Search

The development of self-powered sensors with interference-resistant detection is a priority area of research for the next generation of wearable electronic devices. Nevertheless, the presence of multiple stimuli in the actual environment will result in crosstalk with the sensor, thereby hindering the ability to obtain an accurate response to a singular stimulus. Here, we present a self-powered sensor composed of silk-based conductive composite fibers (CNFA@ESF), which is capable of energy storage and sensing. The fabricated CNFA@ESF exhibits excellent mechanical performance, as well as flexibility that can withstand various deformations. The CNFA@ESF provides a good areal capacitance (44.44 mF cm -2 ), high-rate capability, and excellent cycle stability (91 % for 5000 cycles). In addition, CNFA@ESF also shows good sensing performance for multiple signals including strain, temperature, and humidity. It was observed that the assembly of the symmetrical device with a stiff hydrogel surface layer for protection enabled the real-time, interference-free monitoring of temperature signals. Also, the CNFA@ESF can be woven into fabrics and integrated with a solar cell to form a self-powered sensor system, which has been proven to convert and store solar energy to power electronic watches, indicating its huge potential for future wearable electronics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study demonstrates the expanded application of ion-exchange stationary phases (including strong cation exchange, SCX and strong anion exchange, SAX) in supercritical fluid chromatography (SFC), and more importantly, provides a deeper understanding of the retention mechanisms of these two stationary phases when using the same acidic additive. Phenylpropionic acid compounds (belonging to phenolic acids) were selected as probes. On the SCX column, the π-π and polar interactions originating from the bonded benzenesulfonic acid groups were important foundations for prolonging the retention time of solutes, but they were also the main reason for solutes' tailing profiles. It was found that adding 0.1 % phosphoric acid can generate sufficient strength of electrostatic repulsion to obtain satisfactory peak shapes. Here, phosphoric acid can be adsorbed on the surface of the stationary phase to accumulate more negative charges, and at the same time, the phosphate anion and the phenylpropionic acid in mobile phase might combine into the contact ion pair (CIP)- like through the polar interactions to form the apparently negatively charged solute. On the SAX column, phosphate anions generated by ionization of phosphoric acid, were considered as counterions to effectively mask the electrostatic attraction of quaternary ammonium groups, to significantly reduce the retention of phenylpropionic acids, but improve their resolution. Finally, utilizing two developed SFC methods, i.e., SCX with MeOH + 0.1 % phosphoric acid in CO 2 , or SAX with MeOH + 0.3 % phosphoric acid in CO 2 , the baseline separation of the extract of Lonicerae Japonicae Flos was achieved within 6 min and 10 min, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The c-ros oncogene 1 (ROS1), an oncogenic driver, is known to induce non-small cell lung cancer (NSCLC) when overactivated, particularly through the formation of fusion proteins. Traditional targeted therapies focus on inhibiting ROS1 activity with ROS 1 inhibitors to manage cancer progression. However, a new strategy involving the design of protein degraders offers a more potent approach by completely degrading ROS1 fusion oncoproteins, thereby effectively blocking their kinase activity and enhancing anti-tumour potential. Utilizing PROteolysis-TArgeting Chimera (PROTAC) technology and informed by molecular docking and rational design, we report the first ROS1-specific PROTAC, SIAIS039. This degrader effectively targets multiple ROS1 fusion oncoproteins (CD74-ROS1, SDC4-ROS1 and SLC34A2-ROS1) in engineered Ba/F3 cells and HCC78 cells, demonstrating anti-tumour effects against ROS1 fusion-driven cancer cells. It suppresses cell proliferation, induces cell cycle arrest, and apoptosis, and inhibits clonogenicity. The anti-tumour efficacy of SIAIS039 surpasses two approved drugs, crizotinib and entrectinib, and matches that of the top inhibitors, including lorlatinib and taletrectinib. Mechanistic studies confirm that the degradation induced by 039 requires the participation of ROS1 ligands and E3 ubiquitin ligases, and involves the proteasome and ubiquitination. In addition, 039 exhibited excellent oral bioavailability in a mouse xenograft model, highlighting its potential for clinical application. In conclusion, our study presents a promising and novel therapeutic strategy for ROS1 fusion-positive NSCLC by targeting ROS1 fusion oncoproteins for degradation, laying the foundation for the development of further PROTAC and offering hope for patients with ROS1 fusion-positive NSCLC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Herein, an improved subtraction model was proposed to characterise the polar stationary phases in supercritical fluid chromatography (SFC). Fifteen stationary phases were selected, including two types of aromatic columns, Waters Torus and Viridis series columns, as well as silica and amino columns. Ethylbenzene and Torus 1-AA were defined as the reference solute and column, respectively. Identifying the interaction with the maximum contribution to retention in SFC separation and using it as the initial term is a key step in modelling. The dipole, or induced dipole interaction (θ ' P), replaced the hydrophobic interaction (η ' H) as the starting term. The improved model was expressed as logα=η ' H+β ' A+α ' B+κ ' C+θ ' P+ε ' E+σ ' S, where the term ε ' E indicated that anion exchange interaction was intentionally supplemented. A 7-step modelling process, including bidirectional fitting and residual analysis, was proposed. The obtained column parameters had reasonable physical significance, with the adjusted determination coefficient (R 2 adj ) greater than 0.999 and the standard error (SE) less than 0.029. Methodological validation was further performed using the other four columns and 12 solutes that were not involved in the modelling. The result revealed good predictions of solutes' retention, as demonstrated by R 2 adj from 0.9923 to 0.9979 and SE from 0.0636 to 0.1088. This study indicated the feasibility of using the improved subtraction model to characterise polar stationary phases in SFC, with the most crucial being the determination of an initial term, followed by the addition of a new descriptor and the selection of an appropriate reference column. The study expanded the application scope of the subtraction model in SFC, which will help gain an in-depth understanding of the SFC separation mechanism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024. Published by Elsevier B.V.)

While significant progress has been achieved in utilizing remote sensing technologies for landslide investigation in China, there remains a notable gap in consolidating information on applicable conditions, application stages, and workflows across various remote sensing methodologies. This paper proposes a comprehensive framework for active landslide detection, incorporating multiple stages and data sources, successfully implemented in a vast region of southwestern China. Furthermore, detailed discussions are provided on the effects of the geometric distortion, land cover type, and various InSAR methods on the accuracy of active landslide identification results. Additionally, the paper delves into the advantages of integrated remote sensing technology in active landslide investigation, encompassing the assessment of current landslide activity status, precise delineation of boundaries, identification of different deformation stages, and determination of damage patterns. Through comprehensive analysis of multisource data, it enhances understanding of the active landslide process, ultimately contributing to the mitigation of casualties and property damage., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

With an increasing understanding of the mechanisms of fracture healing, it has been found that nerve injury plays a crucial role in the process, but the specific mechanism is yet to be completely revealed. To address this issue and provide novel insights for fracture treatment, we compiled this review. This review aims to study the impact of nerve injury on fracture healing, exploring the role of neurotrophic factors in the healing process. We first revisited the effects of the central nervous system (CNS) and the peripheral nervous system (PNS) on the skeletal system, and further explained the phenomenon of significantly accelerated fracture healing under nerve injury conditions. Then, from the perspective of neurotrophic factors, we delved into the physiological functions and mechanisms of neurotrophic factors, such as nerve growth factor (NGF), Neuropeptides (NPs), and Brain-derived neurotrophic factor (BDNF), in bone metabolism. These effects include direct actions on bone cells, improvement of local blood supply, regulation of bone growth factors, control of cellular signaling pathways, promotion of callus formation and bone regeneration, and synergistic or antagonistic effects with other endocrine factors, such as Sema3A and Transforming Growth Factor β (TGF-β). Finally, we discussed the treatments of fractures with nerve injuries and the future research directions in this review, suggesting that the relationship between nerve injury and fracture healing, as well as the role of nerve injury in other skeletal diseases., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Peroxyacetyl nitrate (PAN) is a significant indicator of atmospheric photochemical pollution, which can influence the regional distribution of ozone (O 3 ) and hydroxyl radical (OH) through long-range transport. However, investigations of PAN incorporating comprehensive measurement and explicit modeling analysis are limited, hindering complete understandings of its temporal behavior, sources, and impacts on photochemistry. Here we conducted a 1-year continuous observation of PAN and relative atmospheric species in Nanjing located in Yangtze River Delta (YRD). The annual mean concentration of PAN was 0.62 ± 0.49 ppbv and showed a bimodal monthly variation, peaking in April-June and November-January, respectively. This pattern is different from the typical pattern of photochemistry, suggesting important contributions of other non-photochemical processes. We further analyzed the PAN budget using an observation-based model, by which, PAN from local photochemical production and regional source could be decoupled. Our results revealed that local photochemical production of PAN is the sole contributor to PAN in summer, whereas about half of the total PAN concentration is attributed to regional source in winter. Although the formation of PAN can suppress the atmospheric oxidation capacity by consuming the peroxyacetyl radical and nitrogen dioxide (NO 2 ), our analyses suggested this effect is minor at our station (-3.2 ± 1.1 % in summer and - 7.2 ± 2.8 % in winter for O 3 formation). However, it has the potential to enhance O 3 and OH formation by 14.16 % and 5.93 %, if transported to cleaner environments with air pollutants halved. Overall, our study highlights the importance of both local photochemistry and regional process in PAN budget and provides a useful evaluation on the impact of PAN on atmospheric oxidation capacity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Diabetic retinopathy (DR) is one of the most prevalent severe diabetic microvascular complications caused by hyperglycemia. Deciphering the underlying mechanism of vascular injury and finding ways to alleviate hyperglycemia induced microvascular complications is of great necessity. In this study, we identified that a compound ent-9α-hydroxy-15-oxo-16-kauren-19-oic acid (EKO), the diterpenoid isolated and purified from Pteris semipinnata L., exhibited good protective roles against vascular endothelial injury associated with diabetic retinopathy in vitro and in vivo. To further uncover the underlying mechanism, we used unbiased transcriptome sequencing analysis and showed substantial impairment in the focal adhesion pathway upon high glucose and IL-1β stimulation. EKO could effectively improve endothelial focal adhesion pathway by enhancing the expression of two focal adhesion proteins Vinculin and ITGA11. We found that c-fos protein was involved in regulating the expression of Vinculin and ITGA11, a transcription factor component that was downregulated by high glucose and IL-1β stimulation and recovered by EKO. Mechanically, EKO facilitated the binding of deubiquitylation enzyme ATXN3 to c-fos protein and promoted its deubiquitylation, thereby elevating its protein level to enhance the expression of Vinculin and ITGA11. Besides, EKO effectively suppressed ROS production and restored mitochondrial function. In vivo studies, we confirmed EKO could alleviate some of the indicators of diabetic mice. In addition, protein levels of ATXN3 and focal adhesion Vinculin molecule were also verified in vivo. Collectively, our findings addressed the endothelial protective role of natural diterpenoid EKO, with emphasize of mechanism on ATXN3/c-fos/focal adhesion signaling pathway as well as oxygen stress suppression, implicating its therapeutic potential in alleviating vascular endothelium injury and diabetic retinopathy., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

In the last decade, the separation application based on aromatic stationary phases has been demonstrated in supercritical fluid chromatography (SFC). In this paper, four aromatic stationary phases involving aniline (S-aniline), 1-aminonaphthalene (S-1-ami-naph), 1-aminoanthracene (S-1-ami-anth) and 1-aminopyrene (S-1-ami-py) were synthesized based on full porous particles (FPP) silica, which were not end-capped for providing extra electrostatic interaction. Retention mechanism of these phases in SFC was investigated using a linear solvation energy relationship (LSER) model. The aromatic stationary phases with five positive parameters (a, b, s, e and d + ) can provide hydrogen bonding, π-π, dipole-dipole and cation exchange interactions, which belong to the moderate polar phases. The LSER results obtained using routine test solutes demonstrated that the aforementioned interactions of four aromatic stationary phases were influenced by the type and bonding density of the ligand, but to a certain extent. Furthermore, the LSER data verified that the S-1-ami-anth column based on full porous particles silica had higher cation exchange capacity (d + value), compared to the commercialized 1-AA column (based on the ethylene-bridged hybrid particles). The relationship between the d + value and SFC additive was quantitatively proved so as to regulate electrostatic interaction reasonably. This value was greatly increased by phosphoric acid, slightly increased by trifluoroacetic acid and formic acid, but significantly reduced by ammonium formate and diethylamine. Taking the S-1-ami-naph column as an example, better peek shape of the flavonoids was obtained after the addition of 0.1 % phosphoric acid in MeOH while isoquinoline alkaloids were eluted successfully within 11 min after adding 0.1 % diethylamine in MeOH. Combined with the unique π-π interaction and controllable electrostatic interaction, the aromatic stationary phases in this study have been proven to have expandable application potential in SFC separation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The packaging of fresh foods increasingly focuses on renewable and eco-friendly cellulose films, but their low dissolution efficiency and weak mechanical strength greatly limit their wide application, which also cannot be used for smart packaging. Here, a highly efficient synergistic chloride-salt dissolution method was proposed to fabricate robust, transparent, and smart cellulose films. Cellulose films with appropriate Ca 2+ concentration exhibited robust mechanical strength, better thermal stability, high transparency and crystallinity. The metal chelation of Ca 2+ with cellulose chains could induce cellulose chain arrangement during the cellulose regeneration process. Particularly, compared to pure cellulose films, the tensile strength and elongation at break of cellulose films with suitable Ca 2+ were increased by 167 % and 200 %, respectively. Moreover, optimal cellulose films can be used to reflect the quality of the fruit by detecting changes in ethanol gas. Hence, a novel strategy is presented to fabricate robust and transparent cellulose films with great potential application for smart packaging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Accurate prediction of heavy metal accumulation in soil ecosystems is crucial for maintaining healthy soil environments and ensuring high-quality agricultural products, as well as a challenging scientific task. In this study, we constructed a dataset containing 490 sets of multidimensional environmental covariate data and proposed prediction models for heavy metal concentrations (HMC) in a soil-rice system, EL-HMC (including RF-HMC and GBM-HMC), based on Random Forest (RF) and Gradient Boosting Machine (GBM) ensemble learning (EL) techniques. To reasonably evaluate the effectiveness of each model, Multiple linear and Bayesian regressions were selected as benchmark models (BM), and mean absolute error (MAE), root mean square error (RMSE), and determination coefficient R 2 were selected as evaluation indicators. In addition, sensitivity and spatial autocorrelation (SAC) analyses were used to examine the robustness of the model. The results showed that the R 2 values of RF-HMC and GBM-HMC for modeling available cadmium (Cd) concentrations in soil were 0.654 and 0.690, respectively, with an average increase of 48.0 % compared to the BMs. The R 2 values of RF-HMC and GBM-HMC for predicting Cd, lead (Pb), chromium (Cr), and mercury (Hg) concentrations in rice ranged from 0.618 to 0.824 and 0.645 to 0.850, respectively, with an average increase of 58.2 % compared with the BMs. The corresponding MAEs and RMSEs of RF-HMC and GBM-HMC had low error levels. Sensitivity analysis of the input features and the SAC of the prediction bias showed that the EL-HMC models have excellent robustness. Therefore, the EL technology-based prediction models for HMCs proposed herein are practical and feasible, demonstrating better accuracy and stability than the traditional model. This study verifies the application potential of EL technology in pollution ecology and provides a new perspective and solution for sustainable management and precise prevention of heavy metal pollution in farmland soil at the regional scale., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The development of an approach based on simultaneous supercritical fluid extraction-sample cleanup, followed by supercritical fluid chromatography/tandem mass spectrometry (SFE-SFC-MS/MS) was as a tool for the extraction, separation and characterization of indole alkaloids of Uncaria rhynchophylla. A two-step SFE method was designed. A mixture of the U. rhynchophylla sample and an adsorbent named C18SCX with the ratio of 1:1 (w/w) was placed into an extraction cell. The extraction temperature was 40 °C and the pressure was 25 Mpa. In the first step, 10 % EtOH as the co-solvent was used to extract for 60 min, which was considered as a cleanup process to remove non-alkaloid components. In the second step, 0.1 % DEA was added to 10 % EtOH and it extracted for 60 min to obtain the desired extract. By introducing an additional adsorbent, the specificity of SFE towards alkaloids was greatly improved. An SFC-MS/MS method was then utilized for analysis of the SFE extract. Using 2-EP as stationary phase with the gradient elution of 0-10 min, 5-25 % EtOH (+0.05 % DEA) in CO 2 , column temperature 40 °C, and back pressure 13.8 Mpa, 10 peaks were separated within 8 min. Further MS/MS analysis confirmed that nine of the 10 peaks in the SFE extract were indole alkaloids. This study developed a supercritical fluid-based method specifically towards extraction and analysis of alkaloids, which is helpful to the study of alkaline compounds in complex samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This work develops a sustainable and global strategy to enhance fruit preservation efficacy. The dual-use composite coating or film comprises silk fibroin/cellulose nanocrystals (SF/CNC) with superior ductility through a synergistic plasticizing effect of glycerol and natural aloe-emodin powder (AE) as antimicrobial agents. To confirm our strategy, two common fruit preservation materials (edible surface coating-SCA-CS; packaging film-SCA-PF) and five different fruits (strawberries, bananas, apples, blueberries, and guavas) have been used. Moreover, SCA-CS coating with antibacterial and antioxidant activities formed an ultrathin layer on the fruit's surfaces with a thickness of 7.7 μm and could be easily washable. Therefore, bananas and strawberries' shelf-life with SCA-CS coating can be extended for 9 days and 6 days, respectively. The discharge water of SCA-CS has excellent biosafety in an indoor environment with no threat to plant health (microgreens bean sprouts germination as a case study). The plant exhibited positive results within 15 days, and leaves maintained their green color with a germination rate of 97.6 %. The toughness of SCA-PF film increased by 14,685.7 % with a water vapor transmission rate (WPTR) of 17 g mm m -2  day -1 , which confirms that the concept of SCA-PF film and SCA-CS coating are feasible to be used for fruit preservation/packaging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The present paper illustrates the versatility of the supercritical fluid chromatography (SFC) since, for the first time, four spirooxindole alkaloids (SOAs) including two pairs of isomers were separated by using two types of reversed-phase/ ion chromatography (RP/IC) mixed-mode stationary phases. Two mixed-mode stationary phases (C8SAX and C8SCX) was simultaneously provided dispersive and electrostatic interactions, which were suitable for the separation of such alkaloids. This study tried to provide an in-depth understanding of the SFC separation mechanism of the mixed-mode stationary phase through investigation of the impact of changes in mobile phase composition on alkaloids' retention behavior. On C8SAX, due to the strong electrostatic repulsion, there was a very narrow elution window of the alkaloids, of which behaviors were hardly affected by adding diethylamine in mobile phase. When adding formic acid or acidic ammonium formate, the prolonged retention time of alkaloids was presented because of the shielded effect of formate anions on the electrostatic repulsion. In particular, better peak shape and improved resolution were obtained by using acidic ammonium formate due to the deactivation of silanol groups by ammonium cations. On the other hand, both formic acid and acidic ammonium formate can strengthen the electrostatic attraction of C8SCX, causing difficult elution of the alkaloids. Ammonium cations from either the protonated diethylamine or the ionized ammonium formate, were considered as counter ions to effectively mask the electrostatic attraction of C8SCX, to significantly reduce the retention of alkaloids, but improve the resolution. Finally, utilizing two developed SFC methods, i.e., C8SAX with EtOH+ 10 mM acidic ammonium formate in CO 2 , or C8SCX with EtOH+0.1% diethylamine in CO 2 , the baseline separation of corynoxeine and isocorynoxeine, rhynchophylline and isorhynchophylline was achieved within 5 min., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

As transmembrane proteolytic enzyme, matrix metalloproteinase-14 (MMP14) regulates cell migration and cancer metastasis, but how it works at the single molecule level is unclear. Molecular localization is closely related to its function, and revealing its spatial assemble details is thus helpful to understand bio-function. Here, we apply aptamer probe and dSTORM to characterize MMP14 distribution. With demonstrating labeling properties of the probe, we investigate the specific distributed pattern of MMP14 on various cell membranes with different migratory capacities, and find that MMP14 mostly aggregate in clustering state, which becomes more significant with enhancing its hydrolysis efficiency on high-migratory cells. Lots of MMP14 are revealed to be co-localized with its substrate PTK7, and this colocalization decreases with weakening cell migration, suggesting that MMP14 may coordinate cell migration by altering its spatial relationship with substrate proteins. This work will promote a deep understanding of the roles of MMP14 in cell migration and cancer metastasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Urinary acetone in urine is produced from fat metabolism in human body, which can be accelerated in diabetic patients because of insufficient utilization and storage of glucose. In this study, we tried to develop a novel diagnosis method of type 2 diabetes (T2D) through sniffing urinary acetone by a proton transfer reaction mass spectrometry (PTR-MS). A total of 180 T2D patients and 180 healthy volunteers were recruited from three hospitals for multicenter study. Urine samples were collected in the morning when donators were fasting and stored in glass bottles. Acetone in the headspace of these bottles was qualitatively and quantitatively detected by the PTR-MS in 8 h. Using a threshold of 690.1 ppbv, a diagnostic model was established using urinary acetone with an accuracy of 81.3% (sensitivity: 73.3%, specificity: 89.3%) in hospital Ⅰ. In the verification studies, the accuracies were 92.5% (sensitivity: 88.7%, specificity: 96.2%) in hospital Ⅱ and 83.7% (sensitivity: 76.9%, specificity: 90.4%) in hospital Ⅲ, respectively. The accuracy is comparable to that of clinically used diagnosis methods, fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), and glycosylated hemoglobin A1c (HbA1c) test. The sensitivity for 35 newly diagnosed patients was 85.7%. The newly developed technology is completely non-invasive and much more rapid than clinical FPG, OGTT, and HbA1c tests. It has a promising prospect in clinical use. But the applicability in different human races still need more validations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas., Patients and Methods: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world., Results: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance., Conclusion: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers., Competing Interests: Disclosure BL, GW, YX, SC, SC, and ZZ declare employment in Burning Rock Biotech. All other authors have declared no conflicts of interest. Data sharing The authors declare that relevant data supporting the findings of this study are available within the paper and its Supplementary files. Due to ethical and privacy concerns, we are unable to publish the patient-level data in our study, of which readers may contact the corresponding authors for the access for non-commercial purposes., (Copyright © 2023. Published by Elsevier Ltd.)

Phosphotungstic acid covered with CeO 2 hollow nanospheres (CeO 2 @PTA HNSs) has been successfully prepared by a simple method, serving as highly efficient nanozymes for ascorbic acid (AA) colorimetric sensing. In virtue of the unique hollow nanostructures, oxide defects and synergic effects of CeO 2 and PTA, the proposed CeO 2 @PTA HNSs present remarkable intrinsic oxidase-like activity and help capture electrons from 3,3',5,5'-tetramethylbenzidine (TMB). Due to the reducibility of AA, a promising colorimetric sensing platform based on CeO 2 @PTA HNSs has been constructed for quantitative analysis of AA. The present colorimetric detection exhibits a low limit of detection, good selectivity and stability, as well as reliability in orange juice and milk. This work provides a simple surface defect engineering to prepare high-performance oxidase mimics in the application of colorimetric biosensing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: This study evaluated adebrelimab (a programmed death-ligand 1 antibody) plus nab-paclitaxel and carboplatin as perioperative treatment for resectable NSCLC., Methods: Eligible patients had resectable stage II to III NSCLCs without driver gene. Patients received neoadjuvant treatment with three cycles of intravenous adebrelimab (20 mg/kg on day 1), nab-paclitaxel (100 mg/m 2 on days 1, 8, and 15), and carboplatin (area under the curve 5 mg/mL per min on day 1), of each 21-day cycle before surgical resection, and followed by 16 cycles of adebrelimab (20 mg/kg on day 1 in 3 wk) adjuvant treatment. The primary end point was major pathologic response (MPR) per blinded independent pathologic review., Results: A total of 37 patients were enrolled and received planned neoadjuvant therapy. There were 34 patients (91.9%) who underwent surgery. As of data cutoff on January 25, 2022, 19 of the 37 patients (51.4%, 95% confidence interval [CI]: 35.9-66.6) achieved MPR per blinded independent pathologic review and 11 patients (29.7%, 95% CI: 17.5-45.8) achieved pathologic complete response. Furthermore, 26 patients (70.3%, 95% CI: 54.2-82.5) had an objective response per Response Evaluation Criteria in Solid Tumors version 1.1. The 12-month event-free survival rate was 77.8% (95% CI: 54.1-90.3). In addition, 29 patients (78.4%) had grade greater than or equal to three treatment-related adverse events (AEs) and nine (24.3%) had treatment-related serious AEs. No treatment-related deaths occurred. Grade greater than or equal to three surgery-related AEs within 30 or 90 days after surgery were both reported in five patients (14.7%)., Conclusions: Adebrelimab plus nab-paclitaxel and carboplatin as perioperative therapy led to a substantial proportion of MPR and high resectability, with manageable toxicities. On the basis of the phase 1b results, phase 3 trial was initiated., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Silicosis is a diffuse fibrotic lung disease in which excessive inflammatory responses are triggered by silica exposure. Pyroptosis, a pro-inflammatory mode of programmed cell death, is mediated by gasdermin and may play a pivotal role in the development of silicosis. The caspase-1 inhibitor, VX-765, was used in vivo and in vitro to investigate the effects of silica-induced early inflammatory injury and later lung fibrosis. Our findings show that VX-765 reduces inflammatory lung injury by inhibiting silica-induced pyroptosis of alveolar macrophages in a silicosis mouse model. VX-765 limits the infiltration of inflammatory M1 alveolar macrophages, decreasing expression of inflammatory cytokines, including IL-1β, TNF-α, IL-6, CCL2, and CCL3, and down-regulating endogenous DAMPs and inflammatory immune-related cell pattern recognition receptors TLR4 and NLRP3. Furthermore, VX-765 alleviates fibrosis by down-regulating α-smooth muscle actin (α-SMA), collagen, and fibronectin. In this study, we illustrate that Alveolar macrophages pyroptosis occur in the early stages of silicosis, and VX-765 can alleviate the development of silicosis by inhibiting the pyroptosis signaling pathway. These results may provide new insight into the prevention and treatment of early-stage silicosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The long-term consumption of heavy metal-rich rice can cause serious harm to human health. However, the existing health risk assessment (HRA) can only be performed after the rice has been harvested, and this approach belongs to a passive and lagging pattern. This study is the first to explore the feasibility of health risk (HR) prediction by proposing the indirect model CNNHR-IND and the direct model CNNHR-DIR based on the convolutional neural network (CNN) technology. The dataset included 390 pairs of soil-rice samples collected from You County, China, with 17 environmental covariates. The R 2 values for CNNHR-IND for non-carcinogenic and carcinogenic risks were 0.578 and 0.554, respectively, and those for CNNHR-DIR were 0.647 and 0.574, respectively. The results demonstrated that both models performed well, especially CNNHR-DIR had a higher estimation accuracy. The spatial autocorrelation analysis indicated that CNNHR-DIR exerted no systematic bias in the prediction results for health risks, confirming the rationality of the CNNHR-DIR model. The sensitivity analysis further confirmed the generalizability and robustness of CNNHR-DIR. This study proved the feasibility of HR prediction and the potential of CNN technology in HRA, and is significant regarding early risk warnings of rice planting and the sustainable development of public health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Children are susceptible to pneumonia, which affects their growth and development. Immune disorders and unrepaired alveolar mucosal epithelium following pneumonia cause chronic lung injury. The mechanism of chronic lung injury is unknown and lacks animal models for reference. Therefore, we developed a chronic lung injury young mouse model to simulate the pathological process of children. 3-week-old mice were intratracheal instillation of lipopolysaccharide (LPS) every other day for six weeks. Consequently, the histopathology showed damaged integrity of lung tissue, fibrosis, and abnormally distributed alveolar epithelial cells. The total protein concentration in bronchoalveolar lavage fluid (BALF) was increased, alveolar epithelial type (AT) I cells were abnormal distribution, and AT II cells were reduced. The phosphorylation levels of IKBα and the expression levels of NF-κB p65 in lung tissue were up-regulated. In serum and BALF, the IL-6 was oversecretion, nitric oxide (NO) and superoxide dismutase (SOD) were perturbed secretion, oxidative stress imbalance. In addition, blood viscosity, plasma viscosity, and erythrocyte sedimentation rate (ESR) indexes in hemorheology were increased. In conclusion, it is feasible to construct the mouse model of chronic lung injury, and AT I and AT Ⅱ cells were imbalanced, which paves the way for further investigations on the pathogenesis of chronic lung injury and the efficacy of novel treatments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Accurate prediction of the concentration of heavy metals is of great significance for assessing the quality of agricultural products and reducing health risks. However, the complexity and interconnectivity of the farmland ecosystem restricts the improvement of the prediction accuracy of traditional methods. This research explored the application potential of graph neural network (GNN) technology, which can extract and learn information in large-scale networks in detail, in the field of heavy metal prediction for the first time. In this study, a heavy metal prediction model for rice, CoNet-GNN, was proposed with 17 environmental factors as input variables using the co-occurrence network and GNN. Experimental results using a dataset from a field study showed that the R 2 of CoNet-GNN for predicting Cd, Pb, Cr, As, and Hg had outstanding values of 0.872, 0.711, 0.683, 0.489, and 0.824, respectively. Sensitivity analysis further indicated that CoNet-GNN had good stability and robustness. Compared with random forest, gradient boosting, and multilayer perceptron, CoNet-GNN made a remarkable improvement to the prediction accuracy of all studied heavy metals. Therefore, CoNet-GNN can effectively simulate the rich relationships and laws between various factors in the soil-rice system and effectively characterize the influence diffusion path. Furthermore, it provides new ideas for heavy metal prediction based on network research methods and expands the technical scope of heavy metal evaluation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: PPI-refractory gastroesophageal reflux disease (RGERD) is characterized as the existence of reflux symptoms resistant to optimized PPI treatment. Alleviated mucosal integrity has been regarded as one of the mechanisms of RGERD., Methods: RNA sequencing analysis and GSEA were performed. Human biopsy samples, cell lines, and rat models were recruited. Trans-epithelial electrical resistance (TEER) was tested and a FITC-dextran flux assay was performed to detect barrier permeability. Tissue morphology was evaluated using HE staining, while gene expression was measured by qRT-PCR, western blotting, flow cytometry, immunofluorescence, immunohistochemistry, and chromatin immunoprecipitation (ChIP) analysis., Results: The tight junction protein Claudin-1 is significantly weakened in the RGERD epithelium, while levels of EZH2-mediated H3K27me3 were increased. Forced EZH2 expression in epithelial cells led to H3K27me3 accumulation and Claudin-1 suppression, which consequently caused epithelial barrier dysfunction. Notably, studies on esophagogastroduodenal anastomosis (EGDA) rat models showed the attenuation of Claudin-1 level and barrier function could be rescued by an Ezh2 inhibitor GSK126. ChIP analysis followed by qPCR (ChIP-qPCR) revealed H3K27me3 suppressed CLDN1 via accumulating at the TSS area., Conclusion: For the first time, we explored the attenuated tight junction of RGERD, demonstrating a potential underlying mechanism that EZH2-mediated H3K27me3 could impair esophageal epithelial barrier function by suppressing the transcription of CLDN1., Competing Interests: Conflict of Interest None declared., (Copyright © 2021. Published by Elsevier Ltd.)

Simultaneous removal of polycyclic aromatic hydrocarbons (PAHs) in the process of enhancement of sludge dewaterability via oxidation of hydroxyl radicals (•OH) and flocculation of Fe 3+ by Fe 2+ -catalyzing O 3 were investigated as a novel research focus. The results showed that capillary suction time (CST) and water content of dewatered sludge cake (Wc) were reduced from 57.9 s and 85.1% to 13.6 s and 69.65% under the optimum usage of 60 mg/g dry solids (DS) O 3 and 80 mg/g DS FeSO 4 , respectively. The relevant dewatering mechanism of Fe 2+ -catalyzing O 3 treatment was elucidated. It was found that extracellular polymeric substances-bound (EPS-bound) and intracellular water was dramatically released through destroying sludge cells and EPS gel-like structure by produced •OH. In addition, the results of X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) and 13 C NMR spectroscopy revealed that •OH oxidized and mineralized hydrophilic organic matters intensifying hydrophobicity of sludge surface. Moreover, Fe 3+ generated by oxidation of Fe 2+ agglomerated fragmented fine particles into large aggregates and decreased exposure of hydrophilic sites by neutralizing negative charge, which promoted water-solids separation. Meanwhile, sludge surface roughness was decreased which was determined by material type upright confocal laser microscope (CLM). As a consequence, •OH and Fe 3+ were mainly responsible for enhancement of sludge dewaterability. Moreover, more than 40% of removal rate of PAHs was accomplished by Fe 2+ -catalyzed O 3 treatment mitigating the environmental risks of PAHs spread., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Dewatering treatment is an essential step to diminish sludge volume, cut down transportation costs, and improve subsequent disposal efficiency. In this study, ozone-peroxymonosulfate (O 3 /PMS) oxidation process was employed to ameliorate sludge dewaterability. Sludge capillary suction time (CST) and water content (Wc) of dewatered sludge cake could reduce from 70.5 s and 81.93% to 26.7 s and 65.65%, respectively, under the optimal dosage of 30 mg/g TS O 3 and 0.4 mmol/g TS PMS. The increased sludge zeta potential, particle size, and fluidity promoted sludge dewatering performance apparently. The decreased hydrophilic, fluorescent EPS components and proteins/peptides-like + Lipids percentage in EPS as well as the ratio of α-helix/(β-sheet + random coil) of treated EPS protein secondary structure was greatly responsible for the enhanced sludge dewaterability. SO 4 - and OH were detected in ozone-peroxymonosulfate process to crack sludge flocs, eliminate hydrophilic substances and liberate bound water. Moreover, the concentrations of both heavy metals and polycyclic aromatic hydrocarbons (PAHs) of sludge after O 3 /PMS conditioning were decreased, and the stability and toxicity of heavy metals were also reduced, except Zn. In conclusion, this work offered a comprehensive insight based on ozone-peroxymonosulfate (O 3 /PMS) advanced oxidation for improving the sludge dewaterability and environmental implication., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The charismatic giant panda (Ailuropoda melanoleuca) is an iconic species of wildlife conservation worldwide. As the most effective measure to protect giant pandas and their habitats, China has established 67 giant panda nature reserves (GPNR) during the last five decades, which also bring benefits to many sympatric medium- and large-bodied mammals (MLM). To better inform the planning of the GPNR network with the view of preserving regional MLM diversity, we investigated the zeta diversity (a novel index to measure species compositional turnover considering the contributions of both rare and common species) patterns (i.e. zeta decline and retention rate curve) of MLMs across 40 GPNRs. The effects of species' body mass and conservation status on the zeta diversity patterns were tested. Further, we applied the multi-site generalized dissimilarity modelling (MS-GDM) framework to explore the impacts of environmental and geographic distances on MLM turnover. The results indicated that there are a core set of 17 MLM species sympatric with the giant panda in the GPNRs. Species' body mass can affect the patterns of zeta decline and retention rate curves, and the number of large-bodied species shared by multiple GPNRs is higher than that of medium-bodied species across zeta orders. The MS-GDM revealed the important roles of difference in habitat heterogeneity and spatial distance between GPNRs in driving MLM turnover. Consequently, we advocate maintaining and increasing the diversity of (natural) habitats in GPNRs to protect giant panda's sympatric MLM diversity. The government should consider optimizing the GPNR network (e.g. incorporating multiple small GPNRs into one single large reserve) to capture the most turnover of MLMs, and the newly-established Giant Panda National Park is relevant to fulfilling this long-term goal., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Silicosis is a disease characterized by extensive lung nodules and fibrosis caused by the prolonged inhalation of silica in occupational settings. However, the molecular mechanism of silicosis development is complex and not fully understood. Furthermore, the role of necroptosis, a death receptor-mediated and caspase-independent mode of inflammatory cell death, is not well understood in silicosis. Here, we demonstrate that the necroptotic signaling pathway of macrophages is significantly activated in the lungs of silicosis mouse models. Meanwhile, increased M1 macrophage infiltration and up-regulation of pro-inflammatory cytokines (TNF-α, IL-6) were observed in our silicosis model. Notably, the expression of the pro-fibrotic factor, TGF-β1, and fibrosis biomarkers α-SMA and collagen I were also unregulated; however, these phenomena were recovered by Nec-1, an inhibitor specific for RIP1 kinase-dependent necroptosis. We conclude that macrophage-mediated necroptosis promotes the progression of silicosis by enhancing lung inflammatory responses and fibrogenesis in a mouse model of silicosis. These findings provide new insights for drug discovery and clinical treatment of silicosis., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

The separation of structural analogues in natural products has always been one of the challenges in separation science, where supercritical fluid chromatography (SFC) with chiral stationary phases (CSPs) is an unconventional but potential solution. In this study, a preparative two-dimensional chiral SFC (2D cSFC) method that was established with two kinds of CSPs was applied in the isolation of the aliphatic acid derivatives in Piper kadsura (P. kadsura). The RPLC unseparated peaks of two samples A and B of P. kadsura were evenly scattered on the CSP-1 column while they clustered into two groups on the CSP-2 column by SFC. There was impressively complementary selectivity between CSP-1 and CSP-2, which were used for construction of 2D cSFC. The first dimension ( 1 D) separation with CSP-1 fractionated the sample A into six parts by a heart-cutting method and the sample B into nine parts for a comprehensive 2D analysis; then 29 and 71 peaks were respectively found in these parts in the second dimension ( 2 D) separation with CSP-2. Further through 2 D preparative separation, 19 high purity components were obtained, and the chemical structures of two of them were confirmed, including a novel unsaturated aliphatic acid compound (8Z,10Z)-12-methoxyheptadeca-8,10-dienoic acid and a known octadecadienoic acid lactone Lactariolide. The 2D cSFC method presented the superiority of separating the achiral compounds of complex samples., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Owing to modern lifestyles and increasing amounts of medical intervention, clinical infections caused by conditionally pathogenic fungi are becoming increasingly serious. Among these, Candida albicans is the most common. Therefore, the rapid and accurate detection of this pathogenic fungus is important to guiding the selection of clinical therapeutic agents. Recombinase polymerase amplification (RPA) combined with lateral flow strips (LFS) is a promising molecular detection method with the advantages of rapidity, simplicity of operation and high sensitivity. However, this simplicity brings with it the inherent and non-negligible risk of false-positive signals from primer-dimers. In this study, primer-dependent artifacts were eliminated by using probes in the RPA reaction, introducing specific base substitutions to the primer and probe sequences and analyzing and screening the formation of primer-probe complexes. These measures were rigorously tested for efficacy, leading to the creation of an improved RPA-LFS system. The standardized method enabled the specific detection of C. albicans within 25 min at 37 °C without interference. The system had a detection limit of 1 CFU per reaction without DNA purification or 10 2  fg genomic DNA/50 μL. The detection sensitivity was not affected by the presence of other fungal DNA. The RPA-LFS method can therefore be used to detect clinical samples, and the results are accurate and consistent in comparison with those obtained using quantitative PCR. This study provides a paradigm for eliminating the risk of false-positive primer dimers in isothermal amplification assays and establishes a simple and easy method for the detection of C. albicans., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The tension band technique is the most common method for internal fixation of transverse patellar fractures. Titanium cable and high-strength sutures have been successfully applied in this treatment; however, few studies have compared the Nice knot technique using sutures with the standard cable technique. Whether the suture technique (Nice knot) provides preferable results compared with those of the cable technique is unclear., Methods: Forty patients with transverse patellar fractures participated in this study. Twenty patients underwent sutures tension band fixation (Nice knot), and the others were managed with cable tension bands. All patients were followed up at 1, 3, 6, and 12 months. Pain was measured by VAS scores, flexion and extension of the knee were measured in degrees by goniometry, and knee function was evaluated using the Böstman clinical grading scale., Results: The two groups had equal distributions in age, gender, injured side, and fracture classification. The mean operation time in the suture group was shorter (55.75±9.77 minutes versus 64.25±9.63 minutes). The VAS score was comparable in the two groups at the 1-month, 3-month, and 6-month follow-ups; however, the score was lower at 12 months postoperatively in the suture group (P=0.037). No significant difference was found in flexion, extension, Böstman score, or fracture healing time in either group (P>0.05). Postoperative complications were higher in the cable group (9 versus 2) (P = 0.031) but were mostly related to symptomatic soft tissue irritation., Conclusion: The suture tension band technique using braided polyester nonabsorbable sutures tied with Nice knot was as effective as the cable tension band technique for transverse patellar fracture management. However, more convenient operations, less cost and fewer complications were found in suture fixation (Nice knot)., Competing Interests: Declaration of Competing Interest On behalf of all authors, the corresponding authors state that there is no conflict of interest., (Copyright © 2021. Published by Elsevier Ltd.)

The mechano-bactericidal property of nanostructured surfaces has become the focus of intensive research toward the development of a new generation of antibacterial surfaces, especially in the current era of spreading antibiotic resistance. However, the mechanisms underlying nanostructured surfaces mechanically damaging bacteria remain unclear, which ultimately limits translational potential toward real-world applications. Using finite element simulation technique, we developed the three-dimensional thin wall with turgor pressure finite element model (3D-TWTP-FEM) of bacterial cell and verified the reliability of this model by the AFM indentation experiment simulation of the cell, and the cell model is able to simulate suspended bacterial cell and the process of cell adhering to the flat and nanopillar surfaces. Since bacterial cells suffer greater stress and deformation on the nanopillar surfaces, a two-stage model of the elastic and creep deformation stage of the cells on the nanostructured surfaces was developed. The calculations show that the location of the maximum stress/strain on the cells adhered to the nanopillar surfaces is at the liquid-cell-nanopillar three phase contact line. The computational results confirmed the ability of nanostructured surfaces to mechanically lyse bacteria and gave the effect of nanopillar geometry on the efficiency and speed of bacterial cell rupture. This study provides fundamental physical insights into how nanopillar surfaces can serve as effective and fast mechanical antimicrobial materials., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Icotinib has provided survival benefits for patients with advanced, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We aimed to compare icotinib with chemotherapy in patients with EGFR-mutant stage II-IIIA NSCLC after complete tumour resection. Here, we report the results from the preplanned interim analysis of the study., Methods: In this multicentre, randomised, open-label, phase 3 trial done at 29 hospitals in China, eligible patients were aged 18-70 years, had histopathogically confirmed stage II-IIIA NSCLC, had complete resection up to 8 weeks before random assignment, were treatment-naive, and had confirmed activation mutation in exon 19 or exon 21 of the EGFR gene. Participants were randomly assigned (1:1) with an interactive web-based response system to receive either oral icotinib 125 mg thrice daily for 2 years or four 21-day cycles of intravenous chemotherapy (vinorelbine 25 mg/m 2 on days 1 and 8 of each cycle plus cisplatin 75 mg/m 2 on day 1 of each cycle for adenocarcinoma or squamous carcinoma; or pemetrexed 500 mg/m 2 plus cisplatin 75 mg/m 2 on day 1 every 3 weeks for non-squamous carcinoma). The primary endpoint was disease-free survival assessed in the full analysis set. Secondary endpoints were overall survival assessed in the full analysis set and safety assessed in all participants who received study drug. This trial is registered with ClinicalTrials.gov, NCT02448797., Findings: Between June 8, 2015, and August 2, 2019, 322 patients were randomly assigned to icotinib (n=161) or chemotherapy (n=161); the full analysis set included 151 patients in the icotinib group and 132 in the chemotherapy group. Median follow-up in the full analysis set was 24·9 months (IQR 16·6-36·4). 40 (26%) of 151 patients in the icotinib group and 58 (44%) of 132 patients in the chemotherapy group had disease relapse or death. Median disease-free survival was 47·0 months (95% CI 36·4-not reached) in the icotinib group and 22·1 months (16·8-30·4) in the chemotherapy group (stratified hazard ratio [HR] 0·36 [95% CI 0·24-0·55]; p<0·0001). 3-year disease-free survival was 63·9% (95% CI 51·8-73·7) in the icotinib group and 32·5% (21·3-44·2) in the chemotherapy group. Overall survival data are immature with 14 (9%) deaths in the icotinib group and 14 (11%) deaths in the chemotherapy. The HR for overall survival was 0·91 (95% CI 0·42-1·94) in the full analysis set. Treatment-related serious adverse events occurred in two (1%) of 156 patients in the icotinib group and 19 (14%) of 139 patients in the chemotherapy group. No interstitial pneumonia or treatment-related death was observed in either group., Interpretation: Our results suggest that compared with chemotherapy, icotinib significantly improves disease-free survival and has a better tolerability profile in patients with EGFR-mutant stage II-IIIA NSCLC after complete tumour resection., Funding: Betta Pharmaceuticals TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests LM and LD are employees of Betta Pharmaceuticals, which provided funding for the study. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Copper intrauterine device is one of the most adopted contraceptive methods with high effectiveness (over 99 %), low cost, spontaneous reversibility and long-lasting usage. However, the side effects induced from the initial burst release of copper ions (Cu 2+ ) hinder the continuation of the Cu-IUD made of Coarse-Grained Copper (CG Cu). We proposed to tailor the bio-corrosion behaviors of better control of Cu 2+ release via the addition of bioactive Mg into the Ultra-Fine Grained (UFG) Bulk Cu. Thus, UFG bulk Cu with 0.4 wt.% Mg was produced via equal-channel angular pressing. The microstructures of the UFG Cu-0.4Mg was observed using electron backscatter diffraction and transmission electron microscopy techniques. The in vitro long-term corrosion behaviors in simulated uterine fluid, cytotoxicity to four cell lines, in vivo biocompatibility and contraceptive efficacy were all studied on CG Cu, UFG Cu and UFG Cu-0.4Mg materials. The results demonstrate that both the ultrafine grains and the addition of bioactive Mg into Cu contribute to the suppression of the burst release of Cu 2+ in the initial stage and the maintenance of high level Cu 2+ in long-term release. Moreover, the UFG Cu-0.4Mg also exhibited much improved cell and tissue biocompatibility from both the in vitro and in vivo evaluations. Therefore, the contraceptive efficacy of UFG Cu-0.4Mg is still maintained as high as the CG Cu and UFG Cu while the side effects are significantly eased, suggesting the high potential of the UFG Cu-0.4Mg alloy as a new upgrading or alternative material for Cu-IUD. STATEMENT OF SIGNIFICANCE: The side effects from burst release of Cu 2+ at the initial implantation stage of Cu-containing intrauterine devices (Cu-IUD) is one of the main drawbacks of these devices. In this work, an ultra-fine-grained Cu (UFG Cu) alloyed with a low amount of bioactive Mg was used for a Cu-IUD. The UFG Cu-0.4Mg alloy exhibited suppressed burst release of Cu 2+ at initial implantation, while active Cu 2+ release for long-term usage was maintained, comparable to coarse-grained pure Cu. Furthermore, the UFG Cu-0.4Mg alloy displayed significantly improved biocompatibility with human uterus cells and a much decreased inflammatory response within the uterus. Therefore, the side effects from Cu-IUD were eased, while high antifertility efficacy of the UFG Cu-0.4Mg alloy was maintained. The UFG Cu-0.4Mg alloy is promising for Cu-IUD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Significant advances have been achieved in the research evaluating Zn and its alloys as degradable metallic biomaterials mainly for application in bone and blood vessels. In the present study, the degradation behaviors of Zn-0.1Li and Zn-0.8Mg alloys in simulated uterine fluid (SUF) were systematically investigated for 300 days. In vitro viability assays were conducted in different uterine cells (HUSMCs, HEECs, and HESCs), and histological examination after the in vivo implantation into the uterine cavity was performed using pure Zn as control. The immersion test results indicated that both Zn-0.1Li and Zn-0.8Mg alloys exhibited better corrosion resistance than pure Zn, with Zn 3 (PO 4 ) 2 ⋅4H 2 O and CaZn 2 (PO 4 ) 2 ⋅2H 2 O being the main corrosion products detected in the SUF in addition to ZnO. The cell cytotoxicity assays revealed that Zn-0.1Li and Zn-0.8Mg exhibited better cytocompatibility than Zn. Moreover, the in vivo experiments demonstrated that the Zn-0.1Li and Zn-0.8Mg alloys induced less inflammation in the uterine tissue than pure Zn, with CaCO 3 and Zn(HPO 4 )⋅3H 2 O being the major biocorrosion products in addition to ZnO. According to these results, zinc alloys appear to be suitable potential candidate materials for future intrauterine biomedical devices., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: The purpose of this study was to evaluate the accuracy of minute ventilation (V˙ E ) estimation using a novel method based on a non-linear algorithm coupled with cycle-based features. The experiment protocol was well adapted for remote health monitoring applications by exploiting data streams from respiratory magnetometer plethysmography (RMP) during different physical activity (PA) types. Methods Thirteen subjects with an age distribution of 24.1±3.4 years performed thirteen PA ranging from sedentary to moderate intensity (walking at 4 and 6 km/h, running at 9 and 12 km/h, biking at 90 W and 110 W). In total, 3359 temporal segments of 10s were acquired using the Nomics RMP device while the iWorx spirometer was used for reference V˙ E measurements. An artificial neural network (ANN) model based on respiration features was used to estimate V˙ E and compared to the multiple linear regression (MLR) model. We also compared the subject-specific approach with the subject-independent approach. Results The ANN model using subject-specific approach achieved better accuracy for the V˙ E estimation. The bias was between 0.20±0.87 and 0.78±3 l/min with the ANN model as compared to 0.73±3.19 and 4.17±2.61 l/min with the MLR model. Conclusion Our results demonstrated the pertinence of processing data streams from wearable RMP device to estimate the V˙ E with sufficient accuracy for various PA types. Due to its low-complexity and real-time algorithm design, the current approach can be easily integrated into most remote health monitoring applications coupled with wearable sensors., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

An efficient luminous and electronic energy transmission BiOBr based near-infrared (NIR) responsive heterojunction photocatalyst was successfully fabricated through growing BiOBr nanosheets on the superficial layer of the SrF 2 -Bi 2 O 3 -B 2 O 3 /Yb 3+ ,Tb 3+ (SBBF) upconversion glass-ceramic (GC) via a facile in-situ etching GC method (FIEG). A high norfloxacin (NOR) degradation rate of 56% was obtained under 180 min NIR light irradiation for the NIR GC photocatalyst (SBBF/BiOBr-10), and it possesses much enhanced photocatalytic activity compared with that of pure BiOBr under UV-vis-NIR light irradiation. Wherein six intermediate products were identified in the NOR photodegradation process and the possible degradation pathways were proposed. B 3+ , Yb 3+ and Tb 3+ ions in GC can be doped into BiOBr layer during the FIEG process. The core-shell structure of the GC@BiOBr heterojunction photocatalyst is in favor of increasing charge transport and reducing the recombination rate of excited carriers, and it efficiently harvests NIR photons to emit UV and visible light upconversion emissions, which can be utilized during the photocatalysis process. The photocatalyst can be facilely regenerated via HBr etching again, moreover, the low-cost and less time requirement promote the possibility of large-scale fabrication of the efficient photocatalysts., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Abstract: Heavy metals are an indispensable part of industrial and agricultural development. As the cradle of China's industry and an important province for agricultural production, Jilin Province has been an area of concern about heavy metal pollution in the local environment and grains. In this study, we focused on four heavy metals that are harmful to humans: arsenic (As), cadmium (Cd), methylmercury (MeHg), and inorganic arsenic (iAs). We determined the contents of these metals in 341 grain samples by using graphite furnace atomic absorption spectrometry and liquid chromatography-atomic fluorescence spectrometry and compared our results with the limit value of national standards. To evaluate the potential risk to human health, we determined the target hazard quotient and hazard index. Heavy metals were detected at these rates, from high to low: Cd (48%) > iAs (20.8%) > MeHg (4.6%) > Pb (3%). Most of these values are far below the limit of national standards. The target hazard quotient and hazard index were both smaller than 1; thus, we conclude that heavy metal pollution in grains in Jilin Province is not serious and that people are not at high risk from heavy metals in grains., (Copyright ©, International Association for Food Protection.)

Introduction: The prognostic effect and mechanism of skip N2 lung cancer remain unclear. Our study aimed to elucidate the influence of skip N2 on overall survival (OS) and disease-free survival (DFS) compared with N1 and non-skip N2 in patients with lung adenocarcinoma., Patients and Methods: Patients with lung adenocarcinoma and lymph node involvement between May 2011 and December 2015 were retrospectively analyzed. The outcomes of skip N2 patients were compared with N1 and non-skip N2 patients. Prognosis was further investigated according to the N status in different adenocarcinoma subtypes. Univariate and multivariate analyses were carried out to define independent risk factors for OS and DFS., Results: A total of 456 patients with lung adenocarcinoma, 169 with N1 disease, 81 with skip N2 disease, and 206 with non-skip N2 disease, were enrolled in this study. All tumors were invasive adenocarcinoma, and the predominant subtypes were acinar in 252, papillary in 42, solid in 119, micropapillary in 20, and invasive mucinous adenocarcinoma in 23 patients. The DFS and OS of N1 and skip N2 diseases were similar and significantly better than those of patients with non-skip N2 disease. The prognosis according to lymph node status was significantly different in acinar-predominant subtypes in terms of both OS and DFS., Conclusions: Skip N2 disease has a similar prognosis to N1 disease and is significantly better than that of non-skip N2 disease in relation to OS and DFS. Skip N2 has a prognostic advantage in patients with the acinar-predominant subtype., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Seven rare oxylipins, siegesbeckins A-G (1-7) representing further bioactive constituents different from the general terpenyl compounds found in Siegesbeckia species, have been obtained from the aerial parts of Siegesbeckia glabrescens. These isolates were identified to be a series of methyl 4-methylpentanoates incorporating fatty acid moieties of different chain lengths, based on spectroscopic techniques, and their absolute configurations were determined via chemical degradation and comparison of experimental and theoretically calculated ECD spectra. With respect to bioactivity, antibacterial, anti-inflammatory and cytotoxic properties of selected compounds were evaluated. Compounds 1 and 5 showed moderate antibacterial activity against two Gram-positive bacteria with MIC values of 4.3 μg/mL, while 3 showed no pronounced activity in these assays., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declare., (Copyright © 2020. Published by Elsevier B.V.)

As an essential section before final sludge disposal, sludge dewatering has currently been one of the focus issues. In this study, an innovative Fe 2+ /persulfate/tannic acid (TA) process was verified to further strengthen systemic efficacy on enhancing sludge dewaterability, compared with the conventional Fe 2+ /persulfate process. With the efficient TA/Fe 2+ (molar ratio) of 0.25 added in Fe 2+ (0.3 mmol/gTS (total solid))/persulfate (0.6 mmol/gTS) process, sludge dewaterability was enhanced remarkably. Capillary suction time, specific resistance to filtration, and water content of dewatered sludge cake were further reduced by 61.5%, 35.3%, and 6.4% than these in Fe 2+ /persulfate. Sludge supernatant viscosity was further reduced by 86.7% due to the more removal of extracellular polymeric substances (EPS). The secondary structure of EPS protein changed apparently and fluorescent components of EPS decreased distinctly. Sludge functional group contents were observed to be lower. TA effectually increased sludge particle size and heightened sludge flocculability, rendering the large and compact aggregations. Moreover, TA accelerated the recovery of Fe 2+ , facilitating persulfate activation to generate more SO 4 ·- and · OH for EPS disruption and cell lysis in the conditioning system. These findings provided a novel approach based on the Fe 2+ /persulfate process in sludge treatment for desirable dewaterability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Spinal cord injury (SCI) is a destructive polyneuropathy that can result in loss of sensorimotor function and sphincter dysfunction, and even death in critical situations. MicroRNAs (miRs) are a series of non-coding RNA molecules that are involved in transcriptional regulation. Previous studies have demonstrated that modulation of multiple miRs is involved in neurological recovery after SCI. However, the functions of miR-340-5p in SCI remain uncertain. Therefore, we probed the therapeutic effect and mechanism of miR-340-5p in microglia in vitro and in vivo in SCI rats. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were employed to examine the alterations in miR-340-5p and P38 levels in SCI rats. miR-340-5p targets in microglia were ascertained using luciferase reporter assays, immunofluorescence analyses, and western blotting. We also established an SCI model and administered miR-340-5p. The effects of miR-340-5p on the amelioration of inflammation, oxidative stress, and apoptosis following SCI were assessed using immunofluorescence, immunohistochemistry, and histological analyses. Finally, locomotor function recovery was determined using the Basso, Beattie, Bresnahan rating scale. In our study, the expression profiles and luciferase assay results clarified that P38 was a target of miR-340-5p, which was associated with activation of the P38-MAPK signaling pathway. Elevation of miR-340-5p decreased P38 expression, subsequently inhibiting the inflammatory reaction. SCI-induced secondary neuroinflammation was relieved under miR-340-5p treatment. Moreover, by controlling neuroinflammation, the increased levels of miR-340-5p might counter oxidative stress and reduce the degree of apoptosis. We also observed decreasing gliosis and glial scar formation and increasing neurotrophin expression at the chronic stage of SCI. Together, these potential effects of miR-340-5p treatment ultimately improved locomotor function recovery in SCI rats., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

At present, wastewater and sludge management departments are in urgent of the sludge deep-dewatering technique, which can substantially reduce sludge volume, enhance sludge calorific value and save costs. Ozonation pre-oxidation and chitosan (CT) re-flocculation conditioning have been verified to be an efficacious and environmental-friendly approach to realize sludge deep-dewatering. This paper focused on the novel insights into sludge properties under ozonation and CT conditioning. With 60 mg/gTS O 3 and 20 mg/gTS CT, the water content of the conditioned sludge cake satisfied the deep-dewatering level (<60%). The ozone dosage of 60 mg/gTS effectually enhanced the release of soluble COD and retained the inherent organic matters simultaneously, and subsequently, CT could further reduce extracellular biopolymers, especially proteins. Fluorescence analysis indicated that the protein-like substances were largely decomposed into fulvic acid-like and humic acid-like substances after ozonation, and CT could further remove humic acid-like components. Macromolecules were observed to form by CT combining with ozonated extracellular polymers. Low-field NMR technique monitored sludge water states and suggested that water movability weakened after ozonation and enhanced again through CT conditioning. SEM images reflected that CT was available as junction link for ozonated polymers to aggregate into large flocs. Furthermore, the calorific value of conditioned sludge cake increased and sludge cake drying time was saved pronouncedly. The findings provided the systematic and comprehensive insights into the sludge properties in pre-oxidation and re-flocculation conditioning, which would aid in a better understanding of the in-depth dewatering mechanism and developing new dewatering technique., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Concentrated leachate (CL) is commonly featured with high salt and dissolved organic matters (DOM). In this study, molecular transformation of DOM was revealed to identify the reactive mechanisms with (non-) radical reactive species in ozonation, electrolysis and E + -ozonation processes. Chlorine ions were efficiently activated into non-radical reactive chlorine species (RCS) with 245.7 mg/L, which was more dominant in electrolysis. Compared to ozonation, C •OH was increased from 2.6 × 10 -4 mg/L into 5.8 × 10 -4 mg/L and the generation of Cl•/ClO• could be concluded according to the decline of non-radical RCS in E + -ozonation process. For chromophoric and fluorescent DOM, aromatic compounds and polymerization degree dramatically decreased in E + -ozonation. Lipid-like and CRAM/lignin-like compounds were substantially degraded, as •OH and ClO•/Cl• shows an affinity towards oxygen-containing organic compounds via single electron transfer by attracting OH bonds. Especially, carbon/hydrogen/oxygen (CHO-containing) compounds were readily to be degraded with the removal efficiency of 92.5 %, 97.0 % and 98.4 % in electrolysis, ozonation and E + -ozonation, respectively. Moreover, nitrogen atoms have a negative effect on DOM degradation, and thus, carbon/hydrogen/nitrogen and carbon/hydrogen/nitrogen/sulfur (CHN- and CHNS-containing) compounds were considered as refractory compounds. This paper is expected to shed light on the synergetic effect in E + -ozonation and transformation of refractory DOM in CL treatment., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Mixed phenotype acute leukemia (MPAL) is a rare subtype of acute leukemia and its progressive genomic basis over time remains unclear. We aimed to investigate the longitudinal genomic evolution of MPAL from diagnosis to relapse., Methods: We performed whole genome sequencing (WGS) on bone marrow (BM) samples obtained at the four stages of this disease in a male patient with Philadelphia chromosome positive (Ph+) MPAL, including primary, complete cytogenetic remission (CCR), complete molecular remission (CMR), and relapse stage during the 3 year follow-up period., Results: 156 single-nucleotide variants (SNVs) and indels were detected, which exhibited distinctive evolutionary behaviors. Seventeen mutations disappeared quickly upon DCTER treatment and never came back. Seven mutations, although disappeared initially, reoccurred with the withdrawal of TKI treatment. Notably, ten mutations emerged in spite of the active DCTER chemotherapy. Moreover, copy number loss played critical roles in monitoring MPAL progression, displaying 7, 0, 0, and 383 losses at the stages of primary, CCR, CMR, and relapse respectively., Conclusion: This longitudinal genomic investigation of the Ph+ MPAL patient established one MPAL evolution model in which the primary tumor acquired additional variations leading to tumor relapse. Moreover, the event of copy number loss remained a valuable hallmark in the progression of MPAL., (Copyright © 2019. Published by Elsevier Inc.)

Sludge deep-dewatering, capable of reducing water content (Wc) of sludge cake under 60%, is one of the current hot topics in sludge treatment. In this study, a new environmentally friendly two-step approach of ozonation and chitosan (CT) conditioning was proposed and examined to be practicable for sludge deep-dewatering. With 60 mg/gTS ozone and 20 mg/gTS CT conditioning, sludge capillary suction time (CST) and Wc of the dewatered sludge cake decreased from 196.3 s and 84.7% of raw sludge to 15.8 s and 57.5%, respectively. Ozonation treatment could efficiently crack sludge flocs and cells, and release biopolymers, causing the decreases in viscosity, zeta potential and particle size. Subsequently, CT ameliorated the sludge dewaterability successfully by neutralizing negative charges and flocculating colloids to promote the spread of interstitial water. Furthermore, the contents of heavy metals (As, Cd, Cr, Ni, Pb and Zn) in conditioned sludge cake decreased obviously except Cu, but all detected heavy metals contents satisfied the A level of agricultural land (GB4284-2018). For chemical speciation of heavy metals, the proportions of the acid soluble/exchangeable state and the reductive state increased apparently, implying higher toxicity and bioavailability, except Pb. Hence, pretreatments were required to reduce the environmental risk of heavy metals in conditioned sludge cake prior to a further utilization., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Beta diversity describes the variation in species composition between sites and is often influenced by both local and regional processes. Partitioning beta diversity into turnover (species replacement between sites) and nestedness (richness difference between sites) components may enhance our understanding of the mechanisms behind the local and regional drivers determining species composition across spatial scales. We sampled macrophyte communities in 24 lakes in two regions (Yangtze River basin and Yunnan-Guizhou plateau) of China covering broad climate and nutrient gradients. Based on both species and functional approaches, we calculated multiple-site beta diversity using the Sørensen dissimilarity index and partitioned it into turnover and nestedness coefficients crossed with two nested spatial scales: among depths within transects (transect scale) and among transects within lakes (lake scale). The overall species beta diversity and functional beta diversity (i.e. Sørensen coefficient) were significantly lower and thus more homogeneous at lake scale. Across spatial scales, species beta diversity was mainly explained by turnover patterns (56-61%) and functional beta diversity primarily by nestedness patterns (58-65%). Both local and regional drivers contributed to structuring species and functional beta diversity patterns, largely through changes in species turnover and functional nestedness, respectively. Overall, we observed a significant increase in species beta diversity and its turnover component while a decreasing trend in functional beta diversity and its nestedness component at high altitude. Our results further emphasized that the species beta diversity and its turnover component decreased at high total phosphorus concentration (TP) across the two spatial scales, while the functional beta diversity and its nestedness component decreased at high TP at the transect scale. We conclude that understanding of the relative role of local and regional drivers in determining macrophyte diversity patterns may help managers to select the most appropriate conservation strategies for preservation of biodiversity varying with the scale in focus., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Magnesium and its alloys were widely investigated in many body fluid microenvironments including bone, blood, bile, saliva, and urine; however, no study has been conducted in the intrauterine microenvironment. In this study, the degradation behaviors of HP-Mg, Mg-1Ca, and Mg-2Zn alloys in simulated uterine fluid (SUF) were systematically investigated, and then the biological response of four kinds of uterine cells to these materials was observed. For this purpose, the gluteal muscle of rat was used as the implantation position to study the in vivo biocompatibility as a mimic of the intrauterine device (IUD) fixation part. The 120-day immersion test indicated that the Mg-1Ca alloy had a faster degradation rate than the Mg-2Zn alloy and HP-Mg and dissolved entirely in the SUF. Indirect cytotoxicity assay showed that the extracts of HP-Mg, Mg-1Ca, and Mg-2Zn alloys have positive effects on human uterine smooth muscle cells (HUSMC), human endometrial epithelial cells (HEEC), and human endometrial stromal cells (HESC), especially for the Mg-1Ca alloy group. Furthermore, the in vivo experiment showed that HP-Mg, Mg-1Ca, and Mg-2Zn alloy implants cause a light inflammatory response in the initial 3 days, but they were surrounded mainly by connective tissue, and lymphocytes were rarely observed at 4 weeks. Based on the above facts, we believed that it is feasible for using biomedical Mg alloys in obstetrics and gynecology and proposed three kinds of medical device candidates for future R&D. Statement of Significance Magnesium alloys were widely investigated in various body microenvironments including bone, blood, bile, saliva, and urine; however, no study has been conducted in the intrauterine environment. In this work, the degradation behaviors of Mg alloys in simulated uterine fluid were systematically investigated, and then the biological response of four kinds of uterine cells to these materials was observed. For this purpose, the tibialis anterior of a rat model was used as the implantation position to study the in vivo biocompatibility. The comprehensive in vitro and in vivo testing results indicated that biomedical Mg alloys are feasible for use in obstetrics and gynecology. Further, three kinds of medical device candidates were proposed., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Tannic acid (TA), a phenolic compound, may be considered as a sludge conditioning agent on account of its ability to precipitate protein. In this study, the effectiveness of TA conditioning on enhancing waste activated sludge (WAS) dewatering was investigated at various pH values. The results indicated that with the conditioning of 0.15 mmol TA per gram of total solid (TS), the WAS dewaterability was affected distinctly by the pH regulation. The reductions of 86.8% capillary suction time (CST), 96.3% specific resistance of filtration (SRF), and 23.6% water content (Wc) of dewatered sludge cake were achieved at an optimal pH value of 4.0. Meanwhile, obvious alterations were observed in some aspects like supernatant viscosity, zeta potential, particle size and extracellular polymeric substances (EPS) polymers. Correlation analysis indicated that the proteins in slime EPS and loosely bound EPS dominantly governed sludge dewaterability. Fluorescence quenching analysis indicated that in the range of acidity, the increase of pH value afforded more binding sites of sludge EPS for TA. However, the removal of EPS protein depended on the combined effect of TA conditioning and pH regulation. The findings provided a novel approach and explanation of WAS dewaterability enhancement using organic additive conditioning and pH regulation., (Copyright © 2019 Elsevier B.V. All rights reserved.)