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Abstract The lack of new drugs that are effective against antibiotic-resistant bacteria has caused increasing concern in global public health. Based on this study, we report development of a modified antimicrobial drug through structure-based drug design (SBDD) and modular synthesis. The optimal modified compound, F8, was identified, which demonstrated in vitro and in vivo broad-spectrum antibacterial activity against drug-resistant bacteria and effectively mitigated the development of resistance. F8 exhibits significant bactericidal activity against bacteria resistant to antibiotics such as methicillin, polymyxin B, florfenicol (FLO), doxycycline, ampicillin and sulfamethoxazole. In a mouse model of drug-resistant bacteremia, F8 was found to increase survival and significantly reduce bacterial load in infected mice. Multi-omics analysis (transcriptomics, proteomics, and metabolomics) have indicated that ornithine carbamoyl transferase (arcB) is a antimicrobial target of F8. Further molecular docking, Isothermal Titration Calorimetry (ITC), and Differential Scanning Fluorimetry (DSF) studies verified arcB as a effective target for F8. Finally, mechanistic studies suggest that F8 competitively binds to arcB, disrupting the bacterial cell membrane and inducing a certain degree of oxidative damage. Here, we report F8 as a promising candidate drug for the development of antibiotic formulations to combat antibiotic-resistant bacteria-associated infections.

Cannabidiol: (CBD) is a non-psychoactive natural active ingredient from cannabis plant, which has many pharmacological effects, including neuroprotection, antiemetic, anti-inflammatory and anti-skeletal muscle injury. However, the mechanism of its effect on skeletal muscle injury still needs further research. In order to seek a scientifically effective way to combat skeletal muscle injury during exercise, we used healthy SD rats to establish an exercise-induced skeletal muscle injury model by treadmill training, and systematically investigated the effects and mechanisms of CBD, a natural compound in the traditional Chinese medicine Cannabis sativa L., on combating skeletal muscle injury during exercise. CBD effectively improved the fracture of skeletal muscle tissue and reduced the degree of inflammatory cell infiltration. Biochemical indexes such as CK, T, Cor, LDH, SOD, MDA, and GSH-Px in serum of rats returned to normal. Combining transcriptome and network analysis results, CBD may play a protective role in exercise-induced skeletal muscle injury through HIF-1 signaling pathway. The experimental results implied that CBD could down-regulate the expression of IL-6, NF-κB, TNF-α, Keap1, AMPKα2, HIF-1α, BNIP3 and NIX, and raised the protein expression of IL-10, Nrf2 and HO-1. These results indicate that the protective effect of CBD on exercise-induced skeletal muscle injury may be related to the inhibition of oxidative stress and inflammation, thus inhibiting skeletal muscle injury through AMPKα2/HIF-1α/BNIP3/NIX signal pathways.

Abstract Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a common airborne wheat disease. The frequent occurrence at a large scale in China has caused significant yield losses and poses a considerable threat to food security. To effectively manage and forecast the disease, a comprehensive understanding of the long-distance migration patterns of Pst is essential. Shaanxi province, situated in close proximity to the northwestern epidemic areas in China, plays a crucial role as a key overwintering region for Pst. However, it remains uncertain whether Pst, after winter reproduction in Shaanxi province, can extend its spread to the primary wheat regions in the North China Plain. In this study, during February and June 2022, a total of 302 Pst samples were collected from Shaanxi province and the North China Plain. Thirteen pairs of simple sequence repeat (SSR) markers were adopted to analyze the population genetic structure. It was observed that both genetic and genotypic diversities exhibited a discernible decline from the Shaanxi to the North China Plain. Moreover, Shaanxi displayed a close genetic relationship with Henan and Shandong, whereas Henan exhibited the most substantial population exchange with Shaanxi. Further analysis revealed that Shaanxi served as the primary inoculum of Pst in the investigated region, and the spread of Pst to Henan and Shandong originated from Shaanxi. As a result, the epidemics in Shandong further led to the prevailing of the disease in Hebei. Our study enhances the understanding of the epidemiological patterns of wheat stripe rust in the springtime prevalent regions of China, and it provides insights for future disease management.

Abstract Background The triglyceride–glucose (TyG) index and high‐sensitivity C‐reactive protein (hsCRP) are the commonly used biomarkers for insulin resistance and systemic inflammation, respectively. We aimed to investigate the combined association of TyG and hsCRP with the major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS). Methods A total of 9421 patients with CCS were included in this study. The primary endpoint was defined as a composite of MACE covering all‐cause death, nonfatal myocardial infarction, and revascularization. Results During the 2‐year follow‐up period, 660 (7.0%) cases of MACE were recorded. Participants were divided equally into three groups according to TyG levels. Compared with the TyG T1 group, the risk of MACE was significantly higher in the TyG T3 group. It is noteworthy that among patients in the highest tertile of TyG, hsCRP >3 mg/L was significantly associated with an increased risk of MACE, whereas the results were not significant in the medium to low TyG groups. When patients were divided into six groups according to hsCRP and TyG, the Cox regression analysis showed that patients in the TyG T3 and hsCRP >3 mg/L group had a significantly higher risk of MACE than those in the TyG T1 and hsCRP ≤3 mg/L group. However, no significant interaction was found between TyG and hsCRP on the risk of MACE. Conclusion Our study suggests that the concurrent assessment of TyG and hsCRP may be valuable in identifying high‐risk populations and guiding management strategies among CCS patients.

ABSTRACT Stripe rust of wheat is caused by the fungal pathogen Puccinia striiformis f. sp. tritici (Pst). Breeding durably resistant wheat varieties by disrupting the susceptibility (S) gene has an important impact on the control of wheat stripe rust. Mingxian169 (MX169) showed strong stripe rust susceptibility to all the races of Pst. However, molecular mechanisms and responsive genes underlying susceptibility of the wheat variety MX169 to Pst have not been elucidated. Here, we utilized next-generation sequencing technology to analyze transcriptomics data of “MX169” and high-resistance wheat “Zhong4” at 24, 48, and 120 h post-inoculation (hpi) with Pst. Comparative transcriptome analysis revealed 3,494, 2,831, and 2,700 differentially expressed genes (DEGs) at different time points. We observed an upregulation of DEGs involved in photosynthesis, flavonoid biosynthesis, pyruvate metabolism, thiamine metabolism, and other biological processes, suggesting their involvement in MX169’s response to Pst. DEGs encoding transcription factors were also identified. Our study suggested the potential susceptibility gene resources in MX169 related to stripe rust response could be valuable for understanding the mechanisms involved in stripe rust susceptibility and for improving wheat resistance to Pst.IMPORTANCEOur study suggests the potential susceptibility gene resources in MX169 related to stripe rust response could be valuable for understanding the mechanisms involved in stripe rust susceptibility and for improving wheat resistance to Pst.

In the pursuit of sustainability and resilience, urban horticulture holds immense promise for cities. This paper delves into the captivating realm of urban horticulture preferences in Iran, unraveling the factors that shape individuals' inclinations. The results highlight the influence of greenhouse design on urban horticulture preferences. Urban dwellers prioritize cultural ecosystem services over regulating and provisioning services when engaging in urban horticulture activities. Anticipated ecosystem services differ among various socio-demographic groups. Different greenhouse elements evoke distinct perceptions of ecosystem services. However, certain greenhouses can improve the overall perception of ecosystem services due to the strong correlations between different types of services.

Abstract Real-world data on effectiveness and safety of a single non-vitamin K antagonist oral anticoagulant in the Chinese population with atrial fibrillation (AF) are limited. This study reports characteristics of patients treated with edoxaban and factors associated with dosing patterns from routine care in China. ETNA-AF-China (NCT04747496) is a multicentre, prospective, observational study enrolling edoxaban-treated patients from four economic regions with a targeted 2-year follow-up. Of the 4930 patients with AF (mean age: 70.2 ± 9.5 years; male, 57.1%), the mean creatinine clearance (CrCl), CHA2DS2-VASc, and HAS-BLED scores were 71.2 mL/min, 2.9, and 1.6. Overall, 6.4% of patients were perceived as frail by investigators. Available label dose reduction criteria (N = 4232) revealed that 3278 (77.5%) patients received recommended doses and 954 (22.5%) non-recommended doses. Northeast (53.0%) and West (43.1%) regions had the highest prescriptions of 60 mg and 30 mg recommended doses, respectively. Non-recommended 30 mg doses were more frequently prescribed in patients with antiplatelet use and history of heart failure than recommended 60 mg. Multivariate analysis identified advanced age as the strongest associated factor with non-recommended doses. Frailty had the strongest association with 30 mg except for age, and history of TIA was the most relevant factor associated with 60 mg. In conclusion, patients in the ETNA-AF-China study were predominantly aged 65 years and older, had mild-to-moderate renal impairment and good label adherence. Advanced age was associated with non-recommended doses, with frailty most common for non-recommended 30 mg and a history of TIA for the non-recommended 60 mg dose.

Sorghum (Sorghum bicolor), the fifth most important cereal crop globally, serves as a staple food, animal feed, and a bioenergy source. Paclobutrazol-Resistance (PRE) genes play a pivotal role in the response to environmental stress, yet the understanding of their involvement in pest resistance remains limited. In the present study, a total of seven SbPRE genes were found within the sorghum BTx623 genome. Subsequently, their genomic location was studied, and they were distributed on four chromosomes. An analysis of cis-acting elements in SbPRE promoters revealed that various elements were associated with hormones and stress responses. Expression pattern analysis showed differentially tissue-specific expression profiles among SbPRE genes. The expression of some SbPRE genes can be induced by abiotic stress and aphid treatments. Furthermore, through phytohormones and transgenic analyses, we demonstrated that SbPRE4 improves sorghum resistance to aphids by accumulating jasmonic acids (JAs) in transgenic Arabidopsis, giving insights into the molecular and biological function of atypical basic helix-loop-helix (bHLH) transcription factors in sorghum pest resistance.

Abstract Background Stress hyperglycemia ratio (SHR), a novel biomarker of stress hyperglycemia, was proved to be a reliable predictor of short‐term adverse outcomes in patients with acute coronary syndromes (ACS). However, its impact on long‐term prognosis remained controversial. Methods A total of 7662 patients with ACS from a large nationwide prospective cohort between January 2015 and May 2019 were included. SHR was calculated by the following formula: SHR = admission glucose (mmol/L)/(1.59 × HbA1c [%]−2.59). The primary end point was a major adverse cardiovascular event (MACE) during follow‐up, a composite of all‐cause death, myocardial infarction, and unplanned revascularization. The second end point was the separate components of the primary end points. Results During a median follow‐up of 2.1 years, 779 MACE events occurred. After multivariable adjustment, ACS patients with the highest SHR tertile were significantly associated with increased long‐term risks of MACE (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.24–1.88), all‐cause death (HR 1.80, 95% CI 1.29–2.51) and unplanned revascularization (HR 1.44, 95% CI 1.09–1.91). Although significant associations between the highest SHR tertile and risks of MACE and all‐cause death were assessed in both diabetic and nondiabetic patients, the patterns of risk were different in these two groups. Conclusion Elevated SHR was independently associated with a higher risk of long‐term outcomes irrespective of diabetic status, suggesting that SHR was a potential biomarker for risk stratification after ACS.

Abstract Background Stress hyperglycemia was positively associated with poor prognosis in individuals with acute myocardial infarction (AMI). However, admission glucose and stress hyperglycemia ratio (SHR) may not be the best indicator of stress hyperglycemia. We performed this study to evaluate the comparative prognostic value of different measures of hyperglycemia (fasting SHR, fasting plasma glucose [FPG], and hemoglobin A1c [HbA1c]) for in-hospital mortality in AMI patients with or without diabetes. Methods In this prospective, nationwide, multicenter China Acute Myocardial Infarction (CAMI) registry, 5,308 AMI patients including 2081 with diabetes and 3227 without diabetes were evaluated. Fasting SHR was calculated using the formula [(first FPG (mmol/l))/(1.59×HbA1c (%)-2.59)]. According to the quartiles of fasting SHR, FPG and HbA1c, diabetic and non-diabetic patients were divided into four groups, respectively. The primary endpoint was in-hospital mortality. Results Overall, 225 (4.2%) patients died during hospitalization. Individuals in quartile 4 had a significantly higher rate of in-hospital mortality compared with those in quartile 1 in diabetic cohort (9.7% vs. 2.0%; adjusted odds ratio [OR] 4.070, 95% CI 2.014–8.228) and nondiabetic cohort (8.8% vs. 2.2%; adjusted OR 2.976, 95% CI 1.695–5.224). Fasting SHR was also correlated with higher in-hospital mortality when treated as a continuous variable in diabetic and nondiabetic patients. Similar results were observed for FPG either as a continuous variable or a categorical variable. In addition, fasting SHR and FPG, rather than HbA1c, had a moderate predictive value for in-hospital mortality in patients with diabetes (areas under the curve [AUC] for fasting SHR: 0.702; FPG: 0.689) and without diabetes (AUC for fasting SHR: 0.690; FPG: 0.693). The AUC for fasting SHR was not significantly different from that of FPG in diabetic and nondiabetic patients. Moreover, adding fasting SHR or FPG to the original model led to a significant improvement in C-statistic regardless of diabetic status. Conclusions This study indicated that, in individuals with AMI, fasting SHR as well as FPG was strongly associated with in-hospital mortality regardless of glucose metabolism status. Fasting SHR and FPG might be considered as a useful marker for risk stratification in this population. Trial registration: ClinicalTrials.gov NCT01874691.

BackgroundPediatric solid tumor, the abnormal proliferation of solid tissues in children resulting in the formation of tumors, represent a prevailing malignant ailment among the younger population. Extensive literature highlights the inseparable association linking oral microbiome and adult tumors, but due to differences in age of onset, characteristics of onset, etc., there are many differences between Pediatric solid tumors and adult tumors, and therefore, studying the relationship between Pediatric solid tumor and the oral microbiota is also essential.MethodsTo unravel the distinct characteristics of the oral microbiota within Pediatric solid tumor patients, 43 saliva samples, encompassing 23 Pediatric solid tumor patients and 20 healthy controls, were diligently procured. A meticulous screening process ensued, and conducted microbial MiSeq sequencing after screening.ResultsWe documented the oral microbiome attributes among pediatric diagnosed with solid tumors (PST), and meanwhile, we observed a significant trend of decreased oral microbiota diversity in the pediatric solid tumor group. There were notable disparities in microbial communities observed between the two groups, 18 genera including Veillonellaceae, Firmicutes unclassified, Coriobacteriia, Atopobiaceae, Negativicutes, were significantly enriched in PST patients, while 29 genera, including Gammaproteobacteria, Proteobacteria, Burkholderiales, Neisseriaceae, were dominant in the HCs group. It was found that PST group had 16 gene functions, including Amino acid metabolism, Cysteine and methionine metabolism, Photosynthesis antenna proteins, Arginine and proline metabolism, and Aminoacyl tRNA biosynthesi, were significantly dominant, while 29 gene functions that prevailed in HCs.ConclusionThis study characterized the oral microbiota of Pediatric solid tumor patients for the first time, and importantly, targeted biomarkers of oral microbiota may serve as powerful and non-invasive diagnostic tools for pediatric solid tumor patients.

ABSTRACTThe control of Ostrinia furnacalis, a major pest of maize in Xinjiang, is challenging owing to the occurrence of resistant individuals. Entomopathogenic fungi (EPF) are natural insect regulators used as substitutes for synthetic chemical insecticides. The fungus Aspergillus nomius is highly pathogenic to O. furnacalis; however, its virulence characteristics have not been identified. This study aimed to analyse the lethal efficacy, mode of infection on the cuticle, and extracellular enzyme activity of A. nomius against O. furnacalis. We found that the mortality and mycosis of O. furnacalis were dose-dependent when exposed to A. nomius and varied at different life stages. The egg-hatching and adult emergence rates decreased with an increase in conidial suspension. The highest mortality (83.33%, 7 d post-infection [DPI]) and mycosis (74.33%, 7 DPI) and the lowest mortality response (8.52 × 103 conidia mL−1) and median lethal time (4.91 d) occurred in the 3rd instar larvae of O. furnacalis. Scanning electron microscopy indicated that numerous conidia germination and infection structure formation may have contributed to the high pathogenicity of A. nomius against O. furnacalis. There were significant correlations between O. furnacalis mortality and the activities of extracellular protease, lipase, and chitinase of A. nomius. This study revealed the infection process of the highly pathogenic A. nomius against O. furnacalis, providing a theoretical basis and reference for strain improvement and field application of EPF.

【Objective】Glaesserella parasuis (GPS) is the pathogen that causes Gl?sser's disease in pigs. It is one of the most serious bacterial pathogens that harm pig industry. There are many serotypes of this bacterium, and the crossprotection between different serotypes is weak. Serotype 2 is a moderately virulent strain, and the proportion of clinical isolates has been increasing, resulting in increasingly serious harm in recent years. GPS serotype 2 was isolated from nursery pigs in a large-scale pig farm in Henan Province and a series of tests were conducted, and provided reference for scientific prevention and control of the disease.【Method】In this study, lung, trachea, blood and other samples of GPS clinically suspected cases pigs were collected. Bacterial isolation and purification, Gram staining microscopy, routine PCR, guinea pig pathogenicity test, AGAR diffusion drug sensitivity test and other methods were used. Morphological observation, identification, serotyping, virulence gene detection, drug-resistant gene detection, pathogenicity and drug resistance of suspected bacteria were studied.【Result】A strain of GPS was isolated from lung samples and identified as serotype 2. The strain carried virulence genes of vta1, vta2, vta3, wza, ompP2, nanH, cdtA, cdtB, cdtC and espP2, and showed strong virulence to guinea pigs. The strain carried drug-resistant genes aadA1, strA, strB, aphA1, tet(B), sul2, and had strong resistance to penicillin G, kanamycin, amicacin, streptomycin, tetracycline, oxytetracycin, and cotrimoxazole. It had good sensitivity to ceftiofurme, ceftazidime, amoxicillin, ampicillin, levfloxacin, ofloxacin, ennofloxacin and ciprofloxacin, and had significant clinical effect.【Conclusion】The isolates of GPS serotype 2 have strong virulence, can pass through the blood-brain barrier, and have obvious multi-drug resistance. The results of this study provide reference for the epidemiological investigation of GPS serotype 2, pathogenic mechanism, and the formulation of clinical prevention and control measures.

Abstract Metastable ε-Fe2O3 was discovered on a ceramic ware of Deqing kiln of the Tang Dynasty, which coexists with α-Fe2O3 in the brown area between adjacent black glaze areas, and it is the earliest known artificially synthesized ε-Fe2O3. Based on the composition analysis of α-Fe2O3, ε-Fe2O3 and the glass phase around them, it is speculated that some Fe3+ ions were replaced by Al3+ ions during the formation of ε-Fe2O3, and a relatively low CaO content may be required for its crystallization. This work may promote researchers' understanding of ε-Fe2O3 crystals, and provide clues for the artificial synthesis of large ε-Fe2O3 crystals.

With the continuous development and progress of wireless self-organizing network communication technology, how to carry out long-distance cooperative control of multiple intelligences under the framework of an air–ground integrated wireless high-mobility self-organizing network has become a hot and difficult topic that needs to be solved urgently. This paper takes the air–ground integrated wireless high-mobility self-organizing network system as the basic framework and focuses on solving the long-distance cooperative fault-tolerant control of multi-intelligent bodies and the topological stability of a wireless mobile self-organizing network. To solve the above problems, a direct neural network with a robust adaptive fault-tolerant controller is designed in this paper. By constructing a symmetric population neural network model and combining it with the Lyapunov stabilization criterion, the system feedback matrix K has the ability of autonomous adaptive learning, and symmetrically distorts, rotates, or scales the training data to instantly adjust the system’s fault-tolerant corrections and adaptive adjusting factors to resist the unknown disturbances and faults, to achieve the goals of multi-intelligent body stable control and the stable operation of a wireless high-mobility self-organizing network topology. Simulation results show that with the feedback adjustment of the multi-system under the designed controller, the multi-system as a whole has good fault-tolerant performance and autonomous learning approximation performance, and the tracking error asymptotically converges to zero. The experimental results show that the multi-flight subsystems fly stably, the air–ground integrated wireless high-mobility self-organizing network topology has good stability performance, and the maximum relative improvement of the topology stability performance is 50%.

Fusarium crown rot (FCR) in wheat is a prevalent soil-borne disease worldwide and poses a significant threat to the production of wheat (Triticum aestivum) in China, with F. pseudograminearum being the dominant pathogen. Currently, there is a shortage of biocontrol resources to control FCR induced by F. pseudograminearum, along with biocontrol mechanisms. In this study, we have identified 37 strains of biocontrol bacteria displaying antagonistic effects against F. pseudograminearum from over 8000 single colonies isolated from soil samples with a high incidence of FCR. Among them, QY43 exhibited remarkable efficacy in controlling FCR. Further analysis identified the isolate QY43 as Pseudomonas aeruginosa, based on its colony morphology and molecular biology. In vitro, QY43 significantly inhibited the growth, conidial germination, and the pathogenicity of F. pseudograminearum. In addition, QY43 exhibited a broad spectrum of antagonistic activities against several plant pathogens. The genomics analysis revealed that there are genes encoding potential biocontrol factors in the genome of QY43. The experimental results confirmed that QY43 secretes biocontrol factor siderophores and pyocyanin. In summary, QY43 exhibits a broad spectrum of antagonistic activities and the capacity to produce diverse biocontrol factors, thereby showing substantial potential for biocontrol applications to plant disease.

Summary: Patients with coronary artery disease (CAD) at low residual inflammatory risk are often overlooked in research and practice. This study examined the associations between fourteen inflammatory indicators and all-cause mortality in 5,339 CAD patients with baseline high-sensitivity C-reactive protein (hsCRP)

In this paper, we design a power amplifier for this network protocol to combat the Doppler effect caused by the high-speed movement of network nodes and the rapid signal fading failure caused by the long-distance transmission of network nodes, and to extend the communication distance between network nodes, to realize the long-distance transmission under the high-speed movement of network nodes. The overall design of the power amplifier for bi-directional transmission structure, power amplifier transmitter, and low-noise amplifier receiver is used in a four-stage cascade current series negative feedback structure mode, where the signal transmitter selected RFPA5208 and MAX4003 chip, the signal receiver selected TQP3M9037 and SKY16602 chip. The above overall design enables the self-assembled nodes to ensure stable topology and achieve long-spacing transmission even in the high-speed mobile state. The test results show that the output power is 41.5dBm-44.3dBm, the gain is 44dB-45dB, and the noise is 1.6dB when the frequency band range is 2.4GHz-2.5GHz. The experimental results show that when the self-assembling nodes maintain the relative speed of 214km/h, the longest transmission distance of the point-to-point of the amorphous flat terrestrial wireless self-assembling network reaches 16300m, and the longest transmission distance of the point-to-point of the amorphous flat air-to-ground wireless self-assembling network reaches 25100m. The power amplifier designed in this paper has good application value. It provides an individual research basis for future research on the framework of a low-altitude economic fly-by-wire network.

Abnormal bone metabolism and subsequence osteoporotic fractures are common complications of chronic inflammatory diseases. No effective treatment for these bone-related complications is available at present. The chronic inflammatory state in these diseases has been considered as a key factor of bone loss. Therefore, the combination of inflammation inhibition and bone loss suppression may be an important strategy for reducing bone damage associated with inflammatory diseases. Bushen Huoxue Decoction (BSHXD) is a traditional Chinese herbal compound that has demonstrated the ability to improve bone quality and increase bone density. However, the efficacy of BSHXD on inflammatory bone loss and its underlying mechanisms remain unclear. This study aimed to investigate whether BSHXD inhibits inflammatory bone loss in mice and its potential molecular mechanisms. In the present study, the effect of BSHXD on lipopolysaccharide (LPS)-induced M1 polarization of RAW264.7 macrophage and on local inflammatory bone loss model of mouse skull was determined. The results showed that after treating RAW264.7 cells with LPS for 24 h, the expression levels of IL-1β (39.42 ± 3.076 ng/L, p

BackgroundWhether serum apolipoprotein B (ApoB) is a risk factor for the development of Chronic kidney disease (CKD) has not been fully established in the general population. Therefore, our study evaluated the correlation between serum ApoB level and CKD to look for an alternative approach for CKD prevention and treatment in the general population.MethodsThere were 146,533 participants in this cross-sectional study. 3,325 participants with more than 2 measurements were enrolled in the retrospective longitudinal study with at least a 3-year follow-up. ApoB was measured by the immunoturbidimetric method in 6 centers. Our study defined CKD as an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2. The Spearman rank correlation analysis and the Random Forest algorithm were applied to rank the importance of variables determining the levels of eGFR. We used the logistic regression model to explain the correlation between serum ApoB and CKD. We used the Cox model to detect the correlation between baseline serum ApoB and the subsequent occurrence of CKD.ResultsBased on a cross-sectional study, 66.5% of the participants were males, with a median age of 49 (interquartile range [IQR] 43-55). Compared to the non-CKD group, the CKD group has higher levels of lipid profile and fasting glucose as well as the proportion of hypertension and hyperuricemia. The Spearman rank correlation analysis and the Random Forest algorithm revealed that ApoB has the highest correlation with eGFR decline among lipid profiles. The logistic regression analysis revealed that ApoB had a positive correlation with the prevalence of CKD after fully controlling confounders (odds ratio [OR], 1.07; 95% confidence interval [CI]: 1.02-1.11). Moreover, baseline ApoB level was correlated with a new-onset CKD in the longitudinal cohort after full adjustment for confounding factors (hazard ratio [HR], 1.61; 95% CI: 1.02-2.54). The correlation between ApoB level and the new-onset CKD was consistently observed in all sensitivity analyses.ConclusionSerum ApoB had the strongest correlation with CKD among all lipid variables. Moreover, high serum ApoB levels might precede the occurrence of CKD, suggesting that monitoring and reducing serum ApoB levels may provide an alternative method to prevent and treat CKD.

Abstract Orientation control over micropatterned crystalline organic semiconductor film is crucial to achieve high device performance with small variation in organic electronics. Here, using Au patterned SiO2 substrates, a method is reported to realize high‐resolution patterning and orientation control of crystalline organic thin films simultaneously. The vacuum deposited N,N‐dioctyl‐3,4,9,10‐perylene tetracarboxylic diimide (PTCDI‐C8) molecules can selectively diffuse to and nucleate on prepatterned Au stripes, resulting in patterned crystalline films with a preferential orientation distribution. Scanning tunneling microscope and high‐resolution atomic force microscope images reveal that the PTCDI‐C8 molecules first assemble on Au with perylene diimide cores in a laying down configuration, providing nucleation sites at the step edges for directional growth along the a‐axis of the molecule crystal. Subsequent deposition of molecules leads to orientated crystalline films growth due to the π packing of the perylene diimide cores, resulting in orientation control on micropatterned crystalline films. The finding provides a new strategy to grow oriented crystalline films for high device performance uniformity.

Background: Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors arising from chromaffin cells in the adrenal medulla and extra-adrenal ganglia, respectively. The study was aimed to investigate the clinical and genetic characteristics of 22 individuals from six families.Methods: The medical records of six PPGL probands who presented to our hospital between 2016 and 2021 were retrospectively studied. DNA isolated from the probands was analyzed using whole exome sequencing. The identified genetic variants were confirmed by Sanger sequencing and undergone bioinformatic analysis.Results: Six different genetic variants in the six probands were identified, respectively, of which three were novel. A novel von Hippel-Lindau (VHL) variant, c.602T>C (p.L201P), in exon 3 was found. Two novel genetic variants in SDHB (succinate dehydrogenases subunit B), c.423 + 1 G>T and c.662A>G (p.D221G), were identified. Two recurrent genetic variants of VHL, c.C284G (p.P95R) and c.558_560AGAdel (p.186Edel), and one in RET (ret proto-oncogene), c.1901G>A (p.C634Y), were also found. The ClinVar accession number for the present variants are SCV002028348, and SCV002028352 to SCV002028361.Conclusion: Genetic variants in VHL, SDHB and RET were identified in Chinese PPGL patients, which contributed to the knowledge of the genetic etiology and clinical outcome of these tumors.

Solid polymer electrolytes have demonstrated high promise to solve the safety problems caused by conventional liquid electrolytes in lithium ion batteries. However, the inherent flammability of most polymer electrolyte materials remains unresolved, hence hindering their further industrial application. Addressing this challenge, we designed and constructed a thermal-responsive imide-linked covalent organic framework (COF) bearing ortho-positioned hydroxy groups as precursors, which can conduct a thermal rearrangement to transform into a highly crystalline and robust benzoxazole-linked COF upon heating. Benefiting from the release of carbon dioxide through thermal rearrangement reaction, this COF platform exhibited excellent flame retardant properties. By contrast, classic COFs (e.g., boronate ester, imine, olefin, imide linked) were all flammable. Moreover, incorporating polyethylene glycol and Li salt into the COF channels can produce solid polymer electrolytes with outstanding flame retardancy, high ionic conductivity (6.42 ​× ​10−4 ​S ​cm−1) and a high lithium-ion transference number of 0.95. This thermal rearrangement strategy not only opens a new route for the fabrication of ultrastable COFs, but also provides promising perspectives to designing flame-retardant materials for energy-related applications.

The EPIDERMAL PATTERNING FACTOR (EPF) plays a crucial role in plant response to abiotic stress. While the EPF has been extensively studied in model plants such as Arabidopsis thaliana, there is a lack of research on identifying EPF genes in the whole sorghum genome and its response to drought stress. In this study, we employed bioinformatics tools to identify 12 EPF members in sorghum. Phylogenetic tree analysis revealed that SbEPFs can be categorized into four branches. Further examination of the gene structure and protein conservation motifs of EPF family members demonstrated the high conservation of the SbEPF sequence. The promoter region of SbEPFs was found to encompass cis-elements responsive to stress and plant hormones. Moreover, real-time fluorescence quantitative results indicated that the SbEPFs have a tissue-specific expression. Under drought stress treatment, most SbEPF members were significantly up-regulated, indicating their potential role in drought response. Our research findings establish a foundation for investigating the function of SbEPFs and offer candidate genes for stress-resistant breeding and enhanced production in sorghum.

Abstract Background The inhibition of osteogenic differentiation is a major factor in glucocorticoid-induced bone loss, but there is currently no effective treatment. Dopamine, a major neurotransmitter, transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. Although the relevance of the neuroendocrine system in bone metabolism has emerged, the precise effects of dopamine receptor signaling on osteoblastogenesis remain unknown. Methods In vitro, western blotting and immunofluorescence staining were used to observe the expression of dopamine receptors in MC3T3-E1 and BMSCs cells treated with dexamethasone (Dex). In addition, Alizarin red S (ARS) and alkaline phosphatase (ALP) staining and western blotting were used to evaluate the effect of D1R activation on osteogenic differentiation in Dex-induced MC3T3-E1 cells via the ERK1/2 signaling pathway. In vivo, micro-CT and hematoxylin and eosin (H&E), toluidine blue and immunohistochemical staining were used to determine the effect of D1R activation on Dex-induced bone loss. Results We demonstrated that the trend in D1R but not D2-5R was consistent with that of osteogenic markers in the presence of Dex. We also demonstrated that the activation of D1R promoted Dex-induced osteogenic differentiation by activating the ERK1/2 pathway in vitro. We further demonstrated that a D1R agonist could reduce Dex-induced bone loss, while pretreatment with a D1R inhibitor blocked the effect of a D1R agonist in vivo. Conclusions Activation of D1R promotes osteogenic differentiation and reduces Dex-induced bone loss by activating the ERK1/2 pathway. Hence, D1R could serve as a potential therapeutic target for glucocorticoid-induced osteoporosis.

Cadmium (Cd) pollution is a serious threat to plant growth and human health. Although the mechanisms controlling the Cd response have been elucidated in other species, they remain unknown in Sorghum (Sorghum bicolor (L.) Moench), an important C4 cereal crop. Here, one-week-old sorghum seedlings were exposed to different concentrations (0, 10, 20, 50, 100, and 150 μM) of CdCl2 and the effects of these different concentrations on morphological responses were evaluated. Cd stress significantly decreased the activities of the enzymes peroxidase (POD), superoxide dismutase (SOD), glutathione S-transferase (GST) and catalase (CAT), and increased malondialdehyde (MDA) levels, leading to inhibition of plant height, decreases in lateral root density and plant biomass production. Based on these results, 10 μM Cd concentration was chosen for further transcription and metabolic analyses. A total of 2683 genes and 160 metabolites were found to have significant differential abundances between the control and Cd-treated groups. Multi-omics integrative analysis revealed that the flavonoid biosynthesis pathway plays a critical role in regulating Cd stress responses in sorghum. These results provide new insights into the mechanism underlying the response of sorghum to Cd.

Currently, the failure rate for internal fixation in patients with osteoporosis can be reduced by antiosteoporosis therapy alone. However, the administration of anti-osteoporotic drugs is not a complete solution. Therefore, it is necessary to investigate other causes of surgical failure, such as inflammation. In recent years, the inflammation caused by macrophage M1 polarization has garnered wide attention. The purpose of this research is to explore the inhibitory effect of avicularin (AL) on macrophage M1 polarization, by which it ameliorates inflammation, thus alleviating implant instability. We established an osteoporosis mouse model of implant loosening. The mouse tissues were taken out for morphological analysis, staining analysis and bone metabolic index analysis. In in vitro experiments, bone marrow derived macrophages (BMDM) and RAW264.7 cells were polarized to M1 macrophages using lipopolysaccharide (LPS), and analyzed by immunofluorescence (IF) staining, Western blot (WB) and flow cytometry. WB was also used to analyze the nuclear factor kappa-B (NF-κB) pathway. In addition, the expression levels of inflammatory cytokines were detected in cell supernatant using ELISA kits. Through observation of this experiments, we found that AL can inhibit M1 polarization of macrophages. Moreover, it can significantly inhibit the release of inflammatory factors to improve multiple mouse femur parameters. Furthermore, AL inhibited the phosphorylation of IKBα and P65 in the NF-κB pathway. The above data indicate that AL ameliorates inflammatory responses by inhibiting macrophage M1 polarization via its inhibitory effect on the NF-κB pathway, thus alleviating the instability of implants in mice with osteoporosis.

Background: Bivalirudin reduces ischemic and hemorrhagic events in patients undergoing primary percutaneous coronary intervention (PCI), but the safety and efficacy for such individuals are unclear. Our aim was to evaluate the long-term safety and efficacy of bivalirudin in patients undergoing elective PCI. Methods: We examined 957 patients with bivalirudin anticoagulation and 1713 patients with unfractionated heparin (UFH) anticoagulation with and without glycoprotein IIb/IIIa inhibitors (GPI). The primary endpoint was net adverse clinical events (NACE), a composite of death, myocardial infarction, revascularization, stent thrombosis, stroke, and bleeding. The secondary endpoints were bleeding and major adverse cardiovascular and cerebrovascular events (MACCE). Results: In one year of follow-up, 307 (11.5%) NACEs, 72 (2.7%) bleedings, and 249 (9.3%) MACCEs occurred. Statistically, patients with bivalirudin anticoagulation had less NACE [hazard ratio (HR): 0.75, 95% confidence interval (CI): 0.58–0.96, p = 0.021] and bleeding (HR: 0.58, 95% CI: 0.34–0.99, p = 0.045) but not less MACCE, than did those with UFH anticoagulation. Furthermore, the risk of bleeding in the bivalirudin group was lower than in the UFH with GPI group (p = 0.001) but not lower than in the group of UFH without GPI (p = 0.197). Conclusions: In patients who undergo elective PCI, the use of bivalirudin significantly decreased the risk of NACE and bleeding without increasing the risk of MACCE; the reduction of bleeding risk with bivalirudin was mainly attributed to the presence of GPIs in the UFH group.

Fusarium pseudograminearum is one of the major fungal pathogens that cause Fusarium crown rot (FCR) worldwide and can lead to a substantially reduced grain yield and quality. Transcription factors play an important role in regulating growth and pathogenicity in plant pathogens. In this study, we identified a putative Zn(II)2Cys6 fungal-type domain-containing transcription factor and named it FpUme18. The expression of FpUME18 was induced during the infection of wheat by F. pseudograminearum. The ΔFpume18 deletion mutant showed defects in growth, conidial production, and conidial germination. In the responses to the cell wall, salt and oxidative stresses, the ΔFpume18 mutant inhibited the rate of mycelial growth at a higher rate compared with the wild type. The staining of conidia and mycelia with lipophilic dye FM4-64 revealed a delay in endocytosis when FpUME18 was deleted. FpUME18 also positively regulated the expression of phospholipid-related synthesis genes. The deletion of FpUME18 attenuated the pathogenicity of wheat coleoptiles. FpUME18 also participated in the production of the DON toxin by regulating the expression of TRI genes. Collectively, FpUme18 is required for vegetative growth, conidiation, stress response, endocytosis, and full virulence in F. pseudograminearum.

Limited evidence exists on the combined and mediating effects of systemic inflammation on the association between insulin resistance and cardiovascular events in patients with diabetes and chronic coronary syndrome (CCS). This secondary analysis of a multicenter prospective cohort included 4419 diabetic CCS patients. Triglyceride–glucose index (TyG) and high-sensitivity C-reactive protein (hsCRP) were applied to evaluate insulin resistance and systemic inflammation, respectively. The primary endpoint was major adverse cardiac event (MACE). Associations of TyG and hsCRP with cardiovascular events were estimated using Cox regression. A mediation analysis was performed to assess whether hsCRP mediates the relationship between TyG and cardiovascular events. Within a median 2.1-year follow-up period, 405 MACEs occurred. Patients with high levels of TyG and hsCRP experienced the highest MACE risk (hazard ratio = 1.82, 95% confidence interval: 1.24–2.70, p = 0.002) compared to individuals with low levels of both markers. HsCRP significantly mediated 14.37% of the relationship between TyG and MACE (p < 0.001). In diabetic CCS patients, insulin resistance and systemic inflammation synergically increased the risk of cardiovascular events, and systemic inflammation partially mediated the association between insulin resistance and clinical outcomes. Combining TyG and hsCRP can help identify high-risk patients. Controlling inflammation in patients with insulin resistance may bring added benefits.

Abstract Background Oral antiplatelet therapy is the cornerstone of treatment for acute myocardial infaction (AMI). However, detailed usage data on oral antiplatelet therapy are lacking. Methods Using data from a nationally representative sample of patients with AMI, the detailed usage of oral antiplatelet therapy was analyzed in 40,202 consecutive eligible patients. Results The proportions of patients with AMI taking loading doses of aspirin and P2Y12 inhibitors were relatively low (62.2% and 63.6%, respectively), whereas approximately 90% of patients received maintenance doses of aspirin, P2Y12 inhibitors, and dual antiplatelet therapy. The proportions of patients taking loading doses of aspirin and P2Y12 inhibitors gradually decreased with age. Male sex, an educational level of at least college, an interval from onset to treatment of

The increasing penetration of renewable energy has a significant impact on the performance and reliability of the power grid. This is largely because of the uncertainty of the renewable resources and the complex nature of the power system infrastructure. This paper analyzed power grids' vulnerability to cascading failures with respect to the penetration level of renewable energy into the grid. In this paper, a novel power balance technique is used for cascading failure analysis and power grid vulnerability measurement. The proposed approach incorporates a modified optimal power flow algorithm in the grid vulnerability analysis study which accurately reflects the most probable path of cascading failure evolution process with uncertain renewable generation. The simulation results on IEEE 118 bus system, IEEE 300 bus system and 500 bus system showed that increasing penetration of renewable energy have proportionally higher impact on grid vulnerability to cascading failures due to injection of higher uncertainties into the grid. It was also evident that after a certain level of RE penetration, some system might deteriorate rapidly and preventive measures should be taken if and when RE penetration level exceeds that limit.

Background: Patients with diabetes mellitus (DM) are considered to increase the risk of thrombosis and bleeding. However, whether DM is an independent risk factor for events in patients anticoagulated with bivalirudin during elective percutaneous coronary intervention (PCI) is not clear. Methods: Patients anticoagulated with bivalirudin during elective PCI from January 2017 to August 2018 in 3 centers were enrolled. The primary endpoint of thrombotic events was major adverse cardiac and cerebrovascular events (MACCE, including all-cause death, myocardial infarction, ischemic revascularization, stent thrombosis, and stroke); the primary endpoint of bleeding events was Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding. Results: 1152 patients were finally enrolled. After one-year follow-up, 89 (7.7%) MACCE and 21 (1.8%) BARC 2, 3 or 5 bleeding occurred. Multivariate Cox regression analysis showed DM was not an independent risk factor for MACCE (hazard ratio [HR]: 1.029, 95% confidence interval [CI]: 0.674-1.573, P = .893), but peripheral artery disease (PAD) history (HR: 2.200, 95%CI: 1.290-3.751, P = .004) was an independent risk factor for MACCE. DM was not an independent risk factor for BARC 2, 3 or 5 bleeding (HR: 0.732, 95%CI: 0.293-1.831, P = .505), but PAD history (HR: 3.029, 95%CI: 1.102-8.332, P = .032) and low hemoglobin level (HR = 0.972, 95%CI: 0.947-0.998, P = .036) were independent risk factors for BARC 2, 3 or 5 bleeding. Conclusions: DM was not an independent risk factor for one-year thrombotic and bleeding events in patients anticoagulated with bivalirudin during elective PCI. More attention should be paid to PAD history and hemoglobin level to identify high-risk patients.

BackgroundThe prognostic effect of admission blood glucose (ABG) for patients with acute myocardial infarction (AMI) has not been well validated, especially in patients with diabetes. We performed this study to assess the predictive value of ABG for all-cause mortality in AMI patients with different glucose metabolism status.MethodsWe evaluated a total of 6,892 AMI patients from the prospective, nationwide, multicenter CAMI registry, of which 2,820 had diabetes, 2,011 had pre-diabetes, and 2,061 had normal glucose regulation (NGR). Patients were divided into high ABG and low ABG groups according to the optimal cutoff values of ABG to predict 2-year mortality for patients with diabetes, pre-diabetes and NGR, respectively. The primary endpoint was all-cause mortality.ResultsThe optimal cutoff values of ABG for predicting 2-year mortality was 9.0mmol/l, 7.2mmol/l and 6.2mmol/l for patients with diabetes, pre-diabetes and NGR, respectively. Overall, the risk of all-cause mortality in high ABG group was significantly increased compared with that in low ABG group among patients with diabetes (15.2% vs. 8.9%; hazard ratio [HR] 1.787, 95% confidence interval [CI] 1.413-2.260; P

Abstract Green synthesis of crystalline porous materials for energy-related applications is of great significance but very challenging. Here, we create a green strategy to fabricate a highly crystalline olefin-linked pyrazine-based covalent organic framework (COF) with high robustness and porosity under solvent-free conditions. The abundant nitrogen sites, high hydrophilicity, and well-defined one-dimensional nanochannels make the resulting COF an ideal platform to confine and stabilize the H3PO4 network in the pores through hydrogen-bonding interactions. The resulting material exhibits low activation energy (Ea) of 0.06 eV, and ultrahigh proton conductivity across a wide relative humidity (10–90 %) and temperature range (25–80 °C). A realistic proton exchange membrane fuel cell using the olefin-linked COF as the solid electrolyte achieve a maximum power of 135 mW cm−2 and a current density of 676 mA cm−2, which exceeds all reported COF materials.

Abstract The studies on the increasing incidence of thyroid abnormalities are scarce. The aim of this current study was to ascertain the effects of geographical region on thyroid abnormalities under the context of universal salt iodization (USI). We randomly selected 1255 participants residing in inland and 1248 in coast, with the determination of urinary iodine concentration (UIC) and functional and morphological abnormalities of thyroid gland. The median UIC was significantly higher for the inland participants (188.5 μg/L) than the coastal participants (128.5 μg/L; p

Urban renewal to fulfill the updated needs of urban residents is an inevitable product of urbanization at certain stages. And how to effectively prioritize varied attributes to be renewed across scales is a challenging process for urban governance worldwide. This study aimed to fill the existing gaps by merging the prioritization capacity of importance-performance analysis (IPA) and the scalability potential of social media data. The study pioneered establishing a social-media-based improvement index (SMII) for urban renewal. Based on the framework of importance-performance analysis, SMII takes the most overkilled point (the lowest importance but the highest performance) as the origin and calculates the area between other points and the origin. SMII always has the highest value in the quadrant with high importance but low performance. We demonstrate the usage of SMII taking the landscape services of urban park systems as an example. We used SMII to understand the users' evaluation of parks' services across scales and then clarified the priority sequence for future renewal. Among selected parks, we identified three parks that need immediate renewal. Among all the services, we found that recreational activities and social interactions are in highest priority for renewal in Beijing's park systems. The findings suggest that the history and culture services of the Old Summer Place Park need to be improved first for a wide variety of reasons. The findings also reveal multiple temporal changes of varied services. Our study concludes that SMII can clarify problem prioritization and cost-effective guide decision-making for urban park renewal with high scalability both temporally and spatially. Meanwhile, SMII can extend its applications to analyzing various issues in the urban environment on multiple scales for the effective allocation of resources during urban renewal.

Background: This study aimed to investigate the effect of ticagrelor combined with omeprazole on patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). Methods: Eighty-six patients with AMI who underwent primary PCI in Xinxiang Central Hospital between July 2015 and December 2016 were included and divided randomly into the observation group and the control group by the draw, with 43 patients in each group. All patients were routinely treated with dual antiplatelet therapy with aspirin plus ticagrelor. Omeprazole was used in the observation group and placebo was used in the control group. Data of baseline patient characteristics, platelet response index (PRI), ADP-induced platelet aggregation (ADP-Ag), major adverse cardiac events (MACE), and incidence of bleeding events were recorded and compared between both groups. Results: PRI and ADP-Ag at 7 days, 1 month, and 6 months after operation in both groups were significantly lower than those in the same group before administration (p

Injury of corpus cavernosa results in erectile dysfunction, and repair leading to restoration of function is difficult. Here the authors construct 3D printed hydrogel constructs seeded with HIF-1α-expressing muscle derived stem cells to restore corpus function in a rabbit model.

Abstract Background and purpose Targeted therapy and immunotherapy have led to dramatic change in the treatment of lung cancer, however, the overall 5-year survival rate of lung cancer patients is still suboptimal. It is important to exploit new potential of molecularly targeted therapies. High-frequency somatic mutations in KEAP1/NRF2 (27.9%) have been identified in lung squamous cell carcinoma. In this research, we explored the role of KEAP1 somatic mutations in the development of LSCC and whether a nuclear factor erythroid 2-related factor 2(NRF2) inhibitor be potential to target lung cancer carrying KEAP1/NRF2 mutations. Methods Lung cancer cell lines A549 and H460 with loss-of-function mutations in KEAP1 stably transfected with wild-type (WT) KEAP1 or somatic mutations in KEAP1 were used to investigate the functions of somatic mutations in KEAP1. Flow cytometry, plate clone formation experiments, and scratch tests were used to examine reactive oxygen species, proliferation, and migration of these cell lines. Results The expression of NRF2 and its target genes increased, and tumor cell proliferation, migration, and tumor growth were accelerated in A549 and H460 cells stably transfected with KEAP1 mutants compared to control cells with a loss-of-function KEAP1 mutation and stably transfected with WT KEAP1 in both in vitro and in vivo studies. The proliferation of A549 cell line trasfected with the R320Q KEAP1 mutant was inhibited more apparent than that of the A549 cell line trasfected with WT KEAP1 after treatment with NRF2 inhibitor ML385. Conclusion Somatic mutations of KEAP1 identified from patients with LSCC likely promote tumorigenesis mediated by activation of the KEAP1/NRF2 antioxidant stress response pathway. NRF2 inhibition with ML385 could inhibit the proliferation of tumor cells with KEAP1 mutation. Video abstract

Abstract Background Pregnant women, neonates, and school-age children are vulnerable to iodine deficiency. The iodine contents in the environment (drinking water and household salt for cooking) vary by geographical location in China. The aim of this study was to assess the iodine status in vulnerable groups from different geographical zones and analyze the iodine content in household salt and drinking water from these zones. Methods In coastal and inland regions of Zhejiang Province, China, samples of spot urine, drinking water, and household salt for cooking from both pregnant women and school-age children were determined for iodine concentration between 2017 and 2018. Thyroid-stimulating hormone (TSH) levels from neonates born between 2014 and 2015 were acquired from the Newborns Screening Information System. The iodine status of the vulnerable populations was assessed according to the criteria recommended by the World Health Organization. Results The median UIC of pregnant women was significantly lower in the coastal region (113.0 μg/L) than the inland region (134.9 μg/L; p 5 mIU/L) was significantly higher in the coastal region (15.8%) than the inland region (10.5%; p

ObjectiveA Rathke’s cleft cyst (RCC) is a common, benign, cystic disease that often leads to hypophyseal dysfunction or head symptoms. The relationship between RCCs and pituitary gland function is not clear. We therefore carried out a study to examine this relationship in greater detail.MethodsThe study was a retrospective, cohort design in patients diagnosed with a RCC between January 2019 to July 2021 at the First Affiliated Hospital of Zhengzhou University, China.ResultsA total of 221 patients were enrolled and then divided into study cohorts according to the diameter of the RCC, clinical manifestations, and surgical treatment received. The majority of patients were symptomatic (143/221), including 83 cases of dizziness and headache, 9 of vision loss and visual field defect, and 2 of diabetes insipidus. 52 cases had abnormal pituitary function, with 8 cases interestingly showing high adrenocorticotropic-hormone (ACTH) and cortisone levels, while 8 juvenile cases had developed central precocious puberty. Patients with larger RCCs were more likely to present with headaches and dizziness, with subjects who suffered from these symptoms having high ACTH and cortisone levels.ConclusionAlthough the size of a RCC is not an important factor influencing hypopituitary function, we consider that endocrine evaluation should be carried out in all patients with a RCC.

Hyperprolactinemia is a common endocrine disease in women of reproductive age. Research has shown that patients with hyperprolactinemia often have decreased bone mineral density and an increased risk of fractures. However, there is still a lack of effective treatments. Paeoniflorin, one of the primary bioactive components in peony, is widely used in traditional Chinese medicine. Research has shown that paeoniflorin promotes osteoblast differentiation. However, whether paeoniflorin plays a role in hyperprolactinemia-induced osteoblastogenesis inhibition is not yet clear. In this study, we investigated the effect of paeoniflorin on prolactin (PRL)-mediated inhibition of osteoblast function. Our results showed that prolactin significantly reduced the expression of alkaline phosphatase (ALP), Osterix, and runt-related transcription factor 2 (RUNX2) in MC3T3-E1 cells cultured in an osteoblast differentiation medium, suggesting that prolactin inhibited osteoblast function. After treatment with paeoniflorin (PF), the expression of these osteoblast markers was upregulated. In addition, our findings proved that paeoniflorin increased the absorbance values of ALP-positive cells and the areas of alizarin red S (ARS) deposition compared to those in the prolactin group, suggesting that paeoniflorin reversed the PRL-induced reduction in osteoblast differentiation. The PRL-induced activation of nuclear factor kappa B (NF-κB) was significantly reversed by paeoniflorin, indicating that paeoniflorin promoted osteoblast function by inhibiting the NF-κB signaling pathway. In summary, these results showed that paeoniflorin alleviated the inhibitory effect of prolactin on osteoblastogenesis by suppressing the NF-κB signaling pathway.

The science-practice gap has recently been discussed as a critical challenge restricting sustainable growth and development in all facets of our society, including explorations of Recreation Ecosystem Services (RES). To better explore how well the scientific study of RES and its application are connected, this paper aims to synthesize empirical evidence based on an in-depth and systematic literature review. We found that studies of RES have not effectively transformed into the decision-making and long-term planning of our cities. From 2005 to 2020, only 13% of studies referred to specific applications, and about 40% of papers mentioned no applications or practical implications for their research. However, RES research has many potential applications, which can be categorised into six main aspects. In terms of non-spatial improvement: Improved monetary benefits (40%), non-monetary benefits (30%); in terms of spatial improvement: space with high recreational potential or degradation (7%), the relation between supply and demand (7%); and Cross-service governance (16%). After combining the results of various studies, we developed a framework starting from applicable problems and their solutions, which can incorporate the outcomes of RES research while systematically narrowing down the research questions and methods. The framework offers a starting point for further research that can modify and improve in bridging science-practice gaps in RES studies.

This study sought to investigate the prevalence and prognostic significance of malnutrition in patients with an abnormal glycemic status and coronary artery disease (CAD). This secondary analysis of a multicenter prospective cohort included 5710 CAD patients with prediabetes and 9328 with diabetes. Four objective tools were applied to assess the nutritional status of the study population. The primary endpoint was all-cause death. The association of malnutrition with clinical outcomes was examined using Cox proportional hazards regression. The proportion of malnutrition varied from 8% to 57% across the assessment tools. Diabetic patients were more likely to be malnourished than prediabetic patients. During a median follow-up of 2.1 years, 456 all-cause deaths occurred. The adjusted hazard ratios and 95% confidence interval for all-cause deaths of moderate–severe malnutrition defined by different tools ranged from 1.59 (1.03, 2.46) to 2.08 (0.92, 4.73) in prediabetic patients and 1.51 (1.00, 2.34) to 2.41 (1.78, 3.27) in diabetic patients. In conclusion, malnutrition is not rare in CAD patients with abnormal glycemic status. Moderate–severe malnutrition strongly predicted all-cause death regardless of the assessment tool. Assessing the nutritional status for all CAD patients with prediabetes and diabetes to identify individuals at high risk of all-cause death may help the risk assessment and prognosis improvement.

Geometric iterative methods, including progressive iterative approximation and geometric interpolation methods, are efficient for fitting a given data set. With the development of big data technology, the number of fitting data points has become massive, and the progressive iterative approximation for least-squares fitting (LSPIA) is generally applied to fit mass data. Combining the Schulz iterative method for calculating the Moore–Penrose generalized inverse matrix with the traditional LSPIA method, this paper presents an accelerated LSPIA method for tensor product surfaces and shows that the corresponding iterative surface sequence converged to the least-squares fitting surface of the given data set. The iterative format is that of a non-stationary iterative method, and the convergence rate increased rapidly as the iteration number increased. Some numerical examples are provided to illustrate that the proposed method has a faster convergence rate.

Due to climate change and rapid urbanization, contemporary cities face the dual challenges of providing sufficient stormwater management and adequate park services, which potentially conflict over limited space and resources. To solve these problems, cities are increasingly combining stormwater infrastructure with park space in ways that create new efficiencies. To date, most research has focused on the stormwater management performance aspect of these combinations and not the techniques employed to achieve the combined goals. To fill this gap, 23 sponge city parks in Shanghai were investigated to examine the combination of stormwater and park services. Our findings show that stormwater techniques were primarily combined with the park facilities of water areas, paved open spaces, and pathways. Additionally, we found that larger parks employed a wider range of techniques for managing stormwater runoff and supported broader sets of park activities, while those at smaller scales prioritized infiltration, detention, and purification measures, as well as concentrated on social and economic activities. This study is the first to explore SPC parks that integrate stormwater management and park services, thereby providing implications for SPC development in China and insights into the ways that the two properties can be combined in other cities.

This study investigated the association of thrombocytopenia (TP) with in-hospital medication and outcome of patients with acute ST-segment elevated myocardial infarction (STEMI). A total of 16,678 consecutive patients with STEMI from multiple centers that participated in the China Acute Myocardial Infarction registry was included. In-hospital adverse event rates were compared between patients with TP and those with a normal platelet count. Multivariate logistic regression was applied to adjust for confounders. Propensity score matching (PSM) was applied to control for baseline differences. There were 359 patients with baseline TP, accounting for 2.2% of the total cohort. The risk of in-hospital death (11.1% vs 6.0%, P < 0.001); major adverse cardiovascular events (MACE) (11.7% vs 6.4%, P < 0.001); and newly occurred or aggravated heart failure, cardiogenic shock, malignant arrhythmia, acute pulmonary embolism, and bleeding (3.6% vs 1.8%, P = 0.024) were significantly higher in the TP group than in the normal platelet group. After multivariate adjustment, TP was independently associated only with malignant arrhythmia (odds ratio: 1.49; 95% confidence interval: 1.09–2.05, P = 0.014). A total of 289 patients in each group were matched by PSM. The risk of all endpoints was not significantly different between the two matched groups before and after multivariate adjustment. In-hospital outcomes were worse in patients with STEMI and TP than in those with a normal platelet count. However, baseline TP was not independently associated with in-hospital death, MACE, or bleeding risk after multivariate adjustment and controlling for baseline differences.