Carneusones A-F, Benzophenone Derivatives from Sponge-Derived Fungus Aspergillus carneus GXIMD00543.

Six benzophenone derivatives, carneusones A-F (1-6), along with seven known compounds (7-13) were isolated from a strain of sponge-derived marine fungus Aspergillus carneus GXIMD00543. Their chemical structures were elucidated by detailed spectroscopic data and quantum chemical calculations. Compounds 5, 6, and 8 exhibited moderate anti-inflammatory activity on NO secretion using lipopolysaccharide (LPS)-induced RAW 264.7 cells with EC50 values of 34.6 ± 0.9, 20.2 ± 1.8, and 26.8 ± 1.7 µM, while 11 showed potent effect with an EC50 value of 2.9 ± 0.1 µM.

Secofumitremorgins C and D, a pair of atropisomers from saltern-derived fungus Aspergillus fumigatus GXIMD00544.

A pair of atropisomers secofumitremorgins C (1a) and D (1b), together with fifteen known alkaloids (2-16), were isolated from a saltern-derived fungus Aspergillus fumigatus GXIMD00544. The structures of atropisomers 1a and 1b were elucidated by the detailed spectroscopic data, chemical reaction and quantum chemical calculations. Compounds 1 and 8 displayed antifungal spore germination effects against plant pathogenic fungus associated with sugarcane Fusarium sp. with inhibitory rates of 53% and 77% at the concentration of 100 µM, repectively. Atropisomers 1 also exhibited antifouling potential against Balanus amphitrite larval settlement with an inhibitory rate of 96% at the concentration of 100 µM.

Diagnostic value of triglyceride and cystatin C ratio in diabetic kidney disease: a retrospective and prospective cohort study based on renal biopsy.

BACKGROUND: Currently, there is a lack of clinical indicators that can accurately distinguish diabetic kidney disease (DKD) from non-diabetic kidney disease (NDKD) in type 2 diabetes. The purpose of this study was to investigate the diagnostic value of triglyceride and cystatin C (TG/ Cys-C) ratio in DKD. Nowadays, there are few studies on the differential diagnosis of TG/ Cys-C ratio between DKD and NDKD. METHODS: The clinical data of patients with type 2 diabetes complicated with proteinuria who underwent renal biopsy from January 2013 to September 2019 in 2 hospitals in Xuzhou were retrospectively collected. According to the pathological classification of kidney, 25 patients in group DKD and 34 patients in non-diabetic kidney disease (NDKD) group were divided into two groups. The admission information and blood biochemical indexes of all patients with renal biopsy were collected, and the TG / Cys-C ratio was calculated. Logistic regression analysis was used to analyze the related factors of DKD in patients with type 2 diabetes and proteinuria. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of TG/Cys-C ratio for DKD in patients with type 2 diabetes and proteinuria. Another 37 patients with type 2 diabetes complicated by proteinuria who were treated in the Department of Nephrology, four hospitals in Xuzhou from October 2019 to October 2021 were selected as the research objects. The TG/Cys-C value cut-off value selected in the retrospective study was selected as the boundary point and divided into two groups according to the values of greater than or equal to the tangent point and less than the tangential point. Serum triglyceride and cystatin C levels were measured and TG / Cys-C ratio was calculated. All patients underwent ultrasound-guided fine-needle renal biopsy. The positive rates of DKD diagnosis in the two groups were compared to verify the predictive value of TG / Cys-C ratio in the diagnosis of DKD. RESULTS: Retrospective study showed that compared with group NDKD, the DKD group had higher systolic blood pressure, higher cystatin C and creatinine, more diabetic retinopathy, longer duration of diabetes, lower hemoglobin concentration, lower glomerular filtration rate, lower cholesterol, lower triglyceride and lower TG/ Cys-C ratio (P < 0.05).Multivariate Logistic regression analysis showed that TG/Cys-C ratio (OR = 0.429, P = 0.009) was a protective factor for DKD in patients with type 2 diabetes and proteinuria. Diabetic retinopathy (OR = 7.054, P = 0.021) and systolic blood pressure (OR = 1.041, P = 0.047) were independent risk factors for DKD in patients with type 2 diabetes complicated with proteinuria. ROC curve showed that the area under the curve predicted by TG/Cys-C ratio for the diagnosis of DKD was 0.816, the sensitivity was 84%, and the specificity was 67.6%. The tangent value of TG / Cys-C ratio is 2.43. Prospective studies showed that in 37 patients with type 2 diabetes and proteinuria, 29 patients had a TG/Cys-C ratio of less than 2.43. The TG/Cys-C ratio of 8 patients was more than 2.43. Ultrasound guided fine needle aspiration biopsy revealed that 22 of the 29 patients had pathological diagnosis of DKD, sensitivity 91.67%, specificity 46.15%, positive predictive value 75.80%, and negative predictive value 75%. CONCLUSION: In type 2 diabetic patients with proteinuria, the ratio of TG/Cys-C has certain predictive value for the diagnosis of DKD.

A novel FoxM1-PSMB4 axis contributes to proliferation and progression of cervical cancer.

The abnormally high activity of the proteasome system is closely related to the occurrence and development of various tumors. PSMB4 is a non-catalytic subunit for the proteasome assembly. Although the reports from genetic screening have demonstrated it's a driver gene for cell growth in several types of solid tumor, its expression pattern and regulatory mechanisms in malignant diseases are still elusive. Here, we found that PSMB4 is overexpressed in cervical cancer tissues. And knockdown of PSMB4 significantly inhibited cervical cancer cell proliferation. The mechanistic study revealed that FoxM1, a master regulator of cell division, binds directly to the promoter region of PSMB4 and regulates the PSMB4 expression in the mRNA level. In addition, the data analysis from TCGA showed a positive correlation between FxoM1 and PSMB4 in cervical cancer. Furthermore, the loss of functional and rescue experiments confirmed that PSMB4 is required for FoxM1-driven cervical cancer cell proliferation. Collectively, our study explains the phenomenon of dysregulated expression of PSMB4 in cervical cancer tissues and verifies its driver effect on cancer cell proliferation. More importantly, it highlights a FoxM1-PSMB4 axis could be a potential target for the treatment of cervical cancer.

Influence of Soil Properties and Aging on Antimony Toxicity for Barley Root Elongation.

The study explored the Sb toxicity by investigating the impacts of 10% and 20% effective concentrations (EC10 and EC20, respectively) of Sb on the inhibition of barley root elongation in 21 Chinese soils with a wide range of physicochemical properties after aging for 3 months. The results demonstrated that various soil properties profoundly influenced the Sb toxicity which was ranged from 201-2506 mg Sb kg-1 to 323-2973 mg Sb kg-1 under EC10 and EC20, respectively. Soil sand fraction was a significant soil factor responsible for elevating Sb bioavailability. The bioavailable Sb concentration accounted for 2.08%-11.94% of total Sb content in all 21 soil samples and the decreased Sb bioavailability in this study was attributed to soil properties including soil clay fraction, amorphous and crystalloid iron, and oxides of manganese and aluminum. The findings would contribute in developing Sb toxicity threshold for establishing standard for Sb regulation in crop production.

DYRK1A inhibition suppresses STAT3/EGFR/Met signalling and sensitizes EGFR wild-type NSCLC cells to AZD9291.

DYRK1A is considered a potential cancer therapeutic target, but the role of DYRK1A in NSCLC oncogenesis and treatment requires further investigation. In our study, high DYRK1A expression was observed in tumour samples from patients with lung cancer compared with normal lung tissues, and the high levels of DYRK1A were related to a reduced survival time in patients with lung cancer. Meanwhile, the DYRK1A inhibitor harmine could suppress the proliferation of NSCLC cells compared to that of the control. As DYRK1A suppression might be effective in treating NSCLC, we next explored the possible specific molecular mechanisms that were involved. We showed that DYRK1A suppression by siRNA could suppress the levels of EGFR and Met in NSCLC cells. Furthermore, DYRK1A siRNA could inhibit the expression and nuclear translocation of STAT3. Meanwhile, harmine could also regulate the STAT3/EGFR/Met signalling pathway in human NSCLC cells. AZD9291 is effective to treat NSCLC patients with EGFR-sensitivity mutation and T790 M resistance mutation, but the clinical efficacy in patients with wild-type EGFR remains modest. We showed that DYRK1A repression could enhance the anti-cancer effect of AZD9291 by inducing apoptosis and suppressing cell proliferation in EGFR wild-type NSCLC cells. In addition, harmine could enhance the anti-NSCLC activity of AZD9291 by modulating STAT3 pathway. Finally, harmine could enhance the anti-cancer activity of AZD9291 in primary NSCLC cells. Collectively, targeting DYRK1A might be an attractive target for AZD9291 sensitization in EGFR wild-type NSCLC patients.

Suppression of LSD1 enhances the cytotoxic and apoptotic effects of regorafenib in hepatocellular carcinoma cells.

Regorafenib has been approved to treat patients who have HCC progression after sorafenib failure, however, regorafenib also faces the risk of drug resistance and subsequent progression of HCC patients. As LSD1 inhibitors can alleviate acquired resistance to sorafenib, in this context, we are interested to investigate the role of LSD1 in regorafenib treatment. Firstly, over-expressed LSD1 was observed in HCC patients and predicted poor prognosis. However, regorafenib failed to suppress the expression of LSD1 in HCC cells. Thus, we hypothesized that LSD1 inhibition could enhance the anti-HCC activity of regorafenib. As expected, LSD1 knockdown could enhance anti-proliferation effect of regorafenib in HCC cells. LSD1 inhibitor SP2509 could enhance the cytotoxic and apoptotic effects of regorafenib in HCC cells. In addition, clinically used LSD1 inhibitor tranylcypromine also enhanced anti-HCC effect of regorafenib. Furthermore, LSD1 suppressed by SP2590 or tranylcypromine could alleviate the activated p-AKT (ser473) induced by regorafenib in HCC cells. Thus, inhibiting LSD1 might be an attractive target for regorafenib sensitization and clinical HCC therapy, our findings could help to elucidate more effective therapeutic options for HCC patients.

Discerning the Sources of Silver Nanoparticle in a Terrestrial Food Chain by Stable Isotope Tracer Technique.

The increasing use of silver-containing nanoparticles (NPs) in commercial products has led to NP accumulation in the environment and potentially in food webs. Identifying the uptake pathways of different chemical species of NPs, such as Ag2S-NP and metallic AgNPs, into plants is important to understanding their entry into food chains. In this study, soybean Glycine max L. was hydroponically exposed to Ag2S-NPs via their roots (10-50 mg L-1) and stable-isotope-enriched 109AgNPs via their leaves [7.9 µg (g fresh weight)-1]. Less than 29% of Ag in treated leaves (in direct contact with 109AgNP) was accumulated from root uptake of Ag2S-NPs, whereas almost all of the Ag in soybean roots and untreated leaves sourced from Ag2S-NPs. Therefore, Ag2S-NPs are phytoavailable and translocate upward. During trophic transfer the Ag isotope signature was preserved, indicating that accumulated Ag in snails most likely originated from Ag2S-NPs. On average, 78% of the Ag in the untreated leaves was assimilated by snails, reinforcing the considerable trophic availability of Ag2S-NPs via root uptake. By highlighting the importance of root uptake of Ag2S-NPs in plant uptake and trophic transfer to herbivores, our study advances current understanding of the biogeochemical fate of Ag-containing NPs in the terrestrial environment.

Effects of Duloxetine on the Toll-Like Receptor 4 Signaling Pathway in Spinal Dorsal Horn in a Rat Model of Diabetic Neuropathic Pain.

Objective: Although duloxetine has been approved for clinical therapy for diabetic peripheral neuropathic pain, the exact mechanism underlying the anti-allodynic effects in rat models of diabetes mellitus remains obscure. We attempted to identify whether duloxetine exerts anti-allodynic effects via inhibition of the TLR4-Myd88-dependent pathway in diabetic neuropathic pain (DNP) rats. Methods: An animal model of type 1 diabetic neuropathic pain was induced by intraperitoneal streptozotocin in 108 rats randomized into four groups: control, DNP, solvent control + DNP, and DNP + duloxetine. The DNP model establishment was validated, providing the MWT and TWL measurements were less than 80% of the baseline value on d14 after streptozotocin administration. The expressions of TLR4, Myd88, and NF-κB in the spinal dorsal horn were determined 21 days after streptozotocin injection by immunohistochemical assay and Western blot. Results: The results revealed that MWT and TWL in DNP, SC + DNP, and DLX + DNP groups were significantly decreased 14 days after STZ administration vs control (P < 0.05), while the pain thresholds in the DLX + DNP group were partially reversed. The expressions of TLR4, Myd88, and NF-κB in groups C, DNP, and SC + DNP were significantly increased, whereas duloxetine administration significantly downregulated the expressions of TLR4, Myd88, and NF-κB (P < 0.05). Conclusions: Our findings indicated that duloxetine mitigated mechanical and thermal withdrawal thresholds in STZ-injected rats and rescued the overexpression of the TLR4-Myd88-dependent pathway in the spinal dorsal horn in these rats. Whether these changes directly contributed to the reduction of thermal and mechanical withdrawal behavior needs to be further explored.

Sorption kinetics, isotherms, and mechanism of aniline aerofloat to agricultural soils with various physicochemical properties.

Aniline aerofloat (AAF), a high-toxic organic flotation reagent, is widely used in mineral processing industry. However, little information on its environmental fate is available. AAF sorption to four types of agricultural soils at low concentrations (1-10 mg/L) was investigated using batch experiments. AAF sorption kinetics involved both boundary layer diffusion and intraparticle diffusion, following pseudo-second-order kinetics with equilibrium time within 120 min. Both Langmuir and Freundlich models fitted well the AAF sorption with the former better. Sorption of AAF to soils was a spontaneous and favorable physical sorption that was controlled by ion bridge effect and hydrophobic interaction that was related to van der Waals force and π-π coordination based on FTIR analyses. AAF sorption was remarkably affected by soil constituents, positively correlating with the contents of organic matter and clay. The relatively higher logKoc values (3.53-4.66) of AAF at environmental concentrations (1-5 mg/L) imply that soils are serving as a sink of AAF from beneficiation wastewater, posing great potential risks to environment and human health.

The suppression of innate immune response by human rhinovirus C.

Rhinovirus C (RV-C), a newly identified group of human rhinoviruses (RVs), is associated with exacerbation of severe asthma. The type I interferon (IFN) response induced by this virus and the mechanisms of evasion of IFN-mediated innate immunity for RV-C remain unclear. In this study, we constructed a full-length cDNA clone of RV-C (LZ651) from a clinical sample. IFN-ß mRNA and protein levels were not elevated in differentiated Human bronchial epithelial (HBE) cells at the air-liquid interface infected with RV-C, except in the early stage of infection. The ability to attenuate IFN-ß activation was ascribed to 3Cpro of RV-C, and the 40-His site of 3Cpro played an important role. Furthermore, RIG-I was degraded by 3Cpro in a caspase-dependent manner and 3Cpro cleaved MAVS at 148 Q/A, which inhibited IFN signaling. Taken together, our results demonstrate the mechanism by which RV-C circumvents the production of type I IFN in infected cells.

Effect of Organic Matter on Sorption of Zn on Soil: Elucidation by Wien Effect Measurements and EXAFS Spectroscopy.

Soil organic matter (SOM) is the major factor affecting sequestration of heavy metals in soil. The mean free binding energy and the mean free adsorption energy and speciation of Zn in soil, as affected by SOM, were determined by employing Wien effect measurements. The presence of SOM markedly decreased the Zn binding energy in soils in the following order: Top (5.86 kJ mol(-1)) < Bottom (8.66 kJ mol(-1)) < Top OM-free (9.44 kJ mol(-1)) ≈ Bottom OM-free (9.50 kJ mol(-1)). The SOM also significantly decreased the adsorption energy of Zn on black soil particles by reducing nonspecific adsorption of Zn on their surfaces. The speciation of Zn in soils was elucidated by extended X-ray absorption fine structure spectroscopy and microfocus X-ray fluorescence. The results obtained by linear combination fitting of EXAFS spectra revealed that the main forms of Zn in soil were outer-sphere Zn, Zn-illite, Zn-kaolinite, and HA-Zn. As the SOM content increased, the proportion of HA-Zn among the total immobilized Zn increased, and the proportion of nonspecific adsorbed Zn decreased. The present results implied that SOM is an important controlling factor for the environmental behavior of Zn in soils.

Relationship Between the Serum Total Bilirubin and Inflammation in Patients With Psoriasis Vulgaris.

BACKGROUND: Psoriasis is a chronic and recurrent inflammatory skin disease. Previous studies have shown that bilirubin has anti-inflammation and antioxidant effects. However, the various roles of bilirubin in psoriasis patients are still unclear. OBJECTIVE: To investigate the serum total bilirubin (TB) level in the individuals with psoriasis vulgaris and further evaluate the relationship between serum TB concentration and C-reactive protein (CRP) to clarify the effect of bilirubin on inflammation. METHODS: A total of 214 patients with psoriasis vulgaris and 165 age- and gender-matched healthy control subjects were recruited. The peripheral leukocyte count (white blood cell, WBC) and differential, serum biochemical and immunologic indexes including serum TB, immunoglobulin (Ig) G, IgA, IgM, complement C3 and C4 , as well as serum CRP concentrations were measured. RESULTS: Results showed that the serum TB level decreased significantly and peripheral WBC, neutrophil, and serum CRP concentrations increased significantly in patients with psoriasis vulgaris. Meanwhile, the serum CRP was negatively correlated with serum TB levels but positively correlated with peripheral WBC and the Psoriasis Area and Severity Index (PASI). Logistic regression analysis showed that the serum TB was a protective factor for psoriasis vulgaris. CONCLUSION: The present study suggests that lower serum TB is associated with the enhancement of the inflammatory response in psoriasis vulgaris. Therefore, lower serum TB has a prognostic significance for worsening psoriasis vulgaris. Bilirubin may play a crucial role in inflammation by contributing to the inhibition of the inflammatory response.

Surface Electrical Potentials of Root Cell Plasma Membranes: Implications for Ion Interactions, Rhizotoxicity, and Uptake.

Many crop plants are exposed to heavy metals and other metals that may intoxicate the crop plants themselves or consumers of the plants. The rhizotoxicity of heavy metals is influenced strongly by the root cell plasma membrane (PM) surface's electrical potential (ψ0). The usually negative ψ0 is created by negatively charged constituents of the PM. Cations in the rooting medium are attracted to the PM surface and anions are repelled. Addition of ameliorating cations (e.g., Ca2+ and Mg2+) to the rooting medium reduces the effectiveness of cationic toxicants (e.g., Cu2+ and Pb2+) and increases the effectiveness of anionic toxicants (e.g., SeO42- and H2AsO4-). Root growth responses to ions are better correlated with ion activities at PM surfaces ({IZ}0) than with activities in the bulk-phase medium ({IZ}b) (IZ denotes an ion with charge Z). Therefore, electrostatic effects play a role in heavy metal toxicity that may exceed the role of site-specific competition between toxicants and ameliorants. Furthermore, ψ0 controls the transport of ions across the PM by influencing both {IZ}0 and the electrical potential difference across the PM from the outer surface to the inner surface (Em,surf). Em,surf is a component of the driving force for ion fluxes across the PM and controls ion-channel voltage gating. Incorporation of {IZ}0 and Em,surf into quantitative models for root metal toxicity and uptake improves risk assessments of toxic metals in the environment. These risk assessments will improve further with future research on the application of electrostatic theory to heavy metal phytotoxicity in natural soils and aquatic environments.

Persistent production of multiple active species with copper doped zinc gallate nanoparticles for light-independent photocatalytic degradation of organic pollutants.

Photocatalysis is considered as an environmentally friendly and sustainable method as it can produce active species to degrade pollutants. However, its applications are hindered by the turbidity of pollutants and the requirements for continuous or repeated in situ irradiation. To avoid the need for continuous in situ irradiation in the photocatalytic process, herein we report the doping of Cu(II) ions into zinc gallate (ZnGa2O4) as traps to capture photo-generated electrons. In this way, long lifetime charge release and separation were effectively achieved for the persistent degradation of organic dyes in wastewater. The Cu(II) doped ZnGa2O4 (ZGC) nanoparticles with a small size about 7.7 nm synthesized via a hydrothermal method exhibited a persistent photocatalytic activity with continuous production of reactive oxygen species for at least 96 h without in situ irradiation due to its unique electronic structure and carrier transport path, and enabled to degrade 82.2 % of rhodamine B in 1 h. Further investigation revealed that the doped Cu(II) ions occupied the octahedral sites of ZGC and highly increased the persistent production and availability of active species for the persistent degradation of organic dyes under pre-illuminated conditions.

Modeling rhizotoxicity and uptake of Zn and Co singly and in binary mixture in wheat in terms of the cell membrane surface electrical potential.

The usually negative, but variable electrical potential (ψ0) at the cell membrane (CM) surface influences the surface activities of free ions and the electrical driving force for the transport of ions across the CM. The rhizotoxic effects and uptake of Zn(2+) and Co(2+) singly and in binary mixture in wheat ( Triticum aestivum L.) at three pH values (4.5, 5.5, or 6.1) were examined in terms of the free ion activities of Zn(2+), Co(2+), and H(+) at the CM surface (these ions are denoted {M(n+)}(0)). Toxicity and uptake of Zn(2+) or Co(2+) singly to roots were better correlated with {M(2+)}(0) than with their bulk-phase activities. Studies of toxicant interactions using the electrostatic approach and a response-multiplication model for toxicant mixtures indicated that {Co(2+)}(0) significantly enhanced the toxicity of {Zn(2+)}(0), but {Zn(2+)}(0) did not significantly affect the toxicity of {Co(2+)}(0). {H(+)}(0) substantially enhanced the toxicity of both metal ions. Taking ψo into account improved the correspondence (denoted r(2)) between observed and predicted uptake of both Zn(2+) and Co(2+), and each inhibited the uptake of the other. Results showed that r(2) increased from 0.776 to 0.936 for Zn uptake and improved from 0.805 to 0.951 for Co uptake. Thus electrostatic models for metal toxicity and uptake proved superior to models incorporating only bulk-phase activities of ions.

Inhibition mechanisms of Zn precipitation on aluminum oxide by glyphosate: a 31P NMR and Zn EXAFS study.

In this research, the effects of glyphosate (GPS) on Zn sorption/precipitation on γ-alumina were investigated using a batch technique, Zn K-edge EXAFS, and (31)P NMR spectroscopy. The EXAFS analysis revealed that, in the absence of glyphosate, Zn adsorbed on the aluminum oxide surface mainly as bidentate mononuclear surface complexes at pH 5.5, whereas Zn-Al layered double hydroxide (LDH) precipitates formed at pH 8.0. In the presence of glyphosate, the EXAFS spectra of Zn sorption samples at pH 5.5 and 8.0 were very similar, both of which demonstrated that Zn did not directly bind to the mineral surface but bonded with the carboxyl group of glyphosate. Formation of γ-alumina-GPS-Zn ternary surface complexes was further suggested by (31)P solid state NMR data which indicated the glyphosate binds to γ-alumina via a phosphonate group, bridging the mineral surface and Zn. Additionally, we showed the sequence of additional glyphosate and Zn can influence the sorption mechanism. At pH 8, Zn-Al LDH precipitates formed if Zn was added first, and no precipitates formed if glyphosate was added first or simultaneously with Zn. In contrast, at pH 5.5, only γ-alumina-GPS-Zn ternary surface complexes formed regardless of whether glyphosate or Zn was added first or both were added simultaneously.

[Diagnostic value of microtubule-associated protein-2 in small cell lung carcinoma: an analysis of 240 biopsy cases].

OBJECTIVE: To investigate the diagnostic value of microtubule-associated protein-2 (MAP-2) in biopsy of small cell lung carcinoma (SCLC). METHODS: Immunohistochemical technique was applied to detect the expression of synaptophysin (Syn), chromogranin A (CgA), CD56, MAP-2 and TTF-1 in 240 cases of SCLC from 2008 to 2011 in this hospital. RESULTS: The positive rate of MAP-2 expression in SCLC was 95.8% (230/240), which was much higher than that of Syn (57.1%, 137/240), CgA (38.8%, 93/240) and CD56 (89.2%, 214/240). The sensitivity and accuracy of MAP-2 (99.1%, 95.4%) expression were also higher than those of Syn (58.3%, 42.5%), CgA (39.9%, 42.5%) and CD56 (91.5%, 87.9%). CONCLUSIONS: MAP-2 is a new neuroendocrine marker with higher sensitivity and accuracy, and thus recommended to be added to the immunohistochemical panel for the diagnosis of SCLC.

A nomogram diagnostic cardiovascular disease in patients with erythrodermic psoriasis in Chinese.

Objective: Patients with erythrodermic psoriasis (EP) are associated with an increased risk of cardiovascular disease (CVD), because of the more severe inflammation in the skin areas. This study aimed to develop a diagnostic model for the risk of CVD in EP patients based on the available features and multidimensional clinical data. Methods: A total of 298 EP patients from Beijing Hospital of Traditional Chinese Medicine were retrospectively included in this study from May 5th, 2008, to March 3rd, 2022. Of them, 213 patients were selected as the development set by random sampling, and clinical parameters were analyzed by univariate and backward stepwise regression. Whereas the remaining 85 patients were randomly selected as the validation set. The model performance was later assessed in terms of discrimination, calibration, and clinical usefulness. Results: In the development set, the CVD rate was 9%, which was independently correlated with age, glycated albumin (GA>17%), smoking, albumin (ALB<40 g/L), and lipoprotein(a) (Lp(a)>300 mg/L). The area under the ROC curve (AUC) value was 0.83 (95% confidence interval CI, 0.73,0.93). For the validation set of EP patients, the AUC value was 0.85 (95%CI, 0.76,0.94). According to decision curve analysis, our model exhibited favorable clinical applicability. Conclusion: EP patients with age, GA>17%, smoking, ALB<40 g/L, and Lp(a)>300 mg/L are associated with a higher risk of CVD. The nomogram model performs well in predicting the probability of CVD in EP patients, which may help improve perioperative strategies and good treatment outcomes.

Construction and optimization of ecological security network in the Shule River Basin, China.

Construction and optimization of ecological security network is an efficient way to ensure regional ecological security and achieve sustainable development. Based on the morphological spatial pattern analysis method, circuit theory and other methods, we constructed the ecological security network of the Shule River Basin. The PLUS model was used to predict the land use change in 2030, with the aim to explore the current ecological protection direction and propose reasonable optimization strategies. The results showed that there were 20 ecological sources in the Shule River Basin, with a total area of 15774.08 km2, accounting for 12.3% of the total area of study area. The ecological sources were mainly distributed in the south part of the study area. A total of 37 potential ecological corridors were extracted, including 22 important ecological corridors, which showed the overall spatial characteristics of vertical distribution. Meanwhile, 19 ecological pinch points and 17 ecological obstacle points were identified. We predicted that the expansion of construction land would continue to squeeze the ecological space by 2030, and identified 6 warning areas of ecological protection space to effectively avoid conflicts between ecological protection and economic development. After optimization, 14 new ecological sources and 17 stepping stones were added, and the circuitry, ratio of line to node and connectivity index of the ecological security network increased by 18.3%, 15.5%, and 8.2% respectively compared with those before optimization, forming a structurally stable ecological security network. The results could provide scientific basis for ecological security network optimization and ecological restoration.