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Illicit discharges into sewer systems are a widespread concern within China's urban drainage management. They can result in unforeseen environmental contamination and deterioration in the performance of wastewater treatment plants. Consequently, pinpointing the origin of unauthorized discharges in the sewer network is crucial. This study aims to evaluate an integrative method that employs numerical modeling and statistical analysis to determine the locations and characteristics of illicit discharges. The Storm Water Management Model (SWMM) was employed to track water quality variations within the sewer network and examine the concentration profiles of exogenous pollutants under a range of scenarios. The identification technique employed Bayesian inference fused with the Markov chain Monte Carlo sampling method, enabling the estimation of probability distributions for the position of the suspected source, the discharge magnitude, and the commencement of the event. Specifically, the cases involving continuous release and multiple sources were examined. For single-point source identification, where all three parameters are unknown, concentration profiles from two monitoring sites in the path of pollutant transport and dispersion are necessary and sufficient to characterize the pollution source. For the identification of multiple sources, the proposed SWMM-Bayesian strategy with improved sampling is applied, which significantly improves the accuracy. HIGHLIGHTS Identifying pollution sources can be applied for both instantaneous and continuous discharge scenarios.; To characterize a single pollution source, data from two monitoring sites along the pollutant's path are necessary and sufficient.; The strategic placement of monitoring sites and improved sampling enhance the effectiveness and precision of the Bayesian-SWMM approach for identifying multiple unauthorized discharge sources.;

Abstract LHPP has been shown to be a new tumor suppressor, and has a tendency to be under-expressed in a variety of cancers. Oncolytic virotheray is a promising therapeutics for lung cancer in recent decade years. Here we successfully constructed a new recombinant oncolytic adenovirus GD55-LHPP and investigated the effect of GD55-LHPP on the growth of lung cancer cells in vitro and in vivo. The results showed that LHPP had lower expression in either lung cancer cells or clinical lung cancer tissues compared with normal cells or tissues, and GD55-LHPP effectively mediated LHPP expression in lung cancer cells. GD55-LHPP could effectively inhibit the proliferation of lung cancer cell lines and rarely affected normal cell growth. Mechanically, the oncolytic adenovirus GD55-LHPP was able to induce stronger apoptosis of lung cancer cells compared with GD55 through the activation of caspase signal pathway. Notably, GD55-LHPP also activated autophagy-related signal pathway. Further, GD55-LHPP efficiently inhibited tumor growth in lung cancer xenograft in mice and prolonged animal survival rate compared with the control GD55 or PBS. In conclusion, the novel construct GD55-LHPP provides a valuable strategy for lung cancer-targeted therapy and develop the role of tumor suppress gene LHPP in lung cancer gene therapy.

Ventilation is paramount in sanitary and stormwater sewer systems to mitigate odor problems and avert pressure surges. Existing numerical models have constraints in practical applications in actual sewer systems due to insufficient airflow modeling or suitability only for steady-state conditions. This research endeavors to formulate a mathematical model capable of accurately simulating various operational conditions of sewer systems under the natural ventilation condition. The dynamic water flow is modeled using a shock-capturing MacCormack scheme. The dynamic airflow model amalgamates energy and momentum equations, circumventing laborious pressure iteration computations. This model utilizes friction coefficients at interfaces to enhance the description of the momentum exchange in the airflow and provide a logical explanation for air pressure. A systematic analysis indicates that this model can be easily adapted to include complex boundary conditions, facilitating its use for modeling airflow in real sewer networks. Furthermore, this research uncovers a direct correlation between the air-to-water flow rate ratio and the filling ratio under natural ventilation conditions, and an empirical formula encapsulating this relationship is derived. This finding offers insights for practical engineering applications. HIGHLIGHTS The non-steady conditions were considered.; Existing models were improved to address the instability issue in coupled water and air calculations.; The relationship between the airflow and the water level under non-steady conditions was investigated.; The validation of the established model was conducted, demonstrating its effectiveness and feasibility.; Factors influencing the airflow were analyzed.;

Rainfall-derived inflow/infiltration (RDII) modelling during heavy rainfall events is essential for sewer flow management. In this study, two machine learning algorithms, random forest (RF) and long short-term memory (LSTM), were developed for sewer flow prediction and RDII estimation based on field monitoring data. The study implemented feature engineering for extracting physically significant features in sewer flow modelling and investigated the importance of the relevant features. The results from two case studies indicated the superior capability of machine learning models in RDII estimation in the combined and separated sewer systems, and LSTM model outperformed the two models. Compared to traditional methods, machine learning models were capable of simulating the temporal variation in RDII processes and improved prediction accuracy for peak flows and RDII volumes in storm events. HIGHLIGHTS Machine learning models, particularly the LSTM model, outperformed traditional methods in estimating RDII in sewer systems.; Feature engineering techniques allowed for the extraction of physically significant features in sewer flow modelling.; Machine learning models successfully simulated the temporal variation in RDII processes, resulting in improved accuracy for predicting peak flows and RDII volumes during storm events.;

Background: Global warming has provoked more co-occurrence of hot extreme and dry extreme, namely compound hot-dry events (CHDEs). However, their health impacts have seldom been investigated. This study aimed to characterize CHDEs and assess its mortality burden in China from 1990 to 2100. Methods: CHDEs were defined as a day when daily maximum temperature > its 90th percentile and Standardized Precipitation Index

Introduction: While ambient formaldehyde (HCHO) concentrations are increasing worldwide, there was limited research on its health effects. Objectives: To assess the association of long-term exposure to ambient HCHO with the risk of respiratory (RESP) mortality and the associated mortality burden in China. Methods: Annual and seasonal RESP death and tropospheric HCHO vertical columns data were collected in 466 counties/districts across China during 2013–2016. A difference-in-differences approach combined with a generalized linear mixed-effects regression model was employed to assess the exposure-response association between long-term ambient HCHO exposure and RESP mortality risk. Additionally, we computed the attributable fraction (AF) to gauge the proportion of RESP mortality attributable to HCHO exposure. Results: This analysis encompassed 560,929 RESP deaths. The annual mean ambient HCHO concentration across selected counties/districts was 8.02×1015 ± 2.22×1015 molec.cm−2 during 2013–2016. Each 1.00×1015 molec.cm−2 increase in ambient HCHO was associated with a 1.61 % increase [excess risk (ER), 95 % confidence interval (CI): 1.20 %, 2.03 %] in the RESP mortality risk. The AF of RESP mortality attributable to HCHO was 12.16 % (95 %CI:9.33 %, 14.88 %), resulting in an annual average of 125,422 (95 %CI:96,404, 153,410) attributable deaths in China. Stratified analyses suggested stronger associations in individuals aged ≥65 years old (ER=1.87 %, 95 %CI:1.43 %, 2.32 %), in cold seasons (ER=1.00 %, 95 %CI:0.56 %, 1.44 %), in urban areas (ER=1.65 %, 95 %CI:1.15 %, 2.16 %), and in chronic obstructive pulmonary disease patients (ER=1.95 %, 95 %CI:1.42 %, 2.48 %). Conclusions: This study suggested that long-term HCHO exposure may significantly increase the risk of RESP mortality, leading to a substantial mortality burden. Targeted measures should be implemented to control ambient HCHO pollution promptly.

Neonicotinoid insecticides (NEOs) have been extensively approved for application in agricultural production both in China and globally. Previous studies indicated that human exposure to NEOs would have adverse health effects. However, studies on occurrences of NEOs in kidney injury patients and their association with nephrotoxicity are limited. This study investigates the potential correlation between exposure to NEOs and kidney injury within a subset (n = 224) of the population residing in South China. Levels of 8 NEOs and 5 metabolites were quantified in blood samples obtained from both the 110 healthy and 114 kidney injury cohorts in South China. We found that target analytes were frequently detected in samples from the healthy and kidney injury cohorts (61%–100 %). Dinotefuran is the predominant NEO in the healthy (42.3 %) and kidney injury cohort (49.6 %). Significantly positive (p

Chemical Exchange Saturation Transfer (CEST) is a technique that uses specific off-resonance saturation pulses to pre-saturate targeted substances. This process influences the signal intensity of free water, thereby indirectly providing information about the pre-saturated substance. Among the clinical applications of CEST, Amide Proton Transfer (APT) is currently the most well-established. APT can be utilized for the preoperative grading of gliomas. Tumors with higher APTw signals generally indicate a higher likelihood of malignancy. In predicting preoperative molecular typing, APTw values are typically lower in tumors with favorable molecular phenotypes, such as isocitrate dehydrogenase (IDH) mutations, compared to IDH wild-type tumors. For differential diagnosis, the average APTw values of meningiomas are significantly lower than those of high-grade gliomas. Various APTw measurement indices assist in distinguishing central nervous system lesions with similar imaging features, such as progressive multifocal leukoencephalopathy, central nervous system lymphoma, solitary brain metastases, and glioblastoma. Regarding prognosis, APT effectively differentiates between tumor recurrence and treatment effects, and also possesses predictive capabilities for overall survival (OS) and progression-free survival (PFS).

As an important component of the deep tunnel drainage system for dealing with urban waterlogging, the rotating stepped dropshaft has been proposed due to its small air entrainment. However, the hydraulic characteristics inside the shaft still need to be fully studied. In this study, the flow patterns, water velocity, and pressure in the rotating stepped dropshaft under different flow rates and geometric parameters were studied using a three-dimensional numerical model. The results show that increasing the central angle of the step and reducing the step height can both reduce the terminal velocity. A theoretical formula for predicting the terminal velocity was established and well validated. The connection between the shaft and the outlet pipe poses a severe threat to the structural safety due to alternating positive and negative pressures. Wall-attached swirling flow generates a circular high-pressure zone at the bottom of the dropshaft and the larger the flow rate, the greater the pressure gradient at the center of the bottom. By using the momentum theorem and considering the impact pressure range of the swirling flow, the shaft bottom pressure can be predicted reasonably well. HIGHLIGHTS The hydraulic characteristics of rotating stepped dropshafts are analyzed and the terminal velocity is evaluated theoretically and well validated.; The pressure distribution inside rotating stepped dropshafts and the impact effect of the wall-attached swirling flow on the shaft bottom are determined.; A simplified theoretical model is established to predict the impact pressure of the shaft.;

Background: Although the health impacts of ambient ozone (O3) have been widely assessed, studies simultaneously investigating the acute and chronic effects of O3 on mortality from respiratory diseases (RESP) are scarce. Methods: We extracted personal information of all recorded deaths from RESP throughout 2013–2018 in six provinces in China. The daily, seasonal, and annual mean air pollutant concentrations at the township/subdistrict level were estimated by a random forest model. The acute association between the maximum daily average 8h ozone (MDA8 O3) and RESP mortality was examined by a time-stratified case-crossover study design, and the chronic association was estimated by a difference-in-differences (DID) analysis approach. We also calculated the attributable fraction (AF) of RESP mortality attributable to MDA8 O3. Results: There were 1,034,226 RESP deaths included in this study. The excess risks (ERs) of overall RESP mortality for each 10 μg/m3 increase in short-term (lag03 days) and long-term (one-year average) exposure to MDA8 O3 were 0.38 % (95%CI: 0.26 %, 0.50 %) and 4.37 % (3.91 %, 4.84 %), respectively. The AFs of overall RESP mortality ascribed to short- and long-term MDA8 O3 exposures were 3.00 % (2.03 %, 3.95 %) and 29.45 % (26.86 %, 31.95 %), respectively. The average annual number of RESP deaths attributable to short-term MDA8 O3 exposure was 30,790 and 302,254 were attributable to long-term MDA8 O3 exposure across China during 2013–2018. Conclusion: Both short- and long-term exposure to ambient MDA8 O3 were positively associated with RESP mortality, and long-term exposure to MDA8 O3 may lead to a greater RESP mortality burden than short-term exposure to MDA8 O3.

Objective To compare the ability of gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA) and gadobenate dimeglumine (Gd-BOPTA) to display the 3 major features recommended by the Liver Imaging Reporting and Data System (LI-RADS 2018v) for diagnosing hepatocellular carcinoma (HCC). Materials and Methods In this retrospective study, we included 98 HCC lesions that were scanned with either Gd-EOB-DTPA-MR or Gd-BOPTA-M.For each lesion, we collected multiple variables, including size and enhancement pattern in the arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). The lesion-to-liver contrast (LLC) was measured and calculated for each phase and then compared between the 2 contrast agents. A P value 0.750). When conducting a total evaluation of the combined data across the 5 phases, the display efficiency was excellent (AUC > 0.950). Conclusion Gd-BOPTA and Gd-EOB-DTPA are liver-specific contrast agents widely used in clinical practice. They have their own characteristics in displaying the 3 main signs of HCC. For accurate noninvasive diagnosis, the choice of agent should be made according to the specific situation.

This study investigated the hydraulic characteristics of stormwater sumps and their design optimization for sediment retention using physical experiments. Particle image velocimetry was utilized to measure the flow field, and the use of internal structures was investigated for improving solids retention. Results indicate that these internal structures can significantly improve the sediment removal efficiency of suspended solids with an average size of 125 μm, resulting in an efficiency improvement of 20–30%. Additionally, a modified Péclet number was proposed to more accurately evaluate the sediment removal efficiency of stormwater sumps, and recommendations were provided for further improving and optimizing sump design. This study provides insights into the hydraulic characteristics of stormwater sumps and has important implications for optimizing and designing particle removal systems for various industrial and environmental applications. HIGHLIGHTS The study demonstrates that incorporating enhancements leads to a substantial increase (20–30%) in the efficiency of removing suspended solids in stormwater sumps.; The study introduces a modified dimensionless number that provides a more precise evaluation of sediment removal efficiency in stormwater sumps.; The study highlights that scaling, with a ratio of up to 6, can reasonably predict particle removal efficiency.;

A 16-month monitoring program was conducted on a prototype sanitary system in a coastal city in China. The groundwater infiltration (GWI) on dry weather days and the rain-derived inflow and infiltration (RDII) on wet weather days were quantified and analyzed. The proportion of monthly averaged GWI to total flow can be as high as 70% during the observation period mainly due to the high groundwater level. The results also show that the ratio of RDII volume to total rainfall volume (defined as R-value) reaches a limited value of approximately 10% for the studied system when the total rainfall depth increases. A reference indicator Rlim for the limited R-value was proposed for assessing the conditions of sewer systems in terms of RDII. The Rlim value depends on local sewer conditions and in general, a lower Rlim value represents a better performance on RDII and vice versa. This study enriches the case studies on the performance of a specific sanitary sewer system on inflow and infiltration in a typical coastal city with exceptionally high groundwater levels, excess rainfall events in the monitoring season and possible typhoon events, which addresses the unique locational and hydrological properties of a representative coastal city. HIGHLIGHTS The time-period for the ‘minimum night flow method’ should be adjusted accordingly.; High infiltration due to high groundwater levels was observed specifically for the study site.; The ratio of RDII volume to total rainfall volume (R-value) tends to be limited as rainfall increases for all RDII events.; The limited R-value for high rainfall events was proposed for assessing the performance of sewer systems.;

Considering that we still do not fully understand the behavior of air pockets trapped in rainstorm systems and water flow changes inside pipes, the study of actual geysers presents many challenges. In this study, three-dimensional numerical models were developed to investigate the mechanisms of geyser events triggered by rapid filling flows at different scales. The results showed that, in the first stage of the water–air mixture of the prototype model, a large amount of air was released quickly, and the subsequent overflow lasted for a more extended period. The transport capacity of the downstream pipe, as a critical factor, significantly influenced the water–air interaction of the geyser. Restricting the outlet area and increasing the outlet pressure simultaneously resulted in a stronger geyser. The equivalent density of the water–air mixture increased as the scale decreased during the geyser event.

Abstract Objective There are no specific magnetic resonance imaging (MRI) features that distinguish pilocytic astrocytoma (PA) from adamantinomatous craniopharyngioma (ACP). In this study we compared the frequency of a novel enhancement characteristic on MRI (called the cut green pepper sign) in PA and ACP. Methods Consecutive patients with PA (n = 24) and ACP (n = 36) in the suprasellar region were included in the analysis. The cut green pepper sign was evaluated on post-contrast T1WI images independently by 2 neuroradiologists who were unaware of the pathologic diagnosis. The frequency of cut green pepper sign in PA and ACP was compared with Fisher’s exact test. Results The cut green pepper sign was identified in 50% (12/24) of patients with PA, and 5.6% (2/36) with ACP. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the cut green pepper sign for diagnosing PA were 50%, 94.4%, 85.7% and 73.9%, respectively. There was a statistically significant difference in the age of patients with PA with and without the cut green pepper sign (12.3 ± 9.2 years vs. 5.5 ± 4.4 years, p = 0.035). Conclusion The novel cut green pepper sign can help distinguish suprasellar PA from ACP on MRI.

Saxitoxin (STX), an exceptionally potent marine toxin for which no antidote is currently available, is produced by methanogens and cyanobacteria. This poses a significant threat to both shellfish aquaculture and human health. Consequently, the development of a rapid, highly sensitive STX detection method is of great significance. The objective of this research is to create a novel approach for identifying STX. Therefore, amplified luminescent proximity homogeneous assay (AlphaLISA) was established using a direct competition method based on the principles of fluorescence resonance energy transfer and antigen–antibody specific binding. This method is sensitive, rapid, performed without washing, easy to operate, and can detect 8–128 ng/mL of STX in only 10 min. The limit of detection achieved by this method is as low as 4.29 ng/mL with coefficients of variation for the intra-batch and inter-batch analyses ranging from 2.61% to 3.63% and from 7.67% to 8.30%, respectively. In conclusion, our study successfully establishes a simple yet sensitive, rapid, and accurate AlphaLISA method for the detection of STX which holds great potential in advancing research on marine biotoxins.

This study explores the mitigation of cavitation damage in hydraulic engineering through air entrainment. The primary aim is to experimentally analyze the shock wave characteristics emitted by cavitation bubbles adjacent to air bubbles affixed to a tube nozzle. The schlieren optical system is utilized to visualize the shock wave, while a hydrophone measures its pressure. Experiments are conducted on cavitation bubbles induced by the spark-generated method in the vicinity of air bubbles, varying the dimensionless distances and sizes of the air bubbles. The results indicate that (1) The introduction of an air bubble noticeably changes the morphology, kinematic behavior, and shock wave features of the cavitation bubble. (2) Four distinct shock wave patterns are identified based on the quantity and shape of the shock wave, with variations in the cavitation bubble's collapsing behavior and shock wave characteristics across different patterns. (3) The dimensionless distance γ and size δ exert significant influence on the shock wave's quantity, pressure peak, shape, and energy. With γ decreases or δ increases, the shock wave quantity increases while the shock wave intensity decreases. This investigation of the interaction between cavitation bubbles and air bubbles is essential for elucidating the mechanism through which air entrainment mitigates cavitation damage.

The application of turmeric essential oil (TEO), a natural effective antibacterial agent, in food preservation is limited due to high volatility and low stability. This study aimed to improve its stability and release behavior by synthesizing TEO/hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex (IC) in a saturated aqueous solution. An orthogonal experimental design was used to determine the optimal process conditions (HP-β-CD to TEO, g/mL), 16:1; stirring speed, 850 r/min; encapsulation time, 2 h), achieving a comprehensive score value of 85.62% for TEO/HP-β-CD-IC. Through comprehensive characterization, the results showed that TEO was completely embedded in HP-β-CD with increased stability. Free TEO exhibited a weight loss of 67.64% between 30 and 300 °C, while TEO/HP-β-CD-IC had a mass loss of only 9.33%. HP-β-CD and TEO/HP-β-CD-IC showed positive ZP values that were 124.76 mV and 132.16 mV, respectively. The release behavior and release kinetics of TEO/HP-β-CD-ICs were also studied, and the results showed that TEO/HP-β-CD-IC release rate increased under higher temperature and relative humidity—consistent with Fick’s diffusion.

BackgroundM-type phospholipase A2 receptor (PLA2R) is a major auto-antigen of primary membranous nephropathy(PMN). Anti-PLA2R antibody levels are closely associated with disease severity and therapeutic effectiveness. Analysis of PLA2R antigen epitope reactivity may have a greater predictive value for remission compared with total PLA2R-antibody level. This study aims to elucidate the relationship between domain-specific antibody levels and clinical outcomes of PMN.MethodsThis retrospective analysis included 87 patients with PLA2R-associated PMN. Among them, 40 and 47 were treated with rituximab (RTX) and cyclophosphamide (CTX) regimen, respectively. The quantitative detection of -immunoglobulin G (IgG)/-IgG4 targeting PLA2R and its epitope levels in the serum of patients with PMN were obtained through time-resolved fluorescence immunoassays and served as biomarkers in evaluating the treatment effectiveness. A predictive PMN remission possibility nomogram was developed using multivariate logistic regression analysis. Discrimination in the prediction model was assessed using the area under the receiver operating characteristic curve (AUC-ROC).Bootstrap ROC was used to evaluate the performance of the prediction model.ResultsAfter a 6-month treatment period, the remission rates of proteinuria, including complete remission and partial remission in the RTX and CTX groups, were 70% and 70.21% (P = 0.983), respectively. However, there was a significant difference in immunological remission in the PLA2R-IgG4 between the RTX and CTX groups (21.43% vs. 61.90%, P = 0.019). Furthermore, we found differences in PLA2R-CysR-IgG4(P = 0.030), PLA2R-CTLD1-IgG4(P = 0.005), PLA2R-CTLD678-IgG4(P = 0.003), and epitope spreading (P = 0.023) between responders and non-responders in the CTX group. Multivariate logistic analysis showed that higher levels of urinary protein (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.26-0.95; P = 0.035) and higher levels of PLA2R-CTLD1-IgG4 (OR, 0.79; 95%CI,0.62-0.99; P = 0.041) were independent risk factors for early remission. A multivariate model for estimating the possibility of early remission in patients with PMN is presented as a nomogram. The AUC-ROC of our model was 0.721 (95%CI, 0.601-0.840), in consistency with the results obtained with internal validation, for which the AUC-ROC was 0.711 (95%CI, 0.587-0.824), thus, demonstrating robustness.ConclusionsCyclophosphamide can induce immunological remission earlier than rituximab at the span of 6 months. The PLA2R-CTLD1-IgG4 has a better predict value than total PLA2R-IgG for remission of proteinuria at the 6th month.

Background: Kidney injury molecule-1 (Kim-1), a specific marker of kidney injury, is usually not expressed in normal kidneys or at very low levels but is highly expressed in injured renal tubular epithelial cells until the damaged cells recover completely. Therefore, we aimed to develop an efficient and highly sensitive assay to accurately quantify Kim-1 levels in human serum and urine.Methods: In this study, a novel immunoassay was developed and named amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA). Anti-Kim-1 antibodies can be directly coupled to carboxyl-modified donor and acceptor beads for the rapid detection of Kim-1 by double-antibody sandwich method. Serum and urine samples for Kim-1 measurements were obtained from 129 patients with nephropathy and 17 healthy individuals.Results: The linear range of Kim-1 detected by AlphaLISA was 3.83–5000 pg/mL, the coefficients of variation of intra-assay and inter-assay batches were 3.36%–4.71% and 5.61%–11.84%, respectively, and the recovery rate was 92.31%–99.58%. No cross reactions with neutrophil gelatinase-associated lipocalin, liver-type fatty acid binding protein, and matrix metalloproteinase-3 were observed. A good correlation (R2 = 0.9086) was found between the findings of Kim-1-TRFIA and Kim-AlphaLISA for the same set of samples. In clinical trials, both serum and urine Kim-1 levels were significantly higher in patients with nephropathy than in healthy individuals, especially in patients with acute kidney injury. Furthermore, serum Kim-1 was superior to urinary Kim-1 in distinguishing between patients with nephropathy and healthy individuals.Conclusion: The developed Kim-1-AlphaLISA is highly efficient, precise, and sensitive, and it is suitable for the rapid detection of patients with acute kidney injury.

Myeloid-derived suppressor cells (MDSCs) occupy a pivotal role in the intricate pathogenesis of the autoimmune disorder, Type 1 diabetes mellitus (T1DM). Since our previous work demonstrated that trichosanthin (TCS), an active compound of Chinese herb medicine Tian Hua Fen, regulated immune response, we aimed to clarify the efficacy and molecular mechanism of TCS in the treatment of T1DM. To this end, T1DM mouse model was established by streptozotocin (STZ) induction. The mice were randomly divided into normal control group (Ctl), T1DM group (STZ), TCS treated diabetic group (STZ + TCS) and insulin-treated diabetic group (STZ + insulin). Our comprehensive evaluation encompassed variables such as blood glucose, glycosylated hemoglobin, body weight, pertinent biochemical markers, pancreatic histopathology, and the distribution of immune cell populations. Furthermore, we meticulously isolated MDSCs from the bone marrow of T1DM mice, probing into the expressions of genes pertaining to the advanced glycation end product receptor (RAGE)/NF-κB signaling pathway through RT-qPCR. Evidently, TCS exhibited a substantial capacity to effectively counteract the T1DM-induced elevation in random blood glucose, glycosylated hemoglobin, and IL-6 levels in plasma. Pathological scrutiny underscored the ability of TCS to mitigate the damage incurred by islets. Intriguingly, TCS interventions engendered a reduction in the proportion of MDSCs within the bone marrow, particularly within the IL-6+ MDSC subset. In contrast, IL-10+ MDSCs exhibited an elevation following TCS treatment. Moreover, we observed a significant down-regulation of relative mRNA of pro-inflammatory genes, including arginase 1 (Arg1), inducible nitric oxide synthase (iNOS), RAGE and NF-κB, within MDSCs due to the influence of TCS. It decreases total MDSCs and regulates the balance between IL-6+ and IL-10+ MDSCs thus alleviating the symptoms of T1DM. TCS also down-regulates the RAGE/NF-κB signaling pathway, making it a promising alternative therapeutic treatment for T1DM. Collectively, our study offered novel insights into the underlying mechanism by which TCS serves as a promising therapeutic intervention for T1DM.

Abstract Micron- and submicron-sized droplets have extensive applications in biomedical diagnosis and drug delivery. Moreover, accurate high-throughput analysis requires a uniform droplet size distribution and high production rates. Although the previously reported microfluidic coflow step-emulsification method can be used to generate highly monodispersed droplets, the droplet diameter (d) is constrained by the microchannel height (b), $$d\gtrsim 3b$$ d ≳ 3 b , while the production rate is limited by the maximum capillary number of the step-emulsification regime, impeding emulsification of highly viscous liquids. In this paper, we report a novel, gas-assisted coflow step-emulsification method, where air serves as the innermost phase of a precursor hollow-core air/oil/water emulsion. Air gradually diffuses out, producing oil droplets. The size of the hollow-core droplets and the ultrathin oil layer thickness both follow the scaling laws of triphasic step-emulsification. The minimal droplet size attains $$d\approx 1.7b$$ d ≈ 1.7 b , inaccessible in standard all-liquid biphasic step-emulsification. The production rate per single channel is an order-of-magnitude higher than that in the standard all-liquid biphasic step-emulsification and is also superior to alternative emulsification methods. Due to low gas viscosity, the method can also be used to generate micron- and submicron-sized droplets of high-viscosity fluids, while the inert nature of the auxiliary gas offers high versatility.

Due to the fundamental differences between the quantum world and the classical world, some phenomena, such as entanglement and wave–particle duality, only exist in the quantum realm. These peculiar phenomena cannot be demonstrated by classical means: Quantum networks, quantum cryptography, and quantum precision measurements all require quantum sources. Photons are particularly well-suited as quantum sources owing to their minimal interaction with the environment, high flight speed, and ease of interaction with current typical quantum systems. Single-photon sources include pulsed excitation of quantum dots, spontaneous parametric down-conversion, and photon blockade. Herein, we propose that the anti-Jaynes–Cummings model can induce a pronounced photon antibunching effect when subjected to intense cavity dissipation. Similar to the photon blockade caused by strong photon–photon interaction, this antibunching effect is referred to as ’dissipation-induced blockade’. Our findings indicate that the minimum decay rate of a qubit, coupled with a high decay rate for photons, is conducive to achieving strong antibunching within the system. Notably, g(2)(0)

Hemostasis is a crucial process that quickly forms clots at injury sites to prevent bleeding and infections. Dysfunctions in this process can lead to hemorrhagic disorders, such as hemophilia and thrombocytopenia purpura. While hemostatic agents are used in clinical treatments, there is still limited knowledge about potentiators targeting coagulation factors. Recently, LCTx-F2, a procoagulant spider-derived peptide, was discovered. This study employed various methods, including chromogenic substrate analysis and dynamic simulation, to investigate how LCTx-F2 enhances the activity of thrombin and FXIIa. Our findings revealed that LCTx-F2 binds to thrombin and FXIIa in a similar manner, with the N-terminal penetrating the active-site cleft of the enzymes and the intermediate section reinforcing the peptide-enzyme connection. Interestingly, the C-terminal remained at a considerable distance from the enzymes, as evidenced by the retention of affinity for both enzymes using truncated peptide T-F2. Furthermore, results indicated differences in the bonding relationship of critical residues between thrombin and FXIIa, with His13 facilitating binding to thrombin and Arg7 being required for binding to FXIIa. Overall, our study sheds light on the molecular mechanism by which LCTx-F2 potentiates coagulation factors, providing valuable insights that may assist in designing drugs targeting procoagulation factors.

BackgroundAir pollution is a major public health concern. Air Quality Health Index (AQHI) is a very important air quality risk communication tool. However, AQHI is usually constructed by single-pollutant model, which has obvious disadvantages.ObjectiveTo construct an AQHI based on the joint effects of multiple air pollutants (J-AQHI), and to provide a scientific tool for health risk warning and risk communication of air pollution.MethodsData on non-accidental deaths in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces from January 1, 2013 to December 31, 2018 were obtained from the corresponding provincial disease surveillance points systems (DSPS), including date of death, age, gender, and cause of death. Daily meteorological (temperature and relative humidity) and air pollution data (SO2, NO2, CO, PM2.5, PM10, and maximum 8 h O3 concentrations) at the same period were respectively derived from China Meteorological Data Sharing Service System and National Urban Air Quality Real-time Publishing Platform. Lasso regression was first applied to select air pollutants, then a time-stratified case-crossover design was applied. Each case was matched to 3 or 4 control days which were selected on the same days of the week in the same calendar month. Then a distributed lag nonlinear model (DLNM) was used to estimate the exposure-response relationship between selected air pollutants and mortality, which was used to construct the AQHI. Finally, AQHI was classified into four levels according to the air pollutant guidance limit values from World Health Organization Global Air Quality Guidelines (AQG 2021), and the excess risks (ERs) were calculated to compare the AQHI based on single-pollutant model and the J-AQHI based on multi-pollutant model.ResultsPM2.5, NO2, SO2, and O3 were selected by Lasso regression to establish DLNM model. The ERs for an interquartile range (IQR) increase and 95% confidence intervals (CI) for PM2.5, NO2, SO2 and O3 were 0.71% (0.34%–1.09%), 2.46% (1.78%–3.15%), 1.25% (0.9%–1.6%), and 0.27% (−0.11%–0.65%) respectively. The distribution of J-AQHI was right-skewed, and it was divided into four levels, with ranges of 0-1 for low risk, 2-3 for moderate risk, 4-5 for high health risk, and ≥6 for severe risk, and the corresponding proportions were 11.25%, 64.61%, 19.33%, and 4.81%, respectively. The ER (95%CI) of mortality risk increased by 3.61% (2.93–4.29) for each IQR increase of the multi-pollutant based J-AQHI , while it was 3.39% (2.68–4.11) for the single-pollutant based AQHI .ConclusionThe J-AQHI generated by multi-pollutant model demonstrates the actual exposure health risk of air pollution in the population and provides new ideas for further improvement of AQHI calculation methods.

Monitoring the status of blood-brain barrier (BBB) and inhibiting reactive oxygen species (ROS)-mediated oxidative damage are key issues in the treatment of traumatic brain injury (TBI). Here, the authors design a near-infrared-IIb emitting Mn single-atom catalyst for imaging-guided therapy to alleviate ROS mediated neuroinflammation in the brain and simultaneously obtain timely feedback of therapeutic effect, promoting the reconstruction of BBB and recovery of neurological function after TBI in mice.

Injury poses heavy burden on public health, but little evidence on the potential role of climate change on injury exists. Here, the authors collect data during 2013-2019 in six provinces of China to estimate the associations between temperature and injury mortality, and to project future mortality burden attributable to temperature change driven by climate change.

Objective This study aimed to investigate the clinical significance of exostosin 1 (EXT1) in confirmed and suspected lupus membranous nephropathy (LMN).Methods EXT1 was detected in 67 renal tissues of M-type phospholipase A2 receptor (PLA2R)-negative and ANA-positive membranous nephropathy by immunohistochemistry, and cases were divided into confirmed LMN and suspected LMN. The clinicopathological data were compared among the above groups, as well as EXT1-positive group and EXT1-negative group.Results Twenty-two cases (73.3%) of confirmed LMN and six cases (16.2%) of suspected LMN exhibited EXT1 expression on the glomerular basement membrane and/or mesangium area, showing a significant difference (p

BackgroundDrowning is a serious public health problem worldwide. Previous epidemiological studies on the association between meteorological factors and drowning mainly focused on individual weather factors, and the combined effect of mixed exposure to multiple meteorological factors on drowning is unclear. ObjectiveWe aimed to investigate the combined effects of multiple meteorological factors on unintentional drowning mortality in China and to identify the important meteorological factors contributing to drowning mortality. MethodsUnintentional drowning death data (based on International Classification of Diseases, 10th Edition, codes W65-74) from January 1, 2013, to December 31, 2018, were collected from the Disease Surveillance Points System for Guangdong, Hunan, Zhejiang, Yunnan, and Jilin Provinces, China. Daily meteorological data, including daily mean temperature, relative humidity, sunlight duration, and rainfall in the same period were obtained from the Chinese Academy of Meteorological Science Data Center. We constructed a time-stratified case-crossover design and applied a generalized additive model to examine the effect of individual weather factors on drowning mortality, and then used quantile g-computation to estimate the joint effect of the mixed exposure to meteorological factors. ResultsA total of 46,179 drowning deaths were reported in the 5 provinces in China from 2013 to 2018. In an effect analysis of individual exposure, we observed a positive effect for sunlight duration, a negative effect for relative humidity, and U-shaped associations for temperature and rainfall with drowning mortality. In a joint effect analysis of the above 4 meteorological factors, a 2.99% (95% CI 0.26%-5.80%) increase in drowning mortality was observed per quartile rise in exposure mixture. For the total population, sunlight duration was the most important weather factor for drowning mortality, with a 93.1% positive contribution to the overall effects, while rainfall was mainly a negative factor for drowning deaths (90.5%) and temperature and relative humidity contributed 6.9% and –9.5% to the overall effects, respectively. ConclusionsThis study found that mixed exposure to temperature, relative humidity, sunlight duration, and rainfall was positively associated with drowning mortality and that sunlight duration, rather than temperature, may be the most important meteorological factor for drowning mortality. These findings imply that it is necessary to incorporate sunshine hours and temperature into early warning systems for drowning prevention in the future.

Although studies have estimated the associations of PM2.5 with total mortality or cardiopulmonary mortality, few have comprehensively examined cause-specific mortality risk and burden caused by ambient PM2.5. Thus, this study investigated the association of short-term exposure to PM2.5 with cause-specific mortality using a death-spectrum wide association study (DWAS). Individual information of 5,450,764 deaths during 2013–2018 were collected from six provinces in China. Daily PM2.5 concentration in the case and control days were estimated by a random forest model. A time-stratified case-crossover study design was applied to estimate the associations (access risk, ER) of PM2.5 with cause-specific mortality, which was then used to calculate the population-attributable fraction (PAF) of mortality and the corresponding mortality burden caused by PM2.5. Each 10 μg/m3 increase in PM2.5 concentration (lag03) was associated with a 0.80 % [95 % confidence interval (CI): 0.73 %, 0.86 %] rise in total mortality. We found greater mortality effect at PM2.5 concentrations

Preeclampsia (PE) is a pregnancy-specific disorder attributed to deficient extravillous trophoblast (EVT) invasion into the uterus, but the mechanism of EVT invasion remains unclear. In this study, we found significantly elevated expression of microRNA 21 (miR21), which negatively regulates trophoblast invasion and migration, in preeclamptic placentae. Whole-genome RNA sequencing revealed that PPP2R2B, which encodes PP2A Bβ, and the Hippo pathway are downstream targets of miR21. The effects of miR21 on trophoblast mobility were abolished in LATS1T1079A/S909A and YAP-5SA mutants. Moreover, we found that PP2A Bβ dephosphorylates LATS1 via direct protein-protein interactions and thus modulates the phosphorylation and subcellular distribution of YAP. PPP2R2B overexpression ameliorated the miR21-induced LATS1-YAP phosphorylation and cytoplasmic sequestration of YAP, which resulted in the rescue of compromised trophoblast invasion and migration. The upregulation of placental miR21 abundance by placenta-specific nanoparticles loaded with agomir-miR21 during placentation interfered with PPP2R2B and activated the Hippo pathway in the placenta, leading to a PE-like phenotype. Thus, aberrant elevation of miR21 impairs EVT mobility by modulating the PP2A Bβ/Hippo axis, which is one of the causes of PE.

Sumps are commonly used in urban stormwater systems, which can be considered as a simple pretreatment device for stormwater quality control. However, they may function as pollution sources due to sediment washout under high flow conditions. An experimental study was conducted to investigate the scour process of predeposited sediments from a sump and its influencing parameters. Under conditions with large inflows or high sediment deposit, the sediment particles could be resuspended, entrained and flushed out. The washout mass decreased exponentially with time if the sediment bed surface depth was larger than a threshold value; otherwise, the amount of washout would be much smaller. The same scour pattern was observed for all the testing cases, of which the largest scour depth always occurred below the outlet. The deposit below the inlet might increase under conditions with high flow rates and low levels of sediment bed. Dimension analysis was performed and principal non-dimensional parameters were found, including the Péclet number, the pipe Froude number, and the dimensionless particle diameter, which can be used to determine whether the washout would occur and its intensity in a stormwater sump under given conditions. HIGHLIGHTS Maximum scour depth always occurs at the downstream side of stormwater sumps.; Sediment bed surface depth, discharge and particle size affect the washout process.; Péclet number, pipe Froude number and dimensionless particle size are most important to assess sump washout.;

In this study, curcuminoid were extracted from turmeric by ionic liquid-assisted enzymatic method. On the basis of single factor test, five factors including enzymatic hydrolysis time, enzymatic hydrolysis temperature, enzymatic hydrolysis pH, enzyme dosage and ionic liquid dosage were selected as response variables, and the extraction rate of curcuminoid was selected as response value. The response surface optimization test was conducted. The optimal process conditions were determined as follows: Enzymatic hydrolysis pH was 5.4, ionic liquid was 20%, enzyme dosage was 21%, enzymatic hydrolysis time was 90 min, enzymatic hydrolysis temperature was 59 ℃. Under these conditions, the theoretical yield of curcuminoid was 5.922%, the actual yield was 5.882%, and the relative error between the theoretical yield and the theoretical yield was 0.04%. This method can effectively extract curcuminoid from turmeric, providing reference for the development and utilization of curcumin resources.

Objective: The aim of this study is to investigate the amino acid nutrition of different peanut (Arachis hypogaea L.) varieties from Fujian, China. Method: Laifang peanut, Yakou xiaoryukyu peanut, Zhukou small seed peanut, Wenheng Hongyi peanut and Yanghou peanut were selected as experimental materials. The composition of amino acids of peanut kernel was analyzed by an amino acid automatic analyzer after hydrolysis. Based on the obtained data , the amino acid nutrition value was evaluated according to egg protein model and the ideal model recommended by WHO/FAO. A series of indexes, including the amino acid score (AAS), chemical score (CS), and score of ratio coefficient of amino acid (SRC), were calculated. Results: At least 18 amino acids were found in these peanuts. The contents of protein in these peanuts varieties ranged from 29.88~33.18 g/100 g. The contents of essential amino acids, non-essential amino acids, sour amino acids, sweet amino acids, bitter amino acids, essential amino acids for child, medical amino acids, flavoring and coloring amino acids, anti-bacteria amino acids, primary amine amino acids, branched chain amino acids, and aromatic amino acids were 7.83~8.95, 19.71~22.53, 8.93~10.29, 6.01~6.86, 10.24~11.58, 4.12~4.68, 19.44~22.23, 14.28~16.01, 3.63~4.11, 17.11~19.76, 3.95~4.44 and 3.14~3.53 g/100 g，respectively. The highest values of these indexes were found in Yakou xiaoryukyu peanut, which were obviously higher than others except Yanghou peanut (P

The effect of yak collagen peptide on reducing blood sugar was studied by diabetes mice model. A diabetic mouse model was prepared by intraperitoneal injection of alloxan (200 mg/kg) into Kunming mice. The modeled mice were randomly divided into normal group, model group, positive control group (metformin 200 mg/kg) and yak collagen peptide group (200 mg/kg), with 6 mice in each group. Relevant medicines were intragastric administration, given to each group once a day for consecutive 2 weeks, and normal group and model group were given constant volume of normal saline. The blood glucose, body weight, low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC) and high-density lipoprotein (HDL) content of each group were measured after 7 and 14 days of administration. At the same time, pancreatic morphology of mice were detected by HE staining. Compared with the normal group, amount of body weight change and blood sugar content of the model group were significantly different (P

Spatial patterns of leaf carbon (C), nitrogen (N), and phosphorus (P) stoichiometry play a pivotal role in the comprehension of terrestrial ecosystem dynamics, nutrient cycling, in responses to contemporary global climate change, and the evolutionary trajectories of leaf morphology and function. These patterns are not only solely shaped by plant and community composition, but also are profoundly influenced by environmental factors. Therefore, there is a compelling need for an in-depth investigation into individual species to discern the intricate impacts of soil and climate on leaf stoichiometry. In this study, we assessed the C, N, and P concentrations of mature leaves from 20 Phyllostachys propinqua populations in the urban forest across northern China covering a substantial latitudinal gradient. Our findings revealed that the average leaf concentrations of C, N, and P in P. propinqua were recorded at 0.46 g g−1, 23.19 mg g−1, and 1.40 mg g−1, respectively. Notably, we observed that leaf C and P concentrations, as well as the C:N ratios, exhibited significant increases with rising latitude. Conversely, leaf N concentrations and N:P ratios exhibited a marked decline with increasing latitude. These patterns were primarily driven by climate factors such as mean annual temperature (MAT) and lowest temperature (LT). In contrast, we found that only leaf C concentrations were correlated with soil N levels. These results underscored the differential spatial distribution of leaf C, N, and P stoichiometry in urban forest across northern China, predominantly instigated by climatic factors, particularly in regions characterized by lower temperatures. Our findings further suggest that P. propinqua enhances its adaptability to low-temperature environments by elevating leaf C and P concentrations.

Nanocellulose hydrogels are a crucial category of soft biomaterials with versatile applications in tissue engineering, artificial extracellular matrices, and drug-delivery systems. In the present work, a simple and novel method, involving the self-assembly of cellulose nanocrystals (CNCs) induced by tannic acid (TA), was developed to construct a stable hydrogel (SH-CNC/TA) with oriented porous network structures. The gelation process is driven by the H-bonding interaction between the hydroxyl groups of CNCs and the catechol groups of TA, as substantiated by the atoms in molecules topology analysis and FTIR spectra. Interestingly, the assembled hydrogels exhibited a tunable hierarchical porous structure and mechanical moduli by varying the mass ratio of CNCs to TA. Furthermore, these hydrogels also demonstrate rapid self-healing ability due to the dynamic nature of the H-bond. Additionally, the structural stability of the SH-CNC/TA hydrogel could be further enhanced and adjusted by introducing coordination bonding between metal cations and TA. This H-bonding driven self-assembly method may promote the development of smart cellulose hydrogels with unique microstructures and properties for biomedical and other applications.

To reduce the environmental impact of offshore oil and gas, the hydrocarbon discharge regulations tend to become more stringent. One way to reduce the oil discharge is to improve the control systems by introducing new oil-in-water (OiW) sensing technologies and advanced control. De-oiling hydrocyclones are commonly used in offshore facilities for produced water treatment (PWT), but obtaining valid control-oriented models of hydrocyclones has proven challenging. Existing control-oriented models are often based on droplet trajectory analysis. While it has been demonstrated that these models can fit steady-state separation efficiency data, the dynamics of these models have either not been validated experimentally or only describe part of the dynamics. In addition to the inlet OiW concentration, they require the droplet size distribution to be measured, which complicates model validation as well as implementation. This work presents an approach to obtain validated nonlinear models of the discharge concentration, separation efficiency, and discharge rate, which do not require the droplet size distribution to be measured. An exhaustive search approach is used to identify control-oriented polynomial-type Hammerstein–Wiener (HW) models of de-oiling hydrocyclones based on concentration measurements from online OiW monitors. To demonstrate the effectiveness of this modeling approach, a PI controller is designed using the Skogestad internal model control (SIMC) tuning rules to control the discharge OiW concentration directly. The identification experiment emulates an offshore PWT system with installed OiW monitors, which is realistic with the legislative incentive to include online OiW discharge measurements. The proposed approach could enable the application of OiW-based control on existing offshore PWT facilities, resulting in improved de-oiling performance and reduced oil discharge.

IntroductionThe grasslands in the Nature Reserve of Ganshenling, in the south of Hainan Island, were first formed after deforestation disturbance before a natural restoration of shrubs and secondary forests. However, the stages of grassland and shrubs in some parts of Ganshenling regions could not be naturally restored to secondary forests. In addition, the forest form of the secondary forest after 40 years (40a) of succession was similar to that of the secondary forest of 60 years (60a). However, it was not known whether the microorganisms recovered to the level of the secondary forest of 60a. Arbuscular mycorrhizal fungi (AMF) are plant root symbionts that can improve the nitrogen and phosphorus absorption of plants and play a key role in secondary forest succession. An understanding of the essential role of soil AMF in secondary forest succession of tropical rainforest in Ganshenling regions is still limited.MethodsTherefore, the soil of 0–10 cm was collected with the help of a 5-point sampling method in grassland, shrubs, and second tropical lowland rainforest of 40a and 60a. We studied community changes in AMF with the succession and explored the impacts of soil physicochemical properties on soil AMF.ResultsOur findings were as follows: (1) Different successional stages showed divergent effects on soil AMF communities. (2) After 40a recovery, the alpha-diversity indices of AMF recovered to the level of secondary forest of 60a, but the similarity of soil AMF communities only recovered to 25.3%. (3) Species richness of common species, rare species, and all the species of AMF showed a significantly positive correlation with soil nitrogen. (4) OTU10; OTU6, OTU9, and OTU141; OTU3 and OTU38; and OTU2, OTU15, OTU23, and OTU197 were significantly unique AMF for grasslands, shrubs, and secondary forests of 40a and 60a, respectively. (5) The phylogenetic tree and the heatmap of AMF showed that the OTUs in grasslands and shrubs were in contrast to the OTUs in secondary forests of 40a and 60a.DiscussionWe concluded that the succession of a secondary forest after deforestation disturbance was probably limited by its AMF community.

Curcumin (Cur) has antioxidant, anti-inflammatory and other biological activities, but its poor stability, low water solubility and other defects limit the application. Herein, Cur was nanocomposited with soy isolate protein (SPI) and pectin (PE) for the first time and its characterization, bioavailability and antioxidant activity were discussed. The optimal encapsulation process of SPI-Cur-PE was as follow: the addition amount of PE was 4 mg, Cur was 0.6 mg and at pH of 7. It was observed by SEM that SPI-Cur-PE were partially aggregated. The average particle size of SPI-Cur-PE was 210.1 nm and the zeta potential was −31.99 mV. Through XRD, FT-IR and DSC analysis, the SPI-Cur-PE was formed through hydrophobic interaction and electrostatic interaction. The SPI-Cur-PE released more slowly in simulated gastrointestinal treatment and displayed higher photostability and thermal stability. SPI-Cur-PE, SPI-Cur and free Cur had scavenging activities for 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals.

IntroductionAlthough numerous studies have investigated ecosystem-scale soil respiration (SR) at different ecosystem, our understanding of spatial heterogeneity of SR at plot scale is still incomplete, especially in tropical rainforests with complex topography. Further, the ecological factors that drive the variability of SR in tropical rainforests is also poorly understood.MethodsHere, we investigated the spatial variations and control mechanisms of SR in a 60-ha plot of old-growth tropical rainforest with complex topography. Specifically, we sampled a 60-ha plot in intervals of 20 m to measure SR with LI-8100, used semi-variogram of geostatistical tools to examine spatial heterogeneity of SR.ResultsThe mean SR rate in this plot was 4.312 ± 0.0410 (SE) μmol m−2 s−1. Geostatistical analysis indicated that the SR rate at this plot had a moderate spatial dependence, with a nugget-to-sill ratio of 68.1%. The coefficients variance of SR was 36.2% and the patch size was approximately 112 m. Stepwise linear regression analysis (involving a multiple regression tree) revealed that the independent factors regulated different types of SR’s. Liner mix-effect models showed that SR was significantly positively related to soil phosphorus and negatively to the slope in the 60-ha plot. Spatial disturbance of SR along multidimensional habitats that an increase in elevation of the multidimensional habitat, which was accompanied by enhanced SOC and soil phosphorous, also increased its SR in the 60-ha plot.DiscussionThis study would be helpful in designing future field experiments for a better understanding of SR at plot scale.

Background: Although many studies have reported the mortality effect of temperature, there were few studies on the mortality risk of humidity, let alone the joint effect of temperature and humidity. This study aimed to investigate the joint and interaction effect of high temperature and relative humidity on mortality in China, which will deepen understanding the health risk of mixture climate exposure. Methods: The mortality and meteorological data were collected from 353 locations in China (2013–2017 in Jilin, Hunan, Guangdong and Yunnan provinces, 2009–2017 in Zhejiang province, and 2006–2011 in other Provinces). We defined location-specific daily mean temperature ≥ 75th percentile of distribution as high temperature, while minimum mortality relative humidity as the threshold of high relative humidity. A time-series model with a distributed lag non-linear model was first employed to estimate the location-specific associations between humid-hot events and mortality, then we conducted meta-analysis to pool the mortality effect of humid-hot events. Finally, an additive interaction model was used to examine the interactive effect between high temperature and relative humidity. Results: The excess rate (ER) of non-accidental mortality attributed to dry-hot events was 10.18% (95% confidence interval (CI): 8.93%, 11.45%), which was higher than that of wet-hot events (ER = 3.21%, 95% CI: 0.59%, 5.89%). The attributable fraction (AF) of mortality attributed to dry-hot events was 10.00% (95% CI: 9.50%, 10.72%) with higher burden for females, older people, central China, cardiovascular diseases and urban city. While for wet-hot events, AF was much lower (3.31%, 95% CI: 2.60%, 4.30%). We also found that high temperature and low relative humidity had synergistic additive interaction on mortality risk. Conclusion: Dry-hot events may have a higher risk of mortality than wet-hot events, and the joint effect of high temperature and low relative humidity may be greater than the sum of their individual effects.

Abstract Background Hepatocellular carcinoma (HCC) is a highly refractory cancer associated with increasing mortality, which currently lacks effective treatment options. Interleukin-24 (IL-24) is a novel tumor suppressor cytokine that can selectively induce cancer cell apoptosis, and it has been utilized as a cancer gene therapy strategy. The vaccinia virus is a promising strategy for cancer therapy, owing to its direct viral lytic effects, as well as a vehicle to overexpress therapeutic transgenes. Methods We constructed a recombinant oncolytic vaccinia viruse (VG9-IL-24) based on vaccinia virus Guang9 (VG9) harboring the IL-24 gene. In vitro, we assessed the replication of VG9-IL-24 in HCC cell lines and normal liver cells and evaluated the cytotoxicity in different cell lines; then, we determined the expression of IL-24 by RT-PCR and ELISA. We examined apoptosis and cell cycle progression in SMMC-7721 cells treated with VG9-IL-24 by flow cytometry. In vivo, we established the SMMC-7721 xenograft mouse model to evaluate the antitumor effects of VG9-IL-24. Results In vitro, VG9-IL-24 efficiently infected HCC cell lines, but not normal liver cells, and resulted in a high level of IL-24 expression and significant cytotoxicity. Moreover, VG9-IL-24 induced an increase in the proportion of apoptotic cells and blocked the SMMC-7721 cell cycle in the G2/M phase. In vivo, tumor growth was significantly suppressed and the survival was prolonged in VG9-IL-24-treated mice. Conclusions Vaccinia virus VG9-mediated gene therapy might be an innovative treatment for cancer with tumor-specific lysis and apoptosis-inducing effects. VG9-IL-24 exhibited enhanced antitumor effects and is a promising candidate for HCC therapy.

In recent years, three simple tracers (conductivity, turbidity and temperature) have shown their advantages to many other tracers for tracing and assessment of extraneous water (or inflow and infiltration, I/I) into sewer systems due to low detection cost and high monitoring frequency. A better understanding of the error and uncertainty of the three simple tracers on the quantification of I/I will help to improve the reliability and reduce the cost of actual projects. A large-scale experimental model simulating a 36 m long sewer was constructed for conducting extraneous water flow tests including groundwater infiltration, wastewater inflow and hot water inflow under different I/I flow rates and concentrations. The accuracy and uncertainty of the three tracers were estimated, and their correlation with tracer concentration difference before and after extraneous inflow was also analyzed. Experimental results provide guidance for the practical applicability of the three tracers under different I/I conditions. HIGHLIGHTS Large-scale experimental tests were conducted to evaluate three simple tracers for I/I assessment.; The accuracy and uncertainty of three simple tracers were evaluated.; The suitable conditions for each of the three tracers were illustrated.;

Okadaic acid (OA), a marine biotoxin produced by microalgae, poses a significant threat to mariculture, seafood safety, and human health. The establishment of a novel, highly sensitive detection method for OA would have significant practical and scientific implications. Therefore, the purpose of this study was to develop an innovative approach for OA detection. A competitive amplified luminescent proximity homogeneous assay (AlphaLISA) was developed using the principle of specific antigen–antibody binding based on the energy transfer between chemiluminescent microspheres. The method was non-washable, sensitive, and rapid, which could detect 2 × 10−2–200 ng/mL of OA within 15 min, and the detection limit was 4.55 × 10−3 ng/mL. The average intra- and inter-assay coefficients of variation were 2.54% and 6.26%, respectively. Detection of the actual sample results exhibited a good correlation with high-performance liquid chromatography. In conclusion, a simple, rapid, sensitive, and accurate AlphaLISA method was established for detecting OA and is expected to significantly contribute to marine biotoxin research.

Hypoxia and immunosuppression contribute to tumor resistance to radiotherapy (RT). Here the authors design a nanoprobe based on NIR-IIb emitting quantum dots for image-guided RT and modified with catalase to relieve hypoxia in the tumor microenvironment, enhancing the precision and efficacy of RT and promoting anti-tumor immune responses.

Skin cutaneous melanoma is one of the deadly diseases, and more than 50% of the patients have BRAF gene mutations. Evidence suggests that oncogenic BRAF modulates the immune system’s ability to recognize SKCM cells. Due to the complexity of the tumor microenvironment (TME) and a lack of a rational mechanistic basis, it is urgent to investigate the immune infiltration and identify prognostic biomarkers in BRAF mutated SKCM patients. Multiple methods including ESTIMATE algorithm, differential gene analysis, prognostic analysis and immune infiltration analysis were performed to investigate the tumor microenvironment. Based on the patient’s immune score and stromal score, immune-related genes DEGs were identified. Functional analysis revealed that these genes were mainly enriched in biological processes such as immune response, defense response and positive regulation of immune system. Furthermore, we analyzed the immune infiltrating cell components of BRAF mutated patients and revealed 4 hub genes associated with overall survival time. Several cells (Monocyte, Macrophage and Gamma delta cells) have been found to be significantly decreased in immune-high BRAF mutated SKCM group. While CD4+T, CD8+T, CD4 naïve, Tr1, Th2 and many T cell subsets were significantly increased in immune-high group. These immune cells and genes were closely related to each other. This study revealed that the dysregulation of immune function and immune cells may contribute to the poor outcomes of BRAF mutated patients. It is of great significance to our further understanding of the TME and immune dysfunction in BRAF mutated SKCM.

Inflammatory bowel disease (IBD) is a chronic non-specific inflammatory disease of intestinal tract and a common digestive system disease. Current studies have shown that IBD significantly increases the incidence of colorectal cancer (CRC), and is positively correlated with the degree and extent of inflammation of IBD. The relationship between IBD and CRC has attracted extensive attention. However, the relationship between IBD and CRC has not been systematically studied by bibliometrics and visual analysis. This study conducted bibliometric analysis based on 3528 publications from the Core Collection of Web of Science to determine the research status, research hotspots and frontiers of this field. The results show that the number of publications has increased significantly over the past 10 years. The cooperative network analysis shows that the United States, Mayo Clin and Bo Shen are the country, institution and author with the most publications respectively. Belgium, Icahn Sch Med Mt Sinai and Erik Mooiweer are the most collaborative country, institution and author respectively. Analysis of keywords and references showed that inflammation, intestinal flora, and obesity were hot topics in this field. Analysis of keyword outbreaks shows that the gut microbiome and metabolism will be an emerging new research area and a potential hot spot for future research. This study is the first to visually examine the association between IBD and CRC using bibliometrics and visual analysis, and to predict potential future research trends.

BackgroundRadiation-induced skin injury (RISI) is still the most common and severe side effect of radiotherapy. The role of the skin’s microbial barrier in the pathogenesis and progression of RISI needs to be fully investigated.MethodsThis study aimed to explore the alterations in and functions of the skin microbiota in RISI. We applied the unculturable approach to characterize the cutaneous microbiomes of a radiation-induced animal model by sequencing the V1–V3 regions of the 16S ribosomal RNA (rRNA) gene. Combined with the downloaded clinical data of patients, a comprehensive analysis was performed to identify potential radioprotective species and metabolic pathways.ResultsThere were no significant differences in the alpha diversity indices (Sobs, Shannon, Simpson, Ace, and Chao) between the acute radiation injury and control groups. Phylum-level analysis of the RISI microbiomes exhibited significant predominance of Firmicutes (mean abundance = 67%, corrected p = 0.0035). The high abundance of Firmicutes was significantly associated with rapid healing of RISI (average relative abundance = 52%; Kruskal–Wallis: p = 5.7E−4). Among its members, Streptococcus, Staphylococcus, Acetivibrio ethanolgignens group, Peptostreptococcus, Anaerofilum, and UCG-002 [linear discriminant analysis (LDA) > 3, p 0.6, p