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Tong Liu,1 Sheng Yang,1 Yan-ping Cheng,1 Xiao-ling Kong,1 Dan-dan Du,1 Xian Wang,1 Yun-fei Bai,2 Li-hong Yin,1 Yue-pu Pu,1 Ge-yu Liang1 1Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210096, People’s Republic of China; 2State Key Laboratory of Bioelectronics, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, People’s Republic of ChinaCorrespondence: Ge-yu LiangSchool of Public Health, Southeast University, No. 87 Dingjiaqiao, Nanjing 210009, People’s Republic of ChinaTel +86-25-83272572Fax +86-25-832-72583Email lianggeyu@163.comPurpose: Gastric cancer (GC) is aggressive cancer with a high mortality rate worldwide. N6-methyladenosine (m6A) RNA methylation is related to tumorigenesis, which is dynamically regulated by m6A modulators (“writer,” “eraser,” and “reader”). We conducted a comprehensive analysis of the m6A genes of GC patients in TCGA datasets to identify the potential diagnostic biomarkers.Materials and Methods: We analyzed the expression profile of m6A genes in the TCGA cohort and constructed a diagnostic-m6A-score (DMS) by the LASSO-logistic model. In addition, by consensus cluster analysis, we identified two different subgroups of GC risk individuals by the expression profile of m6A modulators, revealing that YTHDF1’s expression variation profile in GC diagnosis. We also performed RT-qPCR and WB verification in 17 pairs of GC specimens and paired adjacent non-tumor tissues and GC cell lines, and verified the expression trend of YTHDF1 in five GEO GC datasets. YTHDF1 expression and clinical features of GC patients were assessed by the UALCAN.Results: The DMS with high specificity and sensitivity (AUC = 0.986) is proven to distinguish cancer from normal controls better. Moreover, we found that the expression profile variation of YTHDF1 was significantly associated with the high-risk subtype of GC patients. RT-qPCR and Western blot results are consistent with silicon analysis, revealing that YTHDF1’s potential oncogene role in GC tumor.Conclusion: In conclusion, we developed the m6A gene-based diagnostic signature for GC and found that YTHDF1 was significantly correlated with the high-risk subtype of GC patients, suggesting that YTHDF1 might be a potential target in GC early diagnosis.Keywords: m6A, RNA methylation, diagnostic signature, YTHDF1, gastric cancer

Single-molecule fluorescence spectroscopy offers unique capabilities for the low-concentration sensing and probing of molecular dynmics. However, employing such a methodology for versatile sensing and diagnostics under point-of-care demands device miniaturization to lab-on-a-chip size. In this study, we numerically design metalenses with high numerical aperture (NA = 1.1), which are composed of silicon nitride nanostructures deposited on a waveguide and can selectively focus guided light into an aqueous solution at two wavelengths of interest in the spectral range of 500-780 nm. Despite the severe chromatic focal shift in the lateral directions owing to the wavelength-dependent propagation constant in a waveguide, segmented on-chip metalenses provide perfectly overlapping focal volumes that meet the requirements for epi-fluorescence light collection. We demonstrate that the molecule detection efficiencies of metalenses designed for the excitation and emission wavelengths of ATTO 490LS, Alexa 555, and APC-Cy7 tandem fluorophores are sufficient to collect several thousand photons per second per molecule at modest excitation rate constants. Such sensitivity provides reliable diffusion fluorescence correlation spectroscopy analysis of single molecules on a chip to extract their concentration and diffusion properties in the nanomolar range. Achromatic on-chip metalenses open new avenues for developing ultra-compact and sensitive devices for precision medicine and environmental monitoring.

To explore the chemical characteristics and environmental factors of groundwater in the Hetao Irrigation Area of Inner Mongolia, five irrigation fields, including UulanBuh, Jiefangzha, Yongji, Yichang, and Wulat, were selected as the research area. From 72 groundwater observation wells, a total of 216 groundwater samples were collected throughout three typical periods： the end of freeze-thaw （March）, the middle of irrigation （July）, and the end of autumn watering （November）. Comprehensive methods were utilized, such as statistical analysis, Piper three-line diagram, Gibbs diagram, ion ratio, and principal component analysis, to explore the changes in the groundwater chemical environment and the environmental driving factors of groundwater component formation. The groundwater drinking suitability was evaluated using the water quality index （WQI）, and the irrigation suitability was analyzed using the USSL and Wilcox plots. The results indicated that the groundwater in the research areas was generally saline, and the total anion and cation concentrations in each period in ascending order were as follows： late freeze-thaw stage, late autumn irrigation stage, and mid-irrigation stage, with Na + and Cl - being the major contributing ions. The chemical type of groundwater was dominated by Cl-Na, followed by Cl·SO 4 -Ca·Mg and a coexistence with SO 4 -Ca·Mg, HCO 3 ·Cl-Na, HCO 3 -Na, and HCO 3 -Ca·Mg. Based on WQI values, the shallow groundwater in Hetao Irrigation District was mainly classified as Class IV and Class V, and the quality was poor in general. According to the USSL diagram and Wilcox diagram, the comprehensive evaluation results showed that the salinity and sodium concentration of shallow groundwater in the irrigation area were generally high. A total of 80.6% of the water samples during the late freeze-thaw period, 76.1% during the mid-irrigation period, and 77.6% during the late autumn irrigation period lacked irrigation suitability. Two major controlling factors of groundwater chemical characteristics were present in the study area, namely, evaporation and rock weathering, and Na + and Cl - mainly came from the dissolution and cation exchange of salt rocks. Agricultural irrigation and drought were the chief driving factors of groundwater chemical evolution in the Hetao Irrigation Area. The study provides technical support for optimizing agricultural management measures and a theoretical reference for rational utilization of groundwater resources in the Yellow River irrigation area of Inner Mongolia.

Polymerase chain reaction (PCR) is the gold standard for nucleic acid amplification and quantification in diverse fields such as life sciences, global health, medicine, agricultural science, forensic science, and environmental science for global sustainability. However, implementing a cost-effective PCR remains challenging for rapid preventive medical action to the widespread pandemic diseases due to the absence of highly efficient and low-cost PCR chip-based POC molecular diagnostics. Here, this work reports an ultrafast metaphotonic PCR chip as a solution of a cost-effective and low-power-consumption POC device for the emerging global challenge of sustainable healthcare. This work designs a near-perfect photonic meta-absorber using ring-shaped titanium nitride to maximize the photothermal effect and realize rapid heating and cooling cycles during the PCR process. This work fabricates a large-area photonic meta-absorber on a 6-inch wafer cost-effectively using simple colloidal lithography. In addition, this work demonstrates 30 thermocycles from 65 (annealing temperature) to 95 °C (denaturation temperature) within 3 min 15 s, achieving an average 16.66 °C s -1 heating rate and 7.77 °C s -1 cooling rate during thermocycling, succeeding rapid metaphotonic PCR. This work believes a metaphotonic PCR chip can be used to create a low-cost, ultrafast molecular diagnostic chip with a meta-absorber., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Sulfur is one of the inorganic elements used by plants to develop and produce phytoalexin to resist certain diseases. This study reported a method for preparing a material for plant disease resistance. Sulfur nanoparticles (SNPs) stabilized in the chitosan-Cu2+ (CS-Cu2+) complex were synthesized by hydrolysis of Na2S2O3 in an acidic medium. The obtained SNPs/CS-Cu2+ complex consisting of 0.32% S, 4% CS, and 0.7% Cu (w/v), contained SNPs with an average size of ~28 nm as measured by transmission electron microscopy images. The X-ray diffraction pattern of the SNPs/CSCu2+ complex showed that SNPs had orthorhombic crystal structures. Interaction between SNPs and the CS-Cu2+ complex was also investigated by ultraviolet-visible. Results in vitro nematicidal effect of materials against Meloidogyne incognita showed that SNPs/CS-Cu2+ complex was more effective in killing second-stage juveniles (J2) nematodes and inhibiting egg hatching than that of CS and CS-Cu2+ complex. The values of LC50 in killing J2 nematodes and EC50 in inhibiting egg hatching of SNPs/CS-Cu2+ complex were 75 and 51 mg/l, respectively. These values were lower than those of CS and the CS-Cu2+ complex. The test results on the nematicidal effect against M. incognita on coffee pots showed that the SNPs/CS-Cu2+ complex was 100% effective at a concentration of 150 mg/l. Therefore, the SNPs/CS-Cu2+ complex could be considered as a biochemical material with potential for agricultural applications to control root-knot nematodes.

This study aims to explore the effects of tetramethylpyrazine(TMP) on pharmacokinetics in plasma and brain dialysate and neuropathic pain in the rat model of partial sciatic nerve injury(SNI), and to investigate the correlation between the analgesic effect of TMP and its concentrations in the plasma and brain dialysate. Male SD rats were randomized into Sham, SNI, and SNI+TMP groups. Mechanical stimulation with von frey filaments and cold spray method were employed to evaluate the mechanical sensitivity and cold sensitivity of rats. Another two groups, Sham+TMP and SNI+TMP, were used to intubate the common jugular vein and implant microdialysis probes into the anterior cingulate gyrus(ACC), respectively.After intraperitoneal injection of TMP at a dose of 80 mg·kg~(-1), automatic blood collection and intracerebral microdialysis(perfusion rate of 1 μL·min~(-1)) systems were used to collect the blood and brain dialysate for 24 h. HSS T3 C_(18) reversed-phase chromatographic column(2.1 mm×50 mm, 2.5 μm) was used for liquid chromatographic separation. Gradient elution was carried out with the mobile phase of methanol-water(containing 0.005% formic acid) at a flow rate of 0.25 mL·min~(-1). Electrospray ion source was used for mass spectrometry, and the scanning mode was multi-reaction monitoring under the positive ion mode. The ion pairs for quantitative analysis were TMP m/z 137/122 and aspirin m/z 179/137, respectively. DAS 2.11 was used to calculate the pharmacokinetic parameters. The optimal time of TMP to exert the analgesia effect and inhibit cold pain sensitivity was 60 min after treatment. The TMP in the plasma and brain dialysate of SNI rats showed the T_(max) of 15 min and 30 min, the C_(max) of(2 866.43±135.39) and(1 462.14±197.38) μg·L~(-1), the AUC_(0-t) of(241 463.30±28 070.31) and(213 115.62±32 570.07) μg·min·L~(-1), the MRT_(0-t) of(353.13±47.73) and(172.16±12.72) min, and the CL_Z of 0.73 and 0.36 L·min·kg~(-1), respectively. The analgesic effect of TMP had a significant correlation with the blood drug concentration in the ACC, which indicated that this method was suitable for the detection of TMP in rat plasma and brain dialysate. The method is accurate, reliable, and sensitive and can realize the important value of the application of correlation analysis theory of "automatic blood collection-microdialysis/PK-PD" in the research on neuropathic pain.

Infrared chiral plasmonic metamaterials based on perpendicularly positioned nanorods enable surface-enhanced vibrational circular dichroism for more selective and sensitive identification of protein fingerprints and enantioselective sensing, which creates a new pathway for chemical or biomedical applications., (© 2023. Changchun Institute of Optics, Fine Mechanics and Physics (CIOMP), CAS.)

Chitosan (CS) is only soluble in weak acid medium, thereby limiting its wide utilisation in the field of biomedicine, food, and agriculture. In this report, we present a method for preparing water-soluble CS oligosaccharides (COSs) at high concentration (∼10%, w/v) via the oxidative hydrolysis of CS powder with molecular weight (Mw) ∼90,000 g/mol) in 2% H 2 O 2 solution at ambient temperature by a two-step process, namely, the heterogeneous hydrolysis step and homogeneous hydrolysis step. The resultant COSs were characterised by gel permeation chromatography (GPC), fourier transforms infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-Vis), proton nuclear magnetic resonance spectroscopy ( 1 H NMR) and X-ray diffraction (XRD) spectroscopy. The resulting products were composed of COSs (Mw of 2000-6600 g/mol) that were completely soluble in water. The results also indicated that the structure of COSs was almost unchanged compared with the original CS unless Mw was low. Accordingly, COSs with low Mw (∼2000 g/mol) and high concentration (10%, w/v) could be effectively prepared by the oxidative hydrolysis of CS powder using hydrogen peroxide under ambient conditions., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Metaphotonic devices, which enable light manipulation at a subwavelength scale and enhance light-matter interactions, have been emerging as a critical pillar in biosensing. Researchers have been attracted to metaphotonic biosensors, as they solve the limitations of the existing bioanalytical techniques, including the sensitivity, selectivity, and detection limit. Here, we briefly introduce types of metasurfaces utilized in various metaphotonic biomolecular sensing domains such as refractometry, surface-enhanced fluorescence, vibrational spectroscopy, and chiral sensing. Further, we list the prevalent working mechanisms of those metaphotonic bio-detection schemes. Furthermore, we summarize the recent progress in chip integration for metaphotonic biosensing to enable innovative point-of-care devices in healthcare. Finally, we discuss the impediments in metaphotonic biosensing, such as its cost effectiveness and treatment for intricate biospecimens, and present a prospect for potential directions for materializing these device strategies, significantly influencing clinical diagnostics in health and safety.

Mass urbanisation and intensive agricultural development across river deltas have driven ecosystem degradation, impacting deltaic socio-ecological systems and reducing their resilience to climate change. Assessments of the drivers of these changes have so far been focused on human activity on the subaerial delta plains. However, the fragile nature of deltaic ecosystems and the need for biodiversity conservation on a global scale require more accurate quantification of the footprint of anthropogenic activity across delta waterways. To address this need, we investigated the potential of deep learning and high spatiotemporal resolution satellite imagery to identify river vessels, using the Vietnamese Mekong Delta (VMD) as a focus area. We trained the Faster R-CNN Resnet101 model to detect two classes of objects: (i) vessels and (ii) clusters of vessels, and achieved high detection accuracies for both classes (f-score = 0.84-0.85). The model was subsequently applied to available PlanetScope imagery across 2018-2021; the resultant detections were used to generate monthly, seasonal and annual products mapping the riverine activity, termed here the Human Waterway Footprint (HWF), with which we showed how waterborne activity has increased in the VMD (from approx. 1650 active vessels in 2018 to 2070 in 2021 - a 25 % increase). Whilst HWF values correlated well with population density estimates (R 2 = 0.59-0.61, p < 0.001), many riverine activity hotspots were located away from population centres and varied spatially across the investigated period, highlighting that more detailed information is needed to fully evaluate the extent, and type, of human footprint on waterways. High spatiotemporal resolution satellite imagery in combination with deep learning methods offers great promise for such monitoring, which can subsequently enable local and regional assessment of environmental impacts of anthropogenic activities on delta ecosystems around the globe., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Free-standing graphene-based paper-like materials have garnered significant interest for various applications because of their tunable physical and chemical properties, along with unique multilayered structures. Because of the layered configuration of graphene paper, characterization of the interactions between graphene sheets is critical for understanding its fundamental properties and applications. We investigate the interlayer cohesion energies in graphene papers using the mode I fracture concept with double cantilever beam specimens. Mechanical separation along the middle of the graphene paper thickness enables the evaluation of interlayer bonding strength in the paper. Starting from graphene oxide paper, the chemical reduction using hydroiodic acid tunes the interlayer cohesion energy from 11.30 ± 0.25 to 4.78 ± 0.18 J/m 2 as the reduction time increases. The interlayer cohesion energy is correlated with the oxygen content, interlayer spacing, and electrical conductivity of graphene papers. This work provides a fundamental characterization of the interlayer cohesion energy of graphene paper and establishes the potential for tunability of the interlayer interactions in graphene paper.

The adhesion of tumor cells to vascular endothelial cells is an important process of tumor metastasis. Studies have shown that tumor could educate vascular endothelial cells to promote tumor metastasis through many ways. However, the effect of tumor cells on the functions of vascular endothelial cells-derived extracellular vesicles (H-EVs) and the mechanisms underlying their effects in tumor-endothelium adhesion in metastasis remain mysterious. In this study, we found that H-EVs promoted the adhesion of triple negative breast cancer cell to endothelial cells and cirGal-3 enhanced the adhesion-promoting effects of H-EVs. The underlying mechanism was related to the upregulation of glycolysis in endothelial cells induced by cirGal-3 which led to the increase of the ICAM-1 expression and its transmission to MDA-MB-231 cells by H-EVs. Targeting of cirGal-3 or glycolysis of vascular endothelium in breast cancer therefore represents a promising therapeutic strategy to reduce metastasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Du, Zheng, Shang, Yang, Sun, Wang, Tang and Guo.)

Abdominal irradiation (IR) destroys the intestinal mucosal barrier, leading to severe intestinal infection. There is an urgent need to find safe and effective treatments to reduce IR-induced intestinal injury. In this study, we reported that metformin protected mice from abdominal IR-induced intestinal injury by improving the composition and diversity of intestinal flora. The elimination of intestinal microbiota (Abx) abrogated the protective effects of metformin on irradiated mice. We further characterized that treatment of metformin increased the murine intestinal abundance of Lactobacillus , which mediated the radioprotective effect. The administration of Lactobacillus or fecal microbiota transplantation (FMT) into Abx mice considerably lessened IR-induced intestinal damage and restored the radioprotective function of metformin in Abx mice. In addition, applying the murine intestinal organoid model, we demonstrated that IR inhibited the formation of intestinal organoids, and metformin alone bore no protective effect on organoids after IR. However, a combination of metformin and Lactobacillus or Lactobacillus alone displayed a strong radioprotection on the organoid formation. We demonstrated that metformin/ Lactobacillus activated the farnesoid X receptor (FXR) signaling in intestinal epithelial cells and hence upregulated tight junction proteins and mucins in intestinal epithelia, increased the number of goblet cells, and augmented the mucus layer thickness to maintain the integrity of intestinal epithelial barrier, which eventually contributed to reduced radiation intestinal injury. In addition, we found that Lactobacillus abundance was significantly increased in the intestine of patients receiving metformin while undergoing abdominal radiotherapy and the abundance was negatively correlated with the diarrhea duration of patients. In conclusion, our results demonstrate that metformin possesses a protective effect on IR-induced intestinal injury by upregulating the abundance of Lactobacillus in the intestine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Liu, Lv, Guo, He, Zhang, Wang, Cui, Yan, Du, Wang, Ding, Liu, Xu and Jian.)

Downregulated DSC2 involved in the metastasis of cancers. Unfortunately, its role on the development of gastric cancer (GC) and the potential mechanisms remain unclear. Bioinformatics analysis, Western blot, qRT-PCR, and immunohistochemistry were performed to detect the DSC2 levels of human GC and normal stomach tissues. The role of DSC2 and the downstream signaling in gastric carcinogenesis were explored by using GC specimens, GC cells with different DSC2 expression, inhibitors, and mouse metastasis models. We found that the level of DSC2 decreased significantly in GC tissues and cells. Recovered DSC2 inhibited the invasion and migration of GC cells both in culture and in xenografts. Mechanistically, DSC2 could not only decrease Snail level and nuclear BRD4 level by forming DSC2/BRD4, but also inhibit nuclear translocation of β -catenin. We concluded that DSC2 inhibited the metastasis of GC, and the underlying mechanisms were closely related to the regulation on nuclear translocation of BRD4 and β -catenin. Our results suggest that DSC2 may serve as a novel therapeutic target for GC., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Chao Sun et al.)

Large amounts of tumor-associated macrophages (TAM), which are predominately localized in hypoxia area of the tumor tissue, are associated with the malignant progression of the tumor. In the present study, we investigated the inhibitory effects of modified citrus pectin (MCP), a natural dietary polysaccharide, on the survival and polarization of TAM in relation to its inhibition on the growth and migration of breast cancer. M2 macrophages polarized from human monocyte THP-1 were chosen as a model for TAM. We showed that MCP (0.06%-1%) concentration-dependently suppressed the survival of TAM through inhibiting glucose uptake with a greater extent in hypoxia than in normoxia. Furthermore, MCP treatment decreased ROS level in TAM through its reducibility and inhibiting galectin-3 expression, leading to inhibition of glucose transporter-1 expression and glucose uptake. In addition, MCP suppressed M2-like polarization via inhibiting STAT3 phosphorylation. Moreover, the tumor-promoting effect of TAM could be restrained by MCP treatment as shown in human breast cancer MDA-MB-231 cells in vitro and in mouse breast cancer 4T1-luc orthotopic and metastasis models. In both tumor tissue and lung tissue of the mouse tumor models, the number of TAM was significantly decreased after MCP treatment. Taken together, MCP may be a promising agent for targeting TAM in tumor hypoxic microenvironment for breast cancer treatment., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Background: Intramuscular antitoxin is recommended in tetanus treatment, but there are few data comparing human and equine preparations. Tetanus toxin acts within the CNS, where there is limited penetration of peripherally administered antitoxin; thus, intrathecal antitoxin administration might improve clinical outcomes compared with intramuscular injection., Methods: In a 2  × 2 factorial trial, all patients aged 16 years or older with a clinical diagnosis of generalised tetanus admitted to the intensive care unit of the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, were eligible for study entry. Participants were randomly assigned first to 3000 IU human or 21 000 U equine intramuscular antitoxin, then to either 500 IU intrathecal human antitoxin or sham procedure. Interventions were delivered by independent clinicians, with attending clinicians and study staff masked to treatment allocations. The primary outcome was requirement for mechanical ventilation. The analysis was done in the intention-to-treat population. The study is registered at ClinicalTrials.gov, NCT02999815; recruitment is completed., Findings: 272 adults were randomly assigned to interventions between Jan 8, 2017, and Sept 29, 2019, and followed up until May, 2020. In the intrathecal allocation, 136 individuals were randomly assigned to sham procedure and 136 to antitoxin; in the intramuscular allocation, 109 individuals were randomly assigned to equine antitoxin and 109 to human antitoxin. 54 patients received antitoxin at a previous hospital, excluding them from the intramuscular antitoxin groups. Mechanical ventilation was given to 56 (43%) of 130 patients allocated to intrathecal antitoxin and 65 (50%) of 131 allocated to sham procedure (relative risk [RR] 0·87, 95% CI 0·66-1·13; p=0·29). For the intramuscular allocation, 48 (45%) of 107 patients allocated to human antitoxin received mechanical ventilation compared with 48 (44%) of 108 patients allocated to equine antitoxin (RR 1·01, 95% CI 0·75-1·36, p=0·95). No clinically relevant difference in adverse events was reported. 22 (16%) of 136 individuals allocated to the intrathecal group and 22 (11%) of 136 allocated to the sham procedure experienced adverse events related or possibly related to the intervention. 16 (15%) of 108 individuals allocated to equine intramuscular antitoxin and 17 (16%) of 109 allocated to human antitoxin experienced adverse events related or possibly related to the intervention. There were no intervention-related deaths., Interpretation: We found no advantage of intramuscular human antitoxin over intramuscular equine antitoxin in tetanus treatment. Intrathecal antitoxin administration was safe, but did not provide overall benefit in addition to intramuscular antitoxin administration., Funding: The Wellcome Trust., Competing Interests: Declaration of interests All authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The failure of a natural dam is an extreme geological event. Palaeo-lake sediments were discovered in the broad Xigazê valley and Dazhuka-Yueju gorge in the middle reach of the Yarlung Tsangpo River in Tibet. However, the sedimentary processes, dam failure, and peak flood of the Xigazê dammed palaeo-lake are poorly understood. Hence, we conducted a field survey of eight lacustrine sedimentary terraces in the area. We divided the sedimentary processes of the palaeo-lake into five stages and deposit types: pre-palaeo-lake sediments (fluvial or aeolian deposits); early stage sediments of the palaeo-lake (coarse sand); main stage palaeo-lake sediments (clayey silt and sand), sediments following the discharge of the palaeo-lake (sand and gravel-cobbles); and cover deposits (aeolian sediments and colluvium). Additionally, the water level along the palaeo-lake was almost constant (3811 m a.s.l.). The dam was likely located at the eastern end of the Dazhuka-Yueju gorge. Based on the water level, dam location and 30-m ASTER GDEM2 data, the capacity of the palaeo-lake was estimated as 22.55 km 3 . To separate the water volume and sediment volume, the sediment surface elevation along the palaeo-lake was simulated based on the elevations of the six lacustrine sedimentary terraces. The volume of the sediment was ~11.56 km 3 , which was calculated from the dam location, sediment surface elevation, and the ASTER GDEM2 data. Finally, subtraction of the sediment volume from the capacity of the palaeo-lake gave a backwater volume of 10.99 km 3 . The peak flood possibly exceeded 3.4 × 10 5  m 3 /s as a moraine dam joined the discharge during the dam failure. However, the dammed event probably had a limited effect on the landforms at downstream because of the presence of another dammed palaeo-lake in the broad Zetang valley; moreover, the bedrock upstream of the dam was protected from erosion., 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.)

Fatty liver and intestinal barrier damage were widespread in most farmed fish, which severely restrict the development of aquaculture. Therefore, there was an urgent need to develop green feed additives to maintain host liver and intestinal health. In this study, a probiotic pili-like protein, Amuc&#95;1100 (AM protein), was anchored to the surface of Lactococcus lactis ZHY1, and the effects of the recombinant bacteria AM-ZHY1 on liver fat accumulation and intestinal health were evaluated. Zebrafish were fed a basal diet, high-fat diet, and high-fat diet with AM-ZHY1 (10 8 cfu/g) or control bacteria ZHY1 for 4 weeks. Treatment with AM-ZHY1 significantly reduced hepatic steatosis in zebrafish. Quantitative PCR ( q PCR) detection showed that the expression of the lipogenesis [peroxisome-proliferator-activated receptors ( PPAR γ), sterol regulatory element-binding proteins-1c ( SREBP-1c ), fatty acid synthase (FAS) , and acetyl-CoA carboxylase 1 ( ACC1 )] and lipid transport genes ( CD36 and FABP6 ) in the liver were significantly downregulated ( p < 0.05), indicating that AM-ZHY1 could reduce liver fat accumulation by inhibiting lipid synthesis and absorption. Moreover, supplementing AM-ZHY1 to a high-fat diet could significantly reduce serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, indicating that liver injury caused by high-fat diets was improved. The expression of tumor necrosis factor ( TNF ) -a and interleukin ( IL ) -6 in the liver decreased significantly ( p < 0.05), while IL-1 β and IL-10 did not change significantly in the AM-ZHY1 group. Compared to the high-fat diet-fed group, the AM-ZHY1 group, but not the ZHY1 group, significantly increased the expression of intestinal tight junction (TJ) proteins ( TJP1a, claudina, claudin7, claudin7b, claudin11a, claudin12 , and claudin15a ; p < 0.05). Compared to the high-fat diet group, the Proteobacteria and Fusobacteria were significantly reduced and increased in the AM-ZHY1 group, respectively. In conclusion, the recombinant bacteria AM-ZHY1 has the capacity to maintain intestinal health by protecting intestinal integrity and improving intestinal flora structure and improving fatty liver disease by inhibiting lipid synthesis and absorption. This study will lay a foundation for the application of AM protein in improving abnormal fat deposition and restoring the intestinal barrier in fish., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Yang, Zhang, Yao, Xia, Gao, Du, Hu, Ran, Liu and Zhou.)

Excitatory toxicity(ET) is an important factor of neuropathic pain(NPP) induced by central sensitization(CS), and the association of pannexin-1(Panx1)-Src-N-methyl-D-aspartate receptor subunit 2 B(NMDAR-2 B) is an important new pathway for ET to initiate CS. The present study confirmed whether the central analgesic effect of Chuanxiong Rhizoma extract(CRE) was achieved through the synchronous regulation of the brain and spinal pathways of Panx1-Src-NMDAR-2 B. In this study, dynamic and simulta-neo-us microdialysis of the brain and spinal cord in vivo combined with behavioristics, high performance liquid chromatography(HPLC)-fluorescence detection, microdialysis analysis(ISCUS~(flex)), ultrasensitive multifactorial electrochemiluminescence immunoassay, ELISA, and Western blot was employed to investigate the protein expression of NMDAR-2 B, Src, and Panx1, extracellular excitatory amino acids, cytokines, energy metabolites, and substance P in spinal dorsal horn(SDH) and anterior cingulate cortex(ACC) after CRE intervention with the rat model of spared sciatic nerve injury(SNI) as the experimental tool. Compared with the sham group, the SNI group exhibited diminished mechanical withdrawal threshold(MWT)(P&lt;0.01), increased cold spray scores(P&lt;0.01), glutamate(Glu), D-serine(D-Ser), and glycine(Gly) in extracellular fluids of ACC, and Glu, D-Ser, interleukin-1β(IL-1β), and lactic acid(Lac) in extracellular fluids of SDH(P&lt;0.05), dwindled tumor necrosis factor(TNF-α)(P&lt;0.05), and elevated protein levels of NMDAR-2 B, Src, and Panx1 in ACC(P&lt;0.05). Compared with the SNI model rats, high-and medium-dose CRE(CRE-H/M) could potentiate the analgesic activity as revealed by the MWT test(P&lt;0.05) and CRE-M enabled the decrease in cold spray scores(P&lt;0.05). CRE-H/M could inhibit the levels of Glu, D-Ser and Gly in the extracellular fluids of ACC(P&lt;0.05), and the levels of Glu in the extracellular fluids of SDH(P&lt;0.05) in SNI rats. CRE-M significantly increased the levels of glucose(Gluc), Lac, interferon-gamma(IFN-γ), keratinocyte chemoattractant/human growth-regulated oncogenes(KC/GRO), and IL-4 in extracellular fluids of SDH in SNI rats(P&lt;0.05). CRE-H/M/L could also inhibit the levels of NMDAR-2 B, Src and Panx1 in ACC and SDH in SNI rats(P&lt;0.05). The central analgesic effect of CRE is presumedly related to the inhibited release of excitatory amino acid transmitters(Glu, D-Ser and Gly) in ACC and SDH of SNI rats, decreased protein expression of NMDAR-2 B, Src and Panx1 in the two regions, and the regulation of the Panx1-Src-NMDAR-2 B pathway in the spinal cord and brain. The above findings partially clarified the scientific basis of clinical analgesic effect of Chuanxiong Rhizoma.

The emergence of graphene paper comprising well-stacked graphene flakes has promoted the application of graphene-based materials in diverse fields such as energy storage devices, membrane desalination, and actuators. The fundamental properties of graphene paper such as mechanical, electrical, and thermal properties are critical to the design and fabrication of paper-based devices. In this study, the interlayer interactions in graphene paper were investigated by double cantilever beam (DCB) fracture tests. Graphene papers fabricated by flow-directed stacking of electrochemically exfoliated few-layer graphene flakes were mechanically separated into two parts, which generated force-displacement responses of the DCB sample. The analysis based on fracture mechanics revealed that the interlayer separation energy of the graphene paper was 9.83 ± 0.06 J/m 2 . The results provided a fundamental understanding of the interfacial properties of graphene papers, which will be useful for developing paper-based devices with mechanical integrity.

Little is known about how tuberculosis (TB) impairs dendritic cell (DC) function and anti-TB immune responses. We previously showed that the B and T lymphocyte attenuator (BTLA), an immune inhibitory receptor, is involved in TB pathogenesis. Here, we examined whether BTLA expression in TB affects phenotypic and functional aspects of DCs. Active TB patients exhibited higher expression of BTLA in myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) subsets compared with healthy controls (HCs). BTLA expression was similarly high in untreated TB, TB relapse, and sputum-bacillus positive TB, but anti-TB therapy reduced TB-driven increases in frequencies of BTLA + DCs. BTLA + DCs in active TB showed decreased expression of the DC maturation marker CD83, with an increased expression of CCR7 in mDCs. BTLA + DCs in active TB displayed a decreased ability to express HLA-DR and to uptake foreign antigen, with a reduced expression of the co-stimulatory molecule CD80, but not CD86. Functionally, BTLA + DCs in active TB showed a decreased production of IL-12 and IFN-α as well as a reduced ability to stimulate allogeneic T-cell proliferative responses. BTLA + mDCs produced larger amounts of IL-4 and TGF-β than BTLA - mDCs in both HCs and APT patients. BTLA + DCs from active TB patients showed a reduced ability to stimulate Mtb antigen-driven Th17 and Th22 polarizations as compared to those from HCs. Conversely, these BTLA + DCs more readily promoted the differentiation of T regulatory cells (Treg) and Th2 than those from HCs. These findings suggest that TB-driven BTLA expression in DCs impairs the expression of functional DC surrogate markers and suppress the ability of DCs to induce anti-TB Th17 and Th22 response while promoting Th2 and Foxp3 + Tregs., (Copyright © 2020 Zhang, Lu, Wang, Liu, Chen, Shen, Luo, Xu, Peng, Luo, Huang, Wu, Zheng, Yi, Chen and Xu.)

Reprogrammed glucose metabolism is essential for tumor initiation and development, especially for pancreatic ductal adenocarcinoma (PDAC). Most cancer cells rely on aerobic glycolysis, a phenomenon termed "the Warburg effect", to support uncontrolled proliferation and evade apoptosis. However, the direct regulators of the Warburg effect remain areas of active investigation. In this study, we found that the highly conserved transcription factor, TWIST1, is a crucial regulator of aerobic glycolysis in PDAC. Genetic silencing of TWIST1 significantly inhibited the glycolytic phenotypes of PDAC cells as revealed by reduced glucose uptake, lactate production, and extracellular acidification rate, which can be restored by re-expression of siRNA-resistant TWIST1. Moreover, tamoxifen-inducible expression of TWIST1 promoted the Warburg metabolism of PDAC cells. Mechanistically, by luciferase reporter assay and chromatin immunoprecipitation experiment, we showed that TWIST1 can directly increase the expression of several glycolytic genes, including SLC2A1, HK2, ENO1, and PKM2. Of note, the transcriptional regulation by TWIST1 was not dependent on HIF1α or c-Myc. In The Cancer Genome Atlas and Gene Expression Omnibus accession GSE15471, we confirmed that TWIST1 was closely associated with the glycolysis pathway. Collectively, our findings indicate that TWIST1 is likely to act as important regulator of the Warburg effect in PDAC., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: When humans breathe compressed air or N 2 -O 2 mixtures at three to four atmospheres pressure, they will experience nitrogen narcosis that may possibly lead to a diving accident, but the underlying mechanisms remain unclear., Methods: Mice were exposed to 1.6 MPa breathing a N 2 -O 2 mixture adjusted to deliver an inspired PO 2 of 32-42 kPa. The electroencephalogram (EEG) and forced swimming test were used to evaluate the narcotic effect of nitrogen. Neuronal activity was observed via c-Fos expression in cortex and hippocampus tissue after decompressing to the surface. To further investigate underlying molecular mechanisms, we incubated cultured hippocampal neurons with various NMDA concentrations, and measured expression of NMDA receptors and its down-stream signal with or without 1.6 MPa N 2 -O 2 exposure., Results: Both the frequency of the EEG and the drowning time using the forced swimming test were significantly decreased during exposure to 1.6 MPa N 2 -O 2 (P < 0.001). Additionally, in cultured hippocampal neurons, the increased levels of phosphorylated NR2B and cAMP-response element binding protein (CREB) induced by NMDA stimulation were significantly inhibited by exposure to 1.6 MPa N 2 -O 2 ., Conclusions: Our findings indicated that NR2B-containing NMDA receptors were inhibited during nitrogen narcosis., (Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in electronic and other forms.)

Graphene powders obtained via the reduction of graphene oxide flakes have been widely used in various applications as they can be synthesized in large quantities with outstanding properties. The electrical conductivity of graphene powders is critical for their uses in fabricating high-performance devices or materials. Here, we investigated the bulk electrical conductivity of reduced graphene oxide (rGO) powders depending on the applied pressure and additional thermal annealing. The electrical conductivity of the rGO powders was correlated with the change in the carbon-to-oxygen ratio via additional thermal reduction. Furthermore, the effect of the morphology of the rGO powders was studied through electromechanical measurements. This study provides a reliable method for the electromechanical characterization of rGO powders and a better understanding of the electrical conductivity of graphene-based materials.

There is mounting concern about how to support decision-makers in driving sustainable water resources management; science needs to support the decision-making process to promote evidence-based decisions. To this end, sustainability assessment is considered a useful technique, which provides enough information to assist management. This study proposed a groundwater sustainability assessment framework, which is developed from a regular sustainability assessment approach and analytical hierarchy process (AHP). In the proposed framework, the three main pillars (environmental, social, and economic) of the concept of sustainability were considered the three important sustainability criteria. Hence, we demonstrated the proposed framework for a Hanoi case study with focus on the environmental sustainability criterion. The concept of AHP was used to create the main sustainability components (the three criteria, associated with their aspects and indicators) of a hierarchy, which appropriately cover environmental sustainability issues of groundwater resources in the target area. Based on the available reliable data of the current problems in Hanoi, we proposed three main sustainability aspects (quantity, quality, and management) and, accordingly, selected their twelve environmental sustainability indicators. To determine a reasonable sustainability assessment, we considered a conventional linear and non-linear relationship between the indicators and the corresponding sustainability indices. As for the results from the Hanoi case study, the environmental sustainability indices obtained from using a combined linear and non-linear relationship case appropriately reflect the current situation, that is, the environmental sustainability assessment is close to reality. The sustainability indices of the quantity, quality, and management aspects of groundwater were appropriately assessed at acceptable levels, resulting in Hanoi being rated at the acceptable level in the final environmental sustainability index. The variability of the environmental sustainability indices indicated that the current groundwater abstraction networks are heavily concentrated in a few specific areas in Hanoi, which is not optimal for utilizing the rich natural recharge resources of the area. Improvement of the current poor groundwater quality and strict enforcement of environmental regulations are essential to enhancing the environmental sustainability and, more importantly, to drive Hanoi towards sustainable groundwater resources., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Myopia is the leading cause of visual impairments worldwide. Some studies revealed that visual experience in early life affected the final myopia, indicating that environmental factors play an impellent role in the development of myopia. However, risk factors of myopia are still not identified among adolescents in China. A total of 4104 cases of myopia symptom and 3306 emmetropia controls were selected from students in primary and middle schools in Wuhan in 2008. We identified the risk factors associated with myopia symptom by multivariate logistic regression in this cross-sectional study and constructed a risk score system for myopia symptom. The value of the area under the receiver operating characteristic curve (ROC) was 0.735. Furthermore, we followed up 93 students aged 7-9 years for one year and calculated the total points using the score system. We found no significant difference between the final myopia symptom and the results predicted by the total points by pair chi-square test (P>0.05). The score system had a modest ability to estimate the risk factors of myopia symptom. Using this score system, we could identify the students who are at risk of myopia symptom in the future according to their behaviors and environmental factors, and take measures to slow the progress of myopia symptom.

Background: In multiple sclerosis, development of screening tools for remyelination-promoting molecules is timely., Objective: A Xenopus transgenic line allowing conditional ablation of myelinating oligodendrocytes has been adapted for in vivo screening of remyelination-favoring molecules., Methods: In this transgenic, the green fluorescent protein reporter is fused to E. coli nitroreductase and expressed specifically in myelinating oligodendrocytes. Nitroreductase converts the innocuous pro-drug metronidazole to a cytotoxin. Spontaneous remyelination occurs after metronidazole-induced demyelinating responses. As tadpoles are transparent, these events can be monitored in vivo and quantified. At the end of metronidazole-induced demyelination, tadpoles were screened in water containing the compounds tested. After 72 h, remyelination was assayed by counting numbers of oligodendrocytes per optic nerve., Results: Among a battery of molecules tested, siponimod, a dual agonist of sphingosine-1-phosphate receptor 1 and 5, was among the most efficient favoring remyelination. Crispr/cas9 gene editing showed that the promyelinating effect of siponimod involves the sphingosine-1-phosphate receptor 5., Conclusion: This Xenopus transgenic line constitutes a simple in vivo screening platform for myelin repair therapeutics. We validated several known promyelinating compounds and demonstrated that the strong remyelinating efficacy of siponimod implicates the sphingosine-1-phosphate receptor 5.

We have developed 7-diethylaminocoumarin-based chromophores that photoisomerize with visible light. These photoswitches possess many desirable attributes, including large extinction coefficients (18 600-59 100 M-1 cm-1), high quantum yields (0.45-0.50) and resistance to photofatigue. Additionally, time-resolved spectroscopy indicates that both isomerization reactions are complete in less than 1 ns.

Objective: To investigate the significance of variation in ADGRV1 (also known as GPR98, MASS1, and VLGR1), MEF2C, and other genes at the 5q14.3 chromosomal locus in myoclonic epilepsy., Methods: We studied the epilepsy phenotypes of 4 individuals with 5q14.3 deletion and found that all had myoclonic seizures. We then screened 6 contiguous genes at 5q14.3, MEF2C, CETN3, MBLAC2, POLR3G, LYSMD3, and ADGRV1, in a 95-patient cohort with epilepsy and myoclonic seizures. Of these genes, point mutations in MEF2C cause a phenotype involving seizures and intellectual disability. A role for ADGRV1 in epilepsy has been proposed previously, based on a recessive mutation in the Frings mouse model of audiogenic seizures, as well as a shared homologous region with another epilepsy gene, LGI1., Results: Six patients from the myoclonic epilepsy cohort had likely pathogenic ultra-rare ADGRV1 variants, and statistical analysis showed that ultra-rare variants were significantly overrepresented when compared to healthy population data from the Genome Aggregation Database. Of the remaining genes, no definite pathogenic variants were identified., Significance: Our data suggest that the ADGRV1 variation contributes to epilepsy with myoclonic seizures, although the inheritance pattern may be complex in many cases. In patients with 5q14.3 deletion and epilepsy, ADGRV1 haploinsufficiency likely contributes to seizure development. The latter is a shift from current thinking, as MEF2C haploinsufficiency has been considered the main cause of epilepsy in 5q14.3 deletion syndrome. In cases of 5q14.3 deletion and epilepsy, seizures likely occur due to haploinsufficiency of one or both of ADGRV1 and MEF2C., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Aims: Clear cell meningioma (CCM) is a rare subtype of meningioma and shows not only unusual histology, but also unique clinical features. Recently, SMARCE1 mutations have been shown to cause spinal and cranial CCMs. We present 12 cases which were diagnosed with CCM in a single institution between 1997 and 2014, and investigate their SMARCE1 mutation status., Methods and Results: To investigate the SMARCE1 mutation status of these tumours, we used a combination of Sanger sequencing and multiplex ligation-dependent probe amplification analysis and also performed SMARCE1 immunohistochemical staining. We found both SMARCE1 mutational hits, including novel SMARCE1 mutations, in six of eight tested patients. Immunohistochemical analysis showed loss of SMARCE1 protein staining in all but two cases. Two individuals who were diagnosed originally with CCM were negative for SMARCE1 mutations, but tested positive for NF2 mutations. As a result, these two tumours were re-analysed and eventually reclassified, as a microcystic and a mixed pattern of meningothelial meningioma with focal clear cell areas, respectively., Conclusions: These results expand the spectrum of pathogenic variants in SMARCE1 and show that mutation screening can help to facilitate meningioma classification. This may have implications for prognosis and future clinical management of patients, as CCMs are classed as grade II tumours, while microcystic and meningothelial meningiomas are classed as grade I., (© 2016 John Wiley & Sons Ltd.)

The need for alternative approaches to the use of vertebrate animals for hazard assessment of chemicals and pollutants has become of increasing importance. It is now the first consideration when initiating a vertebrate ecotoxicity test, to ensure that unnecessary use of vertebrate organisms is minimized wherever possible. For some regulatory purposes, the use of vertebrate organisms for environmental risk assessments has been banned; in other situations, the number of organisms tested has been dramatically reduced or the severity of the procedure refined. However, there is still a long way to go to achieve a complete replacement of vertebrate organisms to generate environmental hazard data. The development of animal alternatives is based not just on ethical considerations but also on reducing the cost of performing vertebrate ecotoxicity tests and in some cases on providing better information aimed at improving environmental risk assessments. The present Focus article provides an overview of the considerable advances that have been made toward alternative approaches for ecotoxicity assessments over the last few decades. Environ Toxicol Chem 2016;35:2637-2646. © 2016 SETAC., (© 2016 SETAC.)

In this paper we consider the nearness symmetric solution of the matrix equation AXB = C to a given matrix [Formula: see text] in the sense of the Frobenius norm. By discussing equivalent form of the considered problem, we derive some necessary and sufficient conditions for the matrix [Formula: see text] is a solution of the considered problem. Based on the idea of the alternating variable minimization with multiplier method, we propose two iterative methods to compute the solution of the considered problem, and analyze the global convergence results of the proposed algorithms. Numerical results illustrate the proposed methods are more effective than the existing two methods proposed in Peng et al. (Appl Math Comput 160:763-777, 2005) and Peng (Int J Comput Math 87: 1820-1830, 2010).