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The genus Fritillaria has attracted great attention because of its medicinal and ornamental values. At least three reasons, including the accurate discrimination between various Fritillaria species, protection and sustainable development of rare Fritillaria resources as well as understanding of relationship of some perplexing species, have prompted phylogenetic analyses and development of molecular markers for Fritillaria species. Here we determined the complete chloroplast (CP) genomes for F. unibracteata, F. przewalskii, F. delavayi, and F. sinica through Illumina sequencing, followed by de novo assembly. The lengths of the genomes ranged from 151,076 in F. unibracteata to 152,043 in F. przewalskii. Those CP genomes displayed a typical quadripartite structure, all including a pair of inverted repeats (26,078 to 26,355 bp) separated by the large single-copy (81,383 to 81,804 bp) and small single-copy (17,537 to 17,569 bp) regions. Fritillaria przewalskii, F. delavayi, and F. sinica equivalently encoded 133 unique genes consisting of 38 transfer RNA genes, eight ribosomal RNA genes, and 87 protein coding genes, whereas F. unibracteata contained 132 unique genes due to absence of the rps16 gene. Subsequently, comparative analysis of the complete CP genomes revealed that ycf1, trnL, trnF, ndhD, trnN-trnR, trnE-trnT, trnN, psbM-trnD, atpI, and rps19 to be useful molecular markers in taxonomic studies owning to their interspecies variations. Based on the comprehensive CP genome data collected from 53 species in Fritillaria and Lilium genera, a phylogenomic study was carried out with three Cardiocrinum species and five Amana species as outgroups. The results of the phylogenetic analysis showed that Fritillaria was a sister to Lilium, and the interspecies relationships within subgenus Fritillaria were well resolved. Furthermore, phylogenetic analysis based on the CP genome was proved to be a promising method in selecting potential novel medicinal resources to substitute current medicinal species that are on the verge of extinction.

Abstract The absence of tumor antigens leads to a low response rate, which represents a major challenge in immune checkpoint blockade (ICB) therapy. Pyroptosis, which releases tumor antigens and damage‐associated molecular patterns (DAMPs) that induce antitumor immunity and boost ICB efficiency, potentially leads to injury when occurring in normal tissues. Therefore, a strategy and highly efficient agent to induce tumor‐specific pyroptosis but reduce pyroptosis in normal tissues is urgently required. Here, a smart tumor microenvironmental reactive oxygen species (ROS)/glutathione (GSH) dual‐responsive nano‐prodrug (denoted as MCPP) with high paclitaxel (PTX) and photosensitizer purpurin 18 (P18) loading is rationally designed. The ROS/GSH dual‐responsive system facilitates the nano‐prodrug response to high ROS/GSH in the tumor microenvironment and achieves optimal drug release in tumors. ROS generated by P18 after laser irradiation achieves controlled release and induces tumor cell pyroptosis with PTX by chemo‐photodynamic therapy. Pyroptotic tumor cells release DAMPs, thus initiating adaptive immunity, boosting ICB efficiency, achieving tumor regression, generating immunological memory, and preventing tumor recurrence. Mechanistically, chemo‐photodynamic therapy and control‐release PTX synergistically induce gasdermin E (GSDME)‐related pyroptosis. It is speculated that inspired chemo‐photodynamic therapy using the presented nano‐prodrug strategy can be a smart strategy to trigger pyroptosis and augment ICB efficiency.

Background and ObjectivesThis study aimed to compare the efficacy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S) to TACE plus lenvatinib (TACE-L) for the treatment of HCC with portal vein tumor thrombus (PVTT).MethodsThis cohort study recruited patients from September 2017 to September 2020. A total of 59 and 57 consecutive patients were treated with TACE-L and TACE-S, respectively.ResultsBefore propensity score matching (PSM), comparing TACE-L to TACE-S, the median overall survival (OS) time was 16.4 months and 12.7 months, respectively [hazard ratio (HR) 1.34; 95% confidence interval (CI): 0.81–2.20; p = 0.25]. The median progression-free survival (PFS) time was 8.4 months and 7.43 months, respectively (HR 1.54; 95% CI: 0.98–2.41; p = 0.081). After PSM, the median OS time was 18.97 months and 10.77 months, respectively (HR 2.21; 95% CI: 1.12–4.38; p = 0.022); the median PFS time was 10.6 months (95% CI: 6.6–18.0 months) and 5.4 months (95% CI: 4.2–8.1 months), respectively (HR 2.62; 95% CI: 1.43–4.80; p = 0.002). After PSM, the overall response rate (ORR) was 66.8% vs. 33.3% [odds ratio (OR) 0.85; 1.05–6.90; p = 0.037].ConclusionBoth TACE-L and TACE-S are safe, well-tolerated treatments for HCC with PVTT. In HCC with PVTT, TACE-L was significantly superior to TACE-S with respect to OS, PFS, and ORR. A larger-scale randomized clinical trial is needed.

The parsley extract (PLE) was prepared using absolute ethyl alcohol. The PLE and synergistic iodide were firstly utilized as efficacious corrosion inhibitors to slow down the corrosion rate of carbon steel-Q235 in 0.5 mol/L H2SO4 solution. The anti-corrosion performance was researched by weight loss method, electrochemical tests, surface analysis and quantum chemistry calculation. Results of electrochemical and weight loss tests show that the synergetic PLE and I− exhibit the optimal corrosion inhibition efficiency 99%. The combined inhibitor displays the favorable long-term corrosion inhibition effect, and the inhibition efficiency can maintain more than 90% after 144 h immersion. The introduction of I− makes carbon steel surface with higher negative charge amount, which could be beneficial to the interaction between corrosion inhibitor and Fe atoms. The adsorption behavior obeys the Langmuir isotherm adsorption, and involves chemical and physical adsorption. On the basis of electrochemical consequences and theoretical calculation, the adsorption process and anti-corrosion mechanisms are further explored.

On the basis of the discrete element method (DEM), the movement of seed particles during the filling process of a wheat hole-wheel variable seed-metering device was numerically simulated. The impact of various model hole structures, filling postures, and vibration frequencies on the performance of filling was investigated. The results demonstrated that the average speed and filling posture of seeds varied significantly between models. The research demonstrated that the planter’s filling effect was greatly enhanced by raising the average seed population speed in the confined region. Wheat seeds can be filled in the “flat” and “side” postures because the type of hole is conducive to smooth seed filling and the seed in the type of hole is not readily lost owing to vibration. The seed-metering devices adapt well to a vibrational environment, and the vibration factor has no discernible effect on the seed metering rate. The model holes (e.g., inverted fin-shaped holes) with the highest seed filling rate in the simulation test are employed in the bench test to validate the simulation model. The seed rate range was 300–3200 g/min, while the frequency of vibration was 0–10 Hz. Results indicated that the coefficient of variation of the stability of the total seeding rate was less than 1.3%, that the seeding rate of each row was consistent, and that the coefficient of variation was less than 3%, demonstrating that the simulation model was accurate and met the requirements of wheat agronomic seeding.

Parkinson’s disease (PD) is a neurodegenerative disorder closely related to immunity. An important aspect of the pathogenesis of PD is the interaction between α-synuclein and a series of immune cells. Studies have shown that accumulation of α-synuclein can induce an autoimmune response that accelerates the progression of PD. This study discusses the mechanisms underlying the interaction between α-synuclein and the immune system. During the development of PD, abnormally accumulated α-synuclein becomes an autoimmune antigen that binds to Toll-like receptors (TLRs) that activate microglia, which differentiate into the microglia type 1 (M1) subtype. The microglia activate intracellular inflammatory pathways, induce the release of proinflammatory cytokines, and promote the differentiation of cluster of differentiation 4 + (CD4 +) T cells into proinflammatory T helper type 1 (Th1) and T helper type 17 (Th17) subtypes. Given the important role of α-synuclein in the immune system of the patients with PD, identifying potential targets of immunotherapy related to α-synuclein is critical for slowing disease progression. An enhanced understanding of immune-associated mechanisms in PD can guide the development of associated therapeutic strategies in the future.

Background: Alcohol dependence, a global public health problem, leads to structural and functional damage in the brain. Alcohol dependence patients present complex and varied clinical manifestations and live with general complaints existing in contemporary society, making most people with alcohol dependence hard to identify. Therefore, it is important to find potential biomarkers for the diagnosis and evaluation of alcohol dependence. In the study, we explored potential biomarkers for the diagnosis and monitoring of diseases and evaluated brain structural changes in alcohol dependence patients.Methods: Enzyme-linked immunosorbent assay (ELSA) was employed to detect the expression of serum nucleotide-binding oligomerization domain containing 3 (NLRP3) and single-molecule array (Simoa) assay was used to detect the expression of serum neurofilament light (NfL) in 50 alcohol dependence patients and 50 controls with no drinking history. Alcohol consumption was measured by standard drinks. Neuropsychological assessments, including the Montreal cognitive assessment (MoCA), Pittsburgh sleep quality index (PSQI), generalized anxiety disorder (GAD-7), and patient health questionnaire-9 (PHQ-9), were conducted to evaluate cognitive function and psychological state. The degree of white matter lesions (WMLs) was rated using the Fazekas scale based on magnetic resonance imaging analysis. White matter structure was quantified using the voxel-based morphometry method. The correlations between NLRP3 levels, NfL levels, neuropsychological dysfunction, the degree of WMLs, and white matter volume (WMV) were analyzed in alcohol dependence patients.Results: Serum NLRP3 and NfL levels were higher in the alcohol dependence group. NLRP3 levels were irrelevant to monthly alcohol assumption as well as to the MoCA, PSQI, GAD-7, PHQ-9, and Fazekas scale scores and WMV. NfL levels were positively correlated with the PSQI and PHQ-9 scores as well as the degree of WMLs and negatively correlated with the MoCA scores and WMV. No associations were evident between NfL and monthly alcohol assumption and GAD-7 scores in the alcohol dependence group.Conclusion: This study supports the potential value of serum NfL as a non-invasive biomarker in alcohol dependence. The association with neuropsychological dysfunction and degree of WMLs has implications to use NfL as a promising biomarker to assess the severity of brain damage as well as the progression and prognosis of alcohol dependence.

PurposeThe aim of the study was to compare the clinical outcomes of induction chemotherapy (IC) followed by definitive concurrent chemoradiotherapy (dCCRT) versus chemoradiotherapy alone in patients with esophageal squamous cell carcinoma (ESCC) on the basis of a clinical scoring model.MethodsA retrospective review of 599 patients with ESCC treated with dCCRT at our institution from 2010 to 2019 was conducted. The patients were divided into two groups based on whether they received IC. A clinical scoring model was performed using the significant variables obtained from the multivariate analysis. The PFS and OS rates were estimated using the Kaplan–Meier method.ResultsDuring the study period, 182 patients receiving IC followed by dCCRT and 417 dCCRT alone were identified. No significant differences in the PFS and OS rates were observed between the IC group (P=0.532) and the non-IC group (P=0.078). A clinical scoring model was constructed based on independent prognostic factors with scores ranging from 0 to 10.4. The patients were divided into high- and low-risk groups by using the median score as the cutoff value. The PFS rate of patients receiving IC was higher than that of patients treated without IC (P=0.034), while there was no improvement in the OS rate (P=0.794) in the high-risk group. No significant differences in the PFS (P=0.207) or OS (P=0.997) rate were found between the two treatment groups in the low-risk group.ConclusionsThe addition of IC followed by dCCRT for patients with ESCC might be associated with better PFS rates based on a clinical scoring model but has no impact on OS rates. Further prospective studies are warranted for the validation of this model.

There is a large international trade in live birds, which could affect wild bird populations at both national and global scales. It is thus crucial to understand the temporal and geographical dynamics of international trade in wildlife periodically to inform management. We characterized the international legal trade in live birds of species listed in the Appendices of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) by China from 2010 to 2019, and investigated the potential factors influencing this trade. According to the CITES Trade Database, China imported more than 90,000 live birds of about 130 species and exported only 603 live birds of 10 species from 2010 to 2019, indicating that China was a major importer of this group. Most bird species imported by China were Psittaciformes (e.g., Grey Parrot Psittacus erithacus, accounting for 86% of the total imported individuals), while most birds exported from China were Psittaciformes (75%; e.g., Fischer's Lovebird Agapornis fischeri) and Falconiformes (24%; e.g., Saker Falcon Falco cherrug,). These species were traded for different purposes such as commercial activities, zoo, and personal needs. Trading partners included over 40 countries: South Africa, Mali, Guyana, and Suriname were the main exporters of live birds to China, while Qatar and Saudi Arabia were the main importers of live birds from China. The optimal generalized linear model suggested that the bird species richness imported to China was only positively correlated with bird-keeping culture of the exporting countries, which contributed a large quantity (77.87%) to the variation of the bird species richness in trade based on the hierarchical partitioning analyses. Our results may have broad implications for better management of international bird trade with China, including improving population monitoring within their native ranges and invasion risk assessment of the most highly-traded wild-caught and non-native species, improving monitoring and reporting their trade, etc. Further studies are needed to look at trade in particular groups of birds (e.g. Psittaciformes and Falconiformes) for better understanding and management.

Traditional soaking method takes days to remove cassava cyanide. Ten minutes of ultrasonic pretreatment (UPT) was found to be a new effective method to eliminate both cyanogenic glycosides and hydrogen cyanide in cassava. Here, the parameters of UPT were optimized and the underlying mechanisms were investigated. 40.36% and 24.95% of hydrogen cyanide and cyanogenic glycosides in cassava juice were eliminated under 10 min of UPT (45℃, 81 W). UPT before boiling enhanced the total cyanide elimination to 41.94%. The degradation patterns of hydrogen cyanide and cyanogenic glycosides were different. Ultrasound directly eliminated hydrogen cyanide and indirectly degraded cyanogenic glycosides through promoting enzymatic hydrolysis. The β-glucosidase activity was increased by 17.99% induced by ultrasound. This was supported by the movement of hydrophobic residual and the rearrangement of the secondary structure of the molecular as found in fluorescence, CD, FTIR, DSC and TG analysis. This study revealed that UPT acted as a fast and simple technical way in improving cassava safety.

Texture analysis (TA) is a newly arisen field that can detect the invisible MRI signal changes among image pixels. Myocardial infarction (MI) is cardiomyocyte necrosis caused by myocardial ischemia and hypoxia, becoming the primary cause of death and disability worldwide. In recent years, various TA studies have been performed in patients with MI and show a good clinical application prospect. This review briefly presents the main pathogenesis and pathophysiology of MI, introduces the overview and workflow of TA, and summarizes multiple magnetic resonance TA (MRTA) clinical applications in MI. We also discuss the facing challenges currently for clinical utilization and propose the prospect.

Summary: Genetically diverse mouse populations are powerful tools for characterizing the regulation of the proteome and its relationship to whole-organism phenotypes. We used mass spectrometry to profile and quantify the abundance of 6,798 proteins in liver tissue from mice of both sexes across 58 Collaborative Cross (CC) inbred strains. We previously collected liver proteomics data from the related Diversity Outbred (DO) mice and their founder strains. We show concordance across the proteomics datasets despite being generated from separate experiments, allowing comparative analysis. We map protein abundance quantitative trait loci (pQTLs), identifying 1,087 local and 285 distal in the CC mice and 1,706 local and 414 distal in the DO mice. We find that regulatory effects on individual proteins are conserved across the mouse populations, in particular for local genetic variation and sex differences. In comparison, proteins that form complexes are often co-regulated, displaying varying genetic architectures, and overall show lower heritability and map fewer pQTLs. We have made this resource publicly available to enable quantitative analyses of the regulation of the proteome.

Active compounds were always incorporated into biopolymer films in order to enrich and/or enhance their functions. However, the strong volatility of the active compounds and the weak interactions between the compounds and the polymer matrix always leads to an initial burst release and later unstable load of the volatile compounds. Thus, in order to develop a composite film with the function of sustained release of active substance, stearic acid (SA) was incorporated into carboxymethyl cellulose (CMC) films as a secondary carrier for the carvacrol loading and releasing. A two-step homogenization method including high-speed shear homogenizer (HSH) and high-press homogenizer (HPH) was employed to modify the film-forming emulsions. Lipid particle size and rheology behavior of the emulsions were determined, and the microstructure of their final films was characterized by scanning electron microscope (SEM) and X-ray diffraction (XRD). The release behavior of carvacrol from the films was also investigated as well. The results showed that the greatest intensity of homogenization (HSH at 22,000 rpm for 3 min plus HPH at 60 MPa for 10 cycles) resulted in the lowest lipid particle size in the film-forming emulsion and the most homogenous internal structure in final films. The release behavior of carvacrol indicated that the controllable size and distribution of lipid particles could be an effective method to ensure the sustained release of carvacrol from polysaccharide-based films, and furtherly regulate the release rate in a certain range.

Objectives: To assess ultra-early neuroprognostic significance of GFAP, NF-L, UCH-L1, tau, and S100B concentrations, change trajectory, and combination profile after Out-of-Hospital Cardiac Arrest (OHCA). Methods: Prospective enrollment of 22 OHCA and 10 control patients at an academic tertiary care center between May 1, 2017 and January 28, 2020. Blood was collected within one hour of return of spontaneous circulation (ROSC) (H0), at hours 6 (H6), 12, 18, 24, and daily or until discharge or death. Biomarker concentrations, multifactor score, and trajectory change were assessed and compared to final neurologic status (good vs poor Cerebral Performance Category; CPC 1–2 vs CPC 3–5, respectively). Results: 10 patients had good and 12 had poor neurologic outcomes. Poor outcome patients had higher biomarker concentrations and combined biomarker scores at early time points. The earliest significant difference between good and poor outcome patients’ serum biomarkers were at H12 for GFAP (good median: 425 pg/mL [IQR:370−630] vs poor: 5954[1712–65,055] pg/mL; p

Summary: A liquid biopsy is a noninvasive approach for detecting double-stranded circulating tumor DNA (ctDNA) of 90–320 nucleotides in blood plasma from patients with cancer. Most techniques employed for ctDNA detection are time consuming and require expensive DNA purification kits. Electrochemiluminescence resonance energy transfer (ECL-RET) biosensors exhibit high sensitivity, a wide response range, and are promising for straightforward sensing applications. Until now, ECL-RET biosensors have been designed for sensing short single-stranded oligonucleotides of less than 45 nucleotides. In this work, an ECL-RET biosensor comprising graphitic carbon nitride quantum dots was assessed for the amplification-free detection in the blood plasma of DNA molecules coding for the EGFR L858R mutation, which is associated with non-small-cell lung cancer. Following a low-cost pre-treatment, the highly specific ECL-RET biosensor quantified double-stranded EGFR L858R DNA of 159 nucleotides diluted into the blood within a linear range of 0.01 fM to 1 pM, demonstrating its potential for noninvasive biopsies.

Background: Several cardiovascular risk factors have been suggested to be associated with anthracycline-induced cardiotoxicity, but their quantitative effects have not reached a consensus.Methods: We searched PubMed, EMBASE, and Cochrane Library databases for manuscripts published from inception to February 2021, which reported the results of cardiotoxicity due to anthracycline chemotherapy without trastuzumab. Cardiotoxicity defined by any reduction of left ventricular eject fraction (LVEF) to below 50% or a >10% reduction from baseline was defined as the primary endpoint. Odd ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model meta-analysis.Results: A total of 7,488 patients receiving anthracycline chemotherapy without trastuzumab were included, who had at least one risk factor at baseline. Hypertension (OR: 1.99; 95% CI: 1.43–2.76), diabetes mellitus (OR: 1.74; 95% CI: 1.11–2.74), and obesity (OR: 1.72; 95% CI: 1.13–2.61) were associated with increased risk of cardiotoxicity. In addition, the relative reduction of global longitudinal strain (GLS) from baseline after anthracycline treatment could significantly improve the detection ability of cardiotoxicity (28.5%, 95% CI: 22.1–35.8% vs. 16.4%, 95% CI: 13.4–19.9%) compared with LVEF. The early detection rate of anthracycline-induced cardiotoxicity (3 months after chemotherapy) by GLS was 30.2% (95% CI: 24.9–36.1%), which is similar with the overall result of GLS.Conclusions: Hypertension, diabetes mellitus, and obesity are associated with increased risk of anthracycline-induced cardiotoxicity, which indicates that corresponding protective strategies should be used during and after anthracycline treatment. The findings of higher detection rate and better early detection ability for cardiotoxicity than LVEF added new proofs for the advantages of GLS in detection of AIC.

Pestalotiod fungi are associated with a wide variety of plants worldwide and occur as endophytes, pathogens, and saprobes. The present study provides an updated phylogeny for genera Neopestalotiopsis, Pestalotiopsis, and Seiridium using fresh collections from woody oil plants (Camellia oleifera, Olea europaea, Paeonia suffruticosa, Sapium sebiferum, and Vernicia fordii) in Sichuan Province, China. We coupled morphology and combined sequence data analyses of ITS, tub2, and tef1-α for Neopestalotiopsis and Pestalotiopsis, with ITS, LSU, tub2, tef1-α, and rpb2 for Seiridium. Three novel species of Neopestalotiopsis (N. mianyangensis, N. paeonia-suffruticosa, N. terricola) and three of Seiridium (S. guangyuanum, S. vernicola, S. oleae), were found. Three other species, Pestalotiopsis kenyana, Seiridium ceratosporum, and S. rosarum were identified and reported as new records. All isolated species are fully described and illustrated. Additionally, the sexual morph of Pestalotiopsis kenyana is described for the first time. Pathogenicity tests revealed that Neopestalotiopsis mianyangensis, N. paeonia-suffruticosa, N. terricola, Pestalotiopsis kenyana, Seiridium guangyuanum, S. vernicola, and S. oleae are pathogenic on detached olive leaves.

This study investigates the seasonal variation of dust aerosol vertical distribution using polarized Micropulse lidar (MPL) measurements at the Atmospheric Radiation Measurement (ARM) North Slope of Alaska (NSA) observatory from January 2013 to September 2017. For the first time, multi-year aerosol backscatter coefficients are retrieved at the ARM NSA site from MPL measurements and are consistent with co-located high spectral resolution lidar (HSRL) measurements. The high-quality aerosol backscatter coefficient retrievals are used to derive the particle depolarization ratio (PDR) at the wavelength of 532 nm, which is used to identify the presence of dust aerosols. The annual cycles of the vertical distributions of dust backscatter coefficient and PDR and dust aerosol optical depth (DAOD) show that aerosol loading has a maximum in late winter and early spring but a minimum in late summer and early autumn. Vertically, dust aerosol occurs in the entire troposphere in spring and winter and in the low and middle troposphere in summer and autumn. Because dust aerosols are effective ice nuclei, the seasonality of dust aerosol vertical distribution has important implications for the Arctic climate through aerosol–cloud–radiation interactions, primarily through impacting mixed-phase cloud processes.

Accurately determining the atmospheric boundary layer height (ABLH) is needed when one is addressing the air quality-related issues in highly urbanized areas, as well as when one is investigating issues that are related to the emission and transport of dust aerosols over the source region. In this study, we propose a new ABLH retrieval method, which is named ADEILP (ABLH that is determined by polarization lidar); it is based on the short-term polarized lidar observation that took place during the intensive field campaign in July 2021 in Tazhong, the hinterland of Taklimakan Desert. Furthermore, we conducted comparisons between the ABLH that was identified using a radiosonde (ABLHsonde), the ABLH that was identified by ERA5 (ABLHERA5) and the ABHL that was identified by ADELIP (ABLHADELIP), and we discussed the implications of the dust events. The ADELIP method boasts remarkable advancements in two parts: (1) the lidar volume linear depolarization ratio (VLDR) that represented the aerosol type was adopted, which is very effective in distinguishing between the different types of boundary layers (e.g., mixing layer and residual layer); (2) the idea of breaking up the entire layer into sub-layers was applied on the basis of the continues wavelet transform (CWT) method, which is favorable when one is considering the effect of fine stratification in an aerosol layer. By combining the appropriate height limitations, these factors ensured that there was good robustness of the ADELIP method, thereby enabling it to deal with complex boundary layer structures. The comparisons revealed that ABLHADELIP shows good consistency with ABLHsonde and ABLHERA5 for non-dust events. Nevertheless, the ADELIP method overestimated the stable boundary layer and underestimated the heights of the mixing layer. The dust events seem to be a possible reason for the great difference between ABLHERA5 and ABLHsonde. Thus, it is worth suggesting that the influence that is caused by the differences of the vertical profile in the ERA5 product should be carefully considered when the issues on dust events are involved. Overall, these findings support the climatological analysis of the atmosphere boundary layer and the vertical distribution characteristics of aerosols over typical climatic zones.

Using photodeposition and plasma, Pt-N co-modified TiO2 nanotube electrodes were created. Several techniques, such as SEM, XRD, UV-VIS-DRS, XPS, and PL, were used to analyze the electrode shape, crystalline structure, light absorption range, elemental composition, and photogenerated carrier recombination efficiency. Using the electrochemical workstation, EIS and I-t were utilized to examine the electrochemical characteristics. The results indicated that the diameter of the TiO2 nanotube tubes was around 90 nm, and that the photodeposition duration affected the amount of Pt particles deposited. The deposited Pt particles efficiently reduced the photogenerated carrier complexation rate of the N-TiO2 nanotube electrode, contributing to the separation of electron-hole pairs and light utilization. Electrochemical studies indicated that Pt-N co-modified TiO2 increased the electrode’s oxidation and electrical conductivity, as well as its photoelectrocatalytic capacity. Oxytetracycline degradation in simulated wastewater by a Pt-N co-modified TiO2 nanotube electrode revealed the exceptional PEC activity, and the oxytetracycline degradation processes followed primary kinetics. •O2− and •OH played a significant role in the photoelectrocatalytic degradation of oxytetracycline, resulting in a novel method for oxytetracycline degradation.

As a widely clinical detection method, ultrasonography (US) has been applied to the diagnosis of breast cancer. In this paper, the multi-element synthetic aperture focusing (M-SAF) is applied to the ring array of breast ultrasonography (US) imaging, which addresses the problem of low imaging quality due to the single active element for each emission and the reception in the synthetic aperture focusing. In order to determine the optimal sub-aperture size, the formula is derived for calculating the internal sound pressure of the ring array with a 200 mm diameter, and the sound pressure distribution is analyzed. The ring array with 1024 elements (1024 ring array) is established in COMSOL Multiphysics 5.6, and the optimal sub-aperture size is 16 elements, according to the sound field beam simulation and the directivity research. Based on the existing experimental conditions, the ring array with 256 elements (256 ring array) is simulated and verified by experiments. The simulation has a spatial resolution evaluation in the k-Wave toolbox, and the experiment uses nylon rope and breast model imaging. The results show that if the sub-aperture size has four elements, the imaging quality is the highest. Specifically, the spatial resolution is the best, and the sound pressure amplitude and signal-to-noise ratio (SNR) are maintained at a high level in the reconstructed image. The optimal sub-aperture theory is verified by the two kinds of ring arrays, which also provide a theoretical basis for the application of the multi-element synthetic aperture focusing technology (M-SAF) in ring arrays.

Neural interfaces provide a window for bio-signal modulation and recording with the assistance of neural microelectrodes. However, shrinking the size of electrodes results in high electrochemical impedance and low capacitance, thus limiting the stimulation/recording efficiency. In order to achieve critical stability and low power consumption, here, nanocone-shaped platinum (Pt) with an extensive surface area is proposed as an adhesive layer on a bare Pt substrate, followed by the deposition of a thin layer of iridium oxide (IrOx) to fabricate high-performance nanocone-array-based Pt-IrOx neural microelectrodes (200 μm in diameter). A uniform nanocone-shaped Pt with significant roughness is created via controlling the ratio of NH4+ and Pt4+ ions in the electrolyte, which can be widely applicable for batch production on multichannel flexible microelectrode arrays (fMEAs) and various substrates with different dimensions. The Pt-IrOx nanocomposite-coated microelectrode presents a significantly low impedance down to 0.72 ± 0.04 Ω cm2 at 1 kHz (reduction of ~92.95%). The cathodic charge storage capacity (CSCc) and charge injection capacity (CIC) reaches up to 52.44 ± 2.53 mC cm−2 and 4.39 ± 0.36 mC cm−2, respectively. Moreover, superior chronic stability and biocompatibility are also observed. The modified microelectrodes significantly enhance the adhesion of microglia, the major immune cells in the central nervous system. Therefore, such a coating strategy presents great potential for biomedical and other practical applications.

This study proposes a novel lightweight grape detection method. First, the backbone network of our method is Uniformer, which captures long-range dependencies and further improves the feature extraction capability. Then, a Bi-directional Path Aggregation Network (BiPANet) is presented to fuse low-resolution feature maps with strong semantic information and high-resolution feature maps with detailed information. BiPANet is constructed by introducing a novel cross-layer feature enhancement strategy into the Path Aggregation Network, which fuses more feature information with a significant reduction in the number of parameters and computational complexity. To improve the localization accuracy of the optimal bounding boxes, a Reposition Non-Maximum Suppression (R-NMS) algorithm is further proposed in post-processing. The algorithm performs repositioning operations on the optimal bounding boxes by using the position information of the bounding boxes around the optimal bounding boxes. Experiments on the WGISD show that our method achieves 87.7% mAP, 88.6% precision, 78.3% recall, 83.1% F1 score, and 46 FPS. Compared with YOLOx, YOLOv4, YOLOv3, Faster R-CNN, SSD, and RetinaNet, the mAP of our method is increased by 0.8%, 1.7%, 3.5%, 21.4%, 2.5%, and 13.3%, respectively, and the FPS of our method is increased by 2, 8, 2, 26, 0, and 10, respectively. Similar conclusions can be obtained on another grape dataset. Encouraging experimental results show that our method can achieve better performance than other recognized detection methods in the grape detection tasks.

The current wastewater treatment method shows low efficiency in treating wastewater with high concentrations of chemical mechanical pulp (CMP). Therefore, a chlorine dioxide Pretreatment Anaerobic Treatment (DPAT) was developed and applied to treat the CMP wastewater to obtain higher efficiency, obtaining the following results: The biodegradability of CMP wastewater improved after chlorine dioxide pretreatment. The COD of wastewater treated with chlorine dioxide was reduced from 5634 mg/L to 660 mg/L. The removal rate for chemical oxygen demand (COD) was 88.29%, 29.13% higher than the common anaerobic treatment. The reasons for the high efficiency of the DPAT treatment were that chlorine dioxide pretreatment removed the toxic substances in the original wastewater and thereby promoted the proliferation and growth of the anaerobe. The results show that pretreatment with chlorine dioxide can effectively enhance the biodegradability of high-concentration CMP wastewater. Therefore, DPAT treatment of high-concentration CMP wastewater is beneficial to environmental protection.

In recent years, multibeam sonar has become the most effective and sensitive tool for the detection and quantitation of underwater gas leakage and its rise through the water column. Motivated by recent research, this paper presents an efficient method for the detection and quantitation of gas leakage based on a 300-kHz multibeam sonar. In the proposed gas leakage detection method based on multibeam sonar water column images, not only the backscattering strength of the gas bubbles but also the size and aspect ratio of a gas plume are used to isolate interference objects. This paper also presents a volume-scattering strength optimization model to estimate the gas flux. The bubble size distribution, volume, and flux of gas leaks are determined by matching the theoretical and measured values of the volume-scattering strength of the gas bubbles. The efficiency and effectiveness of the proposed method have been verified by a case study at the artificial gas leakage site in the northern South China Sea. The results show that the leaking gas flux is approximately between 29.39 L/min and 56.43 L/min under a bubble radius ranging from 1 mm to 12 mm. The estimated results are in good agreement with the recorded data (32–67 L/min) for gas leaks generated by an air compressor. The experimental results demonstrate that the proposed method can achieve effective and accurate detection and quantitation of gas leakages.

Multi-principal elements alloys (MPEAs) have been attracted extensive attention in industry due to their extraordinary properties. However, owning to their large degree of freedom in composition design, finding the principal influence factors of the material properties and further coordinating a desirable combination of conflicting properties is always a challenge. In this respect, we have developed a strategy on studying the MPEAs for its composition design in a certain mechanical property by high throughput preparation of powder metallurgy and by machine learning. We chose Zr-Ti-Nb-O alloys as target materials. To unveil key features that mainly influence the mechanical properties, models selection, features screening, and further features importance ordering were performed. The results indicate that the strength and plasticity are dominated by Λ parameter, difference of atomic radius, difference of shear modulus, etc. The prediction error for the strength and plasticity can reach to below 10% and 16%, respectively. According to analysis of the key features, a strength model is modified and used for evaluating the contributions of solid solution strengthening among principle and trace elements. The strategy proposed here will be applicable on element selections for a large variety of material property modulations in the MPEAs prepared by powder metallurgy.

ABSTRACT: Background: Induction of autoantigen-specific Treg cells that suppress tissue-specific autoimmunity without compromising beneficial immune responses is the holy-grail for immunotherapy to autoimmune diseases. Methods: In a model of experimental autoimmune uveitis (EAU) that mimics human uveitis, ocular inflammation was induced by immunization with retinal antigen interphotoreceptor retinoid-binding protein (IRBP). Mice were given intraperitoneal injection of αCD4 antibody (Ab) after the onset of disease, followed by administration of IRBP. EAU was evaluated clinically and functionally. Splenocytes, CD4+CD25− and CD4+CD25+ T cells were sorted and cultured with IRBP or αCD3 Ab. T cell proliferation and cytokine production were assessed. Findings: The experimental approach resulted in remission of ocular inflammation and rescue of visual function in mice with established EAU. Mechanistically, the therapeutic effect was mediated by induction of antigen-specific Treg cells that inhibited IRBP-driven Th17 response in TGF-β and IL-10 dependent fashion. Importantly, the Ab-mediated immune tolerance could be achieved in EAU mice by administration of retinal autoantigens, arrestin but not limited to IRBP only, in an antigen-nonspecific bystander manner. Further, these EAU-suppressed tolerized mice did not compromise their anti-tumor T immunity in melanoma model. Interpretation: We successfully addressed a specific immunotherapy of EAU by in vivo induction of autoantigen-specific Treg cells without compromising host overall T cell immunity, which should have potential implication for patients with autoimmune uveitis. Funding: This study was supported by the Natural Science Foundation of Guangdong Province and the Fundamental Research Fund of the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center.

BackgroundHepatoblastoma (HB) is the most common malignant embryonic liver tumor type in children under 3 years of age. In the present study, the next generation sequencing (NGS) method was used to detect the genotype characteristics of HB and summarize the correlation between the common mutation genotypes noted in this disease and the clinical treatment and prognosis. The results may aid clinical prognosis and the successful application of targeted drugs.MethodsInitially, DNA was extracted from tumor tissue specimens and peripheral blood derived from 19 pediatric patients with HB. Subsequently, DNA panel and NGS methods were used to detect tumor diagnosis and the expression levels of treatment-associated genes, followed by the summary of genotype characteristics. In addition, in order to further assess the application of immunotherapy in HB, immunohistochemical detection of programmed cell death 1 ligand 1 (PDL1) was performed in combination with tumor mutation burden (TMB) and DNA mismatch repair status analysis. Furthermore, the clinical treatment effect and prognosis of the pediatric patients were statistically analyzed according to the characteristics of the genotype. Overall prognosis and prognostic analyses in different groups were performed by Kaplan-Meier and log-rank tests, respectively. Finally, expression validation and diagnostic analysis of commonly reported genes were performed in the GSE75271 dataset, which was obtained from the Gene Expression Omnibus (GEO) database.ResultsIn the present study, certain mutated genes, including nuclear factor erythroid 2-related factor 2 (NFE2L2), catenin β1 (CTNNB1), MYCN, tumor protein p53, axis inhibition protein 1 (AXIN1) and adenomatous polyposis coli (APC) were associated with the pathogenesis of HB. During TMB and DNA mismatch repair status analyses, pediatric patients had a low TMB. All of them did not present with microsatellite instability. The immunohistochemical results indicated lower expression levels of PDL1 in HB. The complete remission (CR) rate of pediatric patients in the gene abnormality group was lower than that of the non-reported disease-associated gene abnormality group. The 2-year overall survival rate and disease-free survival rate of 19 pediatric patients with HB were 72.1% and 42.4%, respectively. Receiver operating characteristic (ROC) analysis demonstrated that CTNNB1, NFE2L2, AXIN1, APC, MYCN and insulin growth factor 2 (IGF2) may be potential biomarkers that could be used for the diagnosis of HB.ConclusionThe genotype changes in HB were more common and the CR rate of the pediatric patients with an altered genotype was lower than that of pediatric patients without an altered genotype. In addition, pediatric patients with HB exhibited lower TMB compared with adult patients. Moreover, the data indicated that CTNNB1, NFE2L2, AXIN1, APC, MYCN and IGF2 may be potential biomarkers that can be used for the diagnosis of HB.

The strawberry (Fragaria × ananassa) is an economically important fruit throughout the world. The large R2R3-MYB gene family participates in a variety of plant functions, including anthocyanin biosynthesis. The present study is the first genome-wide analysis of the MYB gene family in the octoploid strawberry and describes the identification and characterization of the family members using the recently sequenced F. × ananassa genome. Specifically, we aimed to identify the key MYBs involved in petal coloration in the pink-flowered strawberry, which increases its ornamental value. A comprehensive, genome-wide analysis of F. × ananassa R2R3-FaMYBs was performed, investigating gene structures, phylogenic relationships, promoter regions, chromosomal locations, and collinearity. A total of 393 R2R3-FaMYB genes were identified in the F. × ananassa genome and divided into 36 subgroups based on phylogenetic analysis. Most genes with similar functions in the same subgroup exhibited similar exon-intron structures and motif compositions. These R2R3-FaMYBs were unevenly distributed over 28 chromosomes. The expansion of the R2R3-FaMYB gene family in the F. × ananassa genome was found to be caused mainly by segmental duplication. The Ka/Ks analysis indicated that duplicated R2R3-FaMYBs mostly experienced purifying selection and showed limited functional divergence after the duplication events. To elucidate which R2R3-FaMYB genes were associated with anthocyanin biosynthesis in the petals of the pink-flowered strawberry, we compared transcriptional changes in different flower developmental stages using RNA-seq. There were 131 differentially expressed R2R3-FaMYB genes identified in the petals, of which three genes, FaMYB28, FaMYB54, and FaMYB576, appeared likely, based on the phylogenetic analysis, to regulate anthocyanin biosynthesis. The qRT-PCR showed that these three genes were more highly expressed in petals than in other tissues (fruit, leaf, petiole and stolon) and their expressions were higher in red compared to pink and white petals. These results facilitate the clarification on the roles of the R2R3-FaMYB genes in petal coloration in the pink-flowered strawberry. This work provides useful information for further functional analysis on the R2R3-FaMYB gene family in F. × ananassa.

Usher syndrome 2A (USH2A) is one of the most common genes associated with Usher syndrome type II (USH2) and nonsyndromic autosomal recessive retinitis pigmentosa (arRP). Here, we describe the generation and characterization of two human induced pluripotent stem cell (hiPSC) lines from a RP patient with compound heterogeneous USH2A variants and a USH2 patient with homozygous USH2A variant. Blood samples were obtained and peripheral blood mononuclear cells (PBMCs) were reprogrammed using the non-integrative Sendai virus to generate the iPSC lines. The established hiPSC lines retained the disease-associated variants and showed normal karyotype, pluripotency and differentiation capacity.

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases globally. Despite continuous improvement of treatment methods, high postoperative recurrence rate remains an urgent problem. In order to determine the mechanism underlying recurrence of liver cancer and identify prognostic genes, data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were integrated and analyzed. Differentially expressed genes (DEGs) between HCC tissue and normal liver tissue were identified, and a protein–protein interaction network was constructed to find hub genes. Clinical correlation analysis and disease-free survival (DFS) analysis were performed using the R language and GEPIA to identify relapse-related genes. Correlation analysis was used to identify a potential regulatory axis. Dual-luciferase reporter gene assay was used to confirm the reliability of the long non-coding RNA (lncRNA)–microRNA (miRNA)–mRNA regulatory axis. Immune infiltration analysis was performed using the TIMER database. Correlations between immune gene markers and ASF1B were verified using quantitative real-time polymerase chain reaction (RT-qPCR). In this work, we found that nine lncRNAs and five mRNAs were significantly overexpressed in HCC tissues from patients with recurrence. SNHG3, LINC00205, ASF1B, AURKB, CCNB1, CDKN3, and DTL were also closely related to HCC grade and stage. Survival analysis showed that these seven DEGs were significantly correlated with poor DFS. Correlation analysis identified SNHG3–miR-214-3p–ASF1B as a potential regulatory axis. Dual-luciferase reporter gene assay showed that SNHG3 and ASF1B directly bound to miR-214-3p. ASF1B was negatively regulated by miRNA-214-3p, and overexpression of SNHG3 could inhibit the expression of miRNA-214-3p. In addition, ASF1B was positively correlated with immune infiltration. A reduction in ASF1B could markedly inhibit the expression of CD86, CD8, STAT1, STAT4, CD68, and PD1 in HCC cells. Flow cytometry showed that SNHG3 promoted the PD-1 expression by regulating ASF1B. Meanwhile, elevated ASF1B predicted poor prognosis of HCC patients in subgroups with decreased B cells, CD8+ T cells, or neutrophils, and those with enriched CD4+ T cells. In conclusion, we found that a novel lncRNA SNHG3/miR-214-3p/ASF1B axis could promote the recurrence of HCC by regulating immune infiltration.

Pseudomonas aeruginosa, a major cause of nosocomial infection, can survive under diverse environmental conditions. Its great adaptive ability is dependent on its multiple signaling systems such as the two-component system (TCS). A TCS FleS/FleR has been previously identified to positively regulate a variety of virulence-related traits in P. aeruginosa PAO1 including motility and biofilm formation which are involved in the acute and chronic infections, respectively. However, the molecular mechanisms underlying these regulations are still unclear. In this study, we first analyzed the regulatory roles of each domains in FleS/FleR and characterized key residues in the FleS-HisKA, FleR-REC and FleR-AAA domains that are essential for the signaling. Next, we revealed that FleS/FleR regulates biofilm formation in a c-di-GMP and FleQ dependent manner. Lastly, we demonstrated that FleR can regulate flagellum biosynthesis independently without FleS, which explains the discrepant regulation of swimming motility by FleS and FleR.

Obesity is a chronic metabolic disease caused by genetic and environmental factors that has become a serious global health problem. There is evidence that gut microbiota is closely related to the occurrence and development of obesity. Erchen Decoction (ECD), a traditional Chinese medicine, has been widely used for clinical treatment and basic research of obesity and related metabolic diseases in recent years. It can significantly improve insulin resistance (IR) and lipid metabolism disorders. However, there is no microbiological study on its metabolic regulation. In this study, we investigated the effects of ECD on obesity, especially lipid metabolism and the composition and function of gut microbiota in Zucker diabetic fatty (ZDF) rats, and explored the correlation between the biomarkers of gut microbiota and metabolite and host phenotype. The results showed that ECD could reduce body weight, improve IR and lipid metabolism, and reduce the concentration of free fatty acids (FFA) released from white adipose tissue (WAT) due to excessive lipolysis by interfering with the insulin receptor substrate 1 (IRS1)/protein kinase B (AKT)/protein kinase A (PKA)/hormone-sensitive triglyceride lipase (HSL) signaling pathway in ZDF rats. Additionally, ECD gradually adjusted the overall structure of changed gut microbiota, reversed the relative abundance of six genera, and changed the function of gut microbiota by reducing the content of propionic acid, a metabolite of gut microbiota, in ZDF rats. A potentially close relationship between biomarkers, especially Prevotella, Blautia, and Holdemania, propionic acid and host phenotypes were demonstrated through correlation analysis. The results suggested that the beneficial effects of ECD on obesity, especially lipid metabolism disorders, are related to the regulation of gut microbiota in ZDF rats. This provides a basis for further research on the mechanism and clinical application of ECD to improve obesity via gut microbiota.

The study on the mechanism driving the spatial patterns of biological diversity along elevational gradients is a main focus in ecology, biogeography, and conservation biology. Based on the intraspecific variability of tadpole communities in 18 mountainous streams, the present study quantified the spatial patterns of taxonomic and functional diversity, and the environmental factors underlying the process of spatial distribution and diversity. First, our results illustrated that both elevation and microhabitat features (e.g., water pH, dissolve oxygen, current velocity, chlorophyll a, and ammonium nitrogen) determined tadpole community compositions. Second, the richness of functional entities showed a hump-shape response to the change of elevation. However, no significant relationships were detected between other diversity indices at both taxonomic and functional levels and site elevation. Finally, microhabitat environmental variables were the primary drivers of the taxonomic variation and functional diversity in tadpole communities. However, the relative contribution to the variation of specific diversity indices differed among microhabitat environmental variables. Our results supported the claim that the assembly of montane communities is determined by both spatial processes and environmental filtering. Importantly, tadpole taxonomic and functional diversities were strongly determined by microhabitat features in mountainous streams, providing evidence that microhabitat should be a priority in this study of tadpole diversity conservation. This study suggests that tadpole diversity should be considered in the long-time monitoring of species conservation, as the tadpole is part of the life history in amphibians.

Guided tissue regeneration (GTR) is a promising treatment for periodontal tissue defects, which generally uses a membrane to build a mechanical barrier from the gingival epithelium and hold space for the periodontal regeneration especially the tooth-supporting bone. However, existing membranes possess insufficient mechanical properties and limited bioactivity for periodontal bone regenerate. Herein, fish collagen and polyvinyl alcohol (Col/PVA) dual-layer membrane were developed via a combined freezing/thawing and layer coating method. This dual-layer membrane had a clear but contact boundary line between collagen and PVA layers, which were both hydrophilic. The dual membrane had an elongation at break of 193 ± 27% and would undergo an in vitro degradation duration of more than 17 days. Further cell experiments showed that compared with the PVA layer, the collagen layer not only presented good cytocompatibility with rat bone marrow-derived mesenchymal stem cells (BMSCs), but also promoted the osteogenic genes (RUNX2, ALP, OCN, and COL1) and protein (ALP) expression of BMSCs. Hence, the currently developed dual-layer membranes could be used as a stable barrier with a stable degradation rate and selectively favor the bone tissue to repopulate the periodontal defect. The membranes could meet the challenges encountered by GTR for superior defect repair, demonstrating great potential in clinical applications.

Misgurnus anguillicaudatus is a highly valued, aquaculture-relevant food fish in East Asian countries. In this study, the complete mitochondrial genome of Poyang loach was obtained by PCR. The genome is 16,646 bp in length, including 2 ribosomal RNA genes. 13 protein-coding genes, 22 transfer RNA genes, and a non-coding control region, the gene composition and order of the species were similar to most reported from other vertebrates. The phylogenetic tree showed that Misgurnus family got together for one branch, which includes Poyang M. anguillicaudatus, and the other loaches had their own branches.

Abstract Background Fat storage is required for the life cycle of many organisms. The primary fat depot for most vertebrates is white adipose tissue. However, in primitive vertebrates (e.g., agnathan group and elasmobranchs), the liver is usually responsible for fat storage. Among the vertebrates, amphibians have a unique status, as their larvae live in the water and exhibit some primitive traits that are similar to fish. Although it has been recognized that adult frogs use their abdominal white adipose tissue as a primary fat depot, how tadpoles store their fat is still inconclusive. The metabolic traits and physiological functions of primitive fat depots may have wide-ranging implications on the pathology of abnormal lipid deposition in mammals and the evolution of fat storage. Results Rana omeimontis tadpoles used their liver as the primary fat depot. In sufficiently fed tadpoles at stage 30–31, the hepatosomatic index (HSI) reached up to 7%, and triglycerides (TG) accounted for 15% of liver weight. Their liver resembled white adipose tissue in histological morphology, characterized by polygonal hepatocytes filled with fat. Their liver metabolic composition was unique, characterized by the dominance of maltotriose, arachidonic acid and dipeptides in soluble carbohydrates, free fatty acids and amino acids. Hepatic fat was the major metabolic fuel of fasted R. omeimontis tadpoles, which had similar reserve mobilization and allocation patterns as mammals. From a developmental perspective, hepatic fat was important to fuel late metamorphic climax. Interestingly, starvation induced accelerated metamorphosis in tadpoles with high HSI (4.96 ± 0.21%). However, this phenomenon was not observed in tadpoles with low HSI (2.71 ± 0.16%), even though they had similar initial body weight and developmental stage. Hepatic fat abundance was the most prominent difference between the two groups. Conclusion To the best of our knowledge, this is the first report that liver can be the primary fat depot in vertebrates with higher evolutionary status than bony fish. The unique hepatic histological and metabolic traits likely either guard their liver against lipotoxicity or make their hepatocytes adapt to fat accumulation. This fatty liver could be a primitive counterpart of mammalian white adipose tissue (WAT). In addition, our study showed that the hepatic reserves of tadpoles, especially TG content, may provide body condition signals to modulate metamorphosis.

With the increasing demand worldwide for power grid interconnection, a growing number of related projects are under planning or construction. Despite the rapid growth of cross-border interconnection projects, the systematic research on profit models for these projects is insufficient. This paper first analyzes the profit sources of interconnection projects. Based on the analysis results, profit models are considered under different regulatory systems for three types of crossborder interconnection projects: fully market-oriented, semi-marketization, and fully supervised. Finally, measures for increasing the profitability and sustainable development of power interconnection projects are proposed. Keywords: Profit model, Power interconnection, Regulatory system, Physical transmission rights, Financial transmission rights

Abstract Background Bleeker’s yellow tail (Xenocypris davidi Bleeker, YT) and topmouth culter (Culter alburnus Basilewsky, TC) are both famous and important economic freshwater fish in China. YT, a kind of omnivorous fish, has strong resistance. TC, a kind of carnivorous fish, has high-quality meat but poor resistance. Distant hybridization can integrate the advantages of both parents. There has been no previous report regarding hybrid fish derived from female YT × male TC. It is expected that hybridization of these two kinds of fish will result in F1 hybrids with improved characteristics, such as faster growth rate, stronger resistance, and high-quality meat, which are of great significance in fish genetic breeding. Results In this study, we investigated the main biological characteristics of diploid hybrid fish derived from female YT × male TC. The hybrids had an intermediate number of upper lateral line scales between those for YT and TC. The hybrids were diploids with 48 chromosomes and had the same karyotype formula as their parents. The hybrids generated variations in 5S rDNA (designated class IV: 212 bp) and lost specific 5S rDNA derived from the maternal parent (designated class II: 221 bp), which might be related to hybridization. In terms of reproductive traits, all the tested female hybrids exhibited normal gonadal development, and the two-year-old F1 females produced mature eggs. However, all the tested testes of the male hybrids could not produce mature sperm. It is possible that the hybrid lineage will be established by back-crossing the fertile female hybrids and their parents. Conclusions Obtaining a fertile female hybrid fish made the creation of a new type of fish possible, which was significant in fish genetic breeding.

BACKGROUND In current ecological environmental monitoring, the standard methods used to determine the total contents of inorganic elements, such as heavy metals in soil, include atomic absorption spectrometry (AAS), atomic fluorescence spectrometry (AFS) and wavelength dispersive X-ray fluorescence spectrometry (WDXRF). OBJECTIVES To evaluate the quality, validity and mutual comparability of the results obtained by different analytical methods. METHODS Twenty actual soil samples of different types from different regions in China were selected and inserted into the national soil environmental monitoring sample batch blind, and sent to 3-5 laboratories. AAS/AFS, WDXRF and portable X-ray fluorescence spectrometry (p-XRF) were used to determine the total amount of Cr, Ni, Cu, Zn, As, Hg, Cd, Pb, V and Mn in parallel. RESULTS The content of these elements was equally distributed at levels of ≤ 1.0, 1.0-2.0, 2.0-10.0, and 10.0. The results show that 85% samples had better inter-laboratory relative deviation (RD) of the WDXRF method in terms of Cr, Ni, Cu, Zn and Pb. On the other hand, 60% samples had better RD using AFS method for the As determination. Element content had more obvious effect on RD for WDXRF method. Generally, the inter-laboratory precision control was good for both AAS/AFS and WDXRF methods, and the WDXRF method was more desirable. Through further analysis of the parallelism between AAS/AFS and WDXRF methods (evaluated as the relative deviation RD' of the analytical results of these two methods), it showed that almost all the RD' of Cr, Ni, Cu and Zn was less than 20%, and more than eighty percent RD' of As and Pb was less than 20%. The results of Pearson correlation and linear relationship analysis also show that the analytical results of two methods were highly comparable. Additionally, there was also good comparability between the results of AAS/AFS and p-XRF methods for determination of Cr, Ni, Cu, Zn, Pb and As. CONCLUSIONS AAS/AFS method and WDXRF method have equivalent test results. In actual monitoring task, the determination of Cd and Hg with lower contents should be determined by AAS/AFS which have lower detection limits. WDXRF should be chosen for the analysis large quantities of soil. Under specific experimental conditions, the p-XRF method also can obtain an acceptable quantitative results.

Abstract In this paper, we use the instantaneous Bethe–Salpeter method to calculate the semi-leptonic and non-leptonic production of the orbitally excited scalar $$ D_0^* $$ D0∗ in B meson decays. When the final state is 1P state $$ D_0^*(2400) $$ D0∗(2400) , our theoretical decay rate is consistent with experimental data. For $$ D_J^*(3000) $$ DJ∗(3000) final state, which was observed by LHCb collaboration recently and here treated as the orbitally excited scalar $$D^{*}_{0}(2P)$$ D0∗(2P) , its rate is in the order of $$ 10^{-4} \sim 10^{-6}$$ 10-4∼10-6 . We find the special node structure of $$D^{*}_{0}(2P)$$ D0∗(2P) wave function possibly results in the suppression of its branching ratio and the abnormal uncertainty. The 3P states production rate is in the order of $$ 10^{-5}$$ 10-5 .

Abstract Background Pembrolizumab is approved for patients with metastatic, microsatellite instability (MSI)‐high or mismatch repair‐deficient (dMMR) solid tumors. However, very few men with prostate cancer were included in these initial studies. Methods We performed a single institution retrospective review of men with metastatic castrate‐resistant prostate cancer (mCRPC) who were treated with pembrolizumab. The primary objective was to describe the clinical efficacy of pembrolizumab associated with patient and genomic characteristics. Results We identified 48 men who received ≥1 cycle of pembrolizumab for mCRPC. Of these, 94% (45/48) had ≥3 prior lines of therapy for mCRPC. Somatic tumor sequencing was available in 18/48 men (38%). We found that 17% (8/48) had a ≥50% confirmed PSA decline with pembrolizumab, and 8% (4/48) had a ≥90% PSA decline with durations of response ranging from 3.1 to 16.3 months. Two of these four men had mutations in LRP1b, one of whom also had MSH2 loss and was MSI‐H and TMB‐high. Despite prior progression on enzalutamide, 48% (23/48) of men were treated with concurrent enzalutamide. The median PSA progression‐free‐survival was 1.8 months (range 0.4‐13.7 months), with 31% of patients remaining on pembrolizumab therapy and 54% of men remain alive with a median follow‐up of 7.1 months. Conclusions In a heavily pretreated population of men with mCRPC, pembrolizumab was associated with a ≥50% PSA decline in 17% (8/48) of men, including a dramatic ≥90% PSA response in 8% (4/48), two of whom harbored pathogenic LRP1b mutations suggesting that LRP1b mutations may enrich for PD‐1 inhibitor responsiveness in prostate cancer.

Background: Peripheral neuropathies are often caused by disruption of genes responsible for myelination or axonal transport. In particular, impairment in mitochondrial fission and fusion are known causes of peripheral neuropathies. However, the causal mechanisms for peripheral neuropathy gene mutations are not always known. While loss of function mutations in MYH14 typically cause non-syndromic hearing loss, the recently described R941L mutation in MYH14, encoding the non-muscle myosin protein isoform NMIIC, leads to a complex clinical presentation with an unexplained peripheral neuropathy phenotype. Methods: Confocal microscopy was used to examine mitochondrial dynamics in MYH14 patient fibroblast cells, as well as U2OS and M17 cells overexpressing NMIIC. The consequence of the R941L mutation on myosin activity was modeled in C. elegans. Findings: We describe the third family carrying the R941L mutation in MYH14, and demonstrate that the R941L mutation impairs non-muscle myosin protein function. To better understand the molecular basis of the peripheral neuropathy phenotype associated with the R941L mutation, which has been hindered by the fact that NMIIC is largely uncharacterized, we have established a previously unrecognized biological role for NMIIC in mediating mitochondrial fission in human cells. Notably, the R941L mutation acts in a dominant-negative fashion to inhibit mitochondrial fission, especially in the cell periphery. In addition, we observed alterations to the organization of the mitochondrial genome. Interpretation: As impairments in mitochondrial fission cause peripheral neuropathy, this insight into the function of NMIIC likely explains the peripheral neuropathy phenotype associated with the R941L mutation. Fund: This study was supported by the Alberta Children's Hospital Research Institute, the Canadian Institutes of Health Research and the Care4Rare Canada Consortium. Keywords: Mitochondria, Mitochondrial fission, Peripheral neuropathy, Non-muscle myosin, mtDNA, Caenorhabditis elegans

Abstract This work documents the first version of the U.S. Department of Energy (DOE) new Energy Exascale Earth System Model (E3SMv1). We focus on the standard resolution of the fully coupled physical model designed to address DOE mission‐relevant water cycle questions. Its components include atmosphere and land (110‐km grid spacing), ocean and sea ice (60 km in the midlatitudes and 30 km at the equator and poles), and river transport (55 km) models. This base configuration will also serve as a foundation for additional configurations exploring higher horizontal resolution as well as augmented capabilities in the form of biogeochemistry and cryosphere configurations. The performance of E3SMv1 is evaluated by means of a standard set of Coupled Model Intercomparison Project Phase 6 (CMIP6) Diagnosis, Evaluation, and Characterization of Klima simulations consisting of a long preindustrial control, historical simulations (ensembles of fully coupled and prescribed SSTs) as well as idealized CO2 forcing simulations. The model performs well overall with biases typical of other CMIP‐class models, although the simulated Atlantic Meridional Overturning Circulation is weaker than many CMIP‐class models. While the E3SMv1 historical ensemble captures the bulk of the observed warming between preindustrial (1850) and present day, the trajectory of the warming diverges from observations in the second half of the twentieth century with a period of delayed warming followed by an excessive warming trend. Using a two‐layer energy balance model, we attribute this divergence to the model's strong aerosol‐related effective radiative forcing (ERFari+aci = −1.65 W/m2) and high equilibrium climate sensitivity (ECS = 5.3 K).

Grain of indica rice accumulates more toxic cadmium (Cd) than japonica, but the underlying genetic basis is unclear. Here, the authors show that natural variation of OsCd1 contributes to divergence in grain Cd accumulation and transferring japonica allele to indica rice leads to reduced Cd accumulation.

The Markov chain random field (MCRF) model is a spatial statistical approach for modeling categorical spatial variables in multiple dimensions. However, this approach tends to be computationally costly when dealing with large data sets because of its sequential simulation processes. Therefore, improving its computational efficiency is necessary in order to run this model on larger sizes of spatial data. In this study, we suggested four parallel computing solutions by using both central processing unit (CPU) and graphics processing unit (GPU) for executing the sequential simulation algorithm of the MCRF model, and compared them with the nonparallel computing solution on computation time spent for a land cover post-classification. The four parallel computing solutions are: (1) multicore processor parallel computing (MP), (2) parallel computing by GPU-accelerated nearest neighbor searching (GNNS), (3) MP with GPU-accelerated nearest neighbor searching (MP-GNNS), and (4) parallel computing by GPU-accelerated approximation and GPU-accelerated nearest neighbor searching (GA-GNNS). Experimental results indicated that all of the four parallel computing solutions are at least 1.8× faster than the nonparallel solution. Particularly, the GA-GNNS solution with 512 threads per block is around 83× faster than the nonparallel solution when conducting a land cover post-classification with a remotely sensed image of 1000 × 1000 pixels.