Modulating PCGF4/BMI1 Stability Is an Efficient Metastasis-Regulatory Strategy Used by Distinct Subtypes of Cancer-Associated Fibroblasts in Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm prone to metastasis. Whether cancer-associated fibroblasts (CAFs) affect the metastasis of ICC is unclear. Herein, ICC patient-derived CAF lines and related cancerous cell lines were established and the effects of CAFs on the tumor progressive properties of the ICC cancerous cells were analyzed. CAFs could be classified into cancer-restraining or cancer-promoting categories based on distinct tumorigenic effects. The RNA-sequencing analyses of ICC cancerous cell lines identified polycomb group ring finger 4 (PCGF4; alias BMI1) as a potential metastasis regulator. The changes of PCGF4 levels in ICC cells mirrored the restraining or promoting effects of CAFs on ICC migration. Immunohistochemical analyses on the ICC tissue microarrays indicated that PCGF4 was negatively correlated with overall survival of ICC. The promoting effects of PCGF4 on cell migration, drug resistance activity, and stemness properties were confirmed. Mechanistically, cancer-restraining CAFs triggered the proteasome-dependent degradation of PCGF4, whereas cancer-promoting CAFs enhanced the stability of PCGF4 via activating the IL-6/phosphorylated STAT3 pathway. In summary, the current data identified the role of CAFs in ICC metastasis and revealed a new mechanism of the CAFs on ICC progression in which PCGF4 acted as the key effector by both categories of CAFs. These findings shed light on developing comprehensive therapeutic strategies for ICC.

Relocation of lower pole renal stones helps improve the stone-free rate during flexible ureteroscopy with a low complication rate.

OBJECTIVE: To compare the efficacy and safety of relocating the lower pole stones to a favorable pole during flexible ureteroscopy with in situ lithotripsy for the treatment of 10-20 mm lower pole stone (LPS). METHODS: This study was a prospective analysis of patient outcomes who underwent an FURS procedure for the treatment of 10-20 mm lower pole renal stones from January 2020 to November 2022. The patients were randomized into a relocation group or in situ group. The LPSs were relocated into a calyx, during lithotripsy in the relocation group was performed, whereas the in situ group underwent FURS without relocation. All the procedures were performed by the same surgeon. The patients' demographic data, stone characteristics, perioperative parameters and outcomes, stone-free rate (SFR), complications, and overall costs were assessed retrospectively. RESULTS: A total of 90 patients were enrolled and analyzed in this study (45 per group) with no significant differences between the two groups in terms of age, gender, BMI, diabetes, hypertension, stone size, number, laterality, composition, and density. The mean operation time, total energy consumption, postoperative stay, and complications were similar between the groups. Both groups had similar SFR at 1 day postoperative follow-up (p = 0.091), while the relocation group achieved significantly higher SFR 3 months later (97.8% vs 84.4%, p = 0.026). The relocation group also had a significantly higher WisQol score than the in situ group (126.98 vs 110.18, p < 0.001). CONCLUSION: A satisfactory SFR with a relatively low complication rate was achieved by the relocation technique during the FURS procedure.

Neutrophil-to-lymphocyte ratio at admission for early diagnosis, severity assessment, and prognosis of acute traumatic spinal cord injury.

STUDY DESIGN: A retrospective study. OBJECTIVE: This study examined the value of neutrophil-to-lymphocyte ratio at admission for early diagnosis, severity assessment, and prognosis of acute traumatic SCI. SETTING: The First People's Hospital of Neijiang, China. METHODS: This was a single-center, retrospective, cohort study of patients treated within 12 h of acute SCI between January 2018 and October 2022. Ninety-four SCI patients were selected as the Observation group, including 26 with complete injury (AIS grade A) and 68 with incomplete injury (AIS grade B-D), while 94 patients with simple spinal fracture were randomly selected as the Control group. Eighty-one observation group patients underwent surgical treatment, of which 33 had a higher AIS grade (Good prognosis subgroup) and 48 a lower or equal grade post-surgery (Poor prognosis subgroup). Univariate and multivariate analyses were performed to assess predictors of early diagnosis, severity, and 6-month outcome. RESULTS: Initial white blood cell count, neutrophil count, monocyte count, and NLR were higher in the Observation group than the Control group, while lymphocyte count was lower in the Observation group. Multivariate logistic regression analysis identified NLR as an independent predictor of early diagnosis. Spinal canal encroachment ≥50%, neutrophil count, and NLR were higher in the complete injury subgroup, and spinal canal encroachment ≥50% was an independent predictor of complete injury, while NLR was not. The NLR was higher in the poor prognosis subgroup and was an independent risk factor. CONCLUSIONS: Peripheral blood NLR is useful for early diagnosis of acute SCI and is predictive of clinical outcome.

Low-dose radiation-induced SUMOylation of NICD1 negatively regulates osteogenic differentiation in BMSCs.

Various biological effects of ionizing radiation, especially continuous exposure to low-dose radiation (LDR), have attracted considerable attention. Impaired bone structure caused by LDR has been reported, but little is known about the mechanism involved in the disruption of bone metabolism. In this study, given that LDR was found to (at a cumulative dose of 0.10 Gy) disturb the serum Mg2+ level and Notch1 signal in the mouse femur tissues, the effects of LDR on osteogenesis and the underlying molecular mechanisms were investigated based on an in vitro culture system for bone marrow stromal cells (BMSCs). Our data showed that cumulative LDR suppressed the osteogenic potential in BMSCs as a result of upregulation of Notch1 signaling. Further analyses indicated that the upregulation of NICD1 (Notch1 intracellular domain), the key intracellular domain for Notch1 signaling, under LDR was a consequence of enhanced protein stabilization caused by SUMOylation (small ubiquitin-like modification). Specifically, the downregulation of SENP1 (sentrin/SUMO-specific protease 1) expression induced by LDR enhanced the SUMOylation of NICD1, causing the accumulation of Notch1 signaling, which eventually inhibited the osteogenic potential of BMSCs. In conclusion, this work expounded on the mechanisms underlying the impacts of LDR on bone metabolism and shed light on the research on bone regeneration under radiation.

Anti-inflammatory activity of a new lactone isolated from the leaves of Ardisia crenata Sims.

One new lactone (1) named Ardisicreolide C, together with three saponin compounds, Ardisiacrispin B (2), Ardisicrenoside A (3), Ardisiacrispin A (4) were isolated and identified from the leaves of Ardisia crenata Sims. The structures of 1-4 were elucidated by 1D, 2D-NMR and HR-MS spectra and together with the published data. In view of structures with lactone moieties showed good anti-inflammatory activity, the anti-inflammatory effects of Ardisicreolide C on LPS-induced RAW264.7 cells were evaluated by enzyme linked immunosorbent assay (ELISA) method. As a result, Ardisicreolide C could reduce release of nitric oxide (NO), tumour necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), interleukin 4 (IL-4) and interleukin 10 (IL-10) of the cell supernatant to exert anti-inflammatory activity. This indicates that the leaves as non-medicinal parts of Ardisia crenata Sims contain compounds with good anti-inflammatory activity, which provides a new direction for the discovery of anti-inflammatory drugs.

Discovery of Potential Anti-Microbial Molecules and Spectrum Correlation Effect of Ardisia crenata Sims via High-Performance Liquid Chromatography Fingerprints and Molecular Docking.

Ardisia crenata Sims, an important ethnic medicine, is recorded in the Chinese Pharmacopoeia for treating laryngeal diseases and upper respiratory tract infections. This study aimed to evaluate the antimicrobial effect of extracts and potential antimicrobial compounds of A. crenata Sims. It was found that the roots of A. crenata Sims have a potential inhibitory effect on Candida albicans and Aspergillus flavus, with MICs of 1.56 mg/mL and 0.39 mg/mL, and the leaves of A. crenata Sims have a potential inhibitory effect on Pseudomonas aeruginosa and Staphylococcus aureus, with MICs of 3.12 mg/mL and 6.77 mg/mL, respectively. Meanwhile, five compounds including one catechin and four bergenins were obtained from roots. These components were identified on the fingerprint spectrum, representing chromatographic peaks 16, 21, 22, 23, and 25, respectively. Among these, 11-ß-d-glucopyranosyl-bergenin and (-)-gallocatechin showed potential inhibition for Staphylococcus aureus and Pseudomonas aeruginosa with MIC of 0.26 and 0.33 mg/mL, respectively. The roots, stems, and leaves of A. crenata Sims are very similar in chemical composition, with large differences in content. Principal component analysis (PCA) and Hierarchical cluster analysis (HCA) showed that 16 batches of A. crenata Sims could be divided into four main production areas: Guizhou, Jiangsu, Guangxi, and Jiangxi. Furthermore, molecular docking results showed that 11-ß-d-glucopyranosyl-bergenin had a better affinity for Casein lytic proteinase P (ClpP), and (-)-gallocatechin possessed a strong affinity for LasA hydrolysis protease and LasB elastase. These findings suggest catechin and bergenins from A. crenata Sims can be used as antimicrobial activity molecules.

NK cells are never alone: crosstalk and communication in tumour microenvironments.

Immune escape is a hallmark of cancer. The dynamic and heterogeneous tumour microenvironment (TME) causes insufficient infiltration and poor efficacy of natural killer (NK) cell-based immunotherapy, which becomes a key factor triggering tumour progression. Understanding the crosstalk between NK cells and the TME provides new insights for optimising NK cell-based immunotherapy. Here, we present new advances in direct or indirect crosstalk between NK cells and 9 specialised TMEs, including immune, metabolic, innervated niche, mechanical, and microbial microenvironments, summarise TME-mediated mechanisms of NK cell function inhibition, and highlight potential targeted therapies for NK-TME crosstalk. Importantly, we discuss novel strategies to overcome the inhibitory TME and provide an attractive outlook for the future.

Cell fate conversion prediction by group sparse optimization method utilizing single-cell and bulk OMICs data.

Cell fate conversion by overexpressing defined factors is a powerful tool in regenerative medicine. However, identifying key factors for cell fate conversion requires laborious experimental efforts; thus, many of such conversions have not been achieved yet. Nevertheless, cell fate conversions found in many published studies were incomplete as the expression of important gene sets could not be manipulated thoroughly. Therefore, the identification of master transcription factors for complete and efficient conversion is crucial to render this technology more applicable clinically. In the past decade, systematic analyses on various single-cell and bulk OMICs data have uncovered numerous gene regulatory mechanisms, and made it possible to predict master gene regulators during cell fate conversion. By virtue of the sparse structure of master transcription factors and the group structure of their simultaneous regulatory effects on the cell fate conversion process, this study introduces a novel computational method predicting master transcription factors based on group sparse optimization technique integrating data from multi-OMICs levels, which can be applicable to both single-cell and bulk OMICs data with a high tolerance of data sparsity. When it is compared with current prediction methods by cross-referencing published and validated master transcription factors, it possesses superior performance. In short, this method facilitates fast identification of key regulators, give raise to the possibility of higher successful conversion rate and in the hope of reducing experimental cost.

Tumor cell density dependent IL-8 secretion induces the fluctuation of tregs/CD8 + T cells infiltration in hepatocellular carcinoma: one prompt for the existence of density checkpoint.

BACKGROUND: Tumor cell density is a basic pathological feature of solid tumors. Chemotherapy, radiotherapy, and targeted therapy reduce tumor cell density, whereas unrestricted tumor cell proliferation promotes this feature. The impact of tumor cells on the microenvironment following changes in tumor cell density is still unclear. In this study, we focused on the response of key immune cell subsets to tumor cell density in hepatocellular carcinoma (HCC). METHODS: We determined the density of tumor and immune cells in the same area by section staining. We then identified potential mediators using polymerase chain reaction (PCR), enzyme-linked immunofluorescence assay (ELISA), 3D and co-culture, flow cytometry, and lentivirus intervention. The mechanism of lactate promotion was verified using lactate tests, bioinformatics, western blotting, and the above methods. The IL-8/DAPK1/lactate/regulatory T cell (Treg) axis was verified using a mouse liver cancer model. Tumor mutation burden was calculated using maftools in R. RESULTS: We found that the Treg/CD8 + T cell ratio is not consistent with tumor cell density in HCC, and a decreased Treg/CD8 + T cell ratio in the range of 5000-6000 cells/mm2 may elicit the possibility for immunotherapy in an immunosuppressive microenvironment. We showed that IL-8 mediates this immune fluctuation and promotes the infiltration of Tregs through the DAPK1/pyruvate kinase activity/lactate axis in HCC. Based on tumor ploidy and mutation burden data, we discussed the potential significance of immune fluctuation in the homeostasis of HCC mutation burden and proposed a "density checkpoint" and "entropy model" to describe this phenomenon. CONCLUSIONS: In summary, we report the mode of infiltration of Tregs/CD8 + T cells in response to tumor cell density and provide a new theoretical basis for IL-8 as a therapeutic target and the selection of an immunotherapy window in HCC.

Urbanization in developing countries overrides catchment productivity in fueling inland water CO2 emissions.

We compiled a nationwide dataset of carbon dioxide (CO2 ) efflux from 1405 measurements, and found that lakes, reservoirs, and rivers emit a total of 61.9 ± 55.3 TgC as CO2 each year, corresponding to ~6.3% of the annual total national CO2 emission in 2020. Our analysis showed that the presence of anthropogenic disturbances in catchments strongly influences the emission of CO2 from these waters in the non-pristine areas, masking the catchment productivity effect on the emission of CO2 . Our results highlight the need for adjusting climate change models for taking into account anthropogenic effects on CO2 emissions from inland waters.

Hydrological Controls on Dissolved Organic Matter Composition throughout the Aquatic Continuum of the Watershed of Selin Co, the Largest Lake on the Tibetan Plateau.

Alpine river and lake systems on the Tibetan Plateau are highly sensitive indicators and amplifiers of global climate change and important components of the carbon cycle. Dissolved organic matter (DOM) encompasses organic carbon in aquatic systems, yet knowledge about DOM variation throughout the river-lake aquatic continuum within alpine regions is limited. We used optical spectroscopy, ultrahigh-resolution mass spectrometry (Fourier transform ion cyclotron resonance mass spectrometry), and stable water isotopic measurements to evaluate linkages between DOM composition and hydrological connection. We investigated glacial influences on DOM composition throughout the watershed of Selin Co, including upstream glacier-fed rivers and downstream-linked lakes. We found that the dissolved organic carbon concentration increased, whereas specific ultraviolet absorbance (SUVA254) decreased along the river-lake continuum. Relative to rivers, the downstream lakes had low relative abundances of polyphenolic and condensed aromatic compounds and humic-like substances but increased relative abundances of aliphatics and protein-like compounds. SUVA254 decreased while protein-like components increased with enriched stable water isotope δ2H-H2O, indicating that DOM aromaticity declined while autochthonous production increased along the flow paths. Glacier meltwater contributed to elevated relative abundances of aliphatic and protein-like compounds in headwater streams, while increased relative abundances of aromatics and humic-like DOM were found in glacier-fed lakes than downstream lakes. We conclude that changes in hydrological conditions, including glacier melt driven by a warming climate, will significantly alter DOM composition and potentially their biogeochemical function in surface waters on the Tibetan Plateau.

Sunlight irradiation promotes both the chemodiversity of terrestrial DOM and the biodiversity of bacterial community in a subalpine lake.

Alpine lake habitats are evolving into subalpine lakes under the scenario of climate change, where the vegetation are promoted due to increasing temperature and precipitation. The abundant terrestrial dissolved organic matter (TDOM) leached from watershed soil into subalpine lakes would undergo strong photochemical reaction due to the high altitude, with the potential to alter DOM composition and affect the bacterial communities. To reveal the transformation of TDOM by both photochemical and microbial processes in a typical subalpine lake, Lake Tiancai (located 200 m below the tree line) was chosen. TDOM was extracted from the surrounding soil of Lake Tiancai and then subjected to the photo/micro-processing for 107 days. The transformation of TDOM was analyzed by Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and fluorescence spectroscopy, and the shift of bacterial communities was analyzed using 16s rRNA gene sequencing technology. Dissolved organic carbon and light-absorbing components (a350) decay accounted for approximately 40% and 80% of the original, respectively, in the sunlight process, but both less than 20% in the microbial process for 107 days. The photochemical process promoted the chemodiversity as there were ∼7000 molecules after sunlight irradiation, compared to ∼3000 molecules in the original TDOM. Light promoted the production of highly unsaturated molecules and aliphatics, which were significantly associated with Bacteroidota, suggesting that light may influence bacterial communities by regulating the DOM molecules. Carboxylic-rich alicyclic molecules were generated in both photochemical and biological processes, suggesting TDOM was converted to a stable pool over time. Our finding on the transformation of terrestrial DOM and the alternation of bacterial community under the simultaneously photochemical and microbial processes will help to reveal the response of the carbon cycle and lake system structure to climate change for high-altitude lakes.

Quasi-TPPs/Fano resonance systems based on an MDM waveguide structure and its sensing application.

In this paper, quasi-Tamm plasmon polaritons (TPPs)/Fano resonance systems based on metal-dielectric-metal (MDM) waveguides are proposed. TPPs are surface electromagnetic modes formed at the interface between a metal and a one-dimensional dielectric photonic crystal (PhC). A metal plasmonic Bragg reflector (PBR) in a MDM waveguide is equivalent to a dielectric PhC, which is realized by periodic MDM waveguide width modulation and leads to the photonic bandgap. By introducing a thin Ag baffle and a PBR in MDM waveguide core, the quasi-TPPs are excited at the interface between the Ag baffle and the PBR, when the phase-matching condition is met. The proposed structure can be fabricated with focused ion beam or electron beam direct-writing lithography, avoiding complex fabrication procedures of manufacturing dielectric PhC by filling the MDM waveguide core with different dielectric materials. Furthermore, an MDM waveguide side-coupled resonator system is constructed to generate Fano resonance by placing a PBR on the side of the MDM waveguide and an Ag baffle in the waveguide core. The Fano resonance originates from the interference between a broad continuum state provided by the Ag baffle and a discrete state provided by quasi-TPPs. The sensing performance of the Fano resonance system is investigated. In this design, the open PBR structure replaces the traditional closed resonant cavity, which makes it more convenient to contact with analytes. The numerical simulations demonstrate that a high sensitivity of 1500 nm/RIU and figure of merit value of 4.08×105 are achieved.

Terpenoids with Cytotoxic Activity from Roots of Ardisia crispa.

Three new terpenoids, ardisiacrispins G-I (1, 4 and 8), and eight known compounds, cyclamiretin A (2), psychotrianoside G (3), 3-hydroxy-ß-damascone (5), megastigmane (6), corchoionol C (7), zingiberoside B (9), angelicoidenol (10), trans-linalool-3,6-oxide-ß-D-glucopyranoside (11) were isolated from the roots of Ardisia crispa. The chemical structures of all isolated compounds were elucidated by extensive spectroscopic analyses, such as HR-ESI-MS, 1D and 2D NMR spectra. Ardisiacrispin G (1) represents the oleanolic-type scaffold featuring a rare 15,16- epoxy system. All compounds were evaluated for the cytotoxicity against two cancer cell lines (U87 MG and HepG2) in vitro. Compounds 1, 8 and 9 exhibited moderate cytotoxic activity with IC50 values ranging from 7.6±1.1 to 28.8±3.2 µM.

New Monoterpenoid Indole Hybrids from Gelsemium elegans with Anti-Inflammatory and Osteoclast Inhibitory Activities.

Gelsegansymines A (1) and B (2), two new indole alkaloids along with six known analogues (3-8) were isolated from the aerial parts of Gelsemium elegans. Their structures were elucidated by means of spectroscopic techniques. Structurally, compounds 1 and 2 possessed the rare cage-like gelsedine skeleton hybrid with bicyclic monoterpenoid. The anti-inflammatory activities of isolated compounds (1-3) were tested on LPS induced RAW264.7 cells. Under the treated concentration without toxicity for cells, the cytokines levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were evaluated by Griess method and enzyme-linked immunosorbent assay (ELISA). The results showed that compounds 1-3 exhibited anti-inflammatory activities with dose-dependent manner range from 12.5 to 50 µmol/L. Furthermore, the inhibitory activities of compounds 1 and 2 on receptor activator of NF-κB ligand (RANKL) induced osteoclast formation were tested in vitro. Compounds 1 and 2 at 5 µmol/L exhibited the significant inhibitory effect on the osteoclastogenesis induced by RANKL. This work reported the anti-inflammatory and osteoclast inhibitory activities of new monoterpenoid indole hybrids, which may inspire the further light on the related traditional application research of G. elegans.

Unraveling the Role of Anthropogenic and Natural Drivers in Shaping the Molecular Composition and Biolability of Dissolved Organic Matter in Non-pristine Lakes.

Lakes receive and actively process terrestrial dissolved organic matter (DOM) and play an important role in the global carbon cycle. Urbanization results in elevated inputs of nonpoint-source DOM to headwater streams. Retention of water in lakes allows time for alteration and transformation of the chemical composition of DOM by microbes and UV radiation. Yet, it remains unclear how anthropogenic and natural drivers impact the composition and biolability of DOM in non-pristine lakes. We used optical spectroscopy, Fourier transform ion cyclotron mass spectrometry, stable isotopic measurements, and laboratory bioincubations to investigate the chemical composition and biolability of DOM across two large data sets of lakes associated with a large gradient of urbanization in lowland Eastern China, encompassing a total of 99 lakes. We found that increased urban land use, gross domestic products, and population density in the catchment were associated with an elevated trophic level index, higher chlorophyll-a, higher bacterial abundance, and a higher amount of organic carbon with proportionally higher contribution of aliphatic and peptide-like DOM fractions, which can be highly biolabile. Catchment areas, water depth, lake area: catchment area, gross primary productivity, δ18O-H2O, and bacterial abundance, however, had comparatively little linkage with DOM composition and biolability. Urban land use is currently intensifying in many developing countries, and our results anticipate an increase in the level of biolabile aliphatic DOM from nonpoint sources and accelerated carbon cycling in lake ecosystems in such regions.

Changes in Water Chemistry Associated with Rainstorm Events Increase Carbon Emissions from the Inflowing River Mouth of a Major Drinking Water Reservoir.

Large reservoirs are hotspots for carbon emissions, and the continued input and decomposition of terrestrial dissolved organic matter (DOM) from upstream catchments is an important source of carbon emissions. Rainstorm events can cause a surge in DOM input; however, periodic sampling often fails to fully capture the impact of these discrete rainstorm events on carbon emissions. We conducted a set of frequent observations prior to and following a rainstorm event in a major reservoir Lake Qiandao (China; 580 km2) from June to July 2021 to investigate how rainstorms alter water chemistry and CO2 and CH4 emissions. We found that the mean CO2 efflux (FCO2) (13.2 ± 9.3 mmol m-2 d-1) and CH4 efflux (FCH4) (0.12 ± 0.02 mmol m-2 d-1) in the postrainstorm campaign were significantly higher than those in the prerainstorm campaign (-3.8 ± 3.0 and +0.06 ± 0.02 mmol m-2 d-1, respectively). FCO2 and FCH4 increased with increasing nitrogen and phosphorus levels, elevated DOM absorption (a350), specific UV absorbance SUVA254, and terrestrial humic-like fluorescence. Furthermore, FCO2 and FCH4 decreased with increasing chlorophyll-a (Chl-a), dissolved oxygen (DO), and pH. A five-day laboratory anoxic bioincubation experiment further revealed a depletion of terrestrial-DOM concurrent with increased CO2 and CH4 production. We conclude that rainstorms boost the emission of CO2 and CH4 fueled by the surge and decomposition of fresh terrestrially derived biolabile DOM in this and likely many other reservoir's major inflowing river mouths.

High-resolution temporal detection of cyanobacterial blooms in a deep and oligotrophic lake by high-frequency buoy data.

Cyanobacterial blooms are increasing in magnitude, frequency, and duration worldwide. However, our knowledge of cyanobacterial blooms dynamics and driving mechanisms is still limited due to their high spatiotemporal variability. To determine the potential driving mechanisms of cyanobacterial blooms in oligotrophic lakes, we collected a high-frequency depth profile of chlorophyll fluorescence (ChlF) and synchronous water quality, hydrometeorological data in early spring 2016 in oligotrophic Lake Qiandaohu. The vertical distribution of ChlF exhibited two patterns, "aggregated" and "discrete", using Morisita's index, and the aggregated ChlF presented subsurface chlorophyll maxima during the thermal stratification period. The ChlF concentration was positively correlated with water temperature and negatively correlated with turbidity. Significantly linear relationships were observed between ChlF vertical structure parameters (e.g., Morisita's index, subsurface chlorophyll maxima depth and thickness) and thermal stratification parameters (e.g., mixing layer depth and relative water column stability). After rainstorm floods, the ChlF pattern suddenly change from "aggregated" to "discrete" and a ChlF concentration <1 µg/L was observed for 7-11 days with a significant increase in the mixing depth layer and turbidity. The results suggest that cyanobacterial blooms are robustly associated with thermal stratification and rainstorm floods in the deep and oligotrophic lake. Thermal stratification boosts surface phytoplankton accumulation by increasing water temperature, enhancing light availability and restricting phytoplankton vertical distribution. Rainstorm floods interrupt the accumulation by disrupting thermal stratification and decreasing the available light. Furthermore, wind speed and air temperature both regulate the phytoplankton dynamics by affecting thermal stratification. Our research quantifies the cyanobacterial bloom dynamics and their relationship between environmental factors, improving our knowledge of the driving mechanisms of cyanobacterial bloom for the protection of drinking water safety and aquatic organism health in lakes.

RefineNet-based 2D and 3D automatic segmentations for clinical target volume and organs at risks for patients with cervical cancer in postoperative radiotherapy.

PURPOSE: An accurate and reliable target volume delineation is critical for the safe and successful radiotherapy. The purpose of this study is to develop new 2D and 3D automatic segmentation models based on RefineNet for clinical target volume (CTV) and organs at risk (OARs) for postoperative cervical cancer based on computed tomography (CT) images. METHODS: A 2D RefineNet and 3D RefineNetPlus3D were adapted and built to automatically segment CTVs and OARs on a total of 44 222 CT slices of 313 patients with stage I-III cervical cancer. Fully convolutional networks (FCNs), U-Net, context encoder network (CE-Net), UNet3D, and ResUNet3D were also trained and tested with randomly divided training and validation sets, respectively. The performances of these automatic segmentation models were evaluated by Dice similarity coefficient (DSC), Jaccard similarity coefficient, and average symmetric surface distance when comparing them with manual segmentations with the test data. RESULTS: The DSC for RefineNet, FCN, U-Net, CE-Net, UNet3D, ResUNet3D, and RefineNet3D were 0.82, 0.80, 0.82, 0.81, 0.80, 0.81, and 0.82 with a mean contouring time of 3.2, 3.4, 8.2, 3.9, 9.8, 11.4, and 6.4 s, respectively. The generated RefineNetPlus3D demonstrated a good performance in the automatic segmentation of bladder, small intestine, rectum, right and left femoral heads with a DSC of 0.97, 0.95, 091, 0.98, and 0.98, respectively, with a mean computation time of 6.6 s. CONCLUSIONS: The newly adapted RefineNet and developed RefineNetPlus3D were promising automatic segmentation models with accurate and clinically acceptable CTV and OARs for cervical cancer patients in postoperative radiotherapy.

A new ent-kaurane diterpenoid from the pericarps of Datura metel.

A new ent-kaurane diterpenoid, named kaurane daturoside A (1), was isolated from the 70%-EtOH extract of dried pericarps of Datura metel L., along with six known terpenoids, 16α,17-dihydroxy-ent-kauran-19-diglycoside (2), cyclosieversioside F (3), astragaloside II (4), ginsenoside Rg1 (5), astrojanoside A (6), celerioside E (7). The isolated structures were elucidated by means of spectroscopic analyses, and the compounds 2, 3, 7 were separated from Solanaceae for the first time. Meanwhile, among isolates, compounds 2 and 5 exhibited anti-inflammatory activities against LPS-activated RAW264.7 cells (IC50<11.00 µM).