Search

Abstract Ionogels are promising material candidates for ionotronics due to their excellent ionic conductivity, stretchability, and thermal stability. However, it is challenging to develop 3D printable ionogels with both excellent electrical and mechanical properties. Here, we report a highly conductive and stretchable nanostructured (CSN) ionogel for 3D printing ionotronic sensors. We propose the photopolymerization-induced microphase separation strategy to prepare the CSN ionogels comprising continuous conducting nanochannels intertwined with cross-linked polymeric framework. The resultant CSN ionogels simultaneously achieves high ionic conductivity (over 3 S m−1), high stretchability (over 1500%), low degree of hysteresis (0.4% at 50% strain), wide-temperature-range thermostability (−72 to 250 °C). Moreover, its high compatible with DLP 3D printing enables the fabrication of complex ionogel micro-architectures with high resolution (up to 5 μm), which allows us to manufacture capacitive sensors with superior sensing performances. The proposed CSN ionogel paves an efficient way to manufacture the next-generation capacitive sensors with enhanced performance.

Abstract The purpose of this study was to investigate the causal association between unhealthy lifestyle style factors and the risk of colorectal cancer, with the aim of preventing the occurrence of colorectal cancer by modifying unhealthy lifestyles. A two-sample Mendelian randomization (MR) approach was employed in this study, utilizing the inverse-variance weighted method as the primary research method. This MR analysis analyzed data of 3022 colorectal cancer cases and 174,006 controls from the FinnGen database. Single nucleotide polymorphisms (SNPs) associated with unhealthy lifestyle factors were selected as instrumental variables (IVs), including two obesity-related indicators, BMI (body mass index) and WHR (waist-to-hip ratio). Four phenotypes of smoking (smoking initiation, ever smoked, smoking per day, smoking cessation) and one phenotype of alcohol consumption (drinks per week). Four phenotypes of physical activity (accelerometer-based physical activity, moderate-to-vigorous physical activity, vigorous physical activity, strenuous sports or other exercises). All SNPs were obtained from published genome-wide association studies. The study found that the obesity-related indicator, higher WHR (OR = 1.38, 95% CI 1.12–1.70; P = 0.002) were associated with an increased risk of colorectal cancer, and two smoking phenotypes, cigarettes per day(OR = 1.30, 95% CI 1.01–1.68; P = 0.042)and smoking initiation (OR = 3.48, 95% CI 1.15–10.55; P = 0.028), were potentially associated with an increased risk of colorectal cancer. However, there was no evidence to suggest that physical activities and alcohol consumption were associated with colorectal cancer (all p > 0.05). In addition, the study detected no pleiotropy (all p > 0.05). This MR analysis indicates a causal association between a higher waist-to-hip ratio and the risk of colorectal cancer and a suggestive association between smoking and the risk of colorectal cancer among Europeans. These findings contribute to the understanding of the etiology of colorectal cancer and have potential implications for its prevention.

Abstract Mouse models of autosomal dominant polycystic kidney disease (ADPKD) show that intact primary cilia are required for cyst growth following the inactivation of polycystin-1. The signaling pathways underlying this process, termed cilia-dependent cyst activation (CDCA), remain unknown. Using translating ribosome affinity purification RNASeq on mouse kidneys with polycystin-1 and cilia inactivation before cyst formation, we identify the differential ‘CDCA pattern’ translatome specifically dysregulated in kidney tubule cells destined to form cysts. From this, Glis2 emerges as a candidate functional effector of polycystin signaling and CDCA. In vitro changes in Glis2 expression mirror the polycystin- and cilia-dependent changes observed in kidney tissue, validating Glis2 as a cell culture-based indicator of polycystin function related to cyst formation. Inactivation of Glis2 suppresses polycystic kidney disease in mouse models of ADPKD, and pharmacological targeting of Glis2 with antisense oligonucleotides slows disease progression. Glis2 transcript and protein is a functional target of CDCA and a potential therapeutic target for treating ADPKD.

Abstract The microenvironment mediated by the microglia (MG) M1/M2 phenotypic switch plays a decisive role in the neuronal fate and cognitive function of Alzheimer's disease (AD). However, the impact of metabolic reprogramming on microglial polarization and its underlying mechanism remains elusive. This study reveals that cordycepin improved cognitive function and memory in APP/PS1 mice, as well as attenuated neuronal damage by triggering MG‐M2 polarization and metabolic reprogramming characterized by increased OXPHOS and glycolysis, rather than directly protecting neurons. Simultaneously, cordycepin partially alleviates mitochondrial damage in microglia induced by inhibitors of OXPHOS and glycolysis, further promoting MG‐M2 transformation and increasing neuronal survival. Through confirmation of cordycepin distribution in the microglial mitochondria via mitochondrial isolation followed by HPLC‐MS/MS techniques, HKII and PDK2 are further identified as potential targets of cordycepin. By investigating the effects of HKII and PDK2 inhibitors, the mechanism through which cordycepin targeted HKII to elevate ECAR levels in the glycolysis pathway while targeting PDK2 to enhance OCR levels in PDH‐mediated OXPHOS pathway, thereby inducing MG‐M2 polarization, promoting neuronal survival and exerting an anti‐AD role is elucidated.

Abstract The applications of silica-based glass have evolved alongside human civilization for thousands of years. High-precision manufacturing of three-dimensional (3D) fused silica glass objects is required in various industries, ranging from everyday life to cutting-edge fields. Advanced 3D printing technologies have emerged as a potent tool for fabricating arbitrary glass objects with ultimate freedom and precision. Stereolithography and femtosecond laser direct writing respectively achieved their resolutions of ~50 μm and ~100 nm. However, fabricating glass structures with centimeter dimensions and sub-micron features remains challenging. Presented here, our study effectively bridges the gap through engineering suitable materials and utilizing one-photon micro-stereolithography (OμSL)-based 3D printing, which flexibly creates transparent and high-performance fused silica glass components with complex, 3D sub-micron architectures. Comprehensive characterizations confirm that the final material is stoichiometrically pure silica with high quality, defect-free morphology, and excellent optical properties. Homogeneous volumetric shrinkage further facilitates the smallest voxel, reducing the size from 2.0 × 2.0 × 1.0 μm3 to 0.8 × 0.8 × 0.5 μm3. This approach can be used to produce fused silica glass components with various 3D geometries featuring sub-micron details and millimetric dimensions. This showcases promising prospects in diverse fields, including micro-optics, microfluidics, mechanical metamaterials, and engineered surfaces.

Summary: Hydrodesulfurization (HDS) is a commonly used route for producing clean fuels in modern refinery. Herein, ammonium/amine-intercalated MoS2 catalysts with various content of 1T phase and S vacancies have been successfully synthesized. Along with the increment of 1T phase and S vacancies of MoS2, the initial reaction rate of the HDS of dibenzothiophene (DBT) can be improved from 0.09 to 0.55 μmol·gcat−1·s−1, accounting for a remarkable activity compared to the-state-of-the-art catalysts. In a combinatory study via the activity evaluation and catalysts characterization, we found that the intercalation species of MoS2 played a key role in generating more 1T phase and S vacancies through the ‘intercalation-deintercalation’ processes, and the hydrogenation and desulfurization of HDS can be significantly promoted by 1T phase and S vacancies on MoS2, respectively. This study provides a practically meaningful guidance for developing more advanced HDS catalysts by the intercalated MoS2-derived materials with an in-depth understanding of structure-function relationships.

Abstract The anomalous Hall effect (AHE) that emerges in antiferromagnetic metals shows intriguing physics and offers numerous potential applications. Magnets with a rutile crystal structure have recently received attention as a possible platform for a collinear-antiferromagnetism-induced AHE. RuO2 is a prototypical candidate material, however the AHE is prohibited at zero field by symmetry because of the high-symmetry [001] direction of the Néel vector at the ground state. Here, we show AHE at zero field in Cr-doped rutile, Ru0.8Cr0.2O2. The magnetization, transport and density functional theory calculations indicate that appropriate doping of Cr at Ru sites reconstructs the collinear antiferromagnetism in RuO2, resulting in a rotation of the Néel vector from [001] to [110] while maintaining a collinear antiferromagnetic state. The AHE with vanishing net moment in the Ru0.8Cr0.2O2 exhibits an orientation dependence consistent with the [110]-oriented Hall vector. These results demonstrate that material engineering by doping is a useful approach to manipulate AHE in antiferromagnetic metals.

Abstract Retinal ischemia‒reperfusion (I/R) injury can cause significant damage to human retinal neurons, greatly compromising their functions. Existing interventions have been proven to have little effect. Ferroptosis is a newly discovered type of programmed cell death that has been found to be involved in the process of ischemia‒reperfusion in multiple organs throughout the body. Studies have shown that it is also present in retinal ischemia‒reperfusion injury. A rat model of retinal ischemia‒reperfusion injury was constructed and treated with deferoxamine. In this study, we found the accumulation of Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), and the consumption of glutathione (GSH) via ELISA testing; increased expression of transferrin; and decreased expression of ferritin, SLC7A11, and GPX4 via Western blotting (WB) and real-time PCR testing. Structural signs of ferroptosis (mitochondrial shrinkage) were observed across multiple cell types, including retinal ganglion cells (RGCs), photoreceptor cells, and pigment epithelial cells. Changes in visual function were detected by F-VEP and ERG. The results showed that iron and oxidative stress were increased in the retinal ischemia‒reperfusion injury model, resulting in ferroptosis and tissue damage. Deferoxamine protects the structural and functional soundness of the retina by inhibiting ferroptosis through the simultaneous inhibition of hemochromatosis, the initiation of transferrin, and the degradation of ferritin and activating the antioxidant capacity of the System Xc-GSH-GPX4 pathway.

Abstract Urethral stricture refers to the narrowing of the urethral lumen. While previous studies have hinted at inflammation as the initial driver of this condition, the reasons and mechanisms behind its progression remain largely unknown. By Atomic force microscope (AFM), researchers measured the matrix stiffness of urethra to be 5.23 ± 0.37 kPa for normal tissue and 41.59 ± 2.48 kPa for stricture urethral scar. Similar results were observed in rat urethral stricture models, where the matrix stiffness of normal urethra was 4.29 ± 0.82 kPa, while 32.94 ± 7.12 kPa for urethral stricture scar. Notably, the matrix stiffness increased in rat models over time. To further investigate, polyacrylamide hydrogels were employed to mimic different levels of stiffness for normal and stricture condition. Interestingly, higher matrix stiffness led to an increased fibroblast-to-myofibroblast transition (FMT) in rat urethral fibroblasts, indicated by enhanced expression of α-SMA and Collagen I, as well as changing in the morphology of fibroblast. RNA-seq analysis suggested that Igfbp3/Smads might regulate the progressive FMT in urethral stricture. In the experiment where the expression of Igfbp3 was inhibited, increasing matrix stiffness lose the potential to stimulate FMT progression and the expression of p-Smad2/3 decreased. On the contrary, overexpression of Igfbp3 promoted the process of FMT in urethral fibroblasts. In conclusion, Igfbp3/Smad pathway appeared to be involved in the progression of urethral fibrosis. This finding suggested that Igfbp3/Smad might be an promising target for future research and treatment in this filed.

Abstract Neutral H2 formation via intramolecular hydrogen migration in hydrocarbon molecules plays a vital role in many chemical and biological processes. Here, employing cold target recoil ion momentum spectroscopy (COLTRIMS) and pump-probe technique, we find that the non-adiabatic coupling between the ground and excited ionic states of ethane through conical intersection leads to a significantly high yield of neutral H2 fragment. Based on the analysis of fingerprints that are sensitive to orbital symmetry and electronic state energies in the photoelectron momentum distributions, we tag the initial electronic population of both the ground and excited ionic states and determine the branching ratios of H2 formation channel from those two states. Incorporating theoretical simulation, we established the timescale of the H2 formation to be ~1300 fs. We provide a comprehensive characterization of H2 formation in ionic states of ethane mediated by conical intersection and reveals the significance of non-adiabatic coupling dynamics in the intramolecular hydrogen migration.

Abstract In this study, a series of true triaxial loading tests were carried out on coal-measure sandstone after high temperature treatment by using a self-developed true triaxial test system combined with acoustic emission (AE) monitoring, and the mass loss, deformation characteristics and loss failure mode of sandstone before and after heat treatment were systematically studied. It is found that the true triaxial mechanical properties of sandstone after high temperature treatment are closely related to temperature, and the peak strength, maximum principal strain, volume strain, minimum fracture angle and elastic modulus, which all showed bimodal changes, and 800 °C is the threshold temperature of the first four parameters. The transition temperature of the elastic modulus is 400 °C. It is found that the test results of true triaxial high temperature sandstone are in good agreement with the existing true triaxial theory and test results. The failure forms of the samples at different temperatures show inverted “Y” or inverted “N” shapes. Shear failure occurs when the temperature is below 400 °C, and shear-tension failure occurs when the temperature is above 600 °C. At the same time, it is found that the AE signal has four periods, namely the quiet period, growth period, explosion period and decline period. The number of AE events corresponds to the deviatoric stress interval well. Experimental study of the mechanical properties of sandstone under the coupling effect of high temperature and true triaxial stress has guiding significance for the parameter selection and safety evaluation of roof sandstone in underground coal gasification.

The advents in continuous fibre-reinforced polymer additive manufacturing (CFRP-AM) present unprecedented opportunities for the rapid development of next-generation high-performance composites with selectively and spatially distributed reinforcement. However, the widely adopted 3-degree-of-freedom motion configuration in current CFRP-AM systems hinders the exploration of composite structures with non-planar fibre layouts. This work presents a novel conformal CFRP-AM system to fabricate grid-stiffened shell structures leveraging its multi-DoF motion to pattern spatial features. The system integrates a 6-axis robot with an optimally designed co-extrusion module and operates through a design-to-manufacturing workflow. The proposed workflow includes three steps: system calibration, conformal toolpath generation, and process implementation. The conformal toolpath generation is a surface-mapping-based method that allows a simultaneous exploration of various geometric designs and their toolpaths. Experimental comparisons were made between parts fabricated by different processes, i.e., planar and conformal based, with different toolpaths, i.e., shells filled with zigzag and arc-offset patterns, and with various geometric designs, i.e., stiffener ribs with different crossline angles. The results manifest that the proposed system can significantly improve the compression strength and stiffness of grid-stiffened shell structures. Meanwhile, the additional design freedom on process and structure opens up a new possibility to customise their mechanical performance.

Named entity recognition (NER) is the localization and classification of entities with specific meanings in text data, usually used for applications such as relation extraction, question answering, etc. Chinese is a language with Chinese characters as the basic unit, but a Chinese named entity is normally a word containing several characters, so both the relationships between words and those between characters play an important role in Chinese NER. At present, a large number of studies have demonstrated that reasonable word information can effectively improve deep learning models for Chinese NER. Besides, graph convolution can help deep learning models perform better for sequence labeling. Therefore, in this article, we combine word information and graph convolution and propose our Lattice-Transformer-Graph (LTG) deep learning model for Chinese NER. The proposed model pays more attention to additional word information through position-attention, and therefore can learn relationships between characters by using lattice-transformer. Moreover, the adapted graph convolutional layer enables the model to learn both richer character relationships and word relationships and hence helps to recognize Chinese named entities better. Our experiments show that compared with 12 other state-of-the-art models, LTG achieves the best results on the public datasets of Microsoft Research Asia, Resume, and WeiboNER, with the F1 score of 95.89%, 96.81%, and 72.32%, respectively.

Mutations in the gene encoding PC1 cause ADPKD, a common genetic renal disease. Here, the authors show that expression of the C-terminal 200 amino acids of the large PC1 protein in mouse models of ADPKD suppresses cystic disease through an interaction with the mitochondrial enzyme NNT.

Abstract The occlusion of dentinal tubules has become a rapid and effective method for treating dentin hypersensitivity. Accurate evaluation of dentin occlusion is critical to illustrate the efficacy of oral care products and to optimize dental therapy in the clinics, which is limited by the conventional two-dimensional (2-D) characterization methods. Here, we demonstrate the visualization of the dentin occlusion via three-dimensional (3-D) characterization using a focused ion beam-scanning electron microscopy (FIB-SEM) tomography. Using the “Slice and View” approach, the material used for occluding dentin tubules is imaged with a very high-resolution voxel (10 nm × 10 nm × 20 nm) from 2-D SEM images and then reconstructed into a 3-D volume, which presents the mode of action of toothpaste for treating dentin hypersensitivity. Meanwhile, quantitative analysis of the depth of occlusion is successfully obtained. This work validates the feasibility of FIB-SEM tomography in the analysis of dentin occlusion within the complicated networks of dentine tubules at the nanoscale, and provides a novel approach to facilitate the research and development of oral care products.

Abstract A deformable microfluidic system and a fluidic dynamic model have been successfully coupled to understand the dynamic fluid–structure interaction in transient flow, designed to understand the dentine hypersensitivity caused by hydrodynamic theory. The Polydimethylsiloxane thin sidewalls of the microfluidic chip are deformed with air pressure ranging from 50 to 500 mbar to move the liquid meniscus in the central liquid channel. The experiments show that the meniscus sharply increased in the first 10th of second and the increase is nonlinearly proportional to the applied pressure. A theoretical model is developed based on the unsteady Bernoulli equation and can well predict the ending point of the liquid displacement as well as the dynamics process, regardless of the wall thickness. Moreover, an overshooting and oscillation phenomenon is observed by reducing the head loss coefficient by a few orders which could be the key to explain the dentine hypersensitivity caused by the liquid movement in the dentine tubules.

Abstract Prostate cancer (PCa) is a common malignant disease among men and biochemical recurrence (BCR) is considered to be a decisive risk factor for clinical recurrence and PCa metastasis. Clarifying the genes related to BCR and its possible pathways is vital for providing diagnosis and treatment methods to delay the progress of BCR. An analysis of data concerning PCa from previous datasets of The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) was performed. Immunohistochemical (IHC) staining were used to evaluate the expression of SLC14A1 in prostate tissues. Kaplan–Meier analysis, Pearson correlation, and single sample Gene Set Enrichment Analysis (ssGSEA) were used to identify the potential pathway and molecular mechanism of the function of SLC14A1 in BCR of PCa. The expression of SLC14A1 is significantly reduced in prostate cancer cells and tissue comparing to normal prostate epithelial cell and para-cancerous tissue. As indicated by Kaplan–Meier analysis, High expression of SLC14A1 could increase the BCR-free survival time of PCa patients. This effect might be related to the interaction with miRNAs (has-miR-508, has-mir-514a2, and has-mir-449a) and the infiltration of B cells. SLC14A1 is a novel important gene associated with BCR of PCa, and further studies of its molecular mechanism may delay the progress of BCR.

Catalysed oxidative C-C bond formation reactions are important in the synthesis of natural products, but poorly tolerated by polyphenolic flavones. Here the authors report the reactivity of molecular oxygen in alkaline water without added catalyst for the synthesis of a collection of flavone dimers and trimers.

Antimicrobial toxins are secreted by bacteria to kill rival species. Here the authors report the mechanism of inhibition of EsaD, a toxin secreted by some S. aureus strains to kill competitors that lack the antitoxin EsaG, showing marked mechanistic differences to other Type II toxin-antitoxin systems.

Genome-wide profiling of chromatin accessibility by DNase-seq or ATAC-seq has been widely used to identify regulatory DNA elements and transcription factor binding sites. Here the authors develop a computational model, SELMA, to estimate and correct enzymatic cleavage biases in chromatin accessibility profiling data.

Abstract Secondary epidermoid cyst of the penis is a very rare epidermoid cyst that occurs in the penis. The purpose of this study was to investigate the relationship between the occurrence of secondary epidermoid cyst of penis and circumcision-related factors, and to provide possible reasonable and effective suggestions for circumcision. The data of all patients who visited the clinic for epidermoid cysts of the penis from September 2000 to September 2021 in Xiangya Hospital were collected. A retrospective study was carried out on whether the patients had been circumcised and the surgical method, anesthesia method, cyst location, surgical age, postoperative wound infection, whether they were phimosis patients, and the level of the surgeon. Among the 24 patients followed up, 95.8% had a history of circumcision, and only 4.2% had no history of circumcision, and the more traumatic surgical methods developed secondary epidermoid cyst of the penis after surgery the higher the probability. Injecting anesthesia at the base of the penis increases the chances of developing a secondary epidermoid cyst of the penis. Postoperative secondary epidermoid cyst of the penis were mainly located in the anterior segment and posterior segment, and the anterior segment had a higher proportion, followed by the posterior segment. Secondary epidermoid cyst of the penis occur mainly in adults. Postoperative wound infection accelerates the appearance of secondary epidermoid cyst of the penis. Patients with phimosis have an increased probability of developing secondary epidermoid cysts of the penis after surgery. The incidence of secondary epidermoid cysts and postoperative infection after manual circumcision by the attending physician was higher than that of the chief physician. Circumcision, injection of anesthesia at the base of the penis, ligation of the penis, and postoperative wound infection may be the etiologies and triggers of secondary epidermoid cysts of the penis. Adults and phimosis patients may be high-risk groups. Lower-level surgeons may increase the odds of postoperative secondary epidermoid cysts of the penis, and it is recommended that surgery be performed by a clinically-experienced, higher-level surgeon. The indications for circumcision should be strictly evaluated and the operation should be performed as soon as possible, and the less invasive surgical method and anesthesia method should be selected. Reduce irrelevant operations during surgery and avoid wound infection after surgery.

Abstract Urethral stricture is related to scar tissue fibrosis, but its pathogenesis is still unclear. This study aims to explore the regulatory mechanism of circular RNA (circRNA) in the occurrence and development of urethral stricture. CircRNA microarray was employed to analyze circRNA expression profiles between human urethral scar tissue and normal urethral tissue. The results of circRNA microarray showed that there were 296 differentially expressed genes between urethral scar tissue and normal urethral tissue. The enrichment analysis of Kyoto encyclopedia of genes and genomes showed that these circRNAs were significantly correlated with ECM–receptor interaction. The first nine differentially expressed circRNA were selected to predict the circRNA–miRNA network. RT-qPCR results showed that circ_0047339 was upregulated considerably in urethral scar tissue. Urethral scar fibroblasts were isolated from human urethral scar tissue and cultured in vitro. After silencing circ_0047339, the proliferation of urethral scar cells decreased significantly, and the expressions of Collagen I (COL-1) and α-smooth muscle actin (α-SMA) also reduced. As a competing endogenous RNA, circ_0047339 could increase the expression of TSP-1 by competitively binding miR-4691-5p. In addition, miR-4691-5p mimic transfection could inhibit the proliferation of urethral scar fibroblasts and the presentation of thrombospondin-1 (TSP-1), α-SMA and COL-1, while circ_0047339 overexpression eliminated this inhibition. Our results showed that circ_0047339 might promote the growth and fibrosis of urethral scar fibroblasts through miR-4691-5p/TSP-1 axis, thus promoting the development of urethral stricture.

Abstract Triple‐negative breast cancer (TNBC) is a highly lethal malignancy with limited therapy options. TWIST1, a key transcriptional factor of epithelial‐mesenchymal transition (EMT), contributes to self‐renewal of cancer stem‐like cells (CSCs), chemo‐resistance, metastasis, and TNBC‐related death. However, the mechanism by which TWIST1 is deregulated in TNBC remains elusive. Here, USP29 is identified as a bona fide deubiquitinase of TWIST1. The deubiquitination of TWIST1 catalyzed by USP29 is required for its stabilization and subsequent EMT and CSC functions in TNBC, thereby conferring chemotherapeutic resistance and metastasis. Furthermore, the results unexpectedly reveal that CDK1 functions as the direct USP29 activator. Mechanistically, CDK1‐mediated phosphorylation of USP29 is essential for its deubiquitinase activity toward TWIST1 and TWIST1 driven‐malignant phenotypes in TNBC, which could be markedly mitigated by the genetic ablation or pharmacological inhibition of CDK1. Moreover, the histological analyses show that CDK1 and USP29 are highly upregulated in TNBC samples, which positively correlate with the expression of TWIST1. Taken together, the findings reveal a previously unrecognized tumor‐promoting function and clinical significance of the CDK1‐USP29 axis through stabilizing TWIST1 and provide the preclinical evidence that targeting this axis is an appealing therapeutic strategy to conquer chemo‐resistance and metastasis in TNBC.

The Arctic stratospheric ozone depletion event in spring 2020 was the most severe compared with previous years. We retrieved the critical indicator ozone vertical column density (VCD) using zenith scattered light differential optical absorption spectroscopy (ZSL-DOAS) from March 2017 to September 2021 in Ny-Ålesund, Svalbard, Norway. The average ozone VCD over Ny-Ålesund between 18 March and 18 April 2020 was approximately 274.8 Dobson units (DU), which was only 64.7 ± 0.1% of that recorded in other years (2017, 2018, 2019, and 2021). The daily peak difference was 195.7 DU during this period. The retrieved daily averages of ozone VCDs were compared with satellite observations from the Global Ozone Monitoring Experiment-2 (GOME-2), a Brewer spectrophotometer, and a Système d’Analyze par Observation Zénithale (SAOZ) spectrometer at Ny-Ålesund. As determined using the empirical cumulative density function, ozone VCDs from the ZSL-DOAS dataset were strongly correlated with data from the GOME-2 and SAOZ at lower and higher values, and ozone VCDs from the Brewer instrument were overestimated. The resulting Pearson correlation coefficients were relatively high at 0.97, 0.87, and 0.91, respectively. In addition, the relative deviations were 2.3%, 3.1%, and 3.5%, respectively. Sounding and ERA5 data indicated that severe ozone depletion occurred between mid-March and mid-April 2020 in the 16–20 km altitude range over Ny-Ålesund, which was strongly associated with the overall persistently low temperatures in the winter of 2019/2020. Using ZSL-DOAS observations, we obtained ozone VCDs and provided evidence for the unprecedented ozone depletion during the Arctic spring of 2020. This is essential for the study of polar ozone changes and their effect on climate change and ecological conditions.

Abstract Scanning Electron Microscope/Focused Ion Beam (SEM/FIB) system has become valuable and popular tool for the analysis of biological materials such as dentine structures. According to physiological and anatomical studies, dentine structures are a complicated system containing collagen fibers, nanocrystalline hydroxyapatite, and numerous networks of tubular pores. During a routine FIB milling process, collagen fibers and other organic structures are vaporized, which increases the number of pores on the milled surface of the dentine. This causes the final cross-section to be more porous than the pristine sample. Unfortunately, little attention has been paid to the collagen fiber loss and how to preserve them during a FIB milling process. In this work, we present a novel and simple approach to preserve the organic portions of the dentine structure through metal staining. By using this method, the porosity of the dentine structure after the FIB milling process is significantly reduced similar to the pristine sample. This indicates that the organic portion of the dentine structure is well protected by the metal staining. This approach enables the SEM/FIB system to generate super-high quality SEM images with less ion beam damage; and the SEM images can better reflect the original condition of the dentine structure. Further, serial energy-dispersive X-ray spectroscopy (EDS) mapping of the stained dentine structure is achieved without an additional metal coating; and three-dimensional (3-D) elemental mapping of an occluded dentine is achieved with a significantly reduced data acquisition time.

Biomass burning emissions have been shown to influence clouds in the Atlantic, but its influence in other regions is not well known. Here, the authors show that biomass burning aerosols increase the low-cloud cover over subtropical southeastern Asia by a similar magnitude than over the Atlantic.

The Yersinia outer protein J (YopJ) family of effectors, which are present in many plant and animal pathogens are non-canonical acetyltransferases that are activated by the eukaryote-specific cofactor inositol hexaphosphate (InsP6). Here, the authors combine X-ray crystallography, biochemical and functional analyses to characterise the structure and activation mechanism of the YopJ family effector PopP2 from the plant pathogen Ralstonia solanacearum and observe that InsP6 binding induces major conformational changes in PopP2 with a helix-to-strand fold-switching in its catalytic core.

Although pyrethrum is used to repel insects for centuries, the underlying mechanism has been enigmatic. Liu et al. found that specific components of pyrethrum mediate repellency by targeting olfactory receptors and/or voltage-gated sodium channels in Aedes aegypti mosquitoes.

Abstract Polymer coatings are commonly used to protect carbon steels from corrosion but they are susceptible to weathering and many of them have environmental concerns. Therefore, we studied the possibility of an environmentally favorable inorganic magnesium phosphate cement (MPC) coating for protecting mild steel. A formulation suitable for coating steel was developed by compositional modification [i.e., incremental replacement of dead-burned magnesia (MgO) with magnesium hydroxide (Mg(OH)2)] to a road-repair MPC. This modification yielded an acceptable working time and prevented pore formation at the coating-steel interface. Corrosion monitoring by linear polarization and electrochemical impedance spectroscopy for 14 days found that, the MPC coating substantially increased the linear polarization resistance (Rp) [e.g., day 1: (8.2 ± 1.7) × 103 (nadir value) vs. 495 ± 55 Ω cm−2] and charge transfer resistance (Rct) (e.g., day 1: 9.3 × 103 vs. 3.8 × 102 Ω cm−2). The coated steel underwent neutral sodium chloride (NaCl) salt spray for 2400 h without visible rusting. Immersion for 24 h in liquids simulating the pore fluid indicated that, passivation by the excess MgO in the coating was a major contributor to its anti-corrosive property. Tafel polarization in the liquids found that, corrosion current density (Icorr) followed the rank: 3.5% NaCl solution (6.0 µA cm−2) > 3.5% NaCl solution containing MgO (3.6 µA cm−2) > 3.5% NaCl solution containing fragmented MPC (1.7 µA cm−2), suggesting that a physical barrier effect and dissolved phosphate ions improved its protection. This study shows that, MPC coating is a promising durable and environmentally favorable anti-corrosive material for protecting steel structures in some applications.

Reducing methane (CH4) emissions from anthropogenic activities is critical to climate change mitigation efforts. However, there is still considerable uncertainty over the amount of fugitive CH4 emissions due to large-scale area sources and heterogeneous emission distributions. To reduce the uncertainty and improve the spatial and temporal resolutions, a new hybrid method was developed combining optical remote sensing (ORS), computed tomography (CT), and inverse-dispersion modeling techniques on the basis of which a multi-path scanning system was developed. It uses a horizontal radial plume mapping path configuration and adapts a Lagrangian stochastic dispersion mode into CT reconstruction. The emission map is finally calculated by using a minimal curvature tomographic reconstruction algorithm, which introduces smooth constraints at each pixel. Two controlled-release experiments of CH4 were conducted with different configurations, showing relative errors of only 2% and 3%. Compared with results from the single-path inverse-dispersion method (5–175%), the new method can not only derive the emission distribution but also obtain a more accurate emission rate. The outcome of this research would bring broad application of the ORS-CT and inverse-dispersion techniques to other gases and sources.

Kucha is a rare variety of tea tree that produces the non-stimulatory theacrine instead of caffeine. Here the authors show that theacrine synthase from Kucha has N9-methyltransferase activity resulting from amino acid substitutions that explain substrate specificity and could potentially guide production of caffeine-free tea.

Coastal lagoons are among the most vulnerable and economically significant ecosystems on Earth. Songkhla Lake, connected with the Gulf of Thailand, is the second largest lake in Southeast Asia and supports the development of the fishery, transportation, and tourism industries in southern Thailand. With increasing anthropogenic disturbances, the lake is facing acute ecological problems and further research is needed. Here, we provide 55-year record of grain size, color reflectance, magnetic susceptibility, total organic carbon, total nitrogen, and trace element (As, Hg, Pb, Cr, Ni, Cu, and Zn) concentrations of sediment core SKL8-2 collected from Songkhla Lake. These records reveal a three-stage sedimentary and input history of trace metals under anthropogenic effects: 1) From 1964 to 1982, it was a natural terrigenous input period with a relative reduction environment when the channel connecting Songkhla Lake and the Gulf of Thailand was closed. 2) Trace metal concentrations, organic carbon content, b* value, and magnetic susceptibility changed abruptly in 1982. During 1982–2000, the sources of trace metals were more complex than during 1964–1982 and mainly came from urban wastewater, industrial effluent, and fishery discharge. 3) From 2000 to 2019, contamination signals of Pb, Hg, As, Zn, and Ni emerged in the first decade because of the rapid development and poor sewage treatment around nearby cities.

Pyrethroid insecticides stabilize the open state of insect sodium channels. Previous mutational, electrophysiological, and computational analyses led to the development of homology models predicting two pyrethroid receptor sites, PyR1 and PyR2. Many of the naturally occurring sodium channel mutations, which confer knockdown resistance (kdr) to pyrethroids, are located within or close to these receptor sites, indicating that these mutations impair pyrethroid binding. However, the mechanism of the state-dependent action of pyrethroids and the mechanisms by which kdr mutations beyond the receptor sites confer resistance remain unclear. Recent advances in protein structure prediction using the AlphaFold2 (AF2) neural network allowed us to generate a new model of the mosquito sodium channel AaNav1-1, with the activated voltage-sensing domains (VSMs) and the presumably inactivated pore domain (PM). We further employed Monte Carlo energy minimizations to open PM and deactivate VSM-I and VSM-II to generate additional models. The docking of a Type II pyrethroid deltamethrin in the models predicted its interactions with many known pyrethroid-sensing residues in the PyR1 and PyR2 sites and revealed ligand-channel interactions that stabilized the open PM and activated VSMs. Our study confirms the predicted two pyrethroid receptor sites, explains the state-dependent action of pyrethroids, and proposes the mechanisms of the allosteric effects of various kdr mutations on pyrethroid action. The AF2-based models may assist in the structure-based design of new insecticides.

A detailed sensitivity analysis of ozone density profile retrieval was applied to scattering solar radiance spectra measured with the SCanning Imaging Absorption spectroMeter for Atmospheric CHartographY (SCIAMACHY) instrument aboard the ENVIronmental SATellite (ENVISAT). The vertical density distribution of ozone between 10 and 69 km was obtained using the weighted multiplicative algebraic reconstruction technique and the radiative transfer model for SCIAMACHY. This study investigates the error sources for the retrieved ozone profiles, which are relevant to explain the difference between two independent instruments. The numerical simulation method was adapted to quantify the impact of various error sources on the retrieval accuracy of ozone profiles. First, the tangent height (TH) registration was found to be the largest error source. Assuming an aerosol-free atmosphere, under the condition of background aerosol, the ozone profile showed a negative deviation of ~2–10% below 40 km. With an incorrect a priori profile, ozone estimates may result in a 5–10% average error at the upper and lower boundaries. The ozone retrieval error caused by the uncertainty of surface albedo, ozone absorption cross-section, temperature, pressure profile, and low clouds was relatively small. The random error caused by the disturbance of the measurement vector obeying a Gaussian distribution did not exceed 5%. Second, the estimation of various error sources for different solar zenith angles was investigated. The error sources most strongly dependent on SZAs were aerosols, surface albedo, and clouds. Finally, the error estimation of the ozone retrieval between the northern hemisphere (NH) and the southern hemisphere (SH) was investigated, revealing that there were no strong interhemispheric differences, except for cloud height. These results can be used for interpretation of instrumental comparisons and validation of SCIAMACHY ozone profiles retrieved from different algorithms in a rigorous manner.

Tuning the environment of catalytic active sites may improve the selectivity of heterogeneous catalysts. Here, the authors modify the outer-sphere environment of active sites in hydroformylation catalysts by encapsulating the active sites in nanovessels formed by ion pair-directed supramolecular assembly.

Rotaviruses are of great medical significance because they cause gastroenteritis in children. Here the authors provide insights into the mechanism of viral mRNA transcription by determining the in situ cryo-EM structures of a working rotavirus’ RNA-dependent-RNA polymerase, which is of interest for antiviral drug design.

BackgroundKeloid disease is hard to fully eradicate. Recurrence and other unsatisfactory results were found in many patients. No current therapeutic modality has been determined to be most effective for treating keloid scars. Intralesional corticosteroid injections is most commonly recommended for primary management of small and young keloids as well as hypertrophic scars. However, it's difficult for patients to adhere to long-term triamcinolone acetonide injection therapy because of the pain, inconvenience or complications including hormonal imbalance or irregular menstruation.ObjectiveWe aimed to determine whether and how Strontium-90 brachytherapy as an adjuvant radiation could affect keloid recurrence after intralesional triamcinolone and 5-fluorouracil injections.MethodsWe included keloid patients from March 2019 to September 2019 and randomly allocated them to two groups after 3 intralesional triamcinolone and 5-fluorouracil injections at 3 weeks interval. The experimental group received Strontium-90 brachytherapy at a total dose of 15-20Gy, while the control group didn't receive any adjuvant treatment. We performed both Vancouver Scar Scale scoring and Color Doppler ultrasound examination to monitor and evaluate lesions regularly. A one-year follow-up was completed for each patient.Results31 patients who had 42 keloids in total were recruited. We found intralesional triamcinolone and 5-fluorouracil injections could effectively reduce the thickness and modify the hardness of small and young keloids. Strontium-90 brachytherapy reduced the one-year recurrence rate from 85.7 percent to 44.4 percent after 3 intralesional triamcinolone and 5-fluorouracil injections. The lesions' thickness or elasticity was not affected by Strontium-90 brachytherapy.ConclusionStrontium-90 brachytherapy as an adjuvant radiation could effectively reduce small sized keloids recurrence after intralesional triamcinolone and 5-fluorouracil injections. It worked by enhancing the lesions' stability post-injection.Trial registrationThe clinical trial registration number: ChiCTR2000030141. Name of trial registry: Chinese Clinical Trial Registry (http://www.chictr.org.cn/).

Most chiral molecules and structures in living organisms exist as single enantiomers, but why? Here, the authors investigated surface-mediated homochirality on the single-molecule level and show that it can be triggered by the chirality unbalance of two adsorption configuration monomers.

Shape complementarity is the primary way to control the symmetry of nanoparticle assemblies. Here, the authors introduce a governing force that dominates symmetry control of nanorod superlattices, using it to obtain an unexpected and highly thermostable tetragonal lattice.

Whether the spin-degenerate counterpart of Lorentz-violating Weyl fermions, the Dirac fermions, can be realized remains as an open question. Here, Yan et al. report experimental evidence of such type-II Dirac fermions in bulk PtTe2 single crystal with a pair of strongly tilted Dirac cones.

Abstract Previous trial evidence suggested potential risk of serious urinary tract infections (UTIs) and genital infections in type 2 diabetes patients using sodium glucose co-transporter-2 inhibitors (SGLT2) inhibitors. We conducted a systematic review and meta-analysis to assess the effects of SGLT2 inhibitors on UTIs and genital infections in patients with type 2 diabetes. In total, 77 RCTs involving 50,820 participants were eligible. The meta-analyses of randomized controlled trials (RCTs) showed no significant difference in UTIs between SGLT2 inhibitors versus control (2,526/29,086 vs. 1,278/14,940; risk ratio (RR) 1.05, 95% confidence interval (CI) 0.98 to 1.12; moderate quality evidence), but suggested increased risk of genital infections with SGLT2 inhibitors (1,521/24,017 vs. 216/12,552; RR 3.30, 95% CI 2.74 to 3.99; moderate quality evidence). Subgroup analyses by length of follow up (interaction p = 0.005), type of control (interaction p = 0.04) and individual SGLT2 inhibitors (interaction p = 0.03) also showed statistically significant differences in genital infections. The upcoming major trials may provide important additional insights on UTIs, and more efforts are needed to address comparative effects of each individual SGLT2 inhibitors on the infections.

Abstract Little is known about how nematode ecology differs across elevational gradients. We investigated the soil nematode community along a ~2,200 m elevational range on Mt. Norikura, Japan, by sequencing the 18S rRNA gene. As with many other groups of organisms, nematode diversity showed a high correlation with elevation, and a maximum in mid-elevations. While elevation itself, in the context of the mid domain effect, could predict the observed unimodal pattern of soil nematode communities along the elevational gradient, mean annual temperature and soil total nitrogen concentration were the best predictors of diversity. We also found nematode community composition showed strong elevational zonation, indicating that a high degree of ecological specialization that may exist in nematodes in relation to elevation-related environmental gradients and certain nematode OTUs had ranges extending across all elevations, and these generalized OTUs made up a greater proportion of the community at high elevations – such that high elevation nematode OTUs had broader elevational ranges on average, providing an example consistent to Rapoport’s elevational hypothesis. This study reveals the potential for using sequencing methods to investigate elevational gradients of small soil organisms, providing a method for rapid investigation of patterns without specialized knowledge in taxonomic identification.

Abstract There is no consensus on the involvement of zinc (Zn) dysfunctions in Parkinson’s Disease (PD). We performed a meta-analysis to evaluate whether circulating Zn levels in the serum, plasma, and cerebrospinal fluid (CSF) are altered in PD. Twenty-three published studies were selected by searching the databases of PubMed and China National Knowledge Infrastructure (CNKI). A total of 803 PD patients and 796 controls, 342 PD patients and 392 controls, and 135 PD patients and 93 controls were included to study Zn levels in the serum, plasma, and CSF, respectively. Our meta-analysis showed that the serum Zn levels were significantly lower in PD patients compared with health controls (SMD = −0.59; 95% CI [−1.06, −0.12]; P = 0.014). A reduced Zn levels in PD patients were found when serum and plasma studies were analyzed together (SMD = −0.60, 95% CI [−0.98; −0.22]; p = 0.002). PD patients had a tendency toward reduced CSF Zn levels compared with health controls (SMD = −0.50; 95% CI [−1.76, 0.76]; P = 0.439), but no statistical significance was obtained and this data did not allow conclusions due to a small sample size of CSF studies. This study suggests that reduced Zn levels in the serum and plasma are associated with an increased risk for PD.

The writing part in Chinese language tests is badly in need of a mature automated essay scoring system. In this paper, we propose a new approach applied to automated Chinese essay scoring (ACES), called contextualized latent semantic indexing (CLSI), of which Genuine CLSI and Modified CLSI are two versions. The n-gram language model and the weighted finite-state transducer (WFST), two critical components, are used to extract context information in our ACES system. Not only does CLSI improve conventional latent semantic indexing (LSI), but bridges the gap between latent semantics and their context information, which is absent in LSI. Moreover, CLSI can score essays from the perspectives of language fluency and contents, and address the local overrating and underrating problems caused by LSI. Experimental results show that CLSI outperforms LSI, Regularized LSI, and latent Dirichlet allocation in many aspects, and thus, proves to be an effective approach.

Spin polarization in non-magnetic solids has mainly been limited to non-centrosymmetric materials. Here, the authors identify a helical spin texture in the centrosymmetric semiconductor platinum diselenide, and suggest it arises from a local dipole induced Rashba effect rather than the usual spin-splitting.

To experimentally confirm the predicted type-II Weyl fermions in transition metal dichalcogenide, the evidence of inversion symmetry breaking is required. Here, Zhanget al. report Raman spectroscopic evidence for the inversion symmetry breaking in MoTe2.

Leishmania donovani is a protozoan parasite that can cause fatal infections in humans. Here the authors present a high resolution cryoEM structure of the L. donovani80S ribosome and compare it to its human counterpart to provide insight into the basis for drug selectivity towards this eukaryotic parasite.

The lateral septal nucleus (LS) plays a critical role in emotionality, social behavior and feeding processes, through neural connections with the hippocampus and hypothalamus. We investigated the neural circuits of LS by using herpes simplex virus 1 strain H129 (H129) and pseudorabies virus stain Bartha (PRV). Virus H129 indicates that LS directly projects to some cerebral nuclei (nucleus accumbens, bed nuclei of the stria terminalis and amygdala), part of the hypothalamus (median preoptic, paraventricular, dorsomedial nucleus and lateral area), thalamus (medial habenula, the paraventricular, parataenial and reuniens nuclei, and the medial line nuclei) and the pontine central gray. Then the LS has secondary projections to the CA3 and CA1 field of the hippocampal formation, lateral and medial preoptic area, and the mammillary body. PRV tracing shows that LS are mainly receiving primary inputs from the amygdala, hippocampus, hypothalamic, thalamus, midbrain and hindbrain, and secondary inputs from dorsal and central linear nucleus raphe, the lateral part of the superior central nucleus raphe, the ventral anterior-lateral complex, the intermediodorsal nucleus, the central medial nucleus, the rhomboid nucleus, and the submedial nucleus of the thalamus. The neural circuit data revealed here could help to understand and further research on the function of LS.

The Eurasian otter (Lutra lutra) is an endangered species for which diet analyses are needed as part of its conservation efforts. Eurasian otters feed on vertebrates, such as fishes, and invertebrates, such as crustaceans, but their detailed taxonomies are not fully understood in part due to limited resolving power of traditional morphological identification methods. Here, we used high-throughput sequencing (HTS)-based DNA metabarcoding approaches to analyze diet profiles of Eurasian otters inhabiting a marshy estuary area in Korea. We investigated their diet profiles based on spraint sampling followed by DNA metabarcoding analyses targeting 12S rRNA gene region for vertebrates, 16S rRNA gene region for invertebrates, and cytochrome c oxidase 1 (COI) gene region for fishes. For the vertebrate analysis, a blocking oligonucleotide (OBS1) was designed to suppress amplification of DNA fragments derived from the otters. The 12S rRNA gene sequencing assay detected species belonging to fishes (95%) and amphibians (3.3%). Fishes detected by 12S rRNA gene sequencing included crucian carp (Carassius auratus), mullets (Mugil spp.), bluegill (Lepomis macrochirus), and northern snakehead (Channa argus), which were also detected by COI gene sequencing. Among invertebrates, mud flat crabs (Helicana spp.) and shrimps (Palaemon spp.) were abundant. The designed blocking oligonucleotide OBS1 effectively inhibited amplification of the otter's DNA, with only up to 0.21% of vertebrate sequence reads assigned to the otter. This study demonstrated that HTS-based DNA metabarcoding methods were useful to provide in-depth information regarding diet profiles of the otters at our sampling site. By using HTS-based DNA metabarcoding approaches, future research will explore detailed taxonomies of their diets across locations and seasons.

A broadband coherent perfect absorption (CPA) scheme consisting of an optical resonator coupled with three-level atoms excited by single cavity mode is proposed and analyzed. We show the output light field from the system is completely suppressed under specific conditions when the system is excited in linear and nonlinear regimes by two identical light fields from two ends of optical cavity. An analytical broadband CPA criterion for central and sideband excitations of cavity quantum electrodynamics system is derived in linear regime. Moreover, we show the resonant excitation criterion for CPA is greatly extended in nonlinear regime. A new type of bistability behavior is found. The output field intensity and the bistability curve can be well tuned by dynamically adjusting system parameters. Our results demonstrate that the CPA is quite universal, and it should be useful in a variety of applications in optical logic and optical communication devices.