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Abstract The construction of large reservoirs has modified the process of water and sediment transport downstream, resulting in changes in the morphology of the river cross-section. Changes in water and sand transport and cross-sectional morphology are reflected in the rating curve at the cross-section. This study analyzed the variations in the rating curve at the Huayuankou (HYK) section and their influencing factors, and conducted water level predictions based on this relationship. The findings revealed that while the annual mean water level has shown a declining tendency over the past 20 years, the annual mean discharge has shown a constant pattern. The rating curve at this stretch narrowed from a rope-loop type curve in its natural condition to a more stable single curve as a result of the construction of the dam upstream of the HYK section. The effect of pre-flood section morphology and the water–sediment process on the scattering degree of the rating curve is inverse; increasing roughness and hydraulic radius decreases scattering degree, while increasing sand content and sand transport rate increases scattering degree. Using the measured data from 2020 as an example, the feasibility of predicting cross-sectional water levels using the rating curve was verified. The prediction results were accurate when the flow was between 1000 and 2800 m3/s; However, when the flow was between 2800 and 4000 m3/s, the forecast results were typically slightly lower than the measured values. Overall, the method demonstrates good predictive accuracy. Insight from the method can be used to predict water levels to better inform decision making about water resources management, and flood emergency response in the lower Yellow River.

Eutrophication resulting from anthropogenic activities has been recognized as a significant driver of changes in ecosystem functioning. Furthermore, it may exacerbate the top–down effect and thus exert an important impact on plant growth. To test this hypothesis, we conducted a 3-year manipulative field experiment to investigate the impacts of nitrogen addition and crab herbivory on the growth of Phragmites australis in the salt marsh of the Yellow River Delta. The results demonstrated that a 3-year nitrogen addition can significantly increase the total nitrogen and carbon content of P. australis leaves, thereby enhancing their nutritional value and palatability, as well as increasing the proportion of leaves consumed by crabs. Therefore, nitrogen addition together with crab herbivory had a significant negative effect on P. australis height, leaf length, and leaf breadth in the ambient crab and procedural crab cage treatment compared to the crab exclusion treatment. The structural equation modeling further substantiated these findings. The model revealed a direct and positive correlation between nitrogen addition and leaf nutrient content (path coefficient = 0.34). Additionally, it demonstrated a direct and positive relationship between leaf nutrient content and the proportion of leaves consumed by crabs (path coefficient = 0.22). Simultaneously, there was an observed negative correlation (path coefficient = − 0.37) between the proportion of leaves consumed by crabs and plant functional traits, represented by leaf length in the model, during 2018. Moreover, the crab exclusion treatment significantly reduced the proportion of leaves consumed by crabs and thus enhanced the P. australis individuals, leaf number, and biomass. Overall, crab herbivory had a significant detrimental top–down effect on the growth of P. australis, and nitrogen enrichment may exacerbate this top–down effect. The findings of our study highlight the combined adverse effects of nutrient enrichment and top–down on plant functional traits and plant growth. The findings of this study will contribute to a comprehensive understanding of the underlying factors influencing vegetation degradation in coastal wetland, thereby establishing a solid theoretical framework for the conservation and management of wetland ecosystems within the context of global environmental change.

Background Previous studies have suggested the potential synergistic antitumor activity when combining immune checkpoint inhibitors with anti-angiogenic agents in various solid tumors. We aimed to assess the efficacy and safety of camrelizumab (a humanized programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) for patients with advanced mucosal melanoma (MM), and explore-related biomarkers.Methods We conducted a single-center, open-label, single-arm, phase II study. Patients with unresectable or recurrent/metastatic MM received camrelizumab and apatinib. The primary endpoint was the confirmed objective response rate (ORR).Results Between April 2019 and June 2022, 32 patients were enrolled, with 50.0% previously received systemic therapy. Among 28 patients with evaluable response, the confirmed ORR was 42.9%, the disease control rate was 82.1%, and the median progression-free survival (PFS) was 8.05 months. The confirmed ORR was 42.9% (6/14) in both treatment-naïve and previously treated patients. Notably, treatment-naïve patients had a median PFS of 11.89 months, and those with prior treatment had a median PFS of 6.47 months. Grade 3 treatment-related adverse events were transaminase elevation, rash, hyperbilirubinemia, proteinuria, hypertension, thrombocytopenia, hand-foot syndrome and diarrhea. No treatment-related deaths were observed. Higher tumor mutation burden (TMB), increased T-cell receptor (TCR) diversity, and altered receptor tyrosine kinase (RTK)/RAS pathway correlated with better tumor response.Conclusion Camrelizumab plus apatinib provided promising antitumor activity with acceptable toxicity in patients with advanced MM. TMB, TCR diversity and RTK/RAS pathway genes were identified as potential predictive biomarkers and warrant further validation.Trial registration number Chinese Clinical Trial Registry, ChiCTR1900023277.

Abstract Introduction Acral melanoma (AM) is the most common subtype of malignant melanoma in China, with a very poor prognosis. Despite the frequent reporting of trauma events in AM cases, the precise etiology of AM remains elusive. Methods A retrospective analysis was conducted on a cohort of 303 AM patients at Nanjing Drum Tower Hospital. The patients were categorized into four distinct groups based on different patterns of disease onset: trauma type (Type 1), pigmented nevus type (Type 2), pigmented nevi with trauma (Type 3), and pigmented nevi with natural ulceration (Type 4). Differences in clinicopathological features, genetic alterations, and tumor immune microenvironment (TIME) were analyzed. Results Traumatic events accounted for a large proportion of AM cases. Among these categories, Type 1 patients displayed the least favorable pathological traits and an immunosuppressive TIME. Common copy number variations (CNVs) were observed in CCND1, RB1, FGF19, and IL7R, while CNVs in CDK4 and TERT occurred less frequently in patients with a history of trauma (Type 1 and Type 3). Type 2 patients exhibited the most favorable pathological characteristics and genetic profiles, and demonstrated the lowest incidence of CCDN1 and RB1 CNVs but had the highest CDK4 CNVs. In contrast, the pathological behavior of Type 3 and Type 4 patients was in between Type 1 and Type 2. And patients in Type 3 and Type 4 displayed a more favorable overall microenvironment. Conclusion This study provides a clinical classification of Chinese AM based on diverse clinical onset characteristics and highlights the important role of trauma in AM. These findings may help to guide the diagnosis, treatment, and prognosis of AM patients. Further investigations are imperative to elucidate the underlying mechanisms governing the association between trauma and AM.

As a prerequisite and foundation for studying the evolution mechanism of river channels, an in-depth understanding of the cross-sectional morphology adjustment is required. As a starting point, it is crucial to systematically summarize and generalize the research findings on channel morphological adjustment obtained to date, particularly in the context of the significant changes in the water and sediment conditions of large rivers that have occurred worldwide. This paper provides a comprehensive review of the research findings on the three following aspects of the Lower Yellow River: the transverse distribution of overbank flow velocity, the transverse distribution of suspended sediment concentration, and the morphological adjustment of the river cross-section. There are various equations available to predict the lateral depth–average flow velocity distribution. These equations are classified into the two following categories: empirical and theoretical formulas. Theoretical formulas are obtained through consideration of the cross-sectional morphology, accounting for inertial force terms caused by secondary flow, and momentum transfer between the main channel and its floodplain. Similarly, empirical equations and theoretical formulas for sediment concentration transverse distribution are also summarized, given the different influencing factors and assumptions. We also discuss the morphological adjustment of river cross-sections based on the analysis of measured data, mathematical model calculation, and the physical model test. In particular, we propose the idea of revealing channel cross-section morphology evolution mechanisms from the theoretical level of water and sediment movement and distribution. This review aims to enhance understanding of overbank flow, sediment transport, and channel morphology in the Lower Yellow River and may also serve to some extent as a reference for the evolution and management of channels in other rivers.

The construction of large-scale water diversion projects has effectively alleviated the current situation of the uneven distribution of water resources in China. However, due to the siltation of very fine sediment and organic matter on the side wall of an open channel, and the slow velocity of the side wall flow field, it is easy for epipelic algae to be produced, which affects water quality. Because prototype observation cannot be used to predict the series of flow in real time, and the calculation of the mathematical model is affected by parameter limitations, these two methods often cannot truly reflect the hydrodynamic characteristics of an open channel with epipelic algae. Therefore, by referring to the design parameters of the water diversion project channel, this study took the epipelic algae growing on the side wall of an open channel as the research object and used the scale of 1:30 to carry out a generalized flume experiment. Through the analysis of the physical characteristics of the prototype sample, and the simulation of the cohesive force between the oblique side wall and the epipelic algae, multi-group and multi-series hydrodynamic tests were carried out. The velocity distribution law and flow field distribution law were analyzed. The research results show that the presence of epipelic algae has a certain hindering effect on the flow velocity and significantly reduces the range of the peak velocity of the channel along the water depth. The position of the maximum velocity on the vertical line of the channel flow appears at the relative water depth of 0.6. In the case of small flow, the epipelic algae group only reduces the average flow rate of the channel by 5~6%; in the case of large flow, the effect of epipelic algae on the channel flow rate is minimal. This paper includes important scientific guiding significance and practical value for the regulation of water quantity and water quality safety, as well as the protection of long-distance projects.

AimWe aimed to evaluate the efficacy and safety of individualized chemotherapy combined with sequential immunotherapy based on BRCA1 mRNA expression in unresectable pancreatic cancer.MethodsThe expression of BRCA1 mRNA in tumor tissues of 25 patients with pancreatic cancer was detected in this retrospective study. Patients in the medium and high expression groups were treated with paclitaxel-based chemotherapy: albumin paclitaxel 125mg/m2, gemcitabine 1g/m2, day 1. Patients in the low expression group were treated with oxaliplatin-based chemotherapy: oxaliplatin 85mg/m2, gemcitabine 1g/m2, day 1. Sequential GM-CSF and IL-2 immunotherapy were applied. Patient condition, treatment efficacy and safety were assessed every 4 cycles.ResultsA total of 25 patients were enrolled in the study. All of them were observed for toxic side effects and 24 of them were evaluated for efficacy. The median overall survival and median progression-free survival were 11.9 months and 6.3 months. The disease control rate was 91.7%, of which 37.5% (9/24) patients achieved partial remission (PR), 54.2% (13/24) patients achieved stable disease (SD) and 8.3% (2/24) patients were assessed as progressive disease(PD). Of the 15 patients with medium or high expression in BRCA1 mRNA, 7 achieved PR and 8 achieved SD. Of the 9 patients with low BRCA1 mRNA expression, 2 achieved PR, 5 achieved SD and 2 had PD. The proportion of eosinophils in the blood of some patients with good therapeutic effects was significantly higher than that before treatment. Hematological and non-hematological toxicity during the treatment were mostly grade 1~2. The two most common grade 3 to 4 adverse events were fever and thrombocytopenia.ConclusionOur results suggest that individualized selection of chemotherapy combined with sequential immunotherapy according to BRCA1 mRNA expression level in unresectable pancreatic cancer could control the disease and have controllable adverse reactions.

In the coastal wetland, nitrogen is a limiting element for plant growth and reproduction. However, nitrogen inputs increase annually due to the rise in nitrogen emissions from human activity in coastal wetlands. Nitrogen additions may alter the coastal wetlands’ soil properties, bacterial compositions, and plant growth. The majority of nitrogen addition studies, however, are conducted in grasslands and forests, and the relationship between soil properties, bacterial compositions, and plant growth driven by nitrogen addition is poorly understood in coastal marshes. We conducted an experiment involving nitrogen addition in the Phragmites australis population of the tidal marsh of the Yellow River Delta. Since 2017, four nitrogen addition levels (N0:0 g • m-2 • year-1, N1:5 g • m-2 • year-1, N2:20 g • m-2 • year-1, N3:50 g • m-2 • year-1) have been established in the experiment. From 2017 to 2020, we examined soil properties and plant traits. In 2018, we also measured soil bacterial composition. We analyzed the effect of nitrogen addition on soil properties, plant growth, reproduction, and plant nutrients using linear mixed-effect models. Moreover, structural equation modeling (SEM) was utilized to determine the direct and indirect effects of nitrogen addition, soil properties, and bacterial diversity on plant growth. The results demonstrated that nitrogen addition significantly affected plant traits of P. australis. N1 and N2 levels generally resulted in higher plant height, diameter, leaf length, leaf breadth, and leaf TC than N0 and N3 levels. Nitrogen addition had significantly impacted soil properties, including pH, salinity, soil TC, and soil TS. The SEM revealed that nitrogen addition had a direct and positive influence on plant height. By modifying soil bacterial diversity, nitrogen addition also had an small indirect and positive impact on plant height. However, nitrogen addition had a great negative indirect impact on plant height through altering soil properties. Thus, nitrogen inputs may directly enhance the growth of P. australis at N1 and N2 levels. Nonetheless, the maximum nitrogen addition (N3) may impede P. australis growth by reducing soil pH. Therefore, to conserve the coastal tidal marsh, it is recommended that an excess of nitrogen input be regulated.

Water-use characteristics are important aspects of plant adaptation to environmental factors. While water-use efficiency (WUE) and water sources used by plants in arid habitats are commonly studied, water-use strategies of plants in coastal wetlands are poorly studied. Although ample water is available in coastal wetlands, water conditions vary among seasons, suggesting that the plant in coastal wetlands may need to adapt to seasonal changes in water availability.To uncover temporal variation in plant water-use strategies in the coastal wetland, we investigated WUE and water sources used by Phragmites australis in the tidal marsh of the Yellow River Delta employing stable isotopic composition indicators. Temporal variation of δ13C and δ18O in leaf organic matter were measured in two years (2018 and 2019) along with plant traits and environmental factors, to determine the factors affecting δ13C and δ18O in leaf organic matter. Water sources (rainfall, soil water in different depths, tidal water, and groundwater) were sampled for δ18O composition in the early growth season (2019 May, June, and July) to determine water sources using the Bayesian mixing model MixSIAR.We found that P. australis had high WUE in spring and autumn, but WUE declined during summer. Changes in WUE were explained by variation in plant height, leaf nutrient concentrations (C: N, total N, total S), leaf traits (leaf length and leaf number), soil electronic conductivity (EC), soil pH, soil nutrients (NO3-N at 0–30 cm soil depth, total S at 0–30 cm soil depth, available P at the soil depths of 0–10 cm and 40–50 cm, and total C at the 30–40 cm soil depth). Spring drought may enhance WUE through increasing soil salinity (i.e., EC) and lowering pH. Water uptake in the early growth season was composed mainly of rainfall, soil water, and groundwater. However, tidal water (i.e., ocean water) was not a main water source. To sum up, leaf WUE varied with seasons in the coastal wetland, which may be related to plant traits and soil factors, particularly salinity and pH. The plant in the tidal marsh may not take up ocean water, even though it is really abundant. Precipitation is still an important water source promoting growth of these plants in the coastal wetland, therefore, to conserve them, supplementing fresh water in the drought season is suggested.

We report on the fabrication and characterization of nanopatterned superconducting quantum interference devices (SQUIDs) based on grain boundary Josephson junctions in epitaxially grown multilayer YBa2Cu3O7 (YBCO)/SiTrO3 (STO) thin films. Nanopatterning is performed by Ga+ focused ion beam milling. The evolution of the electric transport and noise properties of the YBCO nanoSQUIDs over a time span of more than one year are recorded and analyzed. We find that the multilayer YBCO/STO nanoSQUIDs show stable and high performance over time. The critical current decreases within ∼40 days by 30%–50% and then remains almost constant without obvious decline trend for nanoSQUIDs with STO layer as the interface even more than 380 days, which demonstrates the superiority of STO as the capping layer. Moreover, we find that the multilayer nanoSQUIDs have about an order of magnitude smaller low-frequency excess flux noise (compared to similar single layer devices) with root-mean-square spectral density ∼5–6 µΦ0/Hz1/2 at 1 Hz. For one device, we show that the low-frequency excess noise does not degrade within three months.

The worldwide problem of reservoir sedimentation has perplexed the water conservancy industry. The problem of reservoir sedimentation is particularly serious in sandy rivers in China and directly affects the normal function of reservoirs. Due to its effect on the economy and environmental protection, the self-priming pipeline dredging and sediment discharge technology has broad application prospects. Nevertheless, there are pressing problems in the transportation of slurry particles in the pipeline system of this new technology. The purpose of this study is to use physical model tests to analyze the influence of the sediment transport rate and pipeline velocity on the motion state of particles (aggregation transport, jump transport, and suspension transport) when a heterogeneous flow with different particle sizes is transported in the pipeline. The results indicate that under the same pipeline velocity and sediment transport rate, the thickness of the static particle accumulation layer decreases with the increase in particle size in the state of aggregation and transportation, and the smaller the particle size, the greater the particle movement speed in the case of aggregation and suspension transportation. During jump transportation, the velocity of particles above the critical inflection point Y’ increases with the decrease in particle size. The opposite is found below the critical inflection point Y’. At the same particle size and sediment transport rate, when the pipeline velocity increases, the particle transport transits from aggregation transport to jump transport and then to suspension transport. The larger the pipeline velocity, the greater the overall movement speed of particles. When gathering and conveying, if the pipeline flow rate increases by 1.5, the maximum movement speed of particles increases by 3.3. The curvature of the vertical velocity curve of the particles during jump transportation is not affected by the pipeline velocity. The particle velocity at the highest point increases with the increase in the pipeline velocity. During suspension transportation, the difference between the maximum and minimum vertical particle distribution velocities is exponentially related to the pipeline velocity. At the same pipe velocity and particle size, the overall particle velocity decreases with the increase in sediment transport rate.

This paper performs a numerical investigation on the kinetic behaviors of dry granular flows generated by the collapse of granular columns with different fractal particle size distributions (FPSDs) using the discrete element method. The FPSD has a remarkable impact on the regime and mobility of a granular flow. As the fractal dimension of a granular assembly increases, the translational velocities of the particles increase in the horizontal direction, whereas the rotational velocities decrease. The number of particles involved in the horizontal spreading increases due to the decreasing intensity of the contact shearing particle behavior. These increased translational velocities in the horizontal direction effectively facilitate particle spreading. A boundary layer is formed at the front bottom of the granular body in which the clockwise rotational velocities of particles are significantly increased, thereby benefiting particle spreading. The whole front of the granular flow obtains an immense spreading velocity. Moreover, the translational and rotational characteristics are dependent on the particle size. Smaller particles tend to translate and rotate faster than larger particles because of the greater particle contact forces of the former. As the fractal dimension increases, medium- and large-size particles obtain less kinetic energy than do small-size particles. Therefore, small-size particles play a crucial role in the mobility of granular flows in a granular assembly with a high fractal dimension.

The construction of a river regulation project has changed the cross-sectional shape of a river and significantly impacted the evolution of the river regime. In this paper, an asymmetry index was proposed to characterize the changes in the shape of the river cross-section and the distribution of water and sediment factors. According to the transverse distribution formula of the river section and water and sediment factors, the asymmetry of the cross-sectional shape as well as water and sediment factors along with the transverse distribution in the wandering reach of the lower Yellow River before and after the construction project was calculated, respectively. The results showed that the cross-sectional shape of the river channel before and after the building was asymmetric, and the cross-sectional shape of the river channel after the construction was more asymmetric than that of the free development channel without engineering constraints; at the same time, under the action of a limited control boundary, the asymmetry of cross-section flow velocity and sediment concentration and other water and sediment factors along the transverse distribution were more prominent, the flow velocity and sediment concentration along the transverse distribution increased, the river flow was more concentrated, and the sediment transport capacity of the channel improved significantly under a large flow (5000 m3/s). This study revealed the positive effect of river regulation projects on the river regime evolution of the wandering river and provided new ideas for the study of river regime evolution.

The change of water and sediment conditions in wandering channels has a great impact on the stability of river regime. The quantitative relationship between them is still unclear. The qualitative influence of water and sediment conditions on the river regime stability was analyzed by a model test. The response relationship between the upward or downward moving distance of the main stream zone and water and sediment conditions was quantitatively studied by using the measured water and sediment data and large-section data over the years. The results showed that when the upstream water and sediment inflow conditions change, the stability of a wandering channel with relatively stable river regime under the control of finite boundary will still change. When the river channel is at 1000 m3/s under the action of long-term small water, or silting thickness is about 0.53 m, the main stream next to the project moves upwards about 1170 m along the way. In the case of a large flood, such as 8000 m3/s, or scouring depth is about 0.39 m, the main stream next to the project moves downwards about 870 m along the way. The study provides a certain scientific basis for river regime stability and river flood control early warning, and provides a certain method reference for quantitative study of river regime evolution of other rivers at home and abroad.