half‐life of 1.22‐3.79 hours. The absorption and elimination of anaprazole in the human body appeared to basically follow linear kinetics. After repeated dosing, steady‐state concentrations of anaprazole, its isomer, and primary metabolites were achieved, with a median time to reach maximum plasma concentration of 3‐3.75 hours and a mean elimination half‐life of 1.61‐2.27 hours for anaprazole. There was no significant drug accumulation after multiple‐dose oral administration. In conclusion, anaprazole sodium enteric‐coated tablets were found to be safe and well tolerated in healthy Chinese individuals. Anaprazole is absorbed and metabolized consistently in the human body without any accumulation. [ABSTRACT FROM AUTHOR]

We analysed an observation with the Nuclear Spectroscopic Telescope Array of the black hole X-ray binary MAXI J1535−571 in the soft intermediate state, in which we detected a 2.5-ks long flare. Our spectral fitting results suggest that MAXI J1535−571 possesses a high spin of |$0.97_{-0.10}^{+0.02}$| and a low inclination of approximately 24°. We observed a gradual increase in the inner disc radius, as determined from fits to the continuum spectrum. This trend is inconsistent with an increased flux ratio of the thermal component, as well as the source evolving towards the soft state. This inconsistency may be attributed to a gradual decrease of the colour correction factor. Additionally, with a flare velocity of approximately 0.5 c and a higher hardness ratio during the flare period, the quasi-simultaneous detection of a type-B QPO in the Neutron Star Interior Composition Explorer data, and quasi-simultaneous ejecta launch through radio observations collectively provide strong evidence supporting the possibility that the flare originated from a discrete jet ejection. [ABSTRACT FROM AUTHOR]

Colon cancer (COAD) is a prevalent gastrointestinal tumor, composed of a few cancer stem cells (CSCs). High expression of RNF183 drives colorectal cancer metastasis, but its role in COAD cell stemness is still unclear. Bioinformatics analyzed expression and enriched pathway of RNF183 in COAD tissue. IHC analyzed RNF183 protein expression in tumor tissue. CD133 + CD44+ CSCs were sorted by flow cytometry, and RNF183 expression in COAD cells or CSCs was detected by qPCR, western blot and immunofluorescence. CCK-8 assay assessed cell viability, and sphere formation assay tested cell sphere-forming ability. Western blot measured protein expression of stem cell markers. qPCR assayed expression of fatty acid oxidation genes. The ability of fatty acid oxidation was analyzed by detecting fatty acid metabolism. RNF183 was highly expressed in COAD and CD133 + CD44+ CSCs, and was enriched in fatty acid metabolism pathway. RNF183 expression was positively correlated with enzymes involved in fatty acid oxidation. RNF183 could promote COAD stemness and fatty acid oxidation. Rescue experiments showed that Orlistat (a fatty acid oxidation inhibitor) reversed stimulative impact of RNF183 overexpression on COAD stemness. RNF183 promoted COAD stemness by affecting fatty acid oxidation, which may be a new therapeutic target for inhibiting COAD development. [ABSTRACT FROM AUTHOR]

Background: There existed evidence that type 2 diabetes mellitus (T2DM) prevalence and control rate have seasonal variation. Our study aimed to examine the ambient temperature and fasting plasma glucose (FPG) association and estimate temperature-adjusted T2DM prevalence and control rate.Methods: Four cross-sectional health surveys with 26,350 respondents were conducted in Guangdong Province from 2007 to 2015. Multistage cluster sampling was used to recruit study participants. The data of demographic characteristics, lifestyle factors, diet and use of hypoglycemic medicine, height, weight, FPG and meteorological information were collected. And an inverse distance-weighted method was employed to estimate daily temperature exposures at the individual' s residential district/county. Base on World Health Organization 2006 criteria, participants were divided into normal fasting glucose (NFG) participants (n = 23,877), known T2DM patients (n = 916) and newly detected T2DM patients (n = 1557). Generalized additive mixed model was employed to evaluate the nonlinear associations between temperature and FPG among different T2DM subgroups. The T2DM prevalence and control rate were estimated based on temperature-FPG association.Results: The curves of temperature and FPG were downward parabola for total, NFG and known T2DM groups, while it was "U"-shaped for newly detected T2DM patients. When temperature decreased from 30 °C to 4 °C, the FPG significantly increased 0.24 (95%CI: 0.15, 0.33) mmol/L, 0.10 (95%CI: 0.06, 0.14) mmol/L and 1.34 (95%CI: 0.56, 2.12) mmol/L in total, NFG and known T2DM groups, respectively. Compared to 19 °C, newly detected T2DM patients' FPGs were increased 0.73 (95%CI: 0.13, 1.30) mmol/L at 4 °C and 0.53 (0.00, 1.07) mmol/L at 30 °C. The model-estimated temperature-adjusted T2DM prevalence had a down and up trend, with 9.7% at 5 °C, 8.9% at 20 °C and 9.4% at 30 °C, respectively. At 5, 10, 15, 20, 25 and 30 °C, the model-estimated temperature-adjusted T2DM control rates were 33.2, 35.4, 38.2, 43.6, 49.1 and 55.2%.Conclusion: Temperature was negatively associated with FPG for NFG and known T2DM subgroups, while their association was U-shape for newly detected T2DM patients. Hence, the temperature-adjusted T2DM prevalence show a dip/peak pattern and T2DM control rate display a rising trend when temperature increase. Our findings suggest temperature should be considered in T2DM clinic management and epidemiological survey. [ABSTRACT FROM AUTHOR]

Background: The prognosis for patients with stage II/III non–small cell lung cancer (NSCLC) is unsatisfactory, even after complete tumor resection and adjuvant chemotherapy. Here, we assessed the prognostic and predictive value of immunogenomic signatures for stage II/III NSCLC in Chinese patients. Methods: A total of 91 paired resected stage II/III NSCLC and normal tissues, including 47 squamous cell lung carcinomas (SCC) and 44 lung adenocarcinomas (ADC), were collected and analyzed using whole exome sequencing (WES) to identify immunogenomic signatures for association with clinicopathological variables and disease‐free survival (DFS). Results: Higher neoantigen load (NAL, >2 neoantigens/Mb) exhibited better DFS for SCC patients (p = 0.021) but not ADC patients. A benefit from adjuvant chemotherapy was correlated with lower NAL (≤2 neoantigens/Mb) (p = 0.009). However, tumor mutation burden (TMB), mutations of individual gene, oncogene pathways, and antigen presentation machinery genes, and human leukocyte antigen (HLA)‐I number and HLA‐I loss of heterozygosity (LOH) had no prognostic or predictive value for DFS of SCC or ADC patients. Conclusions: NAL is a useful biomarker for lung SCC prognosis and prediction of chemotherapy responses in Chinese patients. The predictive value of NAL for adjuvant immunotherapy should be further explored in patients with resected NSCLC. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy is a revolutionary strategy in cancer therapy, but the resistance of which is one of the important challenges. Detecting the regulation of immune cells and biomarkers concerning immune checkpoint blockade (ICB) therapy is of great significance.Methods: Here, we firstly constructed regulation networks for 11 immune cell clusters by integrating biological pathway data and single cell sequencing data in metastatic melanoma with or without ICB therapy. We then dissected these regulation networks and identified differently expressed genes between responders and non-responders. Finally, we trained and validated a logistic regression model based on ligands and receptors in the regulation network to predict ICB therapy response.Results: We discovered the regulation of genes across eleven immune cell stats. Functional analysis indicated that these stat-specific networks consensually enriched in immune response corrected pathways and highlighted antigen processing and presentation as a core pathway in immune cell regulation. Furthermore, some famous ligands like SIRPA, ITGAM, CD247and receptors like CD14, IL2 and HLA-G were differently expressed between cells of responders and non-responders. A predictive model of gene sets containing ligands and receptors performed accuracy prediction with AUCs above 0.7 in a validation dataset suggesting that they may be server as biomarkers for predicting immunotherapy response.Conclusions: In summary, our study presented the gene-gene regulation landscape across 11 immune cell clusters and analysis of these networks revealed several important aspects and immunotherapy response biomarkers, which may provide novel insights into immune related mechanisms and immunotherapy response prediction. [ABSTRACT FROM AUTHOR]