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Abstract Label-free detection techniques for single particles and molecules play an important role in basic science, disease diagnostics, and nanomaterial investigations. While fluorescence-based methods are tools for single molecule detection and imaging, they are limited by available molecular probes and photoblinking and photobleaching. Photothermal microscopy has emerged as a label-free imaging technique capable of detecting individual nanoabsorbers with high sensitivity. Whispering gallery mode (WGM) microresonators can confine light in a small volume for enhanced light-matter interaction and thus are a promising ultra-sensitive photothermal microscopy platform. Previously, microtoroid optical resonators were combined with photothermal microscopy to detect 250 nm long gold nanorods and 100 nm long polymers. Here, we combine microtoroids with photothermal microscopy to spatially detect single 5 nm diameter quantum dots (QDs) with a signal-to-noise ratio exceeding 104. Photothermal images were generated by point-by-point scanning of the pump laser. Single particle detection was confirmed for 18 nm QDs by high sensitivity fluorescence imaging and for 5 nm QDs via comparison with theory. Our system demonstrates the capability to detect a minimum heat dissipation of 0.75 pW. To achieve this, we integrated our microtoroid based photothermal microscopy setup with a low amplitude modulated pump laser and utilized the proportional-integral-derivative controller output as the photothermal signal source to reduce noise and enhance signal stability. The heat dissipation of these QDs is below that from single dye molecules. We anticipate that our work will have application in a wide variety of fields, including the biological sciences, nanotechnology, materials science, chemistry, and medicine.

Abstract Background Limited data are available regarding the risk factors for fistula-in-ano (FIA) in infants and toddlers, potentially affecting their daily lives. Objectives The purpose of this study was to identify potential risk factors for FIA in infants and toddlers, in order to implement early preventive interventions, avoid disease progression, and develop therapeutic strategies. Design and settings A retrospective case-control study was conducted, comparing 41 infants and toddlers diagnosed with FIA with 41 healthy controls, between August 2020 and December 2021. Independent variables (a) maternal characteristics during pregnancy and delivery, (b) perinatal characteristics, dietary behaviors, and defecation-related behaviors in infants and toddlers, (c) family dietary behaviors. Results Mothers of infants and toddlers with FIA had given birth more times in the past, while the infants and toddlers themselves had less mealtime, a higher rate of exclusive breastfeeding, frequent loose stools, and a larger proportion of used wipes, experiencing perianal skin anomalies. The logistic regression analysis revealed that there are four significant risk factors associated with the development of FIA in infants and toddlers, including the number of previous deliveries by the mother (OR 6.327), defecation frequency score (OR 5.351), stool consistency score (OR 5.017), and cleaning with wipes after defecation (OR 8.089). Conclusion Based on our data, it appeared that FIA in infants and toddlers could be attributed to several factors. These included an increased number of previous deliveries by mothers, frequent loose stools, and repeated wipe use. To prevent the occurrence and worsening of the disease, it is important to improve the frequency and consistency of stooling and provide proper care. Further research is required to verify these findings in other clinical settings.

Abstract Many fouling-resistant materials have been grafted or coated on the RO membrane surface for fouling-resistance. However, these modified RO membranes still exhibit a fast flux drop towards small charged organic foulants. Herein, we creatively use the quantum chemistry method to screen the thiol group having a close to zero interaction energy with small charged organic foulants. Thus, we selected a small molecule of 2-aminoethanethiol (AET) having a fouling-resistant thiol group and a reactive amine group for RO membrane surface modification. The water permeance of the AET-grafted RO membrane increases from 2.6 ± 0.1 L m−2 h−1 bar−1 to 3.2 ± 0.05 L m−2 h−1 bar−1, 23% higher than that of the pristine membrane. Moreover, the AET-grafted RO membrane exhibits excellent fouling resistance against charged surfactants. Our study offers insights on the design of fouling-resistant molecules for antifouling surface modification of RO membranes towards small charged organic foulants.

Summary: Background: Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC. Methods: Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II–III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154). Findings: Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3–67.6) and 41 of 70 (58.6%, 95% CI 46.2–70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1–2). Interpretation: Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation. Funding: National Natural Science Foundation of China, Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals.

Acrylamide is an important chemical in great global demand for the synthesis of polyacrylamide. A facile and benign approach of concentrating high osmotic acrylamide aqueous solution at a low temperature is needed to replace the current energy-intensive and cost-expensive thermal flash evaporation process. For the first time, a multi-stage forward osmosis (FO) process has been developed to concentrate acrylamide solution from 200 g/L to 600 g/L. Thin-film composite (TFC) membrane was fabricated and used for the multi-stage FO process. Acrylamide feed solution (FS) with various concentrations was systematically characterized in terms of viscosity and osmotic pressure (OP). Draw solutes including NaCl and MgCl2 were tested, and their reverse salt fluxes were measured with the quantification of their accumulative contents in the resultant concentrated acrylamide solution. Different operation modes including AL-FS (active layer facing FS) and AL-DS (active layer facing DS) were explored to optimize the system efficiency of the FO concentration process. Both single- and multi-stage FO operations were investigated, and their performances were quantified to assess the efficiency of the concentration of acrylamide solution. The results demonstrate that the multi-stage FO operation could dramatically improve the system efficiency for the concentration of acrylamide solution better than the single-stage FO process, and the draw concentration renewal at Stages II, III, and IV led to a water flux increase of 18.56%, 17.52%, and 18.43%, respectively. Moreover, the accumulated MgCl2 in the final 600 g/L acrylamide solution was below 3.7 g/L, less than 0.62 wt% impurity in the product of acrylamide. Our work provides a practical insight into the viability and optimization of a multi-stage FO process for concentrating high osmotic chemicals.

IntroductionThis study was aimed at testing a moderated mediation model of teaching mindfulness and teachers’ collective efficacy in the relationships between the organizational climate of kindergartens and teacher professional learning.MethodsA sample of 1,095 kindergarten teachers completed self-report questionnaires assessing their perceptions of the organizational climate of kindergartens, collective efficacy, teaching mindfulness, and professional learning.ResultsControlling for teaching experience and kindergarten level, the results show that kindergarten organizational climate significantly and positively predicted teacher professional learning and the collective efficacy of teachers played a partial mediating role between them.Furthermore, moderation analysis revealed that teaching mindfulness moderated the relationship between kindergarten organizational climate and teacher professional learning.DiscussionThese results expand our understanding of how the organizational climate of kindergartens affects teacher professional learning. In practice, professional learning of kindergarten teachers can be facilitated by creating an open organizational climate and improving their ability to perceive the collective. Furthermore, the moderating role of teaching mindfulness suggests that intervening in teachers’ teaching mindfulness possibly is an influential way to maximize the impact of kindergarten organizational climate on professional learning.

Prostate cancer screening using prostate-specific antigen (PSA) testing is controversial but remains prevalent in many countries. There is little information in Sweden or elsewhere on the spatial variation in PSA testing. This study aims to describe the spatio-temporal variation in PSA testing prior to a prostate cancer diagnosis in the Stockholm region at the municipality and small area levels. A population-based register study comprised men aged 40 years and over living in the Stockholm region during 2007-2016. For Stockholm in 2016, we reported the proportion of men who had a PSA test for the preceding one, two, five and ten years by ten-year age groups. The age-standardised proportion of men having a PSA test was reported for municipalities by calendar years. We used spatial smoothing for calculating the age-standardised proportion of men having a PSA test in a small area for each calendar year. In 2016, 74.0% and 77.8% of men aged 60-69 and 70-79 years respectively had taken a PSA test in the previous ten years. The municipalities of Danderyd and Ekerö showed high proportions of PSA testing. A marked heterogeneity in such proportions within each municipality was observed. The odds ratio for having a PSA test for those born in Sweden was 2.22 (95% CI 2.00-2.52). Opportunistic PSA testing is widespread with three quarters of men in their sixties and seventies having had a test in the preceding decade. We found evidence for marked geographical heterogeneity, where more affluent and metropolitan areas had higher levels of testing. Variations in PSA testing was associated with socio-economic position and demographic factors including education, income and country of birth.

Changes in land use types are often influenced by human activities, natural factors, and other factors. To explore the changes in land use types, in this paper, we focused on Jinzhai County in Anhui Province. Landsat series data from 2000 to 2020 were utilized as the primary remote sensing data source and combined with land use investigations, and the land use types were classified to better analyze their changes in Jinzhai County from 2000 to 2020. The main calculation indicators, such as the land use change rate and land use transfer matrix, were used to study the proportions of the different land use types during the past two decades, the comprehensive land use dynamics, and the directions of change of the different land use types.

Background: Rett syndrome (RTT), caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2), severely impairs learning and memory. We previously showed that forniceal deep brain stimulation (DBS) stimulates hippocampal neurogenesis with concomitant improvements in hippocampal-dependent learning and memory in a mouse model of RTT. Objectives: To determine the duration of DBS benefits; characterize DBS effects on hippocampal neurogenesis; and determine whether DBS influences MECP2 genotype and survival of newborn dentate granular cells (DGCs) in RTT mice. Methods: Chronic DBS was delivered through an electrode implanted in the fimbria-fornix. We tested separate cohorts of mice in contextual and cued fear memory at different time points after DBS. We then examined neurogenesis, DGC apoptosis, and the expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) after DBS by immunohistochemistry. Results: After two weeks of forniceal DBS, memory improvements lasted between 6 and 9 weeks. Repeating DBS every 6 weeks was sufficient to maintain the improvement. Forniceal DBS stimulated the birth of more MeCP2-positive than MeCP2-negative DGCs and had no effect on DGC survival. It also increased the expression of BDNF but not VEGF in the RTT mouse dentate gyrus. Conclusion: Improvements in learning and memory from forniceal DBS in RTT mice extends well beyond the treatment period and can be maintained by repeated DBS. Stimulation of BDNF expression correlates with improvements in hippocampal neurogenesis and memory benefits.

Green terror cichlid (Aequidens rivulatus) is a popular tropical freshwater ornamental fish. In 2021, an unknown disease was observed in cultured A. rivulatus in Tianjin, China, with a cumulative mortality rate of 25% within 7 days of onset. The main clinical signs were scale loss, skin ulceration, and slight bleeding. Histopathological observation revealed obvious damage to the liver, spleen, and kidney of diseased fish. In addition, abundant granulomas were observed in the spleen and head kidney of the diseased fish. To define the potential pathogens from A. rivulatus, bacteria were isolated from the visceral tissue of diseased fish with conventional methods. An artificial infection experiment was carried out to prove the pathogenicity of the isolated bacteria. The strains HG-2021-1 and HG-2021-3 were isolated from diseased fish and identified as being responsible for the disease. They were identified as Streptococcus iniae based on physiological and biochemical tests, lctO gene detection, and 16S rRNA gene sequence analysis. According to the result of multilocus sequence typing (MLST), HG-2021-1 and HG-2021-3 belong to different genotypes of S. iniae. Furthermore, they were found to contain the virulence genes pgmA, scpI, cpsD, and pdi, and the median lethal dose (LD50) for A. rivulatus was 1.8 × 106 Colony-Forming Units (CFU)/mL and 6.6 × 106 CFU/mL, respectively. To our knowledge, this is the first report of fish coinfected by two genotypes of S. iniae.

Based on remote sensing images from National Polar-orbiting Partnership—Visible Infrared Imaging Radiometer Suite–like data and related statistical yearbook data acquired at 5-year intervals from 2000 to 2020, the urbanized areas of cities in Anhui Province, China, were extracted. The characteristics of their spatial and temporal expansion were analyzed in combination with the migration path of the urban center of gravity along with measures of the speed and intensity of urban expansion. In addition, the urban development trends in Anhui were evaluated by combining a nighttime light index with spatial autocorrelation and local autocorrelation methods to reveal the characteristics of the level of urban development and internal structural changes in each city in Anhui. The results show that the cities in Anhui are concentrated in two belt areas in the Yangtze and Huai river basins, and that they expanded outward, with several original urbanized areas as the center. The rate of urban expansion reached its lowest point during 2005–2010 and peaked during 2015–2020. The urbanized areas in Anhui were distributed in a northwest–southeast direction, while the center of urban gravity remained in Hefei City during the study period. The total amount of nighttime light in Anhui’s urbanized areas increased by nearly 10 times over 20 years, with the period of 2010–2020 experiencing particularly high increases in nighttime light. The grayness values of urban lights in each period show clear spatial correlation.

Metastasis is one of the leading causes of cancer-related deaths. A comprehensive comparison of the differences between primary and metastatic cancers within the same organ can aid in understanding the growth mechanisms of cancer cells at metastatic sites, thereby helping to develop more effective targeted treatment strategies. Primary liver cancer is one of the most common types of cancer, and the liver is also one of the main metastatic sites. In this paper, we utilize single-cell RNA-Seq data to compare primary liver cancer and colorectal liver metastases from multiple perspectives, including cell types and proportions, activity of various cell types, cell–cell communication, mRNA expression differences within the same types of cells, key factors associated with cell proliferation, etc. Our analysis results show the following: (i) Compared to primary tissue, metastatic tissue contains more cytotoxic T cells and exhausted T cells, and it retains some specific characteristics of the primary site. (ii) Cells of the same type exhibit functional differences between primary and metastatic cancers, with metastatic cancer cells showing lower metabolism levels and immune cells exhibiting stronger immune activity. (iii) Interactions between monocytes and hepato-associated cells are strong in primary cancer, while depleted T cells frequently communicate with hepatocytes in metastatic cancer. (iv) Proliferation-related genes in primary and metastatic cancers are mainly involved in cell energy supply and basic metabolism activity, respectively.

BackgroundThe latissimus dorsi flap (LDF) is the most commonly used autologous flap for breast reconstruction (BR) in China. We conducted this study to explore the current status of BR using LDF with/without implants.MethodsThis study was a single-center retrospective study that included breast tumor patients who underwent LDF breast reconstruction at Fudan University Shanghai Cancer Center (FUSCC) between 2000 and 2021.ResultsWe analyzed 4918 patients who underwent postmastectomy BR, including 1730 patients (35.2%) with autologous flaps. LDF was used for BR in 1093 (22.2%) patients, and an abdominal flap was used in 637 (13.0%) patients. The proportion of LDFs used in autologous BR patients decreased each year and dropped to approximately 65.0% after 2013 due to the increased use of abdominal flaps. Among these patients, 609 underwent extended LDF (ELDF) BR, 455 underwent LDF BR with implants, and 30 received a LDF as a salvage flap due to previous flap or implant failure. Patients who underwent ELDF reconstruction were older and had a higher BMI than those who received a LDF with implants. There was no significant difference in the mean postoperative hospital stay, neoadjuvant chemotherapy rates, or adjuvant radiotherapy rates between the two groups. Major complications requiring surgical intervention occurred in 25 patients (2.29%). There was no significant difference in the incidence of major complications between the two groups (P=0.542).ConclusionsLDF breast reconstruction is a well-developed and safe procedure. The duration of postoperative hospitalization nor the incidence of major complications was affected by implant use.

Purpose: Changes in biological features and functional status make management decisions in older women with primary breast cancer complicated. We aimed to provide an overview of the clinicopathological characteristics and survival outcomes of older breast cancer patients based on the current treatment strategies. Methods: Female patients diagnosed with primary invasive breast cancer at Fudan University Shanghai Cancer Centre from 2008 to 2016 were included. Patients were divided into a younger group (

Abstract PROteolysis TArgeting Chimeras (PROTACs) technology is a new protein-degradation strategy that has emerged in recent years. It uses bifunctional small molecules to induce the ubiquitination and degradation of target proteins through the ubiquitin–proteasome system. PROTACs can not only be used as potential clinical treatments for diseases such as cancer, immune disorders, viral infections, and neurodegenerative diseases, but also provide unique chemical knockdown tools for biological research in a catalytic, reversible, and rapid manner. In 2019, our group published a review article “PROTACs: great opportunities for academia and industry” in the journal, summarizing the representative compounds of PROTACs reported before the end of 2019. In the past 2 years, the entire field of protein degradation has experienced rapid development, including not only a large increase in the number of research papers on protein-degradation technology but also a rapid increase in the number of small-molecule degraders that have entered the clinical and will enter the clinical stage. In addition to PROTAC and molecular glue technology, other new degradation technologies are also developing rapidly. In this article, we mainly summarize and review the representative PROTACs of related targets published in 2020–2021 to present to researchers the exciting developments in the field of protein degradation. The problems that need to be solved in this field will also be briefly introduced.

Postzygotic mutations are acquired in normal tissues throughout an individual’s lifetime and hold clues for identifying mutagenic factors. Here, we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals. In blood, sperm, and muscle cells, we resolved three common types of mutational signatures. Signatures A and B represent clock-like mutational processes, and the polymorphisms of epigenetic regulation genes influence the proportion of signature B in mutation profiles. Notably, signature C, characterized by C>T transitions at GpCpN sites, tends to be a feature of diverse normal tissues. Mutations of this type are likely to occur early during embryonic development, supported by their relatively high allelic frequencies, presence in multiple tissues, and decrease in occurrence with age. Almost none of the public datasets for tumors feature this signature, except for 19.6% of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1 (HIF-1) signaling pathway. Moreover, the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α. Thus, embryonic hypoxia may explain this novel signature across multiple normal tissues. Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C>T transitions at GpCpN sites; and individuals’ genetic background may also influence their postzygotic mutation profiles.

Nano-micro calcium carbonate has a small particle size, uniform distribution, and good dispersion performance, offering great research value and development prospects. It has been widely used as a filler material for rubber, paper, ink, pigments, and coatings. Developing an efficient and controllable approach to preparing nano-micro calcium carbonate with adjustable morphology and controllable size has significant economic and environmental benefits. This study reports the controllable synthesis of nano-micro calcium carbonate meditated by additive engineering. The effects of various additives including inorganic acids, organic acids, alcohol, and surfactants on the particle size and morphology of the prepared materials were investigated. SEM, FT-IR and other characterization methods were used to analyze the prepared nano-micro calcium carbonate particle size, dispersion, and uniformity. The results showed that the particle size of calcium carbonate was 4~7 μm with a cubic structure. The particle size of calcium carbonate prepared by adding surfactant additives is in the range of 1~4 μm, and the crystal shape of calcium carbonate changes from calcite to vaterite after adding sodium dodecyl benzene sulfonate. With the aid of additives, the calcium carbonate particles dispersed more evenly. The mechanism of the controllable synthesis of nano-micro calcium carbonate mediated by additive engineering is elucidated and discussed. SDBS was found to be the best additive for preparing nano-micro calcium carbonate, and the synthesis conditions were explored and optimized.

Insulin-like androgenic gland hormone (IAG) is a key regulator of male sexual differentiation in crustaceans that plays important roles in secondary sexual characteristics and testicular development. As a hormone, IAG interacts with its membrane receptor to initiate downstream signal pathways to exert its biological functions. In this study, we isolated a full-length cDNA of an insulin-like receptor (Sp-IR) from the mud crab Scylla paramamosain. Sequence analysis revealed that this receptor consists of a Fu domain, two L domains, three FN-III domains, a transmembrane domain, and a tyrosine kinase domain, classifying it as a member of the tyrosine kinase insulin-like receptors family. Our results also suggested that Sp-IR was highly expressed in the testis and AG in males. Its expression in the testis peaked in stage I but significantly decreased in stages II and III (p < 0.01). Next, both short- and long-term RNA interference (RNAi) experiments were performed on males in stage I to explore Sp-IR function in mud crabs. The results showed that Sp-vasa and Sp-Dsx expression levels in the testis were significantly down-regulated after the specific knockdown of Sp-IR by RNAi. Additionally, the long-term knockdown of Sp-IR led to a considerable decrease in the volume of seminiferous tubules, accompanied by large vacuoles and a reduced production of secondary spermatocytes and spermatids. In conclusion, our results indicated that Sp-IR is involved in testicular development and plays a crucial role in transitioning from primary to secondary spermatocytes. This study provided a molecular basis for the subsequent analysis of the mechanism on male sexual differentiation in Brachyuran crabs.

Abstract A second‐order adaptive integral terminal sliding mode controller is proposed for the trajectory tracking control of robotic manipulators with uncertainties. A second‐order integral terminal sliding mode surface is designed for which an integral sliding mode (ISM) surface and a fast nonsingular integral terminal sliding mode surface are combined. By using the ISM surface, the reaching phase is removed, which enhances system robustness. The steady‐state error is reduced because of the presence of an error integral term. A fast second‐order nonsingular integral terminal sliding mode surface is employed to ensure that the ISM surface is able to converge to zero rapidly within a finite period of time without leading to a singularity problem. The control input of the proposed controller is continuous. Thus, the chattering phenomenon is removed. An adaptation technique is employed to estimate the upper bound of unknown lumped disturbance. The second‐order derivative of position is calculated using a robust differentiator, making it practical. Simulations and experiments show that the proposed scheme improves the tracking performance and eliminates chattering.

BackgroundNeoadjuvant chemotherapy (NAC) has evolved significantly and has been widely accepted for downstaging disease in early-stage and locally advanced breast cancer patients. Since the optimal surgical intervention for patients receiving NAC remains controversial, we aim to investigate the survival outcome of patients treated with different surgical management.MethodsA retrospective, nested case-control study was conducted in patients with invasive breast cancer that underwent NAC at Fudan University Shanghai Cancer Center from January 2010 to June 2019. Based on surgical intervention, patients were divided into mastectomy and breast conservation groups. Patients were matched on age at diagnosis, menopausal status, the year of the surgery, post neoadjuvant therapy pathological tumor (ypT) stage, post neoadjuvant therapy pathological node (ypN) stage, molecular subtypes, and axillary surgery by propensity score matching.ResultsA total of 2080 patients were enrolled in this study. Among them, 1819 (87.5%) patients were categorized as mastectomy group, and 261 (12.5%) patients were classed as breast conservation group. Over 9-years of research, the proportion of breast conservation steadily increased in patients after NAC. Data showed that younger (P

Abstract Adverse myocardial remodeling, manifesting pathologically as myocardial hypertrophy and fibrosis, often follows myocardial infarction (MI) and results in cardiac dysfunction. In this study, an obvious epicardial adipose tissue (EAT) was observed in the rat model of MI and the EAT weights were positively correlated with cardiomyocyte size and myocardial fibrosis areas in the MI 2- and 4-week groups. Then, rat cardiomyocyte cell line H9C2 and primary rat cardiac fibroblasts were cultured in conditioned media generated from EAT of rats in the MI 4-week group (EAT-CM). Functionally, EAT-CM enlarged the cell surface area of H9C2 cells and reinforced cardiac fibroblast activation into myofibroblasts by elevating intracellular reactive oxygen species (ROS) levels. Mechanistically, miR-134-5p was upregulated by EAT-CM in both H9C2 cells and primary rat cardiac fibroblasts. miR-134-5p knockdown promoted histone H3K14 acetylation of manganese superoxide dismutase and catalase by upregulating lysine acetyltransferase 7 expression, thereby decreasing ROS level. An in vivo study showed that miR-134-5p knockdown limited adverse myocardial remodeling in the rat model of MI, manifesting as alleviation of cardiomyocyte hypertrophy and fibrosis. In general, our study clarified a new pathological mechanism involving an EAT/miRNA axis that explains the adverse myocardial remodeling occurring after MI.

Abstract Nitrate (NO3 −) pollution is a serious global problem, and the quantitative analysis of its sources contributions is essential for devising effective water-related environmental-protection policies. The Shengjin Lake basin, located in the middle to lower reaches of the Yangtze River in China was selected as the research area in our study. We first grouped 29 surface water samples and 33 groundwater samples using cluster analysis, and then analyzed potential nitrate sources for each dataset of δ15N–NO3 − and δ18O–NO3 − isotope values by applying a Bayesian isotope-mixing model. Our results show that the nitrogen pollution in the surface-ground water in the study area seriously exceeded to class V of the Environmental Quality Standard of Surface Water of China. The NO3 − in surface water from the mid-upper reaches of the drainage basin mainly originates from soil nitrogen (SN) and chemical fertilizer (CF), with contribution rates of 48% and 32%, respectively, and the NO3 − in downstream areas mainly originates from CF and manure and sewage (MS), with contribution rates of 48% and 33%, respectively. For the groundwater samples, NO3 − mainly originates from MS, CF, and SN in the mid-upper reaches of the drainage basin and the northside of Dadukou near the Yangtze River, with contribution rates of 34%, 31%, and 29%, respectively, whereas NO3 − in the lower reaches and the middle part of Dadukou mainly originates from MS, with a contribution rate of 83%. The nitrogen conversion of surface water in lakes and in the mid-upper reaches is mainly affected by water mixing, while the groundwater and surface water in the lower plains are mainly affected by denitrification. The method proposed in this study can expand the ideas for tracking nitrate pollution in areas with complex terrain, and the relevant conclusions can provide a theoretical basis for surface and groundwater pollution control in the hilly basin of Yangtze River.

Estimates of aboveground biomass (AGB) in forests and the associated uncertainty are important pieces of information outlined in the United Nations Framework Convention on Climate Change. Traditional integrated surveying methods require high inputs of manpower and material resources, whereas remote sensing technology can be used to improve the efficiency of forest resources surveying at a lower measurement cost. Previous studies have primarily utilized spectral information and textural features as the main modeling factors for AGB prediction models, however, few studies have examined how different modeling factors affect prediction accuracy in detail. At the same time, uncertainties in AGB are usually determine by a data set producing a single prediction result, ignoring the model uncertainty due by residual variability in the prediction results. To solve the above problems, this study focuses on Milin County of the Tibet Autonomous Region of China as the research area and uses data from the Landsat Operational Land Imager, digital elevation models (DEM), and the national forest inventory (NFI) to extract and analyze spectral information, textural features, and terrain factors. Four regression models based on different combinations of variables were established using a combination of random forest and Monte Carlo simulation methods (RF-MC), and the uncertainties of each model were determined. The purpose of this paper is to study the influence of different types of variable factors on AGB inversion and to measure the model uncertainty resulting from changes in the variable factors. The coefficient of determination (R2), mean absolute error (MAE), and root mean square error (RMSE) were used to evaluate the fit and accuracy of the model, while the relative root mean square error (rRMSE) was used to quantify the uncertainty. The results show that the degree of fitting and accuracy are greatest for the RF-MC model based on three kinds of variables (spectrum and plot data + DEM + texture characteristics) the best (R2 = 0.85, RMSE = 11.76 t/ha, MAE = 8.49 t/ha, rRMSE = 5.97 %), which performed better than the RF-MC model based on two variables (spectrum and plot data + texture characteristics, R2 = 0.78, RMSE = 13.93 t/ha, MAE = 10.01 t/ha, rRMSE = 7.07 % or spectrum and plot data + DEM, R2 = 0.69, RMSE = 16.75 t/ha, MAE = 14.62 t/ha, rRMSE = 8.49 %) and the RF-MC model based on a single variable (spectrum and plot data, R2 = 0.49, RMSE = 21.39 t/ha, MAE = 19.84 t/ha, rRMSE = 10.86 %). The range of the predicted model value is 150.6–227.8 t/ha, which is close to the actual value. The RF-MC method based on multifeature is demonstrated to be effective in the practical application of AGB inversion, and different types of modeling variables have a certain impact on the accuracy of AGB inversion. This study provides a theoretical basis for improving the accuracy of AGB estimates and the selection of modeling variables, while also contributing to continued improvements in remote sensing-based systems for monitoring forest resources.

Background: Doxorubicin resistance remains a major therapeutic challenge leading to poor survival prognosis and treatment failure in breast cancer. Although doxorubicin induces massive changes in the transcriptional landscape are well known, potential diagnostic or therapeutic targets associated with the reorganization of three-dimensional (3D) chromatin architecture have not yet been systematically investigated.Methods: Here we performed in situ high-throughput chromosome conformation capture (Hi-C) on parental and doxorubicin-resistant MCF7 (MCF7-DR) human breast cancer cells, followed by integrative analysis of HiC, ATAC-seq, RNA-seq and TCGA data.Results: It revealed that A/B compartment switching was positively correlated to genome-wide differential gene expression. The genome of MCF7-DR cells was spatially reorganized into smaller topologically associating domains (TADs) and chromatin loops. We also revealed the contribution of increased chromatin accessibility and potential transcription factor families, including CTCF, AP-1 and bHLH, to gained TADs or loops. Intriguingly, we observed two condensed genomic regions (∼20 kb) with decreased chromatin accessibility flanking TAD boundaries, which might play a critical role in the formation or maintenance of TADs. Finally, combining data from TCGA, we identified a number of gained and lost enhancer-promoter interactions and their corresponding differentially expressed genes involved in chromatin organization and breast cancer signaling pathways, including FA2H, FOXA1 and JRKL, which might serve as potential treatment targets for breast cancer.Conclusion: These data uncovered a close connection between 3D genome reorganization, chromatin accessibility as well as gene transcription and provide novel insights into the epigenomic mechanisms involving doxorubicin resistance in breast cancer.

Phycocyanin (PC) concentration is used as an indicator to characterize cyanobacteria biomass while monitoring eutrophication in inland water. Remote sensing provides useful methods for quantifying PC concentration; however, there is a shortage of datasets for the long-term monitoring of PC concentration when only a single remote sensing data is used. Therefore, PC concentrations obtained from multisource remote sensing images should be compared before integrating them for long-term monitoring. In this study, machine learning (ML) regression algorithms are used to develop PC concentration retrieval models suitable for Moderate Resolution Imaging Spectroradiometer (MODIS) and Sentinel-3 Ocean and Land Colour Instrument (OLCI) images, and their accuracies are compared. The two optimal retrieval models are applied to satellite images acquired on the same days to compare the spatial consistency of the two PC concentration retrieval results. The results show that the sensitive spectral range of PC concentration is 560–680 nm. Among the ML regression algorithms, gradient boosted tree (GBT) regression exhibits the highest PC retrieval accuracy for both the MODIS images (R2 = 0.82, RMSE = 61.9 μg/L) and OLCI images (R2 = 0.86, RMSE = 45.44 μg/L). The PC concentrations retrieved from the MODIS and OLCI images acquired in bloom and no-bloom periods have a high spatial consistency in most areas of Chaohu Lake. Their correlation coefficient also exceeds 0.7, and the average relative error reaches 0.293 μg/L. However, a large difference exists in areas with high PC concentrations, which may cause by the poor applicability of atmospheric correction algorithms and PC retrieval models in these areas. The proposed PC concentration retrieval models developed using GBT regression in this paper can expend the idea for the quantitative retrieval of other inland water quality parameters in inland water, and the conclusions should enable the effective integration of MODIS and OLCI images for the time series monitoring of PC concentrations in reservoirs and lakes.

The lined seahorse (Hippocampus erectus) is an aquacultural species in China and has important economic and ornamental value. However, the species is affected by disease, which restricts their large-scale cultivation. In 2021, a disease was observed in cultured seahorses in Tianjin, China, with a cumulative mortality rate of 20%. The symptoms observed in the moribund seahorse included a weak swimming capacity, discolored body surface, enlarged liver and kidneys, and numerous white nodules in the parenchymatous organs. The strains HM-2021-1 and HM-2021-2 were isolated from diseased seahorses and were identified as being responsible for the disease. It demonstrated the potential to infect seahorse, and the cumulative mortalities of the seahorses artificially infected with strains HM-2021-1 and HM-2021-2 were 93.3% and 90.0%. The pathogen was identified as Mycobacterium chelonae based on physiological and biochemical tests, and 16S rDNA, rpoB, and Hsp65 gene sequence analysis. To our knowledge, this study is the first report of M. chelonae associated with diseased seahorses in China.

Hydropower is the largest source of renewable energy in the world and currently dominates flexible electricity production capacity. However, climate variations remain major challenges for efficient production planning, especially the annual forecasting of periodically variable inflows and their effects on electricity generation. This study presents a model that assesses the impact of forecast quality on the efficiency of hydropower operations. The model uses ensemble forecasting and stepwise linear optimisation combined with receding horizon control to simulate runoff and the operation of a cascading hydropower system. In the first application, the model framework is applied to the Dalälven River basin in Sweden. The efficiency of hydropower operations is found to depend significantly on the linkage between the representative biannual hydrologic regime and the regime actually realised in a future scenario. The forecasting error decreases when considering periodic hydroclimate fluctuations, such as the dry–wet year variability evident in the runoff in the Dalälven River, which ultimately increases production efficiency by approximately 2% (at its largest), as is shown in scenarios 1 and 2. The corresponding potential hydropower production is found to vary by 80 GWh/year. The reduction in forecasting error when considering biennial periodicity corresponds to a production efficiency improvement of about 0.33% (or 13.2 GWh/year).

Abstract Regarded as the third pole of the Earth, the Tibetan Plateau (TP) is a region with complex terrain. Vegetation is widely distributed in the southeastern part of the plateau. However, the land use and land cover changes (LULCC) on the TP have not been sufficiently studied. In this study, we propose a method of studying the dynamic changes in the land cover on the TP. Landsat OLI images (2013 and 2015) were selected to extract the LULCC information of Nyingchi County, the DEM was used to extract objects’ land curved surface area and analyze their three-dimensional dynamic change information, which realized a four-dimensional monitoring of the forestry information on time and spatial level. The results showed that the forest area in 2015 decreased by 7.25%, of which the coniferous forest areas decreased by 25.14%, broad-leaved forest areas increased by 12.65%, and shrubbery areas increased by 14.62%. Compared with traditional LULCC detection methods, the change detection is no longer focused on the two-dimensional space, which helps determine the three-dimensional land use and land cover changes and their distribution. Thus, dynamic spatial changes can be observed. This study provides scientific support for the vegetation restoration and natural resource management on the TP.

Pectin, cellulose, and hemicellulose constitute the primary cell wall in eudicots and function in multiple developmental processes in plants. Root hairs are outgrowths of specialized epidermal cells that absorb water and nutrients from the soil. Cell wall architecture influences root hair development, but how cell wall remodeling might enable enhanced root hair formation in response to phosphate (P) deficiency remains relatively unclear. Here, we found that POLYGALACTURONASE INVOLVED IN EXPANSION 2 (PGX2) functions in conditional root hair development. Under low P conditions, a PGX2 activation tagged line (PGX2AT) displays bubble-like root hairs and abnormal callose deposition and superoxide accumulation in roots. We found that the polar localization and trafficking of PIN2 are altered in PGX2AT roots in response to P deficiency. We also found that actin filaments were less compact but more stable in PGX2AT root hair cells and that actin filament skewness in PGX2AT root hairs was recovered by treatment with 1-N-naphthylphthalamic acid (NPA), an auxin transport inhibitor. These results demonstrate that activation tagging of PGX2 affects cell wall remodeling, auxin signaling, and actin microfilament orientation, which may cooperatively regulate root hair development in response to P starvation.

Myocardial ischemia/reperfusion injury (MI/RI) is a serious pathophysiological process relating to cardiovascular disease. Oroxin A (OA) is a natural flavonoid glycoside with various biological activities. However, its effect on the pathophysiological process of MI/RI has not yet been reported. The aim of this study was to determine whether OA could alleviate MI/RI induced inflammation and pyroptosis in vivo and in vitro, providing a novel therapeutic regimen for the treatment of MI/RI. A high-throughput drug screening strategy was employed to test 2,661 natural compound libraries that can alleviate MI/RI in vivo and in vitro. The rat model of MI/RI was established by ligating the left anterior descending (LAD) coronary artery. H9c2 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to simulate MI/RI. The results show that OA is able to significantly inhibit apoptosis, pyroptosis and the inflammation response (TNF-α, IL-6, IL-8, IL-10, IL-1β, IL-18) in vivo and in vitro, and reduce the release of myocardial enzymes (cTnI, cTnT, CK-MB, LDH, AST). In the rat MI/RI model, OA can not only improve cardiac function and reduce inflammatory cell infiltration but also reduce myocardial infarct size. The results revealed that OA is an effective remedy against MI/RI as it reduces the inflammatory response and inhibits pyroptosis. This may provide a new therapeutic target for the clinical treatment of MI/RI.

Peripheral nerve injury (PNI) results in loss of neural control and severe disabilities in patients. Promoting functional nerve recovery by accelerating angiogenesis is a promising neuroprotective treatment strategy. Here, we identified a bioactive Radix Astragalus polysaccharide (RAP) extracted from traditional Chinese medicine (TCM) as a potent enhancer of axonal regeneration and remyelination. Notably, RAP promoted functional recovery and delayed gastrocnemius muscle atrophy in a rat model of sciatic nerve crush injury. Further, RAP treatment may induce angiogenesis in vivo. Moreover, our in vitro results showed that RAP promotes endothelial cell (EC) migration and tube formation. Altogether, our results show that RAP can enhance functional recovery by accelerating angiogenesis, which was probably related to the activation of AKT/eNOS signaling pathway, thereby providing a polysaccharide-based therapeutic strategy for PNI.

Abstract Background Incidence and prevalence of prostate cancer in Sweden have increased markedly due to prostate-specific antigen (PSA) testing. Moreover, new diagnostic tests and treatment technologies are expected to further increase the overall costs. Our aims were (i) to estimate the societal costs for existing testing, diagnosis, management and treatment of prostate cancer, and (ii) to provide reference values for future cost-effectiveness analyses of prostate cancer screening and treatment. Methods Taking a societal perspective, this study aimed to investigate the annual cost of prostate cancer in Sweden using a prevalence-based cost-of-illness approach. Resource utilisation and related costs within Stockholm Region during 2016 were quantified using data from the Stockholm PSA and Biopsy Register and other health and population registers. Costs included: (i) direct medical costs for health care utilisation at primary care, hospitals, palliative care and prescribed drugs; (ii) informal care; and (iii) indirect costs due to morbidity and premature mortality. The resource utilisation was valued using unit costs for direct medical costs and the human capital method for informal care and indirect costs. Costs for the Stockholm region were extrapolated to Sweden based on cancer prevalence and the average costs by age and resource type. Results The societal costs due to prostate cancer in Stockholm in 2016 were estimated to be €64 million Euro (€Mn), of which the direct medical costs, informal care and productivity losses represented 62, 28 and 10% of the total costs, respectively. The total annual costs extrapolated to Sweden were calculated to be €281 Mn. The average direct medical cost, average costs for informal care and productivity losses per prevalent case were €1510, €828 and €271, respectively. These estimates were sensitive to assumptions related to the proportion of primary care visits associated with PSA testing and the valuation method for informal care. Conclusion The societal costs due to prostate cancer were substantial and constitute a considerable burden to Swedish society. Data from this study are relevant for future cost-effectiveness evaluations of prostate cancer screening and treatment.

Regarding the rapid development of urban agglomeration (UA) in Guangdong Province in the past two decades, this study revealed the temporal and spatial evolution of the urban pattern of the province and the current urbanization process. This study determined the geographical spatial distribution and change in the UA lighting scale in Guangdong Province, analyzed the relationship between the lighting change and development and the dynamic evolution of the gross domestic product, and explored the expansion intensity and center of gravity migration direction of UA. The results showed that from 2000 to 2020, the lighting scale of the border areas of Guangdong Province was lower than that of the inland areas, whereas the lighting growth rate of the border areas was higher than that of the inland areas. The built-up area steadily expanded from the center to the outside within the time range of the study, and the center of gravity of the ellipse tended to shift northwest. The study provides visual and scientific data for the spatiotemporal evolution of the urban pattern in Guangdong Province and has important reference significance for analyzing urbanization development and planning urban construction.

The genus Alexandrium is one of the major harmful algal blooms (HABs)-forming dinoflagellate group and at least half of ~40 described species have been reported to produce paralytic shellfish toxins (PSTs). The potentially harmful species Alexandrium insuetum has been reported from many countries of Asia and Europe, and to have paralytic shellfish poisoning toxicity, but no mortality of marine animals was observed during its bloom. Therefore, it is ecologically important to characterize the possible toxicity and toxins of this organism. In this study, based on the establishment of two clonal cultures through cyst germination collected from the Yellow Sea, we identified A. insuetum from China as the first record via light microscopy (LM) and scanning electron microscopy (SEM) observations and phylogenetic analyses. The cultures of A. insuetum were further observed to be toxic to finfish and zooplankton and deleterious to rotifer eggs via laboratory bioassays. The exposure bioassays using rotifer (Brachionus plicatilis), brine shrimp (Artemia salina), and larval finfish (Oryzias melastigma) demonstrated that A. insuetum caused significant lethal effects on finfish and zooplankton species. Rotifer bioassays using cell-free culture medium, heat-treated cultures, and water, methanol, and trichloromethane extracts of algal cells revealed that A. insuetum produced heat-labile, water-soluble toxin(s) that could be excreted from A. insuetum cells and steadily accumulated in the medium during the growth phases. Hatching success of rotifer eggs was also found to be seriously affected by the exposure to A. insuetum. Importantly, ultra-high performance liquid chromatography-tandem mass spectrometry [UPLC (or LC)-MS-MS] analyses suggest the above-described toxicity of A. insuetum was caused by neither PSTs nor spiroimines (13-desmethyl spirolide C and gymnodimine). Collectively, our findings demonstrated the novel toxicity to finfish and zooplankton in A. insuetum, which is ecologically important in not only possibly contributing to population dynamics and even the formation of HABs of the species, but also affecting the on-the-spot survival and the reproduction potency of marine animals. The present work is believed to set a cornerstone for the monitoring and risk assessment of the species along the coastal waters of China and for understanding the general ecology of A. insuetum.

Background and PurposeAlthough tumor size and nodal status are the most important prognostic factors, it is believed that nodal status outperforms tumor size as a prognostic factor. In particular, when patients have a nodal stage greater than N2 (more than nine positive lymph nodes), it is well accepted that tumor size does not retain its prognostic value. Even in the newest American Joint Committee on Cancer (AJCC) prognostic staging system, which includes molecular subtype as an important prognostic factor, T1-3N2 patients are categorized as the same population. The same is true for T1-4N3 patients. Moreover, some physicians have speculated that for tumors staged N2 or greater, the smaller the tumor is, the more aggressive the tumor. Thus, this study aims to investigate the prognostic value of tumor stage (T stage) in patients with extensive nodal involvement and to compare the survival of T4N × M0 and T × N3M0.Patients and MethodsFemale breast cancer patients with nine or more positive lymph nodes or with T4 tumors were identified in the SEER registry between 2010 and 2015. The effect of T stage on breast cancer-specific survival (BCSS) was assessed using the Kaplan–Meier survival curve method and risk-adjusted Cox proportional hazard regression modeling. Survival comparison of T4NxM0 and TxN3M0 patients was also achieved using the Kaplan–Meier survival curve method and risk-adjusted Cox proportional hazard regression model.ResultsOverall, 21,696 women with N2-3 tumors were included from 284,073 patients.T stage, nodal stage (N stage), ER, PR, HER2 and grade were all independent prognostic factors (p

To obtain accurate trajectory tracking with robustness and faithful force feedback in a practical application, a sliding mode controller (SMC) combined with a compensation controller based on a nonlinear disturbance observer (DOB) is proposed. The DOB estimates the disturbances arising mainly from the uncertain dynamic model of a surgical manipulator, frictional forces and external interaction forces, and compensates for these disturbances in the control law. Accordingly, it alleviates the chattering problem caused by the SMC and improves tracking performance. The surgical teleoperation system using the proposed SMC-DOB is proved to be asymptotically stable using Lyapunov theory. The simulation and experiment results show that the surgical manipulator with the SMC-DOB can better track the trajectory of the master even in the presence of disturbances and the interaction forces between the instrument and the patient's tissues are faithfully presented to the surgeon.

Background/Aims: Cardiac fibrosis is a major cause of diverse cardiovascular diseases. MicroRNAs have recently been proven a novel class of regulators of cardiac fibrosis. In this study, we sought to investigate the role of miR-323a-3p and its mechanisms in regulating cardiac fibrosis. Methods: The transverse aortic constriction (TAC) mice model was induced and neonatal cardiac fibroblasts (CFs) were cultured. MTT (3- [4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay was used to detect the cell viability. Echocardiography was used to evaluate cardiac function. Masson’s Trichrome stain was used to evaluate the development of fibrosis. Luciferase activity assay was performed to confirm the miRNA’s binding site. Real-time PCR and Western blot were used to evaluate the level of mRNA and protein. Results: MiR-323a-3p was found up-regulated in myocardial tissues subjected to TAC and in CFs cultured with Angiotensin Ⅱ (Ang Ⅱ). Overexpression of miR-323a-3p significantly increased the mRNA levels of collagen Ⅰ, collagen Ⅲ, MMP2 and MMP9, while inhibition of miR-323a-3p prevented the proliferation, collagen production and the protein level of transforming growth factor (TGF-β) in rat neonatal CFs. Strikingly, injection of antagomiR-323a-3p elevated cardiac function and inhibited the expression of TGF-β in the TAC mice. TIMP3 was a direct target of miR-323a-3p, as the overexpression of miR-323a-3p decreased the protein and mRNA levels of TIMP3. In the CFs with pre-treatment of Ang Ⅱ, siRNA-TIMP abolished the effects of AMO-323a-3p on the inhibition of the proliferation of CFs, the down-regulation of collagen Ⅰ and collagen Ⅲ, and the expression of TGF-β. Conclusion: Our findings provide evidence that miR-323a-3p promotes cardiac fibrosis via miR-323a-3p-TIMP3-TGF-β pathway. miR-323a-3p may be a new marker for cardiac fibrosis progression and that inhibition of miR-323a-3p may be a promising therapeutic target for the treatment of cardiac fibrosis.

Abstract The popularity of cloud hosting services also brings in new security chal- lenges: it has been reported that these services are increasingly utilized by miscreants for their malicious online activities. Mitigating this emerging threat, posed by such “bad repositories” (simply Bar), is challenging due to the different hosting strategy to traditional hosting service, the lack of direct observations of the repositories by those outside the cloud, the reluctance of the cloud provider to scan its customers’ repositories without their consent, and the unique evasion strategies employed by the adversary. In this paper, we took the first step toward understanding and detecting this emerging threat. Using a small set of “seeds” (i.e., confirmed Bars), we identified a set of collective features from the websites they serve (e.g., attempts to hide Bars), which uniquely characterize the Bars. These features were utilized to build a scanner that detected over 600 Bars on leading cloud platforms like Amazon, Google, and 150 K sites, including popular ones like groupon.com , using them. Highlights of our study include the pivotal roles played by these repositories on malicious infrastructures and other important discoveries include how the adversary exploited legitimate cloud repositories and why the adversary uses Bars in the first place that has never been reported. These findings bring such malicious services to the spotlight and contribute to a better understanding and ultimately eliminating this new threat.

Magnetic composite adsorbent (MCA) was prepared successfully using laterite nickel ore. The effectiveness of MCA as an adsorbent was evaluated for removal trimethylamine from aqueous environment. In this technological route, the utilization of solid wastes, wastewater treatment and adsorbent recovery were considered comprehensively. The MCA was characterized by techniques, including XRD, SEM, TEM, EDS, VSM and adsorption-desorption of nitrogen at 77 K. The adsorption processes were best described by pseudo-second-order kinetic model and controlled by intraparticle and surface diffusion processes. Langmuir and Freundlich isotherm models were used to match the adsorption equilibrium data. Freundlich isotherm was the best fitting curve for the sorption equilibrium data. The adsorption mechanism was further interpreted by Gibbs free energy, entropy and enthalpy calculated by thermodynamic equation. The negative values of Gibbs free energy changes (ΔG) manifest that the adsorbing process is spontaneous. The results show that laterite nickel ore can be made into MCA for organic amine removal from polluted water.

This study focuses on exploiting the main component of traditional nickel metallurgical waste for use as a valuable material that can be applied in the removal of organic amines from water systems. Silicon compounds from metallurgic waste were converted into dissolvable sodium silicate by roasting the waste with alkali. Silica with adsorption capacity was combined with magnetic NiFe cores by the carbonation decomposition of purified silicate solution. The composite magnetic adsorbent was characterized, and its adsorption mechanism for organic amines was investigated. The effects of the initial trimethylamine concentration, contact time and temperature on the adsorption efficiency of the composite adsorbent towards trimethylamine were investigated. It was found that the adsorption fit the Freundlich mode well. The adsorption kinetics can be described by a pseudo-second-order kinetic model. The adsorption capacity reached 55.8 μg/mg at 293 K. The use of metallurgical waste to prepare the magnetic composite adsorbent has three advantages, which include benefiting the environment by reducing the amount of solid waste and costs associated with constructing and maintaining storage facilities, generating valuable products in an economical manner and conveniently recycling used adsorbents to avoid secondary pollution.

ObjectivesThe European Randomized Study of Screening for Prostate Cancer found that prostate-specific antigen (PSA) screening reduced prostate cancer mortality, however the costs and harms from screening may outweigh any mortality reduction. Compared with screening using the PSA test alone, using the Stockholm3 Model (S3M) as a reflex test for PSA ≥ 1 ng/mL has the same sensitivity for Gleason score ≥ 7 cancers while the relative positive fractions for Gleason score 6 cancers and no cancer were 0.83 and 0.56, respectively. The cost-effectiveness of the S3M test has not previously been assessed.MethodsWe undertook a cost-effectiveness analysis from a lifetime societal perspective. Using a microsimulation model, we simulated for: (i) no prostate cancer screening; (ii) screening using the PSA test; and (iii) screening using the S3M test as a reflex test for PSA values ≥ 1, 1.5 and 2 ng/mL. Screening strategies included quadrennial re-testing for ages 55-69 years performed by a general practitioner. Discounted costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated.ResultsComparing S3M with a reflex threshold of 2 ng/mL with screening using the PSA test, S3M had increased effectiveness, reduced lifetime biopsies by 30%, and increased societal costs by 0.4%. Relative to the PSA test, the S3M reflex thresholds of 1, 1.5 and 2 ng/mL had ICERs of 170,000, 60,000 and 6,000 EUR/QALY, respectively. The S3M test was more cost-effective at higher biopsy costs.ConclusionsProstate cancer screening using the S3M test for men with an initial PSA ≥ 2.0 ng/mL was cost-effective compared with screening using the PSA test alone.

OBJECTIVES: Retinoblastoma (RB) is a highly malignant eye tumor with a low survival rate and a high metastatic rate. The current work was designed to investigate the potential roles of microRNA-144 (miR-144) in the diagnosis and prognosis of RB. METHODS: miR-144 expression levels in RB tissues and adjacent normal tissues, as well as serum samples from RB patients and healthy controls were measured. The association between miR-144 expression levels and clinical features were analyzed. Moreover, diagnostic and prognostic values of miR-144 in RB were verified by receiver operating characteristic analysis and Kaplan-Meier survival assays. RESULTS: The expression level of miR-144 was markedly decreased in tumor tissues of RB patients, and the expression level of miR-144 was positively associated with tumor size and metastasis in RB patients. Moreover, miR-144 can distinguish tumor tissues from normal tissues with high specificity and sensitivity, and RB patients with lower miR-144 expression have shorter overall and disease-free survival rates than those with higher miR-144 expression. Alternatively, miR-144 also decreased in the serum of RB patients in comparison with healthy subjects, and miR-144 expression levels in the tissue samples and serum were positively correlated. Furthermore, miR-144 levels in the serum of RB patients sensitively distinguished RB patients from healthy controls. CONCLUSIONS: miR-144 expression was downregulated in serum and tissue samples of RB patients and may function as a diagnostic and prognostic marker for RB.

We previously showed that NUDT21-spanning copy-number variations (CNVs) are associated with intellectual disability (Gennarino et al., 2015). However, the patients’ CNVs also included other genes. To determine if reduced NUDT21 function alone can cause disease, we generated Nudt21+/- mice to mimic NUDT21-deletion patients. We found that although these mice have 50% reduced Nudt21 mRNA, they only have 30% less of its cognate protein, CFIm25. Despite this partial protein-level compensation, the Nudt21+/- mice have learning deficits, cortical hyperexcitability, and misregulated alternative polyadenylation (APA) in their hippocampi. Further, to determine the mediators driving neural dysfunction in humans, we partially inhibited NUDT21 in human stem cell-derived neurons to reduce CFIm25 by 30%. This induced APA and protein level misregulation in hundreds of genes, a number of which cause intellectual disability when mutated. Altogether, these results show that disruption of NUDT21-regulated APA events in the brain can cause intellectual disability.

Mutations in genes encoding synaptic proteins cause many neurodevelopmental disorders, with the majority affecting postsynaptic apparatuses and much fewer in presynaptic proteins. Syntaxin-binding protein 1 (STXBP1, also known as MUNC18-1) is an essential component of the presynaptic neurotransmitter release machinery. De novo heterozygous pathogenic variants in STXBP1 are among the most frequent causes of neurodevelopmental disorders including intellectual disabilities and epilepsies. These disorders, collectively referred to as STXBP1 encephalopathy, encompass a broad spectrum of neurologic and psychiatric features, but the pathogenesis remains elusive. Here we modeled STXBP1 encephalopathy in mice and found that Stxbp1 haploinsufficiency caused cognitive, psychiatric, and motor dysfunctions, as well as cortical hyperexcitability and seizures. Furthermore, Stxbp1 haploinsufficiency reduced cortical inhibitory neurotransmission via distinct mechanisms from parvalbumin-expressing and somatostatin-expressing interneurons. These results demonstrate that Stxbp1 haploinsufficient mice recapitulate cardinal features of STXBP1 encephalopathy and indicate that GABAergic synaptic dysfunction is likely a crucial contributor to disease pathogenesis.

Porosity change is a common characteristic of natural soils in fluid-solid interaction problems, which can lead to an obvious change of the soil-water retention curve (SWRC). The influence of porosity on soil water retention phenomena is investigated by a theoretical model and an experimental test in this study. A model expressing the change in suction with porosity and effective saturation is put forward theoretically. The model is based on an idealization of three-phase porous materials, the pore structures of which are homogeneous and isotropic. It accounts for the porosity effect on soil water retention, using four parameters with clear physical meanings. The presented model can obtain the SWRC at any porosity, which will reduce the test number required in characterizing the hydraulic behavior of soil. A laboratory experiment for loamy sand with different porosities is performed. The test results show that suction has a significant variation with changes in porosity and decreases with the increase of porosity. The formulation is verified by both the test data and the literature data for FEBEX bentonite and Boom clay. The very good agreements between measured and predicted results show that the SWRC model is reliable and feasible for various soils.

High-spatial-resolution images play an important role in land cover classification, and object-based image analysis (OBIA) presents a good method of processing high-spatial-resolution images. Segmentation, as the most important premise of OBIA, significantly affects the image classification and target recognition results. However, scale selection for image segmentation is difficult and complicated for OBIA. The main challenge in image segmentation is the selection of the optimal segmentation parameters and an algorithm that can effectively extract the image information. This paper presents an approach that can effectively select an optimal segmentation scale based on land object average areas. First, 20 different segmentation scales were used for image segmentation. Next, the classification and regression tree model (CART) was used for image classification based on 20 different segmentation results, where four types of features were calculated and used, including image spectral bands value, texture value, vegetation indices, and spatial feature indices, respectively. WorldView-3 images were used as the experimental data to verify the validity of the proposed method for the selection of the optimal segmentation scale parameter. In order to decide the effect of the segmentation scale on the object area level, the average areas of different land objects were estimated based on the classification results. Experiments based on the multi-scale segmentation scale testify to the validity of the land object’s average area-based method for the selection of optimal segmentation scale parameters. The study results indicated that segmentation scales are strongly correlated with an object’s average area, and thus, the optimal segmentation scale of every land object can be obtained. In this regard, we conclude that the area-based segmentation scale selection method is suitable to determine optimal segmentation parameters for different land objects. We hope the segmentation scale selection method used in this study can be further extended and used for different image segmentation algorithms.

Clinical trials are currently underway to assess the efficacy of forniceal deep brain stimulation (DBS) for improvement of memory in Alzheimer’s patients, and forniceal DBS has been shown to improve learning and memory in a mouse model of Rett syndrome (RTT), an intellectual disability disorder caused by loss-of-function mutations in MECP2. The mechanism of DBS benefits has been elusive, however, so we assessed changes in gene expression, splice isoforms, DNA methylation, and proteome following acute forniceal DBS in wild-type mice and mice lacking Mecp2. We found that DBS upregulates genes involved in synaptic function, cell survival, and neurogenesis and normalized expression of ~25% of the genes altered in Mecp2-null mice. Moreover, DBS induced expression of 17–24% of the genes downregulated in other intellectual disability mouse models and in post-mortem human brain tissue from patients with Major Depressive Disorder, suggesting forniceal DBS could benefit individuals with a variety of neuropsychiatric disorders.

Spinocerebellar ataxia type 1 (SCA1) is characterized by adult-onset cerebellar degeneration with attendant loss of motor coordination. Bulbar function is eventually impaired and patients typically die from an inability to clear the airway. We investigated whether motor neuron degeneration is at the root of bulbar dysfunction by studying SCA1 knock-in (Atxn1154Q/+) mice. Spinal cord and brainstem motor neurons were assessed in Atxn1154Q/+ mice at 1, 3 and 6 months of age. Specifically, we assessed breathing physiology, diaphragm histology and electromyography, and motor neuron histology and immunohistochemistry. Atxn1154Q/+ mice show progressive neuromuscular respiratory abnormalities, neurogenic changes in the diaphragm, and motor neuron degeneration in the spinal cord and brainstem. Motor neuron degeneration is accompanied by reactive astrocytosis and accumulation of Atxn1 aggregates in the motor neuron nuclei. This observation correlates with previous findings in SCA1 patient tissue. Atxn1154Q/+ mice develop bulbar dysfunction because of motor neuron degeneration. These findings confirm the Atxn1154Q/+ line as a SCA1 model with face and construct validity for this understudied disease feature. Furthermore, this model is suitable for studying the pathogenic mechanism driving motor neuron degeneration in SCA1 and possibly other degenerative motor neuron diseases. From a clinical standpoint, the data indicate that pulmonary function testing and employment of non-invasive ventilator support could be beneficial in SCA1 patients. The physiological tests used in this study might serve as valuable biomarkers for future therapeutic interventions and clinical trials. This article has an associated First Person interview with the first author of the paper.